Large-scale mapping of mutations affecting zebrafish development.

PubMed

Geisler, Robert; Rauch, Gerd-Jörg; Geiger-Rudolph, Silke; Albrecht, Andrea; van Bebber, Frauke; Berger, Andrea; Busch-Nentwich, Elisabeth; Dahm, Ralf; Dekens, Marcus P S; Dooley, Christopher; Elli, Alexandra F; Gehring, Ines; Geiger, Horst; Geisler, Maria; Glaser, Stefanie; Holley, Scott; Huber, Matthias; Kerr, Andy; Kirn, Anette; Knirsch, Martina; Konantz, Martina; Küchler, Axel M; Maderspacher, Florian; Neuhauss, Stephan C; Nicolson, Teresa; Ober, Elke A; Praeg, Elke; Ray, Russell; Rentzsch, Brit; Rick, Jens M; Rief, Eva; Schauerte, Heike E; Schepp, Carsten P; Schönberger, Ulrike; Schonthaler, Helia B; Seiler, Christoph; Sidi, Samuel; Söllner, Christian; Wehner, Anja; Weiler, Christian; Nüsslein-Volhard, Christiane

2007-01-09

Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations.

Initial Evidence for the Reliability and Validity of the Student Risk Screening Scale with Elementary Age English Learners

ERIC Educational Resources Information Center

Lane, Kathleen Lynne; Richards-Tutor, Catherine; Oakes, Wendy Peia; Connor, Kristin

2014-01-01

We report findings of a validation study exploring the Student Risk Screening Scale (SRSS; Drummond, 1994) for use with English learners (ELs) attending a large suburban elementary school. First, we explored the reliability of the SRSS by examining internal consistency, with results indicating adequate internal consistency (0.83). Second, we…

Screening and large-scale expression of membrane proteins in mammalian cells for structural studies.

PubMed

Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H; Michel, Jennifer Carlisle; Claxton, Derek P; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K Christopher; Gouaux, Eric

2014-11-01

Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in overexpression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient production of baculovirus and robust expression of the target protein. In this protocol, we show how to use small-scale transient transfection and fluorescence-detection size-exclusion chromatography (FSEC) experiments using a GFP-His8-tagged candidate protein to screen for monodispersity and expression level. Once promising candidates are identified, we describe how to generate baculovirus, transduce HEK293S GnTI(-) (N-acetylglucosaminyltransferase I-negative) cells in suspension culture and overexpress the candidate protein. We have used these methods to prepare pure samples of chicken acid-sensing ion channel 1a (cASIC1) and Caenorhabditis elegans glutamate-gated chloride channel (GluCl) for X-ray crystallography, demonstrating how to rapidly and efficiently screen hundreds of constructs and accomplish large-scale expression in 4-6 weeks.

Screening and large-scale expression of membrane proteins in mammalian cells for structural studies

PubMed Central

Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H.; Michel, Jennifer Carlisle; Claxton, Derek P.; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K. Christopher; Gouaux, Eric

2014-01-01

Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in over-expression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient production of baculovirus and robust expression of the target protein. In this protocol we show how to use small-scale transient transfection and fluorescence-detection, size-exclusion chromatography (FSEC) experiments using a GFP-His8 tagged candidate protein to screen for monodispersity and expression level. Once promising candidates are identified, we describe how to generate baculovirus, transduce HEK293S GnTI− (N-acetylglucosaminyltransferase I-negative) cells in suspension culture, and over-express the candidate protein. We have used these methods to prepare pure samples of chicken acid-sensing ion channel 1a (cASIC1) and Caenorhabditis elegans glutamate-gated chloride channel (GluCl), for X-ray crystallography, demonstrating how to rapidly and efficiently screen hundreds of constructs and accomplish large-scale expression in 4-6 weeks. PMID:25299155

Optimization of a Fluorescence-Based Assay for Large-Scale Drug Screening against Babesia and Theileria Parasites

PubMed Central

Terkawi, Mohamed Alaa; Youssef, Mohamed Ahmed; El Said, El Said El Shirbini; Elsayed, Gehad; El-Khodery, Sabry; El-Ashker, Maged; Elsify, Ahmed; Omar, Mosaab; Salama, Akram; Yokoyama, Naoaki; Igarashi, Ikuo

2015-01-01

A rapid and accurate assay for evaluating antibabesial drugs on a large scale is required for the discovery of novel chemotherapeutic agents against Babesia parasites. In the current study, we evaluated the usefulness of a fluorescence-based assay for determining the efficacies of antibabesial compounds against bovine and equine hemoparasites in in vitro cultures. Three different hematocrits (HCTs; 2.5%, 5%, and 10%) were used without daily replacement of the medium. The results of a high-throughput screening assay revealed that the best HCT was 2.5% for bovine Babesia parasites and 5% for equine Babesia and Theileria parasites. The IC50 values of diminazene aceturate obtained by fluorescence and microscopy did not differ significantly. Likewise, the IC50 values of luteolin, pyronaridine tetraphosphate, nimbolide, gedunin, and enoxacin did not differ between the two methods. In conclusion, our fluorescence-based assay uses low HCT and does not require daily replacement of culture medium, making it highly suitable for in vitro large-scale drug screening against Babesia and Theileria parasites that infect cattle and horses. PMID:25915529

Optimization of a Fluorescence-Based Assay for Large-Scale Drug Screening against Babesia and Theileria Parasites.

PubMed

Rizk, Mohamed Abdo; El-Sayed, Shimaa Abd El-Salam; Terkawi, Mohamed Alaa; Youssef, Mohamed Ahmed; El Said, El Said El Shirbini; Elsayed, Gehad; El-Khodery, Sabry; El-Ashker, Maged; Elsify, Ahmed; Omar, Mosaab; Salama, Akram; Yokoyama, Naoaki; Igarashi, Ikuo

2015-01-01

A rapid and accurate assay for evaluating antibabesial drugs on a large scale is required for the discovery of novel chemotherapeutic agents against Babesia parasites. In the current study, we evaluated the usefulness of a fluorescence-based assay for determining the efficacies of antibabesial compounds against bovine and equine hemoparasites in in vitro cultures. Three different hematocrits (HCTs; 2.5%, 5%, and 10%) were used without daily replacement of the medium. The results of a high-throughput screening assay revealed that the best HCT was 2.5% for bovine Babesia parasites and 5% for equine Babesia and Theileria parasites. The IC50 values of diminazene aceturate obtained by fluorescence and microscopy did not differ significantly. Likewise, the IC50 values of luteolin, pyronaridine tetraphosphate, nimbolide, gedunin, and enoxacin did not differ between the two methods. In conclusion, our fluorescence-based assay uses low HCT and does not require daily replacement of culture medium, making it highly suitable for in vitro large-scale drug screening against Babesia and Theileria parasites that infect cattle and horses.

Uncertainty Quantification in High Throughput Screening: Applications to Models of Endocrine Disruption, Cytotoxicity, and Zebrafish Development (GRC Drug Safety)

EPA Science Inventory

Using uncertainty quantification, we aim to improve the quality of modeling data from high throughput screening assays for use in risk assessment. ToxCast is a large-scale screening program that analyzes thousands of chemicals using over 800 assays representing hundreds of bioche...

ARQiv-HTS, a versatile whole-organism screening platform enabling in vivo drug discovery at high-throughput rates

PubMed Central

White, David T; Eroglu, Arife Unal; Wang, Guohua; Zhang, Liyun; Sengupta, Sumitra; Ding, Ding; Rajpurohit, Surendra K; Walker, Steven L; Ji, Hongkai; Qian, Jiang; Mumm, Jeff S

2017-01-01

The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed ‘ARQiv-HTS’. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification. We also outline what we see as best practice strategies for leveraging the power of ARQiv-HTS for zebrafish-based drug discovery, and address technical challenges of applying zebrafish to large-scale chemical screens. Finally, we provide a detailed protocol for a recently completed inaugural ARQiv-HTS effort, which involved the identification of compounds that elevate insulin reporter activity. Compounds that increased the number of insulin-producing pancreatic beta cells represent potential new therapeutics for diabetic patients. For this effort, individual screening sessions took 1 week to conclude, and sessions were performed iteratively approximately every other day to increase throughput. At the conclusion of the screen, more than a half million drug-treated larvae had been evaluated. Beyond this initial example, however, the ARQiv-HTS platform is adaptable to almost any reporter-based assay designed to evaluate the effects of chemical compounds in living small-animal models. ARQiv-HTS thus enables large-scale whole-organism drug discovery for a variety of model species and from numerous disease-oriented perspectives. PMID:27831568

CORALINA: a universal method for the generation of gRNA libraries for CRISPR-based screening.

PubMed

Köferle, Anna; Worf, Karolina; Breunig, Christopher; Baumann, Valentin; Herrero, Javier; Wiesbeck, Maximilian; Hutter, Lukas H; Götz, Magdalena; Fuchs, Christiane; Beck, Stephan; Stricker, Stefan H

2016-11-14

The bacterial CRISPR system is fast becoming the most popular genetic and epigenetic engineering tool due to its universal applicability and adaptability. The desire to deploy CRISPR-based methods in a large variety of species and contexts has created an urgent need for the development of easy, time- and cost-effective methods enabling large-scale screening approaches. Here we describe CORALINA (comprehensive gRNA library generation through controlled nuclease activity), a method for the generation of comprehensive gRNA libraries for CRISPR-based screens. CORALINA gRNA libraries can be derived from any source of DNA without the need of complex oligonucleotide synthesis. We show the utility of CORALINA for human and mouse genomic DNA, its reproducibility in covering the most relevant genomic features including regulatory, coding and non-coding sequences and confirm the functionality of CORALINA generated gRNAs. The simplicity and cost-effectiveness make CORALINA suitable for any experimental system. The unprecedented sequence complexities obtainable with CORALINA libraries are a necessary pre-requisite for less biased large scale genomic and epigenomic screens.

Screening for Psychosocial Distress amongst War-Affected Children: Cross-Cultural Construct Validity of the CPDS

ERIC Educational Resources Information Center

Jordans, M. J. D.; Komproe, I. H.; Tol, W. A.; De Jong, J. T. V. M.

2009-01-01

Background: Large-scale psychosocial interventions in complex emergencies call for a screening procedure to identify individuals at risk. To date there are no screening instruments that are developed within low- and middle-income countries and validated for that purpose. The present study assesses the cross-cultural validity of the brief,…

Role of optometry school in single day large scale school vision testing

PubMed Central

Anuradha, N; Ramani, Krishnakumar

2015-01-01

Background: School vision testing aims at identification and management of refractive errors. Large-scale school vision testing using conventional methods is time-consuming and demands a lot of chair time from the eye care professionals. A new strategy involving a school of optometry in single day large scale school vision testing is discussed. Aim: The aim was to describe a new approach of performing vision testing of school children on a large scale in a single day. Materials and Methods: A single day vision testing strategy was implemented wherein 123 members (20 teams comprising optometry students and headed by optometrists) conducted vision testing for children in 51 schools. School vision testing included basic vision screening, refraction, frame measurements, frame choice and referrals for other ocular problems. Results: A total of 12448 children were screened, among whom 420 (3.37%) were identified to have refractive errors. 28 (1.26%) children belonged to the primary, 163 to middle (9.80%), 129 (4.67%) to secondary and 100 (1.73%) to the higher secondary levels of education respectively. 265 (2.12%) children were referred for further evaluation. Conclusion: Single day large scale school vision testing can be adopted by schools of optometry to reach a higher number of children within a short span. PMID:25709271

Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation.

PubMed

D'Aiuto, Leonardo; Zhi, Yun; Kumar Das, Dhanjit; Wilcox, Madeleine R; Johnson, Jon W; McClain, Lora; MacDonald, Matthew L; Di Maio, Roberto; Schurdak, Mark E; Piazza, Paolo; Viggiano, Luigi; Sweet, Robert; Kinchington, Paul R; Bhattacharjee, Ayantika G; Yolken, Robert; Nimgaonka, Vishwajit L; Nimgaonkar, Vishwajit L

2014-01-01

Induced pluripotent stem cell (iPSC)-based technologies offer an unprecedented opportunity to perform high-throughput screening of novel drugs for neurological and neurodegenerative diseases. Such screenings require a robust and scalable method for generating large numbers of mature, differentiated neuronal cells. Currently available methods based on differentiation of embryoid bodies (EBs) or directed differentiation of adherent culture systems are either expensive or are not scalable. We developed a protocol for large-scale generation of neuronal stem cells (NSCs)/early neural progenitor cells (eNPCs) and their differentiation into neurons. Our scalable protocol allows robust and cost-effective generation of NSCs/eNPCs from iPSCs. Following culture in neurobasal medium supplemented with B27 and BDNF, NSCs/eNPCs differentiate predominantly into vesicular glutamate transporter 1 (VGLUT1) positive neurons. Targeted mass spectrometry analysis demonstrates that iPSC-derived neurons express ligand-gated channels and other synaptic proteins and whole-cell patch-clamp experiments indicate that these channels are functional. The robust and cost-effective differentiation protocol described here for large-scale generation of NSCs/eNPCs and their differentiation into neurons paves the way for automated high-throughput screening of drugs for neurological and neurodegenerative diseases.

Screening large-scale association study data: exploiting interactions using random forests.

PubMed

Lunetta, Kathryn L; Hayward, L Brooke; Segal, Jonathan; Van Eerdewegh, Paul

2004-12-10

Genome-wide association studies for complex diseases will produce genotypes on hundreds of thousands of single nucleotide polymorphisms (SNPs). A logical first approach to dealing with massive numbers of SNPs is to use some test to screen the SNPs, retaining only those that meet some criterion for further study. For example, SNPs can be ranked by p-value, and those with the lowest p-values retained. When SNPs have large interaction effects but small marginal effects in a population, they are unlikely to be retained when univariate tests are used for screening. However, model-based screens that pre-specify interactions are impractical for data sets with thousands of SNPs. Random forest analysis is an alternative method that produces a single measure of importance for each predictor variable that takes into account interactions among variables without requiring model specification. Interactions increase the importance for the individual interacting variables, making them more likely to be given high importance relative to other variables. We test the performance of random forests as a screening procedure to identify small numbers of risk-associated SNPs from among large numbers of unassociated SNPs using complex disease models with up to 32 loci, incorporating both genetic heterogeneity and multi-locus interaction. Keeping other factors constant, if risk SNPs interact, the random forest importance measure significantly outperforms the Fisher Exact test as a screening tool. As the number of interacting SNPs increases, the improvement in performance of random forest analysis relative to Fisher Exact test for screening also increases. Random forests perform similarly to the univariate Fisher Exact test as a screening tool when SNPs in the analysis do not interact. In the context of large-scale genetic association studies where unknown interactions exist among true risk-associated SNPs or SNPs and environmental covariates, screening SNPs using random forest analyses can significantly reduce the number of SNPs that need to be retained for further study compared to standard univariate screening methods.

Screensaver: an open source lab information management system (LIMS) for high throughput screening facilities

PubMed Central

2010-01-01

Background Shared-usage high throughput screening (HTS) facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. Results We have developed Screensaver, a free, open source, web-based lab information management system (LIMS), to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. Conclusions The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities. PMID:20482787

Screensaver: an open source lab information management system (LIMS) for high throughput screening facilities.

PubMed

Tolopko, Andrew N; Sullivan, John P; Erickson, Sean D; Wrobel, David; Chiang, Su L; Rudnicki, Katrina; Rudnicki, Stewart; Nale, Jennifer; Selfors, Laura M; Greenhouse, Dara; Muhlich, Jeremy L; Shamu, Caroline E

2010-05-18

Shared-usage high throughput screening (HTS) facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. We have developed Screensaver, a free, open source, web-based lab information management system (LIMS), to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities.

SFN-SIQ, SFNSL and skin biopsy of 55 cases with small fibre involvement.

PubMed

Sun, Bo; Li, Yifan; Liu, Lizhi; Chen, Zhaohui; Ling, Li; Yang, Fei; Liu, Jiexiao; Liu, Hong; Huang, Xusheng

2018-05-01

Purpose/aim of the study: To date, there are no validated screening scales for small fibre neuropathy. This study investigated the small-fibre neuropathy and the symptom inventory questionnaire as well as the small fibre neuropathy screening list for small fibre neuropathy diagnosis. Fifty-five patients were divided into small fibre neuropathy and mixed fibre damage groups. Relevant scales, nerve conduction studies and skin biopsies were performed. Relationships between the intraepidermal nerve fibre density and different scales as well as the diagnostic and cut-off values (score at which Youden's index is largest) were determined. Compared with healthy Chinese participants, 20 patients were diagnosed with small fibre neuropathy. Intraepidermal nerve fibre density was moderately and highly correlated with the small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list, respectively. The diagnostic values were moderate and high for the small fibre neuropathy-symptom inventory questionnaire (cut-off value = 5, sensitivity = 80%, specificity = 81.8%) and small fibre neuropathy screening list (cut-off value = 8, sensitivity = 94.1%, specificity = 90.9%), respectively. There were no significant differences in the visual analogue scale between the small fibre neuropathy group, mixed small and large fibre neuropathy group, pure large fibre neuropathy group and the normal group. Small fibre neuropathy-symptom inventory questionnaire and small fibre neuropathy screening list represent potential small fibre neuropathy screening tools. Abbreviations EMG electromyography ENA anti-extractable nuclear antigens ESR erythrocyte sedimentation rate IENFD intraepidermal nerve fibre density IGT impaired glucose tolerance NCS nerve conduction studies NDS neuropathy disability score OGTT oral glucose tolerance test PGP protein gene product PN peripheral neuropathy ROC receiver operating characteristic curve ROC-AUC area under the ROC curve SFN small fibre neuropathy SFN-SIQ small-fibre neuropathy and symptom inventory questionnaire SFNSL small fibre neuropathy screening list VAS visual analogue scale WHO World Health Organization.

Implementing Routine Suicide Risk Screening for Psychiatric Outpatients With Serious Mental Disorders: I. Qualitative Results

PubMed Central

Lang, Michelle; Uttaro, Thomas; Caine, Eric; Carpinello, Sharon; Felton, Chip

2010-01-01

The objective of this study was to acquire process information, clinician and client feedback during implementation of a routine suicide risk screening program for outpatients with serious mental disorders. We studied implementation of a suicide-screening tool in a large public mental health outpatient facility in New York City. Most clinical staff who provided an opinion indicated screening was useful, feasible and helpful; most clients did not mind screening. Facilitators to program implementation included administrative support and ease of use. Barriers included consent, misperceptions, and concerns regarding potential liability. It is feasible to implement a suicide-screening tool in a public outpatient clinic. However, even experienced clinicians harbor unfounded myths. Effective large scale use will require vigorous training and oversight. PMID:19363752

Chemically intuited, large-scale screening of MOFs by machine learning techniques

NASA Astrophysics Data System (ADS)

Borboudakis, Giorgos; Stergiannakos, Taxiarchis; Frysali, Maria; Klontzas, Emmanuel; Tsamardinos, Ioannis; Froudakis, George E.

2017-10-01

A novel computational methodology for large-scale screening of MOFs is applied to gas storage with the use of machine learning technologies. This approach is a promising trade-off between the accuracy of ab initio methods and the speed of classical approaches, strategically combined with chemical intuition. The results demonstrate that the chemical properties of MOFs are indeed predictable (stochastically, not deterministically) using machine learning methods and automated analysis protocols, with the accuracy of predictions increasing with sample size. Our initial results indicate that this methodology is promising to apply not only to gas storage in MOFs but in many other material science projects.

ScreenBEAM: a novel meta-analysis algorithm for functional genomics screens via Bayesian hierarchical modeling | Office of Cancer Genomics

Cancer.gov

Functional genomics (FG) screens, using RNAi or CRISPR technology, have become a standard tool for systematic, genome-wide loss-of-function studies for therapeutic target discovery. As in many large-scale assays, however, off-target effects, variable reagents' potency and experimental noise must be accounted for appropriately control for false positives.

Determination of the SNPP VIIRS SDSM Screen Relative Transmittance From Both Yaw Maneuver and Regular On-Orbit Data

NASA Technical Reports Server (NTRS)

Lei, Ning; Chen, Xuexia; Xiong, Xiaoxiong

2015-01-01

The Visible Infrared Imaging Radiometer Suiteaboard the Suomi National Polar-orbiting Partnership (SNPP) satellite performs radiometric calibration of its reflective solar bands primarily through observing a sunlit onboard solar diffuser (SD). The SD bidirectional reflectance distribution function(BRDF) degradation factor is determined by an onboard SD stability monitor (SDSM), which observes the Sun through a pinhole screen and the sunlit SD. The transmittance of the SDSM pinhole screen over a range of solar angles was determined prelaunch and used initially to determine the BRDF degradation factor.The degradation-factor-versus-time curves were found to have a number of very large unphysical undulations likely due to the inaccuracy in the prelaunch determined SDSM screen transmittance.To refine the SDSM screen transmittance, satellite yaw maneuvers were carried out. With the SDSM screen relative transmittance determined from the yaw maneuver data, the computed BRDFdegradation factor curves still have large unphysical ripples, indicating that the projected solar horizontal angular step size in the yaw maneuver data is too large to resolve the transmittance at a fine angular scale. We develop a methodology to use both the yaw maneuver and a small portion of regular on-orbit data to determine the SDSM screen relative transmittance at a fine angular scale. We determine that the error standard deviation of the calculated relative transmittance ranges from 0.00030 (672 nm) to 0.00092 (926 nm). With the newly determined SDSM screen relative transmittance, the computed BRDF degradation factor behaves much more smoothly over time.

Prostate-specific antigen screening in a high-risk population: lessons from the community and how they relate to large-scale population-based studies.

PubMed

Shelton, Jeremy B; Barocas, Daniel A; Conway, Frances; Hart, Kathleen; Nelson, Kinloch; Richstone, Lee; Gonzalez, Ricardo R; Raman, Jay D; Scherr, Douglas S

2005-05-01

To estimate the incidence of prostate cancer among African-American men and Caribbean immigrants to the United States, to assess the applicability of large-scale prostate screening trials to a community screening program, and to recruit unscreened men. African-American and Caribbean-American men were targeted with a community-based prostate cancer screening program in Jamaica, New York. Serum prostate-specific antigen determination and digital rectal examination were used to determine abnormal findings. The incidence of an abnormal screening examination was used to project the incidence of prostate cancer, which was compared with that in other reported trials. The projected incidence of prostate cancer among African-Americans and Caribbean-Americans older than 50 years was 8% and 7%, respectively, similar to that reported in other trials of African-American men. The projected incidence of prostate cancer in Caribbean-American men aged 40 to 49 years was 1%, the same as the high rate reported among Caribbean men. As in other trials, a family history of prostate cancer and age were strong predictors of abnormal findings. Of the recruited men older than 50 years, 58% had never been screened compared with 42% nationally. Large population-based screening trials have identified ethnic groups at high risk of prostate cancer. This trial detected high rates of abnormal screening findings by targeting ethnicity. The incidence of an abnormal examination was high in Caribbean-American men younger than 50 years old. Finally, this trial successfully recruited underscreened men.

Large-scale microfluidics providing high-resolution and high-throughput screening of Caenorhabditis elegans poly-glutamine aggregation model

NASA Astrophysics Data System (ADS)

Mondal, Sudip; Hegarty, Evan; Martin, Chris; Gökçe, Sertan Kutal; Ghorashian, Navid; Ben-Yakar, Adela

2016-10-01

Next generation drug screening could benefit greatly from in vivo studies, using small animal models such as Caenorhabditis elegans for hit identification and lead optimization. Current in vivo assays can operate either at low throughput with high resolution or with low resolution at high throughput. To enable both high-throughput and high-resolution imaging of C. elegans, we developed an automated microfluidic platform. This platform can image 15 z-stacks of ~4,000 C. elegans from 96 different populations using a large-scale chip with a micron resolution in 16 min. Using this platform, we screened ~100,000 animals of the poly-glutamine aggregation model on 25 chips. We tested the efficacy of ~1,000 FDA-approved drugs in improving the aggregation phenotype of the model and identified four confirmed hits. This robust platform now enables high-content screening of various C. elegans disease models at the speed and cost of in vitro cell-based assays.

Small molecule screening with laser cytometry can be used to identify pro-survival molecules in human embryonic stem cells.

PubMed

Sherman, Sean P; Pyle, April D

2013-01-01

Differentiated cells from human embryonic stem cells (hESCs) provide an unlimited source of cells for use in regenerative medicine. The recent derivation of human induced pluripotent cells (hiPSCs) provides a potential supply of pluripotent cells that avoid immune rejection and could provide patient-tailored therapy. In addition, the use of pluripotent cells for drug screening could enable routine toxicity testing and evaluation of underlying disease mechanisms. However, prior to establishment of patient specific cells for cell therapy it is important to understand the basic regulation of cell fate decisions in hESCs. One critical issue that hinders the use of these cells is the fact that hESCs survive poorly upon dissociation, which limits genetic manipulation because of poor cloning efficiency of individual hESCs, and hampers production of large-scale culture of hESCs. To address the problems associated with poor growth in culture and our lack of understanding of what regulates hESC signaling, we successfully developed a screening platform that allows for large scale screening for small molecules that regulate survival. In this work we developed the first large scale platform for hESC screening using laser scanning cytometry and were able to validate this platform by identifying the pro-survival molecule HA-1077. These small molecules provide targets for both improving our basic understanding of hESC survival as well as a tool to improve our ability to expand and genetically manipulate hESCs for use in regenerative applications.

Large scale nanoparticle screening for small molecule analysis in laser desorption ionization mass spectrometry

DOE PAGES

Yagnik, Gargey B.; Hansen, Rebecca L.; Korte, Andrew R.; ...

2016-08-30

Nanoparticles (NPs) have been suggested as efficient matrixes for small molecule profiling and imaging by laser-desorption ionization mass spectrometry (LDI-MS), but so far there has been no systematic study comparing different NPs in the analysis of various classes of small molecules. Here, we present a large scale screening of 13 NPs for the analysis of two dozen small metabolite molecules. Many NPs showed much higher LDI efficiency than organic matrixes in positive mode and some NPs showed comparable efficiencies for selected analytes in negative mode. Our results suggest that a thermally driven desorption process is a key factor for metalmore » oxide NPs, but chemical interactions are also very important, especially for other NPs. Furthermore, the screening results provide a useful guideline for the selection of NPs in the LDI-MS analysis of small molecules.« less

Large scale nanoparticle screening for small molecule analysis in laser desorption ionization mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yagnik, Gargey B.; Hansen, Rebecca L.; Korte, Andrew R.

Nanoparticles (NPs) have been suggested as efficient matrixes for small molecule profiling and imaging by laser-desorption ionization mass spectrometry (LDI-MS), but so far there has been no systematic study comparing different NPs in the analysis of various classes of small molecules. Here, we present a large scale screening of 13 NPs for the analysis of two dozen small metabolite molecules. Many NPs showed much higher LDI efficiency than organic matrixes in positive mode and some NPs showed comparable efficiencies for selected analytes in negative mode. Our results suggest that a thermally driven desorption process is a key factor for metalmore » oxide NPs, but chemical interactions are also very important, especially for other NPs. Furthermore, the screening results provide a useful guideline for the selection of NPs in the LDI-MS analysis of small molecules.« less

Developing science gateways for drug discovery in a grid environment.

PubMed

Pérez-Sánchez, Horacio; Rezaei, Vahid; Mezhuyev, Vitaliy; Man, Duhu; Peña-García, Jorge; den-Haan, Helena; Gesing, Sandra

2016-01-01

Methods for in silico screening of large databases of molecules increasingly complement and replace experimental techniques to discover novel compounds to combat diseases. As these techniques become more complex and computationally costly we are faced with an increasing problem to provide the research community of life sciences with a convenient tool for high-throughput virtual screening on distributed computing resources. To this end, we recently integrated the biophysics-based drug-screening program FlexScreen into a service, applicable for large-scale parallel screening and reusable in the context of scientific workflows. Our implementation is based on Pipeline Pilot and Simple Object Access Protocol and provides an easy-to-use graphical user interface to construct complex workflows, which can be executed on distributed computing resources, thus accelerating the throughput by several orders of magnitude.

Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge

PubMed Central

Gallicchio, Emilio; Deng, Nanjie; He, Peng; Wickstrom, Lauren; Perryman, Alexander L.; Santiago, Daniel N.; Forli, Stefano; Olson, Arthur J.; Levy, Ronald M.

2014-01-01

As part of the SAMPL4 blind challenge, filtered AutoDock Vina ligand docking predictions and large scale binding energy distribution analysis method binding free energy calculations have been applied to the virtual screening of a focused library of candidate binders to the LEDGF site of the HIV integrase protein. The computational protocol leveraged docking and high level atomistic models to improve enrichment. The enrichment factor of our blind predictions ranked best among all of the computational submissions, and second best overall. This work represents to our knowledge the first example of the application of an all-atom physics-based binding free energy model to large scale virtual screening. A total of 285 parallel Hamiltonian replica exchange molecular dynamics absolute protein-ligand binding free energy simulations were conducted starting from docked poses. The setup of the simulations was fully automated, calculations were distributed on multiple computing resources and were completed in a 6-weeks period. The accuracy of the docked poses and the inclusion of intramolecular strain and entropic losses in the binding free energy estimates were the major factors behind the success of the method. Lack of sufficient time and computing resources to investigate additional protonation states of the ligands was a major cause of mispredictions. The experiment demonstrated the applicability of binding free energy modeling to improve hit rates in challenging virtual screening of focused ligand libraries during lead optimization. PMID:24504704

The validity of military screening for mental health problems: diagnostic accuracy of the PCL, K10 and AUDIT scales in an entire military population.

PubMed

Searle, Amelia K; Van Hooff, Miranda; McFarlane, Alexander C; Davies, Christopher E; Fairweather-Schmidt, A Kate; Hodson, Stephanie E; Benassi, Helen; Steele, Nicole

2015-03-01

Depression, alcohol use disorders and post-traumatic stress disorder (PTSD) are serious issues among military personnel due to their impact on operational capability and individual well-being. Several military forces screen for these disorders using scales including the Kessler Psychological Distress Scale (K10), Alcohol Use Disorders Identification Test (AUDIT), and Post-traumatic Stress Disorder Checklist (PCL). However, it is unknown whether established cutoffs apply to military populations. This study is the first to test the diagnostic accuracy of these three scales in a population-based military cohort. A large sample of currently-serving Australian Defence Force (ADF) Navy, Army and Air Force personnel (n = 24,481) completed the K10, AUDIT and PCL-C (civilian version). Then, a stratified sub-sample (n = 1798) completed a structured diagnostic interview detecting 30-day disorder. Data were weighted to represent the ADF population (n = 50,049). Receiver operating characteristic (ROC) analyses suggested all three scales had acceptable sensitivity and specificity, with areas under the curve from 0.75 to 0.93. AUDIT and K10 screening cutoffs closely paralleled established cutoffs, whereas the PCL-C screening cutoff resembled that recommended for US military personnel. These self-report scales represent a cost-effective and clinically-useful means of screening personnel for disorder. Military populations may need lower cutoffs than civilians to screen for PTSD. Copyright © 2014 John Wiley & Sons, Ltd.

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.

PubMed

Pan, Joshua; Meyers, Robin M; Michel, Brittany C; Mashtalir, Nazar; Sizemore, Ann E; Wells, Jonathan N; Cassel, Seth H; Vazquez, Francisca; Weir, Barbara A; Hahn, William C; Marsh, Joseph A; Tsherniak, Aviad; Kadoch, Cigall

2018-05-23

Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex. Finally, by integrating functional networks with large protein-protein interaction networks, we discovered novel protein complexes involving recently evolved genes of unknown function. Taken together, these findings demonstrate the utility of genetic perturbation screens alone, and in combination with large-scale biophysical data, to enhance our understanding of mammalian protein complexes in normal and disease states. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Its Associated Research Resource

PubMed Central

2013-01-01

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses’ Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues. PMID:24115361

Colorado Learning Difficulties Questionnaire:Validation of a parent-report screening measure

PubMed Central

Willcutt, Erik G.; Boada, Richard; Riddle, Margaret W.; Chhabildas, Nomita; DeFries, John C.; Pennington, Bruce F.

2011-01-01

This study evaluated the internal structure and convergent and discriminant evidence for the Colorado Learning Difficulties Questionnaire (CLDQ), a 20-item parent-report rating scale that was developed to provide a brief screening measure for learning difficulties. CLDQ ratings were obtained from parents of children in two large community samples and two samples from clinics that specialize in the assessment of learning disabilities and related disorders (total N = 8,004). Exploratory and confirmatory factor analyses revealed five correlated but separable dimensions that were labeled reading, math, social cognition, social anxiety, and spatial difficulties. Results revealed strong convergent and discriminant evidence for the CLDQ Reading scale, suggesting that this scale may provide a useful method to screen for reading difficulties in both research studies and clinical settings. Results are also promising for the other four CLDQ scales, but additional research is needed to refine each of these measures. PMID:21574721

Opportunities and challenges for the use of large-scale surveys in public health research: A comparison of the assessment of cancer screening behaviors

PubMed Central

Hamilton, Jada G.; Breen, Nancy; Klabunde, Carrie N.; Moser, Richard P.; Leyva, Bryan; Breslau, Erica S.; Kobrin, Sarah C.

2014-01-01

Large-scale surveys that assess cancer prevention and control behaviors are a readily-available, rich resource for public health researchers. Although these data are used by a subset of researchers who are familiar with them, their potential is not fully realized by the research community for reasons including lack of awareness of the data, and limited understanding of their content, methodology, and utility. Until now, no comprehensive resource existed to describe and facilitate use of these data. To address this gap and maximize use of these data, we catalogued the characteristics and content of four surveys that assessed cancer screening behaviors in 2005, the most recent year with concurrent periods of data collection: the National Health Interview Survey, Health Information National Trends Survey, Behavioral Risk Factor Surveillance System, and California Health Interview Survey. We documented each survey's characteristics, measures of cancer screening, and relevant correlates; examined how published studies (n=78) have used the surveys’ cancer screening data; and reviewed new cancer screening constructs measured in recent years. This information can guide researchers in deciding how to capitalize on the opportunities presented by these data resources. PMID:25300474

General relativistic screening in cosmological simulations

NASA Astrophysics Data System (ADS)

Hahn, Oliver; Paranjape, Aseem

2016-10-01

We revisit the issue of interpreting the results of large volume cosmological simulations in the context of large-scale general relativistic effects. We look for simple modifications to the nonlinear evolution of the gravitational potential ψ that lead on large scales to the correct, fully relativistic description of density perturbations in the Newtonian gauge. We note that the relativistic constraint equation for ψ can be cast as a diffusion equation, with a diffusion length scale determined by the expansion of the Universe. Exploiting the weak time evolution of ψ in all regimes of interest, this equation can be further accurately approximated as a Helmholtz equation, with an effective relativistic "screening" scale ℓ related to the Hubble radius. We demonstrate that it is thus possible to carry out N-body simulations in the Newtonian gauge by replacing Poisson's equation with this Helmholtz equation, involving a trivial change in the Green's function kernel. Our results also motivate a simple, approximate (but very accurate) gauge transformation—δN(k )≈δsim(k )×(k2+ℓ-2)/k2 —to convert the density field δsim of standard collisionless N -body simulations (initialized in the comoving synchronous gauge) into the Newtonian gauge density δN at arbitrary times. A similar conversion can also be written in terms of particle positions. Our results can be interpreted in terms of a Jeans stability criterion induced by the expansion of the Universe. The appearance of the screening scale ℓ in the evolution of ψ , in particular, leads to a natural resolution of the "Jeans swindle" in the presence of superhorizon modes.

Extended Essay Marking on Screen: Is Examiner Marking Accuracy Influenced by Marking Mode?

ERIC Educational Resources Information Center

Johnson, Martin; Hopkin, Rebecca; Shiell, Hannah; Bell, John F.

2012-01-01

In the UK and elsewhere, large-scale educational assessment agencies are shifting the mode of school examination marking towards having examiners mark examination scripts on screen rather than on paper. This shift has prompted questions about whether the mode of marking might influence examiner marking accuracy, particularly in relation to…

Lifetime evaluation of large format CMOS mixed signal infrared devices

NASA Astrophysics Data System (ADS)

Linder, A.; Glines, Eddie

2015-09-01

New large scale foundry processes continue to produce reliable products. These new large scale devices continue to use industry best practice to screen for failure mechanisms and validate their long lifetime. The Failure-in-Time analysis in conjunction with foundry qualification information can be used to evaluate large format device lifetimes. This analysis is a helpful tool when zero failure life tests are typical. The reliability of the device is estimated by applying the failure rate to the use conditions. JEDEC publications continue to be the industry accepted methods.

The Center for Optimized Structural Studies (COSS) platform for automation in cloning, expression, and purification of single proteins and protein-protein complexes.

PubMed

Mlynek, Georg; Lehner, Anita; Neuhold, Jana; Leeb, Sarah; Kostan, Julius; Charnagalov, Alexej; Stolt-Bergner, Peggy; Djinović-Carugo, Kristina; Pinotsis, Nikos

2014-06-01

Expression in Escherichia coli represents the simplest and most cost effective means for the production of recombinant proteins. This is a routine task in structural biology and biochemistry where milligrams of the target protein are required in high purity and monodispersity. To achieve these criteria, the user often needs to screen several constructs in different expression and purification conditions in parallel. We describe a pipeline, implemented in the Center for Optimized Structural Studies, that enables the systematic screening of expression and purification conditions for recombinant proteins and relies on a series of logical decisions. We first use bioinformatics tools to design a series of protein fragments, which we clone in parallel, and subsequently screen in small scale for optimal expression and purification conditions. Based on a scoring system that assesses soluble expression, we then select the top ranking targets for large-scale purification. In the establishment of our pipeline, emphasis was put on streamlining the processes such that it can be easily but not necessarily automatized. In a typical run of about 2 weeks, we are able to prepare and perform small-scale expression screens for 20-100 different constructs followed by large-scale purification of at least 4-6 proteins. The major advantage of our approach is its flexibility, which allows for easy adoption, either partially or entirely, by any average hypothesis driven laboratory in a manual or robot-assisted manner.

A Population-Level Data Analytics Portal for Self-Administered Lifestyle and Mental Health Screening.

PubMed

Zhang, Xindi; Warren, Jim; Corter, Arden; Goodyear-Smith, Felicity

2016-01-01

This paper describes development of a prototype data analytics portal for analysis of accumulated screening results from eCHAT (electronic Case-finding and Help Assessment Tool). eCHAT allows individuals to conduct a self-administered lifestyle and mental health screening assessment, with usage to date chiefly in the context of primary care waiting rooms. The intention is for wide roll-out to primary care clinics, including secondary school based clinics, resulting in the accumulation of population-level data. Data from a field trial of eCHAT with sexual health questions tailored to youth were used to support design of a data analytics portal for population-level data. The design process included user personas and scenarios, screen prototyping and a simulator for generating large-scale data sets. The prototype demonstrates the promise of wide-scale self-administered screening data to support a range of users including practice managers, clinical directors and health policy analysts.

First-principles simulations of doping-dependent mesoscale screening of adatoms in graphene

NASA Astrophysics Data System (ADS)

Mostofi, Arash; Corsetti, Fabiano; Wong, Dillon; Crommie, Michael; Lischner, Johannes

Adsorbed atoms and molecules play an important role in controlling and tuning the functional properties of 2D materials. Understanding and predicting this phenomenon from theory is challenging because of the need to capture both the local chemistry of the adsorbate-substrate interaction and its complex interplay with the long-range screening response of the substrate. To address this challenge, we have developed a first-principles multi-scale approach that combines linear-scaling density-functional theory, continuum screening theory and large-scale tight-binding simulations. Focussing on the case of a calcium adatom on graphene, we draw comparison between the effect of (i) non-linearity, (ii) intraband and interband transitions, and (iii) the exchange-correlation potential, thus providing insight into the relative importance of these different factors on the screening response. We also determine the charge transfer from the adatom to the graphene substrate (the key parameter used in continuum screening models), showing it to be significantly larger than previous estimates. AM and FC acknowledge support of the EPSRC under Grant EP/J015059/1, and JL under Grant EP/N005244/1.

Large datasets, logistics, sharing and workflow in screening.

PubMed

Cook, Tessa S

2018-03-29

Cancer screening initiatives exist around the world for different malignancies, most frequently breast, colorectal, and cervical cancer. A number of cancer registries exist to collect relevant data, but while these data may include imaging findings, they rarely, if ever, include actual images. Additionally, the data submitted to the registry are usually correlated with eventual cancer diagnoses and patient outcomes, rather than used with the individual's future screenings. Developing screening programs that allow for images to be submitted to a central location in addition to patient meta data and used for comparison to future screening exams would be very valuable in increasing access to care and ensuring that individuals are effectively screened at appropriate intervals. It would also change the way imaging results and additional patient data are correlated to eventual outcomes. However, it introduces logistical challenges surrounding secure storage and transmission of data to subsequent screening sites. In addition, in the absence of standardized protocols for screening, comparing current and prior imaging, especially from different equipment, can be challenging. Implementing a large-scale screening program with an image-enriched screening registry-effectively, an image-enriched electronic screening record-also requires that incentives exist for screening sites, physicians, and patients to participate; to maximize coverage, participation may have to be supported by government agencies. Workflows will also have to be adjusted to support registry participation for all screening patients in an effort to create a large, robust data set that can be used for future screening efforts as well as research initiatives.center.

Prospective CO 2 saline resource estimation methodology: Refinement of existing US-DOE-NETL methods based on data availability

DOE PAGES

Goodman, Angela; Sanguinito, Sean; Levine, Jonathan S.

2016-09-28

Carbon storage resource estimation in subsurface saline formations plays an important role in establishing the scale of carbon capture and storage activities for governmental policy and commercial project decision-making. Prospective CO 2 resource estimation of large regions or subregions, such as a basin, occurs at the initial screening stages of a project using only limited publicly available geophysical data, i.e. prior to project-specific site selection data generation. As the scale of investigation is narrowed and selected areas and formations are identified, prospective CO 2 resource estimation can be refined and uncertainty narrowed when site-specific geophysical data are available. Here, wemore » refine the United States Department of Energy – National Energy Technology Laboratory (US-DOE-NETL) methodology as the scale of investigation is narrowed from very large regional assessments down to selected areas and formations that may be developed for commercial storage. In addition, we present a new notation that explicitly identifies differences between data availability and data sources used for geologic parameters and efficiency factors as the scale of investigation is narrowed. This CO 2 resource estimation method is available for screening formations in a tool called CO 2-SCREEN.« less

Prospective CO 2 saline resource estimation methodology: Refinement of existing US-DOE-NETL methods based on data availability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goodman, Angela; Sanguinito, Sean; Levine, Jonathan S.

Carbon storage resource estimation in subsurface saline formations plays an important role in establishing the scale of carbon capture and storage activities for governmental policy and commercial project decision-making. Prospective CO 2 resource estimation of large regions or subregions, such as a basin, occurs at the initial screening stages of a project using only limited publicly available geophysical data, i.e. prior to project-specific site selection data generation. As the scale of investigation is narrowed and selected areas and formations are identified, prospective CO 2 resource estimation can be refined and uncertainty narrowed when site-specific geophysical data are available. Here, wemore » refine the United States Department of Energy – National Energy Technology Laboratory (US-DOE-NETL) methodology as the scale of investigation is narrowed from very large regional assessments down to selected areas and formations that may be developed for commercial storage. In addition, we present a new notation that explicitly identifies differences between data availability and data sources used for geologic parameters and efficiency factors as the scale of investigation is narrowed. This CO 2 resource estimation method is available for screening formations in a tool called CO 2-SCREEN.« less

Large-scale high-throughput computer-aided discovery of advanced materials using cloud computing

NASA Astrophysics Data System (ADS)

Bazhirov, Timur; Mohammadi, Mohammad; Ding, Kevin; Barabash, Sergey

Recent advances in cloud computing made it possible to access large-scale computational resources completely on-demand in a rapid and efficient manner. When combined with high fidelity simulations, they serve as an alternative pathway to enable computational discovery and design of new materials through large-scale high-throughput screening. Here, we present a case study for a cloud platform implemented at Exabyte Inc. We perform calculations to screen lightweight ternary alloys for thermodynamic stability. Due to the lack of experimental data for most such systems, we rely on theoretical approaches based on first-principle pseudopotential density functional theory. We calculate the formation energies for a set of ternary compounds approximated by special quasirandom structures. During an example run we were able to scale to 10,656 CPUs within 7 minutes from the start, and obtain results for 296 compounds within 38 hours. The results indicate that the ultimate formation enthalpy of ternary systems can be negative for some of lightweight alloys, including Li and Mg compounds. We conclude that compared to traditional capital-intensive approach that requires in on-premises hardware resources, cloud computing is agile and cost-effective, yet scalable and delivers similar performance.

Screening for Language Delay: Growth Trajectories of Language Ability in Low- and High-Performing Children

ERIC Educational Resources Information Center

Klem, Marianne; Hagtvet, Bente; Hulme, Charles; Gustafsson, Jan-Eric

2016-01-01

Purpose: This study investigated the stability and growth of preschool language skills and explores latent class analysis as an approach for identifying children at risk of language impairment. Method: The authors present data from a large-scale 2-year longitudinal study, in which 600 children were assessed with a language-screening tool…

A qualitative analysis of bus simulator training on transit incidents : a case study in Florida. [Summary].

DOT National Transportation Integrated Search

2013-01-01

The simulator was once a very expensive, large-scale mechanical device for training military pilots or astronauts. Modern computers, linking sophisticated software and large-screen displays, have yielded simulators for the desktop or configured as sm...

Decision aid on breast cancer screening reduces attendance rate: results of a large-scale, randomized, controlled study by the DECIDEO group

PubMed Central

Bourmaud, Aurelie; Soler-Michel, Patricia; Oriol, Mathieu; Regnier, Véronique; Tinquaut, Fabien; Nourissat, Alice; Bremond, Alain; Moumjid, Nora; Chauvin, Franck

2016-01-01

Controversies regarding the benefits of breast cancer screening programs have led to the promotion of new strategies taking into account individual preferences, such as decision aid. The aim of this study was to assess the impact of a decision aid leaflet on the participation of women invited to participate in a national breast cancer screening program. This Randomized, multicentre, controlled trial. Women aged 50 to 74 years, were randomly assigned to receive either a decision aid or the usual invitation letter. Primary outcome was the participation rate 12 months after the invitation. 16 000 women were randomized and 15 844 included in the modified intention-to-treat analysis. The participation rate in the intervention group was 40.25% (3174/7885 women) compared with 42.13% (3353/7959) in the control group (p = 0.02). Previous attendance for screening (RR = 6.24; [95%IC: 5.75-6.77]; p < 0.0001) and medium household income (RR = 1.05; [95%IC: 1.01-1.09]; p = 0.0074) were independently associated with attendance for screening. This large-scale study demonstrates that the decision aid reduced the participation rate. The decision aid activate the decision making process of women toward non-attendance to screening. These results show the importance of promoting informed patient choices, especially when those choices cannot be anticipated. PMID:26883201

Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening.

PubMed

Takayama, Kazuo; Mizuguchi, Hiroyuki

2017-02-01

Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicity screening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicity screening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicity screening. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are able to replicate indefinitely and differentiate into most of the body's cell types, including hepatocytes. It is expected that hepatocyte-like cells generated from human ES/iPS cells (human ES/iPS-HLCs) will be a useful tool for drug toxicity screening. To apply human ES/iPS-HLCs to various applications including drug toxicity screening, homogenous and functional HLCs must be differentiated from human ES/iPS cells. In this review, we will introduce the current status of hepatocyte differentiation technology from human ES/iPS cells and a novel method to predict drug-induced liver injury using human ES/iPS-HLCs. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Reverse Fluorescence Enhancement and Colorimetric Bimodal Signal Readout Immunochromatography Test Strip for Ultrasensitive Large-Scale Screening and Postoperative Monitoring.

PubMed

Yao, Yingyi; Guo, Weisheng; Zhang, Jian; Wu, Yudong; Fu, Weihua; Liu, Tingting; Wu, Xiaoli; Wang, Hanjie; Gong, Xiaoqun; Liang, Xing-Jie; Chang, Jin

2016-09-07

Ultrasensitive and quantitative fast screening of cancer biomarkers by immunochromatography test strip (ICTS) is still challenging in clinic. The gold nanoparticles (NPs) based ICTS with colorimetric readout enables a quick spectrum screening but suffers from nonquantitative performance; although ICTS with fluorescence readout (FICTS) allows quantitative detection, its sensitivity still deserves more efforts and attentions. In this work, by taking advantages of colorimetric ICTS and FICTS, we described a reverse fluorescence enhancement ICTS (rFICTS) with bimodal signal readout for ultrasensitive and quantitative fast screening of carcinoembryonic antigen (CEA). In the presence of target, gold NPs aggregation in T line induced colorimetric readout, allowing on-the-spot spectrum screening in 10 min by naked eye. Meanwhile, the reverse fluorescence enhancement signal enabled more accurately quantitative detection with better sensitivity (5.89 pg/mL for CEA), which is more than 2 orders of magnitude lower than that of the conventional FICTS. The accuracy and stability of the rFICTS were investigated with more than 100 clinical serum samples for large-scale screening. Furthermore, this rFICTS also realized postoperative monitoring by detecting CEA in a patient with colon cancer and comparing with CT imaging diagnosis. These results indicated this rFICTS is particularly suitable for point-of-care (POC) diagnostics in both resource-rich and resource-limited settings.

Computational catalyst screening: Scaling, bond-order and catalysis

DOE PAGES

Abild-Pedersen, Frank

2015-10-01

Here, the design of new and better heterogeneous catalysts needed to accommodate the growing demand for energy from renewable sources is an important challenge for coming generations. Most surface catalyzed processes involve a large number of complex reaction networks and the energetics ultimately defines the turn-over-frequency and the selectivity of the process. In order not to get lost in the large quantities of data, simplification schemes that still contain the key elements of the reaction are required. Adsorption and transition state scaling relations constitutes such a scheme that not only maps the reaction relevant information in terms of few parametersmore » but also provides an efficient way of screening for new materials in a continuous multi-dimensional energy space. As with all relations they impose certain restrictions on what can be achieved and in this paper, I show why these limitations exist and how we can change the behavior through an energy-resolved approach that still maintains the screening capabilities needed in computational catalysis.« less

GENASIS Basics: Object-oriented utilitarian functionality for large-scale physics simulations (Version 2)

NASA Astrophysics Data System (ADS)

Cardall, Christian Y.; Budiardja, Reuben D.

2017-05-01

GenASiS Basics provides Fortran 2003 classes furnishing extensible object-oriented utilitarian functionality for large-scale physics simulations on distributed memory supercomputers. This functionality includes physical units and constants; display to the screen or standard output device; message passing; I/O to disk; and runtime parameter management and usage statistics. This revision -Version 2 of Basics - makes mostly minor additions to functionality and includes some simplifying name changes.

GPURFSCREEN: a GPU based virtual screening tool using random forest classifier.

PubMed

Jayaraj, P B; Ajay, Mathias K; Nufail, M; Gopakumar, G; Jaleel, U C A

2016-01-01

In-silico methods are an integral part of modern drug discovery paradigm. Virtual screening, an in-silico method, is used to refine data models and reduce the chemical space on which wet lab experiments need to be performed. Virtual screening of a ligand data model requires large scale computations, making it a highly time consuming task. This process can be speeded up by implementing parallelized algorithms on a Graphical Processing Unit (GPU). Random Forest is a robust classification algorithm that can be employed in the virtual screening. A ligand based virtual screening tool (GPURFSCREEN) that uses random forests on GPU systems has been proposed and evaluated in this paper. This tool produces optimized results at a lower execution time for large bioassay data sets. The quality of results produced by our tool on GPU is same as that on a regular serial environment. Considering the magnitude of data to be screened, the parallelized virtual screening has a significantly lower running time at high throughput. The proposed parallel tool outperforms its serial counterpart by successfully screening billions of molecules in training and prediction phases.

Preparation of fosmid libraries and functional metagenomic analysis of microbial community DNA.

PubMed

Martínez, Asunción; Osburne, Marcia S

2013-01-01

One of the most important challenges in contemporary microbial ecology is to assign a functional role to the large number of novel genes discovered through large-scale sequencing of natural microbial communities that lack similarity to genes of known function. Functional screening of metagenomic libraries, that is, screening environmental DNA clones for the ability to confer an activity of interest to a heterologous bacterial host, is a promising approach for bridging the gap between metagenomic DNA sequencing and functional characterization. Here, we describe methods for isolating environmental DNA and constructing metagenomic fosmid libraries, as well as methods for designing and implementing successful functional screens of such libraries. © 2013 Elsevier Inc. All rights reserved.

Assessing Bodily Preoccupations is sufficient: clinically effective screening for hypochondriasis.

PubMed

Höfling, Volkmar; Weck, Florian

2013-12-01

Hypochondriasis is a persistent psychiatric disorder and is associated with increased utilisation of health care services. However, effective psychiatric consultation interventions and CBT treatments are available. In the present study, we provide evidence of clinically effective screening for hypochondriasis. We describe the clinically effective identification of patients with a high probability of suffering from hypochondriasis. This identification is achieved by means of two brief standardised screening instruments, namely the Bodily Preoccupation (BP) Scale with 3 items and the Whiteley-7 (WI-7) with 7 items. Both the BP scale and the WI-7 were examined in a sample of 228 participants (72 with hypochondriasis, 80 with anxiety disorders and 76 healthy controls) in a large psychotherapy outpatients' unit, applying the DSM-IV criteria. Cut-off values for the BP scale and the WI-7 were computed to identify patients with a high probability of suffering from hypochondriasis. Additionally, other self-report symptom severity scales were completed in order to examine discriminant and convergent validity. Data was collected from June 2010 to March 2013. The BP scale and the WI-7 discriminated significantly between patients with hypochondriasis and those with an anxiety disorder (d=2.42 and d=2.34). Cut-off values for these two screening scales could be provided, thus identifying patients with a high probability of suffering from hypochondriasis. In order to reduce costs, the BP scale or the WI-7 should be applied in medical or primary care settings, to screen for patients with a high probability of hypochondriasis and to transfer them to further assessment and effective treatment. © 2013.

Low-Cost, Disposable, Flexible and Highly Reproducible Screen Printed SERS Substrates for the Detection of Various Chemicals

PubMed Central

Wu, Wei; Liu, Li; Dai, Zhigao; Liu, Juhua; Yang, Shuanglei; Zhou, Li; Xiao, Xiangheng; Jiang, Changzhong; Roy, Vellaisamy A.L.

2015-01-01

Ideal SERS substrates for sensing applications should exhibit strong signal enhancement, generate a reproducible and uniform response, and should be able to fabricate in large-scale and low-cost. Herein, we demonstrate low-cost, highly sensitive, disposable and reproducible SERS substrates by means of screen printing Ag nanoparticles (NPs) on a plastic PET (Polyethylene terephthalate) substrates. While there are many complex methods for the fabrication of SERS substrates, screen printing is suitable for large-area fabrication and overcomes the uneven radial distribution. Using as-printed Ag substrates as the SERS platform, detection of various commonly known chemicals have been done. The SERS detection limit of Rhodamine 6G (R6G) is higher than the concentration of 1 × 10−10 M. The relative standard deviation (RSD) value for 784 points on the detection of R6G and Malachite green (MG) is less than 20% revealing a homogeneous SERS distribution and high reproducibility. Moreover, melamine (MA) is detected in fresh liquid-milk without additional pretreatment, which may accelerate the application of rapid on-line detection of MA in liquid milk. Our screen printing method highlights the use of large-scale printing strategies for the fabrication of well-defined functional nanostructures with applications well beyond the field of SERS sensing. PMID:25974125

Screening for Lung Cancer

PubMed Central

Mazzone, Peter J.; Naidich, David P.; Bach, Peter B.

2013-01-01

Background: Lung cancer is by far the major cause of cancer deaths largely because in the majority of patients it is at an advanced stage at the time it is discovered, when curative treatment is no longer feasible. This article examines the data regarding the ability of screening to decrease the number of lung cancer deaths. Methods: A systematic review was conducted of controlled studies that address the effectiveness of methods of screening for lung cancer. Results: Several large randomized controlled trials (RCTs), including a recent one, have demonstrated that screening for lung cancer using a chest radiograph does not reduce the number of deaths from lung cancer. One large RCT involving low-dose CT (LDCT) screening demonstrated a significant reduction in lung cancer deaths, with few harms to individuals at elevated risk when done in the context of a structured program of selection, screening, evaluation, and management of the relatively high number of benign abnormalities. Whether other RCTs involving LDCT screening are consistent is unclear because data are limited or not yet mature. Conclusions: Screening is a complex interplay of selection (a population with sufficient risk and few serious comorbidities), the value of the screening test, the interval between screening tests, the availability of effective treatment, the risk of complications or harms as a result of screening, and the degree with which the screened individuals comply with screening and treatment recommendations. Screening with LDCT of appropriate individuals in the context of a structured process is associated with a significant reduction in the number of lung cancer deaths in the screened population. Given the complex interplay of factors inherent in screening, many questions remain on how to effectively implement screening on a broader scale. PMID:23649455

MouseNet database: digital management of a large-scale mutagenesis project.

PubMed

Pargent, W; Heffner, S; Schäble, K F; Soewarto, D; Fuchs, H; Hrabé de Angelis, M

2000-07-01

The Munich ENU Mouse Mutagenesis Screen is a large-scale mutant production, phenotyping, and mapping project. It encompasses two animal breeding facilities and a number of screening groups located in the general area of Munich. A central database is required to manage and process the immense amount of data generated by the mutagenesis project. This database, which we named MouseNet(c), runs on a Sybase platform and will finally store and process all data from the entire project. In addition, the system comprises a portfolio of functions needed to support the workflow management of the core facility and the screening groups. MouseNet(c) will make all of the data available to the participating screening groups, and later to the international scientific community. MouseNet(c) will consist of three major software components:* Animal Management System (AMS)* Sample Tracking System (STS)* Result Documentation System (RDS)MouseNet(c) provides the following major advantages:* being accessible from different client platforms via the Internet* being a full-featured multi-user system (including access restriction and data locking mechanisms)* relying on a professional RDBMS (relational database management system) which runs on a UNIX server platform* supplying workflow functions and a variety of plausibility checks.

Dynamic security contingency screening and ranking using neural networks.

PubMed

Mansour, Y; Vaahedi, E; El-Sharkawi, M A

1997-01-01

This paper summarizes BC Hydro's experience in applying neural networks to dynamic security contingency screening and ranking. The idea is to use the information on the prevailing operating condition and directly provide contingency screening and ranking using a trained neural network. To train the two neural networks for the large scale systems of BC Hydro and Hydro Quebec, in total 1691 detailed transient stability simulation were conducted, 1158 for BC Hydro system and 533 for the Hydro Quebec system. The simulation program was equipped with the energy margin calculation module (second kick) to measure the energy margin in each run. The first set of results showed poor performance for the neural networks in assessing the dynamic security. However a number of corrective measures improved the results significantly. These corrective measures included: 1) the effectiveness of output; 2) the number of outputs; 3) the type of features (static versus dynamic); 4) the number of features; 5) system partitioning; and 6) the ratio of training samples to features. The final results obtained using the large scale systems of BC Hydro and Hydro Quebec demonstrates a good potential for neural network in dynamic security assessment contingency screening and ranking.

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

PubMed

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 including, but not limited to, phosphorylation, cytoskeleton organization, axonal transport, regulation of cellular proteostasis, transcription, RNA metabolism, cell cycle regulation, and apoptosis. We discuss the utility and application of invertebrate models in elucidating the cellular and molecular functions of novel and uncharacterized disease modifiers identified in large-scale screens as well as for investigating the function of genes identified as risk factors in genome-wide association studies from human patients in the post-genomic era. In this review, we combined and summarized several large-scale modifier screens performed in invertebrate models to identify modifiers of tau toxicity. A summary of the screens show that diverse cellular processes are implicated in the modification of tau toxicity. Kinases and phosphatases are the most predominant class of modifiers followed by components required for cellular proteostasis and axonal transport and cytoskeleton elements. © 2016 International Society for Neurochemistry.

A parametrisation of modified gravity on nonlinear cosmological scales

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lombriser, Lucas, E-mail: llo@roe.ac.uk

2016-11-01

Viable modifications of gravity on cosmological scales predominantly rely on screening mechanisms to recover Einstein's Theory of General Relativity in the Solar System, where it has been well tested. A parametrisation of the effects of such modifications in the spherical collapse model is presented here for the use of modelling the modified nonlinear cosmological structure. The formalism allows an embedding of the different screening mechanisms operating in scalar-tensor theories through large values of the gravitational potential or its first or second derivatives as well as of linear suppression effects or more general transitions between modified and Einstein gravity limits. Eachmore » screening or suppression mechanism is parametrised by a time, mass, and environment dependent screening scale, an effective modified gravitational coupling in the fully unscreened limit that can be matched to linear theory, the exponent of a power-law radial profile of the screened coupling, determined by derivatives, symmetries, and potentials in the scalar field equation, and an interpolation rate between the screened and unscreened limits. Along with generalised perturbative methods, the parametrisation may be used to formulate a nonlinear extension to the linear parametrised post-Friedmannian framework to enable generalised tests of gravity with the wealth of observations from the nonlinear cosmological regime.« less

Large-scale annotation of small-molecule libraries using public databases.

PubMed

Zhou, Yingyao; Zhou, Bin; Chen, Kaisheng; Yan, S Frank; King, Frederick J; Jiang, Shumei; Winzeler, Elizabeth A

2007-01-01

While many large publicly accessible databases provide excellent annotation for biological macromolecules, the same is not true for small chemical compounds. Commercial data sources also fail to encompass an annotation interface for large numbers of compounds and tend to be cost prohibitive to be widely available to biomedical researchers. Therefore, using annotation information for the selection of lead compounds from a modern day high-throughput screening (HTS) campaign presently occurs only under a very limited scale. The recent rapid expansion of the NIH PubChem database provides an opportunity to link existing biological databases with compound catalogs and provides relevant information that potentially could improve the information garnered from large-scale screening efforts. Using the 2.5 million compound collection at the Genomics Institute of the Novartis Research Foundation (GNF) as a model, we determined that approximately 4% of the library contained compounds with potential annotation in such databases as PubChem and the World Drug Index (WDI) as well as related databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and ChemIDplus. Furthermore, the exact structure match analysis showed 32% of GNF compounds can be linked to third party databases via PubChem. We also showed annotations such as MeSH (medical subject headings) terms can be applied to in-house HTS databases in identifying signature biological inhibition profiles of interest as well as expediting the assay validation process. The automated annotation of thousands of screening hits in batch is becoming feasible and has the potential to play an essential role in the hit-to-lead decision making process.

Reaching the Unreachable: Novel Approaches to Telemedicine Screening of Underserved Populations for Vitreoretinal Disease.

PubMed

Murchison, Ann P; Haller, Julia A; Mayro, Eileen; Hark, Lisa; Gower, Emily; Huisingh, Carrie; Rhodes, Lindsay; Friedman, David S; Lee, David J; Lam, Byron L

2017-07-01

Telemedicine involves electronic communication between a physician in one location and a patient in another location to provide remote medical care. Ophthalmologists are increasingly employing telemedicine, particularly in retinal disease screening and monitoring. Telemedicine has been utilized to decrease barriers to care and yield greater patient satisfaction and lower costs, while maintaining high sensitivity and specificity. This review discusses common patient barriers to eye care, innovative approaches to retinal disease screening and monitoring using telemedicine, and eye care policy initiatives needed to enact large-scale telemedicine eye disease screening programs.

WISDOM-II: screening against multiple targets implicated in malaria using computational grid infrastructures.

PubMed

Kasam, Vinod; Salzemann, Jean; Botha, Marli; Dacosta, Ana; Degliesposti, Gianluca; Isea, Raul; Kim, Doman; Maass, Astrid; Kenyon, Colin; Rastelli, Giulio; Hofmann-Apitius, Martin; Breton, Vincent

2009-05-01

Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the Plasmodium parasite, some are promising targets to carry out rational drug discovery. Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR), and on a new promising one, glutathione-S-transferase. In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate in silico docking and in information technology to design and operate large scale grid infrastructures. On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, In vitro results are underway for all the targets against which screening is performed. The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software on computational grids in finding hits against three different targets (PfGST, PfDHFR, PvDHFR (wild type and mutant forms) implicated in malaria. Grid-enabled virtual screening approach is proposed to produce focus compound libraries for other biological targets relevant to fight the infectious diseases of the developing world.

High-content screening in microfluidic devices.

PubMed

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2010-08-01

Miniaturization is the key to advancing the state of the art in high-content screening (HCS) in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. The advantages of this technology are discussed, including cost savings, high-throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration and scaling. The reader will understand the capabilities of anew microfluidics-based platform for HCS and the advantages it provides over conventional plate-based HCS. Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery.

Equivalence principle implications of modified gravity models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hui, Lam; Nicolis, Alberto; Stubbs, Christopher W.

2009-11-15

Theories that attempt to explain the observed cosmic acceleration by modifying general relativity all introduce a new scalar degree of freedom that is active on large scales, but is screened on small scales to match experiments. We demonstrate that if such screening occurs via the chameleon mechanism, such as in f(R) theory, it is possible to have order unity violation of the equivalence principle, despite the absence of explicit violation in the microscopic action. Namely, extended objects such as galaxies or constituents thereof do not all fall at the same rate. The chameleon mechanism can screen the scalar charge formore » large objects but not for small ones (large/small is defined by the depth of the gravitational potential and is controlled by the scalar coupling). This leads to order one fluctuations in the ratio of the inertial mass to gravitational mass. We provide derivations in both Einstein and Jordan frames. In Jordan frame, it is no longer true that all objects move on geodesics; only unscreened ones, such as test particles, do. In contrast, if the scalar screening occurs via strong coupling, such as in the Dvali-Gabadadze-Porrati braneworld model, equivalence principle violation occurs at a much reduced level. We propose several observational tests of the chameleon mechanism: 1. small galaxies should accelerate faster than large galaxies, even in environments where dynamical friction is negligible; 2. voids defined by small galaxies would appear larger compared to standard expectations; 3. stars and diffuse gas in small galaxies should have different velocities, even if they are on the same orbits; 4. lensing and dynamical mass estimates should agree for large galaxies but disagree for small ones. We discuss possible pitfalls in some of these tests. The cleanest is the third one where the mass estimate from HI rotational velocity could exceed that from stars by 30% or more. To avoid blanket screening of all objects, the most promising place to look is in voids.« less

Dynamic screening in a two-species asymmetric exclusion process

NASA Astrophysics Data System (ADS)

Kim, Kyung Hyuk; den Nijs, Marcel

2007-08-01

The dynamic scaling properties of the one-dimensional Burgers equation are expected to change with the inclusion of additional conserved degrees of freedom. We study this by means of one-dimensional (1D) driven lattice gas models that conserve both mass and momentum. The most elementary version of this is the Arndt-Heinzel-Rittenberg (AHR) process, which is usually presented as a two-species diffusion process, with particles of opposite charge hopping in opposite directions and with a variable passing probability. From the hydrodynamics perspective this can be viewed as two coupled Burgers equations, with the number of positive and negative momentum quanta individually conserved. We determine the dynamic scaling dimension of the AHR process from the time evolution of the two-point correlation functions, and find numerically that the dynamic critical exponent is consistent with simple Kardar-Parisi-Zhang- (KPZ) type scaling. We establish that this is the result of perfect screening of fluctuations in the stationary state. The two-point correlations decay exponentially in our simulations and in such a manner that in terms of quasiparticles, fluctuations fully screen each other at coarse grained length scales. We prove this screening rigorously using the analytic matrix product structure of the stationary state. The proof suggests the existence of a topological invariant. The process remains in the KPZ universality class but only in the sense of a factorization, as (KPZ)2 . The two Burgers equations decouple at large length scales due to the perfect screening.

High-throughput image analysis of tumor spheroids: a user-friendly software application to measure the size of spheroids automatically and accurately.

PubMed

Chen, Wenjin; Wong, Chung; Vosburgh, Evan; Levine, Arnold J; Foran, David J; Xu, Eugenia Y

2014-07-08

The increasing number of applications of three-dimensional (3D) tumor spheroids as an in vitro model for drug discovery requires their adaptation to large-scale screening formats in every step of a drug screen, including large-scale image analysis. Currently there is no ready-to-use and free image analysis software to meet this large-scale format. Most existing methods involve manually drawing the length and width of the imaged 3D spheroids, which is a tedious and time-consuming process. This study presents a high-throughput image analysis software application - SpheroidSizer, which measures the major and minor axial length of the imaged 3D tumor spheroids automatically and accurately; calculates the volume of each individual 3D tumor spheroid; then outputs the results in two different forms in spreadsheets for easy manipulations in the subsequent data analysis. The main advantage of this software is its powerful image analysis application that is adapted for large numbers of images. It provides high-throughput computation and quality-control workflow. The estimated time to process 1,000 images is about 15 min on a minimally configured laptop, or around 1 min on a multi-core performance workstation. The graphical user interface (GUI) is also designed for easy quality control, and users can manually override the computer results. The key method used in this software is adapted from the active contour algorithm, also known as Snakes, which is especially suitable for images with uneven illumination and noisy background that often plagues automated imaging processing in high-throughput screens. The complimentary "Manual Initialize" and "Hand Draw" tools provide the flexibility to SpheroidSizer in dealing with various types of spheroids and diverse quality images. This high-throughput image analysis software remarkably reduces labor and speeds up the analysis process. Implementing this software is beneficial for 3D tumor spheroids to become a routine in vitro model for drug screens in industry and academia.

Detection of large scale 3' deletions in the PMS2 gene amongst Colon-CFR participants: have we been missing anything?

PubMed

Clendenning, Mark; Walsh, Michael D; Gelpi, Judith Balmana; Thibodeau, Stephen N; Lindor, Noralane; Potter, John D; Newcomb, Polly; LeMarchand, Loic; Haile, Robert; Gallinger, Steve; Hopper, John L; Jenkins, Mark A; Rosty, Christophe; Young, Joanne P; Buchanan, Daniel D

2013-09-01

Current screening practices have been able to identify PMS2 mutations in 78 % of cases of colorectal cancer from the Colorectal Cancer Family Registry (Colon CFR) which showed solitary loss of the PMS2 protein. However the detection of large-scale deletions in the 3' end of the PMS2 gene has not been possible due to technical difficulties associated with pseudogene sequences. Here, we utilised a recently described MLPA/long-range PCR-based approach to screen the remaining 22 % (n = 16) of CRC-affected probands for mutations in the 3' end of the PMS2 gene. No deletions encompassing any or all of exons 12 through 15 were identified; therefore, our results suggest that 3' deletions in PMS2 are not a frequent occurrence in such families.

Prognostic value of nutritional risk screening 2002 scale in nasopharyngeal carcinoma: A large-scale cohort study.

PubMed

Peng, Hao; Chen, Bin-Bin; Tang, Ling-Long; Chen, Lei; Li, Wen-Fei; Zhang, Yuan; Mao, Yan-Ping; Sun, Ying; Liu, Li-Zhi; Tian, Li; Guo, Ying; Ma, Jun

2018-06-01

Little is known about the value of the nutritional risk screening 2002 (NRS2002) scale in nasopharyngeal carcinoma (NPC). We conducted a large-scale study to address this issue. We employed a big-data intelligence database platform at our center and identified 3232 eligible patients treated between 2009 and 2013. Of the 3232 (12.9% of 24 986) eligible patients, 469 (14.5%), 13 (0.4%), 953 (29.5%), 1762 (54.5%) and 35 (1.1%) had NRS2002 scores of 1, 2, 3, 4 and 5, respectively. Survival outcomes were comparable between patients with NRS2002 <3 and ≥3 (original scale). However, patients with NRS2002 ≤3 vs >3 (regrouping scale) had significantly different 5-year disease-free survival (DFS; 82.7% vs 75.0%, P < .001), overall survival (OS; 88.8% vs 84.1%, P = .001), distant metastasis-free survival (DMFS; 90.2% vs 85.9%, P = .001) and locoregional relapse-free survival (LRRFS; 91.6% vs 87.2%, P = .001). Therefore, we proposed a revised NRS2002 scale, and found that it provides a better risk stratification than the original or regrouping scales for predicting DFS (area under the curve [AUC] = 0.530 vs 0.554 vs 0.577; P < .05), OS (AUC = 0.534 vs 0.563 vs 0.582; P < .05), DMFS (AUC = 0.531 vs 0.567 vs 0.590; P < .05) and LRRFS (AUC = 0.529 vs 0.542 vs 0.564; P < .05 except scale A vs B). Our proposed NRS2002 scale represents a simple, clinically useful tool for nutritional risk screening in NPC. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Pilot study of large-scale production of mutant pigs by ENU mutagenesis.

PubMed

Hai, Tang; Cao, Chunwei; Shang, Haitao; Guo, Weiwei; Mu, Yanshuang; Yang, Shulin; Zhang, Ying; Zheng, Qiantao; Zhang, Tao; Wang, Xianlong; Liu, Yu; Kong, Qingran; Li, Kui; Wang, Dayu; Qi, Meng; Hong, Qianlong; Zhang, Rui; Wang, Xiupeng; Jia, Qitao; Wang, Xiao; Qin, Guosong; Li, Yongshun; Luo, Ailing; Jin, Weiwu; Yao, Jing; Huang, Jiaojiao; Zhang, Hongyong; Li, Menghua; Xie, Xiangmo; Zheng, Xuejuan; Guo, Kenan; Wang, Qinghua; Zhang, Shibin; Li, Liang; Xie, Fei; Zhang, Yu; Weng, Xiaogang; Yin, Zhi; Hu, Kui; Cong, Yimei; Zheng, Peng; Zou, Hailong; Xin, Leilei; Xia, Jihan; Ruan, Jinxue; Li, Hegang; Zhao, Weiming; Yuan, Jing; Liu, Zizhan; Gu, Weiwang; Li, Ming; Wang, Yong; Wang, Hongmei; Yang, Shiming; Liu, Zhonghua; Wei, Hong; Zhao, Jianguo; Zhou, Qi; Meng, Anming

2017-06-22

N-ethyl-N-nitrosourea (ENU) mutagenesis is a powerful tool to generate mutants on a large scale efficiently, and to discover genes with novel functions at the whole-genome level in Caenorhabditis elegans, flies, zebrafish and mice, but it has never been tried in large model animals. We describe a successful systematic three-generation ENU mutagenesis screening in pigs with the establishment of the Chinese Swine Mutagenesis Consortium. A total of 6,770 G1 and 6,800 G3 pigs were screened, 36 dominant and 91 recessive novel pig families with various phenotypes were established. The causative mutations in 10 mutant families were further mapped. As examples, the mutation of SOX10 (R109W) in pig causes inner ear malfunctions and mimics human Mondini dysplasia, and upregulated expression of FBXO32 is associated with congenital splay legs. This study demonstrates the feasibility of artificial random mutagenesis in pigs and opens an avenue for generating a reservoir of mutants for agricultural production and biomedical research.

Intelligent Interfaces for Mining Large-Scale RNAi-HCS Image Databases

PubMed Central

Lin, Chen; Mak, Wayne; Hong, Pengyu; Sepp, Katharine; Perrimon, Norbert

2010-01-01

Recently, High-content screening (HCS) has been combined with RNA interference (RNAi) to become an essential image-based high-throughput method for studying genes and biological networks through RNAi-induced cellular phenotype analyses. However, a genome-wide RNAi-HCS screen typically generates tens of thousands of images, most of which remain uncategorized due to the inadequacies of existing HCS image analysis tools. Until now, it still requires highly trained scientists to browse a prohibitively large RNAi-HCS image database and produce only a handful of qualitative results regarding cellular morphological phenotypes. For this reason we have developed intelligent interfaces to facilitate the application of the HCS technology in biomedical research. Our new interfaces empower biologists with computational power not only to effectively and efficiently explore large-scale RNAi-HCS image databases, but also to apply their knowledge and experience to interactive mining of cellular phenotypes using Content-Based Image Retrieval (CBIR) with Relevance Feedback (RF) techniques. PMID:21278820

Large-Scale Chemical Similarity Networks for Target Profiling of Compounds Identified in Cell-Based Chemical Screens

PubMed Central

Lo, Yu-Chen; Senese, Silvia; Li, Chien-Ming; Hu, Qiyang; Huang, Yong; Damoiseaux, Robert; Torres, Jorge Z.

2015-01-01

Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are limited to single or sequential ligand analysis that have limited capabilities for accurate deconvolution of a large number of compounds with diverse chemical structures. Here, we present CSNAP (Chemical Similarity Network Analysis Pulldown), a new computational target identification method that utilizes chemical similarity networks for large-scale chemotype (consensus chemical pattern) recognition and drug target profiling. Our benchmark study showed that CSNAP can achieve an overall higher accuracy (>80%) of target prediction with respect to representative chemotypes in large (>200) compound sets, in comparison to the SEA approach (60–70%). Additionally, CSNAP is capable of integrating with biological knowledge-based databases (Uniprot, GO) and high-throughput biology platforms (proteomic, genetic, etc) for system-wise drug target validation. To demonstrate the utility of the CSNAP approach, we combined CSNAP's target prediction with experimental ligand evaluation to identify the major mitotic targets of hit compounds from a cell-based chemical screen and we highlight novel compounds targeting microtubules, an important cancer therapeutic target. The CSNAP method is freely available and can be accessed from the CSNAP web server (http://services.mbi.ucla.edu/CSNAP/). PMID:25826798

Sparse Measurement Systems: Applications, Analysis, Algorithms and Design

ERIC Educational Resources Information Center

Narayanaswamy, Balakrishnan

2011-01-01

This thesis deals with "large-scale" detection problems that arise in many real world applications such as sensor networks, mapping with mobile robots and group testing for biological screening and drug discovery. These are problems where the values of a large number of inputs need to be inferred from noisy observations and where the…

Interaction of Vortex Rings and Steady Jets with Permeable Screens of Varied Porosity

NASA Astrophysics Data System (ADS)

Musta, Mustafa

2013-11-01

Vortex ring and steady jet interaction with a porous matrix formed from several parallel, transparent permeable screens with the same grid geometry for open area ratios (φ) 49.5% - 83.8% was studied previously using digital particle image velocimetry (DPIV) at jet Reynolds number (Re) of 1000-3000. Vortex ring results showed that unlike the experiments with thin screens, a transmitted vortex ring, which has a similar diameter to the primary one, wasn't formed. Instead a centerline vortex ring like structure formed and its diameter, circulation, and dissipation time decreased as φ decreased. However, for the case of screens φ = 55.7% with large screen spacing, reformation of large scale weak vortex rings was observed downstream of the first screen. The present work experimentally investigates the interaction of vortex rings and steady jets with screens of decreasing φ (83.8%-49.5%) in the flow direction. A piston type vortex ring generator was used and measurements were made using DPIV. The vortex ring results show that the size and circulation of the vortex ring like flow structure was changed based on the screen φ within the permeable screen matrix. Similarly, steady jet flow structure and the local turbulent kinetic energy was changed based on the local screen φ.

Large Scale Screening of Low Cost Ferritic Steel Designs For Advanced Ultra Supercritical Boiler Using First Principles Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouyang, Lizhi

Advanced Ultra Supercritical Boiler (AUSC) requires materials that can operate in corrosive environment at temperature and pressure as high as 760°C (or 1400°F) and 5000psi, respectively, while at the same time maintain good ductility at low temperature. We develop automated simulation software tools to enable fast large scale screening studies of candidate designs. While direct evaluation of creep rupture strength and ductility are currently not feasible, properties such as energy, elastic constants, surface energy, interface energy, and stack fault energy can be used to assess their relative ductility and creeping strength. We implemented software to automate the complex calculations tomore » minimize human inputs in the tedious screening studies which involve model structures generation, settings for first principles calculations, results analysis and reporting. The software developed in the project and library of computed mechanical properties of phases found in ferritic steels, many are complex solid solutions estimated for the first time, will certainly help the development of low cost ferritic steel for AUSC.« less

Large-scale Topographical Screen for Investigation of Physical Neural-Guidance Cues

NASA Astrophysics Data System (ADS)

Li, Wei; Tang, Qing Yuan; Jadhav, Amol D.; Narang, Ankit; Qian, Wei Xian; Shi, Peng; Pang, Stella W.

2015-03-01

A combinatorial approach was used to present primary neurons with a large library of topographical features in the form of micropatterned substrate for high-throughput screening of physical neural-guidance cues that can effectively promote different aspects of neuronal development, including axon and dendritic outgrowth. Notably, the neuronal-guidance capability of specific features was automatically identified using a customized image processing software, thus significantly increasing the screening throughput with minimal subjective bias. Our results indicate that the anisotropic topographies promote axonal and in some cases dendritic extension relative to the isotropic topographies, while dendritic branching showed preference to plain substrates over the microscale features. The results from this work can be readily applied towards engineering novel biomaterials with precise surface topography that can serve as guidance conduits for neuro-regenerative applications. This novel topographical screening strategy combined with the automated processing capability can also be used for high-throughput screening of chemical or genetic regulatory factors in primary neurons.

Methodology for enabling high-throughput simultaneous saccharification and fermentation screening of yeast using solid biomass as a substrate.

PubMed

Elliston, Adam; Wood, Ian P; Soucouri, Marie J; Tantale, Rachelle J; Dicks, Jo; Roberts, Ian N; Waldron, Keith W

2015-01-01

High-throughput (HTP) screening is becoming an increasingly useful tool for collating biological data which would otherwise require the employment of excessive resources. Second generation biofuel production is one such process. HTP screening allows the investigation of large sample sets to be undertaken with increased speed and cost effectiveness. This paper outlines a methodology that will enable solid lignocellulosic substrates to be hydrolyzed and fermented at a 96-well plate scale, facilitating HTP screening of ethanol production, whilst maintaining repeatability similar to that achieved at a larger scale. The results showed that utilizing sheets of biomass of consistent density (handbills), for paper, and slurries of pretreated biomass that could be pipetted allowed standardized and accurate transfers to 96-well plates to be achieved (±3.1 and 1.7%, respectively). Processing these substrates by simultaneous saccharification and fermentation (SSF) at various volumes showed no significant difference on final ethanol yields, either at standard shake flask (200 mL), universal bottle (10 mL) or 96-well plate (1 mL) scales. Substrate concentrations of up to 10% (w/v) were trialed successfully for SSFs at 1 mL volume. The methodology was successfully tested by showing the effects of steam explosion pretreatment on both oilseed rape and wheat straws. This methodology could be used to replace large shake flask reactions with comparatively fast 96-well plate SSF assays allowing for HTP experimentation. Additionally this method is compatible with a number of standardized assay techniques such as simple colorimetric, High-performance liquid chromatography (HPLC) and Nuclear magnetic resonance (NMR) spectroscopy. Furthermore this research has practical uses in the biorefining of biomass substrates for second generation biofuels and novel biobased chemicals by allowing HTP SSF screening, which should allow selected samples to be scaled up or studied in more detail.

Reply: Comparison of slope instability screening tools following a large storm event and application to forest management and policy

NASA Astrophysics Data System (ADS)

Whittaker, Kara A.; McShane, Dan

2013-02-01

A large storm event in southwest Washington State triggered over 2500 landslides and provided an opportunity to assess two slope stability screening tools. The statistical analysis conducted demonstrated that both screening tools are effective at predicting where landslides were likely to take place (Whittaker and McShane, 2012). Here we reply to two discussions of this article related to the development of the slope stability screening tools and the accuracy and scale of the spatial data used. Neither of the discussions address our statistical analysis or results. We provide greater detail on our sampling criteria and also elaborate on the policy and management implications of our findings and how they complement those of a separate investigation of landslides resulting from the same storm. The conclusions made in Whittaker and McShane (2012) stand as originally published unless future analysis indicates otherwise.

Improvement of a rapid screening test for chronic granulomatous disease.

PubMed

Iacobini, M; Duse, M; Di Coste, A; Balducci, L

2013-01-01

Diagnosis of CGD is made by demonstrating absent or markedly reduced oxidase activity in stimulated neutrophils. The screening test proposed is based upon the naked eye evaluation of the reduction of NBT on a solid surface. It seems to be a useful tool for rapid and inexpensive detection of CGD patients, especially for large-scale screening purposes. The test was carried out on forty-five subjects: two males affected by CGD, three female carriers and forty healthy donors. The test confirmed the results obtained with flow cytometric and NBT assays.

1001 Ways to run AutoDock Vina for virtual screening

NASA Astrophysics Data System (ADS)

Jaghoori, Mohammad Mahdi; Bleijlevens, Boris; Olabarriaga, Silvia D.

2016-03-01

Large-scale computing technologies have enabled high-throughput virtual screening involving thousands to millions of drug candidates. It is not trivial, however, for biochemical scientists to evaluate the technical alternatives and their implications for running such large experiments. Besides experience with the molecular docking tool itself, the scientist needs to learn how to run it on high-performance computing (HPC) infrastructures, and understand the impact of the choices made. Here, we review such considerations for a specific tool, AutoDock Vina, and use experimental data to illustrate the following points: (1) an additional level of parallelization increases virtual screening throughput on a multi-core machine; (2) capturing of the random seed is not enough (though necessary) for reproducibility on heterogeneous distributed computing systems; (3) the overall time spent on the screening of a ligand library can be improved by analysis of factors affecting execution time per ligand, including number of active torsions, heavy atoms and exhaustiveness. We also illustrate differences among four common HPC infrastructures: grid, Hadoop, small cluster and multi-core (virtual machine on the cloud). Our analysis shows that these platforms are suitable for screening experiments of different sizes. These considerations can guide scientists when choosing the best computing platform and set-up for their future large virtual screening experiments.

1001 Ways to run AutoDock Vina for virtual screening.

PubMed

Jaghoori, Mohammad Mahdi; Bleijlevens, Boris; Olabarriaga, Silvia D

2016-03-01

Large-scale computing technologies have enabled high-throughput virtual screening involving thousands to millions of drug candidates. It is not trivial, however, for biochemical scientists to evaluate the technical alternatives and their implications for running such large experiments. Besides experience with the molecular docking tool itself, the scientist needs to learn how to run it on high-performance computing (HPC) infrastructures, and understand the impact of the choices made. Here, we review such considerations for a specific tool, AutoDock Vina, and use experimental data to illustrate the following points: (1) an additional level of parallelization increases virtual screening throughput on a multi-core machine; (2) capturing of the random seed is not enough (though necessary) for reproducibility on heterogeneous distributed computing systems; (3) the overall time spent on the screening of a ligand library can be improved by analysis of factors affecting execution time per ligand, including number of active torsions, heavy atoms and exhaustiveness. We also illustrate differences among four common HPC infrastructures: grid, Hadoop, small cluster and multi-core (virtual machine on the cloud). Our analysis shows that these platforms are suitable for screening experiments of different sizes. These considerations can guide scientists when choosing the best computing platform and set-up for their future large virtual screening experiments.

A deep learning and novelty detection framework for rapid phenotyping in high-content screening

PubMed Central

Sommer, Christoph; Hoefler, Rudolf; Samwer, Matthias; Gerlich, Daniel W.

2017-01-01

Supervised machine learning is a powerful and widely used method for analyzing high-content screening data. Despite its accuracy, efficiency, and versatility, supervised machine learning has drawbacks, most notably its dependence on a priori knowledge of expected phenotypes and time-consuming classifier training. We provide a solution to these limitations with CellCognition Explorer, a generic novelty detection and deep learning framework. Application to several large-scale screening data sets on nuclear and mitotic cell morphologies demonstrates that CellCognition Explorer enables discovery of rare phenotypes without user training, which has broad implications for improved assay development in high-content screening. PMID:28954863

Electrostatic analogy for symmetron gravity

NASA Astrophysics Data System (ADS)

Ogden, Lillie; Brown, Katherine; Mathur, Harsh; Rovelli, Kevin

2017-12-01

The symmetron model is a scalar-tensor theory of gravity with a screening mechanism that suppresses the effect of the symmetron field at high densities characteristic of the Solar System and laboratory scales but allows it to act with gravitational strength at low density on the cosmological scale. We elucidate the screening mechanism by showing that in the quasistatic Newtonian limit there are precise analogies between symmetron gravity and electrostatics for both strong and weak screening. For strong screening we find that large dense bodies behave in a manner analogous to perfect conductors in electrostatics. Based on this analogy we find that the symmetron field exhibits a lightning rod effect wherein the field gradients are enhanced near the ends of pointed or elongated objects. An ellipsoid placed in a uniform symmetron gradient is shown to experience a torque. By symmetry there is no gravitational torque in this case. Hence this effect unmasks the symmetron and might serve as the basis for future laboratory experiments. The symmetron force between a point mass and a large dense body includes a component corresponding to the interaction of the point mass with its image in the larger body. None of these effects have counterparts in the Newtonian limit of Einstein gravity. We discuss the similarities between symmetron gravity and the chameleon model as well as the differences between the two.

Large scale generation of micro-droplet array by vapor condensation on mesh screen piece

PubMed Central

Xie, Jian; Xu, Jinliang; He, Xiaotian; Liu, Qi

2017-01-01

We developed a novel micro-droplet array system, which is based on the distinct three dimensional mesh screen structure and sintering and oxidation induced thermal-fluid performance. Mesh screen was sintered on a copper substrate by bonding the two components. Non-uniform residue stress is generated along weft wires, with larger stress on weft wire top location than elsewhere. Oxidation of the sintered package forms micro pits with few nanograsses on weft wire top location, due to the stress corrosion mechanism. Nanograsses grow elsewhere to show hydrophobic behavior. Thus, surface-energy-gradient weft wires are formed. Cooling the structure in a wet air environment nucleates water droplets on weft wire top location, which is more “hydrophilic” than elsewhere. Droplet size is well controlled by substrate temperature, air humidity and cooling time. Because warp wires do not contact copper substrate and there is a larger conductive thermal resistance between warp wire and weft wire, warp wires contribute less to condensation but function as supporting structure. The surface energy analysis of drops along weft wires explains why droplet array can be generated on the mesh screen piece. Because the commercial material is used, the droplet system is cost effective and can be used for large scale utilization. PMID:28054635

Large scale generation of micro-droplet array by vapor condensation on mesh screen piece.

PubMed

Xie, Jian; Xu, Jinliang; He, Xiaotian; Liu, Qi

2017-01-05

We developed a novel micro-droplet array system, which is based on the distinct three dimensional mesh screen structure and sintering and oxidation induced thermal-fluid performance. Mesh screen was sintered on a copper substrate by bonding the two components. Non-uniform residue stress is generated along weft wires, with larger stress on weft wire top location than elsewhere. Oxidation of the sintered package forms micro pits with few nanograsses on weft wire top location, due to the stress corrosion mechanism. Nanograsses grow elsewhere to show hydrophobic behavior. Thus, surface-energy-gradient weft wires are formed. Cooling the structure in a wet air environment nucleates water droplets on weft wire top location, which is more "hydrophilic" than elsewhere. Droplet size is well controlled by substrate temperature, air humidity and cooling time. Because warp wires do not contact copper substrate and there is a larger conductive thermal resistance between warp wire and weft wire, warp wires contribute less to condensation but function as supporting structure. The surface energy analysis of drops along weft wires explains why droplet array can be generated on the mesh screen piece. Because the commercial material is used, the droplet system is cost effective and can be used for large scale utilization.

Large scale generation of micro-droplet array by vapor condensation on mesh screen piece

NASA Astrophysics Data System (ADS)

Xie, Jian; Xu, Jinliang; He, Xiaotian; Liu, Qi

2017-01-01

We developed a novel micro-droplet array system, which is based on the distinct three dimensional mesh screen structure and sintering and oxidation induced thermal-fluid performance. Mesh screen was sintered on a copper substrate by bonding the two components. Non-uniform residue stress is generated along weft wires, with larger stress on weft wire top location than elsewhere. Oxidation of the sintered package forms micro pits with few nanograsses on weft wire top location, due to the stress corrosion mechanism. Nanograsses grow elsewhere to show hydrophobic behavior. Thus, surface-energy-gradient weft wires are formed. Cooling the structure in a wet air environment nucleates water droplets on weft wire top location, which is more “hydrophilic” than elsewhere. Droplet size is well controlled by substrate temperature, air humidity and cooling time. Because warp wires do not contact copper substrate and there is a larger conductive thermal resistance between warp wire and weft wire, warp wires contribute less to condensation but function as supporting structure. The surface energy analysis of drops along weft wires explains why droplet array can be generated on the mesh screen piece. Because the commercial material is used, the droplet system is cost effective and can be used for large scale utilization.

ESRI applications of GIS technology: Mineral resource development

NASA Technical Reports Server (NTRS)

Derrenbacher, W.

1981-01-01

The application of geographic information systems technology to large scale regional assessment related to mineral resource development, identifying candidate sites for related industry, and evaluating sites for waste disposal is discussed. Efforts to develop data bases were conducted at scales ranging from 1:3,000,000 to 1:25,000. In several instances, broad screening was conducted for large areas at a very general scale with more detailed studies subsequently undertaken in promising areas windowed out of the generalized data base. Increasingly, the systems which are developed are structured as the spatial framework for the long-term collection, storage, referencing, and retrieval of vast amounts of data about large regions. Typically, the reconnaissance data base for a large region is structured at 1:250,000 scale, data bases for smaller areas being structured at 1:25,000, 1:50,000 or 1:63,360. An integrated data base for the coterminous US was implemented at a scale of 1:3,000,000 for two separate efforts.

High-throughput cocrystal slurry screening by use of in situ Raman microscopy and multi-well plate.

PubMed

Kojima, Takashi; Tsutsumi, Shunichirou; Yamamoto, Katsuhiko; Ikeda, Yukihiro; Moriwaki, Toshiya

2010-10-31

Cocrystal has attracted much attention in order to improve poor physicochemical properties, since cocrystal former crystallize with the ionic drugs as well as nonionic drugs. Cocrystal screening was usually conducted by crystallization, slurry and co-grinding techniques, however sensitivity, cost and time for screening were limited because of issues such as dissociation of cocrystal during crystallization and cost and time required for slurry and co-grinding methods. To overcome these issues, novel high-throughput cocrystal slurry screening was developed by using in situ Raman microscope and a multi-well plate. Cocrystal screening of indomethacin was conducted with 46 cocrystal formers and potential cocrystals were prepared on a large scale for the characterization with powder X-ray diffractometry, thermal analysis, and Raman microscopy and (1)H NMR spectroscopy. Compared with the characterization of scale-up cocrystals, the cocrystal screening indicated that indomethacin structured novel cocrystals with D/L-mandelic acid, nicotinamide, lactamide and benzamide which was not obtained in the screening with crystallization technique previously reported. In addition, the screening provided not only information of cocrystal formation within a day but also information of equilibrium of cocrystal formation and polymorphic transformation in one screening. Information obtained in this screening allows effective solid form selection by saving cost and time for the development. Copyright © 2010 Elsevier B.V. All rights reserved.

Evaluation of scaling-up of HPV self-collection offered by community health workers at home visits to increase screening among socially vulnerable under-screened women in Jujuy Province, Argentina.

PubMed

Arrossi, Silvina; Paolino, Melisa; Thouyaret, Laura; Laudi, Rosa; Campanera, Alicia

2017-02-13

Self-collection has been proposed as a strategy to increase cervical screening coverage among hard-to-reach women. However, evaluations of the implementation of this strategy on a large scale are scarce. This paper describes the process and measurement of the scaling-up of self-collection offered by community health workers during home visits as a strategy to reach under-screened women aged 30+ with public health coverage, defined as the target women. We used an adaptation of the Health System Framework to analyze key drivers of scaling-up. A content analysis approach was used to collect and analyze information from different sources. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) model was used to evaluate the impact of the strategy. HPV self-collection was scaled-up in the province of Jujuy in 2014 after a RCT (Self-collection Modality Trial, initials EMA in Spanish) was carried out locally in 2012 and demonstrated effectiveness of the strategy to increase screening uptake. Facilitators of scaling-up were the organizational capacity of the provincial health system, sustainable funding for HPV testing, and local consensus about the value of the technology. Reach: In 2014, 9% (2983/33,245) of target women were screened through self-collection in the Jujuy public health sector. Effectiveness: In 2014, 17% (n = 5657/33,245) of target women were screened with any HPV test (self-collected and clinician-collected tests) vs. 11.7% (4579/38,981) in 2013, the pre-scaling-up period (p < 0.0001). Training about the strategy was provided to 84.2% (n = 609/723) of total community health workers (CHWs). Of 414 HPV+ women, 77.5% (n = 320) had follow-up procedures. Of 113 women with positive triage, 66.4% (n = 75) had colposcopic diagnosis. Treatment was provided to 80.7% of CIN2+ women (n = 21/26). Adoption: Of trained CHWs, 69.3% (n = 422/609) had at least one woman with self-collection; 85.2% (n = 315/368) of CHWs who responded to an evaluation survey were satisfied with self-collection strategy. Maintenance: During 2015, 100.0% (723/723) CHWs were operational and 63.8% (461/723) had at least one woman with self-collection. The strategy was successfully scaled-up, with a high level of adoption among CHWs, which resulted in increased screening among socially vulnerable under-screened women.

Integrated Energy Solutions | NREL

Science.gov Websites

Transitions A man and woman standing in front of a large, color 3D visualization screen that spans the height a woman and a man testing a scaled model of a microgrid controller in a laboratory setting

Multiplexed analysis of protein-ligand interactions by fluorescence anisotropy in a microfluidic platform.

PubMed

Cheow, Lih Feng; Viswanathan, Ramya; Chin, Chee-Sing; Jennifer, Nancy; Jones, Robert C; Guccione, Ernesto; Quake, Stephen R; Burkholder, William F

2014-10-07

Homogeneous assay platforms for measuring protein-ligand interactions are highly valued due to their potential for high-throughput screening. However, the implementation of these multiplexed assays in conventional microplate formats is considerably expensive due to the large amounts of reagents required and the need for automation. We implemented a homogeneous fluorescence anisotropy-based binding assay in an automated microfluidic chip to simultaneously interrogate >2300 pairwise interactions. We demonstrated the utility of this platform in determining the binding affinities between chromatin-regulatory proteins and different post-translationally modified histone peptides. The microfluidic chip assay produces comparable results to conventional microtiter plate assays, yet requires 2 orders of magnitude less sample and an order of magnitude fewer pipetting steps. This approach enables one to use small samples for medium-scale screening and could ease the bottleneck of large-scale protein purification.

Detection of large scale 3′ deletions in the PMS2 gene amongst Colon-CFR participants – have we been missing anything?

PubMed Central

Clendenning, Mark; Walsh, Michael D; Gelpi, Judith Balmana; Thibodeau, Stephen N.; Lindor, Noralane; Potter, John D.; Newcomb, Polly; LeMarchand, Loic; Haile, Robert; Gallinger, Steve; Hopper, John L.; Jenkins, Mark A.; Rosty, Christophe; Young, Joanne P.; Buchanan, Daniel D.

2013-01-01

Current screening practices have been able to identify PMS2 mutations in 78% of cases of colorectal cancer from the Colorectal Cancer Family Registry (Colon CFR) which showed solitary loss of the PMS2 protein. However the detection of large-scale deletions in the 3′ end of the PMS2 gene has not been possible due to technical difficulties associated with pseudogene sequences. Here, we utilised a recently described MLPA/long-range PCR-based approach to screen the remaining 22% (n = 16) of CRC-affected probands for mutations in the 3′ end of the PMS2 gene. No deletions encompassing any or all of exons 12 through 15 were identified; therefore, our results suggest that 3′ deletions in PMS2 are not a frequent occurrence in such families. PMID:23288611

Population Screening for Chronic Q-Fever Seven Years after a Major Outbreak

PubMed Central

Morroy, Gabriëlla; van der Hoek, Wim; Albers, Jelle; Coutinho, Roel A.; Bleeker-Rovers, Chantal P.; Schneeberger, Peter M.

2015-01-01

Introduction From 2007 through 2010, the Netherlands experienced a large Q-fever epidemic, with 4,107 notifications. The most serious complication of Q-fever is chronic Q-fever. Method In 2014, we contacted all 2,161 adult inhabitants of the first village in the Netherlands affected by the Q-fever epidemic and offered to test for antibodies against Coxiella burnetii using immunofluorescence assay (IFA) to screen for chronic infections and assess whether large-scale population screening elsewhere is warranted. Results Of the 1,517 participants, 33.8% were IFA-positive. Six IFA-positive participants had an IgG phase I titer ≥1:512. Two of these six participants were previously diagnosed with chronic Q-fever. Chronic infection was diagnosed in one of the other four participants after clinical examination. Conclusions Seven years after the initial outbreak, seroprevalence remains high, but the yield of screening the general population for chronic Q-fever is low. A policy of screening known high-risk groups for chronic Q-fever in outbreak areas directly following an outbreak might be more efficient than population screening. A cost-effectiveness analysis should also be performed before initiating a population screening program for chronic Q-fever. PMID:26132155

Tuberculosis screening prior to anti-tumor necrosis factor therapy among patients with immune-mediated inflammatory diseases in Japan: a longitudinal study using a large-scale health insurance claims database.

PubMed

Tomio, Jun; Yamana, Hayato; Matsui, Hiroki; Yamashita, Hiroyuki; Yoshiyama, Takashi; Yasunaga, Hideo

2017-11-01

Tuberculosis screening is recommended for patients with immune-mediated inflammatory diseases (IMIDs) prior to anti-tumor necrosis factor (TNF) therapy. However, adherence to the recommended practice is unknown in the current clinical setting in Japan. We used a large-scale health insurance claims database in Japan to conduct a longitudinal observational study. Of more than two million beneficiaries in the database between 2013 and 2014, we enrolled those with IMIDs aged 15-69 years who had initiated anti-TNF therapy. We defined tuberculosis screening primarily as tuberculin skin test and/or interferon-gamma release assay (TST/IGRA) within 2 months before commencing anti-TNF therapy. We analyzed the proportions of the patients who had undergone tuberculosis screening and the associations with primary disease, type of anti-TNF agent, methotrexate prescription prior to anti-TNF therapy, and treatment for latent tuberculosis infection (LTBI). Of 385 patients presumed to have initiated anti-TNF therapy, 252 (66%) had undergone tuberculosis screening by TST/IGRA (22% TST, 56% IGRA, and 12% both TST and IGRA), and 231 (60%) had undergone TST/IGRA and radiography. Patients with psoriasis tended to be more likely to undergo tuberculosis screening than those with other diseases; however, this association was not statistically significant. Treatment for LTBI was provided to 43 (11%) patients; 123 (32%) received neither TST/IGRA nor LTBI treatment. Tuberculosis screening was often not performed prior to anti-TNF therapy despite the guidelines' recommendations; thus, patients could be put at unnecessary risk of reactivation of tuberculosis. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Test-retest reliability of the Capute scales for neurodevelopmental screening of a high risk sample: Impact of test-retest interval and degree of neonatal risk.

PubMed

McCurdy, M; Bellows, A; Deng, D; Leppert, M; Mahone, E; Pritchard, A

2015-01-01

Reliable and valid screening and assessment tools are necessary to identify children at risk for neurodevelopmental disabilities who may require additional services. This study evaluated the test-retest reliability of the Capute Scales in a high-risk sample, hypothesizing adequate reliability across 6- and 12-month intervals. Capute Scales scores (N = 66) were collected via retrospective chart review from a NICU follow-up clinic within a large urban medical center spanning three age-ranges: 12-18, 19-24, and 25-36 months. On average, participants were classified as very low birth weight and premature. Reliability of the Capute Scales was evaluated with intraclass correlation coefficients across length of test-retest interval, age at testing, and degree of neonatal complications. The Capute Scales demonstrated high reliability, regardless of length of test-retest interval (ranging from 6 to 14 months) or age of participant, for all index scores, including overall Developmental Quotient (DQ), language-based skill index (CLAMS) and nonverbal reasoning index (CAT). Linear regressions revealed that greater neonatal risk was related to poorer test-retest reliability; however, reliability coefficients remained strong. The Capute Scales afford clinicians a reliable and valid means of screening and assessing for neurodevelopmental delay within high-risk infant populations.

Improved sugar yields from biomass sorghum feedstocks: comparing low-lignin mutants and pretreatment chemistries.

PubMed

Godin, Bruno; Nagle, Nick; Sattler, Scott; Agneessens, Richard; Delcarte, Jérôme; Wolfrum, Edward

2016-01-01

For biofuel production processes to be economically efficient, it is essential to maximize the production of monomeric carbohydrates from the structural carbohydrates of feedstocks. One strategy for maximizing carbohydrate production is to identify less recalcitrant feedstock cultivars by performing some type of experimental screening on a large and diverse set of candidate materials, or by identifying genetic modifications (random or directed mutations or transgenic plants) that provide decreased recalcitrance. Economic efficiency can also be increased using additional pretreatment processes such as deacetylation, which uses dilute NaOH to remove the acetyl groups of hemicellulose prior to dilute acid pretreatment. In this work, we used a laboratory-scale screening tool that mimics relevant thermochemical pretreatment conditions to compare the total sugar yield of three near-isogenic brown midrib ( bmr ) mutant lines and the wild-type (WT) sorghum cultivar. We then compared results obtained from the laboratory-scale screening pretreatment assay to a large-scale pretreatment system. After pretreatment and enzymatic hydrolysis, the bmr mutants had higher total sugar yields than the WT sorghum cultivar. Increased pretreatment temperatures increased reactivity for all sorghum samples reducing the differences observed at lower reaction temperatures. Deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples, and reduced the differences in total sugar yields among them, but solubilized a sizable fraction of the non-structural carbohydrates. The general trends of increased total sugar yield in the bmr mutant compared to the WT seen at the laboratory scale were observed at the large-scale system. However, in the larger reactor system, the measured total sugar yields were lower and the difference in total sugar yield between the WT and bmr sorghum was larger. Sorghum bmr mutants, which have a reduced lignin content showed higher total sugar yields than the WT cultivar after dilute acid pretreatment and enzymatic hydrolysis. Deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples. However, since deacetylation also solubilizes a large fraction of the non-structural carbohydrates, the ability to derive value from these solubilized sugars will depend greatly on the proposed conversion process.

Improved sugar yields from biomass sorghum feedstocks: comparing low-lignin mutants and pretreatment chemistries

DOE PAGES

Godin, Bruno; Nagle, Nick; Sattler, Scott; ...

2016-11-21

For biofuel production processes to be economically efficient, it is essential to maximize the production of monomeric carbohydrates from the structural carbohydrates of feedstocks. One strategy for maximizing carbohydrate production is to identify less recalcitrant feedstock cultivars by performing some type of experimental screening on a large and diverse set of candidate materials, or by identifying genetic modifications (random or directed mutations or transgenic plants) that provide decreased recalcitrance. Economic efficiency can also be increased using additional pretreatment processes such as deacetylation, which uses dilute NaOH to remove the acetyl groups of hemicellulose prior to dilute acid pretreatment. In thismore » work, we used a laboratory-scale screening tool that mimics relevant thermochemical pretreatment conditions to compare the total sugar yield of three near-isogenic brown midrib (bmr) mutant lines and the wild-type (WT) sorghum cultivar. We then compared results obtained from the laboratory-scale screening pretreatment assay to a large-scale pretreatment system. After pretreatment and enzymatic hydrolysis, the bmr mutants had higher total sugar yields than the WT sorghum cultivar. Increased pretreatment temperatures increased reactivity for all sorghum samples reducing the differences observed at lower reaction temperatures. Deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples, and reduced the differences in total sugar yields among them, but solubilized a sizable fraction of the non-structural carbohydrates. The general trends of increased total sugar yield in the bmr mutant compared to the WT seen at the laboratory scale were observed at the large-scale system. However, in the larger reactor system, the measured total sugar yields were lower and the difference in total sugar yield between the WT and bmr sorghum was larger. Sorghum bmr mutants, which have a reduced lignin content showed higher total sugar yields than the WT cultivar after dilute acid pretreatment and enzymatic hydrolysis. In conclusion, deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples. However, since deacetylation also solubilizes a large fraction of the non-structural carbohydrates, the ability to derive value from these solubilized sugars will depend greatly on the proposed conversion process.« less

Improved sugar yields from biomass sorghum feedstocks: comparing low-lignin mutants and pretreatment chemistries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Godin, Bruno; Nagle, Nick; Sattler, Scott

For biofuel production processes to be economically efficient, it is essential to maximize the production of monomeric carbohydrates from the structural carbohydrates of feedstocks. One strategy for maximizing carbohydrate production is to identify less recalcitrant feedstock cultivars by performing some type of experimental screening on a large and diverse set of candidate materials, or by identifying genetic modifications (random or directed mutations or transgenic plants) that provide decreased recalcitrance. Economic efficiency can also be increased using additional pretreatment processes such as deacetylation, which uses dilute NaOH to remove the acetyl groups of hemicellulose prior to dilute acid pretreatment. In thismore » work, we used a laboratory-scale screening tool that mimics relevant thermochemical pretreatment conditions to compare the total sugar yield of three near-isogenic brown midrib (bmr) mutant lines and the wild-type (WT) sorghum cultivar. We then compared results obtained from the laboratory-scale screening pretreatment assay to a large-scale pretreatment system. After pretreatment and enzymatic hydrolysis, the bmr mutants had higher total sugar yields than the WT sorghum cultivar. Increased pretreatment temperatures increased reactivity for all sorghum samples reducing the differences observed at lower reaction temperatures. Deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples, and reduced the differences in total sugar yields among them, but solubilized a sizable fraction of the non-structural carbohydrates. The general trends of increased total sugar yield in the bmr mutant compared to the WT seen at the laboratory scale were observed at the large-scale system. However, in the larger reactor system, the measured total sugar yields were lower and the difference in total sugar yield between the WT and bmr sorghum was larger. Sorghum bmr mutants, which have a reduced lignin content showed higher total sugar yields than the WT cultivar after dilute acid pretreatment and enzymatic hydrolysis. In conclusion, deacetylation prior to dilute acid pretreatment increased the total sugar yield for all four sorghum samples. However, since deacetylation also solubilizes a large fraction of the non-structural carbohydrates, the ability to derive value from these solubilized sugars will depend greatly on the proposed conversion process.« less

Full-scale high-speed ``Edgerton'' retroreflective shadowgraphy of gunshots

NASA Astrophysics Data System (ADS)

Settles, Gary

2005-11-01

Almost 1/2 century ago, H. E. ``Doc'' Edgerton demonstrated a simple and elegant direct-shadowgraph technique for imaging large-scale events like explosions and gunshots. Only a retroreflective screen, flashlamp illumination, and an ordinary view camera were required. Retroreflective shadowgraphy has seen occasional use since then, but its unique combination of large scale, simplicity and portability has barely been tapped. It functions well in environments hostile to most optical diagnostics, such as full-scale outdoor daylight ballistics and explosives testing. Here, shadowgrams cast upon a 2.4 m square retroreflective screen are imaged by a Photron Fastcam APX-RS digital camera that is capable of megapixel image resolution at 3000 frames/sec up to 250,000 frames/sec at lower resolution. Microsecond frame exposures are used to examine the external ballistics of several firearms, including a high-powered rifle, an AK-47 submachine gun, and several pistols and revolvers. Muzzle blast phenomena and the mechanism of gunpowder residue deposition on the shooter's hands are clearly visualized. In particular, observing the firing of a pistol with and without a silencer (suppressor) suggests that some of the muzzle blast energy is converted by the silencer into supersonic jet noise.

Reliability and Validity of the KIPPPI: An Early Detection Tool for Psychosocial Problems in Toddlers

PubMed Central

Kruizinga, Ingrid; Jansen, Wilma; de Haan, Carolien L.; Raat, Hein

2012-01-01

Background The KIPPPI (Brief Instrument Psychological and Pedagogical Problem Inventory) is a Dutch questionnaire that measures psychosocial and pedagogical problems in 2-year olds and consists of a KIPPPI Total score, Wellbeing scale, Competence scale, and Autonomy scale. This study examined the reliability, validity, screening accuracy and clinical application of the KIPPPI. Methods Parents of 5959 2-year-old children in the Rotterdam area, the Netherlands, were invited to participate in the study. Parents of 3164 children (53.1% of all invited parents) completed the questionnaire. The internal consistency was evaluated and in subsamples the test-retest reliability and concurrent validity with regard to the Child Behavioral Checklist (CBCL). Discriminative validity was evaluated by comparing scores of parents who worried about their child’s upbringing and parent’s that did not. Screening accuracy of the KIPPPI was evaluated against the CBCL by calculating the Receiver Operating Characteristic (ROC) curves. The clinical application was evaluated by the relation between KIPPPI scores and the clinical decision made by the child health professionals. Results Psychometric properties of the KIPPPI Total score, Wellbeing scale, Competence scale and Autonomy scale were respectively: Cronbach’s alphas: 0.88, 0.86, 0.83, 0.58. Test-retest correlations: 0.80, 0.76, 0.73, 0.60. Concurrent validity was as hypothesised. The KIPPPI was able to discriminate between parents that worried about their child and parents that did not. Screening accuracy was high (>0.90) for the KIPPPI Total score and for the Wellbeing scale. The KIPPPI scale scores and clinical decision of the child health professional were related (p<0.05), indicating a good clinical application. Conclusion The results in this large-scale study of a diverse general population sample support the reliability, validity and clinical application of the KIPPPI Total score, Wellbeing scale and Competence scale. Also, the screening accuracy of the KIPPPI Total score and Wellbeing scale were supported. The Autonomy scale needs further study. PMID:23185388

High content screening in microfluidic devices

PubMed Central

Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

2011-01-01

Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

Consumer preferences for teledermoscopy screening to detect melanoma early.

PubMed

Spinks, Jean; Janda, Monika; Soyer, H Peter; Whitty, Jennifer A

2016-01-01

'Store and forward' teledermoscopy is a technology with potential advantages for melanoma screening. Any large-scale implementation of this technology is dependent on consumer acceptance. To investigate preferences for melanoma screening options compared with skin self-examination in adults considered to be at increased risk of developing skin cancer. A discrete choice experiment was completed by 35 consumers, all of whom had prior experience with the use of teledermoscopy, in Queensland, Australia. Participants made 12 choices between screening alternatives described by seven attributes including monetary cost. A mixed logit model was used to estimate the relative weights that consumers place on different aspects of screening, along with the marginal willingness to pay for teledermoscopy as opposed to screening at a clinic. Overall, participants preferred screening/diagnosis by a health professional rather than skin self-examination. Key drivers of screening choice were for results to be reviewed by a dermatologist; a higher detection rate; fewer non-cancerous moles being removed in relation to every skin cancer detected; and less time spent away from usual activities. On average, participants were willing to pay AUD110 to have teledermoscopy with dermatologist review available to them as a screening option. Consumers preferentially value aspects of care that are more feasible with a teledermoscopy screening model, as compared with other skin cancer screening and diagnosis options. This study adds to previous literature in the area which has relied on the use of consumer satisfaction scales to assess the acceptability of teledermoscopy. © The Author(s) 2015.

MIPHENO: Data normalization for high throughput metabolic analysis.

EPA Science Inventory

High throughput methodologies such as microarrays, mass spectrometry and plate-based small molecule screens are increasingly used to facilitate discoveries from gene function to drug candidate identification. These large-scale experiments are typically carried out over the course...

Evaluation of the reliability and validity for X16 balance testing scale for the elderly.

PubMed

Ju, Jingjuan; Jiang, Yu; Zhou, Peng; Li, Lin; Ye, Xiaolei; Wu, Hongmei; Shen, Bin; Zhang, Jialei; He, Xiaoding; Niu, Chunjin; Xia, Qinghua

2018-05-10

Balance performance is considered as an indicator of functional status in the elderly, a large scale population screening and evaluation in the community context followed by proper interventions would be of great significance at public health level. However, there has been no suitable balance testing scale available for large scale studies in the unique community context of urban China. A balance scale named X16 balance testing scale was developed, which was composed of 3 domains and 16 items. A total of 1985 functionally independent and active community-dwelling elderly adults' balance abilities were tested using the X16 scale. The internal consistency, split-half reliability, content validity, construct validity, discriminant validity of X16 balance testing scale were evaluated. Factor analysis was performed to identify alternative factor structure. The Eigenvalues of factors 1, 2, and 3 were 8.53, 1.79, and 1.21, respectively, and their cumulative contribution to the total variance reached 72.0%. These 3 factors mainly represented domains static balance, postural stability, and dynamic balance. The Cronbach alpha coefficient for the scale was 0.933. The Spearman correlation coefficients between items and its corresponding domains were ranged from 0.538 to 0.964. The correlation coefficients between each item and its corresponding domain were higher than the coefficients between this item and other domains. With the increase of age, the scores of balance performance, domains static balance, postural stability, and dynamic balance in the elderly declined gradually (P < 0.001). With the increase of age, the proportion of the elderly with intact balance performance decreased gradually (P < 0.001). The reliability and validity of the X16 balance testing scale is both adequate and acceptable. Due to its simple and quick use features, it is practical to be used repeatedly and routinely especially in community setting and on large scale screening.

Fabrication of aluminum-carbon composites

NASA Technical Reports Server (NTRS)

Novak, R. C.

1973-01-01

A screening, optimization, and evaluation program is reported of unidirectional carbon-aluminum composites. During the screening phase both large diameter monofilament and small diameter multifilament reinforcements were utilized to determine optimum precursor tape making and consolidation techniques. Difficulty was encountered in impregnating and consolidating the multifiber reinforcements. Large diameter monofilament reinforcement was found easier to fabricate into composites and was selected to carry into the optimization phase in which the hot pressing parameters were refined and the size of the fabricated panels was scaled up. After process optimization the mechanical properties of the carbon-aluminum composites were characterized in tension, stress-rupture and creep, mechanical fatigue, thermal fatigue, thermal aging, thermal expansion, and impact.

Large-scale functional RNAi screen in C. elegans identifies genes that regulate the dysfunction of mutant polyglutamine neurons

PubMed Central

2012-01-01

Background A central goal in Huntington's disease (HD) research is to identify and prioritize candidate targets for neuroprotective intervention, which requires genome-scale information on the modifiers of early-stage neuron injury in HD. Results Here, we performed a large-scale RNA interference screen in C. elegans strains that express N-terminal huntingtin (htt) in touch receptor neurons. These neurons control the response to light touch. Their function is strongly impaired by expanded polyglutamines (128Q) as shown by the nearly complete loss of touch response in adult animals, providing an in vivo model in which to manipulate the early phases of expanded-polyQ neurotoxicity. In total, 6034 genes were examined, revealing 662 gene inactivations that either reduce or aggravate defective touch response in 128Q animals. Several genes were previously implicated in HD or neurodegenerative disease, suggesting that this screen has effectively identified candidate targets for HD. Network-based analysis emphasized a subset of high-confidence modifier genes in pathways of interest in HD including metabolic, neurodevelopmental and pro-survival pathways. Finally, 49 modifiers of 128Q-neuron dysfunction that are dysregulated in the striatum of either R/2 or CHL2 HD mice, or both, were identified. Conclusions Collectively, these results highlight the relevance to HD pathogenesis, providing novel information on the potential therapeutic targets for neuroprotection in HD. PMID:22413862

Large-scale functional RNAi screen in C. elegans identifies genes that regulate the dysfunction of mutant polyglutamine neurons.

PubMed

Lejeune, François-Xavier; Mesrob, Lilia; Parmentier, Frédéric; Bicep, Cedric; Vazquez-Manrique, Rafael P; Parker, J Alex; Vert, Jean-Philippe; Tourette, Cendrine; Neri, Christian

2012-03-13

A central goal in Huntington's disease (HD) research is to identify and prioritize candidate targets for neuroprotective intervention, which requires genome-scale information on the modifiers of early-stage neuron injury in HD. Here, we performed a large-scale RNA interference screen in C. elegans strains that express N-terminal huntingtin (htt) in touch receptor neurons. These neurons control the response to light touch. Their function is strongly impaired by expanded polyglutamines (128Q) as shown by the nearly complete loss of touch response in adult animals, providing an in vivo model in which to manipulate the early phases of expanded-polyQ neurotoxicity. In total, 6034 genes were examined, revealing 662 gene inactivations that either reduce or aggravate defective touch response in 128Q animals. Several genes were previously implicated in HD or neurodegenerative disease, suggesting that this screen has effectively identified candidate targets for HD. Network-based analysis emphasized a subset of high-confidence modifier genes in pathways of interest in HD including metabolic, neurodevelopmental and pro-survival pathways. Finally, 49 modifiers of 128Q-neuron dysfunction that are dysregulated in the striatum of either R/2 or CHL2 HD mice, or both, were identified. Collectively, these results highlight the relevance to HD pathogenesis, providing novel information on the potential therapeutic targets for neuroprotection in HD. © 2012 Lejeune et al; licensee BioMed Central Ltd.

RNAi Screening in Spodoptera frugiperda.

PubMed

Ghosh, Subhanita; Singh, Gatikrushna; Sachdev, Bindiya; Kumar, Ajit; Malhotra, Pawan; Mukherjee, Sunil K; Bhatnagar, Raj K

2016-01-01

RNA interference is a potent and precise reverse genetic approach to carryout large-scale functional genomic studies in a given organism. During the past decade, RNAi has also emerged as an important investigative tool to understand the process of viral pathogenesis. Our laboratory has successfully generated transgenic reporter and RNAi sensor line of Spodoptera frugiperda (Sf21) cells and developed a reversal of silencing assay via siRNA or shRNA guided screening to investigate RNAi factors or viral pathogenic factors with extraordinary fidelity. Here we describe empirical approaches and conceptual understanding to execute successful RNAi screening in Spodoptera frugiperda 21-cell line.

Production of arrays of chemically distinct nanolitre plugs via repeated splitting in microfluidic devices.

PubMed

Adamson, David N; Mustafi, Debarshi; Zhang, John X J; Zheng, Bo; Ismagilov, Rustem F

2006-09-01

This paper reports a method for the production of arrays of nanolitre plugs with distinct chemical compositions. One of the primary constraints on the use of plug-based microfluidics for large scale biological screening is the difficulty of fabricating arrays of chemically distinct plugs on the nanolitre scale. Here, using microfluidic devices with several T-junctions linked in series, a single input array of large (approximately 320 nL) plugs was split to produce 16 output arrays of smaller (approximately 20 nL) plugs; the composition and configuration of these arrays were identical to that of the input. This paper shows how the passive break-up of plugs in T-junction microchannel geometries can be used to produce a set of smaller-volume output arrays useful for chemical screening from a single large-volume array. A simple theoretical description is presented to describe splitting as a function of the Capillary number, the capillary pressure, the total pressure difference across the channel, and the geometric fluidic resistance. By accounting for these considerations, plug coalescence and plug-plug contamination can be eliminated from the splitting process and the symmetry of splitting can be preserved. Furthermore, single-outlet splitting devices were implemented with both valve- and volume-based methods for coordinating the release of output arrays. Arrays of plugs containing commercial sparse matrix screens were obtained from the presented splitting method and these arrays were used in protein crystallization trials. The techniques presented in this paper may facilitate the implementation of high-throughput chemical and biological screening.

Q Sepharose micro-column chromatography: A simple screening method for identifying beta thalassemia traits and hemoglobin E carriers.

PubMed

Wong, Peerapon; Sritippayawan, Suchila; Suwannakhon, Narutchala; Tapprom, Akamon; Deoisares, Rawisut; Sanguansermsri, Torpong

2016-11-01

For beta thalassemia control program in pregnancy, mass screening of the carrier state by determination of the hemoglobin (Hb) A 2 and Hb E proportions and mutation analysis is a preferred method for making prenatal diagnoses. Q Sepharose micro-column chromatography, developed for the determination of Hb A 2 and Hb E for screening purposes, was compared with high performance liquid chromatography (HPLC) to ascertain its relative accuracy and reliability. Results using Q Sepharose micro-column chromatography in 350 blood specimens, including 50 samples genetically proven to be beta thalassemia heterozygotes, were compared to HPLC for validation. An additional study was conducted to test a clinical application on a large-scale survey for beta thalassemia in 1581 pregnant women and their spouses. The mean (±SD) Hb A 2 proportions in the normal and genetically proven beta thalassemia heterozygotes were 2.70±0.40% and 6.30±1.23%, respectively, as determined by Q-Sepharose micro-column chromatography, and 2.65±0.31% and 5.37±0.96%, respectively, as determined by HPLC. The mean Hb E proportions in the Hb E heterozygotes were 23.25±4.13% and 24.72±3.5% as determined by Q Sepharose micro-column chromatography and HPLC, respectively. In the large-scale survey for beta thalassemia, 23 at risk couples were detected. Seven affected fetuses were identified by prenatal diagnosis. Q Sepharose micro-column chromatography was found to be reliable, reproducible and well-suited for large-scale surveys. Additionally, by being reusable and convenient, this simple and economical chromatography method may be an alternative means to screen for beta thalassemia and Hb E carriers in the mass population. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

PinAPL-Py: A comprehensive web-application for the analysis of CRISPR/Cas9 screens.

PubMed

Spahn, Philipp N; Bath, Tyler; Weiss, Ryan J; Kim, Jihoon; Esko, Jeffrey D; Lewis, Nathan E; Harismendy, Olivier

2017-11-20

Large-scale genetic screens using CRISPR/Cas9 technology have emerged as a major tool for functional genomics. With its increased popularity, experimental biologists frequently acquire large sequencing datasets for which they often do not have an easy analysis option. While a few bioinformatic tools have been developed for this purpose, their utility is still hindered either due to limited functionality or the requirement of bioinformatic expertise. To make sequencing data analysis of CRISPR/Cas9 screens more accessible to a wide range of scientists, we developed a Platform-independent Analysis of Pooled Screens using Python (PinAPL-Py), which is operated as an intuitive web-service. PinAPL-Py implements state-of-the-art tools and statistical models, assembled in a comprehensive workflow covering sequence quality control, automated sgRNA sequence extraction, alignment, sgRNA enrichment/depletion analysis and gene ranking. The workflow is set up to use a variety of popular sgRNA libraries as well as custom libraries that can be easily uploaded. Various analysis options are offered, suitable to analyze a large variety of CRISPR/Cas9 screening experiments. Analysis output includes ranked lists of sgRNAs and genes, and publication-ready plots. PinAPL-Py helps to advance genome-wide screening efforts by combining comprehensive functionality with user-friendly implementation. PinAPL-Py is freely accessible at http://pinapl-py.ucsd.edu with instructions and test datasets.

Does the evidence support population-wide screening for type 2 diabetes? No.

PubMed

Shaw, Jonathan E

2017-11-01

Large-scale, centrally-coordinated screening for undiagnosed type 2 diabetes is an attractive option to reduce the mortality and morbidity resulting from inadequately controlled diabetes. However, there is limited research examining the direct consequences of such screening programmes on outcomes such as cardiovascular disease and death. Two papers published in this edition of Diabetologia (DOIs: 10.1007/s00125-017-4323-2 and 10.1007/s00125-017-4299-y ) examine data from one of the very few trials conducted in this area. Overall, there was little benefit that could be directly related to the screening programme. In part, this was due to the high levels of opportunistic screening in the control group. Thus, when there are high levels of opportunistic screening for type 2 diabetes, there remains no clear evidence of benefit of centrally-coordinated screening programmes that approach individuals outside usual healthcare settings.

Pilot study of large-scale production of mutant pigs by ENU mutagenesis

PubMed Central

Hai, Tang; Cao, Chunwei; Shang, Haitao; Guo, Weiwei; Mu, Yanshuang; Yang, Shulin; Zhang, Ying; Zheng, Qiantao; Zhang, Tao; Wang, Xianlong; Liu, Yu; Kong, Qingran; Li, Kui; Wang, Dayu; Qi, Meng; Hong, Qianlong; Zhang, Rui; Wang, Xiupeng; Jia, Qitao; Wang, Xiao; Qin, Guosong; Li, Yongshun; Luo, Ailing; Jin, Weiwu; Yao, Jing; Huang, Jiaojiao; Zhang, Hongyong; Li, Menghua; Xie, Xiangmo; Zheng, Xuejuan; Guo, Kenan; Wang, Qinghua; Zhang, Shibin; Li, Liang; Xie, Fei; Zhang, Yu; Weng, Xiaogang; Yin, Zhi; Hu, Kui; Cong, Yimei; Zheng, Peng; Zou, Hailong; Xin, Leilei; Xia, Jihan; Ruan, Jinxue; Li, Hegang; Zhao, Weiming; Yuan, Jing; Liu, Zizhan; Gu, Weiwang; Li, Ming; Wang, Yong; Wang, Hongmei; Yang, Shiming; Liu, Zhonghua; Wei, Hong; Zhao, Jianguo; Zhou, Qi; Meng, Anming

2017-01-01

N-ethyl-N-nitrosourea (ENU) mutagenesis is a powerful tool to generate mutants on a large scale efficiently, and to discover genes with novel functions at the whole-genome level in Caenorhabditis elegans, flies, zebrafish and mice, but it has never been tried in large model animals. We describe a successful systematic three-generation ENU mutagenesis screening in pigs with the establishment of the Chinese Swine Mutagenesis Consortium. A total of 6,770 G1 and 6,800 G3 pigs were screened, 36 dominant and 91 recessive novel pig families with various phenotypes were established. The causative mutations in 10 mutant families were further mapped. As examples, the mutation of SOX10 (R109W) in pig causes inner ear malfunctions and mimics human Mondini dysplasia, and upregulated expression of FBXO32 is associated with congenital splay legs. This study demonstrates the feasibility of artificial random mutagenesis in pigs and opens an avenue for generating a reservoir of mutants for agricultural production and biomedical research. DOI: http://dx.doi.org/10.7554/eLife.26248.001 PMID:28639938

False-Positive Tuberculin Skin Test Results Among Low-Risk Healthcare Workers Following Implementation of Fifty-Dose Vials of Purified Protein Derivative.

PubMed

Collins, Jeffrey M; Hunter, Mary; Gordon, Wanda; Kempker, Russell R; Blumberg, Henry M; Ray, Susan M

2018-06-01

Following large declines in tuberculosis transmission the United States, large-scale screening programs targeting low-risk healthcare workers are increasingly a source of false-positive results. We report a large cluster of presumed false-positive tuberculin skin test results in healthcare workers following a change to 50-dose vials of Tubersol tuberculin.Infect Control Hosp Epidemiol 2018;39:750-752.

Harmonizing Screening for Gambling Problems in Epidemiological Surveys – Development of the Rapid Screener for Problem Gambling (RSPG)

PubMed Central

Challet-Bouju, Gaëlle; Perrot, Bastien; Romo, Lucia; Valleur, Marc; Magalon, David; Fatséas, Mélina; Chéreau-Boudet, Isabelle; Luquiens, Amandine; Grall-Bronnec, Marie; Hardouin, Jean-Benoit

2016-01-01

Background and aims The aim of this study was to test the screening properties of several combinations of items from gambling scales, in order to harmonize screening of gambling problems in epidemiological surveys. The objective was to propose two brief screening tools (three items or less) for a use in interviews and self-administered questionnaires. Methods We tested the screening properties of combinations of items from several gambling scales, in a sample of 425 gamblers (301 non-problem gamblers and 124 disordered gamblers). Items tested included interview-based items (Pathological Gambling section of the DSM-IV, lifetime history of problem gambling, monthly expenses in gambling, and abstinence of 1 month or more) and self-report items (South Oaks Gambling Screen, Gambling Attitudes, and Beliefs Survey). The gold standard used was the diagnosis of a gambling disorder according to the DSM-5. Results Two versions of the Rapid Screener for Problem Gambling (RSPG) were developed: the RSPG-Interview (RSPG-I), being composed of two interview items (increasing bets and loss of control), and the RSPG-Self-Assessment (RSPG-SA), being composed of three self-report items (chasing, guiltiness, and perceived inability to stop). Discussion and conclusions We recommend using the RSPG-SA/I for screening problem gambling in epidemiological surveys, with the version adapted for each purpose (RSPG-I for interview-based surveys and RSPG-SA for self-administered surveys). This first triage of potential problem gamblers must be supplemented by further assessment, as it may overestimate the proportion of problem gamblers. However, a first triage has the great advantage of saving time and energy in large-scale screening for problem gambling. PMID:27348558

Conference Summary

NASA Technical Reports Server (NTRS)

Begelman, Mitchell C.

1997-01-01

At the end of three days' spirited discussion of the type 2 Seyfert galaxy NGC 1068, what do we think we understand about this object? New observations, particularly in the infrared and radio are helping to resolve old problems, while drawing attention to new ones. It appears that NGC 1068 is a relatively normal spiral galaxy in which large-scale gravitational disturbances are funneling matter into the nucleus. A collimated outflow disturbs the interstellar medium out to kiloparsec scales, but the nucleus itself is hidden behind an opaque screen. Radio observations have now pierced the screen, and suggest that at the center of it all, a 10-20 million solar mass black hole is accreting at close to its Eddington limit.

SLIDE - a web-based tool for interactive visualization of large-scale -omics data.

PubMed

Ghosh, Soumita; Datta, Abhik; Tan, Kaisen; Choi, Hyungwon

2018-06-28

Data visualization is often regarded as a post hoc step for verifying statistically significant results in the analysis of high-throughput data sets. This common practice leaves a large amount of raw data behind, from which more information can be extracted. However, existing solutions do not provide capabilities to explore large-scale raw datasets using biologically sensible queries, nor do they allow user interaction based real-time customization of graphics. To address these drawbacks, we have designed an open-source, web-based tool called Systems-Level Interactive Data Exploration, or SLIDE to visualize large-scale -omics data interactively. SLIDE's interface makes it easier for scientists to explore quantitative expression data in multiple resolutions in a single screen. SLIDE is publicly available under BSD license both as an online version as well as a stand-alone version at https://github.com/soumitag/SLIDE. Supplementary Information are available at Bioinformatics online.

Current screening and treatments in retinopathy of prematurity in the US

PubMed Central

Suelves, Ana M; Shulman, Julia P

2016-01-01

Retinopathy of prematurity (ROP) is a complex disease characterized by an aberrant developmental retinal angiogenesis in preterm infants and can carry significant visual morbidity, including retinal detachment and blindness. Though large scale, randomized clinical trials have improved our understanding of the pathophysiology and progression of the disease, the management of ROP remains a challenge for ophthalmologists. This review addresses the up-to-date screening approach, diagnosis, and treatment guidelines for ROP in the US. PMID:28539800

Current screening and treatments in retinopathy of prematurity in the US.

PubMed

Suelves, Ana M; Shulman, Julia P

2016-01-01

Retinopathy of prematurity (ROP) is a complex disease characterized by an aberrant developmental retinal angiogenesis in preterm infants and can carry significant visual morbidity, including retinal detachment and blindness. Though large scale, randomized clinical trials have improved our understanding of the pathophysiology and progression of the disease, the management of ROP remains a challenge for ophthalmologists. This review addresses the up-to-date screening approach, diagnosis, and treatment guidelines for ROP in the US.

Performance Studies on Distributed Virtual Screening

PubMed Central

Krüger, Jens; de la Garza, Luis; Kohlbacher, Oliver; Nagel, Wolfgang E.

2014-01-01

Virtual high-throughput screening (vHTS) is an invaluable method in modern drug discovery. It permits screening large datasets or databases of chemical structures for those structures binding possibly to a drug target. Virtual screening is typically performed by docking code, which often runs sequentially. Processing of huge vHTS datasets can be parallelized by chunking the data because individual docking runs are independent of each other. The goal of this work is to find an optimal splitting maximizing the speedup while considering overhead and available cores on Distributed Computing Infrastructures (DCIs). We have conducted thorough performance studies accounting not only for the runtime of the docking itself, but also for structure preparation. Performance studies were conducted via the workflow-enabled science gateway MoSGrid (Molecular Simulation Grid). As input we used benchmark datasets for protein kinases. Our performance studies show that docking workflows can be made to scale almost linearly up to 500 concurrent processes distributed even over large DCIs, thus accelerating vHTS campaigns significantly. PMID:25032219

Knowledge-Based Methods To Train and Optimize Virtual Screening Ensembles

PubMed Central

2016-01-01

Ensemble docking can be a successful virtual screening technique that addresses the innate conformational heterogeneity of macromolecular drug targets. Yet, lacking a method to identify a subset of conformational states that effectively segregates active and inactive small molecules, ensemble docking may result in the recommendation of a large number of false positives. Here, three knowledge-based methods that construct structural ensembles for virtual screening are presented. Each method selects ensembles by optimizing an objective function calculated using the receiver operating characteristic (ROC) curve: either the area under the ROC curve (AUC) or a ROC enrichment factor (EF). As the number of receptor conformations, N, becomes large, the methods differ in their asymptotic scaling. Given a set of small molecules with known activities and a collection of target conformations, the most resource intense method is guaranteed to find the optimal ensemble but scales as O(2N). A recursive approximation to the optimal solution scales as O(N2), and a more severe approximation leads to a faster method that scales linearly, O(N). The techniques are generally applicable to any system, and we demonstrate their effectiveness on the androgen nuclear hormone receptor (AR), cyclin-dependent kinase 2 (CDK2), and the peroxisome proliferator-activated receptor δ (PPAR-δ) drug targets. Conformations that consisted of a crystal structure and molecular dynamics simulation cluster centroids were used to form AR and CDK2 ensembles. Multiple available crystal structures were used to form PPAR-δ ensembles. For each target, we show that the three methods perform similarly to one another on both the training and test sets. PMID:27097522

Large scale variation in DNA copy number in chicken breeds

USDA-ARS?s Scientific Manuscript database

Background Detecting genetic variation is a critical step in elucidating the molecular mechanisms underlying phenotypic diversity. Until recently, such detection has mostly focused on single nucleotide polymorphisms (SNPs) because of the ease in screening complete genomes. Another type of variant, c...

Assessing the influence of rater and subject characteristics on measures of agreement for ordinal ratings.

PubMed

Nelson, Kerrie P; Mitani, Aya A; Edwards, Don

2017-09-10

Widespread inconsistencies are commonly observed between physicians' ordinal classifications in screening tests results such as mammography. These discrepancies have motivated large-scale agreement studies where many raters contribute ratings. The primary goal of these studies is to identify factors related to physicians and patients' test results, which may lead to stronger consistency between raters' classifications. While ordered categorical scales are frequently used to classify screening test results, very few statistical approaches exist to model agreement between multiple raters. Here we develop a flexible and comprehensive approach to assess the influence of rater and subject characteristics on agreement between multiple raters' ordinal classifications in large-scale agreement studies. Our approach is based upon the class of generalized linear mixed models. Novel summary model-based measures are proposed to assess agreement between all, or a subgroup of raters, such as experienced physicians. Hypothesis tests are described to formally identify factors such as physicians' level of experience that play an important role in improving consistency of ratings between raters. We demonstrate how unique characteristics of individual raters can be assessed via conditional modes generated during the modeling process. Simulation studies are presented to demonstrate the performance of the proposed methods and summary measure of agreement. The methods are applied to a large-scale mammography agreement study to investigate the effects of rater and patient characteristics on the strength of agreement between radiologists. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing.

PubMed

Lim, Hansaim; Poleksic, Aleksandar; Yao, Yuan; Tong, Hanghang; He, Di; Zhuang, Luke; Meng, Patrick; Xie, Lei

2016-10-01

Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and side effect prediction. The software and benchmark are available at https://github.com/hansaimlim/REMAP.

Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing

PubMed Central

Poleksic, Aleksandar; Yao, Yuan; Tong, Hanghang; Meng, Patrick; Xie, Lei

2016-01-01

Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and side effect prediction. The software and benchmark are available at https://github.com/hansaimlim/REMAP. PMID:27716836

Comparison of 2 ultrafiltration systems for the concentration of seeded viruses from environmental waters.

PubMed

Olszewski, John; Winona, Linda; Oshima, Kevin H

2005-04-01

The use of ultrafiltration as a concentration method to recover viruses from environmental waters was investigated. Two ultrafiltration systems (hollow fiber and tangential flow) in a large- (100 L) and small-scale (2 L) configuration were able to recover greater than 50% of multiple viruses (bacteriophage PP7 and T1 and poliovirus type 2) from varying water turbidities (10-157 nephelometric turbidity units (NTU)) simultaneously. Mean recoveries (n = 3) in ground and surface water by the large-scale hollow fiber ultrafiltration system (100 L) were comparable to recoveries observed in the small-scale system (2 L). Recovery of seeded viruses in highly turbid waters from small-scale tangential flow (2 L) (screen and open channel) and hollow fiber ultrafilters (2 L) (small pilot) were greater than 70%. Clogging occurred in the hollow fiber pencil module and when particulate concentrations exceeded 1.6 g/L and 5.5 g/L (dry mass) in the screen and open channel filters, respectively. The small pilot module was able to filter all concentrates without clogging. The small pilot hollow fiber ultrafilter was used to test recovery of seeded viruses from surface waters from different geographical regions in 10-L volumes. Recoveries >70% were observed from all locations.

The Vainshtein mechanism in the cosmic web

DOE Office of Scientific and Technical Information (OSTI.GOV)

Falck, Bridget; Koyama, Kazuya; Zhao, Gong-bo

We investigate the dependence of the Vainshtein screening mechanism on the cosmic web morphology of both dark matter particles and halos as determined by ORIGAMI. Unlike chameleon and symmetron screening, which come into effect in regions of high density, Vainshtein screening instead depends on the dimensionality of the system, and screened bodies can still feel external fields. ORIGAMI is well-suited to this problem because it defines morphologies according to the dimensionality of the collapsing structure and does not depend on a smoothing scale or density threshold parameter. We find that halo particles are screened while filament, wall, and void particlesmore » are unscreened, and this is independent of the particle density. However, after separating halos according to their large scale cosmic web environment, we find no difference in the screening properties of halos in filaments versus halos in clusters. We find that the fifth force enhancement of dark matter particles in halos is greatest well outside the virial radius. We confirm the theoretical expectation that even if the internal field is suppressed by the Vainshtein mechanism, the object still feels the fifth force generated by the external fields, by measuring peculiar velocities and velocity dispersions of halos. Finally, we investigate the morphology and gravity model dependence of halo spins, concentrations, and shapes.« less

A three-dimensional refractive index model for simulation of optical wave propagation in atmospheric turbulence

NASA Astrophysics Data System (ADS)

Paramonov, P. V.; Vorontsov, A. M.; Kunitsyn, V. E.

2015-10-01

Numerical modeling of optical wave propagation in atmospheric turbulence is traditionally performed with using the so-called "split"-operator method, when the influence of the propagation medium's refractive index inhomogeneities is accounted for only within a system of infinitely narrow layers (phase screens) where phase is distorted. Commonly, under certain assumptions, such phase screens are considered as mutually statistically uncorrelated. However, in several important applications including laser target tracking, remote sensing, and atmospheric imaging, accurate optical field propagation modeling assumes upper limitations on interscreen spacing. The latter situation can be observed, for instance, in the presence of large-scale turbulent inhomogeneities or in deep turbulence conditions, where interscreen distances become comparable with turbulence outer scale and, hence, corresponding phase screens cannot be statistically uncorrelated. In this paper, we discuss correlated phase screens. The statistical characteristics of screens are calculated based on a representation of turbulent fluctuations of three-dimensional (3D) refractive index random field as a set of sequentially correlated 3D layers displaced in the wave propagation direction. The statistical characteristics of refractive index fluctuations are described in terms of the von Karman power spectrum density. In the representation of these 3D layers by corresponding phase screens, the geometrical optics approximation is used.

Identification and Screening of Carcass Pretreatment ...

EPA Pesticide Factsheets

Technical Fact Sheet Managing the treatment and disposal of large numbers of animal carcasses following a foreign animal disease (FAD) outbreak is a challenging endeavor. Pretreatment of the infectious carcasses might facilitate the disposal of the carcasses by simplifying the transportation, reducing the pathogen load in the carcasses, or by isolating the pathogen from the environment to minimize spread of any pathogens.This brief summarizes information contained in U.S. Environmental Protection Agency (EPA) report (EPA/600/R-15/053) entitled Identification and Screening of Infectious Carcass Pretreatment Alternatives. This brief describes how each of eleven pretreatment methods can be used prior to, and in conjunction with, six commonly used large-scale carcass disposal options

Screening and productivity of penicillin antibiotic from Penicillium sp.

PubMed

Sivakumari, V; Dhinakaran, J; Rajendran, A

2009-10-01

This paper highlights the antagonism effect of Penicillium isolates, which were screened against the test organisms such as Staphylococcus aureus, E. coli and Penicillium sp. Penicillium notatum and Penicillium chrysogenum isolates were used for penicillin biosynthesis. The antibacterial activities of fermented crude penicillin extract were assayed by disc diffusion method. Maximum antibacterial activity was observed in Gram positive organisms (Staphylococcus aureus) when compared with Gram negative organisms. The isolated Penicillium chrysogenum can be used for large-scale penicillin antibiotic production.

Enrichment assessment of multiple virtual screening strategies for Toll-like receptor 8 agonists based on a maximal unbiased benchmarking data set.

PubMed

Pei, Fen; Jin, Hongwei; Zhou, Xin; Xia, Jie; Sun, Lidan; Liu, Zhenming; Zhang, Liangren

2015-11-01

Toll-like receptor 8 agonists, which activate adaptive immune responses by inducing robust production of T-helper 1-polarizing cytokines, are promising candidates for vaccine adjuvants. As the binding site of toll-like receptor 8 is large and highly flexible, virtual screening by individual method has inevitable limitations; thus, a comprehensive comparison of different methods may provide insights into seeking effective strategy for the discovery of novel toll-like receptor 8 agonists. In this study, the performance of knowledge-based pharmacophore, shape-based 3D screening, and combined strategies was assessed against a maximum unbiased benchmarking data set containing 13 actives and 1302 decoys specialized for toll-like receptor 8 agonists. Prior structure-activity relationship knowledge was involved in knowledge-based pharmacophore generation, and a set of antagonists was innovatively used to verify the selectivity of the selected knowledge-based pharmacophore. The benchmarking data set was generated from our recently developed 'mubd-decoymaker' protocol. The enrichment assessment demonstrated a considerable performance through our selected three-layer virtual screening strategy: knowledge-based pharmacophore (Phar1) screening, shape-based 3D similarity search (Q4_combo), and then a Gold docking screening. This virtual screening strategy could be further employed to perform large-scale database screening and to discover novel toll-like receptor 8 agonists. © 2015 John Wiley & Sons A/S.

A large scale virtual screen of DprE1.

PubMed

Wilsey, Claire; Gurka, Jessica; Toth, David; Franco, Jimmy

2013-12-01

Tuberculosis continues to plague the world with the World Health Organization estimating that about one third of the world's population is infected. Due to the emergence of MDR and XDR strains of TB, the need for novel therapeutics has become increasing urgent. Herein we report the results of a virtual screen of 4.1 million compounds against a promising drug target, DrpE1. The virtual compounds were obtained from the Zinc docking site and screened using the molecular docking program, AutoDock Vina. The computational hits have led to the identification of several promising lead compounds. Copyright © 2013 Elsevier Ltd. All rights reserved.

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

NASA Astrophysics Data System (ADS)

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-10-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

A Comparative Analysis of Coprologic Diagnostic Methods for Detection of Toxoplama gondii in Cats

PubMed Central

Salant, Harold; Spira, Dan T.; Hamburger, Joseph

2010-01-01

The relative role of transmission of Toxoplasma gondii infection from cats to humans appears to have recently increased in certain areas. Large-scale screening of oocyst shedding in cats cannot rely on microscopy because oocyst identification lacks sensitivity and specificity, or on bioassays, which require test animals and weeks before examination. We compared a sensitive and species-specific coprologic–polymerase chain reaction (copro-PCR) for detection of T. gondii infected cats with microscopy and a bioassay. In experimentally infected cats followed over time, microscopy was positive occasionally, and positive copro-PCR and bioassay results were obtained continuously from days 2 to 24 post-infection. The copro-PCR is at least as sensitive and specific as the bioassay and is capable of detecting infective oocysts during cat infection. Therefore, this procedure can be used as the new gold standard for determining potential cat infectivity. Its technologic advantages over the bioassay make it superior for large-scale screening of cats. PMID:20439968

Distributed rendering for multiview parallax displays

NASA Astrophysics Data System (ADS)

Annen, T.; Matusik, W.; Pfister, H.; Seidel, H.-P.; Zwicker, M.

2006-02-01

3D display technology holds great promise for the future of television, virtual reality, entertainment, and visualization. Multiview parallax displays deliver stereoscopic views without glasses to arbitrary positions within the viewing zone. These systems must include a high-performance and scalable 3D rendering subsystem in order to generate multiple views at real-time frame rates. This paper describes a distributed rendering system for large-scale multiview parallax displays built with a network of PCs, commodity graphics accelerators, multiple projectors, and multiview screens. The main challenge is to render various perspective views of the scene and assign rendering tasks effectively. In this paper we investigate two different approaches: Optical multiplexing for lenticular screens and software multiplexing for parallax-barrier displays. We describe the construction of large-scale multi-projector 3D display systems using lenticular and parallax-barrier technology. We have developed different distributed rendering algorithms using the Chromium stream-processing framework and evaluate the trade-offs and performance bottlenecks. Our results show that Chromium is well suited for interactive rendering on multiview parallax displays.

Enabling Large-Scale Design, Synthesis and Validation of Small Molecule Protein-Protein Antagonists

PubMed Central

Koes, David; Khoury, Kareem; Huang, Yijun; Wang, Wei; Bista, Michal; Popowicz, Grzegorz M.; Wolf, Siglinde; Holak, Tad A.; Dömling, Alexander; Camacho, Carlos J.

2012-01-01

Although there is no shortage of potential drug targets, there are only a handful known low-molecular-weight inhibitors of protein-protein interactions (PPIs). One problem is that current efforts are dominated by low-yield high-throughput screening, whose rigid framework is not suitable for the diverse chemotypes present in PPIs. Here, we developed a novel pharmacophore-based interactive screening technology that builds on the role anchor residues, or deeply buried hot spots, have in PPIs, and redesigns these entry points with anchor-biased virtual multicomponent reactions, delivering tens of millions of readily synthesizable novel compounds. Application of this approach to the MDM2/p53 cancer target led to high hit rates, resulting in a large and diverse set of confirmed inhibitors, and co-crystal structures validate the designed compounds. Our unique open-access technology promises to expand chemical space and the exploration of the human interactome by leveraging in-house small-scale assays and user-friendly chemistry to rationally design ligands for PPIs with known structure. PMID:22427896

Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians.

PubMed

Newmark, Phillip A; Reddien, Peter W; Cebrià, Francesc; Sánchez Alvarado, Alejandro

2003-09-30

Freshwater planarian flatworms are capable of regenerating complete organisms from tiny fragments of their bodies; the basis for this regenerative prowess is an experimentally accessible stem cell population that is present in the adult planarian. The study of these organisms, classic experimental models for investigating metazoan regeneration, has been revitalized by the application of modern molecular biological approaches. The identification of thousands of unique planarian ESTs, coupled with large-scale whole-mount in situ hybridization screens, and the ability to inhibit planarian gene expression through double-stranded RNA-mediated genetic interference, provide a wealth of tools for studying the molecular mechanisms that regulate tissue regeneration and stem cell biology in these organisms. Here we show that, as in Caenorhabditis elegans, ingestion of bacterially expressed double-stranded RNA can inhibit gene expression in planarians. This inhibition persists throughout the process of regeneration, allowing phenotypes with disrupted regenerative patterning to be identified. These results pave the way for large-scale screens for genes involved in regenerative processes.

Biased ligand quantification in drug discovery: from theory to high throughput screening to identify new biased μ opioid receptor agonists

PubMed Central

Winpenny, David; Clark, Mellissa

2016-01-01

Background and Purpose Biased GPCR ligands are able to engage with their target receptor in a manner that preferentially activates distinct downstream signalling and offers potential for next generation therapeutics. However, accurate quantification of ligand bias in vitro is complex, and current best practice is not amenable for testing large numbers of compound. We have therefore sought to apply ligand bias theory to an industrial scale screening campaign for the identification of new biased μ receptor agonists. Experimental Approach μ receptor assays with appropriate dynamic range were developed for both Gαi‐dependent signalling and β‐arrestin2 recruitment. Δlog(Emax/EC50) analysis was validated as an alternative for the operational model of agonism in calculating pathway bias towards Gαi‐dependent signalling. The analysis was applied to a high throughput screen to characterize the prevalence and nature of pathway bias among a diverse set of compounds with μ receptor agonist activity. Key Results A high throughput screening campaign yielded 440 hits with greater than 10‐fold bias relative to DAMGO. To validate these results, we quantified pathway bias of a subset of hits using the operational model of agonism. The high degree of correlation across these biased hits confirmed that Δlog(Emax/EC50) was a suitable method for identifying genuine biased ligands within a large collection of diverse compounds. Conclusions and Implications This work demonstrates that using Δlog(Emax/EC50), drug discovery can apply the concept of biased ligand quantification on a large scale and accelerate the deliberate discovery of novel therapeutics acting via this complex pharmacology. PMID:26791140

A Screening Test for Wilson's Disease and its Application to Psychiatric Patients

PubMed Central

Cox, Diane Wilson

1967-01-01

Varied modes of onset make the early diagnosis of Wilson's disease difficult. A deficiency of serum ceruloplasmin, usually characteristic of the disease, was used as the basis for a screening test. Simple test materials and provision for handling about 50 plasma samples simultaneously made this test feasible for large-scale screening. The screening test was applied to 336 persons hospitalized for psychiatric disorders, to detect patients with Wilson's disease before the classical symptoms appeared. Two patients with ceruloplasmin levels below the normal limits were detected but did not have Wilson's disease. Further application of the screening test to relatives of patients known to have Wilson's disease and to individuals with any symptoms of the disease (hepatic disease, extrapyramidal dysfunction, psychiatric disorders, behaviour problems in children) would aid in early diagnosis and more effective treatment. ImagesFig. 1 PMID:6017170

web cellHTS2: a web-application for the analysis of high-throughput screening data.

PubMed

Pelz, Oliver; Gilsdorf, Moritz; Boutros, Michael

2010-04-12

The analysis of high-throughput screening data sets is an expanding field in bioinformatics. High-throughput screens by RNAi generate large primary data sets which need to be analyzed and annotated to identify relevant phenotypic hits. Large-scale RNAi screens are frequently used to identify novel factors that influence a broad range of cellular processes, including signaling pathway activity, cell proliferation, and host cell infection. Here, we present a web-based application utility for the end-to-end analysis of large cell-based screening experiments by cellHTS2. The software guides the user through the configuration steps that are required for the analysis of single or multi-channel experiments. The web-application provides options for various standardization and normalization methods, annotation of data sets and a comprehensive HTML report of the screening data analysis, including a ranked hit list. Sessions can be saved and restored for later re-analysis. The web frontend for the cellHTS2 R/Bioconductor package interacts with it through an R-server implementation that enables highly parallel analysis of screening data sets. web cellHTS2 further provides a file import and configuration module for common file formats. The implemented web-application facilitates the analysis of high-throughput data sets and provides a user-friendly interface. web cellHTS2 is accessible online at http://web-cellHTS2.dkfz.de. A standalone version as a virtual appliance and source code for platforms supporting Java 1.5.0 can be downloaded from the web cellHTS2 page. web cellHTS2 is freely distributed under GPL.

A measure of association for ordered categorical data in population-based studies

PubMed Central

Nelson, Kerrie P; Edwards, Don

2016-01-01

Ordinal classification scales are commonly used to define a patient’s disease status in screening and diagnostic tests such as mammography. Challenges arise in agreement studies when evaluating the association between many raters’ classifications of patients’ disease or health status when an ordered categorical scale is used. In this paper, we describe a population-based approach and chance-corrected measure of association to evaluate the strength of relationship between multiple raters’ ordinal classifications where any number of raters can be accommodated. In contrast to Shrout and Fleiss’ intraclass correlation coefficient, the proposed measure of association is invariant with respect to changes in disease prevalence. We demonstrate how unique characteristics of individual raters can be explored using random effects. Simulation studies are conducted to demonstrate the properties of the proposed method under varying assumptions. The methods are applied to two large-scale agreement studies of breast cancer screening and prostate cancer severity. PMID:27184590

Chromatin Landscapes of Retroviral and Transposon Integration Profiles

PubMed Central

Badhai, Jitendra; Rust, Alistair G.; Rad, Roland; Hilkens, John; Berns, Anton; van Lohuizen, Maarten; Wessels, Lodewyk F. A.; de Ridder, Jeroen

2014-01-01

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very large datasets consisting of to unselected integrations in the mouse genome for the Sleeping Beauty (SB) and piggyBac (PB) transposons, and the Mouse Mammary Tumor Virus (MMTV). We analyzed (epi)genomic features to generate bias maps at both local and genome-wide scales. MMTV showed a remarkably uniform distribution of integrations across the genome. More distinct preferences were observed for the two transposons, with PB showing remarkable resemblance to bias profiles of the Murine Leukemia Virus. Furthermore, we present a model where target site selection is directed at multiple scales. At a large scale, target site selection is similar across systems, and defined by domain-oriented features, namely expression of proximal genes, proximity to CpG islands and to genic features, chromatin compaction and replication timing. Notable differences between the systems are mainly observed at smaller scales, and are directed by a diverse range of features. To study the effect of these biases on integration sites occupied under selective pressure, we turned to insertional mutagenesis (IM) screens. In IM screens, putative cancer genes are identified by finding frequently targeted genomic regions, or Common Integration Sites (CISs). Within three recently completed IM screens, we identified 7%–33% putative false positive CISs, which are likely not the result of the oncogenic selection process. Moreover, results indicate that PB, compared to SB, is more suited to tag oncogenes. PMID:24721906

ENCoRE: an efficient software for CRISPR screens identifies new players in extrinsic apoptosis.

PubMed

Trümbach, Dietrich; Pfeiffer, Susanne; Poppe, Manuel; Scherb, Hagen; Doll, Sebastian; Wurst, Wolfgang; Schick, Joel A

2017-11-25

As CRISPR/Cas9 mediated screens with pooled guide libraries in somatic cells become increasingly established, an unmet need for rapid and accurate companion informatics tools has emerged. We have developed a lightweight and efficient software to easily manipulate large raw next generation sequencing datasets derived from such screens into informative relational context with graphical support. The advantages of the software entitled ENCoRE (Easy NGS-to-Gene CRISPR REsults) include a simple graphical workflow, platform independence, local and fast multithreaded processing, data pre-processing and gene mapping with custom library import. We demonstrate the capabilities of ENCoRE to interrogate results from a pooled CRISPR cellular viability screen following Tumor Necrosis Factor-alpha challenge. The results not only identified stereotypical players in extrinsic apoptotic signaling but two as yet uncharacterized members of the extrinsic apoptotic cascade, Smg7 and Ces2a. We further validated and characterized cell lines containing mutations in these genes against a panel of cell death stimuli and involvement in p53 signaling. In summary, this software enables bench scientists with sensitive data or without access to informatic cores to rapidly interpret results from large scale experiments resulting from pooled CRISPR/Cas9 library screens.

Validity of the International HIV Dementia Scale as assessed in a socioeconomically underdeveloped region of Southern China: assessing the influence of educational attainment.

PubMed

Dang, Chao; Wei, Bo; Long, JianXiong; Zhou, MengXiao; Han, XinXin; Zhao, TingTing

2015-04-01

In 2012, more than 80,000 cases of HIV infection were recorded in the Southern Chinese minority autonomous region of Guangxi Zhuang, where the occurrence of HIV-associated dementia remains high. The International HIV Dementia Scale is a relatively simple-to-administer screening scale for HIV-associated neurocognitive disorders. However, clinical experience in utilizing the scale with large Chinese samples is currently lacking, especially among individuals with limited formal schooling. In this study, a full neuropsychological evaluation the gold standard was conducted to identify the incidence/prevalence of HIV-associated neurocognitive disorders in a socioeconomically underdeveloped region of Southern China and to locate the optimal cut-off scale value using receiver operating characteristic curves. The highest Youden index of the scale was 0.450, with a corresponding cut-off point of 7.25. The sensitivity and specificity were 0.737 and 0.713, respectively. These results suggest that the scale is an effective and feasible screening tool for HIV-associated neurocognitive disorders in poorer regions of China with fewer well-educated residents. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A large-scale RNA interference screen identifies genes that regulate autophagy at different stages.

PubMed

Guo, Sujuan; Pridham, Kevin J; Virbasius, Ching-Man; He, Bin; Zhang, Liqing; Varmark, Hanne; Green, Michael R; Sheng, Zhi

2018-02-12

Dysregulated autophagy is central to the pathogenesis and therapeutic development of cancer. However, how autophagy is regulated in cancer is not well understood and genes that modulate cancer autophagy are not fully defined. To gain more insights into autophagy regulation in cancer, we performed a large-scale RNA interference screen in K562 human chronic myeloid leukemia cells using monodansylcadaverine staining, an autophagy-detecting approach equivalent to immunoblotting of the autophagy marker LC3B or fluorescence microscopy of GFP-LC3B. By coupling monodansylcadaverine staining with fluorescence-activated cell sorting, we successfully isolated autophagic K562 cells where we identified 336 short hairpin RNAs. After candidate validation using Cyto-ID fluorescence spectrophotometry, LC3B immunoblotting, and quantitative RT-PCR, 82 genes were identified as autophagy-regulating genes. 20 genes have been reported previously and the remaining 62 candidates are novel autophagy mediators. Bioinformatic analyses revealed that most candidate genes were involved in molecular pathways regulating autophagy, rather than directly participating in the autophagy process. Further autophagy flux assays revealed that 57 autophagy-regulating genes suppressed autophagy initiation, whereas 21 candidates promoted autophagy maturation. Our RNA interference screen identifies identified genes that regulate autophagy at different stages, which helps decode autophagy regulation in cancer and offers novel avenues to develop autophagy-related therapies for cancer.

Associative learning performance is impaired in zebrafish (Danio rerio) by the NMDA-R antagonist MK-801

PubMed Central

Sison, Margarette; Gerlai, Robert

2011-01-01

The zebrafish is gaining popularity in behavioral neuroscience perhaps because of a promise of efficient large scale mutagenesis and drug screens that could identify a substantial number of yet undiscovered molecular players involved in complex traits. Learning and memory are complex functions of the brain and the analysis of their mechanisms may benefit from such large scale zebrafish screens. One bottleneck in this research is the paucity of appropriate behavioral screening paradigms, which may be due to the relatively uncharacterized nature of the behavior of this species. Here we show that zebrafish exhibit good learning performance in a task adapted from the mammalian literature, a plus maze in which zebrafish are required to associate a neutral visual stimulus with the presence of conspecifics, the rewarding unconditioned stimulus. Furthermore, we show that MK-801, a non-competitive NMDA-R antagonist, impairs memory performance in this maze when administered right after training or just before recall but not when given before training at a dose that does not impair motor function, perception or motivation. These results suggest that the plus maze associative learning paradigm has face and construct validity and that zebrafish may become an appropriate and translationally relevant study species for the analysis of the mechanisms of vertebrate, including mammalian, learning and memory. PMID:21596149

Chloroplast 2010: A Database for Large-Scale Phenotypic Screening of Arabidopsis Mutants1[W][OA

PubMed Central

Lu, Yan; Savage, Linda J.; Larson, Matthew D.; Wilkerson, Curtis G.; Last, Robert L.

2011-01-01

Large-scale phenotypic screening presents challenges and opportunities not encountered in typical forward or reverse genetics projects. We describe a modular database and laboratory information management system that was implemented in support of the Chloroplast 2010 Project, an Arabidopsis (Arabidopsis thaliana) reverse genetics phenotypic screen of more than 5,000 mutants (http://bioinfo.bch.msu.edu/2010_LIMS; www.plastid.msu.edu). The software and laboratory work environment were designed to minimize operator error and detect systematic process errors. The database uses Ruby on Rails and Flash technologies to present complex quantitative and qualitative data and pedigree information in a flexible user interface. Examples are presented where the database was used to find opportunities for process changes that improved data quality. We also describe the use of the data-analysis tools to discover mutants defective in enzymes of leucine catabolism (heteromeric mitochondrial 3-methylcrotonyl-coenzyme A carboxylase [At1g03090 and At4g34030] and putative hydroxymethylglutaryl-coenzyme A lyase [At2g26800]) based upon a syndrome of pleiotropic seed amino acid phenotypes that resembles previously described isovaleryl coenzyme A dehydrogenase (At3g45300) mutants. In vitro assay results support the computational annotation of At2g26800 as hydroxymethylglutaryl-coenzyme A lyase. PMID:21224340

CImbinator: a web-based tool for drug synergy analysis in small- and large-scale datasets.

PubMed

Flobak, Åsmund; Vazquez, Miguel; Lægreid, Astrid; Valencia, Alfonso

2017-08-01

Drug synergies are sought to identify combinations of drugs particularly beneficial. User-friendly software solutions that can assist analysis of large-scale datasets are required. CImbinator is a web-service that can aid in batch-wise and in-depth analyzes of data from small-scale and large-scale drug combination screens. CImbinator offers to quantify drug combination effects, using both the commonly employed median effect equation, as well as advanced experimental mathematical models describing dose response relationships. CImbinator is written in Ruby and R. It uses the R package drc for advanced drug response modeling. CImbinator is available at http://cimbinator.bioinfo.cnio.es , the source-code is open and available at https://github.com/Rbbt-Workflows/combination_index . A Docker image is also available at https://hub.docker.com/r/mikisvaz/rbbt-ci_mbinator/ . asmund.flobak@ntnu.no or miguel.vazquez@cnio.es. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Large-scale image-based profiling of single-cell phenotypes in arrayed CRISPR-Cas9 gene perturbation screens.

PubMed

de Groot, Reinoud; Lüthi, Joel; Lindsay, Helen; Holtackers, René; Pelkmans, Lucas

2018-01-23

High-content imaging using automated microscopy and computer vision allows multivariate profiling of single-cell phenotypes. Here, we present methods for the application of the CISPR-Cas9 system in large-scale, image-based, gene perturbation experiments. We show that CRISPR-Cas9-mediated gene perturbation can be achieved in human tissue culture cells in a timeframe that is compatible with image-based phenotyping. We developed a pipeline to construct a large-scale arrayed library of 2,281 sequence-verified CRISPR-Cas9 targeting plasmids and profiled this library for genes affecting cellular morphology and the subcellular localization of components of the nuclear pore complex (NPC). We conceived a machine-learning method that harnesses genetic heterogeneity to score gene perturbations and identify phenotypically perturbed cells for in-depth characterization of gene perturbation effects. This approach enables genome-scale image-based multivariate gene perturbation profiling using CRISPR-Cas9. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Cystic fibrosis heterozygote screening in 5,161 pregnant women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witt, D.R.; Hallam, P.; Blumberg, B.

A screening program for cystic fibrosis (CF) heterozygotes was conducted in a large HMO prenatal population, to evaluate the level of interest among eligible patients, the effectiveness of prescreening education, attitudes toward the screening process, psychological effects, and utilization of prenatal diagnosis and its outcomes. The heterozygote identification rate and frequency of specific CFTR mutations were also assessed. Identified carriers were offered genetic counseling and testing of male partners. Prenatal diagnosis was offered if both partners were identified as carriers. A total of 5,161 women underwent carrier testing; 947 others completed survey instruments only. The acceptance rate of screening wasmore » high (78%), and pretest education by videotape was generally effective. Adverse psychological effects were not reported. Participants generally found screening to be desirable and useful. Screening identified 142 female heterozygotes, 109 couples in which the male partner was not a carrier, and 7 high-risk couples. The incidence of R117H mutations was much higher than expected. The number of identified carriers was much lower in Hispanics than in Caucasians. We conclude that large-scale prenatal screening for CF heterozygotes in the absence of a family history of CF is an acceptable method for identifying couples at risk for affected fetuses. Sufficient pretest education can be accomplished efficiently, test insensitivity is well accepted, adverse psychological events are not observed, and general patient satisfaction is high. 66 refs., 1 fig., 8 tabs.« less

Virtual gastrointestinal colonoscopy in combination with large bowel endoscopy: Clinical application

PubMed Central

He, Qing; Rao, Ting; Guan, Yong-Song

2014-01-01

Although colorectal cancer (CRC) has no longer been the leading cancer killer worldwide for years with the exponential development in computed tomography (CT) or magnetic resonance imaging, and positron emission tomography/CT as well as virtual colonoscopy for early detection, the CRC related mortality is still high. The objective of CRC screening is to reduce the burden of CRC and thereby the morbidity and mortality rates of the disease. It is believed that this goal can be achieved by regularly screening the average-risk population, enabling the detection of cancer at early, curable stages, and polyps before they become cancerous. Large-scale screening with multimodality imaging approaches plays an important role in reaching that goal to detect polyps, Crohn’s disease, ulcerative colitis and CRC in early stage. This article reviews kinds of presentative imaging procedures for various screening options and updates detecting, staging and re-staging of CRC patients for determining the optimal therapeutic method and forecasting the risk of CRC recurrence and the overall prognosis. The combination use of virtual colonoscopy and conventional endoscopy, advantages and limitations of these modalities are also discussed. PMID:25320519

Developing a Drosophila Model of Schwannomatosis

DTIC Science & Technology

2012-08-01

the entire Drosophila melanogaster genome and compared...et al., 2009; Hanahan and Weinberg, 2011). Over the last decade, the fruit fly Drosophila melanogaster has become an important model system for cancer...studies. Reduced redundancy in the Drosophila genome compared with that of humans, coupled with the ability to conduct large-scale genetic screens

Techniques for inventorying manmade impacts in roadway environments.

Treesearch

Dale R. Potter; J. Alan. Wagar

1971-01-01

Four techniques for inventorying manmade impacts along roadway corridors were devised and compared. Ground surveillance and ground photography techniques recorded impacts within the corridor visible from the road. Techniques on large- and small-scale aerial photography recorded impacts within a more complete corridor that included areas screened from the road by...

Method for replicating an array of nucleic acid probes

DOEpatents

Cantor, Charles R.; Przetakiewicz, Marek; Smith, Cassandra L.; Sano, Takeshi

1998-01-01

The invention relates to the replication of probe arrays and methods for replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5'- and/or 3'-overhangs.

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing

PubMed Central

Fang, Ye; Ding, Yun; Feinstein, Wei P.; Koppelman, David M.; Moreno, Juana; Jarrell, Mark; Ramanujam, J.; Brylinski, Michal

2016-01-01

Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300

DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0.

PubMed

Jiang, Xiaohui; Kumar, Kamal; Hu, Xin; Wallqvist, Anders; Reifman, Jaques

2008-09-08

Small-molecule docking is an important tool in studying receptor-ligand interactions and in identifying potential drug candidates. Previously, we developed a software tool (DOVIS) to perform large-scale virtual screening of small molecules in parallel on Linux clusters, using AutoDock 3.05 as the docking engine. DOVIS enables the seamless screening of millions of compounds on high-performance computing platforms. In this paper, we report significant advances in the software implementation of DOVIS 2.0, including enhanced screening capability, improved file system efficiency, and extended usability. To keep DOVIS up-to-date, we upgraded the software's docking engine to the more accurate AutoDock 4.0 code. We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs. We also implemented an algorithm to output docked ligands in an industry standard format, sd-file format, which can be easily interfaced with other modeling programs. Finally, we constructed a wrapper-script interface to enable automatic rescoring of docked ligands by arbitrarily selected third-party scoring programs. The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability. The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands. The new DOVIS 2.0 package is freely available to the public under the GNU General Public License.

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

PubMed

Fang, Ye; Ding, Yun; Feinstein, Wei P; Koppelman, David M; Moreno, Juana; Jarrell, Mark; Ramanujam, J; Brylinski, Michal

2016-01-01

Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.

Affordable proteomics: the two-hybrid systems.

PubMed

Gillespie, Marc

2003-06-01

Numerous proteomic methodologies exist, but most require a heavy investment in expertise and technology. This puts these approaches out of reach for many laboratories and small companies, rarely allowing proteomics to be used as a pilot approach for biomarker or target identification. Two proteomic approaches, 2D gel electrophoresis and the two-hybrid systems, are currently available to most researchers. The two-hybrid systems, though accommodating to large-scale experiments, were originally designed as practical screens, that by comparison to current proteomics tools were small-scale, affordable and technically feasible. The screens rapidly generated data, identifying protein interactions that were previously uncharacterized. The foundation for a two-hybrid proteomic investigation can be purchased as separate kits from a number of companies. The true power of the technique lies not in its affordability, but rather in its portability. The two-hybrid system puts proteomics back into laboratories where the output of the screens can be evaluated by researchers with experience in the particular fields of basic research, cancer biology, toxicology or drug development.

Measures of Agreement Between Many Raters for Ordinal Classifications

PubMed Central

Nelson, Kerrie P.; Edwards, Don

2015-01-01

Screening and diagnostic procedures often require a physician's subjective interpretation of a patient's test result using an ordered categorical scale to define the patient's disease severity. Due to wide variability observed between physicians’ ratings, many large-scale studies have been conducted to quantify agreement between multiple experts’ ordinal classifications in common diagnostic procedures such as mammography. However, very few statistical approaches are available to assess agreement in these large-scale settings. Existing summary measures of agreement rely on extensions of Cohen's kappa [1 - 5]. These are prone to prevalence and marginal distribution issues, become increasingly complex for more than three experts or are not easily implemented. Here we propose a model-based approach to assess agreement in large-scale studies based upon a framework of ordinal generalized linear mixed models. A summary measure of agreement is proposed for multiple experts assessing the same sample of patients’ test results according to an ordered categorical scale. This measure avoids some of the key flaws associated with Cohen's kappa and its extensions. Simulation studies are conducted to demonstrate the validity of the approach with comparison to commonly used agreement measures. The proposed methods are easily implemented using the software package R and are applied to two large-scale cancer agreement studies. PMID:26095449

Billion-scale production of hepatocyte-like cells from human induced pluripotent stem cells.

PubMed

Yamashita, Tomoki; Takayama, Kazuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki

2018-02-19

Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells are expected to be utilized in drug screening and regenerative medicine. However, hepatocyte-like cells have not been fully used in such applications because it is difficult to produce such cells on a large scale. In this study, we tried to establish a method to mass produce hepatocyte-like cells using a three-dimensional (3D) cell culture bioreactor called the Rotary Cell Culture System (RCCS). RCCS enabled us to obtain homogenous hepatocyte-like cells on a billion scale (>10 9  cells). The gene expression levels of some hepatocyte markers (alpha-1 antitrypsin, cytochrome (CYP) 1A2, CYP2D6, and hepatocyte nuclear factor 4alpha) were higher in 3D-cultured hepatocyte-like cells than in 2D-cultured hepatocyte-like cells. This result suggests that RCCS could provide more suitable conditions for hepatocyte maturation than the conventional 2D cell culture conditions. In addition, more than 90% of hepatocyte-like cells were positive for albumin and could uptake low-density lipoprotein in the culture medium. We succeeded in the large-scale production of homogenous and functional hepatocyte-like cells from human iPS cells. This technology will be useful in drug screening and regenerative medicine, which require enormous numbers of hepatocyte-like cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Large-Area Cross-Aligned Silver Nanowire Electrodes for Flexible, Transparent, and Force-Sensitive Mechanochromic Touch Screens.

PubMed

Cho, Seungse; Kang, Saewon; Pandya, Ashish; Shanker, Ravi; Khan, Ziyauddin; Lee, Youngsu; Park, Jonghwa; Craig, Stephen L; Ko, Hyunhyub

2017-04-25

Silver nanowire (AgNW) networks are considered to be promising structures for use as flexible transparent electrodes for various optoelectronic devices. One important application of AgNW transparent electrodes is the flexible touch screens. However, the performances of flexible touch screens are still limited by the large surface roughness and low electrical to optical conductivity ratio of random network AgNW electrodes. In addition, although the perception of writing force on the touch screen enables a variety of different functions, the current technology still relies on the complicated capacitive force touch sensors. This paper demonstrates a simple and high-throughput bar-coating assembly technique for the fabrication of large-area (>20 × 20 cm 2 ), highly cross-aligned AgNW networks for transparent electrodes with the sheet resistance of 21.0 Ω sq -1 at 95.0% of optical transmittance, which compares favorably with that of random AgNW networks (sheet resistance of 21.0 Ω sq -1 at 90.4% of optical transmittance). As a proof of concept demonstration, we fabricate flexible, transparent, and force-sensitive touch screens using cross-aligned AgNW electrodes integrated with mechanochromic spiropyran-polydimethylsiloxane composite film. Our force-sensitive touch screens enable the precise monitoring of dynamic writings, tracing and drawing of underneath pictures, and perception of handwriting patterns with locally different writing forces. The suggested technique provides a robust and powerful platform for the controllable assembly of nanowires beyond the scale of conventional fabrication techniques, which can find diverse applications in multifunctional flexible electronic and optoelectronic devices.

Posttraumatic stress and tendency to panic in the aftermath of the chlorine gas disaster in Graniteville, South Carolina.

PubMed

Ginsberg, Jay P; Holbrook, Joseph R; Chanda, Debjani; Bao, Haikun; Svendsen, Erik R

2012-09-01

Relatively little is known about psychological effects of environmental hazard disasters. This study examines the development of posttraumatic stress (PTS) and tendency to limited panic attack after a large chlorine spill in a community. In January 2005, a large chlorine spill occurred in Graniteville, SC. Acute injuries were quantified on an ordinal severity scale. Eight to ten months later, participating victims completed the Short Screening Scale for PTSD (n = 225) and the Holden Psychological Screening Inventory (HPSI) (n = 193) as part of a public health intervention. Forced expiratory volume in 1 s (FEV(1)) and forced vital capacity were likewise measured via spirometry. Two sets of univariate logistic regression models were fit to detect independent effects of each potential covariate and risk factor on PTS score and tendency to panic. A supplemental analysis examined whether poor lung function may be a confounder and/or effect modifier of the effect of acute injury on PTS score and panic. Of those who completed psychological screening, 36.9% exhibited PTS symptoms. FEV(1), acute injury, and the HPSI psychiatric subscale were independently associated with increased PTS score. Acute injury severity scale and female sex were associated with tendency to panic. Immediate acute injury severity and poor lung function later were independently associated with PTS symptomotology. The high prevalence of PTS and endorsement of tendency to panic within our sample show a need for mental health treatment after a chemical hazard disaster. Mental health personnel should be considerate of those with serious physical injuries.

The brief multidimensional students' life satisfaction scale-college version.

PubMed

Zullig, Keith J; Huebner, E Scott; Patton, Jon M; Murray, Karen A

2009-01-01

To investigate the psychometric properties of the BMSLSS-College among 723 college students. Internal consistency estimates explored scale reliability, factor analysis explored construct validity, and known-groups validity was assessed using the National College Youth Risk Behavior Survey and Harvard School of Public Health College Alcohol Study. Criterion-related validity was explored through analyses with the CDC's health-related quality of life scale and a social isolation scale. Acceptable internal consistency reliability, construct, known-groups, and criterion-related validity were established. Findings offer preliminary support for the BMSLSS-C; it could be useful in large-scale research studies, applied screening contexts, and for program evaluation purposes toward achieving Healthy People 2010 objectives.

Sensitivity of 2-[18F]fluoro-2-deoxyglucose positron emission tomography for advanced colorectal neoplasms: a large-scale analysis of 7505 asymptomatic screening individuals.

PubMed

Sekiguchi, Masau; Kakugawa, Yasuo; Terauchi, Takashi; Matsumoto, Minori; Saito, Hiroshi; Muramatsu, Yukio; Saito, Yutaka; Matsuda, Takahisa

2016-12-01

The sensitivity of 2-[ 18 F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for advanced colorectal neoplasms among healthy subjects is not yet fully understood. The present study aimed to clarify the sensitivity by analyzing large-scale data from an asymptomatic screening population. A total of 7505 asymptomatic screenees who underwent both FDG-PET and colonoscopy at our Cancer Screening Division between February 2004 and March 2013 were analyzed. FDG-PET and colonoscopy were performed on consecutive days, and each examination was interpreted in a blinded fashion. The results of the two examinations were compared for each of the divided six colonic segments, with those from colonoscopy being set as the reference. The relationships between the sensitivity of FDG-PET and clinicopathological features of advanced neoplasms were also evaluated. Two hundred ninety-one advanced neoplasms, including 24 invasive cancers, were detected in 262 individuals. Thirteen advanced neoplasms (advanced adenomas) were excluded from the analysis because of the coexistence of lesions in the same colonic segment. The sensitivity, specificity, and positive and negative predictive values of FDG-PET for advanced neoplasms were 16.9 % [95 % confidence interval (CI) 12.7-21.8 %], 99.3 % (95 % CI 99.2-99.4 %), 13.5 % (95 % CI 10.1-17.6 %), and 99.4 % (95 % CI 99.3-99.5 %), respectively. The sensitivity was lower for lesions with less advanced histological grade, of smaller size, and flat-type morphology, and for those located in the proximal part of the colon. FDG-PET is believed to be difficult to use as a primary screening tool in population-based colorectal cancer screening because of its low sensitivity for advanced neoplasms. Even when it is used in opportunistic cancer screening, the limit of its sensitivity should be considered.

Unlocking nature’s treasure-chest: screening for oleaginous algae

PubMed Central

Slocombe, Stephen P.; Zhang, QianYi; Ross, Michael; Anderson, Avril; Thomas, Naomi J.; Lapresa, Ángela; Rad-Menéndez, Cecilia; Campbell, Christine N.; Black, Kenneth D.; Stanley, Michele S.; Day, John G.

2015-01-01

Micro-algae synthesize high levels of lipids, carbohydrates and proteins photoautotrophically, thus attracting considerable interest for the biotechnological production of fuels, environmental remediation, functional foods and nutraceuticals. Currently, only a few micro-algae species are grown commercially at large-scale, primarily for “health-foods” and pigments. For a range of potential products (fuel to pharma), high lipid productivity strains are required to mitigate the economic costs of mass culture. Here we present a screen concentrating on marine micro-algal strains, which if suitable for scale-up would minimise competition with agriculture for water. Mass-Spectrophotometric analysis (MS) of nitrogen (N) and carbon (C) was subsequently validated by measurement of total fatty acids (TFA) by Gas-Chromatography (GC). This identified a rapid and accurate screening strategy based on elemental analysis. The screen identified Nannochloropsis oceanica CCAP 849/10 and a marine isolate of Chlorella vulgaris CCAP 211/21A as the best lipid producers. Analysis of C, N, protein, carbohydrate and Fatty Acid (FA) composition identified a suite of strains for further biotechnological applications e.g. Dunaliella polymorpha CCAP 19/14, significantly the most productive for carbohydrates, and Cyclotella cryptica CCAP 1070/2, with utility for EPA production and N-assimilation. PMID:26202369

Large-scale systematic analysis of 2D fingerprint methods and parameters to improve virtual screening enrichments.

PubMed

Sastry, Madhavi; Lowrie, Jeffrey F; Dixon, Steven L; Sherman, Woody

2010-05-24

A systematic virtual screening study on 11 pharmaceutically relevant targets has been conducted to investigate the interrelation between 8 two-dimensional (2D) fingerprinting methods, 13 atom-typing schemes, 13 bit scaling rules, and 12 similarity metrics using the new cheminformatics package Canvas. In total, 157 872 virtual screens were performed to assess the ability of each combination of parameters to identify actives in a database screen. In general, fingerprint methods, such as MOLPRINT2D, Radial, and Dendritic that encode information about local environment beyond simple linear paths outperformed other fingerprint methods. Atom-typing schemes with more specific information, such as Daylight, Mol2, and Carhart were generally superior to more generic atom-typing schemes. Enrichment factors across all targets were improved considerably with the best settings, although no single set of parameters performed optimally on all targets. The size of the addressable bit space for the fingerprints was also explored, and it was found to have a substantial impact on enrichments. Small bit spaces, such as 1024, resulted in many collisions and in a significant degradation in enrichments compared to larger bit spaces that avoid collisions.

FIELD DEMONSTRATION OF INNOVATIVE LEAK DETECTION/LOCATION TECHNOLOGIES COUPLED WITH WALL-THICKNESS SCREENING FOR WATER MAINS

EPA Science Inventory

The U.S. Environmental Protection Agency sponsored a large-scale field demonstration of innovative leak detection/location and condition assessment technologies on a 76-year old, 2,500-ft long, cement-lined, 24-in. cast iron water main in Louisville, KY from July through Septembe...

Method for replicating an array of nucleic acid probes

DOEpatents

Cantor, C.R.; Przetakiewicz, M.; Smith, C.L.; Sano, T.

1998-08-18

The invention relates to the replication of probe arrays and methods for replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5{prime}- and/or 3{prime}-overhangs. 16 figs.

Using Association Mapping in Teosinte (Zea Mays ssp Parviglumis) to Investigate the Function of Selection-Candidate Genes

USDA-ARS?s Scientific Manuscript database

Large-scale screens of the maize genome identified 48 genes that show the putative signature of artificial selection during maize domestication or improvement. These selection-candidate genes may act as quantitative trait loci (QTL) that control the phenotypic differences between maize and its proge...

Psychiatric Illness in a Cohort of Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Sinnema, Margje; Boer, Harm; Collin, Philippe; Maaskant, Marian A.; van Roozendaal, Kees E. P.; Schrander-Stumpel, Constance T. R. M.; Curfs, Leopold M. G.

2011-01-01

Previous studies have suggested an association between PWS and comorbid psychiatric illness. Data on prevalence rates of psychopathology is still scarce. This paper describes a large-scale, systematic study investigating the prevalence of psychiatric illness in a Dutch adult PWS cohort. One hundred and two individuals were screened for psychiatric…

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

PubMed Central

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-01-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes. PMID:27767027

Screening of lipid composition for scalable fabrication of solvent free lipid microarrays

NASA Astrophysics Data System (ADS)

Ghazanfari, Lida; Lenhert, Steven

2016-12-01

Liquid microdroplet arrays on surfaces are a promising approach to the miniaturization of laboratory processes such as high throughput screening. The fluid nature of these droplets poses unique challenges and opportunities in their fabrication and application, particularly for the scalable integration of multiple materials over large areas and immersion into cell culture solution. Here we use pin spotting and nanointaglio printing to screen a library of lipids and their mixtures for their compatibility with these fabrication processes, as well as stability upon immersion into aqueous solution. More than 200 combinations of natural and synthetic oils composed of fatty acids, triglycerides, and hydrocarbons were tested for their pin-spotting and nanointaglio print quality and their ability to contain the fluorescent compound TRITC upon immersion in water. A combination of castor oil and hexanoic acid at the ratio of 1:1 (w/w) was found optimal for producing reproducible patterns that are stable upon immersion into water. This method is capable of large scale nano-materials integration.

Protein-protein interaction specificity is captured by contact preferences and interface composition.

PubMed

Nadalin, Francesca; Carbone, Alessandra

2018-02-01

Large-scale computational docking will be increasingly used in future years to discriminate protein-protein interactions at the residue resolution. Complete cross-docking experiments make in silico reconstruction of protein-protein interaction networks a feasible goal. They ask for efficient and accurate screening of the millions structural conformations issued by the calculations. We propose CIPS (Combined Interface Propensity for decoy Scoring), a new pair potential combining interface composition with residue-residue contact preference. CIPS outperforms several other methods on screening docking solutions obtained either with all-atom or with coarse-grain rigid docking. Further testing on 28 CAPRI targets corroborates CIPS predictive power over existing methods. By combining CIPS with atomic potentials, discrimination of correct conformations in all-atom structures reaches optimal accuracy. The drastic reduction of candidate solutions produced by thousands of proteins docked against each other makes large-scale docking accessible to analysis. CIPS source code is freely available at http://www.lcqb.upmc.fr/CIPS. alessandra.carbone@lip6.fr. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes.

PubMed

Bentzen, Amalie Kai; Marquard, Andrea Marion; Lyngaa, Rikke; Saini, Sunil Kumar; Ramskov, Sofie; Donia, Marco; Such, Lina; Furness, Andrew J S; McGranahan, Nicholas; Rosenthal, Rachel; Straten, Per Thor; Szallasi, Zoltan; Svane, Inge Marie; Swanton, Charles; Quezada, Sergio A; Jakobsen, Søren Nyboe; Eklund, Aron Charles; Hadrup, Sine Reker

2016-10-01

Identification of the peptides recognized by individual T cells is important for understanding and treating immune-related diseases. Current cytometry-based approaches are limited to the simultaneous screening of 10-100 distinct T-cell specificities in one sample. Here we use peptide-major histocompatibility complex (MHC) multimers labeled with individual DNA barcodes to screen >1,000 peptide specificities in a single sample, and detect low-frequency CD8 T cells specific for virus- or cancer-restricted antigens. When analyzing T-cell recognition of shared melanoma antigens before and after adoptive cell therapy in melanoma patients, we observe a greater number of melanoma-specific T-cell populations compared with cytometry-based approaches. Furthermore, we detect neoepitope-specific T cells in tumor-infiltrating lymphocytes and peripheral blood from patients with non-small cell lung cancer. Barcode-labeled pMHC multimers enable the combination of functional T-cell analysis with large-scale epitope recognition profiling for the characterization of T-cell recognition in various diseases, including in small clinical samples.

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

PubMed

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.

Molecular diagnosis of malaria by photo-induced electron transfer fluorogenic primers: PET-PCR.

PubMed

Lucchi, Naomi W; Narayanan, Jothikumar; Karell, Mara A; Xayavong, Maniphet; Kariuki, Simon; DaSilva, Alexandre J; Hill, Vincent; Udhayakumar, Venkatachalam

2013-01-01

There is a critical need for developing new malaria diagnostic tools that are sensitive, cost effective and capable of performing large scale diagnosis. The real-time PCR methods are particularly robust for large scale screening and they can be used in malaria control and elimination programs. We have designed novel self-quenching photo-induced electron transfer (PET) fluorogenic primers for the detection of P. falciparum and the Plasmodium genus by real-time PCR. A total of 119 samples consisting of different malaria species and mixed infections were used to test the utility of the novel PET-PCR primers in the diagnosis of clinical samples. The sensitivity and specificity were calculated using a nested PCR as the gold standard and the novel primer sets demonstrated 100% sensitivity and specificity. The limits of detection for P. falciparum was shown to be 3.2 parasites/µl using both Plasmodium genus and P. falciparum-specific primers and 5.8 parasites/µl for P. ovale, 3.5 parasites/µl for P. malariae and 5 parasites/µl for P. vivax using the genus specific primer set. Moreover, the reaction can be duplexed to detect both Plasmodium spp. and P. falciparum in a single reaction. The PET-PCR assay does not require internal probes or intercalating dyes which makes it convenient to use and less expensive than other real-time PCR diagnostic formats. Further validation of this technique in the field will help to assess its utility for large scale screening in malaria control and elimination programs.

Sachem: a chemical cartridge for high-performance substructure search.

PubMed

Kratochvíl, Miroslav; Vondrášek, Jiří; Galgonek, Jakub

2018-05-23

Structure search is one of the valuable capabilities of small-molecule databases. Fingerprint-based screening methods are usually employed to enhance the search performance by reducing the number of calls to the verification procedure. In substructure search, fingerprints are designed to capture important structural aspects of the molecule to aid the decision about whether the molecule contains a given substructure. Currently available cartridges typically provide acceptable search performance for processing user queries, but do not scale satisfactorily with dataset size. We present Sachem, a new open-source chemical cartridge that implements two substructure search methods: The first is a performance-oriented reimplementation of substructure indexing based on the OrChem fingerprint, and the second is a novel method that employs newly designed fingerprints stored in inverted indices. We assessed the performance of both methods on small, medium, and large datasets containing 1, 10, and 94 million compounds, respectively. Comparison of Sachem with other freely available cartridges revealed improvements in overall performance, scaling potential and screen-out efficiency. The Sachem cartridge allows efficient substructure searches in databases of all sizes. The sublinear performance scaling of the second method and the ability to efficiently query large amounts of pre-extracted information may together open the door to new applications for substructure searches.

ZebraZoom: an automated program for high-throughput behavioral analysis and categorization

PubMed Central

Mirat, Olivier; Sternberg, Jenna R.; Severi, Kristen E.; Wyart, Claire

2013-01-01

The zebrafish larva stands out as an emergent model organism for translational studies involving gene or drug screening thanks to its size, genetics, and permeability. At the larval stage, locomotion occurs in short episodes punctuated by periods of rest. Although phenotyping behavior is a key component of large-scale screens, it has not yet been automated in this model system. We developed ZebraZoom, a program to automatically track larvae and identify maneuvers for many animals performing discrete movements. Our program detects each episodic movement and extracts large-scale statistics on motor patterns to produce a quantification of the locomotor repertoire. We used ZebraZoom to identify motor defects induced by a glycinergic receptor antagonist. The analysis of the blind mutant atoh7 revealed small locomotor defects associated with the mutation. Using multiclass supervised machine learning, ZebraZoom categorized all episodes of movement for each larva into one of three possible maneuvers: slow forward swim, routine turn, and escape. ZebraZoom reached 91% accuracy for categorization of stereotypical maneuvers that four independent experimenters unanimously identified. For all maneuvers in the data set, ZebraZoom agreed with four experimenters in 73.2–82.5% of cases. We modeled the series of maneuvers performed by larvae as Markov chains and observed that larvae often repeated the same maneuvers within a group. When analyzing subsequent maneuvers performed by different larvae, we found that larva–larva interactions occurred as series of escapes. Overall, ZebraZoom reached the level of precision found in manual analysis but accomplished tasks in a high-throughput format necessary for large screens. PMID:23781175

[Epidemiological methods used in studies in the prevalence of Tourette syndrome].

PubMed

Stefanoff, Paweł; Mazurek, Jacek

2003-01-01

Tourette syndrome (TS) prevalence was studied since the early 80-ies. Its clinical course is characterised by co-occurrence of motor and vocal tics. Results of previous epidemiological studies were surprisingly divergent: the prevalence varied from 0.5 to 115 cases per 10,000 population. The disease previously recognised as extremely rare and severe is now considered as quite common, with often moderate course. Selected methods used in studies of TS prevalence and analysis of their possible impact on study results are presented. The studies were divided into 3 groups: studies of the hospitalised population, large-scale screenings and studies involving school population, basing on characteristic and size of population, methods of selection of subjects, diagnostic and screening methods used. Studies of the hospitalised population involved patients with most severe symptoms, in different age groups, different methods of final diagnosis confirmation were used. TS prevalence varied from 0.5 up to 15 cases per 10,000 population. Procedures used in large-scale screening studies made possible the elimination of potential selection bias. Large populations were studied using transparent and repetitive confirmation of diagnoses. Their validity was additionally checked in parallel validity studies. TS prevalence was in the range 4.3 to 10 cases per 10,000 population. The highest TS prevalence was obtained in studies involving schoolchildren. Data were gathered from multiple sources: from parents, teachers and children, as well as from classroom observation. Diagnoses were made by experienced clinicians. TS prevalence obtained in school population studies was between 36.2 up to 115 per 10,000 population.

Conditional screening for ultra-high dimensional covariates with survival outcomes

PubMed Central

Hong, Hyokyoung G.; Li, Yi

2017-01-01

Identifying important biomarkers that are predictive for cancer patients’ prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization. The recently developed variable screening methods, though powerful in many practical setting, fail to incorporate prior information on the importance of each biomarker and are less powerful in detecting marginally weak while jointly important signals. We propose a new conditional screening method for survival outcome data by computing the marginal contribution of each biomarker given priorily known biological information. This is based on the premise that some biomarkers are known to be associated with disease outcomes a priori. Our method possesses sure screening properties and a vanishing false selection rate. The utility of the proposal is further confirmed with extensive simulation studies and analysis of a diffuse large B-cell lymphoma dataset. We are pleased to dedicate this work to Jack Kalbfleisch, who has made instrumental contributions to the development of modern methods of analyzing survival data. PMID:27933468

Feasibility of telemammography as biomedical application for breast imaging

NASA Astrophysics Data System (ADS)

Beckerman, Barbara G.; Batsell, Stephen G.; MacIntyre, Lawrence P.; Sarraf, Hamed S.; Gleason, Shaun S.; Schnall, Mitchell D.

1999-07-01

Mammographic screening is an important tool in the early detection of breast cancer. The migration of mammography from the current mode of x-ray mammography using a film screen image detector and display to a digital technology provides an opportunity to improve access and performance of breast cancer screening. The sheer size and volume of the typical screening exam, the need to have previous screening data readily available, and the need to view other breast imaging data together to provide a common consensus and to plan treatment, make telemammography an ideal application for breast imaging. For telemammography to be a viable option, it must overcome the technical challenges related to transmission, archiving, management, processing and retrieval of large data sets. Researchers from the University of Pennsylvania, the University of Chicago and Lockheed Martin Energy Systems/Oak Ridge National Laboratory have developed a framework for transmission of large-scale medical images over high-speed networks, leveraged existing high-speed networks between research and medical facilities; tested the feasibility of point-to-point transmission of mammographic images in a near-real time environment; evaluated network performance and transmission scenarios; and investigated the impact of image preprocessing on an experimental computer-aided diagnosis system. Results of the initial study are reported here.

DOVIS: an implementation for high-throughput virtual screening using AutoDock.

PubMed

Zhang, Shuxing; Kumar, Kamal; Jiang, Xiaohui; Wallqvist, Anders; Reifman, Jaques

2008-02-27

Molecular-docking-based virtual screening is an important tool in drug discovery that is used to significantly reduce the number of possible chemical compounds to be investigated. In addition to the selection of a sound docking strategy with appropriate scoring functions, another technical challenge is to in silico screen millions of compounds in a reasonable time. To meet this challenge, it is necessary to use high performance computing (HPC) platforms and techniques. However, the development of an integrated HPC system that makes efficient use of its elements is not trivial. We have developed an application termed DOVIS that uses AutoDock (version 3) as the docking engine and runs in parallel on a Linux cluster. DOVIS can efficiently dock large numbers (millions) of small molecules (ligands) to a receptor, screening 500 to 1,000 compounds per processor per day. Furthermore, in DOVIS, the docking session is fully integrated and automated in that the inputs are specified via a graphical user interface, the calculations are fully integrated with a Linux cluster queuing system for parallel processing, and the results can be visualized and queried. DOVIS removes most of the complexities and organizational problems associated with large-scale high-throughput virtual screening, and provides a convenient and efficient solution for AutoDock users to use this software in a Linux cluster platform.

DrishtiCare: a telescreening platform for diabetic retinopathy powered with fundus image analysis.

PubMed

Joshi, Gopal Datt; Sivaswamy, Jayanthi

2011-01-01

Diabetic retinopathy is the leading cause of blindness in urban populations. Early diagnosis through regular screening and timely treatment has been shown to prevent visual loss and blindness. It is very difficult to cater to this vast set of diabetes patients, primarily because of high costs in reaching out to patients and a scarcity of skilled personnel. Telescreening offers a cost-effective solution to reach out to patients but is still inadequate due to an insufficient number of experts who serve the diabetes population. Developments toward fundus image analysis have shown promise in addressing the scarcity of skilled personnel for large-scale screening. This article aims at addressing the underlying issues in traditional telescreening to develop a solution that leverages the developments carried out in fundus image analysis. We propose a novel Web-based telescreening solution (called DrishtiCare) integrating various value-added fundus image analysis components. A Web-based platform on the software as a service (SaaS) delivery model is chosen to make the service cost-effective, easy to use, and scalable. A server-based prescreening system is employed to scrutinize the fundus images of patients and to refer them to the experts. An automatic quality assessment module ensures transfer of fundus images that meet grading standards. An easy-to-use interface, enabled with new visualization features, is designed for case examination by experts. Three local primary eye hospitals have participated and used DrishtiCare's telescreening service. A preliminary evaluation of the proposed platform is performed on a set of 119 patients, of which 23% are identified with the sight-threatening retinopathy. Currently, evaluation at a larger scale is under process, and a total of 450 patients have been enrolled. The proposed approach provides an innovative way of integrating automated fundus image analysis in the telescreening framework to address well-known challenges in large-scale disease screening. It offers a low-cost, effective, and easily adoptable screening solution to primary care providers. © 2010 Diabetes Technology Society.

High- and low-throughput scoring of fat mass and body fat distribution in C. elegans

PubMed Central

Wählby, Carolina; Lee-Conery, Annie; Bray, Mark-Anthony; Kamentsky, Lee; Larkins-Ford, Jonah; Sokolnicki, Katherine L.; Veneskey, Matthew; Michaels, Kerry; Carpenter, Anne E.; O’Rourke, Eyleen J.

2014-01-01

Fat accumulation is a complex phenotype affected by factors such as neuroendocrine signaling, feeding, activity, and reproductive output. Accordingly, the most informative screens for genes and compounds affecting fat accumulation would be those carried out in whole living animals. Caenorhabditis elegans is a well-established and effective model organism, especially for biological processes that involve organ systems and multicellular interactions, such as metabolism. Every cell in the transparent body of C. elegans is visible under a light microscope. Consequently, an accessible and reliable method to visualize worm lipid-droplet fat depots would make C. elegans the only metazoan in which genes affecting not only fat mass but also body fat distribution could be assessed at a genome-wide scale. Here we present a radical improvement in oil red O worm staining together with high-throughput image-based phenotyping. The three-step sample preparation method is robust, formaldehyde-free, and inexpensive, and requires only 15 minutes of hands-on time to process a 96-well plate. Together with our free and user-friendly automated image analysis package, this method enables C. elegans sample preparation and phenotype scoring at a scale that is compatible with genome-wide screens. Thus we present a feasible approach to small-scale phenotyping and large-scale screening for genetic and/or chemical perturbations that lead to alterations in fat quantity and distribution in whole animals. PMID:24784529

Study on the Mechanisms of Active Compounds in Traditional Chinese Medicine for the Treatment of Influenza Virus by Virtual Screening.

PubMed

Ai, Haixin; Wu, Xuewei; Qi, Mengyuan; Zhang, Li; Hu, Huan; Zhao, Qi; Zhao, Jian; Liu, Hongsheng

2018-06-01

In recent years, new strains of influenza virus such as H7N9, H10N8, H5N6 and H5N8 had continued to emerge. There was an urgent need for discovery of new anti-influenza virus drugs as well as accurate and efficient large-scale inhibitor screening methods. In this study, we focused on six influenza virus proteins that could be anti-influenza drug targets, including neuraminidase (NA), hemagglutinin (HA), matrix protein 1 (M1), M2 proton channel (M2), nucleoprotein (NP) and non-structural protein 1 (NS1). Structure-based molecular docking was utilized to identify potential inhibitors for these drug targets from 13144 compounds in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The results showed that 56 compounds could inhibit more than two drug targets simultaneously. Further, we utilized reverse docking to study the interaction of these compounds with host targets. Finally, the 22 compound inhibitors could stably bind to host targets with high binding free energy. The results showed that the Chinese herbal medicines had a multi-target effect, which could directly inhibit influenza virus by the target viral protein and indirectly inhibit virus by the human target protein. This method was of great value for large-scale virtual screening of new anti-influenza virus compounds.

High-Content Microfluidic Screening Platform Used To Identify σ2R/Tmem97 Binding Ligands that Reduce Age-Dependent Neurodegeneration in C. elegans SC_APP Model.

PubMed

Mondal, Sudip; Hegarty, Evan; Sahn, James J; Scott, Luisa L; Gökçe, Sertan Kutal; Martin, Chris; Ghorashian, Navid; Satarasinghe, Praveen Navoda; Iyer, Sangeetha; Sae-Lee, Wisath; Hodges, Timothy R; Pierce, Jonathan T; Martin, Stephen F; Ben-Yakar, Adela

2018-05-16

The nematode Caenorhabditis elegans, with tractable genetics and a well-defined nervous system, provides a unique whole-animal model system to identify novel drug targets and therapies for neurodegenerative diseases. Large-scale drug or target screens in models that recapitulate the subtle age- and cell-specific aspects of neurodegenerative diseases are limited by a technological requirement for high-throughput analysis of neuronal morphology. Recently, we developed a single-copy model of amyloid precursor protein (SC_APP) induced neurodegeneration that exhibits progressive degeneration of select cholinergic neurons. Our previous work with this model suggests that small molecule ligands of the sigma 2 receptor (σ2R), which was recently cloned and identified as transmembrane protein 97 (TMEM97), are neuroprotective. To determine structure-activity relationships for unexplored chemical space in our σ2R/Tmem97 ligand collection, we developed an in vivo high-content screening (HCS) assay to identify potential drug leads. The HCS assay uses our recently developed large-scale microfluidic immobilization chip and automated imaging platform. We discovered norbenzomorphans that reduced neurodegeneration in our C. elegans model, including two compounds that demonstrated significant neuroprotective activity at multiple doses. These findings provide further evidence that σ2R/Tmem97-binding norbenzomorphans may represent a new drug class for treating neurodegenerative diseases.

Posttraumatic stress disorder in veterans and military personnel: epidemiology, screening, and case recognition.

PubMed

Gates, Margaret A; Holowka, Darren W; Vasterling, Jennifer J; Keane, Terence M; Marx, Brian P; Rosen, Raymond C

2012-11-01

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that affects 7-8% of the general U.S. population at some point during their lifetime; however, the prevalence is much higher among certain subgroups, including active duty military personnel and veterans. In this article, we review the empirical literature on the epidemiology and screening of PTSD in military and veteran populations, including the availability of sensitive and reliable screening tools. Although estimates vary across studies, evidence suggests that the prevalence of PTSD in deployed U.S. military personnel may be as high as 14-16%. Prior studies have identified trauma characteristics and pre- and posttrauma factors that increase risk of PTSD among veterans and military personnel. This information may help to inform prevention and screening efforts, as screening programs could be targeted to high-risk populations. Large-scale screening efforts have recently been implemented by the U.S. Departments of Defense and Veterans Affairs. Given the prevalence and potential consequences of PTSD among veterans and active duty military personnel, development and continued evaluation of effective screening methods is an important public health need.

A phase screen model for simulating numerically the propagation of a laser beam in rain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lukin, I P; Rychkov, D S; Falits, A V

2009-09-30

The method based on the generalisation of the phase screen method for a continuous random medium is proposed for simulating numerically the propagation of laser radiation in a turbulent atmosphere with precipitation. In the phase screen model for a discrete component of a heterogeneous 'air-rain droplet' medium, the amplitude screen describing the scattering of an optical field by discrete particles of the medium is replaced by an equivalent phase screen with a spectrum of the correlation function of the effective dielectric constant fluctuations that is similar to the spectrum of a discrete scattering component - water droplets in air. Themore » 'turbulent' phase screen is constructed on the basis of the Kolmogorov model, while the 'rain' screen model utiises the exponential distribution of the number of rain drops with respect to their radii as a function of the rain intensity. Theresults of the numerical simulation are compared with the known theoretical estimates for a large-scale discrete scattering medium. (propagation of laser radiation in matter)« less

Study of LANDSAT-D thematic mapper performance as applied to hydrocarbon exploration

NASA Technical Reports Server (NTRS)

Everett, J. R. (Principal Investigator)

1983-01-01

Two fully processed test tapes were enhanced and evaluated at scales up to 1:10,000, using both hardcopy output and interactive screen display. A large scale, the Detroit, Michigan scene shows evidence of an along line data slip every sixteenth line in TM channel 2. Very large scale products generated in false color using channels 1,3, and 4 should be very acceptable for interpretation at scales up to 1:50,000 and useful for change mapping probably up to scale 1:24,000. Striping visible in water bodies for both natural and color products indicates that the detector calibration is probably performing below preflight specification. For a set of 512 x 512 windows within the NE Arkansas scene, the variance-covariance matrices were computed and principal component analyses performed. Initial analysis suggests that the shortwave infrared TM 5 and 6 channels are a highly significant data source. The thermal channel (TM 7) shows negative correlation with TM 1 and 4.

The electrostatic persistence length of polymers beyond the OSF limit.

PubMed

Everaers, R; Milchev, A; Yamakov, V

2002-05-01

We use large-scale Monte Carlo simulations to test scaling theories for the electrostatic persistence length l(e) of isolated, uniformly charged polymers with Debye-Hückel intrachain interactions in the limit where the screening length kappa(-1) exceeds the intrinsic persistence length of the chains. Our simulations cover a significantly larger part of the parameter space than previous studies. We observe no significant deviations from the prediction l(e) proportional to kappa(-2) by Khokhlov and Khachaturian which is based on applying the Odijk-Skolnick-Fixman theories of electrostatic bending rigidity and electrostatically excluded volume to the stretched de Gennes-Pincus-Velasco-Brochard polyelectrolyte blob chain. A linear or sublinear dependence of the persistence length on the screening length can be ruled out. We show that previous results pointing into this direction are due to a combination of excluded-volume and finite chain length effects. The paper emphasizes the role of scaling arguments in the development of useful representations for experimental and simulation data.

Should acute Q-fever patients be screened for valvulopathy to prevent endocarditis?

PubMed

de Lange, Marit M A; Gijsen, Laura E V; Wielders, Cornelia C H; van der Hoek, Wim; Scheepmaker, Arko; Schneeberger, Peter M

2018-02-20

Echocardiographic screening of acute Q-fever patients and antibiotic prophylaxis for patients with cardiac valvulopathy are considered an important approach to prevent chronic Q-fever-related endocarditis. During a large Q-fever epidemic in the Netherlands, routine screening echocardiography was discontinued, raising controversy in the international literature. We followed a cohort of acute Q-fever patients to estimate the risk for developing chronic Q-fever, and we evaluated the impact of screening in patients who were not yet known to have a valvulopathy. The study population consisted of patients diagnosed with acute Q-fever in 2007 and 2008. We retrospectively reviewed all screening echocardiographs and checked for development of chronic Q-fever eight years after the acute episode. Risks of developing chronic Q-fever in relation to the presence or absence of valvulopathy were analysed with logistic regression. The cohort included 509 patients, of whom 306 received echocardiographic screening. There was no significant difference (p-value=0.22) in occurrence of chronic Q-fever between patients with a newly detected valvulopathy (2/84, 2.4%) and those with no valvulopathy (12/202, 5.9%). Two patients with a newly detected valvulopathy, who did not receive antibiotic prophylaxis, developed chronic Q-fever at a later stage. We found no difference in outcome between patients with and without a valvulopathy newly detected by echocardiographic screening. In retrospect, the two above-mentioned patients could have benefitted from antibiotic prophylaxis, but its omission must be weighed against the unnecessary large-scale and long-term use of antibiotics that would have resulted from universal echocardiographic screening.

Inflation of the screening length induced by Bjerrum pairs.

PubMed

Zwanikken, Jos; van Roij, René

2009-10-21

Within a modified Poisson-Boltzmann theory we study the effect of Bjerrum pairs on the typical length scale [Formula: see text] over which electric fields are screened in electrolyte solutions, taking into account a simple association-dissociation equilibrium between free ions and Bjerrum pairs. At low densities of Bjerrum pairs, this length scale is well approximated by the Debye length [Formula: see text], with ρ(s) the free-ion density. At high densities of Bjerrum pairs, however, we find [Formula: see text], which is significantly larger than 1/κ due to the enhanced effective permittivity of the electrolyte, caused by the polarization of Bjerrum pairs. We argue that this mechanism may explain the recently observed anomalously large colloid-free zones between an oil-dispersed colloidal crystal and a colloidal monolayer at the oil-water interface.

Materials for stem cell factories of the future

NASA Astrophysics Data System (ADS)

Celiz, Adam D.; Smith, James G. W.; Langer, Robert; Anderson, Daniel G.; Winkler, David A.; Barrett, David A.; Davies, Martyn C.; Young, Lorraine E.; Denning, Chris; Alexander, Morgan R.

2014-06-01

Polymeric substrates are being identified that could permit translation of human pluripotent stem cells from laboratory-based research to industrial-scale biomedicine. Well-defined materials are required to allow cell banking and to provide the raw material for reproducible differentiation into lineages for large-scale drug-screening programs and clinical use. Yet more than 1 billion cells for each patient are needed to replace losses during heart attack, multiple sclerosis and diabetes. Producing this number of cells is challenging, and a rethink of the current predominant cell-derived substrates is needed to provide technology that can be scaled to meet the needs of millions of patients a year. In this Review, we consider the role of materials discovery, an emerging area of materials chemistry that is in large part driven by the challenges posed by biologists to materials scientists.

Screening for Posttraumatic Stress Disorder among Somali ex-combatants: A validation study

PubMed Central

Odenwald, Michael; Lingenfelder, Birke; Schauer, Maggie; Neuner, Frank; Rockstroh, Brigitte; Hinkel, Harald; Elbert, Thomas

2007-01-01

Background In Somalia, a large number of active and former combatants are affected by psychological problems such as Posttraumatic Stress Disorder (PTSD). This disorder impairs their ability to re-integrate into civilian life. However, many screening instruments for Posttraumatic Stress Disorder used in post-conflict settings have limited validity. Here we report on development and validation of a screening tool for PTSD in Somali language with a sample of ex-combatants. Methods We adapted the Posttraumatic Diagnostic Scale (PDS) to reflect linguistic and cultural differences within the Somali community so that local interviewers could be trained to administer the scale. For validation purposes, a randomly selected group of 135 Somali ex-combatants was screened by trained local interviewers; 64 of them were then re-assessed by trained clinical psychologists using the Composite International Diagnostic Interview (CIDI) and the Self-Report Questionnaire (SRQ-20). Results The screening instrument showed good internal consistency (Cronbach's α = .86), convergent validity with the CIDI (sensitivity = .90; specificity = .90) as well as concurrent validity: positive cases showed higher SRQ-20 scores, higher prevalence of psychotic symptoms, and higher levels of intake of the local stimulant drug khat. Compared to a single cut-off score, the multi-criteria scoring, in keeping with the DSM-IV, produced more diagnostic specificity. Conclusion The results provide evidence that our screening instrument is a reliable and valid method to detect PTSD among Somali ex-combatants. A future Disarmament, Demobilization and Reintegration Program in Somalia is recommended to screen for PTSD in order to identify ex-combatants with special psycho-social needs. PMID:17822562

Large-scale image region documentation for fully automated image biomarker algorithm development and evaluation.

PubMed

Reeves, Anthony P; Xie, Yiting; Liu, Shuang

2017-04-01

With the advent of fully automated image analysis and modern machine learning methods, there is a need for very large image datasets having documented segmentations for both computer algorithm training and evaluation. This paper presents a method and implementation for facilitating such datasets that addresses the critical issue of size scaling for algorithm validation and evaluation; current evaluation methods that are usually used in academic studies do not scale to large datasets. This method includes protocols for the documentation of many regions in very large image datasets; the documentation may be incrementally updated by new image data and by improved algorithm outcomes. This method has been used for 5 years in the context of chest health biomarkers from low-dose chest CT images that are now being used with increasing frequency in lung cancer screening practice. The lung scans are segmented into over 100 different anatomical regions, and the method has been applied to a dataset of over 20,000 chest CT images. Using this framework, the computer algorithms have been developed to achieve over 90% acceptable image segmentation on the complete dataset.

Preliminary Evaluation of a Brief Autism Screener for Young Children.

PubMed

Zahorodny, Walter; Shenouda, Josephine; Mehta, Uday; Yee, Emily; Garcia, Patricia; Rajan, Mangala; Goldfarb, Madeleine

2018-04-01

Our objective was to assess the operating characteristics of the Psychological Development Questionnaire-1 (PDQ-1), an autism screener for use with young children. In Phase 1, we evaluated the concordance of the PDQ-1 with established autism scales, determined test-retest reliability, and identified a risk threshold score. In Phase 2, a population of 1959 toddler-age children was prospectively screened through multiple pediatric practices in a diverse metropolitan region, using the new instrument. Screen-positive children were referred for diagnostic evaluation. Screened children received follow-up at age 4 years to identify autism cases missed by screening and to specify the scale's psychometric properties. By screening a diverse population of low risk children, age 18 to 36 months, with the PDQ-1, we detected individuals with autism who had not come to professional attention. Overall, the PDQ-1 showed a positive predictive value (PPV) of 88%, with a sensitivity of 85% and specificity of 99% in a low risk population. High specificity, good sensitivity, and PPV were observed across the 18 to 36 month age-range. The findings provide preliminary empirical support for this parent report-based indicator of toddler psychological development and suggest that the PDQ-1 may be a useful supplement to developmental surveillance of autism. Additional research is needed with high risk samples and large, unselected populations under real-world conditions.

Preliminary Evaluation of a Brief Autism Screener for Young Children

PubMed Central

Shenouda, Josephine; Mehta, Uday; Yee, Emily; Garcia, Patricia; Rajan, Mangala; Goldfarb, Madeleine

2018-01-01

ABSTRACT: Objective: Our objective was to assess the operating characteristics of the Psychological Development Questionnaire-1 (PDQ-1), an autism screener for use with young children. Methods: In Phase 1, we evaluated the concordance of the PDQ-1 with established autism scales, determined test-retest reliability, and identified a risk threshold score. In Phase 2, a population of 1959 toddler-age children was prospectively screened through multiple pediatric practices in a diverse metropolitan region, using the new instrument. Screen-positive children were referred for diagnostic evaluation. Screened children received follow-up at age 4 years to identify autism cases missed by screening and to specify the scale's psychometric properties. Results: By screening a diverse population of low risk children, age 18 to 36 months, with the PDQ-1, we detected individuals with autism who had not come to professional attention. Overall, the PDQ-1 showed a positive predictive value (PPV) of 88%, with a sensitivity of 85% and specificity of 99% in a low risk population. High specificity, good sensitivity, and PPV were observed across the 18 to 36 month age-range. Conclusion: The findings provide preliminary empirical support for this parent report–based indicator of toddler psychological development and suggest that the PDQ-1 may be a useful supplement to developmental surveillance of autism. Additional research is needed with high risk samples and large, unselected populations under real-world conditions. PMID:29300209

Screening for personality disorder in incarcerated adolescent boys: preliminary validation of an adolescent version of the standardised assessment of personality - abbreviated scale (SAPAS-AV).

PubMed

Kongerslev, Mickey; Moran, Paul; Bo, Sune; Simonsen, Erik

2012-07-30

Personality disorder (PD) is associated with significant functional impairment and an elevated risk of violent and suicidal behaviour. The prevalence of PD in populations of young offenders is likely to be high. However, because the assessment of PD is time-consuming, it is not routinely assessed in this population. A brief screen for the identification of young people who might warrant further detailed assessment of PD could be particularly valuable for clinicians and researchers working in juvenile justice settings. We adapted a rapid screen for the identification of PD in adults (Standardised Assessment of Personality - Abbreviated Scale; SAPAS) for use with adolescents and then carried out a study of the reliability and validity of the adapted instrument in a sample of 80 adolescent boys in secure institutions. Participants were administered the screen and shortly after an established diagnostic interview for DSM-IV PDs. Nine days later the screen was readministered. A score of 3 or more on the screening interview correctly identified the presence of DSM-IV PD in 86% of participants, yielding a sensitivity and specificity of 0.87 and 0.86 respectively. Internal consistency was modest but comparable to the original instrument. 9-days test-retest reliability for the total score was excellent. Convergent validity correlations with the total number of PD criteria were large. This study provides preliminary evidence of the validity, reliability, and usefulness of the screen in secure institutions for adolescent male offenders. It can be used in juvenile offender institutions with limited resources, as a brief, acceptable, staff-administered routine screen to identify individuals in need of further assessment of PD or by researchers conducting epidemiological surveys.

Screening for personality disorder in incarcerated adolescent boys: preliminary validation of an adolescent version of the standardised assessment of personality – abbreviated scale (SAPAS-AV)

PubMed Central

2012-01-01

Background Personality disorder (PD) is associated with significant functional impairment and an elevated risk of violent and suicidal behaviour. The prevalence of PD in populations of young offenders is likely to be high. However, because the assessment of PD is time-consuming, it is not routinely assessed in this population. A brief screen for the identification of young people who might warrant further detailed assessment of PD could be particularly valuable for clinicians and researchers working in juvenile justice settings. Method We adapted a rapid screen for the identification of PD in adults (Standardised Assessment of Personality – Abbreviated Scale; SAPAS) for use with adolescents and then carried out a study of the reliability and validity of the adapted instrument in a sample of 80 adolescent boys in secure institutions. Participants were administered the screen and shortly after an established diagnostic interview for DSM-IV PDs. Nine days later the screen was readministered. Results A score of 3 or more on the screening interview correctly identified the presence of DSM-IV PD in 86% of participants, yielding a sensitivity and specificity of 0.87 and 0.86 respectively. Internal consistency was modest but comparable to the original instrument. 9-days test-retest reliability for the total score was excellent. Convergent validity correlations with the total number of PD criteria were large. Conclusion This study provides preliminary evidence of the validity, reliability, and usefulness of the screen in secure institutions for adolescent male offenders. It can be used in juvenile offender institutions with limited resources, as a brief, acceptable, staff-administered routine screen to identify individuals in need of further assessment of PD or by researchers conducting epidemiological surveys. PMID:22846474

Metabolic Syndrome, Obesity, and Related Risk Factors among College Men and Women

ERIC Educational Resources Information Center

Morrell, Jesse S.; Lofgren, Ingrid E.; Burke, Joanne D.; Reilly, Ruth A.

2012-01-01

Objectives: The primary objective of this study was to characterize the prevalence of overweight/obesity, metabolic syndrome (MbS) and its criteria, and nutrient intakes of college-age men and women via a large-scale screening. Participants and Methods: From August 2005 to July 2008, 2,722 subjects were recruited for the ongoing, cross-sectional…

An imputed forest composition map for New England screened by species range boundaries

Treesearch

Matthew J. Duveneck; Jonathan R. Thompson; B. Tyler Wilson

2015-01-01

Initializing forest landscape models (FLMs) to simulate changes in tree species composition requires accurate fine-scale forest attribute information mapped continuously over large areas. Nearest-neighbor imputation maps, maps developed from multivariate imputation of field plots, have high potential for use as the initial condition within FLMs, but the tendency for...

Droplet-based microfluidic flow injection system with large-scale concentration gradient by a single nanoliter-scale injection for enzyme inhibition assay.

PubMed

Cai, Long-Fei; Zhu, Ying; Du, Guan-Sheng; Fang, Qun

2012-01-03

We described a microfluidic chip-based system capable of generating droplet array with a large scale concentration gradient by coupling flow injection gradient technique with droplet-based microfluidics. Multiple modules including sample injection, sample dispersion, gradient generation, droplet formation, mixing of sample and reagents, and online reaction within the droplets were integrated into the microchip. In the system, nanoliter-scale sample solution was automatically injected into the chip under valveless flow injection analysis mode. The sample zone was first dispersed in the microchannel to form a concentration gradient along the axial direction of the microchannel and then segmented into a linear array of droplets by immiscible oil phase. With the segmentation and protection of the oil phase, the concentration gradient profile of the sample was preserved in the droplet array with high fidelity. With a single injection of 16 nL of sample solution, an array of droplets with concentration gradient spanning 3-4 orders of magnitude could be generated. The present system was applied in the enzyme inhibition assay of β-galactosidase to preliminarily demonstrate its potential in high throughput drug screening. With a single injection of 16 nL of inhibitor solution, more than 240 in-droplet enzyme inhibition reactions with different inhibitor concentrations could be performed with an analysis time of 2.5 min. Compared with multiwell plate-based screening systems, the inhibitor consumption was reduced 1000-fold. © 2011 American Chemical Society

Finding Horndeski theories with Einstein gravity limits

DOE Office of Scientific and Technical Information (OSTI.GOV)

McManus, Ryan; Lombriser, Lucas; Peñarrubia, Jorge, E-mail: ryanm@roe.ac.uk, E-mail: llo@roe.ac.uk, E-mail: jorpega@roe.ac.uk

The Horndeski action is the most general scalar-tensor theory with at most second-order derivatives in the equations of motion, thus evading Ostrogradsky instabilities and making it of interest when modifying gravity at large scales. To pass local tests of gravity, these modifications predominantly rely on nonlinear screening mechanisms that recover Einstein's Theory of General Relativity in regions of high density. We derive a set of conditions on the four free functions of the Horndeski action that examine whether a specific model embedded in the action possesses an Einstein gravity limit or not. For this purpose, we develop a new andmore » surprisingly simple scaling method that identifies dominant terms in the equations of motion by considering formal limits of the couplings that enter through the new terms in the modified action. This enables us to find regimes where nonlinear terms dominate and Einstein's field equations are recovered to leading order. Together with an efficient approximation of the scalar field profile, one can then further evaluate whether these limits can be attributed to a genuine screening effect. For illustration, we apply the analysis to both a cubic galileon and a chameleon model as well as to Brans-Dicke theory. Finally, we emphasise that the scaling method also provides a natural approach for performing post-Newtonian expansions in screened regimes.« less

Validation and adaptation of the Norwegian version of Hayes Ability Screening Index for intellectual difficulties in a psychiatric sample.

PubMed

Søndenaa, Erik; Nygård, Øyvind; Nøttestad, Jim Aage; Linaker, Olav Martin

2011-02-01

Intellectual disabilities (ID) among psychiatric patients have traditionally been neglected. A lack of convenient instruments and competency in ID may have worsened the conditions and treatment availability for these patients. Validation and adaptation of a screening instrument for ID (Hayes Ability Screening Index; HASI) in a psychiatric hospital setting. This is a cross-sectional study of 50 psychiatric patients in two Norwegian psychiatric hospitals comparing results of the HASI with the Wechsler Abbreviated Scale of Intelligence (WASI). The HASI correlated well with the standard IQ test used (r= 0.67, P< 0.001). At a stated cut-off score of 85, the HASI had a sensitivity of 100% and specificity of 34%. The HASI is a valid and time-saving screening instrument for ID among psychiatric patients. The prescribed cut-off score, however, resulted in a large number of false positives.

[Screening for intellectual disability among adults].

PubMed

Søndenaa, Erik; Linaker, Olav; Bjørgen, Tale Gjertine; Nøttestad, Jim Aage

2010-08-12

Instigation of proper measures in case of intellectual disability is often conditioned by a diagnosis. Our aim was to assess whether the Hayes Ability Screening Index (HASI) is a suitable screening instrument for intellectual disability among adults. The article is based on three former studies aimed at validating HASI for use among patients referred for neuropsychological examination, prison inmates and psychiatric inpatients in community mental health centres. The sample consisted of 264 persons. The HASI correlated with the more comprehensive scales of assessing intellectual functioning (Wechsler tests) (r = 0.73, p < 0.001). With a cut-off value of 85, HASI had a sensitivity of 0.97 and a specificity of 0.61 in relation to an IQ < 70. HASI is associated with few false negatives, but a large number of false positives. This implies that an intellectual disability is concluded in too many cases; a positive screening should be followed up with a more thorough assessment.

A Screen Space GPGPU Surface LIC Algorithm for Distributed Memory Data Parallel Sort Last Rendering Infrastructures

NASA Astrophysics Data System (ADS)

Loring, B.; Karimabadi, H.; Rortershteyn, V.

2015-10-01

The surface line integral convolution(LIC) visualization technique produces dense visualization of vector fields on arbitrary surfaces. We present a screen space surface LIC algorithm for use in distributed memory data parallel sort last rendering infrastructures. The motivations for our work are to support analysis of datasets that are too large to fit in the main memory of a single computer and compatibility with prevalent parallel scientific visualization tools such as ParaView and VisIt. By working in screen space using OpenGL we can leverage the computational power of GPUs when they are available and run without them when they are not. We address efficiency and performance issues that arise from the transformation of data from physical to screen space by selecting an alternate screen space domain decomposition. We analyze the algorithm's scaling behavior with and without GPUs on two high performance computing systems using data from turbulent plasma simulations.

siRNA screen identifies QPCT as a druggable target for Huntington's disease.

PubMed

Jimenez-Sanchez, Maria; Lam, Wun; Hannus, Michael; Sönnichsen, Birte; Imarisio, Sara; Fleming, Angeleen; Tarditi, Alessia; Menzies, Fiona; Dami, Teresa Ed; Xu, Catherine; Gonzalez-Couto, Eduardo; Lazzeroni, Giulia; Heitz, Freddy; Diamanti, Daniela; Massai, Luisa; Satagopam, Venkata P; Marconi, Guido; Caramelli, Chiara; Nencini, Arianna; Andreini, Matteo; Sardone, Gian Luca; Caradonna, Nicola P; Porcari, Valentina; Scali, Carla; Schneider, Reinhard; Pollio, Giuseppe; O'Kane, Cahir J; Caricasole, Andrea; Rubinsztein, David C

2015-05-01

Huntington's disease (HD) is a currently incurable neurodegenerative condition caused by an abnormally expanded polyglutamine tract in huntingtin (HTT). We identified new modifiers of mutant HTT toxicity by performing a large-scale 'druggable genome' siRNA screen in human cultured cells, followed by hit validation in Drosophila. We focused on glutaminyl cyclase (QPCT), which had one of the strongest effects on mutant HTT-induced toxicity and aggregation in the cell-based siRNA screen and also rescued these phenotypes in Drosophila. We found that QPCT inhibition induced the levels of the molecular chaperone αB-crystallin and reduced the aggregation of diverse proteins. We generated new QPCT inhibitors using in silico methods followed by in vitro screening, which rescued the HD-related phenotypes in cell, Drosophila and zebrafish HD models. Our data reveal a new HD druggable target affecting mutant HTT aggregation and provide proof of principle for a discovery pipeline from druggable genome screen to drug development.

An Automatic Quality Control Pipeline for High-Throughput Screening Hit Identification.

PubMed

Zhai, Yufeng; Chen, Kaisheng; Zhong, Yang; Zhou, Bin; Ainscow, Edward; Wu, Ying-Ta; Zhou, Yingyao

2016-09-01

The correction or removal of signal errors in high-throughput screening (HTS) data is critical to the identification of high-quality lead candidates. Although a number of strategies have been previously developed to correct systematic errors and to remove screening artifacts, they are not universally effective and still require fair amount of human intervention. We introduce a fully automated quality control (QC) pipeline that can correct generic interplate systematic errors and remove intraplate random artifacts. The new pipeline was first applied to ~100 large-scale historical HTS assays; in silico analysis showed auto-QC led to a noticeably stronger structure-activity relationship. The method was further tested in several independent HTS runs, where QC results were sampled for experimental validation. Significantly increased hit confirmation rates were obtained after the QC steps, confirming that the proposed method was effective in enriching true-positive hits. An implementation of the algorithm is available to the screening community. © 2016 Society for Laboratory Automation and Screening.

High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells.

PubMed

Zhou, Yuexin; Zhu, Shiyou; Cai, Changzu; Yuan, Pengfei; Li, Chunmei; Huang, Yanyi; Wei, Wensheng

2014-05-22

Targeted genome editing technologies are powerful tools for studying biology and disease, and have a broad range of research applications. In contrast to the rapid development of toolkits to manipulate individual genes, large-scale screening methods based on the complete loss of gene expression are only now beginning to be developed. Here we report the development of a focused CRISPR/Cas-based (clustered regularly interspaced short palindromic repeats/CRISPR-associated) lentiviral library in human cells and a method of gene identification based on functional screening and high-throughput sequencing analysis. Using knockout library screens, we successfully identified the host genes essential for the intoxication of cells by anthrax and diphtheria toxins, which were confirmed by functional validation. The broad application of this powerful genetic screening strategy will not only facilitate the rapid identification of genes important for bacterial toxicity but will also enable the discovery of genes that participate in other biological processes.

A Screen Space GPGPU Surface LIC Algorithm for Distributed Memory Data Parallel Sort Last Rendering Infrastructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loring, Burlen; Karimabadi, Homa; Rortershteyn, Vadim

2014-07-01

The surface line integral convolution(LIC) visualization technique produces dense visualization of vector fields on arbitrary surfaces. We present a screen space surface LIC algorithm for use in distributed memory data parallel sort last rendering infrastructures. The motivations for our work are to support analysis of datasets that are too large to fit in the main memory of a single computer and compatibility with prevalent parallel scientific visualization tools such as ParaView and VisIt. By working in screen space using OpenGL we can leverage the computational power of GPUs when they are available and run without them when they are not.more » We address efficiency and performance issues that arise from the transformation of data from physical to screen space by selecting an alternate screen space domain decomposition. We analyze the algorithm's scaling behavior with and without GPUs on two high performance computing systems using data from turbulent plasma simulations.« less

STELLAR STRUCTURE AND TESTS OF MODIFIED GRAVITY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Philip; Hui, Lam, E-mail: pchang@cita.utoronto.ca, E-mail: lhui@astro.columbia.edu

2011-05-01

Theories that attempt to explain cosmic acceleration by modifying gravity typically introduces a long-range scalar force that needs to be screened on small scales. One common screening mechanism is the chameleon, where the scalar force is screened in environments with a sufficiently deep gravitational potential, but acts unimpeded in regions with a shallow gravitational potential. This leads to a variation in the overall gravitational G with environment. We show that such a variation can occur within a star itself, significantly affecting its evolution and structure, provided that the host galaxy is unscreened. The effect is most pronounced for red giants,more » which would be smaller by a factor of tens of percent and thus hotter by hundreds of Kelvin, depending on the parameters of the underlying scalar-tensor theory. Careful measurements of these stars in suitable environments (nearby dwarf galaxies not associated with groups or clusters) would provide constraints on the chameleon mechanism that are four orders of magnitude better than current large-scale structure limits and two orders of magnitude better than present solar system tests.« less

Fabrication and Characterization of Flexible and Miniaturized Humidity Sensors Using Screen-Printed TiO2 Nanoparticles as Sensitive Layer

PubMed Central

Dubourg, Georges; Segkos, Apostolos; Katona, Jaroslav; Radović, Marko; Savić, Slavica; Crnojević-Bengin, Vesna

2017-01-01

This paper describes the fabrication and the characterization of an original example of a miniaturized resistive-type humidity sensor, printed on flexible substrate in a large-scale manner. The fabrication process involves laser ablation for the design of interdigitated electrodes on PET (Poly-Ethylene Terephthalate) substrate and a screen-printing process for the deposition of the sensitive material, which is based on TiO2 nanoparticles. The laser ablation process was carefully optimized to obtain micro-scale and well-resolved electrodes on PET substrate. A functional paste based on cellulose was prepared in order to allow the precise screen-printing of the TiO2 nanoparticles as sensing material on the top of the electrodes. The current against voltage (I–V) characteristic of the sensor showed good linearity and potential for low-power operation. The results of a humidity-sensing investigation and mechanical testing showed that the fabricated miniaturized sensors have excellent mechanical stability, sensing characteristics, good repeatability, and relatively fast response/recovery times operating at room temperature. PMID:28800063

Genome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening

PubMed Central

Joung, Julia; Konermann, Silvana; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Platt, Randall J.; Brigham, Mark D.; Sanjana, Neville E.; Zhang, Feng

2017-01-01

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified from the screen, we further describe strategies for confirming the screening phenotype as well as genetic perturbation through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9–15 weeks followed by 4–5 weeks of validation. PMID:28333914

Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening.

PubMed

Joung, Julia; Konermann, Silvana; Gootenberg, Jonathan S; Abudayyeh, Omar O; Platt, Randall J; Brigham, Mark D; Sanjana, Neville E; Zhang, Feng

2017-04-01

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified by the screen, we further describe strategies for confirming the screening phenotype, as well as genetic perturbation, through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9-15 weeks, followed by 4-5 weeks of validation.

An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs.

PubMed

Kim, Wooseong; Hendricks, Gabriel Lambert; Lee, Kiho; Mylonakis, Eleftherios

2017-06-01

The emergence of antibiotic-resistant and -tolerant bacteria is a major threat to human health. Although efforts for drug discovery are ongoing, conventional bacteria-centered screening strategies have thus far failed to yield new classes of effective antibiotics. Therefore, new paradigms for discovering novel antibiotics are of critical importance. Caenorhabditis elegans, a model organism used for in vivo, offers a promising solution for identification of anti-infective compounds. Areas covered: This review examines the advantages of C. elegans-based high-throughput screening over conventional, bacteria-centered in vitro screens. It discusses major anti-infective compounds identified from large-scale C. elegans-based screens and presents the first clinically-approved drugs, then known bioactive compounds, and finally novel small molecules. Expert opinion: There are clear advantages of using a C. elegans-infection based screening method. A C. elegans-based screen produces an enriched pool of non-toxic, efficacious, potential anti-infectives, covering: conventional antimicrobial agents, immunomodulators, and anti-virulence agents. Although C. elegans-based screens do not denote the mode of action of hit compounds, this can be elucidated in secondary studies by comparing the results to target-based screens, or conducting subsequent target-based screens, including the genetic knock-down of host or bacterial genes.

Clinical comparative study with a large-area amorphous silicon flat-panel detector: image quality and visibility of anatomic structures on chest radiography.

PubMed

Fink, Christian; Hallscheidt, Peter J; Noeldge, Gerd; Kampschulte, Annette; Radeleff, Boris; Hosch, Waldemar P; Kauffmann, Günter W; Hansmann, Jochen

2002-02-01

The objective of this study was to compare clinical chest radiographs of a large-area, flat-panel digital radiography system and a conventional film-screen radiography system. The comparison was based on an observer preference study of image quality and visibility of anatomic structures. Routine follow-up chest radiographs were obtained from 100 consecutive oncology patients using a large-area, amorphous silicon flat-panel detector digital radiography system (dose equivalent to a 400-speed film system). Hard-copy images were compared with previous examinations of the same individuals taken on a conventional film-screen system (200-speed). Patients were excluded if changes in the chest anatomy were detected or if the time interval between the examinations exceeded 1 year. Observer preference was evaluated for the image quality and the visibility of 15 anatomic structures using a five-point scale. Dose measurements with a chest phantom showed a dose reduction of approximately 50% with the digital radiography system compared with the film-screen radiography system. The image quality and the visibility of all but one anatomic structure of the images obtained with the digital flat-panel detector system were rated significantly superior (p < or = 0.0003) to those obtained with the conventional film-screen radiography system. The image quality and visibility of anatomic structures on the images obtained by the flat-panel detector system were perceived as equal or superior to the images from conventional film-screen chest radiography. This was true even though the radiation dose was reduced approximately 50% with the digital flat-panel detector system.

Multi-scale Visualization of Molecular Architecture Using Real-Time Ambient Occlusion in Sculptor.

PubMed

Wahle, Manuel; Wriggers, Willy

2015-10-01

The modeling of large biomolecular assemblies relies on an efficient rendering of their hierarchical architecture across a wide range of spatial level of detail. We describe a paradigm shift currently under way in computer graphics towards the use of more realistic global illumination models, and we apply the so-called ambient occlusion approach to our open-source multi-scale modeling program, Sculptor. While there are many other higher quality global illumination approaches going all the way up to full GPU-accelerated ray tracing, they do not provide size-specificity of the features they shade. Ambient occlusion is an aspect of global lighting that offers great visual benefits and powerful user customization. By estimating how other molecular shape features affect the reception of light at some surface point, it effectively simulates indirect shadowing. This effect occurs between molecular surfaces that are close to each other, or in pockets such as protein or ligand binding sites. By adding ambient occlusion, large macromolecular systems look much more natural, and the perception of characteristic surface features is strongly enhanced. In this work, we present a real-time implementation of screen space ambient occlusion that delivers realistic cues about tunable spatial scale characteristics of macromolecular architecture. Heretofore, the visualization of large biomolecular systems, comprising e.g. hundreds of thousands of atoms or Mega-Dalton size electron microscopy maps, did not take into account the length scales of interest or the spatial resolution of the data. Our approach has been uniquely customized with shading that is tuned for pockets and cavities of a user-defined size, making it useful for visualizing molecular features at multiple scales of interest. This is a feature that none of the conventional ambient occlusion approaches provide. Actual Sculptor screen shots illustrate how our implementation supports the size-dependent rendering of molecular surface features.

Basic Scale on Insomnia complaints and Quality of Sleep (BaSIQS): reliability, initial validity and normative scores in higher education students.

PubMed

Allen Gomes, Ana; Ruivo Marques, Daniel; Meia-Via, Ana Maria; Meia-Via, Mariana; Tavares, José; Fernandes da Silva, Carlos; Pinto de Azevedo, Maria Helena

2015-04-01

Based on successive samples totaling more than 5000 higher education students, we scrutinized the reliability, structure, initial validity and normative scores of a brief self-report seven-item scale to screen for the continuum of nighttime insomnia complaints/perceived sleep quality, used by our team for more than a decade, henceforth labeled the Basic Scale on Insomnia complaints and Quality of Sleep (BaSIQS). In study/sample 1 (n = 1654), the items were developed based on part of a larger survey on higher education sleep-wake patterns. The test-retest study was conducted in an independent small group (n = 33) with a 2-8 week gap. In study/sample 2 (n = 360), focused mainly on validity, the BaSIQS was completed together with the Pittsburgh Sleep Quality Index (PSQI). In study 3, a large recent sample of students from universities all over the country (n = 2995) answered the BaSIQS items, based on which normative scores were determined, and an additional question on perceived sleep problems in order to further analyze the scale's validity. Regarding reliability, Cronbach alpha coefficients were systematically higher than 0.7, and the test-retest correlation coefficient was greater than 0.8. Structure analyses revealed consistently satisfactory two-factor and single-factor solutions. Concerning validity analyses, BaSIQS scores were significantly correlated with PSQI component scores and overall score (r = 0.652 corresponding to a large association); mean scores were significantly higher in those students classifying themselves as having sleep problems (p < 0.0001, d = 0.99 corresponding to a large effect size). In conclusion, the BaSIQS is very easy to administer, and appears to be a reliable and valid scale in higher education students. It might be a convenient short tool in research and applied settings to rapidly assess sleep quality or screen for insomnia complaints, and it may be easily used in other populations with minor adaptations.

EXTINCTION AND DUST GEOMETRY IN M83 H II REGIONS: AN HUBBLE SPACE TELESCOPE/WFC3 STUDY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guilin; Calzetti, Daniela; Hong, Sungryong

We present Hubble Space Telescope/WFC3 narrow-band imaging of the starburst galaxy M83 targeting the hydrogen recombination lines (Hβ, Hα, and Paβ), which we use to investigate the dust extinction in the H II regions. We derive extinction maps with 6 pc spatial resolution from two combinations of hydrogen lines (Hα/Hβ and Hα/Paβ), and show that the longer wavelengths probe larger optical depths, with A{sub V} values larger by ≳1 mag than those derived from the shorter wavelengths. This difference leads to a factor ≳2 discrepancy in the extinction-corrected Hα luminosity, a significant effect when studying extragalactic H II regions. By comparing thesemore » observations to a series of simple models, we conclude that a large diversity of absorber/emitter geometric configurations can account for the data, implying a more complex physical structure than the classical foreground ''dust screen'' assumption. However, most data points are bracketed by the foreground screen and a model where dust and emitters are uniformly mixed. When averaged over large (≳100-200 pc) scales, the extinction becomes consistent with a ''dust screen'', suggesting that other geometries tend to be restricted to more local scales. Moreover, the extinction in any region can be described by a combination of the foreground screen and the uniform mixture model with weights of 1/3 and 2/3 in the center (≲2 kpc), respectively, and 2/3 and 1/3 for the rest of the disk. This simple prescription significantly improves the accuracy of the dust extinction corrections and can be especially useful for pixel-based analyses of galaxies similar to M83.« less

A new system for parallel drug screening against multiple-resistant HIV mutants based on lentiviral self-inactivating (SIN) vectors and multi-colour analyses

PubMed Central

2013-01-01

Background Despite progress in the development of combined antiretroviral therapies (cART), HIV infection remains a significant challenge for human health. Current problems of cART include multi-drug-resistant virus variants, long-term toxicity and enormous treatment costs. Therefore, the identification of novel effective drugs is urgently needed. Methods We developed a straightforward screening approach for simultaneously evaluating the sensitivity of multiple HIV gag-pol mutants to antiviral drugs in one assay. Our technique is based on multi-colour lentiviral self-inactivating (SIN) LeGO vector technology. Results We demonstrated the successful use of this approach for screening compounds against up to four HIV gag-pol variants (wild-type and three mutants) simultaneously. Importantly, the technique was adapted to Biosafety Level 1 conditions by utilising ecotropic pseudotypes. This allowed upscaling to a large-scale screening protocol exploited by pharmaceutical companies in a successful proof-of-concept experiment. Conclusions The technology developed here facilitates fast screening for anti-HIV activity of individual agents from large compound libraries. Although drugs targeting gag-pol variants were used here, our approach permits screening compounds that target several different, key cellular and viral functions of the HIV life-cycle. The modular principle of the method also allows the easy exchange of various mutations in HIV sequences. In conclusion, the methodology presented here provides a valuable new approach for the identification of novel anti-HIV drugs. PMID:23286882

Cystic fibrosis carrier screening in a North American population.

PubMed

Zvereff, Val V; Faruki, Hawazin; Edwards, Marcia; Friedman, Kenneth J

2014-07-01

The aim of this study was to compare the mutation frequency distribution for a 32-mutation panel and a 69-mutation panel used for cystic fibrosis carrier screening. Further aims of the study were to examine the race-specific detection rates provided by both panels and to assess the performance of extended panels in large-scale, population-based cystic fibrosis carrier screening. Although genetic screening for the most common CFTR mutations allows detection of nearly 90% of cystic fibrosis carriers, the large number of other mutations, and their distribution within different ethnic groups, limits the utility of general population screening. Patients referred for cystic fibrosis screening from January 2005 through December 2010 were tested using either a 32-mutation panel (n = 1,601,308 individuals) or a 69-mutation panel (n = 109,830). The carrier frequencies observed for the 69-mutation panel study population (1/36) and Caucasian (1/27) and African-American individuals (1/79) agree well with published cystic fibrosis carrier frequencies; however, a higher carrier frequency was observed for Hispanic-American individuals (1/48) using the 69-mutation panel as compared with the 32-mutation panel (1/69). The 69-mutation panel detected ~20% more mutations than the 32-mutation panel for both African-American and Hispanic-American individuals. Expanded panels using race-specific variants can improve cystic fibrosis carrier detection rates within specific populations. However, it is important that the pathogenicity and the relative frequency of these variants are confirmed.

Annotating novel genes by integrating synthetic lethals and genomic information

PubMed Central

Schöner, Daniel; Kalisch, Markus; Leisner, Christian; Meier, Lukas; Sohrmann, Marc; Faty, Mahamadou; Barral, Yves; Peter, Matthias; Gruissem, Wilhelm; Bühlmann, Peter

2008-01-01

Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W) as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process. PMID:18194531

Molecular Diagnosis of Malaria by Photo-Induced Electron Transfer Fluorogenic Primers: PET-PCR

PubMed Central

Lucchi, Naomi W.; Narayanan, Jothikumar; Karell, Mara A.; Xayavong, Maniphet; Kariuki, Simon; DaSilva, Alexandre J.; Hill, Vincent; Udhayakumar, Venkatachalam

2013-01-01

There is a critical need for developing new malaria diagnostic tools that are sensitive, cost effective and capable of performing large scale diagnosis. The real-time PCR methods are particularly robust for large scale screening and they can be used in malaria control and elimination programs. We have designed novel self-quenching photo-induced electron transfer (PET) fluorogenic primers for the detection of P. falciparum and the Plasmodium genus by real-time PCR. A total of 119 samples consisting of different malaria species and mixed infections were used to test the utility of the novel PET-PCR primers in the diagnosis of clinical samples. The sensitivity and specificity were calculated using a nested PCR as the gold standard and the novel primer sets demonstrated 100% sensitivity and specificity. The limits of detection for P. falciparum was shown to be 3.2 parasites/µl using both Plasmodium genus and P. falciparum-specific primers and 5.8 parasites/µl for P. ovale, 3.5 parasites/µl for P. malariae and 5 parasites/µl for P. vivax using the genus specific primer set. Moreover, the reaction can be duplexed to detect both Plasmodium spp. and P. falciparum in a single reaction. The PET-PCR assay does not require internal probes or intercalating dyes which makes it convenient to use and less expensive than other real-time PCR diagnostic formats. Further validation of this technique in the field will help to assess its utility for large scale screening in malaria control and elimination programs. PMID:23437209

GenASiS Basics: Object-oriented utilitarian functionality for large-scale physics simulations

DOE PAGES

Cardall, Christian Y.; Budiardja, Reuben D.

2015-06-11

Aside from numerical algorithms and problem setup, large-scale physics simulations on distributed-memory supercomputers require more basic utilitarian functionality, such as physical units and constants; display to the screen or standard output device; message passing; I/O to disk; and runtime parameter management and usage statistics. Here we describe and make available Fortran 2003 classes furnishing extensible object-oriented implementations of this sort of rudimentary functionality, along with individual `unit test' programs and larger example problems demonstrating their use. Lastly, these classes compose the Basics division of our developing astrophysics simulation code GenASiS (General Astrophysical Simulation System), but their fundamental nature makes themmore » useful for physics simulations in many fields.« less

Current challenges and future perspectives of plant and agricultural biotechnology.

PubMed

Moshelion, Menachem; Altman, Arie

2015-06-01

Advances in understanding plant biology, novel genetic resources, genome modification, and omics technologies generate new solutions for food security and novel biomaterials production under changing environmental conditions. New gene and germplasm candidates that are anticipated to lead to improved crop yields and other plant traits under stress have to pass long development phases based on trial and error using large-scale field evaluation. Therefore, quantitative, objective, and automated screening methods combined with decision-making algorithms are likely to have many advantages, enabling rapid screening of the most promising crop lines at an early stage followed by final mandatory field experiments. The combination of novel molecular tools, screening technologies, and economic evaluation should become the main goal of the plant biotechnological revolution in agriculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Diabetes Mellitus Type 2 on Salivary Glucose – A Systematic Review and Meta-Analysis of Observational Studies

PubMed Central

Mascarenhas, Paulo; Fatela, Bruno; Barahona, Isabel

2014-01-01

Background Early screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM. Methods and Findings We conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge's g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37). Conclusions Our systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients. PMID:25025218

Biological Concerns on the Selection of Animal Models for Teratogenic Testing.

PubMed

Alves-Pimenta, Sofia; Colaço, Bruno; Oliveira, Paula A; Venâncio, Carlos

2018-01-01

During pregnancy fetus can be exposed to a variety of chemicals which may induce abortion and malformations. Due to the amounts of new substances coming into the market every year, a high demand for a rapid, reliable, and cost-effective method to detect potential toxicity is necessary. Different species have been used as animal models for teratogen screening, most of them sharing similar development processes with humans. However, the application of embryology knowledge to teratology is hampered by the complexity of the reproduction processes.The present chapter outlines the essential development periods in different models, and highlights the similarities and differences between species, advantages and disadvantages of each group, and specific sensitivities for teratogenic tests. These models can be organized into the following categories: (1) invertebrate species such Caenorhabditis elegans and Drosophila melanogaster, which have become ideal for screening simple mechanisms in the early periods of reproductive cycle, allowing for rapid results and minor ethical concerns; (2) vertebrate nonmammalian species such Xenopus laevis and Danio rerio, important models to assess teratogenic potential in later development with fewer ethical requirements; and (3) the mammalian species Mus musculus, Rattus norvegicus, and Oryctolagus cuniculus, phylogenetically more close to humans, essential to assess complex specialized processes, that occur later in development.Rules for development toxicology tests require the use of mammalian species. However, ethical concerns and costs limit their use in large-scale screening. By contrast, invertebrate and vertebrate nonmammalian species are increasing as alternative animal models, as these organisms combine less ethical requirements, low costs and culture conditions compatible with large-scale screening. In contrast to the in vitro techniques, their main advantage is to allow for high-throughput screening in a whole-animal context, not dependent on the prior identification of a target. In this chapter, the biological development of the animals most used in teratogenic tests is adressed with the aims of maximizing human translation, reducing the number of animals used, and the time to market for new drugs.

Summer 2017 Microfluidics Research Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mcculloch, Quinn

Liquid-liquid Extraction (LLE), also known as solvent extraction, represents a large subset of chemistry where one or more solutes are transferred across an interface between two immiscible liquids. This type of chemistry is used in industrial scale processes to purify solvents, refine ore, process petroleum, treat wastewater, and much more. Although LLE has been successfully employed at the macroscale, where many liters/kgs of species are processed at large flow rates, LLE stands to benefit from lab-on-a-chip technology, where reactions take place quickly and efficiently at the microscale. A device, called a screen contactor, has been invented at Los Alamos Nationalmore » Laboratory (LANL) to perform solvent extraction at the microscale. This invention has been submitted to LANL’s Feynman Center for Innovation, and has been filed for provisional patent under U.S. Patent Application No. 62/483,107 1. The screen contactor consists of a housing that contains two different screen materials, flametreated stainless steel and polyether ether ketone (PEEK) thermoplastic, that are uniquely wetted by either an aqueous or an organic liquid phase, respectively. Liquids in this device flow longitudinally through the screens. The fine pore size of the screens (tens of microns) provide large capillary/adhesional forces while maintaining small hydraulic pressure drops. These physical characteristics are paramount to efficient microscale liquid phase separation. To demonstrate mass transfer using the screen contactor, a well-known chemical system 2 consisting of water and n-decane as solvents and trimethylamine (TEA) as a solute was selected. TEA is basic in water so its concentration can easily be quantified using a digital pH meter and an experimentally determined base dissociation constant. Characterization of this solvent system and its behavior in the screen contactor have been the focus of my research activities this summer. In the following sections, I have detailed experimental results that have been gathered.« less

Single-field consistency relations of large scale structure part III: test of the equivalence principle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Creminelli, Paolo; Gleyzes, Jérôme; Vernizzi, Filippo

2014-06-01

The recently derived consistency relations for Large Scale Structure do not hold if the Equivalence Principle (EP) is violated. We show it explicitly in a toy model with two fluids, one of which is coupled to a fifth force. We explore the constraints that galaxy surveys can set on EP violation looking at the squeezed limit of the 3-point function involving two populations of objects. We find that one can explore EP violations of order 10{sup −3}÷10{sup −4} on cosmological scales. Chameleon models are already very constrained by the requirement of screening within the Solar System and only a verymore » tiny region of the parameter space can be explored with this method. We show that no violation of the consistency relations is expected in Galileon models.« less

Miniaturized integration of a fluorescence microscope

PubMed Central

Ghosh, Kunal K.; Burns, Laurie D.; Cocker, Eric D.; Nimmerjahn, Axel; Ziv, Yaniv; Gamal, Abbas El; Schnitzer, Mark J.

2013-01-01

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals towards relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including semiconductor light source and sensor. This device enables high-speed cellular-level imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens. PMID:21909102

Miniaturized integration of a fluorescence microscope.

PubMed

Ghosh, Kunal K; Burns, Laurie D; Cocker, Eric D; Nimmerjahn, Axel; Ziv, Yaniv; Gamal, Abbas El; Schnitzer, Mark J

2011-09-11

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor. This device enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tessore, Nicolas; Metcalf, R. Benton; Winther, Hans A.

A number of alternatives to general relativity exhibit gravitational screening in the non-linear regime of structure formation. We describe a set of algorithms that can produce weak lensing maps of large scale structure in such theories and can be used to generate mock surveys for cosmological analysis. By analysing a few basic statistics we indicate how these alternatives can be distinguished from general relativity with future weak lensing surveys.

From drug to protein: using yeast genetics for high-throughput target discovery.

PubMed

Armour, Christopher D; Lum, Pek Yee

2005-02-01

The budding yeast Saccharomyces cerevisiae has long been an effective eukaryotic model system for understanding basic cellular processes. The genetic tractability and ease of manipulation in the laboratory make yeast well suited for large-scale chemical and genetic screens. Several recent studies describing the use of yeast genetics for high-throughput drug target identification are discussed in this review.

STEREOMATRIX 3-D display system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whiteside, Stephen Earl

1973-08-01

STEREOMATRIX is a large-screen interactive 3-D laser display system which presents computer-generated wire figures stereoscopically. The presented image can be rotated, translated, and scaled by the system user and the perspective of the image is changed according to the position of the user. A cursor may be positioned in three dimensions to identify points and allows communication with the computer.

Among-provence variability of gas exchange and growth in response to long-term elevated CO2 exposure

Treesearch

James L.J. Houpis; Paul D. Anderson; James C. Pushnik; David J. Anschel

1999-01-01

Genetic variability can have profound effects on the interpretation of results from elevated CO2 studies, and future forest management decisions. Information on which varieties are best suited to future atmospheric conditions is needed to develop future forest management practices. A large-scale screening study of the effects of elevated CO

Automated aray assembly, phase 2

NASA Technical Reports Server (NTRS)

Daiello, R. V.

1979-01-01

A manufacturing process suitable for the large-scale production of silicon solar array modules at a cost of less than $500/peak kW is described. Factors which control the efficiency of ion implanted silicon solar cells, screen-printed thick film metallization, spray-on antireflection coating process, and panel assembly are discussed. Conclusions regarding technological readiness or cost effectiveness of individual process steps are presented.

Volunteers Oriented Interface Design for the Remote Navigation of Rescue Robots at Large-Scale Disaster Sites

NASA Astrophysics Data System (ADS)

Yang, Zhixiao; Ito, Kazuyuki; Saijo, Kazuhiko; Hirotsune, Kazuyuki; Gofuku, Akio; Matsuno, Fumitoshi

This paper aims at constructing an efficient interface being similar to those widely used in human daily life, to fulfill the need of many volunteer rescuers operating rescue robots at large-scale disaster sites. The developed system includes a force feedback steering wheel interface and an artificial neural network (ANN) based mouse-screen interface. The former consists of a force feedback steering control and a six monitors’ wall. It provides a manual operation like driving cars to navigate a rescue robot. The latter consists of a mouse and a camera’s view displayed in a monitor. It provides a semi-autonomous operation by mouse clicking to navigate a rescue robot. Results of experiments show that a novice volunteer can skillfully navigate a tank rescue robot through both interfaces after 20 to 30 minutes of learning their operation respectively. The steering wheel interface has high navigating speed in open areas, without restriction of terrains and surface conditions of a disaster site. The mouse-screen interface is good at exact navigation in complex structures, while bringing little tension to operators. The two interfaces are designed to switch into each other at any time to provide a combined efficient navigation method.

Fast selection of miRNA candidates based on large-scale pre-computed MFE sets of randomized sequences.

PubMed

Warris, Sven; Boymans, Sander; Muiser, Iwe; Noback, Michiel; Krijnen, Wim; Nap, Jan-Peter

2014-01-13

Small RNAs are important regulators of genome function, yet their prediction in genomes is still a major computational challenge. Statistical analyses of pre-miRNA sequences indicated that their 2D structure tends to have a minimal free energy (MFE) significantly lower than MFE values of equivalently randomized sequences with the same nucleotide composition, in contrast to other classes of non-coding RNA. The computation of many MFEs is, however, too intensive to allow for genome-wide screenings. Using a local grid infrastructure, MFE distributions of random sequences were pre-calculated on a large scale. These distributions follow a normal distribution and can be used to determine the MFE distribution for any given sequence composition by interpolation. It allows on-the-fly calculation of the normal distribution for any candidate sequence composition. The speedup achieved makes genome-wide screening with this characteristic of a pre-miRNA sequence practical. Although this particular property alone will not be able to distinguish miRNAs from other sequences sufficiently discriminative, the MFE-based P-value should be added to the parameters of choice to be included in the selection of potential miRNA candidates for experimental verification.

MEGADOCK: An All-to-All Protein-Protein Interaction Prediction System Using Tertiary Structure Data

PubMed Central

Ohue, Masahito; Matsuzaki, Yuri; Uchikoga, Nobuyuki; Ishida, Takashi; Akiyama, Yutaka

2014-01-01

The elucidation of protein-protein interaction (PPI) networks is important for understanding cellular structure and function and structure-based drug design. However, the development of an effective method to conduct exhaustive PPI screening represents a computational challenge. We have been investigating a protein docking approach based on shape complementarity and physicochemical properties. We describe here the development of the protein-protein docking software package “MEGADOCK” that samples an extremely large number of protein dockings at high speed. MEGADOCK reduces the calculation time required for docking by using several techniques such as a novel scoring function called the real Pairwise Shape Complementarity (rPSC) score. We showed that MEGADOCK is capable of exhaustive PPI screening by completing docking calculations 7.5 times faster than the conventional docking software, ZDOCK, while maintaining an acceptable level of accuracy. When MEGADOCK was applied to a subset of a general benchmark dataset to predict 120 relevant interacting pairs from 120 x 120 = 14,400 combinations of proteins, an F-measure value of 0.231 was obtained. Further, we showed that MEGADOCK can be applied to a large-scale protein-protein interaction-screening problem with accuracy better than random. When our approach is combined with parallel high-performance computing systems, it is now feasible to search and analyze protein-protein interactions while taking into account three-dimensional structures at the interactome scale. MEGADOCK is freely available at http://www.bi.cs.titech.ac.jp/megadock. PMID:23855673

Single-cell analysis of population context advances RNAi screening at multiple levels

PubMed Central

Snijder, Berend; Sacher, Raphael; Rämö, Pauli; Liberali, Prisca; Mench, Karin; Wolfrum, Nina; Burleigh, Laura; Scott, Cameron C; Verheije, Monique H; Mercer, Jason; Moese, Stefan; Heger, Thomas; Theusner, Kristina; Jurgeit, Andreas; Lamparter, David; Balistreri, Giuseppe; Schelhaas, Mario; De Haan, Cornelis A M; Marjomäki, Varpu; Hyypiä, Timo; Rottier, Peter J M; Sodeik, Beate; Marsh, Mark; Gruenberg, Jean; Amara, Ali; Greber, Urs; Helenius, Ari; Pelkmans, Lucas

2012-01-01

Isogenic cells in culture show strong variability, which arises from dynamic adaptations to the microenvironment of individual cells. Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image-based RNAi screens. We developed a comprehensive computational approach that employs Bayesian and multivariate methods at the single-cell level. We applied these methods to 45 RNA interference screens of various sizes, including 7 druggable genome and 2 genome-wide screens, analysing 17 different mammalian virus infections and four related cell physiological processes. Analysing cell-based screens at this depth reveals widespread RNAi-induced changes in the population context of individual cells leading to indirect RNAi effects, as well as perturbations of cell-to-cell variability regulators. We find that accounting for indirect effects improves the consistency between siRNAs targeted against the same gene, and between replicate RNAi screens performed in different cell lines, in different labs, and with different siRNA libraries. In an era where large-scale RNAi screens are increasingly performed to reach a systems-level understanding of cellular processes, we show that this is often improved by analyses that account for and incorporate the single-cell microenvironment. PMID:22531119

Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.

PubMed

Kutchukian, Peter S; Wassermann, Anne Mai; Lindvall, Mika K; Wright, S Kirk; Ottl, Johannes; Jacob, Jaison; Scheufler, Clemens; Marzinzik, Andreas; Brooijmans, Natasja; Glick, Meir

2015-06-01

A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits. © 2014 Society for Laboratory Automation and Screening.

Newborn screening of metabolic disorders: recent progress and future developments.

PubMed

Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

2008-01-01

Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation.

Automated Docking Screens: A Feasibility Study

PubMed Central

2009-01-01

Molecular docking is the most practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCK Blaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCK Blaster recapitulates the crystal ligand pose within 2 Å rmsd 50−60% of the time; inferior to an expert, but respectrable. Half the time the ligand also ranked among the top 5% of 100 physically matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2 Å rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org. PMID:19719084

Optimization of a resazurin-based microplate assay for large-scale compound screenings against Klebsiella pneumoniae.

PubMed

Kim, Hyung Jun; Jang, Soojin

2018-01-01

A new resazurin-based assay was evaluated and optimized using a microplate (384-well) format for high-throughput screening of antibacterial molecules against Klebsiella pneumoniae . Growth of the bacteria in 384-well plates was more effectively measured and had a > sixfold higher signal-to-background ratio using the resazurin-based assay compared with absorbance measurements at 600 nm. Determination of minimum inhibitory concentrations of the antibiotics revealed that the optimized assay quantitatively measured antibacterial activity of various antibiotics. An edge effect observed in the initial assay was significantly reduced using a 1-h incubation of the bacteria-containing plates at room temperature. There was an approximately 10% decrease in signal variability between the edge and the middle wells along with improvement in the assay robustness ( Z ' = 0.99). This optimized resazurin-based assay is an efficient, inexpensive, and robust assay that can quantitatively measure antibacterial activity using a high-throughput screening system to assess a large number of compounds for discovery of new antibiotics against K. pneumoniae .

Robotic implementation of assays: tissue-nonspecific alkaline phosphatase (TNAP) case study.

PubMed

Chung, Thomas D Y

2013-01-01

Laboratory automation and robotics have "industrialized" the execution and completion of large-scale, enabling high-capacity and high-throughput (100 K-1 MM/day) screening (HTS) campaigns of large "libraries" of compounds (>200 K-2 MM) to complete in a few days or weeks. Critical to the success these HTS campaigns is the ability of a competent assay development team to convert a validated research-grade laboratory "benchtop" assay suitable for manual or semi-automated operations on a few hundreds of compounds into a robust miniaturized (384- or 1,536-well format), well-engineered, scalable, industrialized assay that can be seamlessly implemented on a fully automated, fully integrated robotic screening platform for cost-effective screening of hundreds of thousands of compounds. Here, we provide a review of the theoretical guiding principles and practical considerations necessary to reduce often complex research biology into a "lean manufacturing" engineering endeavor comprising adaption, automation, and implementation of HTS. Furthermore we provide a detailed example specifically for a cell-free in vitro biochemical, enzymatic phosphatase assay for tissue-nonspecific alkaline phosphatase that illustrates these principles and considerations.

Novel Computational Approaches to Drug Discovery

NASA Astrophysics Data System (ADS)

Skolnick, Jeffrey; Brylinski, Michal

2010-01-01

New approaches to protein functional inference based on protein structure and evolution are described. First, FINDSITE, a threading based approach to protein function prediction, is summarized. Then, the results of large scale benchmarking of ligand binding site prediction, ligand screening, including applications to HIV protease, and GO molecular functional inference are presented. A key advantage of FINDSITE is its ability to use low resolution, predicted structures as well as high resolution experimental structures. Then, an extension of FINDSITE to ligand screening in GPCRs using predicted GPCR structures, FINDSITE/QDOCKX, is presented. This is a particularly difficult case as there are few experimentally solved GPCR structures. Thus, we first train on a subset of known binding ligands for a set of GPCRs; this is then followed by benchmarking against a large ligand library. For the virtual ligand screening of a number of Dopamine receptors, encouraging results are seen, with significant enrichment in identified ligands over those found in the training set. Thus, FINDSITE and its extensions represent a powerful approach to the successful prediction of a variety of molecular functions.

Automated docking screens: a feasibility study.

PubMed

Irwin, John J; Shoichet, Brian K; Mysinger, Michael M; Huang, Niu; Colizzi, Francesco; Wassam, Pascal; Cao, Yiqun

2009-09-24

Molecular docking is the most practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCK Blaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCK Blaster recapitulates the crystal ligand pose within 2 A rmsd 50-60% of the time; inferior to an expert, but respectrable. Half the time the ligand also ranked among the top 5% of 100 physically matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2 A rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org .

Development of a high-content screening assay panel to accelerate mechanism of action studies for oncology research.

PubMed

Towne, Danli L; Nicholl, Emily E; Comess, Kenneth M; Galasinski, Scott C; Hajduk, Philip J; Abraham, Vivek C

2012-09-01

Efficient elucidation of the biological mechanism of action of novel compounds remains a major bottleneck in the drug discovery process. To address this need in the area of oncology, we report the development of a multiparametric high-content screening assay panel at the level of single cells to dramatically accelerate understanding the mechanism of action of cell growth-inhibiting compounds on a large scale. Our approach is based on measuring 10 established end points associated with mitochondrial apoptosis, cell cycle disruption, DNA damage, and cellular morphological changes in the same experiment, across three multiparametric assays. The data from all of the measurements taken together are expected to help increase our current understanding of target protein functions, constrain the list of possible targets for compounds identified using phenotypic screens, and identify off-target effects. We have also developed novel data visualization and phenotypic classification approaches for detailed interpretation of individual compound effects and navigation of large collections of multiparametric cellular responses. We expect this general approach to be valuable for drug discovery across multiple therapeutic areas.

Essential attributes identified in the design of a Laboratory Information Management System for a high throughput siRNA screening laboratory.

PubMed

Grandjean, Geoffrey; Graham, Ryan; Bartholomeusz, Geoffrey

2011-11-01

In recent years high throughput screening operations have become a critical application in functional and translational research. Although a seemingly unmanageable amount of data is generated by these high-throughput, large-scale techniques, through careful planning, an effective Laboratory Information Management System (LIMS) can be developed and implemented in order to streamline all phases of a workflow. Just as important as data mining and analysis procedures at the end of complex processes is the tracking of individual steps of applications that generate such data. Ultimately, the use of a customized LIMS will enable users to extract meaningful results from large datasets while trusting the robustness of their assays. To illustrate the design of a custom LIMS, this practical example is provided to highlight the important aspects of the design of a LIMS to effectively modulate all aspects of an siRNA screening service. This system incorporates inventory management, control of workflow, data handling and interaction with investigators, statisticians and administrators. All these modules are regulated in a synchronous manner within the LIMS. © 2011 Bentham Science Publishers

Temperature trend biases

NASA Astrophysics Data System (ADS)

Venema, Victor; Lindau, Ralf

2016-04-01

In an accompanying talk we show that well-homogenized national dataset warm more than temperatures from global collections averaged over the region of common coverage. In this poster we want to present auxiliary work about possible biases in the raw observations and on how well relative statistical homogenization can remove trend biases. There are several possible causes of cooling biases, which have not been studied much. Siting could be an important factor. Urban stations tend to move away from the centre to better locations. Many stations started inside of urban areas and are nowadays more outside. Even for villages the temperature difference between the centre and edge can be 0.5°C. When a city station moves to an airport, which often happened around WWII, this takes the station (largely) out of the urban heat island. During the 20th century the Stevenson screen was established as the dominant thermometer screen. This screen protected the thermometer much better against radiation than earlier designs. Deficits of earlier measurement methods have artificially warmed the temperatures in the 19th century. Newer studies suggest we may have underestimated the size of this bias. Currently we are in a transition to Automatic Weather Stations. The net global effect of this transition is not clear at this moment. Irrigation on average decreases the 2m-temperature by about 1 degree centigrade. At the same time, irrigation has increased significantly during the last century. People preferentially live in irrigated areas and weather stations serve agriculture. Thus it is possible that there is a higher likelihood that weather stations are erected in irrigated areas than elsewhere. In this case irrigation could lead to a spurious cooling trend. In the Parallel Observations Science Team of the International Surface Temperature Initiative (ISTI-POST) we are studying influence of the introduction of Stevenson screens and Automatic Weather Stations using parallel measurements, as well as the influence of relocations. Previous validation studies of statistical homogenizations unfortunately have some caveats when it comes to the large-scale trends. The main problem is that the validation datasets had a relatively large signal to noise ratio (SNR), i.e., they had a large break variance relative to the variance of the noise of the difference time series. Our recent work on multiple breakpoint detection methods shows that SNR is very important and that for a SNR around 0.5 the segmentation is about as good as a random segmentation. If the corrections are computed with a composite reference that also contains breaks, the bias due to network-wide transitions that are executed over short periods will reduce the obvious breaks in the single stations, but may not reduce the large-scale bias much. The joint correction method using a decomposition approach (ANOVA) can remove the bias when all breaks (predictors) are known. Any error in the predictors will, however, lead to undercorrection of any large-scale trend biases.

Quantitative maps of genetic interactions in yeast - comparative evaluation and integrative analysis.

PubMed

Lindén, Rolf O; Eronen, Ville-Pekka; Aittokallio, Tero

2011-03-24

High-throughput genetic screening approaches have enabled systematic means to study how interactions among gene mutations contribute to quantitative fitness phenotypes, with the aim of providing insights into the functional wiring diagrams of genetic interaction networks on a global scale. However, it is poorly known how well these quantitative interaction measurements agree across the screening approaches, which hinders their integrated use toward improving the coverage and quality of the genetic interaction maps in yeast and other organisms. Using large-scale data matrices from epistatic miniarray profiling (E-MAP), genetic interaction mapping (GIM), and synthetic genetic array (SGA) approaches, we carried out here a systematic comparative evaluation among these quantitative maps of genetic interactions in yeast. The relatively low association between the original interaction measurements or their customized scores could be improved using a matrix-based modelling framework, which enables the use of single- and double-mutant fitness estimates and measurements, respectively, when scoring genetic interactions. Toward an integrative analysis, we show how the detections from the different screening approaches can be combined to suggest novel positive and negative interactions which are complementary to those obtained using any single screening approach alone. The matrix approximation procedure has been made available to support the design and analysis of the future screening studies. We have shown here that even if the correlation between the currently available quantitative genetic interaction maps in yeast is relatively low, their comparability can be improved by means of our computational matrix approximation procedure, which will enable integrative analysis and detection of a wider spectrum of genetic interactions using data from the complementary screening approaches.

Techniques for Large-Scale Bacterial Genome Manipulation and Characterization of the Mutants with Respect to In Silico Metabolic Reconstructions.

PubMed

diCenzo, George C; Finan, Turlough M

2018-01-01

The rate at which all genes within a bacterial genome can be identified far exceeds the ability to characterize these genes. To assist in associating genes with cellular functions, a large-scale bacterial genome deletion approach can be employed to rapidly screen tens to thousands of genes for desired phenotypes. Here, we provide a detailed protocol for the generation of deletions of large segments of bacterial genomes that relies on the activity of a site-specific recombinase. In this procedure, two recombinase recognition target sequences are introduced into known positions of a bacterial genome through single cross-over plasmid integration. Subsequent expression of the site-specific recombinase mediates recombination between the two target sequences, resulting in the excision of the intervening region and its loss from the genome. We further illustrate how this deletion system can be readily adapted to function as a large-scale in vivo cloning procedure, in which the region excised from the genome is captured as a replicative plasmid. We next provide a procedure for the metabolic analysis of bacterial large-scale genome deletion mutants using the Biolog Phenotype MicroArray™ system. Finally, a pipeline is described, and a sample Matlab script is provided, for the integration of the obtained data with a draft metabolic reconstruction for the refinement of the reactions and gene-protein-reaction relationships in a metabolic reconstruction.

NASA's Hyperwall Revealing the Big Picture

NASA Technical Reports Server (NTRS)

Sellers, Piers

2011-01-01

NASA:s hyperwall is a sophisticated visualization tool used to display large datasets. The hyperwall, or video wall, is capable of displaying multiple high-definition data visualizations and/or images simultaneously across an arrangement of screens. Functioning as a key component at many NASA exhibits, the hyperwall is used to help explain phenomena, ideas, or examples of world change. The traveling version of the hyperwall is typically comprised of nine 42-50" flat-screen monitors arranged in a 3x3 array (as depicted below). However, it is not limited to monitor size or number; screen sizes can be as large as 52" and the arrangement of screens can include more than nine monitors. Generally, NASA satellite and model data are used to highlight particular themes in atmospheric, land, and ocean science. Many of the existing hyperwall stories reveal change across space and time, while others display large-scale still-images accompanied by descriptive, story-telling captions. Hyperwall content on a variety of Earth Science topics already exists and is made available to the public at: eospso.gsfc.nasa.gov/hyperwall. Keynote and PowerPoint presentations as well as Summary of Story files are available for download on each existing topic. New hyperwall content and accompanying files will continue being developed to promote scientific literacy across a diverse group of audience members. NASA invites the use of content accessible through this website but requests the user to acknowledge any and all data sources referenced in the content being used.

Gravimetric enrichment of high lipid and starch accumulating microalgae.

PubMed

Hassanpour, Morteza; Abbasabadi, Mahsa; Ebrahimi, Sirous; Hosseini, Maryam; Sheikhbaglou, Ahmad

2015-11-01

This study presents gravimetric enrichment of mixed culture to screen starch and lipid producing species separately in a sequencing batch reactor. In the enriched starch-producing mixed culture photobioreactor, the starch content at the end of steady state batch became 3.42 times the beginning of depletion. Whereas in the enriched lipid-producing photobioreactor, the lipid content at the end of steady state batch became 3 times the beginning of famine phase. The obtained results revealed that the gravimetric enrichment is a suitable screening method for specific production of storage compounds in none-sterile large-scaled condition. Copyright © 2015 Elsevier Ltd. All rights reserved.

New-type planar field emission display with superaligned carbon nanotube yarn emitter.

PubMed

Liu, Peng; Wei, Yang; Liu, Kai; Liu, Liang; Jiang, Kaili; Fan, Shoushan

2012-05-09

With the superaligned carbon nanotube yarn as emitter, we have fabricated a 16 × 16 pixel field emission display prototype by adopting screen printing and laser cutting technologies. A planar diode field emission structure has been adopted. A very sharp carbon nanotube yarn tip emitter can be formed by laser cutting. Low voltage phosphor was coated on the anode electrodes also by screen printing. With a specially designed circuit, we have demonstrated the dynamic character display with the field emission display prototype. The emitter material and fabrication technologies in this paper are both easy to scale up to large areas.

Cosmological Higgs-Axion Interplay for a Naturally Small Electroweak Scale.

PubMed

Espinosa, J R; Grojean, C; Panico, G; Pomarol, A; Pujolàs, O; Servant, G

2015-12-18

Recently, a new mechanism to generate a naturally small electroweak scale has been proposed. It exploits the coupling of the Higgs boson to an axionlike field and a long era in the early Universe where the axion unchains a dynamical screening of the Higgs mass. We present a new realization of this idea with the new feature that it leaves no sign of new physics at the electroweak scale, and up to a rather large scale, 10^{9}  GeV, except for two very light and weakly coupled axionlike states. One of the scalars can be a viable dark matter candidate. Such a cosmological Higgs-axion interplay could be tested with a number of experimental strategies.

Evaluation of human embryonic stem cells and their differentiated fibroblastic progenies as cellular models for in vitro genotoxicity screening.

PubMed

Vinoth, Kumar Jayaseelan; Manikandan, Jayapal; Sethu, Swaminathan; Balakrishnan, Lakshmidevi; Heng, Alexis; Lu, Kai; Hande, Manoor Prakash; Cao, Tong

2014-08-20

This study evaluated human embryonic stem cells (hESC) and their differentiated fibroblastic progenies as cellular models for genotoxicity screening. The DNA damage response of hESCs and their differentiated fibroblastic progenies were compared to a fibroblastic cell line (HEPM, CRL1486) and primary cultures of peripheral blood lymphocytes (PBL), upon exposure to Mitomycin C, gamma irradiation and H2O2. It was demonstrated that hESC-derived fibroblastic progenies (H1F) displayed significantly higher chromosomal aberrations, micronuclei formation and double strand break (DSB) formation, as compared to undifferentiated hESC upon exposure to genotoxic stress. Nevertheless, H1F cell types displayed comparable sensitivities to genotoxic challenge as HEPM and PBL, both of which are representative of somatic cell types commonly used for genotoxicity screening. Subsequently, transcriptomic and pathways analysis identified differential expression of critical genes involved in cell death and DNA damage response upon exposure to gamma irradiation. The results thus demonstrate that hESC-derived fibroblastic progenies are as sensitive as commonly-used somatic cell types for genotoxicity screening. Moreover, hESCs have additional advantages, such as their genetic normality compared to immortalized cell lines, as well as their amenability to scale-up for producing large, standardized quantities of cells for genotoxicity screening on an industrial scale, something which can never be achieved with primary cell cultures. Copyright © 2014. Published by Elsevier B.V.

Neurobehavioral Mutants Identified in an ENU Mutagenesis Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, Melloni N.; Dunning, Jonathan P; Wiley, Ronald G

2007-01-01

We report on a behavioral screening test battery that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and employed a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open field mutants (one displaying hyper-locomotion, the other hypo-locomotion), four tail suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsivenessmore » to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning and memory mutant (displaying reduced response to the conditioned stimulus) These findings highlight the utility of a set of behavioral tasks used in a high throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.« less

Retinal Imaging Techniques for Diabetic Retinopathy Screening

PubMed Central

Goh, James Kang Hao; Cheung, Carol Y.; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

2016-01-01

Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. PMID:26830491

Retinal Imaging Techniques for Diabetic Retinopathy Screening.

PubMed

Goh, James Kang Hao; Cheung, Carol Y; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

2016-02-01

Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. © 2016 Diabetes Technology Society.

Cervical screening in HPV-vaccinated populations.

PubMed

Canfell, K

2018-06-01

Cervical screening with cytology has been the basis for substantial reductions in cervical cancer incidence and mortality in most high-income countries over the last few decades. More recently, there have been two key, parallel developments which have prompted a major re-consideration of cervical screening. The first is the emergence of evidence on the improved sensitivity of human papillomavirus (HPV) DNA testing compared to cytology, and the second is the large-scale deployment of prophylactic vaccination against HPV. A key challenge to be overcome before HPV screening could be introduced into national cervical screening programs was the specificity of an infection, for detection of precancerous lesions. This has been done in three ways: (1) by considering the appropriate age for starting HPV screening (30 years in unvaccinated populations and 25 years in populations with mature vaccination programs and high vaccine uptake) and the appropriate screening interval; (2) via development of clinical HPV tests, which are (by design) not as sensitive to low viral loads; and (3) by introducing effective triaging for HPV-positive women, which further risk-stratifies women before referral for diagnostic evaluation. This review discusses these major developments and describes how the benefits of HPV screening are being optimized in both unvaccinated and vaccinated populations.

Studying circadian rhythm and sleep using genetic screens in Drosophila.

PubMed

Axelrod, Sofia; Saez, Lino; Young, Michael W

2015-01-01

The power of Drosophila melanogaster as a model organism lies in its ability to be used for large-scale genetic screens with the capacity to uncover the genetic basis of biological processes. In particular, genetic screens for circadian behavior, which have been performed since 1971, allowed researchers to make groundbreaking discoveries on multiple levels: they discovered that there is a genetic basis for circadian behavior, they identified the so-called core clock genes that govern this process, and they started to paint a detailed picture of the molecular functions of these clock genes and their encoded proteins. Since the discovery that fruit flies sleep in 2000, researchers have successfully been using genetic screening to elucidate the many questions surrounding this basic animal behavior. In this chapter, we briefly recall the history of circadian rhythm and sleep screens and then move on to describe techniques currently employed for mutagenesis and genetic screening in the field. The emphasis lies on comparing the newer approaches of transgenic RNA interference (RNAi) to classical forms of mutagenesis, in particular in their application to circadian behavior and sleep. We discuss the different screening approaches in light of the literature and published and unpublished sleep and rhythm screens utilizing ethyl methanesulfonate mutagenesis and transgenic RNAi from our lab. © 2015 Elsevier Inc. All rights reserved.

Development of a fragile X syndrome (FXS) knowledge scale: towards a modified multidimensional measure of informed choice for FXS population carrier screening.

PubMed

Ames, Alice G; Jaques, Alice; Ukoumunne, Obioha C; Archibald, Alison D; Duncan, Rony E; Emery, Jon; Metcalfe, Sylvia A

2015-02-01

Genetic carrier screening is increasingly possible for many conditions, but it is important to ensure decisions are informed. The multidimensional measure of informed choice (MMIC) is a quantitative instrument developed to evaluate informed choice in prenatal screening for Down syndrome, measuring knowledge, attitudes and uptake. To apply the MMIC in other screening settings, the knowledge scale must be modified. To develop and validate a modified MMIC knowledge scale for use with women undergoing carrier screening for fragile X syndrome (FXS). Responses to MMIC items were collected through questionnaires as part of a FXS carrier screening pilot study in a preconception setting in Melbourne, Australia. Ten knowledge scale items were developed using a modified Delphi technique. Cronbach's alpha and factor analysis were used to validate the new FXS knowledge scale. We summarized the knowledge, attitudes and informed choice status based on the modified MMIC. Two hundred and eighty-five women were recruited, 241 eligible questionnaires were complete for analysis. The FXS knowledge scale items measured one salient construct and were internally consistent (alpha = 0.70). 71% (172/241) of participants were classified as having good knowledge, 70% (169/241) had positive attitudes and 27% (65/241) made an informed choice to accept or decline screening. We present the development of a knowledge scale as part of a MMIC to evaluate informed choice in population carrier screening for FXS. This can be used as a template by other researchers to develop knowledge scales for other conditions for use in the MMIC. © 2012 John Wiley & Sons Ltd.

CellCognition: time-resolved phenotype annotation in high-throughput live cell imaging.

PubMed

Held, Michael; Schmitz, Michael H A; Fischer, Bernd; Walter, Thomas; Neumann, Beate; Olma, Michael H; Peter, Matthias; Ellenberg, Jan; Gerlich, Daniel W

2010-09-01

Fluorescence time-lapse imaging has become a powerful tool to investigate complex dynamic processes such as cell division or intracellular trafficking. Automated microscopes generate time-resolved imaging data at high throughput, yet tools for quantification of large-scale movie data are largely missing. Here we present CellCognition, a computational framework to annotate complex cellular dynamics. We developed a machine-learning method that combines state-of-the-art classification with hidden Markov modeling for annotation of the progression through morphologically distinct biological states. Incorporation of time information into the annotation scheme was essential to suppress classification noise at state transitions and confusion between different functional states with similar morphology. We demonstrate generic applicability in different assays and perturbation conditions, including a candidate-based RNA interference screen for regulators of mitotic exit in human cells. CellCognition is published as open source software, enabling live-cell imaging-based screening with assays that directly score cellular dynamics.

Validating the Learning Disability Screening Questionnaire against the Weschler Adult Intelligence Scale, Fourth Edition

ERIC Educational Resources Information Center

McKenzie, Karen; Sharples, Phil; Murray, Aja L.

2015-01-01

The Learning Disability Screening Questionnaire (LDSQ), a brief screening tool for intellectual disability, was originally validated against the Weschler Adult Intelligence Scale, Third Edition (WAIS-III), which was superseded by the Weschler Adult Intelligence Scale, Fourth Edition (WAIS-IV) in the United Kingdom in 2010. This study examines the…

Summary measures of agreement and association between many raters' ordinal classifications.

PubMed

Mitani, Aya A; Freer, Phoebe E; Nelson, Kerrie P

2017-10-01

Interpretation of screening tests such as mammograms usually require a radiologist's subjective visual assessment of images, often resulting in substantial discrepancies between radiologists' classifications of subjects' test results. In clinical screening studies to assess the strength of agreement between experts, multiple raters are often recruited to assess subjects' test results using an ordinal classification scale. However, using traditional measures of agreement in some studies is challenging because of the presence of many raters, the use of an ordinal classification scale, and unbalanced data. We assess and compare the performances of existing measures of agreement and association as well as a newly developed model-based measure of agreement to three large-scale clinical screening studies involving many raters' ordinal classifications. We also conduct a simulation study to demonstrate the key properties of the summary measures. The assessment of agreement and association varied according to the choice of summary measure. Some measures were influenced by the underlying prevalence of disease and raters' marginal distributions and/or were limited in use to balanced data sets where every rater classifies every subject. Our simulation study indicated that popular measures of agreement and association are prone to underlying disease prevalence. Model-based measures provide a flexible approach for calculating agreement and association and are robust to missing and unbalanced data as well as the underlying disease prevalence. Copyright © 2017 Elsevier Inc. All rights reserved.

Data management in large-scale collaborative toxicity studies: how to file experimental data for automated statistical analysis.

PubMed

Stanzel, Sven; Weimer, Marc; Kopp-Schneider, Annette

2013-06-01

High-throughput screening approaches are carried out for the toxicity assessment of a large number of chemical compounds. In such large-scale in vitro toxicity studies several hundred or thousand concentration-response experiments are conducted. The automated evaluation of concentration-response data using statistical analysis scripts saves time and yields more consistent results in comparison to data analysis performed by the use of menu-driven statistical software. Automated statistical analysis requires that concentration-response data are available in a standardised data format across all compounds. To obtain consistent data formats, a standardised data management workflow must be established, including guidelines for data storage, data handling and data extraction. In this paper two procedures for data management within large-scale toxicological projects are proposed. Both procedures are based on Microsoft Excel files as the researcher's primary data format and use a computer programme to automate the handling of data files. The first procedure assumes that data collection has not yet started whereas the second procedure can be used when data files already exist. Successful implementation of the two approaches into the European project ACuteTox is illustrated. Copyright © 2012 Elsevier Ltd. All rights reserved.

Large-scale image region documentation for fully automated image biomarker algorithm development and evaluation

PubMed Central

Reeves, Anthony P.; Xie, Yiting; Liu, Shuang

2017-01-01

Abstract. With the advent of fully automated image analysis and modern machine learning methods, there is a need for very large image datasets having documented segmentations for both computer algorithm training and evaluation. This paper presents a method and implementation for facilitating such datasets that addresses the critical issue of size scaling for algorithm validation and evaluation; current evaluation methods that are usually used in academic studies do not scale to large datasets. This method includes protocols for the documentation of many regions in very large image datasets; the documentation may be incrementally updated by new image data and by improved algorithm outcomes. This method has been used for 5 years in the context of chest health biomarkers from low-dose chest CT images that are now being used with increasing frequency in lung cancer screening practice. The lung scans are segmented into over 100 different anatomical regions, and the method has been applied to a dataset of over 20,000 chest CT images. Using this framework, the computer algorithms have been developed to achieve over 90% acceptable image segmentation on the complete dataset. PMID:28612037

A forward-advancing wave expansion method for numerical solution of large-scale sound propagation problems

NASA Astrophysics Data System (ADS)

Rolla, L. Barrera; Rice, H. J.

2006-09-01

In this paper a "forward-advancing" field discretization method suitable for solving the Helmholtz equation in large-scale problems is proposed. The forward wave expansion method (FWEM) is derived from a highly efficient discretization procedure based on interpolation of wave functions known as the wave expansion method (WEM). The FWEM computes the propagated sound field by means of an exclusively forward advancing solution, neglecting the backscattered field. It is thus analogous to methods such as the (one way) parabolic equation method (PEM) (usually discretized using standard finite difference or finite element methods). These techniques do not require the inversion of large system matrices and thus enable the solution of large-scale acoustic problems where backscatter is not of interest. Calculations using FWEM are presented for two propagation problems and comparisons to data computed with analytical and theoretical solutions and show this forward approximation to be highly accurate. Examples of sound propagation over a screen in upwind and downwind refracting atmospheric conditions at low nodal spacings (0.2 per wavelength in the propagation direction) are also included to demonstrate the flexibility and efficiency of the method.

Tapered Screened Channel PMD for Cryogenic Liquids

NASA Astrophysics Data System (ADS)

Dodge, Franklin T.; Green, Steve T.; Walter, David B.

2004-02-01

If a conventional spacecraft propellant management device (PMD) of the screened channel type were employed with a cryogenic liquid, vapor bubbles generated within the channel by heat transfer could ``dry out'' the channel screens and thereby cause the channels to admit large amounts of vapor from the tank into the liquid outflow. This paper describes a new tapered channel design that passively `pumps' bubbles away from the outlet port and vents them into the tank. A predictive mathematical model of the operating principle is presented and discussed. Scale-model laboratory tests were conducted and the mathematical model agreed well with the measured rates of bubble transport velocity. Finally, an example of the use of the predictive model for a realistic spacecraft application is presented. The model predicts that bubble clearing rates are acceptable even in tanks up to 2 m in length.

Challenges and the state of the technology for printed sensor arrays for structural monitoring

NASA Astrophysics Data System (ADS)

Joshi, Shiv; Bland, Scott; DeMott, Robert; Anderson, Nickolas; Jursich, Gregory

2017-04-01

Printed sensor arrays are attractive for reliable, low-cost, and large-area mapping of structural systems. These sensor arrays can be printed on flexible substrates or directly on monitored structural parts. This technology is sought for continuous or on-demand real-time diagnosis and prognosis of complex structural components. In the past decade, many innovative technologies and functional materials have been explored to develop printed electronics and sensors. For example, an all-printed strain sensor array is a recent example of a low-cost, flexible and light-weight system that provides a reliable method for monitoring the state of aircraft structural parts. Among all-printing techniques, screen and inkjet printing methods are well suited for smaller-scale prototyping and have drawn much interest due to maturity of printing procedures and availability of compatible inks and substrates. Screen printing relies on a mask (screen) to transfer a pattern onto a substrate. Screen printing is widely used because of the high printing speed, large selection of ink/substrate materials, and capability of making complex multilayer devices. The complexity of collecting signals from a large number of sensors over a large area necessitates signal multiplexing electronics that need to be printed on flexible substrate or structure. As a result, these components are subjected to same deformation, temperature and other parameters for which sensor arrays are designed. The characteristics of these electronic components, such as transistors, are affected by deformation and other environmental parameters which can lead to erroneous sensed parameters. The manufacturing and functional challenges of the technology of printed sensor array systems for structural state monitoring are the focus of this presentation. Specific examples of strain sensor arrays will be presented to highlight the technical challenges.

Turkish translation and adaptation of Champion's Health Belief Model Scales for breast cancer mammography screening.

PubMed

Yilmaz, Meryem; Sayin, Yazile Yazici

2014-07-01

To examine the translation and adaptation process from English to Turkish and the validity and reliability of the Champion's Health Belief Model Scales for Mammography Screening. Its aim (1) is to provide data about and (2) to assess Turkish women's attitudes and behaviours towards mammography. The proportion of women who have mammography is lower in Turkey. The Champion's Health Belief Model Scales for Mammography Screening-Turkish version can be helpful to determine Turkish women's health beliefs, particularly about mammography. Cross-sectional design was used to collect survey data from Turkish women: classical measurement method. The Champion's Health Belief Model Scales for Mammography Screening was translated from English to Turkish. Again, it was back translated into English. Later, the meaning and clarity of the scale items were evaluated by a bilingual group representing the culture of the target population. Finally, the tool was evaluated by two bilingual professional researchers in terms of content validity, translation validity and psychometric estimates of the validity and reliability. The analysis included a total of 209 Turkish women. The validity of the scale was confirmed by confirmatory factor analysis and criterion-related validity testing. The Champion's Health Belief Model Scales for Mammography Screening aligned to four factors that were coherent and relatively independent of each other. There was a statistically significant relationship among all of the subscale items: the positive and high correlation of the total item test score and high Cronbach's α. The scale has a strong stability over time: the Champion's Health Belief Model Scales for Mammography Screening demonstrated acceptable preliminary values of reliability and validity. The Champion's Health Belief Model Scales for Mammography Screening is both a reliable and valid instrument that can be useful in measuring the health beliefs of Turkish women. It can be used to provide data about healthcare practices required for mammography screening and breast cancer prevention. This scale will show nurses that nursing intervention planning is essential for increasing Turkish women's participation in mammography screening. © 2013 John Wiley & Sons Ltd.

Enterprise PACS and image distribution.

PubMed

Huang, H K

2003-01-01

Around the world now, because of the need to improve operation efficiency and better cost effective healthcare, many large-scale healthcare enterprises have been formed. Each of these enterprises groups hospitals, medical centers, and clinics together as one enterprise healthcare network. The management of these enterprises recognizes the importance of using PACS and image distribution as a key technology in cost-effective healthcare delivery in the enterprise level. As a result, many large-scale enterprise level PACS/image distribution pilot studies, full design and implementation, are underway. The purpose of this paper is to provide readers an overall view of the current status of enterprise PACS and image distribution. reviews three large-scale enterprise PACS/image distribution systems in USA, Germany, and South Korean. The concept of enterprise level PACS/image distribution, its characteristics and ingredients are then discussed. Business models for enterprise level implementation available by the private medical imaging and system integration industry are highlighted. One current system under development in designing a healthcare enterprise level chest tuberculosis (TB) screening in Hong Kong is described in detail. Copyright 2002 Elsevier Science Ltd.

What are key factors influencing malnutrition screening in community-dwelling elderly populations by general practitioners? A large cross-sectional survey in two areas of France.

PubMed

Gaboreau, Y; Imbert, P; Jacquet, J-P; Marchand, O; Couturier, P; Gavazzi, G

2013-11-01

Malnutrition is associated with a high morbi-mortality in elderly populations and their institutionalization at an early stage. The incidence is well known despite being often under-diagnosed in primary care. General practitioners (GPs) have a key role in home care. What are the factors affecting malnutrition-screening implementation by French GPs? We conducted a cross-sectional survey in two areas in the southeast of France (Savoie and Isère). In May 2008, an anonymized survey was sent by e-mail and/or post to all GPs with a large clinical practice. Two months later, reminder letters were sent. Potential barriers were measured by dichotomous scale. On GPs' characteristics (socio-demographic, medical training, geriatric practice and knowledge), multiple regression logistic was performed to identify others factors affecting malnutrition screening. In all, 493 GPs (26.85%) answered and 72.2% felt that malnutrition screening was useful although only 26.6% implemented it each year and 11.9% every 2-5 years. The main barriers to the implementation were patient selection (60.4%) and forgetting to screen (26.6%). Minor barriers were lack of knowledge (19.5%) or time (15%). New factors were identified: unsuitable working conditions (19.1%), insufficient motivation (6.8%) or technical support (7.2%). The quality of malnutrition information received was found to be the only promoter of annual screening (odds ratio=1.44 (1.087-1.919); P=0.011). This survey is the first in France to reveal GPs' factors affecting malnutrition implementation. New obstacles were identified in this survey. The hope of implementing regular malnutrition screening by GPs seems to lie with the quality of malnutrition information received.

Diagnostic performance of an indirect enzyme-linked immunosorbent assay (ELISA) to detect bovine leukemia virus antibodies in bulk-tank milk samples.

PubMed

Nekouei, Omid; Durocher, Jean; Keefe, Greg

2016-07-01

This study assessed the diagnostic performance of a commercial ELISA for detecting bovine leukemia virus antibodies in bulk-tank milk samples from eastern Canada. Sensitivity and specificity of the test were estimated at 97.2% and 100%, respectively. The test was recommended as a cost-efficient tool for large-scale screening programs.

Diagnostic performance of an indirect enzyme-linked immunosorbent assay (ELISA) to detect bovine leukemia virus antibodies in bulk-tank milk samples

PubMed Central

Nekouei, Omid; Durocher, Jean; Keefe, Greg

2016-01-01

This study assessed the diagnostic performance of a commercial ELISA for detecting bovine leukemia virus antibodies in bulk-tank milk samples from eastern Canada. Sensitivity and specificity of the test were estimated at 97.2% and 100%, respectively. The test was recommended as a cost-efficient tool for large-scale screening programs. PMID:27429469

Ranking the shade tolerance of forty-five candidate groundcovers for agroforestry plantings

Treesearch

J.W. Van Sambeek; N.E. Navarrete-Tindall; H.E. Garrett; C.-H. Lin; R.L. McGraw; D.C. Wallace

2007-01-01

Several large-scale screening trials evaluating native and introduced herbaceous ground covers have been conducted in the last half century. Most trials have used shade cloth to evaluate growth of potted plants under moderate shade (45 to 55 percent of full sunlight) similar to what might be found in many agroforestry practices and heavy shade (20 to 30 percent of full...

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

PubMed

Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

2015-09-18

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

PubMed Central

Guyon, Laurent; Lajaunie, Christian; fer, Frédéric; bhajun, Ricky; sulpice, Eric; pinna, Guillaume; campalans, Anna; radicella, J. Pablo; rouillier, Philippe; mary, Mélissa; combe, Stéphanie; obeid, Patricia; vert, Jean-Philippe; gidrol, Xavier

2015-01-01

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID:26382112

High-throughput screens in mammalian cells using the CRISPR-Cas9 system.

PubMed

Peng, Jingyu; Zhou, Yuexin; Zhu, Shiyou; Wei, Wensheng

2015-06-01

As a powerful genome-editing tool, the clustered regularly interspaced short palindromic repeats (CRISPR)-clustered regularly interspaced short palindromic repeats-associated protein 9 (Cas9) system has been quickly developed into a large-scale function-based screening strategy in mammalian cells. This new type of genetic library is constructed through the lentiviral delivery of single-guide RNA collections that direct Cas9 or inactive dead Cas9 fused with effectors to interrogate gene function or regulate gene transcription in targeted cells. Compared with RNA interference screening, the CRISPR-Cas9 system demonstrates much higher levels of effectiveness and reliability with respect to both loss-of-function and gain-of-function screening. Unlike the RNA interference strategy, a CRISPR-Cas9 library can target both protein-coding sequences and regulatory elements, including promoters, enhancers and elements transcribing microRNAs and long noncoding RNAs. This powerful genetic tool will undoubtedly accelerate the mechanistic discovery of various biological processes. In this mini review, we summarize the general procedure of CRISPR-Cas9 library mediated functional screening, system optimization strategies and applications of this new genetic toolkit. © 2015 FEBS.

Methods to identify and analyze gene products involved in neuronal intracellular transport using Drosophila

PubMed Central

Neisch, Amanda L.; Avery, Adam W.; Machame, James B.; Li, Min-gang; Hays, Thomas S.

2017-01-01

Proper neuronal function critically depends on efficient intracellular transport and disruption of transport leads to neurodegeneration. Molecular pathways that support or regulate neuronal transport are not fully understood. A greater understanding of these pathways will help reveal the pathological mechanisms underlying disease. Drosophila melanogaster is the premier model system for performing large-scale genetic functional screens. Here we describe methods to carry out primary and secondary genetic screens in Drosophila aimed at identifying novel gene products and pathways that impact neuronal intracellular transport. These screens are performed using whole animal or live cell imaging of intact neural tissue to ensure integrity of neurons and their cellular environment. The primary screen is used to identify gross defects in neuronal function indicative of a disruption in microtubule-based transport. The secondary screens, conducted in both motoneurons and dendritic arborization neurons, will confirm the function of candidate gene products in intracellular transport. Together, the methodologies described here will support labs interested in identifying and characterizing gene products that alter intracellular transport in Drosophila. PMID:26794520

Disrupted coupling of large-scale networks is associated with relapse behaviour in heroin-dependent men

PubMed Central

Li, Qiang; Liu, Jierong; Wang, Wei; Wang, Yarong; Li, Wei; Chen, Jiajie; Zhu, Jia; Yan, Xuejiao; Li, Yongbin; Li, Zhe; Ye, Jianjun; Wang, Wei

2018-01-01

Background It is unknown whether impaired coupling among 3 core large-scale brain networks (salience [SN], default mode [DMN] and executive control networks [ECN]) is associated with relapse behaviour in treated heroin-dependent patients. Methods We conducted a prospective resting-state functional MRI study comparing the functional connectivity strength among healthy controls and heroin-dependent men who had either relapsed or were in early remission. Men were considered to be either relapsed or in early remission based on urine drug screens during a 3-month follow-up period. We also examined how the coupling of large-scale networks correlated with relapse behaviour among heroin-dependent men. Results We included 20 controls and 50 heroin-dependent men (26 relapsed and 24 early remission) in our analyses. The relapsed men showed greater connectivity than the early remission and control groups between the dorsal anterior cingulate cortex (key node of the SN) and the dorsomedial prefrontal cortex (included in the DMN). The relapsed men and controls showed lower connectivity than the early remission group between the left dorsolateral prefrontal cortex (key node of the left ECN) and the dorsomedial prefrontal cortex. The percentage of positive urine drug screens positively correlated with the coupling between the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex, but negatively correlated with the coupling between the left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex. Limitations We examined deficits in only 3 core networks leading to relapse behaviour. Other networks may also contribute to relapse. Conclusion Greater coupling between the SN and DMN and lower coupling between the left ECN and DMN is associated with relapse behaviour. These findings may shed light on the development of new treatments for heroin addiction. PMID:29252165

Large-Scale Test of Dynamic Correlation Processors: Implications for Correlation-Based Seismic Pipelines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dodge, D. A.; Harris, D. B.

Correlation detectors are of considerable interest to the seismic monitoring communities because they offer reduced detection thresholds and combine detection, location and identification functions into a single operation. They appear to be ideal for applications requiring screening of frequent repeating events. However, questions remain about how broadly empirical correlation methods are applicable. We describe the effectiveness of banks of correlation detectors in a system that combines traditional power detectors with correlation detectors in terms of efficiency, which we define to be the fraction of events detected by the correlators. This paper elaborates and extends the concept of a dynamic correlationmore » detection framework – a system which autonomously creates correlation detectors from event waveforms detected by power detectors; and reports observed performance on a network of arrays in terms of efficiency. We performed a large scale test of dynamic correlation processors on an 11 terabyte global dataset using 25 arrays in the single frequency band 1-3 Hz. The system found over 3.2 million unique signals and produced 459,747 screened detections. A very satisfying result is that, on average, efficiency grows with time and, after nearly 16 years of operation, exceeds 47% for events observed over all distance ranges and approaches 70% for near regional and 90% for local events. This observation suggests that future pipeline architectures should make extensive use of correlation detectors, principally for decluttering observations of local and near-regional events. Our results also suggest that future operations based on correlation detection will require commodity large-scale computing infrastructure, since the numbers of correlators in an autonomous system can grow into the hundreds of thousands.« less

Large-Scale Test of Dynamic Correlation Processors: Implications for Correlation-Based Seismic Pipelines

DOE PAGES

Dodge, D. A.; Harris, D. B.

2016-03-15

Correlation detectors are of considerable interest to the seismic monitoring communities because they offer reduced detection thresholds and combine detection, location and identification functions into a single operation. They appear to be ideal for applications requiring screening of frequent repeating events. However, questions remain about how broadly empirical correlation methods are applicable. We describe the effectiveness of banks of correlation detectors in a system that combines traditional power detectors with correlation detectors in terms of efficiency, which we define to be the fraction of events detected by the correlators. This paper elaborates and extends the concept of a dynamic correlationmore » detection framework – a system which autonomously creates correlation detectors from event waveforms detected by power detectors; and reports observed performance on a network of arrays in terms of efficiency. We performed a large scale test of dynamic correlation processors on an 11 terabyte global dataset using 25 arrays in the single frequency band 1-3 Hz. The system found over 3.2 million unique signals and produced 459,747 screened detections. A very satisfying result is that, on average, efficiency grows with time and, after nearly 16 years of operation, exceeds 47% for events observed over all distance ranges and approaches 70% for near regional and 90% for local events. This observation suggests that future pipeline architectures should make extensive use of correlation detectors, principally for decluttering observations of local and near-regional events. Our results also suggest that future operations based on correlation detection will require commodity large-scale computing infrastructure, since the numbers of correlators in an autonomous system can grow into the hundreds of thousands.« less

Utilization of Stop-flow Micro-tubing Reactors for the Development of Organic Transformations.

PubMed

Toh, Ren Wei; Li, Jie Sheng; Wu, Jie

2018-01-04

A new reaction screening technology for organic synthesis was recently demonstrated by combining elements from both continuous micro-flow and conventional batch reactors, coined stop-flow micro-tubing (SFMT) reactors. In SFMT, chemical reactions that require high pressure can be screened in parallel through a safer and convenient way. Cross-contamination, which is a common problem in reaction screening for continuous flow reactors, is avoided in SFMT. Moreover, the commercially available light-permeable micro-tubing can be incorporated into SFMT, serving as an excellent choice for light-mediated reactions due to a more effective uniform light exposure, compared to batch reactors. Overall, the SFMT reactor system is similar to continuous flow reactors and more superior than batch reactors for reactions that incorporate gas reagents and/or require light-illumination, which enables a simple but highly efficient reaction screening system. Furthermore, any successfully developed reaction in the SFMT reactor system can be conveniently translated to continuous-flow synthesis for large scale production.

Detection, prevention, and rehabilitation of amblyopia.

PubMed

Spiritus, M

1997-10-01

The necessity of visual preschool screening for reducing the prevalence of amblyopia is widely accepted. The beneficial results of large-scale screening programs conducted in Scandinavia are reported. Screening monocular visual acuity at 3.5 to 4 years of age appears to be an excellent basis for detecting and treating amblyopia and an acceptable compromise between the pitfalls encountered in screening younger children and the cost-to-benefit ratio. In this respect, several preschoolers' visual acuity charts have been evaluated. New recently developed small-target random stereotests and binocular suppression tests have also been developed with the aim of correcting the many false negatives (anisometropic amblyopia or bilateral high ametropia) induced by the usual stereotests. Longitudinal studies demonstrate that correction of high refractive errors decreases the risk of amblyopia and does not impede emmetropization. The validity of various photoscreening and videoscreening procedures for detecting refractive errors in infants prior to the onset of strabismus or amblyopia, as well as alternatives to conventional occlusion therapy, is discussed.

Novel microscopy-based screening method reveals regulators of contact-dependent intercellular transfer

PubMed Central

Michael Frei, Dominik; Hodneland, Erlend; Rios-Mondragon, Ivan; Burtey, Anne; Neumann, Beate; Bulkescher, Jutta; Schölermann, Julia; Pepperkok, Rainer; Gerdes, Hans-Hermann; Kögel, Tanja

2015-01-01

Contact-dependent intercellular transfer (codeIT) of cellular constituents can have functional consequences for recipient cells, such as enhanced survival and drug resistance. Pathogenic viruses, prions and bacteria can also utilize this mechanism to spread to adjacent cells and potentially evade immune detection. However, little is known about the molecular mechanism underlying this intercellular transfer process. Here, we present a novel microscopy-based screening method to identify regulators and cargo of codeIT. Single donor cells, carrying fluorescently labelled endocytic organelles or proteins, are co-cultured with excess acceptor cells. CodeIT is quantified by confocal microscopy and image analysis in 3D, preserving spatial information. An siRNA-based screening using this method revealed the involvement of several myosins and small GTPases as codeIT regulators. Our data indicates that cellular protrusions and tubular recycling endosomes are important for codeIT. We automated image acquisition and analysis to facilitate large-scale chemical and genetic screening efforts to identify key regulators of codeIT. PMID:26271723

Evaluation of Indoor Air Quality Screening Strategies: A Step-Wise Approach for IAQ Screening.

PubMed

Wong, Ling-Tim; Mui, Kwok-Wai; Tsang, Tsz-Wun

2016-12-14

Conducting a full indoor air quality (IAQ) assessment in air-conditioned offices requires large-scale material and manpower resources. However, an IAQ index can be adopted as a handy screening tool to identify any premises (with poor IAQ) that need more comprehensive IAQ assessments to prioritize IAQ improvements. This study proposes a step-wise IAQ screening protocol to facilitate its cost-effective management among building owners and managers. The effectiveness of three IAQ indices, namely θ₁ (with one parameter: CO₂), θ₂ (with two parameters: CO₂ and respirable suspended particulates, RSP) and θ₃ (with three parameters: CO₂, RSP, and total volatile organic compounds, TVOC) are evaluated. Compared in a pairwise manner with respect to the minimum satisfaction levels as stated in the IAQ Certification Scheme by the Hong Kong Environmental Protection Department, the results show that a screening test with more surrogate IAQ parameters is good at identifying both lower and higher risk groups for unsatisfactory IAQ, and thus offers higher resolution. Through the sensitivity and specificity for identifying IAQ problems, the effectiveness of alternative IAQ screening methods with different monitoring parameters is also reported.

Surveillance of Populations at Risk of Cholangiocarcinoma Development in Rural Communities of Thailand Using the Korat-CCA Verbal Screening Test.

PubMed

Kaewpitoon, Soraya J; Rujirakul, Ratana; Loyd, Ryan A; Panpimanmas, Sukij; Matrakool, Likit; Tongtawee, Taweesak; Kompor, Porntip; Norkaew, Jun; Chavengkun, Wasugree; Wakkhuwattapong, Parichart; Kujapun, Jirawoot; Ponphimai, Sukanya; Phatisena, Tanida; Eaksunti, Thawatchai; Polsripradist, Poowadol; Joosiri, Apinya; Sukkasam, Inchat; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

2016-01-01

Cholangiocarcinoma (CCA) is a serious problem in Thailand, particularly in the northeastern region. Active surveillance in rural communities with an appropriat low-cost screening tool is required to facilitate early detection. Therefore, this study aimed to investigate the population at risk of CCA in Bua Yai district, Nakhon Ratchasima province, Northeastern Thailand using the Korat-CCA verbal screening test (KCVST) during June to October 2015. Reliability of KCVST demonstrated a Cronbach alpha coefficient=0.75 Stepwise-multiple regression showed that alcohol consumption was important for CCA screened, followed by agriculture and pesticide use, under-cooked cyprinoid fish consumption, praziquantel use, naïve northeastern people, opisthorchiasis, family relatives with CCA, and cholangitis or cholecystitis or gallstones, respectively. Population at risk for CCA was classified to low risk (63.4%), moderate risk (33.7%), and high risk (1.32%) for CCA. When CCA was screened using ultrasonography, 4 of 32 high risk participants had an abnormal biliary tract with dilated bile ducts. This study indicates that KCVST is a potential useful too which decrease the cost of large scale CCA screening.

Evaluation of Indoor Air Quality Screening Strategies: A Step-Wise Approach for IAQ Screening

PubMed Central

Wong, Ling-tim; Mui, Kwok-wai; Tsang, Tsz-wun

2016-01-01

Conducting a full indoor air quality (IAQ) assessment in air-conditioned offices requires large-scale material and manpower resources. However, an IAQ index can be adopted as a handy screening tool to identify any premises (with poor IAQ) that need more comprehensive IAQ assessments to prioritize IAQ improvements. This study proposes a step-wise IAQ screening protocol to facilitate its cost-effective management among building owners and managers. The effectiveness of three IAQ indices, namely θ1 (with one parameter: CO2), θ2 (with two parameters: CO2 and respirable suspended particulates, RSP) and θ3 (with three parameters: CO2, RSP, and total volatile organic compounds, TVOC) are evaluated. Compared in a pairwise manner with respect to the minimum satisfaction levels as stated in the IAQ Certification Scheme by the Hong Kong Environmental Protection Department, the results show that a screening test with more surrogate IAQ parameters is good at identifying both lower and higher risk groups for unsatisfactory IAQ, and thus offers higher resolution. Through the sensitivity and specificity for identifying IAQ problems, the effectiveness of alternative IAQ screening methods with different monitoring parameters is also reported. PMID:27983667

Identification of the hot-spot areas for sickle cell disease using cord blood screening at a district hospital: an Indian perspective.

PubMed

Dixit, Sujata; Sahu, Pushpansu; Kar, Shantanu Kumar; Negi, Sapna

2015-10-01

Sickle cell disease (SCD), a genetic disorder often reported late, can be identified early in life, and hot-spot areas may be identified to conduct genetic epidemiology studies. This study was undertaken to estimate prevalence and to identify hot spot area for SCD in Kalahandi district, by screening cord blood of neonates delivered at the district hospital as first-hand information. Kalahandi District Hospital selected for the study is predominated by tribal population with higher prevalence of SCD as compared to other parts of Odisha. Cord blood screening of SCD was carried out on 761 newborn samples of which 13 were screened to be homozygous for SCD. Information on area of parent's residence was also collected. Madanpur Rampur area was found to be with the highest prevalence of SCD (10.52 %) and the gene distribution did not follow Hardy-Weinberg Equation indicating un-natural selection. The approach of conducting neonatal screening in a district hospital for identification of SCD is feasible and appropriate for prioritizing area for the implementation of large-scale screening and planning control measures thereof.

Data and animal management software for large-scale phenotype screening.

PubMed

Ching, Keith A; Cooke, Michael P; Tarantino, Lisa M; Lapp, Hilmar

2006-04-01

The mouse N-ethyl-N-nitrosourea (ENU) mutagenesis program at the Genomics Institute of the Novartis Research Foundation (GNF) uses MouseTRACS to analyze phenotype screens and manage animal husbandry. MouseTRACS is a Web-based laboratory informatics system that electronically records and organizes mouse colony operations, prints cage cards, tracks inventory, manages requests, and reports Institutional Animal Care and Use Committee (IACUC) protocol usage. For efficient phenotype screening, MouseTRACS identifies mutants, visualizes data, and maps mutations. It displays and integrates phenotype and genotype data using likelihood odds ratio (LOD) plots of genetic linkage between genotype and phenotype. More detailed mapping intervals show individual single nucleotide polymorphism (SNP) markers in the context of phenotype. In addition, dynamically generated pedigree diagrams and inventory reports linked to screening results summarize the inheritance pattern and the degree of penetrance. MouseTRACS displays screening data in tables and uses standard charts such as box plots, histograms, scatter plots, and customized charts looking at clustered mice or cross pedigree comparisons. In summary, MouseTRACS enables the efficient screening, analysis, and management of thousands of animals to find mutant mice and identify novel gene functions. MouseTRACS is available under an open source license at http://www.mousetracs.sourceforge.net.

A Comparison between SRSS-IE and SSiS-PSG Scores: Examining Convergent Validity

ERIC Educational Resources Information Center

Lane, Kathleen Lynne; Oakes, Wendy Peia; Common, Eric Alan; Zorigian, Kris; Brunsting, Nelson C.; Schatschneider, Christopher

2015-01-01

We report findings of a validation study comparing two screening tools: the Student Risk Screening Scale-Internalizing and Externalizing (SRSS-IE, an adapted version of the Student Risk Screening Scale) and the Social Skills Improvement System-Performance Screening Guide (SSiS-PSG). Participants included 458 kindergarten through fifth-grade…

Clinical and experimental characteristics of "hypothetically psychosis prone" college students.

PubMed

Cadenhead, K; Kumar, C; Braff, D

1996-01-01

The study of individuals at the boundaries of schizophrenia has historically involved genetic relatives of schizophrenia patients or individuals who meet criteria for schizotypal personality disorder (SPD). Recently, many investigators have turned to the use of psychometric scales, developed to measure psychotic traits or vulnerability to developing schizophrenia, to screen large populations of college students in order to identify individuals who are "psychosis prone" or "schizotypal". To help answer the question of whether students identified with psychometric scales are indeed psychosis prone, we screened 1115 college students with the Perceptual Aberration/ Magical Ideation (PerMag) and Physical Anhedonia (PhysAn) Scales. Individuals who scored 2 standard deviations (SD) above the mean on the scales were selected as experimental subjects (N = 13 PerMag, N = 10 PhysAn) and a subpopulation of matched subjects who scored less than 0.5 SD above the mean were selected as control subjects (N = 24). All subjects then received a full battery of tests, including structured clinical interviews, the MMPI, and psychophysiological measures of information processing, including prepulse inhibition and habituation of the human startle response, visual backward masking and reaction time measures. The results suggest that the PerMag scale, but not the PhysAn scale, identifies individuals with some psychotic, affective and anxiety symptoms when compared to the controls. Neither scale predicts a diagnosis of schizotypal personality disorder or deficits on measures of information processing that characterize schizophrenia or schizotypal personality disordered patients.

Study and design of cryogenic propellant acquisition systems. Volume 1: Design studies

NASA Technical Reports Server (NTRS)

Burge, G. W.; Blackmon, J. B.

1973-01-01

An in-depth study and selection of practical propellant surface tension acquisition system designs for two specific future cryogenic space vehicles, an advanced cryogenic space shuttle auxiliary propulsion system and an advanced space propulsion module is reported. A supporting laboratory scale experimental program was also conducted to provide design information critical to concept finalization and selection. Designs using localized pressure isolated surface tension screen devices were selected for each application and preliminary designs were generated. Based on these designs, large scale acquisition prototype hardware was designed and fabricated to be compatible with available NASA-MSFC feed system hardware.

Grid-enabled mammographic auditing and training system

NASA Astrophysics Data System (ADS)

Yap, M. H.; Gale, A. G.

2008-03-01

Effective use of new technologies to support healthcare initiatives is important and current research is moving towards implementing secure grid-enabled healthcare provision. In the UK, a large-scale collaborative research project (GIMI: Generic Infrastructures for Medical Informatics), which is concerned with the development of a secure IT infrastructure to support very widespread medical research across the country, is underway. In the UK, there are some 109 breast screening centers and a growing number of individuals (circa 650) nationally performing approximately 1.5 million screening examinations per year. At the same, there is a serious, and ongoing, national workforce issue in screening which has seen a loss of consultant mammographers and a growth in specially trained technologists and other non-radiologists. Thus there is a need to offer effective and efficient mammographic training so as to maintain high levels of screening skills. Consequently, a grid based system has been proposed which has the benefit of offering very large volumes of training cases that the mammographers can access anytime and anywhere. A database, spread geographically across three university systems, of screening cases is used as a test set of known cases. The GIMI mammography training system first audits these cases to ensure that they are appropriately described and annotated. Subsequently, the cases are utilized for training in a grid-based system which has been developed. This paper briefly reviews the background to the project and then details the ongoing research. In conclusion, we discuss the contributions, limitations, and future plans of such a grid based approach.

The impact of new forms of large-scale general practice provider collaborations on England's NHS: a systematic review.

PubMed

Pettigrew, Luisa M; Kumpunen, Stephanie; Mays, Nicholas; Rosen, Rebecca; Posaner, Rachel

2018-03-01

Over the past decade, collaboration between general practices in England to form new provider networks and large-scale organisations has been driven largely by grassroots action among GPs. However, it is now being increasingly advocated for by national policymakers. Expectations of what scaling up general practice in England will achieve are significant. To review the evidence of the impact of new forms of large-scale general practice provider collaborations in England. Systematic review. Embase, MEDLINE, Health Management Information Consortium, and Social Sciences Citation Index were searched for studies reporting the impact on clinical processes and outcomes, patient experience, workforce satisfaction, or costs of new forms of provider collaborations between general practices in England. A total of 1782 publications were screened. Five studies met the inclusion criteria and four examined the same general practice networks, limiting generalisability. Substantial financial investment was required to establish the networks and the associated interventions that were targeted at four clinical areas. Quality improvements were achieved through standardised processes, incentives at network level, information technology-enabled performance dashboards, and local network management. The fifth study of a large-scale multisite general practice organisation showed that it may be better placed to implement safety and quality processes than conventional practices. However, unintended consequences may arise, such as perceptions of disenfranchisement among staff and reductions in continuity of care. Good-quality evidence of the impacts of scaling up general practice provider organisations in England is scarce. As more general practice collaborations emerge, evaluation of their impacts will be important to understand which work, in which settings, how, and why. © British Journal of General Practice 2018.

Genetics of Resistant Hypertension: the Missing Heritability and Opportunities.

PubMed

Teixeira, Samantha K; Pereira, Alexandre C; Krieger, Jose E

2018-05-19

Blood pressure regulation in humans has long been known to be a genetically determined trait. The identification of causal genetic modulators for this trait has been unfulfilling at the least. Despite the recent advances of genome-wide genetic studies, loci associated with hypertension or blood pressure still explain a very low percentage of the overall variation of blood pressure in the general population. This has precluded the translation of discoveries in the genetics of human hypertension to clinical use. Here, we propose the combined use of resistant hypertension as a trait for mapping genetic determinants in humans and the integration of new large-scale technologies to approach in model systems the multidimensional nature of the problem. New large-scale efforts in the genetic and genomic arenas are paving the way for an increased and granular understanding of genetic determinants of hypertension. New technologies for whole genome sequence and large-scale forward genetic screens can help prioritize gene and gene-pathways for downstream characterization and large-scale population studies, and guided pharmacological design can be used to drive discoveries to the translational application through better risk stratification and new therapeutic approaches. Although significant challenges remain in the mapping and identification of genetic determinants of hypertension, new large-scale technological approaches have been proposed to surpass some of the shortcomings that have limited progress in the area for the last three decades. The incorporation of these technologies to hypertension research may significantly help in the understanding of inter-individual blood pressure variation and the deployment of new phenotyping and treatment approaches for the condition.

Conceptualization and Assessment of Hypersexual Disorder: A Systematic Review of the Literature.

PubMed

Montgomery-Graham, Stephanie

2017-04-01

Despite the rejection of hypersexual disorder (HD) as a new diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), clinical and research interest in HD continues. To systematically review the existing scientific literature on the conceptualization and assessment of HD and out-of-control sexual behavior. Studies were identified from PsychInfo, PubMed, JSTOR, Google Scholar, and Scholar's Portal using an exhaustive list of key terms. Of 299 total articles identified and screened, 252 were excluded, and 47 are included in this review. To review two categories of articles: HD conceptualization and HD psychometric assessment. First, results of the review of theoretical conceptualizations of HD reflected a large proportion of the peer-reviewed literature devoted to discussing conceptualizations of HD without reaching consensus. Second, results of the review of HD psychometric assessments were analyzed using Hunsley and Mash's (2008) criteria to evaluate psychometric adequacy of evidence-based assessment measurements. The six most researched measurements of HD were evaluated, including the Hypersexual Disorder Screening Inventory, the Hypersexual Behavior Inventory, the Sexual Compulsivity Scale, the Sexual Addiction Screening Test, the Sexual Addiction Screening Test-Revised, and the Compulsive Sexual Behavior Inventory. Psychometric properties of the scales are reviewed, evaluated, and discussed. The Hypersexual Disorder Screening Inventory, the measurement proposed for the clinical screening of HD by the DSM-5 workgroup, currently has the strongest psychometric support. Future research and clinical directions are discussed in light of findings after the literature review and synthesis. Montgomery-Graham S. Conceptualization and Assessment of Hypersexual Disorder: A Systematic Review of the Literature. Sex Med Rev 2017;5:146-162. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Association of Antenatal Depression Symptoms and Antidepressant Treatment With Preterm Birth.

PubMed

Venkatesh, Kartik K; Riley, Laura; Castro, Victor M; Perlis, Roy H; Kaimal, Anjali J

2016-05-01

To evaluate the association of antenatal depression symptoms with preterm birth and small for gestational age (SGA). This was an observational cohort study conducted among women who completed Edinburgh Postnatal Depression Scale screening and delivered at 20 weeks of gestation or greater. The primary outcomes were preterm birth and an SGA neonate at birth (less than 10th percentile for gestational age); the primary predictor was an Edinburgh Postnatal Depression Scale antepartum score of 10 or greater, indicating symptoms of depression. Logistic regression models were used with and without consideration of antidepressant exposure during pregnancy. Among 7,267 women, 831 (11%) screened positive for depression. In multivariable analyses adjusting for maternal age, race, income, body mass index, tobacco use, lifetime diagnosis of major depression and anxiety, diabetes, hypertension, and preeclampsia, women who screened positive for depression experienced an increased risk of preterm birth (less than 37 weeks of gestation) (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.04-1.55) and very preterm birth (less than 32 weeks of gestation) (adjusted OR 1.82, 95% CI 1.09-3.02) as well as of having an SGA neonate (adjusted OR 1.28, 95% CI 1.04-1.58). In secondary analyses, among women who were treated with an antidepressant during pregnancy (19% of those who screened positive and 5% of those who screened negative), depressive symptoms were not associated with a significantly increased risk of preterm and very preterm birth or an SGA neonate. In a large cohort of women screened for depression antepartum, those with depressive symptoms had an increased likelihood of preterm and very preterm delivery as well having an SGA neonate. Such risk was not apparent among women who were treated with an antidepressant medication.

Screening for Adolescent Problematic Internet Use: Validation of the Problematic and Risky Internet Use Screening Scale (PRIUSS).

PubMed

Jelenchick, Lauren A; Eickhoff, Jens; Zhang, Chong; Kraninger, Kristina; Christakis, Dimitri A; Moreno, Megan A

2015-01-01

Problematic Internet use (PIU) is an emerging health concern that lacks screening measures validated for use with adolescents and young adults. This study aimed to validate the Problematic and Risky Internet Use Screening Scale (PRIUSS) for use with older adolescents and to increase its clinical utility by determining scoring guidelines and assessing the relationship between PIU and other mental health conditions. This cross-sectional survey study took place at a large, public Midwestern university among 330 older adolescents aged 18 to 25 years. Confirmatory factor analysis and Spearman's correlations were used to assess the PRIUSS' structural and construct validity, respectively. A risk-based scoring cutoff was estimated using a Bayesian latent class modeling approach to computing a receiver operating characteristic curve. The confirmatory factor analysis indices for the 3-factor model indicated an acceptable fit (goodness-of-fit index 0.89, root mean square error of approximation 0.07). A cutoff of 25 (sensitivity 0.80, 95% confidence interval [CI] 0.47-0.99; specificity 0.79, 95% CI 0.73-0.84) is proposed for identifying those at risk for PIU. Participants at risk for PIU were at significantly greater odds of also reporting symptoms of attention-deficit/hyperactivity disorder (odds ratio [OR] 2.36 95% CI 1.21-4.62, P = .009), depression (OR 3.25, 95% CI 1.65-6.42, P = .008), and social anxiety (OR 3.77, 95% CI 2.06-6.89, P < .000). The PRIUSS demonstrated validity as a PIU screening instrument for adolescents and young adults. Screening for PIU may also help to identify those at high reciprocal risk for other mental health conditions. Copyright © 2015. Published by Elsevier Inc.

Screening Accuracy of Level 2 Autism Spectrum Disorder Rating Scales: A Review of Selected Instruments

ERIC Educational Resources Information Center

Norris, Megan; Lecavalier, Luc

2010-01-01

The goal of this review was to examine the state of Level 2, caregiver-completed rating scales for the screening of Autism Spectrum Disorders (ASDs) in individuals above the age of three years. We focused on screening accuracy and paid particular attention to comparison groups. Inclusion criteria required that scales be developed post ICD-10, be…

Alcoholism, Psychopathology and Sensation-Seeking: Differences Between Male Dui First Offenders and Recidivists

DTIC Science & Technology

1994-01-01

scales from the Drug Use Screening Inventory: Behavior Pattern Domain and Psychiatric Disorder Domain. The following scales from the Zuckerman ...1992). Validation of the adolescent Drug Use Screening Inventory: Preliminary findings. -Py hogyof Addictive Behaviors.6(4), 233-36. Tennen, H... Drug Use Screening Inventory - Revised (Behavior and Psychiatry Scales) ..................................... 58 Measures of Sensation-seeking and

Application of chemical arrays in screening elastase inhibitors.

PubMed

Gao, Feng; Du, Guan-Hua

2006-06-01

Protein chip technology provides a new and useful tool for high-throughput screening of drugs because of its high performance and low sample consumption. In order to screen elastase inhibitors on a large scale, we designed a composite microarray integrating enzyme chip containing chemical arrays on glass slides to screen for enzymatic inhibitors. The composite microarray includes an active proteinase film, screened chemical arrays distributed on the film, and substrate microarrays to demonstrate change of color. The detection principle is that elastase hydrolyzes synthetic colorless substrates and turns them into yellow products. Because yellow is difficult to detect, bromochlorophenol blue (BPB) was added into substrate solutions to facilitate the detection process. After the enzyme had catalyzed reactions for 2 h, effects of samples on enzymatic activity could be determined by detecting color change of the spots. When chemical samples inhibited enzymatic activity, substrates were blue instead of yellow products. If the enzyme retained its activity, the yellow color of the products combined with blue of BPB to make the spots green. Chromogenic differences demonstrated whether chemicals inhibited enzymatic activity or not. In this assay, 11,680 compounds were screened, and two valuable chemical hits were identified, which demonstrates that this assay is effective, sensitive and applicable for high-throughput screening (HTS).

US screening of international travelers for radioactive contamination after the Japanese nuclear plant disaster in March 2011.

PubMed

Wilson, Todd; Chang, Arthur; Berro, Andre; Still, Aaron; Brown, Clive; Demma, Andrew; Nemhauser, Jeffrey; Martin, Colleen; Salame-Alfie, Adela; Fisher-Tyler, Frieda; Smith, Lee; Grady-Erickson, Onalee; Alvarado-Ramy, Francisco; Brunette, Gary; Ansari, Armin; McAdam, David; Marano, Nina

2012-10-01

On March 11, 2011, a magnitude 9.0 earthquake and subsequent tsunami damaged nuclear reactors at the Fukushima Daiichi complex in Japan, resulting in radionuclide release. In response, US officials augmented existing radiological screening at its ports of entry (POEs) to detect and decontaminate travelers contaminated with radioactive materials. During March 12 to 16, radiation screening protocols detected 3 travelers from Japan with external radioactive material contamination at 2 air POEs. Beginning March 23, federal officials collaborated with state and local public health and radiation control authorities to enhance screening and decontamination protocols at POEs. Approximately 543 000 (99%) travelers arriving directly from Japan at 25 US airports were screened for radiation contamination from March 17 to April 30, and no traveler was detected with contamination sufficient to require a large-scale public health response. The response highlighted synergistic collaboration across government levels and leveraged screening methods already in place at POEs, leading to rapid protocol implementation. Policy development, planning, training, and exercising response protocols and the establishment of federal authority to compel decontamination of travelers are needed for future radiological responses. Comparison of resource-intensive screening costs with the public health yield should guide policy decisions, given the historically low frequency of contaminated travelers arriving during radiological disasters.

Verification and large scale clinical evaluation of a national standard protocol for Salmonella spp./Shigella spp. screening using real-time PCR combined with guided culture.

PubMed

Tang, Xi-Jun; Yang, Ze; Chen, Xin-Bin; Tian, Wen-Fang; Tu, Cheng-Ning; Wang, Hai-Bo

2018-02-01

Salmonella spp./Shigella spp. are often associated with food poisoning and fecal-oral transmission of acute gastroenteritis that requires strict monitoring, especially among people who would handle food and water. In 2014, the National Health and Family Planning Commission of the P. R. China issued a national standard protocol (recommendatory) for the screening of Salmonella spp./Shigella spp.. However, its performance has not been fully studied. Whether it was suitable for use in our laboratory was still unknown. In the current study, the new protocol was first verified by various experiments and then its clinical performance was evaluated in about 20,000 stool samples over a three-year period. Verification results showed that the new protocol was highly specific and reproducible. Sensitivity (as defined as the lower limit of detection) of the new protocol at the PCR step was 10 3 CFU/mL and 10 1 CFU/mL for Salmonella spp. and Shigella spp., while that at the guided culture step was 10 4 CFU/mL and 10 3 CFU/mL, respectively. The large scale clinical evaluation indicated that the new protocol could increase the positivity rate by two fold and decrease the workload/median turnaround time significantly. In conclusion, the protocol was verified and evaluated and was proven to be a valuable platform for the rapid, specific, sensitive and high-throughput screening of Salmonella spp./Shigella spp. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent research progress with phospholipase C from Bacillus cereus.

PubMed

Lyu, Yan; Ye, Lidan; Xu, Jun; Yang, Xiaohong; Chen, Weiwei; Yu, Hongwei

2016-01-01

Phospholipase C (PLC) catalyzes the hydrolysis of phospholipids to produce phosphate monoesters and diacylglycerol. It has many applications in the enzymatic degumming of plant oils. PLC Bc , a bacterial PLC from Bacillus cereus, is an optimal choice for this activity in terms of its wide substrate spectrum, high activity, and approved safety. Unfortunately, its large-scale production and reliable high-throughput screening of PLC Bc remain challenging. Herein, we summarize the research progress regarding PLC Bc with emphasis on the screening methods, expression systems, catalytic mechanisms and inhibitor of PLC Bc . This review hopefully will inspire new achievements in related areas, to promote the sustainable development of PLC Bc and its application.

Microplate-Based Method for High-Throughput Screening (HTS) of Chromatographic Conditions Studies for Recombinant Protein Purification.

PubMed

Carvalho, Rimenys J; Cruz, Thayana A

2018-01-01

High-throughput screening (HTS) systems have emerged as important tools to provide fast and low cost evaluation of several conditions at once since it requires small quantities of material and sample volumes. These characteristics are extremely valuable for experiments with large number of variables enabling the application of design of experiments (DoE) strategies or simple experimental planning approaches. Once, the capacity of HTS systems to mimic chromatographic purification steps was established, several studies were performed successfully including scale down purification. Here, we propose a method for studying different purification conditions that can be used for any recombinant protein, including complex and glycosylated proteins, using low binding filter microplates.

Transmission system protection screening for integration of offshore wind power plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sajadi, A.; Strezoski, L.; Clark, K.

This paper develops an efficient methodology for protection screening of large-scale transmission systems as part of the planning studies for the integration of offshore wind power plants into the power grid. This methodology avails to determine whether any upgrades are required to the protection system. The uncertainty is considered in form of variability of the power generation by offshore wind power plant. This paper uses the integration of a 1000 MW offshore wind power plant operating in Lake Erie into the FirstEnergy/PJM service territory as a case study. This study uses a realistic model of a 63,000-bus test system thatmore » represents the U.S. Eastern Interconnection.« less

Transmission system protection screening for integration of offshore wind power plants

DOE PAGES

Sajadi, A.; Strezoski, L.; Clark, K.; ...

2018-02-21

This paper develops an efficient methodology for protection screening of large-scale transmission systems as part of the planning studies for the integration of offshore wind power plants into the power grid. This methodology avails to determine whether any upgrades are required to the protection system. The uncertainty is considered in form of variability of the power generation by offshore wind power plant. This paper uses the integration of a 1000 MW offshore wind power plant operating in Lake Erie into the FirstEnergy/PJM service territory as a case study. This study uses a realistic model of a 63,000-bus test system thatmore » represents the U.S. Eastern Interconnection.« less

An HTRF® Assay for the Protein Kinase ATM.

PubMed

Adams, Phillip; Clark, Jonathan; Hawdon, Simon; Hill, Jennifer; Plater, Andrew

2017-01-01

Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase that plays a key role in the regulation of DNA damage pathways and checkpoint arrest. In recent years, there has been growing interest in ATM as a therapeutic target due to its association with cancer cell survival following genotoxic stress such as radio- and chemotherapy. Large-scale targeted drug screening campaigns have been hampered, however, by technical issues associated with the production of sufficient quantities of purified ATM and the availability of a suitable high-throughput assay. Using a purified, functionally active recombinant ATM and one of its physiological substrates, p53, we have developed an in vitro FRET-based activity assay that is suitable for high-throughput drug screening.

Goldstone models of modified gravity

NASA Astrophysics Data System (ADS)

Brax, Philippe; Valageas, Patrick

2017-02-01

We investigate scalar-tensor theories where matter couples to the scalar field via a kinetically dependent conformal coupling. These models can be seen as the low-energy description of invariant field theories under a global Abelian symmetry. The scalar field is then identified with the Goldstone mode of the broken symmetry. It turns out that the properties of these models are very similar to the ones of ultralocal theories where the scalar-field value is directly determined by the local matter density. This leads to a complete screening of the fifth force in the Solar System and between compact objects, through the ultralocal screening mechanism. On the other hand, the fifth force can have large effects in extended structures with large-scale density gradients, such as galactic halos. Interestingly, it can either amplify or damp Newtonian gravity, depending on the model parameters. We also study the background cosmology and the linear cosmological perturbations. The background cosmology is hardly different from its Λ -CDM counterpart while cosmological perturbations crucially depend on whether the coupling function is convex or concave. For concave functions, growth is hindered by the repulsiveness of the fifth force while it is enhanced in the convex case. In both cases, the departures from the Λ -CDM cosmology increase on smaller scales and peak for galactic structures. For concave functions, the formation of structure is largely altered below some characteristic mass, as smaller structures are delayed and would form later through fragmentation, as in some warm dark matter scenarios. For convex models, small structures form more easily than in the Λ -CDM scenario. This could lead to an over-abundance of small clumps. We use a thermodynamic analysis and show that although convex models have a phase transition between homogeneous and inhomogeneous phases, on cosmological scales the system does not enter the inhomogeneous phase. On the other hand, for galactic halos, the coexistence of small and large substructures in their outer regions could lead to observational signatures of these models.

An outdoor test facility for the large-scale production of microalgae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, D.A.; Weissman, J.; Goebel, R.

The goal of the US Department of EnergySolar Energy Research Institute's Aquatic Species Program is to develop the technology base to produce liquid fuels from microalgae. This technology is being initially developed for the desert Southwest. As part of this program an outdoor test facility has been designed and constructed in Roswell, New Mexico. The site has a large existing infrastructure, a suitable climate, and abundant saline groundwater. This facility will be used to evaluate productivity of microalgae strains and conduct large-scale experiments to increase biomass productivity while decreasing production costs. Six 3-m/sup 2/ fiberglass raceways were constructed. Several microalgaemore » strains were screened for growth, one of which had a short-term productivity rate of greater than 50 g dry wt m/sup /minus/2/ d/sup /minus/1/. Two large-scale, 0.1-ha raceways have also been built. These are being used to evaluate the performance trade-offs between low-cost earthen liners and higher cost plastic liners. A series of hydraulic measurements is also being carried out to evaluate future improved pond designs. Future plans include a 0.5-ha pond, which will be built in approximately 2 years to test a scaled-up system. This unique facility will be available to other researchers and industry for studies on microalgae productivity. 6 refs., 9 figs., 1 tab.« less

An Arrayed Genome-Scale Lentiviral-Enabled Short Hairpin RNA Screen Identifies Lethal and Rescuer Gene Candidates

PubMed Central

Bhinder, Bhavneet; Antczak, Christophe; Ramirez, Christina N.; Shum, David; Liu-Sullivan, Nancy; Radu, Constantin; Frattini, Mark G.

2013-01-01

Abstract RNA interference technology is becoming an integral tool for target discovery and validation.; With perhaps the exception of only few studies published using arrayed short hairpin RNA (shRNA) libraries, most of the reports have been either against pooled siRNA or shRNA, or arrayed siRNA libraries. For this purpose, we have developed a workflow and performed an arrayed genome-scale shRNA lethality screen against the TRC1 library in HeLa cells. The resulting targets would be a valuable resource of candidates toward a better understanding of cellular homeostasis. Using a high-stringency hit nomination method encompassing criteria of at least three active hairpins per gene and filtered for potential off-target effects (OTEs), referred to as the Bhinder–Djaballah analysis method, we identified 1,252 lethal and 6 rescuer gene candidates, knockdown of which resulted in severe cell death or enhanced growth, respectively. Cross referencing individual hairpins with the TRC1 validated clone database, 239 of the 1,252 candidates were deemed independently validated with at least three validated clones. Through our systematic OTE analysis, we have identified 31 microRNAs (miRNAs) in lethal and 2 in rescuer genes; all having a seed heptamer mimic in the corresponding shRNA hairpins and likely cause of the OTE observed in our screen, perhaps unraveling a previously unknown plausible essentiality of these miRNAs in cellular viability. Taken together, we report on a methodology for performing large-scale arrayed shRNA screens, a comprehensive analysis method to nominate high-confidence hits, and a performance assessment of the TRC1 library highlighting the intracellular inefficiencies of shRNA processing in general. PMID:23198867

Intact mass detection, interpretation, and visualization to automate Top-Down proteomics on a large scale

PubMed Central

Durbin, Kenneth R.; Tran, John C.; Zamdborg, Leonid; Sweet, Steve M. M.; Catherman, Adam D.; Lee, Ji Eun; Li, Mingxi; Kellie, John F.; Kelleher, Neil L.

2011-01-01

Applying high-throughput Top-Down MS to an entire proteome requires a yet-to-be-established model for data processing. Since Top-Down is becoming possible on a large scale, we report our latest software pipeline dedicated to capturing the full value of intact protein data in automated fashion. For intact mass detection, we combine algorithms for processing MS1 data from both isotopically resolved (FT) and charge-state resolved (ion trap) LC-MS data, which are then linked to their fragment ions for database searching using ProSight. Automated determination of human keratin and tubulin isoforms is one result. Optimized for the intricacies of whole proteins, new software modules visualize proteome-scale data based on the LC retention time and intensity of intact masses and enable selective detection of PTMs to automatically screen for acetylation, phosphorylation, and methylation. Software functionality was demonstrated using comparative LC-MS data from yeast strains in addition to human cells undergoing chemical stress. We further these advances as a key aspect of realizing Top-Down MS on a proteomic scale. PMID:20848673

Health Effects of Embedded Depleted Uranium Fragments.

DTIC Science & Technology

1996-11-15

18]. The metabolic (approximately 99.8%). DU emits alpha (a), beta models required to estimate the chemical and radio- (3), and weak gamma ( y ...for the large-scale screening of patients who choosing an animal model for carcinogenesis stud- may be at increased risk of developing cancer . ies...appears warranted biomarkers for neoplastic tissues. since it is likely to provide better assurance of detecting changes that are associated with Cancer

The Development of High Temperature Thermoplastic Composite Materials for Additive Manufactured Autoclave Tooling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kunc, Vlastimil; Duty, Chad E.; Lindahl, John M.

2017-08-01

In this work, ORNL and Techmer investigated and screened different high temperature thermoplastic reinforced materials to fabricate composite molds for autoclave processes using Additive Manufacturing (AM) techniques. This project directly led to the development and commercial release of two printable, high temperature composite materials available through Techmer PM. These new materials are targeted for high temperature tooling made via large scale additive manufacturing.

APPLICATION OF CDNA MICROARRAY TECHNOLOGY TO IN VITRO TOXICOLOGY AND THE SELECTION OF GENES FOR A REAL TIME RT-PCR-BASED SCREEN FOR OXIDATIVE STRESS IN HEP-G2 CELLS

EPA Science Inventory

Large-scale analysis of gene expression using cDNA microarrays promises the
rapid detection of the mode of toxicity for drugs and other chemicals. cDNA
microarrays were used to examine chemically-induced alterations of gene
expression in HepG2 cells exposed to oxidative ...

Emory University: High-Throughput Protein-Protein Interaction Dataset for Lung Cancer-Associated Genes | Office of Cancer Genomics

Cancer.gov

To discover novel PPI signaling hubs for lung cancer, CTD2 Center at Emory utilized large-scale genomics datasets and literature to compile a set of lung cancer-associated genes. A library of expression vectors were generated for these genes and utilized for detecting pairwise PPIs with cell lysate-based TR-FRET assays in high-throughput screening format. Read the abstract.

[Fool's gold standards in language screening. Sensitivity and specificity of the Hessian child language screening test (Kindersprachscreening, KiSS)].

PubMed

Neumann, K; Holler-Zittlau, I; van Minnen, S; Sick, U; Zaretsky, Y; Euler, H A

2011-01-01

The German Kindersprachscreening (KiSS) is a universal speech and language screening test for large-scale identification of Hessian kindergarten children requiring special educational language training or clinical speech/language therapy. To calculate the procedural screening validity, 257 children (aged 4.0 to 4.5 years) were tested using KiSS and four language tests (Reynell Development Language Scales III, Patholinguistische Diagnostik, PLAKSS, AWST-R). The majority or consensus judgements of three speech-language professionals, based on the language test results, served as a reference criterion. The base (fail) rates of the professionals were either self-determined or preset based on known prevalence rates. Screening validity was higher for preset than for self-determined base rates due to higher inter-judge agreement. The confusion matrices of the overall index classification of the KiSS (speech-language abnormalities with educational or clinical needs) with the fixed base rate expert judgement about language impairment, including fluency or voice disorders, yielded a sensitivity of 88% and a specificity of 78%, for just language impairment 84% and 75%, respectively. Specificities for disorders requiring clinical diagnostics in the KiSS (language impairment alone or combined with fluency/voice disorders) related to the test-based consensus expert judgment was about 93%. Sensitivities were unsatisfactory because the differentiation between educational and clinical needs requires improvement. Since the judgement concordances between the speech-language professionals was only moderate, the development of a comprehensive German reference test for speech and language disorders with evidence-based algorithmic decision rules rather than subjective clinical judgement is advocated.

Clinical Costs of Colorectal Cancer Screening in 5 Federally Funded Demonstration Programs

PubMed Central

Tangka, Florence K. L.; Subramanian, Sujha; Beebe, Maggie C.; Hoover, Sonja; Royalty, Janet; Seeff, Laura C.

2016-01-01

BACKGROUND The Centers for Disease Control and Prevention initiated the Colorectal Cancer Screening Demonstration Program (CRCSDP) to explore the feasibility of establishing a large-scale colorectal cancer (CRC) screening program for underserved populations in the United States. The authors of this report assessed the clinical costs incurred at each of the 5 participating sites during the demonstration period. METHODS By using data on payments to providers by each of the 5 CRCSDP sites, the authors estimated costs for specific clinical services and overall clinical costs for each of the 2 CRC screening methods used by the sites: colonoscopy and fecal occult blood test (FOBT). RESULTS Among CRCSDP clients who were at average risk for CRC and for whom complete cost data were available, 2131 were screened by FOBT, and 1888 were screened by colonoscopy. The total average clinical cost per individual screened by FOBT (including costs for screening, diagnosis, initial surveillance, office visits, and associated clinical services averaged across all individuals who received screening FOBT) ranged from $48 in Nebraska to $149 in Greater Seattle. This compared with an average clinical cost per individual for all services related to the colonoscopy screening ranging from $654 in St. Louis to $1600 in Baltimore City. CONCLUSIONS Variations in how sites contracted with providers and in the services provided through CRCSDP affected the cost of clinical services and the complexity of collecting cost data. Health officials may find these data useful in program planning and budgeting. PMID:23868481

Identifiability in N-mixture models: a large-scale screening test with bird data.

PubMed

Kéry, Marc

2018-02-01

Binomial N-mixture models have proven very useful in ecology, conservation, and monitoring: they allow estimation and modeling of abundance separately from detection probability using simple counts. Recently, doubts about parameter identifiability have been voiced. I conducted a large-scale screening test with 137 bird data sets from 2,037 sites. I found virtually no identifiability problems for Poisson and zero-inflated Poisson (ZIP) binomial N-mixture models, but negative-binomial (NB) models had problems in 25% of all data sets. The corresponding multinomial N-mixture models had no problems. Parameter estimates under Poisson and ZIP binomial and multinomial N-mixture models were extremely similar. Identifiability problems became a little more frequent with smaller sample sizes (267 and 50 sites), but were unaffected by whether the models did or did not include covariates. Hence, binomial N-mixture model parameters with Poisson and ZIP mixtures typically appeared identifiable. In contrast, NB mixtures were often unidentifiable, which is worrying since these were often selected by Akaike's information criterion. Identifiability of binomial N-mixture models should always be checked. If problems are found, simpler models, integrated models that combine different observation models or the use of external information via informative priors or penalized likelihoods, may help. © 2017 by the Ecological Society of America.

Riding on irrelevant operators

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Rham, Claudia; Ribeiro, Raquel H., E-mail: Claudia.deRham@case.edu, E-mail: RaquelHRibeiro@case.edu

2014-11-01

We investigate the stability of a class of derivative theories known as P(X) and Galileons against corrections generated by quantum effects. We use an exact renormalisation group approach to argue that these theories are stable under quantum corrections at all loops in regions where the kinetic term is large compared to the strong coupling scale. This is the regime of interest for screening or Vainshtein mechanisms, and in inflationary models that rely on large kinetic terms. Next, we clarify the role played by the symmetries. While symmetries protect the form of the quantum corrections, theories equipped with more symmetries domore » not necessarily have a broader range of scales for which they are valid. We show this by deriving explicitly the regime of validity of the classical solutions for P(X) theories including Dirac-Born-Infeld (DBI) models, both in generic and for specific background field configurations. Indeed, we find that despite the existence of an additional symmetry, the DBI effective field theory has a regime of validity similar to an arbitrary P(X) theory. We explore the implications of our results for both early and late universe contexts. Conversely, when applied to static and spherical screening mechanisms, we deduce that the regime of validity of typical power-law P(X) theories is much larger than that of DBI.« less

Fast selection of miRNA candidates based on large-scale pre-computed MFE sets of randomized sequences

PubMed Central

2014-01-01

Background Small RNAs are important regulators of genome function, yet their prediction in genomes is still a major computational challenge. Statistical analyses of pre-miRNA sequences indicated that their 2D structure tends to have a minimal free energy (MFE) significantly lower than MFE values of equivalently randomized sequences with the same nucleotide composition, in contrast to other classes of non-coding RNA. The computation of many MFEs is, however, too intensive to allow for genome-wide screenings. Results Using a local grid infrastructure, MFE distributions of random sequences were pre-calculated on a large scale. These distributions follow a normal distribution and can be used to determine the MFE distribution for any given sequence composition by interpolation. It allows on-the-fly calculation of the normal distribution for any candidate sequence composition. Conclusion The speedup achieved makes genome-wide screening with this characteristic of a pre-miRNA sequence practical. Although this particular property alone will not be able to distinguish miRNAs from other sequences sufficiently discriminative, the MFE-based P-value should be added to the parameters of choice to be included in the selection of potential miRNA candidates for experimental verification. PMID:24418292

Evaluation of a Public-sector, Provider-initiated Cryptococcal Antigen Screening and Treatment Program, Western Cape, South Africa

PubMed Central

Smith, Mariette; Smith, Rachel; Osler, Meg; Kelly, Nicola; Cross, Anna; Boulle, Andrew; Meintjes, Graeme; Govender, Nelesh P.

2016-01-01

Background Screening for serum cryptococcal antigen (CrAg) may identify those at risk for disseminated cryptococcal disease (DCD), and pre-emptive fluconazole treatment may prevent progression to DCD. In August 2012, the Western Cape Province (WC), South Africa, adopted provider-initiated CrAg screening. We evaluated the implementation and effectiveness of this large-scale public-sector program during its first year, September 1, 2012—August 31, 2013. Methods We used data from the South African National Health Laboratory Service, WC provincial HIV program, and nationwide surveillance data for DCD. We assessed the proportion of eligible patients screened for CrAg (CrAg test done within 30 days of CD4 date) and the prevalence of CrAg positivity. Incidence of DCD among those screened was compared with those not screened. Results Of 4,395 eligible patients, 26.6% (n=1170) were screened. The proportion of patients screened increased from 15.9% in September 2012 to 36.6% in August 2013. The prevalence of positive serum CrAg was 2.1%. Treatment data were available for 13 of 24 CrAg-positive patients; nine of 13 were treated with fluconazole. Nine (0.8%) incident cases of DCD occurred among the 1170 patients who were screened for CrAg vs. 49 (1.5%) incident cases among the 3225 patients not screened (p=0.07). Conclusions Relatively few eligible patients were screened under the WC provider-initiated CrAg screening program. Unscreened patients were nearly twice as likely to develop DCD. CrAg screening can reduce the burden of DCD, but needs to be implemented well. To improve screening rates, countries should consider laboratory-based reflexive screening when possible. PMID:26926942

Hybrid multiphoton volumetric functional imaging of large-scale bioengineered neuronal networks

NASA Astrophysics Data System (ADS)

Dana, Hod; Marom, Anat; Paluch, Shir; Dvorkin, Roman; Brosh, Inbar; Shoham, Shy

2014-06-01

Planar neural networks and interfaces serve as versatile in vitro models of central nervous system physiology, but adaptations of related methods to three dimensions (3D) have met with limited success. Here, we demonstrate for the first time volumetric functional imaging in a bioengineered neural tissue growing in a transparent hydrogel with cortical cellular and synaptic densities, by introducing complementary new developments in nonlinear microscopy and neural tissue engineering. Our system uses a novel hybrid multiphoton microscope design combining a 3D scanning-line temporal-focusing subsystem and a conventional laser-scanning multiphoton microscope to provide functional and structural volumetric imaging capabilities: dense microscopic 3D sampling at tens of volumes per second of structures with mm-scale dimensions containing a network of over 1,000 developing cells with complex spontaneous activity patterns. These developments open new opportunities for large-scale neuronal interfacing and for applications of 3D engineered networks ranging from basic neuroscience to the screening of neuroactive substances.

Assessment of the uncertainty and predictive power of large-scale predictors for nonlinear precipitation downscaling in the European Arctic (Invited)

NASA Astrophysics Data System (ADS)

Sauter, T.

2013-12-01

Despite the extensive research on downscaling methods there is still little consensus about the choice of useful atmospheric predictor variables. Besides the general decision of a proper statistical downscaling model, the selection of an informative predictor set is crucial for the accuracy and stability of the resulting downscaled time series. These requirements must be fullfilled by both the atmospheric variables and the predictor domains in terms of geographical location and spatial extend, to which in general not much attention is paid. However, only a limited number of studies is interested in the predictive capability of the predictor domain size or shape, and the question to what extent variability of neighboring grid points influence local-scale events. In this study we emphasized the spatial relationships between observed daily precipitation and selected number of atmospheric variables for the European Arctic. Several nonlinear regression models are used to link the large-scale predictors obtained from reanalysed Weather Research and Forecast model runs to the local-scale observed precipitation. Inferences on the sources of uncertainty are then drawn from variance based sensitivity measures, which also permit to capture interaction effects between individual predictors. The information is further used to develop more parsimonious downscaling models with only small decreases in accuracy. Individual predictors (without interactions) account for almost 2/3 of the total output variance, while the remaining fraction is solely due to interactions. Neglecting predictor interactions in the screening process will lead to some loss of information. Hence, linear screening methods are insufficient as they neither account for interactions nor for non-additivity as given by many nonlinear prediction algorithms.

A powerful nonparametric method for detecting differentially co-expressed genes: distance correlation screening and edge-count test.

PubMed

Zhang, Qingyang

2018-05-16

Differential co-expression analysis, as a complement of differential expression analysis, offers significant insights into the changes in molecular mechanism of different phenotypes. A prevailing approach to detecting differentially co-expressed genes is to compare Pearson's correlation coefficients in two phenotypes. However, due to the limitations of Pearson's correlation measure, this approach lacks the power to detect nonlinear changes in gene co-expression which is common in gene regulatory networks. In this work, a new nonparametric procedure is proposed to search differentially co-expressed gene pairs in different phenotypes from large-scale data. Our computational pipeline consisted of two main steps, a screening step and a testing step. The screening step is to reduce the search space by filtering out all the independent gene pairs using distance correlation measure. In the testing step, we compare the gene co-expression patterns in different phenotypes by a recently developed edge-count test. Both steps are distribution-free and targeting nonlinear relations. We illustrate the promise of the new approach by analyzing the Cancer Genome Atlas data and the METABRIC data for breast cancer subtypes. Compared with some existing methods, the new method is more powerful in detecting nonlinear type of differential co-expressions. The distance correlation screening can greatly improve computational efficiency, facilitating its application to large data sets.

Data-driven process decomposition and robust online distributed modelling for large-scale processes

NASA Astrophysics Data System (ADS)

Shu, Zhang; Lijuan, Li; Lijuan, Yao; Shipin, Yang; Tao, Zou

2018-02-01

With the increasing attention of networked control, system decomposition and distributed models show significant importance in the implementation of model-based control strategy. In this paper, a data-driven system decomposition and online distributed subsystem modelling algorithm was proposed for large-scale chemical processes. The key controlled variables are first partitioned by affinity propagation clustering algorithm into several clusters. Each cluster can be regarded as a subsystem. Then the inputs of each subsystem are selected by offline canonical correlation analysis between all process variables and its controlled variables. Process decomposition is then realised after the screening of input and output variables. When the system decomposition is finished, the online subsystem modelling can be carried out by recursively block-wise renewing the samples. The proposed algorithm was applied in the Tennessee Eastman process and the validity was verified.

[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].

PubMed

Uesawa, Yoshihiro

2018-01-01

　Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

Validation of the Arab Youth Mental Health scale as a screening tool for depression/anxiety in Lebanese children

PubMed Central

2011-01-01

Background Early detection of common mental disorders, such as depression and anxiety, among children and adolescents requires the use of validated, culturally sensitive, and developmentally appropriate screening instruments. The Arab region has a high proportion of youth, yet Arabic-language screening instruments for mental disorders among this age group are virtually absent. Methods We carried out construct and clinical validation on the recently-developed Arab Youth Mental Health (AYMH) scale as a screening tool for depression/anxiety. The scale was administered with 10-14 year old children attending a social service center in Beirut, Lebanon (N = 153). The clinical assessment was conducted by a child and adolescent clinical psychiatrist employing the DSM IV criteria. We tested the scale's sensitivity, specificity, and internal consistency. Results Scale scores were generally significantly associated with how participants responded to standard questions on health, mental health, and happiness, indicating good construct validity. The results revealed that the scale exhibited good internal consistency (Cronbach's alpha = 0.86) and specificity (79%). However, it exhibited moderate sensitivity for girls (71%) and poor sensitivity for boys (50%). Conclusions The AYMH scale is useful as a screening tool for general mental health states and a valid screening instrument for common mental disorders among girls. It is not a valid instrument for detecting depression and anxiety among boys in an Arab culture. PMID:21435213

The Strengths and Difficulties Self-Report Questionnaire as a screening instrument in Norwegian community samples.

PubMed

Rønning, John A; Handegaard, Bjørn Helge; Sourander, Andre; Mørch, Willy-Tore

2004-04-01

This study reports on the application of the Norwegian self-report version of the Strengths and Difficulties Questionnaire (SDQ-S). The application of the SDQ-S was not motivated by a wish to reveal the prevalence of psychiatric disorders, but rather to set the stage for routine screening as part of schools' efforts to inform themselves about the life of adolescents at school. The survey included 4167 young people aged 11 to 16 years, attending 66 primary and secondary schools in Northern Norway. The respondents comprised 80.2% of the total population in these grades in the target area. Structural analysis of the instrument, including confirmatory factor analysis, internal consistency and intra- and cross-scale correlations revealed somewhat variable psychometric properties. Model modification suggested several ways of improving the structural psychometric properties of the SDQ-S. Norwegian cut-off points were similar to those found in other Scandinavian studies. About one third of the subjects reported at least minor perceived difficulties, while about 5% reported definite or severe difficulties. These difficulties were strongly associated with all symptom scales. Girls reported a significantly higher level of emotional problems and better prosocial functioning. Boys reported significantly higher scores on the externalising scales and on peer problems. The SDQ-S may be judged as an efficient and economical screening instrument for preventive research on large community samples. However, efforts should be made to improve its psychometric structure.

Screening for trauma‐related symptoms via a smartphone app: The validity of Smart Assessment on your Mobile in referred police officers

PubMed Central

Bakker, Anne; Schrieken, Bart A.L.; Hoofwijk, Marthe C.; Olff, Miranda

2017-01-01

Abstract To facilitate easily accessible screening for trauma‐related symptoms, a web‐based application called Smart Assessment on your Mobile (SAM) was developed. In this study, we examined whether SAM was able to accurately identify posttraumatic stress disorder (PTSD) and depression in adults. Eighty‐nine referred police officers completed SAM, containing the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM)‐5 (PCL‐5) and the Depression Anxiety and Stress Scale (DASS‐21), on their own device prior to a diagnostic interview where the Clinician‐Administered PTSD Scale for DSM‐5 (CAPS‐5) and Structured Clinical Interview for DSM‐IV (SCID‐I/P) were administered. Results showed a substantial agreement between SAM and the diagnostic interview in the assessment of PTSD and depression. An optimal trade‐off between sensitivity (89%) and specificity (68%) levels was found at a cut‐off score of 31 on the PTSD Checklist for DSM‐5 (area under the curve = 0.845, 95% CI [0.765, 0.925], diagnostic odds ratio = 15.97). This is one of the first studies to support the validity and reliability of a mobile screener following trauma. SAM may facilitate screening for trauma‐related symptoms on a large scale and could be a first step in a stepped‐care model for trauma survivors to help identify individuals who need further diagnostics and care. PMID:28948699

Structural Validity of the MACI Psychopathy and Narcissism Scales: Evidence of Multidimensionality and Implications for Use in Research and Screening

ERIC Educational Resources Information Center

Penney, Stephanie R.; Moretti, Marlene M.; Da Silva, Kimberley S.

2008-01-01

This study investigated the psychometric properties and predictive validity of three self-report scales (the Psychopathy Content Scale, the Psychopathy-16 scale, and the Egotistic scale) derived from the Millon Adolescent Clinical Inventory (MACI) to screen for the presence of psychopathic and narcissistic personality characteristics. Exploratory…

OMERO and Bio-Formats 5: flexible access to large bioimaging datasets at scale

NASA Astrophysics Data System (ADS)

Moore, Josh; Linkert, Melissa; Blackburn, Colin; Carroll, Mark; Ferguson, Richard K.; Flynn, Helen; Gillen, Kenneth; Leigh, Roger; Li, Simon; Lindner, Dominik; Moore, William J.; Patterson, Andrew J.; Pindelski, Blazej; Ramalingam, Balaji; Rozbicki, Emil; Tarkowska, Aleksandra; Walczysko, Petr; Allan, Chris; Burel, Jean-Marie; Swedlow, Jason

2015-03-01

The Open Microscopy Environment (OME) has built and released Bio-Formats, a Java-based proprietary file format conversion tool and OMERO, an enterprise data management platform under open source licenses. In this report, we describe new versions of Bio-Formats and OMERO that are specifically designed to support large, multi-gigabyte or terabyte scale datasets that are routinely collected across most domains of biological and biomedical research. Bio- Formats reads image data directly from native proprietary formats, bypassing the need for conversion into a standard format. It implements the concept of a file set, a container that defines the contents of multi-dimensional data comprised of many files. OMERO uses Bio-Formats to read files natively, and provides a flexible access mechanism that supports several different storage and access strategies. These new capabilities of OMERO and Bio-Formats make them especially useful for use in imaging applications like digital pathology, high content screening and light sheet microscopy that create routinely large datasets that must be managed and analyzed.

Flow-induced resonance of screen-covered cavities

NASA Technical Reports Server (NTRS)

Soderman, Paul T.

1990-01-01

An experimental study of screen-covered cavities exposed to airflow tangent to the screen is described. The term screen refers to a thin metal plate perforated with a repetitive pattern of round holes. The purpose was to find the detailed aerodynamic and acoustic mechanisms responsible for screen-covered cavity resonance and to find ways to control the pressure oscillations. Results indicate that strong cavity acoustic resonances are created by screen orifices that shed vortices which couple resonance by choosing hole spacings such that shed vortices do not arrive at a downstream orifice in synchronization with cavity pressure oscillations. The proper hole pattern is effective at all airspeeds. It was also discovered that a reduction of orifice size tended to weaken the screen/cavity interaction regardless of hole pattern, probably because of viscous flow losses at the orifices. The screened cavities that resonated did so at much higher frequencies than the equivalent open cavity. The classical large eddy phenomenon occurs at the relatively small scale of the orifices (the excitation is typically of high frequency). The wind tunnel study was made at airspeeds from 0 to 100m/sec. The 457-mm-long by 1.09-m-high rectangular cavities had length-to-depth ratios greater than one, which is indicative of shallow cavities. The cavity screens were perforated in straight rows and columns with hole diameters ranging from 1.59 to 6.35 mm and with porosities from 2.6 to 19.6 percent.

Revisiting the impact of mobile phone screen size on user comprehension of health information.

PubMed

Alghamdi, Ebtisam; Yunus, Faisel; Househ, Mowafa

2014-01-01

Abstract goes here. This is completion of the research and update of the previous work that was published in 2013[1]. The paper describes our recent experimental study of the impact of mobile screen size on the user comprehension of health information and application structures. An experiment was conducted to measure the impact of screen size on user comprehension and retention. Participants were given the same simple scenario, which consisted of searching from different menus, navigating and reading some contents. They were timed and tracked for correctness. Also, a follow-up survey was given to each participant that consisted of a rating scale to assess usability features, comprehension and retention abilities of the participants based on different mobile screen sizes. Results showed that there was a significant difference between mobile phone screen size and the time taken to read the contents, which was at its highest on small screens (p-value=0.02). Also, reading characters was hardest on a small screen (p-value=0.003). In addition, there was a significant difference between the three screen sizes regarding the organization of the application's information, showing that the smaller the screen size, the more organized the information. On the other hand, there was no significant impact of screen size on user comprehension, retention scores, number of errors or effective task completion but it was generally better if a large screen size was used. This study concludes that the screen size is not the main concern in comprehension of the contents or application structure. However, reading speed improves with the larger screen size and positively influences the task completion and understanding of the application elements.

Internet-Assisted Parent Training Intervention for Disruptive Behavior in 4-Year-Old Children: A Randomized Clinical Trial.

PubMed

Sourander, Andre; McGrath, Patrick J; Ristkari, Terja; Cunningham, Charles; Huttunen, Jukka; Lingley-Pottie, Patricia; Hinkka-Yli-Salomäki, Susanna; Kinnunen, Malin; Vuorio, Jenni; Sinokki, Atte; Fossum, Sturla; Unruh, Anita

2016-04-01

There is a large gap worldwide in the provision of evidence-based early treatment of children with disruptive behavioral problems. To determine whether an Internet-assisted intervention using whole-population screening that targets the most symptomatic 4-year-old children is effective at 6 and 12 months after the start of treatment. This 2-parallel-group randomized clinical trial was performed from October 1, 2011, through November 30, 2013, at a primary health care clinic in Southwest Finland. Data analysis was performed from August 6, 2015, to December 11, 2015. Of a screened population of 4656 children, 730 met the screening criteria indicating a high level of disruptive behavioral problems. A total of 464 parents of 4-year-old children were randomized into the Strongest Families Smart Website (SFSW) intervention group (n = 232) or an education control (EC) group (n = 232). The SFSW intervention, an 11-session Internet-assisted parent training program that included weekly telephone coaching. Child Behavior Checklist version for preschool children (CBCL/1.5-5) externalizing scale (primary outcome), other CBCL/1.5-5 scales and subscores, Parenting Scale, Inventory of Callous-Unemotional Traits, and the 21-item Depression, Anxiety, and Stress Scale. All data were analyzed by intention to treat and per protocol. The assessments were made before randomization and 6 and 12 months after randomization. Of the children randomized, 287 (61.9%) were male and 79 (17.1%) lived in other than a family with 2 biological parents. At 12-month follow-up, improvement in the SFSW intervention group was significantly greater compared with the control group on the following measures: CBCL/1.5-5 externalizing scale (effect size, 0.34; P < .001), internalizing scale (effect size, 0.35; P < .001), and total scores (effect size, 0.37; P < .001); 5 of 7 syndrome scales, including aggression (effect size, 0.36; P < .001), sleep (effect size, 0.24; P = .002), withdrawal (effect size, 0.25; P = .005), anxiety (effect size, 0.26; P = .003), and emotional problems (effect size, 0.31; P = .001); Inventory of Callous-Unemotional Traits callousness scores (effect size, 0.19; P = .03); and self-reported parenting skills (effect size, 0.53; P < .001). The study reveals the effectiveness and feasibility of an Internet-assisted parent training intervention offered for parents of preschool children with disruptive behavioral problems screened from the whole population. The strategy of population-based screening of children at an early age to offering parent training using digital technology and telephone coaching is a promising public health strategy for providing early intervention for a variety of child mental health problems. clinicaltrials.gov Identifier: NCT01750996.

The micro-environmental impact of volatile organic compound emissions from large-scale assemblies of people in a confined space

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dutta, Tanushree

Large-scale assemblies of people in a confined space can exert significant impacts on the local air chemistry due to human emissions of volatile organics. Variations of air-quality in such small scale can be studied by quantifying fingerprint volatile organic compounds (VOCs) such as acetone, toluene, and isoprene produced during concerts, movie screenings, and sport events (like the Olympics and the World Cup). This review summarizes the extent of VOC accumulation resulting from a large population in a confined area or in a small open area during sporting and other recreational activities. Apart from VOCs emitted directly from human bodies (e.g.,more » perspiration and exhaled breath), those released indirectly from other related sources (e.g., smoking, waste disposal, discharge of food-waste, and use of personal-care products) are also discussed. Although direct and indirect emissions of VOCs from human may constitute <1% of the global atmospheric VOCs budget, unique spatiotemporal variations in VOCs species within a confined space can have unforeseen impacts on the local atmosphere to lead to acute human exposure to harmful pollutants.« less

Visual analysis of inter-process communication for large-scale parallel computing.

PubMed

Muelder, Chris; Gygi, Francois; Ma, Kwan-Liu

2009-01-01

In serial computation, program profiling is often helpful for optimization of key sections of code. When moving to parallel computation, not only does the code execution need to be considered but also communication between the different processes which can induce delays that are detrimental to performance. As the number of processes increases, so does the impact of the communication delays on performance. For large-scale parallel applications, it is critical to understand how the communication impacts performance in order to make the code more efficient. There are several tools available for visualizing program execution and communications on parallel systems. These tools generally provide either views which statistically summarize the entire program execution or process-centric views. However, process-centric visualizations do not scale well as the number of processes gets very large. In particular, the most common representation of parallel processes is a Gantt char t with a row for each process. As the number of processes increases, these charts can become difficult to work with and can even exceed screen resolution. We propose a new visualization approach that affords more scalability and then demonstrate it on systems running with up to 16,384 processes.

Screening mosaic F1 females for mutations affecting zebrafish heart induction and patterning.

PubMed

Alexander, J; Stainier, D Y; Yelon, D

1998-01-01

The genetic pathways underlying the induction and anterior-posterior patterning of the heart are poorly understood. The recent emergence of the zebrafish model system now allows a classical genetic approach to such challenging problems in vertebrate development. Two large-scale screens for mutations affecting zebrafish embryonic development have recently been completed; among the hundreds of mutations identified were several that affect specific aspects of cardiac morphogenesis, differentiation, and function. However, very few mutations affecting induction and/or anterior-posterior patterning of the heart were identified. We hypothesize that a directed approach utilizing molecular markers to examine these particular steps of heart development will uncover additional such mutations. To test this hypothesis, we are conducting two parallel screens for mutations that affect either the induction or the anterior-posterior patterning of the zebrafish heart. As an indicator of cardiac induction, we examine expression of nkx2.5, the earliest known marker of precardiac mesoderm; to assess anterior-posterior patterning, we distinguish ventricle from atrium with antibodies that recognize different myosin heavy chain isoforms. In order to expedite the examination of a large number of mutations, we are screening the haploid progeny of mosaic F1 females. In these ongoing screens, we have identified four mutations that affect nkx2.5 expression as well as 21 that disrupt either ventricular or atrial development and thus far have recovered several of these mutations, demonstrating the value of our approach. Future analysis of these and other cardiac mutations will provide further insight into the processes of induction and anterior-posterior patterning of the heart.

Novel Acoustic Loading of a Mass Spectrometer: Toward Next-Generation High-Throughput MS Screening.

PubMed

Sinclair, Ian; Stearns, Rick; Pringle, Steven; Wingfield, Jonathan; Datwani, Sammy; Hall, Eric; Ghislain, Luke; Majlof, Lars; Bachman, Martin

2016-02-01

High-throughput, direct measurement of substrate-to-product conversion by label-free detection, without the need for engineered substrates or secondary assays, could be considered the "holy grail" of drug discovery screening. Mass spectrometry (MS) has the potential to be part of this ultimate screening solution, but is constrained by the limitations of existing MS sample introduction modes that cannot meet the throughput requirements of high-throughput screening (HTS). Here we report data from a prototype system (Echo-MS) that uses acoustic droplet ejection (ADE) to transfer femtoliter-scale droplets in a rapid, precise, and accurate fashion directly into the MS. The acoustic source can load samples into the MS from a microtiter plate at a rate of up to three samples per second. The resulting MS signal displays a very sharp attack profile and ions are detected within 50 ms of activation of the acoustic transducer. Additionally, we show that the system is capable of generating multiply charged ion species from simple peptides and large proteins. The combination of high speed and low sample volume has significant potential within not only drug discovery, but also other areas of the industry. © 2015 Society for Laboratory Automation and Screening.

Vainshtein screening in scalar-tensor theories before and after GW170817: Constraints on theories beyond Horndeski

NASA Astrophysics Data System (ADS)

Dima, Alexandru; Vernizzi, Filippo

2018-05-01

Screening mechanisms are essential features of dark energy models mediating a fifth force on large scales. We study the regime of strong scalar field nonlinearities, known as Vainshtein screening, in the most general scalar-tensor theories propagating a single scalar degree of freedom. We first develop an effective approach to parametrize cosmological perturbations beyond linear order for these theories. In the quasistatic limit, the fully nonlinear effective Lagrangian contains six independent terms, one of which starts at cubic order in perturbations. We compute the two gravitational potentials around a spherical body. Outside and near the body, screening reproduces standard gravity, with a modified gravitational coupling. Inside the body, the two potentials are different and depend on the density profile, signalling the breaking of the Vainshtein screening. We provide the most general expressions for these modifications, revising and extending previous results. We apply our findings to show that the combination of the GW170817 event, the Hulse-Taylor pulsar and stellar structure physics, constrain the parameters of these general theories at the level of 10-1, and of Gleyzes-Langlois-Piazza-Vernizzi theories at the level of 10-2.

Binding-Site Assessment by Virtual Fragment Screening

PubMed Central

Huang, Niu; Jacobson, Matthew P.

2010-01-01

The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules) would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock ∼11000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors. PMID:20404926

Development of cultural belief scales for mammography screening.

PubMed

Russell, Kathleen M; Champion, Victoria L; Perkins, Susan M

2003-01-01

To develop instruments to measure culturally related variables that may influence mammography screening behaviors in African American women. Instrumentation methodology. Community organizations and public housing in the Indianapolis, IN, area. 111 African American women with a mean age of 60.2 years and 64 Caucasian women with a mean age of 60 years. After item development, scales were administered. Data were analyzed by factor analysis, item analysis via internal consistency reliability using Cronbach's alpha, and independent t tests and logistic regression analysis to test theoretical relationships. Personal space preferences, health temporal orientation, and perceived personal control. Space items were factored into interpersonal and physical scales. Temporal orientation items were loaded on one factor, creating a one-dimensional scale. Control items were factored into internal and external control scales. Cronbach's alpha coefficients for the scales ranged from 0.76-0.88. Interpersonal space preference, health temporal orientation, and perceived internal control scales each were predictive of mammography screening adherence. The three tested scales were reliable and valid. Scales, on average, did not differ between African American and Caucasian populations. These scales may be useful in future investigations aimed at increasing mammography screening in African American and Caucasian women.

Flap noise measurements for STOL configurations using external upper surface blowing

NASA Technical Reports Server (NTRS)

Dorsch, R. G.; Reshotko, M.; Olsen, W. A.

1972-01-01

Screening tests of upper surface blowing on externally blown flaps configurations were conducted. Noise and turning effectiveness data were obtained with small-scale, engine-over-the-wing models. One large model was tested to determine scale effects. Nozzle types included circular, slot, D-shaped, and multilobed. Tests were made with and without flow attachment devices. For STOL applications the particular multilobed mixer and the D-shaped nozzles tested were found to offer little or no noise advantage over the round convergent nozzle. High aspect ratio slot nozzles provided the quietest configurations. In general, upper surface blowing was quieter than lower surface blowing for equivalent EBF models.

United States Department of Agriculture-Agricultural Research Service research programs in biological control of plant diseases.

PubMed

Roberts, Daniel P; Lohrke, Scott M

2003-01-01

A number of USDA-ARS programs directed at overcoming impediments to the use of biocontrol agents on a commercial scale are described. These include improvements in screening techniques, taxonomic studies to identify beneficial strains more precisely, and studies on various aspects of the large-scale production of biocontrol agents. Another broad area of studies covers the ecological aspects of biocontrol agents-their interaction with the pathogen, with the plant and with other aspects of the environmental complex. Examples of these studies are given and their relevance to the further development and expansion of biocontrol agents is discussed.

Engineering of Paraoxonases for Pre- and Post-treatment of Intoxication by a Broad Spectrum of Nerve Agents and Pesticides

DTIC Science & Technology

2014-08-01

chemical warfare nerve agents (CWNA). Enzymes identified in these screens should be capable of catalytically neutralizing the target agent under...soluble form. 4. Large-scale production of selected enzyme candidates, and their kinetic, structural and pharmacological evaluation 6...employed, with an enzyme protein concentration of 0.5-2 mM in the assay cuvette, the activity measured was indistinguishable from the rate of

Lower Limb Function in Elderly Korean Adults Is Related to Cognitive Function.

PubMed

Kim, A-Sol; Ko, Hae-Jin

2018-05-01

Patients with cognitive impairment have decreased lower limb function. Therefore, we aimed to investigate the relationship between lower limb function and cognitive disorders to determine whether lower limb function can be screened to identify cognitive decline. Using Korean National Health Insurance Service-National Sample Cohort database data, we assessed the cognitive and lower limb functioning of 66-year-olds who underwent national health screening between 2010 and 2014. Cognitive function was assessed via a questionnaire. Timed Up-and-Go (TUG) and one-leg-standing (OLS) tests were performed to evaluate lower limb function. Associations between cognitive and lower limb functions were analyzed, and optimal cut-off points for these tests to screen for cognitive decline, were determined. Cognitive function was significantly correlated with TUG interval ( r = 0.414, p < 0.001) and OLS duration ( r = −0.237, p < 0.001). Optimal cut-off points for screening cognitive disorders were >11 s and ≤12 s for TUG interval and OLS duration, respectively. Among 66-year-olds who underwent national health screening, a significant correlation between lower limb and cognitive function was demonstrated. The TUG and OLS tests are useful screening tools for cognitive disorders in elderly patients. A large-scale prospective cohort study should be conducted to investigate the causal relationship between cognitive and lower limb function.

Using Rasch Rating Scale Methodology to Examine a Behavioral Screener for Preschoolers at Risk

ERIC Educational Resources Information Center

DiStefano, Christine; Greer, Fred W.; Kamphaus, R. W.; Brown, William H.

2014-01-01

A screening instrument used to identify young children at risk for behavioral and emotional difficulties, the Behavioral and Emotional Screening System Teacher Rating Scale-Preschool was examined. The Rasch Rating Scale Method was used to provide additional information about psychometric properties of items, respondents, and the response scale.…

XRIndex: a brief screening tool for individual differences in security threat detection in x-ray images

PubMed Central

Rusconi, Elena; Ferri, Francesca; Viding, Essi; Mitchener-Nissen, Timothy

2015-01-01

X-ray imaging is a cost-effective technique at security checkpoints that typically require the presence of human operators. We have previously shown that self-reported attention to detail can predict threat detection performance with small-vehicle x-ray images (Rusconi et al., 2012). Here, we provide evidence for the generality of such a link by having a large sample of naïve participants screen more typical dual-energy x-ray images of hand luggage. The results show that the Attention to Detail score from the autism-spectrum quotient (AQ) questionnaire (Baron-Cohen et al., 2001) is a linear predictor of threat detection accuracy. We then develop and fine-tune a novel self-report scale for security screening: the XRIndex, which improves on the Attention to Detail scale for predictive power and opacity to interpretation. The XRIndex is not redundant with any of the Big Five personality traits. We validate the XRIndex against security x-ray images with an independent sample of untrained participants and suggest that the XRIndex may be a useful aid for the identification of suitable candidates for professional security training with a focus on x-ray threat detection. Further studies are needed to determine whether this can also apply to trained professionals. PMID:26321935

Large-scale identification of chemically induced mutations in Drosophila melanogaster

PubMed Central

Haelterman, Nele A.; Jiang, Lichun; Li, Yumei; Bayat, Vafa; Sandoval, Hector; Ugur, Berrak; Tan, Kai Li; Zhang, Ke; Bei, Danqing; Xiong, Bo; Charng, Wu-Lin; Busby, Theodore; Jawaid, Adeel; David, Gabriela; Jaiswal, Manish; Venken, Koen J.T.; Yamamoto, Shinya

2014-01-01

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of ∼3500 to 35 single-nucleotide variants per chromosome. By combining WGS with a rough mapping method based on large duplications, we were able to map 274 (∼70%) mutations. We show that these mutations are causative, using small 80-kb duplications that rescue lethality. Hence, our findings demonstrate that combining rough mapping with WGS dramatically expands the toolkit necessary for assigning function to genes. PMID:25258387

Disordered gambling and co-morbidity of psychiatric disorders among college students: an examination of problem drinking, anxiety and depression.

PubMed

Martin, Ryan J; Usdan, Stuart; Cremeens, Jennifer; Vail-Smith, Karen

2014-06-01

We assessed the occurrence of co-morbid psychiatric disorders (i.e., problem drinking, anxiety, and depression) among college students who met the threshold for disordered gambling. The participants included a large sample of undergraduate students (n = 1,430) who were enrolled in an introductory health course at a large, southeastern university in Spring 2011 and completed an online assessment that included scales to assess disordered gambling, problem drinking, anxiety, and depression. We calculated screening scores, computed prevalence rates for each disorder, and calculated Pearson correlations and Chi square tests to examine correlations and co-morbid relationships between the four disorders. Analyses indicated that all disorders were significantly associated (p < .01) except for disordered gambling and anxiety. Because college students who experience disordered gambling (and other psychiatric disorders) are at increased risk of experiencing co-occurring disorders, it might be useful for college health professionals to concurrently screen and intervene for co-occurring disorders.

Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance.

PubMed

Marcotte, Richard; Sayad, Azin; Brown, Kevin R; Sanchez-Garcia, Felix; Reimand, Jüri; Haider, Maliha; Virtanen, Carl; Bradner, James E; Bader, Gary D; Mills, Gordon B; Pe'er, Dana; Moffat, Jason; Neel, Benjamin G

2016-01-14

Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole-genome small hairpin RNA (shRNA) "dropout screens" on 77 breast cancer cell lines. Using a hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify vulnerabilities in breast cancer, including candidate "drivers," and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, effects of existing anti-cancer drugs, and opportunities for combination therapy. Finally, we demonstrate the utility of this large dataset by identifying BRD4 as a potential target in luminal breast cancer and PIK3CA mutations as a resistance determinant for BET-inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimized ratiometric calcium sensors for functional in vivo imaging of neurons and T lymphocytes.

PubMed

Thestrup, Thomas; Litzlbauer, Julia; Bartholomäus, Ingo; Mues, Marsilius; Russo, Luigi; Dana, Hod; Kovalchuk, Yuri; Liang, Yajie; Kalamakis, Georgios; Laukat, Yvonne; Becker, Stefan; Witte, Gregor; Geiger, Anselm; Allen, Taylor; Rome, Lawrence C; Chen, Tsai-Wen; Kim, Douglas S; Garaschuk, Olga; Griesinger, Christian; Griesbeck, Oliver

2014-02-01

The quality of genetically encoded calcium indicators (GECIs) has improved dramatically in recent years, but high-performing ratiometric indicators are still rare. Here we describe a series of fluorescence resonance energy transfer (FRET)-based calcium biosensors with a reduced number of calcium binding sites per sensor. These 'Twitch' sensors are based on the C-terminal domain of Opsanus troponin C. Their FRET responses were optimized by a large-scale functional screen in bacterial colonies, refined by a secondary screen in rat hippocampal neuron cultures. We tested the in vivo performance of the most sensitive variants in the brain and lymph nodes of mice. The sensitivity of the Twitch sensors matched that of synthetic calcium dyes and allowed visualization of tonic action potential firing in neurons and high resolution functional tracking of T lymphocytes. Given their ratiometric readout, their brightness, large dynamic range and linear response properties, Twitch sensors represent versatile tools for neuroscience and immunology.

The World Health Organization Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale for DSM-5.

PubMed

Ustun, Berk; Adler, Lenard A; Rudin, Cynthia; Faraone, Stephen V; Spencer, Thomas J; Berglund, Patricia; Gruber, Michael J; Kessler, Ronald C

2017-05-01

Recognition that adult attention-deficit/hyperactivity disorder (ADHD) is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD screening scales for use in community, workplace, and primary care settings. However, these scales are all calibrated to DSM-IV criteria, which are narrower than the recently developed DSM-5 criteria. To update for DSM-5 criteria and improve the operating characteristics of the widely used World Health Organization Adult ADHD Self-Report Scale (ASRS) for screening. Probability subsamples of participants in 2 general population surveys (2001-2003 household survey [n = 119] and 2004-2005 managed care subscriber survey [n = 218]) who completed the full 29-question self-report ASRS, with both subsamples over-sampling ASRS-screened positives, were blindly administered a semistructured research diagnostic interview for DSM-5 adult ADHD. In 2016, the Risk-Calibrated Supersparse Linear Integer Model, a novel machine-learning algorithm designed to create screening scales with optimal integer weights and limited numbers of screening questions, was applied to the pooled data to create a DSM-5 version of the ASRS screening scale. The accuracy of the new scale was then confirmed in an independent 2011-2012 clinical sample of patients seeking evaluation at the New York University Langone Medical Center Adult ADHD Program (NYU Langone) and 2015-2016 primary care controls (n = 300). Data analysis was conducted from April 4, 2016, to September 22, 2016. The sensitivity, specificity, area under the curve (AUC), and positive predictive value (PPV) of the revised ASRS. Of the total 637 participants, 44 (37.0%) household survey respondents, 51 (23.4%) managed care respondents, and 173 (57.7%) NYU Langone respondents met DSM-5 criteria for adult ADHD in the semistructured diagnostic interview. Of the respondents who met DSM-5 criteria for adult ADHD, 123 were male (45.9%); mean (SD) age was 33.1 (11.4) years. A 6-question screening scale was found to be optimal in distinguishing cases from noncases in the first 2 samples. Operating characteristics were excellent at the diagnostic threshold in the weighted (to the 8.2% DSM-5/Adult ADHD Clinical Diagnostic Scale population prevalence) data (sensitivity, 91.4%; specificity, 96.0%; AUC, 0.94; PPV, 67.3%). Operating characteristics were similar despite a much higher prevalence (57.7%) when the scale was applied to the NYU Langone clinical sample (sensitivity, 91.9%; specificity, 74.0%; AUC, 0.83; PPV, 82.8%). The new ADHD screening scale is short, easily scored, detects the vast majority of general population cases at a threshold that also has high specificity and PPV, and could be used as a screening tool in specialty treatment settings.

The relationship between postpartum depression, domestic violence, childhood violence, and substance use: epidemiologic study of a large community sample.

PubMed

Dennis, Cindy-Lee; Vigod, Simone

2013-04-01

The objective of this study was to determine the contribution of interpersonal violence and substance use to the prediction of postpartum depressive symptomatology. A community-based sample of 634 women in British Columbia, Canada was screened for interpersonal violence and substance use using the Antenatal Psychosocial Health Assessment (ALPHA) form. Of these women, 497 (78%) subsequently completed questionnaires at 8 weeks postpartum to assess for depressive symptomatology using the Edinburgh Postnatal Depression Scale (EPDS). A predictive model for postpartum depressive symptomatology (EPDS > 9) was developed using regression analysis. Findings suggest that women who experience past or current interpersonal violence or personal or partner substance use problems should be considered for targeted screening for postpartum depression (PPD).

Improved Cloud and Snow Screening in MAIAC Aerosol Retrievals Using Spectral and Spatial Analysis

NASA Technical Reports Server (NTRS)

Lyapustin, A.; Wang, Y.; Laszlo, I.; Kokrkin, S.

2012-01-01

An improved cloud/snow screening technique in the Multi-Angle Implementation of Atmospheric Correction (MAIAC) algorithm is described. It is implemented as part of MAIAC aerosol retrievals based on analysis of spectral residuals and spatial variability. Comparisons with AERONET aerosol observations and a large-scale MODIS data analysis show strong suppression of aerosol optical thickness outliers due to unresolved clouds and snow. At the same time, the developed filter does not reduce the aerosol retrieval capability at high 1 km resolution in strongly inhomogeneous environments, such as near centers of the active fires. Despite significant improvement, the optical depth outliers in high spatial resolution data are and will remain the problem to be addressed by the application-dependent specialized filtering techniques.

Automated Protocol for Large-Scale Modeling of Gene Expression Data.

PubMed

Hall, Michelle Lynn; Calkins, David; Sherman, Woody

2016-11-28

With the continued rise of phenotypic- and genotypic-based screening projects, computational methods to analyze, process, and ultimately make predictions in this field take on growing importance. Here we show how automated machine learning workflows can produce models that are predictive of differential gene expression as a function of a compound structure using data from A673 cells as a proof of principle. In particular, we present predictive models with an average accuracy of greater than 70% across a highly diverse ∼1000 gene expression profile. In contrast to the usual in silico design paradigm, where one interrogates a particular target-based response, this work opens the opportunity for virtual screening and lead optimization for desired multitarget gene expression profiles.

Infant outcomes among women with Zika virus infection during pregnancy: results of a large prenatal Zika screening program.

PubMed

Adhikari, Emily H; Nelson, David B; Johnson, Kathryn A; Jacobs, Sara; Rogers, Vanessa L; Roberts, Scott W; Sexton, Taylor; McIntire, Donald D; Casey, Brian M

2017-03-01

Zika virus infection during pregnancy is a known cause of congenital microcephaly and other neurologic morbidities. We present the results of a large-scale prenatal screening program in place at a single-center health care system since March 14, 2016. Our aims were to report the baseline prevalence of travel-associated Zika infection in our pregnant population, determine travel characteristics of women with evidence of Zika infection, and evaluate maternal and neonatal outcomes compared to women without evidence of Zika infection. This is a prospective, observational study of prenatal Zika virus screening in our health care system. We screened all pregnant women for recent travel to a Zika-affected area, and the serum was tested for those considered at risk for infection. We compared maternal demographic and travel characteristics and perinatal outcomes among women with positive and negative Zika virus tests during pregnancy. Comprehensive neurologic evaluation was performed on all infants delivered of women with evidence of possible Zika virus infection during pregnancy. Head circumference percentiles by gestational age were compared for infants delivered of women with positive and negative Zika virus test results. From March 14 through Oct. 1, 2016, a total of 14,161 pregnant women were screened for travel to a Zika-affected country. A total of 610 (4.3%) women reported travel, and test results were available in 547. Of these, evidence of possible Zika virus infection was found in 29 (5.3%). In our population, the prevalence of asymptomatic or symptomatic Zika virus infection among pregnant women was 2/1000. Women with evidence of Zika virus infection were more likely to have traveled from Central or South America (97% vs 12%, P < .001). There were 391 deliveries available for analysis. There was no significant difference in obstetric or neonatal morbidities among women with or without evidence of possible Zika virus infection. Additionally, there was no difference in mean head circumference of infants born to women with positive vs negative Zika virus testing. No microcephalic infants born to women with Zika infection were identified, although 1 infant with hydranencephaly was born to a woman with unconfirmed possible Zika disease. Long-term outcomes for infants exposed to maternal Zika infection during pregnancy are yet unknown. Based on a large-scale prenatal Zika screening program in an area with a predominantly Hispanic population, we identified that 4% were at risk from reported travel with only 2/1000 infected. Women traveling from heavily affected areas were most at risk for infection. Neonatal head circumference percentiles among infants born to women with evidence of possible Zika virus infection during pregnancy were not reduced when compared to infants born to women without infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultra-High-Throughput Screening of Natural Product Extracts to Identify Proapoptotic Inhibitors of Bcl-2 Family Proteins.

PubMed

Hassig, Christian A; Zeng, Fu-Yue; Kung, Paul; Kiankarimi, Mehrak; Kim, Sylvia; Diaz, Paul W; Zhai, Dayong; Welsh, Kate; Morshedian, Shana; Su, Ying; O'Keefe, Barry; Newman, David J; Rusman, Yudi; Kaur, Harneet; Salomon, Christine E; Brown, Susan G; Baire, Beeraiah; Michel, Andrew R; Hoye, Thomas R; Francis, Subhashree; Georg, Gunda I; Walters, Michael A; Divlianska, Daniela B; Roth, Gregory P; Wright, Amy E; Reed, John C

2014-09-01

Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally relevant PPIs. The screens were conducted in 1536-well format and displayed satisfactory overall HTS statistics, with Z'-factor values ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied, and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source, and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra-high-throughput screening using natural product sources and highlight some of the challenges associated with this approach. © 2014 Society for Laboratory Automation and Screening.

The Nonmydriatic Fundus Camera in Diabetic Retinopathy Screening: A Cost-Effective Study with Evaluation for Future Large-Scale Application

PubMed Central

Scarpa, Giuseppe; Urban, Francesca; Tessarin, Michele; Gallo, Giovanni; Midena, Edoardo

2016-01-01

Aims. The study aimed to present the experience of a screening programme for early detection of diabetic retinopathy (DR) using a nonmydriatic fundus camera, evaluating the feasibility in terms of validity, resources absorption, and future advantages of a potential application, in an Italian local health authority. Methods. Diabetic patients living in the town of Ponzano, Veneto Region (Northern Italy), were invited to be enrolled in the screening programme. The “no prevention strategy” with the inclusion of the estimation of blindness related costs was compared with screening costs in order to evaluate a future extensive and feasible implementation of the procedure, through a budget impact approach. Results. Out of 498 diabetic patients eligible, 80% was enrolled in the screening programme. 115 patients (34%) were referred to an ophthalmologist and 9 cases required prompt treatment for either proliferative DR or macular edema. Based on the pilot data, it emerged that an extensive use of the investigated screening programme, within the Greater Treviso area, could prevent 6 cases of blindness every year, resulting in a saving of €271,543.32 (−13.71%). Conclusions. Fundus images obtained with a nonmydriatic fundus camera could be considered an effective, cost-sparing, and feasible screening tool for the early detection of DR, preventing blindness as a result of diabetes. PMID:27885337

High-throughput screening of hybridoma supernatants using multiplexed fluorescent cell barcoding on live cells.

PubMed

Lu, Mei; Chan, Brian M; Schow, Peter W; Chang, Wesley S; King, Chadwick T

2017-12-01

With current available assay formats using either immobilized protein (ELISA, enzyme-linked immunosorbent assay) or immunostaining of fixed cells for primary monoclonal antibody (mAb) screening, researchers often fail to identify and characterize antibodies that recognize the native conformation of cell-surface antigens. Therefore, screening using live cells has become an integral and important step contributing to the successful identification of therapeutic antibody candidates. Thus the need for developing high-throughput screening (HTS) technologies using live cells has become a major priority for therapeutic mAb discovery and development. We have developed a novel technique called Multiplexed Fluorescent Cell Barcoding (MFCB), a flow cytometry-based method based upon the Fluorescent Cell Barcoding (FCB) technique and the Luminex fluorescent bead array system, but is applicable to high-through mAb screens on live cells. Using this technique in our system, we can simultaneously identify or characterize the antibody-antigen binding of up to nine unique fluorescent labeled cell populations in the time that it would normally take to process a single population. This has significantly reduced the amount of time needed for the identification of potential lead candidates. This new technology enables investigators to conduct large-scale primary hybridoma screens using flow cytometry. This in turn has allowed us to screen antibodies more efficiently than before and streamline identification and characterization of lead molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparing the validity of the K6 when assessing depression, anxiety, and PTSD among male and female jail detainees.

PubMed

Kubiak, Sheryl Pimlott; Beeble, Marisa; Bybee, Deborah

2012-12-01

A lack of a consistent and valid approach to screening within the jail often hinders identification and treatment. Furthermore, screening instruments developed for jail populations are often inadequate in detecting serious depression and anxiety disorders in women. While the remedy thus far has been the use of separate screening instruments for men and women, others have suggested that the K6, a six-item measure validated in large epidemiologic studies, may hold promise. Building on prior research, this study assesses the validity of the K6 in detecting depression, posttraumatic stress disorder, and anxiety disorders among 494 male and 515 female jail detainees. The authors found that 15% of males and 36% of females meet criteria for serious mental illness on the K6, with receiver operating characteristics--area under the curve scores of .84 and .93, respectively. This study not only establishes the validity and efficiency of using the K6 for screening within jails but also suggests a need for adjusting scale cut points.

Development and application of a fluorescent glucose uptake assay for the high-throughput screening of non-glycoside SGLT2 inhibitors.

PubMed

Wu, Szu-Huei; Yao, Chun-Hsu; Hsieh, Chieh-Jui; Liu, Yu-Wei; Chao, Yu-Sheng; Song, Jen-Shin; Lee, Jinq-Chyi

2015-07-10

Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors are of current interest as a treatment for type 2 diabetes. Efforts have been made to discover phlorizin-related glycosides with good SGLT2 inhibitory activity. To increase structural diversity and better understand the role of non-glycoside SGLT2 inhibitors on glycemic control, we initiated a research program to identify non-glycoside hits from high-throughput screening. Here, we report the development of a novel, fluorogenic probe-based glucose uptake system based on a Cu(I)-catalyzed [3+2] cycloaddition. The safer processes and cheaper substances made the developed assay our first priority for large-scale primary screening as compared to the well-known [(14)C]-labeled α-methyl-D-glucopyranoside ([(14)C]-AMG) radioactive assay. This effort culminated in the identification of a benzimidazole, non-glycoside SGLT2 hit with an EC50 value of 0.62 μM by high-throughput screening of 41,000 compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of screen-printed electrodes for dielectric elastomer (DE) membranes: influence of screen dimensions and electrode thickness on actuator performance

NASA Astrophysics Data System (ADS)

Fasolt, Bettina; Hodgins, Micah; Seelecke, Stefan

2016-04-01

Screen printing is used as a method for printing electrodes on silicone thin films for the fabrication of dielectric elastomer transducers (DET). This method can be used to manufacture a multitude of patternable designs for actuator and sensor applications, implementing the same method for prototyping as well as large-scale production. The fabrication of DETs does not only require the development of a flexible, highly conductive electrode material, which adheres to a stretched and unstretched silicone film, but also calls for a thorough understanding of the effects of the different printing parameters. This work studies the influence of screen dimensions (open area, mesh thickness) as well as the influence of multiple-layer- printing on the electrode stiffness, electrical resistance and capacitance as well as actuator performance. The investigation was conducted in a custom-built testing device, which enabled an electro-mechanical characterization of the DET, simultaneously measuring parameters such as strain, voltage, current, force, sheet resistance, capacitance and membrane thickness. Magnified pictures of the electrodes will additionally illustrate the effects of the different printing parameters.

Sinking towards destiny: High throughput measurement of phytoplankton sinking rates through time-resolved fluorescence plate spectroscopy.

PubMed

Bannon, Catherine C; Campbell, Douglas A

2017-01-01

Diatoms are marine primary producers that sink in part due to the density of their silica frustules. Sinking of these phytoplankters is crucial for both the biological pump that sequesters carbon to the deep ocean and for the life strategy of the organism. Sinking rates have been previously measured through settling columns, or with fluorimeters or video microscopy arranged perpendicularly to the direction of sinking. These side-view techniques require large volumes of culture, specialized equipment and are difficult to scale up to multiple simultaneous measures for screening. We established a method for parallel, large scale analysis of multiple phytoplankton sinking rates through top-view monitoring of chlorophyll a fluorescence in microtitre well plates. We verified the method through experimental analysis of known factors that influence sinking rates, including exponential versus stationary growth phase in species of different cell sizes; Thalassiosira pseudonana CCMP1335, chain-forming Skeletonema marinoi RO5A and Coscinodiscus radiatus CCMP312. We fit decay curves to an algebraic transform of the decrease in fluorescence signal as cells sank away from the fluorometer detector, and then used minimal mechanistic assumptions to extract a sinking rate (m d-1) using an RStudio script, SinkWORX. We thereby detected significant differences in sinking rates as larger diatom cells sank faster than smaller cells, and cultures in stationary phase sank faster than those in exponential phase. Our sinking rate estimates accord well with literature values from previously established methods. This well plate-based method can operate as a high throughput integrative phenotypic screen for factors that influence sinking rates including macromolecular allocations, nutrient availability or uptake rates, chain-length or cell size, degree of silification and progression through growth stages. Alternately the approach can be used to phenomically screen libraries of mutants.

A high-throughput screening approach to discovering good forms of biologically inspired visual representation.

PubMed

Pinto, Nicolas; Doukhan, David; DiCarlo, James J; Cox, David D

2009-11-01

While many models of biological object recognition share a common set of "broad-stroke" properties, the performance of any one model depends strongly on the choice of parameters in a particular instantiation of that model--e.g., the number of units per layer, the size of pooling kernels, exponents in normalization operations, etc. Since the number of such parameters (explicit or implicit) is typically large and the computational cost of evaluating one particular parameter set is high, the space of possible model instantiations goes largely unexplored. Thus, when a model fails to approach the abilities of biological visual systems, we are left uncertain whether this failure is because we are missing a fundamental idea or because the correct "parts" have not been tuned correctly, assembled at sufficient scale, or provided with enough training. Here, we present a high-throughput approach to the exploration of such parameter sets, leveraging recent advances in stream processing hardware (high-end NVIDIA graphic cards and the PlayStation 3's IBM Cell Processor). In analogy to high-throughput screening approaches in molecular biology and genetics, we explored thousands of potential network architectures and parameter instantiations, screening those that show promising object recognition performance for further analysis. We show that this approach can yield significant, reproducible gains in performance across an array of basic object recognition tasks, consistently outperforming a variety of state-of-the-art purpose-built vision systems from the literature. As the scale of available computational power continues to expand, we argue that this approach has the potential to greatly accelerate progress in both artificial vision and our understanding of the computational underpinning of biological vision.

Large scale germplasm screening for identification of novel rice blast resistance sources

PubMed Central

Vasudevan, Kumar; Vera Cruz, Casiana M.; Gruissem, Wilhelm; Bhullar, Navreet K.

2014-01-01

Rice is a major cereal crop that contributes significantly to global food security. Biotic stresses, including the rice blast fungus, cause severe yield losses that significantly impair rice production worldwide. The rapid genetic evolution of the fungus often overcomes the resistance conferred by major genes after a few years of intensive agricultural use. Therefore, resistance breeding requires continuous efforts of enriching the reservoir of resistance genes/alleles to effectively tackle the disease. Seed banks represent a rich stock of genetic diversity, however, they are still under-explored for identifying novel genes and/or their functional alleles. We conducted a large-scale screen for new rice blast resistance sources in 4246 geographically diverse rice accessions originating from 13 major rice-growing countries. The accessions were selected from a total collection of over 120,000 accessions based on their annotated rice blast resistance information in the International Rice Genebank. A two-step resistance screening protocol was used involving natural infection in a rice uniform blast nursery and subsequent artificial infections with five single rice blast isolates. The nursery-resistant accessions showed varied disease responses when infected with single isolates, suggesting the presence of diverse resistance genes/alleles in this accession collection. In addition, 289 accessions showed broad-spectrum resistance against all five single rice blast isolates. The selected resistant accessions were genotyped for the presence of the Pi2 resistance gene, thereby identifying potential accessions for isolation of allelic variants of this blast resistance gene. Together, the accession collection with broad spectrum and isolate specific blast resistance represent the core material for isolation of previously unknown blast resistance genes and/or their allelic variants that can be deployed in rice breeding programs. PMID:25324853

HPV self-sampling in Japanese women: A feasibility study in a population with limited experience of tampon use.

PubMed

Hanley, Sharon Jb; Fujita, Hiromasa; Yokoyama, Susumu; Kunisawa, Shiori; Tamakoshi, Akiko; Dong, Peixin; Kobayashi, Noriko; Watari, Hidemichi; Kudo, Masataka; Sakuragi, Noriaki

2016-09-01

Cervical cancer incidence and mortality is increasing in Japanese women under age 50. Screening uptake is low and proactive recommendations for human papillomavirus vaccination have been suspended. Other cervical cancer prevention initiatives are urgently needed. We assessed whether human papillomavirus self-sampling might be an acceptable alternative to physician-led screening, particularly in women with limited experience of tampon use. We also sought to identify any practical, logistical, or safety issues in women already attending for screening, before carrying out further large-scale studies in non-responders. In total, 203 women aged 20-49 attending their annual workplace healthcheck in Sapporo, northern Japan, performed unsupervised human papillomavirus self-sampling before undergoing a physician-led cervical smear and human papillomavirus test, and completing a measure of acceptability for both tests. Ninety per cent of participants stated they would use self-sampling again. They found instructions easy to follow and reported no issues with the usability of the self-sampling device. Compared with physician-led testing, women found self-sampling significantly less painful, less embarrassing and could relax more (p < 0.001), regardless of history of tampon use, which was associated with negative experiences in physician sampling (p = 0.034). Women lacked confidence the test had been performed correctly, despite no unsatisfactory samples. No safety issues were reported. Self-sampling was highly acceptable in this population of women. They could perform the test safely unsupervised, but lacked confidence the test has been carried out correctly. Japanese women need to be educated about the accuracy of human papillomavirus self-sampling and further large-scale studies are necessary in non-responders. © The Author(s) 2016.

A High-Throughput Screening Approach to Discovering Good Forms of Biologically Inspired Visual Representation

PubMed Central

Pinto, Nicolas; Doukhan, David; DiCarlo, James J.; Cox, David D.

2009-01-01

While many models of biological object recognition share a common set of “broad-stroke” properties, the performance of any one model depends strongly on the choice of parameters in a particular instantiation of that model—e.g., the number of units per layer, the size of pooling kernels, exponents in normalization operations, etc. Since the number of such parameters (explicit or implicit) is typically large and the computational cost of evaluating one particular parameter set is high, the space of possible model instantiations goes largely unexplored. Thus, when a model fails to approach the abilities of biological visual systems, we are left uncertain whether this failure is because we are missing a fundamental idea or because the correct “parts” have not been tuned correctly, assembled at sufficient scale, or provided with enough training. Here, we present a high-throughput approach to the exploration of such parameter sets, leveraging recent advances in stream processing hardware (high-end NVIDIA graphic cards and the PlayStation 3's IBM Cell Processor). In analogy to high-throughput screening approaches in molecular biology and genetics, we explored thousands of potential network architectures and parameter instantiations, screening those that show promising object recognition performance for further analysis. We show that this approach can yield significant, reproducible gains in performance across an array of basic object recognition tasks, consistently outperforming a variety of state-of-the-art purpose-built vision systems from the literature. As the scale of available computational power continues to expand, we argue that this approach has the potential to greatly accelerate progress in both artificial vision and our understanding of the computational underpinning of biological vision. PMID:19956750

Cost-Savings to Medicare From Pre-Medicare Colorectal Cancer Screening.

PubMed

Goede, Simon L; Kuntz, Karen M; van Ballegooijen, Marjolein; Knudsen, Amy B; Lansdorp-Vogelaar, Iris; Tangka, Florence K; Howard, David H; Chin, Joseph; Zauber, Ann G; Seeff, Laura C

2015-07-01

Many individuals have not received recommended colorectal cancer (CRC) screening before they become Medicare eligible at the age of 65. We aimed to estimate the long-term implications of increased CRC screening in the pre-Medicare population (50-64 y) on costs in the pre-Medicare and Medicare populations (65+ y). We used 2 independently developed microsimulation models [Microsimulation Screening Analysis Colon (MISCAN) and Simulation Model of CRC (SimCRC)] to project CRC screening and treatment costs under 2 scenarios, starting in 2010: "current trends" (60% of the population up-to-date with screening recommendations) and "enhanced participation" (70% up-to-date). The population was scaled to the projected US population for each year between 2010 and 2060. Costs per year were derived by age group (50-64 and 65+ y). By 2060, the discounted cumulative total costs in the pre-Medicare population were $35.7 and $28.1 billion higher with enhanced screening participation, than in the current trends scenario ($252.1 billion with MISCAN and $239.5 billion with SimCRC, respectively). Because of CRC treatment savings with enhanced participation, cumulative costs in the Medicare population were $18.3 and $32.7 billion lower (current trends: $423.5 billion with MISCAN and $372.8 billion with SimCRC). Over the 50-year time horizon an estimated 60% (MISCAN) and 89% (SimCRC) of the increased screening costs could be offset by savings in Medicare CRC treatment costs. Increased CRC screening participation in the pre-Medicare population could reduce CRC incidence and mortality, whereas the additional screening costs can be largely offset by long-term Medicare treatment savings.

Introduction of molecular HPV testing as the primary technology in cervical cancer screening: Acting on evidence to change the current paradigm.

PubMed

Tota, Joseph E; Bentley, James; Blake, Jennifer; Coutlée, François; Duggan, Máire A; Ferenczy, Alex; Franco, Eduardo L; Fung-Kee-Fung, Michael; Gotlieb, Walter; Mayrand, Marie-Hélène; McLachlin, Meg; Murphy, Joan; Ogilvie, Gina; Ratnam, Sam

2017-05-01

Since being introduced in the 1940s, cervical cytology - despite its limitations - has had unequivocal success in reducing cervical cancer burden in many countries. However, we now know that infection with human papillomavirus (HPV) is a necessary cause of cervical cancer and there is overwhelming evidence from large-scale clinical trials, feasibility studies and real-world experience that supports the introduction of molecular testing for HPV as the primary technology in cervical cancer screening (i.e., "HPV primary screening"). While questions remain about the most appropriate age groups for screening, screening interval and triage approach, these should not be considered barriers to implementation. Many countries are in various stages of adopting HPV primary screening, whereas others have not taken any major steps towards introduction of this approach. As a group of clinical experts and researchers in cervical cancer prevention from across Canada, we have jointly authored this comprehensive examination of the evidence to implement HPV primary screening. Our intention is to create a common understanding among policy makers, agencies, clinicians, researchers and other stakeholders about the evidence concerning HPV primary screening to catalyze the adoption of this improved approach to cervical cancer prevention. With the first cohort of vaccinated girls now turning 21, the age when routine screening typically begins, there is increased urgency to introduce HPV primary screening, whose performance may be less adversely affected compared with cervical cytology as a consequence of reduced lesion prevalence post-vaccination. Published by Elsevier Inc.

Evaluating cost and resource use associated with pulse oximetry screening for critical congenital heart disease: Empiric estimates and sources of variation.

PubMed

Reeder, Matthew R; Kim, Jaewhan; Nance, Amy; Krikov, Sergey; Feldkamp, Marcia L; Randall, Harper; Botto, Lorenzo D

2015-11-01

Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is being implemented in the United States and internationally; however, few data are available on the associated in-hospital costs and use of resources. Time and motion study in well-baby nurseries at two large urban hospitals in Utah using different approaches to pulse oximetry screening. Two observers recorded the time for each screening step together with provider and equipment characteristics. Structured questionnaire provided additional information on labor and equipment costs. Fifty-three CCHD screens were observed. At site A (n = 22), screening was mostly done by medical assistants (95%) using disposable probes (100%); at site B (n = 31), screening was mostly performed by certified nursing assistants (90%) using reusable probes (90%). Considering only first screens (n = 53), the median screen time was 8.6 min (range: 3.2-23.2), with no significant difference between sites. The overall cost ($ in 2014) of screening per baby was $24.52 at site A and $2.60 at site B. Nearly all the variation in cost (90%) was due to the cost of disposable probes; labor costs were similar between sites. CCHD screening by means of pulse oximetry is reasonably fast for most babies, leading to relative small labor costs with little variation by provider type. The main driver of costs is equipment: in a high throughput setting, reusable probes are currently associated with considerable cost saving compared with disposable probes. As programs expand to universal screening, improved and cheaper technologies could lead to considerable economies of scale. © 2015 Wiley Periodicals, Inc.

Cervical cancer patterns with automation-assisted and conventional cytological screening: a randomized study.

PubMed

Anttila, Ahti; Pokhrel, Arun; Kotaniemi-Talonen, Laura; Hakama, Matti; Malila, Nea; Nieminen, Pekka

2011-03-01

The purpose was to evaluate alternative cytological screening methods in population-based screening for cervical cancer up to cancer incidence and mortality outcome. Automation-assisted screening was compared to conventional cytological screening in a randomized design. The study was based on follow-up of 503,391 women invited in the Finnish cervical cancer screening program during 1999-2003. The endpoints were incident cervical cancer, severe intraepithelial neoplasia and deaths from cervical cancer. One third of the women had been randomly allocated to automation-assisted screening and two thirds to conventional cytology. Information on cervical cancer and severe neoplasia were obtained through 1999-2007 from a linkage between screening and cancer registry files. There were altogether 3.2 million woman-years at risk, and the average follow-up time was 6.3 years. There was no difference in the risk of cervical cancer between the automation-assisted and conventional screening methods; the relative risk (RR) of cervical cancer between the study and control arm was 1.00 (95% confidence interval [CI] = 0.76-1.29) among all invited and 1.08 (95% CI = 0.76-1.51) among women who were test negative at entry. Comparing women who were test negative with nonscreened, RR of cervical cancer incidence was 0.26, 95% CI = 0.19-0.36 and of mortality 0.24 (0.13-0.43). Both methods were valid for screening. Because cervical cancer is rare in our country, we cannot rule out small differences between methods. Evidence on alternative methods for cervical cancer screening is increasing and it is thus feasible to evaluate new methods in large-scale population-based screening programs up to cancer outcome. Copyright © 2010 UICC.

Screening for anxiety disorders in patients with coronary artery disease.

PubMed

Bunevicius, Adomas; Staniute, Margarita; Brozaitiene, Julija; Pop, Victor J M; Neverauskas, Julius; Bunevicius, Robertas

2013-03-11

Anxiety disorders are prevalent and associated with poor prognosis in patients with coronary artery disease (CAD). However, studies examining screening of anxiety disorders in CAD patients are lacking. In the present study we evaluated the prevalence of anxiety disorders in patients with CAD and diagnostic utility of self-rating scales for screening of anxiety disorders. Five-hundred and twenty-three CAD patients not receiving psychotropic treatments at initiation of rehabilitation program completed self-rating scales (Hospital Anxiety and Depression Scale or HADS; Spielberger State-Anxiety Inventory or SSAI; and Spielberger Trait-Anxiety Inventory or STAI) and were interviewed for generalized anxiety disorder (GAD), social phobia, panic disorder and agoraphobia (Mini-International Neuropsychiatric Interview or MINI). Thirty-eight (7%) patients were diagnosed with anxiety disorder(s), including GAD (5%), social phobia (2%), agoraphobia (1%) and panic disorder (1%). Areas under the ROC curve of the HADS Anxiety subscale (HADS-A), STAI and SSAI for screening of any anxiety disorder were .81, .80 and .72, respectively. Optimal cut-off values for screening of any anxiety disorders were ≥ 8 for the HADS-A (sensitivity = 82%; specificity = 76%; and positive predictive value (PPV) = 21%); ≥ 45 for the STAI (sensitivity = 89%; specificity = 56%; and PPV = 14%); and ≥ 40 for the SSAI (sensitivity = 84%; specificity = 55%; PPV = 13%). In a subgroup of patients (n = 340) scoring below the optimal major depressive disorder screening cut-off value of HADS-Depression subscale (score <5), the HADS-A, STAI and SSAI had moderate-high sensitivity (range from 69% to 89%) and low PPVs (≤ 22%) for GAD and any anxiety disorders. Anxiety disorders are prevalent in CAD patients but can be reliably identified using self-rating scales. Anxiety self-rating scales had comparable sensitivities but the HADS-A had greater specificity and PPV when compared to the STAI and SSAI for screening of anxiety disorders. However, false positive rates were high, suggesting that patients with positive screening results should undergo psychiatric interview prior to initiating treatment for anxiety disorders and that routine use of anxiety self-rating scales for screening purposes can increase healthcare costs. Anxiety screening has incremental value to depression screening for identifying anxiety disorders.

Large-scale protein-protein interaction analysis in Arabidopsis mesophyll protoplasts by split firefly luciferase complementation.

PubMed

Li, Jian-Feng; Bush, Jenifer; Xiong, Yan; Li, Lei; McCormack, Matthew

2011-01-01

Protein-protein interactions (PPIs) constitute the regulatory network that coordinates diverse cellular functions. There are growing needs in plant research for creating protein interaction maps behind complex cellular processes and at a systems biology level. However, only a few approaches have been successfully used for large-scale surveys of PPIs in plants, each having advantages and disadvantages. Here we present split firefly luciferase complementation (SFLC) as a highly sensitive and noninvasive technique for in planta PPI investigation. In this assay, the separate halves of a firefly luciferase can come into close proximity and transiently restore its catalytic activity only when their fusion partners, namely the two proteins of interest, interact with each other. This assay was conferred with quantitativeness and high throughput potential when the Arabidopsis mesophyll protoplast system and a microplate luminometer were employed for protein expression and luciferase measurement, respectively. Using the SFLC assay, we could monitor the dynamics of rapamycin-induced and ascomycin-disrupted interaction between Arabidopsis FRB and human FKBP proteins in a near real-time manner. As a proof of concept for large-scale PPI survey, we further applied the SFLC assay to testing 132 binary PPIs among 8 auxin response factors (ARFs) and 12 Aux/IAA proteins from Arabidopsis. Our results demonstrated that the SFLC assay is ideal for in vivo quantitative PPI analysis in plant cells and is particularly powerful for large-scale binary PPI screens.

A comparison of effectiveness of hepatitis B screening and linkage to care among foreign-born populations in clinical and nonclinical settings.

PubMed

Chandrasekar, Edwin; Kaur, Ravneet; Song, Sharon; Kim, Karen E

2015-01-01

Hepatitis B (HBV) is an urgent, unmet public health issue that affects Asian Americans disproportionately. Of the estimated 1.2 million living with chronic hepatitis B in USA, more than 50% are of Asian ethnicity, despite the fact that Asian Americans constitute less than 6% of the total US population. The Centers for Disease Control and Prevention recommends HBV screening of persons who are at high risk for the disease. Yet, large numbers of Asian Americans have not been diagnosed or tested, in large part because of perceived cultural and linguistic barriers. Primary care physicians are at the front line of the US health care system, and are in a position to identify individuals and families at risk. Clinical settings integrated into Asian American communities, where physicians are on staff and wellness care is emphasized, can provide testing for HBV. In this study, the Asian Health Coalition and its community partners conducted HBV screenings and follow-up linkage to care in both clinical and nonclinical settings. The nonclinic settings included health fair events organized by churches and social services agencies, and were able to reach large numbers of individuals. Twice as many Asian Americans were screened in nonclinical settings than in health clinics. Chi-square and independent samples t-test showed that participants from the two settings did not differ in test positivity, sex, insurance status, years of residence in USA, or education. Additionally, the same proportion of individuals found to be infected in the two groups underwent successful linkage to care. Nonclinical settings were as effective as clinical settings in screening for HBV, as well as in making treatment options available to those who tested positive; demographic factors did not confound the similarities. Further research is needed to evaluate if linkage to care can be accomplished equally efficiently on a larger scale.

Improving Universal Suicide Prevention Screening in Primary Care by Reducing False Negatives

DTIC Science & Technology

2017-09-01

develop a shortened version of the Suicide Cognitions Scale (SCS) and to evaluate its efficacy as a universal suicide prevention screen for use in... Cognitions Scale (SCS) and to evaluate its efficacy as a universal suicide prevention screen for use in military primary care clinics. We propose to

Development and Initial Validation of the Symptoms and Assets Screening Scale

ERIC Educational Resources Information Center

Downs, Andrew; Boucher, Laura A.; Campbell, Duncan G.; Dasse, Michelle

2013-01-01

Objective: To develop and test a screening measure of mental health symptoms and well-being in college students, the Symptoms and Assets Screening Scale (SASS). Participants: Participants were 758 college students at 2 universities in the Northwest sampled between October 2009 and April 2011. Methods: Participants completed the SASS, as well as…

A Rating Scale to Screen Symptoms of Psychiatric Disorders in Children

ERIC Educational Resources Information Center

Scholte, Evert M.; Van Berckelaer-Onnes, Ina; Van der Ploeg, Jan D.

2008-01-01

To be able to offer children with developmental disorders adequate help, professionals working in special needs education must use a screening device to assess the specific psychiatric difficulties of the children. In this paper the psychometric properties of an easy-to-use parental rating scale to screen symptoms of major psychiatric disorders…

Modelling and mitigating refractive propagation effects in precision pulsar timing observations

NASA Astrophysics Data System (ADS)

Shannon, R. M.; Cordes, J. M.

2017-01-01

To obtain the most accurate pulse arrival times from radio pulsars, it is necessary to correct or mitigate the effects of the propagation of radio waves through the warm and ionized interstellar medium. We examine both the strength of propagation effects associated with large-scale electron-density variations and the methodology used to estimate infinite frequency arrival times. Using simulations of two-dimensional phase-varying screens, we assess the strength and non-stationarity of timing perturbations associated with large-scale density variations. We identify additional contributions to arrival times that are stochastic in both radio frequency and time and therefore not amenable to correction solely using times of arrival. We attribute this to the frequency dependence of the trajectories of the propagating radio waves. We find that this limits the efficacy of low-frequency (metre-wavelength) observations. Incorporating low-frequency pulsar observations into precision timing campaigns is increasingly problematic for pulsars with larger dispersion measures.

The Child Play Behavior and Activity Questionnaire: A Parent-Report Measure of Childhood Gender-Related Behavior in China

PubMed Central

Winter, Sam; Xie, Dong

2008-01-01

Boys and girls establish relatively stable gender stereotyped behavior patterns by middle childhood. Parent-report questionnaires measuring children’s gender-related behavior enable researchers to conduct large-scale screenings of community samples of children. For school-aged children, two parent-report instruments, the Child Game Participation Questionnaire (CGPQ) and the Child Behavior and Attitude Questionnaire (CBAQ), have long been used for measuring children’s sex-dimorphic behaviors in Western societies, but few studies have been conducted using these measures for Chinese populations. The current study aimed to empirically examine and modify the two instruments for their applications to Chinese society. Parents of 486 Chinese boys and 417 Chinese girls (6–12 years old) completed a questionnaire comprising items from the CGPQ and CBAQ, and an additional 14 items specifically related to Chinese gender-specific games. Items revealing gender differences in a Chinese sample were identified and used to construct a Child Play Behavior and Activity Questionnaire (CPBAQ). Four new scales were generated through factor analysis: a Gender Scale, a Girl Typicality Scale, a Boy Typicality Scale, and a Cross-Gender Scale (CGS). These scales had satisfactory internal reliabilities and large effect sizes for gender. The CPBAQ is believed to be a promising instrument for measuring children’s gender-related behavior in China. PMID:18719986

Investigating the disparities in cervical cancer screening among Namibian women.

PubMed

Kangmennaang, Joseph; Thogarapalli, Nandini; Mkandawire, Paul; Luginaah, Isaac

2015-08-01

We examined the influence of knowledge and information, health care access and different socio-economic variables on women's decision to screen for cervical cancer using a nationally representative dataset. We use hierarchical binary logit regression models to explore the determinants of screening for cervical cancer among women who reported hearing about cervical cancer. This enabled us to include the effect of unobserved heterogeneity at the cluster level that may affect screening behaviors. Among women who have heard about cervical cancer (N=6542), only 39% of them did undergo screening with a mean age of 33 years. The univariate results reveal that women who are educated, insured, can afford money needed for treatment and reported distance not a barrier to accessing healthcare were more likely to screen. Our multivariate results indicate that insured women (OR=1.89, p=0.001) and women who had access to information through education and contact with a health worker (OR=1.41, p=0.001) were more likely to undertake screening compared to uninsured women and those with no contact with a health personnel, after controlling for relevant variables. The adoption of a universal health insurance scheme that ensures equity in access to health care and extension of public health information targeting women in rural communities especially within the Caprivi region may be needed for a large scale increase in cervical cancer screening in Namibia. Copyright © 2015 Elsevier Inc. All rights reserved.

Do they actually work across borders? Evaluation of two measures of psychological distress as screening instruments in a non Anglo-Saxon country.

PubMed

Carrà, G; Sciarini, P; Segagni-Lusignani, G; Clerici, M; Montomoli, C; Kessler, R C

2011-03-01

Screening scales can be useful in searching for common mental disorders in primary care and in tracking relevant prevalence and correlates in community surveys. However, it is important to document their validity, before using them. We developed Italian versions of the widely-used K10 and K6 screening scales following the WHO forward-translation and back-translation protocol. To evaluate their effectiveness as screens for DSM-IV 12-month mood or anxiety disorders and "serious mental illness" (SMI), the scales were validated in a two-stage clinical reappraisal survey. In the first-phase, the scales were administered to 605 people. In the second-phase, a sub-sample of 147 first-phase respondents over-sampling screened positives was administered the 12-month version of the Structured Clinical Interview for DSM-IV Axis I Disorders as a clinical gold standard. Performance of the scales in screening for chosen disorders was assessed by calculating area under the receiver operating characteristic curve and stratum-specific likelihood ratios. Both the K10 and K6 performed well in detecting DSM-IV mood disorders, anxiety disorders, and serious mental illness (SMI), with areas under the curve (AUCs) (95% CIs) between 0.82 (0.75-0.89) and 0.91 (0.85-0.96). The Italian versions of the K6 and K10 scales have good psychometric properties, making them attractive inexpensive screens for mood disorders, anxiety disorders, and SMI. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gratia, Pierre; Hu, Wayne; Enrico Fermi Institute and Kavli Institute for Cosmological Physics, University of Chicago,South Ellis Avenue, Chicago, IL 60637

Attempts to modify gravity in the infrared typically require a screening mechanism to ensure consistency with local tests of gravity. These screening mechanisms fit into three broad classes; we investigate theories which are capable of exhibiting more than one type of screening. Specifically, we focus on a simple model which exhibits both Vainshtein and kinetic screening. We point out that due to the two characteristic length scales in the problem, the type of screening that dominates depends on the mass of the sourcing object, allowing for different phenomenology at different scales. We consider embedding this double screening phenomenology in amore » broader cosmological scenario and show that the simplest examples that exhibit double screening are radiatively stable.« less

RESOLVING THE ROTATION MEASURE OF THE M87 JET ON KILOPARSEC SCALES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Algaba, J. C.; Asada, K.; Nakamura, M., E-mail: algaba@asiaa.sinica.edu.tw

2016-06-01

We investigate the distribution of Faraday rotation measure (RM) in the M87 jet at arcsecond scales by using archival polarimetric Very Large Array data at 8, 15, 22 and 43 GHz. We resolve the structure of the RM in several knots along the jet for the first time. We derive the power spectrum in the arcsecond-scale jet and find indications that the RM cannot be associated with a turbulent magnetic field with a 3D Kolmogorov spectrum. Our analysis indicates that the RM probed on jet scales has a significant contribution of a Faraday screen associated with the vicinity of themore » jet, in contrast with that on kiloparsec scales, typically assumed to be disconnected from the jet. Comparison with previous RM analyses suggests that the magnetic fields giving rise to the RMs observed in jet scales have different properties and are well less turbulent than those observed in the lobes.« less

Exome Pool-Seq in neurodevelopmental disorders.

PubMed

Popp, Bernt; Ekici, Arif B; Thiel, Christian T; Hoyer, Juliane; Wiesener, Antje; Kraus, Cornelia; Reis, André; Zweier, Christiane

2017-12-01

High throughput sequencing has greatly advanced disease gene identification, especially in heterogeneous entities. Despite falling costs this is still an expensive and laborious technique, particularly when studying large cohorts. To address this problem we applied Exome Pool-Seq as an economic and fast screening technology in neurodevelopmental disorders (NDDs). Sequencing of 96 individuals can be performed in eight pools of 12 samples on less than one Illumina sequencer lane. In a pilot study with 96 cases we identified 27 variants, likely or possibly affecting function. Twenty five of these were identified in 923 established NDD genes (based on SysID database, status November 2016) (ACTB, AHDC1, ANKRD11, ATP6V1B2, ATRX, CASK, CHD8, GNAS, IFIH1, KCNQ2, KMT2A, KRAS, MAOA, MED12, MED13L, RIT1, SETD5, SIN3A, TCF4, TRAPPC11, TUBA1A, WAC, ZBTB18, ZMYND11), two in 543 (SysID) candidate genes (ZNF292, BPTF), and additionally a de novo loss-of-function variant in LRRC7, not previously implicated in NDDs. Most of them were confirmed to be de novo, but we also identified X-linked or autosomal-dominantly or autosomal-recessively inherited variants. With a detection rate of 28%, Exome Pool-Seq achieves comparable results to individual exome analyses but reduces costs by >85%. Compared with other large scale approaches using Molecular Inversion Probes (MIP) or gene panels, it allows flexible re-analysis of data. Exome Pool-Seq is thus well suited for large-scale, cost-efficient and flexible screening in characterized but heterogeneous entities like NDDs.

TaqMan Real-Time PCR Assays To Assess Arbuscular Mycorrhizal Responses to Field Manipulation of Grassland Biodiversity: Effects of Soil Characteristics, Plant Species Richness, and Functional Traits▿ †

PubMed Central

König, Stephan; Wubet, Tesfaye; Dormann, Carsten F.; Hempel, Stefan; Renker, Carsten; Buscot, François

2010-01-01

Large-scale (temporal and/or spatial) molecular investigations of the diversity and distribution of arbuscular mycorrhizal fungi (AMF) require considerable sampling efforts and high-throughput analysis. To facilitate such efforts, we have developed a TaqMan real-time PCR assay to detect and identify AMF in environmental samples. First, we screened the diversity in clone libraries, generated by nested PCR, of the nuclear ribosomal DNA internal transcribed spacer (ITS) of AMF in environmental samples. We then generated probes and forward primers based on the detected sequences, enabling AMF sequence type-specific detection in TaqMan multiplex real-time PCR assays. In comparisons to conventional clone library screening and Sanger sequencing, the TaqMan assay approach provided similar accuracy but higher sensitivity with cost and time savings. The TaqMan assays were applied to analyze the AMF community composition within plots of a large-scale plant biodiversity manipulation experiment, the Jena Experiment, primarily designed to investigate the interactive effects of plant biodiversity on element cycling and trophic interactions. The results show that environmental variables hierarchically shape AMF communities and that the sequence type spectrum is strongly affected by previous land use and disturbance, which appears to favor disturbance-tolerant members of the genus Glomus. The AMF species richness of disturbance-associated communities can be largely explained by richness of plant species and plant functional groups, while plant productivity and soil parameters appear to have only weak effects on the AMF community. PMID:20418424

DNA-encoded chemistry: enabling the deeper sampling of chemical space.

PubMed

Goodnow, Robert A; Dumelin, Christoph E; Keefe, Anthony D

2017-02-01

DNA-encoded chemical library technologies are increasingly being adopted in drug discovery for hit and lead generation. DNA-encoded chemistry enables the exploration of chemical spaces four to five orders of magnitude more deeply than is achievable by traditional high-throughput screening methods. Operation of this technology requires developing a range of capabilities including aqueous synthetic chemistry, building block acquisition, oligonucleotide conjugation, large-scale molecular biological transformations, selection methodologies, PCR, sequencing, sequence data analysis and the analysis of large chemistry spaces. This Review provides an overview of the development and applications of DNA-encoded chemistry, highlighting the challenges and future directions for the use of this technology.

Research on the photoelectric measuring method of warhead fragment velocity

NASA Astrophysics Data System (ADS)

Liu, Ji; Yu, Lixia; Zhang, Bin; Liu, Xiaoyan

2016-09-01

The velocity of warhead fragment is the key criteria to determine its mutilation efficiency. But owing to the small size, larger quantity, irregular shape, high speed, arbitrary direction, large dispersion of warhead fragment and adverse environment, the test of fragment velocity parameter is very difficult. The paper designed an optoelectronic system to measure the average velocity of warhead fragments accurately. The apparatus included two parallel laser screens spaced apart at a known fixed distance for providing time measurement between start and stop signals. The large effective screen area was composed of laser source, retro-reflector and large area photo-diode. Whenever a moving fragment interrupted two optical screens, the system would generate a target signal. Due to partial obscuration of the incident energy and the poor test condition of the explosion, fragment target signal is easily disturbed. Therefore, fragments signal processing technology has become a key technology of the system. The noise of signal was reduced by employing wavelet decomposition and reconstruction. The time of fragment passing though the target was obtained by adopting peak detection algorithm. Based on the method of search peak in different width scale and waveform trend by using optima wavelet, the problem of rolling waveform was solved. Lots of fragments experiments of the different types of the warheads were conducted. Experimental results show that: warhead fragments capture rate of system is better than 98%, which can give velocity of each fragment in the density of less than 20 pieces per m2.

Simulating large atmospheric phase screens using a woofer-tweeter algorithm.

PubMed

Buscher, David F

2016-10-03

We describe an algorithm for simulating atmospheric wavefront perturbations over ranges of spatial and temporal scales spanning more than 4 orders of magnitude. An open-source implementation of the algorithm written in Python can simulate the evolution of the perturbations more than an order-of-magnitude faster than real time. Testing of the implementation using metrics appropriate to adaptive optics systems and long-baseline interferometers show accuracies at the few percent level or better.

Screening of Various Herbicide Modes of Action for Selective Control of Algae Responsible for Harmful Blooms

DTIC Science & Technology

2009-01-01

that have selective activity against harmful algal blooms (HAB). The U.S. Army Corps of Engineers is responsible for managing numerous large reservoirs...systems, some of the enzyme-inhibiting herbicides may be active against algal species responsible for harmful blooms. The U.S. Army Engineer Research...small-scale flask studies to determine if these new chemistries are active against organisms responsible for HAB and if they show potential for

A solid-phase assay for the detection of anti-sperm antibodies.

PubMed

Okada, H; Kamidono, S; Owens, G R; Nagamatsu, G R; Addonizio, J C

1993-05-01

ELISA is an ideal assay method for a large-scale screening of anti-sperm antibodies among a large number of infertile males. However, conventional ELISA with whole spermatozoa needs time-consuming steps of centrifugation. A solid-phase assay used for detecting anti-sperm antibodies was established. This assay is suitable not only for detecting circulating anti-sperm antibodies of IgG, IgM, and IgA subclass simultaneously but also for screening hybridomas secreting anti-sperm monoclonal antibodies (mAbs). The microtiter plates, on which solubilized sperm antigens are fixed, can be stored at -80 degrees C for up to six months without losing reactivity with anti-sperm antibodies. Using this assay, 53 sera (13 were proven positive and 40 were proven negative for sperm agglutination antibody) were tested. Although the false-negative rate was 0%, the false-positive rate was 32%. One thousand one hundred sixty-five supernatants from hybridomas constructed with splenocytes of mice who were hyperimmunized with human sperm and nonsecreting myeloma cells were tested by this solid-phase assay and two anti-sperm mAb secreting clones were selected and established. It is recommended that for research work this assay could be used for the first screening of the hybridoma secreting anti-sperm mAb, and for clinical use this assay might be suitable for the first screening of sera of infertile patients. However, conventional bioassays should follow to confirm the biological meaning of the positivity.

Inference of RhoGAP/GTPase regulation using single-cell morphological data from a combinatorial RNAi screen.

PubMed

Nir, Oaz; Bakal, Chris; Perrimon, Norbert; Berger, Bonnie

2010-03-01

Biological networks are highly complex systems, consisting largely of enzymes that act as molecular switches to activate/inhibit downstream targets via post-translational modification. Computational techniques have been developed to perform signaling network inference using some high-throughput data sources, such as those generated from transcriptional and proteomic studies, but comparable methods have not been developed to use high-content morphological data, which are emerging principally from large-scale RNAi screens, to these ends. Here, we describe a systematic computational framework based on a classification model for identifying genetic interactions using high-dimensional single-cell morphological data from genetic screens, apply it to RhoGAP/GTPase regulation in Drosophila, and evaluate its efficacy. Augmented by knowledge of the basic structure of RhoGAP/GTPase signaling, namely, that GAPs act directly upstream of GTPases, we apply our framework for identifying genetic interactions to predict signaling relationships between these proteins. We find that our method makes mediocre predictions using only RhoGAP single-knockdown morphological data, yet achieves vastly improved accuracy by including original data from a double-knockdown RhoGAP genetic screen, which likely reflects the redundant network structure of RhoGAP/GTPase signaling. We consider other possible methods for inference and show that our primary model outperforms the alternatives. This work demonstrates the fundamental fact that high-throughput morphological data can be used in a systematic, successful fashion to identify genetic interactions and, using additional elementary knowledge of network structure, to infer signaling relations.

Easier Said Than Done: Keys to Successful Implementation of the Distress Assessment and Response Tool (DART) Program.

PubMed

Li, Madeline; Macedo, Alyssa; Crawford, Sean; Bagha, Sabira; Leung, Yvonne W; Zimmermann, Camilla; Fitzgerald, Barbara; Wyatt, Martha; Stuart-McEwan, Terri; Rodin, Gary

2016-05-01

Systematic screening for distress in oncology clinics has gained increasing acceptance as a means to improve cancer care, but its implementation poses enormous challenges. We describe the development and implementation of the Distress Assessment and Response Tool (DART) program in a large urban comprehensive cancer center. DART is an electronic screening tool used to detect physical and emotional distress and practical concerns and is linked to triaged interprofessional collaborative care pathways. The implementation of DART depended on clinician education, technological innovation, transparent communication, and an evaluation framework based on principles of change management and quality improvement. There have been 364,378 DART surveys completed since 2010, with a sustained screening rate of > 70% for the past 3 years. High staff satisfaction, increased perception of teamwork, greater clinical attention to the psychosocial needs of patients, patient-clinician communication, and patient satisfaction with care were demonstrated without a resultant increase in referrals to specialized psychosocial services. DART is now a standard of care for all patients attending the cancer center and a quality performance indicator for the organization. Key factors in the success of DART implementation were the adoption of a programmatic approach, strong institutional commitment, and a primary focus on clinic-based response. We have demonstrated that large-scale routine screening for distress in a cancer center is achievable and has the potential to enhance the cancer care experience for both patients and staff. Copyright © 2016 by American Society of Clinical Oncology.

Improved automatic estimation of winds at the cloud top of Venus using superposition of cross-correlation surfaces

NASA Astrophysics Data System (ADS)

Ikegawa, Shinichi; Horinouchi, Takeshi

2016-06-01

Accurate wind observation is a key to study atmospheric dynamics. A new automated cloud tracking method for the dayside of Venus is proposed and evaluated by using the ultraviolet images obtained by the Venus Monitoring Camera onboard the Venus Express orbiter. It uses multiple images obtained successively over a few hours. Cross-correlations are computed from the pair combinations of the images and are superposed to identify cloud advection. It is shown that the superposition improves the accuracy of velocity estimation and significantly reduces false pattern matches that cause large errors. Two methods to evaluate the accuracy of each of the obtained cloud motion vectors are proposed. One relies on the confidence bounds of cross-correlation with consideration of anisotropic cloud morphology. The other relies on the comparison of two independent estimations obtained by separating the successive images into two groups. The two evaluations can be combined to screen the results. It is shown that the accuracy of the screened vectors are very high to the equatorward of 30 degree, while it is relatively low at higher latitudes. Analysis of them supports the previously reported existence of day-to-day large-scale variability at the cloud deck of Venus, and it further suggests smaller-scale features. The product of this study is expected to advance the dynamics of venusian atmosphere.

Evaluating large-scale propensity score performance through real-world and synthetic data experiments.

PubMed

Tian, Yuxi; Schuemie, Martijn J; Suchard, Marc A

2018-06-22

Propensity score adjustment is a popular approach for confounding control in observational studies. Reliable frameworks are needed to determine relative propensity score performance in large-scale studies, and to establish optimal propensity score model selection methods. We detail a propensity score evaluation framework that includes synthetic and real-world data experiments. Our synthetic experimental design extends the 'plasmode' framework and simulates survival data under known effect sizes, and our real-world experiments use a set of negative control outcomes with presumed null effect sizes. In reproductions of two published cohort studies, we compare two propensity score estimation methods that contrast in their model selection approach: L1-regularized regression that conducts a penalized likelihood regression, and the 'high-dimensional propensity score' (hdPS) that employs a univariate covariate screen. We evaluate methods on a range of outcome-dependent and outcome-independent metrics. L1-regularization propensity score methods achieve superior model fit, covariate balance and negative control bias reduction compared with the hdPS. Simulation results are mixed and fluctuate with simulation parameters, revealing a limitation of simulation under the proportional hazards framework. Including regularization with the hdPS reduces commonly reported non-convergence issues but has little effect on propensity score performance. L1-regularization incorporates all covariates simultaneously into the propensity score model and offers propensity score performance superior to the hdPS marginal screen.

Development of new non-invasive tests for colorectal cancer screening: the relevance of information on adenoma detection.

PubMed

Haug, Ulrike; Knudsen, Amy B; Lansdorp-Vogelaar, Iris; Kuntz, Karen M

2015-06-15

Researchers are actively pursuing the development of a new non-invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers' perspective) for a cohort of US 50-years-old persons to whom CRC screening is offered from age 50-75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70 and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29-44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT's sensitivity for CRC, adherence rates favoring the NIT, and the NIT's unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN-COLON) confirmed the superiority of the immunochemical FOBT over an NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large-scale) evaluation. © 2014 UICC.

Microfluidic glycosyl hydrolase screening for biomass-to-biofuel conversion.

PubMed

Bharadwaj, Rajiv; Chen, Zhiwei; Datta, Supratim; Holmes, Bradley M; Sapra, Rajat; Simmons, Blake A; Adams, Paul D; Singh, Anup K

2010-11-15

The hydrolysis of biomass to fermentable sugars using glycosyl hydrolases such as cellulases and hemicellulases is a limiting and costly step in the conversion of biomass to biofuels. Enhancement in hydrolysis efficiency is necessary and requires improvement in both enzymes and processing strategies. Advances in both areas in turn strongly depend on the progress in developing high-throughput assays to rapidly and quantitatively screen a large number of enzymes and processing conditions. For example, the characterization of various cellodextrins and xylooligomers produced during the time course of saccharification is important in the design of suitable reactors, enzyme cocktail compositions, and biomass pretreatment schemes. We have developed a microfluidic-chip-based assay for rapid and precise characterization of glycans and xylans resulting from biomass hydrolysis. The technique enables multiplexed separation of soluble cellodextrins and xylose oligomers in around 1 min (10-fold faster than HPLC). The microfluidic device was used to elucidate the mode of action of Tm_Cel5A, a novel cellulase from hyperthermophile Thermotoga maritima . The results demonstrate that the cellulase is active at 80 °C and effectively hydrolyzes cellodextrins and ionic-liquid-pretreated switchgrass and Avicel to glucose, cellobiose, and cellotriose. The proposed microscale approach is ideal for quantitative large-scale screening of enzyme libraries for biomass hydrolysis, for development of energy feedstocks, and for polysaccharide sequencing.

Utility and prevalence of imaging for underlying cancer in unprovoked pulmonary embolism.

PubMed

Homewood, R; Medford, A R

2015-01-01

Current guidelines state that patients over 40 years of age with a first unprovoked pulmonary embolism should be offered limited screening for possible cancer and considered for intensive screening (abdomino-pelvic computed tomography and mammography), despite no evidence for the latter. The aim of this study was to evaluate the clinical utility and cost of intensive screening in routine clinical practice. Methods All patients diagnosed with a first unprovoked pulmonary embolism between January 2014 and June 2014 in a single large UK teaching hospital were included. The information management department searched for patients with an International Classification of Diseases 10 discharge diagnosis of pulmonary embolism and limited to 'acute pulmonary embolism with/without cor pulmonale'. Only patients with unprovoked pulmonary embolism were included. Patients with chronic medical conditions predisposing to pulmonary embolism were excluded. NHS costs were obtained from the Trust Finance Department. These costs were used to generate the costs of limited versus intensive screening, and then scaled up using adult population census information and assuming the same incidence of idiopathic pulmonary embolism to estimate the annual NHS cost of intensive screening. Results Ninety-two patients were diagnosed with pulmonary embolism, and 25 met the inclusion criteria. Clinical examination was often incomplete (84%). Limited screening was often missed (urinalysis 100%, serum calcium 64%). Intensive screening was performed in the majority of cases (68%, all abdomino-pelvic computed tomography with no cancer detected) with an £88 excess cost per patient. Conclusion Intensive screening in first unprovoked pulmonary embolism has a low yield, is costly and should not replace thorough clinical examination and basic screening.

The World Health Organization Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale for DSM-5

PubMed Central

Ustun, Berk; Adler, Lenard A.; Rudin, Cynthia; Faraone, Stephen V.; Spencer, Thomas J.; Berglund, Patricia; Gruber, Michael J.

2017-01-01

Importance Recognition that adult attention-deficit/hyperactivity disorder (ADHD) is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD screening scales for use in community, workplace, and primary care settings. However, these scales are all calibrated to DSM-IV criteria, which are narrower than the recently developed DSM-5 criteria. Objectives To update for DSM-5 criteria and improve the operating characteristics of the widely used World Health Organization Adult ADHD Self-Report Scale (ASRS) for screening. Design, Setting, and Participants Probability subsamples of participants in 2 general population surveys (2001-2003 household survey [n = 119] and 2004-2005 managed care subscriber survey [n = 218]) who completed the full 29-question self-report ASRS, with both subsamples over-sampling ASRS-screened positives, were blindly administered a semistructured research diagnostic interview for DSM-5 adult ADHD. In 2016, the Risk-Calibrated Supersparse Linear Integer Model, a novel machine-learning algorithm designed to create screening scales with optimal integer weights and limited numbers of screening questions, was applied to the pooled data to create a DSM-5 version of the ASRS screening scale. The accuracy of the new scale was then confirmed in an independent 2011-2012 clinical sample of patients seeking evaluation at the New York University Langone Medical Center Adult ADHD Program (NYU Langone) and 2015-2016 primary care controls (n = 300). Data analysis was conducted from April 4, 2016, to September 22, 2016. Main Outcomes and Measures The sensitivity, specificity, area under the curve (AUC), and positive predictive value (PPV) of the revised ASRS. Results Of the total 637 participants, 44 (37.0%) household survey respondents, 51 (23.4%) managed care respondents, and 173 (57.7%) NYU Langone respondents met DSM-5 criteria for adult ADHD in the semistructured diagnostic interview. Of the respondents who met DSM-5 criteria for adult ADHD, 123 were male (45.9%); mean (SD) age was 33.1 (11.4) years. A 6-question screening scale was found to be optimal in distinguishing cases from noncases in the first 2 samples. Operating characteristics were excellent at the diagnostic threshold in the weighted (to the 8.2% DSM-5/Adult ADHD Clinical Diagnostic Scale population prevalence) data (sensitivity, 91.4%; specificity, 96.0%; AUC, 0.94; PPV, 67.3%). Operating characteristics were similar despite a much higher prevalence (57.7%) when the scale was applied to the NYU Langone clinical sample (sensitivity, 91.9%; specificity, 74.0%; AUC, 0.83; PPV, 82.8%). Conclusions and Relevance The new ADHD screening scale is short, easily scored, detects the vast majority of general population cases at a threshold that also has high specificity and PPV, and could be used as a screening tool in specialty treatment settings. PMID:28384801

The effect of Interaction Anxiousness Scale and Brief Social Phobia Scale for screening social anxiety disorder in college students: a study on discriminative validity.

PubMed

Cao, Jianqin; Yang, Jinwei; Zhou, Yuqiu; Chu, Fuliu; Zhao, Xiwu; Wang, Weiren; Wang, Yunlong; Peng, Tao

2016-12-01

Social anxiety disorder (SAD) is one of the most prevalent mental health problems, but there is little research concerning the effective screening instruments in practice. This study was designed to examine the discriminative validity of Interaction Anxiousness Scale (IAS) and Brief Social Phobia Scale (BSPS) for the screening of SAD through the compared and combined analysis. Firstly, 421 Chinese undergraduates were screened by the IAS and BSPS. Secondly, in the follow-up stage, 248 students were interviewed by the Structured Clinical Interview for DSM-IV. Receiver operating characteristic (ROC) analysis was used, and the related psychometric characters were checked. The results indicated that the ROC in these two scales demonstrated discrimination is in satisfactory level (range: 0.7-0.8). However, the highest agreement (92.17%) was identified when a cut-off point of 50 measured by the IAS and a cut-off point of 34 by the BSPS were combined, also with higher PPV, SENS, SPEC and OA than that reached when BSPS was used individually, as well as PPV, SPEC and OA in IAS. The findings indicate that the combination of these two scales is valid as the general screening instrument for SAD in maximizing the discriminative validity.

Evaluating training of screening, brief intervention, and referral to treatment (SBIRT) for substance use: Reliability of the MD3 SBIRT Coding Scale.

PubMed

DiClemente, Carlo C; Crouch, Taylor Berens; Norwood, Amber E Q; Delahanty, Janine; Welsh, Christopher

2015-03-01

Screening, brief intervention, and referral to treatment (SBIRT) has become an empirically supported and widely implemented approach in primary and specialty care for addressing substance misuse. Accordingly, training of providers in SBIRT has increased exponentially in recent years. However, the quality and fidelity of training programs and subsequent interventions are largely unknown because of the lack of SBIRT-specific evaluation tools. The purpose of this study was to create a coding scale to assess quality and fidelity of SBIRT interactions addressing alcohol, tobacco, illicit drugs, and prescription medication misuse. The scale was developed to evaluate performance in an SBIRT residency training program. Scale development was based on training protocol and competencies with consultation from Motivational Interviewing coding experts. Trained medical residents practiced SBIRT with standardized patients during 10- to 15-min videotaped interactions. This study included 25 tapes from the Family Medicine program coded by 3 unique coder pairs with varying levels of coding experience. Interrater reliability was assessed for overall scale components and individual items via intraclass correlation coefficients. Coder pair-specific reliability was also assessed. Interrater reliability was excellent overall for the scale components (>.85) and nearly all items. Reliability was higher for more experienced coders, though still adequate for the trained coder pair. Descriptive data demonstrated a broad range of adherence and skills. Subscale correlations supported concurrent and discriminant validity. Data provide evidence that the MD3 SBIRT Coding Scale is a psychometrically reliable coding system for evaluating SBIRT interactions and can be used to evaluate implementation skills for fidelity, training, assessment, and research. Recommendations for refinement and further testing of the measure are discussed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

An effective method to screen sodium-based layered materials for sodium ion batteries

NASA Astrophysics Data System (ADS)

Zhang, Xu; Zhang, Zihe; Yao, Sai; Chen, An; Zhao, Xudong; Zhou, Zhen

2018-03-01

Due to the high cost and insufficient resource of lithium, sodium-ion batteries are widely investigated for large-scale applications. Typically, insertion-type materials possess better cyclic stability than alloy-type and conversion-type ones. Therefore, in this work, we proposed a facile and effective method to screen sodium-based layered materials based on Materials Project database as potential candidate insertion-type materials for sodium ion batteries. The obtained Na-based layered materials contains 38 kinds of space group, which reveals that the credibility of our screening approach would not be affected by the space group. Then, some important indexes of the representative materials, including the average voltage, volume change and sodium ion mobility, were further studied by means of density functional theory computations. Some materials with extremely low volume changes and Na diffusion barriers are promising candidates for sodium ion batteries. We believe that our classification algorithm could also be used to search for other alkali and multivalent ion-based layered materials, to accelerate the development of battery materials.

Expert Opinion Editorial Tissue Engineered Blood Vessels as Promising Tools for Testing Drug Toxicity

PubMed Central

Truskey, George A.; Fernandez, Cristina E.

2015-01-01

Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in rodents and some larger animals, primarily with drugs affecting vascular tone, but not in humans; however, DIVI observed in animal studies often precludes a drug candidate from continuing along the development pipeline. Thus, there is great interest by the pharmaceutical industry to identify quantifiable human biomarkers of DIVI. Small scale endothelialized tissue-engineered blood vessels using human cells represent a promising approach to screen drug candidates and developed alternatives to cancer therapeutics in vitro. We identify several technical challenges that remain to be addressed, including high throughput systems to screen large numbers of candidates, identification of suitable cell sources, and establishing and maintaining a differentiated state of the vessel wall cells. Adequately addressing these challenges should yield novel platforms to screen drugs and develop new therapeutics to treat cardiovascular disease. PMID:26028128

Drosophila as a screening tool to study human neurodegenerative diseases.

PubMed

Lenz, Sarah; Karsten, Peter; Schulz, Jörg B; Voigt, Aaron

2013-11-01

In an aging society, research involving neurodegenerative disorders is of paramount importance. Over the past few years, research on Alzheimer's and Parkinson's diseases has made tremendous progress. Experimental studies, however, rely mostly on transgenic animal models, preferentially using mice. Although experiments on mice have enormous advantages, they also have some inherent limitations, some of which can be overcome by the use of Drosophila melanogaster as an experimental animal. Among the major advantages of using the fly is its small genome, which can also be modified very easily. The fact that its genome lends itself to diverse alterations (e. g. mutagenesis, transposons) has made the fly a useful organism to perform large-scale and genome-wide screening approaches. This has opened up an entirely new field of experimental research aiming to elucidate genetic interactions and screen for modifiers of disease processes in vivo. Here, we provide a brief overview of how flies can be used to analyze molecular mechanisms underlying human neurodegenerative diseases. © 2013 International Society for Neurochemistry.

A cloud-based system for automatic glaucoma screening.

PubMed

Fengshou Yin; Damon Wing Kee Wong; Ying Quan; Ai Ping Yow; Ngan Meng Tan; Gopalakrishnan, Kavitha; Beng Hai Lee; Yanwu Xu; Zhuo Zhang; Jun Cheng; Jiang Liu

2015-08-01

In recent years, there has been increasing interest in the use of automatic computer-based systems for the detection of eye diseases including glaucoma. However, these systems are usually standalone software with basic functions only, limiting their usage in a large scale. In this paper, we introduce an online cloud-based system for automatic glaucoma screening through the use of medical image-based pattern classification technologies. It is designed in a hybrid cloud pattern to offer both accessibility and enhanced security. Raw data including patient's medical condition and fundus image, and resultant medical reports are collected and distributed through the public cloud tier. In the private cloud tier, automatic analysis and assessment of colour retinal fundus images are performed. The ubiquitous anywhere access nature of the system through the cloud platform facilitates a more efficient and cost-effective means of glaucoma screening, allowing the disease to be detected earlier and enabling early intervention for more efficient intervention and disease management.

Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

PubMed

Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

2016-08-18

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

PubMed Central

Potter, Paul K.; Bowl, Michael R.; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E.; Simon, Michelle M.; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V.; Law, Gemma; MacLaren, Robert E.; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H.; Foster, Russell G.; Jackson, Ian J.; Peirson, Stuart N.; Thakker, Rajesh V.; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M.; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D. M.

2016-01-01

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

An automated compound screening for anti-aging effects on the function of C. elegans sensory neurons.

PubMed

Bazopoulou, Daphne; Chaudhury, Amrita R; Pantazis, Alexandros; Chronis, Nikos

2017-08-24

Discovery of molecular targets or compounds that alter neuronal function can lead to therapeutic advances that ameliorate age-related neurodegenerative pathologies. Currently, there is a lack of in vivo screening technologies for the discovery of compounds that affect the age-dependent neuronal physiology. Here, we present a high-throughput, microfluidic-based assay for automated manipulation and on-chip monitoring and analysis of stimulus-evoked calcium responses of intact C. elegans at various life stages. First, we successfully applied our technology to quantify the effects of aging and age-related genetic and chemical factors in the calcium transients of the ASH sensory neuron. We then performed a large-scale screen of a library of 107 FDA-approved compounds to identify hits that prevented the age-dependent functional deterioration of ASH. The robust performance of our assay makes it a valuable tool for future high-throughput applications based on in vivo functional imaging.

In silico screening of drug-membrane thermodynamics reveals linear relations between bulk partitioning and the potential of mean force

NASA Astrophysics Data System (ADS)

Menichetti, Roberto; Kanekal, Kiran H.; Kremer, Kurt; Bereau, Tristan

2017-09-01

The partitioning of small molecules in cell membranes—a key parameter for pharmaceutical applications—typically relies on experimentally available bulk partitioning coefficients. Computer simulations provide a structural resolution of the insertion thermodynamics via the potential of mean force but require significant sampling at the atomistic level. Here, we introduce high-throughput coarse-grained molecular dynamics simulations to screen thermodynamic properties. This application of physics-based models in a large-scale study of small molecules establishes linear relationships between partitioning coefficients and key features of the potential of mean force. This allows us to predict the structure of the insertion from bulk experimental measurements for more than 400 000 compounds. The potential of mean force hereby becomes an easily accessible quantity—already recognized for its high predictability of certain properties, e.g., passive permeation. Further, we demonstrate how coarse graining helps reduce the size of chemical space, enabling a hierarchical approach to screening small molecules.

Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds.

PubMed

de-Souza-Silva, Calliandra Maria; Guilhelmelli, Fernanda; Zamith-Miranda, Daniel; de Oliveira, Marco Antônio; Nosanchuk, Joshua Daniel; Silva-Pereira, Ildinete; Albuquerque, Patrícia

2018-02-14

Fungal infections have become an important medical condition in the last decades, but the number of available antifungal drugs is limited. In this scenario, the search for new antifungal drugs is necessary. The protocol reported here details a method to screen peptides for their antifungal properties. It is based on the broth microdilution susceptibility test from the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines with modifications to suit the research of antimicrobial peptides as potential new antifungals. This protocol describes a functional assay to evaluate the activity of antifungal compounds and may be easily modified to suit any particular class of molecules under investigation. Since the assays are performed in 96-well plates using small volumes, a large-scale screening can be completed in a short amount of time, especially if carried out in an automation setting. This procedure illustrates how a standardized and adjustable clinical protocol can help the bench-work pursuit of new molecules to improve the therapy of fungal diseases.

Implementing Routine Health Literacy Assessment in Hospital and Primary Care Patients

PubMed Central

Cawthon, Courtney; Mion, Lorraine C.; Willens, David E.; Roumie, Christianne L.; Kripalani, Sunil

2014-01-01

Background Patients with inadequate health literacy often have poorer health outcomes and increased utilization and costs, compared to those with adequate health literacy skills. The Institute of Medicine has recommended that health literacy assessment be incorporated into health care information systems, which would facilitate large-scale studies of the effects of health literacy, as well as evaluation of system interventions to improve care by addressing health literacy. As part of the Health Literacy Screening (HEALS) study, a brief health literacy screen (BHLS) was incorporated into the electronic health record (EHR) at a large academic medical center. Methods Changes were implemented to the nursing intake documentation across all adult hospital units, the emergency department, and three primary care practices. The change involved replacing previous education screening items with the BHLS. Implementation was based on a quality improvement framework, with a focus on acceptability, adoption, appropriateness, feasibility, fidelity and sustainability. Support was gained from nursing leadership, education and training was provided, a documentation change was rolled out, feedback was obtained, and uptake of the new health literacy screening items was monitored. Results Between November 2010 and April 2012, there were 55,611 adult inpatient admissions, and from November 2010 to September 2011, 23,186 adult patients made 39,595 clinic visits to the three primary care practices. The completion (uptake) rate in the hospital for November 2010 through April 2012 was 91.8%. For outpatient clinics, the completion rate between November 2010 and October 2011 was 66.6%. Conclusions Although challenges exist, it is feasible to incorporate health literacy screening into clinical assessment and EHR documentation. Next steps are to evaluate the association of health literacy with processes and outcomes of care across inpatient and outpatient populations. PMID:24716329

Economies of scale in federally-funded state-organized public health programs: results from the National Breast and Cervical Cancer Early Detection Programs

PubMed Central

Trogdon, Justin G.; Subramanian, Sujha; Crouse, Wesley

2018-01-01

This study investigates the existence of economies of scale in the provision of breast and cervical cancer screening and diagnostic services by state National Breast and Cervical Cancer Early Detection Program (NBCCEDP) grantees. A translog cost function is estimated as a system with input factor share equations. The estimated cost function is then used to determine output levels for which average costs are decreasing (i.e., economies of scale exist). Data were collected from all state NBCCEDP programs and District of Columbia for program years 2006–2007, 2008–2009 and 2009–2010 (N =147). Costs included all programmatic and in-kind contributions from federal and non-federal sources, allocated to breast and cervical cancer screening activities. Output was measured by women served, women screened and cancers detected, separately by breast and cervical services for each measure. Inputs included labor, rent and utilities, clinical services, and quasi-fixed factors (e.g., percent of women eligible for screening by the NBCCEDP). 144 out of 147 program-years demonstrated significant economies of scale for women served and women screened; 136 out of 145 program-years displayed significant economies of scale for cancers detected. The cost data were self-reported by the NBCCEDP State programs. Quasi-fixed inputs were allowed to affect costs but not economies of scale or the share equations. The main analysis accounted for clustering of observations within State programs, but it did not make full use of the panel data. The average cost of providing breast and cervical cancer screening services decreases as the number of women screened and served increases. PMID:24326873

Screening for Depressive Disorders Using the Mood and Anxiety Symptoms Questionnaire Anhedonic Depression Scale: A Receiver-Operating Characteristic Analysis

ERIC Educational Resources Information Center

Bredemeier, Keith; Spielberg, Jeffery M.; Silton, Rebecca Levin; Berenbaum, Howard; Heller, Wendy; Miller, Gregory A.

2010-01-01

The present study examined the utility of the anhedonic depression scale from the Mood and Anxiety Symptoms Questionnaire (MASQ-AD scale) as a way to screen for depressive disorders. Using receiver-operating characteristic analysis, we examined the sensitivity and specificity of the full 22-item MASQ-AD scale, as well as the 8- and 14-item…

Systematic Screening at the Middle School Level: Score Reliability and Validity of the Student Risk Screening Scale

ERIC Educational Resources Information Center

Lane, Kathleen Lynne; Parks, Robin J.; Kalberg, Jemma Robertson; Carter, Erik W.

2007-01-01

This article presents findings of two studies, one conducted with middle school students (n = 500) in a rural setting and a second conducted with middle school students (n = 528) in an urban setting, of the reliability and validity of the "Student Risk Screening Scale" (SRSS; Drummond, 1994). Results revealed high internal consistency, test-retest…

Interpretation of Errors Made by Mandarin-Speaking Children on the Preschool Language Scales--5th Edition Screening Test

ERIC Educational Resources Information Center

Ren, Yonggang; Rattanasone, Nan Xu; Wyver, Shirley; Hinton, Amber; Demuth, Katherine

2016-01-01

We investigated typical errors made by Mandarin-speaking children when measured by the Preschool Language Scales-fifth edition, Screening Test (PLS-5 Screening Test). The intention was to provide preliminary data for the development of a guideline for early childhood educators and psychologists who use the test with Mandarin-speaking children.…

Clinical utility of the brunel mood scale in screening for post-traumatic stress risk in a military population.

PubMed

van Wijk, Charles H; Martin, Jarred H; Hans-Arendse, Chesray

2013-04-01

Measures of mood states and post-traumatic stress (PTS) symptoms are commonplace in many studies. However, the conventional application of these measures conjointly raises questions whether they actually correlate, and whether mood states have a meaningful role in predicting PTS symptoms. This study aimed to assess the degree to which the Brunel Mood Scale (BRUMS) and the Impact of Event Scale-Revised (IES-R) would be useful in detecting adverse psychological experiences (e.g., PTS). A sample of South African Navy sailors (N = 103) completed the BRUMS during demobilization after a traumatic deployment, and 6 weeks later completed a repeat BRUMS and the IES-R. Significant correlations were found between some BRUMS and IES-R subscales, but the lack of other subscale correlations indicates that the two measures probably tap different expressions of psychological distress following exposure to adverse events. Greater mood distress correlated with more severe PTS. A BRUMS total mood distress score cutoff of ≥24 gave a sensitivity of 100% and specificity of 79% for severe PTS 6 weeks later. Using a BRUMS score of ≥24 at demobilization to assess for possible elevated PTS response later could be useful in the screening of large groups of people. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

Psychometric properties of responses by clinicians and older adults to a 6-item Hebrew version of the Hamilton Depression Rating Scale (HAM-D6)

PubMed Central

2013-01-01

Background The Hamilton Depression Rating Scale (HAM-D) is commonly used as a screening instrument, as a continuous measure of change in depressive symptoms over time, and as a means to compare the relative efficacy of treatments. Among several abridged versions, the 6-item HAM-D6 is used most widely in large degree because of its good psychometric properties. The current study compares both self-report and clinician-rated versions of the Hebrew version of this scale. Methods A total of 153 Israelis 75 years of age on average participated in this study. The HAM-D6 was examined using confirmatory factor analytic (CFA) models separately for both patient and clinician responses. Results Reponses to the HAM-D6 suggest that this instrument measures a unidimensional construct with each of the scales’ six items contributing significantly to the measurement. Comparisons between self-report and clinician versions indicate that responses do not significantly differ for 4 of the 6 items. Moreover, 100% sensitivity (and 91% specificity) was found between patient HAM-D6 responses and clinician diagnoses of depression. Conclusion These results indicate that the Hebrew HAM-D6 can be used to measure and screen for depressive symptoms among elderly patients. PMID:23281688

Development of a Climate Resilience Screening Index (CRSI) and its potential for application in the U.S. - Conference Abstract

EPA Science Inventory

A Climate Resilience Screening Index is being developed that is applicable at multiple scales for the United States. Those scales include national, state, county and community. The index will be applied at the first three scales and at selected communities. The index was devel...

Development of a Climate Resilience Screening Index (CRSI) and its potential for application in the U.S.

EPA Science Inventory

A Climate Resilience Screening Index is being developed that is applicable at multiple scales for the United States. Those scales include national, state, county and community. The index will be applied at the first three scales and at selected communities. The index was devel...

Screening Women Aged 50-59 for CRC Using Fecal Occult Blood Test Produces Outcomes Similar to Men Undergoing Screening Colonoscopy.

PubMed

Mooers, Harrison M; Holub, Jennifer L; Lieberman, David A

2018-06-13

Average-risk women aged 50-59 years have a lower incidence and mortality of colorectal cancer relative to age-matched men, calling into question the benefit of screening colonoscopy in this age group. We aimed to determine whether FOBT is an effective initial screening test in 50-59-year-old women. We conducted a cross-sectional study using a computerized endoscopic report generator. We identified 320,906 individuals who had average-risk screening colonoscopy and 32,369 who had colonoscopy for positive FOBT. The primary outcome was the positive predictive value (PPV) of FOBT for large polyp(s) greater than 9 mm, as a surrogate for advanced neoplasia. Among patients aged 50-59 years undergoing screening colonoscopy, men were more likely than women to have large polyps (6.3 vs 4.2%, p < 0.0001). Black women undergoing screening colonoscopy had higher rates of large polyps compared to non-Black women. The PPV in FOBT-positive men aged 50-54 (11.5%) and 55-59 (14.4%) was higher than in women aged 50-54 (6.1%) and 55-59 (5.4%). Despite this lower PPV, women aged 50-54 with a positive FOBT had a similar rate of large polyps as 50-54-year-old men undergoing screening colonoscopy (6.1 vs 6.3%, p = 0.626). CRC screening with FOBT identifies 50-59-year-old men and women with a higher risk of large polyps. Since younger women have a lower risk of large polyps than men, screening with FOBT in 50-59-year-old non-Black women could be an effective screening strategy, with outcomes similar to the use of screening colonoscopy in 50-59-year-old men.

Screening for depressive disorders using the Mood and Anxiety Symptoms Questionnaire Anhedonic Depression Scale: a receiver-operating characteristic analysis.

PubMed

Bredemeier, Keith; Spielberg, Jeffery M; Silton, Rebecca Levin; Berenbaum, Howard; Heller, Wendy; Miller, Gregory A

2010-09-01

The present study examined the utility of the anhedonic depression scale from the Mood and Anxiety Symptoms Questionnaire (MASQ-AD scale) as a way to screen for depressive disorders. Using receiver-operating characteristic analysis, we examined the sensitivity and specificity of the full 22-item MASQ-AD scale, as well as the 8- and 14-item subscales, in relation to both current and lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.) depressive disorder diagnoses in two nonpatient samples. As a means of comparison, the sensitivity and specificity of a measure of a relevant personality dimension, Neuroticism, was also examined. Results from both samples support the clinical utility of the MASQ-AD scale as a means of screening for depressive disorders. Findings were strongest for the MASQ-AD 8-item subscale and when predicting current depression status. Furthermore, the MASQ-AD 8-item subscale outperformed the Neuroticism measure under certain conditions. The overall usefulness of the MASQ-AD scale as a screening device is discussed, as are possible cutoff scores for use in research.

Screen time is associated with depression and anxiety in Canadian youth.

PubMed

Maras, Danijela; Flament, Martine F; Murray, Marisa; Buchholz, Annick; Henderson, Katherine A; Obeid, Nicole; Goldfield, Gary S

2015-04-01

This study examined the relationships between screen time and symptoms of depression and anxiety in a large community sample of Canadian youth. Participants were 2482 English-speaking grade 7 to 12 students. Cross-sectional data collected between 2006 and 2010 as part of the Research on Eating and Adolescent Lifestyles (REAL) study were used. Mental health status was assessed using the Children's Depression Inventory and the Multidimensional Anxiety Scale for Children-10. Screen time (hours/day of TV, video games, and computer) was assessed using the Leisure-Time Sedentary Activities questionnaire. Linear multiple regressions indicated that after controlling for age, sex, ethnicity, parental education, geographic area, physical activity, and BMI, duration of screen time was associated with severity of depression (β=0.23, p<0.001) and anxiety (β=0.07, p<0.01). Video game playing (β=0.13, p<.001) and computer use (β=0.17, p<0.001) but not TV viewing were associated with more severe depressive symptoms. Video game playing (β=0.11, p<0.001) was associated with severity of anxiety. Screen time may represent a risk factor or marker of anxiety and depression in adolescents. Future research is needed to determine if reducing screen time aids the prevention and treatment of these psychiatric disorders in youth. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Ultra High Throughput Screening of Natural Product Extracts to Identify Pro-apoptotic Inhibitors of Bcl-2 Family Proteins

PubMed Central

Hassig, Christian A.; Zeng, Fu-Yue; Kung, Paul; Kiankarimi, Mehrak; Kim, Sylvia; Diaz, Paul W.; Zhai, Dayong; Welsh, Kate; Morshedian, Shana; Su, Ying; O'Keefe, Barry; Newman, David J.; Rusman, Yudi; Kaur, Harneet; Salomon, Christine E.; Brown, Susan G.; Baire, Beeraiah; Michel, Andrew R.; Hoye, Thomas R.; Francis, Subhashree; Georg, Gunda I.; Walters, Michael A.; Divlianska, Daniela B.; Roth, Gregory P.; Wright, Amy E.; Reed, John C.

2015-01-01

Anti-apoptotic Bcl-2 family proteins are validated cancer targets comprised of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). While several isoform-selective inhibitors have been developed using structure-based design or high throughput screening (HTS) of synthetic chemical libraries, no large scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six anti-apoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally-relevant PPIs. The screens were conducted in 1,536-well format and displayed satisfactory overall HTS statistics, with Z’-factor values ranging from 0.72 to 0.83, and a hit confirmation rate between 16-64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra high throughput screening using natural product sources and highlight some of the challenges associated with this approach. PMID:24870016

Lung cancer risk prediction to select smokers for screening CT--a model based on the Italian COSMOS trial.

PubMed

Maisonneuve, Patrick; Bagnardi, Vincenzo; Bellomi, Massimo; Spaggiari, Lorenzo; Pelosi, Giuseppe; Rampinelli, Cristiano; Bertolotti, Raffaella; Rotmensz, Nicole; Field, John K; Decensi, Andrea; Veronesi, Giulia

2011-11-01

Screening with low-dose helical computed tomography (CT) has been shown to significantly reduce lung cancer mortality but the optimal target population and time interval to subsequent screening are yet to be defined. We developed two models to stratify individual smokers according to risk of developing lung cancer. We first used the number of lung cancers detected at baseline screening CT in the 5,203 asymptomatic participants of the COSMOS trial to recalibrate the Bach model, which we propose using to select smokers for screening. Next, we incorporated lung nodule characteristics and presence of emphysema identified at baseline CT into the Bach model and proposed the resulting multivariable model to predict lung cancer risk in screened smokers after baseline CT. Age and smoking exposure were the main determinants of lung cancer risk. The recalibrated Bach model accurately predicted lung cancers detected during the first year of screening. Presence of nonsolid nodules (RR = 10.1, 95% CI = 5.57-18.5), nodule size more than 8 mm (RR = 9.89, 95% CI = 5.84-16.8), and emphysema (RR = 2.36, 95% CI = 1.59-3.49) at baseline CT were all significant predictors of subsequent lung cancers. Incorporation of these variables into the Bach model increased the predictive value of the multivariable model (c-index = 0.759, internal validation). The recalibrated Bach model seems suitable for selecting the higher risk population for recruitment for large-scale CT screening. The Bach model incorporating CT findings at baseline screening could help defining the time interval to subsequent screening in individual participants. Further studies are necessary to validate these models.

The Bergen Shopping Addiction Scale: reliability and validity of a brief screening test.

PubMed

Andreassen, Cecilie S; Griffiths, Mark D; Pallesen, Ståle; Bilder, Robert M; Torsheim, Torbjørn; Aboujaoude, Elias

2015-01-01

Although excessive and compulsive shopping has been increasingly placed within the behavioral addiction paradigm in recent years, items in existing screens arguably do not assess the core criteria and components of addiction. To date, assessment screens for shopping disorders have primarily been rooted within the impulse-control or obsessive-compulsive disorder paradigms. Furthermore, existing screens use the terms 'shopping,' 'buying,' and 'spending' interchangeably, and do not necessarily reflect contemporary shopping habits. Consequently, a new screening tool for assessing shopping addiction was developed. Initially, 28 items, four for each of seven addiction criteria (salience, mood modification, conflict, tolerance, withdrawal, relapse, and problems), were constructed. These items and validated scales (i.e., Compulsive Buying Measurement Scale, Mini-International Personality Item Pool, Hospital Anxiety and Depression Scale, Rosenberg Self-Esteem Scale) were then administered to 23,537 participants (M age = 35.8 years, SD age = 13.3). The highest loading item from each set of four pooled items reflecting the seven addiction criteria were retained in the final scale, The Bergen Shopping Addiction Scale (BSAS). The factor structure of the BSAS was good (RMSEA = 0.064, CFI = 0.983, TLI = 0.973) and coefficient alpha was 0.87. The scores on the BSAS converged with scores on the Compulsive Buying Measurement Scale (CBMS; 0.80), and were positively correlated with extroversion and neuroticism, and negatively with conscientiousness, agreeableness, and intellect/imagination. The scores of the BSAS were positively associated with anxiety, depression, and low self-esteem and inversely related to age. Females scored higher than males on the BSAS. The BSAS is the first scale to fully embed shopping addiction within an addiction paradigm. A recommended cutoff score for the new scale and future research directions are discussed.

The Bergen Shopping Addiction Scale: reliability and validity of a brief screening test

PubMed Central

Andreassen, Cecilie S.; Griffiths, Mark D.; Pallesen, Ståle; Bilder, Robert M.; Torsheim, Torbjørn; Aboujaoude, Elias

2015-01-01

Although excessive and compulsive shopping has been increasingly placed within the behavioral addiction paradigm in recent years, items in existing screens arguably do not assess the core criteria and components of addiction. To date, assessment screens for shopping disorders have primarily been rooted within the impulse-control or obsessive-compulsive disorder paradigms. Furthermore, existing screens use the terms ‘shopping,’ ‘buying,’ and ‘spending’ interchangeably, and do not necessarily reflect contemporary shopping habits. Consequently, a new screening tool for assessing shopping addiction was developed. Initially, 28 items, four for each of seven addiction criteria (salience, mood modification, conflict, tolerance, withdrawal, relapse, and problems), were constructed. These items and validated scales (i.e., Compulsive Buying Measurement Scale, Mini-International Personality Item Pool, Hospital Anxiety and Depression Scale, Rosenberg Self-Esteem Scale) were then administered to 23,537 participants (Mage = 35.8 years, SDage = 13.3). The highest loading item from each set of four pooled items reflecting the seven addiction criteria were retained in the final scale, The Bergen Shopping Addiction Scale (BSAS). The factor structure of the BSAS was good (RMSEA = 0.064, CFI = 0.983, TLI = 0.973) and coefficient alpha was 0.87. The scores on the BSAS converged with scores on the Compulsive Buying Measurement Scale (CBMS; 0.80), and were positively correlated with extroversion and neuroticism, and negatively with conscientiousness, agreeableness, and intellect/imagination. The scores of the BSAS were positively associated with anxiety, depression, and low self-esteem and inversely related to age. Females scored higher than males on the BSAS. The BSAS is the first scale to fully embed shopping addiction within an addiction paradigm. A recommended cutoff score for the new scale and future research directions are discussed. PMID:26441749

Active Learning Strategies for Phenotypic Profiling of High-Content Screens.

PubMed

Smith, Kevin; Horvath, Peter

2014-06-01

High-content screening is a powerful method to discover new drugs and carry out basic biological research. Increasingly, high-content screens have come to rely on supervised machine learning (SML) to perform automatic phenotypic classification as an essential step of the analysis. However, this comes at a cost, namely, the labeled examples required to train the predictive model. Classification performance increases with the number of labeled examples, and because labeling examples demands time from an expert, the training process represents a significant time investment. Active learning strategies attempt to overcome this bottleneck by presenting the most relevant examples to the annotator, thereby achieving high accuracy while minimizing the cost of obtaining labeled data. In this article, we investigate the impact of active learning on single-cell-based phenotype recognition, using data from three large-scale RNA interference high-content screens representing diverse phenotypic profiling problems. We consider several combinations of active learning strategies and popular SML methods. Our results show that active learning significantly reduces the time cost and can be used to reveal the same phenotypic targets identified using SML. We also identify combinations of active learning strategies and SML methods which perform better than others on the phenotypic profiling problems we studied. © 2014 Society for Laboratory Automation and Screening.

Application of Titration-Based Screening for the Rapid Pilot Testing of High-Throughput Assays.

PubMed

Zhang, Ji-Hu; Kang, Zhao B; Ardayfio, Ophelia; Ho, Pei-i; Smith, Thomas; Wallace, Iain; Bowes, Scott; Hill, W Adam; Auld, Douglas S

2014-06-01

Pilot testing of an assay intended for high-throughput screening (HTS) with small compound sets is a necessary but often time-consuming step in the validation of an assay protocol. When the initial testing concentration is less than optimal, this can involve iterative testing at different concentrations to further evaluate the pilot outcome, which can be even more time-consuming. Quantitative HTS (qHTS) enables flexible and rapid collection of assay performance statistics, hits at different concentrations, and concentration-response curves in a single experiment. Here we describe the qHTS process for pilot testing in which eight-point concentration-response curves are produced using an interplate asymmetric dilution protocol in which the first four concentrations are used to represent the range of typical HTS screening concentrations and the last four concentrations are added for robust curve fitting to determine potency/efficacy values. We also describe how these data can be analyzed to predict the frequency of false-positives, false-negatives, hit rates, and confirmation rates for the HTS process as a function of screening concentration. By taking into account the compound pharmacology, this pilot-testing paradigm enables rapid assessment of the assay performance and choosing the optimal concentration for the large-scale HTS in one experiment. © 2013 Society for Laboratory Automation and Screening.

[Application of health questionnaires for health management in small- and medium-sized enterprises].

PubMed

Kishida, K; Saito, M; Hasegawa, T; Aoki, S; Suzuki, S

1986-01-01

Two kinds of health questionnaires, the Todai Health Index (THI) and Cumulative Fatigue Index (CFI), were applied as a screening device for health management of workers belonging to small-medium sized enterprises. A total of 495 workers composed of 452 male workers of a glass-bottle manufacturing factory and 43 male workers of a soft-drink bottling factory were the subjects of the present study. It was found that the two kinds of health questionnaires were different from each other and have their own characteristics. Twelve scales of THI were grouped into two, the first consisting of ten scales (SUSY, RESP, EYSK, MOUT, DIGE, IMPU, MENT, DEPR, NERV, and LIFE) and the second consisting of two scales (AGGR and LISC). Nine categories of CFI were grouped into one by using principal factor analysis. It was confirmed that the twelve scale scores of THI obtained at small-medium sized factories differed from those scale scores of a reference group investigated at a large-sized enterprise. It is on the basis of the scales of aggressiveness and lies and also of the scale of mental unstability which characterizes workers, locality, job (clerical or field work), and size of industry (large or small sized) that the difference could be evaluated. Urban life characterized by a life style of staying up late at night and waking up late in the morning has been reflected on the scale of life irregularity. Irregularity of life induced by transformation of working schedule, such as two or three shifts of work and overtime, was also reflected on this scale. Two scales of THI test, i.e., many subjective symptoms and digestive organ complaints, seemed to be the representative scales indicating a close relation between work load and health level. The discriminant score for diagnosis of psychosomatic diseases is considered to be one of the most useful assessments of the individual's health condition. As mentioned above, THI is recommended as a convenient assessment method for health management of workers and for screening individuals or groups requiring health management from the total respondents belonging to small-medium sized enterprises where health administrators or professionals for health services are not available. A combined use of THI and CFI is more effective in evaluating health status of field workers than the independent use of one of these two tests, because the causal relationship between work load and health status cannot be satisfactorily observed, only through THI.

Using pre-screening methods for an effective and reliable site characterization at megasites.

PubMed

Algreen, Mette; Kalisz, Mariusz; Stalder, Marcel; Martac, Eugeniu; Krupanek, Janusz; Trapp, Stefan; Bartke, Stephan

2015-10-01

This paper illustrates the usefulness of pre-screening methods for an effective characterization of polluted sites. We applied a sequence of site characterization methods to a former Soviet military airbase with likely fuel and benzene, toluene, ethylbenzene, and xylene (BTEX) contamination in shallow groundwater and subsoil. The methods were (i) phytoscreening with tree cores; (ii) soil gas measurements for CH4, O2, and photoionization detector (PID); (iii) direct-push with membrane interface probe (MIP) and laser-induced fluorescence (LIF) sensors; (iv) direct-push sampling; and (v) sampling from soil and from groundwater monitoring wells. Phytoscreening and soil gas measurements are rapid and inexpensive pre-screening methods. Both indicated subsurface pollution and hot spots successfully. The direct-push sensors yielded 3D information about the extension and the volume of the subsurface plume. This study also expanded the applicability of tree coring to BTEX compounds and tested the use of high-resolution direct-push sensors for light hydrocarbons. Comparison of screening results to results from conventional soil and groundwater sampling yielded in most cases high rank correlation and confirmed the findings. The large-scale application of non- or low-invasive pre-screening can be of help in directing and focusing the subsequent, more expensive investigation methods. The rapid pre-screening methods also yielded useful information about potential remediation methods. Overall, we see several benefits of a stepwise screening and site characterization scheme, which we propose in conclusion.

Exploiting PubChem for Virtual Screening

PubMed Central

Xie, Xiang-Qun

2011-01-01

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. PMID:21691435

Microcarrier-based platforms for in vitro expansion and differentiation of human pluripotent stem cells in bioreactor culture systems.

PubMed

Badenes, Sara M; Fernandes, Tiago G; Rodrigues, Carlos A V; Diogo, Maria Margarida; Cabral, Joaquim M S

2016-09-20

Human pluripotent stem cells (hPSC) have attracted a great attention as an unlimited source of cells for cell therapies and other in vitro biomedical applications such as drug screening, toxicology assays and disease modeling. The implementation of scalable culture platforms for the large-scale production of hPSC and their derivatives is mandatory to fulfill the requirement of obtaining large numbers of cells for these applications. Microcarrier technology has been emerging as an effective approach for the large scale ex vivo hPSC expansion and differentiation. This review presents recent achievements in hPSC microcarrier-based culture systems and discusses the crucial aspects that influence the performance of these culture platforms. Recent progress includes addressing chemically-defined culture conditions for manufacturing of hPSC and their derivatives, with the development of xeno-free media and microcarrier coatings to meet good manufacturing practice (GMP) quality requirements. Finally, examples of integrated platforms including hPSC expansion and directed differentiation to specific lineages are also presented in this review. Copyright © 2016 Elsevier B.V. All rights reserved.

A resource of large-scale molecular markers for monitoring Agropyron cristatum chromatin introgression in wheat background based on transcriptome sequences.

PubMed

Zhang, Jinpeng; Liu, Weihua; Lu, Yuqing; Liu, Qunxing; Yang, Xinming; Li, Xiuquan; Li, Lihui

2017-09-20

Agropyron cristatum is a wild grass of the tribe Triticeae and serves as a gene donor for wheat improvement. However, very few markers can be used to monitor A. cristatum chromatin introgressions in wheat. Here, we reported a resource of large-scale molecular markers for tracking alien introgressions in wheat based on transcriptome sequences. By aligning A. cristatum unigenes with the Chinese Spring reference genome sequences, we designed 9602 A. cristatum expressed sequence tag-sequence-tagged site (EST-STS) markers for PCR amplification and experimental screening. As a result, 6063 polymorphic EST-STS markers were specific for the A. cristatum P genome in the single-receipt wheat background. A total of 4956 randomly selected polymorphic EST-STS markers were further tested in eight wheat variety backgrounds, and 3070 markers displaying stable and polymorphic amplification were validated. These markers covered more than 98% of the A. cristatum genome, and the marker distribution density was approximately 1.28 cM. An application case of all EST-STS markers was validated on the A. cristatum 6 P chromosome. These markers were successfully applied in the tracking of alien A. cristatum chromatin. Altogether, this study provided a universal method of large-scale molecular marker development to monitor wild relative chromatin in wheat.

Molecular diagnosis of Plasmodium ovale by photo-induced electron transfer fluorogenic primers: PET-PCR

PubMed Central

Akerele, David; Ljolje, Dragan; Talundzic, Eldin; Udhayakumar, Venkatachalam

2017-01-01

Accurate diagnosis of malaria infections continues to be challenging and elusive, especially in the detection of submicroscopic infections. Developing new malaria diagnostic tools that are sensitive enough to detect low-level infections, user friendly, cost effective and capable of performing large scale diagnosis, remains critical. We have designed novel self-quenching photo-induced electron transfer (PET) fluorogenic primers for the detection of P. ovale by real-time PCR. In our study, a total of 173 clinical samples, consisting of different malaria species, were utilized to test this novel PET-PCR primer. The sensitivity and specificity were calculated using nested-PCR as the reference test. The novel primer set demonstrated a sensitivity of 97.5% and a specificity of 99.2% (95% CI 85.2–99.8% and 95.2–99.9% respectively). Furthermore, the limit of detection for P. ovale was found to be 1 parasite/μl. The PET-PCR assay is a new molecular diagnostic tool with comparable performance to other commonly used PCR methods. It is relatively easy to perform, and amiable to large scale malaria surveillance studies and malaria control and elimination programs. Further field validation of this novel primer will be helpful to ascertain the utility for large scale malaria screening programs. PMID:28640824

Molecular diagnosis of Plasmodium ovale by photo-induced electron transfer fluorogenic primers: PET-PCR.

PubMed

Akerele, David; Ljolje, Dragan; Talundzic, Eldin; Udhayakumar, Venkatachalam; Lucchi, Naomi W

2017-01-01

Accurate diagnosis of malaria infections continues to be challenging and elusive, especially in the detection of submicroscopic infections. Developing new malaria diagnostic tools that are sensitive enough to detect low-level infections, user friendly, cost effective and capable of performing large scale diagnosis, remains critical. We have designed novel self-quenching photo-induced electron transfer (PET) fluorogenic primers for the detection of P. ovale by real-time PCR. In our study, a total of 173 clinical samples, consisting of different malaria species, were utilized to test this novel PET-PCR primer. The sensitivity and specificity were calculated using nested-PCR as the reference test. The novel primer set demonstrated a sensitivity of 97.5% and a specificity of 99.2% (95% CI 85.2-99.8% and 95.2-99.9% respectively). Furthermore, the limit of detection for P. ovale was found to be 1 parasite/μl. The PET-PCR assay is a new molecular diagnostic tool with comparable performance to other commonly used PCR methods. It is relatively easy to perform, and amiable to large scale malaria surveillance studies and malaria control and elimination programs. Further field validation of this novel primer will be helpful to ascertain the utility for large scale malaria screening programs.

Large Scale Reduction of Graphite Oxide Project

NASA Technical Reports Server (NTRS)

Calle, Carlos; Mackey, Paul; Falker, John; Zeitlin, Nancy

2015-01-01

This project seeks to develop an optical method to reduce graphite oxide into graphene efficiently and in larger formats than currently available. Current reduction methods are expensive, time-consuming or restricted to small, limited formats. Graphene has potential uses in ultracapacitors, energy storage, solar cells, flexible and light-weight circuits, touch screens, and chemical sensors. In addition, graphite oxide is a sustainable material that can be produced from any form of carbon, making this method environmentally friendly and adaptable for in-situ reduction.

Large-Scale Interaction Profiling of Protein Domains Through Proteomic Peptide-Phage Display Using Custom Peptidomes.

PubMed

Seo, Moon-Hyeong; Nim, Satra; Jeon, Jouhyun; Kim, Philip M

2017-01-01

Protein-protein interactions are essential to cellular functions and signaling pathways. We recently combined bioinformatics and custom oligonucleotide arrays to construct custom-made peptide-phage libraries for screening peptide-protein interactions, an approach we call proteomic peptide-phage display (ProP-PD). In this chapter, we describe protocols for phage display for the identification of natural peptide binders for a given protein. We finally describe deep sequencing for the analysis of the proteomic peptide-phage display.

Integrated reservoir assessment and characterization: Final report, October 1, 1985--September 30, 1988

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honarpour, M.; Szpakiewicz, M.; Sharma, B.

This report covers the development of a generic approach to reservoir characterization, the preliminary studies leading to the selection of an appropriate depositional system for detailed study, the application of outcrop studies to quantified reservoir characterization, and the construction of a quantified geological/engineering model used to screen the effects and scales of various geological heterogeneities within a reservoir. These heterogeneities result in large production/residual oil saturation contrasts over small distances. 36 refs., 124 figs., 38 tabs.

The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale.

PubMed

Di Florio, A; Putnam, K; Altemus, M; Apter, G; Bergink, V; Bilszta, J; Brock, R; Buist, A; Deligiannidis, K M; Devouche, E; Epperson, C N; Guille, C; Kim, D; Lichtenstein, P; Magnusson, P K E; Martinez, P; Munk-Olsen, T; Newport, J; Payne, J; Penninx, B W; O'Hara, M; Robertson-Blackmore, E; Roza, S J; Sharkey, K M; Stuart, S; Tiemeier, H; Viktorin, A; Schmidt, P J; Sullivan, P F; Stowe, Z N; Wisner, K L; Jones, I; Rubinow, D R; Meltzer-Brody, S

2017-04-01

Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset. Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA. Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) 0.01), but not between European countries (∆*CFI < 0.01). Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

Type- and age-specific distribution of human papillomavirus in women attending cervical cancer screening in Finland

PubMed Central

Leinonen, M K; Anttila, A; Malila, N; Dillner, J; Forslund, O; Nieminen, P

2013-01-01

Background: Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening. Methods: 33 043 women (aged 25–65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated. Results: Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4–89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0–67.5) of them. Conclusion: The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer. PMID:24136148

[Results and evaluation of 3 years of a large scale mammography program in the Ariana area of Tunisia].

PubMed

Bouchlaka, A; Ben Abdallah, M; Ben Aissa, R; Zaanouni, E; Kribi, L; Smida, S; M'barek, F; Ben Hamida, A; Boussen, H; Gueddana, N

2009-07-01

To asses and analyse the results of 3 years large scale mammography screening of breast cancer in Ariana state in Tunisia. This program, managed by the Family and Population National Office, was addressing to women aged from 49 to 69 years old residing in a area with adds up a population of 459 700 inhabitants including 52,729 women in the target age population. The screening was including a breast clinical examination and a mammography with two incidences face and external profile. The women was invited at their residence or were sensitized in the reproductive health centers, care and base health centers or by a close relation which heard of the program. An enlightened assent was submitted to the women who wished to profit from the screening. In three years, 9093 mammography were carried out of which 8244 were retained in the analyses, that is to say a rate participation of 9.6%. The rate of women recalled for suspect test was of 18.1% and it was of 13.1% among women of more than 50 years. The rate of practiced surgical biopsies was of 0.5% and the positive predictive value was of 45.5%. The average time between the date of screening and the result of the screening was 9.7 days, more important in the event of tests requiring a complementary assessment (61.7 days). On the whole 40 cancers were detected by the program, that is to say a rough rate of detected cancers, of 4.9 per thousand, in conformity with the recommendations. The percentage of invasive cancers < or = 10 mm was of 24.3 whereas percentages of in situ cancers and of cancers without ganglionic invasion were respectively of 7.7% and of 50.0%. The weakness of our study lay primarily in the rate of participation which remained weak. The methodology adopted for the sensitizing of the women is proven not very effective and did not allow inviting all eligible women. Results of the study are encouraging in spite of its limited impact and made it possible to detect an important rate of cancers of which cancers infra-private clinics.

Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

PubMed

Le Calvez-Kelm, Florence; Lesueur, Fabienne; Damiola, Francesca; Vallée, Maxime; Voegele, Catherine; Babikyan, Davit; Durand, Geoffroy; Forey, Nathalie; McKay-Chopin, Sandrine; Robinot, Nivonirina; Nguyen-Dumont, Tù; Thomas, Alun; Byrnes, Graham B; Hopper, John L; Southey, Melissa C; Andrulis, Irene L; John, Esther M; Tavtigian, Sean V

2011-01-18

Both protein-truncating variants and some missense substitutions in CHEK2 confer increased risk of breast cancer. However, no large-scale study has used full open reading frame mutation screening to assess the contribution of rare missense substitutions in CHEK2 to breast cancer risk. This absence has been due in part to a lack of validated statistical methods for summarizing risk attributable to large numbers of individually rare missense substitutions. Previously, we adapted an in silico assessment of missense substitutions used for analysis of unclassified missense substitutions in BRCA1 and BRCA2 to the problem of assessing candidate genes using rare missense substitution data observed in case-control mutation-screening studies. The method involves stratifying rare missense substitutions observed in cases and/or controls into a series of grades ordered a priori from least to most likely to be evolutionarily deleterious, followed by a logistic regression test for trends to compare the frequency distributions of the graded missense substitutions in cases versus controls. Here we used this approach to analyze CHEK2 mutation-screening data from a population-based series of 1,303 female breast cancer patients and 1,109 unaffected female controls. We found evidence of risk associated with rare, evolutionarily unlikely CHEK2 missense substitutions. Additional findings were that (1) the risk estimate for the most severe grade of CHEK2 missense substitutions (denoted C65) is approximately equivalent to that of CHEK2 protein-truncating variants; (2) the population attributable fraction and the familial relative risk explained by the pool of rare missense substitutions were similar to those explained by the pool of protein-truncating variants; and (3) post hoc power calculations implied that scaling up case-control mutation screening to examine entire biochemical pathways would require roughly 2,000 cases and controls to achieve acceptable statistical power. This study shows that CHEK2 harbors many rare sequence variants that confer increased risk of breast cancer and that a substantial proportion of these are missense substitutions. The study validates our analytic approach to rare missense substitutions and provides a method to combine data from protein-truncating variants and rare missense substitutions into a one degree of freedom per gene test.

The SIMS Screen for feigned mental disorders: the development of detection-based scales.

PubMed

Rogers, Richard; Robinson, Emily V; Gillard, Nathan D

2014-01-01

Time-efficient screens for feigned mental disorders (FMDs) constitute important tools in forensic assessments. The Structured Inventory of Malingered Symptomatology (SIMS) is a 75-item true-false questionnaire that has been extensively studied as an FMD screen. However, the SIMS scales are not based on established detection strategies, and only its total score is utilized as a feigning screen. This investigation develops two new feigning scales based on well-established detection-strategies: rare symptoms (RS) and symptom combinations (SC). They are studied in a between-subjects simulation design using inpatients with partial-malingering (i.e., patients with genuine disorders asked to feign greater disabilities) conditions. Subject to future cross-validation, the SC scale evidenced the highest effect size (d=2.01) and appeared the most effective at ruling out examinees, who have a high likelihood of genuine responding. Copyright © 2014 John Wiley & Sons, Ltd.

Development of a Screening Scale for High-Functioning Pervasive Developmental Disorders Using the Tokyo Child Development Schedule and Tokyo Autistic Behavior Scale

ERIC Educational Resources Information Center

Suzuki, Mayo; Tachimori, Hisateru; Saito, Mari; Koyama, Tomonori; Kurita, Hiroshi

2011-01-01

This study aimed to compile a screening scale for high-functioning pervasive developmental disorders (PDD), using the Tokyo Child Development Schedule (TCDS) and Tokyo Autistic Behavior Scale (TABS). The 72 participants (IQ greater than or equal to 70) were divided into 3 groups after IQ matching depending on their diagnoses: i.e., PDD,…

Initial Evidence for the Reliability and Validity of the Student Risk Screening Scale for Internalizing and Externalizing Behaviors at the Middle School Level

ERIC Educational Resources Information Center

Lane, Kathleen Lynne; Oakes, Wendy Peia; Carter, Erik W.; Lambert, Warren E.; Jenkins, Abbie B.

2013-01-01

We reported findings of an exploratory validation study of a revised universal screening instrument: the Student Risk Screening Scale--Internalizing and Externalizing (SRSS-IE) for use with middle school students. Tested initially for use with elementary-age students, the SRSS-IE was adapted to include seven additional items reflecting…

Complex Genetics of Behavior: BXDs in the Automated Home-Cage.

PubMed

Loos, Maarten; Verhage, Matthijs; Spijker, Sabine; Smit, August B

2017-01-01

This chapter describes a use case for the genetic dissection and automated analysis of complex behavioral traits using the genetically diverse panel of BXD mouse recombinant inbred strains. Strains of the BXD resource differ widely in terms of gene and protein expression in the brain, as well as in their behavioral repertoire. A large mouse resource opens the possibility for gene finding studies underlying distinct behavioral phenotypes, however, such a resource poses a challenge in behavioral phenotyping. To address the specifics of large-scale screening we describe how to investigate: (1) how to assess mouse behavior systematically in addressing a large genetic cohort, (2) how to dissect automation-derived longitudinal mouse behavior into quantitative parameters, and (3) how to map these quantitative traits to the genome, deriving loci underlying aspects of behavior.

Bayley Scales of Infant Development Screening Test-Gross Motor Subtest: efficacy in determining need for services.

PubMed

Jackson, Barbara J; Needelman, Howard; Roberts, Holly; Willet, Sandy; McMorris, Carol

2012-01-01

To identify the efficacy of the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), Screening Test-Gross Motor Subtest (GMS) in identifying infants who are accepted for early intervention services. This retrospective study included 93 infants with a neonatal intensive care experience who participated in a 6-month developmental assessment follow-up visit. All infants were examined using the BSID-III Screening Test-GMS and the Alberta Infant Motor Scale. A binary logical regression analysis was used to determine the best predictors of acceptance status in this sample. The BSID-III Screening Test-GMS accounted for a significant portion of the variance in acceptance status. The results suggest that the BSID-III Screening Test-GMS has great applicability for transdisciplinary/interdisciplinary teams as it effectively identified children who were eligible for early intervention.

A Screening Tool to Measure Eye Contact Avoidance in Boys with Fragile X Syndrome

ERIC Educational Resources Information Center

Hall, Scott S.; Venema, Kaitlin M.

2017-01-01

We examined the reliability, validity and factor structure of the Eye Contact Avoidance Scale (ECAS), a new 15-item screening tool designed to measure eye contact avoidance in individuals with fragile X syndrome (FXS). Internal consistency of the scale was acceptable to excellent and convergent validity with the Social Responsiveness Scale, Second…

Scaling behaviour of Fisher and Shannon entropies for the exponential-cosine screened coulomb potential

NASA Astrophysics Data System (ADS)

Abdelmonem, M. S.; Abdel-Hady, Afaf; Nasser, I.

2017-07-01

The scaling laws are given for the entropies in the information theory, including the Shannon's entropy, its power, the Fisher's information and the Fisher-Shannon product, using the exponential-cosine screened Coulomb potential. The scaling laws are specified, in the r-space, as a function of |μ - μc, nℓ|, where μ is the screening parameter and μc, nℓ its critical value for the specific quantum numbers n and ℓ. Scaling laws for other physical quantities, such as energy eigenvalues, the moments, static polarisability, transition probabilities, etc. are also given. Some of these are reported for the first time. The outcome is compared with the available literatures' results.

Exposing exposure: automated anatomy-specific CT radiation exposure extraction for quality assurance and radiation monitoring.

PubMed

Sodickson, Aaron; Warden, Graham I; Farkas, Cameron E; Ikuta, Ichiro; Prevedello, Luciano M; Andriole, Katherine P; Khorasani, Ramin

2012-08-01

To develop and validate an informatics toolkit that extracts anatomy-specific computed tomography (CT) radiation exposure metrics (volume CT dose index and dose-length product) from existing digital image archives through optical character recognition of CT dose report screen captures (dose screens) combined with Digital Imaging and Communications in Medicine attributes. This institutional review board-approved HIPAA-compliant study was performed in a large urban health care delivery network. Data were drawn from a random sample of CT encounters that occurred between 2000 and 2010; images from these encounters were contained within the enterprise image archive, which encompassed images obtained at an adult academic tertiary referral hospital and its affiliated sites, including a cancer center, a community hospital, and outpatient imaging centers, as well as images imported from other facilities. Software was validated by using 150 randomly selected encounters for each major CT scanner manufacturer, with outcome measures of dose screen retrieval rate (proportion of correctly located dose screens) and anatomic assignment precision (proportion of extracted exposure data with correctly assigned anatomic region, such as head, chest, or abdomen and pelvis). The 95% binomial confidence intervals (CIs) were calculated for discrete proportions, and CIs were derived from the standard error of the mean for continuous variables. After validation, the informatics toolkit was used to populate an exposure repository from a cohort of 54 549 CT encounters; of which 29 948 had available dose screens. Validation yielded a dose screen retrieval rate of 99% (597 of 605 CT encounters; 95% CI: 98%, 100%) and an anatomic assignment precision of 94% (summed DLP fraction correct 563 in 600 CT encounters; 95% CI: 92%, 96%). Patient safety applications of the resulting data repository include benchmarking between institutions, CT protocol quality control and optimization, and cumulative patient- and anatomy-specific radiation exposure monitoring. Large-scale anatomy-specific radiation exposure data repositories can be created with high fidelity from existing digital image archives by using open-source informatics tools.

CRSI (Climate Resilience Screening Index) - Development and Application

EPA Science Inventory

We developed a Climate Resilience Screening Index that is applicable at multiple scales for the United States. Those scales include national, state, county and community. In order to explicitly include domains, indicators and metrics addressing environmental, economic and soci...

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

PubMed

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.

Holistic computational structure screening of more than 12,000 candidates for solid lithium-ion conductor materials

NASA Astrophysics Data System (ADS)

Sendek, Austin D.; Yang, Qian; Cubuk, Ekin D.; Duerloo, Karel-Alexander N.; Cui, Yi; Reed, Evan J.

We present a new type of large-scale computational screening approach for identifying promising candidate materials for solid state electrolytes for lithium ion batteries that is capable of screening all known lithium containing solids. To predict the likelihood of a candidate material exhibiting high lithium ion conductivity, we leverage machine learning techniques to train an ionic conductivity classification model using logistic regression based on experimental measurements reported in the literature. This model, which is built on easily calculable atomistic descriptors, provides new insight into the structure-property relationship for superionic behavior in solids and is approximately one million times faster to evaluate than DFT-based approaches to calculating diffusion coefficients or migration barriers. We couple this model with several other technologically motivated heuristics to reduce the list of candidate materials from the more than 12,000 known lithium containing solids to 21 structures that show promise as electrolytes, few of which have been examined experimentally. Our screening utilizes structures and electronic information contained in the Materials Project database. This work is supported by an Office of Technology Licensing Fellowship through the Stanford Graduate Fellowship Program and a seed Grant from the TomKat Center for Sustainable Energy at Stanford.

Unscreening Modified Gravity in the Matter Power Spectrum.

PubMed

Lombriser, Lucas; Simpson, Fergus; Mead, Alexander

2015-06-26

Viable modifications of gravity that may produce cosmic acceleration need to be screened in high-density regions such as the Solar System, where general relativity is well tested. Screening mechanisms also prevent strong anomalies in the large-scale structure and limit the constraints that can be inferred on these gravity models from cosmology. We find that by suppressing the contribution of the screened high-density regions in the matter power spectrum, allowing a greater contribution of unscreened low densities, modified gravity models can be more readily discriminated from the concordance cosmology. Moreover, by variation of density thresholds, degeneracies with other effects may be dealt with more adequately. Specializing to chameleon gravity as a worked example for screening in modified gravity, employing N-body simulations of f(R) models and the halo model of chameleon theories, we demonstrate the effectiveness of this method. We find that a percent-level measurement of the clipped power at k<0.3h/Mpc can yield constraints on chameleon models that are more stringent than what is inferred from Solar System tests or distance indicators in unscreened dwarf galaxies. Finally, we verify that our method is also applicable to the Vainshtein mechanism.

Ion-selective gold-thiol film on integrated screen-printed electrodes for analysis of Cu(II) ions.

PubMed

Li, Meng; Zhou, Hao; Shi, Lei; Li, Da-Wei; Long, Yi-Tao

2014-02-07

A novel type of ion-selective electrode (ISE) was manufactured for detecting trace amounts of Cu(II) ions. The basic substrates of ISE were fabricated using screen-printing technology, which could produce disposable electrodes on a large-scale with good repeatability. Moreover, the printed integrated three-electrode system of ISE could be directly used to read out the open-circuit potentials by a handheld device through a USB port. The ion-selective film was composed of gold nanorods (GNRs) and 6-(bis(pyridin-2-ylmethyl)amino)hexane-1-thiol (compound ), which were layer-by-layer modified on the electrode through an easily controlled self-assembly method. Compound contained the 2,2'-dipyridylamine (dpa) group that could coordinate with Cu(II) ions to form a 2 : 1 complex, therefore the screen-printed ISEs exhibited Nernstian potentiometric responses to Cu(II) ions with a detection limit of 6.3 × 10(-7) mol L(-1) over the range of 1.0 × 10(-6) to 1.0 × 10(-2) mol L(-1). The easily prepared screen-printed ion-selective electrode reported here was appropriate for in field analysis and pollutant detection in remote environments.

Psychosocial Issues Related to Thyroid Examination After a Radiation Disaster.

PubMed

Midorikawa, Sanae; Tanigawa, Koichi; Suzuki, Satoru; Ohtsuru, Akira

2017-03-01

A thyroid ultrasound examination program has been conducted in the aftermath of the Fukushima Daiichi Nuclear Power Plant accident to address concerns about the increased risk of thyroid cancer similar to those experienced by local residents after the 1986 Chernobyl accident. This is the second-largest thyroid cancer screening in younger age ever, following only that conducted after Chernobyl. As the natural history of thyroid cancer in younger populations is not well characterized, large-scale screening using thyroid ultrasound could result in overdiagnosis, even with careful planning, as has been experienced in South Korea. Awareness regarding the thyroid gland is generally low among residents, who tend to directly associate examination results with radiation exposure and are likely to develop newfound anxiety and feelings of self-condemnation and guilt. We reviewed the dilemma surrounding cancer screening and particularly underscored the need to address psychosocial issues associated with possible overdiagnosis. We modified our approach to address individual and social anxiety induced by results of screening conducted after the Fukushima accident. These findings and our experiences regarding the psychosocial issues related to thyroid examination should assist residents in their lifelong decision making and help them prepare for future disasters.

Metasurface Salisbury screen: achieving ultra-wideband microwave absorption.

PubMed

Zhou, Ziheng; Chen, Ke; Zhao, Junming; Chen, Ping; Jiang, Tian; Zhu, Bo; Feng, Yijun; Li, Yue

2017-11-27

The metasurfaces have recently been demonstrated to provide full control of the phase responses of electromagnetic (EM) wave scattering over subwavelength scales, enabling a wide range of practical applications. Here, we propose a comprehensive scheme for the efficient and flexible design of metasurface Salisbury screen (MSS) capable of absorbing the impinging EM wave in an ultra-wide frequency band. We show that properly designed reflective metasurface can be used to substitute the metallic ground of conventional Salisbury screen for generating diverse resonances in a desirable way, thus providing large controllability over the absorption bandwidth. Based on this concept, we establish an equivalent circuit model to qualitatively analysis the resonances in MSS and design algorithms to optimize the overall performance of the MSS. Experiments have been carried out to demonstrate that the absorption bandwidth from 6 GHz to 30 GHz with an efficiency higher than 85% can be achieved by the proposal, which is apparently much larger than that of conventional Salisbury screen (7 GHz - 17 GHz). The proposed concept of MSS could offer opportunities for flexibly designing thin electromagnetic absorbers with simultaneously ultra-wide bandwidth, polarization insensitivity, and wide incident angle, exhibiting promising potentials for many applications such as in EM compatibility, stealth technique, etc.

A human factors approach to range scheduling for satellite control

NASA Technical Reports Server (NTRS)

Wright, Cameron H. G.; Aitken, Donald J.

1991-01-01

Range scheduling for satellite control presents a classical problem: supervisory control of a large-scale dynamic system, with unwieldy amounts of interrelated data used as inputs to the decision process. Increased automation of the task, with the appropriate human-computer interface, is highly desirable. The development and user evaluation of a semi-automated network range scheduling system is described. The system incorporates a synergistic human-computer interface consisting of a large screen color display, voice input/output, a 'sonic pen' pointing device, a touchscreen color CRT, and a standard keyboard. From a human factors standpoint, this development represents the first major improvement in almost 30 years to the satellite control network scheduling task.

Development of an Immunoassay for Rapid Detection of Ganglioside GM1 Mimicry in Campylobacter jejuni Strains

PubMed Central

Prendergast, Martina M.; Kosunen, Timo U.; Moran, Anthony P.

2001-01-01

Mimicry of peripheral nerve gangliosides by Campylobacter jejuni lipopolysaccharides (LPSs) has been proposed to induce cross-reacting antiganglioside antibodies in Guillain-Barré syndrome (GBS). Because current methods for LPS characterization are labor-intensive and inhibit the screening of large numbers of strains, a rapid GM1 epitope screening assay was developed. Biomass from two agar plates of confluent growth yielded sufficient LPS using a novel phenol-water and ether extraction procedure. Extracts of LPS were reacted with cholera toxin (GM1 ligand), peanut agglutinin (Galβ1→3GalNAc ligand), and anti-GM1 antibodies. After the assay was validated, 12 of 59 (20%) C. jejuni serostrains, including four serotypes that have not previously been associated with GBS, reacted with two or more anti-GM1 ganglioside reagents. Subsequently, LPS extracts from 5 of 7 (71%) C. jejuni isolates and 2 of 3 (67%) C. jejuni culture collection strains bore GM1 structures. Overall, the assay system was reliable, efficient, and reproducible and may be adapted for large-scale epidemiological studies. PMID:11283076

Fast computation of an optimal controller for large-scale adaptive optics.

PubMed

Massioni, Paolo; Kulcsár, Caroline; Raynaud, Henri-François; Conan, Jean-Marc

2011-11-01

The linear quadratic Gaussian regulator provides the minimum-variance control solution for a linear time-invariant system. For adaptive optics (AO) applications, under the hypothesis of a deformable mirror with instantaneous response, such a controller boils down to a minimum-variance phase estimator (a Kalman filter) and a projection onto the mirror space. The Kalman filter gain can be computed by solving an algebraic Riccati matrix equation, whose computational complexity grows very quickly with the size of the telescope aperture. This "curse of dimensionality" makes the standard solvers for Riccati equations very slow in the case of extremely large telescopes. In this article, we propose a way of computing the Kalman gain for AO systems by means of an approximation that considers the turbulence phase screen as the cropped version of an infinite-size screen. We demonstrate the advantages of the methods for both off- and on-line computational time, and we evaluate its performance for classical AO as well as for wide-field tomographic AO with multiple natural guide stars. Simulation results are reported.

Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015.

PubMed

Deng, Nanjie; Flynn, William F; Xia, Junchao; Vijayan, R S K; Zhang, Baofeng; He, Peng; Mentes, Ahmet; Gallicchio, Emilio; Levy, Ronald M

2016-09-01

We describe binding free energy calculations in the D3R Grand Challenge 2015 for blind prediction of the binding affinities of 180 ligands to Hsp90. The present D3R challenge was built around experimental datasets involving Heat shock protein (Hsp) 90, an ATP-dependent molecular chaperone which is an important anticancer drug target. The Hsp90 ATP binding site is known to be a challenging target for accurate calculations of ligand binding affinities because of the ligand-dependent conformational changes in the binding site, the presence of ordered waters and the broad chemical diversity of ligands that can bind at this site. Our primary focus here is to distinguish binders from nonbinders. Large scale absolute binding free energy calculations that cover over 3000 protein-ligand complexes were performed using the BEDAM method starting from docked structures generated by Glide docking. Although the ligand dataset in this study resembles an intermediate to late stage lead optimization project while the BEDAM method is mainly developed for early stage virtual screening of hit molecules, the BEDAM binding free energy scoring has resulted in a moderate enrichment of ligand screening against this challenging drug target. Results show that, using a statistical mechanics based free energy method like BEDAM starting from docked poses offers better enrichment than classical docking scoring functions and rescoring methods like Prime MM-GBSA for the Hsp90 data set in this blind challenge. Importantly, among the three methods tested here, only the mean value of the BEDAM binding free energy scores is able to separate the large group of binders from the small group of nonbinders with a gap of 2.4 kcal/mol. None of the three methods that we have tested provided accurate ranking of the affinities of the 147 active compounds. We discuss the possible sources of errors in the binding free energy calculations. The study suggests that BEDAM can be used strategically to discriminate binders from nonbinders in virtual screening and to more accurately predict the ligand binding modes prior to the more computationally expensive FEP calculations of binding affinity.

Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015

NASA Astrophysics Data System (ADS)

Deng, Nanjie; Flynn, William F.; Xia, Junchao; Vijayan, R. S. K.; Zhang, Baofeng; He, Peng; Mentes, Ahmet; Gallicchio, Emilio; Levy, Ronald M.

2016-09-01

We describe binding free energy calculations in the D3R Grand Challenge 2015 for blind prediction of the binding affinities of 180 ligands to Hsp90. The present D3R challenge was built around experimental datasets involving Heat shock protein (Hsp) 90, an ATP-dependent molecular chaperone which is an important anticancer drug target. The Hsp90 ATP binding site is known to be a challenging target for accurate calculations of ligand binding affinities because of the ligand-dependent conformational changes in the binding site, the presence of ordered waters and the broad chemical diversity of ligands that can bind at this site. Our primary focus here is to distinguish binders from nonbinders. Large scale absolute binding free energy calculations that cover over 3000 protein-ligand complexes were performed using the BEDAM method starting from docked structures generated by Glide docking. Although the ligand dataset in this study resembles an intermediate to late stage lead optimization project while the BEDAM method is mainly developed for early stage virtual screening of hit molecules, the BEDAM binding free energy scoring has resulted in a moderate enrichment of ligand screening against this challenging drug target. Results show that, using a statistical mechanics based free energy method like BEDAM starting from docked poses offers better enrichment than classical docking scoring functions and rescoring methods like Prime MM-GBSA for the Hsp90 data set in this blind challenge. Importantly, among the three methods tested here, only the mean value of the BEDAM binding free energy scores is able to separate the large group of binders from the small group of nonbinders with a gap of 2.4 kcal/mol. None of the three methods that we have tested provided accurate ranking of the affinities of the 147 active compounds. We discuss the possible sources of errors in the binding free energy calculations. The study suggests that BEDAM can be used strategically to discriminate binders from nonbinders in virtual screening and to more accurately predict the ligand binding modes prior to the more computationally expensive FEP calculations of binding affinity.

Skin disease prevalence study in schoolchildren in rural Côte d'Ivoire: Implications for integration of neglected skin diseases (skin NTDs).

PubMed

Yotsu, Rie Roselyne; Kouadio, Kouamé; Vagamon, Bamba; N'guessan, Konan; Akpa, Amari Jules; Yao, Aubin; Aké, Julien; Abbet Abbet, Rigobert; Tchamba Agbor Agbor, Barbine; Bedimo, Roger; Ishii, Norihisa; Fuller, L Claire; Hay, Roderick; Mitjà, Oriol; Drechsler, Henning; Asiedu, Kingsley

2018-05-01

Early detection of several skin-related neglected tropical diseases (skin NTDs)-including leprosy, Buruli ulcer, yaws, and scabies- may be achieved through school surveys, but such an approach has seldom been tested systematically on a large scale in endemic countries. Additionally, a better understanding of the spectrum of skin diseases and the at-risk populations to be encountered during such surveys is necessary to facilitate the process. We performed a school skin survey for selected NTDs and the spectrum of skin diseases, among primary schoolchildren aged 5 to 15 in Côte d'Ivoire, West Africa. This 2-phase survey took place in 49 schools from 16 villages in the Adzopé health district from November 2015 to January 2016. The first phase involved a rapid visual examination of the skin by local community healthcare workers (village nurses) to identify any skin abnormality. In a second phase, a specialized medical team including dermatologists performed a total skin examination of all screened students with any skin lesion and provided treatment where necessary. Of a total of 13,019 children, 3,504 screened positive for skin lesions and were listed for the next stage examination. The medical team examined 1,138 of these children. The overall prevalence of skin diseases was 25.6% (95% CI: 24.3-26.9%). The predominant diagnoses were fungal infections (n = 858, prevalence: 22.3%), followed by inflammatory skin diseases (n = 265, prevalence: 6.9%). Skin diseases were more common in boys and in children living along the main road with heavy traffic. One case of multi-bacillary type leprosy was detected early, along with 36 cases of scabies. Our survey was met with very good community acceptance. We carried out the first large-scale integrated, two-phase pediatric multi-skin NTD survey in rural Côte d'Ivoire, effectively reaching a large population. We found a high prevalence of skin diseases in children, but only limited number of skin NTDs. With the lessons learned, we plan to expand the project to a wider area to further explore its potential to better integrate skin NTD screening in the public health agenda.

Home-based screening for biliary atresia using infant stool colour cards: a large-scale prospective cohort study and cost-effectiveness analysis.

PubMed

Schreiber, Richard A; Masucci, Lisa; Kaczorowski, Janusz; Collet, J P; Lutley, Pamela; Espinosa, Victor; Bryan, Stirling

2014-09-01

Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada. A prospective study at BC Women's Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline "passive" strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon. 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60-94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is $213,584 and the gain in life years is 9.7 ($22,000 per life-year gained). A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes.

PubMed

Ju, Kou-San; Gao, Jiangtao; Doroghazi, James R; Wang, Kwo-Kwang A; Thibodeaux, Christopher J; Li, Steven; Metzger, Emily; Fudala, John; Su, Joleen; Zhang, Jun Kai; Lee, Jaeheon; Cioni, Joel P; Evans, Bradley S; Hirota, Ryuichi; Labeda, David P; van der Donk, Wilfred A; Metcalf, William W

2015-09-29

Although natural products have been a particularly rich source of human medicines, activity-based screening results in a very high rate of rediscovery of known molecules. Based on the large number of natural product biosynthetic genes in microbial genomes, many have proposed "genome mining" as an alternative approach for discovery efforts; however, this idea has yet to be performed experimentally on a large scale. Here, we demonstrate the feasibility of large-scale, high-throughput genome mining by screening a collection of over 10,000 actinomycetes for the genetic potential to make phosphonic acids, a class of natural products with diverse and useful bioactivities. Genome sequencing identified a diverse collection of phosphonate biosynthetic gene clusters within 278 strains. These clusters were classified into 64 distinct groups, of which 55 are likely to direct the synthesis of unknown compounds. Characterization of strains within five of these groups resulted in the discovery of a new archetypical pathway for phosphonate biosynthesis, the first (to our knowledge) dedicated pathway for H-phosphinates, and 11 previously undescribed phosphonic acid natural products. Among these compounds are argolaphos, a broad-spectrum antibacterial phosphonopeptide composed of aminomethylphosphonate in peptide linkage to a rare amino acid N(5)-hydroxyarginine; valinophos, an N-acetyl l-Val ester of 2,3-dihydroxypropylphosphonate; and phosphonocystoximate, an unusual thiohydroximate-containing molecule representing a new chemotype of sulfur-containing phosphonate natural products. Analysis of the genome sequences from the remaining strains suggests that the majority of the phosphonate biosynthetic repertoire of Actinobacteria has been captured at the gene level. This dereplicated strain collection now provides a reservoir of numerous, as yet undiscovered, phosphonate natural products.

AA9int: SNP Interaction Pattern Search Using Non-Hierarchical Additive Model Set.

PubMed

Lin, Hui-Yi; Huang, Po-Yu; Chen, Dung-Tsa; Tung, Heng-Yuan; Sellers, Thomas A; Pow-Sang, Julio; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Hamdy, Freddie; Neal, David E; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen N; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Lu, Yong-Jie; Park, Jong Y

2018-06-07

The use of single nucleotide polymorphism (SNP) interactions to predict complex diseases is getting more attention during the past decade, but related statistical methods are still immature. We previously proposed the SNP Interaction Pattern Identifier (SIPI) approach to evaluate 45 SNP interaction patterns/patterns. SIPI is statistically powerful but suffers from a large computation burden. For large-scale studies, it is necessary to use a powerful and computation-efficient method. The objective of this study is to develop an evidence-based mini-version of SIPI as the screening tool or solitary use and to evaluate the impact of inheritance mode and model structure on detecting SNP-SNP interactions. We tested two candidate approaches: the 'Five-Full' and 'AA9int' method. The Five-Full approach is composed of the five full interaction models considering three inheritance modes (additive, dominant and recessive). The AA9int approach is composed of nine interaction models by considering non-hierarchical model structure and the additive mode. Our simulation results show that AA9int has similar statistical power compared to SIPI and is superior to the Five-Full approach, and the impact of the non-hierarchical model structure is greater than that of the inheritance mode in detecting SNP-SNP interactions. In summary, it is recommended that AA9int is a powerful tool to be used either alone or as the screening stage of a two-stage approach (AA9int+SIPI) for detecting SNP-SNP interactions in large-scale studies. The 'AA9int' and 'parAA9int' functions (standard and parallel computing version) are added in the SIPI R package, which is freely available at https://linhuiyi.github.io/LinHY_Software/. hlin1@lsuhsc.edu. Supplementary data are available at Bioinformatics online.

Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes

PubMed Central

Ju, Kou-San; Gao, Jiangtao; Doroghazi, James R.; Wang, Kwo-Kwang A.; Thibodeaux, Christopher J.; Li, Steven; Metzger, Emily; Fudala, John; Su, Joleen; Zhang, Jun Kai; Lee, Jaeheon; Cioni, Joel P.; Evans, Bradley S.; Hirota, Ryuichi; Labeda, David P.; van der Donk, Wilfred A.; Metcalf, William W.

2015-01-01

Although natural products have been a particularly rich source of human medicines, activity-based screening results in a very high rate of rediscovery of known molecules. Based on the large number of natural product biosynthetic genes in microbial genomes, many have proposed “genome mining” as an alternative approach for discovery efforts; however, this idea has yet to be performed experimentally on a large scale. Here, we demonstrate the feasibility of large-scale, high-throughput genome mining by screening a collection of over 10,000 actinomycetes for the genetic potential to make phosphonic acids, a class of natural products with diverse and useful bioactivities. Genome sequencing identified a diverse collection of phosphonate biosynthetic gene clusters within 278 strains. These clusters were classified into 64 distinct groups, of which 55 are likely to direct the synthesis of unknown compounds. Characterization of strains within five of these groups resulted in the discovery of a new archetypical pathway for phosphonate biosynthesis, the first (to our knowledge) dedicated pathway for H-phosphinates, and 11 previously undescribed phosphonic acid natural products. Among these compounds are argolaphos, a broad-spectrum antibacterial phosphonopeptide composed of aminomethylphosphonate in peptide linkage to a rare amino acid N5-hydroxyarginine; valinophos, an N-acetyl l-Val ester of 2,3-dihydroxypropylphosphonate; and phosphonocystoximate, an unusual thiohydroximate-containing molecule representing a new chemotype of sulfur-containing phosphonate natural products. Analysis of the genome sequences from the remaining strains suggests that the majority of the phosphonate biosynthetic repertoire of Actinobacteria has been captured at the gene level. This dereplicated strain collection now provides a reservoir of numerous, as yet undiscovered, phosphonate natural products. PMID:26324907

Factors predicting health practitioners' awareness of UNHS program in Malaysian non-public hospitals.

PubMed

Ismail, Abdussalaam Iyanda; Abdul Majid, Abdul Halim; Zakaria, Mohd Normani; Abdullah, Nor Azimah Chew; Hamzah, Sulaiman; Mukari, Siti Zamratol-Mai Sarah

2018-06-01

The current study aims to examine the effects of human resource (measured with the perception of health workers' perception towards UNHS), screening equipment, program layout and screening techniques on healthcare practitioners' awareness (measured with knowledge) of universal newborn hearing screening (UNHS) in Malaysian non-public hospitals. Via cross sectional approach, the current study collected data using a validated questionnaire to obtain information on the awareness of UNHS program among the health practitioners and to test the formulated hypotheses. 51, representing 81% response rate, out of 63 questionnaires distributed to the health professionals were returned and usable for statistical analysis. The survey instruments involving healthcare practitioners' awareness, human resource, program layout, screening instrument, and screening techniques instruments were adapted and scaled with 7-point Likert scale ranging from 1 (little) to 7 (many). Partial Least Squares (PLS) algorithm and bootstrapping techniques were employed to test the hypotheses of the study. With the result involving beta values, t-values and p-values (i.e. β=0.478, t=1.904, p<0.10; β=0.809, t=3.921, p<0.01; β= -0.436, t=1.870, p<0.10), human resource, measured with training, functional equipment and program layout, are held to be significant predictors of enhanced knowledge of health practitioners. Likewise, program layout, human resource, screening technique and screening instrument explain 71% variance in health practitioners' awareness. Health practitioners' awareness is explained by program layout, human resource, and screening instrument with effect size (f2) of 0.065, 0.621, and 0.211 respectively, indicating that program layout, human resource, and screening instrument have small, large and medium effect size on health practitioners' awareness respectively. However, screening technique has zero effect on health practitioners' awareness, indicating the reason why T-statistics is not significant. Having started the UNHS program in 2003, non-public hospitals have more experienced and well-trained employees dealing with the screening tools and instrument, and the program layout is well structured in the hospitals. Yet, the issue of homogeneity exists. Non-public hospitals charge for the service they render, and, in turn, they would ensure quality service, given that they are profit-driven and/or profit-making establishments, and that they would have no option other than provision of value-added and innovative services. The employees in the non-public hospitals have less screening to carry out, given the low number of babies delivered in the private hospitals. In addition, non-significant relationship between screening techniques and healthcare practitioners' awareness of UNHS program is connected with the fact that the techniques that are practiced among public and non-public hospital are similar and standardized. Limitations and suggestions were discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Implementation of the Alarm Distress Baby Scale as a universal screening instrument in primary care: feasibility, acceptability, and predictors of professionals' adherence to guidelines.

PubMed

Smith-Nielsen, Johanne; Lønfeldt, Nicole; Guedeney, Antoine; Væver, Mette Skovgaard

2018-03-01

Infant socioemotional development is often held under informal surveillance, but a formal screening program is needed to ensure systematic identification of developmental risk. Even when screening programs exist, they are often ineffective because health care professionals do not adhere to screening guidelines, resulting in low screening prevalence rates. To examine feasibility and acceptability of implementing universal screening for infant socioemotional problems with the Alarm Distress Baby Scale in primary care. The following questions were addressed: Is it possible to obtain acceptable screening prevalence rates within a 1-year period? How do the primary care workers (in this case, health visitors) experience using the instrument? Are attitudes toward using the instrument related to screening prevalence rates? A longitudinal mixed-method study (surveys, data from the health visitors' digital filing system, and qualitative coding of answers to open-ended questions) was undertaken. Health visitors in three of five districts of the City of Copenhagen, Denmark (N=79). We describe and evaluate the implementation process from the date the health visitors started the training on how to use the Alarm Distress Baby Scale to one year after they began using the instrument in practice. To monitor screening prevalence rates and adherence to guidelines, we used three data extractions (6, 9, and 12 months post-implementation) from the electronic filing system. Surveys including both quantitative and open-ended questions (pre- and post-implementation) were used to examine experiences with and attitudes towards the instrument. Descriptive and inferential statistical and qualitative content analyses were used. Screening prevalence rates increased during the first year: Six months after implementation 47% (n=405) of the children had been screened; 12 months after implementation 79% (n=789) of the children were screened (the same child was not counted more than once). Most (92%) of the health visitors reported that the instrument made a positive contribution to their work. The majority (81%) also reported that it posed a challenge in their daily work at least to some degree. The health visitors' attitudes (positive and negative) toward the Alarm Distress Baby Scale, measured 7 months post-implementation, significantly predicted screening prevalence rates 12 months post-implementation. Adding the Alarm Distress Baby Scale to an established surveillance program is feasible and accepTable Screening prevalence rates may be related to the primary care worker's attitude toward the instrument, i.e. successful implementation relies on an instrument that adds value to the work of the screener. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Edinburgh Postnatal Depression Scale: Screening Tool for Postpartum Anxiety as Well? Findings from a Confirmatory Factor Analysis of the Hebrew Version.

PubMed

Bina, Rena; Harrington, Donna

2016-04-01

The Edinburgh Postnatal Depression Scale (EPDS) was originally created as a uni-dimensional scale to screen for postpartum depression (PPD); however, evidence from various studies suggests that it is a multi-dimensional scale measuring mainly anxiety in addition to depression. The factor structure of the EPDS seems to differ across various language translations, raising questions regarding its stability. This study examined the factor structure of the Hebrew version of the EPDS to assess whether it is uni- or multi-dimensional. Seven hundred and fifteen (n = 715) women were screened at 6 weeks postpartum using the Hebrew version of the EPDS. Confirmatory factor analysis (CFA) was used to test four models derived from the literature. Of the four CFA models tested, a 9-item two factor model fit the data best, with one factor representing an underlying depression construct and the other representing an underlying anxiety construct. for Practice The Hebrew version of the EPDS appears to consist of depression and anxiety sub-scales. Given the widespread PPD screening initiatives, anxiety symptoms should be addressed in addition to depressive symptoms, and a short scale, such as the EPDS, assessing both may be efficient.

Contribution to the epidemiology of postnatal depression in Germany--implications for the utilization of treatment.

PubMed

v Ballestrem, C-L; Strauss, M; Kächele, H

2005-05-01

Using a longitudinal screening model, 772 mothers were screened for postnatal depression after delivery in Stuttgart (Germany). This model contained the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Depression Scale (HAMD). The first screening was 6-8 weeks after delivery with the EPDS. Mothers with high scores in the first screening had a second screening 9-12 weeks after delivery with the EPDS at least three weeks after the first. Mothers with high scores in both screenings were investigated with the Hamilton Depression Scale (HAMD). Classification was performed with the DSM-IV. After observation until the third month after delivery, 3.6% (N = 28) of the 772 mothers were diagnosed with postnatal depression. Various methods of therapy were offered to those mothers. 18% (N = 5) accepted one or more of these methods of treatment. The rest of the mothers with postnatal depression refused--mostly for attitudinal or practical reasons. 13.4% of the mothers showed high scores in the first screening but not in the second. For those mothers a longitudinal observation is currently being performed to distinguish between a depressive episode and a depression with oscillating symptoms.

Screening for depressive disorders using the MASQ anhedonic depression scale: A receiver-operator characteristic analysis

PubMed Central

Bredemeier, Keith; Spielberg, Jeffrey M.; Silton, Rebecca Levin; Berenbaum, Howard; Heller, Wendy; Miller, Gregory A.

2010-01-01

The present study examined the utility of the anhedonic depression scale from the Mood and Anxiety Symptoms Questionnaire (MASQ-AD) as a way to screen for depressive disorders. Using receiver-operator characteristic analysis, the sensitivity and specificity of the full 22-item MASQ-AD scale, as well as the 8 and 14-item subscales, were examined in relation to both current and lifetime DSM-IV depressive disorder diagnoses in two nonpatient samples. As a means of comparison, the sensitivity and specificity of a measure of a relevant personality dimension, neuroticism, was also examined. Results from both samples support the clinical utility of the MASQ-AD scale as a means of screening for depressive disorders. Findings were strongest for the MASQ-AD 8-item subscale and when predicting current depression status. Furthermore, the MASQ-AD 8-item subscale outperformed the neuroticism measure under certain conditions. The overall usefulness of the MASQ-AD scale as a screening device is discussed, as well as possible cutoff scores for use in research. PMID:20822283

Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing

PubMed Central

Liao, Can; Yin, Ai-hua; Peng, Chun-fang; Fu, Fang; Yang, Jie-xia; Li, Ru; Chen, Yang-yi; Luo, Dong-hong; Zhang, Yong-ling; Ou, Yan-mei; Li, Jian; Wu, Jing; Mai, Ming-qin; Hou, Rui; Wu, Frances; Luo, Hongrong; Li, Dong-zhi; Liu, Hai-liang; Zhang, Xiao-zhuang; Zhang, Kang

2014-01-01

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting. PMID:24799683

Virtual screening methods as tools for drug lead discovery from large chemical libraries.

PubMed

Ma, X H; Zhu, F; Liu, X; Shi, Z; Zhang, J X; Yang, S Y; Wei, Y Q; Chen, Y Z

2012-01-01

Virtual screening methods have been developed and explored as useful tools for searching drug lead compounds from chemical libraries, including large libraries that have become publically available. In this review, we discussed the new developments in exploring virtual screening methods for enhanced performance in searching large chemical libraries, their applications in screening libraries of ~ 1 million or more compounds in the last five years, the difficulties in their applications, and the strategies for further improving these methods.

DPubChem: a web tool for QSAR modeling and high-throughput virtual screening.

PubMed

Soufan, Othman; Ba-Alawi, Wail; Magana-Mora, Arturo; Essack, Magbubah; Bajic, Vladimir B

2018-06-14

High-throughput screening (HTS) performs the experimental testing of a large number of chemical compounds aiming to identify those active in the considered assay. Alternatively, faster and cheaper methods of large-scale virtual screening are performed computationally through quantitative structure-activity relationship (QSAR) models. However, the vast amount of available HTS heterogeneous data and the imbalanced ratio of active to inactive compounds in an assay make this a challenging problem. Although different QSAR models have been proposed, they have certain limitations, e.g., high false positive rates, complicated user interface, and limited utilization options. Therefore, we developed DPubChem, a novel web tool for deriving QSAR models that implement the state-of-the-art machine-learning techniques to enhance the precision of the models and enable efficient analyses of experiments from PubChem BioAssay database. DPubChem also has a simple interface that provides various options to users. DPubChem predicted active compounds for 300 datasets with an average geometric mean and F 1 score of 76.68% and 76.53%, respectively. Furthermore, DPubChem builds interaction networks that highlight novel predicted links between chemical compounds and biological assays. Using such a network, DPubChem successfully suggested a novel drug for the Niemann-Pick type C disease. DPubChem is freely available at www.cbrc.kaust.edu.sa/dpubchem .

Prevalence and consequences of chromosomal abnormalities in Canadian commercial swine herds.

PubMed

Quach, Anh T; Revay, Tamas; Villagomez, Daniel A F; Macedo, Mariana P; Sullivan, Alison; Maignel, Laurence; Wyss, Stefanie; Sullivan, Brian; King, W Allan

2016-09-12

Structural chromosome abnormalities are well known as factors that reduce fertility rate in domestic pigs. According to large-scale national cytogenetic screening programs that are implemented in France, it is estimated that new chromosome abnormalities occur at a rate of 0.5 % in fertility-unproven boars. This work aimed at estimating the prevalence and consequences of chromosome abnormalities in commercial swine operations in Canada. We found pig carriers at a frequency of 1.64 % (12 out of 732 boars). Carrier pigs consistently showed lower fertility values. The total number of piglets born for litters from carrier boars was between 4 and 46 % lower than the herd average. Similarly, carrier boars produced litters with a total number of piglets born alive that was between 6 and 28 % lower than the herd average. A total of 12 new structural chromosome abnormalities were identified. Reproductive performance is significantly reduced in sires with chromosome abnormalities. The incidence of such abnormal sires appears relatively high in populations without routine cytogenetic screening such as observed for Canada in this study. Systematic cytogenetic screening of potential breeding boars would minimise the risk of carriers of chromosome aberrations entering artificial insemination centres. This would avoid the large negative effects on productivity for the commercial sow herds and reduce the risk of transmitting abnormalities to future generations in nucleus farms.

Facile synthesis of Prussian blue nanocubes/silver nanowires network as a water-based ink for the direct screen-printed flexible biosensor chips.

PubMed

Yang, Pengqi; Peng, Jingmeng; Chu, Zhenyu; Jiang, Danfeng; Jin, Wanqin

2017-06-15

The large-scale fabrication of nanocomposite based biosensors is always a challenge in the technology commercialization from laboratory to industry. In order to address this issue, we have designed a facile chemical method of fabricated nanocomposite ink applied to the screen-printed biosensor chip. This ink can be derived in the water through the in-situ growth of Prussian blue nanocubes (PBNCs) on the silver nanowires (AgNWs) to construct a composite nanostructure by a facile chemical method. Then a miniature flexible biosensor chip was screen-printed by using the prepared nanocomposite ink. Due to the synergic effects of the large specific surface area, high conductivity and electrocatalytic activity from AgNWs and PBNCs, the as-prepared biosensor chip exhibited a fast response (<3s)， a wider linear response from 0.01 to 1.3mM with an ultralow LOD=5µm, and the ultrahigh sensitivities of 131.31 and 481.20µAmM -1 cm -2 for the detections of glucose and hydrogen peroxide (H 2 O 2 ), respectively. Furthermore, the biosensor chip exhibited excellent stability, good reproducibility and high anti-interference ability towards physiological substances under a very low working potential of -0.05. Hence, the proposed biosensor chip also showed a promising potential for the application in practical analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection

PubMed Central

Wang, Yu; Chen, Pei-Min; Liu, Rong-Bin

2018-01-01

This review article summarizes the research advances of the plasma-based SEPT9 gene methylation assay for the clinical detection of colorectal cancer and its limitations. Colorectal cancer is a common malignancy with a poor prognosis and a high mortality, for which early detection and diagnosis are particularly crucial for the high-risk groups. Increasing evidence supported that SEPT9 gene methylation is associated with the pathogenesis of colorectal cancer and that detecting the level of methylation of SEPT9 in the peripheral blood can be used for screening of colorectal cancer in susceptible populations. In recent years, the data obtained in clinical studies demonstrated that the SEPT9 gene methylation assay has a good diagnostic performance with regard to both sensitivity and specificity with the advantage of better acceptability, convenience and compliance with serological testing compared with fecal occult blood tests and carcinoembryonic antigen for colorectal cancer (CRC). Furthermore, the combination of multiple methods or markers has become a growing trend for CRC detection and screening. Nevertheless, the clinical availability of the methylated SEPT9 assay is still limited because of the large degree of sample heterogeneity caused by demographic characteristics, pathological features, comorbidities and/or technique selection. Another factor is the cost-effectiveness of colorectal cancer screening strategies that hinders its large-scale application. In addition, improvements in its accuracy in detecting adenomas and premalignant polyps are required. PMID:29375744

A New Targeted CFTR Mutation Panel Based on Next-Generation Sequencing Technology.

PubMed

Lucarelli, Marco; Porcaro, Luigi; Biffignandi, Alice; Costantino, Lucy; Giannone, Valentina; Alberti, Luisella; Bruno, Sabina Maria; Corbetta, Carlo; Torresani, Erminio; Colombo, Carla; Seia, Manuela

2017-09-01

Searching for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) is a key step in the diagnosis of and neonatal and carrier screening for cystic fibrosis (CF), and it has implications for prognosis and personalized therapy. The large number of mutations and genetic and phenotypic variability make this search a complex task. Herein, we developed, validated, and tested a laboratory assay for an extended search for mutations in CFTR using a next-generation sequencing-based method, with a panel of 188 CFTR mutations customized for the Italian population. Overall, 1426 dried blood spots from neonatal screening, 402 genomic DNA samples from various origins, and 1138 genomic DNA samples from patients with CF were analyzed. The assay showed excellent analytical and diagnostic operative characteristics. We identified and experimentally validated 159 (of 188) CFTR mutations. The assay achieved detection rates of 95.0% and 95.6% in two large-scale case series of CF patients from central and northern Italy, respectively. These detection rates are among the highest reported so far with a genetic test for CF based on a mutation panel. This assay appears to be well suited for diagnostics, neonatal and carrier screening, and assisted reproduction, and it represents a considerable advantage in CF genetic counseling. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.