WorldWideScience

Sample records for global molecular screening

  1. Molecular HIV screening.

    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 in galactosemia

    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.

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

    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 ...

  4. Electron screening in molecular fusion reactions

    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.)

  5. Diabetic retinopathy screening: global and local perspective.

    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.

  6. Fecal Molecular Markers for Colorectal Cancer Screening

    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.

  7. Molecular science solving global problems

    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

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

    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 ...

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

    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).

  10. Recharging of a screened ion on the molecular ion

    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

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

    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, ...

  12. Local-global classifier fusion for screening chest radiographs

    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.

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

    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. Colorectal Cancer in Iran: Molecular Epidemiology and Screening Strategies

    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.

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

    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.

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

    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.

  17. Identifying the Molecular Origin of Global Warming

    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.

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

    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.

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

    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

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

    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 ...

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

    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 ...

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

    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-.

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

    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...

  4. Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.

    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.

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

    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

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

    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.

  7. Rapid screening of operational freshwater availability using global models

    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

  8. Global cost-effectiveness of GDM screening and management

    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...

  9. Global Molecular Epidemiology of IMP-Producing Enterobacteriaceae.

    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.

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

    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…

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

    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.

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

    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

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

    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

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

    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.…

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

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

    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.

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

    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

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

    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.

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

    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.

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

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

    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.

  2. Coproscopy and molecular screening for detection of intestinal protozoa.

    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.

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

    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.

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

    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

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

    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

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

    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

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

    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.

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

    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

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

    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

  10. Screens

    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).

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

    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.

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

    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.

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

    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.

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

    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.

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

    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/.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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 (\

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

    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

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

    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.

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

    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.

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

    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.

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

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

    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.

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

    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

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

    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

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

    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.

  19. 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.

    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.

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

    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

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

    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.

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

    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.

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

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

    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.

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

    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.

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

    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

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

    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

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

    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

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

    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.

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

    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%.

  11. Targeting acetylcholinesterase: identification of chemical leads by high throughput screening, structure determination and molecular modeling.

    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

  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.

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

    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...

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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

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

    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.

  1. Screening of molecular cell targets for carcinogenic heterocyclic aromatic amines by using CALUX® reporter gene assays.

    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.

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

    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

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

    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

  4. Localizing Global Medicine: Challenges and Opportunities in Cervical Screening in an Indigenous Community in Ecuador.

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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...

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

  18. Conformation guides molecular efficacy in docking screens of activated β-2 adrenergic G protein coupled receptor.

    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.

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

    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.

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

    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.

  1. Globalization

    Tulio Rosembuj

    2006-12-01

    Full Text Available There is no singular globalization, nor is the result of an individual agent. We could start by saying that global action has different angles and subjects who perform it are different, as well as its objectives. The global is an invisible invasion of materials and immediate effects.

  2. Globalization

    Tulio Rosembuj

    2006-01-01

    There is no singular globalization, nor is the result of an individual agent. We could start by saying that global action has different angles and subjects who perform it are different, as well as its objectives. The global is an invisible invasion of materials and immediate effects.

  3. Global Screening of Antiviral Genes that Suppress Baculovirus Transgene Expression in Mammalian Cells.

    Wang, Chia-Hung; Naik, Nenavath Gopal; Liao, Lin-Li; Wei, Sung-Chan; Chao, Yu-Chan

    2017-09-15

    Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death. Silencing of RIP1 did not affect viral entry or cell viability, but it did inhibit nuclear translocation of the IRF3 and NF-κB transcription factors. Also, activation of downstream signaling mediators (such as TBK1 and IRF7) was affected, and subsequent interferon and cytokine gene expression levels were abolished. Further, Necrostatin-1 (Nec-1)-an inhibitor of RIP1 kinase activity-dramatically increased baculoviral transgene expression in RIP1-silenced cells. Using baculovirus as a model system, this study presents an initial investigation of large numbers of human cell antiviral innate immune response factors against a "nonadaptive virus." In addition, our study has made baculovirus a more efficient gene transfer vector for some of the most frequently used mammalian cell systems.

  4. A globally applicable location-specific screening model for assessing the relative risk of pesticide leaching

    Whelan, M.J.; Davenport, E.J.; Smith, B.G.

    2007-01-01

    A screening model of pesticide leaching loss is described which forms part of a multi-criteria risk-based indicator system called PRoMPT (Pesticide Risk Management and Profiling Tool). The leaching model evaluates pesticide fate in soil for any application rate and time of application (including multiple applications), for any land-based location in the world. It considers a generic evaluative environment with fixed dimensions and soil properties. The soil profile is conceptualised as a number of discrete layers. Equilibrium partitioning between adsorbed and dissolved chemical (based on the organic carbon-water partition coefficient [K OC ]) is assumed in each time step, in each layer. Non-leaching losses are described using first order kinetics. Drainage is assumed to be uniform throughout the soil profile but varies temporally. The drainage rate, which can be augmented by evapotranspiration-adjusted irrigation, is derived from long-term mean monthly water balance model calculations performed for 30 arc-minute grid cells across the entire ice-free land surface of the earth. Although, such predictions are approximate, they do capture the seasonality and relative magnitude of drainage and allow the model to be applied anywhere, without the need for extensive data compilation. PRoMPT predictions are shown to be consistent with those made by more sophisticated models (PRZM, PELMO and PEARL) for the FOCUS groundwater scenarios

  5. A globally applicable location-specific screening model for assessing the relative risk of pesticide leaching

    Whelan, M.J. [Unilever Safety and Environmental Assurance Centre, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom)]. E-mail: mick.whelan@unilever.com; Davenport, E.J. [Unilever Safety and Environmental Assurance Centre, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom); Smith, B.G. [Unilever Sustainable Agriculture Team, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom)

    2007-05-15

    A screening model of pesticide leaching loss is described which forms part of a multi-criteria risk-based indicator system called PRoMPT (Pesticide Risk Management and Profiling Tool). The leaching model evaluates pesticide fate in soil for any application rate and time of application (including multiple applications), for any land-based location in the world. It considers a generic evaluative environment with fixed dimensions and soil properties. The soil profile is conceptualised as a number of discrete layers. Equilibrium partitioning between adsorbed and dissolved chemical (based on the organic carbon-water partition coefficient [K {sub OC}]) is assumed in each time step, in each layer. Non-leaching losses are described using first order kinetics. Drainage is assumed to be uniform throughout the soil profile but varies temporally. The drainage rate, which can be augmented by evapotranspiration-adjusted irrigation, is derived from long-term mean monthly water balance model calculations performed for 30 arc-minute grid cells across the entire ice-free land surface of the earth. Although, such predictions are approximate, they do capture the seasonality and relative magnitude of drainage and allow the model to be applied anywhere, without the need for extensive data compilation. PRoMPT predictions are shown to be consistent with those made by more sophisticated models (PRZM, PELMO and PEARL) for the FOCUS groundwater scenarios.

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

    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.

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

    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.

  8. Bioassay and Molecular Screening of Pectinase Enzyme in halophilic bacteria from Salt Lake, Iran

    Zohre Nasrollahzadeh

    2018-06-01

    Discussion and conclusion: Quantitative evaluation showed that production and activity of pectinase enzyme in R2S25 strain increased simultaneously with increasing the growth of selected strain in logarithmic phase. Molecular study also showed that the genuses of Martelella, Aeromocrobium, Planococcus, Marinobacter, Virgibacillus, Kocuria and Micrococcus contain the pectinase gene.

  9. Coordinating Center: Molecular and Cellular Findings of Screen-Detected Lesions | Division of Cancer Prevention

    The Molecular and Cellular Characterization of Screen‐Detected Lesions ‐ Coordinating Center and Data Management Group will provide support for the participating studies responding to RFA CA14‐10. The coordinating center supports three main domains: network coordination, statistical support and computational analysis and protocol development and database support. Support for

  10. Application of molecular imaging combined with genetic screening in diagnosing MELAS, diabetes and recurrent pancreatitis.

    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.

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

    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.

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

    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)

  13. Antioxidant properties and global metabolite screening of the probiotic yeast Saccharomyces cerevisiae var. boulardii.

    Datta, Suprama; Timson, David J; Annapure, Uday S

    2017-07-01

    Saccharomyces cerevisiae var. boulardii is the only yeast species with probiotic properties. It is considered to have therapeutic significance in gastrointestinal disorders. In the present study, a comparative physiological study between this yeast and Saccharomyces cerevisiae (BY4742) was performed by evaluating two prominent traits of probiotic species, responses to different stress conditions and antioxidant capacity. A global metabolite profile was also developed aiming to identify which therapeutically important secondary metabolites are produced. Saccharomyces cerevisiae var. boulardii showed no significant difference in growth patterns but greater stress tolerance compared to S. cerevisiae. It also demonstrated a six- to 10-fold greater antioxidant potential (judged by the 1,1-diphenyl-2-picrylhydrazyl assay), with a 70-fold higher total phenolic content and a 20-fold higher total flavonoid content in the extracellular fraction. These features were clearly differentiated by principal component analysis and further indicated by metabolite profiling. The extracellular fraction of the S. cerevisiae var. boulardii cultures was found to be rich in polyphenolic metabolites: vanillic acid, cinnamic acid, phenyl ethyl alcohol (rose oil), erythromycin, amphetamine and vitamin B 6 , which results in the antioxidant capacity of this strain. The present study presents a new perspective for differentiating the two genetically related strains of yeast, S. cerevisiae and S. cerevisiae var. boulardii by assessing their metabolome fingerprints. In addition to the correlation of the phenotypic properties with the secretory metabolites of these two yeasts, the present study also emphasizes the potential to exploit S. cerevisiae var. boulardii in the industrial production of these metabolites. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  14. Globalization

    Andru?cã Maria Carmen

    2013-01-01

    The field of globalization has highlighted an interdependence implied by a more harmonious understanding determined by the daily interaction between nations through the inducement of peace and the management of streamlining and the effectiveness of the global economy. For the functioning of the globalization, the developing countries that can be helped by the developed ones must be involved. The international community can contribute to the institution of the development environment of the gl...

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

    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.

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

    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.

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

    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.

  18. MORPHO-MOLECULAR SCREENING OF RICE (ORYZA SATIVA L. GENOTYPES AT SEEDLING STAGE FOR SALT TOLERANCE

    Ali Julfiker Md. Masud

    2014-10-01

    Full Text Available Providing adequate food to meet an escalating population is one of the gravest problems the humankind is now facing. To resolve this crisis identification of salt tolerant rice variety is very vital. So, in this research, ten rice genotypes were used to screen salinity tolerance at the seedling stage in hydroponic system using SSR markers. Salinity screening was done at glasshouse following IRRI standard protocol using two setups of salinized and non-salinized conditions. Genotypes under controlled condition had longer root and shoot length then salt stress genotypes. Parental polymorphism survey was done with ten SSR markers viz., RM336, RM510, RM7075, RM407, RM3201b, RM10748, AP3206f, RM3412, RM585, RM11504 and all were selected to evaluate salt tolerance in rice genotypes. The number of alleles per locus ranged from 3 (AP3206f to 9 (RM336, with an average of 6.1 alleles across 10 loci obtained in the study. The polymorphic information content values ranged from of 0.54 (AP3206f to a high of 0.86 (RM336 with an average of 0.74. The pair-wise comparisons of Nei’s (1973 genetic distance (D between varieties were computed from combined data for the 10 primers, ranged from 0.30 to 0.90 with an average of 0.86, while the similarity index based analysis ranged from 0.00 to 0.70. Finally, the FL-478, FL-378, Binadhan-8 and Binadhan-10 were selected as salt tolerant because they showed tolerance in phenotypic analysis. These phenotypically selected tolerant genotypes could be used for the selection of suitable parents and development of salt tolerant rice varieties.

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

    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.

  20. Anti-inflammatory and antioxidant properties of Piper species: a perspective from screening to molecular mechanisms.

    Kumar, Sarvesh; Malhotra, Shashwat; Prasad, Ashok K; Van der Eycken, Erik V; Bracke, Marc E; Stetler-Stevenson, William G; Parmar, Virinder S; Ghosh, Balaram

    2015-01-01

    Identifying novel therapeutic agents from natural sources and their possible intervention studies has been one of the major areas in biomedical research in recent years. Piper species are highly important - commercially, economically and medicinally. Our groups have been working for more than two decades on the identification and characterization of novel therapeutic lead molecules from Piper species. We have extensively studied the biological activities of various extracts of Piper longum and Piper galeatum, and identified and characterized novel molecules from these species. Using synthetic chemistry, various functional groups of the lead molecules were modified and structure activity relationship (SAR) studies identified synthetic molecules with better efficacy and lower IC50 values. Moreover, the mechanisms of actions of some of these molecules were studied at the molecular level. The objective of this review is to summarize experimental data published from our laboratories and others on antioxidant and anti-inflammatory potentials of Piper species and their chemical constituents.

  1. Molecular surveillance of true nontypeable Haemophilus influenzae: an evaluation of PCR screening assays.

    Binks, Michael J; Temple, Beth; Kirkham, Lea-Ann; Wiertsema, Selma P; Dunne, Eileen M; Richmond, Peter C; Marsh, Robyn L; Leach, Amanda J; Smith-Vaughan, Heidi C

    2012-01-01

    Unambiguous identification of nontypeable Haemophilus influenzae (NTHi) is not possible by conventional microbiology. Molecular characterisation of phenotypically defined NTHi isolates suggests that up to 40% are Haemophilus haemolyticus (Hh); however, the genetic similarity of NTHi and Hh limits the power of simple molecular techniques such as PCR for species discrimination. Here we assess the ability of previously published and novel PCR-based assays to identify true NTHi. Sixty phenotypic NTHi isolates, classified by a dual 16S rRNA gene PCR algorithm as NTHi (n = 22), Hh (n = 27) or equivocal (n = 11), were further characterised by sequencing of the 16S rRNA and recA genes then interrogated by PCR-based assays targeting the omp P2, omp P6, lgtC, hpd, 16S rRNA, fucK and iga genes. The sequencing data and PCR results were used to define NTHi for this study. Two hpd real time PCR assays (hpd#1 and hpd#3) and the conventional iga PCR assay were equally efficient at differentiating study-defined NTHi from Hh, each with a receiver operator characteristic curve area of 0.90 [0.83; 0.98]. The hpd#1 and hpd#3 assays were completely specific against a panel of common respiratory bacteria, unlike the iga PCR, and the hpd#3 assay was able to detect below 10 copies per reaction. Our data suggest an evolutionary continuum between NTHi and Hh and therefore no single gene target could completely differentiate NTHi from Hh. The hpd#3 real time PCR assay proved to be the superior method for discrimination of NTHi from closely related Haemophilus species with the added potential for quantification of H. influenzae directly from specimens. We suggest the hpd#3 assay would be suitable for routine NTHi surveillance and to assess the impact of antibiotics and vaccines, on H. influenzae carriage rates, carriage density, and disease.

  2. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

    Lynch, HT; Lynch, PM; Lanspa, SJ; Snyder, CL; Lynch, JF; Boland, CR

    2010-01-01

    More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC’s proximal occurrence (70–80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10–25% of familial CRC. PMID:19659756

  3. Metagenomic-Based Screening and Molecular Characterization of Cowpea-Infecting Viruses in Burkina Faso.

    Palanga, Essowè; Filloux, Denis; Martin, Darren P; Fernandez, Emmanuel; Gargani, Daniel; Ferdinand, Romain; Zabré, Jean; Bouda, Zakaria; Neya, James Bouma; Sawadogo, Mahamadou; Traore, Oumar; Peterschmitt, Michel; Roumagnac, Philippe

    2016-01-01

    Cowpea, (Vigna unguiculata L. (Walp)) is an annual tropical grain legume. Often referred to as "poor man's meat", cowpea is one of the most important subsistence legumes cultivated in West Africa due to the high protein content of its seeds. However, African cowpea production can be seriously constrained by viral diseases that reduce yields. While twelve cowpea-infecting viruses have been reported from Africa, only three of these have so-far been reported from Burkina Faso. Here we use a virion-associated nucleic acids (VANA)-based metagenomics method to screen for the presence of cowpea viruses from plants collected from the three agro-climatic zones of Burkina Faso. Besides the three cowpea-infecting virus species which have previously been reported from Burkina Faso (Cowpea aphid borne mosaic virus [Family Potyviridae], the Blackeye cowpea mosaic virus-a strain of Bean common mosaic virus-[Family Potyviridae] and Cowpea mottle virus [Family Tombusviridae]) five additional viruses were identified: Southern cowpea mosaic virus (Sobemovirus genus), two previously uncharacterised polerovirus-like species (Family Luteoviridae), a previously uncharacterised tombusvirus-like species (Family Tombusviridae) and a previously uncharacterised mycotymovirus-like species (Family Tymoviridae). Overall, potyviruses were the most prevalent cowpea viruses (detected in 65.5% of samples) and the Southern Sudan zone of Burkina Faso was found to harbour the greatest degrees of viral diversity and viral prevalence. Partial genome sequences of the two novel polerovirus-like and tombusvirus-like species were determined and RT-PCR primers were designed for use in Burkina Faso to routinely detect all of these cowpea-associated viruses.

  4. Metagenomic-Based Screening and Molecular Characterization of Cowpea-Infecting Viruses in Burkina Faso.

    Essowè Palanga

    Full Text Available Cowpea, (Vigna unguiculata L. (Walp is an annual tropical grain legume. Often referred to as "poor man's meat", cowpea is one of the most important subsistence legumes cultivated in West Africa due to the high protein content of its seeds. However, African cowpea production can be seriously constrained by viral diseases that reduce yields. While twelve cowpea-infecting viruses have been reported from Africa, only three of these have so-far been reported from Burkina Faso. Here we use a virion-associated nucleic acids (VANA-based metagenomics method to screen for the presence of cowpea viruses from plants collected from the three agro-climatic zones of Burkina Faso. Besides the three cowpea-infecting virus species which have previously been reported from Burkina Faso (Cowpea aphid borne mosaic virus [Family Potyviridae], the Blackeye cowpea mosaic virus-a strain of Bean common mosaic virus-[Family Potyviridae] and Cowpea mottle virus [Family Tombusviridae] five additional viruses were identified: Southern cowpea mosaic virus (Sobemovirus genus, two previously uncharacterised polerovirus-like species (Family Luteoviridae, a previously uncharacterised tombusvirus-like species (Family Tombusviridae and a previously uncharacterised mycotymovirus-like species (Family Tymoviridae. Overall, potyviruses were the most prevalent cowpea viruses (detected in 65.5% of samples and the Southern Sudan zone of Burkina Faso was found to harbour the greatest degrees of viral diversity and viral prevalence. Partial genome sequences of the two novel polerovirus-like and tombusvirus-like species were determined and RT-PCR primers were designed for use in Burkina Faso to routinely detect all of these cowpea-associated viruses.

  5. Molecular surveillance of true nontypeable Haemophilus influenzae: an evaluation of PCR screening assays.

    Michael J Binks

    Full Text Available BACKGROUND: Unambiguous identification of nontypeable Haemophilus influenzae (NTHi is not possible by conventional microbiology. Molecular characterisation of phenotypically defined NTHi isolates suggests that up to 40% are Haemophilus haemolyticus (Hh; however, the genetic similarity of NTHi and Hh limits the power of simple molecular techniques such as PCR for species discrimination. METHODOLOGY/PRINCIPAL FINDINGS: Here we assess the ability of previously published and novel PCR-based assays to identify true NTHi. Sixty phenotypic NTHi isolates, classified by a dual 16S rRNA gene PCR algorithm as NTHi (n = 22, Hh (n = 27 or equivocal (n = 11, were further characterised by sequencing of the 16S rRNA and recA genes then interrogated by PCR-based assays targeting the omp P2, omp P6, lgtC, hpd, 16S rRNA, fucK and iga genes. The sequencing data and PCR results were used to define NTHi for this study. Two hpd real time PCR assays (hpd#1 and hpd#3 and the conventional iga PCR assay were equally efficient at differentiating study-defined NTHi from Hh, each with a receiver operator characteristic curve area of 0.90 [0.83; 0.98]. The hpd#1 and hpd#3 assays were completely specific against a panel of common respiratory bacteria, unlike the iga PCR, and the hpd#3 assay was able to detect below 10 copies per reaction. CONCLUSIONS/SIGNIFICANCE: Our data suggest an evolutionary continuum between NTHi and Hh and therefore no single gene target could completely differentiate NTHi from Hh. The hpd#3 real time PCR assay proved to be the superior method for discrimination of NTHi from closely related Haemophilus species with the added potential for quantification of H. influenzae directly from specimens. We suggest the hpd#3 assay would be suitable for routine NTHi surveillance and to assess the impact of antibiotics and vaccines, on H. influenzae carriage rates, carriage density, and disease.

  6. Cytogenetic and molecular screening of the DAZ gene family in a population of infertile males

    Nubia Amparo Ruiz Suárez

    2003-01-01

    Full Text Available The purpose of this study was to evalúate the frequency of Y chromosome structural, numerical, chromosomal and genetic abnormalities, as well as DAZ gene microdeletions in the Y chromosome in a population of infertile males. Genetic abnormalities have been established to date in up to 24% of males having severe abnormalities in their sperm (Dohle et al. 2002; deletion of the DAZ gene family (deleted in azoospermia is the most common cause. It has been found in 6% of the oligozoospermias and in 12% of the azoospermias (Van Landuyt et al. 2000. A popula­tion of 20 azoospermic and 10 oligozoospermic males was studied. Five males having normal sperm parameters were used as controls. Each sample was karyotyped (QFQ banding and underwent sY254, sY255 and sY257 mo­lecular amplification. Genetic study revealed alterations in 16.6% of the cases: 6.6% at chromosome level and 10% at molecule level. No chromosomal or molecular gene alterations were detected in control males. The frequencies found lead to a broader population-based study being recommended. They confirmed the need for performing judicious genetic counselling in infertile couples with male factor infertility to avoid or minimise the risks of trans-mitting these abnormalities to offspring and provide better prognosis for assisted reproductive techniques in such patients. Key words: azoospermia; oligozoospermia; microdeletions; ICSI

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

    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

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

    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

  9. Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

    Kumar, Ambuj [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India); Purohit, Rituraj, E-mail: riturajpurohit@gmail.com [Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India)

    2012-10-15

    Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R{sub g}), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

  10. Molecularly imprinted polymer (MIP) membrane assisted direct spray ionization mass spectrometry for agrochemicals screening in foodstuffs.

    Pereira, Igor; Rodrigues, Marcella Ferreira; Chaves, Andréa Rodrigues; Vaz, Boniek Gontijo

    2018-02-01

    Paper spray ionization (PSI) has some limitations such as low sensitivity and ionization suppression when complex samples are analyzed. The use of sample preparation devices directly coupled to MS can avoid these restrictions. Molecularly imprinted polymers (MIPs) are materials widely used as adsorbent in sample preparation methods such as solid-phase extraction and solid-phase microextraction, and they can provide specifics cavities with affinity to a target molecule. Here, we introduce a new MIP membrane spray ionization method combining MIP and PSI. MIP was synthesized directly on a cellulose membrane. Monuron and 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) were used as template molecules in MIP synthesis for diuron and 2,4-D (2,4-dichlorophenoxyacetic acid) analyte sequesters, respectively. Apple, banana and grape methanolic extracts were used as matrices. The MIP membrane spray showed signal intensities of diuron and 2,4-D that were much higher compared to those obtained by non-imprinted polymers(NIP). Calibration curves exhibited R 2 > 0.99 for diuron and 2,4-D in all fruit extracts analyzed. LODs were found less than 0.60µgL -1 and LLOQs were found less than 2.00µgL -1 . The coefficients of variation and relative errors were less than 15% for almost all analyses. The apparent recovery test results ranged between 92,5% and 116.9%. Finally, the MIP membrane spray method was employed for the quantification of diuron and 2,4-D in real samples. Diuron contents were only found in three bananas (4.0, 6.5, and 9.9µgL -1 ). The proposed MIP membrane spray ionization method was straightforward, fast to carry out and provided satisfactory results for analyses of diuron and 2,4-D in apple, banana and grape samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Computational screening and molecular dynamics simulation of disease associated nsSNPs in CENP-E

    Kumar, Ambuj; Purohit, Rituraj

    2012-01-01

    Aneuploidy and chromosomal instability (CIN) are hallmarks of most solid tumors. Mutations in centroemere proteins have been observed in promoting aneuploidy and tumorigenesis. Recent studies reported that Centromere-associated protein-E (CENP-E) is involved in inducing cancers. In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. Y63H point mutation found to be associated with cancer using SIFT, Polyphen, PhD-SNP, MutPred, CanPredict and Dr. Cancer tools. Further we investigated the binding affinity of ATP molecule to the CENP-E motor domain. Complementarity scores obtained from docking studies showed significant loss in ATP binding affinity of mutant structure. Molecular dynamics simulation was carried to examine the structural consequences of Y63H mutation. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R g ), solvent accessibility surface area (SASA), energy value, hydrogen bond (NH Bond), eigenvector projection, trace of covariance matrix and atom density analysis results showed notable loss in stability for mutant structure. Y63H mutation was also shown to disrupt the native conformation of ATP binding region in CENP-E motor domain. Docking studies for remaining 18 mutations at 63rd residue position as well as other two computationally predicted disease associated mutations S22L and P69S were also carried to investigate their affect on ATP binding affinity of CENP-E motor domain. Our study provided a promising computational methodology to study the tumorigenic consequences of nsSNPs that have not been characterized and clear clue to the wet lab scientist.

  12. Globalization

    Plum, Maja

    Globalization is often referred to as external to education - a state of affair facing the modern curriculum with numerous challenges. In this paper it is examined as internal to curriculum; analysed as a problematization in a Foucaultian sense. That is, as a complex of attentions, worries, ways...... of reasoning, producing curricular variables. The analysis is made through an example of early childhood curriculum in Danish Pre-school, and the way the curricular variable of the pre-school child comes into being through globalization as a problematization, carried forth by the comparative practices of PISA...

  13. Globalization

    F. Gerard Adams

    2008-01-01

    The rapid globalization of the world economy is causing fundamental changes in patterns of trade and finance. Some economists have argued that globalization has arrived and that the world is “flat†. While the geographic scope of markets has increased, the author argues that new patterns of trade and finance are a result of the discrepancies between “old†countries and “new†. As the differences are gradually wiped out, particularly if knowledge and technology spread worldwide, the t...

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

    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.

  15. 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.

    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.

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

    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.

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

    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.

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

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

    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.

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

    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.

  1. Global landscape assessment of screening technologies for medicine quality assurance: stakeholder perceptions and practices from ten countries.

    Roth, Lukas; Nalim, Ameena; Turesson, Beth; Krech, Laura

    2018-04-25

    The spread of substandard and falsified (SF) medical products constitutes a growing global public health concern. Some countries use portable, handheld screening technologies (STs) in the field to accelerate detection of SF medicines and reduce the number of medicine samples that undergo costly and time-consuming confirmatory analysis. A multi-country, multi-stakeholder landscape assessment utilizing qualitative methodology was used to examine practices and perceptions related to the use of STs. Qualitative interview guides were designed using the results of a literature review and comprised of open-ended questions with the study participants, who were from national medicine regulatory authorities, pharmaceutical manufacturers, pharmacies, and distributors. Ten geographically and economically diverse countries were selected: Argentina, China, Egypt, India, Jordan, Mexico, Nigeria, Philippines, the United States, and Zimbabwe. Of the completed 53 interviews, 32 were in-person, 16 were phone interviews, and 5 were via written questionnaires. Data analysis shows a wide variation in understanding and usage of STs in different sectors. Virtually all of the study participants indicated a lack of objective, accessible information on STs to advise them on what technologies would be beneficial for their needs. Study participants also described their ideal capabilities of the next generation of STs, including shareable spectral libraries, lower acquisition costs, lesser training requirements, and in-country maintenance and technical support. The results and recommendations presented in this article can be used to help regulators communicate and justify their needs to acquire and invest in new STs. There is a need for additional standardized, trustworthy and scientifically sound evaluations of STs, and to support regulators to effectively deploy the most promising technologies. ST manufacturers can take into account some of the limitations of the technologies the interviewees

  2. Planetary Biology and Microbial Ecology: Molecular Ecology and the Global Nitrogen cycle

    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.

  3. 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

    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

  4. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study.

    van Ingen, Jakko; Kohl, Thomas A; Kranzer, Katharina; Hasse, Barbara; Keller, Peter M; Katarzyna Szafrańska, Anna; Hillemann, Doris; Chand, Meera; Schreiber, Peter Werner; Sommerstein, Rami; Berger, Christoph; Genoni, Michele; Rüegg, Christian; Troillet, Nicolas; Widmer, Andreas F; Becker, Sören L; Herrmann, Mathias; Eckmanns, Tim; Haller, Sebastian; Höller, Christiane; Debast, Sylvia B; Wolfhagen, Maurice J; Hopman, Joost; Kluytmans, Jan; Langelaar, Merel; Notermans, Daan W; Ten Oever, Jaap; van den Barselaar, Peter; Vonk, Alexander B A; Vos, Margreet C; Ahmed, Nada; Brown, Timothy; Crook, Derrick; Lamagni, Theresa; Phin, Nick; Smith, E Grace; Zambon, Maria; Serr, Annerose; Götting, Tim; Ebner, Winfried; Thürmer, Alexander; Utpatel, Christian; Spröer, Cathrin; Bunk, Boyke; Nübel, Ulrich; Bloemberg, Guido V; Böttger, Erik C; Niemann, Stefan; Wagner, Dirk; Sax, Hugo

    2017-01-01

    Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of

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

    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...

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

    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.

  7. Molecular mechanisms responsive to dehydration may impact the invasiveness of perennial weeds under global climate change

    Leafy spurge is an invasive perennial weed in the great plains of the US and Canada. The ability of this herbaceous weed to regenerate new shoot growth from an abundance of crown and root buds after severe abiotic stress is critical for survival. Due to its adaptable and aggressive nature, global cl...

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

    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. DNA detection and single nucleotide mutation identification using SERS for molecular diagnostics and global health

    Ngo, Hoan T.; Gandra, Naveen; Fales, Andrew M.; Taylor, Steve M.; Vo-Dinh, Tuan

    2017-02-01

    Nucleic acid-based molecular diagnostics at the point-of-care (POC) and in resource-limited settings is still a challenge. We present a sensitive yet simple DNA detection method with single nucleotide polymorphism (SNP) identification capability. The detection scheme involves sandwich hybridization of magnetic beads conjugated with capture probes, target sequences, and ultrabright surface-enhanced Raman Scattering (SERS) nanorattles conjugated with reporter probes. Upon hybridization, the sandwich probes are concentrated at the detection focus controlled by a magnetic system for SERS measurements. The ultrabright SERS nanorattles, consisting of a core and a shell with resonance Raman reporters loaded in the gap space between the core and the shell, serve as SERS tags for ultrasensitive signal detection. Specific DNA sequences of the malaria parasite Plasmodium falciparum and dengue virus 1 (DENV1) were used as the model marker system. Detection limit of approximately 100 attomoles was achieved. Single nucleotide polymorphism (SNP) discrimination of wild type malaria DNA and mutant malaria DNA, which confers resistance to artemisinin drugs, was also demonstrated. The results demonstrate the molecular diagnostic potential of the nanorattle-based method to both detect and genotype infectious pathogens. The method's simplicity makes it a suitable candidate for molecular diagnosis at the POC and in resource-limited settings.

  10. Global plant-responding mechanisms to salt stress: physiological and molecular levels and implications in biotechnology.

    Tang, Xiaoli; Mu, Xingmin; Shao, Hongbo; Wang, Hongyan; Brestic, Marian

    2015-01-01

    The increasing seriousness of salinization aggravates the food, population and environmental issues. Ameliorating the salt-resistance of plants especially the crops is the most effective measure to solve the worldwide problem. The salinity can cause damage to plants mainly from two aspects: hyperosmotic and hyperionic stresses leading to the restrain of growth and photosynthesis. To the adverse effects, the plants derive corresponding strategies including: ion regulation and compartmentalization, biosynthesis of compatible solutes, induction of antioxidant enzymes and plant hormones. With the development of molecular biology, our understanding of the molecular and physiology knowledge is becoming clearness. The complex signal transduction underlying the salt resistance is being illuminated brighter and clearer. The SOS pathway is the central of the cell signaling in salt stress. The accumulation of the compatible solutes and the activation of the antioxidant system are the effective measures for plants to enhance the salt resistance. How to make full use of our understanding to improve the output of crops is a huge challenge for us, yet the application of the genetic engineering makes this possible. In this review, we will discuss the influence of the salt stress and the response of the plants in detail expecting to provide a particular account for the plant resistance in molecular, physiological and transgenic fields.

  11. Pandemics, pathogenicity and changing molecular epidemiology of cholera in the era of global warming.

    Chowdhury, Fazle Rabbi; Nur, Zannatun; Hassan, Nazia; von Seidlein, Lorenz; Dunachie, Susanna

    2017-03-07

    Vibrio cholerae, a Gram-negative, non-spore forming curved rod is found in diverse aquatic ecosystems around the planet. It is classified according to its major surface antigen into around 206 serogroups, of which O1 and O139 cause epidemic cholera. A recent spatial modelling technique estimated that around 2.86 million cholera cases occur globally every year, and of them approximately 95,000 die. About 1.3 billion people are currently at risk of infection from cholera. Meta-analysis and mathematical modelling have demonstrated that due to global warming the burden of vector-borne diseases like malaria, leishmaniasis, meningococcal meningitis, viral encephalitis, dengue and chikungunya will increase in the coming years in the tropics and beyond. This review offers an overview of the interplay between global warming and the pathogenicity and epidemiology of V. cholerae. Several distinctive features of cholera survival (optimal thriving at 15% salinity, 30 °C water temperature, and pH 8.5) indicate a possible role of climate change in triggering the epidemic process. Genetic exchange (ctxAB, zot, ace, cep, and orfU) between strains and transduction process allows potential emergence of new toxigenic clones. These processes are probably controlled by precise environmental signals such as optimum temperature, sunlight and osmotic conditions. Environmental influences on phytoplankton growth and chitin remineralization will be discussed alongside the interplay of poor sanitary conditions, overcrowding, improper sewage disposal and global warming in promoting the growth and transmission of this deadly disease. The development of an effective early warning system based on climate data could help to prevent and control future outbreaks. It may become possible to integrate real-time monitoring of oceanic regions, climate variability and epidemiological and demographic population dynamics to predict cholera outbreaks and support the design of cost-effective public health

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

    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.

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

    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.

  14. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 7 - Pathogenesis and Molecular Biology.

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review (2011-15) and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identified facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of virulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain

  15. The pharmaceuticalisation of security: Molecular biomedicine, antiviral stockpiles, and global health security.

    Elbe, Stefan

    2014-12-01

    Pharmaceuticals are now critical to the security of populations. Antivirals, antibiotics, next-generation vaccines, and antitoxins are just some of the new 'medical countermeasures' that governments are stockpiling in order to defend their populations against the threat of pandemics and bioterrorism. How has security policy come to be so deeply imbricated with pharmaceutical logics and solutions? This article captures, maps, and analyses the 'pharmaceuticalisation' of security. Through an in-depth analysis of the prominent antiviral medication Tamiflu , it shows that this pharmaceutical turn in security policy is intimately bound up with the rise of a molecular vision of life promulgated by the biomedical sciences. Caught in the crosshairs of powerful commercial, political, and regulatory pressures, governments are embracing a molecular biomedicine promising to secure populations pharmaceutically in the twenty-first century. If that is true, then the established disciplinary view of health as a predominantly secondary matter of 'low' international politics is mistaken. On the contrary, the social forces of health and biomedicine are powerful enough to influence the core practices of international politics - even those of security. For a discipline long accustomed to studying macrolevel processes and systemic structures, it is in the end also our knowledge of the minute morass of molecules that shapes international relations.

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

    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.

  17. 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.

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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

  3. Global patterns of insect diversification: towards a reconciliation of fossil and molecular evidence?

    Condamine, Fabien L; Clapham, Matthew E; Kergoat, Gael J

    2016-01-18

    Macroevolutionary studies of insects at diverse taxonomic scales often reveal dynamic evolutionary patterns, with multiple inferred diversification rate shifts. Responses to major past environmental changes, such as the Cretaceous Terrestrial Revolution, or the development of major key innovations, such as wings or complete metamorphosis are usually invoked as potential evolutionary triggers. However this view is partially contradicted by studies on the family-level fossil record showing that insect diversification was relatively constant through time. In an attempt to reconcile both views, we investigate large-scale insect diversification dynamics at family level using two distinct types of diversification analyses on a molecular timetree representing ca. 82% of the extant families, and reassess the insect fossil diversity using up-to-date records. Analyses focusing on the fossil record recovered an early burst of diversification, declining to low and steady rates through time, interrupted by extinction events. Phylogenetic analyses showed that major shifts of diversification rates only occurred in the four richest holometabolous orders. Both suggest that neither the development of flight or complete metamorphosis nor the Cretaceous Terrestrial Revolution environmental changes induced immediate changes in diversification regimes; instead clade-specific innovations likely promoted the diversification of major insect orders.

  4. Global Modeling of Uranium Molecular Species Formation Using Laser-Ablated Plasmas

    Curreli, Davide; Finko, Mikhail; Azer, Magdi; Armstrong, Mike; Crowhurst, Jonathan; Radousky, Harry; Rose, Timothy; Stavrou, Elissaios; Weisz, David; Zaug, Joseph

    2016-10-01

    Uranium is chemically fractionated from other refractory elements in post-detonation nuclear debris but the mechanism is poorly understood. Fractionation alters the chemistry of the nuclear debris so that it no longer reflects the chemistry of the source weapon. The conditions of a condensing fireball can be simulated by a low-temperature plasma formed by vaporizing a uranium sample via laser heating. We have developed a global plasma kinetic model in order to model the chemical evolution of U/UOx species within an ablated plasma plume. The model allows to track the time evolution of the density and energy of an uranium plasma plume moving through an oxygen atmosphere of given fugacity, as well as other relevant quantities such as average electron and gas temperature. Comparison of model predictions with absorption spectroscopy of uranium-ablated plasmas provide preliminary insights on the key chemical species and evolution pathways involved during the fractionation process. This project was sponsored by the DoD, Defense Threat Reduction Agency, Grant HDTRA1-16-1-0020. This work was performed in part under the auspices of the U.S. DoE by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  5. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study.

    van Ingen, Jakko; Kohl, Thomas A; Kranzer, Katharina; Hasse, Barbara; Keller, Peter M; Katarzyna Szafrańska, Anna; Hillemann, Doris; Chand, Meera; Schreiber, Peter Werner; Sommerstein, Rami; Berger, Christoph; Genoni, Michele; Rüegg, Christian; Troillet, Nicolas; Widmer, Andreas F; Becker, Sören L; Herrmann, Mathias; Eckmanns, Tim; Haller, Sebastian; Höller, Christiane; Debast, Sylvia B; Wolfhagen, Maurice J; Hopman, Joost; Kluytmans, Jan; Langelaar, Merel; Notermans, Daan W; Ten Oever, Jaap; van den Barselaar, Peter; Vonk, Alexander B A; Vos, Margreet C; Ahmed, Nada; Brown, Timothy; Crook, Derrick; Lamagni, Theresa; Phin, Nick; Smith, E Grace; Zambon, Maria; Serr, Annerose; Götting, Tim; Ebner, Winfried; Thürmer, Alexander; Utpatel, Christian; Spröer, Cathrin; Bunk, Boyke; Nübel, Ulrich; Bloemberg, Guido V; Böttger, Erik C; Niemann, Stefan; Wagner, Dirk; Sax, Hugo

    2017-10-01

    Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection

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

    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.

  7. Virtual screening approach to identifying influenza virus neuraminidase inhibitors using molecular docking combined with machine-learning-based scoring function.

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

    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.

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

    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.

  10. Contribution of two molecular assays as compared to selective culture for MRSA screening in a low MRSA prevalence population

    Nulens, E; Descheemaeker, P; Deurenberg, R H; Stobberingh, E E; Gordts, B

    BACKGROUND: As the prompt detection of methicillin-resistant Staphylococcus aureus (MRSA) carriers upon admission is fundamental in the MRSA prevention strategy of our hospital, the infection control team is eagerly seeking the most sensitive and rapid screening method. The aim of this study was to

  11. Complementing in vitro screening assays with in silico molecular chemistry tools to examine potential in vivo metabolite-mediated effects

    High-throughput in vitro assays offer a rapid, cost-efficient means to screen thousands of chemicals across hundreds of pathway-based toxicity endpoints. However, one main concern involved with the use of in vitro assays is the erroneous omission of chemicals that are inactive un...

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

    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.

  13. 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.

    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.

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

    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

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

    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

  16. What's next? Perspectives and future needs of cervical screening in Europe in the era of molecular testing and vaccination

    Lynge, Elsebeth; Antilla, Ahti; Arbyn, Marc

    2009-01-01

    controlled trials have found HPV-testing to increase the detection rate of cervical intraepithelial neoplasia grade 2+, CIN2+, compared with cytology. Two studies found a decreased detection rate of CIN3+ in the HPV-testing arm at the subsequent screening. Randomised controlled trials found that women......AIM: To outline the perspectives for future control of cervical cancer in Europe. METHODS: Review of current status for major cervical cancer control tools. The review was based on PubMed searches for cervical cancer prevention, Human Papillomavirus, HPV-test, HPV-vaccination, and treatment...... with large loop excision of the transformation zone, LLETZ. RESULTS: Recent studies suggest that condom use offers some but not complete protection against HPV-infection. High quality cytology screening with good population coverage reduces the incidence and mortality of cervical cancer. Randomised...

  17. Case report: lymphogranuloma venereum proctitis-from rapid screening to molecular confirmation of a masked sexually transmitted disease.

    Markowicz, Mateusz; Grilnberger, Evelyn; Huber, Florian; Leibl, Gabriele; Abrahamian, Heidemarie; Gartner, Manfred; Huber, Monika; Chott, Andreas; Reiter, Michael; Stanek, Gerold

    2013-08-01

    Proctitis caused by Chlamydia trachomatis L2b can manifest with very mild, nonspecific symptoms, and appropriate diagnostic evaluation is crucial. The case report demonstrates that rapid screening test, detection of specific antibodies in serum, and direct pathogen identification by PCR performed on tissue sample or rectal swab allow successful diagnosis of the still emerging sexually transmitted disease among homosexual patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Post-travel screening of asymptomatic long-term travelers to the tropics for intestinal parasites using molecular diagnostics.

    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.

  19. Combinatorial screening of halide perovskite thin films and solar cells by mask-defined IR laser molecular beam epitaxy

    Kawashima, Kazuhiro; Okamoto, Yuji; Annayev, Orazmuhammet; Toyokura, Nobuo; Takahashi, Ryota; Lippmaa, Mikk; Itaka, Kenji; Suzuki, Yoshikazu; Matsuki, Nobuyuki; Koinuma, Hideomi

    2017-01-01

    Abstract As an extension of combinatorial molecular layer epitaxy via ablation of perovskite oxides by a pulsed excimer laser, we have developed a laser molecular beam epitaxy (MBE) system for parallel integration of nano-scaled thin films of organic?inorganic hybrid materials. A pulsed infrared (IR) semiconductor laser was adopted for thermal evaporation of organic halide (A-site: CH3NH3I) and inorganic halide (B-site: PbI2) powder targets to deposit repeated A/B bilayer films where the thic...

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

    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.

  1. 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.

    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

  2. Fragment-based virtual screening approach and molecular dynamics simulation studies for identification of BACE1 inhibitor leads.

    Manoharan, Prabu; Ghoshal, Nanda

    2018-05-01

    Traditional structure-based virtual screening method to identify drug-like small molecules for BACE1 is so far unsuccessful. Location of BACE1, poor Blood Brain Barrier permeability and P-glycoprotein (Pgp) susceptibility of the inhibitors make it even more difficult. Fragment-based drug design method is suitable for efficient optimization of initial hit molecules for target like BACE1. We have developed a fragment-based virtual screening approach to identify/optimize the fragment molecules as a starting point. This method combines the shape, electrostatic, and pharmacophoric features of known fragment molecules, bound to protein conjugate crystal structure, and aims to identify both chemically and energetically feasible small fragment ligands that bind to BACE1 active site. The two top-ranked fragment hits were subjected for a 53 ns MD simulation. Principle component analysis and free energy landscape analysis reveal that the new ligands show the characteristic features of established BACE1 inhibitors. The potent method employed in this study may serve for the development of potential lead molecules for BACE1-directed Alzheimer's disease therapeutics.

  3. Tay-Sachs Carrier Screening by Enzyme and Molecular Analyses in the New York City Minority Population.

    Mehta, Nikita; Lazarin, Gabriel A; Spiegel, Erica; Berentsen, Kathleen; Brennan, Kelly; Giordano, Jessica; Haque, Imran S; Wapner, Ronald

    2016-09-01

    Carrier screening for Tay-Sachs disease is performed by sequence analysis of the HEXA gene and/or hexosaminidase A enzymatic activity testing. Enzymatic analysis (EA) has been suggested as the optimal carrier screening method, especially in non-Ashkenazi Jewish (non-AJ) individuals, but its utilization and efficacy have not been fully evaluated in the general population. This study assesses the reliability of EA in comparison with HEXA sequence analysis in non-AJ populations. Five hundred eight Hispanic and African American patients (516 samples) had EA of their leukocytes performed and 12 of these patients who tested positive by EA ("carriers") had subsequent HEXA gene sequencing performed. Of the 508 patients, 25 (4.9%) were EA positive and 40 (7.9%) were inconclusive. Of the 12 patients who were sequenced, 11 did not carry a pathogenic variant and one carried a likely deleterious mutation (NM_000520.4(HEXA):c.1510C>T). High inconclusive rates and poor correlation between positive/inconclusive enzyme results and identification of pathogenic mutations suggest that ethnic-specific recalibration of reference ranges for EA may be necessary. Alternatively, HEXA gene sequencing could be performed.

  4. Smoke screen? The globalization of production, transnational lobbying and the international political economy of plain tobacco packaging.

    Curran, Louise; Eckhardt, Jappe

    2017-01-01

    In 2012 Australia became the first country in the world to introduce plain tobacco packaging in an effort to reduce tobacco consumption. This move was vehemently opposed by the tobacco industry, which challenged it on several levels: nationally, bilaterally and multilaterally at the World Trade Organization (WTO). The political behavior of the tobacco companies in this case is puzzling both in terms of scale, operating at multiple levels at the same time and in terms of the countries mobilized in their defence. WTO litigation is typically the result of Multi National Enterprises (MNEs) lobbying their own government, but here third countries were mobilized. Lobbying in third country contexts, with the objective of accessing multilateral dispute settlement systems, has been little studied. We thus know very little about the driving factors behind such activities, how target governments are selected and what lobbying strategies are used. This paper draws on emerging research on transnational lobbying and a case study of the PP case to explore these issues in detail and, by doing so, aims to further our theoretical understanding of the political economy of international trade in the context of increasing regime complexity and globalization of production.

  5. Smoke screen? The globalization of production, transnational lobbying and the international political economy of plain tobacco packaging

    Curran, Louise; Eckhardt, Jappe

    2017-01-01

    In 2012 Australia became the first country in the world to introduce plain tobacco packaging in an effort to reduce tobacco consumption. This move was vehemently opposed by the tobacco industry, which challenged it on several levels: nationally, bilaterally and multilaterally at the World Trade Organization (WTO). The political behavior of the tobacco companies in this case is puzzling both in terms of scale, operating at multiple levels at the same time and in terms of the countries mobilized in their defence. WTO litigation is typically the result of Multi National Enterprises (MNEs) lobbying their own government, but here third countries were mobilized. Lobbying in third country contexts, with the objective of accessing multilateral dispute settlement systems, has been little studied. We thus know very little about the driving factors behind such activities, how target governments are selected and what lobbying strategies are used. This paper draws on emerging research on transnational lobbying and a case study of the PP case to explore these issues in detail and, by doing so, aims to further our theoretical understanding of the political economy of international trade in the context of increasing regime complexity and globalization of production. PMID:28630533

  6. 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.

    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.

  7. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

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

    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.

  9. [Neonatal screening of hemoglobinopathies and G6PD deficiency in Catalonia (Spain). Molecular study of sickle cell disease associated with alpha thalassemia and G6PD deficiency].

    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.

  10. A High Throughput, 384-Well, Semi-Automated, Hepatocyte Intrinsic Clearance Assay for Screening New Molecular Entities in Drug Discovery.

    Heinle, Lance; Peterkin, Vincent; de Morais, Sonia M; Jenkins, Gary J; Badagnani, Ilaria

    2015-01-01

    A high throughput, semi-automated clearance screening assay in hepatocytes was developed allowing a scientist to generate data for 96 compounds in one week. The 384-well format assay utilizes a Thermo Multidrop Combi and an optimized LC-MS/MS method. The previously reported LCMS/ MS method reduced the analytical run time by 3-fold, down to 1.2 min injection-to-injection. The Multidrop was able to deliver hepatocytes to 384-well plates with minimal viability loss. Comparison of results from the new 384-well and historical 24-well assays yielded a correlation of 0.95. In addition, results obtained for 25 marketed drugs with various metabolism pathways had a correlation of 0.75 when compared with literature values. Precision was maintained in the new format as 8 compounds tested in ≥39 independent experiments had coefficients of variation ≤21%. The ability to predict in vivo clearances using the new stability assay format was also investigated using 22 marketed drugs and 26 AbbVie compounds. Correction of intrinsic clearance values with binding to hepatocytes (in vitro data) and plasma (in vivo data) resulted in a higher in vitro to in vivo correlation when comparing 22 marketed compounds in human (0.80 vs 0.35) and 26 AbbVie Discovery compounds in rat (0.56 vs 0.17), demonstrating the importance of correcting for binding in clearance studies. This newly developed high throughput, semi-automated clearance assay allows for rapid screening of Discovery compounds to enable Structure Activity Relationship (SAR) analysis based on high quality hepatocyte stability data in sufficient quantity and quality to drive the next round of compound synthesis.

  11. Magnetic high throughput screening system for the development of nano-sized molecularly imprinted polymers for controlled delivery of curcumin.

    Piletska, Elena V; Abd, Bashar H; Krakowiak, Agata S; Parmar, Anitha; Pink, Demi L; Wall, Katie S; Wharton, Luke; Moczko, Ewa; Whitcombe, Michael J; Karim, Kal; Piletsky, Sergey A

    2015-05-07

    Curcumin is a versatile anti-inflammatory and anti-cancer agent known for its low bioavailability, which could be improved by developing materials capable of binding and releasing drug in a controlled fashion. The present study describes the preparation of magnetic nano-sized Molecularly Imprinted Polymers (nanoMIPs) for the controlled delivery of curcumin and their high throughput characterisation using microtitre plates modified with magnetic inserts. NanoMIPs were synthesised using functional monomers chosen with the aid of molecular modelling. The rate of release of curcumin from five polymers was studied under aqueous conditions and was found to correlate well with the binding energies obtained computationally. The presence of specific monomers was shown to be significant in ensuring effective binding of curcumin and to the rate of release obtained. Characterisation of the polymer particles was carried out using dynamic light scattering (DLS) technique and scanning electron microscopy (SEM) in order to establish the relationship between irradiation time and particle size. The protocols optimised during this study could be used as a blueprint for the development of nanoMIPs capable of the controlled release of potentially any compound of interest.

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

    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.

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

    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.

  14. Biochemical and molecular characteristics of patients with organic acidaemias and urea cycle disorders identified through newborn screening.

    Barends, M; Pitt, J; Morrissy, S; Tzanakos, N; Boneh, A

    2014-01-01

    In recent years it has become clear that newborn screening (NBS) programmes using tandem mass spectrometry identify "patients" with "classical" inborn errors of metabolism who are asymptomatic. This observation raises issues regarding medicalization of "non-diseases," potentially unnecessary treatment and unnecessary anxiety to parents. This study aims to identify possible markers that may assist in predicting the need for treatment of infants with "classical" organic acidaemias (OA) and urea cycle disorders (UCD) diagnosed through NBS. Medical records of all patients with classical OA and UCD detected through the Victorian NBS programme from February 2002 to January 2014, or diagnosed clinically between 1990 and January 2002 were retrospectively reviewed. Neonatal presentation did not always predict the need for on-going strict treatment. Blood concentrations of amino acids and acyl-carnitines and the changes thereof in follow-up samples correlated with severity in citrullinaemia-I, possibly isovaleric acidaemia but not in argininosuccinic aciduria or propionic acidaemia. Some specific mutations correlate with "attenuated" citrullinaemia-I. Gender may affect clinical outcome in propionic acidaemia. Changes in blood concentration of certain metabolites (amino acids, acyl-carnitines) in the first weeks of life may be predictive of the need for treatment in some disorders but not in others. Mutation analysis may be predictive in some disorders but whether or not this should be considered as second-tier testing in NBS should be discussed separately. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Molecular screening of bovine raw milk for the presence of Shiga toxin-producing Escherichia coli (STEC on dairy farms

    Tatiane Vendramin

    2014-09-01

    Full Text Available Milkborne transmission of Shiga toxin- producing Escherichia coli (STEC has raised considerable concern due to recent outbreaks worldwide and poses a threat to public health. The aim of this study was to develop a sensitive and specific multiplex PCR assay to detect the presence of STEC in bovine raw milk. To identify E. coli (ATCC 25922 contamination, the gene uspA was used, and PCR sensitivity and specificity were accessed by testing diluted samples ranging from 2 to 2.0 × 10(6 CFU/mL. To detect STEC, the stx1 and stx2 genes were selected as targets. After reaction standardization, the multiplex assay was tested in raw milk collected from 101 cows on dairy farms. PCR assay for E. coli detection had a specificity of 100% and sensitivity of 79% (P<0.0001, with a lower detection limit of 2 CFU/mL. Multiplex PCR assay had 100% sensitivity for E. coli positive raw milk samples, and 31.1% were contaminated with STEC, 28.3% of stx2, and 1.9% of stx1. The multiplex PCR assay described in the present study can be employed to identify and screen E. coli harboring stx1 and stx2 genes in raw milk on dairy farms and in industries.

  16. 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.

    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.

  17. In silico screening, genotyping, molecular dynamics simulation and activity studies of SNPs in pyruvate kinase M2.

    Ponnusamy Kalaiarasan

    Full Text Available Role of, 29-non-synonymous, 15-intronic, 3-close to UTR, single nucleotide polymorphisms (SNPs and 2 mutations of Human Pyruvate Kinase (PK M2 were investigated by in-silico and in-vitro functional studies. Prediction of deleterious substitutions based on sequence homology and structure based servers, SIFT, PANTHER, SNPs&GO, PhD-SNP, SNAP and PolyPhen, depicted that 19% emerged common between all the mentioned programs. SNPeffect and HOPE showed three substitutions (C31F, Q310P and S437Y in-silico as deleterious and functionally important. In-vitro activity assays showed C31F and S437Y variants of PKM2 with reduced activity, while Q310P variant was catalytically inactive. The allosteric activation due to binding of fructose 1-6 bisphosphate (FBP was compromised in case of S437Y nsSNP variant protein. This was corroborated through molecular dynamics (MD simulation study, which was also carried out in other two variant proteins. The 5 intronic SNPs of PKM2, associated with sporadic breast cancer in a case-control study, when subjected to different computational analyses, indicated that 3 SNPs (rs2856929, rs8192381 and rs8192431 could generate an alternative transcript by influencing splicing factor binding to PKM2. We propose that these, potentially functional and important variations, both within exons and introns, could have a bearing on cancer metabolism, since PKM2 has been implicated in cancer in the recent past.

  18. Depression Screening

    ... 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 ...

  19. Development of a molecularly imprinted polymer tailored on disposable screen-printed electrodes for dual detection of EGFR and VEGF using nano-liposomal amplification strategy.

    Johari-Ahar, Mohammad; Karami, Pari; Ghanei, Mostafa; Afkhami, Abbas; Bagheri, Hasan

    2018-06-01

    This work demonstrates the development of a gold screen-printed electrode (Au-SPE)-based biosensor modified with a molecularly imprinted polymer and amplified using antibody-conjugated nano-liposomes. The developed biosensor was utilized for dual determination of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) as cancer biomarkers. To prepare this biosensor, Au-SPE was modified with 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester) via self-assembly method and then the target proteins (EGFR and VEGF) were covalently attached to the modified SPE. To synthesize the molecularly imprinted polymer, monomers of acrylamide and N,N'-methylenebis(acrylamide) were polymerized around the EGFR and VEGF templates, and to characterize the prepared biosensor, electrochemical impedance spectroscopy was used for analyses of surface changes in the engineered electrodes. To produce reliable electrochemical signals, nano-liposomes which were loaded with Cd(II) and Cu(II) cations and decorated with antibodies specific for EGFR and VEGF were used as an efficient tool for detection of target biomarkers. In the analysis step, potentiometric striping analysis (PSA), as an electrochemical technique, was utilized for sensitive determination of these cations. The limits of detection (LODs) of EGFR and VEGF analyses were found to be 0.01 and 0.005 pg mL -1 with the linear dynamic ranges (LDRs) of 0.05-50000 and 0.01-7000 pg mL -1 , respectively. Moreover, the proposed biosensor was successfully used for sensitive, reproducible, and specific detection of EGFR and VEGF in real samples. Due to the SPE nature of the developed biosensor, we envision that this sensing tool has capability of being integrated with lab-on-a-chip (LOC), microfluidics, and micro total analysis systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. In-bead screening

    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....

  1. In Silico Identification of Potent PPAR-γ Agonists from Traditional Chinese Medicine: A Bioactivity Prediction, Virtual Screening, and Molecular Dynamics Study

    Kuan-Chung Chen

    2014-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs related to regulation of lipid metabolism, inflammation, cell proliferation, differentiation, and glucose homeostasis by controlling the related ligand-dependent transcription of networks of genes. They are used to be served as therapeutic targets against metabolic disorder, such as obesity, dyslipidemia, and diabetes; especially, PPAR-γ is the most extensively investigated isoform for the treatment of dyslipidemic type 2 diabetes. In this study, we filter compounds of traditional Chinese medicine (TCM using bioactivities predicted by three distinct prediction models before the virtual screening. For the top candidates, the molecular dynamics (MD simulations were also utilized to investigate the stability of interactions between ligand and PPAR-γ protein. The top two TCM candidates, 5-hydroxy-L-tryptophan and abrine, have an indole ring and carboxyl group to form the H-bonds with the key residues of PPAR-γ protein, such as residues Ser289 and Lys367. The secondary amine group of abrine also stabilized an H-bond with residue Ser289. From the figures of root mean square fluctuations (RMSFs, the key residues were stabilized in protein complexes with 5-Hydroxy-L-tryptophan and abrine as control. Hence, we propose 5-hydroxy-L-tryptophan and abrine as potential lead compounds for further study in drug development process with the PPAR-γ protein.

  2. International Cancer Screening Network

    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.

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

    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)

  4. Molecular and cytological characterization of the global Musa germplasm collection provides insights into the treasure of banana diversity

    Christelová, Pavla; De Langhe, E.; Hřibová, Eva; Čížková, Jana; Sardos, J.; Hušáková, Markéta; Van den Houwe, I.; Sutanto, A.; Kepler, A.K.; Swennen, R.; Roux, N.; Doležel, Jaroslav

    2017-01-01

    Roč. 26, č. 4 (2017), s. 801-824 ISSN 0960-3115 R&D Projects: GA MŠk(CZ) LO1204; GA MŠk(CZ) LG12021; GA MŠk LG15017 Institutional support: RVO:61389030 Keywords : genetic-linkage map * aab group * balbisiana colla * acuminata colla * black sigatoka * population-structure * marker analysis * flow-cytometry * plantain musa * aflp markers * Classification * Gene bank * Genetic diversity * ITC collection * Microsatellites * Musa Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 2.265, year: 2016

  5. Global transcriptomic profiling of aspen trees under elevated [CO2] to identify potential molecular mechanisms responsible for enhanced radial growth.

    Wei, Hairong; Gou, Jiqing; Yordanov, Yordan; Zhang, Huaxin; Thakur, Ramesh; Jones, Wendy; Burton, Andrew

    2013-03-01

    Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)].

  6. A Similarity Search Using Molecular Topological Graphs

    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.

  7. Global gene expression profiling in PAI-1 knockout murine heart and kidney: molecular basis of cardiac-selective fibrosis.

    Asish K Ghosh

    Full Text Available Fibrosis is defined as an abnormal matrix remodeling due to excessive synthesis and accumulation of extracellular matrix proteins in tissues during wound healing or in response to chemical, mechanical and immunological stresses. At present, there is no effective therapy for organ fibrosis. Previous studies demonstrated that aged plasminogen activator inhibitor-1 (PAI-1 knockout mice develop spontaneously cardiac-selective fibrosis without affecting any other organs. We hypothesized that differential expressions of profibrotic and antifibrotic genes in PAI-1 knockout hearts and unaffected organs lead to cardiac selective fibrosis. In order to address this prediction, we have used a genome-wide gene expression profiling of transcripts derived from aged PAI-1 knockout hearts and kidneys. The variations of global gene expression profiling were compared within four groups: wildtype heart vs. knockout heart; wildtype kidney vs. knockout kidney; knockout heart vs. knockout kidney and wildtype heart vs. wildtype kidney. Analysis of illumina-based microarray data revealed that several genes involved in different biological processes such as immune system processing, response to stress, cytokine signaling, cell proliferation, adhesion, migration, matrix organization and transcriptional regulation were affected in hearts and kidneys by the absence of PAI-1, a potent inhibitor of urokinase and tissue-type plasminogen activator. Importantly, the expressions of a number of genes, involved in profibrotic pathways including Ankrd1, Pi16, Egr1, Scx, Timp1, Timp2, Klf6, Loxl1 and Klotho, were deregulated in PAI-1 knockout hearts compared to wildtype hearts and PAI-1 knockout kidneys. While the levels of Ankrd1, Pi16 and Timp1 proteins were elevated during EndMT, the level of Timp4 protein was decreased. To our knowledge, this is the first comprehensive report on the influence of PAI-1 on global gene expression profiling in the heart and kidney and its implication

  8. Molecular and morphological systematics of the Ellisellidae (Coelenterata: Octocorallia): Parallel evolution in a globally distributed family of octocorals

    Bilewitch, Jaret P.

    2014-04-01

    The octocorals of the Ellisellidae constitute a diverse and widely distributed family with subdivisions into genera based on colonial growth forms. Branching patterns are repeated in several genera and congeners often display region-specific variations in a given growth form. We examined the systematic patterns of ellisellid genera and the evolution of branching form diversity using molecular phylogenetic and ancestral morphological reconstructions. Six of eight included genera were found to be polyphyletic due to biogeographical incompatibility with current taxonomic assignments and the creation of at least six new genera plus several reassignments among existing genera is necessary. Phylogenetic patterns of diversification of colony branching morphology displayed a similar transformation order in each of the two primary ellisellid clades, with a sea fan form estimated as the most-probable common ancestor with likely origins in the Indo-Pacific region. The observed parallelism in evolution indicates the existence of a constraint on the genetic elements determining ellisellid colonial morphology. However, the lack of correspondence between levels of genetic divergence and morphological diversity among genera suggests that future octocoral studies should focus on the role of changes in gene regulation in the evolution of branching patterns. © 2014 Elsevier Inc.

  9. Global Molecular and Morphological Effects of 24-Hour Chromium(VI)Exposure on Shewanella oneidensis MR-1

    Chourey, Karuna [ORNL; Thompson, Melissa R [ORNL; Morrell-Falvey, Jennifer L [ORNL; Verberkmoes, Nathan C [ORNL; Brown, Steven D [ORNL; Shah, Manesh B [ORNL; Zhou, Jizhong [ORNL; Doktycz, Mitchel John [ORNL; Hettich, Robert {Bob} L [ORNL; Thompson, Dorothea K [ORNL

    2006-01-01

    The biological impact of 24-h ("chronic") chromium(VI) [Cr(VI) or chromate] exposure on ShewanellaoneidensisMR-1 was assessed by analyzing cellular morphology as well as genome-wide differential gene and protein expression profiles. Cells challenged aerobically with an initial chromate concentration of 0.3 mM in complex growth medium were compared to untreated control cells grown in the absence of chromate. At the 24-h time point at which cells were harvested for transcriptome and proteome analyses, no residual Cr(VI) was detected in the culture supernatant, thus suggesting the complete uptake and/or reduction of this metal by cells. In contrast to the untreated control cells, Cr(VI)-exposed cells formed apparently aseptate, nonmotile filaments that tended to aggregate. Transcriptome profiling and mass spectrometry-based proteomic charac terization revealed that the principal molecular response to 24-h Cr(VI) exposure was the induction of prophage-related genes and their encoded products as well as a number of functionally undefined hypothetical genes that were located within the integrated phage regions of the MR-1 genome. In addition, genes with annotated functions in DNA metabolism, cell division, biosynthesis and degradation of the murein (pepti doglycan) sacculus, membrane response, and general environmental stress protection were upregulated, while genes encoding chemotaxis, motility, and transport/binding proteins were largely repressed under conditions of 24-h chromate treatment.

  10. Molecular and morphological systematics of the Ellisellidae (Coelenterata: Octocorallia): Parallel evolution in a globally distributed family of octocorals

    Bilewitch, Jaret P.; Ekins, Merrick; Hooper, John; Degnan, Sandie M.

    2014-01-01

    The octocorals of the Ellisellidae constitute a diverse and widely distributed family with subdivisions into genera based on colonial growth forms. Branching patterns are repeated in several genera and congeners often display region-specific variations in a given growth form. We examined the systematic patterns of ellisellid genera and the evolution of branching form diversity using molecular phylogenetic and ancestral morphological reconstructions. Six of eight included genera were found to be polyphyletic due to biogeographical incompatibility with current taxonomic assignments and the creation of at least six new genera plus several reassignments among existing genera is necessary. Phylogenetic patterns of diversification of colony branching morphology displayed a similar transformation order in each of the two primary ellisellid clades, with a sea fan form estimated as the most-probable common ancestor with likely origins in the Indo-Pacific region. The observed parallelism in evolution indicates the existence of a constraint on the genetic elements determining ellisellid colonial morphology. However, the lack of correspondence between levels of genetic divergence and morphological diversity among genera suggests that future octocoral studies should focus on the role of changes in gene regulation in the evolution of branching patterns. © 2014 Elsevier Inc.

  11. Role of orbital dynamics and cloud-cloud collisions in the formation of giant molecular clouds in global spiral structures

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

    1987-01-01

    The role of orbit crowding and cloud-cloud collisions in the formation of GMCs and their organization in global spiral structure is investigated. Both N-body simulations of the cloud system and a detailed analysis of individual particle orbits are used to develop a conceptual understanding of how individual clouds participate in the collective density response. Detailed comparisons are made between a representative cloud-particle simulation in which the cloud particles collide inelastically with one another and give birth to and subsequently interact with young star associations and stripped down simulations in which the cloud particles are allowed to follow ballistic orbits in the absence of cloud-cloud collisions or any star formation processes. Orbit crowding is then related to the behavior of individual particle trajectories in the galactic potential field. The conceptual picture of how GMCs are formed in the clumpy ISMs of spiral galaxies is formulated, and the results are compared in detail with those published by other authors. 68 references

  12. Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma.

    Fritz, Stefan; Fernandez-del Castillo, Carlos; Mino-Kenudson, Mari; Crippa, Stefano; Deshpande, Vikram; Lauwers, Gregory Y; Warshaw, Andrew L; Thayer, Sarah P; Iafrate, A John

    2009-03-01

    To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.

  13. Genetic affinities within a large global collection of pathogenic Leptospira: implications for strain identification and molecular epidemiology.

    Kishore Nalam

    Full Text Available Leptospirosis is an important zoonosis with widespread human health implications. The non-availability of accurate identification methods for the individualization of different Leptospira for outbreak investigations poses bountiful problems in the disease control arena. We harnessed fluorescent amplified fragment length polymorphism analysis (FAFLP for Leptospira and investigated its utility in establishing genetic relationships among 271 isolates in the context of species level assignments of our global collection of isolates and strains obtained from a diverse array of hosts. In addition, this method was compared to an in-house multilocus sequence typing (MLST method based on polymorphisms in three housekeeping genes, the rrs locus and two envelope proteins. Phylogenetic relationships were deduced based on bifurcating Neighbor-joining trees as well as median joining network analyses integrating both the FAFLP data and MLST based haplotypes. The phylogenetic relationships were also reproduced through Bayesian analysis of the multilocus sequence polymorphisms. We found FAFLP to be an important method for outbreak investigation and for clustering of isolates based on their geographical descent rather than by genome species types. The FAFLP method was, however, not able to convey much taxonomical utility sufficient to replace the highly tedious serotyping procedures in vogue. MLST, on the other hand, was found to be highly robust and efficient in identifying ancestral relationships and segregating the outbreak associated strains or otherwise according to their genome species status and, therefore, could unambiguously be applied for investigating phylogenetics of Leptospira in the context of taxonomy as well as gene flow. For instance, MLST was more efficient, as compared to FAFLP method, in clustering strains from the Andaman island of India, with their counterparts from mainland India and Sri Lanka, implying that such strains share genetic

  14. Machine Learning Approaches Toward Building Predictive Models for Small Molecule Modulators of miRNA and Its Utility in Virtual Screening of Molecular Databases.

    Periwal, Vinita; Scaria, Vinod

    2017-01-01

    The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules. Here, we describe a computational strategy based on machine learning for creation of predictive models from high-throughput biological screens for virtual screening of small molecules with the potential to inhibit microRNAs. Such models could be potentially used for computational prioritization of small molecules before performing high-throughput biological assay.

  15. Molecular recognition and self-assembly special feature: A general protocol for creating high-throughput screening assays for reaction yield and enantiomeric excess applied to hydrobenzoin.

    Shabbir, Shagufta H; Regan, Clinton J; Anslyn, Eric V

    2009-06-30

    A general approach to high-throughput screening of enantiomeric excess (ee) and concentration was developed by using indicator displacement assays (IDAs), and the protocol was then applied to the vicinal diol hydrobenzoin. The method involves the sequential utilization of what we define herein as screening, training, and analysis plates. Several enantioselective boronic acid-based receptors were screened by using 96-well plates, both for their ability to discriminate the enantiomers of hydrobenzoin and to find their optimal pairing with indicators resulting in the largest optical responses. The best receptor/indicator combination was then used to train an artificial neural network to determine concentration and ee. To prove the practicality of the developed protocol, analysis plates were created containing true unknown samples of hydrobenzoin generated by established Sharpless asymmetric dihydroxylation reactions, and the best ligand was correctly identified.

  16. Sequential Analysis of Global Gene Expression Profiles in Immature and In vitro Matured Bovine Oocytes: Potential Molecular Markers of Oocyte Maturation

    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

  17. OMI/Aura NO2 Cloud-Screened Total and Tropospheric Column Daily L3 Global 0.25deg Lat/Lon Grid V003

    National Aeronautics and Space Administration — The OMI/Aura Level-3 Global Gridded(0.25x0.25 deg) Nitrogen Dioxide Product "OMNO2d" is now released (Jan 10, 2013) to the public from the NASA Goddard Earth...

  18. Molecular screening for Candida orthopsilosis and Candida metapsilosis among Danish Candida parapsilosis group blood culture isolates: proposal of a new RFLP profile for differentiation

    Mirhendi, Hossein; Bruun, Brita; Schønheyder, Henrik Carl

    2010-01-01

    Candida orthopsilosis and Candida metapsilosis are recently described species phenotypically indistinguishable from Candida parapsilosis . We evaluated phenotyping and molecular methods for the detection of these species among 79 unique blood culture isolates of the C. parapsilosis group obtained...

  19. Comparison the diagnostic value of serological and molecular methods for screening and detecting Chlamydia trachomatis in semen of infertile men: A cross-sectional study

    Amin Khoshakhlagh

    2017-12-01

    Full Text Available Background: Chlamydia trachomatis (CT with damaging effects on sperm quality parameters can often cause infertility in men. Objective: The main objective of this study was to determine the diagnostic value of polymerase chain reaction (PCR and enzyme linked immuno sorbent assay (ELISA for screening and detecting CT in semen samples of infertile men. Materials and Methods: In this cross-sectional study, 465 men referring to the clinical laboratory of Royan Institute were chosen for primary screening and detection of the presence of CT. 93 samples were normozoospermia with normal sperm parameters i.e. sperm number, motility and morphology (Asymptomatic and 372 had abnormal sperm parameters (Symptomatic in semen analysis. ELISA test was performed as the screening test. Samples with optical density (OD >0.200 were selected as the case and asymptomatic samples with OD 0.400 as the ELISA positive, the diagnostic value of CT-ELISA positive in symptomatic and asymptomatic infertile patients were 0.019 (7 of 372 and 0.021 (2 of 93, respectively. There was no relationship between the presence of CT infection and different sperm abnormalities. Conclusion: The anti-CT IgA ELISA test may be introduced as an appropriate tool for screening purpose in the seminal plasma to select suspicious samples for PCR confirmatory tests.

  20. Optimizing virtual fragment screening for GPCRs: Identification of novel ligands for the histamine H3 receptor using ligand- and structure-based molecular fingerprints

    Sirci, F.; Istyastono, E.P.; Vischer, H.F.; Nijmeijer, S.; Kuijer, M.; Kooistra, A.J.; Wijtmans, M.; Mannhold, R.; Leurs, R.; de Esch, I.J.P.; de Graaf, C.

    2012-01-01

    Virtual fragment screening (VFS) is a promising new method that uses computer models to identify small, fragment-like biologically active molecules as useful starting points for fragment-based drug discovery (FBDD). Training sets of true active and inactive fragment-like molecules to construct and

  1. Toxicology screen

    ... 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 ...

  2. Toward a Molecular Understanding of the Interaction of Dual Specificity Phosphatases with Substrates: Insights from Structure-Based Modeling and High Throughput Screening

    Bakan, Ahmet; Lazo, John S; Wipf, Peter; Brummond, Kay M; Bahar, Ivet

    2008-01-01

    Dual-specificity phosphatases (DSPs) are important, but poorly understood, cell signaling enzymes that remove phosphate groups from tyrosine and serine/threonine residues on their substrate. Deregulation of DSPs has been implicated in cancer, obesity, diabetes, inflammation, and Alzheimer’s disease. Due to their biological and biomedical significance, DSPs have increasingly become the subject of drug discovery high-throughput screening (HTS) and focused compound library development efforts. P...

  3. Molecular modeling

    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.

  4. 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.

    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.

  5. Preimplantation genetic screening.

    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.

  6. Impact of Molecular Screening for Point Mutations and Rearrangements in Routine Air-Dried Fine-Needle Aspiration Samples of Thyroid Nodules

    Eszlinger, Markus; Krogdahl, Annelise; Münz, Sina

    2014-01-01

    Background: The diagnostic limitations of thyroid fine-needle aspiration (FNA), such as the indeterminate category, can be partially overcome by molecular analyses. However, until now, rearrangements have only been detected in fresh FNA material and the number of follicular thyroid carcinomas (FT...

  7. Feasibility of a molecular screening method for detection of Salmonella enterica and Campylobacter jejuni in a routine community-based clinical microbiology laboratory

    Schuurman, T.; de Boer, R. F.; van Zanten, E.; van Slochteren, K. R.; Scheper, H. R.; Dijk-Alberts, B. G.; Moller, A. V. M.; Kooistra-Smid, A. M. D.

    Conventional diagnostic methods for the detection of Salmonella enterica and Campylobacter jejuni are laborious and time-consuming procedures, resulting in final results, for the majority of specimens, only after 3 to 4 days. Molecular detection can improve the time to reporting of the final results

  8. Integrating HIV, hepatitis B and syphilis screening and treatment through the Maternal, Newborn and Child Health platform to reach global elimination targets

    Joseph Woodring

    2017-12-01

    Full Text Available Every year, an estimated 180 000 babies in the Western Pacific Region are infected by hepatitis B, 13 000 by syphilis and 1400 by HIV through mother-to-child transmission.1 These infections can be largely prevented by antenatal screening, treatment and timely vaccination for newborns. Despite challenges in controlling each disease, major achievements have been made. National immunization programmes have reduced the regional hepatitis B prevalence from over 8% in 1990 to 0.93% among children born in 2012. In addition, HIV testing and treatment have helped keep the regional prevalence of HIV infections at 0.1%. In contrast, the number of maternal syphilis cases is still high in the Western Pacific Region, with an estimated 45 million cases in 2012. Elimination of mother-to-child transmission of these infections cannot be achieved through vertically applied programming and require using and augmenting to the shared Maternal, Newborn and Child Health platform to coordinate, integrate and enable cost efficiencies for these elimination efforts. The Regional Framework for Triple Elimination of Mother-to-Child Transmission of HIV, Hepatitis B and Syphilis in Asia and the Pacific 2018–2030 offers such a coordinated approach towards achieving the triple elimination of mother-to-child transmission of HIV, hepatitis B and syphilis and provides guidance for decision-makers, managers and health professionals working in programmes addressing maternal, newborn and child health, HIV, hepatitis, sexually transmitted infections and immunization.

  9. Colon cancer screening

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  10. Valid screening questions useful to diagnose hand and forearm eczema are available in the Spanish language, a new tool for global research.

    Martí-Margarit, Anna; Manresa, Josep M; Herdman, Mike; Pujol, Ramon; Serra, Consol; Flyvholm, Mary-Ann; Giménez-Arnau, Ana M

    2015-04-01

    Hand eczema is an impacting cutaneous disease. Globally valid tools that help to diagnose hand and forearm eczema are required. To validate the questions to detect hand and/or forearm eczema included in the "Nordic Occupational Skin Questionnaire" (NOSQ-2002) in the Spanish language. A prospective pilot study was conducted with 80 employees of a cleaning company and a retrospective one involving 2,546 individuals. The responses were analysed for sensitivity, specificity and positive and negative predictive values. The final diagnosis according to the patients' hospital records, the specialty care records and the physical examination was taken as gold standard. The Dermatology Life Quality Index (DLQI) was also evaluated. Sensitivity and specificity, in a worst case scenario (WC) combining both questions, were 96.5% and 66.7%, respectively, and in a per protocol (PP) analysis, were 96.5% and 75.2%. The questions validated detected eczema effectively, making this tool suitable for use e.g. in multicentre epidemiological studies or clinical trials.

  11. Molecular docking.

    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.

  12. Identification of novel potential scaffold for class I HDACs inhibition: An in-silico protocol based on virtual screening, molecular dynamics, mathematical analysis and machine learning.

    Fan, Cong; Huang, Yanxin

    2017-09-23

    Histone deacetylases (HDACs) family has been widely reported as an important class of enzyme targets for cancer therapy. Much effort has been made in discovery of novel scaffolds for HDACs inhibition besides existing hydroxamic acids, cyclic peptides, benzamides, and short-chain fatty acids. Herein we set up an in-silico protocol which not only could detect potential Zn 2+ chelation bonds but also still adopted non-bonded model to be effective in discovery of Class I HDACs inhibitors, with little human's subjective visual judgment involved. We applied the protocol to screening of Chembridge database and selected out 7 scaffolds, 3 with probability of more than 99%. Biological assay results demonstrated that two of them exhibited HDAC-inhibitory activity and are thus considerable for structure modification to further improve their bio-activity. Copyright © 2017. Published by Elsevier Inc.

  13. Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

    Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

    2009-06-01

    It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

  14. Chapter 2. Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.

    Mas-Coma, Santiago; Valero, María Adela; Bargues, María Dolores

    2009-01-01

    almost total genetic isolation. Recent sequencing results suggest that present assumptions on fasciolid-lymnaeid specificity might be wrong. The crucial role of lymnaeids in fascioliasis transmission, epidemiology and control was the reason for launching a worldwide lymnaeid molecular characterization initiative. This initiative has already furnished useful results on several continents. A standardized methodology for fasciolids and lymnaeids is proposed herein in order that future work is undertaken on a comparable basis. A complete understanding of molecular epidemiology is expected to help greatly in designing global actions and local interventions for control of fascioliasis.

  15. Rapid molecular screening of black carbon (biochar) thermosequences obtained from chestnut wood and rice straw: A pyrolysis-GC/MS study

    Kaal, Joeri; Schneider, Maximilian P.W.; Schmidt, Michael W.I.

    2012-01-01

    Rice straw and chestnut wood were heated between 200 and 1000 °C (T CHAR ) to produce Black C ‘thermosequences’. The molecular properties of the charred residues were assessed by pyrolysis-GC/MS to investigate the relation between charring intensity and pyrolysis fingerprint. Samples obtained at T CHAR > 500 °C (wood) or >700 °C (straw) gave low quality pyrograms and poor reproducibility because of high thermal stability, but pyrolysis-GC/MS allowed to track the thermal degradation of the main biocomponents (polysaccharides, lignin, methylene chain-based aliphatics, triterpenoids, chlorophyll and proteins) in the lower temperature range, mostly occurring between T CHAR 250 and 500 °C. With increasing T CHAR , the charred residues of these biocomponents lose characteristic functional groups, aromatise and finally condense into non-pyrolysable biomass. The proportions of the pyrolysis products of unspecific origin (benzene, toluene, PAHs, etc.), increase with charring intensity, while the ratios that reflect the abundance of alkyl cross-linkages between aromatic moieties (e.g. benzene/toluene, naphthalene/alkylnaphthalene) decrease. These results provide the guidelines to using pyrolysis-GC/MS for the molecular characterisation of different components in Black C and biochar, which is an important parameter for predicting Black C/biochar behaviour in soil. Results are consistent with earlier studies of these samples using the BPCA (benzenepolycarboxylic acid) method and the ring current-induced 13 C benzene chemical shift NMR (Nuclear Magnetic Resonance) approach. Pyrolysis-GC/MS provides more information on molecular structures in the low temperature range (T CHAR ≤ 500 °C) while the BPCA and NMR ring current methods provide more reliable estimations of charring intensity, especially at higher temperatures (T CHAR ≥ 500 °C). -- Highlights: ► Charred rice straw and chestnut wood (200–1000 °C) analysed by pyrolysis-GC/MS. ► Pyrolysis-GC/MS allows

  16. Current Cervical Carcinoma Screening Guidelines

    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.

  17. Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: Application to diagnosis and blood screening for posttransfusion hepatitis

    Miyamura, Tatsuo; Saito, Izumu (National Institute of Health, Tokyo (Japan)); Katayama, Tohru (Tokyo National Chest Hospital (Japan)); Kikuchi, Shu; Tateda, Akira (Sendai National Hospital (Japan)); Houghton, M.; Choo, Quilim; Kuo, G. (Chiron Corporation, Emeryville, CA (USA))

    1990-02-01

    A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatits (NANBH). The authors have assayed for antibodies reacting with the encoded antigen in sera from posttransfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. Of the 15 well-defined cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11 (73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented.

  18. Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: Application to diagnosis and blood screening for posttransfusion hepatitis

    Miyamura, Tatsuo; Saito, Izumu; Katayama, Tohru; Kikuchi, Shu; Tateda, Akira; Houghton, M.; Choo, Quilim; Kuo, G.

    1990-01-01

    A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatits (NANBH). The authors have assayed for antibodies reacting with the encoded antigen in sera from posttransfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. Of the 15 well-defined cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11 (73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented

  19. Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity.

    Miraglia del Giudice, E; Santoro, N; Cirillo, G; Raimondo, P; Grandone, A; D'Aniello, A; Di Nardo, M; Perrone, L

    2004-03-01

    To test whether ghrelin variants could play a role in modulating some aspects of the obese phenotype during childhood. We screened the ghrelin gene in 300 Italian obese children and adolescents (mean age 10.5+/-3.2 y; range 4-19 y) and 200 controls by using the single-strand conformation polymorphism and the restriction fragment length polymoprhism analysis. No mutations were detected with the exception of two previously described polymorphisms, Arg51Gln and Leu72Met. For both variations, allelic frequencies were similar between patients and controls. Interestingly, we showed that the Leu72Met polymorphism was associated with differences in the age at obesity onset. Patients with the Met72 allele became obese earlier than homozygous patients for the wild Leu72 allele. The logrank test comparing the plots of the complement of Kaplan-Meier estimates between the two groups of patients was statistically significant (Pghrelin variations cause the obesity due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems to play a role in anticipating the onset of obesity among children suggesting, therefore, that ghrelin may be involved in the pathophysiology of human adiposity.

  20. Identification of novel PfDHODH inhibitors as antimalarial agents via pharmacophore-based virtual screening followed by molecular docking and in vivo antimalarial activity.

    Vyas, V K; Qureshi, G; Ghate, M; Patel, H; Dalai, S

    2016-06-01

    Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) catalyses the fourth reaction of de novo pyrimidine biosynthesis in parasites, and represents an important target for the treatment of malaria. In this study, we describe pharmacophore-based virtual screening combined with docking study and biological evaluation as a rational strategy for identification of novel hits as antimalarial agents. Pharmacophore models were established from known PfDHODH inhibitors using the GALAHAD module with IC50 values ranging from 0.033 μM to 142 μM. The best pharmacophore model consisted of three hydrogen bond acceptor, one hydrogen bond donor and one hydrophobic features. The pharmacophore models were validated through receiver operating characteristic and Günere-Henry scoring methods. The best pharmacophore model as a 3D search query was searched against the IBS database. Several compounds with different structures (scaffolds) were retrieved as hit molecules. Among these compounds, those with a QFIT value of more than 81 were docked in the PfDHODH enzyme to further explore the binding modes of these compounds. In silico pharmacokinetic and toxicities were predicted for the best docked molecules. Finally, the identified hits were evaluated in vivo for their antimalarial activity in a parasite inhibition assay. The hits reported here showed good potential to become novel antimalarial agents.

  1. Screen dealing

    Barlow, J.W.

    1991-01-01

    The screen dealing system provides a facility whereby buyers and sellers of spot thermal coal can make bids and offers via the medium of the Reuters screen. A sale results when a market participant notifies his acceptance of a price to a central dealing desk. Use of the system is available to all genuine participants in the coal trade. This paper reports that it provides a focus for information and for the visible making of coal prices. For years screen trading has been used successfully to trade other commodities. At last coal is being traded electronically. It makes sense. It works. Users like it

  2. 5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones: As potent urease inhibitors; synthesis, in vitro screening, and molecular modeling study.

    Shamim, Shahbaz; Khan, Khalid Mohammed; Salar, Uzma; Ali, Farman; Lodhi, Muhammad Arif; Taha, Muhammad; Khan, Farman Ali; Ashraf, Sajda; Ul-Haq, Zaheer; Ali, Muhammad; Perveen, Shahnaz

    2018-02-01

    5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones 1-43 were synthesized in a "one-pot" three component reaction and structurally characterized by various spectroscopic techniques such as 1 H, 13 C NMR, EI-MS, HREI-MS, and IR. All compounds were evaluated for their in vitro urease inhibitory activity. It is worth mentioning that except derivatives 1, 11, 12, and 14, all were found to be more potent than the standard thiourea (IC 50  = 21.25 ± 0.15 µM) and showed their urease inhibitory potential in the range of IC 50  = 3.70 ± 0.5-20.14 ± 0.1 µM. Structure-activity relationship (SAR) was rationalized by looking at the varying structural features of the molecules. However, molecular modeling study was performed to confirm the binding interactions of the molecules (ligand) with the active site of enzyme. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. In Silico Screening and Molecular Dynamics Simulation of Disease-Associated nsSNP in TYRP1 Gene and Its Structural Consequences in OCA3

    Balu Kamaraj

    2013-01-01

    Full Text Available Oculocutaneous albinism type III (OCA3, caused by mutations of TYRP1 gene, is an autosomal recessive disorder characterized by reduced biosynthesis of melanin pigment in the hair, skin, and eyes. The TYRP1 gene encodes a protein called tyrosinase-related protein-1 (Tyrp1. Tyrp1 is involved in maintaining the stability of tyrosinase protein and modulating its catalytic activity in eumelanin synthesis. Tyrp1 is also involved in maintenance of melanosome structure and affects melanocyte proliferation and cell death. In this work we implemented computational analysis to filter the most probable mutation that might be associated with OCA3. We found R326H and R356Q as most deleterious and disease associated by using PolyPhen 2.0, SIFT, PANTHER, I-mutant 3.0, PhD-SNP, SNP&GO, Pmut, and Mutpred tools. To understand the atomic arrangement in 3D space, the native and mutant (R326H and R356Q structures were modelled. Finally the structural analyses of native and mutant Tyrp1 proteins were investigated using molecular dynamics simulation (MDS approach. MDS results showed more flexibility in native Tyrp1 structure. Due to mutation in Tyrp1 protein, it became more rigid and might disturb the structural conformation and catalytic function of the structure and might also play a significant role in inducing OCA3. The results obtained from this study would facilitate wet-lab researches to develop a potent drug therapies against OCA3.

  4. Airport Screening

    Health Physics Society Specialists in Radiation Safety Airport Screening Fact Sheet Adopted: May 2011 Photo courtesy of Dan ... a safe level. An American National Standards Institute/Health Physics Society industry standard states that the maxi- mum ...

  5. Hypertension screening

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  6. Carrier Screening

    ... How accurate is carrier screening? No test is perfect. In a small number of cases, test results ... in which an egg is removed from a woman’s ovary, fertilized in a laboratory with the man’s ...

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

    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.

  8. Molecular Modelling

    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.

  9. Preparation of Low Molecular Weight Chondroitin Sulfates, Screening of a High Anti-Complement Capacity of Low Molecular Weight Chondroitin Sulfate and Its Biological Activity Studies in Attenuating Osteoarthritis.

    Li, Lian; Li, Yan; Feng, Danyang; Xu, Linghua; Yin, Fengxin; Zang, Hengchang; Liu, Chunhui; Wang, Fengshan

    2016-10-11

    Chondroitin sulfate (CS) plays important roles in the complement system. However, the CS structure is complicated due to different sources and the number and positions of sulfate groups. The objective of this study was to prepare different low molecular weight chondroitin sulfates (LMWCSs) and to investigate the biological activity in anti-complement capacity. A series of LMWCSs was prepared from different sources and characterized by ultraviolet-visible (UV) spectroscopy, high-performance liquid chromatography (HPLC), size exclusion chromatography-multiangle laser light scattering (SEC-MALLS) and nuclear magnetic resonance (NMR) spectroscopy. Hemolytic, anti-complement 3 deposition capacity and cell viability assays were carried out to investigate the biological activities in vitro. The results showed that LMWCS prepared from shark cartilage with the oxidative degradation method (LMWCS-S-O) had the best anti-complement capacity. LMWCS-S-O could inhibit the alternative pathway of the complement system and protect chondrocytes from cell death. The attenuating effect of LMWCS-S-O on Osteoarthritis (OA) was investigated by destabilization of the medial meniscus (DMM) model in vivo. Functional wind-up, histological and C5b-9 analyses were used to evaluate the treatment effect on the OA model. In vivo results showed that LMWCS-S-O could attenuate OA. LMWCS-S-O with a high content of ΔDi-2,6diS and ΔDi-6S could be used for attenuating OA through regulating the complement system.

  10. Preparation of Low Molecular Weight Chondroitin Sulfates, Screening of a High Anti-Complement Capacity of Low Molecular Weight Chondroitin Sulfate and Its Biological Activity Studies in Attenuating Osteoarthritis

    Lian Li

    2016-10-01

    Full Text Available Chondroitin sulfate (CS plays important roles in the complement system. However, the CS structure is complicated due to different sources and the number and positions of sulfate groups. The objective of this study was to prepare different low molecular weight chondroitin sulfates (LMWCSs and to investigate the biological activity in anti-complement capacity. A series of LMWCSs was prepared from different sources and characterized by ultraviolet-visible (UV spectroscopy, high-performance liquid chromatography (HPLC, size exclusion chromatography-multiangle laser light scattering (SEC-MALLS and nuclear magnetic resonance (NMR spectroscopy. Hemolytic, anti-complement 3 deposition capacity and cell viability assays were carried out to investigate the biological activities in vitro. The results showed that LMWCS prepared from shark cartilage with the oxidative degradation method (LMWCS-S-O had the best anti-complement capacity. LMWCS-S-O could inhibit the alternative pathway of the complement system and protect chondrocytes from cell death. The attenuating effect of LMWCS-S-O on Osteoarthritis (OA was investigated by destabilization of the medial meniscus (DMM model in vivo. Functional wind-up, histological and C5b-9 analyses were used to evaluate the treatment effect on the OA model. In vivo results showed that LMWCS-S-O could attenuate OA. LMWCS-S-O with a high content of ΔDi-2,6diS and ΔDi-6S could be used for attenuating OA through regulating the complement system.

  11. [Detection of Staphylococcus aureus resistant to methicillin (MRSA) by molecular biology (Cepheid GeneXpert IL, GeneOhm BD, Roche LightCycler, Hyplex Evigene I2A) versus screening by culture: Economic and practical strategy for the laboratory].

    Laudat, P; Demondion, E; Jouannet, C; Charron, J; Chillou, C; Salaun, V; Mankikian, B

    2012-06-01

    Patients admitted in cardiac surgery and cardiac ICU at the Clinic Saint-Gatien (Tours) are screened for MRSA at the entrance by nasal swab and culture on blood agar and selective chromogenic medium made by addition of cefoxitin: BBL CHROMagar MRSA-II BD (result obtained at Day +1). We wanted to assess the molecular biology techniques available to obtain a result at day 0 for the majority of patients and to define an economic and practical strategy for the laboratory. We studied four molecular biology techniques: Cepheid GeneXpert (Cepheid) GeneOhm (BD), LightCycler (Roche) and Hyplex (I2A). Upon reception, nasal swabs were treated by culture, considered as reference, and one of the techniques of molecular biology, according to the manufacturer's notice. We conducted four studies between April 2008 and February 2009 to obtain a significant sample for each of them. By screening we mean a method that allows us to exclude MRSA carriage for patients waiting for surgery, and not to change patient management: for example, lack of isolation measures specific to entrance, no modification of antibiotic prophylaxis during surgery and no isolation measures in the immediate postoperative period. The criteria we considered for this evaluation were: (1) technician time: time to perform one or a series of sample(s) n=10 or more (about 2h for all techniques except GeneXpert 75min), level of skilled competences (no specific training for GeneXpert); (2) results: turnaround time (all molecular biology techniques), ease of reading and results interpretations (no specialized training required for GeneXpert), failure or not (12% of failure of internal controls for GeneOhm); (3) economic: cost for one or a series of sample(s) (n=10 or more), if we considered X as the reference culture cost (10 X Hyplex and LightCycler, 20 X and 40 X for GeneXpert GeneOhm); (4) NPV: 100% for GeneXpert and LightCycler. At same sensitivity, no technique, including culture, can solve alone our problem, which

  12. Distrofia miotônica tipo 1 em pacientes com catarata: diagnóstico molecular para triagem e aconselhamento genético Myotonic dystrophy type 1 in cataract patients: Molecular diagnosis for screening and genetic counseling

    María Verónica Muñoz Rojas

    2005-02-01

    premutation was found. CONCLUSIONS: These results emphazise the importance of screening for MD1 gene carriers among cataract patients, and further genetic counselling.

  13. Molecular Basis for Saccharomyces cerevisiae Biofilm Development

    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...

  14. Luminescent screens

    Lu, C.-I.

    1982-01-01

    Luminescent screens which are useful for such purposes as intensifying screens for radiographs are comprised of a support bearing a layer of finely divided particles of a phosphor dispersed in a cross-linked polymeric matrix formed by heat-curing of a coating composition comprising an unsaturated cross-linkable polymer, a polymerizable acrylic monomer, a thermoplastic polyurethane elastomer, and a heat-activatable polymerization initiator. The phosphor layer includes voids formed by evaporation of an evaporable component which is present in the coating composition from which such layer is formed. (author)

  15. Alcohol Use Screening

    ... 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 ...

  16. Hearing Screening

    Johnson-Curiskis, Nanette

    2012-01-01

    Hearing levels are threatened by modern life--headsets for music, rock concerts, traffic noises, etc. It is crucial we know our hearing levels so that we can draw attention to potential problems. This exercise requires that students receive a hearing screening for their benefit as well as for making the connection of hearing to listening.

  17. Vision Screening

    ... an efficient and cost-effective method to identify children with visual impairment or eye conditions that are likely to lead ... main goal of vision screening is to identify children who have or are at ... visual impairment unless treated in early childhood. Other problems that ...

  18. How important are intertidal ecosystems for global biogeochemical cycles? Molecular and isotopic evidence for major outwelling of photo-bleached dissolved organic matter from mangroves.

    Dittmar, T.; Cooper, W. T.; Koch, B. P.; Kattner, G.

    2006-05-01

    Organic matter, which is dissolved in low concentrations in the vast waters of the oceans, contains a total amount of carbon similar to atmospheric carbon dioxide. To understand global biogeochemical cycles it is crucial to quantify the sources of marine dissolved organic carbon (DOC). We investigated the impact of mangroves, the dominant intertidal vegetation of the tropics, on marine DOC inventories. Stable carbon- isotopes, ultrahigh-resolution mass spectrometry (FTICRMS), lignin-derived phenols and proton nuclear magnetic resonance spectroscopy showed that mangroves are the main source of terrigenous DOC on the shelf off Northern Brazil. Sunlight efficiently destroyed aromatic molecules during transport offshore, removing about one third of mangrove-derived DOC. The remainder was refractory and may thus be distributed over the oceans. On a global scale, we estimate that mangroves account for more than 10 percent of the terrestrially- derived, refractory DOC transported to the ocean, while they cover less than 0.1 percent of the continents' surface.

  19. Vision Screening

    1993-01-01

    The Visi Screen OSS-C, marketed by Vision Research Corporation, incorporates image processing technology originally developed by Marshall Space Flight Center. Its advantage in eye screening is speed. Because it requires no response from a subject, it can be used to detect eye problems in very young children. An electronic flash from a 35 millimeter camera sends light into a child's eyes, which is reflected back to the camera lens. The photorefractor then analyzes the retinal reflexes generated and produces an image of the child's eyes, which enables a trained observer to identify any defects. The device is used by pediatricians, day care centers and civic organizations that concentrate on children with special needs.

  20. It takes a global village

    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

  1. Molecular screening for erythromycin resistance genes in ...

    Aghomotsegin

    2015-07-15

    Jul 15, 2015 ... in Streptococcus pyogenes isolated from Iraqi patients with tonsilo-pharyngites. Hassan .... is an automated colorimetric method used for identification of bacteria and for .... counter medicines in private pharmacies against the regulations. ... Effect of telithromycin on erythromycin resistant S. pyogenes. In this ...

  2. The global reciprocal reprogramming between mycobacteriophage SWU1 and mycobacterium reveals the molecular strategy of subversion and promotion of phage infection

    Xiangyu eFan

    2016-01-01

    Full Text Available Bacteriophages are the viruses of bacteria, which have contributed extensively to our understanding of life and modern biology. The phage-mediated bacterial growth inhibition represents immense untapped source for novel antimicrobials. Insights into the interaction between mycobacteriophage and Mycobacterium host will inform better utilizing of mycobacteriophage. In this study, RNA sequencing technology (RNA-seq was used to explore the global response of Mycobacterium smegmatis mc2 155 at an early phase of infection with mycobacteriophage SWU1, key host metabolic processes of M. smegmatis mc2 155 shut off by SWU1, and the responsible phage proteins. The results of RNA-seq were confirmed by Real-time PCR and functional assay. 1174 genes of M. smegmatis mc2 155 (16.9% of the entire encoding capacity were differentially regulated by phage infection. These genes belong to six functional categories: (i signal transduction, (ii cell energetics, (iii cell wall biosynthesis, (iv DNA, RNA, and protein biosynthesis, (v iron uptake, (vi central metabolism. The transcription patterns of phage SWU1 were also characterized. This study provided the first global glimpse of the reciprocal reprogramming between the mycobacteriophage and Mycobacterium host.

  3. Water screen

    Kutepov, A.I.; Fedotov, I.N.; Prokopov, O.I.

    1981-01-01

    The invention refers to ventilation and can be used for repair-fitting operations in a blasting-dangerous gas condition, for example, during elimination of gas-oil gushers, repair of gas-oil pipelines, equipment etc. In order to improve safety of labor, the nozzle adapters of the water collector are oriented towards each other. The collector is installed on a support with the possibility of rotating and vertical movement. The proposed screen excludes the possibility of blasting-dangerous concentrations of gases and guarantees extinguishing of the impact spark during operation of the tool.

  4. RBC Antibody Screen

    ... 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 ...

  5. Mental Health Screening Center

    ... 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 ...

  6. Breast cancer screening

    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. Molecular similarity measures.

    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.

  8. Molecular characterization of wild-type measles viruses in Tamil Nadu, India, during 2005-2006: relationship of genotype D8 strains from Tamil Nadu to global strains.

    Duraisamy, Raja; Rota, Paul A; Palani, Gunasekaran; Elango, Varalakshmi; Sambasivam, Mohana; Lowe, Luis; Lopareva, Elena; Ramamurty, Nalini

    2012-02-01

    Molecular characterization of measles viruses is a valuable tool for measuring the effectiveness of measles control and elimination programmes. WHO recommends that virological surveillance be conducted during all phases of measles control to document circulation of indigenous strains and trace future importation. This report describes the genetic characterization of wild type measles viruses from Tamil Nadu, India isolated between January 2005 and January 2006. In the study, 304 suspected measles cases (292 from 56 outbreaks and 12 sporadic cases) were investigated. Blood samples were collected from suspected measles outbreaks and 11 suspected sporadic cases and tested for the presence of measles and rubella specific IgM. Based on serological results, 53 outbreaks were confirmed as measles, 2 as a combination of measles and rubella, and 1 negative for both. Eight sporadic cases were confirmed as measles and one as rubella. Throat swab and urine samples were collected for virus isolation and 28 isolates were obtained. Sequencing and analysis showed that 3 isolates belonged to genotype D4 and 25 to genotype D8. Comparison of the genotype D8 sequences from Tamil Nadu with previously reported genotype D8 sequences from India and abroad showed six distinct clusters with Tamil Nadu strains forming two clusters. This study has established baseline molecular data and is the first report that describes genetic diversity of circulating measles strains in Tamil Nadu, a state in India. D8 has multiple lineages and this has been linked with importation of measles into the USA and UK. Copyright © 2011 Wiley Periodicals, Inc.

  9. First time molecular detection and phylogenetic relationships of torque teno sus virus 1 and 2 in domestic pigs in Uganda: further evidence for a global distribution

    Brink Matilda

    2012-02-01

    Full Text Available Abstract Background Torque teno sus virus 1 (TTSuV1 and 2 (TTSuV2 are small, single-stranded circular DNA viruses belonging to the Anelloviridae family. Available studies clearly show that both viruses are widely distributed in the pig populations in America, Europe and Asia, although the impact of the infection is still unclear. Currently, the situation in domestic pig populations on the African continent is not known. Therefore, the aim of this study was to investigate the possible presence of the two viruses in domestic pigs in Uganda, and describe the phylogenetic relationships to those in the rest of the world. Results Ninety-five serum samples from six districts in Uganda were used, and PCR using TTSuV1 and 2 specific primers for the UTR region was run for viral nucleic acid detection. The positive samples were sequenced, and phylogenetic analyses performed in order to compare the Ugandan sequences with sequences from other parts of the world. The prevalence of TTSuV1 and 2 in the selected domestic pigs were estimated at 16.8% and 48.4% respectively, with co-infection found in 13.7%. The sequence identity was 90-100% between the Ugandan TTSuV1; and 63-100% between the Ugandan TTSuV2 sequences. Conclusion This is the first report on the presence of TTSuV1 and 2 in domestic pigs in Uganda. These results highlight the importance of screening for emerging viruses given the globalisation of human activities.

  10. Interface Screenings

    Thomsen, Bodil Marie Stavning

    2015-01-01

    In Wim Wenders' film Until the End of the World (1991), three different diagrams for the visual integration of bodies are presented: 1) GPS tracking and mapping in a landscape, 2) video recordings layered with the memory perception of these recordings, and 3) data-created images from dreams...... and memories. From a transvisual perspective, the question is whether or not these (by now realized) diagrammatic modes involving the body in ubiquitous global media can be analysed in terms of the affects and events created in concrete interfaces. The examples used are filmic as felt sensations...

  11. Global Liver Gene Expression Analysis on a Murine Metabolic Syndrome Model Treated by Low-molecular-weight Lychee Fruit Polyphenol (Oligonol®).

    Uchiyama, Hironobu; Uehara, Kaori; Nagashima, Takayuki; Nakata, Akifumi; Sato, Keisuke; Mihara, Yoshihiro; Komatsu, Ken-Ich; Takanari, Jun; Shimizu, Shigeomi; Wakame, Koji

    2016-07-01

    Oligonol® (OLG) is a low-molecular-weight lychee fruit polyphenol mainly containing catechin-type monomers and oligomers of proanthocyanidins. Dietary OLG supplementation reportedly improves lipid metabolism disorder and lowers the visceral fat level in animal and human studies. Thus, we investigated the mechanism behind the protective and beneficial effects of OLG on a Western diet (WD)-induced metabolic syndrome (MetS) of a murine model. Using the C57BL/6J mouse for the MetS model, mice were divided into three groups: control (normal diet: ND), Western diet (WD) and WD + 0.5% OLG (OLG) groups. The WD group was fed a high-calorie (high fructose plus high fat) diet for 12 weeks to develop MetS. At week 12, all mice were sacrificed and the blood and liver were obtained for histological and biological examinations and RNA sequencing (RNA-Seq). Body weight, liver weight, plasma triglycerides (TG), total cholesterol (T-Cho) and alanine aminotransferase (ATS) levels of both OLG groups were significantly lower than those of the WD group. On histological examination of the liver, the area of fatty deposits was shown to be suppressed by OLG administration. Expression gene analysis in the liver of WD- versus OLG-fed mice by RNA-Seq showed that 464/45,706 genes exhibited a significant change of expression (corrected p-value metabolism-related genes Lpin1, Adig and Cidea were regulated by OLG administration. OLG may function to suppress MetS and the progression of geriatric diseases in WD-fed mice by regulating the expression of lipid metabolism, inflammation and tumor-related genes in the liver. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Global warning, global warming

    Benarde, M.A.

    1992-01-01

    This book provides insights into the formidable array of issues which, in a warmer world, could impinge upon every facet of readers lives. It examines climatic change and long-term implications of global warming for the ecosystem. Topics include the ozone layer and how it works; the greenhouse effect; the dangers of imbalance and its effects on human and animal life; disruptions to the basic ecology of the planet; and the real scientific evidence for and against aberrant climatic shifts. The author also examines workable social and political programs and changes that must be instituted to avoid ecological disaster

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

    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.

  14. Taking place, screening place

    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...

  15. Against Globalization

    Philipsen, Lotte; Baggesgaard, Mads Anders

    2013-01-01

    In order to understand globalization, we need to consider what globalization is not. That is, in order to understand the mechanisms and elements that work toward globalization, we must, in a sense, read against globalization, highlighting the limitations of the concept and its inherent conflicts....... Only by employing this as a critical practice will we be analytically able to gain a dynamic understanding of the forces of globalization as they unfold today and as they have developed historically....

  16. SUPER-screening

    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.

  17. Skin Cancer Screening

    ... 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 ...

  18. Screening for Cancer

    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.

  19. Colorectal Cancer Screening

    ... 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 ...

  20. Screen time and children

    ... page: //medlineplus.gov/ency/patientinstructions/000355.htm Screen time and children To use the sharing features on ... videos is considered unhealthy screen time. Current Screen Time Guidelines Children under age 2 should have no ...

  1. Stomach (Gastric) Cancer Screening

    ... Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is screening? Go ... are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a disease in ...

  2. The Diabetic Retinopathy Screening Workflow

    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

  3. Global Strategy

    Li, Peter Ping

    2013-01-01

    Global strategy differs from domestic strategy in terms of content and process as well as context and structure. The content of global strategy can contain five key elements, while the process of global strategy can have six major stages. These are expounded below. Global strategy is influenced...... by rich and complementary local contexts with diverse resource pools and game rules at the national level to form a broad ecosystem at the global level. Further, global strategy dictates the interaction or balance between different entry strategies at the levels of internal and external networks....

  4. Prenatal screening and genetics

    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...

  5. Global Europa

    Manners, Ian

    2010-01-01

    at the mythology of ‘global Europa' - the EU in the world. It concludes with a reflection on the way in which the many diverse myths of global Europa compete for daily attention, whether as lore, ideology, or pleasure. In this respect the mythology of global Europa is part of our everyday existence, part of the EU...

  6. Global usability

    Douglas, Ian

    2011-01-01

    The concept of usability has become an increasingly important consideration in the design of all kinds of technology. As more products are aimed at global markets and developed through internationally distributed teams, usability design needs to be addressed in global terms. Interest in usability as a design issue and specialist area of research and education has developed steadily in North America and Europe since the 1980's. However, it is only over the last ten years that it has emerged as a global concern. Global Usability provides an introduction to the important issues in globalizing des

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

    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.

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

    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

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

    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

  10. High throughput screening of starch structures using carbohydrate microarrays

    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...

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

    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 ...

  12. SHADOW GLOBALIZATION

    Larissa Mihaylovna Kapitsa

    2014-01-01

    The article reviews some development trends brought about by globalization, particularly, a growing tax evasion and tax avoidance, an expansion of illicit financial flows and the proliferation of a global criminal network. The author draws attention to some new phenomena, particularly, cosmopolitanization of some parts of national elites and a deepening divide between national interests and the private interests of elites as a consequence of financial globalization. Modern mass media, both Ru...

  13. Global Mindset

    Sørensen, Olav Jull

    2016-01-01

    The concept of Global Mindset (GM) – the way to think about the global reality – is on the agenda of multinational companies concomitant with the increase in global complexity, uncertainty and diversity. In spite of a number of studies, the concept is still fluid and far from a managerial.......e. the capability to sense (quickly), reflect (constructively) and act purposefully (for mutual benefit). A case on an MNC is used at the end to show the organizational manifestations of a GM....

  14. Comparative analysis of pharmacophore screening tools.

    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

  15. Global Microbial Identifier

    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...

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

    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-.

  17. Gendering Globalization

    Siim, Birte

    2009-01-01

    The current global financial situation bluntly and brutally brings home the fact that the global and local are closely connected in times of opportunity as well as crises. The articles in this issue of Asia Insights are about ontra-action between Asia, particularly China, and the Nordic countries...

  18. Developing Globalization

    Hansen, Annette Skovsted

    2017-01-01

    This chapter is the first qualitative micro case study of one aspect of globalization: personal networks as a concrete outcome of development assistance spending. The empirical findings related in this paper present circumstantial evidence that Japanese foreign aid has contributed to globalization...

  19. Global Uddannelse

    Jensen, Niels Rosendal

    Antologien handler om "demokratiproblemer i den globale sammenhæng" (del I) og "demokratiproblemer i uddannelse og for de offentligt ansatte" (del II), bundet sammen af et mellemstykke, der rækker ud mod begge poler både det globale og det lokale ved at knytte det til forholdet mellem marked...

  20. Global Mindsets

    Global Mindsets: Exploration and Perspectives seeks to tackle a topic that is relatively new in research and practice, and is considered by many to be critical for firms seeking to conduct global business. It argues that multiple mindsets exist (across and within organizations), that they operate...... in a global context, and that they are dynamic and undergo change and action. Part of the mindset(s) may depend upon place, situation and context where individuals and organizations operate. The book will examine the notion of "mindset" is situational and dynamic, especially in a global setting, why...... it is important for future scholars and managers and how it could be conceptualized. Global Mindsets: Exploration and Perspectives is split into two major sections; the first examines where the literature currently is with respect to the knowledge in the field and what conceptual frameworks guide the thinking...

  1. Global warming

    Anon.

    1992-01-01

    Canada's Green Plan strategy for dealing with global warming is being implemented as a multidepartmental partnership involving all Canadians and the international community. Many of the elements of this strategy are built on an existing base of activities predating the Green Plan. Elements of the strategy include programs to limit emissions of greenhouse gases, such as initiatives to encourage more energy-efficient practices and development of alternate fuel sources; studies and policy developments to help Canadians prepare and adapt to climate change; research on the global warming phenomenon; and stimulation of international action on global warming, including obligations arising out of the Framework Convention on Climate Change. All the program elements have been approved, funded, and announced. Major achievements to date are summarized, including improvements in the Energy Efficiency Act, studies on the socioeconomic impacts of global warming, and participation in monitoring networks. Milestones associated with the remaining global warming initiatives are listed

  2. Magnetismo Molecular (Molecular Magentism)

    Reis, Mario S [Universidade Federal Fluminense, Brasil; Moreira Dos Santos, Antonio F [ORNL

    2010-07-01

    The new synthesis processes in chemistry open a new world of research, new and surprising materials never before found in nature can now be synthesized and, as a wonderful result, observed a series of physical phenomena never before imagined. Among these are many new materials the molecular magnets, the subject of this book and magnetic properties that are often reflections of the quantum behavior of these materials. Aside from the wonderful experience of exploring something new, the theoretical models that describe the behavior these magnetic materials are, in most cases, soluble analytically, which allows us to know in detail the physical mechanisms governing these materials. Still, the academic interest in parallel this subject, these materials have a number of properties that are promising to be used in technological devices, such as in computers quantum magnetic recording, magnetocaloric effect, spintronics and many other devices. This volume will journey through the world of molecular magnets, from the structural description of these materials to state of the art research.

  3. Screening for Glaucoma

    Understanding Task Force Recommendations Screening for Glaucoma The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Glaucoma . This final recommendation statement ...

  4. Liver (Hepatocellular) Cancer Screening

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  5. Hearing Loss: Screening Newborns

    ... of this page please turn JavaScript on. Feature: Hearing Loss Screening Newborns Past Issues / Spring 2015 Table ... deafness, which account for most cases. Screening Newborns' Hearing Now Standard In 1993, children born in the ...

  6. Cervical Cancer Screening

    ... Cancer found early may be easier to treat. Cervical cancer screening is usually part of a woman's health ... may do more tests, such as a biopsy. Cervical cancer screening has risks. The results can sometimes be ...

  7. Screening for Cervical Cancer

    Understanding Task Force Recommendations Screening for Cervical Cancer The U.S. Preventive Services Task Force (Task Force) has issued final recommendations on Screening for Cervical Cancer . These recommendations are for women ...

  8. Between Stage and Screen

    Tornqvist, Egil

    1996-01-01

    Ingmar Bergman is worldwide known as a film and stage director. Yet no-one has attempted to compare his stage and screen activities. In Between stage and screen Egil Tornqvist examines formal and thematical correspondences and differences between a number of Bergman's stage, screen, and radio

  9. SHADOW GLOBALIZATION

    Larissa Mihaylovna Kapitsa

    2014-01-01

    Full Text Available The article reviews some development trends brought about by globalization, particularly, a growing tax evasion and tax avoidance, an expansion of illicit financial flows and the proliferation of a global criminal network. The author draws attention to some new phenomena, particularly, cosmopolitanization of some parts of national elites and a deepening divide between national interests and the private interests of elites as a consequence of financial globalization. Modern mass media, both Russian and foreign, tend to interpret globalization processes exclusively from the position of conformism, and for some of the researchers globalization became the "sacred cow", which one may only worship. Critical analysis of the processes associated with globalization is given a hostile reception. In response to criticism of globalization, one can hear the very same argument: "globalization in inevitable!" Such a state of affairs, the very least, causes perplexity. Some of the world development trends been observed over the past years raise serious concerns about the security and welfare of the peoples of the world. One of such trends has been the globalization of shadow economic activities. Methods of fight against the criminal economy been applied in international practice can be grouped into: 1 punitive enforcement (or criminal-legal methods and 2 socio-economic methods. As the results of various research works evidence punitive enforcement methods not supported by socio-economic measures not effective enough. Toughening the control over criminal economic activities in the absence of preventive and corrective actions aiming to neutralize institutional, social and other stimuli facilitating criminalization of economic activities can result in large losses of financial assets in the form of mass capital flight

  10. Shadow Globalization

    Larissa Mihaylovna Kapitsa

    2014-01-01

    Full Text Available The article reviews some development trends brought about by globalization, particularly, a growing tax evasion and tax avoidance, an expansion of illicit financial flows and the proliferation of a global criminal network. The author draws attention to some new phenomena, particularly, cosmopolitanization of some parts of national elites and a deepening divide between national interests and the private interests of elites as a consequence of financial globalization. Modern mass media, both Russian and foreign, tend to interpret globalization processes exclusively from the position of conformism, and for some of the researchers globalization became the "sacred cow", which one may only worship. Critical analysis of the processes associated with globalization is given a hostile reception. In response to criticism of globalization, one can hear the very same argument: "globalization in inevitable!" Such a state of affairs, the very least, causes perplexity. Some of the world development trends been observed over the past years raise serious concerns about the security and welfare of the peoples of the world. One of such trends has been the globalization of shadow economic activities. Methods of fight against the criminal economy been applied in international practice can be grouped into: 1 punitive enforcement (or criminal-legal methods and 2 socio-economic methods. As the results of various research works evidence punitive enforcement methods not supported by socio-economic measures not effective enough. Toughening the control over criminal economic activities in the absence of preventive and corrective actions aiming to neutralize institutional, social and other stimuli facilitating criminalization of economic activities can result in large losses of financial assets in the form of mass capital flight

  11. Global Rome

    Is 21st-century Rome a global city? Is it part of Europe's core or periphery? This volume examines the “real city” beyond Rome's historical center, exploring the diversity and challenges of life in neighborhoods affected by immigration, neoliberalism, formal urban planning, and grassroots social...... movements. The contributors engage with themes of contemporary urban studies–the global city, the self-made city, alternative modernities, capital cities and nations, urban change from below, and sustainability. Global Rome serves as a provocative introduction to the Eternal City and makes an original...

  12. Screening for colorectal cancer.

    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. Screening for Prediabetes Using Machine Learning Models

    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.

  14. Molecular hematology

    Provan, Drew; Gribben, John

    2010-01-01

    ... The molecular basis of hemophilia, 219 Paul LF Giangrande 4 The genetics of acute myeloid leukemias, 42 Carolyn J Owen & Jude Fitzgibbon 19 The molecular basis of von Willebrand disease, 233 Luciano Baronc...

  15. Global Managers

    Barakat, Livia L.; Lorenz, Melanie P.; Ramsey, Jase R.

    2016-01-01

    Purpose: – The purpose of this paper is to examine the effect of cultural intelligence (CQ) on the job performance of global managers. Design/methodology/approach: – In total, 332 global managers were surveyed from multinational companies operating in Brazil. The mediating effect of job...... satisfaction was tested on the CQ-job performance relationship. Findings: – The findings suggest that job satisfaction transmits the effect of CQ to job performance, such that global managers high in CQ exhibit more job satisfaction in an international setting, and therefore perform better at their jobs....... Practical implications: – Results imply that global managers should increase their CQ in order to improve their job satisfaction and ultimately perform better in an international context. Originality/value: – The authors make three primary contributions to the international business literature. First...

  16. Globalization & technology

    Narula, Rajneesh

    Technology and globalization are interdependent processes. Globalization has a fundamental influence on the creation and diffusion of technology, which, in turn, affects the interdependence of firms and locations. This volume examines the international aspect of this interdependence at two levels...... of innovation" understanding of learning. Narula and Smith reconcile an important paradox. On the one hand, locations and firms are increasingly interdependent through supranational organisations, regional integration, strategic alliances, and the flow of investments, technologies, ideas and people...

  17. Another globalization

    Prof. Ph.D. Ion Bucur

    2007-01-01

    Finding the anachronisms and the failures of the present globalization, as well as the vitiated system of world-wide government, has stimulated the debates regarding the identification of a more equitable form of globalization to favor the acceleration of the economic increase and the reduction of poverty.The deficiency of the present international economic institutions, especially the lack of transparency and democratic responsibility, claims back with acuteness the reformation of ...

  18. Gendered globalization

    Milwertz, Cecilia Nathansen; Cai, Yiping

    2017-01-01

    Both the People’s Republic of China (PRC) and Nordic countries (Sweden, Iceland, Denmark, Norway and Finland) view gender equality as a social justice issue and are politically committed towards achieving gender equality nationally and internationally. Since China has taken a proactive position...... on globalization and global governance, gender equality is possibly an area that China may wish to explore in collaboration with the Nordic countries....

  19. Screen Practice in Curating

    Toft, Tanya Søndergaard

    2014-01-01

    During the past one and a half decade, a curatorial orientation towards "screen practice" has expanded the moving image and digital art into the public domain, exploring alternative artistic uses of the screen. The emergence of urban LED screens in the late 1990s provided a new venue that allowed...... for digital art to expand into public space. It also offered a political point of departure, inviting for confrontation with the Spectacle and with the politics and ideology of the screen as a mass communication medium that instrumentalized spectator positions. In this article I propose that screen practice...... to the dispositif of screen practice in curating, resulting in a medium-based curatorial discourse. With reference to the nomadic exhibition project Nordic Outbreak that I co-curated with Nina Colosi in 2013 and 2014, I suggest that the topos of the defined visual display area, frequently still known as "the screen...

  20. Global warming

    Hulme, M

    1998-01-01

    Global warming-like deforestation, the ozone hole and the loss of species- has become one of the late 20the century icons of global environmental damage. The threat, is not the reality, of such a global climate change has motivated governments. businesses and environmental organisations, to take serious action ot try and achieve serious control of the future climate. This culminated last December in Kyoto in the agreement for legally-binding climate protocol. In this series of three lectures I will provide a perspective on the phenomenon of global warming that accepts the scientific basis for our concern, but one that also recognises the dynamic interaction between climate and society that has always exited The future will be no different. The challenge of global warning is not to pretend it is not happening (as with some pressure groups), nor to pretend it threatens global civilisation (as with other pressure groups), and it is not even a challenge to try and stop it from happening-we are too far down the ro...

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

    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.

  2. Global distribution of novel rhinovirus genotype

    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. Automated Groundwater Screening

    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

  4. Global biogeography since Pangaea.

    McIntyre, Sarah R N; Lineweaver, Charles H; Groves, Colin P; Chopra, Aditya

    2017-06-14

    The break-up of the supercontinent Pangaea around 180 Ma has left its imprint on the global distribution of species and resulted in vicariance-driven speciation. Here, we test the idea that the molecular clock dates, for the divergences of species whose geographical ranges were divided, should agree with the palaeomagnetic dates for the continental separations. Our analysis of recently available phylogenetic divergence dates of 42 pairs of vertebrate taxa, selected for their reduced ability to disperse, demonstrates that the divergence dates in phylogenetic trees of continent-bound terrestrial and freshwater vertebrates are consistent with the palaeomagnetic dates of continental separation. © 2017 The Author(s).

  5. Global Issues

    Seitz, J.L.

    2001-10-15

    Global Issues is an introduction to the nature and background of some of the central issues - economic, social, political, environmental - of modern times. This new edition of this text has been fully updated throughout and features expanded sections on issues such as global warming, biotechnology, and energy. Fully updated throughout and features expanded sections on issues such as global warming, biotechnology, and energy. An introduction to the nature and background of some of the central issues - economic, social, political, environmental - of modern times. Covers a range of perspectives on a variety of societies, developed and developing. Extensively illustrated with diagrams and photographs, contains guides to further reading, media, and internet resources, and includes suggestions for discussion and studying the material. (author)

  6. Global Inequality

    Niño-Zarazúa, Miguel; Roope, Laurence; Tarp, Finn

    2017-01-01

    This paper measures trends in global interpersonal inequality during 1975–2010 using data from the most recent version of the World Income Inequality Database (WIID). The picture that emerges using ‘absolute,’ and even ‘centrist’ measures of inequality, is very different from the results obtained...... using standard ‘relative’ inequality measures such as the Gini coefficient or Coefficient of Variation. Relative global inequality has declined substantially over the decades. In contrast, ‘absolute’ inequality, as captured by the Standard Deviation and Absolute Gini, has increased considerably...... and unabated. Like these ‘absolute’ measures, our ‘centrist’ inequality indicators, the Krtscha measure and an intermediate Gini, also register a pronounced increase in global inequality, albeit, in the case of the latter, with a decline during 2005 to 2010. A critical question posed by our findings is whether...

  7. Global Inequality

    Niño-Zarazúa, Miguel; Roope, Laurence; Tarp, Finn

    2017-01-01

    This paper measures trends in global interpersonal inequality during 1975–2010 using data from the most recent version of the World Income Inequality Database (WIID). The picture that emerges using ‘absolute,’ and even ‘centrist’ measures of inequality, is very different from the results obtained...... by centrist measures such as the Krtscha, could return to 1975 levels, at today's domestic and global per capita income levels, but this would require quite dramatic structural reforms to reduce domestic inequality levels in most countries....... using standard ‘relative’ inequality measures such as the Gini coefficient or Coefficient of Variation. Relative global inequality has declined substantially over the decades. In contrast, ‘absolute’ inequality, as captured by the Standard Deviation and Absolute Gini, has increased considerably...

  8. Global Programs

    Lindberg Christensen, Lars; Russo, P.

    2009-05-01

    IYA2009 is a global collaboration between almost 140 nations and more than 50 international organisations sharing the same vision. Besides the common brand, mission, vision and goals, IAU established eleven cornerstones programmes to support the different IYA2009 stakeholder to organize events, activities under a common umbrella. These are global activities centred on specific themes and are aligned with IYA2009's main goals. Whether it is the support and promotion of women in astronomy, the preservation of dark-sky sites around the world or educating and explaining the workings of the Universe to millions, the eleven Cornerstones are key elements in the success of IYA2009. However, the process of implementing global projects across cultural boundaries is challenging and needs central coordination to preserve the pre-established goals. During this talk we will examine the ups and downs of coordinating such a project and present an overview of the principal achievements for the Cornerstones so far.

  9. Global rotation

    Rosquist, K.

    1980-01-01

    Global rotation in cosmological models is defined on an observational basis. A theorem is proved saying that, for rigid motion, the global rotation is equal to the ordinary local vorticity. The global rotation is calculated in the space-time homogeneous class III models, with Godel's model as a special case. It is shown that, with the exception of Godel's model, the rotation in these models becomes infinite for finite affine parameter values. In some directions the rotation changes sign and becomes infinite in a direction opposite to the local vorticity. The points of infinite rotation are identified as conjugate points along the null geodesics. The physical interpretation of the infinite rotation is discussed, and a comparison with the behaviour of the area distance at conjugate points is given. (author)

  10. Screening for abdominalt aortaaneurisme

    Lindholt, J S; Juul, Svend; Henneberg, E W

    1997-01-01

    rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...... on uncertain assumptions concerning prevalence, incidence and risk of rupture. Therefore a randomized trial screening of 65-73 year old males is taking place in the County of Viborg in Denmark. Udgivelsesdato: 1997-Mar-24...

  11. Another globalization

    Prof. Ph.D. Ion Bucur

    2007-05-01

    Full Text Available Finding the anachronisms and the failures of the present globalization, as well as the vitiated system of world-wide government, has stimulated the debates regarding the identification of a more equitable form of globalization to favor the acceleration of the economic increase and the reduction of poverty.The deficiency of the present international economic institutions, especially the lack of transparency and democratic responsibility, claims back with acuteness the reformation of the architecture of the international institutional system and the promotion of those economical policies which must ensure the stability world-wide economy and the amelioration of the international equity.

  12. Measuring Globalization

    Andersen, Torben M.; Herbertsson, Tryggvi Thor

    2003-01-01

    The multivariate technique of factor analysis is used to combine several indicators of economic integration and international transactions into a single measure or index of globalization. The index is an alternative to the simple measure of openness based on trade, and it produces a ranking of countries over time for 23 OECD countries. Ireland is ranked as the most globalized country during the 1990?s, while the UK was at the top during the 1980?s. Some of the most notable changes in the rank...

  13. Going global

    Meade, W.; Poirier, J.L.

    1992-01-01

    This article discusses the global market for independent power projects and the increased competition and strategic alliances that are occurring to take advantage of the increasing demand. The topics of the article include the amount of involvement of US companies in the global market, the forces driving the market toward independent power, markets in the United Kingdom, North America, Turkey, Central America, South America, the Caribbean, Europe, the Federal Republic of Germany, India, the former Eastern European countries, Asia and the Pacific nations, and niche markets

  14. Cathode ray tube screens

    Cockayne, B.; Robbins, D.J.; Glasper, J.L.

    1982-01-01

    An improved cathode ray tube screen is described which consists of a single- or a poly-crystalline slice of a material such as yttrium aluminium garnet in which dopants such as Tb 3 + , Eu 3 + , Ce 3 + or Tm 3 + are ion implanted to different depths or in different areas of the screen. Annealing the screen removes lattice damage caused by the ion implanting and assists the diffusion of the dopant into the crystal. (U.K.)

  15. Colorectal Cancer Screening

    Quintero, Enrique; Saito, Yutaka; Hassan, Cessare; Senore, Carlo

    2012-01-01

    Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should wo...

  16. Colorectal cancer screening

    Plumb, A. A.; Halligan, S.

    2015-01-01

    Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. In addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can...

  17. Screening for colorectal cancer

    Nielsen, Hans J.; Jakobsen, Karen V.; Christensen, Ib J.

    2011-01-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....

  18. [Overdiagnosis in cancer screening].

    Cervera Deval, J; Sentís Crivillé, M; Zulueta, J J

    2015-01-01

    In screening programs, overdiagnosis is defined as the detection of a disease that would have gone undetected without screening when that disease would not have resulted in morbimortality and was treated unnecessarily. Overdiagnosis is a bias inherent in screening and an undesired effect of secondary prevention and improved sensitivity of diagnostic techniques. It is difficult to discriminate a priori between clinically relevant diagnoses and those in which treatment is unnecessary. To minimize the effects of overdiagnosis, screening should be done in patients at risk. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  19. Cancer screening guidelines.

    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.

  20. Obesity Prevention and Screening.

    Mackey, Eleanor R; Olson, Alexandra; DiFazio, Marc; Cassidy, Omni

    2016-03-01

    Obesity is widespread, associated with several physical and psychosocial comorbidities, and is difficult to treat. Prevention of obesity across the lifespan is critical to improving the health of individuals and society. Screening and prevention efforts in primary care are an important step in addressing the obesity epidemic. Each period of human development is associated with unique risks, challenges, and opportunities for prevention and intervention. Screening tools for overweight/obesity, although imperfect, are quick and easy to administer. Screening should be conducted at every primary care visit and tracked longitudinally. Screening tools and cutoffs for overweight and obesity vary by age group. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. ScreenOS Cookbook

    Brunner, Stefan; Delcourt, David

    2008-01-01

    In the only book that completely covers ScreenOS, six key members of Juniper Network's ScreenOS development team help you troubleshoot secure networks using ScreenOS firewall appliances. Over 200 recipes address a wide range of security issues, provide step-by-step solutions, and include discussions of why the recipes work, so you can easily set up and keep ScreenOS systems on track. The easy-to-follow format enables you to find the topic and specific recipe you need right away.

  2. Mammography screening in Denmark

    Vejborg, Ilse; Mikkelsen, Ellen Margrethe; Garne, Jens Peter

    2011-01-01

    Mammography screening is offered healthy women, and a high standard on professional and organizational level is mandatory not only in the screening programme but even in the diagnostic work-up and treatment. The main goal is to achieve a substantial reduction in disease specific mortality......, but it is not possible to evaluate the effect on mortality until several years later, and continuously monitoring of the quality of all aspects of a screening programme is necessary. Based on other European guidelines, 11 quality indicators have been defined, and guidelines concerning organizational requirements...... for a Danish screening programme as well as recommendations for the radiographic and radiological work have been drawn up....

  3. Molecular screening of deafness in Algeria: high genetic heterogeneity involving DFNB1 and the Usher loci, DFNB2/USH1B, DFNB12/USH1D and DFNB23/USH1F.

    Ammar-Khodja, Fatima; Faugère, Valérie; Baux, David; Giannesini, Claire; Léonard, Susana; Makrelouf, Mohamed; Malek, Rahia; Djennaoui, Djamel; Zenati, Akila; Claustres, Mireille; Roux, Anne-Françoise

    2009-01-01

    A systematic approach, involving haplotyping and genotyping, to the molecular diagnosis of non-syndromic deafness within 50 families and 9 sporadic cases from Algeria is described. Mutations at the DFNB1 locus (encompassing the GJB2 and GJB6 genes) are responsible for more than half of autosomal recessive prelingual non-syndromic deafness in various populations. A c.35delG mutation can account for up to 85% of GJB2 mutations and two large deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) have also been reported in several population groups. In view of the genetic heterogeneity a strategy was developed which involved direct analysis of DFNB1. In negative familial cases, haplotype analysis was carried out, where possible, to exclude DFNB1 mutations. Following this, haplotype analysis of five Usher syndrome loci, sometimes involved in autosomal non-syndromic hearing loss, was carried out to identify cases in which Usher gene sequencing was indicated. When homozygosity was observed at a locus in a consanguineous family, the corresponding gene was exhaustively sequenced. Pathogenic DFNB1 genotypes were identified in 40% of the cases. Of the 21 cases identified with 2 pathogenic mutations, c.35delG represented 76% of the mutated alleles. The additional mutations were one nonsense, two missense and one splicing mutation. Four additional patients were identified with a single DFNB1 mutation. None carried the large deletions. Three families with non-syndromic deafness carried novel unclassified variants (UVs) in MYO7A (1 family) and CDH23 (2 families) of unknown pathogenic effect. Additionally, molecular diagnosis was carried out on two Usher type I families and pathogenic mutations in MYO7A and PCDH15 were found.

  4. Global Games

    van Bottenburg, Maarten

    2001-01-01

    Why is soccer the sport of choice in South America, while baseball has soared to popularity in the Carribean? How did cricket become India's national sport, while China is a stronghold of table tennis? In Global Games, Maarten van Bottenburg asserts that it is the 'hidden competition' of social and

  5. Going global?

    Fejerskov, Adam Moe; Rasmussen, Christel

    2016-01-01

    occurred at a more micro level. This article explores this issue by studying the international activities of Danish foundations. It finds that grant-making on global issues is increasing, and that several foundations have undergone transformations in their approach to grantmaking, making them surprisingly...

  6. Justice Globalism

    Wilson, Erin; Steger, Manfred; Siracusa, Joseph; Battersby, Paul

    2014-01-01

    The pursuit of a global order founded on universal rules extends beyond economics into the normative spheres of law, politics and justice. Justice globalists claim universal principles applicable to all societies irrespective of religion or ideology. This view privileges human rights, democracy and

  7. Touch screens go optical

    Hanson, Steen Grüner; Jakobsen, Michael Linde; Pedersen, Henrik Chresten

    2012-01-01

    A simple optical implementation of a touch screen is made possible by disrupting the total internal reflection in a 2D waveguide.......A simple optical implementation of a touch screen is made possible by disrupting the total internal reflection in a 2D waveguide....

  8. EIA screening in Denmark

    Nielsen, Eskild Holm; Christensen, Per; Kørnøv, Lone

    2005-01-01

    The article points out that EIA screening is effectively a regulatory instrument and it can be a cost-effective instrument with environmental benefits.......The article points out that EIA screening is effectively a regulatory instrument and it can be a cost-effective instrument with environmental benefits....

  9. Substance Abuse Screening

    ... information is collected, stored or sent over the Internet. To ensure complete privacy, exit your web browser after completing this screening. ... information is collected, stored or sent over the Internet. To ensure complete privacy, exit your web browser after completing this screening. ...

  10. [Towards a molecular psychiatry].

    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.

  11. Molecular diagnosis and immunotherapy.

    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. Endophytic bacteria from Piper tuberculatum Jacq.: isolation, molecular characterization, and in vitro screening for the control of Fusarium solani f. sp piperis, the causal agent of root rot disease in black pepper (Piper nigrum L.).

    Nascimento, S B; Lima, A M; Borges, B N; de Souza, C R B

    2015-07-06

    Endophytic bacteria have been found to colonize internal tissues in many different plants, where they can have several beneficial effects, including defense against pathogens. In this study, we aimed to identify endophytic bacteria associated with roots of the tropical piperaceae Piper tuberculatum, which is known for its resistance to infection by Fusarium solani f. sp piperis, the causal agent of black pepper (Piper nigrum) root rot disease in the Amazon region. Based on 16S rRNA gene sequence analysis, we isolated endophytes belonging to 13 genera: Bacillus, Paenibacillus, Pseudomonas, Enterobacter, Rhizobium, Sinorhizobium, Agrobacterium, Ralstonia, Serratia, Cupriavidus, Mitsuaria, Pantoea, and Staphylococcus. The results showed that 56.52% of isolates were associated with the phylum Proteobacteria, which comprised α, β, and γ classes. Other bacteria were related to the phylum Firmicutes, including Bacillus, which was the most abundant genus among all isolates. Antagonistic assays revealed that Pt12 and Pt13 isolates, identified as Pseudomonas putida and Pseudomonas sp, respectively, were able to inhibit F. solani f. sp piperis growth in vitro. We describe, for the first time, the molecular identification of 23 endophytic bacteria from P. tuberculatum, among which two Pseudomonas species have the potential to control the pathogen responsible for root rot disease in black pepper in the Amazon region.

  13. Screen-film mammography

    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

  14. Screening for abdominalt aortaaneurisme

    Lindholt, Jes Sanddal; Juul, Søren; Henneberg, E W

    1997-01-01

    In spite of increasing number of elective resections of abdominal aortic aneurysms (AAA) the mortality or ruptured AAA is increasing. The advantages of elective operations are obvious; the lethality is 2-6% while the lethality of ruptured AAA is 75-95%. However, AAA seldom causes symptoms before...... rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...

  15. Global swindle of global warming

    Zeiler, W.

    2007-01-01

    Voor sommige mensen is het nog steeds niet aannemelijk dat we te maken hebben met de effecten van ‘Global Warming’, de opwarming van de aarde door voornamelijk de broeikasgassen die vrijkomen bij de verbranding van fossiele brandstoffen. In de media worden voor- en tegenstanders aan het woord

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

    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.

  17. Molecular Diagnostics

    Choe, Hyonmin; Deirmengian, Carl A.; Hickok, Noreen J.; Morrison, Tiffany N.; Tuan, Rocky S.

    2015-01-01

    Orthopaedic infections are complex conditions that require immediate diagnosis and accurate identification of the causative organisms to facilitate appropriate management. Conventional methodologies for diagnosis of these infections sometimes lack accuracy or sufficient rapidity. Current molecular diagnostics are an emerging area of bench-to-bedside research in orthopaedic infections. Examples of promising molecular diagnostics include measurement of a specific biomarker in the synovial fluid...

  18. Molecular genetics

    Parkinson, D.R.; Krontiris, T.G.

    1986-01-01

    In this chapter the authors review new findings concerning the molecular genetics of malignant melanoma in the context of other information obtained from clinical, epidemiologic, and cytogenetic studies in this malignancy. These new molecular approaches promise to provide a more complete understanding of the mechanisms involved in the development of melanoma, thereby suggesting new methods for its treatment and prevention

  19. Molecular Modeling

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 5. Molecular Modeling: A Powerful Tool for Drug Design and Molecular Docking. Rama Rao Nadendla. General Article Volume 9 Issue 5 May 2004 pp 51-60. Fulltext. Click here to view fulltext PDF. Permanent link:

  20. Conceived globals

    Cheraghi, Maryam; Schøtt, Thomas

    2016-01-01

    and culture which have separate effects. Being man, young, educated and having entrepreneurial competencies promote transnational networking extensively. Networking is embedded in culture, in the way that transnational networking is more extensive in secular-rational culture than in traditional culture.......A firm may be conceived global, in the sense that, before its birth, the founding entrepreneur has a transnational network of advisors which provides an embedding for organising the upstart that may include assembling resources and marketing abroad. The purpose is to account for the entrepreneurs...... the intending, starting and operating phases, fairly constantly with only small fluctuations. The firm is conceived global in terms of the entrepreneur's transnational networking already in the pre-birth phase, when the entrepreneur is intending to start the firm. These phase effects hardly depend on attributes...

  1. Global Derivatives

    Andersen, Torben Juul

    approaches to dealing in the global business environment." - Sharon Brown-Hruska, Commissioner, Commodity Futures Trading Commission, USA. "This comprehensive survey of modern risk management using derivative securities is a fine demonstration of the practical relevance of modern derivatives theory to risk......" provides comprehensive coverage of different types of derivatives, including exchange traded contracts and over-the-counter instruments as well as real options. There is an equal emphasis on the practical application of derivatives and their actual uses in business transactions and corporate risk...... management situations. Its key features include: derivatives are introduced in a global market perspective; describes major derivative pricing models for practical use, extending these principles to valuation of real options; practical applications of derivative instruments are richly illustrated...

  2. Energy globalization

    Tierno Andres

    1997-01-01

    Toward the future, the petroleum could stop to be the main energy source in the world and the oil companies will only survive if they are adjusted to the new winds that blow in the general energy sector. It will no longer be enough to be the owner of the resource (petroleum or gas) so that a company subsists and be profitable in the long term. The future, it will depend in great measure of the vision with which the oil companies face the globalization concept that begins to experience the world in the energy sector. Concepts like globalization, competition, integration and diversification is something that the companies of the hydrocarbons sector will have very present. Globalization means that it should be been attentive to what happens in the world, beyond of the limits of its territory, or to be caught by competitive surprises that can originate in very distant places. The search of cleaner and friendlier energy sources with the means it is not the only threat that it should fear the petroleum. Their substitution for electricity in the big projects of massive transport, the technology of the communications, the optic fiber and the same relationships with the aboriginal communities are aspects that also compete with the future of the petroleum

  3. Global overeksponering

    Rosenstand, Claus A. Foss

    2007-01-01

    forandringer. Den globale orientering kommer blandt andet til udtryk i det relativt store internationale netværk, som bakker de unge op i deres protester - enten ved tilstedeværelse i København eller andre sympatiaktioner. Siden den 11. september, 2001, er globale realiteter blevet eksponeret i massemedierne...... så bliver der blændet fuldt op for linsen d. 11. september, 2001 til en global verden, hvor de demokratiske værdier ikke gælder. Lad mig blot give et eksempel: Guatanamo. Jeg skal hverken tale for eller imod den måde verden er indrettet på - da det er denne analyse uvedkommende - men blot pege på...... med væsentligt større kraft end tidligere. Før den 11. september blev globaliseringen udelukkende tegnet af jetsettet. Altså internationale politikere, kulturkoryfæer, videnskabsfolk og forretningsfolk, der har handler ud fra kendte rationaler. Men jetsettet har ikke længere den privilegeret position...

  4. Screening for skin cancer.

    Helfand, M; Mahon, S M; Eden, K B; Frame, P S; Orleans, C T

    2001-04-01

    Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past 2 decades. Nonmelanoma skin cancer is seldom lethal, but, if advanced, can cause severe disfigurement and morbidity. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of nonmelanoma skin cancer might prevent major disfigurement and to a lesser extent prevent mortality. Current recommendations from professional societies regarding screening for skin cancer vary. To examine published data on the effectiveness of routine screening for skin cancer by a primary care provider, as part of an assessment for the U.S. Preventive Services Task Force. We searched the MEDLINE database for papers published between 1994 and June 1999, using search terms for screening, physical examination, morbidity, and skin neoplasms. For information on accuracy of screening tests, we used the search terms sensitivity and specificity. We identified the most important studies from before 1994 from the Guide to Clinical Preventive Services, second edition, and from high-quality reviews. We used reference lists and expert recommendations to locate additional articles. Two reviewers independently reviewed a subset of 500 abstracts. Once consistency was established, the remainder were reviewed by one reviewer. We included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost effectiveness. We abstracted the following descriptive information from full-text published studies of screening and recorded it in an electronic database: type of screening study, study design, setting, population, patient recruitment, screening test description, examiner, advertising targeted at high-risk groups or not targeted, reported risk factors of participants, and procedure for referrals. We also abstracted the yield of screening data including probabilities and numbers

  5. Dynamic screening in solar and stellar nuclear reactions

    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.)

  6. Molecular imaging: current status and emerging strategies

    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.

  7. Screening sensitivity theory

    Oblow, E.M.; Perey, F.G.

    1984-01-01

    A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

  8. Molecular geometry

    Rodger, Alison

    1995-01-01

    Molecular Geometry discusses topics relevant to the arrangement of atoms. The book is comprised of seven chapters that tackle several areas of molecular geometry. Chapter 1 reviews the definition and determination of molecular geometry, while Chapter 2 discusses the unified view of stereochemistry and stereochemical changes. Chapter 3 covers the geometry of molecules of second row atoms, and Chapter 4 deals with the main group elements beyond the second row. The book also talks about the complexes of transition metals and f-block elements, and then covers the organometallic compounds and trans

  9. Screening for novel laccase-producing microbes.

    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

  10. Risks of Colorectal Cancer Screening

    ... 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 ...

  11. Cervical cancer - screening and prevention

    Cancer cervix - screening; HPV - cervical cancer screening; Dysplasia - cervical cancer screening; Cervical cancer - HPV vaccine ... Almost all cervical cancers are caused by HPV (human papilloma virus). HPV is a common virus that spreads through sexual contact. Certain ...

  12. Global safety

    Dorien J. DeTombe

    2010-08-01

    Full Text Available Global Safety is a container concept referring to various threats such as HIV/Aids, floods and terrorism; threats with different causes and different effects. These dangers threaten people, the global economy and the slity of states. Policy making for this kind of threats often lack an overview of the real causes and the interventions are based on a too shallow analysis of the problem, mono-disciplinary and focus mostly only on the effects. It would be more appropriate to develop policy related to these issues by utilizing the approaches, methods and tools that have been developed for complex societal problems. Handling these complex societal problems should be done multidisciplinary instead of mono-disciplinary. In order to give politicians the opportunity to handle complex problems multidisciplinary, multidisciplinary research institutes should be created. These multidisciplinary research institutes would provide politicians with better approaches to handle this type of problem. In these institutes the knowledge necessary for the change of these problems can be created through the use of the Compram methodology which has been developed specifically for handling complex societal problems. In a six step approach, experts, actors and policymakers discuss the content of the problem and the possible changes. The framework method uses interviewing, the Group Decision Room, simulation models and scenario's in a cooperative way. The methodology emphasizes the exchange of knowledge and understanding by communication among and between the experts, actors and politicians meanwhile keeping emotion in mind. The Compram methodology will be further explained in relation to global safety in regard to terrorism, economy, health care and agriculture.

  13. Global ambitions

    Scruton, M.

    1996-01-01

    The article discusses global ambitions concerning the Norwegian petroleum industry. With the advent of the NORSOK (Forum for development and operation) cost reduction programme and a specific focus on key sectors of the market, the Norwegian oil industry is beginning to market its considerable technological achievements internationally. Obviously, the good fortune of having tested this technology in a very demanding domestic arena means that Norwegian offshore support companies, having succeeded at home, are perfectly poised to export their expertise to the international sector. Drawing on the traditional strengths of the country's maritime heritage, with mobile rig and specialized vessel business featuring strongly, other key technologies have been developed. 5 figs., 1 tab

  14. Molecular Electronics

    Jennum, Karsten Stein

    This thesis includes the synthesis and characterisation of organic compounds designed for molecular electronics. The synthesised organic molecules are mainly based on two motifs, the obigo(phenyleneethynylenes) (OPE)s and tetrathiafulvalene (TTF) as shown below. These two scaffolds (OPE and TTF......) are chemically merged together to form cruciform-like structures that are an essential part of the thesis. The cruciform molecules were subjected to molecular conductance measurements to explore their capability towards single-crystal field-effect transistors (Part 1), molecular wires, and single electron......, however, was obtained by a study of a single molecular transistor. The investigated OPE5-TTF compound was captured in a three-terminal experiment, whereby manipulation of the molecule’s electronic spin was possible in different charge states. Thus, we demonstrated how the cruciform molecules could...

  15. Molecular sciences

    Anon.

    1975-01-01

    The research in molecular sciences summarized includes photochemistry, radiation chemistry, geophysics, electromechanics, heavy-element oxidizers , heavy element chemistry collisions, atoms, organic solids. A list of publications is included

  16. Prostate Cancer Screening

    ... treat. There is no standard screening test for prostate cancer. Researchers are studying different tests to find those ... PSA level may be high if you have prostate cancer. It can also be high if you have ...

  17. SCREENING FOR CERVICAL CANCER

    Enrique

    Cervical cancer remains a major health concern worldwide, especially in devel- ... Important aspects of cervical cancer screening include the age at which .... High-risk types HPV (16,18) are impli- cated in the pathogenesis of cervical cancer.

  18. Breast Cancer Screening

    Altaf, Fadwa J.

    2004-01-01

    Breast cancer is a very common health problem in Saudi females that can be reduced by early detection through introducing breast cancer screening. Literature review reveals significant reduction in breast cancer incidence and outcome after the beginning of breast cancer screening. The objectives of this article are to highlight the significance of breast cancer screening in different international societies and to write the major guidelines of breast cancer screening in relation to other departments involved with more emphasis on the Pathology Department guidelines in tissue handling, diagnostic criteria and significance of the diagnosis. This article summaries and acknowledges major work carried out before, and recommends similar modified work in order to meet the requirement for the Saudi society. (author)

  19. Urine drug screen

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  20. Breast cancer screening

    Vandenbroucke, A.

    1987-01-01

    Many studies have shown that breast cancer screening is able to reduce breast cancer mortality, including the HIP study, the Swedish Trial and the Netherlands studies. Mammography is considered as the most effective method for breast cancer screening but it might be unfeasible for some reasons: - the population acceptability of the method might be low. Indeed, most populations of the South of Europe are less compliant to mass screening than populations of the North of Europe; - the medical equipment and personnel - radiologists and pathologists - might be insufficient; - it might be too costly for the National Health Service, specially where the incidence rate of breast cancer is relatively low (i.e. Greece, Portugal). The validity of screening tests is judged by their sensitivity and their specificity

  1. Neonatal cystic fibrosis screening test

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

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

    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

  3. Lung cancer screening: Update

    Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

    2015-09-15

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

  4. Lung cancer screening: Update

    Kim, Hyea Young

    2015-01-01

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers

  5. A new focus for the International Cancer Screening Network

    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.

  6. Global health and global health ethics

    Benatar, S. R; Brock, Gillian

    2011-01-01

    ...? What are our responsibilities and how can we improve global health? Global Health and Global Health Ethics addresses these questions from the perspective of a range of disciplines, including medicine, philosophy and the social sciences...

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

    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.

  8. Global teaching of global seismology

    Stein, S.; Wysession, M.

    2005-12-01

    Our recent textbook, Introduction to Seismology, Earthquakes, & Earth Structure (Blackwell, 2003) is used in many countries. Part of the reason for this may be our deliberate attempt to write the book for an international audience. This effort appears in several ways. We stress seismology's long tradition of global data interchange. Our brief discussions of the science's history illustrate the contributions of scientists around the world. Perhaps most importantly, our discussions of earthquakes, tectonics, and seismic hazards take a global view. Many examples are from North America, whereas others are from other areas. Our view is that non-North American students should be exposed to North American examples that are type examples, and that North American students should be similarly exposed to examples elsewhere. For example, we illustrate how the Euler vector geometry changes a plate boundary from spreading, to strike-slip, to convergence using both the Pacific-North America boundary from the Gulf of California to Alaska and the Eurasia-Africa boundary from the Azores to the Mediterranean. We illustrate diffuse plate boundary zones using western North America, the Andes, the Himalayas, the Mediterranean, and the East Africa Rift. The subduction zone discussions examine Japan, Tonga, and Chile. We discuss significant earthquakes both in the U.S. and elsewhere, and explore hazard mitigation issues in different contexts. Both comments from foreign colleagues and our experience lecturing overseas indicate that this approach works well. Beyond the specifics of our text, we believe that such a global approach is facilitated by the international traditions of the earth sciences and the world youth culture that gives students worldwide common culture. For example, a video of the scene in New Madrid, Missouri that arose from a nonsensical earthquake prediction in 1990 elicits similar responses from American and European students.

  9. [Organized breast cancer screening].

    Rouëssé, Jacques; Sancho-Garnier, Hélèn

    2014-02-01

    Breast screening programs are increasingly controversial, especially regarding two points: the number of breast cancer deaths they avoid, and the problem of over-diagnosis and over-treatment. The French national breast cancer screening program was extended to cover the whole country in 2004. Ten years later it is time to examine the risk/benefit ratio of this program and to discuss the need for change. Like all forms of cancer management, screening must be regularly updated, taking into account the state of the art, new evidence, and uncertainties. All screening providers should keep themselves informed of the latest findings. In the French program, women aged 50-74 with no major individual or familial risk factors for breast cancer are offered screening mammography and clinical breast examination every two years. Images considered non suspicious of malignancy by a first reader are re-examined by a second reader. The devices and procedures are subjected to quality controls. Participating radiologists (both public and private) are required to read at least 500 mammographies per year. The program's national participation rate was 52.7 % in 2012. When individual screening outside of the national program is taken into account (nearly 15 % of women), coverage appears close to the European recommendation of 65 %. Breast cancer mortality has been falling in France by 0.6 % per year for over 30 years, starting before mass screening was implemented, and by 1.5 % since 2005. This decline can be attributed in part to earlier diagnosis and better treatment, so that the specific impact of screening cannot easily be measured. Over-treatment, defined as the detection and treatment of low-malignancy tumors that would otherwise not have been detected in a person's lifetime, is a major negative effect of screening, but its frequency is not precisely known (reported to range from 1 % to 30 %). In view of these uncertainties, it would be advisable to modify the program in order to

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

    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.

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

    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.

  12. Molecular fountain.

    Strecker, Kevin E.; Chandler, David W.

    2009-09-01

    A molecular fountain directs slowly moving molecules against gravity to further slow them to translational energies that they can be trapped and studied. If the molecules are initially slow enough they will return some time later to the position from which they were launched. Because this round trip time can be on the order of a second a single molecule can be observed for times sufficient to perform Hz level spectroscopy. The goal of this LDRD proposal was to construct a novel Molecular Fountain apparatus capable of producing dilute samples of molecules at near zero temperatures in well-defined user-selectable, quantum states. The slowly moving molecules used in this research are produced by the previously developed Kinematic Cooling technique, which uses a crossed atomic and molecular beam apparatus to generate single rotational level molecular samples moving slowly in the laboratory reference frame. The Kinematic Cooling technique produces cold molecules from a supersonic molecular beam via single collisions with a supersonic atomic beam. A single collision of an atom with a molecule occurring at the correct energy and relative velocity can cause a small fraction of the molecules to move very slowly vertically against gravity in the laboratory. These slowly moving molecules are captured by an electrostatic hexapole guiding field that both orients and focuses the molecules. The molecules are focused into the ionization region of a time-of-flight mass spectrometer and are ionized by laser radiation. The new molecular fountain apparatus was built utilizing a new design for molecular beam apparatus that has allowed us to miniaturize the apparatus. This new design minimizes the volumes and surface area of the machine allowing smaller pumps to maintain the necessary background pressures needed for these experiments.

  13. Screening for nutritional rickets in a community.

    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.

  14. Globalizing Denmark

    Selmer, Jan; Lauring, Jakob

    2013-01-01

    countries to keep up the process of globalization may be substantial, and the economic gains for such countries from adjusting to a more internationally integrated world economy are clear. However, in small- population economies, especially social-democratic welfare states, the internal pressure......This exploratory article examines the paradox of being open-minded while ethnocentric as expressed in Danish international management practices at the micro level. With a population of 5.4 million, Denmark is one of the smallest of the European countries. The pressure on many small advanced...... to integrate counteracts to some extent the need to maintain openness to differences. Thus, a strong economy and a feeling of smug ethnocentrism in Denmark generate a central paradox in thinking about internationalization in Danish society....

  15. Global Geomorphology

    Douglas, I.

    1985-01-01

    Any global view of landforms must include an evaluation of the link between plate tectonics and geomorphology. To explain the broad features of the continents and ocean floors, a basic distinction between the tectogene and cratogene part of the Earth's surface must be made. The tectogene areas are those that are dominated by crustal movements, earthquakes and volcanicity at the present time and are essentially those of the great mountain belts and mid ocean ridges. Cratogene areas comprise the plate interiors, especially the old lands of Gondwanaland and Laurasia. Fundamental as this division between plate margin areas and plate interiors is, it cannot be said to be a simple case of a distinction between tectonically active and stable areas. Indeed, in terms of megageomorphology, former plate margins and tectonic activity up to 600 million years ago have to be considered.

  16. Global engineering

    Plass, L.

    2001-01-01

    This article considers the challenges posed by the declining orders in the plant engineering and contracting business in Germany, the need to remain competitive, and essential preconditions for mastering the challenge. The change in engineering approach is illustrated by the building of a methanol plant in Argentina by Lurgi with the basic engineering completed in Frankfurt with involvement of key personnel from Poland, completely engineered subsystems from a Brazilian subsupplier, and detailed engineering work in Frankfurt. The production of methanol from natural gas using the LurgiMega/Methanol process is used as a typical example of the industrial plant construction sector. The prerequisites for successful global engineering are listed, and error costs in plant construction, possible savings, and process intensification are discussed

  17. Global warming

    Houghton, John

    2005-01-01

    'Global warming' is a phrase that refers to the effect on the climate of human activities, in particular the burning of fossil fuels (coal, oil and gas) and large-scale deforestation, which cause emissions to the atmosphere of large amounts of 'greenhouse gases', of which the most important is carbon dioxide. Such gases absorb infrared radiation emitted by the Earth's surface and act as blankets over the surface keeping it warmer than it would otherwise be. Associated with this warming are changes of climate. The basic science of the 'greenhouse effect' that leads to the warming is well understood. More detailed understanding relies on numerical models of the climate that integrate the basic dynamical and physical equations describing the complete climate system. Many of the likely characteristics of the resulting changes in climate (such as more frequent heat waves, increases in rainfall, increase in frequency and intensity of many extreme climate events) can be identified. Substantial uncertainties remain in knowledge of some of the feedbacks within the climate system (that affect the overall magnitude of change) and in much of the detail of likely regional change. Because of its negative impacts on human communities (including for instance substantial sea-level rise) and on ecosystems, global warming is the most important environmental problem the world faces. Adaptation to the inevitable impacts and mitigation to reduce their magnitude are both necessary. International action is being taken by the world's scientific and political communities. Because of the need for urgent action, the greatest challenge is to move rapidly to much increased energy efficiency and to non-fossil-fuel energy sources

  18. Global gamesmanship.

    MacMillan, Ian C; van Putten, Alexander B; McGrath, Rita Gunther

    2003-05-01

    Competition among multinationals these days is likely to be a three-dimensional game of global chess: The moves an organization makes in one market are designed to achieve goals in another in ways that aren't immediately apparent to its rivals. The authors--all management professors-call this approach "competing under strategic interdependence," or CSI. And where this interdependence exists, the complexity of the situation can quickly overwhelm ordinary analysis. Indeed, most business strategists are terrible at anticipating the consequences of interdependent choices, and they're even worse at using interdependency to their advantage. In this article, the authors offer a process for mapping the competitive landscape and anticipating how your company's moves in one market can influence its competitive interactions in others. They outline the six types of CSI campaigns--onslaughts, contests, guerrilla campaigns, feints, gambits, and harvesting--available to any multiproduct or multimarket corporation that wants to compete skillfully. They cite real-world examples such as the U.S. pricing battle Philip Morris waged with R.J. Reynolds--not to gain market share in the domestic cigarette market but to divert R.J. Reynolds's resources and attention from the opportunities Philip Morris was pursuing in Eastern Europe. And, using data they collected from their studies of consumer-products companies Procter & Gamble and Unilever, the authors describe how to create CSI tables and bubble charts that present a graphical look at the competitive landscape and that may uncover previously hidden opportunities. The CSI mapping process isn't just for global corporations, the authors explain. Smaller organizations that compete with a portfolio of products in just one national or regional market may find it just as useful for planning their next business moves.

  19. Physics in Screening Environments

    Certik, Ondrej

    In the current study, we investigated atoms in screening environments like plasmas. It is common practice to extract physical data, such as temperature and electron densities, from plasma experiments. We present results that address inherent computational difficulties that arise when the screening approach is extended to include the interaction between the atomic electrons. We show that there may arise an ambiguity in the interpretation of physical properties, such as temperature and charge density, from experimental data due to the opposing effects of electron-nucleus screening and electron-electron screening. The focus of the work, however, is on the resolution of inherent computational challenges that appear in the computation of two-particle matrix elements. Those enter already at the Hartree-Fock level. Furthermore, as examples of post Hartree-Fock calculations, we show second-order Green's function results and many body perturbation theory results of second order. A self-contained derivation of all necessary equations has been included. The accuracy of the implementation of the method is established by comparing standard unscreened results for various atoms and molecules against literature for Hartree-Fock as well as Green's function and many body perturbation theory. The main results of the thesis are presented in the chapter called Screened Results, where the behavior of several atomic systems depending on electron-electron and electron-nucleus Debye screening was studied. The computer code that we have developed has been made available for anybody to use. Finally, we present and discuss results obtained for screened interactions. We also examine thoroughly the computational details of the calculations and particular implementations of the method.

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

    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.

  1. Análisis genético molecular del Oso Andino ( Tremarctos ornatus en el norte de los andes (Venezuela, Colombia, Ecuador: Una visión global

    M. Ruiz-García

    2001-07-01

    G10B, G10C y G10X. Un exhaustivo análisis genético poblacional permitió determinar los siguientes aspectos fundamentales: (1 No existencia de equilibrio Hardy-Weinberg ni en el conjunto global de muestras ni en el conjunto particular de muestras para cada uno de esos países, al utilizar los tests exactos con cadenas de Markov y con el método de Fisher.

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

    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.

  3. Newborn hearing screening.

    Stewart, D L; Pearlman, A

    1994-11-01

    Congenital deafness is a relatively common problem with an incidence of 1/300 to 1/1000. Most states have no mass screening program for hearing loss, but the state of Kentucky compiles a High Risk Registry which is a historical survey of parents relating to risk factors for hearing loss. Unfortunately this survey can miss 50% of those who have a hearing deficit. If not detected prior to discharge, there is often a delay in diagnosis of deafness which prevents early intervention. We report 2 years' experience at Kosair Children's Hospital where 1,987 infants admitted to well baby, intermediate, or intensive care nurseries were screened using the ALGO-1 screener (Natus Medical Inc, Foster City, CA) which is a modified auditory brain stem evoked response (ABR). Our screening of this population led to an 11% incidence of referral for complete audiological evaluation. There were no significant complications. Forty-eight infants were found to have nonspecified, sensorineural, or conductive hearing loss. The positive predictive value of the test was 96%. Therefore, we feel that the use of the modified ABR in the newborn is a timely, cost efficient method of screening for hearing loss and should be used for mass screening of all newborns.

  4. Exploiting PubChem for Virtual Screening.

    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.

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

    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

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

    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

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

    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

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

    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

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

    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

  10. Screening for oral cancer.

    Jitender, Solanki; Sarika, Gupta; Varada, Hiremath R; Omprakash, Yadav; Mohsin, Khan

    2016-11-01

    Oral cancer is considered as a serious health problem resulting in high morbidity and mortality. Early detection and prevention play a key role in controlling the burden of oral cancer worldwide. The five-year survival rate of oral cancer still remains low and delayed diagnosis is considered as one of the major reasons. This increases the demand for oral screening. Currently, screening of oral cancer is largely based on visual examination. Various evidence strongly suggest the validity of visual inspection in reducing mortality in patients at risk for oral cancer. Simple visual examination is accompanied with adjunctive techniques for subjective interpretation of dysplastic changes. These include toluidine blue staining, brush biopsy, chemiluminescence and tissue autofluorescence. This review highlights the efficacy of various diagnostic methods in screening of oral cancer. © 2016 Old City Publishing, Inc.

  11. Radiographic intensifying screens

    Van Landeghem, W.K.; Suys, A.R.

    1979-01-01

    A fluorescent x-ray image intensifying screen is described which comprises discrete particles of fluorescent material dispersed in a binder layer. Intensifying screens are employed to increase the exposure of a photosensitive plate or film without increasing the x-ray exposure dose when struck by x-rays. The screen has an outermost layer containing solid particulate material protruding from a coherent film-forming organic binder medium and having a static friction coefficient at room temperature not higher than 0.50 on steel. The outermost layer may be characterized by micro-unevennesses of at least 3 μm and at least 9 protruding particles per 0.35 sq. cm. These particles have a static friction coefficient less than 0.3 and are made of a solid polystyrene, polyaklylene and/or a solid organic fluorinated polymer. (JTA)

  12. Screening Risk Evaluation methodology

    Hopper, K.M.

    1994-01-01

    The Screening Risk Evaluation (SRE) Guidance document is a set of guidelines provided for the uniform implementation of SREs performed on D ampersand D facilities. These guidelines are designed specifically for the completion of the second (semi-quantitative screening) phase of the D ampersand D Risk-Based Process. The SRE Guidance produces screening risk scores reflecting levels of risk through the use of risk ranking indices. Five types of possible risk are calculated from the SRE: current releases, worker exposures, future releases, physical hazards, and criticality. The Current Release Index (CRI) calculates the risk to human health and the environment from ongoing or probable releases within a one year time period. The Worker Exposure Index (WEI) calculates the risk to workers, occupants, and visitors in D ampersand D facilities of contaminant exposure. The Future Release Index (FRI) calculates the risk of future releases of contaminants, after one year, to human health and the environment. The Physical Hazards Index (PHI) calculates the risk-to human health due to factors other than that of contaminants. The index of Criticality is approached as a modifying factor to the entire SRE, due to the fact that criticality issues are strictly regulated under DOE. Screening risk results will be tabulated in matrix form and Total Risk will be calculated (weighted equation) to produce a score on which to base early action recommendations. Other recommendations from the screening risk scores will be made based either on individual index scores or from reweighted Total Risk calculations. All recommendations based on the SRE will be made based on a combination of screening risk scores, decision drivers, and other considerations, determined on a project by project basis. The SRE is the first and most important step in the overall D ampersand D project level decision making process

  13. Newborn screening for galactosaemia.

    Lak, Rohollah; Yazdizadeh, Bahareh; Davari, Majid; Nouhi, Mojtaba; Kelishadi, Roya

    2017-12-23

    Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the

  14. Colorectal cancer screening

    McLoughlin, Monica Ramona

    2008-01-01

    Colorectal cancer is a major public health burden and is the most common cause of mortality from cancer in Europe. Over the last two decades robust evidence from randomised clinical trials and case-control series have confirmed that the mortality from colorectal cancer can be reduced by screening. The challenge over the next decade is how to implement this in clinical practice. This is what we set out to answer with this thesis. Not all individuals are equal when it comes to screening and tho...

  15. Molecular spectroscopy

    Kokh, Eh.; Zonntag, B.

    1981-01-01

    The latest investigation results on molecular spectroscopy with application of synchrotron radiation in the region of vacuum ultraviolet are generalized. Some results on investigation of excited, superexcited and ionized molecule states with the use of adsorption spectroscopy, photoelectron spectroscopy, by fluorescent and mass-spectrometric methods are considered [ru

  16. Molecular Foundry

    . New Study Indicates Greater Capacity for Carbon Storage in the Earth's Subsurface A team of Foundry minerals which make up the dominant clays in the Earth's deep subsurface. Doubling Down on Energy Storage identify molecular components within small volumes of biological samples, such as blood or urine. Industry

  17. Molecular farming

    Merck, K.B.; Vereijken, J.M.

    2006-01-01

    Molecular Farming is a new and emerging technology that promises relatively cheap and flexible production of large quantities of pharmaceuticals in genetically modified plants. Many stakeholders are involved in the production of pharmaceuticals in plants, which complicates the discussion on the

  18. Molecular gastronomy

    This, Hervé

    2005-01-01

    For centuries, cooks have been applying recipes without looking for the mechanisms of the culinary transformations. A scientific discipline that explores these changes from raw ingredients to eating the final dish, is developing into its own field, termed molecular gastronomy. Here, one of the founders of the discipline discusses its aims and importance.

  19. Molecular Star

    In molecular self-assembly, molecules put themselves together in a predefined way ... work has been already published in Chemistry- A European Jour- nal in the September ... prevalent in matter ranging from atoms to molecules to biomolecules; it is also ... erate chemical forces are reversible and dynamic in nature mean-.

  20. Molecular ferromagnetism

    Epstein, A.J.

    1990-01-01

    This past year has been one of substantial advancement in both the physics and chemistry of molecular and polymeric ferromagnets. The specific heat studies of (DMeFc)(TCNE) have revealed a cusp at the three-dimensional ferromagnetic transition temperature with a crossover to primarily 1-D behavior at higher temperatures. This paper discusses these studies

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

    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.

  2. Lunar Dust Mitigation Screens

    Knutson, Shawn; Holloway, Nancy

    With plans for the United States to return to the moon, and establish a sustainable human presence on the lunar surface many issues must be successfully overcome. Lunar dust is one of a number of issues with the potential to create a myriad of problems if not adequately addressed. Samples of dust brought back from Apollo missions show it to be soft, yet sharp and abrasive. The dust consists of a variety of morphologies including spherical, angular blocks, shards, and a number of irregular shapes. One of the main issues with lunar dust is its attraction to stick to anything it comes in contact with (i.e. astronauts, equipment, habitats, etc.). Ionized radiation from the sun strikes the moon's surface and creates an electrostatic charge on the dust. Further, the dust harbors van der Waals forces making it especially difficult to separate once it sticks to a surface. During the Apollo missions, it was discovered that trying to brush the lunar dust from spacesuits was not effective, and rubbing it caused degradation of the suit material. Further, when entering the lunar module after moonwalks, the astronauts noted that the dust was so prolific inside the cabin that they inhaled and ingested it, causing at least one of them, Harrison "Jack" Schmidt, to report irritation of the throat and lungs. It is speculated that the dust could also harm an astronaut's nervous and cardiovascular systems, especially during an extended stay. In addition to health issues, the dust can also cause problems by scouring reflective coatings off of thermal blankets, and roughening surfaces of windows and optics. Further, panels on solar cells and photovoltaics can also be compromised due to dust sticking on the surfaces. Lunar dust has the capacity to penetrate seals, interfere with connectors, as well as mechanisms on digging machines, all of which can lead to problems and failure. To address lunar dust issues, development of electrostatic screens to mitigate dust on sur-faces is currently

  3. Global challenges

    Blix, H.

    1990-01-01

    A major challenge now facing the world is the supply of energy needed for growth and development in a manner which is not only economically viable but also environmentally acceptable and sustainable in view of the demands of and risks to future generations. The internationally most significant pollutants from energy production through fossil fuels are SO 2 and NO x which cause acid rain, and CO 2 which is the most significant contributor to the greenhouse effect. Nuclear power, now providing about 17% of the world's electricity and 5% of the primary energy already is making a notable contribution to avoiding these emissions. While the industrialized countries will need more energy and especially electricity in the future, the needs of the developing countries are naturally much larger and present a tremendous challenge to the shaping of the world's future energy supply system. The advanced countries will have to accept special responsibilities, as they can most easily use advanced technologies and they have been and remain the main contributors to the environmental problems we now face. Energy conservation and resort to new renewable energy sources, though highly desirable, appear inadequate alone to meet the challenges. The world can hardly afford to do without an increased use of nuclear power, although it is strongly contested in many countries. The objections raised against the nuclear option focus on safety, waste management and disposal problems and the risk for proliferation of nuclear weapons. These issues are not without their problems. The risk of proliferation exists but will not appreciably diminish with lesser global reliance on nuclear power. The waste issue is more of a political than a technical problem. The use of nuclear power, or any other energy source, will never be at zero risk, but the risks are constantly reduced by new techniques and practices. The IAEA sees it as one of its priority tasks to promote such techniques. (author)

  4. Approaches to virtual screening and screening library selection.

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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....

  10. Screening for Atrial Fibrillation

    Freedman, Ben; Camm, John; Calkins, Hugh

    2017-01-01

    Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed...

  11. Early Dementia Screening

    Peter K. Panegyres

    2016-01-01

    Full Text Available As the population of the world increases, there will be larger numbers of people with dementia and an emerging need for prompt diagnosis and treatment. Early dementia screening is the process by which a patient who might be in the prodromal phases of a dementing illness is determined as having, or not having, the hallmarks of a neurodegenerative condition. The concepts of mild cognitive impairment, or mild neurocognitive disorder, are useful in analyzing the patient in the prodromal phase of a dementing disease; however, the transformation to dementia may be as low as 10% per annum. The search for early dementia requires a comprehensive clinical evaluation, cognitive assessment, determination of functional status, corroborative history and imaging (including MRI, FDG-PET and maybe amyloid PET, cerebrospinal fluid (CSF examination assaying Aβ1–42, T-τ and P-τ might also be helpful. Primary care physicians are fundamental in the screening process and are vital in initiating specialist investigation and treatment. Early dementia screening is especially important in an age where there is a search for disease modifying therapies, where there is mounting evidence that treatment, if given early, might influence the natural history—hence the need for cost-effective screening measures for early dementia.

  12. Hazard screening application guide

    1992-06-01

    The basic purpose of hazard screening is to group precesses, facilities, and proposed modifications according to the magnitude of their hazards so as to determine the need for and extent of follow on safety analysis. A hazard is defined as a material, energy source, or operation that has the potential to cause injury or illness in human beings. The purpose of this document is to give guidance and provide standard methods for performing hazard screening. Hazard screening is applied to new and existing facilities and processes as well as to proposed modifications to existing facilities and processes. The hazard screening process evaluates an identified hazards in terms of the effects on people, both on-site and off-site. The process uses bounding analyses with no credit given for mitigation of an accident with the exception of certain containers meeting DOT specifications. The process is restricted to human safety issues only. Environmental effects are addressed by the environmental program. Interfaces with environmental organizations will be established in order to share information

  13. Radiological protective screen

    Flaugnatti, R.B.

    1976-01-01

    A radiological screen for placing on a patient's skin is discussed, comprising a flat jacket containing a fine particulate filler and a settable resin binder, the fine particulate filler being of a material which absorbs medical radiation, and the jacket including a window to transmit such radiation through the flat jacket. 16 claims, 4 drawing figures

  14. Screening Devices at School

    Ratner, Helene Gad

    2011-01-01

    ethnographic data from a Danish school, the article explores,first, the script and agencement of the SMTTE and, second, how the screening properties of the SMTTE are achieved, including how these properties challenge management-­‐teacher relations when the SMTTE travels to other networks at the school...

  15. Colorec tal cancer screening

    2009-05-12

    May 12, 2009 ... The operator must be skilled in the management of adverse events. • The operator must arrange appropriate follow-up of histopathological results. • The operator must provide appropriate recommendations for follow-up surveil- lance and screening. The average- risk person has a lifetime risk of developing.

  16. [ASCUS in screening].

    Caprara, L; Monari, F; De Bianchi, P S; Amadori, A; Bondi, A

    2001-12-01

    The significance and use of the cytological diagnosis "atypical squamous cells of undetermined significance" (ASCUS) remain a major problem in cervical cancer screening. The prevalence of ASCUS by patient age has seldom been investigated. The present paper reports the prevalence of ASCUS in a large series of screening Pap smears from the Italian region of Emilia-Romagna. The study was based on the data collected by the Department of Health of the Emilia-Romagna Region for the first 3-year round (1997-1999) of a population-based screening programme (target age, 25-64 years). The age-specific frequency of ASCUS has been calculated as a prevalence rate per 1000 screened patients. A total of 597,386 women participated in the programme. Women diagnosed with ASCUS (n = 8205 or 13.7 per 1000) accounted for 49% of the recalls for colposcopy (n = 16,871, or 28.2 per 1000). The prevalence of diagnoses of low-grade squamous intraepithelial lesions (LG-SIL) decreased progressively with age while that of high-grade SIL was slightly higher between 30 and 39 years. The prevalence of ASCUS peaked at age 45-49 years (17.3 per 1000 subjects). The observed peak reflects the prevalence of (1) cytological changes closely associated with perimenopausal age and at least compatible with the ASCUS diagnosis, and (2) cytological abnormalities induced by hormone replacement therapy.

  17. Screening for lung cancer

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

    In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...

  18. Screening for asbestbetingede sygdomme?

    Brauer, Charlotte; Baandrup, Ulrik; Jacobsen, Peter

    2009-01-01

    in asbestos-exposed populations. Data do not currently support implementation of screening programs for asbestos-exposed persons in Denmark. Since mesothelioma is most often an occupational disease, these patients should be admitted to an occupational clinic for aetiological evaluation. Udgivelsesdato: 2009...

  19. SEA Screening of voluntary Climate Change Plans

    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. Molecular screening for Yq microdeletion in men with idiopathic ...

    Unknown

    tility and 25 age-matched fertile controls were included in this study. ... son of the data on AZF deletions from different laboratories ... Clinical features in men with azoospermia factor microdeletions. ... This quantitative decline in semen quality.

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

    2014-08-01

    Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202- 4302...study appointments, includ- ing contacting subjects before appointments, providing minimal financial remuneration for attendance at each visit, and...upper lobe–predominant emphysema observed in HIV subjects. Despite patient navigators and remuneration for contin- ued participation, this study is

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

    SAM

    2014-06-25

    Jun 25, 2014 ... the genomic DNA, the frozen samples were ground and DNA was extracted .... RFLP analysis, no evidence of segregation was found in ... Figure 1. RFLP locus R2430E linked to resistance to Meloidogyne arenaria in peanut.

  3. Molecular screening of pituitary adenomas for gene mutations and rearrangements

    Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

    1993-07-01

    Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.

  4. Miniature and Molecularly Specific Optical Screening Technologies for Breast Cancer

    2011-10-01

    generated by the photodiode. When we expanded to a 4x4 probe for imaging, we used a multi-channel transimpedance amplifier (Multiboard, SolGel Technologies...GmbH) so that the signals can be read simultaneously. The transimpedance amplifier circuitry was assembled within a small metal housing and powered...600 nm) greater than 2/cm. We started designing a new integrateded transimpedance amplifier (ITIA) array, which will also have multplexed ADC

  5. Molecular screening for Yq microdeletion in men with idiopathic ...

    Unknown

    used to define three regions on Yq (AZFa, AZFb and AZFc) which are critical for spermatogenesis and are recurrently deleted in infertile males. ... factor is therefore responsible in about 50% of infertile couples. Forty to fifty percent of these men have ... ethically not possible in these cases. 2.1 PCR analysis. In cytogenetically ...

  6. Engineering aspects of Passavant screening

    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

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

    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 ...

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

    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 ...

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

    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...

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

    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.

  11. Imaging and Screening of Kidney Cancer.

    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.

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

    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.

  13. Interaction between molecular complexes in dispersive media

    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

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

    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 ...

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

    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 ...

  16. Molecular scale

    Christopher H. Childers

    2016-03-01

    Full Text Available This manuscript demonstrates the molecular scale cure rate dependence of di-functional epoxide based thermoset polymers cured with amines. A series of cure heating ramp rates were used to determine the influence of ramp rate on the glass transition temperature (Tg and sub-Tg transitions and the average free volume hole size in these systems. The networks were comprised of 3,3′-diaminodiphenyl sulfone (33DDS and diglycidyl ether of bisphenol F (DGEBF and were cured at ramp rates ranging from 0.5 to 20 °C/min. Differential scanning calorimetry (DSC and NIR spectroscopy were used to explore the cure ramp rate dependence of the polymer network growth, whereas broadband dielectric spectroscopy (BDS and free volume hole size measurements were used to interrogate networks’ molecular level structural variations upon curing at variable heating ramp rates. It was found that although the Tg of the polymer matrices was similar, the NIR and DSC measurements revealed a strong correlation for how these networks grow in relation to the cure heating ramp rate. The free volume analysis and BDS results for the cured samples suggest differences in the molecular architecture of the matrix polymers due to cure heating rate dependence.

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

    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

  18. Screening for chlamydial infection.

    Nelson, H D; Helfand, M

    2001-04-01

    To examine data on the effectiveness of screening for chlamydial infection by a physician or other health care professional. Specifically, we examine the evidence that early treatment of chlamydial infection improves health outcomes, as well as evidence of the effectiveness of screening strategies in nonpregnant women, pregnant women, and men, and the accuracy of tests used for screening. This review updates the literature since the last recommendation of the U.S. Preventive Services Task Force published in 1996. We searched the topic of chlamydia in the MEDLINE, HealthSTAR, and Cochrane Library databases from January 1994 to July 2000, supplemented by reference lists of relevant articles and from experts in the field. Articles published prior to 1994 and research abstracts were cited if particularly important to the key questions or to the interpretation of included articles. A single reader reviewed all English abstracts. Articles were selected for full review if they were about Chlamydia trachomatis genitourinary infections in nonpregnant women, pregnant women, or men and were relevant to key questions in the analytic framework. Investigators read the full-text version of the retrieved articles and applied additional eligibility criteria. For all topics, we excluded articles if they did not provide sufficient information to determine the methods for selecting subjects and for analyzing data. We systematically reviewed three types of studies about screening in nonpregnant women that relate to three key questions: (1) studies about the effectiveness of screening programs in reducing prevalence rates of infection, (2) studies about risk factors for chlamydial infection in women, and (3) studies about chlamydial screening tests in women. Our search found too few studies on pregnant women to systematically review, although pertinent studies are described. We systematically reviewed two types of studies about screening in men: (1) studies about prevalence rates and

  19. Molecular shape and medicinal chemistry: a perspective.

    Nicholls, Anthony; McGaughey, Georgia B; Sheridan, Robert P; Good, Andrew C; Warren, Gregory; Mathieu, Magali; Muchmore, Steven W; Brown, Scott P; Grant, J Andrew; Haigh, James A; Nevins, Neysa; Jain, Ajay N; Kelley, Brian

    2010-05-27

    The eight contributions here provide ample evidence that shape as a volume or as a surface is a vibrant and useful concept when applied to drug discovery. It provides a reliable scaffold for "decoration" with chemical intuition (or bias) for virtual screening and lead optimization but also has its unadorned uses, as in library design, ligand fitting, pose prediction, or active site description. Computing power has facilitated this evolution by allowing shape to be handled precisely without the need to reduce down to point descriptors or approximate metrics, and the diversity of resultant applications argues for this being an important step forward. Certainly, it is encouraging that as computation has enabled our intuition, molecular shape has consistently surprised us in its usefulness and adaptability. The first Aurelius question, "What is the essence of a thing?", seems well answered, however, the third, "What do molecules do?", only partly so. Are the topics covered here exhaustive, or is there more to come? To date, there has been little published on the use of the volumetric definition of shape described here as a QSAR variable, for instance, in the prediction or classification of activity, although other shape definitions have been successful applied, for instance, as embodied in the Compass program described above in "Shape from Surfaces". Crystal packing is a phenomenon much desired to be understood. Although powerful models have been applied to the problem, to what degree is this dominated purely by the shape of a molecule? The shape comparison described here is typically of a global nature, and yet some importance must surely be placed on partial shape matching, just as the substructure matching of chemical graphs has proved useful. The approach of using surfaces, as described here, offers some flavor of this, as does the use of metrics that penalize volume mismatch less than the Tanimoto, e.g., Tversky measures. As yet, there is little to go on as to how

  20. Heuristic lipophilicity potential for computer-aided rational drug design: Optimizations of screening functions and parameters

    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.

  1. Spintronics: The molecular way

    Cornia, Andrea; Seneor, Pierre

    2017-05-01

    Molecular spintronics is an interdisciplinary field at the interface between organic spintronics, molecular magnetism, molecular electronics and quantum computing, which is advancing fast and promises large technological payoffs.

  2. 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.

    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

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

    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.

  4. Screening for Chronic Kidney Disease

    Understanding Task Force Recommendations Screening for Chronic Kidney Disease The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation on Screening for Chronic Kidney Disease (CKD) . This recommendation ...

  5. Glucose screening tests during pregnancy

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... screening test between 24 and 28 weeks of pregnancy. The test may be done earlier if you ...

  6. Risks of Endometrial Cancer Screening

    ... Health history and certain medicines can affect the risk of developing endometrial cancer. Anything that increases your ... have abnormal vaginal bleeding, check with your doctor. Risks of Endometrial Cancer Screening Key Points Screening tests ...

  7. Risks of Esophageal Cancer Screening

    ... alcohol use, and Barrett esophagus can affect the risk of developing esophageal cancer. Anything that increases the ... tissue gives off less light than normal tissue. Risks of Esophageal Cancer Screening Key Points Screening tests ...

  8. Risks of Cervical Cancer Screening

    ... women. Human papillomavirus (HPV) infection is the major risk factor for cervical cancer. Although most women with ... clinical trials is available from the NCI website . Risks of Cervical Cancer Screening Key Points Screening tests ...

  9. Mammographic screening programmes in Europe

    Giordano, Livia; von Karsa, Lawrence; Tomatis, Mariano

    2012-01-01

    To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe.......To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe....

  10. Molecular Testing for Gastrointestinal Cancer

    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.

  11. Exploring Urban Screens

    Zlatan Krajina

    2009-12-01

    Full Text Available There is a tautological tendency in the widespread claims that urban space is 'me-diated'. Never before has the citizen, it is argued, been confronted with such an unprecedented array of signage. I depart from the rhetoric of 'biggest-ever-saturation' as not necessarily untrue, but as insufficient in exploring the diverse spatial operations of urban screens. I examine some contemporary cases of ani-mated architectural surfaces, informational panels, and advertising billboards, with reference to much longer standing cultural practices of spatial management in modern cities, such as illumination, to suggest that the contemporary display media do not mediate the city anew but re-invent urban space as a field of ubiqui-tous mediation. From that standpoint I suggest exploring urban screens as a both singular visual agents and indivisible items in plural structural assemblages, b complementary forces of public illumination, and c complex perceptual platforms in visual play of scale and distance.

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

    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.

  13. An experience of qualified preventive screening: shiraz smart screening software.

    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.

  14. Ellipticity Weakens Chameleon Screening

    Burrage, Clare; Copeland, Edmund J.; Stevenson, James

    2014-01-01

    The chameleon mechanism enables a long range fifth force to be screened in dense environments when non-trivial self interactions of the field cause its mass to increase with the local density. To date, chameleon fifth forces have mainly been studied for spherically symmetric sources, however the non-linear self interactions mean that the chameleon responds to changes in the shape of the source differently to gravity. In this work we focus on ellipsoidal departures from spherical symmetry and ...

  15. New generation expandable sand screens

    Syltøy, Christer

    2014-01-01

    Master's thesis in Petroleum engineering This thesis aims to give a general insight into sand control and various sorts of sand control measures and applications of sand control tools. Special focus will be given to expandable sand screens – a technology which came about in the late 1990’s through the use of flexible, expandable tubulars as base pipe in sand screens. More specifically Darcy’s Hydraulic Endurance Screens, a compliant sand screen system using hydraulic activation, and the fu...

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

    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.

  17. SCREENING FOR PERSONALITY DISORDERS

    Morse, Jennifer Q.; Pilkonis, Paul A.

    2010-01-01

    A brief but valid self-report measure to screen for personality disorders (PDs) would be a valuable tool in making decisions about further assessment and in planning optimal treatments. In psychiatric and nonpsychiatric samples, we compared the validity of three screening measures: the PD scales from the Inventory of Interpersonal Problems, a self-report version of the Iowa Personality Disorder Screen, and the self-directedness scale of the Temperament and Character Inventory. Despite their different theoretical origins, the screeners were highly correlated in a range from .71 to .77. As a result, the use of multiple screeners was not a significant improvement over any individual screener, and no single screener stood out as clearly superior to the others. Each performed modestly in predicting the presence of any PD diagnosis in both the psychiatric and nonpsychiatric groups. Performance was best when predicting a more severe PD diagnosis in the psychiatric sample. The results also highlight the potential value of multiple assessments when relying on self-reports. PMID:17492920

  18. Automated screening for retinopathy

    A. S. Rodin

    2014-07-01

    Full Text Available Retinal pathology is a common cause of an irreversible decrease of central vision commonly found amongst senior population. Detection of the earliest signs of retinal diseases can be facilitated by viewing retinal images available from the telemedicine networks. To facilitate the process of retinal images, screening software applications based on image recognition technology are currently on the various stages of development.Purpose: To develop and implement computerized image recognition software that can be used as a decision support technologyfor retinal image screening for various types of retinopathies.Methods: The software application for the retina image recognition has been developed using C++ language. It was tested on dataset of 70 images with various types of pathological features (age related macular degeneration, chorioretinitis, central serous chorioretinopathy and diabetic retinopathy.Results: It was shown that the system can achieve a sensitivity of 73 % and specificity of 72 %.Conclusion: Automated detection of macular lesions using proposed software can significantly reduce manual grading workflow. In addition, automated detection of retinal lesions can be implemented as a clinical decision support system for telemedicine screening. It is anticipated that further development of this technology can become a part of diagnostic image analysis system for the electronic health records.

  19. Screening Resonances In Plasmas

    Winkler, P.

    1998-01-01

    When it was suggested that a new recombination mechanism (Resonant Radiative Recombination (RRR)) which, based on very general physical arguments, should happen in dense plasmas and promises to provide useful information for the local temperature and density diagnostics of plasmas, they assumed the existence of screening resonances. For model potentials the existence of screening resonances has been demonstrated beyond reasonable doubt in a number of calculations. The key question, how well those potentials describe the dominant effects of a real plasma remains open. The relation of theoretical predictions to experimentally measurable effects is an important issue at the present stage of their research. In particular, RRR is expected to account for enhanced recombination rates of low energetic electrons with their ions, since the first stage is the resonant capture of a slow electron by an atom or ion. The mechanism that traps an electron is a combination of complicated many-body interactions of the ions and electrons. For clarity they start here, however, with a discussion in terms of local potential traps the shapes of which are determined predominantly and in an average way by two factors: the degree of screening present at the ionic site and the degree of short-range order in the immediate neighborhood of this ion

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

    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