Sample records for target product profiles

  1. Target validation: linking target and chemical properties to desired product profile.

    PubMed

    Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

    2011-01-01

    The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

  2. What's the Regulatory Value of a Target Product Profile?

    PubMed

    Breder, Christopher D; Du, Wenny; Tyndall, Adria

    2017-07-01

    Target product profiles (TPPs) are used as a regulatory tool for dialog on clinical development or manufacturing plans. Drugs and biologics approved by the FDA that mention TPPs are associated with more efficient regulatory review times, perhaps as a result of increased planning or because the TPP promotes well-organized regulatory dialog. Published by Elsevier Ltd.

  3. Multiplexed Thiol Reactivity Profiling for Target Discovery of Electrophilic Natural Products.

    PubMed

    Tian, Caiping; Sun, Rui; Liu, Keke; Fu, Ling; Liu, Xiaoyu; Zhou, Wanqi; Yang, Yong; Yang, Jing

    2017-11-16

    Electrophilic groups, such as Michael acceptors, expoxides, are common motifs in natural products (NPs). Electrophilic NPs can act through covalent modification of cysteinyl thiols on functional proteins, and exhibit potent cytotoxicity and anti-inflammatory/cancer activities. Here we describe a new chemoproteomic strategy, termed multiplexed thiol reactivity profiling (MTRP), and its use in target discovery of electrophilic NPs. We demonstrate the utility of MTRP by identifying cellular targets of gambogic acid, an electrophilic NP that is currently under evaluation in clinical trials as anticancer agent. Moreover, MTRP enables simultaneous comparison of seven structurally diversified α,β-unsaturated γ-lactones, which provides insights into the relative proteomic reactivity and target preference of diverse structural scaffolds coupled to a common electrophilic motif and reveals various potential druggable targets with liganded cysteines. We anticipate that this new method for thiol reactivity profiling in a multiplexed manner will find broad application in redox biology and drug discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Constructing target product profiles (TPPs) to help vaccines overcome post-approval obstacles

    PubMed Central

    Lee, Bruce Y.; Burke, Donald S.

    2012-01-01

    As history has demonstrated, post-approval obstacles can impede a vaccine’s use and potentially lead to its withdrawal. Addressing these potential obstacles when changes in a vaccine’s technology can still be easily made may improve a vaccine’s chances of success. Augmented vaccine target product profiles (TPPs) can help vaccine scientists better understand and anticipate these obstacles and galvanize conversations among various vaccine stakeholders (e.g., scientists, marketers, business development managers, policy makers, public health officials, health care workers, third party payors, etc.) earlier in a vaccine’s development. PMID:19782109

  5. New developments in anti-malarial target candidate and product profiles.

    PubMed

    Burrows, Jeremy N; Duparc, Stephan; Gutteridge, Winston E; Hooft van Huijsduijnen, Rob; Kaszubska, Wiweka; Macintyre, Fiona; Mazzuri, Sébastien; Möhrle, Jörg J; Wells, Timothy N C

    2017-01-13

    A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

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

    PubMed Central

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

    2015-01-01

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

  7. Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles

    PubMed Central

    Ade, Maria Paz; Baird, J. Kevin; Cheng, Qin; Cunningham, Jane; Dhorda, Mehul; Drakeley, Chris; Felger, Ingrid; Gamboa, Dionicia; Harbers, Matthias; Herrera, Socrates; Lucchi, Naomi; Mayor, Alfredo; Mueller, Ivo; Sattabongkot, Jetsumon; Ratsimbason, Arsène; Richards, Jack; Tanner, Marcel; González, Iveth J.

    2017-01-01

    The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria. PMID:28369085

  8. Target product profiles for the diagnosis of Taenia solium taeniasis, neurocysticercosis and porcine cysticercosis.

    PubMed

    Donadeu, Meritxell; Fahrion, Anna S; Olliaro, Piero L; Abela-Ridder, Bernadette

    2017-09-01

    Target Product Profiles (TPPs) are process tools providing product requirements to guide researchers, developers and manufacturers in their efforts to develop effective and useful products such as biologicals, drugs or diagnostics. During a WHO Stakeholders Meeting on Taenia solium diagnostics, several TPPs were initiated to address diagnostic needs for different stages in the parasite's transmission (taeniasis, human and porcine cysticercosis). Following the meeting, draft TPPs were completed and distributed for consultation to 100 people/organizations, including experts in parasitology, human and pig cysticercosis, diagnostic researchers and manufacturers, international organizations working with neglected or zoonotic diseases, Ministries of Health and Ministries of Livestock in some of the endemic countries, WHO regional offices and other interested parties. There were 53 respondents. All comments and feedback received were considered and discussions were held with different experts according to their area of expertise. The comments were consolidated and final TPPs are presented here. They are considered to be live documents which are likely to undergo review and updating in the future when new knowledge and technologies become available.

  9. Target product profiles for the diagnosis of Taenia solium taeniasis, neurocysticercosis and porcine cysticercosis

    PubMed Central

    Fahrion, Anna S.; Olliaro, Piero L.; Abela-Ridder, Bernadette

    2017-01-01

    Target Product Profiles (TPPs) are process tools providing product requirements to guide researchers, developers and manufacturers in their efforts to develop effective and useful products such as biologicals, drugs or diagnostics. During a WHO Stakeholders Meeting on Taenia solium diagnostics, several TPPs were initiated to address diagnostic needs for different stages in the parasite’s transmission (taeniasis, human and porcine cysticercosis). Following the meeting, draft TPPs were completed and distributed for consultation to 100 people/organizations, including experts in parasitology, human and pig cysticercosis, diagnostic researchers and manufacturers, international organizations working with neglected or zoonotic diseases, Ministries of Health and Ministries of Livestock in some of the endemic countries, WHO regional offices and other interested parties. There were 53 respondents. All comments and feedback received were considered and discussions were held with different experts according to their area of expertise. The comments were consolidated and final TPPs are presented here. They are considered to be live documents which are likely to undergo review and updating in the future when new knowledge and technologies become available. PMID:28892472

  10. Laser range profiling for small target recognition

    NASA Astrophysics Data System (ADS)

    Steinvall, Ove; Tulldahl, Michael

    2016-05-01

    The detection and classification of small surface and airborne targets at long ranges is a growing need for naval security. Long range ID or ID at closer range of small targets has its limitations in imaging due to the demand on very high transverse sensor resolution. It is therefore motivated to look for 1D laser techniques for target ID. These include vibrometry, and laser range profiling. Vibrometry can give good results but is also sensitive to certain vibrating parts on the target being in the field of view. Laser range profiling is attractive because the maximum range can be substantial, especially for a small laser beam width. A range profiler can also be used in a scanning mode to detect targets within a certain sector. The same laser can also be used for active imaging when the target comes closer and is angular resolved. The present paper will show both experimental and simulated results for laser range profiling of small boats out to 6-7 km range and a UAV mockup at close range (1.3 km). We obtained good results with the profiling system both for target detection and recognition. Comparison of experimental and simulated range waveforms based on CAD models of the target support the idea of having a profiling system as a first recognition sensor and thus narrowing the search space for the automatic target recognition based on imaging at close ranges. The naval experiments took place in the Baltic Sea with many other active and passive EO sensors beside the profiling system. Discussion of data fusion between laser profiling and imaging systems will be given. The UAV experiments were made from the rooftop laboratory at FOI.

  11. Laser range profiling for small target recognition

    NASA Astrophysics Data System (ADS)

    Steinvall, Ove; Tulldahl, Michael

    2017-03-01

    Long range identification (ID) or ID at closer range of small targets has its limitations in imaging due to the demand for very high-transverse sensor resolution. This is, therefore, a motivation to look for one-dimensional laser techniques for target ID. These include laser vibrometry and laser range profiling. Laser vibrometry can give good results, but is not always robust as it is sensitive to certain vibrating parts on the target being in the field of view. Laser range profiling is attractive because the maximum range can be substantial, especially for a small laser beam width. A range profiler can also be used in a scanning mode to detect targets within a certain sector. The same laser can also be used for active imaging when the target comes closer and is angularly resolved. Our laser range profiler is based on a laser with a pulse width of 6 ns (full width half maximum). This paper will show both experimental and simulated results for laser range profiling of small boats out to a 6 to 7-km range and a unmanned arrial vehicle (UAV) mockup at close range (1.3 km). The naval experiments took place in the Baltic Sea using many other active and passive electro-optical sensors in addition to the profiling system. The UAV experiments showed the need for a high-range resolution, thus we used a photon counting system in addition to the more conventional profiler used in the naval experiments. This paper shows the influence of target pose and range resolution on the capability of classification. The typical resolution (in our case 0.7 m) obtainable with a conventional range finder type of sensor can be used for large target classification with a depth structure over 5 to 10 m or more, but for smaller targets such as a UAV a high resolution (in our case 7.5 mm) is needed to reveal depth structures and surface shapes. This paper also shows the need for 3-D target information to build libraries for comparison of measured and simulated range profiles. At closer ranges

  12. Package design and nutritional profile of foods targeted at children in supermarkets in Montevideo, Uruguay.

    PubMed

    Giménez, Ana; Saldamando, Luis de; Curutchet, María Rosa; Ares, Gastón

    2017-06-12

    Marketing of unhealthy products has been identified as one of the main characteristics of the food environment that negatively affects children's eating patterns. Restrictions on advertising of unhealthy foods to children have already been imposed in different countries. However, marketing strategies are not limited to broadcast and digital advertising, but also include package design. In this context, the current study aimed to describe the food products targeted at children and sold in supermarkets in Montevideo, Uruguay, in terms of package design and nutrient profile. Two supermarkets in Montevideo were selected for data collection. In each supermarket, all products targeted at children were identified. Products were analyzed in terms of package design and nutritional profile, considering the Pan American Health Organization Nutrient Profile Model. A total of 180 unique products were identified, which included a wide range of product categories. The great majority of the products corresponded to ultra-processed products with excessive amounts of sodium, free sugars, total fat, saturated fat, and/or trans fat, which are not recommended for frequent consumption. Several marketing strategies were identified in the design of packages to attract children's attention and drive their preferences. The most common strategies were the inclusion of cartoon characters, bright colors, childish lettering, and a wide range of claims related to health and nutrition, as well as the products' sensory and hedonic characteristics. The study's findings provide additional evidence on the need to regulate packaging of products targeted at children.

  13. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

    PubMed

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

  14. TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

    NASA Astrophysics Data System (ADS)

    Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

    2016-05-01

    Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

  15. Advances in identification and validation of protein targets of natural products without chemical modification.

    PubMed

    Chang, J; Kim, Y; Kwon, H J

    2016-05-04

    Covering: up to February 2016Identification of the target proteins of natural products is pivotal to understanding the mechanisms of action to develop natural products for use as molecular probes and potential therapeutic drugs. Affinity chromatography of immobilized natural products has been conventionally used to identify target proteins, and has yielded good results. However, this method has limitations, in that labeling or tagging for immobilization and affinity purification often result in reduced or altered activity of the natural product. New strategies have recently been developed and applied to identify the target proteins of natural products and synthetic small molecules without chemical modification of the natural product. These direct and indirect methods for target identification of label-free natural products include drug affinity responsive target stability (DARTS), stability of proteins from rates of oxidation (SPROX), cellular thermal shift assay (CETSA), thermal proteome profiling (TPP), and bioinformatics-based analysis of connectivity. This review focuses on and reports case studies of the latest advances in target protein identification methods for label-free natural products. The integration of newly developed technologies will provide new insights and highlight the value of natural products for use as biological probes and new drug candidates.

  16. Linear sine wave profiling to machine instability targets

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

    Schmidt, Derek William; Martinez, John Israel

    2016-08-01

    Specialized machining processes and programming have been developed to deliver thin tin and copper Richtmyer-Meshkov instability targets that have different amplitude perturbations across the face of one 4-in.-diameter target. Typical targets have anywhere from two to five different regions of sine waves that have different amplitudes varying from 4 to 200 μm across the face of the target. The puck is composed of multiple rings that are zero press fit together and diamond turned to create a flat platform with a tolerance of 2 μm for the shock experiment. A custom software program was written in Labview to write themore » point-to-point program for the diamond-turning profiler through the X-Y-Z movements to cut the pure planar straight sine wave geometry. As a result, the software is optimized to push the profile of the whole part into the face while eliminating any unneeded passes that do not cut any material.« less

  17. RobOKoD: microbial strain design for (over)production of target compounds.

    PubMed

    Stanford, Natalie J; Millard, Pierre; Swainston, Neil

    2015-01-01

    Sustainable production of target compounds such as biofuels and high-value chemicals for pharmaceutical, agrochemical, and chemical industries is becoming an increasing priority given their current dependency upon diminishing petrochemical resources. Designing these strains is difficult, with current methods focusing primarily on knocking-out genes, dismissing other vital steps of strain design including the overexpression and dampening of genes. The design predictions from current methods also do not translate well-into successful strains in the laboratory. Here, we introduce RobOKoD (Robust, Overexpression, Knockout and Dampening), a method for predicting strain designs for overproduction of targets. The method uses flux variability analysis to profile each reaction within the system under differing production percentages of target-compound and biomass. Using these profiles, reactions are identified as potential knockout, overexpression, or dampening targets. The identified reactions are ranked according to their suitability, providing flexibility in strain design for users. The software was tested by designing a butanol-producing Escherichia coli strain, and was compared against the popular OptKnock and RobustKnock methods. RobOKoD shows favorable design predictions, when predictions from these methods are compared to a successful butanol-producing experimentally-validated strain. Overall RobOKoD provides users with rankings of predicted beneficial genetic interventions with which to support optimized strain design.

  18. Mass Spectrometry Based Ultrasensitive DNA Methylation Profiling Using Target Fragmentation Assay.

    PubMed

    Lin, Xiang-Cheng; Zhang, Ting; Liu, Lan; Tang, Hao; Yu, Ru-Qin; Jiang, Jian-Hui

    2016-01-19

    Efficient tools for profiling DNA methylation in specific genes are essential for epigenetics and clinical diagnostics. Current DNA methylation profiling techniques have been limited by inconvenient implementation, requirements of specific reagents, and inferior accuracy in quantifying methylation degree. We develop a novel mass spectrometry method, target fragmentation assay (TFA), which enable to profile methylation in specific sequences. This method combines selective capture of DNA target from restricted cleavage of genomic DNA using magnetic separation with MS detection of the nonenzymatic hydrolysates of target DNA. This method is shown to be highly sensitive with a detection limit as low as 0.056 amol, allowing direct profiling of methylation using genome DNA without preamplification. Moreover, this method offers a unique advantage in accurately determining DNA methylation level. The clinical applicability was demonstrated by DNA methylation analysis using prostate tissue samples, implying the potential of this method as a useful tool for DNA methylation profiling in early detection of related diseases.

  19. Impact of Profiling Technologies in the Understanding of Recombinant Protein Production

    NASA Astrophysics Data System (ADS)

    Vijayendran, Chandran; Flaschel, Erwin

    Since expression profiling methods have been available in a high throughput fashion, the implication of these technologies in the field of biotechnology has increased dramatically. Microarray technology is one such unique and efficient methodology for simultaneous exploration of expression levels of numerous genes. Likewise, two-dimensional gel electrophoresis or multidimensional liquid chromatography coupled with mass spectrometry are extensively utilised for studying expression levels of numerous proteins. In the field of biotechnology these highly parallel analytical methods have paved the way to study and understand various biological phenomena depending on expression patterns. The next phenomenological level is represented by the metabolome and the (metabolic) fluxome. However, this chapter reviews gene and protein profiling and their impact on understanding recombinant protein production. We focus on the computational methods utilised for the analyses of data obtained from these profiling technologies as well as prominent results focusing on recombinant protein expression with Escherichia coli. Owing to the knowledge accumulated with respect to cellular signals triggered during recombinant protein production, this field is on the way to design strategies for developing improved processes. Both gene and protein profiling have exhibited a handful of functional categories to concentrate on in order to identify target genes and proteins, respectively, involved in the signalling network with major impact on recombinant protein production.

  20. RobOKoD: microbial strain design for (over)production of target compounds

    PubMed Central

    Stanford, Natalie J.; Millard, Pierre; Swainston, Neil

    2015-01-01

    Sustainable production of target compounds such as biofuels and high-value chemicals for pharmaceutical, agrochemical, and chemical industries is becoming an increasing priority given their current dependency upon diminishing petrochemical resources. Designing these strains is difficult, with current methods focusing primarily on knocking-out genes, dismissing other vital steps of strain design including the overexpression and dampening of genes. The design predictions from current methods also do not translate well-into successful strains in the laboratory. Here, we introduce RobOKoD (Robust, Overexpression, Knockout and Dampening), a method for predicting strain designs for overproduction of targets. The method uses flux variability analysis to profile each reaction within the system under differing production percentages of target-compound and biomass. Using these profiles, reactions are identified as potential knockout, overexpression, or dampening targets. The identified reactions are ranked according to their suitability, providing flexibility in strain design for users. The software was tested by designing a butanol-producing Escherichia coli strain, and was compared against the popular OptKnock and RobustKnock methods. RobOKoD shows favorable design predictions, when predictions from these methods are compared to a successful butanol-producing experimentally-validated strain. Overall RobOKoD provides users with rankings of predicted beneficial genetic interventions with which to support optimized strain design. PMID:25853130

  1. Effects of the plasma profiles on photon and pair production in ultrahigh intensity laser solid interaction

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

    Tian, Y. X.; Jin, X. L., E-mail: jinxiaolin@uestc.edu.cn; Yan, W. Z.

    The model of photon and pair production in strong field quantum electrodynamics is implemented into our 1D3V particle-in-cell code with Monte Carlo algorithm. Using this code, the evolution of the particles in ultrahigh intensity laser (∼10{sup 23} W/cm{sup 2}) interaction with aluminum foil target is observed. Four different initial plasma profiles are considered in the simulations. The effects of initial plasma profiles on photon and pair production, energy spectra, and energy evolution are analyzed. The results imply that one can set an optimal initial plasma profile to obtain the desired photon distributions.

  2. Advancing prevention of sexually transmitted infections through point-of-care testing: target product profiles and landscape analysis.

    PubMed

    Toskin, Igor; Murtagh, Maurine; Peeling, Rosanna W; Blondeel, Karel; Cordero, Joanna; Kiarie, James

    2017-12-01

    Advancing the field of point-of-care testing (POCT) for STIs can rapidly and substantially improve STI control and prevention by providing targeted, essential STI services (case detection and screening). POCT enables definitive diagnosis and appropriate treatment in a single visit and home and community-based testing. Since 2014, the WHO Department of Reproductive Health and Research, in collaboration with technical partners, has completed four landscape analyses of promising diagnostics for use at or near the point of patient care to detect syphilis, Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis and the human papillomavirus. The analyses comprised a literature review and interviews. Two International Technical Consultations on STI POCTs (2014 and 2015) resulted in the development of target product profiles (TPP). Experts in STI microbiology, laboratory diagnostics, clinical management, public health and epidemiology participated in the consultations with representation from all WHO regions. The landscape analysis identified diagnostic tests that are either available on the market, to be released in the near future or in the pipeline. The TPPs specify 28 analytical and operational characteristics of POCTs for use in different populations for surveillance, screening and case management. None of the tests that were identified in the landscape analysis met all of the targets of the TPPs. More efforts of the global health community are needed to accelerate access to affordable quality-assured STI POCTs, particularly in low- and middle-income countries, by supporting the development of new diagnostic platforms as well as strengthening the validation and implementation of existing diagnostics according to internationally endorsed standards and the best available evidence. © World Health Organization 2017. Licensee BMJ Publishing Group Limited. This is an open access article distributed under the terms of the Creative Commons Attribution IGO

  3. Network-assisted target identification for haploinsufficiency and homozygous profiling screens

    PubMed Central

    Wang, Sheng

    2017-01-01

    Chemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale. Drug target identification and elucidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain difficult. Here, we present GIT (Genetic Interaction Network-Assisted Target Identification), a network analysis method for drug target identification in haploinsufficiency profiling (HIP) and homozygous profiling (HOP) screens. With the drug-induced phenotypic fitness defect of the deletion of a gene, GIT also incorporates the fitness defects of the gene’s neighbors in the genetic interaction network. On three genome-scale yeast chemical genomic screens, GIT substantially outperforms previous scoring methods on target identification on HIP and HOP assays, respectively. Finally, we showed that by combining HIP and HOP assays, GIT further boosts target identification and reveals potential drug’s mechanism of action. PMID:28574983

  4. Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

    PubMed

    Fang, J; Cai, C; Wang, Q; Lin, P; Zhao, Z; Cheng, F

    2017-03-01

    Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  5. Optical bi-sensorial measurement system for production control of extruded profiles

    NASA Astrophysics Data System (ADS)

    Weckenmann, A.; Bernstein, J.

    2008-09-01

    Extruded profiles are semi-finished products (made out of steel, brass, aluminum, synthetics...) which are appointed for wide applications in manufacturing of technical products. As yet used optical sensors in process control working to the shading technology detect the object's shadow orthographically to the axis of illumination. As a consequence they record it unattached by the profiles coat in measurement range at any point of the measured profile with high precision. As a matter of fact, concave zones cannot be captured. Alternatively the measurement of concave zones can be arranged by light-section systems. These do not comply with the required accuracy, are comparatively slow and moreover affected by dislocations of the section of the profile. A measurement system including a light-section and a shading system combines the advantages of both optical systems. It is to serve with a reliable conception for the assembly of a bi-sensorial measurement system consisting of both systems as well as suitable methods of analysis for the in-line inspection of concave profiles. As a result it contains conclusions concerning requirements of the light source, the arrangement of this source and the cameras, obtainable precision and sampling rate as well as the essential synchronization of both systems. After designing an appropriate prototype, the selected light-section system and the shading system will be synchronized and aligned. Therefore, the metered geometrical data will be merged for the evaluation of form deviation. So, developed and adapted software supports and contains proposals to the uncertainty after successful tests. The system and a calibration method will be proved in production where robustness will be a most critical despite of heat, dust and vibrations. The target uncertainty of less than 0.1 mm at every section of the profiles coat has to be met.

  6. Design and evaluation of multi-indicator profiles for targeted-selective treatment against gastrointestinal nematodes at housing in adult dairy cows.

    PubMed

    Ravinet, Nadine; Lehebel, Anne; Bareille, Nathalie; Lopez, Carlos; Chartier, Christophe; Chauvin, Alain; Madouasse, Aurélien

    2017-04-15

    Targeted-selective treatments against gastrointestinal nematode (GIN) in adult dairy cows require the identification of "cows to treat", i.e. cows whose milk production (MP) would increase after treatment. This study aimed at quantifying the ability of multi-indicator profiles to identify such cows. A randomized controlled clinical trial was conducted at housing in 25 French pasturing dairy herds. In each herd, treated cows received fenbendazole orally, control cows remained untreated. Daily MP was recorded and the MP variation between the pre- and post-visit periods was calculated (ΔMP) for each cow. ΔMP was modelled with control cows data (n=412) (piecewise linear mixed model). Estimated parameters were applied to treated cows data (n=414) to predict the expected ΔMP in treated cows if they had not been treated. Treated cows with an observed ΔMP (with treatment) higher than the expected ΔMP (without treatment) were labelled as "cows to treat". Herds where at least 50% of the young cows were "cows to treat" were qualified as "herds to target". To characterize such cows and herds, the available candidate indicators were (i) at the cow-level: parity, stage of lactation and production level, faecal egg count (FEC), serum pepsinogen level and anti-Ostertagia antibody level (expressed as ODR); (ii) at the herd-level: bulk tank milk (BTM) Ostertagia ODR, Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving, and percentage of positive FEC. These indicators were tested one-by-one or in combination to assess their ability to characterize "herds to target" and "cows to treat" (Chi-square tests). 115 out of 414 treated cows (27.8%) were considered as "cows to treat", and 9 out of 22 herds were qualified as "herds to target". The indicators retained to profile such cows and herds were the parity, the production level, the BTM Ostertagia ODR and the TEC. Multi-indicator profiles were much more specific than single indicator

  7. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

    PubMed

    Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

    2016-10-01

    Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Targeted metabolomic profiling in rat tissues reveals sex differences.

    PubMed

    Ruoppolo, Margherita; Caterino, Marianna; Albano, Lucia; Pecce, Rita; Di Girolamo, Maria Grazia; Crisci, Daniela; Costanzo, Michele; Milella, Luigi; Franconi, Flavia; Campesi, Ilaria

    2018-03-16

    Sex differences affect several diseases and are organ-and parameter-specific. In humans and animals, sex differences also influence the metabolism and homeostasis of amino acids and fatty acids, which are linked to the onset of diseases. Thus, the use of targeted metabolite profiles in tissues represents a powerful approach to examine the intermediary metabolism and evidence for any sex differences. To clarify the sex-specific activities of liver, heart and kidney tissues, we used targeted metabolomics, linear discriminant analysis (LDA), principal component analysis (PCA), cluster analysis and linear correlation models to evaluate sex and organ-specific differences in amino acids, free carnitine and acylcarnitine levels in male and female Sprague-Dawley rats. Several intra-sex differences affect tissues, indicating that metabolite profiles in rat hearts, livers and kidneys are organ-dependent. Amino acids and carnitine levels in rat hearts, livers and kidneys are affected by sex: male and female hearts show the greatest sexual dimorphism, both qualitatively and quantitatively. Finally, multivariate analysis confirmed the influence of sex on the metabolomics profiling. Our data demonstrate that the metabolomics approach together with a multivariate approach can capture the dynamics of physiological and pathological states, which are essential for explaining the basis of the sex differences observed in physiological and pathological conditions.

  9. Optimising diagnosis of viraemic hepatitis C infection: the development of a target product profile.

    PubMed

    Ivanova Reipold, Elena; Easterbrook, Philippa; Trianni, Alessandra; Panneer, Nivedha; Krakower, Douglas; Ongarello, Stefano; Roberts, Teri; Miller, Veronica; Denkinger, Claudia

    2017-11-01

    The current low access to virological testing to confirm chronic viraemic HCV infection in low- and middle-income countries (LMIC) is limiting the rollout of hepatitis C (HCV) care. Existing tests are complex, costly and require sophisticated laboratory infrastructure. Diagnostic manufacturers need guidance on the optimal characteristics a virological test needs to have to ensure the greatest impact on HCV diagnosis and treatment in LMIC. Our objective was to develop a target product profile (TPP) for diagnosis of HCV viraemia using a global stakeholder consensus-based approach. Based on the standardised process established to develop consensus-based TPPs, we followed five key steps. (i) Identifying key potential global stakeholders for consultation and input into the TPP development process. (ii) Informal priority-setting exercise with key experts to identify the needs that should be the highest priority for the TPP development; (iii) Defining the key TPP domains (scope, performance and operational characteristics and price). (iv) Delphi-like process with larger group of key stakeholder to facilitate feedback on the key TPP criteria and consensus building based on pre-defined consensus criteria. (v) A final consensus-gathering meeting for discussions around disputed criteria. A complementary values and preferences survey helped to assess trade-offs between different key characteristics. The following key attributes for the TPP for a test to confirm HCV viraemic infection were identified: The scope defined is for both HCV detection as well as confirmation of cure. The timeline of development for tests envisioned in the TPP is 5 years. The test should be developed for use by health-care workers or laboratory technicians with limited training in countries with a medium to high prevalence of HCV (1.5-3.5% and >3.5%) and in high-risk populations in low prevalence settings (<1.5%). A clinical sensitivity at a minimum of 90% is considered sufficient (analytical

  10. Small target detection using bilateral filter and temporal cross product in infrared images

    NASA Astrophysics Data System (ADS)

    Bae, Tae-Wuk

    2011-09-01

    We introduce a spatial and temporal target detection method using spatial bilateral filter (BF) and temporal cross product (TCP) of temporal pixels in infrared (IR) image sequences. At first, the TCP is presented to extract the characteristics of temporal pixels by using temporal profile in respective spatial coordinates of pixels. The TCP represents the cross product values by the gray level distance vector of a current temporal pixel and the adjacent temporal pixel, as well as the horizontal distance vector of the current temporal pixel and a temporal pixel corresponding to potential target center. The summation of TCP values of temporal pixels in spatial coordinates makes the temporal target image (TTI), which represents the temporal target information of temporal pixels in spatial coordinates. And then the proposed BF filter is used to extract the spatial target information. In order to predict background without targets, the proposed BF filter uses standard deviations obtained by an exponential mapping of the TCP value corresponding to the coordinate of a pixel processed spatially. The spatial target image (STI) is made by subtracting the predicted image from the original image. Thus, the spatial and temporal target image (STTI) is achieved by multiplying the STI and the TTI, and then targets finally are detected in STTI. In experimental result, the receiver operating characteristics (ROC) curves were computed experimentally to compare the objective performance. From the results, the proposed algorithm shows better discrimination of target and clutters and lower false alarm rates than the existing target detection methods.

  11. The Variation of Work Productivity and Muscle Activities at Different Levels of Production Target

    NASA Astrophysics Data System (ADS)

    Nur, Nurhayati Mohd; Dawal, Siti Zawiah Md; Dahari, Mahidzal; Zuhairah Mahmud Zuhudi, Nurul

    2017-10-01

    This paper aims to investigate the variation of work productivity and muscle activities among workers performing industrial repetitive tasks at four different levels of production target. The work productivity and muscle activities data were recorded from twenty workers at four levels of production target corresponding to “participative (PS1)”, “normal (PS2)”, “high (PS3)” and “very high (PS4)”. The results showed that worker productivity was found to increase at higher production target and there was a significant change (p < 0.005) in work productivity across the four different production targets. The muscle activities were found to increase at higher production target and correspond to more discomfort and a higher rate of muscle fatigue. The results indicated that working with a higher production target results in higher worker productivity, but could lead to higher risk of WMSDs.

  12. Development of Water Target for Radioisotope Production

    NASA Astrophysics Data System (ADS)

    Tripp, Nathan

    2011-10-01

    Ongoing studies of plant physiology at TUNL require a supply of nitrogen-13 for use as a radiotracer. Production of nitrogen-13 using a water target and a proton beam follows the nuclear reaction 16-O(p,a)13-N. Unfortunately the irradiation of trace amounts of oxygen-18 within a natural water target produces fluorine-18 by the reaction 18-O(p, n)18-F. The presence of this second radioisotope reduces the efficacy of nitrogen-13 as a radiotracer. Designing a natural water target for nitrogen-13 production at TUNL required the design of several new systems to address the problems inherent in nitrogen-13 production. A heat exchanger cools the target water after irradiation within the target cell. The resulting improved thermal regulation of the target water prevents the system from overheating and minimizes the effect of the cavitations occurring within the target. Alumina pellets within a scrubbing unit remove the fluorine-18 contamination from the irradiated water. The modular design of the water target apparatus makes the system highly adaptable, allowing for easy reuse and adaptation of the different components into future projects. The newly designed and constructed water target should meet the current and future needs of TUNL researchers in the production of nitrogen-13. This TUNL REU project was funded in part by a grant from the National Science Foundation (NSF) NSF-PHY-08-51813.

  13. Proposed industrial recovered materials utilization targets for the metals and metal products industry

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

    None

    1979-05-01

    Set targets for increased utilization of energy-saving recovered materials in the metals and metal products industries (ferrous, aluminium, copper, zinc, and lead) are discussed. Data preparation and methodology development and analysis of the technological and economic factors in order to prepare draft targets for the use of recovered materials are covered. Chapter 2 provides an introductory discussion of the factors that affect the recovery and reuse of secondary materials and the competition between the primary and secondary metals industries. Chapter 3 presents general profiles for the major industrial segments comprising SIC 33, including industry structure, process technology, materials and recyclingmore » flow, and future trends for the 5 industries: ferrous, aluminium, copper, zinc, and lead. Chapter 4 presents the evaluation of recycling targets for those industries. (MCW)« less

  14. Evaluation of the 3-GeV proton beam profile at the spallation target of the JSNS

    NASA Astrophysics Data System (ADS)

    Meigo, Shin-ichiro; Noda, Fumiaki; Ishikura, Syuichi; Futakawa, Masatoshi; Sakamoto, Shinichi; Ikeda, Yujiro

    2006-06-01

    At JSNS, 3-GeV protons beam is delivered from rapid cycling synchrotron (RCS) to the spallation neutron target. In order to reduce the damage of pitting on the target container, the peak current density should be kept as small as possible. In this study, the beam profile at spallation neutron target is evaluated. The phase-space distribution, including the space-charge effect, is calculated with SIMPSONS code. The beam profile on the target is obtained with the transfer matrix from exit of RCS to the target. As for injection to RCS, two methods of correlated and anti-correlated painting are considered. By using anti-correlated painting for injection of beam at RCS, it is found the shape of beam becomes flatter than the distribution by using correlated painting. As other aspect for the study of target, in order to carry out target performance test especially for the study of pitting issue, it is better to have the beam profile variety from the beginning of facility. The adjustable range for the beam profile at the beginning is also studied. Although the beam shape is narrow and the duty is very low, the strong enough peak density is achievable equivalent as 1 MW.

  15. The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

    PubMed

    Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

    2016-01-01

    The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

  16. Identifying antimalarial compounds targeting dihydrofolate reductase-thymidylate synthase (DHFR-TS) by chemogenomic profiling.

    PubMed

    Aroonsri, Aiyada; Akinola, Olugbenga; Posayapisit, Navaporn; Songsungthong, Warangkhana; Uthaipibull, Chairat; Kamchonwongpaisan, Sumalee; Gbotosho, Grace O; Yuthavong, Yongyuth; Shaw, Philip J

    2016-07-01

    The mode of action of many antimalarial drugs is unknown. Chemogenomic profiling is a powerful method to address this issue. This experimental approach entails disruption of gene function and phenotypic screening for changes in sensitivity to bioactive compounds. Here, we describe the application of reverse genetics for chemogenomic profiling in Plasmodium. Plasmodium falciparum parasites harbouring a transgenic insertion of the glmS ribozyme downstream of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene were used for chemogenomic profiling of antimalarial compounds to identify those which target DHFR-TS. DHFR-TS expression can be attenuated by exposing parasites to glucosamine. Parasites with attenuated DHFR-TS expression were significantly more sensitive to antifolate drugs known to target DHFR-TS. In contrast, no change in sensitivity to other antimalarial drugs with different modes of action was observed. Chemogenomic profiling was performed using the Medicines for Malaria Venture (Switzerland) Malaria Box compound library, and two compounds were identified as novel DHFR-TS inhibitors. We also tested the glmS ribozyme in Plasmodium berghei, a rodent malaria parasite. The expression of reporter genes with downstream glmS ribozyme could be attenuated in transgenic parasites comparable with that obtained in P. falciparum. The chemogenomic profiling method was applied in a P. berghei line expressing a pyrimethamine-resistant Toxoplasma gondii DHFR-TS reporter gene under glmS ribozyme control. Parasites with attenuated expression of this gene were significantly sensitised to antifolates targeting DHFR-TS, but not other drugs with different modes of action. In conclusion, these data show that the glmS ribozyme reverse genetic tool can be applied for identifying primary targets of antimalarial compounds in human and rodent malaria parasites. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  17. Release 2 data products from the Ozone Mapping and Profiler Suite (OMPS) Limb Profiler

    NASA Astrophysics Data System (ADS)

    Xu, Philippe Q.; Bhartia, Pawan K.; Jaross, Glen R.; DeLand, Matthew T.; Larsen, Jack C.; Fleig, Albert; Kahn, Daniel; Zhu, Tong; Chen, Zhong; Gorkavyi, Nick; Warner, Jeremy; Linda, Michael; Chen, Hong G.; Kowitt, Mark; Haken, Michael; Hall, Peter

    2014-10-01

    The OMPS Limb Profiler (LP) was launched on board the NASA Suomi National Polar-orbiting Partnership (SNPP) satellite in October 2011. OMPS-LP is a limb-scattering hyperspectral sensor that provides ozone profiling capability at 1.8 km vertical resolution from cloud top to 60 km altitude. The use of three parallel slits allows global coverage in approximately four days. We have recently completed a full reprocessing of all LP data products, designated as Release 2, that improves the accuracy and quality of these products. Level 1 gridded radiance (L1G) changes include intra-orbit and seasonal correction of variations in wavelength registration, revised static and intra-orbit tangent height adjustments, and simplified pixel selection from multiple images. Ozone profile retrieval changes include removal of the explicit aerosol correction, exclusion of channels contaminated by stratospheric OH emission, a revised instrument noise characterization, improved synthetic solar spectrum, improved pressure and temperature ancillary data, and a revised ozone climatology. Release 2 data products also include aerosol extinction coefficient profiles derived with the prelaunch retrieval algorithm. Our evaluation of OMPS LP Release 2 data quality is good. Zonal average ozone profile comparisons with Aura MLS data typically show good agreement, within 5-10% over the altitude range 20-50 km between 60°S and 60°N. The aerosol profiles agree well with concurrent satellite measurements such as CALIPSO and OSIRIS, and clearly detect exceptional events such as volcanic eruptions and the Chelyabinsk bolide in February 2013.

  18. Release 2 data products from the Ozone Mapping and Profiler Suite (OMPS) Limb Profiler

    NASA Technical Reports Server (NTRS)

    Xu, Q. Philippe; Bhartia, Pawan K.; Jaross, Glen R.; Deland, Matthew T.; Larsen, Jack C.; Fleig, Albert; Kahn, Daniel; Zhu, Tong; Chen, Zhong; Gorkavyi, Nick; hide

    2014-01-01

    The OMPS Limb Profiler (LP) was launched on board the NASA Suomi National Polar-orbiting Partnership (SNPP) satellite in October 2011. OMPS-LP is a limb-scattering hyperspectral sensor that provides ozone profiling capability at 1.5 km vertical resolution from cloud top to 60 km altitude. The use of three parallel slits allows global coverage in approximately four days. We have recently completed a full reprocessing of all LP data products, designated as Release 2, that improves the accuracy and quality of these products. Level 1 gridded radiance (L1G) changes include intra-orbit and seasonal correction of variations in wavelength registration, revised static and intra-orbit tangent height adjustments, and simplified pixel selection from multiple images. Ozone profile retrieval changes include removal of the explicit aerosol correction, exclusion of channels contaminated by stratospheric OH emission, a revised instrument noise characterization, improved synthetic solar spectrum, improved pressure and temperature ancillary data, and a revised ozone climatology. Release 2 data products also include aerosol extinction coefficient profiles derived with the prelaunch retrieval algorithm. Our evaluation of OMPS LP Release 2 data quality is good. Zonal average ozone profile comparisons with Aura MLS data typically show good agreement, within 5-10% over the altitude range 20-50 km between 60 deg S and 60 deg N. The aerosol profiles agree well with concurrent satellite measurements such as CALIPSO and OSIRIS, and clearly detect exceptional events such as volcanic eruptions and the Chelyabinsk bolide in February 2013.

  19. Molecular profiling of intrahepatic cholangiocarcinoma: the search for new therapeutic targets.

    PubMed

    Oliveira, Douglas V N P; Zhang, Shanshan; Chen, Xin; Calvisi, Diego F; Andersen, Jesper B

    2017-04-01

    Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary tumor of the liver and a highly lethal disease. Therapeutic options for advanced iCCA are limited and ineffective due to the largely incomplete understanding of the molecular pathogenesis of this deadly tumor. Areas covered: The present review article outlines the main studies and resulting discoveries on the molecular profiling of iCCA, with a special emphasis on the different techniques used for this purpose, the diagnostic and prognostic markers identified, as well as the genes and pathways that could be potentially targeted with innovative therapies. Expert commentary: Molecular profiling has led to the identification of distinct iCCA subtypes, characterized by peculiar genetic alterations and transcriptomic features. Targeted therapies against some of the identified genes are ongoing and hold great promise to improve the prognosis of iCCA patients.

  20. Beauty and charm production at fixed-target experiments

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

    Erik E. Gottschalk

    Fixed-target experiments continue to provide insights into the physics of particle production in strong interactions. The experiments are performed with different types of beam particles of varying energies, and many different target materials. Studies of beauty and charm production are of particular interest, since experimental results can be compared to perturbative QCD calculations. It is in this context that recent results from fixed-target experiments on beauty and charm production will be reviewed.

  1. ampliMethProfiler: a pipeline for the analysis of CpG methylation profiles of targeted deep bisulfite sequenced amplicons.

    PubMed

    Scala, Giovanni; Affinito, Ornella; Palumbo, Domenico; Florio, Ermanno; Monticelli, Antonella; Miele, Gennaro; Chiariotti, Lorenzo; Cocozza, Sergio

    2016-11-25

    CpG sites in an individual molecule may exist in a binary state (methylated or unmethylated) and each individual DNA molecule, containing a certain number of CpGs, is a combination of these states defining an epihaplotype. Classic quantification based approaches to study DNA methylation are intrinsically unable to fully represent the complexity of the underlying methylation substrate. Epihaplotype based approaches, on the other hand, allow methylation profiles of cell populations to be studied at the single molecule level. For such investigations, next-generation sequencing techniques can be used, both for quantitative and for epihaplotype analysis. Currently available tools for methylation analysis lack output formats that explicitly report CpG methylation profiles at the single molecule level and that have suited statistical tools for their interpretation. Here we present ampliMethProfiler, a python-based pipeline for the extraction and statistical epihaplotype analysis of amplicons from targeted deep bisulfite sequencing of multiple DNA regions. ampliMethProfiler tool provides an easy and user friendly way to extract and analyze the epihaplotype composition of reads from targeted bisulfite sequencing experiments. ampliMethProfiler is written in python language and requires a local installation of BLAST and (optionally) QIIME tools. It can be run on Linux and OS X platforms. The software is open source and freely available at http://amplimethprofiler.sourceforge.net .

  2. RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma.

    PubMed

    Arora, Shilpi; Gonzales, Irma M; Hagelstrom, R Tanner; Beaudry, Christian; Choudhary, Ashish; Sima, Chao; Tibes, Raoul; Mousses, Spyro; Azorsa, David O

    2010-08-18

    Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma.

  3. Target-depth estimation in active sonar: Cramer-Rao bounds for a bilinear sound-speed profile.

    PubMed

    Mours, Alexis; Ioana, Cornel; Mars, Jérôme I; Josso, Nicolas F; Doisy, Yves

    2016-09-01

    This paper develops a localization method to estimate the depth of a target in the context of active sonar, at long ranges. The target depth is tactical information for both strategy and classification purposes. The Cramer-Rao lower bounds for the target position as range and depth are derived for a bilinear profile. The influence of sonar parameters on the standard deviations of the target range and depth are studied. A localization method based on ray back-propagation with a probabilistic approach is then investigated. Monte-Carlo simulations applied to a summer Mediterranean sound-speed profile are performed to evaluate the efficiency of the estimator. This method is finally validated on data in an experimental tank.

  4. Models for estimating photosynthesis parameters from in situ production profiles

    NASA Astrophysics Data System (ADS)

    Kovač, Žarko; Platt, Trevor; Sathyendranath, Shubha; Antunović, Suzana

    2017-12-01

    The rate of carbon assimilation in phytoplankton primary production models is mathematically prescribed with photosynthesis irradiance functions, which convert a light flux (energy) into a material flux (carbon). Information on this rate is contained in photosynthesis parameters: the initial slope and the assimilation number. The exactness of parameter values is crucial for precise calculation of primary production. Here we use a model of the daily production profile based on a suite of photosynthesis irradiance functions and extract photosynthesis parameters from in situ measured daily production profiles at the Hawaii Ocean Time-series station Aloha. For each function we recover parameter values, establish parameter distributions and quantify model skill. We observe that the choice of the photosynthesis irradiance function to estimate the photosynthesis parameters affects the magnitudes of parameter values as recovered from in situ profiles. We also tackle the problem of parameter exchange amongst the models and the effect it has on model performance. All models displayed little or no bias prior to parameter exchange, but significant bias following parameter exchange. The best model performance resulted from using optimal parameter values. Model formulation was extended further by accounting for spectral effects and deriving a spectral analytical solution for the daily production profile. The daily production profile was also formulated with time dependent growing biomass governed by a growth equation. The work on parameter recovery was further extended by exploring how to extract photosynthesis parameters from information on watercolumn production. It was demonstrated how to estimate parameter values based on a linearization of the full analytical solution for normalized watercolumn production and from the solution itself, without linearization. The paper complements previous works on photosynthesis irradiance models by analysing the skill and consistency of

  5. Strategies for target identification of antimicrobial natural products.

    PubMed

    Farha, Maya A; Brown, Eric D

    2016-05-04

    Covering: 2000 to 2015Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical-based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs.

  6. Laser beam-profile impression and target thickness impact on laser-accelerated protons

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

    Schollmeier, M.; Harres, K.; Nuernberg, F.

    Experimental results on the influence of the laser focal spot shape onto the beam profile of laser-accelerated protons from gold foils are reported. The targets' microgrooved rear side, together with a stack of radiochromic films, allowed us to deduce the energy-dependent proton source-shape and size, respectively. The experiments show, that shape and size of the proton source depend only weakly on target thickness as well as shape of the laser focus, although they strongly influence the proton's intensity distribution. It was shown that the laser creates an electron beam that closely follows the laser beam topology, which is maintained duringmore » the propagation through the target. Protons are then accelerated from the rear side with an electron created electric field of a similar shape. Simulations with the Sheath-Accelerated Beam Ray-tracing for IoN Analysis code SABRINA, which calculates the proton distribution in the detector for a given laser-beam profile, show that the electron distribution during the transport through a thick target (50 {mu}m Au) is only modified due to multiple small angle scattering. Thin targets (10 {mu}m) show large source sizes of over 100 {mu}m diameter for 5 MeV protons, which cannot be explained by multiple scattering only and are most likely the result of refluxing electrons.« less

  7. High power neutron production targets

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

    Wender, S.

    1996-06-01

    The author describes issues of concern in the design of targets and associated systems for high power neutron production facilities. The facilities include uses for neutron scattering, accelerator driven transmutation, accelerator production of tritium, short pulse spallation sources, and long pulse spallation sources. Each of these applications requires a source with different design needs and consequently different implementation in practise.

  8. The SPES High Power ISOL production target

    NASA Astrophysics Data System (ADS)

    Andrighetto, A.; Corradetti, S.; Ballan, M.; Borgna, F.; Manzolaro, M.; Scarpa, D.; Monetti, A.; Rossignoli, M.; Silingardi, R.; Mozzi, A.; Vivian, G.; Boratto, E.; De Ruvo, L.; Sattin, N.; Meneghetti, G.; Oboe, R.; Guerzoni, M.; Margotti, A.; Ferrari, M.; Zenoni, A.; Prete, G.

    2016-11-01

    SPES (Selective Production of Exotic Species) is a facility under construction at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro), aimed to produce intense neutron-rich radioactive ion beams (RIBs). These will be obtained using the ISOL (Isotope Separation On-Line) method, bombarding a uranium carbide target with a proton beam of 40MeV energy and currents up to 200μA. The target configuration was designed to obtain a high number of fissions, up to 1013 per second, low power deposition and fast release of the produced isotopes. The exotic isotopes generated in the target are ionized, mass separated and re-accelerated by the ALPI superconducting LINAC at energies of 10AMeV and higher, for masses in the region of A = 130 amu , with an expected rate on the secondary target up to 109 particles per second. In this work, recent results on the R&D activities regarding the SPES RIB production target-ion source system are reported.

  9. Expanding the product profile of a microbial alkane biosynthetic pathway.

    PubMed

    Harger, Matthew; Zheng, Lei; Moon, Austin; Ager, Casey; An, Ju Hye; Choe, Chris; Lai, Yi-Ling; Mo, Benjamin; Zong, David; Smith, Matthew D; Egbert, Robert G; Mills, Jeremy H; Baker, David; Pultz, Ingrid Swanson; Siegel, Justin B

    2013-01-18

    Microbially produced alkanes are a new class of biofuels that closely match the chemical composition of petroleum-based fuels. Alkanes can be generated from the fatty acid biosynthetic pathway by the reduction of acyl-ACPs followed by decarbonylation of the resulting aldehydes. A current limitation of this pathway is the restricted product profile, which consists of n-alkanes of 13, 15, and 17 carbons in length. To expand the product profile, we incorporated a new part, FabH2 from Bacillus subtilis , an enzyme known to have a broader specificity profile for fatty acid initiation than the native FabH of Escherichia coli . When provided with the appropriate substrate, the addition of FabH2 resulted in an altered alkane product profile in which significant levels of n-alkanes of 14 and 16 carbons in length are produced. The production of even chain length alkanes represents initial steps toward the expansion of this recently discovered microbial alkane production pathway to synthesize complex fuels. This work was conceived and performed as part of the 2011 University of Washington international Genetically Engineered Machines (iGEM) project.

  10. Comparison of the nutritional content of products, with and without nutrient claims, targeted at children in Brazil.

    PubMed

    Rodrigues, Vanessa Mello; Rayner, Mike; Fernandes, Ana Carolina; de Oliveira, Renata Carvalho; Proença, Rossana Pacheco da Costa; Fiates, Giovanna Medeiros Rataichesck

    2016-06-01

    Many children's food products highlight positive attributes on their front-of-package labels in the form of nutrient claims. This cross-sectional study investigated all retailed packaged foods (n 5620) in a major Brazilian supermarket, in order to identify the availability of products targeted at children, and to compare the nutritional content of products with and without nutrient claims on labels. Data on energy, carbohydrate, protein, fibre, Na and total and SFA content, along with the presence and type of nutrient claims, were obtained in-store from labels of all products. Products targeted at children were identified, divided into eight food groups and compared for their nutritional content per 100 g/ml and the presence of nutrient claims using the Mann-Whitney U test (P<0·05). Of the 535 food products targeted at children (9·5 % of all products), 270 (50·5 %) displayed nutrient claims on their labels. Children's products with nutrient claims had either a similar or worse nutritional content than their counterparts without nutrient claims. The major differences among groups were found in Group 8 (e.g. sauces and ready meals), in which children's products bearing nutrient claims had higher energy, carbohydrate, Na and total and SFA content per 100 g/ml than products without nutrient claims (P<0·05). This suggests that, to prevent misleading parents who are seeking healthier products for their children, the regulation on the use of nutrient claims should be revised, so that only products with appropriate nutrient profiles are allowed to display them.

  11. Genetic tumor profiling and genetically targeted cancer therapy.

    PubMed

    Goetsch, Cathleen M

    2011-02-01

    To discuss how understanding and manipulation of tumor genetics information and technology shapes cancer care today and what changes might be expected in the near future. Published articles, web resources, clinical practice. Advances in our understanding of genes and their regulation provide a promise of more personalized cancer care, allowing selection of the most safe and effective therapy in an individual situation. Rapid progress in the technology of tumor profiling and targeted cancer therapies challenges nurses to keep up-to-date to provide quality patient education and care. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Target design optimization for an electron accelerator driven subcritical facility with circular and square beam profiles.

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

    Gohar, M. Y. A; Sofu, T.; Zhong, Z.

    2008-10-30

    A subcritical facility driven by an electron accelerator is planned at the Kharkov Institute of Physics and Technology (KIPT) in Ukraine for medical isotope production, materials research, training, and education. The conceptual design of the facility is being pursued through collaborations between ANL and KIPT. As part of the design effort, the high-fidelity analyses of various target options are performed with formulations to reflect the realistic configuration and the three dimensional geometry of each design. This report summarizes the results of target design optimization studies for electron beams with two different beam profiles. The target design optimization is performed viamore » the sequential neutronic, thermal-hydraulic, and structural analyses for a comprehensive assessment of each configuration. First, a target CAD model is developed with proper emphasis on manufacturability to provide a basis for separate but consistent models for subsequent neutronic, thermal-hydraulic, and structural analyses. The optimizations are pursued for maximizing the neutron yield, streamlining the flow field to avoid hotspots, and minimizing the thermal stresses to increase the durability. In addition to general geometric modifications, the inlet/outlet channel configurations, target plate partitioning schemes, flow manipulations and rates, electron beam diameter/width options, and cladding material choices are included in the design optimizations. The electron beam interactions with the target assembly and the neutronic response of the subcritical facility are evaluated using the MCNPX code. the results for the electron beam energy deposition, neutron generation, and utilization in the subcritical pile are then used to characterize the axisymmetric heat generation profiles in the target assembly with explicit simulations of the beam tube, the coolant, the clad, and the target materials. Both tungsten and uranium are considered as target materials. Neutron spectra from

  13. A Targeted Quantitative Proteomics Strategy for Global Kinome Profiling of Cancer Cells and Tissues*

    PubMed Central

    Xiao, Yongsheng; Guo, Lei; Wang, Yinsheng

    2014-01-01

    Kinases are among the most intensively pursued enzyme superfamilies as targets for anti-cancer drugs. Large data sets on inhibitor potency and selectivity for more than 400 human kinases became available recently, offering the opportunity to design rationally novel kinase-based anti-cancer therapies. However, the expression levels and activities of kinases are highly heterogeneous among different types of cancer and even among different stages of the same cancer. The lack of effective strategy for profiling the global kinome hampers the development of kinase-targeted cancer chemotherapy. Here, we introduced a novel global kinome profiling method, based on our recently developed isotope-coded ATP-affinity probe and a targeted proteomic method using multiple-reaction monitoring (MRM), for assessing simultaneously the expression of more than 300 kinases in human cells and tissues. This MRM-based assay displayed much better sensitivity, reproducibility, and accuracy than the discovery-based shotgun proteomic method. Approximately 250 kinases could be routinely detected in the lysate of a single cell line. Additionally, the incorporation of iRT into MRM kinome library rendered our MRM kinome assay easily transferrable across different instrument platforms and laboratories. We further employed this approach for profiling kinase expression in two melanoma cell lines, which revealed substantial kinome reprogramming during cancer progression and demonstrated an excellent correlation between the anti-proliferative effects of kinase inhibitors and the expression levels of their target kinases. Therefore, this facile and accurate kinome profiling assay, together with the kinome-inhibitor interaction map, could provide invaluable knowledge to predict the effectiveness of kinase inhibitor drugs and offer the opportunity for individualized cancer chemotherapy. PMID:24520089

  14. Proteome-Wide Profiling of Targets of Cysteine reactive Small Molecules by Using Ethynyl Benziodoxolone Reagents.

    PubMed

    Abegg, Daniel; Frei, Reto; Cerato, Luca; Prasad Hari, Durga; Wang, Chao; Waser, Jerome; Adibekian, Alexander

    2015-09-07

    In this study, we present a highly efficient method for proteomic profiling of cysteine residues in complex proteomes and in living cells. Our method is based on alkynylation of cysteines in complex proteomes using a "clickable" alkynyl benziodoxolone bearing an azide group. This reaction proceeds fast, under mild physiological conditions, and with a very high degree of chemoselectivity. The formed azide-capped alkynyl-cysteine adducts are readily detectable by LC-MS/MS, and can be further functionalized with TAMRA or biotin alkyne via CuAAC. We demonstrate the utility of alkynyl benziodoxolones for chemical proteomics applications by identifying the proteomic targets of curcumin, a diarylheptanoid natural product that was and still is part of multiple human clinical trials as anticancer agent. Our results demonstrate that curcumin covalently modifies several key players of cellular signaling and metabolism, most notably the enzyme casein kinase I gamma. We anticipate that this new method for cysteine profiling will find broad application in chemical proteomics and drug discovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Multiplexed, quantitative, and targeted metabolite profiling by LC-MS/MRM.

    PubMed

    Wei, Ru; Li, Guodong; Seymour, Albert B

    2014-01-01

    Targeted metabolomics, which focuses on a subset of known metabolites representative of biologically relevant metabolic pathways, is a valuable tool to discover biomarkers and link disease phenotypes to underlying mechanisms or therapeutic modes of action. A key advantage of targeted metabolomics, compared to discovery metabolomics, is its immediate readiness for extracting biological information derived from known metabolites and quantitative measurements. However, simultaneously analyzing hundreds of endogenous metabolites presents a challenge due to their diverse chemical structures and properties. Here we report a method which combines different chromatographic separation conditions, optimal ionization polarities, and the most sensitive triple-quadrupole MS-based data acquisition mode, multiple reaction monitoring (MRM), to quantitatively profile 205 endogenous metabolites in 10 min.

  16. A target for production of radioxenons

    NASA Technical Reports Server (NTRS)

    Blue, J. W.; Leonard, R.; Jha, S.; Sodd, V. J.; Vincent, J. S.

    1976-01-01

    A liquid cesium target has been developed which allows the production and separate identification of the neutron deficient isotopes of xenon. The present report describes irradiations utilizing 34 to 41 MeV protons to produce millicurie quantities of Xe-127 and Xe-129m. At higher energies, however, the target could be used without modification to produce xenon isotopes as light as 119.

  17. Method for fabricating .sup.99 Mo production targets using low enriched uranium, .sup.99 Mo production targets comprising low enriched uranium

    DOEpatents

    Wiencek, Thomas C.; Matos, James E.; Hofman, Gerard L.

    1997-01-01

    A radioisotope production target and a method for fabricating a radioisotope production target is provided, wherein the target comprises an inner cylinder, a foil of fissionable material circumferentially contacting the outer surface of the inner cylinder, and an outer hollow cylinder adapted to receive the substantially foil-covered inner cylinder and compress tightly against the foil to provide good mechanical contact therewith. The method for fabricating a primary target for the production of fission products comprises preparing a first substrate to receive a foil of fissionable material so as to allow for later removal of the foil from the first substrate, preparing a second substrate to receive the foil so as to allow for later removal of the foil from the second substrate; attaching the first substrate to the second substrate such that the foil is sandwiched between the first substrate and second substrate to prevent foil exposure to ambient atmosphere, and compressing the exposed surfaces of the first and second substrate to assure snug mechanical contact between the foil, the first substrate and the second substrate.

  18. Method for fabricating {sup 99}Mo production targets using low enriched uranium, {sup 99}Mo production targets comprising low enriched uranium

    DOEpatents

    Wiencek, T.C.; Matos, J.E.; Hofman, G.L.

    1997-03-25

    A radioisotope production target and a method for fabricating a radioisotope production target is provided, wherein the target comprises an inner cylinder, a foil of fissionable material circumferentially contacting the outer surface of the inner cylinder, and an outer hollow cylinder adapted to receive the substantially foil-covered inner cylinder and compress tightly against the foil to provide good mechanical contact therewith. The method for fabricating a primary target for the production of fission products comprises preparing a first substrate to receive a foil of fissionable material so as to allow for later removal of the foil from the first substrate, preparing a second substrate to receive the foil so as to allow for later removal of the foil from the second substrate; attaching the first substrate to the second substrate such that the foil is sandwiched between the first substrate and second substrate to prevent foil exposure to ambient atmosphere, and compressing the exposed surfaces of the first and second substrate to assure snug mechanical contact between the foil, the first substrate and the second substrate. 3 figs.

  19. Method for fabricating .sup.99 Mo production targets using low enriched uranium, .sup.99 Mo production targets comprising low enriched uranium

    DOEpatents

    Wiencek, Thomas C [Orland Park, IL; Matos, James E [Oak Park, IL; Hofman, Gerard L [Downers Grove, IL

    2000-12-12

    A radioisotope production target and a method for fabricating a radioisotope production target is provided, wherein the target comprises an inner cylinder, a foil of fissionable material circumferentially contacting the outer surface of the inner cylinder, and an outer hollow cylinder adapted to receive the substantially foil-covered inner cylinder and compress tightly against the foil to provide good mechanical contact therewith. The method for fabricating a primary target for the production of fission products comprises preparing a first substrate to receive a foil of fissionable material so as to allow for later removal of the foil from the first substrate, preparing a second substrate to receive the foil so as to allow for later removal of the foil from the second substrate; attaching the first substrate to the second substrate such that the foil is sandwiched between the first substrate and second substrate to prevent foil exposure to ambient atmosphere, and compressing the exposed surfaces of the first and second substrate to assure snug mechanical contact between the foil, the first substrate and the second substrate.

  20. The RIB production target for the SPES project

    NASA Astrophysics Data System (ADS)

    Monetti, Alberto; Andrighetto, Alberto; Petrovich, Carlo; Manzolaro, Mattia; Corradetti, Stefano; Scarpa, Daniele; Rossetto, Francesco; Martinez Dominguez, Fernando; Vasquez, Jesus; Rossignoli, Massimo; Calderolla, Michele; Silingardi, Roberto; Mozzi, Aldo; Borgna, Francesca; Vivian, Gianluca; Boratto, Enrico; Ballan, Michele; Prete, Gianfranco; Meneghetti, Giovanni

    2015-10-01

    Facilities making use of the Isotope Separator On-Line (ISOL) method for the production of Radioactive Ion Beams (RIB) attract interest because they can be used for nuclear structure and reaction studies, astrophysics research and interdisciplinary applications. The ISOL technique is based on the fast release of the nuclear reaction products from the chosen target material together with their ionization into short-lived nuclei beams. Within this context, the SPES (Selective Production of Exotic Species) facility is now under construction in Italy at INFN-LNL (Istituto Nazionale di Fisica Nucleare — Laboratori Nazionali di Legnaro). The SPES facility will produce RIBs mainly from n-rich isotopes obtained by a 40 MeV cyclotron proton beam (200 μA) directly impinging on a uranium carbide multi-foil fission target. The aim of this work is to describe and update, from a comprehensive point of view, the most important results obtained by the analysis of the on-line behavior of the SPES production target assembly. In particular an improved target configuration has been studied by comparing different codes and physics models: the thermal analyses and the isotope production are re-evaluated. Then some consequent radioprotection aspects, which are essential for the installation and operation of the facility, are presented.

  1. Effects of oncoming target velocities on rapid force production and accuracy of force production intensity and timing.

    PubMed

    Ohta, Yoichi

    2017-12-01

    The present study aimed to clarify the effects of oncoming target velocities on the ability of rapid force production and accuracy and variability of simultaneous control of both force production intensity and timing. Twenty male participants (age: 21.0 ± 1.4 years) performed rapid gripping with a handgrip dynamometer to coincide with the arrival of an oncoming target by using a horizontal electronic trackway. The oncoming target velocities were 4, 8, and 12 m · s -1 , which were randomly produced. The grip force required was 30% of the maximal voluntary contraction. Although the peak force (Pf) and rate of force development (RFD) increased with increasing target velocity, the value of the RFD to Pf ratio was constant across the 3 target velocities. The accuracy of both force production intensity and timing decreased at higher target velocities. Moreover, the intrapersonal variability in temporal parameters was lower in the fast target velocity condition, but constant variability in 3 target velocities was observed in force intensity parameters. These results suggest that oncoming target velocity does not intrinsically affect the ability for rapid force production. However, the oncoming target velocity affects accuracy and variability of force production intensity and timing during rapid force production.

  2. Industrial recovered-materials-utilization targets for the textile-mill-products industry

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

    None

    1979-01-01

    The Congress, in the National Energy Conservation and Policy Act of 1978 (NECPA), directed the Department of Energy to establish materials recovery targets for the metals and metal products, paper and allied products, rubber, and textile-mill-products industries. The targets were developed to provide incentives for using energy-saving recorded materials and to provied a yardstick for measuring progress and improvement in this endeavor. The NECPA indicates that the targets should represent the maximum technically and economically feasible increase in the use of energy-saving recovered materials that each industry can achieve progressively by January 1, 1987. Materials affected by recovered-materials targets includemore » and are limited to aluminum, copper, lead, zinc, iron, steel, paper and associated products, textile-mill, products, and rubber. Using information gathered from the textile-mill-products industry and from other textile-relaed sources, DOE has developed recovered materials targets for that industry. This report presents those targets and their basis and justification. Following an overview of the textile industry, the chapters are: Textile-Mill-Products Industry Operations; Economic Analysis of the Textile-Mill-Products Industry; Governmental and Regulatory Influence on the US Textile Industry; Current Mill Use of Recovered Materials in the Textile-Mill-Products Industry; Limitations on the Use of Recovered Materials in the US Textile-Mill-Products Industry; Materials-Recovery Targets; and Government and Industry Actions That Could Increase the Use of Recovered Materials.« less

  3. Staphylococcus aureus methicillin resistance detected by HPLC-MS/MS targeted metabolic profiling.

    PubMed

    Schelli, Katie; Rutowski, Joshua; Roubidoux, Julia; Zhu, Jiangjiang

    2017-03-15

    Recently, novel bioanalytical methods, such as NMR and mass spectrometry based metabolomics approaches, have started to show promise in providing rapid, sensitive and reproducible detection of Staphylococcus aureus antibiotic resistance. Here we performed a proof-of-concept study focused on the application of HPLC-MS/MS based targeted metabolic profiling for detecting and monitoring the bacterial metabolic profile changes in response to sub-lethal levels of methicillin exposure. One hundred seventy-seven targeted metabolites from over 20 metabolic pathways were specifically screened and one hundred and thirty metabolites from in vitro bacterial tests were confidently detected from both methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA and MRSA, respectively). The metabolic profiles can be used to distinguish the isogenic pairs of MSSA strains from MRSA strains, without or with sub-lethal levels of methicillin exposure. In addition, better separation between MSSA and MRSA strains can be achieved in the latter case using principal component analysis (PCA). Metabolite data from isogenic pairs of MSSA and MRSA strains were further compared without and with sub-lethal levels of methicillin exposure, with metabolic pathway analyses additionally performed. Both analyses suggested that the metabolic activities of MSSA strains were more susceptible to the perturbation of the sub-lethal levels of methicillin exposure compared to the MRSA strains. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Integrative FourD omics approach profiles the target network of the carbon storage regulatory system

    PubMed Central

    Sowa, Steven W.; Gelderman, Grant; Leistra, Abigail N.; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A.; Romeo, Tony; Baldea, Michael

    2017-01-01

    Abstract Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. PMID:28126921

  5. In silico polypharmacology of natural products.

    PubMed

    Fang, Jiansong; Liu, Chuang; Wang, Qi; Lin, Ping; Cheng, Feixiong

    2017-04-27

    Natural products with polypharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Currently, many gaps exist in our knowledge of which compounds interact with which targets, and experimentally testing all possible interactions is infeasible. Recent advances and developments of systems pharmacology and computational (in silico) approaches provide powerful tools for exploring the polypharmacological profiles of natural products. In this review, we introduce recent progresses and advances of computational tools and systems pharmacology approaches for identifying drug targets of natural products by focusing on the development of targeted cancer therapy. We survey the polypharmacological and systems immunology profiles of five representative natural products that are being considered as cancer therapies. We summarize various chemoinformatics, bioinformatics and systems biology resources for reconstructing drug-target networks of natural products. We then review currently available computational approaches and tools for prediction of drug-target interactions by focusing on five domains: target-based, ligand-based, chemogenomics-based, network-based and omics-based systems biology approaches. In addition, we describe a practical example of the application of systems pharmacology approaches by integrating the polypharmacology of natural products and large-scale cancer genomics data for the development of precision oncology under the systems biology framework. Finally, we highlight the promise of cancer immunotherapies and combination therapies that target tumor ecosystems (e.g. clones or 'selfish' sub-clones) via exploiting the immunological and inflammatory 'side' effects of natural products in the cancer post-genomics era. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Quantitative and Systems Pharmacology. 1. In Silico Prediction of Drug-Target Interactions of Natural Products Enables New Targeted Cancer Therapy.

    PubMed

    Fang, Jiansong; Wu, Zengrui; Cai, Chuipu; Wang, Qi; Tang, Yun; Cheng, Feixiong

    2017-11-27

    Natural products with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for natural products at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we proposed a systems pharmacology infrastructure to predict new drug targets and anticancer indications of natural products. Specifically, we reconstructed a global drug-target network with 7,314 interactions connecting 751 targets and 2,388 natural products and built predictive network models via a balanced substructure-drug-target network-based inference approach. A high area under receiver operating characteristic curve of 0.96 was yielded for predicting new targets of natural products during cross-validation. The newly predicted targets of natural products (e.g., resveratrol, genistein, and kaempferol) with high scores were validated by various literature studies. We further built the statistical network models for identification of new anticancer indications of natural products through integration of both experimentally validated and computationally predicted drug-target interactions of natural products with known cancer proteins. We showed that the significantly predicted anticancer indications of multiple natural products (e.g., naringenin, disulfiram, and metformin) with new mechanism-of-action were validated by various published experimental evidence. In summary, this study offers powerful computational systems pharmacology approaches and tools for the development of novel targeted cancer therapies by exploiting the polypharmacology of natural products.

  7. Non-Cooperative Target Recognition by Means of Singular Value Decomposition Applied to Radar High Resolution Range Profiles

    PubMed Central

    López-Rodríguez, Patricia; Escot-Bocanegra, David; Fernández-Recio, Raúl; Bravo, Ignacio

    2015-01-01

    Radar high resolution range profiles are widely used among the target recognition community for the detection and identification of flying targets. In this paper, singular value decomposition is applied to extract the relevant information and to model each aircraft as a subspace. The identification algorithm is based on angle between subspaces and takes place in a transformed domain. In order to have a wide database of radar signatures and evaluate the performance, simulated range profiles are used as the recognition database while the test samples comprise data of actual range profiles collected in a measurement campaign. Thanks to the modeling of aircraft as subspaces only the valuable information of each target is used in the recognition process. Thus, one of the main advantages of using singular value decomposition, is that it helps to overcome the notable dissimilarities found in the shape and signal-to-noise ratio between actual and simulated profiles due to their difference in nature. Despite these differences, the recognition rates obtained with the algorithm are quite promising. PMID:25551484

  8. Target-fueled nuclear reactor for medical isotope production

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

    Coats, Richard L.; Parma, Edward J.

    A small, low-enriched, passively safe, low-power nuclear reactor comprises a core of target and fuel pins that can be processed to produce the medical isotope .sup.99Mo and other fission product isotopes. The fuel for the reactor and the targets for the .sup.99Mo production are the same. The fuel can be low enriched uranium oxide, enriched to less than 20% .sup.235U. The reactor power level can be 1 to 2 MW. The reactor is passively safe and maintains negative reactivity coefficients. The total radionuclide inventory in the reactor core is minimized since the fuel/target pins are removed and processed after 7more » to 21 days.« less

  9. Integrative FourD omics approach profiles the target network of the carbon storage regulatory system.

    PubMed

    Sowa, Steven W; Gelderman, Grant; Leistra, Abigail N; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A; Romeo, Tony; Baldea, Michael; Contreras, Lydia M

    2017-02-28

    Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Beauty and charm production in fixed target experiments

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

    Kidonakis, Nikolaos; Vogt, Ramona

    We present calculations of NNLO threshold corrections for beauty and charm production in {pi}{sup -} p and pp interactions at fixed-target experiments. Recent calculations for heavy quark hadroproduction have included next-to-next-to-leading-order (NNLO) soft-gluon corrections [1] to the double differential cross section from threshold resummation techniques [2]. These corrections are important for near-threshold beauty and charm production at fixed-target experiments, including HERA-B and some of the current and future heavy ion experiments.

  11. Qualitative Analysis of Commercial Social Network Profiles

    NASA Astrophysics Data System (ADS)

    Melendez, Lester; Wolfson, Ouri; Adjouadi, Malek; Rishe, Naphtali

    Social-networking sites have become an integral part of many users' daily internet routine. Commercial enterprises have been quick to recognize this and are subsequently creating profiles for many of their products and services. Commercial enterprises use social network profiles to target and interact with potential customers as well as to provide a gateway for users of the product or service to interact with each other. Many commercial enterprises use the statistics from their product or service's social network profile to tout the popularity and success of the product or service being showcased. They will use statistics such as number of friends, number of daily visits, number of interactions, and other similar measurements to quantify their claims. These statistics are often not a clear indication of the true popularity and success of the product. In this chapter the term product is used to refer to any tangible or intangible product, service, celebrity, personality, film, book, or other entity produced by a commercial enterprise.

  12. Quantitation without Calibration: Response Profile as an Indicator of Target Amount.

    PubMed

    Debnath, Mrittika; Farace, Jessica M; Johnson, Kristopher D; Nesterova, Irina V

    2018-06-21

    Quantitative assessment of biomarkers is essential in numerous contexts from decision-making in clinical situations to food quality monitoring to interpretation of life-science research findings. However, appropriate quantitation techniques are not as widely addressed as detection methods. One of the major challenges in biomarker's quantitation is the need to have a calibration for correlating a measured signal to a target amount. The step complicates the methodologies and makes them less sustainable. In this work we address the issue via a new strategy: relying on position of response profile rather than on an absolute signal value for assessment of a target's amount. In order to enable the capability we develop a target-probe binding mechanism based on a negative cooperativity effect. A proof-of-concept example demonstrates that the model is suitable for quantitative analysis of nucleic acids over a wide concentration range. The general principles of the platform will be applicable toward a variety of biomarkers such as nucleic acids, proteins, peptides, and others.

  13. Profiles of Brain Metastases: Prioritization of Therapeutic Targets.

    PubMed

    Ferguson, Sherise D; Zheng, Siyuan; Xiu, Joanne; Zhou, Shouhao; Khasraw, Mustafa; Brastianos, Priscilla K; Kesari, Santosh; Hu, Jethro; Rudnick, Jeremy; Salacz, Michael E; Piccioni, David; Huang, Suyun; Davies, Michael A; Glitza, Isabella C; Heymach, John V; Zhang, Jianjun; Ibrahim, Nuhad K; DeGroot, John F; McCarty, Joseph; O'Brien, Barbara J; Sawaya, Raymond; Verhaak, Roeland G W; Reddy, Sandeep K; Priebe, Waldemar; Gatalica, Zoran; Spetzler, David; Heimberger, Amy B

    2018-06-19

    We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of non-small cell lung cancer, breast cancer, and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (assayed by immunohistochemistry), and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification, and mutations among brain metastases, extracranial metastases, and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8178 non-small cell lung cancers (5098 primaries; 2787 systemic metastases; 293 brain metastases), 7064 breast cancers (3496 primaries; 3469 systemic metastases; 99 brain metastases), and 1757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1, and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication, and/or repair. This article is protected by copyright. All rights reserved. © 2018 UICC.

  14. Appropriately Targeting Group Interventions for Academic Success Adopting the Clinical Model and PAR Profiles

    ERIC Educational Resources Information Center

    Johnson, Craig W.; Johnson, Ronald; Steigman, Michael; Odo, Chioma; Vijayan, Suvendra; Tata, Devadatta V.

    2016-01-01

    Prevalence of academic risk (PAR) group profiles provide data enabling empirically based group-specialized prescriptions for targeted academic success interventions to increase student retention, completion, and graduation rates, while improving allocation of institutional resources. Postsecondary student attrition engenders student debt,…

  15. Hydrogen isotope and light element profiling in solid tritium targets used for neutron production

    NASA Astrophysics Data System (ADS)

    Earwaker, L. G.; England, J. B. A.; Goldie, D. J.

    1987-04-01

    Five targets consisting of titanium tritide layers on copper backings have been investigated using nuclear reaction analysis. As these targets are commonly used to produce monoenergetic neutrons via the T(p, n) 3 He and T(d, n) 4 He reactions, it is important to know of the presence of other elements which may produce neutrons at different energies. The thicknesses of the titanium tritide layers were measured by observing the T(p, n) 3 He threshold yield curve and also the energy spread of the neutrons using a 3He-filled gridded ion chamber. Elastic recoil analysis with a particle identifying system was used to measure the hydrogen, deuterium, tritium and 3He content, and elastic scattering was used to study the carbon and oxygen. Surprisingly high concentrations of both hydrogen and oxygen were found on all targets, including the three which had never been used. Also surprising was the 3He content which was approximately the same for targets of all ages and conditions of use. As expected, the carbon content increased strongly with use, originating no doubt, from vacuum pump oil. Up to 3% deuterium atoms were observed in unused targets with much higher contents being recorded in used targets.

  16. Streaked x-ray backlighting with twin-slit imager for study of density profile and trajectory of low-density foam target filled with deuterium liquid

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

    Shiraga, H.; Mahigashi, N.; Yamada, T.

    2008-10-15

    Low-density plastic foam filled with liquid deuterium is one of the candidates for inertial fusion target. Density profile and trajectory of 527 nm laser-irradiated planer foam-deuterium target in the acceleration phase were observed with streaked side-on x-ray backlighting. An x-ray imager employing twin slits coupled to an x-ray streak camera was used to simultaneously observe three images of the target: self-emission from the target, x-ray backlighter profile, and the backlit target. The experimentally obtained density profile and trajectory were in good agreement with predictions by one-dimensional hydrodynamic simulation code ILESTA-1D.

  17. Profiling unauthorized natural resource users for better targeting of conservation interventions

    PubMed Central

    Baker, Julia; Twinamatsiko, Medard; Milner‐Gulland, E.J.

    2015-01-01

    Abstract Unauthorized use of natural resources is a key threat to many protected areas. Approaches to reducing this threat include law enforcement and integrated conservation and development (ICD) projects, but for such ICDs to be targeted effectively, it is important to understand who is illegally using which natural resources and why. The nature of unauthorized behavior makes it difficult to ascertain this information through direct questioning. Bwindi Impenetrable National Park, Uganda, has many ICD projects, including authorizing some local people to use certain nontimber forest resources from the park. However, despite over 25 years of ICD, unauthorized resource use continues. We used household surveys, indirect questioning (unmatched count technique), and focus group discussions to generate profiles of authorized and unauthorized resource users and to explore motivations for unauthorized activity. Overall, unauthorized resource use was most common among people from poor households who lived closest to the park boundary and farthest from roads and trading centers. Other motivations for unauthorized resource use included crop raiding by wild animals, inequity of revenue sharing, and lack of employment, factors that created resentment among the poorest communities. In some communities, benefits obtained from ICD were reported to be the greatest deterrents against unauthorized activity, although law enforcement ranked highest overall. Despite the sensitive nature of exploring unauthorized resource use, management‐relevant insights into the profiles and motivations of unauthorized resource users can be gained from a combination of survey techniques, as adopted here. To reduce unauthorized activity at Bwindi, we suggest ICD benefit the poorest people living in remote areas and near the park boundary by providing affordable alternative sources of forest products and addressing crop raiding. To prevent resentment from driving further unauthorized activity, ICDs

  18. Profiling unauthorized natural resource users for better targeting of conservation interventions.

    PubMed

    Harrison, Mariel; Baker, Julia; Twinamatsiko, Medard; Milner-Gulland, E J

    2015-12-01

    Unauthorized use of natural resources is a key threat to many protected areas. Approaches to reducing this threat include law enforcement and integrated conservation and development (ICD) projects, but for such ICDs to be targeted effectively, it is important to understand who is illegally using which natural resources and why. The nature of unauthorized behavior makes it difficult to ascertain this information through direct questioning. Bwindi Impenetrable National Park, Uganda, has many ICD projects, including authorizing some local people to use certain nontimber forest resources from the park. However, despite over 25 years of ICD, unauthorized resource use continues. We used household surveys, indirect questioning (unmatched count technique), and focus group discussions to generate profiles of authorized and unauthorized resource users and to explore motivations for unauthorized activity. Overall, unauthorized resource use was most common among people from poor households who lived closest to the park boundary and farthest from roads and trading centers. Other motivations for unauthorized resource use included crop raiding by wild animals, inequity of revenue sharing, and lack of employment, factors that created resentment among the poorest communities. In some communities, benefits obtained from ICD were reported to be the greatest deterrents against unauthorized activity, although law enforcement ranked highest overall. Despite the sensitive nature of exploring unauthorized resource use, management-relevant insights into the profiles and motivations of unauthorized resource users can be gained from a combination of survey techniques, as adopted here. To reduce unauthorized activity at Bwindi, we suggest ICD benefit the poorest people living in remote areas and near the park boundary by providing affordable alternative sources of forest products and addressing crop raiding. To prevent resentment from driving further unauthorized activity, ICDs should be

  19. miRNA profiling of high, low and non-producing CHO cells during biphasic fed-batch cultivation reveals process relevant targets for host cell engineering.

    PubMed

    Stiefel, Fabian; Fischer, Simon; Sczyrba, Alexander; Otte, Kerstin; Hesse, Friedemann

    2016-05-10

    Fed-batch cultivation of recombinant Chinese hamster ovary (CHO) cell lines is one of the most widely used production modes for commercial manufacturing of recombinant protein therapeutics. Furthermore, fed-batch cultivations are often conducted as biphasic processes where the culture temperature is decreased to maximize volumetric product yields. However, it remains to be elucidated which intracellular regulatory elements actually control the observed pro-productive phenotypes. Recently, several studies have revealed microRNAs (miRNAs) to be important molecular switches of cell phenotypes. In this study, we analyzed miRNA profiles of two different recombinant CHO cell lines (high and low producer), and compared them to a non-producing CHO DG44 host cell line during fed-batch cultivation at 37°C versus a temperature shift to 30°C. Taking advantage of next-generation sequencing combined with cluster, correlation and differential expression analyses, we could identify 89 different miRNAs, which were differentially expressed in the different cell lines and cultivation phases. Functional validation experiments using 19 validated target miRNAs confirmed that these miRNAs indeed induced changes in process relevant phenotypes. Furthermore, computational miRNA target prediction combined with functional clustering identified putative target genes and cellular pathways, which might be regulated by these miRNAs. This study systematically identified novel target miRNAs during different phases and conditions of a biphasic fed-batch production process and functionally evaluated their potential for host cell engineering. Copyright © 2016. Published by Elsevier B.V.

  20. Profiles of the Adult Education Target Population: Information from the 2000 Census. Revised

    ERIC Educational Resources Information Center

    Lasater, Beth; Elliott, Barbara

    2005-01-01

    This report presents national, regional, and state profiles of the target population for adult education, that is, those individuals aged 16 years and over, who have not attained a high school diploma or equivalent and are not currently enrolled in school. The tables contained in this report describe the following characteristics of the target…

  1. Cell culture media supplementation of infrequently used sugars for the targeted shifting of protein glycosylation profiles.

    PubMed

    Hossler, Patrick; Racicot, Christopher; Chumsae, Christopher; McDermott, Sean; Cochran, Keith

    2017-03-01

    Mammalian cells in culture rely on sources of carbohydrates to supply the energy requirements for proliferation. In addition, carbohydrates provide a large source of the carbon supply for supporting various other metabolic activities, including the intermediates involved in the protein glycosylation pathway. Glucose and galactose, in particular, are commonly used sugars in culture media for these purposes. However, there exists a very large repertoire of other sugars in nature, and many that have been chemically synthesized. These sugars are particularly interesting because they can be utilized by cells in culture in distinct ways. In the present work it has been found that many infrequently used sugars, and the corresponding cellular response towards them as substrates, led to differences in the protein N-glycosylation profile of a recombinant glycoprotein. The selective media supplementation of raffinose, trehalose, turanose, palatinose, melezitose, psicose, lactose, lactulose, and mannose were found to be capable of redirecting N-glycan oligosaccharide profiles. Despite this shifting of protein glycosylation, there were no other adverse changes in culture performance, including both cell growth and cellular productivity over a wide range of supplemented sugar concentrations. The approach presented highlights a potential means towards both the targeted shifting of protein glycosylation profiles and ensuring recombinant protein comparability, which up to this point in time has remained under-appreciated for these under-utilized compounds. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:511-522, 2017. © 2017 American Institute of Chemical Engineers.

  2. Chlorination of bisphenol A: non-targeted screening for the identification of transformation products and assessment of estrogenicity in generated water.

    PubMed

    Bourgin, Marc; Bichon, Emmanuelle; Antignac, Jean-Philippe; Monteau, Fabrice; Leroy, Gaëla; Barritaud, Lauriane; Chachignon, Mathilde; Ingrand, Valérie; Roche, Pascal; Le Bizec, Bruno

    2013-11-01

    Besides the performance of water treatments on the removal of micropollutants, concern about the generation of potential biologically active transformation products has been growing. Thus, the detection and structural elucidation of micropollutants transformation products have turned out to be major issues to evaluate comprehensively the efficiency of the processes implemented for drinking water treatment. However, most of existing water treatment studies are carried out at the bench scale with high concentrations and simplified conditions and thus do not reflect realistic conditions. Conversely, this study describes a non-targeted profiling approach borrowed from metabolomic science, using liquid chromatography coupled to high-resolution mass spectrometry, in order to reveal potential chlorination products of bisphenol A (BPA) in real water samples spiked at 50μgL(-1). Targeted measurements first evidenced a fast removal of BPA (>99%) by chlorination with sodium hypochlorite (0.8mgL(-1)) within 10min. Then, the developed differential global profiling approach enabled to reveal 21 chlorination products of BPA. Among them, 17 were brominated compounds, described for the first time, demonstrating the potential interest of this innovative methodology applied to environmental sciences. In parallel to the significant removal of BPA, the estrogenic activity of water samples, evaluated by ER-CALUX assay, was found to significantly decrease after 10min of chlorination. These results confirm that chlorination is effective at removing BPA in drinking water and they may indicate that the generated compounds have significantly lower estrogenic activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Comparison of bulk and pitcher-catcher targets for laser-driven neutron production

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

    Willingale, L.; Maksimchuk, A.; Joglekar, A. S.

    2011-08-15

    Laser-driven d(d, n)-{sup 3}He beam-target fusion neutron production from bulk deuterated plastic (CD) targets is compared with a pitcher-catcher target scheme using an identical laser and detector arrangement. For laser intensities in the range of (1-3) x 10{sup 19} W cm{sup -2}, it was found that the bulk targets produced a high yield (5 x 10{sup 4} neutrons per steradian) beamed preferentially in the laser propagation direction. Numerical modeling shows the importance of considering the temperature adjusted stopping powers to correctly model the neutron production. The bulk CD targets have a high background target temperature leading to a reduced stoppingmore » power for the deuterons, which increases the probability of generating neutrons by fusion. Neutron production from the pitcher-catcher targets was not as efficient since it does not benefit from the reduced stopping power in the cold catcher target. Also, the inhibition of the deuteron acceleration by a proton rich contamination layer significantly reduces the pitcher-catcher neutron production.« less

  4. A Miniaturized Chemical Proteomic Approach for Target Profiling of Clinical Kinase Inhibitors in Tumor Biopsies

    PubMed Central

    Chamrád, Ivo; Rix, Uwe; Stukalov, Alexey; Gridling, Manuela; Parapatics, Katja; Müller, André C.; Altiok, Soner; Colinge, Jacques; Superti-Furga, Giulio; Haura, Eric B.; Bennett, Keiryn L.

    2014-01-01

    While targeted therapy based on the idea of attenuating the activity of a preselected, therapeutically relevant protein has become one of the major trends in modern cancer therapy, no truly specific targeted drug has been developed and most clinical agents have displayed a degree of polypharmacology. Therefore, the specificity of anticancer therapeutics has emerged as a highly important but severely underestimated issue. Chemical proteomics is a powerful technique combining postgenomic drug-affinity chromatography with high-end mass spectrometry analysis and bioinformatic data processing to assemble a target profile of a desired therapeutic molecule. Due to high demands on the starting material, however, chemical proteomic studies have been mostly limited to cancer cell lines. Herein, we report a down-scaling of the technique to enable the analysis of very low abundance samples, as those obtained from needle biopsies. By a systematic investigation of several important parameters in pull-downs with the multikinase inhibitor bosutinib, the standard experimental protocol was optimized to 100 µg protein input. At this level, more than 30 well-known targets were detected per single pull-down replicate with high reproducibility. Moreover, as presented by the comprehensive target profile obtained from miniaturized pull-downs with another clinical drug, dasatinib, the optimized protocol seems to be extendable to other drugs of interest. Sixty distinct human and murine targets were finally identified for bosutinib and dasatinib in chemical proteomic experiments utilizing core needle biopsy samples from xenotransplants derived from patient tumor tissue. Altogether, the developed methodology proves robust and generic and holds many promises for the field of personalized health care. PMID:23901793

  5. Analysis of Operating Strategies Using Different Target Designs For 238Pu Production

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

    Thomas, Tomcy; Sherman, Steven R; Sawhney, Dr. Rapinder

    2017-01-01

    An engineering effort is underway to re-establish capability to produce 238Pu oxide at the kilogram scale in the United States. A multi-step batch process is being developed to produce this important material. Recently, a portion of this process was studied using discrete-event simulation tools to determine whether the conceptual process might achieve its yearly production goal. The study showed the conceptual process can meet the yearly production goal under some circumstances, but process improvements would be needed to ensure greater likelihood of success. This study extends the work performed previously by examining the effects of changing the reactor target designmore » on the yearly process output. Two new reactor target configurations are considered an aluminum-clad reactor target containing 50% greater 237Np oxide content than the original target, and a zirconium alloy-clad target using no aluminum. The results indicate that use of the new aluminum-clad target configuration may allow the process to achieve the same yearly production goal in less time using fewer targets. If the zirconium alloy-clad target is used, then even fewer targets would be needed to reach the production goal, but some process changes would be required to handle the zirconium cladding. The number of days needed to process a target batch to completion, and the steady state 238Pu oxide production rate, for each configuration are compared to the results from the initial simulation study.« less

  6. Characterization of microbial metabolism of Syrah grape products in an in vitro colon model using targeted and non-targeted analytical approaches.

    PubMed

    Aura, Anna-Marja; Mattila, Ismo; Hyötyläinen, Tuulia; Gopalacharyulu, Peddinti; Cheynier, Veronique; Souquet, Jean-Marc; Bes, Magali; Le Bourvellec, Carine; Guyot, Sylvain; Orešič, Matej

    2013-03-01

    Syrah red grapes are used in the production of tannin-rich red wines. Tannins are high molecular weight molecules, proanthocyanidins (PAs), and poorly absorbed in the upper intestine. In this study, gut microbial metabolism of Syrah grape phenolic compounds was investigated. Syrah grape pericarp was subjected to an enzymatic in vitro digestion model, and red wine and grape skin PA fraction were prepared. Microbial conversion was screened using an in vitro colon model with faecal microbiota, by measurement of short-chain fatty acids by gas chromatography (GC) and microbial phenolic metabolites using GC with mass detection (GC-MS). Red wine metabolites were further profiled using two-dimensional GC mass spectrometry (GCxGC-TOFMS). In addition, the effect of PA structure and dose on conversion efficiency was investigated by GC-MS. Red wine exhibited a higher degree of C1-C3 phenolic acid formation than PA fraction or grape pericarp powders. Hydroxyphenyl valeric acid (flavanols and PAs as precursors) and 3,5-dimethoxy-4-hydroxybenzoic acid (anthocyanin as a precursor) were identified from the red wine metabolite profile. In the absence of native grape pericarp or red wine matrix, the isolated PAs were found to be effective in the dose-dependent inhibition of microbial conversions and short-chain fatty acid formation. Metabolite profiling was complementary to targeted analysis. The identified metabolites had biological relevance, because the structures of the metabolites resembled fragments of their grape phenolic precursors or were in agreement with literature data.

  7. Isotope production and target preparation for nuclear astrophysics data

    NASA Astrophysics Data System (ADS)

    Schumann, Dorothea; Dressler, Rugard; Maugeri, Emilio Andrea; Heinitz, Stephan

    2017-09-01

    Targets are in many cases an indispensable ingredient for successful experiments aimed to produce nuclear data. With the recently observed shift to study nuclear reactions on radioactive targets, this task can become extremely challenging. Concerted actions of a certain number of laboratories able to produce isotopes and manufacture radioactive targets are urgently needed. We present here some examples of successful isotope and target production at PSI, in particular the production of 60Fe samples used for half-life measurements and neutron capture cross section experiments, the chemical processing and fabrication of lanthanide targets for capture cross section experiments at n_TOF (European Organization for Nuclear Research (CERN), Switzerland) as well as the recently performed manufacturing of highly-radioactive 7Be targets for the measurement of the 7Be(n,α)4He cross section in the energy range of interest for the Big-Bang nucleosynthesis contributing to the solving of the cosmological Li-problem. The two future projects: "Determination of the half-life and experiments on neutron capture cross sections of 53Mn" and "32Si - a new chronometer for nuclear dating" are briefly described. Moreover, we propose to work on the establishment of a dedicated network on isotope and target producing laboratories.

  8. [Exploring New Drug Targets through the Identification of Target Molecules of Bioactive Natural Products].

    PubMed

    Arai, Masayoshi

    2016-01-01

    With the development of cell biology and microbiology, it has become easy to culture many types of animal cells and microbes, and they are frequently used for phenotypic screening to explore medicinal seeds. On the other hand, it is recognized that cells and pathogenic microbes present in pathologic sites and infected regions of the human body display unique properties different from those under general culture conditions. We isolated several bioactive compounds from marine medicinal resources using constructed bioassay-guided separation focusing on the unique changes in the characteristics of cells and pathogenic microbes (Mycobacterium spp.) in the human body under disease conditions. In addition, we also carried out identification studies of target molecules of the bioactive compounds by methods utilizing the gene expression profile, transformants of cells or microbes, synthetic probe molecules of the isolated compounds, etc., since bioactive compounds isolated from the phenotypic screening system often target new molecules. This review presents our phenotypic screening systems, isolation of bioactive compounds from marine medicinal resources, and target identification of bioactive compounds.

  9. Dairy Cows Productivity and Socio-Economic Profile of Dairy Smallholder’s Communities in Yogyakarta, Indonesia

    NASA Astrophysics Data System (ADS)

    Widyobroto, B. P.; Rochijan; Noviandi, C. T.; Astuti, A.

    2018-02-01

    The objective of this field questionnaire survey was to describe the dairy cow productivity and socio-economic profile of dairy cattle farmers in Daerah Istimewa Yogyakarta smallholder farming communities which have been targeted dairy development policy. The study was conducted on 190 Friesian Holstein (FH) cows maintained under smallholder’s management system in Daerah Istimewa Yogyakarta, Indonesia. A total of 83 farmers were randomly selected and interviewed with structured questionnaire to assess the socio-economic dairy farmer and productivity performance of dairy cows. The number of dairy productivity performance within the normal. Shortages as well as high cost of feed, occurrence of disease, scarce information about feeding and high medicament cost were the main constraints which might have contributed considerably to delayed age at first service, late age at first calving, long calving interval, short lactation length and low milk production. Therefore, strategies designed to solve the existing problem should be important by involving all stakeholders in the formulation and implementation of improvement strategiesor dairy development policy was being implemented and necessary respect to environmental factors affecting agricultural activities such as a constraint on land use and access to water resources.

  10. Beam production of a laser ion source with a rotating hollow cylinder target for low energy positive and negative ions

    NASA Astrophysics Data System (ADS)

    Saquilayan, G. Q.; Wada, M.

    2017-08-01

    A laser ion source that utilizes a hollow cylinder target is being developed for the production of positive and negative ions. Continuous operation of the laser ion source is possible through the design of a rotating target. Ion extraction through a grounded circular aperture was tested for positive and negative ions up to 1 kV. Time-of-flight measurements for the mass separation of ions were made by placing a Faraday cup at locations 0 and 15 mm from the beam extraction axis. Signals corresponding to slow and massive ions were detected with mass at least 380 amu. Investigation on the beam profile suggests a geometrical optimization of the beam forming system is necessary.

  11. Investigating nutrient profiling and Health Star Ratings on core dairy products in Australia.

    PubMed

    Wellard, Lyndal; Hughes, Clare; Watson, Wendy L

    2016-10-01

    To determine whether the ratings from the Australian front-of-pack labelling scheme, Health Star Rating (HSR), and the ability to carry health claims using the Nutrient Profiling Scoring Criterion (NPSC) for core dairy products promote foods consistent with the Australian Dietary Guidelines. The Australian nutrient profiling model used for assessing eligibility for health claims was compared with the nutrient profiling model underpinning the HSR system to determine their agreement when assessing dairy products. Agreement between the extent to which products met nutrient profiling criteria and scored three stars or over using the HSR calculator was determined using Cohen's kappa tests. The four largest supermarket chains in Sydney, Australia. All available products in the milk, hard cheese, soft cheese and yoghurt categories (n 1363) were surveyed in March-May 2014. Nutrition composition and ingredients lists were recorded for each product. There was 'good' agreement between NPSC and HSR overall (κ=0·78; 95 % CI 0·75, 0·81; P<0·001), for hard cheeses (κ=0·72; 95 % CI 0·65, 0·79; P<0·001) and yoghurt (κ=0·79; 95 % CI 0·73, 0·86; P<0·001). There was 'fair' agreement for milk (κ=0·33; 95 % CI 0·20, 0·45; P<0·001) and 'very good' agreement for soft cheese (κ=0·84; 95 % CI 0·75, 0·92; P<0·001). Generally, products tended to have HSR consistent with other products of a similar type within their categories. For dairy products, the HSR scheme largely aligned with the NPSC used for determining eligibility for health claims. Both systems appeared be consistent with the Australian Dietary Guidelines for dairy products, with lower-fat products rating higher.

  12. Cell culture media supplementation of uncommonly used sugars sucrose and tagatose for the targeted shifting of protein glycosylation profiles of recombinant protein therapeutics.

    PubMed

    Hossler, Patrick; McDermott, Sean; Racicot, Christopher; Chumsae, Christopher; Raharimampionona, Haly; Zhou, Yu; Ouellette, David; Matuck, Joseph; Correia, Ivan; Fann, John; Li, Jianmin

    2014-01-01

    Protein glycosylation is an important post-translational modification toward the structure and function of recombinant therapeutics. The addition of oligosaccharides to recombinant proteins has been shown to greatly influence the overall physiochemical attributes of many proteins. It is for this reason that protein glycosylation is monitored by the developer of a recombinant protein therapeutic, and why protein glycosylation is typically considered a critical quality attribute. In this work, we highlight a systematic study toward the supplementation of sucrose and tagatose into cell culture media for the targeted modulation of protein glycosylation profiles on recombinant proteins. Both sugars were found to affect oligosaccharide maturation resulting in an increase in the percentage of high mannose N-glycan species, as well as a concomitant reduction in fucosylation. The latter effect was demonstrated to increase antibody-dependent cell-mediated cytotoxicity for a recombinant antibody. These aforementioned results were found to be reproducible at different scales, and across different Chinese hamster ovary cell lines. Through the selective supplementation of these described sugars, the targeted modulation of protein glycosylation profiles is demonstrated, as well as yet another tool in the cell culture toolbox for ensuring product comparability. © 2014 American Institute of Chemical Engineers.

  13. Targeted and Untargeted Metabolic Profiling of Wild Grassland Plants identifies Antibiotic and Anthelmintic Compounds Targeting Pathogen Physiology, Metabolism and Reproduction.

    PubMed

    French, Katherine E; Harvey, Joe; McCullagh, James S O

    2018-01-26

    Plants traditionally used by farmers to manage livestock ailments could reduce reliance on synthetic antibiotics and anthelmintics but in many cases their chemical composition is unknown. As a case study, we analyzed the metabolite profiles of 17 plant species and 45 biomass samples from agricultural grasslands in England using targeted and untargeted metabolite profiling by liquid-chromatography mass spectrometry. We identified a range of plant secondary metabolites, including 32 compounds with known antimicrobial/anthelmintic properties which varied considerably across the different plant samples. These compounds have been shown previously to target multiple aspects of pathogen physiology and metabolism in vitro and in vivo, including inhibition of quorum sensing in bacteria and egg viability in nematodes. The most abundant bioactive compounds were benzoic acid, myricetin, p-coumaric acid, rhamnetin, and rosmarinic acid. Four wild plants (Filipendula ulmaria (L.) Maxim., Prunella vulgaris L., Centuarea nigra L., and Rhinanthus minor L.) and two forage legumes (Medicago sativa L., Trifolium hybridium L.) contained high levels of these compounds. Forage samples from native high-diversity grasslands had a greater abundance of medicinal compounds than samples from agriculturally improved grasslands. Incorporating plants with antibiotic/anthelmintic compounds into livestock feeds may reduce global drug-resistance and preserve the efficacy of last-resort drugs.

  14. [Analysis of annual exposure to noise among private farmers according to production profile].

    PubMed

    Solecki, Leszek

    2007-01-01

    The objective of the study was the recognition and evaluation of annual exposure to noise among private farmers on selected family farms of three different profiles of agricultural production (plant, animal and mixed). Based on time schedules of agricultural work activities and dosimetric measurements conducted during the whole year, 2 acoustic parameters were determined: total exposure to noise in individual months of the year and equivalent daily exposure to noise. The studies showed that in the case of farms carrying out plant production the highest value of total exposure to noise occurred during the summer-autumn months (July, September, October) and in winter (December, January). On farms of animal production profile the highest values were noted in summer-autumn months (August, October) and winter-spring months (January, March, May, June). On mixed production farms high values occurred in summer-autumn months (August-November) and in April. The distribution of equivalent daily exposure values during the whole year was similar. The results of the study indicated that the greatest noise load occurs on farms carrying out plant and mixed production, whereas the lowest values concerned farms of animal production profile. These values considerably exceed standard values.

  15. Food Production, Management and Services. Ohio's Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    Developed through a modified DACUM (Developing a Curriculum) process involving business, industry, labor, and community agency representatives in Ohio, this document is a comprehensive and verified employer competency profile for food production, management, and service occupations. The list contains units (with and without subunits),…

  16. Electroplating targets for production of unique PET radionuclides

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

    Bui, V.; Sheh, Y.; Finn, R.

    1994-12-31

    The past decade has witnessed the applications of Positron Emission Tomography (PET) evolving from a purely research endeavour to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules i.e. monoclonal antibodies and pepetides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing themore » Memorial Sloan-Kettering Cancer Center cyclotron are examples of target design and development applicable to many medical accelerators.« less

  17. Electroplated targets for production of unique PET radionuclides

    NASA Astrophysics Data System (ADS)

    Bui, V.; Sheh, Y.; Finn, R.; Francesconi, L.; Cai, S.; Schlyer, D.; Wieland, B.

    1995-12-01

    The past decade has witnessed the applications of positron emission tomography (PET) evolving from a purely research endeavor to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in both medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules, i.e. monoclonal antibodies and peptides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing the Memorial Sloan-Kettering Cancer Center (MSKCC) cyclotron are examples of target design and development applicable to many medical accelerators.

  18. Kinome-wide transcriptional profiling of uveal melanoma reveals new vulnerabilities to targeted therapeutics.

    PubMed

    Bailey, Fiona P; Clarke, Kim; Kalirai, Helen; Kenyani, Jenna; Shahidipour, Haleh; Falciani, Francesco; Coulson, Judy M; Sacco, Joseph J; Coupland, Sarah E; Eyers, Patrick A

    2018-03-01

    Metastatic uveal melanoma (UM) is invariably fatal, usually within a year of diagnosis. There are currently no effective therapies, and clinical studies employing kinase inhibitors have so far demonstrated limited success. This is despite common activating mutations in GNAQ/11 genes, which trigger signalling pathways that might predispose tumours to a variety of targeted drugs. In this study, we have profiled kinome expression network dynamics in various human ocular melanomas. We uncovered a shared transcriptional profile in human primary UM samples and across a variety of experimental cell-based models. The poor overall response of UM cells to FDA-approved kinase inhibitors contrasted with much higher sensitivity to the bromodomain inhibitor JQ1, a broad transcriptional repressor. Mechanistically, we identified a repressed FOXM1-dependent kinase subnetwork in JQ1-exposed cells that contained multiple cell cycle-regulated protein kinases. Consistently, we demonstrated vulnerability of UM cells to inhibitors of mitotic protein kinases within this network, including the investigational PLK1 inhibitor BI6727. We conclude that analysis of kinome-wide signalling network dynamics has the potential to reveal actionable drug targets and inhibitors of potential therapeutic benefit for UM patients. © 2017 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons.

  19. Neurobiology of autism gene products: towards pathogenesis and drug targets.

    PubMed

    Kleijer, Kristel T E; Schmeisser, Michael J; Krueger, Dilja D; Boeckers, Tobias M; Scheiffele, Peter; Bourgeron, Thomas; Brose, Nils; Burbach, J Peter H

    2014-03-01

    The genetic heterogeneity of autism spectrum disorders (ASDs) is enormous, and the neurobiology of proteins encoded by genes associated with ASD is very diverse. Revealing the mechanisms on which different neurobiological pathways in ASD pathogenesis converge may lead to the identification of drug targets. The main objective is firstly to outline the main molecular networks and neuronal mechanisms in which ASD gene products participate and secondly to answer the question how these converge. Finally, we aim to pinpoint drug targets within these mechanisms. Literature review of the neurobiological properties of ASD gene products with a special focus on the developmental consequences of genetic defects and the possibility to reverse these by genetic or pharmacological interventions. The regulation of activity-dependent protein synthesis appears central in the pathogenesis of ASD. Through sequential consequences for axodendritic function, neuronal disabilities arise expressed as behavioral abnormalities and autistic symptoms in ASD patients. Several known ASD gene products have their effect on this central process by affecting protein synthesis intrinsically, e.g., through enhancing the mammalian target of rapamycin (mTOR) signal transduction pathway or through impairing synaptic function in general. These are interrelated processes and can be targeted by compounds from various directions: inhibition of protein synthesis through Lovastatin, mTOR inhibition using rapamycin, or mGluR-related modulation of synaptic activity. ASD gene products may all feed into a central process of translational control that is important for adequate glutamatergic regulation of dendritic properties. This process can be modulated by available compounds but may also be targeted by yet unexplored routes.

  20. Covalent Ligand Discovery against Druggable Hotspots Targeted by Anti-cancer Natural Products.

    PubMed

    Grossman, Elizabeth A; Ward, Carl C; Spradlin, Jessica N; Bateman, Leslie A; Huffman, Tucker R; Miyamoto, David K; Kleinman, Jordan I; Nomura, Daniel K

    2017-11-16

    Many natural products that show therapeutic activities are often difficult to synthesize or isolate and have unknown targets, hindering their development as drugs. Identifying druggable hotspots targeted by covalently acting anti-cancer natural products can enable pharmacological interrogation of these sites with more synthetically tractable compounds. Here, we used chemoproteomic platforms to discover that the anti-cancer natural product withaferin A targets C377 on the regulatory subunit PPP2R1A of the tumor-suppressor protein phosphatase 2A (PP2A) complex leading to activation of PP2A activity, inactivation of AKT, and impaired breast cancer cell proliferation. We developed a more synthetically tractable cysteine-reactive covalent ligand, JNS 1-40, that selectively targets C377 of PPP2R1A to impair breast cancer signaling, proliferation, and in vivo tumor growth. Our study highlights the utility of using chemoproteomics to map druggable hotspots targeted by complex natural products and subsequently interrogating these sites with more synthetically tractable covalent ligands for cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Laser one-dimensional range profile and the laser two-dimensional range profile of cylinders

    NASA Astrophysics Data System (ADS)

    Gong, Yanjun; Wang, Mingjun; Gong, Lei

    2015-10-01

    Laser one-dimensional range profile, that is scattering power from pulse laser scattering of target, is a radar imaging technology. The laser two-dimensional range profile is two-dimensional scattering imaging of pulse laser of target. Laser one-dimensional range profile and laser two-dimensional range profile are called laser range profile(LRP). The laser range profile can reflect the characteristics of the target shape and surface material. These techniques were motivated by applications of laser radar to target discrimination in ballistic missile defense. The radar equation of pulse laser is given in this paper. This paper demonstrates the analytical model of laser range profile of cylinder based on the radar equation of the pulse laser. Simulations results of laser one-dimensional range profiles of some cylinders are given. Laser range profiles of cylinder, whose surface material with diffuse lambertian reflectance, is given in this paper. Laser range profiles of different pulse width of cylinder are given in this paper. The influences of geometric parameters, pulse width, attitude on the range profiles are analyzed.

  2. Food Management, Production, and Service. Occupational Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Food Management, Production, and Service Occupational Competency Analysis Profile (OCAP) is one of a series of competency lists, verified by expert workers, that have evolved from a modified DACUM (Developing a Curriculum) job analysis process involving business, industry, labor, and community agency representatives from throughout Ohio. This…

  3. Isotope Dilution-Based Targeted and Nontargeted Carbonyl Neurosteroid/Steroid Profiling.

    PubMed

    Sharp, Sheila; Mitchell, Scott J; Vallée, Monique; Kuzmanova, Elena; Cooper, Michelle; Belelli, Delia; Lambert, Jeremy J; Huang, Jeffrey T-J

    2018-04-17

    Neurosteroids are brain-derived steroids, capable of rapidly modulating neuronal excitability in a nongenomic manner. Dysregulation of their synthesis or metabolism has been implicated in many pathological conditions. Here, we describe an isotope dilution based targeted and nontargeted (ID-TNT) profiling of carbonyl neurosteroids/steroids. The method combines stable isotope dilution, hydroxylamine derivatization, high-resolution MS scanning, and data-dependent MS/MS analysis, allowing absolute quantification of pregnenolone, progesterone, 5α-dihydroprogesterone, 3α,5α-tetrahydroprogesterone, and 3β,5α-tetrahydroprogesterone, and relative quantification of other carbonyl containing steroids. The utility and validity of this approach was tested in an acute stress mouse model and via pharmacological manipulation of the steroid metabolic pathway with finasteride. We report that brain levels of 3α,5α-tetrahydroprogesterone, a potent enhancer of GABA A receptor (GABA A R-mediated inhibitory function, from control mice is in the 5-40 pmol/g range, a value greater than previously reported. The approach allows the use of data from targeted analysis to guide the normalization strategy for nontargeted data. Furthermore, novel findings, including a striking increase of brain pregnenolone following finasteride administration were discovered in this study. Collectively, our results indicate that this approach has distinct advantages for examining targeted and nontargeted neurosteroid/steroid pathways in animal models and could facilitate a better understanding of the physiological and pathological roles of neurosteroids as modulators of brain excitability.

  4. Geographic profiling as a novel spatial tool for targeting infectious disease control

    PubMed Central

    2011-01-01

    Background Geographic profiling is a statistical tool originally developed in criminology to prioritise large lists of suspects in cases of serial crime. Here, we use two data sets - one historical and one modern - to show how it can be used to locate the sources of infectious disease. Results First, we re-analyse data from a classic epidemiological study, the 1854 London cholera outbreak. Using 321 disease sites as input, we evaluate the locations of 13 neighbourhood water pumps. The Broad Street pump - the outbreak's source- ranks first, situated in the top 0.2% of the geoprofile. We extend our study with an analysis of reported malaria cases in Cairo, Egypt, using 139 disease case locations to rank 59 mosquitogenic local water sources, seven of which tested positive for the vector Anopheles sergentii. Geographic profiling ranks six of these seven sites in positions 1-6, all in the top 2% of the geoprofile. In both analyses the method outperformed other measures of spatial central tendency. Conclusions We suggest that geographic profiling could form a useful component of integrated control strategies relating to a wide variety of infectious diseases, since evidence-based targeting of interventions is more efficient, environmentally friendly and cost-effective than untargeted intervention. PMID:21592339

  5. Geographic profiling as a novel spatial tool for targeting infectious disease control.

    PubMed

    Le Comber, Steven C; Rossmo, D Kim; Hassan, Ali N; Fuller, Douglas O; Beier, John C

    2011-05-18

    Geographic profiling is a statistical tool originally developed in criminology to prioritise large lists of suspects in cases of serial crime. Here, we use two data sets--one historical and one modern--to show how it can be used to locate the sources of infectious disease. First, we re-analyse data from a classic epidemiological study, the 1854 London cholera outbreak. Using 321 disease sites as input, we evaluate the locations of 13 neighbourhood water pumps. The Broad Street pump--the outbreak's source--ranks first, situated in the top 0.2% of the geoprofile. We extend our study with an analysis of reported malaria cases in Cairo, Egypt, using 139 disease case locations to rank 59 mosquitogenic local water sources, seven of which tested positive for the vector Anopheles sergentii. Geographic profiling ranks six of these seven sites in positions 1-6, all in the top 2% of the geoprofile. In both analyses the method outperformed other measures of spatial central tendency. We suggest that geographic profiling could form a useful component of integrated control strategies relating to a wide variety of infectious diseases, since evidence-based targeting of interventions is more efficient, environmentally friendly and cost-effective than untargeted intervention.

  6. Representing high throughput expression profiles via perturbation barcodes reveals compound targets.

    PubMed

    Filzen, Tracey M; Kutchukian, Peter S; Hermes, Jeffrey D; Li, Jing; Tudor, Matthew

    2017-02-01

    High throughput mRNA expression profiling can be used to characterize the response of cell culture models to perturbations such as pharmacologic modulators and genetic perturbations. As profiling campaigns expand in scope, it is important to homogenize, summarize, and analyze the resulting data in a manner that captures significant biological signals in spite of various noise sources such as batch effects and stochastic variation. We used the L1000 platform for large-scale profiling of 978 representative genes across thousands of compound treatments. Here, a method is described that uses deep learning techniques to convert the expression changes of the landmark genes into a perturbation barcode that reveals important features of the underlying data, performing better than the raw data in revealing important biological insights. The barcode captures compound structure and target information, and predicts a compound's high throughput screening promiscuity, to a higher degree than the original data measurements, indicating that the approach uncovers underlying factors of the expression data that are otherwise entangled or masked by noise. Furthermore, we demonstrate that visualizations derived from the perturbation barcode can be used to more sensitively assign functions to unknown compounds through a guilt-by-association approach, which we use to predict and experimentally validate the activity of compounds on the MAPK pathway. The demonstrated application of deep metric learning to large-scale chemical genetics projects highlights the utility of this and related approaches to the extraction of insights and testable hypotheses from big, sometimes noisy data.

  7. Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders.

    PubMed

    Sun, Yu; Narayan, Vaibhav A; Wittenberg, Gayle M

    2016-10-21

    Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs. Here we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants. We found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants. These findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at

  8. Gene expression profiling of whole blood: Comparison of target preparation methods for accurate and reproducible microarray analysis

    PubMed Central

    Vartanian, Kristina; Slottke, Rachel; Johnstone, Timothy; Casale, Amanda; Planck, Stephen R; Choi, Dongseok; Smith, Justine R; Rosenbaum, James T; Harrington, Christina A

    2009-01-01

    Background Peripheral blood is an accessible and informative source of transcriptomal information for many human disease and pharmacogenomic studies. While there can be significant advantages to analyzing RNA isolated from whole blood, particularly in clinical studies, the preparation of samples for microarray analysis is complicated by the need to minimize artifacts associated with highly abundant globin RNA transcripts. The impact of globin RNA transcripts on expression profiling data can potentially be reduced by using RNA preparation and labeling methods that remove or block globin RNA during the microarray assay. We compared four different methods for preparing microarray hybridization targets from human whole blood collected in PAXGene tubes. Three of the methods utilized the Affymetrix one-cycle cDNA synthesis/in vitro transcription protocol but varied treatment of input RNA as follows: i. no treatment; ii. treatment with GLOBINclear; or iii. treatment with globin PNA oligos. In the fourth method cDNA targets were prepared with the Ovation amplification and labeling system. Results We find that microarray targets generated with labeling methods that reduce globin mRNA levels or minimize the impact of globin transcripts during hybridization detect more transcripts in the microarray assay compared with the standard Affymetrix method. Comparison of microarray results with quantitative PCR analysis of a panel of genes from the NF-kappa B pathway shows good correlation of transcript measurements produced with all four target preparation methods, although method-specific differences in overall correlation were observed. The impact of freezing blood collected in PAXGene tubes on data reproducibility was also examined. Expression profiles show little or no difference when RNA is extracted from either fresh or frozen blood samples. Conclusion RNA preparation and labeling methods designed to reduce the impact of globin mRNA transcripts can significantly improve the

  9. Targeting Nuclear Receptors with Marine Natural Products

    PubMed Central

    Yang, Chunyan; Li, Qianrong; Li, Yong

    2014-01-01

    Nuclear receptors (NRs) are important pharmaceutical targets because they are key regulators of many metabolic and inflammatory diseases, including diabetes, dyslipidemia, cirrhosis, and fibrosis. As ligands play a pivotal role in modulating nuclear receptor activity, the discovery of novel ligands for nuclear receptors represents an interesting and promising therapeutic approach. The search for novel NR agonists and antagonists with enhanced selectivities prompted the exploration of the extraordinary chemical diversity associated with natural products. Recent studies involving nuclear receptors have disclosed a number of natural products as nuclear receptor ligands, serving to re-emphasize the translational possibilities of natural products in drug discovery. In this review, the natural ligands of nuclear receptors will be described with an emphasis on their mechanisms of action and their therapeutic potentials, as well as on strategies to determine potential marine natural products as nuclear receptor modulators. PMID:24473166

  10. Improving the environmental profile of wood panels via co-production of ethanol and acetic acid.

    PubMed

    Earles, J Mason; Halog, Anthony; Shaler, Stephen

    2011-11-15

    The oriented strand board (OSB) biorefinery is an emerging technology that could improve the building, transportation, and chemical sectors' environmental profiles. By adding a hot water extraction stage to conventional OSB panel manufacturing, hemicellulose polysaccharides can be extracted from wood strands and converted to renewably sourced ethanol and acetic acid. Replacing fossil-based gasoline and acetic acid has the potential to reduce greenhouse gas (GHG) emissions, among other possible impacts. At the same time, hemicellulose extraction could improve the environmental profile of OSB panels by reducing the level of volatile organic compounds (VOCs) emitted during manufacturing. In this study, the life cycle significance of such GHG, VOC, and other emission reductions was investigated. A process model was developed based on a mix of laboratory and industrial-level mass and energy flow data. Using these data a life cycle assessment (LCA) model was built. Sensitive process parameters were identified and used to develop a target production scenario for the OSB biorefinery. The findings suggest that the OSB biorefinery's deployment could substantially improve human and ecosystem health via reduction of select VOCs compared to conventionally produced OSB, gasoline, and acetic acid. Technological advancements are needed, however, to achieve desirable GHG reductions.

  11. Evaluation of a novel ultra small target technology supporting on-product overlay measurements

    NASA Astrophysics Data System (ADS)

    Smilde, Henk-Jan H.; den Boef, Arie; Kubis, Michael; Jak, Martin; van Schijndel, Mark; Fuchs, Andreas; van der Schaar, Maurits; Meyer, Steffen; Morgan, Stephen; Wu, Jon; Tsai, Vincent; Wang, Cathy; Bhattacharyya, Kaustuve; Chen, Kai-Hsiung; Huang, Guo-Tsai; Ke, Chih-Ming; Huang, Jacky

    2012-03-01

    Reducing the size of metrology targets is essential for in-die overlay metrology in advanced semiconductor manufacturing. In this paper, μ-diffraction-based overlay (μDBO) measurements with a YieldStar metrology tool are presented for target-sizes down to 10 × 10 μm2. The μDBO technology enables selection of only the diffraction efficiency information from the grating by efficiently separating it from product structure reflections. Therefore, μDBO targets -even when located adjacent to product environment- give excellent correlation with 40 × 160 μm2 reference targets. Although significantly smaller than standard scribe-line targets, they can achieve total-measurement-uncertainty values of below 0.5 nm on a wide range of product layers. This shows that the new μDBO technique allows for accurate metrology on ultra small in-die targets, while retaining the excellent TMU performance of diffraction-based overlay metrology.

  12. Secondary neutron-production cross sections from heavy-ioninteractions in composite targets.

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

    Heilbronn, L.; Iwata, Y.; Iwase,H.

    Secondary neutron-production cross-sections have been measured from interactions of 290 MeV/nucleon C and 600 MeV/nucleon Ne in a target composed of simulated Martian regolith and polyethylene, and from 400 MeV/nucleon Ne interactions in wall material from the International Space Station. The data were measured between 5 and 80 deg in the laboratory. We report the double-differential cross sections, angular distributions, and total neutron-production cross sections from all three systems. The spectra from all three systems exhibit behavior previously reported in other heavy-ion, neutron production experiments; namely, a peak at forward angles near the energy corresponding to the beam velocity, withmore » the remaining spectra generated by pre-equilibrium and equilibrium processes. The double differential cross sections are fitted with a moving-source parameterization. Also reported are the data without corrections for neutron flux attenuation in the target and other intervening materials, and for neutron production in non-target materials near the target position. These uncorrected spectra are compared with SHIELD-HIT and PHITS transport model calculations. The transport model calculations reproduce the spectral shapes well, but, on average, underestimate the magnitudes of the cross sections.« less

  13. Profile and scientific production of CNPq researchers in cardiology.

    PubMed

    Oliveira, Eduardo Araujo de; Ribeiro, Antonio Luiz Pinho; Quirino, Isabel Gomes; Oliveira, Maria Christina Lopes; Martelli, Daniella Reis; Lima, Leonardo Santos; Colosimo, Enrico Antonio; Lopes, Thais Junqueira; Silva, Ana Cristina Simões; Martelli, Hercílio

    2011-09-01

    Systematic assessments of the scientific production can optimize resource allocation and increase research productivity in Brazil. The aim of this study was to evaluate the profile and scientific production of researchers in the field of Cardiology who have fellowship in Medicine provided by the Conselho Nacional de Desenvolvimento Científico e Tecnológico. The curriculum Lattes of 33 researchers with active fellowships from 2006 to 2008 were included in the analysis. The variables of interest were: gender, affiliation, tutoring of undergraduate, masters and PhD students, and scientific production and its impact. : There was predominance of males (72.7%) and of fellowship level 2 (56.4%). Three states of the Federation were responsible for 94% of the researchers: SP (28; 71.8%), RS (4; 10.3%), e RJ (3; 9.1%). Four institutions are responsible for about 82% of researchers: USP (13; 39.4%), UNESP (5; 15.2%), UFRGS (4; 12.1%) e UNIFESP (3; 9.1%). During all academic careers, the researchers published 2.958 journal articles, with a mean of 89 articles per researcher. Of total, 55% and 75% were indexed at Web of Science and Scopus databases, respectively. The researchers received a total of 19648 citations at the database Web of Science, with a median of 330 citations per researcher (IQ = 198-706). The average number of citations per article was 13.5 citations (SD = 11.6). Our study has shown that researchers in the field of cardiology have a relevant scientific production. The knowledge of the profile of researchers in the field of Cardiology will probably enable effective strategies to qualitatively improve the scientific output of Brazilian researchers.

  14. Distributed micro-radar system for detection and tracking of low-profile, low-altitude targets

    NASA Astrophysics Data System (ADS)

    Gorwara, Ashok; Molchanov, Pavlo

    2016-05-01

    Proposed airborne surveillance radar system can detect, locate, track, and classify low-profile, low-altitude targets: from traditional fixed and rotary wing aircraft to non-traditional targets like unmanned aircraft systems (drones) and even small projectiles. Distributed micro-radar system is the next step in the development of passive monopulse direction finder proposed by Stephen E. Lipsky in the 80s. To extend high frequency limit and provide high sensitivity over the broadband of frequencies, multiple angularly spaced directional antennas are coupled with front end circuits and separately connected to a direction finder processor by a digital interface. Integration of antennas with front end circuits allows to exclude waveguide lines which limits system bandwidth and creates frequency dependent phase errors. Digitizing of received signals proximate to antennas allows loose distribution of antennas and dramatically decrease phase errors connected with waveguides. Accuracy of direction finding in proposed micro-radar in this case will be determined by time accuracy of digital processor and sampling frequency. Multi-band, multi-functional antennas can be distributed around the perimeter of a Unmanned Aircraft System (UAS) and connected to the processor by digital interface or can be distributed between swarm/formation of mini/micro UAS and connected wirelessly. Expendable micro-radars can be distributed by perimeter of defense object and create multi-static radar network. Low-profile, lowaltitude, high speed targets, like small projectiles, create a Doppler shift in a narrow frequency band. This signal can be effectively filtrated and detected with high probability. Proposed micro-radar can work in passive, monostatic or bistatic regime.

  15. Chemical proteomics approaches for identifying the cellular targets of natural products

    PubMed Central

    Sieber, S. A.

    2016-01-01

    Covering: 2010 up to 2016 Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied “in situ” – in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide–alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss ‘competitive mode’ approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed. PMID:27098809

  16. Chemical proteomics approaches for identifying the cellular targets of natural products.

    PubMed

    Wright, M H; Sieber, S A

    2016-05-04

    Covering: 2010 up to 2016Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied "in situ" - in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide-alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss 'competitive mode' approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed.

  17. Simultaneous structure-activity studies and arming of natural products by C-H amination reveal cellular targets of eupalmerin acetate.

    PubMed

    Li, Jing; Cisar, Justin S; Zhou, Cong-Ying; Vera, Brunilda; Williams, Howard; Rodríguez, Abimael D; Cravatt, Benjamin F; Romo, Daniel

    2013-06-01

    Natural products have a venerable history of, and enduring potential for the discovery of useful biological activity. To fully exploit this, the development of chemical methodology that can functionalize unique sites within these complex structures is highly desirable. Here, we describe the use of rhodium(II)-catalysed C-H amination reactions developed by Du Bois to carry out simultaneous structure-activity relationship studies and arming (alkynylation) of natural products at 'unfunctionalized' positions. Allylic and benzylic C-H bonds in the natural products undergo amination while olefins undergo aziridination, and tertiary amine-containing natural products are converted to amidines by a C-H amination-oxidation sequence or to hydrazine sulfamate zwitterions by an unusual N-amination. The alkynylated derivatives are ready for conversion into cellular probes that can be used for mechanism-of-action studies. Chemo- and site-selectivity was studied with a diverse library of natural products. For one of these-the marine-derived anticancer diterpene, eupalmerin acetate-quantitative proteome profiling led to the identification of several protein targets in HL-60 cells, suggesting a polypharmacological mode of action.

  18. Simultaneous structure-activity studies and arming of natural products by C-H amination reveal cellular targets of eupalmerin acetate

    NASA Astrophysics Data System (ADS)

    Li, Jing; Cisar, Justin S.; Zhou, Cong-Ying; Vera, Brunilda; Williams, Howard; Rodríguez, Abimael D.; Cravatt, Benjamin F.; Romo, Daniel

    2013-06-01

    Natural products have a venerable history of, and enduring potential for the discovery of useful biological activity. To fully exploit this, the development of chemical methodology that can functionalize unique sites within these complex structures is highly desirable. Here, we describe the use of rhodium(II)-catalysed C-H amination reactions developed by Du Bois to carry out simultaneous structure-activity relationship studies and arming (alkynylation) of natural products at ‘unfunctionalized’ positions. Allylic and benzylic C-H bonds in the natural products undergo amination while olefins undergo aziridination, and tertiary amine-containing natural products are converted to amidines by a C-H amination-oxidation sequence or to hydrazine sulfamate zwitterions by an unusual N-amination. The alkynylated derivatives are ready for conversion into cellular probes that can be used for mechanism-of-action studies. Chemo- and site-selectivity was studied with a diverse library of natural products. For one of these—the marine-derived anticancer diterpene, eupalmerin acetate—quantitative proteome profiling led to the identification of several protein targets in HL-60 cells, suggesting a polypharmacological mode of action.

  19. Targeted and untargeted-metabolite profiling to track the compositional integrity of ginger during processing using digitally-enhanced HPTLC pattern recognition analysis.

    PubMed

    Ibrahim, Reham S; Fathy, Hoda

    2018-03-30

    Tracking the impact of commonly applied post-harvesting and industrial processing practices on the compositional integrity of ginger rhizome was implemented in this work. Untargeted metabolite profiling was performed using digitally-enhanced HPTLC method where the chromatographic fingerprints were extracted using ImageJ software then analysed with multivariate Principal Component Analysis (PCA) for pattern recognition. A targeted approach was applied using a new, validated, simple and fast HPTLC image analysis method for simultaneous quantification of the officially recognized markers 6-, 8-, 10-gingerol and 6-shogaol in conjunction with chemometric Hierarchical Clustering Analysis (HCA). The results of both targeted and untargeted metabolite profiling revealed that peeling, drying in addition to storage employed during processing have a great influence on ginger chemo-profile, the different forms of processed ginger shouldn't be used interchangeably. Moreover, it deemed necessary to consider the holistic metabolic profile for comprehensive evaluation of ginger during processing. Copyright © 2018. Published by Elsevier B.V.

  20. Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation.

    PubMed

    Webhofer, C; Gormanns, P; Tolstikov, V; Zieglgänsberger, W; Sillaber, I; Holsboer, F; Turck, C W

    2011-12-13

    Currently used antidepressants elevate monoamine levels in the synaptic cleft. There is good reason to assume that this is not the only source for antidepressant therapeutic activities and that secondary downstream effects may be relevant for alleviating symptoms of depression. We attempted to elucidate affected biochemical pathways downstream of monoamine reuptake inhibition by interrogating metabolomic profiles in DBA/2Ola mice after chronic paroxetine treatment. Metabolomic changes were investigated using gas chromatography-mass spectrometry profiling and group differences were analyzed by univariate and multivariate statistics. Pathways affected by antidepressant treatment were related to energy metabolism, amino acid metabolism and hormone signaling. The identified pathways reveal further antidepressant therapeutic action and represent targets for drug development efforts. A comparison of the central nervous system with blood plasma metabolite alterations identified GABA, galactose-6-phosphate and leucine as biomarker candidates for assessment of antidepressant treatment effects in the periphery.

  1. Discovery of novel drug targets and their functions using phenotypic screening of natural products.

    PubMed

    Chang, Junghwa; Kwon, Ho Jeong

    2016-03-01

    Natural products are valuable resources that provide a variety of bioactive compounds and natural pharmacophores in modern drug discovery. Discovery of biologically active natural products and unraveling their target proteins to understand their mode of action have always been critical hurdles for their development into clinical drugs. For effective discovery and development of bioactive natural products into novel therapeutic drugs, comprehensive screening and identification of target proteins are indispensable. In this review, a systematic approach to understanding the mode of action of natural products isolated using phenotypic screening involving chemical proteomics-based target identification is introduced. This review highlights three natural products recently discovered via phenotypic screening, namely glucopiericidin A, ecumicin, and terpestacin, as representative case studies to revisit the pivotal role of natural products as powerful tools in discovering the novel functions and druggability of targets in biological systems and pathological diseases of interest.

  2. Representing high throughput expression profiles via perturbation barcodes reveals compound targets

    PubMed Central

    Kutchukian, Peter S.; Li, Jing; Tudor, Matthew

    2017-01-01

    High throughput mRNA expression profiling can be used to characterize the response of cell culture models to perturbations such as pharmacologic modulators and genetic perturbations. As profiling campaigns expand in scope, it is important to homogenize, summarize, and analyze the resulting data in a manner that captures significant biological signals in spite of various noise sources such as batch effects and stochastic variation. We used the L1000 platform for large-scale profiling of 978 representative genes across thousands of compound treatments. Here, a method is described that uses deep learning techniques to convert the expression changes of the landmark genes into a perturbation barcode that reveals important features of the underlying data, performing better than the raw data in revealing important biological insights. The barcode captures compound structure and target information, and predicts a compound’s high throughput screening promiscuity, to a higher degree than the original data measurements, indicating that the approach uncovers underlying factors of the expression data that are otherwise entangled or masked by noise. Furthermore, we demonstrate that visualizations derived from the perturbation barcode can be used to more sensitively assign functions to unknown compounds through a guilt-by-association approach, which we use to predict and experimentally validate the activity of compounds on the MAPK pathway. The demonstrated application of deep metric learning to large-scale chemical genetics projects highlights the utility of this and related approaches to the extraction of insights and testable hypotheses from big, sometimes noisy data. PMID:28182661

  3. Comprehensive metabolomic, lipidomic and microscopic profiling of Yarrowia lipolytica during lipid accumulation identifies targets for increased lipogenesis

    DOE PAGES

    Pomraning, Kyle R.; Wei, Siwei; Karagiosis, Sue A.; ...

    2015-04-23

    Yarrowia lipolytica is an oleaginous ascomycete yeast that accumulates large amounts of lipids and has potential as a biofuel producing organism. Despite a growing scientific literature focused on lipid production by Y. lipolytica, there remain significant knowledge gaps regarding the key biological processes involved. We applied a combination of metabolomic and lipidomic profiling approaches as well as microscopic techniques to identify and characterize the key pathways involved in de novo lipid accumulation from glucose in batch cultured, wild-type Y. lipolytica. We found that lipids accumulated rapidly and peaked at 48 hours during the five day experiment, concurrent with a shiftmore » in amino acid metabolism. We also report that Y. lipolytica secretes disaccharides early in batch culture and reabsorbs them when extracellular glucose is depleted. Exhaustion of extracellular sugars coincided with thickening of the cell wall, suggesting that genes involved in cell wall biogenesis may be a useful target for improving the efficiency of lipid producing yeast strains.« less

  4. Target and method for the production of fission product molybdenum-99

    DOEpatents

    Vandegrift, G.F.; Vissers, D.R.; Marshall, S.L.; Varma, R.

    1987-10-26

    A target for the reduction of fission product Mo-99 is prepared from uranium of low U-235 enrichment by coating a structural support member with a preparatory coating of a substantially oxide-free substrate metal. Uranium metal is electrodeposited from a molten halide electrolytic bath onto a substrate metal. The electrodeposition is performed at a predetermined direct current rate or by using pulsed plating techniques which permit relaxation of accumulated uranium ion concentrations within the melt. Layers of as much as to 600 mg/cm/sup 2/ of uranium can be prepared to provide a sufficient density to produce acceptable concentrations of fission product Mo-99. 2 figs.

  5. Target and method for the production of fission product molybdenum-99

    DOEpatents

    Vandegrift, George F.; Vissers, Donald R.; Marshall, Simon L.; Varma, Ravi

    1989-01-01

    A target for the reduction of fission product Mo-99 is prepared from uranium of low U-235 enrichment by coating a structural support member with a preparatory coating of a substantially oxide-free substrate metal. Uranium metal is electrodeposited from a molten halide electrolytic bath onto a substrate metal. The electrodeposition is performed at a predetermined direct current rate or by using pulsed plating techniques which permit relaxation of accumulated uranium ion concentrations within the melt. Layers of as much as to 600 mg/cm.sup.2 of uranium can be prepared to provide a sufficient density to produce acceptable concentrations of fission product Mo-99.

  6. Agricultural Products Sales and Service Worker. Ohio's Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    Developed through a modified DACUM (Developing a Curriculum) process involving business, industry, labor, and community agency representatives in Ohio, this document is a comprehensive and verified employer competency profile for agricultural products sales and service occupations. The list contains units (with and without subunits), competencies,…

  7. Ohio Agricultural Business and Production Systems. Technical Competency Profile (TCP).

    ERIC Educational Resources Information Center

    Ray, Gayl M.; Kershaw, Isaac; Mokma, Arnie

    This document describes the essential competencies from secondary through post-secondary associate degree programs for a career in agricultural business and production systems. Following an introduction, the Ohio College Tech Prep standards and program, and relevant definitions are described. Next are the technical competency profiles for these…

  8. Influence of lateral target size on hot electron production and electromagnetic pulse emission from laser-irradiated metallic targets

    NASA Astrophysics Data System (ADS)

    Chen, Zi-Yu; Li, Jian-Feng; Yu, Yong; Wang, Jia-Xiang; Li, Xiao-Ya; Peng, Qi-Xian; Zhu, Wen-Jun

    2012-11-01

    The influences of lateral target size on hot electron production and electromagnetic pulse emission from laser interaction with metallic targets have been investigated. Particle-in-cell simulations at high laser intensities show that the yield of hot electrons tends to increase with lateral target size, because the larger surface area reduces the electrostatic field on the target, owing to its expansion along the target surface. At lower laser intensities and longer time scales, experimental data characterizing electromagnetic pulse emission as a function of lateral target size also show target-size effects. Charge separation and a larger target tending to have a lower target potential have both been observed. The increase in radiation strength and downshift in radiation frequency with increasing lateral target size can be interpreted using a simple model of the electrical capacity of the target.

  9. In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line.

    PubMed

    Wang, Jigang; Zhang, Jianbin; Zhang, Chong-Jing; Wong, Yin Kwan; Lim, Teck Kwang; Hua, Zi-Chun; Liu, Bin; Tannenbaum, Steven R; Shen, Han-Ming; Lin, Qingsong

    2016-02-26

    To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQ(TM) quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway Analysis(TM) (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death.

  10. In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line

    PubMed Central

    Wang, Jigang; Zhang, Jianbin; Zhang, Chong-Jing; Wong, Yin Kwan; Lim, Teck Kwang; Hua, Zi-Chun; Liu, Bin; Tannenbaum, Steven R.; Shen, Han-Ming; Lin, Qingsong

    2016-01-01

    To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQTM quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway AnalysisTM (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death. PMID:26915414

  11. Proposed industrial recovered materials utilization targets for the metals and metal-products industry

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

    None

    1979-05-01

    The introductory chapter provides a discussion of the factors that affect the recovery and reuse of secondary materials and the competition between the primary and secondary metals industries. It discusses these industries in terms of resource characteristics, industry technology, pollution control requirements, market structure, the economics of recycling, and the issues involved in econometrically estimating scrap supply response behavior. It further presents the methodology established by DOE for the metals, textiles, rubber, and pulp and paper industries. The areas in which government policies might have a significant impact on the utilization of primary and secondary metals and on any recyclingmore » targets between now and 1987 are noted. Chapter 3 presents general profiles for the major industrial segments comprising SIC 33. The profiles include such topics as industry structure, process technology, materials and recycling flow, and future trends. Chapter 4 specifically covers the evaluation of recycling targets for the ferrous, aluminum, copper, zinc, and lead industries. (MCW)« less

  12. A Secure and Privacy-Preserving Targeted Ad-System

    NASA Astrophysics Data System (ADS)

    Androulaki, Elli; Bellovin, Steven M.

    Thanks to its low product-promotion cost and its efficiency, targeted online advertising has become very popular. Unfortunately, being profile-based, online advertising methods violate consumers' privacy, which has engendered resistance to the ads. However, protecting privacy through anonymity seems to encourage click-fraud. In this paper, we define consumer's privacy and present a privacy-preserving, targeted ad system (PPOAd) which is resistant towards click fraud. Our scheme is structured to provide financial incentives to all entities involved.

  13. Effects of end products on fermentation profiles in Clostridium carboxidivorans P7 for syngas fermentation.

    PubMed

    Zhang, Jie; Taylor, Steven; Wang, Yi

    2016-10-01

    Clostridium carboxidivorans P7 is a strict anaerobic bacterium capable of converting syngas to biofuels. However, its fermentation profiles is poorly understood. Here, various end-products, including acetic acid, butyric acid, hexanoic acid, ethanol and butanol were supplemented to evaluate their effects on fermentation profiles in C. carboxidivorans at two temperatures. At 37°C, fatty acids addition likely led to more corresponding alcohols production. At 25°C, C2 and C4 fatty acids supplementation resulted in more corresponding higher fatty acids, while supplemented hexanoic acid increased yields of C2 and C4 fatty acids and hexanol. Supplementation of ethanol or butanol caused increased production of C2 and C4 acids at both temperatures; however, long-chain alcohols were still more likely produced at lower temperature. In conclusion, fermentation profiles of C. carboxidivorans can be changed in respond to pre-added end-products and carbon flow may be redirected to desired products by controlling culture conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial.

    PubMed

    Markey, Oonagh; Vasilopoulou, Dafni; Kliem, Kirsty E; Koulman, Albert; Fagan, Colette C; Summerhill, Keith; Wang, Laura Y; Grandison, Alistair S; Humphries, David J; Todd, Susan; Jackson, Kim G; Givens, David I; Lovegrove, Julie A

    2017-05-23

    Dairy products are a major contributor to dietary SFA. Partial replacement of milk SFA with unsaturated fatty acids (FAs) is possible through oleic-acid rich supplementation of the dairy cow diet. To assess adherence to the intervention of SFA-reduced, MUFA-enriched dairy product consumption in the RESET (REplacement of SaturatEd fat in dairy on Total cholesterol) study using 4-d weighed dietary records, in addition to plasma phospholipid FA (PL-FA) status. In a randomised, controlled, crossover design, free-living UK participants identified as moderate risk for CVD (n = 54) were required to replace habitually consumed dairy foods (milk, cheese and butter), with study products with a FA profile typical of retail products (control) or SFA-reduced, MUFA-enriched profile (modified), for two 12-week periods, separated by an 8-week washout period. A flexible food-exchange model was used to implement each isoenergetic high-fat, high-dairy diet (38% of total energy intake (%TE) total fat): control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA). Following the modified diet, there was a smaller increase in SFA (17.2%TE vs. 19.1%TE; p < 0.001) and greater increase in MUFA intake (15.4%TE vs. 11.8%TE; p < 0.0001) when compared with the control. PL-FA analysis revealed lower total SFAs (p = 0.006), higher total cis-MUFAs and trans-MUFAs (both p < 0.0001) following the modified diet. The food-exchange model was successfully used to achieve RESET dietary targets by partial replacement of SFAs with MUFAs in dairy products, a finding reflected in the PL-FA profile and indicative of objective dietary compliance. ClinicalTrials.gov Identifier: NCT02089035 , date 05-01-2014.

  15. Neutron Production from In-situ Heavy Ice Coated Targets at Vulcan

    NASA Astrophysics Data System (ADS)

    Morrison, John; Krygier, A. G.; Kar, S.; Ahmed, H.; Alejo, A.; Clarke, R.; Fuchs, J.; Green, A.; Jung, D.; Kleinschmidt, A.; Najmudin, Z.; Nakamura, H.; Norreys, P.; Notley, M.; Oliver, M.; Roth, M.; Vassura, L.; Zepf, M.; Borghesi, M.; Freeman, R. R.

    2015-05-01

    Laser based neutron production experiments have been performed utilizing ultra-high intensity laser accelerated ions impinging upon a secondary target. The neutron yield from such experiments may be improved if the accelerated ions were primarily deuterons taking advantage of the d-d cross section. Recent experiments have demonstrated that selective deuteron acceleration from in-situ heavy ice coating of targets can produce ion spectra where deuterons comprise > 99 % of the measured ions. Results will be presented from integrated neutron production experiments from heavy ice targets coated in-situ recently performed on the Vulcan laser at Rutherford Appleton Laboratory. We are grateful for the Staff at RAL and acknowledge funding from the US DoE. AFOSR, European Social Fund, and the Czech Republic.

  16. Quantitative multi-target RNA profiling in Epstein-Barr virus infected tumor cells.

    PubMed

    Greijer, A E; Ramayanti, O; Verkuijlen, S A W M; Novalić, Z; Juwana, H; Middeldorp, J M

    2017-03-01

    Epstein-Barr virus (EBV) is etiologically linked to multiple acute, chronic and malignant diseases. Detection of EBV-RNA transcripts in tissues or biofluids besides EBV-DNA can help in diagnosing EBV related syndromes. Sensitive EBV transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. Here we describe a multi-gene quantitative RT-PCR profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and lytic EBV transcripts. These transcripts include (but are not restricted to), EBNA1, EBNA2, LMP1, LMP2, BARTs, EBER1, BARF1 and ZEBRA, Rta, BGLF4 (PK), BXLF1 (TK) and BFRF3 (VCAp18) all of which have been implicated in EBV-driven oncogenesis and viral replication. With this method we determine the amount of RNA copies per infected (tumor) cell in bulk populations of various origin. While we confirm the expected RNA profiles within classic EBV latency programs, this sensitive quantitative approach revealed the presence of rare cells undergoing lytic replication. Inducing lytic replication in EBV tumor cells supports apoptosis and is considered as therapeutic approach to treat EBV-driven malignancies. This sensitive multi-primed quantitative RT-PCR approach can provide broader understanding of transcriptional activity in latent and lytic EBV infection and is suitable for monitoring virus-specific therapy responses in patients with EBV associated cancers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Surface reflectance drives nest box temperature profiles and thermal suitability for target wildlife.

    PubMed

    Griffiths, Stephen R; Rowland, Jessica A; Briscoe, Natalie J; Lentini, Pia E; Handasyde, Kathrine A; Lumsden, Linda F; Robert, Kylie A

    2017-01-01

    .e., levels of canopy cover), to ensure target animals have access to artificial hollows with a broad range of thermal profiles, and can therefore choose boxes with optimal thermal conditions across different seasons.

  18. Surface reflectance drives nest box temperature profiles and thermal suitability for target wildlife

    PubMed Central

    Rowland, Jessica A.; Briscoe, Natalie J.; Lentini, Pia E.; Handasyde, Kathrine A.; Lumsden, Linda F.; Robert, Kylie A.

    2017-01-01

    .e., levels of canopy cover), to ensure target animals have access to artificial hollows with a broad range of thermal profiles, and can therefore choose boxes with optimal thermal conditions across different seasons. PMID:28472147

  19. 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

  20. GENE EXPRESSION PROFILING OF ACCESSIBLE SURROGATE TISSUES TO MONITOR MOLECULAR CHANGES IN INACCESSIBLE TARGET TISSUES FOLLOWING TOXICANT EXPOSURE

    EPA Science Inventory

    Gene Expression Profiling Of Accessible Surrogate Tissues To Monitor Molecular Changes In Inaccessible Target Tissues Following Toxicant Exposure
    John C. Rockett, Chad R. Blystone, Amber K. Goetz, Rachel N. Murrell, Judith E. Schmid and David J. Dix
    Reproductive Toxicology ...

  1. DNA Methylation and Hydroxymethylation Profile of CD34+-Enriched Cell Products Intended for Autologous CD34+ Cell Transplantation.

    PubMed

    Rozman, Jasmina-Ziva; Pohar Perme, Maja; Jez, Mojca; Malicev, Elvira; Krasna, Metka; Vrtovec, Bojan; Rozman, Primoz

    2017-09-01

    Epigenetic dysregulation has been shown to limit functional capacity of aging hematopoietic stem cells, which may contribute to impaired outcome of hematopoietic stem cell-based therapies. The aim of our study was to gain better insight into the epigenetic profile of CD34 + -enriched cell products intended for autologous CD34 + cell transplantation in patients with cardiomyopathy. We found global DNA methylation content significantly higher in immunoselected CD34 + cells compared to leukocytes in leukapheresis products (2.33 ± 1.03% vs. 1.84 ± 0.86%, p = 0.04). Global DNA hydroxymethylation content did not differ between CD34 + cells and leukocytes (p = 0.30). By measuring methylation levels of 94 stem cell transcription factors on a ready-to-use array, we identified 15 factors in which average promoter methylation was significantly different between leukocytes and CD34 + cells. The difference was highest for HOXC12 (58.18 ± 6.47% vs. 13.34 ± 24.18%, p = 0.0009) and NR2F2 (51.65 ± 25.89% vs. 7.66 ± 21.43%, p = 0.0045) genes. Our findings suggest that global DNA methylation and hydroxymethylation patterns as well as target methylation profile of selected genes in CD34 + -enriched cell products do not differ significantly compared to leukapheresis products and, thus, can tell us little about the functional capacity and regenerative properties of CD34 + cells. Future studies should examine other CD34 + cell graft characteristics, which may serve as prognostic tools for autologous CD34 + cell transplantation.

  2. Target assessment for antiparasitic drug discovery

    PubMed Central

    Frearson, Julie A.; Wyatt, Paul G.; Gilbert, Ian H.; Fairlamb, Alan H.

    2010-01-01

    Drug discovery is a high-risk, expensive and lengthy process taking at least 12 years and costing upwards of US$500 million per drug to reach the clinic. For neglected diseases, the drug discovery process is driven by medical need and guided by pre-defined target product profiles. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success. Here we describe criteria used in our drug discovery unit for target assessment and introduce the ‘traffic light’ system as a prioritisation and management tool. We hope this brief review will stimulate basic scientists to acquire additional information necessary for drug discovery. PMID:17962072

  3. Non-targeted metabolite profiling highlights the potential of strawberry leaves as a resource for specific bioactive compounds.

    PubMed

    Kårlund, Anna; Hanhineva, Kati; Lehtonen, Marko; McDougall, Gordon J; Stewart, Derek; Karjalainen, Reijo O

    2017-05-01

    The non-edible parts of horticultural crops, such as leaves, contain substantial amounts of valuable bioactive compounds which are currently only little exploited. For example, strawberry (Fragaria × ananassa) leaves may be a promising bioresource for diverse health-related applications. However, product standardization sets a real challenge, especially when the leaf material comes from varying cultivars. The first step towards better quality control of berry fruit leaf-based ingredients and supplements is to understand metabolites present and their stability in different plant cultivars, so this study surveyed the distribution of potentially bioactive strawberry leaf metabolites in six different strawberry cultivars. Non-targeted metabolite profiling analysis using LC/qTOF-ESI-MS with data processing via principal component analysis and k-means clustering analysis was utilized to examine differences and commonalities between the leaf metabolite profiles. Quercetin and kaempferol derivatives were the dominant flavonol groups in strawberry leaves. Previously described and novel caffeic and chlorogenic acid derivatives were among the major phenolic acids. In addition, ellagitannins were one of the distinguishing compound classes in strawberry leaves. In general, strawberry leaves also contained high levels of octadecatrienoic acid derivatives, precursors of valuable odour compounds. The specific bioactive compounds found in the leaves of different strawberry cultivars offer the potential for the selection of optimized leaf materials for added-value food and non-food applications. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  4. A Target Advertisement System Based on TV Viewer's Profile Reasoning

    NASA Astrophysics Data System (ADS)

    Lim, Jeongyeon; Kim, Munjo; Lee, Bumshik; Kim, Munchurl; Lee, Heekyung; Lee, Han-Kyu

    With the rapidly growing Internet, the Internet broadcasting and web casting service have been one of the well-known services. Specially, it is expected that the IPTV service will be one of the principal services in the broadband network [2]. However, the current broadcasting environment is served for the general public and requires the passive attitude to consume the TV programs. For the advanced broadcasting environments, various research of the personalized broadcasting is needed. For example, the current unidirectional advertisement provides to the TV viewers the advertisement contents, depending on the popularity of TV programs, the viewing rates, the age groups of TV viewers, and the time bands of the TV programs being broadcast. It is not an efficient way to provide the useful information to the TV viewers from customization perspective. If a TV viewer does not need particular advertisement contents, then information may be wasteful to the TV viewer. Therefore, it is expected that the target advertisement service will be one of the important services in the personalized broadcasting environments. The current research in the area of the target advertisement classifies the TV viewers into clustered groups who have similar preference. The digital TV collaborative filtering estimates the user's favourite advertisement contents by using the usage history [1, 4, 5]. In these studies, the TV viewers are required to provide their profile information such as the gender, job, and ages to the service providers via a PC or Set-Top Box (STB) which is connected to digital TV. Based on explicit information, the advertisement contents are provided to the TV viewers in a customized way with tailored advertisement contents. However, the TV viewers may dislike exposing to the service providers their private information because of the misuse of it. In this case, it is difficult to provide appropriate target advertisement service.

  5. Encapsulation methods for solid radionuclide production targets at a medium-energy cyclotron facility

    NASA Astrophysics Data System (ADS)

    Steyn, Gideon; Vermeulen, Christiaan; Isaacs, Eugene

    2018-05-01

    The techniques employed at iThemba LABS for the encapsulation of solid radionuclide production targets, based on cold indentation welding, electron beam welding and laser welding, are described. Some aspects of the target holders and cooling requirements to bombard targets in a tandem configuration with a 66 MeV proton beam, with intensities up to nominally 250 A, are also briefly discussed. These techniques are inter alia suitable for a production regimen compatible with the new generation of commercial, high-intensity 70 MeV cyclotrons.

  6. Imipenem in burn patients: pharmacokinetic profile and PK/PD target attainment.

    PubMed

    Gomez, David S; Sanches-Giraud, Cristina; Silva, Carlindo V; Oliveira, Amanda M Ribas Rosa; da Silva, Joao Manoel; Gemperli, Rolf; Santos, Silvia R C J

    2015-03-01

    Unpredictable pharmacokinetics (PK) in burn patients may result in plasma concentrations below concentrations that are effective against common pathogens. The present study evaluated the imipenem PK profile and pharmacokinetic/pharmacodynamics (PK/PD) correlation in burn patients. Fifty-one burn patients, 38.7 years of age (mean), 68.0 kg, 36.3% total burn surface area (TBSA), of whom 84% (43/51) exhibited thermal injury, 63% inhalation injury and 16% electrical injury (8/51), all of whom were receiving imipenem treatment were investigated. Drug plasma monitoring, PK study (120 sets of plasma levels) and PK/PD correlation were performed in a series of blood samples. Only 250 μl of plasma samples were required for drug plasma measurements using the ultra filtration technique for the purification of biological matrix and quantification using liquid chromatography. Probability of target attainment (PTA) was calculated using a PD target of 40% free drug concentrations above the minimum inhibitory concentration (40%fT>MIC). Significant differences in PK parameters (medians), such as biological half-life (2.2 vs 5.5 h), plasma clearance (16.2 vs 1.4 l h(-1)) and volume of distribution (0.86 vs 0.19 l kg(-1)), were registered in burn patients via comparisons of set periods with normal renal function against periods of renal failure. Correlations between creatinine clearance and total body plasma clearance were also obtained. In addition, the PK profile did not change according to TBSA during sets when renal function was preserved. PTA was >89% for MIC values up to 4 mg l(-1). In conclusion, imipenem efficacy for the control of hospital infection on the basis of PK/PD correlation was guaranteed for burn in patients at the recommended dose regimens for normal renal function (31.1±9.7 mg kg(-1) daily), but the daily dose must be reduced to 17.2±9.7 mg kg(-1) during renal failure to avoid neurotoxicity.

  7. Activity-Based Protein Profiling of Organophosphorus and Thiocarbamate Pesticides Reveals Multiple Serine Hydrolase Targets in Mouse Brain

    PubMed Central

    NOMURA, DANIEL K.; CASIDA, JOHN E.

    2010-01-01

    Organophosphorus (OP) and thiocarbamate (TC) agrochemicals are used worldwide as insecticides, herbicides, and fungicides, but their safety assessment in terms of potential off-targets remains incomplete. In this study, we used a chemoproteomic platform, termed activity-based protein profiling, to broadly define serine hydrolase targets in mouse brain of a panel of 29 OP and TC pesticides. Among the secondary targets identified, enzymes involved in degradation of endocannabinoid signaling lipids, monoacylglycerol lipase and fatty acid amide hydrolase, were inhibited by several OP and TC pesticides. Blockade of these two enzymes led to elevations in brain endocannabinoid levels and dysregulated brain arachidonate metabolism. Other secondary targets include enzymes thought to also play important roles in the nervous system and unannotated proteins. This study reveals a multitude of secondary targets for OP and TC pesticides and underscores the utility of chemoproteomic platforms in gaining insights into biochemical pathways that are perturbed by these toxicants. PMID:21341672

  8. HARP targets pion production cross section and yield measurements: Implications for MiniBooNE neutrino flux

    NASA Astrophysics Data System (ADS)

    Wickremasinghe, Don Athula Abeyarathna

    The prediction of the muon neutrino flux from a 71.0 cm long beryllium target for the MiniBooNE experiment is based on a measured pion production cross section which was taken from a short beryllium target (2.0 cm thick - 5% nuclear interaction length) in the Hadron Production (HARP) experiment at CERN. To verify the extrapolation to our longer target, HARP also measured the pion production from 20.0 cm and 40.0 cm beryllium targets. The measured production yields on targets of 50% and 100% nuclear interaction lengths in the kinematic rage of momentum from 0.75 GeV/c to 6.5 GeV/c and the range of angle from 30 mrad to 210 mrad are presented along with an update of the short target cross sections. The best fitted extended Sanford-Wang (SW) model parameterization for updated short beryllium target positive pion production cross section is presented. Yield measurements for all three targets are also compared with that from the Monte Carlo predictions in the MiniBooNE experiment for different SW parameterization. The comparisons of muon neutrino flux predictions for updated SW model is presented.

  9. Profiling of potential driver mutations in sarcomas by targeted next generation sequencing.

    PubMed

    Andersson, Carola; Fagman, Henrik; Hansson, Magnus; Enlund, Fredrik

    2016-04-01

    Comprehensive genetic profiling by massively parallel sequencing, commonly known as next generation sequencing (NGS), is becoming the foundation of personalized oncology. For sarcomas very few targeted treatments are currently in routine use. In clinical practice the preoperative diagnostic workup of soft tissue tumours largely relies on core needle biopsies. Although mostly sufficient for histopathological diagnosis, only very limited amounts of formalin fixated paraffin embedded tissue are often available for predictive mutation analysis. Targeted NGS may thus open up new possibilities for comprehensive characterization of scarce biopsies. We therefore set out to search for driver mutations by NGS in a cohort of 55 clinically and morphologically well characterized sarcomas using low input of DNA from formalin fixated paraffin embedded tissues. The aim was to investigate if there are any recurrent or targetable aberrations in cancer driver genes in addition to known chromosome translocations in different types of sarcomas. We employed a panel covering 207 mutation hotspots in 50 cancer-associated genes to analyse DNA from nine gastrointestinal stromal tumours, 14 synovial sarcomas, seven myxoid liposarcomas, 22 Ewing sarcomas and three Ewing-like small round cell tumours at a large sequencing depth to detect also mutations that are subclonal or occur at low allele frequencies. We found nine mutations in eight different potential driver genes, some of which are potentially actionable by currently existing targeted therapies. Even though no recurrent mutations in driver genes were found in the different sarcoma groups, we show that targeted NGS-based sequencing is clearly feasible in a diagnostic setting with very limited amounts of paraffin embedded tissue and may provide novel insights into mesenchymal cell signalling and potentially druggable targets. Interestingly, we also identify five non-synonymous sequence variants in 4 established cancer driver genes in DNA

  10. Natural products used as a chemical library for protein-protein interaction targeted drug discovery.

    PubMed

    Jin, Xuemei; Lee, Kyungro; Kim, Nam Hee; Kim, Hyun Sil; Yook, Jong In; Choi, Jiwon; No, Kyoung Tai

    2018-01-01

    Protein-protein interactions (PPIs), which are essential for cellular processes, have been recognized as attractive therapeutic targets. Therefore, the construction of a PPI-focused chemical library is an inevitable necessity for future drug discovery. Natural products have been used as traditional medicines to treat human diseases for millennia; in addition, their molecular scaffolds have been used in diverse approved drugs and drug candidates. The recent discovery of the ability of natural products to inhibit PPIs led us to use natural products as a chemical library for PPI-targeted drug discovery. In this study, we collected natural products (NPDB) from non-commercial and in-house databases to analyze their similarities to small-molecule PPI inhibitors (iPPIs) and FDA-approved drugs by using eight molecular descriptors. Then, we evaluated the distribution of NPDB and iPPIs in the chemical space, represented by the molecular fingerprint and molecular scaffolds, to identify the promising scaffolds, which could interfere with PPIs. To investigate the ability of natural products to inhibit PPI targets, molecular docking was used. Then, we predicted a set of high-potency natural products by using the iPPI-likeness score based on a docking score-weighted model. These selected natural products showed high binding affinities to the PPI target, namely XIAP, which were validated in an in vitro experiment. In addition, the natural products with novel scaffolds might provide a promising starting point for further medicinal chemistry developments. Overall, our study shows the potency of natural products in targeting PPIs, which might help in the design of a PPI-focused chemical library for future drug discovery. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Environmental profile and critical temperature effects on milk production of Holstein cows in desert climate

    NASA Astrophysics Data System (ADS)

    Igono, M. O.; Bjotvedt, G.; Sanford-Crane, H. T.

    1992-06-01

    The environmental profile of central Arizona is quantitatively described using meteorological data between 1971 and 1986. Utilizing ambient temperature criteria of hours per day less than 21° C, between 21 and 27° C, and more than 27° C, the environmental profile of central Arizona consists of varying levels of thermoneutral and heat stress periods. Milk production data from two commercial dairy farms from March 1990 to February 1991 were used to evaluate the seasonal effects identified in the environmental profile. Overall, milk production is lower during heat stress compared to thermoneutral periods. During heat stress, the cool period of hours per day with temperature less than 21° C provides a margin of safety to reduce the effects of heat stress on decreased milk production. Using minimum, mean and maximum ambient temperatures, the upper critical temperatures for milk production are 21, 27 and 32° C, respectively. Using the temperature-humidity index as the thermal environment indicator, the critical values for minimum, mean and maximum THI are 64, 72 and 76, respectively.

  12. Laser range profile of cones

    NASA Astrophysics Data System (ADS)

    Zhou, Wenzhen; Gong, Yanjun; Wang, Mingjun; Gong, Lei

    2016-10-01

    technology. Laser one-dimensional range profile can reflect the characteristics of the target shape and surface material. These techniques were motivated by applications of laser radar to target discrimination in ballistic missile defense. The radar equation of pulse laser about cone is given in this paper. This paper demonstrates the analytical model of laser one-dimensional range profile of cone based on the radar equation of the pulse laser. Simulations results of laser one-dimensional range profiles of some cones are given. Laser one-dimensional range profiles of cone, whose surface material with diffuse lambertian reflectance, is given in this paper. Laser one-dimensional range profiles of cone, whose surface mater with diffuse materials whose retroreflectance can be modeled closely with an exponential term that decays with increasing incidence angles, is given in this paper. Laser one-dimensional range profiles of different pulse width of cone is given in this paper. The influences of surface material, pulse width, attitude on the one-dimensional range are analyzed. The laser two-dimensional range profile is two-dimensional scattering imaging of pulse laser of target. The two-dimensional range profile of roughness target can provide range resolved information. An analytical model of two-dimensional laser range profile of cone is proposed. The simulations of two-dimensional laser range profiles of some cones are given. Laser two-dimensional range profiles of cone, whose surface mater with diffuse lambertian reflectance, is given in this paper. Laser two-dimensional range profiles of cone, whose surface mater with diffuse materials whose retroreflectance can be modeled closely with an exponential term that decays with increasing incidence angles, is given in this paper. The influence of pulse width, surface material on laser two-dimensional range profile is analyzed. Laser one-dimensional range profile and laser two-dimensional range profile are called as laser

  13. Particle production of a graphite target system for the intensity frontier

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

    Ding, X.; Kirk, H.; McDonald, K. T.

    2015-05-03

    A solid graphite target system is considered for an intense muon and/or neutrino source in support of physics at the intensity frontier. We previously optimized the geometric parameters of the beam and target to maximize particle production at low energies by incoming protons with kinetic energy of 6.75 GeV and an rms geometric emittance of 5 mm-mrad using the MARS15(2014) code. In this study, we ran MARS15 with ROOT-based geometry and also considered a mercury-jet target as an upgrade option. The optimization was extended to focused proton beams with transverse emittances from 5 to 50 mm-mrad, showing that the particlemore » production decreases slowly with increasing emittance. We also studied beam-dump configurations to suppress the rate of undesirable high-energy secondary particles in the beam.« less

  14. Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates.

    PubMed

    Hou, X; Tanguay, J; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

    2016-01-21

    In response to the recognized fragility of reactor-produced (99)Mo supply, direct production of (99m)Tc via (100)Mo(p,2n)(99m)Tc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with (99m)Tc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical (99m)Tc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

  15. Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates

    NASA Astrophysics Data System (ADS)

    Hou, X.; Tanguay, J.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

    2016-01-01

    In response to the recognized fragility of reactor-produced 99Mo supply, direct production of 99mTc via 100Mo(p,2n)99mTc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with 99mTc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical 99mTc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

  16. Recommendations for Improving Identification and Quantification in Non-Targeted, GC-MS-Based Metabolomic Profiling of Human Plasma

    PubMed Central

    Wang, Hanghang; Muehlbauer, Michael J.; O’Neal, Sara K.; Newgard, Christopher B.; Hauser, Elizabeth R.; Shah, Svati H.

    2017-01-01

    The field of metabolomics as applied to human disease and health is rapidly expanding. In recent efforts of metabolomics research, greater emphasis has been placed on quality control and method validation. In this study, we report an experience with quality control and a practical application of method validation. Specifically, we sought to identify and modify steps in gas chromatography-mass spectrometry (GC-MS)-based, non-targeted metabolomic profiling of human plasma that could influence metabolite identification and quantification. Our experimental design included two studies: (1) a limiting-dilution study, which investigated the effects of dilution on analyte identification and quantification; and (2) a concentration-specific study, which compared the optimal plasma extract volume established in the first study with the volume used in the current institutional protocol. We confirmed that contaminants, concentration, repeatability and intermediate precision are major factors influencing metabolite identification and quantification. In addition, we established methods for improved metabolite identification and quantification, which were summarized to provide recommendations for experimental design of GC-MS-based non-targeted profiling of human plasma. PMID:28841195

  17. Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target.

    PubMed

    Dufva, Olli; Kankainen, Matti; Kelkka, Tiina; Sekiguchi, Nodoka; Awad, Shady Adnan; Eldfors, Samuli; Yadav, Bhagwan; Kuusanmäki, Heikki; Malani, Disha; Andersson, Emma I; Pietarinen, Paavo; Saikko, Leena; Kovanen, Panu E; Ojala, Teija; Lee, Dean A; Loughran, Thomas P; Nakazawa, Hideyuki; Suzumiya, Junji; Suzuki, Ritsuro; Ko, Young Hyeh; Kim, Won Seog; Chuang, Shih-Sung; Aittokallio, Tero; Chan, Wing C; Ohshima, Koichi; Ishida, Fumihiro; Mustjoki, Satu

    2018-04-19

    Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data. Drug sensitivity profiling further demonstrates the role of the JAK-STAT pathway in the pathogenesis of NK-cell malignancies, identifying NK cells to be highly sensitive to JAK and BCL2 inhibition compared to other hematopoietic cell lineages. Our results provide insight into ANKL genetics and a framework for application of targeted therapies in NK-cell malignancies.

  18. Metabolomic profiling and sensorial quality of 'Golden Delicious', 'Liberty', 'Santana', and 'Topaz' apples grown using organic and integrated production systems.

    PubMed

    Vanzo, Andreja; Jenko, Mojca; Vrhovsek, Urska; Stopar, Matej

    2013-07-03

    Apple quality was investigated in the scab-resistant 'Liberty', 'Santana', and 'Topaz' cultivars and the scab-susceptible 'Golden Delicious' cultivar. Trees subjected to the same crop load were cultivated using either an organic (ORG) or an integrated production (IP) system. Physicochemical properties, phenolic content, and sensorial quality of fruit from both systems were compared. There were no significant differences in fruit mass, starch, and total soluble solid content (the latter was higher in ORG 'Liberty') between ORG and IP fruit, whereas significantly higher flesh firmness was found in ORG fruit (except no difference in 'Golden Delicious'). Significantly higher total phenolic content in ORG fruit was found in 'Golden Delicious', whereas differences in other cultivars were not significant. Targeted metabolomic profiling of multiple classes of phenolics confirmed the impact of the production system on the 'Golden Delicious' phenolic profile as higher levels of 4-hydroxybenzoic acid, neo- and chlorogenic acids, phloridzin, procyanidin B2+B4, -3-O-glucoside and -3-O-galactoside of quercetin, kaempferol-3-O-rutinoside, and rutin being found in ORG fruit. The results obtained suggested that scab resistance influenced the phenolic biosynthesis in relation to the agricultural system. Sensorial evaluation indicated significantly better flavor (except for 'Topaz') and better appearance of IP fruit.

  19. HARP targets pion production cross section and yield measurements. Implications for MiniBooNE neutrino flux

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

    Wickremasinghe, Don Athula Abeyarathna

    2015-07-01

    The prediction of the muon neutrino flux from a 71.0 cm long beryllium target for the MiniBooNE experiment is based on a measured pion production cross section which was taken from a short beryllium target (2.0 cm thick - 5% nuclear interaction length) in the Hadron Production (HARP) experiment at CERN. To verify the extrapolation to our longer target, HARP also measured the pion production from 20.0 cm and 40.0 cm beryllium targets. The measured production yields, d 2N π± (p; θ )=dpd Ω, on targets of 50% and 100% nuclear interaction lengths in the kinematic rage of momentum frommore » 0.75 GeV/c to 6.5 GeV/c and the range of angle from 30 mrad to 210 mrad are presented along with an update of the short target cross sections. The best fitted extended Sanford-Wang (SW) model parameterization for updated short beryllium target π + production cross section is presented. Yield measurements for all three targets are also compared with that from the Monte Carlo predictions in the MiniBooNE experiment for different SW parameterization. The comparisons of v μ flux predictions for updated SW model is presented.« less

  20. Gadolinium-148 and other spallation production cross section measurements for accelerator target facilities

    NASA Astrophysics Data System (ADS)

    Kelley, Karen Corzine

    At the Los Alamos Neutron Science Center accelerator complex, protons are accelerated to 800 MeV and directed to two tungsten targets, Target 4 at the Weapons Neutron Research facility and the 1L target at the Lujan Center. The Department of Energy requires hazard classification analyses to be performed on these targets and places limits on certain radionuclide inventories in the targets to avoid characterizing the facilities as "nuclear facilities." Gadolinium-148 is a radionuclide created from the spallation of tungsten. Allowed isotopic inventories are particularly low for this isotope because it is an alpha-particle emitter with a 75-year half-life. The activity level of Gadolinium-148 is low, but it encompasses almost two-thirds of the total dose burden for the two tungsten targets based on present yield estimates. From a hazard classification standpoint, this severely limits the lifetime of these tungsten targets. The cross section is not well-established experimentally and this is the motivation for measuring the Gadolinium-148 production cross section from tungsten. In a series of experiments at the Weapons Neutron Research facility, Gadolinium-148 production was measured for 600- and 800-MeV protons on tungsten, tantalum, and gold. These experiments used 3 mum thin tungsten, tantalum, and gold foils and 10 mum thin aluminum activation foils. In addition, spallation yields were determined for many short-lived and long-lived spallation products with these foils using gamma and alpha spectroscopy and compared with predictions of the Los Alamos National Laboratory codes CEM2k+GEM2 and MCNPX. The cumulative Gadolinium-148 production cross section measured from tantalum, tungsten, and gold for incident 600-MeV protons were 15.2 +/- 4.0, 8.31 +/- 0.92, and 0.591 +/- 0.155, respectively. The average production cross sections measured at 800 MeV were 28.6 +/- 3.5, 19.4 +/- 1.8, and 3.69 +/- 0.50 for tantalum, tungsten, and gold, respectively. These cumulative

  1. Implementation of a solid target production facility

    NASA Astrophysics Data System (ADS)

    Tochon-Danguy, H. J.; Poniger, S. S.; Sachinidis, J. I.; Panopoulos, H. P.; Scott, A. M.

    2012-12-01

    The desire to utilize long-lived PET isotopes in Australia has significantly increased over the years and several research projects for labelling of peptides, proteins and biomolecules, including labelling of recombinant antibodies has been restricted due to the limited availability of suitable isotopes. This need has led to the recent installation and commissioning of a new facility dedicated to fully automated solid target isotope production, including 24I, 64Cu, 89Zr and 86Y at the Austin Health Centre for PET.

  2. Development of a Ne gas target for {sup 22}Na production by proton irradiation

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

    Mandal, Bidhan Ch., E-mail: mechbidhan@gmail.com; Pal, Gautam; Barua, Luna

    2016-03-15

    The article presents the design and development of a neon gas target for the production of {sup 22}Na using a proton beam from the room temperature cyclotron in Variable Energy Cyclotron Centre, Kolkata. The target design is made to handle a beam power of 85 W (17 MeV, 5 μA). The design is based on simulation using the computer code FLUKA for the beam dump and CFD-CFX for target cooling. The target has been successfully used for the production of {sup 22}Na in a 6 day long 17 MeV, 5 μA proton irradiation run.

  3. Alternate Tritium Production Methods Using A Liquid Lithium Target

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

    Wilson, J.

    For over 60 years, the Savannah River Site’s primary mission has been the production of tritium. From the beginning, the Savannah River National Laboratory (SRNL) has provided the technical foundation to ensure the successful execution of this critical defense mission. SRNL has developed most of the processes used in the tritium mission and provides the research and development necessary to supply this critical component. This project was executed by first developing reactor models that could be used as a neutron source. In parallel to this development calculations were carried out testing the feasibility of accelerator technologies that could also bemore » used for tritium production. Targets were designed with internal moderating material and optimized target was calculated to be capable of 3000 grams using a 1400 MWt sodium fast reactor, 850 grams using a 400 MWt sodium fast reactor, and 100 grams using a 62 MWt reactor, annually.« less

  4. Process and targets for production of no-carrier-added radiotin

    DOEpatents

    Srivastava, Suresh C; Zhuikov, Boris Leonidovich; Ermolaev, Stanislav Victorovich; Konyakhin, Nikolay Alexandrovich; Kokhanyuk, Vladimir Mikhailovich; Khamyanov, Stepan Vladimirovich; Togaeva, Natalya Roaldovna

    2014-04-22

    One embodiment of the present invention includes a process for production and recovery of no-carrier-added radioactive tin (NCA radiotin). An antimony target can be irradiated with a beam of accelerated particles forming NCA radiotin, followed by separation of the NCA radiotin from the irradiated target. The target is metallic Sb in a hermetically sealed shell. The shell can be graphite, molybdenum, or stainless steel. The irradiated target can be removed from the shell by chemical or mechanical means, and dissolved in an acidic solution. Sb can be removed from the dissolved irradiated target by extraction. NCA radiotin can be separated from the remaining Sb and other impurities using chromatography on silica gel sorbent. NCA tin-117m can be obtained from this process. NCA tin-117m can be used for labeling organic compounds and biological objects to be applied in medicine for imaging and therapy of various diseases.

  5. Cyclotron production of 61Cu using natural Zn & enriched 64Zn targets

    NASA Astrophysics Data System (ADS)

    Asad, A. H.; Smith, S. V.; Chan, S.; Jeffery, C. M.; Morandeau, L.; Price, R. I.

    2012-12-01

    Copper-61 (61Cu) shares with 64Cu certain advantages for PET diagnostic imaging, but has a shorter half-life (3.4hr vs. 12.7hr) and a greater probability of positron production per disintegration (61% vs. 17.9%). One important application is for in vivo imaging of hypoxic tissue. In this study 61Cu was produced using the 64Zn(p,α)61Cu reaction on natural Zn or enriched 64Zn targets. The enriched 64Zn (99.82%) was electroplated onto high purity gold or silver foils or onto thin Al discs. A typical target bombardment used 30μA; at 11.7, 14.5 or 17.6MeV over 30-60min. The 61Cu (radiochemical purity of >95%) was separated using a combination of cation and anion exchange columns. The 64Zn target material was recovered after each run, for re-use. In a direct comparison with enriched 64Zn-target results, 61Cu production using the cheaper natZn target proved to be an effective alternative.

  6. Plume Image Profiling of UV Laser Desorbed Biomolecules

    NASA Astrophysics Data System (ADS)

    Merrigan, T. L.; Hunniford, C. A.; Timson, D. J.; Catney, M.; McCullough, R. W.

    2008-12-01

    An experimental system, based upon the techniques of UV and IR laser desorption with time of flight mass spectrometry, has been constructed to enable the production and characterization of neutral biomolecular targets. The feasibility of the laser desorption technique for the purpose of radiation interaction experiments is investigated here. Fluorescent dye tagging and laser induced fluorescence imaging has been used to help characterize the laser produced plumes of biomolecules revealing their spatial density profiles and temporal evolution. Peak target thicknesses of 2×1012 molecules cm-2 were obtained 30 μs after laser desorption.

  7. Targeted Therapy Database (TTD): A Model to Match Patient's Molecular Profile with Current Knowledge on Cancer Biology

    PubMed Central

    Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M.; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

    2010-01-01

    Background The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. Objective To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. Methods To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. Results and Conclusions We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit

  8. Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

    PubMed

    Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

    2010-08-10

    The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the

  9. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    PubMed Central

    Leung, Maxwell C.K.; Phuong, Jimmy; Baker, Nancy C.; Sipes, Nisha S.; Klinefelter, Gary R.; Martin, Matthew T.; McLaurin, Keith W.; Setzer, R. Woodrow; Darney, Sally Perreault; Judson, Richard S.; Knudsen, Thomas B.

    2015-01-01

    Background: Trends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies. Objective: In the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system. Methods: We used U.S. EPA’s animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features. Results: A phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network. Conclusion: Computational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarchy across animal studies consistent with the human TDS hypothesis. We confirmed the known role of estrogen and androgen signaling pathways in rodent TDS, and importantly, broadened the list of molecular targets to include retinoic acid signaling, vascular remodeling proteins, G-protein coupled receptors (GPCRs), and cytochrome P450s. Citation: Leung MC, Phuong J, Baker NC, Sipes NS, Klinefelter GR, Martin MT, McLaurin KW, Setzer RW, Darney SP, Judson RS, Knudsen TB. 2016. Systems toxicology of male

  10. Identifying the cellular targets of natural products using T7 phage display.

    PubMed

    Piggott, Andrew M; Karuso, Peter

    2016-05-04

    Covering: up to the end of 2015While Nature continues to deliver a myriad of potent and structurally diverse biologically active small molecules, the cellular targets and modes of action of these natural products are rarely identified, significantly hindering their development as new chemotherapeutic agents. This article provides an introductory tutorial on the use of T7 phage display as a tool to rapidly identify the cellular targets of natural products and is aimed specifically at natural products chemists who may have only limited experience in molecular biology. A brief overview of T7 phage display is provided, including its strengths, weaknesses, and the type of problems that can and cannot be tackled with this technology. Affinity probe construction is reviewed, including linker design and natural product derivatisation strategies. A detailed description of the T7 phage biopanning procedure is provided, with valuable tips for optimising each step in the process, as well as advice for identifying and avoiding the most commonly encountered challenges and pitfalls along the way. Finally, a brief discussion is provided on techniques for validating the cellular targets identified using T7 phage display.

  11. The biological pump: Profiles of plankton production and consumption in the upper ocean

    NASA Astrophysics Data System (ADS)

    Longhurst, Alan R.; Glen Harrison, W.

    The ‘biological pump’ mediates flux of carbon to the interior of the ocean by interctions between the components of the vertically-structured pelagic ecosystem of the photic zone. Chlorophyll profiles are not a simple indicator of autotrophic biomass or production, because of non-linearities in the physiology of cells and preferential vertical distribution of taxa. Profiles of numbers or biomass of heterotrophs do not correspond with profiles of consumption, because of depth-selection (taxa, seasons) for reasons unconnected with feeding. Depths of highest plant biomass, chlorophyll and growth rate coincide when these depths are shallow, but become progressively separated in profiles where they are deeper - so that highest growth rate lies progressively shallower than the chloropyll maximum. It is still uncertain how plant biomass is distributed in deep profiles. Depths of greatest heterotroph biomass (mesozooplankton) are usually close to depths of fastest plant growth rate, and thus lie shallower than the chlorophyll maximum in profiles where this itself is deep. This correlation is functional, and relates to the role of heterotrophs in excreting metabolic wastes (especially ammonia), which may fuel a significant component of integrated algal production, especially in the oligotrophic ocean. Some, but not all faecal material from mesozooplankton of the photic zone appears in vertical flux below the pycnocine, depending on the size of the source organisms, and the degree of vertical mixing above the pycnocline. Diel, but probably not seasonal, vertical migration is significant in the vertical flux of dissolved nitrogen. Regional generalisations of the vertical relations of the main components of the ‘biological pump’ now appear within reach, and an approach is suggested.

  12. On the Creation of An Urban Boundary Layer Product Using The Radar Wind Profiler of the New York City Meteorological Network

    NASA Astrophysics Data System (ADS)

    Dempsey, M. J.; Booth, J.; Arend, M.; Melecio-Vazquez, D.

    2016-12-01

    The radar wind profiler (RWP) located on the Liberty Science Center in Jersey City, NJ is a part of the New York City Meteorological Network (NYCMetNet). An automatic algorithm based on those by Angevine [1] and Molod [2] is expanded upon and implemented to take RWP signal to noise ratio data and create an urban boundary layer (UBL) height product. Time series of the RWP UBL heights from clear and cloudy days are examined and compared to UBL height time series calculated from thermal data obtained from a NYCMetNet radiometer located on the roof of the Grove School of Engineering at The City College of New York. UBL data from the RWP are also compared to the MERRA (Modern Era Retrospective Analysis for Research and Applications) planetary boundary layer height time series product. A limited seasonal climatology is created from the available RWP data for clear and cloudy days and then compared to a limited seasonal climatology produced from boundary layer data obtained from MERRA and boundary layer data calculated from the CCNY radiometer. As with wind profilers in the NOAA wind profiler network, the signal return to the lowest range gates is not always the result of turbulent scattering, but from scattering from other targets such as the building itself, birds and insects. The algorithm attempts to address this during the daytime, when strong signal returns at the lowest range gates mask the SNR maxima above which are representative of the actual UBL height. Detecting the collapse and fall of the boundary layer meets with limited success, also, from the hours of 2:30pm to 5:00pm. Upper and lower range gates from the wind profiler limit observation of the nighttime boundary layer for heights falling below the lowest range gate and daytime convective boundary layer maxima rising above the highest. Due to the constraints of the instrument and the algorithm it is recommended that the boundary layer height product be constrained to the hours of 8am to 7pm.

  13. Targeted lipidomics analysis identified altered serum lipid profiles in patients with polymyositis and dermatomyositis.

    PubMed

    Raouf, Joan; Idborg, Helena; Englund, Petter; Alexanderson, Helene; Dastmalchi, Maryam; Jakobsson, Per-Johan; Lundberg, Ingrid E; Korotkova, Marina

    2018-05-02

    Polymyositis (PM) and dermatomyositis (DM) are severe chronic autoimmune diseases, characterized by muscle fatigue and low muscle endurance. Conventional treatment includes high doses of glucocorticoids and immunosuppressive drugs; however, few patients recover full muscle function. One explanation of the persistent muscle weakness could be altered lipid metabolism in PM/DM muscle tissue as we previously reported. Using a targeted lipidomic approach we aimed to characterize serum lipid profiles in patients with PM/DM compared to healthy individuals (HI) in a cross-sectional study. Also, in the longitudinal study we compared serum lipid profiles in patients newly diagnosed with PM/DM before and after immunosuppressive treatment. Lipidomic profiles were analyzed in serum samples from 13 patients with PM/DM, 12 HI and 8 patients newly diagnosed with PM/DM before and after conventional immunosuppressive treatment using liquid chromatography tandem mass spectrometry (LC-MS/MS) and a gas-chromatography flame ionization detector (GC-FID). Functional Index (FI), as a test of muscle performance and serum levels of creatine kinase (s-CK) as a proxy for disease activity were analyzed. The fatty acid (FA) composition of total serum lipids was altered in patients with PM/DM compared to HI; the levels of palmitic (16:0) acid were significantly higher while the levels of arachidonic (20:4, n-6) acid were significantly lower in patients with PM/DM. The profiles of serum phosphatidylcholine and triacylglycerol species were changed in patients with PM/DM compared to HI, suggesting disproportionate levels of saturated and polyunsaturated FAs that might have negative effects on muscle performance. After immunosuppressive treatment the total serum lipid levels of eicosadienoic (20:2, n-6) and eicosapentaenoic (20:5, n-3) acids were increased and serum phospholipid profiles were altered in patients with PM/DM. The correlation between FI or s-CK and levels of several lipid species

  14. Fixed-target hadron production experiments

    NASA Astrophysics Data System (ADS)

    Popov, Boris A.

    2015-08-01

    Results from fixed-target hadroproduction experiments (HARP, MIPP, NA49 and NA61/SHINE) as well as their implications for cosmic ray and neutrino physics are reviewed. HARP measurements have been used for predictions of neutrino beams in K2K and MiniBooNE/SciBooNE experiments and are also being used to improve predictions of the muon yields in EAS and of the atmospheric neutrino fluxes as well as to help in the optimization of neutrino factory and super-beam designs. Recent measurements released by the NA61/SHINE experiment are of significant importance for a precise prediction of the J-PARC neutrino beam used for the T2K experiment and for interpretation of EAS data. These hadroproduction experiments provide also a large amount of input for validation and tuning of hadron production models in Monte-Carlo generators.

  15. Production of Y-86 and other radiometals for research purposes using a solution target system.

    PubMed

    Oehlke, Elisabeth; Hoehr, Cornelia; Hou, Xinchi; Hanemaayer, Victoire; Zeisler, Stefan; Adam, Michael J; Ruth, Thomas J; Celler, Anna; Buckley, Ken; Benard, Francois; Schaffer, Paul

    2015-11-01

    Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of (89)Zr, (68)Ga and for the first time (86)Y are discussed. Aqueous solutions containing 1.35-1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, (89)Zr (Asat = 360 MBq/μA and yield = 3.17 MBq/μA), (86)Y (Asat = 31 MBq/μA and yield = 1.44 MBq/μA), and (68)Ga (Asat = 141 MBq/μA and yield = 64 MBq/μA) from one hour long irradiations on a typical medical cyclotron. (68)Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, (68)Ga and (86)Y were successfully used to radiolabel DOTA-based chelators while deferoxamine was used to coordinate

  16. SIMULATED PERFORMANCE OF THE PRODUCTION TARGET FOR THE MUON G-2 EXPERIMENT

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

    Stratakis, D.; Convery, M.; Morgan, J. P.

    The Muon g-2 Experiment plans to use the Fermilab Re-cycler Ring for forming the proton bunches that hit its pro-duction target. The proposed scheme uses one RF system, 80 kV of 2.5 MHz RF. In order to avoid bunch rotations in a mismatched bucket, the 2.5 MHz is ramped adiabatically from 3 to 80 kV in 90 ms. In this study, the interaction of the primary proton beam with the production target for the Muon g-2 Experiment is numerically examined.

  17. Profiling structured product labeling with NDF-RT and RxNorm

    PubMed Central

    2012-01-01

    Background Structured Product Labeling (SPL) is a document markup standard approved by Health Level Seven (HL7) and adopted by United States Food and Drug Administration (FDA) as a mechanism for exchanging drug product information. The SPL drug labels contain rich information about FDA approved clinical drugs. However, the lack of linkage to standard drug ontologies hinders their meaningful use. NDF-RT (National Drug File Reference Terminology) and NLM RxNorm as standard drug ontology were used to standardize and profile the product labels. Methods In this paper, we present a framework that intends to map SPL drug labels with existing drug ontologies: NDF-RT and RxNorm. We also applied existing categorical annotations from the drug ontologies to classify SPL drug labels into corresponding classes. We established the classification and relevant linkage for SPL drug labels using the following three approaches. First, we retrieved NDF-RT categorical information from the External Pharmacologic Class (EPC) indexing SPLs. Second, we used the RxNorm and NDF-RT mappings to classify and link SPLs with NDF-RT categories. Third, we profiled SPLs using RxNorm term type information. In the implementation process, we employed a Semantic Web technology framework, in which we stored the data sets from NDF-RT and SPLs into a RDF triple store, and executed SPARQL queries to retrieve data from customized SPARQL endpoints. Meanwhile, we imported RxNorm data into MySQL relational database. Results In total, 96.0% SPL drug labels were mapped with NDF-RT categories whereas 97.0% SPL drug labels are linked to RxNorm codes. We found that the majority of SPL drug labels are mapped to chemical ingredient concepts in both drug ontologies whereas a relatively small portion of SPL drug labels are mapped to clinical drug concepts. Conclusions The profiling outcomes produced by this study would provide useful insights on meaningful use of FDA SPL drug labels in clinical applications through

  18. Profiling structured product labeling with NDF-RT and RxNorm.

    PubMed

    Zhu, Qian; Jiang, Guoqian; Chute, Christopher G

    2012-12-20

    Structured Product Labeling (SPL) is a document markup standard approved by Health Level Seven (HL7) and adopted by United States Food and Drug Administration (FDA) as a mechanism for exchanging drug product information. The SPL drug labels contain rich information about FDA approved clinical drugs. However, the lack of linkage to standard drug ontologies hinders their meaningful use. NDF-RT (National Drug File Reference Terminology) and NLM RxNorm as standard drug ontology were used to standardize and profile the product labels. In this paper, we present a framework that intends to map SPL drug labels with existing drug ontologies: NDF-RT and RxNorm. We also applied existing categorical annotations from the drug ontologies to classify SPL drug labels into corresponding classes. We established the classification and relevant linkage for SPL drug labels using the following three approaches. First, we retrieved NDF-RT categorical information from the External Pharmacologic Class (EPC) indexing SPLs. Second, we used the RxNorm and NDF-RT mappings to classify and link SPLs with NDF-RT categories. Third, we profiled SPLs using RxNorm term type information. In the implementation process, we employed a Semantic Web technology framework, in which we stored the data sets from NDF-RT and SPLs into a RDF triple store, and executed SPARQL queries to retrieve data from customized SPARQL endpoints. Meanwhile, we imported RxNorm data into MySQL relational database. In total, 96.0% SPL drug labels were mapped with NDF-RT categories whereas 97.0% SPL drug labels are linked to RxNorm codes. We found that the majority of SPL drug labels are mapped to chemical ingredient concepts in both drug ontologies whereas a relatively small portion of SPL drug labels are mapped to clinical drug concepts. The profiling outcomes produced by this study would provide useful insights on meaningful use of FDA SPL drug labels in clinical applications through standard drug ontologies such as NDF-RT and

  19. Neutron-rich isotope production using the uranium carbide multi-foil SPES target prototype

    NASA Astrophysics Data System (ADS)

    Scarpa, D.; Biasetto, L.; Corradetti, S.; Manzolaro, M.; Andrighetto, A.; Carturan, S.; Prete, G.; Zanonato, P.; Stracener, D. W.

    2011-03-01

    In the framework of the R&D program for the SPES (Selective Production of Exotic Species) project of the Istituto Nazionale di Fisica Nucleare (INFN), production yields of neutron-rich isotopes have been measured at the Holifield Radioactive Ion Beam Facility (HRIBF, Oak Ridge National Laboratory, USA). This experiment makes use of the multi-foil SPES target prototype composed of 7 uranium carbide discs, with excess of graphite (ratio C/ U = 4 . 77 isotopes of medium mass (between 72 and 141amu), produced via proton-induced fission of uranium using a 40MeV proton beam, have been collected and analyzed for the target heated at 2000 ° C target temperature.

  20. Creating targeted initial populations for genetic product searches in heterogeneous markets

    NASA Astrophysics Data System (ADS)

    Foster, Garrett; Turner, Callaway; Ferguson, Scott; Donndelinger, Joseph

    2014-12-01

    Genetic searches often use randomly generated initial populations to maximize diversity and enable a thorough sampling of the design space. While many of these initial configurations perform poorly, the trade-off between population diversity and solution quality is typically acceptable for small-scale problems. Navigating complex design spaces, however, often requires computationally intelligent approaches that improve solution quality. This article draws on research advances in market-based product design and heuristic optimization to strategically construct 'targeted' initial populations. Targeted initial designs are created using respondent-level part-worths estimated from discrete choice models. These designs are then integrated into a traditional genetic search. Two case study problems of differing complexity are presented to illustrate the benefits of this approach. In both problems, targeted populations lead to computational savings and product configurations with improved market share of preferences. Future research efforts to tailor this approach and extend it towards multiple objectives are also discussed.

  1. System-level multi-target drug discovery from natural products with applications to cardiovascular diseases.

    PubMed

    Zheng, Chunli; Wang, Jinan; Liu, Jianling; Pei, Mengjie; Huang, Chao; Wang, Yonghua

    2014-08-01

    The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug-target and target-target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.

  2. Secondary neutron-production cross sections from heavy-ion interactions in composite targets

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

    Heilbronn, L.; Iwata, Y.; Murakami, T.

    Secondary neutron-production cross sections have been measured from interactions of 290 MeV/nucleon C and 600 MeV/nucleon Ne in a target composed of simulated Martian regolith and polyethylene, and from 400 MeV/nucleon Ne interactions in wall material from the International Space Station. The data were measured between 5 deg. and 80 deg. in the laboratory. We report the double-differential cross sections, angular distributions, and total neutron-production cross sections from all three systems. The spectra from all three systems exhibit behavior previously reported in other heavy-ion neutron-production experiments, namely, a peak at forward angles near the energy corresponding to the beam velocity,more » with the remaining spectra generated by pre-equilibrium and equilibrium processes. The double-differential cross sections are fitted with a moving-source parametrization. Also reported are the data without corrections for neutron flux attenuation in the target and other intervening materials and for neutron production in nontarget materials near the target position. These uncorrected spectra are compared with SHIELD-HIT and PHITS transport model calculations. The transport model calculations reproduce the spectral shapes well but, on average, underestimate the magnitudes of the cross sections.« less

  3. Neutron-rich isotope production using a uranium carbide - carbon nanotubes SPES target prototype

    NASA Astrophysics Data System (ADS)

    Corradetti, S.; Biasetto, L.; Manzolaro, M.; Scarpa, D.; Carturan, S.; Andrighetto, A.; Prete, G.; Vasquez, J.; Zanonato, P.; Colombo, P.; Jost, C. U.; Stracener, D. W.

    2013-05-01

    The SPES (Selective Production of Exotic Species) project, under development at the Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro (INFN-LNL), is a new-generation Isotope Separation On-Line (ISOL) facility for the production of radioactive ion beams by means of the proton-induced fission of uranium. In the framework of the research on the SPES target, seven uranium carbide discs, obtained by reacting uranium oxide with graphite and carbon nanotubes, were irradiated with protons at the Holifield Radioactive Ion Beam Facility (HRIBF) of Oak Ridge National Laboratory (ORNL). In the following, the yields of several fission products obtained during the experiment are presented and discussed. The experimental results are then compared to those obtained using a standard uranium carbide target. The reported data highlights the capability of the new type of SPES target to produce and release isotopes of interest for the nuclear physics community.

  4. Differential global profiling as a new analytical strategy for revealing micropollutant treatment by-products: application to ethinylestradiol and chlorination water treatment.

    PubMed

    Gervais, Gaël; Bichon, Emmanuelle; Antignac, Jean-Philippe; Monteau, Fabrice; Leroy, Gaëla; Barritaud, Lauriane; Chachignon, Mathilde; Ingrand, Valérie; Roche, Pascal; Le Bizec, Bruno

    2011-06-01

    The detection and structural elucidation of micropollutants treatment by-products are major issues to estimate efficiencies of the processes employed for drinking water production versus endocrine disruptive compounds contamination. This issue was mainly investigated at the laboratory scale and in high concentration conditions. However, potential by-products generated after chlorination can be influenced by the dilution factor employed in real conditions. The present study proposes a new methodology borrowed to the metabolomic science, using liquid chromatography coupled to high-resolution mass spectrometry, in order to reveal potential chlorination by-products of ethinylestradiol in spiked real water samples at the part-per-billion level (5 μg L(-1)). Conventional targeted measurements first demonstrated that chlorination with sodium hypochlorite (0.8 mg L(-1)) led to removals of ethinylestradiol over 97%. Then, the developed differential global profiling approach permitted to reveal eight chlorination by-products of EE2, six of them being described for the first time. Among these eight halogenated compounds, five have been structurally identified, demonstrating the potential capabilities of this new methodology applied to environmental samples. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. A novel approach to transforming a non-targeted metabolic profiling method to a pseudo-targeted method using the retention time locking gas chromatography/mass spectrometry-selected ions monitoring.

    PubMed

    Li, Yong; Ruan, Qiang; Li, Yanli; Ye, Guozhu; Lu, Xin; Lin, Xiaohui; Xu, Guowang

    2012-09-14

    Non-targeted metabolic profiling is the most widely used method for metabolomics. In this paper, a novel approach was established to transform a non-targeted metabolic profiling method to a pseudo-targeted method using the retention time locking gas chromatography/mass spectrometry-selected ion monitoring (RTL-GC/MS-SIM). To achieve this transformation, an algorithm based on the automated mass spectral deconvolution and identification system (AMDIS), GC/MS raw data and a bi-Gaussian chromatographic peak model was developed. The established GC/MS-SIM method was compared with GC/MS-full scan (the total ion current and extracted ion current, TIC and EIC) methods, it was found that for a typical tobacco leaf extract, 93% components had their relative standard deviations (RSDs) of relative peak areas less than 20% by the SIM method, while 88% by the EIC method and 81% by the TIC method. 47.3% components had their linear correlation coefficient higher than 0.99, compared with 5.0% by the EIC and 6.2% by TIC methods. Multivariate analysis showed the pooled quality control samples clustered more tightly using the developed method than using GC/MS-full scan methods, indicating a better data quality. With the analysis of the variance of the tobacco samples from three different planting regions, 167 differential components (p<0.05) were screened out using the RTL-GC/MS-SIM method, but 151 and 131 by the EIC and TIC methods, respectively. The results show that the developed method not only has a higher sensitivity, better linearity and data quality, but also does not need complicated peak alignment among different samples. It is especially suitable for the screening of differential components in the metabolic profiling investigation. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Vending Machines of Food and Beverages and Nutritional Profile of their Products at Schools in Madrid, Spain, 2014-2015.

    PubMed

    Monroy-Parada, Doris Xiomara; Ángeles Moya, María; José Bosqued, María; López, Lázaro; Rodríguez-Artalejo, Fernando; Royo-Bordonada, Miguel Ángel

    2016-06-09

    Policies restricting access to sugary drinks and unhealthy foods in the school environment are associated with healthier consumption patterns. In 2010, Spain approved a Consensus Document regarding Food at Schools with nutritional criteria to improve the nutritional profile of foods and drinks served at schools. The objective of this study was to describe the frequency of food and drink vending machines at secondary schools in Madrid, the products offered at them and their nutritional profile. Cross-sectional study of a random sample of 330 secondary schools in Madrid in 2014-2015. The characteristics of the schools and the existence of vending machines were recorded through the internet and by telephone interview. The products offered in a representative sample of 6 vending machines were identified by in situ inspection, and its nutritional composition was taken from its labeling. Finally, the nutritional profile of each product was analyzed with the United Kingdom profile model, which classifies products as healthy and less healthy. The prevalence of vending machines was 17.3%. Among the products offered, 80.5% were less healthy food and drinks (high in energy, fat or sugar and poor in nutrients) and 10.5% were healthy products. Vending machines are common at secondary schools in Madrid. Most products are vending machines are still less healthy.

  7. Scale-up of high specific activity 186gRe production using graphite-encased thick 186W targets and demonstration of an efficient target recycling process

    DOE PAGES

    Balkin, Ethan R.; Gagnon, Katherine; Dorman, Eric; ...

    2017-08-18

    Production of high specific activity 186gRe is of interest for development of theranostic radiopharmaceuticals. Previous studies have shown that high specific activity 186gRe can be obtained by cyclotron irradiation of enriched 186W via the 186W(d,2n) 186gRe reaction, but most irradiations were conducted at low beam currents and for short durations. In this paper, enriched 186W metal targets were irradiated at high incident deuteron beam currents to demonstrate production rates and contaminants produced when using thick targets. Full-stopping thick targets, as determined using SRIM, were prepared by uniaxial pressing of powdered natural abundance W metal or 96.86% enriched 186W metal encasedmore » between two layers of graphite flakes for target material stabilization. An assessment of structural integrity was made on each target preparation. To assess the performance of graphite-encased thick 186W metal targets, along with the impact of encasing on the separation chemistry, targets were first irradiated using a 22 MeV deuteron beam for 10 min at 10, 20, and 27 μA, with an estimated nominal deuteron energy of 18.7 MeV on the 186W target material (after energy degradation correction from top graphite layer). Gamma-ray spectrometry was performed post EOB on all targets to assess production yields and radionuclidic byproducts. The investigation also evaluated a method to recover and recycle enriched target material from a column isolation procedure. Material composition analyses of target materials, pass-through/wash solutions and recycling process isolates were conducted with SEM, FTIR, XRD, EDS and ICP-MS spectrometry. Finally, to demonstrate scaled-up production, a graphite-encased 186W target made from recycled 186W was irradiated for ~2 h with 18.7 MeV deuterons at a beam current of 27 μA to provide 0.90 GBq (24.3 mCi) of 186gRe, decay-corrected to the end of bombardment. ICP-MS analysis of the isolated 186gRe solution provided data that indicated the

  8. Scale-up of high specific activity 186gRe production using graphite-encased thick 186W targets and demonstration of an efficient target recycling process

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

    Balkin, Ethan R.; Gagnon, Katherine; Dorman, Eric

    Production of high specific activity 186gRe is of interest for development of theranostic radiopharmaceuticals. Previous studies have shown that high specific activity 186gRe can be obtained by cyclotron irradiation of enriched 186W via the 186W(d,2n) 186gRe reaction, but most irradiations were conducted at low beam currents and for short durations. In this paper, enriched 186W metal targets were irradiated at high incident deuteron beam currents to demonstrate production rates and contaminants produced when using thick targets. Full-stopping thick targets, as determined using SRIM, were prepared by uniaxial pressing of powdered natural abundance W metal or 96.86% enriched 186W metal encasedmore » between two layers of graphite flakes for target material stabilization. An assessment of structural integrity was made on each target preparation. To assess the performance of graphite-encased thick 186W metal targets, along with the impact of encasing on the separation chemistry, targets were first irradiated using a 22 MeV deuteron beam for 10 min at 10, 20, and 27 μA, with an estimated nominal deuteron energy of 18.7 MeV on the 186W target material (after energy degradation correction from top graphite layer). Gamma-ray spectrometry was performed post EOB on all targets to assess production yields and radionuclidic byproducts. The investigation also evaluated a method to recover and recycle enriched target material from a column isolation procedure. Material composition analyses of target materials, pass-through/wash solutions and recycling process isolates were conducted with SEM, FTIR, XRD, EDS and ICP-MS spectrometry. Finally, to demonstrate scaled-up production, a graphite-encased 186W target made from recycled 186W was irradiated for ~2 h with 18.7 MeV deuterons at a beam current of 27 μA to provide 0.90 GBq (24.3 mCi) of 186gRe, decay-corrected to the end of bombardment. ICP-MS analysis of the isolated 186gRe solution provided data that indicated the

  9. No cost-saving target too small for this hospital's product reengineering program.

    PubMed

    1998-02-01

    It pays to put every product purchase under the microscope. By creating a multidisciplinary value analysis committee to review staff ideas on potential savings for products, as well as internal services and processes, this New Jersey health care provider is slashing costs and standardizing products across clinical service lines. Learn how the committee operates and what it's doing to get vital employee participation, plus read about specific products targeted for cost reduction.

  10. Perspective of Muon Production Target at J-PARC MLF MUSE

    NASA Astrophysics Data System (ADS)

    Makimura, Shunsuke; Matoba, Shiro; Kawamura, Naritoshi; Matsuzawa, Yukihiro; Tabe, Masato; Aoyagi, Hiroyuki; Kondo, Hiroto; Kobayashi, Yasuo; Fujimori, Hiroshi; Ikedo, Yutaka; Kadono, Ryosuke; Koda, Akihiro; Kojima, Kenji M.; Miyake, Yasuhiro; Nakamura, Jumpei G.; Oishi, Yu; Okabe, Hirotaka; Shimomura, Koichiro; Strasser, Patrick

    A pulsed muon beam with unprecedented intensity will be generated by a 3-GeV 333-microA proton beam on a muon target made of 20-mm thick isotropic graphite at J-PARC MLF MUSE (Muon Science Establishment). The first muon beam was successfully generated on September 26th, 2008. Gradually upgrading the beam intensity, continuous 300-kW proton beam has been operated by a fixed target method without replacements till June of 2014. However, the lifetime of the fixed target was anticipated to be less than 1 year by the proton-irradiation damage of the graphite through 1-MW beam operation. To extend the lifetime, a muon rotating target, in which the radiation damage is distributed to a wider area, was installed in September of 2014, and continuous and stable operation has been successfully performed. Because the muon target becomes highly radioactive by the proton irradiation, the maintenance is conducted by remote handling in the Hot cell. In September of 2015, a scraper No. 1 to collimate the proton beam scattered by the target was replaced for further high-power beam operation. Recently, new developments on monitoring and maintenance of the muon target for higher power operation are in progress. In this article, perspective of muon production target at J-PARC MLF MUSE will be described.

  11. Research and application of online measurement system of tire tread profile in automobile tire production

    NASA Astrophysics Data System (ADS)

    Wang, Pengyao; Chen, Xiangguang; Yang, Kai; Liu, Xuejiao

    2017-01-01

    To improve the measuring efficiency of width and thickness of tire tread in the process of automobile tire production, the actual condition for the tire production process is analyzed, and a fast online measurement system based on moving tire tread of tire specifications is established in this paper. The coordinate data of tire tread profile is acquired by 3D laser sensor, and we use C# language for programming which is an object-oriented programming language to complete the development of client program. The system with laser sensor can provide real-time display of tire tread profile and the data to require in the process of tire production. Experimental results demonstrate that the measuring precision of the system is <= 1mm, it can meet the measurement requirements of the production process, and the system has the characteristics of convenient installation and testing, system stable operation.

  12. Pavement profile viewer and analyzer : product brief.

    DOT National Transportation Integrated Search

    2003-06-01

    Pavement Profile Viewer and Analyzer, or ProVAL, is a software package that imports, displays, and analyzes the characteristics of pavement profiles from many different sources. ProVAL can analyze pavement profiles using several methods, including In...

  13. Preliminary investigations on the use of uranium silicide targets for fission Mo-99 production

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

    Cols, H.; Cristini, P.; Marques, R.

    1997-08-01

    The National Atomic Energy Commission (CNEA) of Argentine Republic owns and operates an installation for production of molybdenum-99 from fission products since 1985, and, since 1991, covers the whole national demand of this nuclide, carrying out a program of weekly productions, achieving an average activity of 13 terabecquerel per week. At present they are finishing an enlargement of the production plant that will allow an increase in the volume of production to about one hundred of terabecquerel. Irradiation targets are uranium/aluminium alloy with 90% enriched uranium with aluminium cladding. In view of international trends held at present for replacing highmore » enrichment uranium (HEU) for enrichment values lower than 20 % (LEU), since 1990 the authors are in contact with the RERTR program, beginning with tests to adapt their separation process to new irradiation target conditions. Uranium silicide (U{sub 3}Si{sub 2}) was chosen as the testing material, because it has an uranium mass per volume unit, so that it allows to reduce enrichment to a value of 20%. CNEA has the technology for manufacturing miniplates of uranium silicide for their purposes. In this way, equivalent amounts of Molybdenum-99 could be obtained with no substantial changes in target parameters and irradiation conditions established for the current process with Al/U alloy. This paper shows results achieved on the use of this new target.« less

  14. An effective identification and quantification method for Ginkgo biloba flavonol glycosides with targeted evaluation of adulterated products.

    PubMed

    Ma, Yuan-Chun; Mani, Ana; Cai, Yaling; Thomson, Jaclyn; Ma, Jie; Peudru, Flavie; Chen, Sarah; Luo, Mai; Zhang, Junzeng; Chapman, Robert G; Shi, Zhen-Tuo

    2016-04-15

    Ginkgo biloba L. (Ginkgoaceae) leaf extract is one of the most popular herbal products on the market, as it contains flavone glycosides (≥ 24%) and terpene lactones (≥ 6%), which are proposed to have significant physiological effects. Unfortunately, the challenging financial climate has resulted in a natural health product market containing adulterated ginkgo products. 42 ginkgo samples were analyzed to establish an HPLC profile for authentic ginkgo and common ginkgo adulterants, and to develop a method capable of easily detecting adulteration in ginkgo commercial products. In this study an efficient and targeted HPLC analysis method was established that is capable of distinguishing flavonol glycosides and aglycones simultaneously for the evaluation of ginkgo powdered extracts (PEs) and finished products in a single, 13 min run. Thirteen ginkgo leaf samples, fifteen standardized powdered extracts, and fourteen commercially available ginkgo products have been analyzed using this new HPLC method. Chromatograms were compared to six standard reference materials: one flavonol glycoside (rutin), three aglycones (quercetin, kaempferol and isorhamnetin), and two isoflavones (genestin and genistein). The quantitative chromatographic data was interpreted by principal component analysis (PCA), which assisted in the detection of unexpected chromatographic features in various adulterated botanical products. Only three of the commercially available ginkgo finished products tested in this study were determined to be authentic, with flavonol glycoside rutin, and aglycones quercetin, kaempferol, and isorhamnetin found to be common adulterants in the ginkgo powdered extract and finished product samples. Despite evidence of adulteration in most of the samples, each of the samples discussed herein met most of the current pharmacopeial standards. It is therefore critical that a preliminary evaluation be utilized to detect adulteration in commercial ginkgo products, prior to the

  15. In situ imaging and proteome profiling indicate andrographolide is a highly promiscuous compound

    NASA Astrophysics Data System (ADS)

    Li, Lin; Wijaya, Hadhi; Samanta, Sanjay; Lam, Yulin; Yao, Shao Q.

    2015-06-01

    Natural products represent an enormous source of pharmacologically useful compounds, and are often used as the starting point in modern drug discovery. Many biologically interesting natural products are however not being pursued as potential drug candidates, partly due to a lack of well-defined mechanism-of-action. Traditional in vitro methods for target identification of natural products based on affinity protein enrichment from crude cellular lysates cannot faithfully recapitulate protein-drug interactions in living cells. Reported herein are dual-purpose probes inspired by the natural product andrographolide, capable of both reaction-based, real-time bioimaging and in situ proteome profiling/target identification in live mammalian cells. Our results confirm that andrographolide is a highly promiscuous compound and engaged in covalent interactions with numerous previously unknown cellular targets in cell type-specific manner. We caution its potential therapeutic effects should be further investigated in detail.

  16. Performance evaluation of non-targeted peak-based cross-sample analysis for comprehensive two-dimensional gas chromatography-mass spectrometry data and application to processed hazelnut profiling.

    PubMed

    Kiefl, Johannes; Cordero, Chiara; Nicolotti, Luca; Schieberle, Peter; Reichenbach, Stephen E; Bicchi, Carlo

    2012-06-22

    The continuous interest in non-targeted profiling induced the development of tools for automated cross-sample analysis. Such tools were found to be selective or not comprehensive thus delivering a biased view on the qualitative/quantitative peak distribution across 2D sample chromatograms. Therefore, the performance of non-targeted approaches needs to be critically evaluated. This study focused on the development of a validation procedure for non-targeted, peak-based, GC×GC-MS data profiling. The procedure introduced performance parameters such as specificity, precision, accuracy, and uncertainty for a profiling method known as Comprehensive Template Matching. The performance was assessed by applying a three-week validation protocol based on CITAC/EURACHEM guidelines. Optimized ¹D and ²D retention times search windows, MS match factor threshold, detection threshold, and template threshold were evolved from two training sets by a semi-automated learning process. The effectiveness of proposed settings to consistently match 2D peak patterns was established by evaluating the rate of mismatched peaks and was expressed in terms of results accuracy. The study utilized 23 different 2D peak patterns providing the chemical fingerprints of raw and roasted hazelnuts (Corylus avellana L.) from different geographical origins, of diverse varieties and different roasting degrees. The validation results show that non-targeted peak-based profiling can be reliable with error rates lower than 10% independent of the degree of analytical variance. The optimized Comprehensive Template Matching procedure was employed to study hazelnut roasting profiles and in particular to find marker compounds strongly dependent on the thermal treatment, and to establish the correlation of potential marker compounds to geographical origin and variety/cultivar and finally to reveal the characteristic release of aroma active compounds. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Volatile profile, lipid oxidation and protein oxidation of irradiated ready-to-eat cured turkey meat products

    NASA Astrophysics Data System (ADS)

    Feng, Xi; Ahn, Dong Uk

    2016-10-01

    Irradiation had little effects on the thiobarbituric acid reactive substances (TBARS) values in ready-to-eat (RTE) turkey meat products, while it increased protein oxidation at 4.5 kGy. The volatile profile analyses indicated that the amount of sulfur compounds increased linearly as doses increased in RTE turkey meat products. By correlation analysis, a positive correlation was found between benzene/ benzene derivatives and alcohols with lipid oxidation, while aldehydes, ketones and alkane, alkenes and alkynes were positively correlated with protein oxidation. Principle component analysis showed that irradiated meat samples can be discriminated by two categories of volatile compounds: Strecker degradation products and radiolytic degradation products. The cluster analysis of volatile data demonstrated that low-dose irradiation had minor effects on the volatile profile of turkey sausages (<1.5 kGy). However, as the doses increased, the differences between the irradiated and non-irradiated cured turkey products became significant.

  18. Specificity in the interaction of natural products with their target proteins--a biochemical and structural insight.

    PubMed

    Venkatraman, Prasanna

    2010-06-01

    Natural products are an abundant source of anti cancer agents. They act as cytotoxic drugs, and inhibitors of apoptosis, transcription, cell proliferation and angiogenesis. While pathways targeted by natural products have been well studied, there is paucity of information about the in vivo molecular target/s of these compounds. This review summarizes some of the natural compounds for which the molecular targets, mechanism of action and structural basis of specificity have been well documented. These examples illustrate that 'off target' binding can be explained on the basis of diversity inherent to biomolecular interactions. There is enough evidence to suggest that natural compounds are potent and versatile warheads that can be optimized for a multi targeted therapeutic intervention in cancer.

  19. GEANT4 simulation of cyclotron radioisotope production in a solid target.

    PubMed

    Poignant, F; Penfold, S; Asp, J; Takhar, P; Jackson, P

    2016-05-01

    The use of radioisotopes in nuclear medicine is essential for diagnosing and treating cancer. The optimization of their production is a key factor in maximizing the production yield and minimizing the associated costs. An efficient approach to this problem is the use of Monte Carlo simulations prior to experimentation. By predicting isotopes yields, one can study the isotope of interest expected activity for different energy ranges. One can also study the target contamination with other radioisotopes, especially undesired radioisotopes of the wanted chemical element which are difficult to separate from the irradiated target and might result in increasing the dose when delivering the radiopharmaceutical product to the patient. The aim of this work is to build and validate a Monte Carlo simulation platform using the GEANT4 toolkit to model the solid target system of the South Australian Health and Medical Research Institute (SAHMRI) GE Healthcare PETtrace cyclotron. It includes a GEANT4 Graphical User Interface (GUI) where the user can modify simulation parameters such as the energy, shape and current of the proton beam, the target geometry and material, the foil geometry and material and the time of irradiation. The paper describes the simulation and presents a comparison of simulated and experimental/theoretical yields for various nuclear reactions on an enriched nickel 64 target using the GEANT4 physics model QGSP_BIC_AllHP, a model recently developed to evaluate with high precision the interaction of protons with energies below 200MeV available in Geant4 version 10.1. The simulation yield of the (64)Ni(p,n)(64)Cu reaction was found to be 7.67±0.074 mCi·μA(-1) for a target energy range of 9-12MeV. Szelecsenyi et al. (1993) gives a theoretical yield of 6.71mCi·μA(-1) and an experimental yield of 6.38mCi·μA(-1). The (64)Ni(p,n)(64)Cu cross section obtained with the simulation was also verified against the yield predicted from the nuclear database TENDL and

  20. Formulation Effects and the Off-target Transport of Pyrethroid Insecticides from Urban Hard Surfaces

    PubMed Central

    Jorgenson, Brant C.; Young, Thomas M.

    2010-01-01

    Controlled rainfall experiments utilizing drop forming rainfall simulators were conducted to study various factors contributing to off-target transport of off-the-shelf formulated pyrethroid insecticides from concrete surfaces. Factors evaluated included active ingredient, product formulation, time between application and rainfall (set time), and rainfall intensity. As much as 60% and as little as 0.8% of pyrethroid applied could be recovered in surface runoff depending primarily on product formulation, and to a lesser extent on product set time. Resulting wash-off profiles during one-hour storm simulations could be categorized based on formulation, with formulations utilizing emulsifying surfactants rather than organic solvents resulting in unique wash-off profiles with overall higher wash-off efficiency. These higher wash-off efficiency profiles were qualitatively replicated by applying formulation-free neat pyrethroid in the presence of independently applied linear alkyl benzene sulfonate (LAS) surfactant, suggesting that the surfactant component of some formulated products may be influential in pyrethroid wash-off from urban hard surfaces. PMID:20524665

  1. Formulation and evaluation of a montelukast sodium orally disintegrating tablet with a similar dissolution profile as the marketed product.

    PubMed

    Chen, Yong; Feng, Tingting; Li, Yong; Du, Bin; Weng, Weiyu

    2017-03-01

    A major challenge of orally disintegrating tablet (ODT) development is predicting its bioequivalence to its corresponding marketed product. Therefore, comparing ODT dissolution profiles to those of the corresponding marketed product is very important. The objective of this study was to develop a 5.2-mg montelukast sodium (MS) ODT with a similar dissolution profile to that of the marketed chewable tablet. Dissolution profiles were examined in different media to screen each formulation. We found that MS dissolution from ODTs in acidic medium heavily depended on manufacturing methods. All MS ODTs prepared using direct compression rapidly disintegrated in acidic medium. However, dispersed MS powders aggregated into sticky masses, resulting in slow dissolution. In contrast, MS ODTs prepared using wet granulation had much faster dissolution rates in acidic medium with no obvious aggregation. Additionally, the optimized formulation, prepared using wet granulation, displayed similar dissolution profiles to the marketed reference in all four types of media examined (f 2  >   50). The in vitro disintegration time of the optimized ODT was 9.5 ± 2.4 s, which meets FDA requirements. In conclusion, the wet granulation preparation method of MS ODTs resulted in a product with equivalent dissolution profiles as those of the marketed product.

  2. Eliciting Production of L2 Target Structures through Priming Activities

    ERIC Educational Resources Information Center

    McDonough, Kim; Trofimovich, Pavel; Neumann, Heike

    2015-01-01

    This study focuses on the pedagogical applications of structural priming research in an English for academic purposes (EAP) context, investigating whether priming activities are an effective tool for eliciting production of target grammatical structures. University students across four EAP classes carried out a total of 6 information-exchange…

  3. Profile and scientific production of CNPq researchers in Nephrology and Urology.

    PubMed

    Oliveira, Eduardo A; Pécoits-Filho, Roberto; Quirino, Isabel G; Oliveira, Maria Christina; Martelli, Daniela Reis; Lima, Leonardo S; Martelli, Hercílio

    2011-03-01

    This study aimed at evaluating the profile and scientific production of researchers in Nephrology and Urology, receiving grants in the area of Clinical Medicine from the Brazilian National Research Council. The standardized online curriculum vitae (Curriculum Lattes) of 39 researchers in Medicine receiving grants in the 2006-2008 triennium were included in the analysis. The variables analyzed were: gender, affiliation, time from completion of the PhD program, scientific production, and supervision of undergraduate students, and master's and PhD programs. Males (74.4%) and category 2 grants (56.4%) predominated. The following three Brazilian states are responsible for 90% of the researchers: São Paulo (28; 71.8%); Rio Grande do Sul (4; 10.3%); and Minas Gerais (3; 7.7%). Four institutions are responsible for 70% of the researchers: UNIFESP (14; 36%); USP (8; 20.5%); UFMG (3, 7.7%); and UNICAMP (3; 7.7%). Considering the academic career, the assessed researchers published 3,195 articles in medical journals, with a median of 75 articles per researcher (QI = 52-100). The researchers received a total of 25,923 citations at the database Web of Science®, with a median of 452 citations per researcher (QI = 161-927). The average number of citations per article was 13.8 citations (SD = 11.6). The Southeastern region of Brazil concentrates researchers in Nephrology and Urology. Our study has shown an increase in the scientific production of most researchers in the last five years. By knowing the profile of researchers in Nephrology and Urology, more effective strategies to encourage the scientific production and the demand for resources to finance research projects can be defined.

  4. Label-free pharmacological profiling based on dynamic mass redistribution for characterization and authentication of hazardous natural products.

    PubMed

    Song, Hui-Peng; Wang, Hong; Zhao, Xiaoai; He, Ling; Zhong, Huailing; Wu, Si-Qi; Li, Ping; Yang, Hua

    2017-07-05

    Natural products are becoming increasingly popular in multiple fields involving medicines, foods and beverages. However, due to the frequent occurrence of poisoning incidents, their toxicity and safety have caused a serious concern. Here we report a method of biosensor-based two-phase pharmacological profiling (BTPP) for discovery, monitor and control of receptor-targeted natural products. BTPP uses a resonant waveguide grating biosensor for label-free and non-invasive detection of intracellular dynamic mass redistribution (DMR), a phenomenon caused by protein relocalization after receptors receiving stimulation from toxicants. The method can not only facilitate the identification of hazardous materials but also quantify their bioactivity by EC 50 . As a proof of concept, the method was successfully applied to recognize Daturae Flos (DF), an herb that can antagonize muscarinic acetylcholine M 2 receptor and further cause poisoning, from other easily confused species. BTPP combined with high performance liquid chromatography revealed that scopolamine and hyoscyamine in DF were the key marker compounds. Moreover, the method accurately picked out 2 M 2 receptor antagonists from 25 natural compounds, displaying its potential in high-throughput screening. This study provides a systematic illustration about the establishment, applicability and advantages of BTPP, which contributes to the safety assessment of natural products in related fields. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Chemical genetic profiling of the microtubule-targeting agent peloruside A in budding yeast Saccharomyces cerevisiae.

    PubMed

    Wilmes, Anja; Hanna, Reem; Heathcott, Rosemary W; Northcote, Peter T; Atkinson, Paul H; Bellows, David S; Miller, John H

    2012-04-15

    Peloruside A, a microtubule-stabilising agent from a New Zealand marine sponge, inhibits mammalian cell division by a similar mechanism to that of the anticancer drug paclitaxel. Wild type budding yeast Saccharomyces cerevisiae (haploid strain BY4741) showed growth sensitivity to peloruside A with an IC(50) of 35μM. Sensitivity was increased in a mad2Δ (Mitotic Arrest Deficient 2) deletion mutant (IC(50)=19μM). Mad2 is a component of the spindle-assembly checkpoint complex that delays the onset of anaphase in cells with defects in mitotic spindle assembly. Haploid mad2Δ cells were much less sensitive to paclitaxel than to peloruside A, possibly because the peloruside binding site on yeast tubulin is more similar to mammalian tubulin than the taxoid site where paclitaxel binds. In order to obtain information on the primary and secondary targets of peloruside A in yeast, a microarray analysis of yeast heterozygous and homozygous deletion mutant sets was carried out. Haploinsufficiency profiling (HIP) failed to provide hits that could be validated, but homozygous profiling (HOP) generated twelve validated genes that interact with peloruside A in cells. Five of these were particularly significant: RTS1, SAC1, MAD1, MAD2, and LSM1. In addition to its known target tubulin, based on these microarray 'hits', peloruside A was seen to interact genetically with other cell proteins involved in the cell cycle, mitosis, RNA splicing, and membrane trafficking. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Candidate EDA targets revealed by expression profiling of primary keratinocytes from Tabby mutant mice

    PubMed Central

    Esibizione, Diana; Cui, Chang-Yi; Schlessinger, David

    2009-01-01

    EDA, the gene mutated in anhidrotic ectodermal dysplasia, encodes ectodysplasin, a TNF superfamily member that activates NF-kB mediated transcription. To identify EDA target genes, we have earlier used expression profiling to infer genes differentially expressed at various developmental time points in Tabby (Eda-deficient) compared to wild-type mouse skin. To increase the resolution to find genes whose expression may be restricted to epidermal cells, we have now extended studies to primary keratinocyte cultures established from E19 wild-type and Tabby skin. Using microarrays bearing 44,000 gene probes, we found 385 preliminary candidate genes whose expression was significantly affected by Eda loss. By comparing expression profiles to those from Eda-A1 transgenic skin, we restricted the list to 38 “candidate EDA targets”, 14 of which were already known to be expressed in hair follicles or epidermis. We confirmed expression changes for 3 selected genes, Tbx1, Bmp7, and Jag1, both in keratinocytes and in whole skin, by Q-PCR and Western blotting analyses. Thus, by the analysis of keratinocytes, novel candidate pathways downstream of EDA were detected. PMID:18848976

  7. The biopharmaceutics risk assessment roadmap for optimizing clinical drug product performance.

    PubMed

    Selen, Arzu; Dickinson, Paul A; Müllertz, Anette; Crison, John R; Mistry, Hitesh B; Cruañes, Maria T; Martinez, Marilyn N; Lennernäs, Hans; Wigal, Tim L; Swinney, David C; Polli, James E; Serajuddin, Abu T M; Cook, Jack A; Dressman, Jennifer B

    2014-11-01

    The biopharmaceutics risk assessment roadmap (BioRAM) optimizes drug product development and performance by using therapy-driven target drug delivery profiles as a framework to achieve the desired therapeutic outcome. Hence, clinical relevance is directly built into early formulation development. Biopharmaceutics tools are used to identify and address potential challenges to optimize the drug product for patient benefit. For illustration, BioRAM is applied to four relatively common therapy-driven drug delivery scenarios: rapid therapeutic onset, multiphasic delivery, delayed therapeutic onset, and maintenance of target exposure. BioRAM considers the therapeutic target with the drug substance characteristics and enables collection of critical knowledge for development of a dosage form that can perform consistently for meeting the patient's needs. Accordingly, the key factors are identified and in vitro, in vivo, and in silico modeling and simulation techniques are used to elucidate the optimal drug delivery rate and pattern. BioRAM enables (1) feasibility assessment for the dosage form, (2) development and conduct of appropriate "learning and confirming" studies, (3) transparency in decision-making, (4) assurance of drug product quality during lifecycle management, and (5) development of robust linkages between the desired clinical outcome and the necessary product quality attributes for inclusion in the quality target product profile. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Concentrations and congener profiles of chlorinated paraffins in domestic polymeric products in China.

    PubMed

    Wang, Chu; Gao, Wei; Liang, Yong; Wang, Yawei; Jiang, Guibin

    2018-03-21

    Chlorinated paraffins (CPs) are widely used in domestic polymeric products as plasticizers and fire retardants. In this study, concentrations and congener profiles of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) were investigated in domestic polymeric products, including plastics, rubber and food packaging in China. The average concentrations of SCCPs in polyethylene terephthalate (PET), polypropylene (PP), polyethylene (PE) and food packaging were 234, 3968, 150 and 188 ng/g, respectively and the corresponding average concentrations of MCCPs in these samples were 37.4, 2537, 208 and 644 ng/g, respectively. The concentrations of CPs in rubber and polyvinylchloride (PVC) were significantly higher than in other matrices. The highest concentrations of SCCPs and MCCPs were found in a PVC cable sheath with 191 mg/g and 145 mg/g, respectively. Congener group profiles analysis indicated C 11 - and C 13 -congener groups were predominant in carbon homologues of SCCPs, and C 14 -congener groups were predominant in MCCPs. High levels of SCCPs and MCCPs in domestic polymeric products implied that they might be a significant source to the environment and human exposure. Copyright © 2018. Published by Elsevier Ltd.

  9. Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products.

    PubMed

    Baptista, Rafael; Bhowmick, Sumana; Nash, Robert J; Baillie, Les; Mur, Luis Aj

    2018-04-01

    Tuberculosis is a major global health hazard. The search for new antimycobacterials has focused on such as screening combinational chemistry libraries or designing chemicals to target predefined pockets of essential bacterial proteins. The relative ineffectiveness of these has led to a reappraisal of natural products for new antimycobacterial drug leads. However, progress has been limited, we suggest through a failure in many cases to define the drug target and optimize the hits using this information. We highlight methods of target discovery needed to develop a drug into a candidate for clinical trials. We incorporate these into suggested analysis pipelines which could inform the research strategies to accelerate the development of new drug leads from natural products.

  10. Improvement of Aspergillus nidulans penicillin production by targeting AcvA to peroxisomes.

    PubMed

    Herr, Andreas; Fischer, Reinhard

    2014-09-01

    Aspergillus nidulans is able to synthesize penicillin and serves as a model to study the regulation of its biosynthesis. Only three enzymes are required to form the beta lactam ring tripeptide, which is comprised of l-cysteine, l-valine and l-aminoadipic acid. Whereas two enzymes, AcvA and IpnA localize to the cytoplasm, AatA resides in peroxisomes. Here, we tested a novel strategy to improve penicillin production, namely the change of the residence of the enzymes involved in the biosynthesis. We tested if targeting of AcvA or IpnA (or both) to peroxisomes would increase the penicillin yield. Indeed, AcvA peroxisomal targeting led to a 3.2-fold increase. In contrast, targeting IpnA to peroxisomes caused a complete loss of penicillin production. Overexpression of acvA, ipnA or aatA resulted in 1.4, 2.8 and 3.1-fold more penicillin, respectively in comparison to wildtype. Simultaneous overexpression of all three enzymes resulted even in 6-fold more penicillin. Combination of acvA peroxisomal targeting and overexpression of the gene led to 5-fold increase of the penicillin titer. At last, the number of peroxisomes was increased through overexpression of pexK. A strain with the double number of peroxisomes produced 2.3 times more penicillin. These results show that penicillin production can be triggered at several levels of regulation, one of which is the subcellular localization of the enzymes. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  11. Comparison of the pharmacological profiles of murine antisense oligonucleotides targeting apolipoprotein B and microsomal triglyceride transfer protein

    PubMed Central

    Lee, Richard G.; Fu, Wuxia; Graham, Mark J.; Mullick, Adam E.; Sipe, Donna; Gattis, Danielle; Bell, Thomas A.; Booten, Sheri; Crooke, Rosanne M.

    2013-01-01

    Therapeutic agents that suppress apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) levels/activity are being developed in the clinic to benefit patients who are unable to reach target LDL-C levels with maximally tolerated lipid-lowering drugs. To compare and contrast the metabolic consequences of reducing these targets, murine-specific apoB or MTP antisense oligonucleotides (ASOs) were administered to chow-fed and high fat-fed C57BL/6 or to chow-fed and Western diet-fed LDLr−/− mice for periods ranging from 2 to 12 weeks, and detailed analyses of various factors affecting fatty acid metabolism were performed. Administration of these drugs significantly reduced target hepatic mRNA and protein, leading to similar reductions in hepatic VLDL/triglyceride secretion. MTP ASO treatment consistently led to increases in hepatic triglyceride accumulation and biomarkers of hepatotoxicity relative to apoB ASO due in part to enhanced expression of peroxisome proliferator activated receptor γ target genes and the inability to reduce hepatic fatty acid synthesis. Thus, although both drugs effectively lowered LDL-C levels in mice, the apoB ASO produced a more positive liver safety profile. PMID:23220583

  12. MicroRNA profiling reveals dysregulated microRNAs and their target gene regulatory networks in cemento-ossifying fibroma.

    PubMed

    Pereira, Thaís Dos Santos Fontes; Brito, João Artur Ricieri; Guimarães, André Luiz Sena; Gomes, Carolina Cavaliéri; de Lacerda, Júlio Cesar Tanos; de Castro, Wagner Henriques; Coimbra, Roney Santos; Diniz, Marina Gonçalves; Gomez, Ricardo Santiago

    2018-01-01

    Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of uncertain pathogenesis, and its treatment results in morbidity. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and may represent therapeutic targets. The purpose of the study was to generate a comprehensive miRNA profile of COF compared to normal bone. Additionally, the most relevant pathways and target genes of differentially expressed miRNA were investigated by in silico analysis. Nine COF and ten normal bone samples were included in the study. miRNA profiling was carried out by using TaqMan® OpenArray® Human microRNA panel containing 754 validated human miRNAs. We identified the most relevant miRNAs target genes through the leader gene approach, using STRING and Cytoscape software. Pathways enrichment analysis was performed using DIANA-miRPath. Eleven miRNAs were downregulated (hsa-miR-95-3p, hsa-miR-141-3p, hsa-miR-205-5p, hsa-miR-223-3p, hsa-miR-31-5p, hsa-miR-944, hsa-miR-200b-3p, hsa-miR-135b-5p, hsa-miR-31-3p, hsa-miR-223-5p and hsa-miR-200c-3p), and five were upregulated (hsa-miR-181a-5p, hsa-miR-181c-5p, hsa-miR-149-5p, hsa-miR-138-5p and hsa-miR-199a-3p) in COF compared to normal bone. Eighteen common target genes were predicted, and the leader genes approach identified the following genes involved in human COF: EZH2, XIAP, MET and TGFBR1. According to the biology of bone and COF, the most relevant KEGG pathways revealed by enrichment analysis were proteoglycans in cancer, miRNAs in cancer, pathways in cancer, p53-, PI3K-Akt-, FoxO- and TGF-beta signalling pathways, which were previously found to be differentially regulated in bone neoplasms, odontogenic tumours and osteogenesis. miRNA dysregulation occurs in COF, and EZH2, XIAP, MET and TGFBR1 are potential targets for functional analysis validation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Chemometric approach to texture profile analysis of kombucha fermented milk products.

    PubMed

    Malbaša, Radomir; Jevrić, Lidija; Lončar, Eva; Vitas, Jasmina; Podunavac-Kuzmanović, Sanja; Milanović, Spasenija; Kovačević, Strahinja

    2015-09-01

    In the present work, relationships between the textural characteristics of fermented milk products obtained by kombucha inoculums with various teas were investigated by using chemometric analysis. The presented data which describe numerically the textural characteristics (firmness, consistency, cohesiveness and index of viscosity) were analysed. The quadratic correlation was determined between the textural characteristics of fermented milk products obtained at fermentation temperatures of 40 and 43 °C, using milk with 0.8, 1.6 and 2.8% milk fat and kombucha inoculums cultivated on the extracts of peppermint, stinging nettle, wild thyme and winter savory. Hierarchical cluster analysis (HCA) was performed to identify the similarities among the fermented products. The best mathematical models predicting the textural characteristics of investigated samples were developed. The results of this study indicate that textural characteristics of sample based on winter savory have a significant effect on textural characteristics of samples based on peppermint, stinging nettle and wild thyme, which can be very useful in the determination of products texture profile.

  14. Ultra-pressure liquid chromatography/tandem mass spectrometry targeted profiling of arachidonic acid and eicosanoids in human colorectal cancer.

    PubMed

    Mal, Mainak; Koh, Poh Koon; Cheah, Peh Yean; Chan, Eric Chun Yong

    2011-03-30

    Cumulative evidence shows that eicosanoids such as prostaglandins, leukotrienes, thromboxanes and hydroxy eicosatetraenoic acids play an important role in associating inflammation with human colorectal cancer (CRC). In this study an ultra-pressure liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed and validated for the targeted profiling of eight relevant eicosanoids and the major metabolic precursor, arachidonic acid (AA), in human colon. Multiple reaction monitoring (MRM) experiments were performed in negative electrospray ionization mode. The metabolites were separated using a C(18) column consisting of 1.7 µm ethylene-bridged hybrid particles (100 × 2.1 mm i.d.) and gradient elution (50 to 95% of solvent B) with a mobile phase comprising water (0.1% formic acid) [solvent A] and acetonitrile (0.1% formic acid) [solvent B] at a flow rate of 0.4 mL/min. The analysis time for each sample was 5.5 min. Our UPLC/MS/MS method demonstrated satisfactory validation results in terms of selectivity, sensitivity, matrix effect, linearity, extraction efficiency, intra- and inter-day precision, accuracy and autosampler stability. The method was applied for the clinical profiling of matched pairs of cancerous and normal colon mucosae obtained from eight colorectal cancer patients. Endogenous levels of AA and selected eicosanoids such as prostaglandin E(2) (PGE(2)), prostacyclin (PGI(2)) [assayed as its stable hydrolytic product 6-keto-prostaglandin(1α) (6-k PGF(1α))] and 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE) were found to be significantly different (p <0.05; paired t-test) between cancerous and normal mucosae. Copyright © 2011 John Wiley & Sons, Ltd.

  15. Diagnosing ion-beam targets, data acquisition, reactor conditions

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

    Mendel, Jr., C. W.

    1982-01-01

    The final lecture will discuss diagnostics of the target. These are very difficult because of the short times, small spatial extent, and extreme values of temperature and pressure. Diagnostics for temperature, density profile, and neutron production will be discussed. A few minutes will be devoted to data acquisition needs. The lecture will end with a discussion of current areas where improvements are needed and future diagnostics that will be required for reactor conditions.

  16. Natural products targeting ER stress pathway for the treatment of cardiovascular diseases.

    PubMed

    Choy, Ker Woon; Murugan, Dharmani; Mustafa, Mohd Rais

    2018-04-21

    Endoplasmic reticulum (ER) is the main organelle for the synthesis, folding, and processing of secretory and transmembrane proteins. Pathological stimuli including hypoxia, ischaemia, inflammation and oxidative stress interrupt the homeostatic function of ER, leading to accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers a complex signalling network referred as the unfolded protein response (UPR). Extensive studies have demonstrated that ER stress plays an important role in the pathogenesis of various cardiovascular diseases such as heart failure, ischemic heart disease and atherosclerosis. The importance of natural products in modern medicine are well recognized and continues to be of interests as a source of novel lead compounds. Natural products targeting components of UPR and reducing ER stress offers an innovative strategic approach to treat cardiovascular diseases. In this review, we discussed several therapeutic interventions using natural products with potential cardiovascular protective properties targeting ER stress signalling pathways. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. E-WOM Review Adoption: Consumers’ Demographic Profile Influence on Green Purchase Intention

    NASA Astrophysics Data System (ADS)

    Rahim, Roslin Abdul; Sulaiman, Zuraidah; Chin, Thoo Ai; Arif, Mohd Shoki Mohd; Hamid, Mohd Hakim Abdul

    2017-06-01

    Nowadays, green products are getting popular in their acceptance by the Malaysian consumers. Due to the advancement of the Internet technologies and the wide spread of electronic word of mouth (E-WOM), consumers seem to be more influenced in purchasing the green products. In this study, consumers’ demographic profiles, such as age, gender, income, education background, and occupation are being explored to investigate their influences on consumers’ green product purchase intention. The purpose of this paper is to showcase the results of the differences between several demographic profile groups on green product purchase intention using descriptive analysis, ANOVA and independent sample T-Test. T-test results showed that there is a statistically significant difference between gender on consumers’ green product purchase intention. Meanwhile, the results generated by ANOVA indicated that there are no significant differences between age, income, education background and occupation on consumers’ green product purchase intention. These results shed light on the potential market segment that should be targeted by marketers and producers of green products in Malaysia.

  18. Metabolomics by Gas Chromatography-Mass Spectrometry: the combination of targeted and untargeted profiling

    PubMed Central

    Fiehn, Oliver

    2016-01-01

    Gas chromatography-mass spectrometry (GC-MS)-based metabolomics is ideal for identifying and quantitating small molecular metabolites (<650 daltons), including small acids, alcohols, hydroxyl acids, amino acids, sugars, fatty acids, sterols, catecholamines, drugs, and toxins, often using chemical derivatization to make these compounds volatile enough for gas chromatography. This unit shows that on GC-MS- based metabolomics easily allows integrating targeted assays for absolute quantification of specific metabolites with untargeted metabolomics to discover novel compounds. Complemented by database annotations using large spectral libraries and validated, standardized standard operating procedures, GC-MS can identify and semi-quantify over 200 compounds per study in human body fluids (e.g., plasma, urine or stool) samples. Deconvolution software enables detection of more than 300 additional unidentified signals that can be annotated through accurate mass instruments with appropriate data processing workflows, similar to liquid chromatography-MS untargeted profiling (LC-MS). Hence, GC-MS is a mature technology that not only uses classic detectors (‘quadrupole’) but also target mass spectrometers (‘triple quadrupole’) and accurate mass instruments (‘quadrupole-time of flight’). This unit covers the following aspects of GC-MS-based metabolomics: (i) sample preparation from mammalian samples, (ii) acquisition of data, (iii) quality control, and (iv) data processing. PMID:27038389

  19. Chemopreventive glucosinolate accumulation in various broccoli and collard tissues: Microfluidic-based targeted transcriptomics for by-product valorization

    PubMed Central

    Becker, Talon M.; Juvik, John A.

    2017-01-01

    Floret, leaf, and root tissues were harvested from broccoli and collard cultivars and extracted to determine their glucosinolate and hydrolysis product profiles using high performance liquid chromatography and gas chromotography. Quinone reductase inducing bioactivity, an estimate of anti-cancer chemopreventive potential, of the extracts was measured using a hepa1c1c7 murine cell line. Extracts from root tissues were significantly different from other tissues and contained high levels of gluconasturtiin and glucoerucin. Targeted gene expression analysis on glucosinolate biosynthesis revealed that broccoli root tissue has elevated gene expression of AOP2 and low expression of FMOGS-OX homologs, essentially the opposite of what was observed in broccoli florets, which accumulated high levels of glucoraphanin. Broccoli floret tissue has significantly higher nitrile formation (%) and epithionitrile specifier protein gene expression than other tissues. This study provides basic information of the glucosinolate metabolome and transcriptome for various tissues of Brassica oleracea that maybe utilized as potential byproducts for the nutraceutical market. PMID:28945821

  20. Chemopreventive glucosinolate accumulation in various broccoli and collard tissues: Microfluidic-based targeted transcriptomics for by-product valorization.

    PubMed

    Lee, Young-Sang; Ku, Kang-Mo; Becker, Talon M; Juvik, John A

    2017-01-01

    Floret, leaf, and root tissues were harvested from broccoli and collard cultivars and extracted to determine their glucosinolate and hydrolysis product profiles using high performance liquid chromatography and gas chromotography. Quinone reductase inducing bioactivity, an estimate of anti-cancer chemopreventive potential, of the extracts was measured using a hepa1c1c7 murine cell line. Extracts from root tissues were significantly different from other tissues and contained high levels of gluconasturtiin and glucoerucin. Targeted gene expression analysis on glucosinolate biosynthesis revealed that broccoli root tissue has elevated gene expression of AOP2 and low expression of FMOGS-OX homologs, essentially the opposite of what was observed in broccoli florets, which accumulated high levels of glucoraphanin. Broccoli floret tissue has significantly higher nitrile formation (%) and epithionitrile specifier protein gene expression than other tissues. This study provides basic information of the glucosinolate metabolome and transcriptome for various tissues of Brassica oleracea that maybe utilized as potential byproducts for the nutraceutical market.

  1. Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

    PubMed Central

    2018-01-01

    Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

  2. Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

    PubMed

    Vu, Hoan; Pedro, Liliana; Mak, Tin; McCormick, Brendan; Rowley, Jessica; Liu, Miaomiao; Di Capua, Angela; Williams-Noonan, Billy; Pham, Ngoc B; Pouwer, Rebecca; Nguyen, Bao; Andrews, Katherine T; Skinner-Adams, Tina; Kim, Jessica; Hol, Wim G J; Hui, Raymond; Crowther, Gregory J; Van Voorhis, Wesley C; Quinn, Ronald J

    2018-04-13

    Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.

  3. Natural Products and Their Mimics as Targets of Opportunity for Discovery

    PubMed Central

    2017-01-01

    Diverse structural types of natural products and their mimics have served as targets of opportunity in our laboratory to inspire the discovery and development of new methods and strategies to assemble polyfunctional and polycyclic molecular architectures. Furthermore, our efforts toward identifying novel compounds having useful biological properties led to the creation of new targets, many of which posed synthetic challenges that required the invention of new methodology. In this Perspective, selected examples of how we have exploited a diverse range of natural products and their mimics to create, explore, and solve a variety of problems in chemistry and biology will be discussed. The journey was not without its twists and turns, but the unexpected often led to new revelations and insights. Indeed, in our recent excursion into applications of synthetic organic chemistry to neuroscience, avoiding the more-traveled paths was richly rewarding. PMID:28738152

  4. Self-vapor cooled targets for production of I-123 at high current accelerators. [using Xe-123 production

    NASA Technical Reports Server (NTRS)

    Blue, J. W.; Scholz, K. L.; Sodd, V. J.

    1974-01-01

    The basic elements of the vapor cooled target system are shown. This system can be operated as a heat pipe or as a conventional condenser. The choice of target fluid is based on the specific nuclear reaction chosen to produce Xe-123. The reaction using I-127 was studied and shown to have a significant yield for bombarding energies from 47 to 63 MeV. The Cs-133 reaction is also included. Xenon-123 is applied to I-123 production in a purer form for thyroid studies.

  5. Arsenate Impact on the Metabolite Profile, Production, and Arsenic Loading of Xylem Sap in Cucumbers (Cucumis sativus L.)

    PubMed Central

    Uroic, M. Kalle; Salaün, Pascal; Raab, Andrea; Feldmann, Jörg

    2012-01-01

    Arsenic uptake and translocation studies on xylem sap focus generally on the concentration and speciation of arsenic in the xylem. Arsenic impact on the xylem sap metabolite profile and its production during short term exposure has not been reported in detail. To investigate this, cucumbers were grown hydroponically and arsenate (AsV) and DMA were used for plant treatment for 24 h. Total arsenic and arsenic speciation in xylem sap was analyzed including a metabolite profiling under AsV stress. Produced xylem sap was quantified and absolute arsenic transported was determined. AsV exposure had a significant impact on the metabolite profile of xylem sap. Four m/z values corresponding to four compounds were up-regulated, one compound down-regulated by AsV exposure. The compound down-regulated was identified to be isoleucine. Furthermore, AsV exposure had a significant influence on sap production, leading to a reduction of up to 96% sap production when plants were exposed to 1000 μg kg−1 AsV. No difference to control plants was observed when plants were exposed to 1000 μg kg−1 DMA. Absolute arsenic amount in xylem sap was the lowest at high AsV exposure. These results show that AsV has a significant impact on the production and metabolite profile of xylem sap. The physiological importance of isoleucine needs further attention. PMID:22536187

  6. TargetSearch--a Bioconductor package for the efficient preprocessing of GC-MS metabolite profiling data.

    PubMed

    Cuadros-Inostroza, Alvaro; Caldana, Camila; Redestig, Henning; Kusano, Miyako; Lisec, Jan; Peña-Cortés, Hugo; Willmitzer, Lothar; Hannah, Matthew A

    2009-12-16

    Metabolite profiling, the simultaneous quantification of multiple metabolites in an experiment, is becoming increasingly popular, particularly with the rise of systems-level biology. The workhorse in this field is gas-chromatography hyphenated with mass spectrometry (GC-MS). The high-throughput of this technology coupled with a demand for large experiments has led to data pre-processing, i.e. the quantification of metabolites across samples, becoming a major bottleneck. Existing software has several limitations, including restricted maximum sample size, systematic errors and low flexibility. However, the biggest limitation is that the resulting data usually require extensive hand-curation, which is subjective and can typically take several days to weeks. We introduce the TargetSearch package, an open source tool which is a flexible and accurate method for pre-processing even very large numbers of GC-MS samples within hours. We developed a novel strategy to iteratively correct and update retention time indices for searching and identifying metabolites. The package is written in the R programming language with computationally intensive functions written in C for speed and performance. The package includes a graphical user interface to allow easy use by those unfamiliar with R. TargetSearch allows fast and accurate data pre-processing for GC-MS experiments and overcomes the sample number limitations and manual curation requirements of existing software. We validate our method by carrying out an analysis against both a set of known chemical standard mixtures and of a biological experiment. In addition we demonstrate its capabilities and speed by comparing it with other GC-MS pre-processing tools. We believe this package will greatly ease current bottlenecks and facilitate the analysis of metabolic profiling data.

  7. Profiling global kinome signatures of the radioresistant MCF-7/C6 breast cancer cells using MRM-based targeted proteomics.

    PubMed

    Guo, Lei; Xiao, Yongsheng; Fan, Ming; Li, Jian Jian; Wang, Yinsheng

    2015-01-02

    Ionizing radiation is widely used in cancer therapy; however, cancer cells often develop radioresistance, which compromises the efficacy of cancer radiation therapy. Quantitative assessment of the alteration of the entire kinome in radioresistant cancer cells relative to their radiosensitive counterparts may provide important knowledge to define the mechanism(s) underlying tumor adaptive radioresistance and uncover novel target(s) for effective prevention and treatment of tumor radioresistance. By employing a scheduled multiple-reaction monitoring analysis in conjunction with isotope-coded ATP affinity probes, we assessed the global kinome of radioresistant MCF-7/C6 cells and their parental MCF-7 human breast cancer cells. We rigorously quantified 120 kinases, of which (1)/3 exhibited significant differences in expression levels or ATP binding affinities. Several kinases involved in cell cycle progression and DNA damage response were found to be overexpressed or hyperactivated, including checkpoint kinase 1 (CHK1), cyclin-dependent kinases 1 and 2 (CDK1 and CDK2), and the catalytic subunit of DNA-dependent protein kinase. The elevated expression of CHK1, CDK1, and CDK2 in MCF-7/C6 cells was further validated by Western blot analysis. Thus, the altered kinome profile of radioresistant MCF-7/C6 cells suggests the involvement of kinases on cell cycle progression and DNA repair in tumor adaptive radioresistance. The unique kinome profiling results also afforded potential effective targets for resensitizing radioresistant cancer cells and counteracting deleterious effects of ionizing radiation exposure.

  8. Gold and isotopically enriched platinium targets for the production of radioactive beams of francium

    NASA Astrophysics Data System (ADS)

    Lipski, A. R.; Orozco, L. A.; Pearson, M. R.; Simsarian, J. E.; Sprouse, G. D.; Zhao, W. Z.

    1999-12-01

    Au and isotopically enriched Pt targets are discussed for the production of radioactive Fr beams. Target foils, serving also as ionizers, have to be heated in order to enhance the diffusion of atoms to the surface for further extraction and injection into the electrostatic transport system.

  9. THE EFFECT OF TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT LONG-EVANS (EKER) RATS.

    EPA Science Inventory

    The effect of a targeted knockout mutation on the transcriptional profile of the kidney in
    Tsc2 mutant Long-Evans (Eker) rats.

    Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting
    for up to 80% of malignant renal neoplasms. Hereditary...

  10. A risk microbiological profile of the Australian red meat industry: risk ratings of hazard-product pairings.

    PubMed

    Sumner, John; Ross, Tom; Jenson, Ian; Pointon, Andrew

    2005-11-25

    A risk profile of microbial hazards across the supply continuum for the beef, sheep and goat meat industries was developed using both a qualitative tool and a semi-quantitative, spreadsheet tool, Risk Ranger. The latter is useful for highlighting factors contributing to food safety risk and for ranking the risk of various product/pathogen combinations. In the present profile the qualitative tool was used as a preliminary screen for a wide range of hazard-product pairings while Risk Ranger was used to rank in order of population health risk pairings for which quantitative data were available and for assessing the effect of hypothetical scenarios. 'High' risk hazard-product pairings identified were meals contaminated with Clostridium perfringens provided by caterers which have not implemented HACCP; kebabs cross-contaminated by Salmonella present in drip trays or served undercooked; meals served in the home cross-contaminated with Salmonella. 'Medium' risk hazard-product pairings identified were ready-to-eat meats contaminated with Listeria monocytogenes and which have extended shelf life; Uncooked Comminuted Fermented Meat (UCFM)/Salami contaminated with Enterohaemorrhagic E. coli (EHEC) and Salmonella; undercooked hamburgers contaminated with EHEC; kebabs contaminated by Salmonella under normal production or following final "flash" heating. Identified 'low' risk hazard-product pairings included cooked, ready-to-eat sausages contaminated with Salmonella; UCFM/Salami contaminated with L. monocytogenes; well-cooked hamburgers contaminated with EHEC. The risk profile provides information of value to Australia's risk managers in the regulatory, processing and R&D sectors of the meat and meat processing industry for the purposes of identifying food safety risks in the industry and for prioritising risk management actions.

  11. Target for production of X-rays

    NASA Astrophysics Data System (ADS)

    Korenev, S. A.

    2004-09-01

    The patented new type of X-ray target is considered in this report. The main concept of the target consists in developing a sandwich structure depositing a coating of materials with high Z on the substrate with low Z, high thermal conductivity and high thermal stability. The target presents multiple layers system. The thermal conditions for X-ray target are discussed. The experimental results for Ta target on the Al and Cu substrates are presented.

  12. Metabolic pathways recruited in the production of a recombinant enveloped virus: mining targets for process and cell engineering.

    PubMed

    Rodrigues, A F; Formas-Oliveira, A S; Bandeira, V S; Alves, P M; Hu, W S; Coroadinha, A S

    2013-11-01

    Biopharmaceuticals derived from enveloped virus comprise an expanding market of vaccines, oncolytic vectors and gene therapy products. Thus, increased attention is given to the development of robust high-titer cell hosts for their manufacture. However, the knowledge on the physiological constraints modulating virus production is still scarce and the use of integrated strategies to improve hosts productivity and upstream bioprocess an under-explored territory. In this work, we conducted a functional genomics study, including the transcriptional profiling and central carbon metabolism analysis, following the metabolic changes in the transition 'parental-to-producer' of two human cell lines producing recombinant retrovirus. Results were gathered into three comprehensive metabolic maps, providing a broad and integrated overview of gene expression changes for both cell lines. Eight pathways were identified to be recruited in the virus production state: amino acid catabolism, carbohydrate catabolism and integration of the energy metabolism, nucleotide metabolism, glutathione metabolism, pentose phosphate pathway, polyamines biosynthesis and lipid metabolism. Their ability to modulate viral titers was experimentally challenged, leading to improved specific productivities of recombinant retrovirus up to 6-fold. Within recruited pathways in the virus production state, we sought for metabolic engineering gene targets in the low producing phenotypes. A mining strategy was used alternative to the traditional approach 'high vs. low producer' clonal comparison. Instead, 'high vs. low producer' from different genetic backgrounds (i.e. cell origins) were compared. Several genes were identified as limiting in the low-production phenotype, including two enzymes from cholesterol biosynthesis, two enzymes from glutathione biosynthesis and the regulatory machinery of polyamines biosynthesis. This is thus a frontier work, bridging fundamentals to technological research and contributing

  13. Electron beam plasma ionizing target for the production of neutron-rich nuclides

    NASA Astrophysics Data System (ADS)

    Panteleev, V. N.; Barzakh, A. E.; Essabaa, S.; Fedorov, D. V.; Ionan, A. M.; Ivanov, V. S.; Lau, C.; Leroy, R.; Lhersonneau, G.; Mezilev, K. A.; Molkanov, P. L.; Moroz, F. V.; Orlov, S. Yu.; Stroe, L.; Tecchio, L. B.; Villari, A. C. C.; Volkov, Yu. M.

    2008-10-01

    The production of neutron-rich Ag, In and Sn isotopes from a uranium carbide target of a high density has been investigated at the IRIS facility in the PLOG (PNPI-Legnaro-GANIL-Orsay) collaboration. The UC target material with a density of 12 g/cm3 was prepared by the method of powder metallurgy in a form of pellets of 2 mm thickness, 11 mm in diameter and grain dimensions of about 20 μm. The uranium target mass of 31 g was exposed at a 1 GeV proton beam of intensity 0.05-0.07 μA. For the ionization of the produced species the electron beam-plasma ionization inside the target container (ionizing target) has been used. It was the first experiment when the new high density UC target material was exploited with the electron-plasma ionization. Yields of Sn isotopes have been measured in the target temperature range of (1900-2100) °C. The yields of some Pd, In and Cd isotopes were measured as well to compare to previously measured ones from a high density uranium carbide target having a ceramic-like structure. For the first time a nickel isotope was obtained from a high density UC target.

  14. Morphological and functional effects of graphene on the synthesis of uranium carbide for isotopes production targets.

    PubMed

    Biasetto, L; Corradetti, S; Carturan, S; Eloirdi, R; Amador-Celdran, P; Staicu, D; Blanco, O Dieste; Andrighetto, A

    2018-05-29

    The development of tailored targets for the production of radioactive isotopes represents an active field in nuclear research. Radioactive beams find applications in nuclear medicine, in astrophysics, matter physics and materials science. In this work, we study the use of graphene both as carbon source for UO 2 carbothermal reduction to produce UC x targets, and also as functional properties booster. At fixed composition, the UC x target grain size, porosity and thermal conductivity represent the three main points that affect the target production efficiency. UC x was synthesized using both graphite and graphene as the source of carbon and the target properties in terms of composition, grain size, porosity, thermal diffusivity and thermal conductivity were studied. The main output of this work is related to the remarkable enhancement achieved in thermal conductivity, which can profitably improve thermal dissipation during operational stages of UC x targets.

  15. Expression Profiling Identifies Klf15 as a Glucocorticoid Target That Regulates Airway Hyperresponsiveness

    PubMed Central

    Masuno, Kiriko; Haldar, Saptarsi M.; Jeyaraj, Darwin; Mailloux, Christina M.; Huang, Xiaozhu; Panettieri, Rey A.; Jain, Mukesh K.

    2011-01-01

    Glucocorticoids (GCs), which activate GC receptor (GR) signaling and thus modulate gene expression, are widely used to treat asthma. GCs exert their therapeutic effects in part through modulating airway smooth muscle (ASM) structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. We therefore used transcription profiling to study the effects of a potent GC, dexamethasone, on human ASM (HASM) gene expression at 4 and 24 hours. After 24 hours of dexamethasone treatment, nearly 7,500 genes had statistically distinguishable changes in expression; quantitative PCR validation of a 40-gene subset of putative GR-regulated genes in 6 HASM cell lines suggested that the early transcriptional targets of GR signaling are similar in independent HASM lines. Gene ontology analysis implicated GR targets in controlling multiple aspects of ASM function. One GR-regulated gene, the transcription factor, Kruppel-like factor 15 (Klf15), was already known to modulate vascular smooth and cardiac muscle function, but had no known role in the lung. We therefore analyzed the pulmonary phenotype of Klf15−/− mice after ovalbumin sensitization and challenge. We found diminished airway responses to acetylcholine in ovalbumin-challenged Klf15−/− mice without a significant change in the induction of asthmatic inflammation. In cultured cells, overexpression of Klf15 reduced proliferation of HASM cells, whereas apoptosis in Klf15−/− murine ASM cells was increased. Together, these results further characterize the GR-regulated gene network in ASM and establish a novel role for the GR target, Klf15, in modulating airway function. PMID:21257922

  16. Assemblies with both target and fuel pins in an isotope-production reactor

    DOEpatents

    Cawley, W.E.; Omberg, R.P.

    1982-08-19

    A method is described for producing tritium in a fast breeder reactor cooled with liquid metal. Lithium target material is placed in pins adjacent to fuel pins in order to increase the tritium production rate.

  17. Phytochemical profiles and antioxidant activity of processed brown rice products.

    PubMed

    Gong, Er Sheng; Luo, Shunjing; Li, Tong; Liu, Chengmei; Zhang, Guowen; Chen, Jun; Zeng, Zicong; Liu, Rui Hai

    2017-10-01

    The phytochemical profiles and antioxidant activity of free, soluble-conjugated, and bound fractions of brown rice and its processed products (textured rice, cooked rice and rice noodle) were studied. Nineteen phenolic acids were identified. Trans-ferulic acid was the most abundant monomeric phenolic acid with trans-trans-8-O-4' diferulic acid being most abundant diferulic acid. Processing increased the content of free phenolic acids, but decreased the content of soluble-conjugated phenolic acids. The content of bound phenolic acids was increased by improved extrusion cooking technology and cooking, but not affected by rice noodle extrusion. The total phenolic contents and antioxidant activities of free and soluble-conjugated fractions were decreased after processing, whereas those of bound fraction were increased by improved extrusion cooking technology and cooking, but not affected by rice noodle extrusion. Results indicated that whole foods designed for reducing chronic disease risk need to consider the effects of processing on phytochemical profiles and antioxidant activity of whole grains. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Investigation of sensory profiles and hedonic drivers of emerging aquaculture fish species.

    PubMed

    Alexi, Niki; Byrne, Derek V; Nanou, Evangelia; Grigorakis, Kriton

    2018-02-01

    The aquaculture sector needs to increase the diversity fish species and their processed products to cover rising consumer demands. Candidates for this diversification have been identified to be meagre, greater amberjack, pikeperch and wreckfish. Yet scientific knowledge on their sensory profiles and consumer hedonic responses is scarce. The aim of the current study was to investigate these aspects, since they are essential for product development and market targeting. Species exhibited different sensory profiles with the exception of the odor/flavor profiles of meagre and greater amberjack, which were similar. Texture was more important than odor/flavor in explaining interspecies differences. Yet the hedonic responses were equally related to texture and odor/flavor. None of the species received negative hedonic scores. Both positive and negative hedonic drivers were identified within the odor/flavor and texture modalities. The distinct profiles of meagre, greater amberjack, pikeperch and wreckfish make these fish species valuable first materials for new product development and for covering markets with different sensory preferences. Differences in fish texture are more easily perceivable, yet small variations in fish odor/flavor can have a great impact on consumers' hedonic responses. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  19. Meat and Seafood Consumption in Relation to Plasma Metabolic Profiles in a Chinese Population: A Combined Untargeted and Targeted Metabolomics Study.

    PubMed

    Lu, Yonghai; Zou, Li; Su, Jin; Tai, E Shyong; Whitton, Clare; Dam, Rob M van; Ong, Choon Nam

    2017-06-30

    We examined the relationship between different patterns of meat and seafood consumption and plasma metabolic profiles in an Asian population. We selected 270 ethnic Chinese men and women from the Singapore Prospective Study Program based on their dietary habits assessed with a validated food frequency questionnaire. Participants were divided into four subgroups: high meat and high seafood ( n = 60), high meat and low seafood ( n = 64), low meat and high seafood ( n = 60), and low meat and low seafood ( n = 86) consumers. Plasma metabolites were measured using both targeted and untargeted mass spectroscopy-based analyses. A total of 42 metabolites differed significantly by dietary group. Higher concentrations of essential amino acids, polyunsaturated fatty acids, and d-glucose were found in high meat and/or seafood consumers as compared with the group with a low consumption of these animal foods. Red meat, poultry, fish, shellfish, soy products, and dairy were each correlated with at least one differential metabolite ( r = -0.308 to 0.448). Some observations, such as the correlation between fish and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), confirmed previous studies. Other observations, such as the correlation between shellfish and phosphatidylethanolamine (p36:4), were novel. We also observed significant correlations between plasma metabolites and clinical characteristics, such as CMPF with fasting blood glucose ( r = 0.401). These findings demonstrate a significant influence of meat and seafood consumption on metabolic profiles in the Asian population.

  20. Meat and Seafood Consumption in Relation to Plasma Metabolic Profiles in a Chinese Population: A Combined Untargeted and Targeted Metabolomics Study

    PubMed Central

    Lu, Yonghai; Zou, Li; Su, Jin; Tai, E. Shyong; Whitton, Clare; van Dam, Rob M.; Ong, Choon Nam

    2017-01-01

    We examined the relationship between different patterns of meat and seafood consumption and plasma metabolic profiles in an Asian population. We selected 270 ethnic Chinese men and women from the Singapore Prospective Study Program based on their dietary habits assessed with a validated food frequency questionnaire. Participants were divided into four subgroups: high meat and high seafood (n = 60), high meat and low seafood (n = 64), low meat and high seafood (n = 60), and low meat and low seafood (n = 86) consumers. Plasma metabolites were measured using both targeted and untargeted mass spectroscopy-based analyses. A total of 42 metabolites differed significantly by dietary group. Higher concentrations of essential amino acids, polyunsaturated fatty acids, and d-glucose were found in high meat and/or seafood consumers as compared with the group with a low consumption of these animal foods. Red meat, poultry, fish, shellfish, soy products, and dairy were each correlated with at least one differential metabolite (r = −0.308 to 0.448). Some observations, such as the correlation between fish and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), confirmed previous studies. Other observations, such as the correlation between shellfish and phosphatidylethanolamine (p36:4), were novel. We also observed significant correlations between plasma metabolites and clinical characteristics, such as CMPF with fasting blood glucose (r = 0.401). These findings demonstrate a significant influence of meat and seafood consumption on metabolic profiles in the Asian population. PMID:28665358

  1. The role of sensory perception in the development and targeting of tobacco products.

    PubMed

    Carpenter, Carrie M; Wayne, Geoffrey Ferris; Connolly, Gregory N

    2007-01-01

    To examine tobacco industry research on smoking-related sensory effects, including differences in sensory perception across smoker groups, and to determine whether this research informed targeted product development and impacted the development of commercial tobacco products. We searched previously secret internal tobacco industry documents available online through document databases housed at Tobacco Documents Online, the British American Tobacco Document Archive and the Legacy Tobacco Documents Library. We identified relevant documents using a snowball sampling method to first search the databases using an initial set of key words and to then establish further search terms. Sensory research is a priority within the tobacco industry directly impacting commercial markets both in the United States and internationally. Sensory factors contribute to smoker satisfaction and product acceptance, and play an important role in controlling puffing behavior. Cigarette manufacturers have capitalized on distinct sensory preferences across gender, age and ethnic groups by tailoring products for specific populations. Regulation of tobacco products is needed to address product changes that are used to reinforce or contribute to tobacco dependence; for instance, the incorporation of additives that target attributes such as smoothness, harshness and aftertaste. Greater understanding of the role of sensory effects on smoking behavior may also help to inform the development of tobacco treatment options that support long-term tobacco abstinence.

  2. Al K x-ray production for incident /sup 16/O ions: The influence of target thickness effects on observed target x-ray yields

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

    Gray, T.J.; Richard, P.; Gealy, G.

    1979-04-01

    Thin solid Al targets ranging in thickness from approx. 1 to 30 ..mu..g/cm/sup 2/ were bombarded by /sup 16/O ions wih incident energies from 0.25 to 2.25 MeV/amu. The effects of target thickness on the measured Al K x-ray yield for ions incident without an initial K-shell vacancy were determined. Comparisons of the data for Al K x-ray production in vanishingly thin targets (and 29-..mu..g/cm/sup 2/ targets) were made to perturbed-stationary-state calculations (PSS) for O ions on Al targets. The PSS calculations contained corrections for Coulomb deflection and binding energy (PSS(CB)) and for Coulomb deflection, binding energy, and polarization (PSS(CBP)).more » Further, two different PSS calculation procedures were employed: calculations without radial cutoffs employed in the binding-energy contribution (PSS), and calculations with radial cutoffs employed in the binding-energy correction (NPSS). The PSS(CBP) calculations agree with the measured Al K x-ray production cross section for data taken in the limit of a vanishingly thin target. The NPSS(CBP) calculations agree with the data taken for a 29-..mu..g/cm/sup 2/ Al target. The latter agreement is fortuitous, as the increase observed in the measured target x-ray yield for the 29-..mu..g/cm/sup 2/ target, in comparison to the yield extracted as rhox ..-->.. 0 at each bombarding energy, is due to K-shell--to--K-shell charge exchange. Comparisons are made with previously published data for /sup 16/O ions incident on finite-thickness Al targets.« less

  3. Targets used in the production of radioactive ion beams at the HRIBF

    NASA Astrophysics Data System (ADS)

    Stracener, D. W.; Alton, G. D.; Auble, R. L.; Beene, J. R.; Mueller, P. E.; Bilheux, J. C.

    2004-03-01

    Radioactive ion beams are produced at the Holifield Radioactive Ion Beam Facility using the Isotope Separation On-Line (ISOL) technique where the atoms are produced in a thick target, transported to an ion source, ionized, and extracted from the ion source to form an ion beam. These radioactive ion beams are then accelerated to energies of a few MeV per nucleon and delivered to experimental stations for use in nuclear physics and nuclear astrophysics experiments. At the heart of this facility is the RIB production target, where the radioactive nuclei are produced using beams of light ions (p, d, 3He, α) to induce nuclear reactions in the target nuclei. Several target materials have been developed and used successfully, including Al 2O 3, HfO 2, SiC, CeS, liquid Ge, liquid Ni, and a low-density matrix of uranium carbide. The details of these targets and some of the target developments that led to the delivery of high-quality radioactive ion beams are discussed in this paper.

  4. Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives: Synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery.

    PubMed

    Quiliano, Miguel; Pabón, Adriana; Moles, Ernest; Bonilla-Ramirez, Leonardo; Fabing, Isabelle; Fong, Kim Y; Nieto-Aco, Diego A; Wright, David W; Pizarro, Juan C; Vettorazzi, Ariane; López de Cerain, Adela; Deharo, Eric; Fernández-Busquets, Xavier; Garavito, Giovanny; Aldana, Ignacio; Galiano, Silvia

    2018-05-25

    Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC 50 s < 0.28 μM), and compounds 55, 56, 64, 70, 71, and 72 showed potent biological activity in chloroquine-sensitive and multidrug-resistant strains (IC 50 s < 0.7 μM for 3D7, D6, FCR-3 and C235). All of these compounds share appropriate drug-likeness profiles and adequate selectivity indexes (77 < SI < 184) as well as lack genotoxicity. In vivo efficacy tests in a mouse model showed compounds 66 and 72 to be promising candidates as they exhibited significant parasitemia reductions of 96.4% and 80.4%, respectively. Additional studies such as liver stage and sporogony inhibition, target exploration of heat shock protein 90 of P. falciparum, targeted delivery by immunoliposomes, and enantiomer characterization were performed and strongly reinforce the hypothesis of 1-aryl-3-substituted propanol derivatives as promising antimalarial compounds. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Prediction of polypharmacological profiles of drugs by the integration of chemical, side effect, and therapeutic space.

    PubMed

    Cheng, Feixiong; Li, Weihua; Wu, Zengrui; Wang, Xichuan; Zhang, Chen; Li, Jie; Liu, Guixia; Tang, Yun

    2013-04-22

    Prediction of polypharmacological profiles of drugs enables us to investigate drug side effects and further find their new indications, i.e. drug repositioning, which could reduce the costs while increase the productivity of drug discovery. Here we describe a new computational framework to predict polypharmacological profiles of drugs by the integration of chemical, side effect, and therapeutic space. On the basis of our previous developed drug side effects database, named MetaADEDB, a drug side effect similarity inference (DSESI) method was developed for drug-target interaction (DTI) prediction on a known DTI network connecting 621 approved drugs and 893 target proteins. The area under the receiver operating characteristic curve was 0.882 ± 0.011 averaged from 100 simulated tests of 10-fold cross-validation for the DSESI method, which is comparative with drug structural similarity inference and drug therapeutic similarity inference methods. Seven new predicted candidate target proteins for seven approved drugs were confirmed by published experiments, with the successful hit rate more than 15.9%. Moreover, network visualization of drug-target interactions and off-target side effect associations provide new mechanism-of-action of three approved antipsychotic drugs in a case study. The results indicated that the proposed methods could be helpful for prediction of polypharmacological profiles of drugs.

  6. A forced-convection gas target for the production of [11C]CH4.

    PubMed

    Uittenbosch, T; Buckley, K; Ruth, T; Martinez, D M; Hoehr, C

    2018-06-15

    A forced-convection gas target for the production of [ 11 C]CH 4 on a 13 MeV cyclotron was constructed and tested. A small fan was incorporated into the back of the target, which mixes the target gas during irradiation. The effect of the forced convection alone on the target operation and the [ 11 C]CH 4 yield was measured. Forced convection improved the target yield by up to 16 ± 4%. In addition, improvement in heat transfer of up to 70% was observed to be a function of fan speed. Operating with forced convection allowed delivery of 21% higher beam currents while still staying in the acceptable pressure rise during irradiation, providing a 25 ± 7% greater yield. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Cancer diagnostics: The journey from histomorphology to molecular profiling.

    PubMed

    Ahmed, Atif A; Abedalthagafi, Malak

    2016-09-06

    Although histomorphology has made significant advances into the understanding of cancer etiology, classification and pathogenesis, it is sometimes complicated by morphologic ambiguities, and other shortcomings that necessitate the development of ancillary tests to complement its diagnostic value. A new approach to cancer patient management consists of targeting specific molecules or gene mutations in the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic profiling methods are increasingly being developed to identify tumor targeted molecular profile that is the basis of targeted therapy. Novel targeted therapy has revolutionized the treatment of gastrointestinal stromal tumor, renal cell carcinoma and other cancers that were previously difficult to treat with standard chemotherapy. In this review, we discuss the role of histomorphology in cancer diagnosis and management and the rising role of molecular profiling in targeted therapy. Molecular profiling in certain diagnostic and therapeutic difficulties may provide a practical and useful complement to histomorphology and opens new avenues for targeted therapy and alternative methods of cancer patient management.

  8. The clinical trial landscape in oncology and connectivity of somatic mutational profiles to targeted therapies.

    PubMed

    Patterson, Sara E; Liu, Rangjiao; Statz, Cara M; Durkin, Daniel; Lakshminarayana, Anuradha; Mockus, Susan M

    2016-01-16

    Precision medicine in oncology relies on rapid associations between patient-specific variations and targeted therapeutic efficacy. Due to the advancement of genomic analysis, a vast literature characterizing cancer-associated molecular aberrations and relative therapeutic relevance has been published. However, data are not uniformly reported or readily available, and accessing relevant information in a clinically acceptable time-frame is a daunting proposition, hampering connections between patients and appropriate therapeutic options. One important therapeutic avenue for oncology patients is through clinical trials. Accordingly, a global view into the availability of targeted clinical trials would provide insight into strengths and weaknesses and potentially enable research focus. However, data regarding the landscape of clinical trials in oncology is not readily available, and as a result, a comprehensive understanding of clinical trial availability is difficult. To support clinical decision-making, we have developed a data loader and mapper that connects sequence information from oncology patients to data stored in an in-house database, the JAX Clinical Knowledgebase (JAX-CKB), which can be queried readily to access comprehensive data for clinical reporting via customized reporting queries. JAX-CKB functions as a repository to house expertly curated clinically relevant data surrounding our 358-gene panel, the JAX Cancer Treatment Profile (JAX CTP), and supports annotation of functional significance of molecular variants. Through queries of data housed in JAX-CKB, we have analyzed the landscape of clinical trials relevant to our 358-gene targeted sequencing panel to evaluate strengths and weaknesses in current molecular targeting in oncology. Through this analysis, we have identified patient indications, molecular aberrations, and targeted therapy classes that have strong or weak representation in clinical trials. Here, we describe the development and disseminate

  9. The Collection 6 'dark-target' MODIS Aerosol Products

    NASA Technical Reports Server (NTRS)

    Levy, Robert C.; Mattoo, Shana; Munchak, Leigh A.; Kleidman, Richard G.; Patadia, Falguni; Gupta, Pawan; Remer, Lorraine

    2013-01-01

    Aerosol retrieval algorithms are applied to Moderate resolution Imaging Spectroradiometer (MODIS) sensors on both Terra and Aqua, creating two streams of decade-plus aerosol information. Products of aerosol optical depth (AOD) and aerosol size are used for many applications, but the primary concern is that these global products are comprehensive and consistent enough for use in climate studies. One of our major customers is the international modeling comparison study known as AEROCOM, which relies on the MODIS data as a benchmark. In order to keep up with the needs of AEROCOM and other MODIS data users, while utilizing new science and tools, we have improved the algorithms and products. The code, and the associated products, will be known as Collection 6 (C6). While not a major overhaul from the previous Collection 5 (C5) version, there are enough changes that there are significant impacts to the products and their interpretation. In its entirety, the C6 algorithm is comprised of three sub-algorithms for retrieving aerosol properties over different surfaces: These include the dark-target DT algorithms to retrieve over (1) ocean and (2) vegetated-dark-soiled land, plus the (3) Deep Blue (DB) algorithm, originally developed to retrieve over desert-arid land. Focusing on the two DT algorithms, we have updated assumptions for central wavelengths, Rayleigh optical depths and gas (H2O, O3, CO2, etc.) absorption corrections, while relaxing the solar zenith angle limit (up to 84) to increase pole-ward coverage. For DT-land, we have updated the cloud mask to allow heavy smoke retrievals, fine-tuned the assignments for aerosol type as function of season location, corrected bugs in the Quality Assurance (QA) logic, and added diagnostic parameters such as topographic altitude. For DT-ocean, improvements include a revised cloud mask for thin-cirrus detection, inclusion of wind speed dependence in the retrieval, updates to logic of QA Confidence flag (QAC) assignment, and

  10. TargetSearch - a Bioconductor package for the efficient preprocessing of GC-MS metabolite profiling data

    PubMed Central

    2009-01-01

    Background Metabolite profiling, the simultaneous quantification of multiple metabolites in an experiment, is becoming increasingly popular, particularly with the rise of systems-level biology. The workhorse in this field is gas-chromatography hyphenated with mass spectrometry (GC-MS). The high-throughput of this technology coupled with a demand for large experiments has led to data pre-processing, i.e. the quantification of metabolites across samples, becoming a major bottleneck. Existing software has several limitations, including restricted maximum sample size, systematic errors and low flexibility. However, the biggest limitation is that the resulting data usually require extensive hand-curation, which is subjective and can typically take several days to weeks. Results We introduce the TargetSearch package, an open source tool which is a flexible and accurate method for pre-processing even very large numbers of GC-MS samples within hours. We developed a novel strategy to iteratively correct and update retention time indices for searching and identifying metabolites. The package is written in the R programming language with computationally intensive functions written in C for speed and performance. The package includes a graphical user interface to allow easy use by those unfamiliar with R. Conclusions TargetSearch allows fast and accurate data pre-processing for GC-MS experiments and overcomes the sample number limitations and manual curation requirements of existing software. We validate our method by carrying out an analysis against both a set of known chemical standard mixtures and of a biological experiment. In addition we demonstrate its capabilities and speed by comparing it with other GC-MS pre-processing tools. We believe this package will greatly ease current bottlenecks and facilitate the analysis of metabolic profiling data. PMID:20015393

  11. Non-target screening to trace ozonation transformation products in a wastewater treatment train including different post-treatments.

    PubMed

    Schollée, Jennifer E; Bourgin, Marc; von Gunten, Urs; McArdell, Christa S; Hollender, Juliane

    2018-05-25

    Ozonation and subsequent post-treatments are increasingly implemented in wastewater treatment plants (WWTPs) for enhanced micropollutant abatement. While this technology is effective, micropollutant oxidation leads to the formation of ozonation transformation products (OTPs). Target and suspect screening provide information about known parent compounds and known OTPs, but for a more comprehensive picture, non-target screening is needed. Here, sampling was conducted at a full-scale WWTP to investigate OTP formation at four ozone doses (2, 3, 4, and 5 mg/L, ranging from 0.3 to 1.0 gO 3 /gDOC) and subsequent changes during five post-treatment steps (i.e., sand filter, fixed bed bioreactor, moving bed bioreactor, and two granular activated carbon (GAC) filters, relatively fresh and pre-loaded). Samples were measured with online solid-phase extraction coupled to liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) using electrospray ionization (ESI) in positive and negative modes. Existing non-target screening workflows were adapted to (1) examine the formation of potential OTPs at four ozone doses and (2) compare the removal of OTPs among five post-treatments. In (1), data processing included principal component analysis (PCA) and chemical knowledge on possible oxidation reactions to prioritize non-target features likely to be OTPs. Between 394 and 1328 unique potential OTPs were detected in positive ESI for the four ozone doses tested; between 12 and 324 unique potential OTPs were detected in negative ESI. At a specific ozone dose of 0.5 gO 3 /gDOC, 27 parent compounds were identified and were related to 69 non-target features selected as potential OTPs. Two OTPs were confirmed with reference standards (venlafaxine N-oxide and chlorothiazide); 34 other potential OTPs were in agreement with literature data and/or reaction mechanisms. In (2), hierarchical cluster analysis (HCA) was applied on profiles detected in positive ESI mode across the

  12. Integrated analysis of numerous heterogeneous gene expression profiles for detecting robust disease-specific biomarkers and proposing drug targets.

    PubMed

    Amar, David; Hait, Tom; Izraeli, Shai; Shamir, Ron

    2015-09-18

    Genome-wide expression profiling has revolutionized biomedical research; vast amounts of expression data from numerous studies of many diseases are now available. Making the best use of this resource in order to better understand disease processes and treatment remains an open challenge. In particular, disease biomarkers detected in case-control studies suffer from low reliability and are only weakly reproducible. Here, we present a systematic integrative analysis methodology to overcome these shortcomings. We assembled and manually curated more than 14,000 expression profiles spanning 48 diseases and 18 expression platforms. We show that when studying a particular disease, judicious utilization of profiles from other diseases and information on disease hierarchy improves classification quality, avoids overoptimistic evaluation of that quality, and enhances disease-specific biomarker discovery. This approach yielded specific biomarkers for 24 of the analyzed diseases. We demonstrate how to combine these biomarkers with large-scale interaction, mutation and drug target data, forming a highly valuable disease summary that suggests novel directions in disease understanding and drug repurposing. Our analysis also estimates the number of samples required to reach a desired level of biomarker stability. This methodology can greatly improve the exploitation of the mountain of expression profiles for better disease analysis. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids.

    PubMed

    Strajhar, Petra; Tonoli, David; Jeanneret, Fabienne; Imhof, Raphaella M; Malagnino, Vanessa; Patt, Melanie; Kratschmar, Denise V; Boccard, Julien; Rudaz, Serge; Odermatt, Alex

    2017-04-15

    The validated OECD test guideline 456 based on human adrenal H295R cells promotes measurement of testosterone and estradiol production as read-out to identify potential endocrine disrupting chemicals. This study aimed to establish optimal conditions for using H295R cells to detect chemicals interfering with the production of key adrenal steroids. H295R cells' supernatants were characterized by liquid chromatography-mass spectrometry (LC-MS)-based steroid profiling, and the influence of experimental conditions including time and serum content was assessed. Steroid profiles were determined before and after incubation with reference compounds and chemicals to be tested for potential disruption of adrenal steroidogenesis. The H295R cells cultivated according to the OECD test guideline produced progestins, glucocorticoids, mineralocorticoids and adrenal androgens but only very low amounts of testosterone. However, testosterone contained in Nu-serum was metabolized during the 48h incubation. Thus, inclusion of positive and negative controls and a steroid profile of the complete medium prior to the experiment (t=0h) was necessary to characterize H295R cells' steroid production and indicate alterations caused by exposure to chemicals. Among the tested chemicals, octyl methoxycinnamate and acetyl tributylcitrate resembled the corticosteroid induction pattern of the positive control torcetrapib. Gene expression analysis revealed that octyl methoxycinnamate and acetyl tributylcitrate enhanced CYP11B2 expression, although less pronounced than torcetrapib. Further experiments need to assess the toxicological relevance of octyl methoxycinnamate- and acetyl tributylcitrate-induced corticosteroid production. In conclusion, the extended profiling and appropriate controls allow detecting chemicals that act on steroidogenesis and provide initial mechanistic evidence for prioritizing chemicals for further investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Targets and methods for target preparation for radionuclide production

    DOEpatents

    Zhuikov, Boris L; Konyakhin, Nicolai A; Kokhanyuk, Vladimir M; Srivastava, Suresh C

    2012-10-16

    The invention relates to nuclear technology, and to irradiation targets and their preparation. One embodiment of the present invention includes a method for preparation of a target containing intermetallic composition of antimony Ti--Sb, Al--Sb, Cu--Sb, or Ni--Sb in order to produce radionuclides (e.g., tin-117 m) with a beam of accelerated particles. The intermetallic compounds of antimony can be welded by means of diffusion welding to a copper backing cooled during irradiation on the beam of accelerated particles. Another target can be encapsulated into a shell made of metallic niobium, stainless steel, nickel or titanium cooled outside by water during irradiation. Titanium shell can be plated outside by nickel to avoid interaction with the cooling water.

  15. A Production System Model of Capturing Reactive Moving Targets. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Jagacinski, R. J.; Plamondon, B. D.; Miller, R. A.

    1984-01-01

    Subjects manipulated a control stick to position a cursor over a moving target that reacted with a computer-generated escape strategy. The cursor movements were described at two levels of abstraction. At the upper level, a production system described transitions among four modes of activity; rapid acquisition, close following, a predictive mode, and herding. Within each mode, differential equations described trajectory-generating mechanisms. A simulation of this two-level model captures the targets in a manner resembling the episodic time histories of human subjects.

  16. Strawberry-flavored yogurts and whey beverages: What is the sensory profile of the ideal product?

    PubMed

    Janiaski, D R; Pimentel, T C; Cruz, A G; Prudencio, S H

    2016-07-01

    This study aimed to evaluate the sensory profile and Brazilian consumers' liking of strawberry-flavored yogurts and whey beverages (fermented or nonfermented) with different fat contents that were sweetened with sugar or nonsugar sweeteners. We also determined the influence of sensory attributes on consumer preferences and the profile of the ideal product. Nonfermented whey beverages (NFWB) and "light" yogurt were less liked. The NFWB were less acidic, less viscous, and with lower smoothness of mouthcoating, sweeter and with a more intense artificial strawberry aroma (ASA) than the fermented products. Low-fat yogurts were more liked, more viscous, and had higher smoothness of mouthcoating than nonfat yogurts. Fermented-whey beverages were as liked as yogurts. Viscosity and smoothness of mouthcoating positively influenced consumer liking. The ideal product had higher levels of brightness, artificial strawberry taste, artificial strawberry aroma, and sweet taste; intermediate smoothness of mouthcoating, color, and viscosity; and low particles, acid taste, and aroma. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. Proteomic profile of Mycobacterium tuberculosis after eupomatenoid-5 induction reveals potential drug targets.

    PubMed

    Ghiraldi-Lopes, Luciana D; Campanerut-Sá, Paula Az; Meneguello, Jean E; Seixas, Flávio Av; Lopes-Ortiz, Mariana A; Scodro, Regiane Bl; Pires, Claudia Ta; da Silva, Rosi Z; Siqueira, Vera Ld; Nakamura, Celso V; Cardoso, Rosilene F

    2017-08-01

    We investigated a proteome profile, protein-protein interaction and morphological changes of Mycobacterium tuberculosis after different times of eupomatenoid-5 (EUP-5) induction to evaluate the cellular response to the drug-induced damages. The bacillus was induced to sub-minimal inhibitory concentration of EUP-5 at 12 h, 24 h and 48 h. The proteins were separated by 2D gel electrophoresis, identified by LC/MS-MS. Scanning electron microscopy and Search Tool for the Retrieval of Interacting Genes/Proteins analyses were performed. EUP-5 impacts mainly in M. tuberculosis proteins of intermediary metabolism and interactome suggests a multisite disturbance that contributes to bacilli death. Scanning electron microscopy revealed the loss of bacillary form. Some of the differentially expressed proteins have the potential to be drug targets such as citrate synthase (Rv0896), phosphoglycerate kinase (Rv1437), ketol-acid reductoisomerase (Rv3001c) and ATP synthase alpha chain (Rv1308).

  18. Ergonomic factors and production target evaluation in eucalyptus timber harvesting operations in mountainous terrains.

    PubMed

    de Souza, Amaury Paulo; Minette, Luciano José; Sanches, André Luis Petean; da Silva, Emília Pio; Rodrigues, Valéria Antônia Justino; de Oliveira, Luciana Aparecida

    2012-01-01

    There are several forest operations involved in Eucalyptus timber harvesting. This study was carried out during brush-cutting; tree felling, bucking, delimbing, piling and manual extraction operations, with the following objectives: a) analyzing, ergonomically, two systems of brush-cutting: one manual and the other semi-mechanized, using two different machines; b) ergonomically evaluating three different brands of pruner machines used in delimbing felled trees. c) determining the feasible target of productivity as a function of ergonomic factors relevant to establish the time of resting pauses for workers in manual and semi-mechanized timber harvesting systems in mountainous terrain. Brush-cutting, either manual or semimechanized, is an activity carried out prior to timber harvesting. It is usually a hard work, with low productivity when compared with mechanized systems. Pruner machines have been used by forest companies, due to the great possibilities to improve productivity, quality and the health of workers. Ergonomics is a discipline that promotes the adequacy of work to the physical and mental characteristics of human beings, seeking to design production systems and products considering relevant aspects, including social, organizational and environmental factors. Companies should consider the ergonomic factor in the determination of daily worker production targets.

  19. Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase.

    PubMed

    Keohane, Colleen E; Steele, Andrew D; Fetzer, Christian; Khowsathit, Jittasak; Van Tyne, Daria; Moynié, Lucile; Gilmore, Michael S; Karanicolas, John; Sieber, Stephan A; Wuest, William M

    2018-02-07

    Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings.

  20. Progress in nutritional and health profile of milk and dairy products: a novel drug target.

    PubMed

    Martemucci, Giovanni; D'Alessandro, Angela Gabriella

    2013-09-01

    There is an increasing focus on diet as a tool to maintain human health and prevent disease. Milk and milk products of ruminants are important source of fat and saturated fatty acids, which are not considered to be very favourable to human health, but are valuable sources of nutrients including bioactive fatty acids (FA), vitamins, and minerals, which can promote positive health effects. The nutritional characteristics of milk and dairy products are related to their composition, which depends on the source species, and varies due to numerous factors, among which the animal diet is the most important. An improvement in milk FA composition and other micronutrients can be reached through an animal feeding strategy. Natural pasture-based farming systems increase microconstituents that are beneficial to human health (CLA, PUFAs, n-3 FAs, antioxidants, vitamins A and E, and Se) and volatile compounds (flavour, and terpenes) in milk and cheese. There are still uncertainties about the health benefits of various milk FAs and other compounds; deep and extensive long-term clinical studies with humans are needed. The contamination of milk and dairy products by heavy metals or dioxins has dramatic negative consequences for human and livestock health and necessitates very urgent consideration and intervention.

  1. Dynamic profiling of different ready-to-drink fermented dairy products: A comparative study using Temporal Check-All-That-Apply (TCATA), Temporal Dominance of Sensations (TDS) and Progressive Profile (PP).

    PubMed

    Esmerino, Erick A; Castura, John C; Ferraz, Juliana P; Tavares Filho, Elson R; Silva, Ramon; Cruz, Adriano G; Freitas, Mônica Q; Bolini, Helena M A

    2017-11-01

    Despite the several differences in ingredients, processes and nutritional values, dairy foods as yogurts, fermented milks and milk beverages are widely accepted worldwide, and although they have their sensory profiling normally covered by descriptive analyses, the temporal perception involved during the consumption are rarely considered. In this sense, the present work aimed to assess the dynamic sensory profile of three categories of fermented dairy products using different temporal methodologies: Temporal Dominance of Sensations (TDS), Progressive Profiling (PP), Temporal CATA (TCATA), and compare the results obtained. The findings showed that the different sensory characteristics among the products are basically related to their commercial identity. Regarding the methods, all of them collected the variations between samples with great correlation between data. In addition, to detect differences in intensities, TCATA showed to be the most sensitive method in detecting textural changes. When using PP, a balanced experimental design considering the number of attributes, time intervals, and food matrix must be weighed. The findings are of interest to guide sensory and consumer practitioners involved in the dairy production to formulate/reformulate their products and help them choosing the most suitable dynamic method to temporally evaluate them. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment.

    PubMed

    Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

    2016-01-27

    To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. API costs per kg were $347-$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128-$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Mass generic production of several TKIs could achieve treatment prices in the range of $128-$4020 per person-year, versus current US prices of $75161-$139,138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

    PubMed

    Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

    2014-08-01

    Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A new, simple and precise method for measuring cyclotron proton beam energies using the activity vs. depth profile of zinc-65 in a thick target of stacked copper foils.

    PubMed

    Asad, A H; Chan, S; Cryer, D; Burrage, J W; Siddiqui, S A; Price, R I

    2015-11-01

    The proton beam energy of an isochronous 18MeV cyclotron was determined using a novel version of the stacked copper-foils technique. This simple method used stacked foils of natural copper forming 'thick' targets to produce Zn radioisotopes by the well-documented (p,x) monitor-reactions. Primary beam energy was calculated using the (65)Zn activity vs. depth profile in the target, with the results obtained using (62)Zn and (63)Zn (as comparators) in close agreement. Results from separate measurements using foil thicknesses of 100, 75, 50 or 25µm to form the stacks also concurred closely. Energy was determined by iterative least-squares comparison of the normalized measured activity profile in a target-stack with the equivalent calculated normalized profile, using 'energy' as the regression variable. The technique exploits the uniqueness of the shape of the activity vs. depth profile of the monitor isotope in the target stack for a specified incident energy. The energy using (65)Zn activity profiles and 50-μm foils alone was 18.03±0.02 [SD] MeV (95%CI=17.98-18.08), and 18.06±0.12MeV (95%CI=18.02-18.10; NS) when combining results from all isotopes and foil thicknesses. When the beam energy was re-measured using (65)Zn and 50-μm foils only, following a major upgrade of the ion sources and nonmagnetic beam controls the results were 18.11±0.05MeV (95%CI=18.00-18.23; NS compared with 'before'). Since measurement of only one Zn monitor isotope is required to determine the normalized activity profile this indirect yet precise technique does not require a direct beam-current measurement or a gamma-spectroscopy efficiency calibrated with standard sources, though a characteristic photopeak must be identified. It has some advantages over published methods using the ratio of cross sections of monitor reactions, including the ability to determine energies across a broader range and without need for customized beam degraders. Copyright © 2015 Elsevier Ltd. All rights

  5. Targeted metabolomics profiles are strongly correlated with nutritional patterns in women.

    PubMed

    Menni, Cristina; Zhai, Guangju; Macgregor, Alexander; Prehn, Cornelia; Römisch-Margl, Werner; Suhre, Karsten; Adamski, Jerzy; Cassidy, Aedin; Illig, Thomas; Spector, Tim D; Valdes, Ana M

    2013-04-01

    Nutrition plays an important role in human metabolism and health. Metabolomics is a promising tool for clinical, genetic and nutritional studies. A key question is to what extent metabolomic profiles reflect nutritional patterns in an epidemiological setting. We assessed the relationship between metabolomic profiles and nutritional intake in women from a large cross-sectional community study. Food frequency questionnaires (FFQs) were applied to 1,003 women from the TwinsUK cohort with targeted metabolomic analyses of serum samples using the Biocrates Absolute-IDQ™ Kit p150 (163 metabolites). We analyzed seven nutritional parameters: coffee intake, garlic intake and nutritional scores derived from the FFQs summarizing fruit and vegetable intake, alcohol intake, meat intake, hypo-caloric dieting and a "traditional English" diet. We studied the correlation between metabolite levels and dietary intake patterns in the larger population and identified for each trait between 14 and 20 independent monozygotic twins pairs discordant for nutritional intake and replicated results in this set. Results from both analyses were then meta-analyzed. For the metabolites associated with nutritional patterns, we calculated heritability using structural equation modelling. 42 metabolite nutrient intake associations were statistically significant in the discovery samples (Bonferroni P  < 4 × 10 -5 ) and 11 metabolite nutrient intake associations remained significant after validation. We found the strongest associations for fruit and vegetables intake and a glycerophospholipid (Phosphatidylcholine diacyl C38:6, P  = 1.39 × 10 -9 ) and a sphingolipid (Sphingomyeline C26:1, P  = 6.95 × 10 -13 ). We also found significant associations for coffee (confirming a previous association with C10 reported in an independent study), garlic intake and hypo-caloric dieting. Using the twin study design we find that two thirds the metabolites associated with nutritional patterns have a

  6. Microscale profiling of photosynthesis-related variables in a highly productive biofilm photobioreactor.

    PubMed

    Li, Tong; Piltz, Bastian; Podola, Björn; Dron, Anthony; de Beer, Dirk; Melkonian, Michael

    2016-05-01

    In the present study depth profiles of light, oxygen, pH and photosynthetic performance in an artificial biofilm of the green alga Halochlorella rubescens in a porous substrate photobioreactor (PSBR) were recorded with microsensors. Biofilms were exposed to different light intensities (50-1,000 μmol photons m(-2) s(-1) ) and CO2 levels (0.04-5% v/v in air). The distribution of photosynthetically active radiation showed almost identical trends for different surface irradiances, namely: a relatively fast drop to a depth of about 250 µm, (to 5% of the incident), followed by a slower decrease. Light penetrated into the biofilm deeper than the Lambert-Beer Law predicted, which may be attributed to forward scattering of light, thus improving the overall light availability. Oxygen concentration profiles showed maxima at a depth between 50 and 150 μm, depending on the incident light intensity. A very fast gas exchange was observed at the biofilm surface. The highest oxygen concentration of 3.2 mM was measured with 1,000 μmol photons m(-2) s(-1) and 5% supplementary CO2. Photosynthetic productivity increased with light intensity and/or CO2 concentration and was always highest at the biofilm surface; the stimulating effect of elevated CO2 concentration in the gas phase on photosynthesis was enhanced by higher light intensities. The dissolved inorganic carbon concentration profiles suggest that the availability of the dissolved free CO2 has the strongest impact on photosynthetic productivity. The results suggest that dark respiration could explain previously observed decrease in growth rate over cultivation time in this type of PSBR. Our results represent a basis for understanding the complex dynamics of environmental variables and metabolic processes in artificial phototrophic biofilms exposed to a gas phase and can be used to improve the design and operational parameters of PSBRs. © 2015 Wiley Periodicals, Inc.

  7. Relationship between the Antifungal Susceptibility Profile and the Production of Virulence-Related Hydrolytic Enzymes in Brazilian Clinical Strains of Candida glabrata

    PubMed Central

    de Oliveira, Jean Carlos Almeida

    2017-01-01

    Candida glabrata is a facultative intracellular opportunistic fungal pathogen in human infections. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to five antifungal agents, the production of seven hydrolytic enzymes related to virulence, and the relationship between these phenotypes in 91 clinical strains of C. glabrata. All C. glabrata strains were susceptible to flucytosine. However, some of these strains showed resistance to amphotericin B (9.9%), fluconazole (15.4%), itraconazole (5.5%), or micafungin (15.4%). Overall, C. glabrata strains were good producers of catalase, aspartic protease, esterase, phytase, and hemolysin. However, caseinase and phospholipase in vitro activities were not detected. Statistically significant correlations were identified between micafungin minimum inhibitory concentration (MIC) and esterase production, between fluconazole and micafungin MIC and hemolytic activity, and between amphotericin B MIC and phytase production. These results contribute to clarify some of the C. glabrata mechanisms of pathogenicity. Moreover, the association between some virulence attributes and the regulation of antifungal resistance encourage the development of new therapeutic strategies involving virulence mechanisms as potential targets for effective antifungal drug development for the treatment of C. glabrata infections. PMID:28814823

  8. Concentrations of synthetic musk compounds in personal care and sanitation products and human exposure profiles through dermal application.

    PubMed

    Roosens, Laurence; Covaci, Adrian; Neels, Hugo

    2007-11-01

    Synthetic musks, such as 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB), musk ketone (MK) and musk xylene (MX), are used as an alternative for natural musk. Due to their widespread use, these synthetic compounds turned up in different environmental compartments, such as wastewater, human and animal tissues. Yet, little is known about their distribution and occurrence in personal care and household products, information needed in order to evaluate the different human exposure routes. This paper gives an overview of the synthetic musk levels in six different product categories: body lotions, perfumes, deodorants, hair care products, shower products and sanitation products. Especially body lotions, perfumes and deodorants contained high levels of synthetic musks. Maximum concentrations of HHCB, AHTN, MX and MK were 22 mg g(-1), 8 mg g(-1), 26 microg g(-1) and 0.5 microg g(-1), respectively. By combining these results with the average usage of consumer products, low-, medium- and high-exposure profiles through dermal application could be estimated. HHCB was the highest contributor to the total amount of synthetic musks in every exposure profile (18-23 700 microg d(-1)). Exposure to MK and MX did not increase substantially (10-20-fold) between low- and high-exposure profiles, indicating that these compounds cover a less broad range. In comparison, exposure to HHCB and AHTN increased up to 10 000 fold between low- and high-exposure.

  9. Cyclotron production of {sup 61}Cu using natural Zn and enriched {sup 64}Zn targets

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

    Asad, A. H.; Smith, S. V.; Chan, S.

    2012-12-19

    Copper-61 ({sup 61}Cu) shares with {sup 64}Cu certain advantages for PET diagnostic imaging, but has a shorter half-life (3.4hr vs. 12.7hr) and a greater probability of positron production per disintegration (61% vs. 17.9%). One important application is for in vivo imaging of hypoxic tissue. In this study {sup 61}Cu was produced using the {sup 64}Zn(p,{alpha}){sup 61}Cu reaction on natural Zn or enriched {sup 64}Zn targets. The enriched {sup 64}Zn (99.82%) was electroplated onto high purity gold or silver foils or onto thin Al discs. A typical target bombardment used 30{mu}A; at 11.7, 14.5 or 17.6MeV over 30-60min. The {sup 61}Cumore » (radiochemical purity of >95%) was separated using a combination of cation and anion exchange columns. The {sup 64}Zn target material was recovered after each run, for re-use. In a direct comparison with enriched {sup 64}Zn-target results, {sup 61}Cu production using the cheaper {sup nat}Zn target proved to be an effective alternative.« less

  10. Fuel pins with both target and fuel pellets in an isotope-production reactor

    DOEpatents

    Cawley, W.E.; Omberg, R.P.

    1982-08-19

    A method is described for producing tritium in a fast breeder reactor cooled with liquid metal. Lithium target pellets are placed in close contact with fissile fuel pellets in order to increase the tritium production rate.

  11. Improved production and processing of ⁸⁹Zr using a solution target.

    PubMed

    Pandey, Mukesh K; Bansal, Aditya; Engelbrecht, Hendrik P; Byrne, John F; Packard, Alan B; DeGrado, Timothy R

    2016-01-01

    The objectives of the present work were to improve the cyclotron production yield of (89)Zr using a solution target, develop a practical synthesis of the hydroxamate resin used to process the target, and develop a biocompatible medium for (89)Zr elution from the hydroxamate resin. A new solution target (BMLT-2) with enhanced heat dissipation capabilities was designed by using helium-cooled dual foils (0.2 mm Al and 25 μ Havar) and an enhanced water-cooled, elongated solution cavity in the target insert. Irradiations were performed with 14 MeV protons on a 2M solution of yttrium nitrate in 1.25 M nitric acid at 40-μA beam current for 2 h in a closed system. Zirconium-89 was separated from Y by use of a hydroxamate resin. A one-pot synthesis of hydroxamate resin was accomplished by activating the carboxylate groups on a carboxymethyl cation exchange resin using methyl chloroformate followed by reaction with hydroxylamine hydrochloride. After trapping of (89)Zr on hydroxamate resin and rinsing the resin with HCl and water to release Y, (89)Zr was eluted with 1.2 M K2HPO4/KH2PO4 buffer (pH3.5). ICP-MS was used to measure metal contaminants in the final (89)Zr solution. The BMLT-2 target produced 349±49 MBq (9.4±1.2 mCi) of (89)Zr at the end of irradiation with a specific activity of 1.18±0.79 GBq/μg. The hydroxamate resin prepared using the new synthesis method showed a trapping efficiency of 93% with a 75 mg resin bed and 96-97% with a 100-120 mg resin bed. The elution efficiency of (89)Zr with 1.2M K2HPO4/KH2PO4 solution was found to be 91.7±3.7%, compared to >95% for 1 M oxalic acid. Elution with phosphate buffer gave very small levels of metal contaminants: Al=0.40-0.86 μg (n=2), Fe=1.22±0.71 μg (n=3), Y=0.29 μg (n=1). The BMLT-2 target allowed doubling of the beam current for production of (89)Zr, resulting in a greater than 2-fold increase in production yield in comparison with a conventional liquid target. The new one-pot synthesis of hydroxamate

  12. Large-angle production of charged pions with incident pion beams on nuclear targets

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

    Apollonio, M.; Chimenti, P.; Giannini, G.

    2009-12-15

    Measurements of the double-differential {pi}{sup {+-}} production cross section in the range of momentum 100{<=}p{<=}800 MeV/c and angle 0.35{<=}{theta}{<=}2.15 rad using {pi}{sup {+-}} beams incident on beryllium, aluminum, carbon, copper, tin, tantalum, and lead targets are presented. The data were taken with the large-acceptance hadron production (HARP) detector in the T9 beam line of the CERN Proton Synchrotron. The secondary pions were produced by beams in a momentum range from 3 to 12.9GeV/c hitting a solid target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was performed using a small-radiusmore » cylindrical time projection chamber placed inside a solenoidal magnet. Incident particles were identified by an elaborate system of beam detectors. Results are obtained for the double-differential cross sections d{sup 2}{sigma}/dp d{theta} at six incident-beam momenta. Data at 3,5,8, and 12GeV/c are available for all targets, while additional data at 8.9 and 12.9GeV/c were taken in positive particle beams on Be and Al targets, respectively. The measurements are compared with several generators of GEANT4 and the MARS Monte Carlo simulation.« less

  13. Measurement of secondary particle production induced by particle therapy ion beams impinging on a PMMA target

    NASA Astrophysics Data System (ADS)

    Toppi, M.; Battistoni, G.; Bellini, F.; Collamati, F.; De Lucia, E.; Durante, M.; Faccini, R.; Frallicciardi, P. M.; Marafini, M.; Mattei, I.; Morganti, S.; Muraro, S.; Paramatti, R.; Patera, V.; Pinci, D.; Piersanti, L.; Rucinski, A.; Russomando, A.; Sarti, A.; Sciubba, A.; Senzacqua, M.; Solfaroli Camillocci, E.; Traini, G.; Voena, C.

    2016-05-01

    Particle therapy is a technique that uses accelerated charged ions for cancer treatment and combines a high irradiation precision with a high biological effectiveness in killing tumor cells [1]. Informations about the secondary particles emitted in the interaction of an ion beam with the patient during a treatment can be of great interest in order to monitor the dose deposition. For this purpose an experiment at the HIT (Heidelberg Ion-Beam Therapy Center) beam facility has been performed in order to measure fluxes and emission profiles of secondary particles produced in the interaction of therapeutic beams with a PMMA target. In this contribution some preliminary results about the emission profiles and the energy spectra of the detected secondaries will be presented.

  14. Biological Targets and Mechanisms of Action of Natural Products from Marine Cyanobacteria

    PubMed Central

    Salvador-Reyes, Lilibeth A.

    2015-01-01

    Marine cyanobacteria are an ancient group of organisms and prolific producers of bioactive secondary metabolites. These compounds are presumably optimized by evolution over billions of years to exert high affinity for their intended biological target in the ecologically relevant organism but likely also possess activity in different biological contexts such as human cells. Screening of marine cyanobacterial extracts for bioactive natural products has largely focused on cancer cell viability; however, diversification of the screening platform led to the characterization of many new bioactive compounds. Targets of compounds have oftentimes been elusive if the compounds were discovered through phenotypic assays. Over the past few years, technology has advanced to determine mechanism of action (MOA) and targets through reverse chemical genetic and proteomic approaches, which has been applied to certain cyanobacterial compounds and will be discussed in this review. Some cyanobacterial molecules are the most-potent-in-class inhibitors and therefore may become valuable tools for chemical biology to probe protein function but also be templates for novel drugs, assuming in vitro potency translates into cellular and in vivo activity. Our review will focus on compounds for which the direct targets have been deciphered or which were found to target a novel pathway, and link them to disease states where target modulation may be beneficial. PMID:25571978

  15. Greenhouse gas and carbon profile of the U.S. forest products industry value chain

    Treesearch

    Linda S. Heath; Van Maltby; Reid Miner; Kenneth E. Skog; James E. Smith; Jay Unwin; Brad Upton

    2010-01-01

    A greenhouse gas and carbon accounting profile was developed for the U.S. forest products industry value chain for 1990 and 2004-2005 by examining net atmospheric fluxes of CO2 and other greenhouse gases (GHGs) using a variety of methods and data sources. Major GHG emission sources include direct and indirect (from purchased electricity...

  16. Effect of flaxseed supplementation rate and processing on the production, fatty acid profile, and texture of milk, butter, and cheese.

    PubMed

    Oeffner, S P; Qu, Y; Just, J; Quezada, N; Ramsing, E; Keller, M; Cherian, G; Goddick, L; Bobe, G

    2013-02-01

    Health and nutrition professionals advise consumers to limit consumption of saturated fatty acids and increase the consumption of foods rich in n-3 fatty acids. Researchers have previously reported that feeding extruded flaxseed, which is high in C18:3n-3, improves the fatty acid profile of milk and dairy products to less saturated fatty acids and to more C18:3n-3. Fat concentrations in milk and butter decreased when cows were fed higher concentrations of extruded flaxseed. The objective of this study was to determine the optimal rate of flaxseed supplementation for improving the fatty acid profile without decreasing production characteristics of milk and dairy products. By using a double 5 × 5 Latin square design, 10 mid- to late-lactation Holstein cows were fed extruded (0, 0.91, 1.81, and 2.72 kg/d) and ground (1.81 kg/d) flaxseed as a top dressing for 2-wk periods each. At the end of each 2-wk treatment period, milk and serum samples were taken. Milk was subsequently manufactured into butter and fresh Mozzarella cheese. Increasing supplementation rates of extruded flaxseed improved the fatty acid profile of milk, butter, and cheese gradually to less saturated and atherogenic fatty acids and to more C18:3n-3 by increasing concentrations of C18:3n-3 in serum. The less saturated fatty acid profile was associated with decreased hardness and adhesiveness of refrigerated butter, which likely cause improved spreadability. Supplementation rates of extruded flaxseed did not affect dry matter intake of the total mixed ration, milk composition, and production of milk, butter, or cheese. Flaxseed processing did not affect production, fatty acid profile of milk, or texture of butter and cheese. Feeding up to 2.72 kg/d of extruded flaxseed to mid- to late-lactation Holstein cows may improve nutritional and functional properties of milk fat without compromising production parameters. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights

  17. Molecular profiles of Quadriceps muscle in myostatin-null mice reveal PI3K and apoptotic pathways as myostatin targets

    PubMed Central

    Chelh, Ilham; Meunier, Bruno; Picard, Brigitte; Reecy, Mark James; Chevalier, Catherine; Hocquette, Jean-François; Cassar-Malek, Isabelle

    2009-01-01

    Background Myostatin (MSTN), a member of the TGF-β superfamily, has been identified as a negative regulator of skeletal muscle mass. Inactivating mutations in the MSTN gene are responsible for the development of a hypermuscular phenotype. In this study, we performed transcriptomic and proteomic analyses to detect altered expression/abundance of genes and proteins. These differentially expressed genes and proteins may represent new molecular targets of MSTN and could be involved in the regulation of skeletal muscle mass. Results Transcriptomic analysis of the Quadriceps muscles of 5-week-old MSTN-null mice (n = 4) and their controls (n = 4) was carried out using microarray (human and murine oligonucleotide sequences) of 6,473 genes expressed in muscle. Proteomic profiles were analysed using two-dimensional gel electrophoresis coupled with mass spectrometry. Comparison of the transcriptomic profiles revealed 192 up- and 245 down- regulated genes. Genes involved in the PI3K pathway, insulin/IGF pathway, carbohydrate metabolism and apoptosis regulation were up-regulated. Genes belonging to canonical Wnt, calcium signalling pathways and cytokine-receptor cytokine interaction were down-regulated. Comparison of the protein profiles revealed 20 up- and 18 down-regulated proteins spots. Knockout of the MSTN gene was associated with up-regulation of proteins involved in glycolytic shift of the muscles and down-regulation of proteins involved in oxidative energy metabolism. In addition, an increased abundance of survival/anti-apoptotic factors were observed. Conclusion All together, these results showed a differential expression of genes and proteins related to the muscle energy metabolism and cell survival/anti-apoptotic pathway (e.g. DJ-1, PINK1, 14-3-3ε protein, TCTP/GSK-3β). They revealed the PI3K and apoptotic pathways as MSTN targets and are in favour of a role of MSTN as a modulator of cell survival in vivo. PMID:19397818

  18. Evanescent acoustic waves: Production and scattering by resonant targets

    NASA Astrophysics Data System (ADS)

    Osterhoudt, Curtis F.

    Small targets with acoustic resonances which may be excited by incident acoustic planewaves are shown to possess high-Q modes ("organ-pipe" modes) which may be suitable for ocean-based calibration and ranging purposes. The modes are modeled using a double point-source model; this, along with acoustic reciprocity and inversion symmetry, is shown to adequately model the backscattering form functions of the modes at low frequencies. The backscattering form-functions are extended to apply to any bistatic acoustic experiment using the targets when the target response is dominated by the modes in question. An interface between two fluids which each approximate an unbounded half-space has been produced in the laboratory. The fluids have different sound speeds. When sound is incident on this interface at beyond the critical angle from within the first fluid, the second fluid is made to evince a region dominated by evanescent acoustic energy. Such a system is shown to be an possible laboratory-based proxy for a flat sediment bottom in the ocean, or sloped (unrippled) bottom in littoral environments. The evanescent sound field is characterized and shown to have complicated features despite the simplicity of its production. Notable among these features is the presence of dips in the soundfield amplitude, or "quasi-nulls". These are proposed to be extremely important when considering the return from ocean-based experiments. The soundfield features are also shown to be accurately predicted and characterized by wavenumber-integration software. The targets which exhibit organ-pipe modes in the free-field are shown to also be excited by the evanescent waves, and may be used as soundfield probes when the target returns are well characterized. Alternately, if the soundfield is well-known, the target parameters may be extracted from back- or bistatic-scattering experiments in evanescent fields. It is shown that the spatial decay rate as measured by a probe directly in the evanescent

  19. Selective ribosome profiling as a tool to study the interaction of chaperones and targeting factors with nascent polypeptide chains and ribosomes

    PubMed Central

    Becker, Annemarie H.; Oh, Eugene; Weissman, Jonathan S.; Kramer, Günter; Bukau, Bernd

    2014-01-01

    A plethora of factors is involved in the maturation of newly synthesized proteins, including chaperones, membrane targeting factors, and enzymes. Many factors act cotranslationally through association with ribosome-nascent chain complexes (RNCs), but their target specificities and modes of action remain poorly understood. We developed selective ribosome profiling (SeRP) to identify substrate pools and points of RNC engagement of these factors. SeRP is based on sequencing mRNA fragments covered by translating ribosomes (general ribosome profiling, RP), combined with a procedure to selectively isolate RNCs whose nascent polypeptides are associated with the factor of interest. Factor–RNC interactions are stabilized by crosslinking, the resulting factor–RNC adducts are then nuclease-treated to generate monosomes, and affinity-purified. The ribosome-extracted mRNA footprints are converted to DNA libraries for deep sequencing. The protocol is specified for general RP and SeRP in bacteria. It was first applied to the chaperone trigger factor and is readily adaptable to other cotranslationally acting factors, including eukaryotic factors. Factor–RNC purification and sequencing library preparation takes 7–8 days, sequencing and data analysis can be completed in 5–6 days. PMID:24136347

  20. Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous‐cell carcinoma

    PubMed Central

    Syed, Nazia; Barbhuiya, Mustafa A.; Pinto, Sneha M.; Nirujogi, Raja Sekhar; Renuse, Santosh; Datta, Keshava K.; Khan, Aafaque Ahmad; Srikumar, Kotteazeth; Prasad, T. S. Keshava; Kumar, M. Vijaya; Kumar, Rekha Vijay; Chatterjee, Aditi; Pandey, Akhilesh

    2015-01-01

    Esophageal squamous‐cell carcinoma (ESCC) is one of the most common malignancies in Asia. Currently, surgical resection of early‐stage tumor is the best available treatment. However, most patients present late when surgery is not an option. Data suggest that chemotherapy regimens are inadequate for clinical management of advanced cancer. Targeted therapy has emerged as one of the most promising approaches to treat several malignancies. A prerequisite for developing targeted therapy is prior knowledge of proteins and pathways that drive proliferation in malignancies. We carried out phosphotyrosine profiling across four different ESCC cell lines and compared it to non‐neoplastic Het‐1A cell line to identify activated tyrosine kinase signaling pathways in ESCC. A total of 278 unique phosphopeptides were identified across these cell lines. This included several tyrosine kinases and their substrates that were hyperphosphorylated in ESCC. Ephrin receptor A2 (EPHA2), a receptor tyrosine kinase, was hyperphosphorylated in all the ESCC cell lines used in the study. EPHA2 is reported to be oncogenic in several cancers and is also known to promote metastasis. Immunohistochemistry‐based studies have revealed EPHA2 is overexpressed in nearly 50% of ESCC. We demonstrated EPHA2 as a potential therapeutic target in ESCC by carrying out siRNA‐based knockdown studies. Knockdown of EPHA2 in ESCC cell line TE8 resulted in significant decrease in cell proliferation and invasion, suggesting it is a promising therapeutic target in ESCC that warrants further evaluation. PMID:25366905

  1. Characterization and fabrication of target materials for RIB generation

    NASA Astrophysics Data System (ADS)

    Welton, R. F.; Janney, M. A.; Mueller, P. E.; Ortman, W. K.; Rauniyar, R.; Stracener, D. W.; Williams, C. L.

    2001-07-01

    This report discusses two techniques developed at the Oak Ridge National Laboratory (ORNL) that are employed for the fabrication and characterization of targets used in the production of Radioactive Ion Beams (RIBs). First, our method of in-house fabrication of uranium carbide targets is discussed. We have found that remarkably uniform coatings of UC2 can be formed on the microstructure of porous C matrices. The technique has been used to form UC2 layers on highly thermally conductive graphitic foams. Targets fabricated in this fashion have been tested under low-intensity proton bombardment and yields of selected radioactive species are reported. This report also describes an off-line test stand for the investigation of effusive and diffusive transport in RIB target/ion sources. Permeation rates of gases and vapors passing through a high temperature membrane or through an effusive channel constructed from the material under investigation are recorded. Diffusion coefficients and adsorption enthalpies, which characterize the interaction of RIB species with materials of the target/ion source, are extracted from the time profile of the recorded data. Examples of diffusion, effusion, and conductance measurements are provided.

  2. Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing.

    PubMed

    Marshall, Owen J; Southall, Tony D; Cheetham, Seth W; Brand, Andrea H

    2016-09-01

    This protocol is an extension to: Nat. Protoc. 2, 1467-1478 (2007); doi:10.1038/nprot.2007.148; published online 7 June 2007The ability to profile transcription and chromatin binding in a cell-type-specific manner is a powerful aid to understanding cell-fate specification and cellular function in multicellular organisms. We recently developed targeted DamID (TaDa) to enable genome-wide, cell-type-specific profiling of DNA- and chromatin-binding proteins in vivo without cell isolation. As a protocol extension, this article describes substantial modifications to an existing protocol, and it offers additional applications. TaDa builds upon DamID, a technique for detecting genome-wide DNA-binding profiles of proteins, by coupling it with the GAL4 system in Drosophila to enable both temporal and spatial resolution. TaDa ensures that Dam-fusion proteins are expressed at very low levels, thus avoiding toxicity and potential artifacts from overexpression. The modifications to the core DamID technique presented here also increase the speed of sample processing and throughput, and adapt the method to next-generation sequencing technology. TaDa is robust, reproducible and highly sensitive. Compared with other methods for cell-type-specific profiling, the technique requires no cell-sorting, cross-linking or antisera, and binding profiles can be generated from as few as 10,000 total induced cells. By profiling the genome-wide binding of RNA polymerase II (Pol II), TaDa can also identify transcribed genes in a cell-type-specific manner. Here we describe a detailed protocol for carrying out TaDa experiments and preparing the material for next-generation sequencing. Although we developed TaDa in Drosophila, it should be easily adapted to other organisms with an inducible expression system. Once transgenic animals are obtained, the entire experimental procedure-from collecting tissue samples to generating sequencing libraries-can be accomplished within 5 d.

  3. Energy release, beam attenuation radiation damage, gas production and accumulation of long-lived activity in Pb, Pb-Bi and Hg targets

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

    Shubin, Yu.N.

    1996-06-01

    The calculation and analysis of the nuclei concentrations and long-lived residual radioactivity accumulated in Pb, Pb-Bi and Hg targets irradiated by 800 MeV, 30 mA proton beam have been performed. The dominating components to the total radioactivity of radionuclides resulting from fission and spallation reactions and radiative capture by both target nuclei and accumulated radioactive nuclei for various irradiation and cooling times were analyzed. The estimations of spectral component contributions of neutron and proton fluxes to the accumulated activity were carried out. The contributions of fission products to the targets activity and partial activities of main long-lived fission products tomore » the targets activity and partial activities of main long-lived fission products were evaluated. The accumulation of Po isotopes due to reactions induced by secondary alpha-particles were found to be important for the Pb target as compared with two-step radiative capture. The production of Tritium in the targets and its contribution to the total targets activity was considered in detail. It is found that total activities of both targets are close to one another.« less

  4. miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells

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

    Qin, Yaguang; Cheng, Chuanyao; Lu, Hong, E-mail: honglu6512@163.com

    miR-4458, a new tumor-suppressor, was reported to down-regulated in human hepatocellular carcinoma. The expression status, roles and inhibitory mechanisms of miR-4458 in other tumors still need to be clarified. The aim of this study is to investigate the effects of miR-4458 and to elucidate the potential mechanism in colon cancer cells. Using bioinformatic databases, we predicted that hexokinase2 (HK2), a rate-limiting enzyme in the glycolytic pathway, was a target of miR-4458, so the effects of miR-4458 on glycolysis and lactate production was assessed in colon cancer cells. We found that miR-4458 was down-regulated and HK2 was up-regulated in colon cancermore » cells. Overexpression of miR-4458 inhibited proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. Luciferase activity assays showed that HK2 was a direct target of miR-4458. Moreover, knockdown of HK2 by specific RNAi also suppressed proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. In conclusion, our findings suggested that miR-4458 inhibited the progression of colon cancer cells by inhibition of glycolysis and lactate production via directly targeting HK2 mRNA. - Highlights: • miR-4458 is down-regulated in colon cancer cells. • miR-4458 suppresses proliferation, glycolysis, and lactate production. • HK2 is a target of miR-4458. • HK2 knockdown inhibits proliferation, glycolysis, and lactate production.« less

  5. Leveraging non-targeted metabolite profiling via statistical genomics

    USDA-ARS?s Scientific Manuscript database

    One of the challenges of systems biology is to integrate multiple sources of data in order to build a cohesive view of the system of study. Here we describe the mass spectrometry based profiling of maize kernels, a model system for genomic studies and a cornerstone of the agroeconomy. Using a networ...

  6. Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment

    PubMed Central

    Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

    2016-01-01

    Objective To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). Background TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Methods Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. Results API costs per kg were $347–$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128–$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Conclusions Mass generic production of several TKIs could achieve treatment prices in the range of $128–$4020 per person-year, versus current US prices of $75161–$139 138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. PMID:26817636

  7. Systemic analysis of genome-wide expression profiles identified potential therapeutic targets of demethylation drugs for glioblastoma.

    PubMed

    Ning, Tongbo; Cui, Hao; Sun, Feng; Zou, Jidian

    2017-09-05

    Glioblastoma represents one of the most aggressive malignant brain tumors with high morbidity and motility. Demethylation drugs have been developed for its treatment with little efficacy has been observed. The purpose of this study was to screen therapeutic targets of demethylation drugs or bioactive molecules for glioblastoma through systemic bioinformatics analysis. We firstly downloaded genome-wide expression profiles from the Gene Expression Omnibus (GEO) and conducted the primary analysis through R software, mainly including preprocessing of raw microarray data, transformation between probe ID and gene symbol and identification of differential expression genes (DEGs). Secondly, functional enrichment analysis was conducted via the Database for Annotation, Visualization and Integrated Discovery (DAVID) to explore biological processes involved in the development of glioblastoma. Thirdly, we constructed protein-protein interaction (PPI) network of interested genes and conducted cross analysis for multi datasets to obtain potential therapeutic targets for glioblastoma. Finally, we further confirmed the therapeutic targets through real-time RT-PCR. As a result, biological processes that related to cancer development, amino metabolism, immune response and etc. were found to be significantly enriched in genes that differential expression in glioblastoma and regulated by 5'aza-dC. Besides, network and cross analysis identified ACAT2, UFC1 and CYB5R1 as novel therapeutic targets of demethylation drugs which also confirmed by real time RT-PCR. In conclusions, our study identified several biological processes and genes that involved in the development of glioblastoma and regulated by 5'aza-dC, which would be helpful for the treatment of glioblastoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    EPA Pesticide Factsheets

    Background: Trends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies.Objective: In the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system.Methods: We used U.S. EPA??s animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA??s in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features. Results: A phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network. Conclusion: Computational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarch

  9. Targeted and untargeted high resolution mass approach for a putative profiling of glycosylated simple phenols in hybrid grapes.

    PubMed

    Barnaba, Chiara; Dellacassa, Eduardo; Nicolini, Giorgio; Giacomelli, Mattia; Roman Villegas, Tomas; Nardin, Tiziana; Larcher, Roberto

    2017-08-01

    Vitis vinifera is one of the most widespread grapevines around the world representing the raw material for high quality wine production. The availability of more resistant interspecific hybrid vine varieties, developed from crosses between Vitis vinifera and other Vitis species, has generated much interest, also due to the low environmental effect of production. However, hybrid grape wine composition and varietal differences between interspecific hybrids have not been well defined, particularly for the simple phenols profile. The dynamic of these phenols in wines, where the glycosylated forms can be transformed into the free ones during winemaking, also raises an increasing health interest by their role as antoxidants in wine consumers. In this work an on-line SPE clean-up device, to reduce matrix interference, was combined with ultra-high liquid chromatography-high resolution mass spectrometry in order to increase understanding of the phenolic composition of hybrid grape varieties. Specifically, the phenolic composition of 4 hybrid grape varieties (red, Cabernet Cantor and Prior; white, Muscaris and Solaris) and 2 European grape varieties (red, Merlot; white, Chardonnay) was investigated, focusing on free and glycosidically bound simple phenols and considering compound distribution in pulp, skin, seeds and wine. Using a targeted approach 53 free simple phenols and 7 glycosidic precursors were quantified with quantification limits ranging from 0.001 to 2mgKg -1 and calibration R 2 of 0.99 for over 86% of compounds. The untargeted approach made it possible to tentatively identify 79 glycosylated precursors of selected free simple phenols in the form of -hexoside (N=30), -pentoside (21), -hexoside-hexoside (17), -hexoside-pentoside (4), -pentoside-hexoside (5) and -pentoside-pentoside (2) derivatives on the basis of accurate mass, isotopic pattern and MS/MS fragmentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer

    PubMed Central

    Lee, John K.; Bangayan, Nathanael J.; Chai, Timothy; Smith, Bryan A.; Pariva, Tiffany E.; Yun, Sangwon; Vashisht, Ajay; Zhang, Qingfu; Park, Jung Wook; Corey, Eva; Huang, Jiaoti; Wohlschlegel, James; Witte, Owen N.

    2018-01-01

    Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer. Here, we show that PrAd and NEPC can be broadly discriminated by cell-surface profiles based on the analysis of prostate cancer gene expression datasets. To overcome a dependence on predictions of human cell-surface genes and an assumed correlation between mRNA levels and protein expression, we integrated transcriptomic and cell-surface proteomic data generated from a panel of prostate cancer cell lines to nominate cell-surface markers associated with these cancer subtypes. FXYD3 and CEACAM5 were validated as cell-surface antigens enriched in PrAd and NEPC, respectively. Given the lack of effective treatments for NEPC, CEACAM5 appeared to be a promising target for cell-based immunotherapy. As a proof of concept, engineered chimeric antigen receptor T cells targeting CEACAM5 induced antigen-specific cytotoxicity in NEPC cell lines. Our findings demonstrate that the surfaceomes of PrAd and NEPC reflect unique cancer differentiation states and broadly represent vulnerabilities amenable to therapeutic targeting. PMID:29686080

  11. Targets for production of the medical radioisotopes with alpha and proton or deuteron beams

    NASA Astrophysics Data System (ADS)

    Stolarz, Anna; Kowalska, J. A.; Jastrzebski, J.; Choiński, J.; Sitarz, M.; Szkliniarz, K.; Trzcińska, A.; Zipper, W.

    2018-05-01

    The research quantities of some medical radioisotopes were produced in reactions induced by 32 MeV internal alpha beam (211At, Sc isotopes), 16 MeV and 28 MeV proton beams (Sc isotopes) and 8 MeV deuteron beam (Sc isotopes). The frame-less targets used for irradiation with internal alpha beam were prepared from elemental (Bi for 211At) and compound (CaCO3 for Sc radioisotopes) materials. The CaCO3 powder targets were also used for production of Sc radioisotopes with proton or deuteron external beams. Methods developed for preparation of the targets suitable for the irradiating beam type are described in this work.

  12. Maternal Phthalate and Personal Care Products Exposure Alters Extracellular Placental miRNA Profile in Twin Pregnancies.

    PubMed

    Zhong, Jia; Baccarelli, Andrea A; Mansur, Abdallah; Adir, Michal; Nahum, Ravit; Hauser, Russ; Bollati, Valentina; Racowsky, Catherine; Machtinger, Ronit

    2018-01-01

    Prenatal exposure to endocrine-disrupting chemicals (EDCs) exerts both short- and long-term adverse effects on the developing fetus. However, the mechanisms underlying these effects have yet to be uncovered. Maternal-fetal signaling is mediated in part by signaling molecules (eg, microRNAs [miRNAs]) contained in extracellular vesicles (EVs) that are released by the placenta into the maternal circulation. We investigated whether maternal exposure to the EDCs phthalates and personal care products alters the miRNA profile of placental-derived EVs circulating in maternal blood. Blood and urine samples from pregnant women with uncomplicated term dichorionic, diamniotic twin pregnancies were analyzed as part of a larger study investigating correlations between exposure of phthalate and personal care products and epigenetic alterations in twin pregnancies. We explored correlations between maternal urinary levels of 13 phthalate and 12 personal care products metabolites and the miRNA profile of placental EVs (EV-miRNAs) circulating in maternal blood. The expression of miR-518e was highest among women with high urinary levels of monobenzyl phthalate and methyl paraben. miR-373-3p was the least expressed in women exposed to high levels of methyl paraben, and miR-543 was significantly downregulated in women exposed to high levels of paraben metabolites, dichlorophenol metabolites, and triclosan. In conclusion, this pilot study reveals that prenatal exposure to EDCs is associated with altered profile of circulating placenta-derived EV-miRNAs. Further studies are needed to generalize these results to singleton pregnancies and to assess whether these alterations are associated with pregnancy complications.

  13. Probiotic Soy Product Supplemented with Isoflavones Improves the Lipid Profile of Moderately Hypercholesterolemic Men: A Randomized Controlled Trial.

    PubMed

    Cavallini, Daniela Cardoso Umbelino; Manzoni, Marla Simone Jovenasso; Bedani, Raquel; Roselino, Mariana Nougalli; Celiberto, Larissa Sbaglia; Vendramini, Regina Célia; de Valdez, Graciela Font; Abdalla, Dulcinéia Saes Parra; Pinto, Roseli Aparecida; Rosetto, Daniella; Valentini, Sandro Roberto; Rossi, Elizeu Antonio

    2016-01-19

    Cardiovascular disease is the leading cause of worldwide morbidity and mortality. Several studies have demonstrated that specific probiotics affect the host's metabolism and may influence the cardiovascular disease risk. The aim of this study was to investigate the influence of an isoflavone-supplemented soy product fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 on cardiovascular risk markers in moderately hypercholesterolemic subjects. Randomized placebo-controlled double-blind trial Setting: São Paulo State University in Araraquara, SP, Brazil. 49 male healthy men with total cholesterol (TC) >5.17 mmol/L and <6.21 mmol/L Intervention: The volunteers have consumed 200 mL of the probiotic soy product (group SP-10(10) CFU/day), isoflavone-supplemented probiotic soy product (group ISP-probiotic plus 50 mg of total isoflavones/100 g) or unfermented soy product (group USP-placebo) for 42 days in a randomized, double-blind study. Lipid profile and additional cardiovascular biomarkers were analyzed on days 0, 30 and 42. Urine samples (24 h) were collected at baseline and at the end of the experiment so as to determine the isoflavones profile. After 42 days, the ISP consumption led to improved total cholesterol, non-HDL-C (LDL + IDL + VLDL cholesterol fractions) and electronegative LDL concentrations (reduction of 13.8%, 14.7% and 24.2%, respectively, p < 0.05). The ISP and SP have prevented the reduction of HDL-C level after 42 days. The C-reactive protein and fibrinogen levels were not improved. The equol production by the ISP group subjects was inversely correlated with electronegative LDL concentration. The results suggest that a regular consumption of this probiotic soy product, supplemented with isoflavones, could contribute to reducing the risk of cardiovascular diseases in moderately hypercholesterolemic men, through the an improvement in lipid profile and antioxidant properties.

  14. Probiotic Soy Product Supplemented with Isoflavones Improves the Lipid Profile of Moderately Hypercholesterolemic Men: A Randomized Controlled Trial

    PubMed Central

    Cardoso Umbelino Cavallini, Daniela; Jovenasso Manzoni, Marla Simone; Bedani, Raquel; Roselino, Mariana Nougalli; Celiberto, Larissa Sbaglia; Vendramini, Regina Célia; de Valdez, Graciela Font; Saes Parra Abdalla, Dulcinéia; Aparecida Pinto, Roseli; Rosetto, Daniella; Roberto Valentini, Sandro; Antonio Rossi, Elizeu

    2016-01-01

    Background: Cardiovascular disease is the leading cause of worldwide morbidity and mortality. Several studies have demonstrated that specific probiotics affect the host’s metabolism and may influence the cardiovascular disease risk. Objectives: The aim of this study was to investigate the influence of an isoflavone-supplemented soy product fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416 on cardiovascular risk markers in moderately hypercholesterolemic subjects. Design: Randomized placebo-controlled double-blind trial Setting: São Paulo State University in Araraquara, SP, Brazil. Participants: 49 male healthy men with total cholesterol (TC) >5.17 mmol/L and <6.21 mmol/L Intervention: The volunteers have consumed 200 mL of the probiotic soy product (group SP-1010 CFU/day), isoflavone-supplemented probiotic soy product (group ISP–probiotic plus 50 mg of total isoflavones/100 g) or unfermented soy product (group USP-placebo) for 42 days in a randomized, double-blind study. Main outcome measures: Lipid profile and additional cardiovascular biomarkers were analyzed on days 0, 30 and 42. Urine samples (24 h) were collected at baseline and at the end of the experiment so as to determine the isoflavones profile. Results: After 42 days, the ISP consumption led to improved total cholesterol, non-HDL-C (LDL + IDL + VLDL cholesterol fractions) and electronegative LDL concentrations (reduction of 13.8%, 14.7% and 24.2%, respectively, p < 0.05). The ISP and SP have prevented the reduction of HDL-C level after 42 days. The C-reactive protein and fibrinogen levels were not improved. The equol production by the ISP group subjects was inversely correlated with electronegative LDL concentration. Conclusions: The results suggest that a regular consumption of this probiotic soy product, supplemented with isoflavones, could contribute to reducing the risk of cardiovascular diseases in moderately hypercholesterolemic men, through the an improvement in

  15. Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis

    PubMed Central

    Loftus, Stacie K.; Baxter, Laura L.; Cronin, Julia C.; Fufa, Temesgen D.; Pavan, William J.

    2017-01-01

    Summary Hypoxia and HIF1α signaling direct tissue-specific gene responses regulating tumor progression, invasion and metastasis. By integrating HIF1α knockdown and hypoxia-induced gene expression changes, this study identifies a melanocyte-specific, HIF1α-dependent/hypoxia-responsive gene expression signature. Integration of these gene expression changes with HIF1α ChIP-Seq analysis identifies 81 HIF1α direct target genes in melanocytes. The expression levels for ten of the HIF1α direct targets – GAPDH, PKM, PPAT, DARS, DTWD1, SEH1L, ZNF292, RLF, AGTRAP, and GPC6 – are significantly correlated with reduced time of Disease Free Status (DFS) in melanoma by logistic regression (P-value =0.0013) and ROC curve analysis (AUC= 0.826, P-value<0.0001). This HIF1α-regulated profile defines a melanocyte-specific response under hypoxia, and demonstrates the role of HIF1α as an invasive cell state gatekeeper in regulating cellular metabolism, chromatin and transcriptional regulation, vascularization and invasion. PMID:28168807

  16. Trends in greenhouse gas emissions from consumption and production of animal food products - implications for long-term climate targets.

    PubMed

    Cederberg, C; Hedenus, F; Wirsenius, S; Sonesson, U

    2013-02-01

    -increase target of 2° might imply a severe constraint on the long-term global consumption of animal food. Due to the relatively limited potential for reducing food-related emissions by higher productivity and technological means, structural changes in food consumption towards less emission-intensive food might be required for meeting the 2° target.

  17. Assessment of candidates for target window material in accelerator-driven molybdenum-99 production

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

    Strons, Philip; Bailey, James; Makarashvili, Vakhtang

    2016-10-01

    NorthStar Medical Technologies is pursuing production of an important medical isotope, Mo-99, through a photo-nuclear reaction of a Mo-100 target using a high-power electron accelerator. The current target utilizes an Inconel 718 window. The purpose of this study was to evaluate other candidate materials for the target window, which separates the high-pressure helium gas inside the target from the vacuum inside the accelerator beamline and is subjected to significant stress. Our initial analysis assessed the properties (density, thermal conductivity, maximum stress, minimum window thickness, maximum temperature, and figure of merit) for a range of materials, from which the three mostmore » promising were chosen: Inconel 718, 250 maraging steel, and standard-grade beryllium. These materials were subjected to further analysis to determine the effects of thermal and mechanical strain versus beam power at varying thicknesses. Both beryllium and the maraging steel were calculated to withstand more than twice as high beam power than Inconel 718.« less

  18. A nutrient profiling system for the (re)formulation of a global food and beverage portfolio.

    PubMed

    Vlassopoulos, Antonis; Masset, Gabriel; Charles, Veronique Rheiner; Hoover, Cassandra; Chesneau-Guillemont, Caroline; Leroy, Fabienne; Lehmann, Undine; Spieldenner, Jörg; Tee, E-Siong; Gibney, Mike; Drewnowski, Adam

    2017-04-01

    To describe the Nestlé Nutritional Profiling System (NNPS) developed to guide the reformulation of Nestlé products, and the results of its application in the USA and France. The NNPS is a category-specific system that calculates nutrient targets per serving as consumed, based on age-adjusted dietary guidelines. Products are aggregated into 32 food categories. The NNPS ensures that excessive amounts of nutrients to limit cannot be compensated for by adding nutrients to encourage. A study was conducted to measure changes in nutrient profiles of the most widely purchased Nestlé products from eight food categories (n = 99) in the USA and France. A comparison was made between the 2009-2010 and 2014-2015 products. The application of the NNPS between 2009-2010 and 2014-2015 was associated with an overall downwards trend for all nutrients to limit. Sodium and total sugars contents were reduced by up to 22 and 31 %, respectively. Saturated Fatty Acids and total fat reductions were less homogeneous across categories, with children products having larger reductions. Energy per serving was reduced by <10 % in most categories, while serving sizes remained unchanged. The NNPS sets feasible and yet challenging targets for public health-oriented reformulation of a varied product portfolio; its application was associated with improved nutrient density in eight major food categories in the USA and France. Confirmatory analyses are needed in other countries and food categories; the impact of such a large-scale reformulation on dietary intake and health remains to be investigated.

  19. GC-MS Profiling of Volatile Components in Different Fermentation Products of Cordyceps Sinensis Mycelia.

    PubMed

    Zhang, Hongyang; Li, Yahui; Mi, Jianing; Zhang, Min; Wang, Yuerong; Jiang, Zhihong; Hu, Ping

    2017-10-24

    The fermentation products of Cordyceps sinensis ( C. sinensis ) mycelia are sustainable substitutes for natural C. sinensis . However, the volatile compositions of the commercial products are still unclear. In this paper, we have developed a simultaneous distillation-extraction (SDE) and gas chromatography-mass spectrometry (GC-MS) method for the profiling of volatile components in five fermentation products. A total of 64, 39, 56, 52, and 44 components were identified in the essential oils of Jinshuibao capsule (JSBC), Bailing capsule (BLC), Zhiling capsule (ZLC), Ningxinbao capsule (NXBC), and Xinganbao capsule (XGBC), respectively. 5,6-Dihydro-6-pentyl-2H-pyran-2-one (massoia lactone) was first discovered as the dominant component in JSBC volatiles. Fatty acids including palmitic acid (C16:0) and linoleic acid (C18:2) were also found to be major volatile compositions of the fermentation products. The multivariate partial least squares-discriminant analysis (PLS-DA) showed a clear discrimination among the different commercial products as well as the counterfeits. This study may provide further chemical evidences for the quality evaluation of the fermentation products of C. sinensis mycelia.

  20. Gene expression profiling in multiple myeloma--reporting of entities, risk, and targets in clinical routine.

    PubMed

    Meissner, Tobias; Seckinger, Anja; Rème, Thierry; Hielscher, Thomas; Möhler, Thomas; Neben, Kai; Goldschmidt, Hartmut; Klein, Bernard; Hose, Dirk

    2011-12-01

    Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification. The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore). The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively. GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities. ©2011 AACR.

  1. Feasibility study Part I - Thermal hydraulic analysis of LEU target for {sup 99}Mo production in Tajoura reactor

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

    Bsebsu, F.M.; Abotweirat, F.; Elwaer, S.

    2008-07-15

    The Renewable Energies and Water Desalination Research Center (REWDRC), Libya, will implement the technology for {sup 99}Mo isotope production using LEU foil target, to obtain new revenue streams for the Tajoura nuclear research reactor and desiring to serve the Libyan hospitals by providing the medical radioisotopes. Design information is presented for LEU target with irradiation device and irradiation Beryllium (Be) unit in the Tajoura reactor core. Calculated results for the reactor core with LEU target at different level of power are presented for steady state and several reactivity induced accident situations. This paper will present the steady state thermal hydraulicmore » design and transient analysis of Tajoura reactor was loaded with LEU foil target for {sup 99}Mo production. The results of these calculations show that the reactor with LEU target during the several cases of transient are in safe and no problems will occur. (author)« less

  2. Identification of testis-specific male contraceptive targets: insights from transcriptional profiling of the cycle of the rat seminiferous epithelium and purified testicular cells.

    PubMed

    Johnston, Daniel S; Jelinsky, Scott A; Zhi, Yu; Finger, Joshua N; Kopf, Gregory S; Wright, William W

    2007-12-01

    In an effort to identify novel targets for the development of nonhormonal male contraceptives, genome-wide transcriptional profiling of the rat testis was performed. Specifically, enzymatically purified spermatogonia plus early spermatocyctes, pachytene spermatocytes, round spermatids, and Sertoli cells was analyzed along with microdissected rat seminiferous tubules at stages I, II-III, IV-V, VI, VIIa,b, VIIc,d, VIII, IX- XI, XII, XIII-XIV of the cycle of the seminiferous epithelium using RAE 230_2.0 microarrays. The combined analysis of these studies identified 16,971 expressed probe sets on the array. How these expression data, combined with additional bioinformatic data analysis and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis, led to the identification of 58 genes that have 1000-fold higher expression transcriptionally in the testis when compared to over 20 other nonreproductive tissues is described. The products of these genes may play important roles in testicular and/or sperm function, and further investigation on their utility as nonhormonal contraceptive targets is warranted. Moreover, these microarray data have been used to expedite the identification of a mutation in RIKEN cDNA 2410004F06 gene as likely being responsible for spermatogenic failure in a line of infertile mice generated by N-ethyl-N-nitrosourea (ENU) mutagenesis. The microarray data and the qRT-PCR data described are available in the Mammalian Reproductive Genetics database (http://mrg.genetics.washington.edu/).

  3. Beam profile measurements for target designators

    NASA Astrophysics Data System (ADS)

    Frank, J. D.

    1985-02-01

    An American aerospace company has conducted a number of investigations with the aim to improve on the tedious slow manual methods of measuring pulsed lasers for rangefinders, giving particular attention to beam divergence which is studied by varying aperture sizes and positions in the laser beam path. Three instruments have been developed to make the involved work easier to perform. One of these, the Automatic Laser Instrumentation and Measurement System (ALIMS), consists of an optical bench, a digital computer, and three bays of associated electronic instruments. ALIMS uses the aperture method to measure laser beam alignment and divergence. The Laser Intensity Profile System (LIPS) consists of a covered optical bench and a two bay electronic equipment and control console. The Automatic Laser Test Set (ALTS) utilizes a 50 x 50 silicon photodiode array to characterize military laser systems automatically. Details regarding the conducted determinations are discussed.

  4. Detailed fatty acid profile of milk, cheese, ricotta and by products, from cows grazing summer highland pastures.

    PubMed

    Bergamaschi, Matteo; Bittante, Giovanni

    2017-08-01

    In this research two-dimensional GC was used to analyse, for the first time, the detailed fatty acid (FA) profiles of 11 dairy matrices: raw milk (evening whole, evening partially skimmed, morning whole, and vat milk), cream, fresh cheese, whey, ricotta, scotta, 6- and 12-month-ripened cheeses, obtained across artisanal cheese- and ricotta-making trials carried out during the summer period while cows were on highland pastures. Samples were collected during 7 cheese- and ricotta-making procedures carried out at 2-week intervals from bulk milk to study possible differences in the transfer and modification of FA. Compared with morning milk, evening milk had fewer de novo synthetised FA. The detailed FA profile of partially skimmed milk differed little from that of evening whole milk before skimming, but the cream obtained differed from partially skimmed milk and from fresh cheese in about half the FA, due mainly to higher contents of all de novo FA, and lower contents of n-3 and n-6 FA. Fresh cheese and whey had similar FA profiles. The ricotta manufacturing process affected the partition of FA between ricotta and scotta, the FA profile of the latter differing in terms of groups and individual FA from the former, whereas ricotta and fresh cheese had similar composition of FA. In general, there was an increase in medium-chain saturated FA, and a decrease in many polyunsaturated FA during the first 6 months of ripening, but not during the second 6 months. Two-dimensional GC yielded a very detailed and informative FA profile on all the 11 dairy products and by-products analysed.

  5. In-situ vacuum deposition technique of lithium on neutron production target for BNCT

    NASA Astrophysics Data System (ADS)

    Ishiyama, S.; Baba, Y.; Fujii, R.; Nakamura, M.; Imahori, Y.

    2012-10-01

    For the purpose of avoiding the radiation blistering of the lithium target for neutron production in BNCT (Boron Neutron Capture Therapy) device, trilaminar Li target, of which palladium thin layer was inserted between cupper substrate and Li layer, was newly designed. In-situ vacuum deposition and electrolytic coating techniques were applied to validate the method of fabrication of the Li/Pd/Cu target, and the layered structures of the synthesized target were characterized. In-situ vacuum re-deposition technique was also established for repairing and maintenance for lithium target damaged. Following conclusions were derived; (1) Uniform lithium layers with the thickness from 1.6 nm to a few hundreds nanometer were formed on Pd/Cu multilayer surface by in situ vacuum deposition technique using metallic lithium as a source material. (2) Re-deposition of lithium layer on Li surface can be achieved by in situ vacuum deposition technique. (3) Small amount of water and carbonate was observed on the top surface of Li. But the thickness of the adsorbed layer was less than monolayer, which will not affect the quality of the Li target. (4) The formation of Pd-Li alloy layer was observed at the Pd and Li interface. The alloy layer would contribute to the stability of the Li layer.

  6. Pentoses and light intensity increase the growth and carbohydrate production and alter the protein profile of Chlorella minutissima.

    PubMed

    Freitas, B C B; Cassuriaga, A P A; Morais, M G; Costa, J A V

    2017-08-01

    High concentrations of carbon, which is considered a necessary element, are required for microalgal growth. Therefore, the identification of alternative carbon sources available in large quantities is increasingly important. This study evaluated the effects of light variation and pentose addition on the carbohydrate content and protein profile of Chlorella minutissima grown in a raceway photobioreactor. The kinetic parameters, carbohydrate content, and protein profile of Chlorella minutissima and its theoretical potential for ethanol production were estimated. The highest cellular concentrations were obtained with a light intensity of 33.75µmol.m -2 .s -1 . Arabinose addition combined with a light intensity of 33.75µmol.m -2 .s -1 increased the carbohydrate content by 53.8% and theoretically produced 39.1mL·100g -1 ethanol. All of the assays showed that a lower light availability altered the protein profile. The luminous intensity affects xylose and arabinose assimilation and augments the carbohydrate content in C. minutissima, making this microalga appropriate for bioethanol production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Modeling of a cyclotron target for the production of 11C with Geant4.

    PubMed

    Chiappiniello, Andrea; Zagni, Federico; Infantino, Angelo; Vichi, Sara; Cicoria, Gianfranco; Morigi, Maria Pia; Marengo, Mario

    2018-04-12

    In medical cyclotron facilities, 11C is produced according to the 14N(p,α)11C reaction and widely employed in studies of prostate and brain cancers by Positron Emission Tomography. It is known from literature [1] that the 11C-target assembly shows a reduction in efficiency during time, meaning a decrease of activity produced at the end of bombardment. This effect might depend on aspects still not completely known. Possible causes of the loss of performance of the 11C-target assembly were addressed by Monte Carlo simulations. Geant4 was used to model the 11C-target assembly of a GE PETtrace cyclotron. The physical and transport parameters to be used in the energy range of medical applications were extracted from literature data and 11C routine productions. The Monte Carlo assessment of 11C saturation yield was performed varying several parameters such as the proton energy and the angle of the target assembly with respect to the proton beam. The estimated 11C saturation yield is in agreement with IAEA data at the energy of interest, while is about the 35% greater than experimental value. A more comprehensive modeling of the target system, including thermodynamic effect, is required. The energy absorbed in the inner layer of the target chamber was up to 46.5 J/mm2 under typical irradiation conditions. This study shows that Geant4 is potentially a useful tool to design and optimize targetry for PET radionuclide productions. Tests to choose the Geant4 physics libraries should be performed before using this tool with different energies and materials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding Histone Deacetylase Inhibitors with Picomolar Affinities.

    PubMed

    Kitir, Betül; Maolanon, Alex R; Ohm, Ragnhild G; Colaço, Ana R; Fristrup, Peter; Madsen, Andreas S; Olsen, Christian A

    2017-09-26

    Histone deacetylases (HDACs) are validated targets for treatment of certain cancer types and play numerous regulatory roles in biology, ranging from epigenetics to metabolism. Small molecules are highly important as tool compounds for probing these mechanisms as well as for the development of new medicines. Therefore, detailed mechanistic information and precise characterization of the chemical probes used to investigate the effects of HDAC enzymes are vital. We interrogated Nature's arsenal of macrocyclic nonribosomal peptide HDAC inhibitors by chemical synthesis and evaluation of more than 30 natural products and analogues. This furnished surprising trends in binding affinities for the various macrocycles, which were then exploited for the design of highly potent class I and IIb HDAC inhibitors. Furthermore, thorough kinetic investigation revealed unexpected inhibitory mechanisms of important tool compounds as well as the approved drug Istodax (romidepsin). This work provides novel inhibitors with varying potencies, selectivity profiles, and mechanisms of inhibition and, importantly, affords insight into known tool compounds that will improve the interpretation of their effects in biology and medicine.

  9. Depth profile of production yields of natPb(p, xn) 206,205,204,203,202,201Bi nuclear reactions

    NASA Astrophysics Data System (ADS)

    Mokhtari Oranj, Leila; Jung, Nam-Suk; Kim, Dong-Hyun; Lee, Arim; Bae, Oryun; Lee, Hee-Seock

    2016-11-01

    Experimental and simulation studies on the depth profiles of production yields of natPb(p, xn) 206,205,204,203,202,201Bi nuclear reactions were carried out. Irradiation experiments were performed at the high-intensity proton linac facility (KOMAC) in Korea. The targets, irradiated by 100-MeV protons, were arranged in a stack consisting of natural Pb, Al, Au foils and Pb plates. The proton beam intensity was determined by activation analysis method using 27Al(p, 3p1n)24Na, 197Au(p, p1n)196Au, and 197Au(p, p3n)194Au monitor reactions and also by Gafchromic film dosimetry method. The yields of produced radio-nuclei in the natPb activation foils and monitor foils were measured by HPGe spectroscopy system. Monte Carlo simulations were performed by FLUKA, PHITS/DCHAIN-SP, and MCNPX/FISPACT codes and the calculated data were compared with the experimental results. A satisfactory agreement was observed between the present experimental data and the simulations.

  10. Optimisation of the manufacturing process of tritide and deuteride targets used for neutron production

    NASA Astrophysics Data System (ADS)

    Monnin, Carole; Bach, Pierre; Tulle, Pierre Alain; van Rompay, Marc; Ballanger, Anne

    2002-03-01

    As a neutron tube manufacturer, SODERN is now in charge of manufacturing tritium targets for accelerators, in cooperation with CEA/DAM/DTMN in Valduc. Specific deuterium and tritium targets are manufactured on request, according to the requirements of the users, starting from titanium targets on copper substrates, and going to more sophisticated devices. The range of possible uses is wide, including thin targets for neutron calibration, thick targets with controlled loading of deuterium and tritium, rotating targets or large size rotating targets for higher lifetimes. The activity of the targets ranges from 3.7×10 10 to 3.7×10 13 Bq (1-1000 Ci), the diameter being up to 30 cm. Sodern and the CEA/Valduc centre have developed different technologies for tritium target manufacture, allowing the selection of the best configuration for each kind of use. In order to optimize the production of high energy neutrons, the performance of tritide and deuteride titanium targets made by different processes has been studied experimentally by bombardment with 120 and 350 kV deuterons provided by electrostatic accelerators. It is then possible to optimize either neutron output or lifetime and stability or thermal behaviour. The importance of the deposit evaporation conditions on the efficiency of neutron emission is clearly demonstrated, as well as the thermomechanical stability of the Ti thin film under deuteron bombardment. The main parameters involved in the target performance are discussed from a thermodynamical approach.

  11. Pathophysiology and immunological profile of myasthenia gravis and its subgroups.

    PubMed

    Romi, Fredrik; Hong, Yu; Gilhus, Nils Erik

    2017-12-01

    Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology. MG should be divided into subgroups based on clinical presentation and immunology. This includes onset age, clinical characteristics, thymic pathology and antibody profile. The immunological profile of these subgroups is determined by the antibodies present. Copyright © 2017. Published by Elsevier Ltd.

  12. Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product-Induced M2 to M1 Macrophage Polarization.

    PubMed

    Luo, Honglin; Zhang, Yaoyao; Sheng, Zhaoan; Luo, Tao; Chen, Jie; Liu, Junjie; Wang, Huifeng; Chen, Miao; Shi, Yunliang; Li, Lequn

    2018-05-22

    Long noncoding RNAs (lncRNAs) are well known regulators of gene expression that play essential roles in macrophage activation and polarization. However, the role of lncRNA in Fasciola gigantica excretory/secretory products (ESP)-induced M2 polarization into M1 macrophages is unclear. Herein, we performed lncRNA profiling of lncRNAs and mRNAs during the ESP-induced macrophage polarization process. F. gigantica ESP was used to induce peritoneal cavity M2 macrophages in BALB/c mice (5-6 weeks old) in vivo, and these cells were subsequently isolated and stimulated with IFN-γ + LPS to induce M1 cells in vitro. LncRNA and mRNA profiling was performed via microarray at the end of both polarization stages. In total, 2,844 lncRNAs (1,579 upregulated and 1,265 downregulated) and 1,782 mRNAs (789 upregulated and 993 downregulated) were differentially expressed in M2 macrophages compared to M1 macrophages, and six lncRNAs were identified during polarization. We selected 34 differentially expressed lncRNAs and mRNAs to validate the results of microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, particularly peptidase activity and carbohydrate metabolism. Furthermore, coding and non-coding gene (CNC) and mRNA-related ceRNA network analyses were conducted to predict lncRNA expression trends and the potential target genes of these lncRNAs and mRNAs. Moreover, we determined that four lncRNAs and four mRNAs might participate in F. gigantica ESP-induced M2 polarization into M1 macrophages. This study illustrates the basic profiling of lncRNAs and mRNAs during F. gigantica ESP-induced M2 polarization into M1 macrophages and deepens our understanding of the mechanism underlying this process. © 2018 The Author(s). Published by S. Karger AG, Basel.

  13. Identifying potential RNAi targets in grain aphid (Sitobion avenae F.) based on transcriptome profiling of its alimentary canal after feeding on wheat plants.

    PubMed

    Zhang, Min; Zhou, Yuwen; Wang, Hui; Jones, Huw; Gao, Qiang; Wang, Dahai; Ma, Youzhi; Xia, Lanqin

    2013-08-16

    The grain aphid (Sitobion avenae F.) is a major agricultural pest which causes significant yield losses of wheat in China, Europe and North America annually. Transcriptome profiling of the grain aphid alimentary canal after feeding on wheat plants could provide comprehensive gene expression information involved in feeding, ingestion and digestion. Furthermore, selection of aphid-specific RNAi target genes would be essential for utilizing a plant-mediated RNAi strategy to control aphids via a non-toxic mode of action. However, due to the tiny size of the alimentary canal and lack of genomic information on grain aphid as a whole, selection of the RNAi targets is a challenging task that as far as we are aware, has never been documented previously. In this study, we performed de novo transcriptome assembly and gene expression analyses of the alimentary canals of grain aphids before and after feeding on wheat plants using Illumina RNA sequencing. The transcriptome profiling generated 30,427 unigenes with an average length of 664 bp. Furthermore, comparison of the transcriptomes of alimentary canals of pre- and post feeding grain aphids indicated that 5490 unigenes were differentially expressed, among which, diverse genes and/or pathways were identified and annotated. Based on the RPKM values of these unigenes, 16 of them that were significantly up or down-regulated upon feeding were selected for dsRNA artificial feeding assay. Of these, 5 unigenes led to higher mortality and developmental stunting in an artificial feeding assay due to the down-regulation of the target gene expression. Finally, by adding fluorescently labelled dsRNA into the artificial diet, the spread of fluorescence signal in the whole body tissues of grain aphid was observed. Comparison of the transcriptome profiles of the alimentary canals of pre- and post-feeding grain aphids on wheat plants provided comprehensive gene expression information that could facilitate our understanding of the molecular

  14. Identifying potential RNAi targets in grain aphid (Sitobion avenae F.) based on transcriptome profiling of its alimentary canal after feeding on wheat plants

    PubMed Central

    2013-01-01

    Background The grain aphid (Sitobion avenae F.) is a major agricultural pest which causes significant yield losses of wheat in China, Europe and North America annually. Transcriptome profiling of the grain aphid alimentary canal after feeding on wheat plants could provide comprehensive gene expression information involved in feeding, ingestion and digestion. Furthermore, selection of aphid-specific RNAi target genes would be essential for utilizing a plant-mediated RNAi strategy to control aphids via a non-toxic mode of action. However, due to the tiny size of the alimentary canal and lack of genomic information on grain aphid as a whole, selection of the RNAi targets is a challenging task that as far as we are aware, has never been documented previously. Results In this study, we performed de novo transcriptome assembly and gene expression analyses of the alimentary canals of grain aphids before and after feeding on wheat plants using Illumina RNA sequencing. The transcriptome profiling generated 30,427 unigenes with an average length of 664 bp. Furthermore, comparison of the transcriptomes of alimentary canals of pre- and post feeding grain aphids indicated that 5490 unigenes were differentially expressed, among which, diverse genes and/or pathways were identified and annotated. Based on the RPKM values of these unigenes, 16 of them that were significantly up or down-regulated upon feeding were selected for dsRNA artificial feeding assay. Of these, 5 unigenes led to higher mortality and developmental stunting in an artificial feeding assay due to the down-regulation of the target gene expression. Finally, by adding fluorescently labelled dsRNA into the artificial diet, the spread of fluorescence signal in the whole body tissues of grain aphid was observed. Conclusions Comparison of the transcriptome profiles of the alimentary canals of pre- and post-feeding grain aphids on wheat plants provided comprehensive gene expression information that could facilitate our

  15. Modelling PET radionuclide production in tissue and external targets using Geant4

    NASA Astrophysics Data System (ADS)

    Amin, T.; Infantino, A.; Lindsay, C.; Barlow, R.; Hoehr, C.

    2017-07-01

    The Proton Therapy Facility in TRIUMF provides 74 MeV protons extracted from a 500 MeV H- cyclotron for ocular melanoma treatments. During treatment, positron emitting radionuclides such as 1C, 15O and 13N are produced in patient tissue. Using PET scanners, the isotopic activity distribution can be measured for in-vivo range verification. A second cyclotron, the TR13, provides 13 MeV protons onto liquid targets for the production of PET radionuclides such as 18F, 13N or 68Ga, for medical applications. The aim of this work was to validate Geant4 against FLUKA and experimental measurements for production of the above-mentioned isotopes using the two cyclotrons. The results show variable degrees of agreement. For proton therapy, the proton-range agreement was within 2 mm for 11C activity, whereas 13N disagreed. For liquid targets at the TR13 the average absolute deviation ratio between FLUKA and experiment was 1.9±2.7, whereas the average absolute deviation ratio between Geant4 and experiment was 0. 6±0.4. This is due to the uncertainties present in experimentally determined reaction cross sections.

  16. Inversely Estimating the Vertical Profile of the Soil CO2 Production Rate in a Deciduous Broadleaf Forest Using a Particle Filtering Method

    PubMed Central

    Sakurai, Gen; Yonemura, Seiichiro; Kishimoto-Mo, Ayaka W.; Murayama, Shohei; Ohtsuka, Toshiyuki; Yokozawa, Masayuki

    2015-01-01

    Carbon dioxide (CO2) efflux from the soil surface, which is a major source of CO2 from terrestrial ecosystems, represents the total CO2 production at all soil depths. Although many studies have estimated the vertical profile of the CO2 production rate, one of the difficulties in estimating the vertical profile is measuring diffusion coefficients of CO2 at all soil depths in a nondestructive manner. In this study, we estimated the temporal variation in the vertical profile of the CO2 production rate using a data assimilation method, the particle filtering method, in which the diffusion coefficients of CO2 were simultaneously estimated. The CO2 concentrations at several soil depths and CO2 efflux from the soil surface (only during the snow-free period) were measured at two points in a broadleaf forest in Japan, and the data were assimilated into a simple model including a diffusion equation. We found that there were large variations in the pattern of the vertical profile of the CO2 production rate between experiment sites: the peak CO2 production rate was at soil depths around 10 cm during the snow-free period at one site, but the peak was at the soil surface at the other site. Using this method to estimate the CO2 production rate during snow-cover periods allowed us to estimate CO2 efflux during that period as well. We estimated that the CO2 efflux during the snow-cover period (about half the year) accounted for around 13% of the annual CO2 efflux at this site. Although the method proposed in this study does not ensure the validity of the estimated diffusion coefficients and CO2 production rates, the method enables us to more closely approach the “actual” values by decreasing the variance of the posterior distribution of the values. PMID:25793387

  17. Agricultural Production. Ohio's Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This list consists of essential competencies from the following specialized Ohio Competency Analysis Profiles: Beef and Sheep Producers; Crop Producer; Dairy Producer; Poultry Producer; and Swine Producer. Developed through a modified DACUM (Developing a Curriculum) process involving business, industry, labor, and community agency representatives…

  18. Dynamic Analysis of the Temperature and the Concentration Profiles of an Industrial Rotary Kiln Used in Clinker Production.

    PubMed

    Rodrigues, Diulia C Q; Soares, Atílio P; Costa, Esly F; Costa, Andréa O S

    2017-01-01

    Cement is one of the most used building materials in the world. The process of cement production involves numerous and complex reactions that occur under different temperatures. Thus, there is great interest in the optimization of cement manufacturing. Clinker production is one of the main steps of cement production and it occurs inside the kiln. In this paper, the dry process of clinker production is analysed in a rotary kiln that operates in counter flow. The main phenomena involved in clinker production is as follows: free residual water evaporation of raw material, decomposition of magnesium carbonate, decarbonation, formation of C3A and C4AF, formation of dicalcium silicate, and formation of tricalcium silicate. The main objective of this study was to propose a mathematical model that realistically describes the temperature profile and the concentration of clinker components in a real rotary kiln. In addition, the influence of different speeds of inlet gas and solids in the system was analysed. The mathematical model is composed of partial differential equations. The model was implemented in Mathcad (available at CCA/UFES) and solved using industrial input data. The proposal model is satisfactory to describe the temperature and concentration profiles of a real rotary kiln.

  19. Influenza neuraminidase: a druggable target for natural products.

    PubMed

    Grienke, Ulrike; Schmidtke, Michaela; von Grafenstein, Susanne; Kirchmair, Johannes; Liedl, Klaus R; Rollinger, Judith M

    2012-01-01

    The imminent threat of influenza pandemics and repeatedly reported emergence of new drug-resistant influenza virus strains demonstrate the urgent need for developing innovative and effective antiviral agents for prevention and treatment. At present, influenza neuraminidase (NA), a key enzyme in viral replication, spread, and pathogenesis, is considered to be one of the most promising targets for combating influenza. Despite the substantial medical potential of NA inhibitors (NAIs), only three of these drugs are currently on the market (zanamivir, oseltamivir, and peramivir). Moreover, sudden changes in NAI susceptibility revealed the urgent need in the discovery/identification of novel inhibitors. Nature offers an abundance of biosynthesized compounds comprising chemical scaffolds of high diversity, which present an infinite pool of chemical entities for target-oriented drug discovery in the battle against this highly contagious pathogen. This review illuminates the increasing research efforts of the past decade (2000-2011), focusing on the structure, function and druggability of influenza NA, as well as its inhibition by natural products. Following a critical discussion of publications describing some 150 secondary plant metabolites tested for their inhibitory potential against influenza NA, the impact of three different strategies to identify and develop novel NAIs is presented: (i) bioactivity screening of herbal extracts, (ii) exploitation of empirical knowledge, and (iii) computational approaches. This work addresses the latest developments in theoretical and experimental research on properties of NA that are and will be driving anti-influenza drug development now and in the near future.

  20. Deuteron irradiation of W and WO 3 for production of high specific activity 186Re: Challenges associated with thick target preparation

    DOE PAGES

    Balkin, Ethan R.; Gagnon, Katherine; Strong, Kevin T.; ...

    2016-06-28

    This investigation evaluated target fabrication and beam parameters for scale-up production of high specific activity 186Re using deuteron irradiation of enriched 186W via the 186W(d,2n) 186Re reaction. Thick W and WO 3 targets were prepared, characterized and evaluated in deuteron irradiations. Full-thickness targets, as determined using SRIM, were prepared by uniaxi-ally pressing powdered natural abundance W and WO 3, or 96.86% enriched 186W, into Al target supports. Alternatively, thick targets were prepared by pressing 186W between two layers of graphite powder or by placing pre-sintered (1105°C, 12 hours) natural abundance WO 3 pellets into an Al target support. Assessments ofmore » structural integrity were made on each target pre-pared. Prior to irradiation, material composition analyses were conducted using SEM, XRD, and Raman spectroscopy. With-in a minimum of 24 hours post irradiation, gamma-ray spectroscopy was performed on all targets to assess production yields and radionuclidic byproducts. Problems were encountered with the structural integrity of some pressed W and WO 3 pellets before and during irradiation, and target material characterization results could be correlated with the structural integrity of the pressed target pellets. Under the conditions studied, the findings suggest that all WO 3 targets prepared and studied were unacceptable. By contrast, 186W metal was found to be a viable target material for 186Re production. Lastly, thick targets prepared with powdered 186W pressed between layers of graphite provided a particularly robust target configuration.« less

  1. Deuteron irradiation of W and WO3 for production of high specific activity (186)Re: Challenges associated with thick target preparation.

    PubMed

    Balkin, Ethan R; Gagnon, Katherine; Strong, Kevin T; Smith, Bennett E; Dorman, Eric F; Emery, Robert C; Pauzauskie, Peter J; Fassbender, Michael E; Cutler, Cathy S; Ketring, Alan R; Jurisson, Silvia S; Wilbur, D Scott

    2016-09-01

    This investigation evaluated target fabrication and beam parameters for scale-up production of high specific activity (186)Re using deuteron irradiation of enriched (186)W via the (186)W(d,2n)(186)Re reaction. Thick W and WO3 targets were prepared, characterized and evaluated in deuteron irradiations. Full-thickness targets, as determined using SRIM, were prepared by uniaxially pressing powdered natural abundance W and WO3, or 96.86% enriched (186)W, into Al target supports. Alternatively, thick targets were prepared by pressing (186)W between two layers of graphite powder or by placing pre-sintered (1105°C, 12h) natural abundance WO3 pellets into an Al target support. Assessments of structural integrity were made on each target prepared. Prior to irradiation, material composition analyses were conducted using SEM, XRD, and Raman spectroscopy. Within a minimum of 24h post irradiation, gamma-ray spectroscopy was performed on all targets to assess production yields and radionuclidic byproducts. Problems were encountered with the structural integrity of some pressed W and WO3 pellets before and during irradiation, and target material characterization results could be correlated with the structural integrity of the pressed target pellets. Under the conditions studied, the findings suggest that all WO3 targets prepared and studied were unacceptable. By contrast, (186)W metal was found to be a viable target material for (186)Re production. Thick targets prepared with powdered (186)W pressed between layers of graphite provided a particularly robust target configuration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Identifying initial molecular targets of PDT: protein and lipid oxidation products

    NASA Astrophysics Data System (ADS)

    Oleinick, Nancy L.; Kim, Junhwan; Rodriguez, Myriam E.; Xue, Liang-yan; Kenney, Malcolm E.; Anderson, Vernon E.

    2009-06-01

    Photodynamic Therapy (PDT) generates singlet oxygen (1O2) which oxidizes biomolecules in the immediate vicinity of its formation. The phthalocyanine photosensitizer Pc 4 localizes to mitochondria and endoplasmic reticulum, and the primary targets of Pc 4-PDT are expected to be lipids and proteins of those membranes. The initial damage then causes apoptosis in cancer cells via the release of cytochrome c (Cyt-c) from mitochondria into the cytosol, followed by the activation of caspases. That damage also triggers the induction of autophagy, an attempt by the cells to eliminate damaged organelles, or when damage is too extensive, to promote cell death. Cyt-c is bound to the cytosolic side of the mitochondrial inner membrane through association with cardiolipin (CL), a phospholipid containing four unsaturated fatty acids and thus easily oxidized by 1O2 or by other oxidizing agents. Increasing evidence suggests that oxidation of CL loosens its association with Cyt-c, and that the peroxidase activity of Cyt-c can oxidize CL. In earlier studies of Cyt-c in homogeneous medium by MALDI-TOF-MS and LC-ESI-MS, we showed that 1O2 generated by Pc 4-PDT oxidized histidine, methionine, tryptophan, and unexpectedly phenylalanine but not tyrosine. Most of the oxidation products were known to be formed by other oxidizing agents, such as hydroxyl radical, superoxide radical anion, and peroxynitrite. However, two products of histidine were unique to 1O2 and may be useful for reporting the action of 1O2 in cells and tissues. These products, as well as CL oxidation products, have now been identified in liposomes and mitochondria after Pc 4-PDT. In mitochondria, the PDT dose-dependent oxidations can be related to specific changes in mitochondrial function, Bcl-2 photodamage, and Cyt-c release. Thus, the role of PDT-generated 1O2 in oxidizing Cyt-c and CL and the interplay between protein and lipid targets may be highly relevant to understanding one mechanism for cell killing by PDT.

  3. Routine 18F- production with 180 μA to 200 μA target beam current on a GE PETtrace 800 cyclotron

    NASA Astrophysics Data System (ADS)

    Eberl, S.; Eriksson, T.; Svedberg, O.; Norling, J.; Henderson, D.; Lam, P.; Bourdier, T.; Fulham, M.

    2012-12-01

    Through upgrades and enhancements, which are now standard on current PETtrace 800 cyclotrons, a GE PETtrace cyclotron installed in 2002 has demonstrated reliable routine [18F]FDG production at total target beam currents of 180 μA without detriment to saturation and [18F]FDG yields. Routine production at 200 μA has been achieved and its evaluation is continuing. Self-shielded target using W/Cu alloy for the target body afforded a reduction in dose rate from the Havar foils by a factor of ˜ 8-10, reducing dose from the targets and need for removing targets during maintenance. The main activation product in the shield is 187W (T1/2 24 h). The 60Co ((T1/2 5.3 y) activation is about 250 times less at 24 h post EOB and is not considered a major issue despite its long half-life.

  4. Assessment of denitrification gaseous end-products in the soil profile under two water table management practices using repeated measures analysis.

    PubMed

    Elmi, Abdirashid A; Astatkie, Tess; Madramootoo, Chandra; Gordon, Robert; Burton, David

    2005-01-01

    The denitrification process and nitrous oxide (N2O) production in the soil profile are poorly documented because most research into denitrification has concentrated on the upper soil layer (0-0.15 m). This study, undertaken during the 1999 and 2000 growing seasons, was designed to examine the effects of water table management (WTM), nitrogen (N) application rate, and depth (0.15, 0.30, and 0.45 m) on soil denitrification end-products (N2O and N2) from a corn (Zea mays L.) field. Water table management treatments were free drainage (FD) with open drains and subirrigation (SI) with a target water table depth of 0.6 m. Fertility treatments (ammonium nitrate) were 120 kg N ha(-1) (N120) and 200 kg N ha(-1) (N200). During both growing seasons greater denitrification rates were measured in SI than in FD, particularly in the surface soil (0-0.15 m) and at the intermediate (0.15-0.30 m) soil depths under N200 treatment. Greater denitrification rates under the SI treatment, however, were not accompanied with greater N2O production. The decrease in N2O production under SI was probably caused by a more complete reduction of N2O to N2, which resulted in lower N2O to (N2O + N2) ratios. Denitrification rate, N2O production and N2O to (N2O + N2) ratios were only minimally affected by N treatments, irrespective of sampling date and soil depth. Overall, half of the denitrification occurred at the 0.15- to 0.30- and 0.30- to 0.45-m soil layers, and under SI, regardless of fertility treatment level. Consequently, sampling of the 0- to 0.15-m soil layer alone may not give an accurate estimation of denitrification losses under SI practice.

  5. Total polyphenols, catechin profiles and antioxidant activity of tea products from purple leaf coloured tea cultivars.

    PubMed

    Kerio, L C; Wachira, F N; Wanyoko, J K; Rotich, M K

    2013-02-15

    Black (aerated) and green (unaerated) tea products, processed from 10 green and 18 purple leaf coloured cultivars of Kenyan origin, and two tea products, from the Japanese cultivars, Yabukita and Yutakamidori, were assayed for total polyphenols (TP) content, individual catechin profiles and in vitro antioxidant capacity (AA). In addition, the phenolic content of the tea products was determined using the Folin-Ciocalteu phenol reagent. Catechin fractions were identified using reverse phase high performance liquid chromatography (HPLC) with a binary gradient elution system. The AA% of the tea products was determined using a 2,2'-diphenyl picrylhydrazyl (DPPH) radical assay method. The results showed that TPs, catechin profiles and antioxidant activities were significantly (p≤0.05) higher in unaerated than in aerated teas. Tea products from the purple leaf coloured tea cultivars had levels of TPs, total catechin (TC) and antioxidant activities similar to those from the green leaf coloured cultivars, except for teas from the Japanese cultivars that were very low in the assayed parameters. Caffeine content was significantly (p≤0.05) lower in products from the purple leaf coloured cultivars than in those from the green leaf coloured tea cultivars. Antioxidant activity (%) was higher in tea products from the Kenyan germplasm than in those from the Japanese cultivars. Antioxidant potency of tea products was significantly (r=0.789(∗∗), p≤0.01) influenced by the total anthocyanin content of the purple leaf coloured cultivars. Cyanidin-3-O-glucoside was the anthocyanin most highly correlated with AA% (r=0.843(∗∗), p≤0.01 in unaerated tea). Total catechins in the unaerated products from the green leaf coloured tea cultivars were also significantly correlated with antioxidant capacity (r=0.818(∗∗), p≤0.01). Results from this study suggest that the antioxidant potency of teas is dependent on the predominant flavonoid compound, the type of tea cultivar and

  6. Doppler Feature Based Classification of Wind Profiler Data

    NASA Astrophysics Data System (ADS)

    Sinha, Swati; Chandrasekhar Sarma, T. V.; Lourde. R, Mary

    2017-01-01

    Wind Profilers (WP) are coherent pulsed Doppler radars in UHF and VHF bands. They are used for vertical profiling of wind velocity and direction. This information is very useful for weather modeling, study of climatic patterns and weather prediction. Observations at different height and different wind velocities are possible by changing the operating parameters of WP. A set of Doppler power spectra is the standard form of WP data. Wind velocity, direction and wind velocity turbulence at different heights can be derived from it. Modern wind profilers operate for long duration and generate approximately 4 megabytes of data per hour. The radar data stream contains Doppler power spectra from different radar configurations with echoes from different atmospheric targets. In order to facilitate systematic study, this data needs to be segregated according the type of target. A reliable automated target classification technique is required to do this job. Classical techniques of radar target identification use pattern matching and minimization of mean squared error, Euclidean distance etc. These techniques are not effective for the classification of WP echoes, as these targets do not have well-defined signature in Doppler power spectra. This paper presents an effective target classification technique based on range-Doppler features.

  7. Evaluation of dairy products available on the Polish market in the context of nutrient profiles. Clear arguments for reformulation of foodstuffs

    PubMed

    Wierzejska, Regina; Siuba-Strzelińska, Magdalena; Jarosz, Mirosław

    Dairy products, which are one of the main groups of products in the diet, are expected to have high nutritional value. The development of food technology often involves changing the nutritional parameters of foodstuffs. The aim of this study was to determine the nutritional value of dairy products, in the context of nutrient profiles. The tested products included yoghurts, yoghurt drinks, kefir, cream cheeses and milk desserts available on the Polish market, basing on the information from unit product packaging. The average sugar content in the group of all products was 11 g/100 g. Milk desserts contained the largest amount of sugar (average 14.7 g/100g), whereas kefir – the smallest amount (average 6 g/100 g) (p <0.0001). Yoghurts and yoghurt drinks intended for children had higher sugar content than products for the general population (14.4 g vs. 10.5 g/100 g) (p <0.0001). As many as 75% of products were sweetened. Taking into account the natural content of lactose, the estimated amount of added sugar ranged from 6.9 - 12.3 g/100 g. The average fat content in the group of all products amounted to 3.8 g/100 g. In the view of WHO profiles, 71% of products exceeded the permissible sugar content (≤ 10 g/100 g) and 36% exceeded the permissible content of saturated fatty acids (≤ 2 g/100 g). Using more liberal profiles developed by the food industry, the proportion of such products was smaller, but still quite high (34% in case of sugar and 26% in case of saturated fatty acids). In terms of the sugar content, according to regulation introduced in Poland, only 29% of the analyzed dairy products could be offer for children at schools. Among them there are all natural (not sweetened) yoghurts and kefir and only 6% of other sweetened products. There is a justified need for the reformulation of dairy products, especially in terms of added sugar.

  8. A Protein Chimera Strategy Supports Production of a Model "Difficult-to-Express" Recombinant Target.

    PubMed

    Hussain, Hirra; Fisher, David I; Roth, Robert G; Abbott, W Mark; Carballo-Amador, Manuel Alejandro; Warwicker, Jim; Dickson, Alan J

    2018-06-22

    Due in part to the needs of the biopharmaceutical industry, there has been an increased drive to generate high quality recombinant proteins in large amounts. However, achieving high yields can be a challenge as the novelty and increased complexity of new targets often makes them 'difficult-to-express'. This study aimed to define the molecular features that restrict the production of a model 'difficult-to-express' recombinant protein, Tissue Inhibitor Metalloproteinase-3 (TIMP-3). Building from experimental data, computational approaches were used to rationalise the re-design of this recombinant target to generate a chimera with enhanced secretion. The results highlight the importance of early identification of unfavourable sequence attributes, enabling the generation of engineered protein forms that bypass 'secretory' bottlenecks and result in efficient recombinant protein production. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Annual nitrate drawdown observed by SOCCOM profiling floats and the relationship to annual net community production

    NASA Astrophysics Data System (ADS)

    Johnson, Kenneth S.; Plant, Joshua N.; Dunne, John P.; Talley, Lynne D.; Sarmiento, Jorge L.

    2017-08-01

    Annual nitrate cycles have been measured throughout the pelagic waters of the Southern Ocean, including regions with seasonal ice cover and southern hemisphere subtropical zones. Vertically resolved nitrate measurements were made using in situ ultraviolet spectrophotometer (ISUS) and submersible ultraviolet nitrate analyzer (SUNA) optical nitrate sensors deployed on profiling floats. Thirty-one floats returned 40 complete annual cycles. The mean nitrate profile from the month with the highest winter nitrate minus the mean profile from the month with the lowest nitrate yields the annual nitrate drawdown. This quantity was integrated to 200 m depth and converted to carbon using the Redfield ratio to estimate annual net community production (ANCP) throughout the Southern Ocean south of 30°S. A well-defined, zonal mean distribution is found with highest values (3-4 mol C m-2 yr-1) from 40 to 50°S. Lowest values are found in the subtropics and in the seasonal ice zone. The area weighted mean was 2.9 mol C m-2 yr-1 for all regions south of 40°S. Cumulative ANCP south of 50°S is 1.3 Pg C yr-1. This represents about 13% of global ANCP in about 14% of the global ocean area.Plain Language SummaryThis manuscript reports on 40 annual cycles of nitrate observed by chemical sensors on SOCCOM <span class="hlt">profiling</span> floats. The annual drawdown in nitrate concentration by phytoplankton is used to assess the spatial variability of annual net community <span class="hlt">production</span> in the Southern Ocean. This ANCP is a key component of the global carbon cycle and it exerts an important control on atmospheric carbon dioxide. We show that the results are consistent with our prior understanding of Southern Ocean ANCP, which has required decades of observations to accumulate. The <span class="hlt">profiling</span> floats now enable annual resolution of this key process. The results also highlight spatial variability in ANCP in the Southern Ocean.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017SPIE10329E..33S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017SPIE10329E..33S"><span>In-line height <span class="hlt">profiling</span> metrology sensor for zero defect <span class="hlt">production</span> control</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Snel, Rob; Winters, Jasper; Liebig, Thomas; Jonker, Wouter</p> <p>2017-06-01</p> <p>Contemporary <span class="hlt">production</span> systems of mechanical precision parts show challenges as increased complexity, tolerances shrinking to sub-microns and yield losses that must be mastered to the extreme. More advanced automation and process control is required to accomplish this task. Often a solution based on feedforward/feedback control is chosen requiring innovative and more advanced in line metrology. This article concentrates first on the context of in line metrology for process control and then on the development of a specific in line height <span class="hlt">profiling</span> sensor. The novel sensor technology is based on full field time domain white light interferometry which is well know from the quality lab. The novel metrology system is to be mounted close to the <span class="hlt">production</span> equipment, as required to minimize time delay in the control loop, and is thereby fully exposed to vibrations. This sensor is innovated to perform in line with an orders of magnitude faster throughput than laboratory instruments; it's robust to withstand the rigors of workshops and has a height resolution that is in the nanometer range.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5391476','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5391476"><span>Glycosylation Benchmark <span class="hlt">Profile</span> for HIV-1 Envelope Glycoprotein <span class="hlt">Production</span> Based on Eleven Env Trimers</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Go, Eden P.; Ding, Haitao; Zhang, Shijian; Ringe, Rajesh P.; Nicely, Nathan; Hua, David; Steinbock, Robert T.; Golabek, Michael; Alin, James; Alam, S. Munir; Cupo, Albert; Haynes, Barton F.; Kappes, John C.; Moore, John P.; Sodroski, Joseph G.</p> <p>2017-01-01</p> <p> important questions are still unanswered. (i) What is the “target” glycosylation <span class="hlt">profile</span>, when the goal is to generate a natively glycosylated protein? (ii) What variables exert the greatest influence on Env glycosylation? We identified numerous sites on Env where the glycosylation <span class="hlt">profile</span> does not deviate in 11 different Env trimers, and we investigated the impact on the divergent glycosylation <span class="hlt">profiles</span> of changing the genotype of the Env sequence, the construct design, the purification method, and the producer cell type. The data presented here give vaccine developers a “glycosylation target” for their immunogens, and they show how protein <span class="hlt">production</span> variables can impact Env glycosylation. PMID:28202756</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009APS..DPPNP8094H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009APS..DPPNP8094H"><span>Optimized Ion Energy <span class="hlt">Profiles</span> for Heavy Ion Direct Drive <span class="hlt">Targets</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Hay, Michael J.; Barnard, John J.; Perkins, L. John; Logan, B. Grant</p> <p>2009-11-01</p> <p>Recent 1-D implosion calculations [1] have characterized pure-DT <span class="hlt">targets</span> delivering gains of 50-90 with less than 0.5 MJ of heavy ion direct drive. With a payload fraction of 1/3, these low-aspect ratio <span class="hlt">targets</span> operate near the peak of rocket efficiency and achieve ˜10% overall coupling efficiencies (vs. the 15-20% efficiencies analytically predicted for less stable, higher-aspect ratio <span class="hlt">targets</span>). In Ref. 1, the ion energy is ramped directly from a 50 MeV foot pulse to a 500 MeV main pulse. In this paper, we instead tune the ion energy throughout the drive to closely match the beam deposition with the inward progress of the ablation front. We will present the ion energy and intensity time histories that maximize drive efficiency and gain for a single <span class="hlt">target</span> at constant integrated drive energy. [1] L. J. Perkins, B. G. Logan, J. J. Barnard, and M. J. Hay. ``High Efficiency High Gain Heavy Ion Direct Drive <span class="hlt">Targets</span>,'' Bulletin of the American Physical Society, vol. 54: DPP, Nov. 2009.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4282061','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4282061"><span>Effects of temperature and glycerol and methanol-feeding <span class="hlt">profiles</span> on the <span class="hlt">production</span> of recombinant galactose oxidase in Pichia pastoris</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Anasontzis, George E; Salazar Penã, Margarita; Spadiut, Oliver; Brumer, Harry; Olsson, Lisbeth</p> <p>2014-01-01</p> <p>Optimization of protein <span class="hlt">production</span> from methanol-induced Pichia pastoris cultures is necessary to ensure high <span class="hlt">productivity</span> rates and high yields of recombinant proteins. We investigated the effects of temperature and different linear or exponential methanol-feeding rates on the <span class="hlt">production</span> of recombinant Fusarium graminearum galactose oxidase (EC 1.1.3.9) in a P. pastoris Mut+ strain, under regulation of the AOX1 promoter. We found that low exponential methanol feeding led to 1.5-fold higher volumetric <span class="hlt">productivity</span> compared to high exponential feeding rates. The duration of glycerol feeding did not affect the subsequent <span class="hlt">product</span> yield, but longer glycerol feeding led to higher initial biomass concentration, which would reduce the oxygen demand and generate less heat during induction. A linear and a low exponential feeding <span class="hlt">profile</span> led to <span class="hlt">productivities</span> in the same range, but the latter was characterized by intense fluctuations in the titers of galactose oxidase and total protein. An exponential feeding <span class="hlt">profile</span> that has been adapted to the apparent biomass concentration results in more stable cultures, but the concentration of recombinant protein is in the same range as when constant methanol feeding is employed. © 2014 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 30:728–735, 2014 PMID:24493559</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017MPLA...3240013A','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017MPLA...3240013A"><span><span class="hlt">Production</span> of copper-64 and gallium-68 with a medical cyclotron using liquid <span class="hlt">targets</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Alves, F.; Alves, V. H. P.; Do Carmo, S. J. C.; Neves, A. C. B.; Silva, M.; Abrunhosa, A. J.</p> <p>2017-06-01</p> <p>This work describes the <span class="hlt">production</span> of two clinically relevant metal radioisotopes 64Cu and 68Ga with a medical cyclotron by the irradiation of liquid <span class="hlt">targets</span>. New results are presented for the implementation of this methodology in a fully automated system, using commercially available equipment. Liquid <span class="hlt">target</span> solutions containing enriched 64Ni and 68Zn were loaded, bombarded and transferred to synthesis modules where a purified solution containing the desired radiometal is obtained and can then be used to further radiolabeling within only one hour after End-Of-Bombardment (EOB). Typical <span class="hlt">production</span> runs using enriched material lead to the <span class="hlt">production</span> of 5 GBq and 6 GBq (0.14 MBq/(μAh ṡ mg) and 1.5 MBq/(μAh ṡ mg)) of 64Cu and 68Ga; although the technique can be used to obtain up to 25 GBq and 40 GBq, respectively, by simply scaling up the amount of the enriched material. Purified solutions containing 64Cu and 68Ga were obtained within 30 min after EOB and used to produce 64Cu-ATSM and 68Ga-DOTA-NOC, respectively, with quality parameters suitable for human use.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27259741','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27259741"><span>Enhanced DNA <span class="hlt">Profiling</span> of the Semen Donor in Late Reported Sexual Assaults: Use of Y-Chromosome-<span class="hlt">Targeted</span> Pre-amplification and Next Generation Y-STR Amplification Systems.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hanson, Erin K; Ballantyne, Jack</p> <p>2016-01-01</p> <p>In some cases of sexual assault the victim may not report the assault for several days after the incident due to various factors. The ability to obtain an autosomal STR <span class="hlt">profile</span> of the semen donor from a living victim rapidly diminishes as the post-coital interval is extended due to the presence of only a small amount of male DNA amidst an overwhelming amount of female DNA. Previously, we have utilized various technological tools to overcome the limitations of male DNA <span class="hlt">profiling</span> in extended interval post-coital samples including the use of Y-chromosome STR <span class="hlt">profiling</span>, cervical sample, and post-PCR purification permitting the recovery of Y-STR <span class="hlt">profiles</span> of the male DNA from samples collected 5-6 days after intercourse. Despite this success, the reproductive biology literature reports the presence of spermatozoa in the human cervix up to 7-10 days post-coitus. Therefore, novel and improved methods for recovery of male <span class="hlt">profiles</span> in extended interval post-coital samples were required. Here, we describe enhanced strategies, including Y-chromosome-<span class="hlt">targeted</span> pre-amplification and next generation Y-STR amplification kits, that have resulted in the ability to obtain probative male <span class="hlt">profiles</span> from samples collected 6-9 days after intercourse.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29564089','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29564089"><span>Sensory <span class="hlt">profiling</span> and consumer acceptability of new dark cocoa bars containing Tuscan autochthonous food <span class="hlt">products</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cantini, Claudio; Salusti, Patrizia; Romi, Marco; Francini, Alessandra; Sebastiani, Luca</p> <p>2018-03-01</p> <p>A new set of cocoa bars named Toscolata ® were developed containing top-quality extra virgin olive oil, dried apples cultivars, and chestnut flour. The present work has been conducted to define the sensory <span class="hlt">profile</span> of these <span class="hlt">products</span> through tasting by trained experts and consumers to study the acceptability, preference, and quality perception. The four sensorial <span class="hlt">profiles</span> of the bars differed in the level of persistence, bitterness, aromaticity, acidity, astringency, and tastiness. In particular, the sour attribute could be traced to the presence of dried apple. Bars containing apple and chestnut flour obtained higher acceptance ratings, compared to those with extra virgin olive oil. The bar with chestnut flour was preferred by consumers who considered it to be sweeter due to the presence of natural sugars, which lowered the bitter sensation of cocoa. These results showed that the selection of the preferred bar by consumers was mainly based on the level of bitterness and, in particular, elderly consumers expressed a strong preference for the sweetest <span class="hlt">product</span>. As far as we know, this is the first study comparing the results of a panel of expert tasters with that of consumers in the tasting of dark chocolate.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25643067','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25643067"><span>A ranking method for the concurrent learning of compounds with various activity <span class="hlt">profiles</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Dörr, Alexander; Rosenbaum, Lars; Zell, Andreas</p> <p>2015-01-01</p> <p>In this study, we present a SVM-based ranking algorithm for the concurrent learning of compounds with different activity <span class="hlt">profiles</span> and their varying prioritization. To this end, a specific labeling of each compound was elaborated in order to infer virtual screening models against multiple <span class="hlt">targets</span>. We compared the method with several state-of-the-art SVM classification techniques that are capable of inferring multi-<span class="hlt">target</span> screening models on three chemical data sets (cytochrome P450s, dehydrogenases, and a trypsin-like protease data set) containing three different biological <span class="hlt">targets</span> each. The experiments show that ranking-based algorithms show an increased performance for single- and multi-<span class="hlt">target</span> virtual screening. Moreover, compounds that do not completely fulfill the desired activity <span class="hlt">profile</span> are still ranked higher than decoys or compounds with an entirely undesired <span class="hlt">profile</span>, compared to other multi-<span class="hlt">target</span> SVM methods. SVM-based ranking methods constitute a valuable approach for virtual screening in multi-<span class="hlt">target</span> drug design. The utilization of such methods is most helpful when dealing with compounds with various activity <span class="hlt">profiles</span> and the finding of many ligands with an already perfectly matching activity <span class="hlt">profile</span> is not to be expected.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29546543','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29546543"><span>MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution <span class="hlt">profiles</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bonnel, David; Legouffe, Raphaël; Eriksson, André H; Mortensen, Rasmus W; Pamelard, Fabien; Stauber, Jonathan; Nielsen, Kim T</p> <p>2018-04-01</p> <p>Generation of skin distribution <span class="hlt">profiles</span> and reliable determination of drug molecule concentration in the <span class="hlt">target</span> region are crucial during the development process of topical <span class="hlt">products</span> for treatment of skin diseases like psoriasis and atopic dermatitis. Imaging techniques like mass spectrometric imaging (MSI) offer sufficient spatial resolution to generate meaningful distribution <span class="hlt">profiles</span> of a drug molecule across a skin section. In this study, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to generate quantitative skin distribution <span class="hlt">profiles</span> based on tissue extinction coefficient (TEC) determinations of four different molecules in cross sections of human skin explants after topical administration. The four drug molecules: roflumilast, tofacitinib, ruxolitinib, and LEO 29102 have different physicochemical properties. In addition, tofacitinib was administrated in two different formulations. The study reveals that with MALDI-MSI, we were able to observe differences in penetration <span class="hlt">profiles</span> for both the four drug molecules and the two formulations and thereby demonstrate its applicability as a screening tool when developing a topical drug <span class="hlt">product</span>. Furthermore, the study reveals that the sensitivity of the MALDI-MSI techniques appears to be inversely correlated to the drug molecules' ability to bind to the surrounding tissues, which can be estimated by their Log D values. Graphical abstract.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28095176','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28095176"><span>A Flexible Workflow for Automated Bioluminescent Kinase Selectivity <span class="hlt">Profiling</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Worzella, Tracy; Butzler, Matt; Hennek, Jacquelyn; Hanson, Seth; Simdon, Laura; Goueli, Said; Cowan, Cris; Zegzouti, Hicham</p> <p>2017-04-01</p> <p>Kinase <span class="hlt">profiling</span> during drug discovery is a necessary process to confirm inhibitor selectivity and assess off-<span class="hlt">target</span> activities. However, cost and logistical limitations prevent <span class="hlt">profiling</span> activities from being performed in-house. We describe the development of an automated and flexible kinase <span class="hlt">profiling</span> workflow that combines ready-to-use kinase enzymes and substrates in convenient eight-tube strips, a bench-top liquid handling device, ADP-Glo Kinase Assay (Promega, Madison, WI) technology to quantify enzyme activity, and a multimode detection instrument. Automated methods were developed for kinase reactions and quantification reactions to be assembled on a Gilson (Middleton, WI) PIPETMAX, following standardized plate layouts for single- and multidose compound <span class="hlt">profiling</span>. Pipetting protocols were customized at runtime based on user-provided information, including compound number, increment for compound titrations, and number of kinase families to use. After the automated liquid handling procedures, a GloMax Discover (Promega) microplate reader preloaded with SMART protocols was used for luminescence detection and automatic data analysis. The functionality of the automated workflow was evaluated with several compound-kinase combinations in single-dose or dose-response <span class="hlt">profiling</span> formats. Known <span class="hlt">target</span>-specific inhibitions were confirmed. Novel small molecule-kinase interactions, including off-<span class="hlt">target</span> inhibitions, were identified and confirmed in secondary studies. By adopting this streamlined <span class="hlt">profiling</span> process, researchers can quickly and efficiently <span class="hlt">profile</span> compounds of interest on site.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1136910','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/1136910"><span>HD gas purification for polarized HDice <span class="hlt">targets</span> <span class="hlt">production</span> at Jefferson Lab</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Whisnant, Charles; D'Angelo, Annalisa; Colaneri, Luca</p> <p>2014-06-01</p> <p>Solid, frozen-spin <span class="hlt">targets</span> of molecular HD were rst developed for nuclear physics by a collaboration between Syracuse University and Brookhaven National Lab. They have been successfully used in measurements with photon beams, rst at the Laser-Electron-Gamma-Source [1] and most recently at Je erson Lab during the running of the E06-101 (g14) experiment [2]. Preparations are underway to utilize the <span class="hlt">targets</span> in future electron experiments after the completion of the 12 GeV JLab upgrade [3]. HD is an attractive <span class="hlt">target</span> since all of the material is polarizable, of low Z, and requires only modest holding elds. At the same time, themore » small contributions from the <span class="hlt">target</span> cell can be subtracted from direct measurements. Reaching the frozen-spin state with both high polarization and a signi cant spin relaxation time requires careful control of H2 and D2 impurities. Commercially available HD contains 0.5 - 2% concentrations of H2 and D2. Low-temperature distillation is required to reduce these concentrations to the 104 level to enable useful <span class="hlt">target</span> <span class="hlt">production</span>. This distillation is done using a column lled with heli-pack C [4] to give good separation e ciency. Approximately 12 moles of commercial HD is condensed into the mechanically refrigerated system at the base temperature of 11K. The system is then isolated and the temperature stabilized at 18K producing liquid HD, which is boiled by a resistive heater. The circulation established by the boil-o condensing throughout the column then ltering back down produces a steady-state isotopic separation permitting the extraction of HD gas with very low H2 and D2 content. A residual gas analyzer initially monitors distillation. Once the H2 concentration falls below its useful operating range, samples are periodically collected for analysis using gas chromatography [5] and Raman scattering. Where the measurement techniques overlap, good agreement is obtained. The operation of the distillery and results of gas analysis will be</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_17 --> <div id="page_18" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="341"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22874497','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22874497"><span>The use of sports references in marketing of food and beverage <span class="hlt">products</span> in supermarkets.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bragg, Marie A; Liu, Peggy J; Roberto, Christina A; Sarda, Vishnu; Harris, Jennifer L; Brownell, Kelly D</p> <p>2013-04-01</p> <p>Food marketing has been identified as a significant driver of the childhood obesity epidemic. The purpose of the present study was to (i) conduct a content analysis of the types of sports references that appear on supermarket food and beverage <span class="hlt">products</span> and (ii) assess each <span class="hlt">product</span>'s nutritional and marketing <span class="hlt">profile</span>. This was a descriptive study. Every <span class="hlt">product</span> featuring sports references on the packaging was purchased in two major supermarkets during 2010. A content analysis was conducted and nutritional evaluations were made based on the Nutrient <span class="hlt">Profile</span> Model, a validated nutrition model. Marketing data were obtained from The Nielsen Company. Two major supermarkets in Connecticut, USA. Food and beverage <span class="hlt">products</span> (n 102) were selected from two supermarkets. The 102 <span class="hlt">products</span> (fifty-three foods and forty-nine beverages) had sports references as part of their packaging: 72·5 % featured a character exercising, 42·2 % were endorsed by a professional sports entity and 34·0 % were child-<span class="hlt">targeted</span>. The median nutrition score for food <span class="hlt">products</span> was 36 (1 = unhealthiest and 100 = healthiest; scores of ≥63 are considered healthy according to this model). More than two-thirds of beverages (69·4 %) were 100 % sugar-sweetened. Children saw significantly more commercials for these <span class="hlt">products</span> than adults. Companies place sports figures on food and beverage <span class="hlt">products</span> that are child-<span class="hlt">targeted</span> and unhealthy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://proteomics.cancer.gov/news_and_announcements/nci-requests-targets-monoclonal-antibody-production-and-characterization','NCI'); return false;" href="https://proteomics.cancer.gov/news_and_announcements/nci-requests-targets-monoclonal-antibody-production-and-characterization"><span>NCI Requests <span class="hlt">Targets</span> for Monoclonal Antibody <span class="hlt">Production</span> and Characterization | Office of Cancer Clinical Proteomics Research</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein <span class="hlt">targets</span> for affinity <span class="hlt">production</span> and distribution. Submissions will be accepted through July 9, 2012.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28902476','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28902476"><span>The healthfulness and prominence of sugar in child-<span class="hlt">targeted</span> breakfast cereals in Canada.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Potvin Kent, Monique; Cameron, Cher; Philippe, Sarah</p> <p>2017-09-01</p> <p>The objective of this study was to compare the nutritional content and healthfulness of child-<span class="hlt">targeted</span> and "not child-<span class="hlt">targeted</span>" breakfast cereals and to assess the predominance of added sugar in these <span class="hlt">products</span>. We collected data on the nutritional content of 262 unique breakfast cereals found in the five largest grocery store chains in Ottawa (Ontario) and Gatineau (Quebec). We noted the first five ingredients and the number of added sugars present in each cereal from the ingredients list. The various cereal brands were then classified as either "healthier" or "less healthy" using the UK Nutrient <span class="hlt">Profile</span> Model. We assessed each cereal to determine if it was child-<span class="hlt">targeted</span> or not, based on set criteria. Statistical comparisons were made between child and not child-<span class="hlt">targeted</span> cereals. 19.8% of all breakfast cereals were child-<span class="hlt">targeted</span>, and these were significantly lower in total and saturated fat. Child-<span class="hlt">targeted</span> cereals were significantly higher in sodium and sugar and lower in fibre and protein, and were three times more likely to be classified as "less healthy" compared to not child-<span class="hlt">targeted</span> cereals. No child-<span class="hlt">targeted</span> cereals were sugar-free, and sugar was the second most common ingredient in 75% of cereals. Six breakfast cereal companies had child-<span class="hlt">targeted</span> <span class="hlt">product</span> lines that consisted entirely of "less healthy" cereals. There is a need for regulations that restrict food marketing to children and youth under the age of 17 on packaging to reduce their appeal to this age group. Children's breakfast cereals also need to be reformulated through government-set <span class="hlt">targets</span>, or through regulation should compliance be deemed unacceptable.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018PPCF...60c5014D','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018PPCF...60c5014D"><span>Influence of micromachined <span class="hlt">targets</span> on laser accelerated proton beam <span class="hlt">profiles</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Dalui, Malay; Permogorov, Alexander; Pahl, Hannes; Persson, Anders; Wahlström, Claes-Göran</p> <p>2018-03-01</p> <p>High intensity laser-driven proton acceleration from micromachined <span class="hlt">targets</span> is studied experimentally in the <span class="hlt">target</span>-normal-sheath-acceleration regime. Conical pits are created on the front surface of flat aluminium foils of initial thickness 12.5 and 3 μm using series of low energy pulses (0.5-2.5 μJ). Proton acceleration from such micromachined <span class="hlt">targets</span> is compared with flat foils of equivalent thickness at a laser intensity of 7 × 1019 W cm-2. The maximum proton energy obtained from <span class="hlt">targets</span> machined from 12.5 μm thick foils is found to be slightly lower than that of flat foils of equivalent remaining thickness, and the angular divergence of the proton beam is observed to increase as the depth of the pit approaches the foil thickness. <span class="hlt">Targets</span> machined from 3 μm thick foils, on the other hand, show evidence of increasing the maximum proton energy when the depths of the structures are small. Furthermore, shallow pits on 3 μm thick foils are found to be efficient in reducing the proton beam divergence by a factor of up to three compared to that obtained from flat foils, while maintaining the maximum proton energy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26867652','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26867652"><span>Radioactive by-<span class="hlt">products</span> of a self-shielded cyclotron and the liquid <span class="hlt">target</span> system for F-18 routine <span class="hlt">production</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kambali, I; Suryanto, H; Parwanto</p> <p>2016-06-01</p> <p>Routine <span class="hlt">production</span> of F-18 radionuclide using proton beams accelerated in a cyclotron could potentially generate residual radioisotopes in the cyclotron vicinity which eventually become major safety concerns over radiation exposure to the workers. In this investigation, a typical 11-MeV proton, self-shielded cyclotron has been assessed for its residual radiation sources in the cyclotron's shielding, tank/chamber, cave wall as well as <span class="hlt">target</span> system. Using a portable gamma ray spectroscopy system, the radiation measurement in the cyclotron environment has been carried out. Experimental results indicate that relatively long-lived radioisotopes such as Mn-54, Zn-65 and Eu-152 are detected in the inner and outer surface of the cyclotron shielding respectively while Mn-54 spectrum is observed around the cyclotron chamber. Weak intensity of Eu-152 radioisotope is again spotted in the inner and outer surface of the cyclotron cave wall. Angular distribution measurement of the Eu-152 shows that the intensity slightly drops with increasing observation angle relative to the proton beam incoming angle. In the <span class="hlt">target</span> system, gamma rays from Co-56, Mn-52, Co-60, Mn-54, Ag-110 m are identified. TALYS-calculated nuclear cross-section data are used to study the origins of the radioactive by-<span class="hlt">products</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018PPCF...60f5003Y','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018PPCF...60f5003Y"><span>Spatiotemporal distributions of pair <span class="hlt">production</span> and cascade in solid <span class="hlt">targets</span> irradiated by ultra-relativistic lasers with different polarizations</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Yuan, T.; Yu, J. Y.; Liu, W. Y.; Weng, S. M.; Yuan, X. H.; Luo, W.; Chen, M.; Sheng, Z. M.; Zhang, J.</p> <p>2018-06-01</p> <p>Two-dimensional particle-in-cell simulations have been performed to study electron-positron pair <span class="hlt">production</span> and cascade development in single ultra-relativistic laser interaction with solid <span class="hlt">targets</span>. The spatiotemporal distributions of particles produced via QED processes are illustrated and their dependence on laser polarizations is investigated. The evolution of particle generation displays clear QED cascade characters. Studies show that although a circularly polarized laser delays the QED process due to the effective ion acceleration, it can reduce the <span class="hlt">target</span> heating and confine high-energy charged particles, which leads to deeper QED cascade order and denser pair plasma <span class="hlt">production</span> than linearly polarized lasers. These findings may benefit the understanding of the coming experimental studies of ultra-relativistic laser <span class="hlt">target</span> interaction in the QED dominated regime.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24615242','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24615242"><span>Correlation analysis of <span class="hlt">targeted</span> proteins and metabolites to assess and engineer microbial isopentenol <span class="hlt">production</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>George, Kevin W; Chen, Amy; Jain, Aakriti; Batth, Tanveer S; Baidoo, Edward E K; Wang, George; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek Soon</p> <p>2014-08-01</p> <p>The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between <span class="hlt">targeted</span> proteins and metabolites and apply it to the microbial <span class="hlt">production</span> of isopentenol, a promising biofuel. Starting with a seven-gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol <span class="hlt">production</span>. Aided by the <span class="hlt">targeted</span> quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high-throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways. © 2014 Wiley Periodicals, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ocg.cancer.gov/node/37','NCI'); return false;" href="https://ocg.cancer.gov/node/37"><span><span class="hlt">TARGET</span> Research Goals</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p><span class="hlt">TARGET</span> researchers use various sequencing and array-based methods to examine the genomes, transcriptomes, and for some diseases epigenomes of select childhood cancers. This “multi-omic” approach generates a comprehensive <span class="hlt">profile</span> of molecular alterations for each cancer type. Alterations are changes in DNA or RNA, such as rearrangements in chromosome structure or variations in gene expression, respectively. Through computational analyses and assays to validate biological function, <span class="hlt">TARGET</span> researchers predict which alterations disrupt the function of a gene or pathway and promote cancer growth, progression, and/or survival. Researchers identify candidate therapeutic <span class="hlt">targets</span> and/or prognostic markers from the cancer-associated alterations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3547856','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3547856"><span>Naphthoquinone Derivatives Exert Their Antitrypanosomal Activity via a Multi-<span class="hlt">Target</span> Mechanism</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Mazet, Muriel; Perozzo, Remo; Bergamini, Christian; Prati, Federica; Fato, Romana; Lenaz, Giorgio; Capranico, Giovanni; Brun, Reto; Bakker, Barbara M.; Michels, Paul A. M.; Scapozza, Leonardo; Bolognesi, Maria Laura; Cavalli, Andrea</p> <p>2013-01-01</p> <p>Background and Methodology Recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid <span class="hlt">profile</span> in cell-based experiments. The lead of this series (B6, 2-phenoxy-1,4-naphthoquinone) showed an ED50 of 80 nM against Trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. A multitarget <span class="hlt">profile</span> for this compound is easily conceivable, because quinones, as natural <span class="hlt">products</span>, serve plants as potent defense chemicals with an intrinsic multifunctional mechanism of action. To disclose such a multitarget <span class="hlt">profile</span> of B6, we exploited a chemical proteomics approach. Principal Findings A functionalized congener of B6 was immobilized on a solid matrix and used to isolate <span class="hlt">target</span> proteins from Trypanosoma brucei lysates. Mass analysis delivered two enzymes, i.e. glycosomal glycerol kinase and glycosomal glyceraldehyde-3-phosphate dehydrogenase, as potential molecular <span class="hlt">targets</span> for B6. Both enzymes were recombinantly expressed and purified, and used for chemical validation. Indeed, B6 was able to inhibit both enzymes with IC50 values in the micromolar range. The multifunctional <span class="hlt">profile</span> was further characterized in experiments using permeabilized Trypanosoma brucei cells and mitochondrial cell fractions. It turned out that B6 was also able to generate oxygen radicals, a mechanism that may additionally contribute to its observed potent trypanocidal activity. Conclusions and Significance Overall, B6 showed a multitarget mechanism of action, which provides a molecular explanation of its promising anti-trypanosomatid activity. Furthermore, the forward chemical genetics approach here applied may be viable in the molecular characterization of novel multitarget ligands. PMID:23350008</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19980162997','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19980162997"><span>Cosmogenic <span class="hlt">Production</span> of Be-7 and Be-10 in Water <span class="hlt">Targets</span></span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Nishiizumi, K.; Finkel, R. C.; Klein, J.; Kohl, C. P.</p> <p>1996-01-01</p> <p>We have measured Be-10(t(sub 1/2) = 1.5 x 10(exp 6) years) and Be-7 (t(sub 1/2) = 53.28 days) concentrations in water <span class="hlt">targets</span> exposed for 1 to 2 years at Echo Lake, Colorado (elevation = 3246 m) and at La Jolla, California (140 m). Neutron monitor data were used to normalize the measured concentrations in order to calculate <span class="hlt">production</span> rates equivalent to the cosmic ray flux averaged over four solar cycles (43 years). The Be-7 <span class="hlt">production</span> rates thus obtained correspond to 6.03 +/- 0.07 x 10(exp -6) atom/g.O/s at Echo Lake and 5.06 +/- 0.20 x 10(exp -7) atom/g.O/ s at La Jolla. The Be-10 <span class="hlt">production</span> rates correspond to 3.14 +/- 0.18 x 10(exp -6) atom/g.O/s at Echo Lake and 2.68 +/- 0.47 x 10(exp -7) atom/g.O/s at La Jolla. When compared with Be-10 <span class="hlt">production</span> rates determined in Be-10-saturated rocks from the Antarctic and with theoretical calculations based on meteorite and lunar sample data, we find that the million-year average <span class="hlt">production</span> rate is about 14 - 17% greater than the present <span class="hlt">production</span> rate averaged over the last four solar cycles. Comparison with <span class="hlt">production</span> rates determined by measuring glacially polished rocks from the Sierra Nevada in California indicates that average <span class="hlt">production</span> (based on a revised 13,000-year deglaciation age and a geographic latitude correction) is a about 11% greater than the average over the last four solar cycles. The measured Be-10/Be-7 <span class="hlt">production</span> ratio in oxygen is 0.52 +/- 0.03 at Echo Lake and 0.55 +/- 0.07 at La Jolla.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25263698','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25263698"><span>Is there a link between selectivity and binding thermodynamics <span class="hlt">profiles</span>?</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Tarcsay, Ákos; Keserű, György M</p> <p>2015-01-01</p> <p>Thermodynamics of ligand binding is influenced by the interplay between enthalpy and entropy contributions of the binding event. The impact of these binding free energy components, however, is not limited to the primary <span class="hlt">target</span> only. Here, we investigate the relationship between binding thermodynamics and selectivity <span class="hlt">profiles</span> by combining publicly available data from broad off-<span class="hlt">target</span> assay <span class="hlt">profiling</span> and the corresponding thermodynamics measurements. Our analysis indicates that compounds binding their primary <span class="hlt">targets</span> with higher entropy contributions tend to hit more off-<span class="hlt">targets</span> compared with those ligands that demonstrated enthalpy-driven binding. Copyright © 2014 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4724657','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4724657"><span>Factors to consider in developing individual pharmaceutical <span class="hlt">product</span> quality risk <span class="hlt">profiles</span> useful to government procurement agencies</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Xu, Wei; Boehm, Garth; Zheng, Qiang</p> <p>2015-01-01</p> <p>Governments that procure pharmaceutical <span class="hlt">products</span> from an Essential Medicine List (EML) bear special responsibility for the quality of these <span class="hlt">products</span>. In this article we examine the possibility of developing a pharmaceutical <span class="hlt">product</span> quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent <span class="hlt">product</span> quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate <span class="hlt">product</span> specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other <span class="hlt">product</span> specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative <span class="hlt">product</span> risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral <span class="hlt">products</span>. We conclude that a <span class="hlt">product</span> specific quality risk <span class="hlt">profile</span> would be enhanced by including a risk assessment for degradation for all <span class="hlt">products</span>, and in the case of solid oral <span class="hlt">products</span>, dissolution. PMID:26904402</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26904402','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26904402"><span>Factors to consider in developing individual pharmaceutical <span class="hlt">product</span> quality risk <span class="hlt">profiles</span> useful to government procurement agencies.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Xu, Wei; Boehm, Garth; Zheng, Qiang</p> <p>2016-01-01</p> <p>Governments that procure pharmaceutical <span class="hlt">products</span> from an Essential Medicine List (EML) bear special responsibility for the quality of these <span class="hlt">products</span>. In this article we examine the possibility of developing a pharmaceutical <span class="hlt">product</span> quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent <span class="hlt">product</span> quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate <span class="hlt">product</span> specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other <span class="hlt">product</span> specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative <span class="hlt">product</span> risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral <span class="hlt">products</span>. We conclude that a <span class="hlt">product</span> specific quality risk <span class="hlt">profile</span> would be enhanced by including a risk assessment for degradation for all <span class="hlt">products</span>, and in the case of solid oral <span class="hlt">products</span>, dissolution.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://proteomics.cancer.gov/news_and_announcements/nci-requests-targets-monoclonal-antibody-production-and-characterization-1','NCI'); return false;" href="https://proteomics.cancer.gov/news_and_announcements/nci-requests-targets-monoclonal-antibody-production-and-characterization-1"><span>NCI Requests <span class="hlt">Targets</span> for Monoclonal Antibody <span class="hlt">Production</span> and Characterization | Office of Cancer Clinical Proteomics Research</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein <span class="hlt">targets</span> for affinity <span class="hlt">production</span> and distribution. Submissions will be accepted through February 5, 2016.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://proteomics.cancer.gov/node/82','NCI'); return false;" href="https://proteomics.cancer.gov/node/82"><span>NCI Requests <span class="hlt">Targets</span> for Monoclonal Antibody <span class="hlt">Production</span> and Characterization | Office of Cancer Clinical Proteomics Research</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein <span class="hlt">targets</span> for affinity <span class="hlt">production</span> and distribution. Submissions will be accepted through July 12, 2013.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29503805','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29503805"><span>Comparing EPA <span class="hlt">production</span> and fatty acid <span class="hlt">profiles</span> of three Phaeodactylum tricornutum strains under western Norwegian climate conditions.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Steinrücken, Pia; Prestegard, Siv Kristin; de Vree, Jeroen Hendrik; Storesund, Julia E; Pree, Bernadette; Mjøs, Svein Are; Erga, Svein Rune</p> <p>2018-03-01</p> <p>Microalgae could provide a sustainable alternative to fish oil as a source for the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, growing microalgae on a large-scale is still more cost-intensive than fish oil <span class="hlt">production</span>, and outdoor <span class="hlt">productivities</span> vary greatly with reactor type, geographic location, climate conditions and microalgae species or even strains. The diatom Phaeodactylum tricornutum has been intensively investigated for its potential in large-scale <span class="hlt">production</span>, due to its robustness and comparatively high growth rates and EPA content. Yet, most research have been performed in southern countries and with a single commercial P . tricornutum strain, while information about <span class="hlt">productivities</span> at higher latitudes and of local strains is scarce. We examined the potential of the climate conditions in Bergen, western Norway for outdoor cultivation of P . tricornutum in flat panel photobioreactors and cultivated three different strains simultaneously, one commercial strain from Spain (Fito) and two local isolates (M28 and B58), to assess and compare their biomass and EPA <span class="hlt">productivities</span>, and fatty acid (FA) <span class="hlt">profiles</span>. The three strains possessed similar biomass <span class="hlt">productivities</span> (average volumetric <span class="hlt">productivities</span> of 0.20, 0.18, and 0.21 g L - 1  d - 1 ), that were lower compared to <span class="hlt">productivities</span> reported from southern latitudes. However, EPA <span class="hlt">productivities</span> differed between the strains (average volumetric <span class="hlt">productivities</span> of 9.8, 5.7 and 6.9 mg L - 1  d - 1 ), due to differing EPA contents (average of 4.4, 3.2 and 3.1% of dry weight), and were comparable to results from Italy. The EPA content of strain Fito of 4.4% is higher than earlier reported for P . tricornutum (2.6-3.1%) and was only apparent under outdoor conditions. A principal component analysis (PCA) of the relative FA composition revealed strain-specific <span class="hlt">profiles</span>. However, including data from laboratory experiments, revealed more significant</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26231135','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26231135"><span>The influence of naphthaleneacetic acid (NAA) and coumarin on flavonoid <span class="hlt">production</span> by fungus Phellinus sp.: modeling of <span class="hlt">production</span> kinetic <span class="hlt">profiles</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ma, Xiao-Kui; Li, Le; Peterson, Eric Charles; Ruan, Tingting; Duan, Xiaoyi</p> <p>2015-11-01</p> <p>For the purpose of improving the fungal <span class="hlt">production</span> of flavonoids, the influence of naphthaleneacetic acid (NAA) and coumarin on flavonoid <span class="hlt">production</span> by fungus Phellinus sp. P0988 was investigated by developing the corresponding kinetics of flavonoid <span class="hlt">production</span> in a 7-L bioreactor. Phellinus sp. was confirmed to form flavonoids in pellets and broth when cultivated in basic medium, and the optimum concentration of NAA and coumarin in medium for flavonoid <span class="hlt">production</span> were determined to be 0.03 and 0.02 g/L, respectively. The developed unstructured mathematical models were in good agreement with the experimental results with respect to flavonoid <span class="hlt">production</span> kinetic <span class="hlt">profiles</span> with NAA and coumarin supplementation at optimum levels and revealed significant accuracy in terms of statistical consistency and robustness. Analysis of these kinetic processes indicated that NAA and coumarin supplementations imposed a stronger positive influence on flavonoid <span class="hlt">production</span> and substrate consumption compared to their effects on cell growth. The separate addition of NAA and coumarin resulted in enhancements in final <span class="hlt">product</span> accumulation and <span class="hlt">productivity</span>, achieving final flavonoid concentrations of 3.60 and 2.75 g/L, respectively, and glucose consumption showed a significant decrease compared to the non-supplemented control as well. Also, the separate presence of NAA and coumarin respectively decreased maintenance coefficients (M s) from 2.48 in the control to 1.39 and 0.22, representing decreases of 43.9 and 91.1 %, respectively. The current study is the first known application of mathematical kinetic models to explore the influence of medium components adding on flavonoid <span class="hlt">production</span> by fungi.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26002902','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26002902"><span>Increasing Avermectin <span class="hlt">Production</span> in Streptomyces avermitilis by Manipulating the Expression of a Novel TetR-Family Regulator and Its <span class="hlt">Target</span> Gene <span class="hlt">Product</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Liu, Wenshuai; Zhang, Qinling; Guo, Jia; Chen, Zhi; Li, Jilun; Wen, Ying</p> <p>2015-08-01</p> <p>Avermectins produced by Streptomyces avermitilis are commercially important anthelmintic agents. The detailed regulatory mechanisms of avermectin biosynthesis remain unclear. Here, we identified SAV3619, a TetR-family transcriptional regulator designated AveT, to be an activator for both avermectin <span class="hlt">production</span> and morphological differentiation in S. avermitilis. AveT was shown to indirectly stimulate avermectin <span class="hlt">production</span> by affecting transcription of the cluster-situated activator gene aveR. AveT directly repressed transcription of its own gene (aveT), adjacent gene pepD2 (sav_3620), sav_7490 (designated aveM), and sav_7491 by binding to an 18-bp perfect palindromic sequence (CGAAACGKTKYCGTTTCG, where K is T or G and Y is T or C and where the underlining indicates inverted repeats) within their promoter regions. aveM (which encodes a putative transmembrane efflux protein belonging to the major facilitator superfamily [MFS]), the important <span class="hlt">target</span> gene of AveT, had a striking negative effect on avermectin <span class="hlt">production</span> and morphological differentiation. Overexpression of aveT and deletion of aveM in wild-type and industrial strains of S. avermitilis led to clear increases in the levels of avermectin <span class="hlt">production</span>. In vitro gel-shift assays suggested that C-5-O-B1, the late pathway precursor of avermectin B1, acts as an AveT ligand. Taken together, our findings indicate positive-feedback regulation of aveT expression and avermectin <span class="hlt">production</span> by a late pathway intermediate and provide the basis for an efficient strategy to increase avermectin <span class="hlt">production</span> in S. avermitilis by manipulation of AveT and its <span class="hlt">target</span> gene <span class="hlt">product</span>, AveM. Copyright © 2015, American Society for Microbiology. All Rights Reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26222226','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26222226"><span>Ultra-processed foods have the worst nutrient <span class="hlt">profile</span>, yet they are the most available packaged <span class="hlt">products</span> in a sample of New Zealand supermarkets.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Luiten, Claire M; Steenhuis, Ingrid Hm; Eyles, Helen; Ni Mhurchu, Cliona; Waterlander, Wilma E</p> <p>2016-02-01</p> <p>To examine the availability of packaged food <span class="hlt">products</span> in New Zealand supermarkets by level of industrial processing, nutrient <span class="hlt">profiling</span> score (NPSC), price (energy, unit and serving costs) and brand variety. Secondary analysis of cross-sectional survey data on packaged supermarket food and non-alcoholic beverages. <span class="hlt">Products</span> were classified according to level of industrial processing (minimally, culinary and ultra-processed) and their NPSC. Packaged foods available in four major supermarkets in Auckland, New Zealand. Packaged supermarket food <span class="hlt">products</span> for the years 2011 and 2013. The majority (84% in 2011 and 83% in 2013) of packaged foods were classified as ultra-processed. A significant positive association was found between the level of industrial processing and NPSC, i.e., ultra-processed foods had a worse nutrient <span class="hlt">profile</span> (NPSC=11.63) than culinary processed foods (NPSC=7.95), which in turn had a worse nutrient <span class="hlt">profile</span> than minimally processed foods (NPSC=3.27), P<0.001. No clear associations were observed between the three price measures and level of processing. The study observed many variations of virtually the same <span class="hlt">product</span>. The ten largest food manufacturers produced 35% of all packaged foods available. In New Zealand supermarkets, ultra-processed foods comprise the largest proportion of packaged foods and are less healthy than less processed foods. The lack of significant price difference between ultra- and less processed foods suggests ultra-processed foods might provide time-poor consumers with more value for money. These findings highlight the need to improve the supermarket food supply by reducing numbers of ultra-processed foods and by reformulating <span class="hlt">products</span> to improve their nutritional <span class="hlt">profile</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29748090','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29748090"><span>Non-<span class="hlt">targeted</span> glycosidic <span class="hlt">profiling</span> of international wines using neutral loss-high resolution mass spectrometry.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Barnaba, C; Dellacassa, E; Nicolini, G; Nardin, T; Serra, M; Larcher, R</p> <p>2018-07-06</p> <p>Many metabolites naturally occur as glycosides, since sugar moieties can be crucial for their biological activity and increase their water solubility. In the plant kingdom they may occur as glycosides or sugar esters, depending on precursor chemical structure, and in wine they have traditionally attracted attention due to their organoleptic properties, such as astringency and bitterness, and because they affect the colour and aroma of wines. A new approach directed at detailed description of glycosides in a large selection of monovarietal wines (8 samples each of Pinot Blanc, Muller Thurgau, Riesling, Traminer, Merlot, Pinot Noir and Cabernet Sauvignon) was developed by combining high performance liquid chromatography with high resolution tandem mass spectrometry. Analytical separation was performed on an Accucore™ Polar Premium LC column, while mass analysis was performed in negative ion mode with an non-<span class="hlt">targeted</span> screening approach, using a Full MS/AIF/NL dd-MS 2 experiment at a resolving power of 140,000 FWHM. Over 280 glycoside-like compounds were detected, of which 133 (including low-molecular weight phenols, flavonoids and monoterpenols) were tentatively identified in the form of pentose (6), deoxyhexose (17), hexose (73), hexose-pentose (16), hexose-deoxyhexose (7), dihexose (5) and hexose ester (9) derivatives. It was not possible to univocally define the corresponding chemical structure for the remaining 149 glycosides. Non-parametric statistical analysis showed it was possible to well characterise the glycosylated <span class="hlt">profile</span> of all red and Traminer wines, while the identified glycosides were almost entirely lacking in Pinot Blanc, Riesling and Muller Thurgau wines. Also Tukey's Honestly Significant Difference test (p < 0.05) and Principal Component Analysis confirmed that it was possible to almost entirely distinguish the selected red wines from each other according to their glycosylated <span class="hlt">profile</span>. Copyright © 2018 Elsevier B.V. All rights reserved.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_18 --> <div id="page_19" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="361"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018GeCoA.220..276M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018GeCoA.220..276M"><span><span class="hlt">Production</span> of 21Ne in depth-<span class="hlt">profiled</span> olivine from a 54 Ma basalt sequence, Eastern Highlands (37° S), Australia</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Matchan, Erin L.; Honda, Masahiko; Barrows, Timothy T.; Phillips, David; Chivas, Allan R.; Fifield, L. Keith; Fabel, Derek</p> <p>2018-01-01</p> <p>In this study we investigate the cosmogenic neon component in olivine samples from a vertical <span class="hlt">profile</span> in order to quantify muogenic 21Ne <span class="hlt">production</span> in this mineral. Samples were collected from an 11 m thick Eocene basalt <span class="hlt">profile</span> in the Eastern Highlands of southeastern Australia. An eruption age of 54.15 ± 0.36 Ma (2σ) was determined from 40Ar/39Ar step-heating experiments (n = 6) on three whole-rock samples. A 36Cl <span class="hlt">profile</span> on the section indicated an apparent steady state erosion rate of 4.7 ± 0.5 m Ma-1. The eruption age was used to calculate in situ produced radiogenic 4He and nucleogenic 3He and 21Ne concentrations in olivine. Olivine mineral separates (n = 4), extracted from the upper two metres of the studied <span class="hlt">profile</span>, reveal cosmogenic 21Ne concentrations that attenuate exponentially with depth. However, olivine (Fo68) extracted from below 2 m does not contain discernible 21Ne aside from magmatic and nucleogenic components, with the exception of one sample that apparently contained equal proportions of nucleogenic and muogenic neon. Modelling results suggest a muogenic neon sea-level high-latitude <span class="hlt">production</span> rate of 0.02 ± 0.04 to 0.9 ± 1.3 atoms g-1 a-1 (1σ), or <2.5% of spallogenic cosmogenic 21Ne <span class="hlt">production</span> at Earth's surface. These data support a key implicit assumption in the literature that accumulation of muogenic 21Ne in olivine in surface samples is likely to be negligible/minimal compared to spallogenic 21Ne.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018ERL....13c4016B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018ERL....13c4016B"><span>The contribution of sectoral climate change mitigation options to national <span class="hlt">targets</span>: a quantitative assessment of dairy <span class="hlt">production</span> in Kenya</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Brandt, Patric; Herold, Martin; Rufino, Mariana C.</p> <p>2018-03-01</p> <p>Reducing greenhouse gas (GHG) emissions from agriculture has become a critical <span class="hlt">target</span> in national climate change policies. More than 80% of the countries in Sub-Saharan Africa (SSA) refer to the reduction of agricultural emissions, including livestock, in their nationally determined contribution (NDC) to mitigate climate change. The livestock sector in Kenya contributes largely to the gross domestic <span class="hlt">product</span> and to GHG emissions from the land use sector. The government has recently pledged in its NDC to curb total GHG emissions by 30% by 2030. Quantifying and linking the mitigation potential of farm practices to national <span class="hlt">targets</span> is required to support realistically the implementation of NDCs. Improvements in feed and manure management represent promising mitigation options for dairy <span class="hlt">production</span>. This study aimed (i) to assess mitigation and food <span class="hlt">production</span> benefits of feed and manure management scenarios, including land use changes covering Kenya’s entire dairy <span class="hlt">production</span> region and (ii) to analyse the contribution of these practices to national <span class="hlt">targets</span> on milk <span class="hlt">production</span> and mitigation, and their biophysical feasibility given the availability of arable land. The results indicate that improving forage quality by increasing the use of Napier grass and supplementing dairy concentrates supports Kenya’s NDC <span class="hlt">target</span>, reduces emission intensities by 26%-31%, partially achieves the national milk <span class="hlt">productivity</span> <span class="hlt">target</span> for 2030 by 38%-41%, and shows high feasibility given the availability of arable land. Covering manure heaps may reduce emissions from manure management by 68%. In contrast, including maize silage in cattle diets would not reduce emission intensities due to the risk of ten-fold higher emissions from the conversion of land required to grow additional maize. The shortage of arable land may render the implementation of these improved feed practices largely infeasible. This assessment provides the first quantitative estimates of the potential of feed</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017HEDP...23..115W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017HEDP...23..115W"><span>Pair <span class="hlt">production</span> by high intensity picosecond laser interacting with thick solid <span class="hlt">target</span> at XingGuangIII</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wu, Yuchi; Dong, Kegong; Yan, Yonghong; Zhu, Bin; Zhang, Tiankui; Chen, Jia; Yu, Minghai; Tan, Fang; Wang, Shaoyi; Han, Dan; Lu, Feng; Gu, Yuqiu</p> <p>2017-06-01</p> <p>An experiment for pair <span class="hlt">production</span> by high intensity laser irradiating thick solid <span class="hlt">targets</span> is present. The <!-?show 146#?->experiment used picosecond beam of the XingGuangIII laser facility, with intensities up to several 1019 W/cm2, pulse durations about 0.8 ps and laser energies around 120 J. Pairs were generated from 1 mm-<!-?show 132#?->thick tantalum disk <span class="hlt">targets</span> with different diameters from 1 mm to 10 mm. Energy spectra of hot electron <!-?show 146#?->from <span class="hlt">target</span><!-?Comment text="rear"?->rear surface represent a Maxwellian distribution and obey a scaling of ∼(Iλ2)0.5. Large quantity of positrons were observed at the <span class="hlt">target</span> rear normal direction with a yield up to 2.8 × 109 e+/sr. Owing to the <span class="hlt">target</span> rear surface sheath field, the positrons behave as a quasi-monoenergetic beam with peak energy of several MeV. Our experiment shows that the peak energy of positron beam is inversely proportional <!-?show 146#?->to the <span class="hlt">target</span> diameter.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28058815','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28058815"><span>Small RNAome <span class="hlt">profiling</span> from human skeletal muscle: novel miRNAs and their <span class="hlt">targets</span> associated with cancer cachexia.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Narasimhan, Ashok; Ghosh, Sunita; Stretch, Cynthia; Greiner, Russell; Bathe, Oliver F; Baracos, Vickie; Damaraju, Sambasivarao</p> <p>2017-06-01</p> <p>MicroRNAs (miRs) are small non-coding RNAs that regulate gene (mRNA) expression. Although the pathological role of miRs have been studied in muscle wasting conditions such as myotonic and muscular dystrophy, their roles in cancer cachexia (CC) are still emerging. The objectives are (i) to <span class="hlt">profile</span> human skeletal muscle expressed miRs; (ii) to identify differentially expressed (DE) miRs between cachectic and non-cachectic cancer patients; (iii) to identify mRNA <span class="hlt">targets</span> for the DE miRs to gain mechanistic insights; and (iv) to investigate if miRs show potential prognostic and predictive value. Study subjects were classified based on the international consensus diagnostic criteria for CC. Forty-two cancer patients were included, of which 22 were cachectic cases and 20 were non-cachectic cancer controls. Total RNA isolated from muscle biopsies were subjected to next-generation sequencing. A total of 777 miRs were <span class="hlt">profiled</span>, and 82 miRs with read counts of ≥5 in 80% of samples were retained for analysis. We identified eight DE miRs (up-regulated, fold change of ≥1.4 at P < 0.05). A total of 191 potential mRNA <span class="hlt">targets</span> were identified for the DE miRs using previously described human skeletal muscle mRNA expression data (n = 90), and a majority of them were also confirmed in an independent mRNA transcriptome dataset. Ingenuity pathway analysis identified pathways related to myogenesis and inflammation. qRT-PCR analysis of representative miRs showed similar direction of effect (P < 0.05), as observed in next-generation sequencing. The identified miRs also showed prognostic and predictive value. In all, we identified eight novel miRs associated with CC. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28125067','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28125067"><span>Enniatin and Beauvericin Biosynthesis in Fusarium Species: <span class="hlt">Production</span> <span class="hlt">Profiles</span> and Structural Determinant Prediction.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Liuzzi, Vania C; Mirabelli, Valentina; Cimmarusti, Maria Teresa; Haidukowski, Miriam; Leslie, John F; Logrieco, Antonio F; Caliandro, Rocco; Fanelli, Francesca; Mulè, Giuseppina</p> <p>2017-01-25</p> <p>Members of the fungal genus Fusarium can produce numerous secondary metabolites, including the nonribosomal mycotoxins beauvericin (BEA) and enniatins (ENNs). Both mycotoxins are synthesized by the multifunctional enzyme enniatin synthetase (ESYN1) that contains both peptide synthetase and S-adenosyl-l-methionine-dependent N -methyltransferase activities. Several Fusarium species can produce ENNs, BEA or both, but the mechanism(s) enabling these differential metabolic <span class="hlt">profiles</span> is unknown. In this study, we analyzed the primary structure of ESYN1 by sequencing esyn1 transcripts from different Fusarium species. We measured ENNs and BEA <span class="hlt">production</span> by ultra-performance liquid chromatography coupled with photodiode array and Acquity QDa mass detector (UPLC-PDA-QDa) analyses. We predicted protein structures, compared the predictions by multivariate analysis methods and found a striking correlation between BEA/ENN-producing <span class="hlt">profiles</span> and ESYN1 three-dimensional structures. Structural differences in the β strand's Asn789-Ala793 and His797-Asp802 portions of the amino acid adenylation domain can be used to distinguish BEA/ENN-producing Fusarium isolates from those that produce only ENN.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29859466','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29859466"><span>Marine natural <span class="hlt">products</span> for multi-<span class="hlt">targeted</span> cancer treatment: A future insight.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kumar, Maushmi S; Adki, Kaveri M</p> <p>2018-05-30</p> <p>Cancer is world's second largest alarming disease, which involves abnormal cell growth and have potential to spread to other parts of the body. Most of the available anticancer drugs are designed to act on specific <span class="hlt">targets</span> by altering the activity of involved transporters and genes. As cancer cells exhibit complex cellular machinery, the regeneration of cancer tissues and chemo resistance towards the therapy has been the main obstacle in cancer treatment. This fact encourages the researchers to explore the multitargeted use of existing medicines to overcome the shortcomings of chemotherapy for alternative and safer treatment strategies. Recent developments in genomics-proteomics and an understanding of the molecular pharmacology of cancer have also challenged researchers to come up with <span class="hlt">target</span>-based drugs. The literature supports the evidence of natural compounds exhibiting antioxidant, antimitotic, anti-inflammatory, antibiotic as well as anticancer activity. In this review, we have selected marine sponges as a prolific source of bioactive compounds which can be explored for their possible use in cancer and have tried to link their role in cancer pathway. To prove this, we revisited the literature for the selection of cancer genes for the multitargeted use of existing drugs and natural <span class="hlt">products</span>. We used Cytoscape network analysis and Search tool for retrieval of interacting genes/ proteins (STRING) to study the possible interactions to show the links between the antioxidants, antibiotics, anti-inflammatory and antimitotic agents and their <span class="hlt">targets</span> for their possible use in cancer. We included total 78 pathways, their genes and natural compounds from the above four pharmacological classes used in cancer treatment for multitargeted approach. Based on the Cytoscape network analysis results, we shortlist 22 genes based on their average shortest path length connecting one node to all other nodes in a network. These selected genes are CDKN2A, FH, VHL, STK11, SUFU, RB1</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014Nanos...6.3742M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014Nanos...6.3742M"><span>Tumor <span class="hlt">targeting</span> <span class="hlt">profiling</span> of hyaluronan-coated lipid based-nanoparticles</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Mizrahy, Shoshy; Goldsmith, Meir; Leviatan-Ben-Arye, Shani; Kisin-Finfer, Einat; Redy, Orit; Srinivasan, Srimeenakshi; Shabat, Doron; Godin, Biana; Peer, Dan</p> <p>2014-03-01</p> <p>Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based <span class="hlt">targeted</span> and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored HA had a significant influence on the affinity towards CD44 on B16F10 murine melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor <span class="hlt">targeting</span> specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular <span class="hlt">targeting</span> beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular <span class="hlt">targeting</span> moiety.Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://proteomics.cancer.gov/news_and_announcements/nci-requests-cancer-targets-monoclonal-antibody-production-and-0','NCI'); return false;" href="https://proteomics.cancer.gov/news_and_announcements/nci-requests-cancer-targets-monoclonal-antibody-production-and-0"><span>NCI Requests Cancer <span class="hlt">Targets</span> for Monoclonal Antibody <span class="hlt">Production</span> and Characterization | Office of Cancer Clinical Proteomics Research</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>In an effort to provide well-characterized monoclonal antibodies to the scientific community, the National Cancer Institute (NCI) Antibody Characterization Program requests cancer-related protein <span class="hlt">targets</span> for affinity <span class="hlt">production</span> and distribution.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16616280','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16616280"><span><span class="hlt">Targeted</span> therapies: a nursing perspective.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kay, Polly</p> <p>2006-02-01</p> <p>To review the development of <span class="hlt">targeted</span> therapies and the biology of relevant therapeutic <span class="hlt">targets</span>. To analyze the relevance of <span class="hlt">targeted</span> agents as part of current clinical practice. Research articles. Several <span class="hlt">targeted</span> agents are now available for clinical use. Their mechanisms of action are more specific against tumor cells than traditional cytotoxics. Monotherapy regimens based on <span class="hlt">targeted</span> agents tend to be better tolerated than chemotherapy, and most combination regimens with <span class="hlt">targeted</span> agents have proven feasible. Their availability has greatly expanded cancer treatment options, especially for chemorefractory patients. Nurses involved in the care of patients with cancer can benefit from an increased understanding of <span class="hlt">targeted</span> therapies, including their mechanisms of action, their efficacy <span class="hlt">profile</span>, as well as prophylaxis and management of adverse events and administration procedures.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2005JPhD...38.1828T','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2005JPhD...38.1828T"><span>Calculations of high-power <span class="hlt">production</span> <span class="hlt">target</span> and beamdump for the GSI future Super-FRS for a fast extraction scheme at the FAIR Facility</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Tahir, N. A.; Weick, H.; Iwase, H.; Geissel, H.; Hoffmann, D. H. H.; Kindler, B.; Lommel, B.; Radon, T.; Münzenberg, G.; Shutov, A.; Sümmerer, K.; Winkler, M.</p> <p>2005-06-01</p> <p>A superconducting fragment separator (Super-FRS) is being designed for the <span class="hlt">production</span> and separation of radioactive isotopes at the future FAIR (Facility for Antiprotons and Ion Research) facility at Darmstadt. This paper discusses various aspects and requirements for the high-power <span class="hlt">production</span> <span class="hlt">target</span> that will be used in the Super-FRS experiments. The <span class="hlt">production</span> <span class="hlt">target</span> must survive over an extended period of time as it will be used during the course of many experiments. The specific power deposited by the high intensity beam that will be generated at the future FAIR facility will be high enough to destroy the <span class="hlt">target</span> in most of the cases as a result of a single shot from the new heavy ion synchrotrons SIS100/300. By using an appropriate beam intensity and focal spot parameters, the <span class="hlt">target</span> would survive after being irradiated once. However, the heat should be dissipated efficiently before the same <span class="hlt">target</span> area is irradiated again. We have considered a wheel shaped solid carbon <span class="hlt">target</span> that rotates around its axis so that different areas of the <span class="hlt">target</span> are irradiated successively. This allows for cooling of the beam heated region by thermal conduction before the same part of the <span class="hlt">target</span> is irradiated a second time. Another attractive option is to use a liquid jet <span class="hlt">target</span> at the Super-FRS. First calculations of a possible liquid lithium <span class="hlt">target</span> are also presented in this paper. One of the advantages of using lithium as a <span class="hlt">target</span> is that it will survive even if one uses a smaller focal spot, which has half the area of that used for a solid carbon <span class="hlt">target</span>. This will significantly improve the isotope resolution. A similar problem associated with these experiments will be safe deposition of the beam energy in a beamdump after its interaction with the <span class="hlt">production</span> <span class="hlt">target</span>. We also present calculations to study the suitability of a proposed beamdump.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28420455','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28420455"><span>Nutrient <span class="hlt">profiling</span> for <span class="hlt">product</span> reformulation: public health impact and benefits for the consumer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lehmann, Undine; Charles, Véronique Rheiner; Vlassopoulos, Antonis; Masset, Gabriel; Spieldenner, Jörg</p> <p>2017-08-01</p> <p>The food industry holds great potential for driving consumers to adopt healthy food choices as (re)formulation of foods can improve the nutritional quality of these foods. Reformulation has been identified as a cost-effective intervention in addressing non-communicable diseases as it does not require significant alterations of consumer behaviour and dietary habits. Nutrient <span class="hlt">profiling</span> (NP), the science of categorizing foods based on their nutrient composition, has emerged as an essential tool and is implemented through many different <span class="hlt">profiling</span> systems to guide reformulation and other nutrition policies. NP systems should be adapted to their specific purposes as it is not possible to design one system that can equally address all policies and purposes, e.g. reformulation and labelling. The present paper discusses some of the key principles and specificities that underlie a NP system designed for reformulation with the example of the Nestlé nutritional <span class="hlt">profiling</span> system. Furthermore, the impact of reformulation at the level of the food <span class="hlt">product</span>, dietary intakes and public health are reviewed. Several studies showed that food and beverage reformulation, guided by a NP system, may be effective in improving population nutritional intakes and thereby its health status. In order to achieve its maximum potential and modify the food environment in a beneficial manner, reformulation should be implemented by the entire food sector. Multi-stakeholder partnerships including governments, food industry, retailers and consumer associations that will state concrete time-bound objectives accompanied by an independent monitoring system are the potential solution.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27605107','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27605107"><span>BeReTa: a systematic method for identifying <span class="hlt">target</span> transcriptional regulators to enhance microbial <span class="hlt">production</span> of chemicals.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kim, Minsuk; Sun, Gwanggyu; Lee, Dong-Yup; Kim, Byung-Gee</p> <p>2017-01-01</p> <p>Modulation of regulatory circuits governing the metabolic processes is a crucial step for developing microbial cell factories. Despite the prevalence of in silico strain design algorithms, most of them are not capable of predicting required modifications in regulatory networks. Although a few algorithms may predict relevant <span class="hlt">targets</span> for transcriptional regulator (TR) manipulations, they have limited reliability and applicability due to their high dependency on the availability of integrated metabolic/regulatory models. We present BeReTa (Beneficial Regulator <span class="hlt">Targeting</span>), a new algorithm for prioritization of TR manipulation <span class="hlt">targets</span>, which makes use of unintegrated network models. BeReTa identifies TR manipulation <span class="hlt">targets</span> by evaluating regulatory strengths of interactions and beneficial effects of reactions, and subsequently assigning beneficial scores for the TRs. We demonstrate that BeReTa can predict both known and novel TR manipulation <span class="hlt">targets</span> for enhanced <span class="hlt">production</span> of various chemicals in Escherichia coli Furthermore, through a case study of antibiotics <span class="hlt">production</span> in Streptomyces coelicolor, we successfully demonstrate its wide applicability to even less-studied organisms. To the best of our knowledge, BeReTa is the first strain design algorithm exclusively designed for predicting TR manipulation <span class="hlt">targets</span>. MATLAB code is available at https://github.com/kms1041/BeReTa (github). byungkim@snu.ac.krSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26868155','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26868155"><span>Evaluation of <span class="hlt">productivity</span> and antioxidant <span class="hlt">profile</span> of solid-state cultivated macrofungi Pleurotus albidus and Pycnoporus sanguineus.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gambato, Gabriela; Todescato, Kelly; Pavão, Elisa Maria; Scortegagna, Angélica; Fontana, Roselei Claudete; Salvador, Mirian; Camassola, Marli</p> <p>2016-05-01</p> <p>The aim of this study was to investigate the <span class="hlt">production</span> <span class="hlt">profile</span> of Pleurotus albidus and Pycnoporus sanguineus on different waste substrates containing natural phenolics, and also to investigate whether phenolic-rich substrates can improve the phenolic content of these macrofungi. The medium formulated with Pinus sp. sawdust (PSW) made possible the highest yields (2.62±0.73%) of P. sanguineus. However, the supplementation of PSW with apple waste (AW) resulted in better P. albidus yields (23.94±2.92%). The results indicated that the substrate composition affected macrofungi <span class="hlt">production</span>, also the chemical composition and the presence of phenolic compounds in the <span class="hlt">production</span> media influence phenolic content and antioxidant activity in macrofungi. Copyright © 2016 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29717604','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29717604"><span>[Design and research progress of zero <span class="hlt">profile</span> cervical Interbody cage].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhu, Jia; Wang, Song; Liao, Zhenhua; Liu, Weiqiang</p> <p>2017-02-01</p> <p>Zero <span class="hlt">profile</span> cervical interbody cage is an improvement of traditional fusion <span class="hlt">products</span> and necessary supplement of emerging artificial intervertebral disc <span class="hlt">products</span>. When applied in Anterior Cervical Decompression Fusion(ACDF), zero <span class="hlt">profile</span> cervical interbody cage can preserve the advantages of traditional fusion and reduce the incidence of postoperative complications. Moreover, zero <span class="hlt">profile</span> cervical interbody cage can be applied under the tabu symptoms of Artificial Cervical Disc Replacement(ACDR). This article summarizes zero <span class="hlt">profile</span> interbody cage <span class="hlt">products</span> that are commonly recognized and widely used in clinical practice in recent years, and reviews the progress of structure design and material research of zero <span class="hlt">profile</span> cervical interbody cage <span class="hlt">products</span>. Based on the latest clinical demands and research progress, this paper also discusses the future development directions of zero <span class="hlt">profile</span> interbody cage.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29934169','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29934169"><span>Nutritional, chemical and antioxidant/pro-oxidant <span class="hlt">profiles</span> of silverskin, a coffee roasting by-<span class="hlt">product</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Costa, Anabela S G; Alves, Rita C; Vinha, Ana F; Costa, Elísio; Costa, Catarina S G; Nunes, M Antónia; Almeida, Agostinho A; Santos-Silva, Alice; Oliveira, M Beatriz P P</p> <p>2018-11-30</p> <p>Coffee silverskin (a coffee roasting by-<span class="hlt">product</span>) contains high amounts of dietary fibre (49% insoluble and 7% soluble) and protein (19%). Potassium (∼5g/100g), magnesium (2g/100g) and calcium (0.6g/100g) are the major macrominerals. The vitamin E <span class="hlt">profile</span> of silverskin comprises α-tocopherol, β-tocopherol, ɣ-tocopherol, δ-tocopherol, β-tocotrienol, ɣ-tocotrienol, and δ-tocotrienol. The fatty acid <span class="hlt">profile</span> is mainly saturated (C16:0 and C22:0), but the total amount of fat is low (2.4%). Caffeine (1.25g/100g), chlorogenic acid (246mg/100g), and 5-hydroxymethylfurfural (5.68mg/100g) are also present in silverskin. Total phenolics and flavonoids are partially responsible for the in vitro antioxidant activity. Silverskin extracts protected erythrocytes from oxidative AAPH- and H 2 O 2 -induced hemolysis, but at high concentrations a pro-oxidant effect on erythrocyte morphology was observed. Copyright © 2017 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22699652','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22699652"><span><span class="hlt">Profile</span> of Brazilian scientific <span class="hlt">production</span> on A/H1N1 pandemic influenza.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Luchs, Adriana</p> <p>2012-06-01</p> <p>In the last few years, bibliometric studies have proliferated, seeking to provide data on world research. This study analyzes the <span class="hlt">profile</span> of the Brazilian scientific <span class="hlt">production</span> in the A (H1N1) influenza field between 2009 and 2011. The research was conducted in MEDLINE, SciELO and LILACS databases, selecting papers in which the term "H1N1" and "Brazil" were defined as the main topics. The data were analyzed taking into consideration the Brazilian state and institution in which the articles were produced, the impact factor of the journal and the language. The research revealed 40 documents (27 from MEDLINE, 16 from SciELO and 24 from LILACS). The journal impact factor ranged from 0.0977 to 8.1230. A similar amount of articles were written in English and Portuguese and São Paulo was the most <span class="hlt">productive</span> state in the country, with 95% of the Brazilian <span class="hlt">production</span> originating from the Southern and Southeastern regions. Linguistic data indicate that previous efforts made in order to improve the scientific <span class="hlt">production</span> of Brazilian researchers making their observations attain a broader scientific audience produced results. It is necessary to assess the scientific studies, especially those conducted with public funds, in order to ensure that the results will benefit society.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018AIPC.1960d0015O','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018AIPC.1960d0015O"><span>A model for prediction of <span class="hlt">profile</span> and flatness of hot and cold rolled flat <span class="hlt">products</span> in four-high mills</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Overhagen, Christian; Mauk, Paul Josef</p> <p>2018-05-01</p> <p>For flat rolled <span class="hlt">products</span>, the thickness <span class="hlt">profile</span> in the transversal direction is one of the most important <span class="hlt">product</span> properties. For further processing, a defined crown of the <span class="hlt">product</span> is necessary. In the rolling process, several mechanical and thermal influences interact with each other to form the strip shape at the roll gap exit. In the present analysis, a process model for rolling of strip and sheet is presented. The core feature of the process model is a two-dimensional stress distribution model based on von Karman's differential equation. Sub models for the mechanical influences of work roll flattening as well as work and backup roll deflection and the thermal influence of work roll expansion have been developed or extended. The two-dimensional stress distribution serves as an input parameter for the roll deformation models. For work roll flattening, a three-dimensional model based on the Boussinesq problem is adopted, while the work and backup roll deflection, including contact flattening is calculated by means of finite beam elements. The thermal work roll crown is calculated with help of an axisymmetric numerical solution of the heat equation for the work roll, considering azimuthal averaging for the boundary conditions at the work roll surface. Results are presented for hot rolling of a strip in a seven-stand finishing train of a hot strip mill, showing the calculated evolution of the strip <span class="hlt">profile</span>. A variation of the strip <span class="hlt">profile</span> from the first to the 20th rolled strip is shown. This variation is addressed to the progressive increase of work roll temperature during the first 20 strips. It is shown that a CVC® system can lead to improvements in strip <span class="hlt">profile</span> and therefore flatness.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018AIPC.1962c0010J','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018AIPC.1962c0010J"><span>Thin and thick <span class="hlt">targets</span> for radioactive ion beam <span class="hlt">production</span> at SPIRAL1 facility</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Jardin, P.; Bajeat, O.; Delahaye, P.; Dubois, M.; Kuchi, V.; Maunoury, L.</p> <p>2018-05-01</p> <p>The upgrade of the Système de <span class="hlt">Production</span> d'Ions Radioactifs Accélérés en Ligne (SPIRAL1) facility will deliver its new Radioactive Ion Beams (RIB) by summer 2017. The goal of the upgrade is an improvement of the performances of the installation in terms of isotopes species and ion charge states [1]. Ion beams are produced using the Isotope Separator On Line Method, consisting in an association of a primary beam of stable ions, a hot <span class="hlt">target</span> and an ion source. The primary beam impinges on the material of the <span class="hlt">target</span>. Radioactive isotopes are produced by nuclear reactions and propagate up to the source, where they are ionized and accelerated to create a RIB. One advantage of SPIRAL1 driver is the variety of its available primary beams, from carbon to uranium with energies up to 95 MeV/A. Within the SPIRAL1 upgrade, they will be combined with <span class="hlt">targets</span> made of a large choice of materials, extending in this way the number of possible nuclear reactions (fusion-evaporation, transfer, fragmentation) for producing a wider range of isotopes, up to regions of the nuclide chart still scarcely explored. Depending on the reaction process, on the collision energy and on the primary beam power, thin and thick <span class="hlt">targets</span> are used. As their functions can be different, their design must cope with specific constraints which will be described. After a presentation of the goals of present and future SPIRAL1 <span class="hlt">Target</span> Ion Source System, the main <span class="hlt">target</span> features, studies and designs under progress are presented.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29928850','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29928850"><span>Importance of <span class="hlt">target</span>-mediated drug disposition for small molecules.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Smith, Dennis A; van Waterschoot, Robert A B; Parrott, Neil J; Olivares-Morales, Andrés; Lavé, Thierry; Rowland, Malcolm</p> <p>2018-06-18</p> <p><span class="hlt">Target</span> concentration is typically not considered in drug discovery. However, if <span class="hlt">targets</span> are expressed at relatively high concentrations and compounds have high affinity, such that most of the drug is bound to its <span class="hlt">target</span>, in vitro screens can give unreliable information on compound affinity. In vivo, a similar situation will generate pharmacokinetic (PK) <span class="hlt">profiles</span> that deviate greatly from those normally expected, owing to <span class="hlt">target</span> binding affecting drug distribution and clearance. Such <span class="hlt">target</span>-mediated drug disposition (TMDD) effects on small molecules have received little attention and might only become apparent during clinical trials, with the potential for data misinterpretation. TMDD also confounds human microdosing approaches by providing therapeutically unrepresentative PK <span class="hlt">profiles</span>. Being aware of these phenomena will improve the likelihood of successful drug discovery and development. Copyright © 2018. Published by Elsevier Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20070196','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20070196"><span><span class="hlt">Targeted</span> marketing and public health.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Grier, Sonya A; Kumanyika, Shiriki</p> <p>2010-01-01</p> <p><span class="hlt">Targeted</span> marketing techniques, which identify consumers who share common needs or characteristics and position <span class="hlt">products</span> or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, <span class="hlt">targeted</span> marketing, particularly of <span class="hlt">products</span> with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand <span class="hlt">targeted</span> marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial <span class="hlt">products</span>, such understanding can foster more socially <span class="hlt">productive</span> <span class="hlt">targeting</span>. For potentially harmful <span class="hlt">products</span>, understanding the nature and scope of <span class="hlt">targeted</span> marketing influences will support identification and implementation of corrective policies.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_19 --> <div id="page_20" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="381"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3255607','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3255607"><span>Modular Engineering of l-Tyrosine <span class="hlt">Production</span> in Escherichia coli</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Juminaga, Darmawi; Baidoo, Edward E. K.; Redding-Johanson, Alyssa M.; Batth, Tanveer S.; Burd, Helcio; Mukhopadhyay, Aindrila; Petzold, Christopher J.</p> <p>2012-01-01</p> <p>Efficient biosynthesis of l-tyrosine from glucose is necessary to make biological <span class="hlt">production</span> economically viable. To this end, we designed and constructed a modular biosynthetic pathway for l-tyrosine <span class="hlt">production</span> in E. coli MG1655 by encoding the enzymes for converting erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) to l-tyrosine on two plasmids. Rational engineering to improve l-tyrosine <span class="hlt">production</span> and to identify pathway bottlenecks was directed by <span class="hlt">targeted</span> proteomics and metabolite <span class="hlt">profiling</span>. The bottlenecks in the pathway were relieved by modifications in plasmid copy numbers, promoter strength, gene codon usage, and the placement of genes in operons. One major bottleneck was due to the bifunctional activities of quinate/shikimate dehydrogenase (YdiB), which caused accumulation of the intermediates dehydroquinate (DHQ) and dehydroshikimate (DHS) and the side <span class="hlt">product</span> quinate; this bottleneck was relieved by replacing YdiB with its paralog AroE, resulting in the <span class="hlt">production</span> of over 700 mg/liter of shikimate. Another bottleneck in shikimate <span class="hlt">production</span>, due to low expression of the dehydroquinate synthase (AroB), was alleviated by optimizing the first 15 codons of the gene. Shikimate conversion to l-tyrosine was improved by replacing the shikimate kinase AroK with its isozyme, AroL, which effectively consumed all intermediates formed in the first half of the pathway. Guided by the protein and metabolite measurements, the best producer, consisting of two medium-copy-number, dual-operon plasmids, was optimized to produce >2 g/liter l-tyrosine at 80% of the theoretical yield. This work demonstrates the utility of <span class="hlt">targeted</span> proteomics and metabolite <span class="hlt">profiling</span> in pathway construction and optimization, which should be applicable to other metabolic pathways. PMID:22020510</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5386245','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5386245"><span>Gene <span class="hlt">targeting</span> by TALEN-induced homologous recombination in goats directs <span class="hlt">production</span> of β-lactoglobulin-free, high-human lactoferrin milk</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Cui, Chenchen; Song, Yujie; Liu, Jun; Ge, Hengtao; Li, Qian; Huang, Hui; Hu, Linyong; Zhu, Hongmei; Jin, Yaping; Zhang, Yong</p> <p>2015-01-01</p> <p>β-Lactoglobulin (BLG) is a major goat’s milk allergen that is absent in human milk. Engineered endonucleases, including transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases, enable <span class="hlt">targeted</span> genetic modification in livestock. In this study, TALEN-mediated gene knockout followed by gene knock-in were used to generate BLG knockout goats as mammary gland bioreactors for large-scale <span class="hlt">production</span> of human lactoferrin (hLF). We introduced precise genetic modifications in the goat genome at frequencies of approximately 13.6% and 6.09% for the first and second sequential <span class="hlt">targeting</span>, respectively, by using <span class="hlt">targeting</span> vectors that underwent TALEN-induced homologous recombination (HR). Analysis of milk from the cloned goats revealed large-scale hLF expression or/and decreased BLG levels in milk from heterozygous goats as well as the absence of BLG in milk from homozygous goats. Furthermore, the TALEN-mediated <span class="hlt">targeting</span> events in somatic cells can be transmitted through the germline after SCNT. Our result suggests that gene <span class="hlt">targeting</span> via TALEN-induced HR may expedite the <span class="hlt">production</span> of genetically engineered livestock for agriculture and biomedicine. PMID:25994151</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25994151','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25994151"><span>Gene <span class="hlt">targeting</span> by TALEN-induced homologous recombination in goats directs <span class="hlt">production</span> of β-lactoglobulin-free, high-human lactoferrin milk.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cui, Chenchen; Song, Yujie; Liu, Jun; Ge, Hengtao; Li, Qian; Huang, Hui; Hu, Linyong; Zhu, Hongmei; Jin, Yaping; Zhang, Yong</p> <p>2015-05-21</p> <p>β-Lactoglobulin (BLG) is a major goat's milk allergen that is absent in human milk. Engineered endonucleases, including transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases, enable <span class="hlt">targeted</span> genetic modification in livestock. In this study, TALEN-mediated gene knockout followed by gene knock-in were used to generate BLG knockout goats as mammary gland bioreactors for large-scale <span class="hlt">production</span> of human lactoferrin (hLF). We introduced precise genetic modifications in the goat genome at frequencies of approximately 13.6% and 6.09% for the first and second sequential <span class="hlt">targeting</span>, respectively, by using <span class="hlt">targeting</span> vectors that underwent TALEN-induced homologous recombination (HR). Analysis of milk from the cloned goats revealed large-scale hLF expression or/and decreased BLG levels in milk from heterozygous goats as well as the absence of BLG in milk from homozygous goats. Furthermore, the TALEN-mediated <span class="hlt">targeting</span> events in somatic cells can be transmitted through the germline after SCNT. Our result suggests that gene <span class="hlt">targeting</span> via TALEN-induced HR may expedite the <span class="hlt">production</span> of genetically engineered livestock for agriculture and biomedicine.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2869221','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2869221"><span>Greenhouse Gas and Carbon <span class="hlt">Profile</span> of the U.S. Forest <span class="hlt">Products</span> Industry Value Chain</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2010-01-01</p> <p>A greenhouse gas and carbon accounting <span class="hlt">profile</span> was developed for the U.S. forest <span class="hlt">products</span> industry value chain for 1990 and 2004−2005 by examining net atmospheric fluxes of CO2 and other greenhouse gases (GHGs) using a variety of methods and data sources. Major GHG emission sources include direct and indirect (from purchased electricity generation) emissions from manufacturing and methane emissions from landfilled <span class="hlt">products</span>. Forest carbon stocks in forests supplying wood to the industry were found to be stable or increasing. Increases in the annual amounts of carbon removed from the atmosphere and stored in forest <span class="hlt">products</span> offset about half of the total value chain emissions. Overall net transfers to the atmosphere totaled 91.8 and 103.5 TgCO2-eq. in 1990 and 2005, respectively, although the difference between these net transfers may not be statistically significant. Net transfers were higher in 2005 primarily because additions to carbon stored in forest <span class="hlt">products</span> were less in 2005. Over this same period, energy-related manufacturing emissions decreased by almost 9% even though forest <span class="hlt">products</span> output increased by approximately 15%. Several types of avoided emissions were considered separately and were collectively found to be notable relative to net emissions. PMID:20355695</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4475989','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4475989"><span>Conserving tropical biodiversity via market forces and spatial <span class="hlt">targeting</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bateman, Ian J.; Coombes, Emma; Fitzherbert, Emily; Binner, Amy; Bad’ura, Tomáš; Carbone, Chris; Fisher, Brendan; Naidoo, Robin; Watkinson, Andrew R.</p> <p>2015-01-01</p> <p>The recent report from the Secretariat of the Convention on Biological Diversity [(2010) Global Biodiversity Outlook 3] acknowledges that ongoing biodiversity loss necessitates swift, radical action. Protecting undisturbed lands, although vital, is clearly insufficient, and the key role of unprotected, private land owned is being increasingly recognized. Seeking to avoid common assumptions of a social planner backed by government interventions, the present work focuses on the incentives of the individual landowner. We use detailed data to show that successful conservation on private land depends on three factors: conservation effectiveness (impact on <span class="hlt">target</span> species), private costs (especially reductions in <span class="hlt">production</span>), and private benefits (the extent to which conservation activities provide compensation, for example, by enhancing the value of remaining <span class="hlt">production</span>). By examining the high-<span class="hlt">profile</span> issue of palm-oil <span class="hlt">production</span> in a major tropical biodiversity hotspot, we show that the levels of both conservation effectiveness and private costs are inherently spatial; varying the location of conservation activities can radically change both their effectiveness and private cost implications. We also use an economic choice experiment to show that consumers' willingness to pay for conservation-grade palm-oil <span class="hlt">products</span> has the potential to incentivize private producers sufficiently to engage in conservation activities, supporting vulnerable International Union for Conservation of Nature Red Listed species. However, these incentives vary according to the scale and efficiency of <span class="hlt">production</span> and the extent to which conservation is <span class="hlt">targeted</span> to optimize its cost-effectiveness. Our integrated, interdisciplinary approach shows how strategies to harness the power of the market can usefully complement existing—and to-date insufficient—approaches to conservation. PMID:26077906</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26077906','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26077906"><span>Conserving tropical biodiversity via market forces and spatial <span class="hlt">targeting</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bateman, Ian J; Coombes, Emma; Fitzherbert, Emily; Binner, Amy; Bad'ura, Tomáš; Carbone, Chris; Fisher, Brendan; Naidoo, Robin; Watkinson, Andrew R</p> <p>2015-06-16</p> <p>The recent report from the Secretariat of the Convention on Biological Diversity [(2010) Global Biodiversity Outlook 3] acknowledges that ongoing biodiversity loss necessitates swift, radical action. Protecting undisturbed lands, although vital, is clearly insufficient, and the key role of unprotected, private land owned is being increasingly recognized. Seeking to avoid common assumptions of a social planner backed by government interventions, the present work focuses on the incentives of the individual landowner. We use detailed data to show that successful conservation on private land depends on three factors: conservation effectiveness (impact on <span class="hlt">target</span> species), private costs (especially reductions in <span class="hlt">production</span>), and private benefits (the extent to which conservation activities provide compensation, for example, by enhancing the value of remaining <span class="hlt">production</span>). By examining the high-<span class="hlt">profile</span> issue of palm-oil <span class="hlt">production</span> in a major tropical biodiversity hotspot, we show that the levels of both conservation effectiveness and private costs are inherently spatial; varying the location of conservation activities can radically change both their effectiveness and private cost implications. We also use an economic choice experiment to show that consumers' willingness to pay for conservation-grade palm-oil <span class="hlt">products</span> has the potential to incentivize private producers sufficiently to engage in conservation activities, supporting vulnerable International Union for Conservation of Nature Red Listed species. However, these incentives vary according to the scale and efficiency of <span class="hlt">production</span> and the extent to which conservation is <span class="hlt">targeted</span> to optimize its cost-effectiveness. Our integrated, interdisciplinary approach shows how strategies to harness the power of the market can usefully complement existing--and to-date insufficient--approaches to conservation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22117038-student-research-beams-sup-radioisotope-production-target-development','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22117038-student-research-beams-sup-radioisotope-production-target-development"><span>Student research with 400keV beams: {sup 13}N radioisotope <span class="hlt">production</span> <span class="hlt">target</span> development</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Fru, L. Che; Clymer, J.; Compton, N.</p> <p>2013-04-19</p> <p>The AN400 Van de Graaff accelerator at the Minnesota State University, Mankato, Applied Nuclear Science Lab has demonstrated utility as an accessible and versatile platform for student research. Despite the limits of low energy, the research team successfully developed projects with applications to the wider radioisotope <span class="hlt">production</span> community. A <span class="hlt">target</span> system has been developed for producing and extracting {sup 13}N by the {sup 12}C(d,n){sup 13}N reaction below 400keV. The system is both reusable and robust, with future applications to higher energy machines producing this important radioisotope for physiological imaging studies with Positron Emission Tomography. Up to 36({+-}1)% of the {supmore » 13}N was extracted from the graphite matrix when 35 A current was externally applied to the graphite <span class="hlt">target</span> while simultaneously flushing the <span class="hlt">target</span> chamber with CO{sub 2} gas.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2830481','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2830481"><span>Zebrafish Behavioral <span class="hlt">Profiling</span> Links Drugs to Biological <span class="hlt">Targets</span> and Rest/Wake Regulation</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Rihel, Jason; Prober, David A.; Arvanites, Anthony; Lam, Kelvin; Zimmerman, Steven; Jang, Sumin; Haggarty, Stephen J.; Kokel, David; Rubin, Lee L.; Peterson, Randall T.; Schier, Alexander F.</p> <p>2010-01-01</p> <p>A major obstacle for the discovery of psychoactive drugs is the inability to predict how small molecules will alter complex behaviors. We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multi-dimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors. Behavioral <span class="hlt">profiling</span> revealed conserved functions of psychotropic molecules and predicted the mechanisms of action of poorly characterized compounds. In addition, behavioral <span class="hlt">profiling</span> implicated new factors such as ether-a-go-go-related gene (ERG) potassium channels and immunomodulators in the control of rest and locomotor activity. These results demonstrate the power of high-throughput behavioral <span class="hlt">profiling</span> in zebrafish to discover and characterize psychotropic drugs and to dissect the pharmacology of complex behaviors. PMID:20075256</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4969288','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4969288"><span>Activation of Phosphatidylcholine-Specific Phospholipase C in Breast and Ovarian Cancer: Impact on MRS-Detected Choline Metabolic <span class="hlt">Profile</span> and Perspectives for <span class="hlt">Targeted</span> Therapy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Podo, Franca; Paris, Luisa; Cecchetti, Serena; Spadaro, Francesca; Abalsamo, Laura; Ramoni, Carlo; Ricci, Alessandro; Pisanu, Maria Elena; Sardanelli, Francesco; Canese, Rossella; Iorio, Egidio</p> <p>2016-01-01</p> <p>Elucidation of molecular mechanisms underlying the aberrant phosphatidylcholine cycle in cancer cells plays in favor of the use of metabolic imaging in oncology and opens the way for designing new <span class="hlt">targeted</span> therapies. The anomalous choline metabolic <span class="hlt">profile</span> detected in cancer by magnetic resonance spectroscopy and spectroscopic imaging provides molecular signatures of tumor progression and response to therapy. The increased level of intracellular phosphocholine (PCho) typically detected in cancer cells is mainly attributed to upregulation of choline kinase, responsible for choline phosphorylation in the biosynthetic Kennedy pathway, but can also be partly produced by activation of phosphatidylcholine-specific phospholipase C (PC-PLC). This hydrolytic enzyme, known for implications in bacterial infection and in plant survival to hostile environmental conditions, is reported to be activated in mitogen- and oncogene-induced phosphatidylcholine cycles in mammalian cells, with effects on cell signaling, cell cycle regulation, and cell proliferation. Recent investigations showed that PC-PLC activation could account for 20–50% of the intracellular PCho <span class="hlt">production</span> in ovarian and breast cancer cells of different subtypes. Enzyme activation was associated with PC-PLC protein overexpression and subcellular redistribution in these cancer cells compared with non-tumoral counterparts. Moreover, PC-PLC coimmunoprecipitated with the human epidermal growth factor receptor-2 (HER2) and EGFR in HER2-overexpressing breast and ovarian cancer cells, while pharmacological PC-PLC inhibition resulted into long-lasting HER2 downregulation, retarded receptor re-expression on plasma membrane and antiproliferative effects. This body of evidence points to PC-PLC as a potential <span class="hlt">target</span> for newly designed therapies, whose effects can be preclinically and clinically monitored by metabolic imaging methods. PMID:27532027</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://proteomics.cancer.gov/news_and_announcements/nci-requests-cancer-targets-monoclonal-antibody-production-and','NCI'); return false;" href="https://proteomics.cancer.gov/news_and_announcements/nci-requests-cancer-targets-monoclonal-antibody-production-and"><span>NCI Requests Cancer <span class="hlt">Targets</span> for Monoclonal Antibody <span class="hlt">Production</span> and Characterization | Office of Cancer Clinical Proteomics Research</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein <span class="hlt">targets</span> for affinity <span class="hlt">production</span> and distribution. Submissions will be accepted through July 11, 2014.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22531358-monte-carlo-studies-entrance-foil-material-target-assembly-fdg-production','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22531358-monte-carlo-studies-entrance-foil-material-target-assembly-fdg-production"><span>A Monte Carlo studies of the entrance foil material in a <span class="hlt">target</span> assembly for FDG <span class="hlt">production</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Merouani, A.; El Khayati, N.; EL Ghayour, A.</p> <p>2015-07-01</p> <p>In this work, a Monte Carlo simulation was performed for different entrance foil Materials in the <span class="hlt">target</span> assembly for [{sup 18}F] FDG <span class="hlt">production</span>, to investigate the neutron generations in the entrance foil. However, the objective is to study a materials that has the more or less similar mechanical properties as the Havar{sup R} foil with less generation of secondary particles and without affecting, the yield of FDG <span class="hlt">production</span>. (authors)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017NIMPB.406..135S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017NIMPB.406..135S"><span><span class="hlt">Production</span> of thin <span class="hlt">targets</span> by implantation for the measurement of the 16O + 16O elastic scattering below the Coulomb barrier</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Silva, H.; Cruz, J.; Sánchez-Benítez, A. M.; Santos, C.; Luís, H.; Fonseca, M.; Jesus, A. P.</p> <p>2017-09-01</p> <p>In recent decades, the processes of fusion of 16O were studied both theoretically and experimentally. However, the theoretical calculations are unable to fit both elastic scattering cross sections and fusion S-factors. The use of 16O thin transmission <span class="hlt">targets</span> is required to measure the elastic forward scattering 16O + 16O reaction. The areal density of the <span class="hlt">target</span> must be high to maximize the reaction <span class="hlt">products</span> yields, but not so high as to allow a correct calculation of the effective beam energy. Besides this, the <span class="hlt">target</span> must withstand beam interactions without noticeable deterioration, and contaminants must be minimal. In this study, the <span class="hlt">production</span> of thin <span class="hlt">targets</span> is performed with an innovative technique. Beam characterization and preliminary spectrum for the elastic scattering are also presented, showing the suitability of these <span class="hlt">targets</span> for the proposed reaction.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5362892','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5362892"><span>Global preamplification simplifies <span class="hlt">targeted</span> mRNA quantification</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kroneis, Thomas; Jonasson, Emma; Andersson, Daniel; Dolatabadi, Soheila; Ståhlberg, Anders</p> <p>2017-01-01</p> <p>The need to perform gene expression <span class="hlt">profiling</span> using next generation sequencing and quantitative real-time PCR (qPCR) on small sample sizes and single cells is rapidly expanding. However, to analyse few molecules, preamplification is required. Here, we studied global and <span class="hlt">target</span>-specific preamplification using 96 optimised qPCR assays. To evaluate the preamplification strategies, we monitored the reactions in real-time using SYBR Green I detection chemistry followed by melting curve analysis. Next, we compared yield and reproducibility of global preamplification to that of <span class="hlt">target</span>-specific preamplification by qPCR using the same amount of total RNA. Global preamplification generated 9.3-fold lower yield and 1.6-fold lower reproducibility than <span class="hlt">target</span>-specific preamplification. However, the performance of global preamplification is sufficient for most downstream applications and offers several advantages over <span class="hlt">target</span>-specific preamplification. To demonstrate the potential of global preamplification we analysed the expression of 15 genes in 60 single cells. In conclusion, we show that global preamplification simplifies <span class="hlt">targeted</span> gene expression <span class="hlt">profiling</span> of small sample sizes by a flexible workflow. We outline the pros and cons for global preamplification compared to <span class="hlt">target</span>-specific preamplification. PMID:28332609</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24384054','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24384054"><span>Pneumococcal vaccine <span class="hlt">targeting</span> strategy for older adults: customized risk <span class="hlt">profiling</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe</p> <p>2014-02-12</p> <p>Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization <span class="hlt">targeting</span>, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine <span class="hlt">targeting</span>. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization <span class="hlt">targeting</span>. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were <span class="hlt">targeted</span> to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine <span class="hlt">targeting</span> performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine <span class="hlt">targeting</span> and resource allocation than current national and international</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5650036','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5650036"><span>The healthfulness and prominence of sugar in child-<span class="hlt">targeted</span> breakfast cereals in Canada</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Monique, Potvin Kent; Cher, Cameron; Sarah, Philippe</p> <p>2017-01-01</p> <p>Abstract Introduction: The objective of this study was to compare the nutritional content and healthfulness of child-<span class="hlt">targeted</span> and “not child-targeted” breakfast cereals and to assess the predominance of added sugar in these <span class="hlt">products</span>. Methods: We collected data on the nutritional content of 262 unique breakfast cereals found in the five largest grocery store chains in Ottawa (Ontario) and Gatineau (Quebec). We noted the first five ingredients and the number of added sugars present in each cereal from the ingredients list. The various cereal brands were then classified as either “healthier” or “less healthy” using the UK Nutrient <span class="hlt">Profile</span> Model. We assessed each cereal to determine if it was child-<span class="hlt">targeted</span> or not, based on set criteria. Statistical comparisons were made between child and not child-<span class="hlt">targeted</span> cereals. Results: 19.8% of all breakfast cereals were child-<span class="hlt">targeted</span>, and these were significantly lower in total and saturated fat. Child-<span class="hlt">targeted</span> cereals were significantly higher in sodium and sugar and lower in fibre and protein, and were three times more likely to be classified as “less healthy” compared to not child-<span class="hlt">targeted</span> cereals. No child-<span class="hlt">targeted</span> cereals were sugar-free, and sugar was the second most common ingredient in 75% of cereals. Six breakfast cereal companies had child-<span class="hlt">targeted</span> <span class="hlt">product</span> lines that consisted entirely of “less healthy” cereals. Conclusion: There is a need for regulations that restrict food marketing to children and youth under the age of 17 on packaging to reduce their appeal to this age group. Children’s breakfast cereals also need to be reformulated through government-set <span class="hlt">targets</span>, or through regulation should compliance be deemed unacceptable. PMID:28902476</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22152703','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22152703"><span>Purchases of ready-to-eat cereals vary across US household sociodemographic categories according to nutritional value and advertising <span class="hlt">targets</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Castetbon, Katia; Harris, Jennifer L; Schwartz, Marlene B</p> <p>2012-08-01</p> <p>To describe ready-to-eat (RTE) cereal purchases in 2008 in the USA according to cereal nutritional quality and marketing strategy and household sociodemographic characteristics. Cross-sectional study of purchases in one year. Each type of cereal was assigned to one of four nutrition quality categories (based on Nutrient <span class="hlt">Profile</span> Index, NPI) and one of four advertising categories based on television exposure and analysis of packaging (child-<span class="hlt">targeted</span>, family-<span class="hlt">targeted</span>, adult-<span class="hlt">targeted</span> and no television advertising). Medians and distributions of purchase indicators were calculated for the cereal categories and the distributions were compared across sociodemographic groups. RTE cereals (n 249) with complete label and nutritional content. RTE cereal purchases according to household sociodemographic characteristics obtained from Nielsen Homescan, a nationally representative panel of households. Purchases of RTE cereals were highest in households with one or more child and lowest in African-American and Asian households, as well as those earning <$US 30 000 per annum. The lowest-quality <span class="hlt">products</span> were purchased by four times as many households as the highest-quality cereals, but loyalty to these <span class="hlt">products</span> was lower. Purchases of cereals by households with children and in African-American and Hispanic households increased as cereal nutritional quality declined. Compared with non-advertised <span class="hlt">products</span>, advertised child-<span class="hlt">targeted</span> cereals were purchased thirteen times more frequently; family-<span class="hlt">targeted</span> brand purchases were ten times higher; and adult-<span class="hlt">targeted</span> cereals were purchased four times more frequently. Our findings suggest that improving the nutritional quality of RTE cereals with advertising <span class="hlt">targeted</span> to children could also lead to increased consumption of healthier <span class="hlt">products</span> by young people.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29093681','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29093681"><span>Quantitative and Systems Pharmacology 3. Network-Based Identification of New <span class="hlt">Targets</span> for Natural <span class="hlt">Products</span> Enables Potential Uses in Aging-Associated Disorders.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fang, Jiansong; Gao, Li; Ma, Huili; Wu, Qihui; Wu, Tian; Wu, Jun; Wang, Qi; Cheng, Feixiong</p> <p>2017-01-01</p> <p>Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural <span class="hlt">products</span> have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural <span class="hlt">products</span>. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), c aenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-<span class="hlt">target</span> network of natural <span class="hlt">products</span> by integrating both experimental and computationally predicted drug-<span class="hlt">target</span> interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural <span class="hlt">products</span> through integration of the curated aging-associated genes and drug-<span class="hlt">target</span> network of natural <span class="hlt">products</span>. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural <span class="hlt">products</span> (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural <span class="hlt">products</span> for treatment of aging-associated disorders.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5651538','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5651538"><span>Quantitative and Systems Pharmacology 3. Network-Based Identification of New <span class="hlt">Targets</span> for Natural <span class="hlt">Products</span> Enables Potential Uses in Aging-Associated Disorders</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Fang, Jiansong; Gao, Li; Ma, Huili; Wu, Qihui; Wu, Tian; Wu, Jun; Wang, Qi; Cheng, Feixiong</p> <p>2017-01-01</p> <p>Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural <span class="hlt">products</span> have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural <span class="hlt">products</span>. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), caenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-<span class="hlt">target</span> network of natural <span class="hlt">products</span> by integrating both experimental and computationally predicted drug-<span class="hlt">target</span> interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural <span class="hlt">products</span> through integration of the curated aging-associated genes and drug-<span class="hlt">target</span> network of natural <span class="hlt">products</span>. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural <span class="hlt">products</span> (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural <span class="hlt">products</span> for treatment of aging-associated disorders. PMID:29093681</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4439112','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4439112"><span>MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly <span class="hlt">Targets</span> Multiple Oncogenes</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Polioudakis, Damon; Abell, Nathan S.; Iyer, Vishwanath R.</p> <p>2015-01-01</p> <p>miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally <span class="hlt">profiled</span>. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression <span class="hlt">profiling</span> to construct a genome wide miR-191 <span class="hlt">target</span> <span class="hlt">profile</span>. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 <span class="hlt">targets</span>, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates <span class="hlt">target</span> expression through coding sequence (CDS) pairing. Our results provide a comprehensive genome wide miR-191 <span class="hlt">target</span> <span class="hlt">profile</span>, and demonstrate miR-191’s regulation of primary human fibroblast proliferation. PMID:25992613</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24569711','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24569711"><span>Tumor <span class="hlt">targeting</span> <span class="hlt">profiling</span> of hyaluronan-coated lipid based-nanoparticles.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mizrahy, Shoshy; Goldsmith, Meir; Leviatan-Ben-Arye, Shani; Kisin-Finfer, Einat; Redy, Orit; Srinivasan, Srimeenakshi; Shabat, Doron; Godin, Biana; Peer, Dan</p> <p>2014-04-07</p> <p>Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based <span class="hlt">targeted</span> and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored HA had a significant influence on the affinity towards CD44 on B16F10 murine melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor <span class="hlt">targeting</span> specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular <span class="hlt">targeting</span> beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular <span class="hlt">targeting</span> moiety.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_20 --> <div id="page_21" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="401"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28589452','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28589452"><span>On-demand microbicide <span class="hlt">products</span>: design matters.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Patel, Sravan Kumar; Rohan, Lisa Cencia</p> <p>2017-12-01</p> <p>Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e., immediately before or after sex) can be part of an effective tool kit utilized to prevent sexual transmission of HIV. The effectiveness of prevention <span class="hlt">products</span> is positively correlated with adherence, which is likely to depend on user acceptability of the <span class="hlt">product</span>. The development of an efficacious and acceptable <span class="hlt">product</span> is therefore paramount for the success of an on-demand <span class="hlt">product</span>. Acceptability of on-demand <span class="hlt">products</span> (e.g., gels, films, and tablets) and their attributes is influenced by a multitude of user-specific factors that span behavioral, lifestyle, socio-economic, and cultural aspects. In addition, physicochemical properties of the drug, anatomical and physiological aspects of anorectal and vaginal compartments, issues relating to large-scale <span class="hlt">production</span>, and cost can impact <span class="hlt">product</span> development. These factors together with user preferences determine the design space of an effective, acceptable, and feasible on-demand <span class="hlt">product</span>. In this review, we summarize the interacting factors that together determine <span class="hlt">product</span> choice and its <span class="hlt">target</span> <span class="hlt">product</span> <span class="hlt">profile</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015AGUFM.B41C0446W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015AGUFM.B41C0446W"><span>Time-Lapse Geophysical Measurements <span class="hlt">targeting</span> Spatial and Temporal Variability in Biogenic Gas <span class="hlt">Production</span> from Peat Soils in a Hydrologically Controlled Wetland in the Florida Everglades</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wright, W. J.; Shahan, T.; Sharp, N.; Comas, X.</p> <p>2015-12-01</p> <p>Peat soils are known to release globally significant amounts of methane (CH4) and carbon dioxide (CO2) to the atmosphere. However, uncertainties still remain regarding the spatio-temporal distribution of gas accumulations and triggering mechanisms of gas releasing events. Furthermore, most research on peatland gas dynamics has traditionally been focused on high latitude peatlands. Therefore, understanding gas dynamics in low-latitude peatlands (e.g. the Florida Everglades) is key to global climate research. Recent studies in the Everglades have demonstrated that biogenic gas flux values may vary when considering different temporal and spatial scales of measurements. The work presented here <span class="hlt">targets</span> spatial variability in gas <span class="hlt">production</span> and release at the plot scale in an approximately 85 m2 area, and <span class="hlt">targets</span> temporal variability with data collected during the spring months of two different years. This study is located in the Loxahatchee Impoundment Landscape Assessment (LILA), a hydrologically controlled, landscape scale (30 Ha) model of the Florida Everglades. Ground penetrating radar (GPR) has been used in the past to investigate biogenic gas dynamics in peat soils, and is used in this study to monitor changes of in situ gas storage. Each year, a grid of GPR <span class="hlt">profiles</span> was collected to image changes in gas distribution in 2d on a weekly basis, and several flux chambers outfitted with time-lapse cameras captured high resolution (hourly) gas flux measurements inside the GPR grid. Combining these methods allows us to use a mass balance approach to estimate spatial variability in gas <span class="hlt">production</span> rates, and capture temporal variability in gas flux rates.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://files.eric.ed.gov/fulltext/EJ833236.pdf','ERIC'); return false;" href="http://files.eric.ed.gov/fulltext/EJ833236.pdf"><span><span class="hlt">Targeting</span> Children in the Cereal Aisle: Promotional Techniques and Content Features on Ready-to-Eat Cereal <span class="hlt">Product</span> Packaging</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Page, Randy; Montgomery, Katie; Ponder, Andrea; Richard, Amanda</p> <p>2008-01-01</p> <p>Background: Despite recent and heightened concern about the marketing of food to children as a health issue, there is little previous research describing the <span class="hlt">product</span> packaging characteristics of specific <span class="hlt">products</span> intensely marketed to children. Purpose: In order to better understand food marketing tactics <span class="hlt">targeting</span> children, the purpose of this…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://files.eric.ed.gov/fulltext/ED388863.pdf','ERIC'); return false;" href="http://files.eric.ed.gov/fulltext/ED388863.pdf"><span>Agriculture <span class="hlt">Products</span> Processing. Occupational Competency Analysis <span class="hlt">Profile</span>.</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Ohio State Univ., Columbus. Vocational Instructional Materials Lab.</p> <p></p> <p>This Occupational Competency Analysis <span class="hlt">Profile</span> (OCAP) contains a competency list verified by expert workers and developed through a modified DACUM (Developing a Curriculum) involving business, industry, labor, and community agency representatives from Ohio. This OCAP identifies the occupational, academic, and employability skills (competencies)…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015PhPl...22i3117K','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015PhPl...22i3117K"><span>Efficient neutron <span class="hlt">production</span> from sub-nanosecond laser pulse accelerating deuterons on <span class="hlt">target</span> front side</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Klir, D.; Krasa, J.; Cikhardt, J.; Dudzak, R.; Krousky, E.; Pfeifer, M.; Rezac, K.; Sila, O.; Skala, J.; Ullschmied, J.; Velyhan, A.</p> <p>2015-09-01</p> <p>Neutron-producing experiments have been carried out on the Prague Asterix Laser System. At the fundamental wavelength of 1.315 μm, the laser pulse of a 600 J energy and 300 ps duration was focused on a thick deuterated-polyethylene <span class="hlt">target</span>. Neutron yields reached (4.1 ± 0.8) × 108 at the peak intensity of ≈3 × 1016 W/cm2. A more detailed analysis of neutron time-of-flight signals showed that a significant fraction of neutron yields was produced both by the 2H(d,n)3He reaction and by other neutron-producing reactions. Neutron energies together with delayed neutron and gamma emission showed that MeV deuterons escaped from a laser-produced plasma and interacted ≈50 ns later with a borosilicate blast-shield glass. In order to increase DD neutron yields and to characterize deuteron beams via nuclear reactions, a secondary deuterated polyethylene <span class="hlt">target</span> was used in a pitcher-catcher scheme at the <span class="hlt">target</span> front side. In this experimental arrangement, the neutron yield reached (2.0 ± 0.5) × 109 with the peak neutron fluence of (2.5 ± 0.5) × 108 n/sr. From the neutron yield, it was calculated that the secondary <span class="hlt">target</span> was bombarded by 2 × 1014 deuterons in the 0.5-2.0 MeV energy range. The neutron yield of 2 × 109 at the laser energy of 600 J implied the <span class="hlt">production</span> efficiency of 3 × 106 n/J. A very important result is that the efficient neutron <span class="hlt">production</span> was achieved with the low contrast, sub-nanosecond laser pulse of the intensity of 1016 W/cm2. The latter parameters can be achieved in a rep-rate mode more easily than ultra-high intensities and contrasts.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA571027','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA571027"><span>Exploring Polypharmacology Using a ROCS-Based <span class="hlt">Target</span> Fishing Approach</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>2012-01-01</p> <p><span class="hlt">target</span> representatives. <span class="hlt">Target</span> <span class="hlt">profiles</span> were then generated for a given query molecule by computing maximal shape/ chemistry overlap between the query...molecule and the drug sets assigned to each protein <span class="hlt">target</span>. The overlap was computed using the program ROCS (Rapid Overlay of Chemical Structures ). We...approaches in off-<span class="hlt">target</span> prediction has been reviewed.9,10 Many structure -based <span class="hlt">target</span> fishing (SBTF) approaches, such as INVDOCK11 and <span class="hlt">Target</span> Fishing Dock</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017NatSR...740376H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017NatSR...740376H"><span>Predicting drug-<span class="hlt">target</span> interactions by dual-network integrated logistic matrix factorization</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Hao, Ming; Bryant, Stephen H.; Wang, Yanli</p> <p>2017-01-01</p> <p>In this work, we propose a dual-network integrated logistic matrix factorization (DNILMF) algorithm to predict potential drug-<span class="hlt">target</span> interactions (DTI). The prediction procedure consists of four steps: (1) inferring new drug/<span class="hlt">target</span> <span class="hlt">profiles</span> and constructing <span class="hlt">profile</span> kernel matrix; (2) diffusing drug <span class="hlt">profile</span> kernel matrix with drug structure kernel matrix; (3) diffusing <span class="hlt">target</span> <span class="hlt">profile</span> kernel matrix with <span class="hlt">target</span> sequence kernel matrix; and (4) building DNILMF model and smoothing new drug/<span class="hlt">target</span> predictions based on their neighbors. We compare our algorithm with the state-of-the-art method based on the benchmark dataset. Results indicate that the DNILMF algorithm outperforms the previously reported approaches in terms of AUPR (area under precision-recall curve) and AUC (area under curve of receiver operating characteristic) based on the 5 trials of 10-fold cross-validation. We conclude that the performance improvement depends on not only the proposed objective function, but also the used nonlinear diffusion technique which is important but under studied in the DTI prediction field. In addition, we also compile a new DTI dataset for increasing the diversity of currently available benchmark datasets. The top prediction results for the new dataset are confirmed by experimental studies or supported by other computational research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26632865','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26632865"><span><span class="hlt">Targeted</span> Metabolomics Approach To Detect the Misuse of Steroidal Aromatase Inhibitors in Equine Sports by Biomarker <span class="hlt">Profiling</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chan, George Ho Man; Ho, Emmie Ngai Man; Leung, David Kwan Kon; Wong, Kin Sing; Wan, Terence See Ming</p> <p>2016-01-05</p> <p>The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of <span class="hlt">target</span> AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast elimination times render the direct detection approach ineffective as the detection window is short. A <span class="hlt">targeted</span> metabolomics approach is a plausible alternative to the conventional direct detection approach for controlling the misuse of AAS in sports. Because the administration of AAS of the same class may trigger similar physiological responses or effects in the body, it may be possible to detect such administrations by monitoring changes in the endogenous steroidal expression <span class="hlt">profile</span>. This study attempts to evaluate the viability of using the <span class="hlt">targeted</span> metabolomics approach to detect the administration of steroidal aromatase inhibitors, namely androst-4-ene-3,6,17-trione (6-OXO) and androsta-1,4,6-triene-3,17-dione (ATD), in horses. Total (free and conjugated) urinary concentrations of 31 endogenous steroids were determined by gas chromatography-tandem mass spectrometry for a group of 2 resting and 2 in-training thoroughbred geldings treated with either 6-OXO or ATD. Similar data were also obtained from a control (untreated) group of in-training thoroughbred geldings (n = 28). Statistical processing and chemometric procedures using principle component analysis and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) have highlighted 7 potential biomarkers that could be used to differentiate urine samples obtained from the control and the treated groups</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28581676','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28581676"><span>Comprehensive genomic <span class="hlt">profiling</span> of different subtypes of nasopharyngeal carcinoma reveals similarities and differences to guide <span class="hlt">targeted</span> therapy.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ali, Siraj M; Yao, Ming; Yao, Jicheng; Wang, Jing; Cheng, Yuwei; Schrock, Alexa B; Chirn, Gung-Wei; Chen, Hui; Mu, Shuo; Gay, Laurie; Elvin, Julia A; Suh, James; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S; Wang, Kai</p> <p>2017-09-15</p> <p>To date, no <span class="hlt">targeted</span> therapy has been approved for nasopharyngeal carcinoma (NPC), and this underscores the need for an in-depth understanding of clinically relevant genomic alterations (CRGAs). Comprehensive genomic <span class="hlt">profiling</span> was performed for 190 NPC patients, including 20 patients with nasopharyngeal adenocarcinoma (NPAC), 62 patients with nasopharyngeal squamous cell carcinoma (NPSCC), and 108 patients with nasopharyngeal undifferentiated carcinoma (NPUC). The associations of genes and pathways with subtypes, Epstein-Barr virus (EBV) infections, and the tumor mutation burden (TMB) were statistically evaluated. Although the overall rates of genomic alterations were similar, the 3 NPC subtypes exhibited different mutational landscapes. Notably, mutations in a proven-treatable <span class="hlt">target</span> gene, isocitrate dehydrogenase 2 (IDH2), were significantly associated with NPUC but not with NPAC or NPSCC. The top 5 ranked CRGAs included CDKN2A (29%), IDH2 (16%), SMARCB1 (7%), PIK3CA (6%), and NF1 (5%) in NPUC; CDKN2A (27%), PIK3CA (23%), FBXW7 (11%), PTEN (11%), and EGFR (8%) in NPSCC; and CDKN2A (20%), KRAS (15%), CCND1 (10%), MAP3K1 (10%), and NOTCH1 (10%) in NPAC. The incidence of EBV infections significantly correlated with the subtypes and with TP53, CDKN2A, and CDKN2B. The TMB status correlated with the subtypes and with LRP1B, FBXW7, and PIK3CA mutations as well as DNA repair, phosphoinositide 3-kinase/mammalian <span class="hlt">target</span> of rapamycin, and mitogen-activated protein kinase pathways. These results indicate that different NPC subtypes harbor different CRGAs. Both EBV infections and the TMB are associated with the NPC subtypes as well as the alterations of individual genes and pathways. The high frequency of IDH2 mutations in NPUC may facilitate potential <span class="hlt">targeted</span> therapy and will ultimately point to new therapeutic strategies. Cancer 2017;123:3628-37. © 2017 American Cancer Society. © 2017 American Cancer Society.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25278433','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25278433"><span>Front-of-pack symbols are not a reliable indicator of <span class="hlt">products</span> with healthier nutrient <span class="hlt">profiles</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Emrich, Teri E; Qi, Ying; Cohen, Joanna E; Lou, Wendy Y; L'Abbe, Mary L</p> <p>2015-01-01</p> <p>Front-of-pack (FOP) nutrition rating systems and symbols are a form of nutrition marketing used on food labels worldwide. In the absence of standardized criteria for their use, it is unclear if FOP symbols are being used to promote <span class="hlt">products</span> more nutritious than <span class="hlt">products</span> without symbols. To compare the amount of calories, saturated fat, sodium, and sugar in <span class="hlt">products</span> with FOP symbols, and different FOP symbol types, to <span class="hlt">products</span> without symbols. The median calorie, saturated fat, sodium, and sugar content per reference amount of <span class="hlt">products</span> with FOP symbols were compared to <span class="hlt">products</span> without FOP symbols using data from the Food Label Information Program, a database of 10,487 Canadian packaged food labels. Ten food categories and 60 subcategories were analyzed. Nutrient content differences were compared using Wilcoxon rank-sum test; differences greater than 25% were deemed nutritionally relevant. <span class="hlt">Products</span> with FOP symbols were not uniformly lower in calories, saturated fat, sodium, and sugar per reference amount than <span class="hlt">products</span> without these symbols in any food category and the majority of subcategories (59/60). None of the different FOP types examined were used to market <span class="hlt">products</span> with overall better nutritional <span class="hlt">profiles</span> than <span class="hlt">products</span> without this type of marketing. FOP symbols are being used to market foods that are no more nutritious than foods without this type of marketing. Because FOP symbols may influence consumer perceptions of <span class="hlt">products</span> and their purchases, it may be a useful public health strategy to set minimum nutritional standards for <span class="hlt">products</span> using FOP symbol marketing. Copyright © 2014 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26140475','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26140475"><span>Sensory and metabolic <span class="hlt">profiles</span> of "Fuji" apples (Malus domestica Borkh.) grown without synthetic agrochemicals: the role of ethylene <span class="hlt">production</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Tanaka, Fukuyo; Miyazawa, Toshio; Okazaki, Keiki; Tatsuki, Miho; Ito, Tsutae</p> <p>2015-01-01</p> <p>Flavors of "Fuji" apple cultivated with or without synthetic agrochemicals were compared using quantitative descriptive analyses (QDA) and metabolite <span class="hlt">profiling</span> for 3 seasons. Experimental plots included conventional crops (with agrochemicals) and organic crops (without agrochemicals) at our institute and organic and conventional farms. Additionally, mass market samples were analyzed. Organic apples were weak in sweetness and floral characteristics and had enhanced green and sour flavors. Most esters and sugars were present in lower concentrations in organic than in conventional apples. Close relation of principal component 1 of QDA and metabolite <span class="hlt">profiles</span>, to ethylene <span class="hlt">production</span> suggested that ethylene is considerably involved in flavor synthesis. Reduced ethylene associated with immaturity accounted for insufficient flavor synthesis and weak aroma and flavor attributes of organic apples. Furthermore, organic apples from the farm were more flavorsome than those from the institute in 2012, suggesting possible recovery of ethylene <span class="hlt">production</span> after a long organic cultivation period.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22075954-routine-sup-sup-production-mu-mu-target-beam-current-ge-pettrace-cyclotron','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22075954-routine-sup-sup-production-mu-mu-target-beam-current-ge-pettrace-cyclotron"><span>Routine {sup 18}F{sup -} <span class="hlt">production</span> with 180 {mu}A to 200 {mu}A <span class="hlt">target</span> beam current on a GE PETtrace 800 cyclotron</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Eberl, S.; Eriksson, T.; Svedberg, O.</p> <p>2012-12-19</p> <p>Through upgrades and enhancements, which are now standard on current PETtrace 800 cyclotrons, a GE PETtrace cyclotron installed in 2002 has demonstrated reliable routine [{sup 18}F]FDG <span class="hlt">production</span> at total <span class="hlt">target</span> beam currents of 180 {mu}A without detriment to saturation and [{sup 18}F]FDG yields. Routine <span class="hlt">production</span> at 200 {mu}A has been achieved and its evaluation is continuing. Self-shielded <span class="hlt">target</span> using W/Cu alloy for the <span class="hlt">target</span> body afforded a reduction in dose rate from the Havar foils by a factor of {approx} 8-10, reducing dose from the <span class="hlt">targets</span> and need for removing <span class="hlt">targets</span> during maintenance. The main activation <span class="hlt">product</span> in the shieldmore » is {sup 187}W (T1/2 24 h). The {sup 60}Co ((T1/2 5.3 y) activation is about 250 times less at 24 h post EOB and is not considered a major issue despite its long half-life.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1375902-permeation-fill-tube-design-inertial-confinement-fusion-target-capsules','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1375902-permeation-fill-tube-design-inertial-confinement-fusion-target-capsules"><span>Permeation fill-tube design for inertial confinement fusion <span class="hlt">target</span> capsules</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Rice, B. S.; Ulreich, J.; Fella, C.; ...</p> <p>2017-03-22</p> <p>A unique approach for permeation filling of nonpermeable inertial confinement fusion <span class="hlt">target</span> capsules with deuterium–tritium (DT) is presented. This process uses a permeable capsule coupled into the final <span class="hlt">target</span> capsule with a 0.03-mm-diameter fill tube. Leak free permeation filling of glow-discharge polymerization (GDP) <span class="hlt">targets</span> using this method have been successfully demonstrated, as well as ice layering of the <span class="hlt">target</span>, yielding an inner ice surface roughness of 1-more » $$\\unicode[STIX]{x03BC}$$m rms (root mean square). Finally, the measured DT ice-thickness <span class="hlt">profile</span> for this experiment was used to validate a thermal model’s prediction of the same thickness <span class="hlt">profile</span>.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26232332','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26232332"><span>Effects of Peptone Supplementation in Different Culture Media on Growth, Metabolic Pathway and <span class="hlt">Productivity</span> of CHO DG44 Cells; a New Insight into Amino Acid <span class="hlt">Profiles</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Davami, Fatemeh; Eghbalpour, Farnaz; Nematollahi, Leila; Barkhordari, Farzaneh; Mahboudi, Fereidoun</p> <p>2015-01-01</p> <p>The optimization of bioprocess conditions towards improved growth <span class="hlt">profile</span> and <span class="hlt">productivity</span> yield is considered of great importance in biopharmaceutical manufacturing. Peptones as efficient sources of nutrients have been studied for their effect on media development; however, their role on metabolic pathway is not well understood. In the present study, the effect of different concentration of peptones on a recombinant Chinese hamster ovary (CHO) cell line grown in three serum-free suspension cultures was determined. Six peptones of different origins and available amino acid <span class="hlt">profiles</span> were investigated regarding their impact on cell growth, <span class="hlt">productivity</span>, and metabolic pathways changes. In optimized feeding strategies, increases of 136% and 159% in volumetric <span class="hlt">productivity</span> (for a low-nutrient culture media) and 55% (for a high-nutrient culture media) were achieved. Furthermore, particular sources of peptones with specific amino acid <span class="hlt">profile</span> developed preferential results for each different culture medium. Two peptones, SoyA2SC and SoyE-110, were the only hydrolysates that showed <span class="hlt">production</span> improvement in all three media. Casein Peptone plus Tryptone N1 and SoyA3SC showed different improved results based on their implemented concentration for each individual basal medium. The amino acid <span class="hlt">profile</span> of peptones may provide clues to identify the most effective feeding strategies for recombinant CHO cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28510271','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28510271"><span>Application of Combination High-Throughput Phenotypic Screening and <span class="hlt">Target</span> Identification Methods for the Discovery of Natural <span class="hlt">Product</span>-Based Combination Drugs.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Isgut, Monica; Rao, Mukkavilli; Yang, Chunhua; Subrahmanyam, Vangala; Rida, Padmashree C G; Aneja, Ritu</p> <p>2018-03-01</p> <p>Modern drug discovery efforts have had mediocre success rates with increasing developmental costs, and this has encouraged pharmaceutical scientists to seek innovative approaches. Recently with the rise of the fields of systems biology and metabolomics, network pharmacology (NP) has begun to emerge as a new paradigm in drug discovery, with a focus on multiple <span class="hlt">targets</span> and drug combinations for treating disease. Studies on the benefits of drug combinations lay the groundwork for a renewed focus on natural <span class="hlt">products</span> in drug discovery. Natural <span class="hlt">products</span> consist of a multitude of constituents that can act on a variety of <span class="hlt">targets</span> in the body to induce pharmacodynamic responses that may together culminate in an additive or synergistic therapeutic effect. Although natural <span class="hlt">products</span> cannot be patented, they can be used as starting points in the discovery of potent combination therapeutics. The optimal mix of bioactive ingredients in natural <span class="hlt">products</span> can be determined via phenotypic screening. The <span class="hlt">targets</span> and molecular mechanisms of action of these active ingredients can then be determined using chemical proteomics, and by implementing a reverse pharmacokinetics approach. This review article provides evidence supporting the potential benefits of natural <span class="hlt">product</span>-based combination drugs, and summarizes drug discovery methods that can be applied to this class of drugs. © 2017 Wiley Periodicals, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28315738','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28315738"><span>Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially <span class="hlt">Targetable</span> Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic <span class="hlt">Profiling</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Schrock, Alexa B; Li, Shuyu D; Frampton, Garrett M; Suh, James; Braun, Eduardo; Mehra, Ranee; Buck, Steven C; Bufill, Jose A; Peled, Nir; Karim, Nagla Abdel; Hsieh, K Cynthia; Doria, Manuel; Knost, James; Chen, Rong; Ou, Sai-Hong Ignatius; Ross, Jeffrey S; Stephens, Philip J; Fishkin, Paul; Miller, Vincent A; Ali, Siraj M; Halmos, Balazs; Liu, Jane J</p> <p>2017-06-01</p> <p>Pulmonary sarcomatoid carcinoma (PSC) is a high-grade NSCLC characterized by poor prognosis and resistance to chemotherapy. Development of <span class="hlt">targeted</span> therapeutic strategies for PSC has been hampered because of limited and inconsistent molecular characterization. Hybrid capture-based comprehensive genomic <span class="hlt">profiling</span> was performed on DNA from formalin-fixed paraffin-embedded sections of 15,867 NSCLCs, including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 megabases (Mb) of sequenced DNA. The median age of the patients with PSC was 67 years (range 32-87), 58% were male, and 78% had stage IV disease. Tumor protein p53 gene (TP53) genomic alterations (GAs) were identified in 74% of cases, which had genomics distinct from TP53 wild-type cases, and 62% featured a GA in KRAS (34%) or one of seven genes currently recommended for testing in the National Comprehensive Cancer Network NSCLC guidelines, including the following: hepatocyte growth factor receptor gene (MET) (13.6%), EGFR (8.8%), BRAF (7.2%), erb-b2 receptor tyrosine kinase 2 gene (HER2) (1.6%), and ret proto-oncogene (RET) (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared with non-PSC NSCLCs (∼3%) (p < 0.0001) and were more prevalent in PSC cases with an adenocarcinoma component. The fraction of PSC with a high TMB (>20 mutations per Mb) was notably higher than in non-PSC NSCLC (20% versus 14%, p = 0.056). Of nine patients with PSC treated with <span class="hlt">targeted</span> or immunotherapies, three had partial responses and three had stable disease. Potentially <span class="hlt">targetable</span> GAs in National Comprehensive Cancer Network NSCLC genes (30%) or intermediate or high TMB (43%, >10 mutations per Mb) were identified in most of the PSC cases. Thus, the use of comprehensive genomic <span class="hlt">profiling</span> in clinical care may provide important treatment options for a historically poorly characterized and difficult to treat disease. Copyright © 2017 International Association for the Study of Lung Cancer. Published</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21413151','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21413151"><span>Towards the <span class="hlt">profiling</span> of the Arabidopsis thaliana plasma membrane transportome by <span class="hlt">targeted</span> proteomics.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Monneuse, Jean-Marc; Sugano, Madeleine; Becue, Thierry; Santoni, Véronique; Hem, Sonia; Rossignol, Michel</p> <p>2011-05-01</p> <p>Plant membranes bear a variety of transporters belonging to multigene families that are affected by environmental and nutritional conditions. In addition, they often display high-sequence identity, making difficult in-depth investigation by current shot-gun strategies. In this study, we set up a <span class="hlt">targeted</span> proteomics approach aimed at identifying and quantifying within single experiments the five major proton pumps of the autoinhibited H(+) ATPases (AHA) family, the 13 plasma membrane intrinsic proteins (PIP) water channels (PIPs), and ten members of ammonium transporters (AMTs) and nitrate transporter (NRT) families. Proteotypic peptides were selected and isotopically labeled heavy versions were used for technical optimization and for quantification of the corresponding light version in biological samples. This approach allowed to quantify simultaneously nine PIPs in leaf membranes and 13 PIPs together with three autoinhibited H(+) ATPases, two ammonium transporters, and two NRTs in root membranes. Similarly, it was used to investigate the effect of a salt stress on the expression of these latter 20 transporters in roots. These novel isoform-specific data were compared with published transcriptome information and revealed a close correlation between PIP isoforms and transcripts levels. The obtained resource is reusable and can be expanded to other transporter families for large-scale <span class="hlt">profiling</span> of membrane transporters. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29915201','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29915201"><span>Comparative assessment of Graves' disease and main extrathyroidal manifestation, Graves' ophthalmopathy, by non-<span class="hlt">targeted</span> metabolite <span class="hlt">profiling</span> of blood and orbital tissue.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ji, Dong Yoon; Park, Se Hee; Park, Soo Jin; Kim, Kyoung Heon; Ku, Cheol Ryong; Shin, Dong Yeob; Yoon, Jin Sook; Lee, Do Yup; Lee, Eun Jig</p> <p>2018-06-18</p> <p>Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were <span class="hlt">profiled</span> and analyzed based on a non-<span class="hlt">targeted</span> primary metabolite <span class="hlt">profiling</span> from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite <span class="hlt">profiles</span> from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29495913','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29495913"><span>Screening of broad spectrum natural pesticides against conserved <span class="hlt">target</span> arginine kinase in cotton pests by molecular modeling.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sakthivel, Seethalakshmi; Habeeb, S K M; Raman, Chandrasekar</p> <p>2018-03-12</p> <p>Cotton is an economically important crop and its <span class="hlt">production</span> is challenged by the diversity of pests and related insecticide resistance. Identification of the conserved <span class="hlt">target</span> across the cotton pest will help to design broad spectrum insecticide. In this study, we have identified conserved sequences by Expressed Sequence Tag <span class="hlt">profiling</span> from three cotton pests namely Aphis gossypii, Helicoverpa armigera, and Spodoptera exigua. One <span class="hlt">target</span> protein arginine kinase having a key role in insect physiology and energy metabolism was studied further using homology modeling, virtual screening, molecular docking, and molecular dynamics simulation to identify potential biopesticide compounds from the Zinc natural database. We have identified four compounds having excellent inhibitor potential against the identified broad spectrum <span class="hlt">target</span> which are highly specific to invertebrates.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23354001','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23354001"><span><span class="hlt">Target</span> identification of small molecules based on chemical biology approaches.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Futamura, Yushi; Muroi, Makoto; Osada, Hiroyuki</p> <p>2013-05-01</p> <p>Recently, a phenotypic approach-screens that assess the effects of compounds on cells, tissues, or whole organisms-has been reconsidered and reintroduced as a complementary strategy of a <span class="hlt">target</span>-based approach for drug discovery. Although the finding of novel bioactive compounds from large chemical libraries has become routine, the identification of their molecular <span class="hlt">targets</span> is still a time-consuming and difficult process, making this step rate-limiting in drug development. In the last decade, we and other researchers have amassed a large amount of phenotypic data through progress in omics research and advances in instrumentation. Accordingly, the <span class="hlt">profiling</span> methodologies using these datasets expertly have emerged to identify and validate specific molecular <span class="hlt">targets</span> of drug candidates, attaining some progress in current drug discovery (e.g., eribulin). In the case of a compound that shows an unprecedented phenotype likely by inhibiting a first-in-class <span class="hlt">target</span>, however, such phenotypic <span class="hlt">profiling</span> is invalid. Under the circumstances, a photo-crosslinking affinity approach should be beneficial. In this review, we describe and summarize recent progress in both affinity-based (direct) and phenotypic <span class="hlt">profiling</span> (indirect) approaches for chemical biology <span class="hlt">target</span> identification.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_21 --> <div id="page_22" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="421"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4460800','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4460800"><span>How are personality trait and <span class="hlt">profile</span> agreement related?</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Allik, Jüri; Borkenau, Peter; Hřebíčková, Martina; Kuppens, Peter; Realo, Anu</p> <p>2015-01-01</p> <p>It is argued that if we compute self-other agreement on some personality traits then we possess no or very little information about the individuals who are the <span class="hlt">targets</span> of this judgment. This idea is largely based on two separate ways of computing self-other agreement: trait agreement (rT) and <span class="hlt">profile</span> agreement (rP), which are typically associated with two different trait-centered and person-centered approaches in personality research. Personality traits of 4115 <span class="hlt">targets</span> from Czech, Belgian, Estonian, and German samples were rated by themselves and knowledgeable informants. We demonstrate that trait agreement can be partialled into individual contributions so that it is possible to show how much each individual pair of judges contributes to agreement on a particular trait. Similarly, it is possible to decompose agreement between two personality <span class="hlt">profiles</span> into the individual contributions of traits from which these <span class="hlt">profiles</span> are assembled. If normativeness is separated from distinctiveness of personality scores and individual <span class="hlt">profiles</span> are ipsatized, then mean <span class="hlt">profile</span> agreement rP becomes identical to mean trait agreement rT. The views that trait-by-trait analysis does not provide information regarding accuracy level of a particular pair of judges and <span class="hlt">profile</span> analysis does not permit assessment of the relative contributions of traits to overall accuracy are not supported. PMID:26106356</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018JPhCS.985a2005H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018JPhCS.985a2005H"><span>Pulse laser ablation of Au, Ag, and Cu metal <span class="hlt">targets</span> in liquid for nanoparticle <span class="hlt">production</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Herbani, Y.; Irmaniar; Nasution, R. S.; Mujtahid, F.; Masse, S.</p> <p>2018-03-01</p> <p>We have fabricated metal and oxide nanoparticles using pulse laser ablation of Au, Ag, and Cu metal <span class="hlt">targets</span> immersed in water. While laser ablation of Au and Ag <span class="hlt">targets</span> in water produced metal nanoparticles which were stable for a month even without any dispersant, we found CuO nanoparticles for Cu <span class="hlt">target</span> due to rapid oxidation of Cu in water resulted in its poor stability. Au, Ag, and CuO nanoparticles <span class="hlt">production</span> were barely identified by naked eyes for their distinctive colour of red, yellow, and dark green colloidal suspensions, respectively. It was also verified using UV-Vis spectrometer that Au, Ag, and CuO colloidal nanoparticles have their respective surface plasmon resonance at 520, 400, and 620 nm. TEM observation showed that particle sizes for all the fabricated nanoparticles were in the range of 20 – 40 nm with crystalline structures.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27331414','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27331414"><span>Underexplored Opportunities for Natural <span class="hlt">Products</span> in Drug Discovery.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>DeCorte, Bart L</p> <p>2016-10-27</p> <p>The importance of natural <span class="hlt">products</span> in the treatment of human disease is well documented. While natural <span class="hlt">products</span> continue to have a profound impact on human health, chemists have succeeded in generating semisynthetic analogues that sometimes overshadow the original natural <span class="hlt">product</span> in terms of clinical significance. Synthetic efforts based on natural <span class="hlt">products</span> have primarily focused on improving their drug-like features while <span class="hlt">targeting</span> utility in the same biological space. A less documented phenomenon is that natural <span class="hlt">products</span> can serve as powerful starting materials to generate drug substances with novel therapeutic utility that is unrelated to the biological space of the natural <span class="hlt">product</span> starting material. In this Perspective, examples of natural <span class="hlt">product</span> derived marketed drugs with therapeutic utility in clinical space that is different from the biological <span class="hlt">profile</span> of the starting material are presented, demonstrating that this is not merely a theoretical concept but both a clinical reality and an underexplored opportunity.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24854387','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24854387"><span>Two-dimensional environmental <span class="hlt">profiles</span> of growth and fumonisin <span class="hlt">production</span> by Fusarium proliferatum on a wheat-based substrate.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cendoya, Eugenia; Farnochi, María Cecilia; Chulze, Sofia Noemi; Ramirez, María Laura</p> <p>2014-07-16</p> <p>The effect of water activity (aW; 0.995, 0.99, 0.98, 0.96, 0.94, 0.92, and 0.90), temperature (15, 25, and 30°C), incubation time (7, 14, 21 and 28days), and their interactions on mycelial growth and fumonisin <span class="hlt">production</span> on wheat-based medium by three Fusarium proliferatum strains isolated from wheat in Argentina was evaluated. Maximum growth rates were obtained at the highest aW (0.995) and 30°C, with growth decreasing as the aW of the medium was reduced. Maximum amounts of total fumonisins (FB1, FB2 and FB3) were produced at 0.99 aW and 25°C after 21 and 28days of incubation for 2 strains, and at 15°C and 0.98 aW after 28days of incubation for the third strain. The fumonisin concentrations varied considerably depending on the aW and temperature interactions assayed. The studied strains had different fumonisin <span class="hlt">production</span> <span class="hlt">profiles</span>. F. proliferatum ITEM 15661 and ITEM 15664 produced FB1 and FB2 whereas F. proliferatum ITEM 15654 was able to produce FB1, FB2 and FB3. Interestingly, fumonisin <span class="hlt">production</span> <span class="hlt">profiles</span> for each particular strain were related to incubation temperatures. Fumonisins were produced from 15 to 30°C and at aW values of 0.92 to 0.995 after 21 to 28days of incubation. However at 7 and 14days of incubation small amounts of fumonisin were produced at aW lower than 0.94. Two-dimensional <span class="hlt">profiles</span> of aW by temperature interactions were developed from these data to identify areas where conditions indicate a significant risk from fumonisin accumulation on wheat. Temperature and aW conditions that resulted in fumonisin <span class="hlt">production</span> are those found during wheat grain development (especially milk and dough stages) in the field. This study provides useful base line data on conditions representing a high and a low risk for contamination of wheat by fumonisins which is becoming of greater concern because this cereal is destined mainly for human consumption. Copyright © 2014 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/14982163','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/14982163"><span>Surface analysis and depth <span class="hlt">profiling</span> of corrosion <span class="hlt">products</span> formed in lead pipes used to supply low alkalinity drinking water.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Davidson, C M; Peters, N J; Britton, A; Brady, L; Gardiner, P H E; Lewis, B D</p> <p>2004-01-01</p> <p>Modern analytical techniques have been applied to investigate the nature of lead pipe corrosion <span class="hlt">products</span> formed in pH adjusted, orthophosphate-treated, low alkalinity water, under supply conditions. Depth <span class="hlt">profiling</span> and surface analysis have been carried out on pipe samples obtained from the water distribution system in Glasgow, Scotland, UK. X-ray diffraction spectrometry identified basic lead carbonate, lead oxide and lead phosphate as the principal components. Scanning electron microscopy/energy-dispersive x-ray spectrometry revealed the crystalline structure within the corrosion <span class="hlt">product</span> and also showed spatial correlations existed between calcium, iron, lead, oxygen and phosphorus. Elemental <span class="hlt">profiling</span>, conducted by means of secondary ion mass spectrometry (SIMS) and secondary neutrals mass spectrometry (SNMS) indicated that the corrosion <span class="hlt">product</span> was not uniform with depth. However, no clear stratification was apparent. Indeed, counts obtained for carbonate, phosphate and oxide were well correlated within the depth range probed by SIMS. SNMS showed relationships existed between carbon, calcium, iron, and phosphorus within the bulk of the scale, as well as at the surface. SIMS imaging confirmed the relationship between calcium and lead and suggested there might also be an association between chloride and phosphorus.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28186197','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28186197"><span>New natural <span class="hlt">products</span> identified by combined genomics-metabolomics <span class="hlt">profiling</span> of marine Streptomyces sp. MP131-18.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Paulus, Constanze; Rebets, Yuriy; Tokovenko, Bogdan; Nadmid, Suvd; Terekhova, Larisa P; Myronovskyi, Maksym; Zotchev, Sergey B; Rückert, Christian; Braig, Simone; Zahler, Stefan; Kalinowski, Jörn; Luzhetskyy, Andriy</p> <p>2017-02-10</p> <p>Marine actinobacteria are drawing more and more attention as a promising source of new natural <span class="hlt">products</span>. Here we report isolation, genome sequencing and metabolic <span class="hlt">profiling</span> of new strain Streptomyces sp. MP131-18 isolated from marine sediment sample collected in the Trondheim Fjord, Norway. The 16S rRNA and multilocus phylogenetic analysis showed that MP131-18 belongs to the genus Streptomyces. The genome of MP131-18 isolate was sequenced, and 36 gene clusters involved in the biosynthesis of 18 different types of secondary metabolites were predicted using antiSMASH analysis. The combined genomics-metabolics <span class="hlt">profiling</span> of the strain led to the identification of several new biologically active compounds. As a result, the family of bisindole pyrroles spiroindimicins was extended with two new members, spiroindimicins E and F. Furthermore, prediction of the biosynthetic pathway for unusual α-pyrone lagunapyrone isolated from MP131-18 resulted in foresight and identification of two new compounds of this family - lagunapyrones D and E. The diversity of identified and predicted compounds from Streptomyces sp. MP131-18 demonstrates that marine-derived actinomycetes are not only a promising source of new natural <span class="hlt">products</span>, but also represent a valuable pool of genes for combinatorial biosynthesis of secondary metabolites.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5301196','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5301196"><span>New natural <span class="hlt">products</span> identified by combined genomics-metabolomics <span class="hlt">profiling</span> of marine Streptomyces sp. MP131-18</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Paulus, Constanze; Rebets, Yuriy; Tokovenko, Bogdan; Nadmid, Suvd; Terekhova, Larisa P.; Myronovskyi, Maksym; Zotchev, Sergey B.; Rückert, Christian; Braig, Simone; Zahler, Stefan; Kalinowski, Jörn; Luzhetskyy, Andriy</p> <p>2017-01-01</p> <p>Marine actinobacteria are drawing more and more attention as a promising source of new natural <span class="hlt">products</span>. Here we report isolation, genome sequencing and metabolic <span class="hlt">profiling</span> of new strain Streptomyces sp. MP131-18 isolated from marine sediment sample collected in the Trondheim Fjord, Norway. The 16S rRNA and multilocus phylogenetic analysis showed that MP131-18 belongs to the genus Streptomyces. The genome of MP131-18 isolate was sequenced, and 36 gene clusters involved in the biosynthesis of 18 different types of secondary metabolites were predicted using antiSMASH analysis. The combined genomics-metabolics <span class="hlt">profiling</span> of the strain led to the identification of several new biologically active compounds. As a result, the family of bisindole pyrroles spiroindimicins was extended with two new members, spiroindimicins E and F. Furthermore, prediction of the biosynthetic pathway for unusual α-pyrone lagunapyrone isolated from MP131-18 resulted in foresight and identification of two new compounds of this family – lagunapyrones D and E. The diversity of identified and predicted compounds from Streptomyces sp. MP131-18 demonstrates that marine-derived actinomycetes are not only a promising source of new natural <span class="hlt">products</span>, but also represent a valuable pool of genes for combinatorial biosynthesis of secondary metabolites. PMID:28186197</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29750520','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29750520"><span>Effects of TT8 and HB12 Silencing on the Relations between the Molecular Structures of Alfalfa ( Medicago sativa) Plants and Their Nutritional <span class="hlt">Profiles</span> and In Vitro Gas <span class="hlt">Production</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lei, Yaogeng; Hannoufa, Abdelali; Prates, Luciana Louzada; Shi, Haitao; Wang, Yuxi; Biligetu, Bill; Christensen, David; Yu, Peiqiang</p> <p>2018-06-06</p> <p>The objective of this study was to investigate the effects of silencing the TT8 and HB12 genes on the nutritive <span class="hlt">profiles</span> and in vitro gas <span class="hlt">production</span> of alfalfa in relation to the spectral molecular structures of alfalfa. TT8-silenced (TT8i, n = 5) and HB12-silenced (HB12i, n = 11) alfalfa were generated by RNA interference (RNAi) and grown with nontransgenic wild type controls (WT, n = 4) in a greenhouse. Alfalfa plants were harvested at early-to-mid vegetative stage. Samples were analyzed for their chemical compositions, CNCPS fractions, and in vitro gas <span class="hlt">production</span>. Correlations and regressions of the nutritional <span class="hlt">profiles</span> and in vitro gas <span class="hlt">production</span> with the molecular spectral structures were also determined. The results showed that the transformed alfalfa had higher digestible fiber and lower crude protein with higher proportions of indigestible protein than WT. HB12 RNAi had lower gas <span class="hlt">production</span> compared with those of the others. Some chemical, CNCPS, and gas-<span class="hlt">production</span> <span class="hlt">profiles</span> were closely correlated with spectral structures and could be well predicted from spectral parameters. In conclusion, the RNAi silencing of TT8 and HB12 in alfalfa altered the chemical, CNCPS and gas-<span class="hlt">production</span> <span class="hlt">profiles</span> of alfalfa, and such alterations were closely correlated with the inherent spectral structures of alfalfa.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28458360','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28458360"><span>Comparison of Dissolution Similarity Assessment Methods for <span class="hlt">Products</span> with Large Variations: f2 Statistics and Model-Independent Multivariate Confidence Region Procedure for Dissolution <span class="hlt">Profiles</span> of Multiple Oral <span class="hlt">Products</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yoshida, Hiroyuki; Shibata, Hiroko; Izutsu, Ken-Ichi; Goda, Yukihiro</p> <p>2017-01-01</p> <p>The current Japanese Ministry of Health Labour and Welfare (MHLW)'s Guideline for Bioequivalence Studies of Generic <span class="hlt">Products</span> uses averaged dissolution rates for the assessment of dissolution similarity between test and reference formulations. This study clarifies how the application of model-independent multivariate confidence region procedure (Method B), described in the European Medical Agency and U.S. Food and Drug Administration guidelines, affects similarity outcomes obtained empirically from dissolution <span class="hlt">profiles</span> with large variations in individual dissolution rates. Sixty-one datasets of dissolution <span class="hlt">profiles</span> for immediate release, oral generic, and corresponding innovator <span class="hlt">products</span> that showed large variation in individual dissolution rates in generic <span class="hlt">products</span> were assessed on their similarity by using the f 2 statistics defined in the MHLW guidelines (MHLW f 2 method) and two different Method B procedures, including a bootstrap method applied with f 2 statistics (BS method) and a multivariate analysis method using the Mahalanobis distance (MV method). The MHLW f 2 and BS methods provided similar dissolution similarities between reference and generic <span class="hlt">products</span>. Although a small difference in the similarity assessment may be due to the decrease in the lower confidence interval for expected f 2 values derived from the large variation in individual dissolution rates, the MV method provided results different from those obtained through MHLW f 2 and BS methods. Analysis of actual dissolution data for <span class="hlt">products</span> with large individual variations would provide valuable information towards an enhanced understanding of these methods and their possible incorporation in the MHLW guidelines.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27642725','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27642725"><span>Neutronic and thermal-hydraulic analysis of fission molybdenum-99 <span class="hlt">production</span> at Tehran Research Reactor using LEU plate <span class="hlt">targets</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Abedi, Ebrahim; Ebrahimkhani, Marzieh; Davari, Amin; Mirvakili, Seyed Mohammad; Tabasi, Mohsen; Maragheh, Mohammad Ghannadi</p> <p>2016-12-01</p> <p>Efficient and safe <span class="hlt">production</span> of molybdenum-99 ( 99 Mo) radiopharmaceutical at Tehran Research Reactor (TRR) via fission of LEU <span class="hlt">targets</span> is studied. Neutronic calculations are performed to evaluate produced 99 Mo activity, core neutronic safety parameters and also the power deposition values in <span class="hlt">target</span> plates during a 7 days irradiation interval. Thermal-hydraulic analysis has been also carried out to obtain thermal behavior of these plates. Using Thermal-hydraulic analysis, it can be concluded that the safety parameters are satisfied in the current study. Consequently, the present neutronic and thermal-hydraulic calculations show efficient 99 Mo <span class="hlt">production</span> is accessible at significant activity values in TRR current core configuration. Copyright © 2016 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2700821','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2700821"><span>Microfluidics for Drug Discovery and Development: From <span class="hlt">Target</span> Selection to <span class="hlt">Product</span> Lifecycle Management</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kang, Lifeng; Chung, Bong Geun; Langer, Robert; Khademhosseini, Ali</p> <p>2009-01-01</p> <p>Microfluidic technologies’ ability to miniaturize assays and increase experimental throughput have generated significant interest in the drug discovery and development domain. These characteristics make microfluidic systems a potentially valuable tool for many drug discovery and development applications. Here, we review the recent advances of microfluidic devices for drug discovery and development and highlight their applications in different stages of the process, including <span class="hlt">target</span> selection, lead identification, preclinical tests, clinical trials, chemical synthesis, formulations studies, and <span class="hlt">product</span> management. PMID:18190858</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.fs.usda.gov/treesearch/pubs/2161','TREESEARCH'); return false;" href="https://www.fs.usda.gov/treesearch/pubs/2161"><span>Enantiospecific Pheromone <span class="hlt">Production</span> and Response <span class="hlt">Profiles</span> for Populations of Pine Engraver, Ips pini (SAY) (Coleoptera: Scolytidae), in British Columbia</span></a></p> <p><a target="_blank" href="http://www.fs.usda.gov/treesearch/">Treesearch</a></p> <p>D.R. Miller; J.H. Borden; K.N. Slessor</p> <p>1996-01-01</p> <p>Analyses of the enantiomeric composition of ipsdienol produced by individual male pine engravers, Ips pini (Say), from six populations in British Columbia, support the hypothesis that New York and Idaho races of this species hybridize in southeastern British Columbia. <span class="hlt">Production</span> <span class="hlt">profiles</span>, expressed as frequency distributions of (+):(-) ipsdienol...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3078864','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3078864"><span>Genome-wide <span class="hlt">target</span> <span class="hlt">profiling</span> of piggyBac and Tol2 in HEK 293: pros and cons for gene discovery and gene therapy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2011-01-01</p> <p>Background DNA transposons have emerged as indispensible tools for manipulating vertebrate genomes with applications ranging from insertional mutagenesis and transgenesis to gene therapy. To fully explore the potential of two highly active DNA transposons, piggyBac and Tol2, as mammalian genetic tools, we have conducted a side-by-side comparison of the two transposon systems in the same setting to evaluate their advantages and disadvantages for use in gene therapy and gene discovery. Results We have observed that (1) the Tol2 transposase (but not piggyBac) is highly sensitive to molecular engineering; (2) the piggyBac donor with only the 40 bp 3'-and 67 bp 5'-terminal repeat domain is sufficient for effective transposition; and (3) a small amount of piggyBac transposases results in robust transposition suggesting the piggyBac transpospase is highly active. Performing genome-wide <span class="hlt">target</span> <span class="hlt">profiling</span> on data sets obtained by retrieving chromosomal <span class="hlt">targeting</span> sequences from individual clones, we have identified several piggyBac and Tol2 hotspots and observed that (4) piggyBac and Tol2 display a clear difference in <span class="hlt">targeting</span> preferences in the human genome. Finally, we have observed that (5) only sites with a particular sequence context can be <span class="hlt">targeted</span> by either piggyBac or Tol2. Conclusions The non-overlapping <span class="hlt">targeting</span> preference of piggyBac and Tol2 makes them complementary research tools for manipulating mammalian genomes. PiggyBac is the most promising transposon-based vector system for achieving site-specific <span class="hlt">targeting</span> of therapeutic genes due to the flexibility of its transposase for being molecularly engineered. Insights from this study will provide a basis for engineering piggyBac transposases to achieve site-specific therapeutic gene <span class="hlt">targeting</span>. PMID:21447194</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25704266','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25704266"><span>Emission and <span class="hlt">profile</span> characteristic of volatile organic compounds emitted from coke <span class="hlt">production</span>, iron smelt, heating station and power plant in Liaoning Province, China.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shi, Jianwu; Deng, Hao; Bai, Zhipeng; Kong, Shaofei; Wang, Xiuyan; Hao, Jiming; Han, Xinyu; Ning, Ping</p> <p>2015-05-15</p> <p>107 kinds of C₂-C₁₂ volatile organic compound (VOC) mass concentrations and <span class="hlt">profiles</span> for four types of coal-fired stationary sources in Liaoning Province were studied by a dilution sampling system and GC-MS analysis method, which are of significant importance with regard to VOC emissions in northeast of China. The results showed that there were some differences among these VOC source <span class="hlt">profiles</span>. The total mass concentrations of analyzed 107 VOC species varied from 10,917 to 19,652 μg m(-3). Halogenated hydrocarbons exhibited higher mass percentages for the VOC source <span class="hlt">profiles</span> of iron smelt (48.8%) and coke <span class="hlt">production</span> plant (37.7%). Aromatic hydrocarbons were the most abundant in heating station plant (69.1%). Ketones, alcohols and acetates held 45.0% of total VOCs in thermal power plant. For non-methane hydrocarbons (NMHCs), which are demanded for photochemical assessment in the USA, toluene and n-hexane were the most abundant species in the iron smelt, coke <span class="hlt">production</span> and thermal power plant, with the mass percentages of 64.8%, 52.7% and 38.6%, respectively. Trimethylbenzene, n-propylbenzene and o,m-ethyltoluene approximately accounted for 70.0% in heating station plant. NMHCs emitted from coke <span class="hlt">production</span>, iron smelt, heating station and power plant listed above presented different chemical reactivities. The average OH loss rate of NMHCs from heating station, was 4 to 5.6 times higher than that of NMHCs from iron smelt, coke <span class="hlt">production</span> and power plant, which implies that VOCs emitted from heating station in northeast of China should be controlled firstly to avoid photochemical ozone pollution and protect human health. There are significant variations in the ratios of benzene/toluene and m, p-xylene/ethylbenzene of these coal-fired source <span class="hlt">profiles</span>. The representativeness of the coal-fired sources studied and the VOC samples collected should be more closely examined. The accuracy of VOC source <span class="hlt">profiles</span> related to coal-fired processes is highly dependent on</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24861758','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24861758"><span>Kidney tissue <span class="hlt">targeted</span> metabolic <span class="hlt">profiling</span> of glucocorticoid-induced osteoporosis and the proposed therapeutic effects of Rhizoma Drynariae studied using UHPLC/MS/MS.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Huang, Yue; Liu, Xinyu; Zhao, Longshan; Li, Famei; Xiong, Zhili</p> <p>2014-06-01</p> <p>Traditional Chinese medicine and modern science have indicated that there is a close relationship between bone and kidney. In light of this, this project was designed to study the metabolic <span class="hlt">profiling</span> by UHPLC/MS/MS of glucocorticoid-induced osteoporosis in kidney tissue and the possible therapeutic effects of Rhizoma Drynariae (RD), a classic traditional Chinese medicine, in improving the kidney function and strengthening bone. Twenty-one Wistar rats were divided into three groups: control group (rats before prednisolone inducing), a model group (prednisolone-induced group) and a treatment group (prednisolone-induced rats that were then administered RD ethanol extracts). By using pattern recognition analysis, a significant change in the metabolic <span class="hlt">profile</span> of kidney tissue samples was observed in the model group and restoration of the <span class="hlt">profile</span> was observed after the administration of RD ethanol extracts. Some significantly changed biomarkers related to osteoporosis such as sphingolipids (C16 dihydrosphingosine, C18 dihydrosphingosine, C18 phytosphingosine, C20 phytosphingosine), lysophosphatidycholines (C16:0 LPC, C18:0 LPC) and phenylalanine were identified. As a complement to the metabolic <span class="hlt">profiling</span> of RD in plasma, these biomarkers suggest that kidney damage, cell cytotoxicity and apoptosis exist in osteoporosis rats, which is helpful in further understanding the underlying process of glucocorticoid-induced osetoporosis and the suggested therapeutic effects of RD. The method shows that tissue <span class="hlt">target</span> metabonomics might provide a powerful tool to further understand the process of disease and the mechanism of therapeutic effect of Chinese medicines. Copyright © 2014 John Wiley & Sons, Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19443325','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19443325"><span>Advertising of OTC <span class="hlt">products</span> in a Nigerian urban setting: content analysis for indications, <span class="hlt">targets</span>, and advertising appeal.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yusuff, Kazeem B; Yusuf, Akeem</p> <p>2009-01-01</p> <p>To identify the indications for which treatments were promoted, the segments of population <span class="hlt">targeted</span>, and the type and extent of advertising appeal used for over-the-counter (OTC) <span class="hlt">products</span> in a Nigerian urban setting. Using a cross-sectional design, the content of advertisements for OTC <span class="hlt">products</span> on radio, television, and billboards in a city in southwestern Nigeria were assessed during a 3-month period. Two coders independently assessed 1,492 advertisements for 49 brands of OTC <span class="hlt">products</span> (interrater reliability [Cohen's kappa] = 0.83 [95% CI 0.80-0.90]). The most frequent indications for OTC <span class="hlt">products</span> were aches and pain (42.9%), anemia/malnutrition (34.8%), and malaria (22.2%). Of advertisements, 92% were <span class="hlt">targeted</span> at the primary end user. Use of appeal related to efficacy (100%), psychosocial enhancement (80%), and ease of use (40%) in visual, written, and audio messages was highest in ads on billboards. Efficacy appeal had the highest frequency across the three advertising media (100%); ease-of-use and safety appeal had the lowest frequency (40% and 7.4%, respectively). Nigerian movie stars were used as brand icons in advertisements of OTC <span class="hlt">products</span> on radio (59.5%), television (52.9%), and billboards (49.6%). The majority of advertisements for OTC <span class="hlt">products</span> in a Nigerian urban setting used advertising appeal related to efficacy and psychosocial enhancement. Promotional efforts by pharmaceutical manufacturers appear to focus on positive emotional appeal to influence drug purchase and use decisions.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009LNCS.5859..276A','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009LNCS.5859..276A"><span>Adaptive User <span class="hlt">Profiles</span> in Pervasive Advertising Environments</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Alt, Florian; Balz, Moritz; Kristes, Stefanie; Shirazi, Alireza Sahami; Mennenöh, Julian; Schmidt, Albrecht; Schröder, Hendrik; Goedicke, Michael</p> <p></p> <p>Nowadays modern advertising environments try to provide more efficient ads by <span class="hlt">targeting</span> costumers based on their interests. Various approaches exist today as to how information about the users' interests can be gathered. Users can deliberately and explicitly provide this information or user's shopping behaviors can be analyzed implicitly. We implemented an advertising platform to simulate an advertising environment and present adaptive <span class="hlt">profiles</span>, which let users setup <span class="hlt">profiles</span> based on a self-assessment, and enhance those <span class="hlt">profiles</span> with information about their real shopping behavior as well as about their activity intensity. Additionally, we explain how pervasive technologies such as Bluetooth can be used to create a <span class="hlt">profile</span> anonymously and unobtrusively.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017EPJWC.15301020L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017EPJWC.15301020L"><span>Neutron <span class="hlt">Productions</span> from thin Be <span class="hlt">target</span> irradiated by 50 MeV/u 238U beam</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Lee, Hee-Seock; Oh, Joo-Hee; Jung, Nam-Suk; Oranj, Leila Mokhtari; Nakao, Noriaki; Uwamino, Yoshitomo</p> <p>2017-09-01</p> <p>Neutrons generated from thin beryllium <span class="hlt">target</span> by 50 MeV/u 238U beam were measured using activation analysis at 15, 30, 45, and 90 degrees from the beam direction. A 0.085 mm-thick Be stripper of RIBF was used as the neutron generating <span class="hlt">target</span>. Activation detectors of bismuth, cobalt, and aluminum were placed out of the stripper chamber. The threshold reactions of 209Bi(n, xn)210-xBi(x=4 8), 59Co(n, xn)60-xCO(x=2 5), 59Co(n, 2nα)54Mn, 27Al(n, α)24Na, and 27Al(n,2nα)22Na were applied to measure the <span class="hlt">production</span> rates of radionuclides. The neutron spectra were obtained using an unfolding method with the SAND-II code. All of <span class="hlt">production</span> rates and neutron spectra were compared with the calculated results using Monte Carlo codes, the PHITS and the FLUKA. The FLUKA results showed better agreement with the measurements than the PHITS. The discrepancy between the measurements and the calculations were discussed.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4649854','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4649854"><span>Effects of Peptone Supplementation in Different Culture Media on Growth, Metabolic Pathway and <span class="hlt">Productivity</span> of CHO DG44 Cells; a New Insight into Amino Acid <span class="hlt">Profiles</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Davami, Fatemeh; Eghbalpour, Farnaz; Nematollahi, Leila; Barkhordari, Farzaneh; Mahboudi, Fereidoun</p> <p>2015-01-01</p> <p>Background: The optimization of bioprocess conditions towards improved growth <span class="hlt">profile</span> and <span class="hlt">productivity</span> yield is considered of great importance in biopharmaceutical manufacturing. Peptones as efficient sources of nutrients have been studied for their effect on media development; however, their role on metabolic pathway is not well understood. Methods: In the present study, the effect of different concentration of peptones on a recombinant Chinese hamster ovary (CHO) cell line grown in three serum-free suspension cultures was determined. Six peptones of different origins and available amino acid <span class="hlt">profiles</span> were investigated regarding their impact on cell growth, <span class="hlt">productivity</span>, and metabolic pathways changes. Results: In optimized feeding strategies, increases of 136% and 159% in volumetric <span class="hlt">productivity</span> (for a low-nutrient culture media) and 55% (for a high-nutrient culture media) were achieved. Furthermore, particular sources of peptones with specific amino acid <span class="hlt">profile</span> developed preferential results for each different culture medium. Two peptones, SoyA2SC and SoyE-110, were the only hydrolysates that showed <span class="hlt">production</span> improvement in all three media. Casein Peptone plus Tryptone N1 and SoyA3SC showed different improved results based on their implemented concentration for each individual basal medium. Conclusion: The amino acid <span class="hlt">profile</span> of peptones may provide clues to identify the most effective feeding strategies for recombinant CHO cells. PMID:26232332</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017AGUFM.C13C0974P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017AGUFM.C13C0974P"><span>CREST-SAFE: Snow LST validation, wetness <span class="hlt">profiler</span> creation, and depth/SWE <span class="hlt">product</span> development</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Perez Diaz, C. L.; Lakhankar, T.; Romanov, P.; Khanbilvardi, R.; Munoz Barreto, J.; Yu, Y.</p> <p>2017-12-01</p> <p>CREST-SAFE: Snow LST validation, wetness <span class="hlt">profiler</span> creation, and depth/SWE <span class="hlt">product</span> development The Field Snow Research Station (also referred to as Snow Analysis and Field Experiment, SAFE) is operated by the NOAA Center for Earth System Sciences and Remote Sensing Technologies (CREST) in the City University of New York (CUNY). The field station is located within the premises of the Caribou Municipal Airport (46°52'59'' N, 68°01'07'' W) and in close proximity to the National Weather Service (NWS) Regional Forecast Office. The station was established in 2010 to support studies in snow physics and snow remote sensing. The Visible Infrared Imager Radiometer Suite (VIIRS) Land Surface Temperature (LST) Environmental Data Record (EDR) and Moderate Resolution Imaging Spectroradiometer (MODIS) LST <span class="hlt">product</span> (provided by the Terra and Aqua Earth Observing System satellites) were validated using in situ LST (T-skin) and near-surface air temperature (T-air) observations recorded at CREST-SAFE for the winters of 2013 and 2014. Results indicate that T-air correlates better than T-skin with VIIRS LST data and that the accuracy of nighttime LST retrievals is considerably better than that of daytime. Several trends in the MODIS LST data were observed, including the underestimation of daytime values and night-time values. Results indicate that, although all the data sets showed high correlation with ground measurements, day values yielded slightly higher accuracy ( 1°C). Additionally, we created a liquid water content (LWC)-<span class="hlt">profiling</span> instrument using time-domain reflectometry (TDR) at CREST-SAFE and tested it during the snow melt period (February-April) immediately after installation in 2014. Results displayed high agreement when compared to LWC estimates obtained using empirical formulas developed in previous studies, and minor improvement over wet snow LWC estimates. Lastly, to improve on global snow cover mapping, a snow <span class="hlt">product</span> capable of estimating snow depth and snow water</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_22 --> <div id="page_23" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="441"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29662210','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29662210"><span>Genome-wide mutant <span class="hlt">profiling</span> predicts the mechanism of a Lipid II binding antibiotic.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Santiago, Marina; Lee, Wonsik; Fayad, Antoine Abou; Coe, Kathryn A; Rajagopal, Mithila; Do, Truc; Hennessen, Fabienne; Srisuknimit, Veerasak; Müller, Rolf; Meredith, Timothy C; Walker, Suzanne</p> <p>2018-06-01</p> <p>Identifying <span class="hlt">targets</span> of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivation mutants. We treated a Staphylococcus aureus transposon library containing 690,000 unique insertions with 32 antibiotics. Upregulation signatures identified from directional biases in insertions revealed known molecular <span class="hlt">targets</span> and resistance mechanisms for the majority of these. Because single-gene upregulation does not always confer resistance, we used a complementary machine-learning approach to predict the mechanism from inactivation mutant fitness <span class="hlt">profiles</span>. This approach suggested the cell wall precursor Lipid II as the molecular <span class="hlt">target</span> of the lysocins, a mechanism we have confirmed. We conclude that docking to membrane-anchored Lipid II precedes the selective bacteriolysis that distinguishes these lytic natural <span class="hlt">products</span>, showing the utility of our approach for nominating the antibiotic mechanism of action.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017SPIE10198E..0QA','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017SPIE10198E..0QA"><span>Supervised non-negative tensor factorization for automatic hyperspectral feature extraction and <span class="hlt">target</span> discrimination</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Anderson, Dylan; Bapst, Aleksander; Coon, Joshua; Pung, Aaron; Kudenov, Michael</p> <p>2017-05-01</p> <p>Hyperspectral imaging provides a highly discriminative and powerful signature for <span class="hlt">target</span> detection and discrimination. Recent literature has shown that considering additional <span class="hlt">target</span> characteristics, such as spatial or temporal <span class="hlt">profiles</span>, simultaneously with spectral content can greatly increase classifier performance. Considering these additional characteristics in a traditional discriminative algorithm requires a feature extraction step be performed first. An example of such a pipeline is computing a filter bank response to extract spatial features followed by a support vector machine (SVM) to discriminate between <span class="hlt">targets</span>. This decoupling between feature extraction and <span class="hlt">target</span> discrimination yields features that are suboptimal for discrimination, reducing performance. This performance reduction is especially pronounced when the number of features or available data is limited. In this paper, we propose the use of Supervised Nonnegative Tensor Factorization (SNTF) to jointly perform feature extraction and <span class="hlt">target</span> discrimination over hyperspectral data <span class="hlt">products</span>. SNTF learns a tensor factorization and a classification boundary from labeled training data simultaneously. This ensures that the features learned via tensor factorization are optimal for both summarizing the input data and separating the <span class="hlt">targets</span> of interest. Practical considerations for applying SNTF to hyperspectral data are presented, and results from this framework are compared to decoupled feature extraction/<span class="hlt">target</span> discrimination pipelines.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27544861','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27544861"><span>Lipase-catalyzed modification of the flavor <span class="hlt">profiles</span> in recombined skim milk <span class="hlt">products</span> by enriching the volatile components.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhang, X M; Ai, N S; Wang, J; Tong, L J; Zheng, F P; Sun, B G</p> <p>2016-11-01</p> <p>The purpose of this study was to modify the amount and composition of volatile components in bovine milk <span class="hlt">products</span>, in an attempt to create a recombined skim milk <span class="hlt">product</span> with full-fat milk flavor but with only 0.5% fat. The experimental plan included lipase-catalyzed hydrolysis and esterification reactions using Palatase 20000L (Novozymes, Bagsværd, Denmark). The results, measured by the methods of volatile compositional analysis and sensory evaluation, showed that the flavor <span class="hlt">profiles</span> of the optimal recombined milk <span class="hlt">products</span> were effectively modified in this way, possessing intensified characteristic volatile flavor components with rather low level of fat contents, and the sensory characters were quite realistic to natural whole milk flavor. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://proteomics.cancer.gov/funding_opportunities/requests-cancer-targets-monoclonal-antibody-production-and-characterization','NCI'); return false;" href="https://proteomics.cancer.gov/funding_opportunities/requests-cancer-targets-monoclonal-antibody-production-and-characterization"><span>Requests Cancer <span class="hlt">Targets</span> for Monoclonal Antibody <span class="hlt">Production</span> and Characterization | Office of Cancer Clinical Proteomics Research</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>In an effort to provide well-characterized monoclonal antibodies to the scientific community, the National Cancer Institute (NCI) Antibody Characterization Program requests cancer-related protein <span class="hlt">targets</span> for affinity <span class="hlt">production</span> and distribution. The program from The Office of Cancer Clinical Proteomics Research provides reagents and other critical resources that support protein and/or peptide measurements and analysis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://proteomics.cancer.gov/node/65','NCI'); return false;" href="https://proteomics.cancer.gov/node/65"><span>Reagent <span class="hlt">Target</span> Request for Monoclonal Antibody <span class="hlt">Production</span> and Characterization | Office of Cancer Clinical Proteomics Research</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>NCI's Antibody Characterization Program provides reagents and other critical resources to support protein/peptide measurements and analysis. In an effort to produce and distribute well-characterized monoclonal antibodies to the scientific community, the program is seeking cancer related protein <span class="hlt">targets</span> for antibody <span class="hlt">production</span> and characterization for distribution to the research community. Submission Period: May 20, 2011 - July 1, 2011.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29175143','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29175143"><span>Electron linear accelerator <span class="hlt">production</span> and purification of scandium-47 from titanium dioxide <span class="hlt">targets</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rotsch, David A; Brown, M Alex; Nolen, Jerry A; Brossard, Thomas; Henning, Walter F; Chemerisov, Sergey D; Gromov, Roman G; Greene, John</p> <p>2018-01-01</p> <p>The photonuclear <span class="hlt">production</span> of no-carrier-added (NCA) 47 Sc from solid Nat TiO 2 and the subsequent chemical processing and purification have been developed. Scandium-47 was produced by the 48 Ti(γ,p) 47 Sc reaction with Bremsstrahlung photons produced from the braking of electrons in a high-Z (W or Ta) convertor. <span class="hlt">Production</span> yields were simulated with the PHITS code (Particle and Heavy Ion Transport-code System) and compared to experimental results. Irradiated TiO 2 <span class="hlt">targets</span> were dissolved in fuming H 2 SO 4 in the presence of Na 2 SO 4 and 47 Sc was purified using the commercially available Eichrom DGA resin. Typical 47 Sc recovery yields were >90% with excellent specific activity for small batches (<185 MBq batches). Copyright © 2017 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1421964-electron-linear-accelerator-production-purification-scandium-from-titanium-dioxide-targets','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1421964-electron-linear-accelerator-production-purification-scandium-from-titanium-dioxide-targets"><span>Electron linear accelerator <span class="hlt">production</span> and purification of scandium-47 from titanium dioxide <span class="hlt">targets</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Rotsch, David A.; Brown, M. Alex; Nolen, Jerry A.; ...</p> <p>2017-11-06</p> <p>Here, the photonuclear <span class="hlt">production</span> of no-carrier-added (NCA) 47Sc from solid NatTiO 2 and the subsequent chemical processing and purification have been developed. Scandium-47 was produced by the 48Ti(γ,p) 47Sc reaction with Bremsstrahlung photons produced from the braking of electrons in a high-Z (W or Ta) convertor. <span class="hlt">Production</span> yields were simulated with the PHITS code (Particle and Heavy Ion Transport-code System) and compared to experimental results. Irradiated TiO 2 <span class="hlt">targets</span> were dissolved in fuming H 2SO 4 in the presence of Na 2SO 4 and 47Sc was purified using the commercially available Eichrom DGA resin. Typical 47Sc recovery yields were >90%more » with excellent specific activity for small batches (<185 MBq batches).« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/1421964-electron-linear-accelerator-production-purification-scandium-from-titanium-dioxide-targets','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/1421964-electron-linear-accelerator-production-purification-scandium-from-titanium-dioxide-targets"><span>Electron linear accelerator <span class="hlt">production</span> and purification of scandium-47 from titanium dioxide <span class="hlt">targets</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Rotsch, David A.; Brown, M. Alex; Nolen, Jerry A.</p> <p></p> <p>Here, the photonuclear <span class="hlt">production</span> of no-carrier-added (NCA) 47Sc from solid NatTiO 2 and the subsequent chemical processing and purification have been developed. Scandium-47 was produced by the 48Ti(γ,p) 47Sc reaction with Bremsstrahlung photons produced from the braking of electrons in a high-Z (W or Ta) convertor. <span class="hlt">Production</span> yields were simulated with the PHITS code (Particle and Heavy Ion Transport-code System) and compared to experimental results. Irradiated TiO 2 <span class="hlt">targets</span> were dissolved in fuming H 2SO 4 in the presence of Na 2SO 4 and 47Sc was purified using the commercially available Eichrom DGA resin. Typical 47Sc recovery yields were >90%more » with excellent specific activity for small batches (<185 MBq batches).« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28639122','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28639122"><span><span class="hlt">Targeting</span> Prostate-Specific Membrane Antigen (PSMA) with F-18-Labeled Compounds: the Influence of Prosthetic Groups on Tumor Uptake and Clearance <span class="hlt">Profile</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bouvet, Vincent; Wuest, Melinda; Bailey, Justin J; Bergman, Cody; Janzen, Nancy; Valliant, John F; Wuest, Frank</p> <p>2017-12-01</p> <p>Prostate-specific membrane antigen (PSMA) is an important biomarker expressed in the majority of prostate cancers. The favorable positron emission tomography (PET) imaging <span class="hlt">profile</span> of the PSMA imaging agent 2-(3-(1-carboxy-5-[(6-[ 18 F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentane-dioic acid [ 18 F]DCFPyL in preclinical prostate cancer models and in prostate cancer patients stimulated the development and validation of other fluorine-containing PSMA inhibitors to further enhance pharmacokinetics and simplify <span class="hlt">production</span> methods. Here, we describe the synthesis and radiopharmacological evaluation of various F-18-labeled PSMA inhibitors which were prepared through different prosthetic group chemistry strategies. Prosthetic groups N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]SFB), 4-[ 18 F]fluorobenzaldehyde, and 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) were used for bioconjugation reactions to PSMA-binding lysine-urea-glutamate scaffold via acylation and oxime formation. All fluorine-containing PSMA inhibitors were tested for their PSMA inhibitory potency in an in vitro competitive binding assay in comparison to an established reference compound [ 125 I]TAAG-PSMA. Tumor uptake and clearance <span class="hlt">profiles</span> of three F-18-labeled PSMA inhibitors ([ 18 F]4, [ 18 F]7, and [ 18 F]8) were studied with dynamic PET imaging using LNCaP tumor-bearing mice. F-18-labeled PSMA inhibitors were synthesized in 32-69 % radiochemical yields using (1) acylation reaction at the primary amino group of the lysine residue with [ 18 F]SFB and (2) oxime formation with 4-[ 18 F]fluorobenzaldehyde and [ 18 F]FDG using the respective aminooxy-functionalized lysine residue. Compound 7 displayed an IC 50 value of 6 nM reflecting very high affinity for PSMA. Compounds 4 and 8 showed IC 50 values of 13 and 62 nM, respectively. The IC 50 value of reference compound DCFPyL was 13 nM. Dynamic PET imaging revealed the following SUV 60min for radiotracer uptake in PSMA(+) LNCaP tumors: 0</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23628475','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23628475"><span>Glioma <span class="hlt">targeting</span> and blood-brain barrier penetration by dual-<span class="hlt">targeting</span> doxorubincin liposomes.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gao, Jian-Qing; Lv, Qing; Li, Li-Ming; Tang, Xin-Jiang; Li, Fan-Zhu; Hu, Yu-Lan; Han, Min</p> <p>2013-07-01</p> <p>Effective chemotherapy for glioblastoma requires a carrier that can penetrate the blood-brain barrier (BBB) and subsequently <span class="hlt">target</span> the glioma cells. Dual-<span class="hlt">targeting</span> doxorubincin (Dox) liposomes were produced by conjugating liposomes with both folate (F) and transferrin (Tf), which were proven effective in penetrating the BBB and <span class="hlt">targeting</span> tumors, respectively. The liposome was characterized by particle size, Dox entrapment efficiency, and in vitro release <span class="hlt">profile</span>. Drug accumulation in cells, P-glycoprotein (P-gp) expression, and drug transport across the BBB in the dual-<span class="hlt">targeting</span> liposome group were examined by using bEnd3 BBB models. In vivo studies demonstrated that the dual-<span class="hlt">targeting</span> Dox liposomes could transport across the BBB and mainly distribute in the brain glioma. The anti-tumor effect of the dual-<span class="hlt">targeting</span> liposome was also demonstrated by the increased survival time, decreased tumor volume, and results of both hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis. The dual-<span class="hlt">targeting</span> Dox liposome could improve the therapeutic efficacy of brain glioma and were less toxic than the Dox solution, showing a dual-<span class="hlt">targeting</span> effect. These results indicate that this dual-<span class="hlt">targeting</span> liposome can be used as a potential carrier for glioma chemotherapy. Copyright © 2013 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4570814','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4570814"><span>Global Identification of MicroRNAs and Their <span class="hlt">Targets</span> in Barley under Salinity Stress</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Cui, Licao; Feng, Kewei; Liu, Fuyan; Du, Xianghong; Tong, Wei; Nie, Xiaojun; Ji, Wanquan; Weining, Song</p> <p>2015-01-01</p> <p>Salinity is a major limiting factor for agricultural <span class="hlt">production</span> worldwide. A better understanding of the mechanisms of salinity stress response will aid efforts to improve plant salt tolerance. In this study, a combination of small RNA and mRNA degradome sequencing was used to identify salinity responsive-miRNAs and their <span class="hlt">targets</span> in barley. A total of 152 miRNAs belonging to 126 families were identified, of which 44 were found to be salinity responsive with 30 up-regulated and 25 down-regulated respectively. The majority of the salinity-responsive miRNAs were up-regulated at the 8h time point, while down-regulated at the 3h and 27h time points. The <span class="hlt">targets</span> of these miRNAs were further detected by degradome sequencing coupled with bioinformatics prediction. Finally, qRT-PCR was used to validate the identified miRNA and their <span class="hlt">targets</span>. Our study systematically investigated the expression <span class="hlt">profile</span> of miRNA and their <span class="hlt">targets</span> in barley during salinity stress phase, which can contribute to understanding how miRNAs respond to salinity stress in barley and other cereal crops. PMID:26372557</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1333066-large-scale-accelerator-production-effective-cross-sections-mev-protons-incident-targets','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1333066-large-scale-accelerator-production-effective-cross-sections-mev-protons-incident-targets"><span>Large Scale Accelerator <span class="hlt">Production</span> of 225Ac: Effective Cross sections for 78-192 MeV Protons Incident on 232Th <span class="hlt">Targets</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Griswold, Justin R; Medvedev, Dmitri G.; Engle, Jonathan W.; ...</p> <p>2016-09-28</p> <p>Actinium-225 and 213Bi have been used successfully in <span class="hlt">targeted</span> alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of 225Ac. The high energy proton spallation reaction on natural thorium metal <span class="hlt">target</span> has been utilized to produce millicurie quantities of 225Ac. The results of sixteen irradiation experiments of Th metal at beam energies between 78 and 200 MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while <span class="hlt">target</span> dissolution and processing was carried out at Oak Ridgemore » National Laboratory (ORNL). Excitation functions for actinium and thorium isotopes as well as for some of the fission <span class="hlt">products</span> are presented. The cross sections for <span class="hlt">production</span> of 225Ac range from 3.6 to 16.7 mb in the incident proton energy range of 78 to 192 MeV. Based on these data, <span class="hlt">production</span> of Curie quantities of 225Ac is possible by irradiating a 5.0 g cm -2232Th <span class="hlt">target</span> for 10 days in either BNL or LANL proton irradiation facilities.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27776333','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27776333"><span>Large scale accelerator <span class="hlt">production</span> of 225Ac: Effective cross sections for 78-192MeV protons incident on 232Th <span class="hlt">targets</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Griswold, J R; Medvedev, D G; Engle, J W; Copping, R; Fitzsimmons, J M; Radchenko, V; Cooley, J C; Fassbender, M E; Denton, D L; Murphy, K E; Owens, A C; Birnbaum, E R; John, K D; Nortier, F M; Stracener, D W; Heilbronn, L H; Mausner, L F; Mirzadeh, S</p> <p>2016-12-01</p> <p>Actinium-225 and 213 Bi have been used successfully in <span class="hlt">targeted</span> alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of 225 Ac. The high-energy proton spallation reaction on natural thorium metal <span class="hlt">targets</span> has been utilized to produce millicurie quantities of 225 Ac. The results of sixteen irradiation experiments of thorium metal at beam energies between 78 and 192MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while <span class="hlt">target</span> dissolution and processing was carried out at Oak Ridge National Laboratory (ORNL). Excitation functions for actinium and thorium isotopes, as well as for some of the fission <span class="hlt">products</span>, are presented. The cross sections for <span class="hlt">production</span> of 225 Ac range from 3.6 to 16.7mb in the incident proton energy range of 78-192MeV. Based on these data, <span class="hlt">production</span> of curie quantities of 225 Ac is possible by irradiating a 5.0gcm -2 232 Th <span class="hlt">target</span> for 10 days in either BNL or LANL proton irradiation facilities. Copyright © 2016 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3989190','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3989190"><span>Whole CMV Proteome Pattern Recognition Analysis after HSCT Identifies Unique Epitope <span class="hlt">Targets</span> Associated with the CMV Status</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Pérez-Bercoff, Lena; Valentini, Davide; Gaseitsiwe, Simani; Mahdavifar, Shahnaz; Schutkowski, Mike; Poiret, Thomas; Pérez-Bercoff, Åsa; Ljungman, Per; Maeurer, Markus J.</p> <p>2014-01-01</p> <p>Cytomegalovirus (CMV) infection represents a vital complication after Hematopoietic Stem Cell Transplantation (HSCT). We screened the entire CMV proteome to visualize the humoral <span class="hlt">target</span> epitope-focus <span class="hlt">profile</span> in serum after HSCT. IgG <span class="hlt">profiling</span> from four patient groups (donor and/or recipient +/− for CMV) was performed at 6, 12 and 24 months after HSCT using microarray slides containing 17174 of 15mer-peptides overlapping by 4 aa covering 214 proteins from CMV. Data were analyzed using maSigPro, PAM and the ‘exclusive recognition analysis (ERA)’ to identify unique CMV epitope responses for each patient group. The ‘exclusive recognition analysis’ of serum epitope patterns segregated best 12 months after HSCT for the D+/R+ group (versus D−/R−). Epitopes were derived from UL123 (IE1), UL99 (pp28), UL32 (pp150), this changed at 24 months to 2 strongly recognized peptides provided from UL123 and UL100. Strongly (IgG) recognized CMV <span class="hlt">targets</span> elicited also robust cytokine <span class="hlt">production</span> in T-cells from patients after HSCT defined by intracellular cytokine staining (IL-2, TNF, IFN and IL-17). High-content peptide microarrays allow epitope <span class="hlt">profiling</span> of entire viral proteomes; this approach can be useful to map relevant <span class="hlt">targets</span> for diagnostics and therapy in patients with well defined clinical endpoints. Peptide microarray analysis visualizes the breadth of B-cell immune reconstitution after HSCT and provides a useful tool to gauge immune reconstitution. PMID:24740411</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/1982IJBm...26..115I','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/1982IJBm...26..115I"><span>Environmental <span class="hlt">profile</span> and milk <span class="hlt">production</span> of Friesian-Zebu crosses in Nigerian Guinea Savanna</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Igono, M. O.; Aliu, Y. O.</p> <p>1982-06-01</p> <p>A 10-year meteorologic data have been collated to enable delienation of the environmental <span class="hlt">profile</span> of the Nigerian Guinea Savanna zone. Three distinct seasons are defined: a hot-dry season which lasts from March to April; a hot-humid season (May to October); and the harmattan season (November to February). The effects of these seasons on milk <span class="hlt">production</span> by half and three-quarter Friesian-Zebu crosses were evaluated during the first 100 days of lactation over a 2-year period. There were no significant differences in milk yield between the genotypes, but at heat intensities above 27‡C, the half cross gave more milk than the three-quarter cross. It is thus recommended that the half Friesian-Zebu cross be selected for milk <span class="hlt">production</span> in the Nigerian Guinea Savanna and that suitable husbandry and managerial adjustments such as provision of adequate clean water, shelter, good quality and silage and night grazing should be evolved to ameliorate the adverse effects of thermal stress and nutritional deficiency during the drier and hotter months of the year.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27249670','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27249670"><span>Napping-Ultra Flash <span class="hlt">Profile</span> as a Tool for Category Identification and Subsequent Model System Formulation of Caramel Corn <span class="hlt">Products</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mayhew, Emily; Schmidt, Shelly; Lee, Soo-Yeun</p> <p>2016-07-01</p> <p>In a novel approach to formulation, the flash descriptive <span class="hlt">profiling</span> technique Napping-Ultra Flash <span class="hlt">Profile</span> (Napping-UFP) was used to characterize a wide range of commercial caramel corn <span class="hlt">products</span>. The objectives were to identify <span class="hlt">product</span> categories, develop model systems based on <span class="hlt">product</span> categories, and correlate analytical parameters with sensory terms generated through the Napping-UFP exercise. In one 2 h session, 12 panelists participated in 4 Napping-UFP exercises, describing and grouping, on a 43×56 cm paper sheet, 12 commercial caramel corn samples by degree of similarity, globally and in terms of aroma-by-mouth, texture, and taste. The coordinates of each sample's placement on the paper sheet and descriptive terms generated by the panelists were used to conduct Multiple Factor Analysis (MFA) and hierarchical clustering of the samples. Strong trends in the clustering of samples across the 4 Napping-UFP exercises resulted in the determination of 3 overarching types of commercial caramel corn: "small-scale dark" (typified by burnt, rich caramel corn), "large-scale light" (typified by light and buttery caramel corn), and "large-scale dark" (typified by sweet and molasses-like caramel corn). Representative samples that best exemplified the properties of each category were used as guides in the formulation of 3 model systems that represent the spread of commercial caramel corn <span class="hlt">products</span>. Analytical testing of the commercial <span class="hlt">products</span>, including aw measurement, moisture content determination, and thermal characterization via differential scanning calorimetry, were conducted and results related to sensory descriptors using Spearman's correlation. © 2016 Institute of Food Technologists®</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24597626','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24597626"><span>Effect of HPMC - E15 LV premium polymer on release <span class="hlt">profile</span> and compression characteristics of chitosan/ pectin colon <span class="hlt">targeted</span> mesalamine matrix tablets and in vitro study on effect of pH impact on the drug release <span class="hlt">profile</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Newton, A M J; Lakshmanan, Prabakaran</p> <p>2014-04-01</p> <p>The study was designed to investigate the in vitro dissolution <span class="hlt">profile</span> and compression characteristics of colon <span class="hlt">targeted</span> matrix tablets prepared with HPMC E15 LV in combination with pectin and Chitosan. The matrix tablets were subjected to two dissolution models in various simulated fluids such as pH 1.2, 6, 6.8, 7.2, 5.5. The fluctuations in colonic pH conditions during IBD (inflammatory bowel disease) and the nature of less fluid content in the colon may limit the expected drug release in the polysaccharide-based matrices when used alone. The Hydrophilic hydroxyl propyl methylcellulose ether premium polymer (HPMC E15 LV) of low viscosity grade was used in the formulation design, which made an excellent modification in physical and compression characteristics of the granules. The release studies indicated that the prepared matrices could control the drug release until the dosage form reaches the colon and the addition HPMC E15 LV showed the desirable changes in the dissolution <span class="hlt">profile</span> by its hydrophilic nature since the colon is known for its less fluid content. The hydrophilic HPMC E15 LV allowed the colonic fluids to enter into the matrix and confirmed the drug release at the <span class="hlt">target</span> site from a poorly water soluble polymer such as Chitosan and also from water soluble Pectin. The dramatic changes occurred in the drug release <span class="hlt">profile</span> and physicochemical characteristics of the Pectin, Chitosan matrix tablets when a premium polymer HPMC E15 LV added in the formulation design in the optimized concentration. Various drug release mechanisms used for the examination of drug release characteristics. Drug release followed the combined mechanism of diffusion, erosion, swelling and polymer entanglement. In recent decade, IBD attracts many patents in novel treatment methods by using novel drug delivery systems.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19760020212','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19760020212"><span>Nominal <span class="hlt">Profile</span> Refinements Report: <span class="hlt">Target</span> in 120 Nautical Mile Circular Orbit</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p></p> <p>1974-01-01</p> <p>The compability of the nominal rendezvous sequence with low <span class="hlt">target</span> orbits is addressed. It was found that for <span class="hlt">targets</span> in low earth orbits certain modifications of the nominal sequence are required to achieve a feasible anytime liftoff capability, notably the use of elliptical phasing orbits and the allowance of up to two days for rendezvous under certain phasing conditions.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26856891','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26856891"><span>A mitochondrial-<span class="hlt">targeted</span> ubiquinone modulates muscle lipid <span class="hlt">profile</span> and improves mitochondrial respiration in obesogenic diet-fed rats.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Coudray, Charles; Fouret, Gilles; Lambert, Karen; Ferreri, Carla; Rieusset, Jennifer; Blachnio-Zabielska, Agnieszka; Lecomte, Jérôme; Ebabe Elle, Raymond; Badia, Eric; Murphy, Michael P; Feillet-Coudray, Christine</p> <p>2016-04-14</p> <p>The prevalence of the metabolic syndrome components including abdominal obesity, dyslipidaemia and insulin resistance is increasing in both developed and developing countries. It is generally accepted that the development of these features is preceded by, or accompanied with, impaired mitochondrial function. The present study was designed to analyse the effects of a mitochondrial-<span class="hlt">targeted</span> lipophilic ubiquinone (MitoQ) on muscle lipid <span class="hlt">profile</span> modulation and mitochondrial function in obesogenic diet-fed rats. For this purpose, twenty-four young male Sprague-Dawley rats were divided into three groups and fed one of the following diets: (1) control, (2) high fat (HF) and (3) HF+MitoQ. After 8 weeks, mitochondrial function markers and lipid metabolism/<span class="hlt">profile</span> modifications in skeletal muscle were measured. The HF diet was effective at inducing the major features of the metabolic syndrome--namely, obesity, hepatic enlargement and glucose intolerance. MitoQ intake prevented the increase in rat body weight, attenuated the increase in adipose tissue and liver weights and partially reversed glucose intolerance. At the muscle level, the HF diet induced moderate TAG accumulation associated with important modifications in the muscle phospholipid classes and in the fatty acid composition of total muscle lipid. These lipid modifications were accompanied with decrease in mitochondrial respiration. MitoQ intake corrected the lipid alterations and restored mitochondrial respiration. These results indicate that MitoQ protected obesogenic diet-fed rats from some features of the metabolic syndrome through its effects on muscle lipid metabolism and mitochondrial activity. These findings suggest that MitoQ is a promising candidate for future human trials in the metabolic syndrome prevention.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25435067','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25435067"><span>Isolation and screening of heterocystous cyanobacterial strains for biodiesel <span class="hlt">production</span> by evaluating the fuel properties from fatty acid methyl ester (FAME) <span class="hlt">profiles</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Anahas, Antonyraj Matharasi Perianaika; Muralitharan, Gangatharan</p> <p>2015-05-01</p> <p>This study reports on the biodiesel quality parameters of eleven heterocystous cyanobacterial strains based on fatty acid methyl esters (FAME) <span class="hlt">profiles</span>. The biomass <span class="hlt">productivity</span> of the tested cyanobacterial strains ranged from 9.33 to 20.67 mg L(-1) d(-1) while the lipid <span class="hlt">productivity</span> varied between 0.65 and 2.358 mg L(-1) d(-1). The highest biomass and lipid <span class="hlt">productivity</span> was observed for Calothrix sp. MBDU 013 but its lipid content is only 11.221 in terms of percent dry weight, next to the Anabaena sphaerica MBDU 105, whose lipid content is high. To identify the most competent isolate, a multi-criteria decision analyses (MCDA) was performed by including the key chemical and physical parameters of biodiesel calculated from FAME <span class="hlt">profiles</span>. The isolate A.sphaerica MBDU 105 is the most promising biodiesel feed stock based on decision vector through Preference Ranking Organisation Method for Enrichment Evaluation (PROMETHEE) and Graphical Analysis for Interactive Assistance (GAIA) analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_23 --> <div id="page_24" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="461"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1345946-bulk-production-evaluation-high-specific-activity-re-cancer-therapy-using-enriched-wo-targets-proton-beam','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1345946-bulk-production-evaluation-high-specific-activity-re-cancer-therapy-using-enriched-wo-targets-proton-beam"><span>Bulk <span class="hlt">production</span> and evaluation of high specific activity 186g Re for cancer therapy using enriched 186 WO 3 <span class="hlt">targets</span> in a proton beam</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Mastren, Tara; Radchenko, Valery; Bach, Hong T.; ...</p> <p>2017-06-01</p> <p>Rhenium-186 g (t 1/2 = 3.72 d) is a β– emitting isotope suitable for theranostic applications. Current <span class="hlt">production</span> methods rely on reactor <span class="hlt">production</span> by way of the reaction 185Re(n,γ) 186gRe, which results in low specific activities limiting its use for cancer therapy. <span class="hlt">Production</span> via charged particle activation of enriched 186W results in a 186gRe <span class="hlt">product</span> with a much specific activity, allowing it to be used more broadly for <span class="hlt">targeted</span> radiotherapy applications. Furthermore, this <span class="hlt">targets</span> the unmet clinical need for more efficient radiotherapeutics.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1345946','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/1345946"><span>Bulk <span class="hlt">production</span> and evaluation of high specific activity 186g Re for cancer therapy using enriched 186 WO 3 <span class="hlt">targets</span> in a proton beam</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Mastren, Tara; Radchenko, Valery; Bach, Hong T.</p> <p></p> <p>Rhenium-186 g (t 1/2 = 3.72 d) is a β– emitting isotope suitable for theranostic applications. Current <span class="hlt">production</span> methods rely on reactor <span class="hlt">production</span> by way of the reaction 185Re(n,γ) 186gRe, which results in low specific activities limiting its use for cancer therapy. <span class="hlt">Production</span> via charged particle activation of enriched 186W results in a 186gRe <span class="hlt">product</span> with a much specific activity, allowing it to be used more broadly for <span class="hlt">targeted</span> radiotherapy applications. Furthermore, this <span class="hlt">targets</span> the unmet clinical need for more efficient radiotherapeutics.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3608689','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3608689"><span>Boron Stress Responsive MicroRNAs and Their <span class="hlt">Targets</span> in Barley</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ozhuner, Esma; Eldem, Vahap; Ipek, Arif; Okay, Sezer; Sakcali, Serdal; Zhang, Baohong; Boke, Hatice; Unver, Turgay</p> <p>2013-01-01</p> <p>Boron stress is an environmental factor affecting plant development and <span class="hlt">production</span>. Recently, microRNAs (miRNAs) have been found to be involved in several plant processes such as growth regulation and stress responses. In this study, miRNAs associated with boron stress were identified and characterized in barley. miRNA <span class="hlt">profiles</span> were also comparatively analyzed between root and leave samples. A total of 31 known and 3 new miRNAs were identified in barley; 25 of them were found to respond to boron treatment. Several miRNAs were expressed in a tissue specific manner; for example, miR156d, miR171a, miR397, and miR444a were only detected in leaves. Additionally, a total of 934 barley transcripts were found to be specifically <span class="hlt">targeted</span> and degraded by miRNAs. In silico analysis of miRNA <span class="hlt">target</span> genes demonstrated that many miRNA <span class="hlt">targets</span> are conserved transcription factors such as Squamosa promoter-binding protein, Auxin response factor (ARF), and the MYB transcription factor family. A majority of these <span class="hlt">targets</span> were responsible for plant growth and response to environmental changes. We also propose that some of the miRNAs in barley such as miRNA408 might play critical roles against boron exposure. In conclusion, barley may use several pathways and cellular processes <span class="hlt">targeted</span> by miRNAs to cope with boron stress. PMID:23555702</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28964362','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28964362"><span>Metabolic <span class="hlt">profiling</span> of glucosinolates and their hydrolysis <span class="hlt">products</span> in a germplasm collection of Brassica rapa turnips.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Klopsch, Rebecca; Witzel, Katja; Börner, Andreas; Schreiner, Monika; Hanschen, Franziska S</p> <p>2017-10-01</p> <p>About 10% of the world's vegetable <span class="hlt">production</span> is generated from Brassicaceae, wherein Brassica rapa is a dominating species. There is growing evidence that glucosinolates (GLSs), main plant secondary metabolites in Brassicales, play an important role in promoting human health. Natural genetic diversity of B. rapa can be explored for vegetable improvement. We analyzed leaves and tubers of 16 B. rapa turnips for their GLS composition by UHPLC-DAD and the corresponding hydrolysis <span class="hlt">products</span> by GC-MS. Thirteen GLSs were identified, 8 aliphatic, 4 indolic and one aromatic. 3-Butenyl GLS was prevailing in both plant organs while in tubers 2-hydroxy-3-butenyl GLS and 2-phenylethyl GLS occurred in high amounts. A total of 24 GLS breakdown <span class="hlt">products</span> were detected in tubers and 16 in leaves. Epithionitriles were the main hydrolysis <span class="hlt">products</span> in both plant organs with 4,5-epithiopentanenitrile and 3-hydroxy-4,5-epithiopentanenitrile being the main compounds. When comparing leaves and tubers, an accumulation of GLSs and their breakdown <span class="hlt">products</span> was observed in tubers compared to leaves. Our analysis achieved the comprehensive <span class="hlt">profiling</span> of all GLS metabolites in a collection of B. rapa turnips, underlining the natural variation not only of intact GLS, but also of their breakdown <span class="hlt">products</span>. Copyright © 2017 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4718574','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4718574"><span>Diverse Molecular <span class="hlt">Targets</span> for Chalcones with Varied Bioactivities</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zhou, Bo; Xing, Chengguo</p> <p>2015-01-01</p> <p>Natural or synthetic chalcones with different substituents have revealed a variety of biological activities that may benefit human health. The underlying mechanisms of action, particularly with respect to the direct cellular <span class="hlt">targets</span> and the modes of interaction with the <span class="hlt">targets</span>, have not been rigorously characterized, which imposes challenges to structure-guided rational development of therapeutic agents or chemical probes with acceptable <span class="hlt">target</span>-selectivity <span class="hlt">profile</span>. This review summarizes literature evidence on chalcones’ direct molecular <span class="hlt">targets</span> in the context of their biological activities. PMID:26798565</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014NIMPA.740..208S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014NIMPA.740..208S"><span>Longitudinal gas-density profilometry for plasma-wakefield acceleration <span class="hlt">targets</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Schaper, Lucas; Goldberg, Lars; Kleinwächter, Tobias; Schwinkendorf, Jan-Patrick; Osterhoff, Jens</p> <p>2014-03-01</p> <p>Precise tailoring of plasma-density <span class="hlt">profiles</span> has been identified as one of the critical points in achieving stable and reproducible conditions in plasma wakefield accelerators. Here, the strict requirements of next generation plasma-wakefield concepts, such as hybrid-accelerators, with densities around 1017 cm-3 pose challenges to <span class="hlt">target</span> fabrication as well as to their reliable diagnosis. To mitigate these issues we combine <span class="hlt">target</span> simulation with fabrication and characterization. The resulting density <span class="hlt">profiles</span> in capillaries with gas jet and multiple in- and outlets are simulated with the fluid code OpenFOAM. Satisfactory simulation results then are followed by fabrication of the desired <span class="hlt">target</span> shapes with structures down to the 10 μm level. The detection of Raman scattered photons using lenses with large collection solid angle allows to measure the corresponding longitudinal density <span class="hlt">profiles</span> at different number densities and allows a detection sensitivity down to the low 1017 cm-3 density range at high spatial resolution. This offers the possibility to gain insight into steep density gradients as for example in gas jets and at the plasma-to-vacuum transition.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25613046','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25613046"><span>Peptide <span class="hlt">profiling</span> of bovine kefir reveals 236 unique peptides released from caseins during its <span class="hlt">production</span> by starter culture or kefir grains.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ebner, Jennifer; Aşçı Arslan, Ayşe; Fedorova, Maria; Hoffmann, Ralf; Küçükçetin, Ahmet; Pischetsrieder, Monika</p> <p>2015-03-18</p> <p>Kefir has a long tradition in human nutrition due to its presupposed health promoting effects. To investigate the potential contribution of bioactive peptides to the physiological effects of kefir, comprehensive analysis of the peptide <span class="hlt">profile</span> was performed by nano-ESI-LTQ-Orbitrap MS coupled to nano-ultrahigh-performance liquid chromatography. Thus, 257 peptides were identified, mainly released from β-casein, followed by αS1-, κ-, and αS2-casein. Most (236) peptides were uniquely detected in kefir, but not in raw milk indicating that the fermentation step does not only increase the proteolytic activity 1.7- to 2.4-fold compared to unfermented milk, but also alters the composition of the peptide fraction. The influence of the microflora was determined by analyzing kefir produced from traditional kefir grains or commercial starter culture. Kefir from starter culture featured 230 peptide sequences and showed a significantly, 1.4-fold higher proteolytic activity than kefir from kefir grains with 127 peptides. A match of 97 peptides in both varieties indicates the presence of a typical kefir peptide <span class="hlt">profile</span> that is not influenced by the individual composition of the microflora. Sixteen of the newly identified peptides were previously described as bioactive, including angiotensin-converting enzyme (ACE)-inhibitory, antimicrobial, immunomodulating, opioid, mineral binding, antioxidant, and antithrombotic effects. The present study describes a comprehensive peptide <span class="hlt">profile</span> of kefir comprising 257 sequences. The peptide list was used to identify 16 bioactive peptides with ACE-inhibitory, antioxidant, antithrombotic, mineral binding, antimicrobial, immunomodulating and opioid activity in kefir. Furthermore, it was shown that a majority of the kefir peptides were not endogenously present in the raw material milk, but were released from milk caseins by proteases of the microbiota and are therefore specific for the <span class="hlt">product</span>. Consequently, the proteolytic activity and the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28842834','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28842834"><span>Knowing where is different from knowing what: Distinct response time <span class="hlt">profiles</span> and accuracy effects for <span class="hlt">target</span> location, orientation, and color probability.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jabar, Syaheed B; Filipowicz, Alex; Anderson, Britt</p> <p>2017-11-01</p> <p>When a location is cued, <span class="hlt">targets</span> appearing at that location are detected more quickly. When a <span class="hlt">target</span> feature is cued, <span class="hlt">targets</span> bearing that feature are detected more quickly. These attentional cueing effects are only superficially similar. More detailed analyses find distinct temporal and accuracy <span class="hlt">profiles</span> for the two different types of cues. This pattern parallels work with probability manipulations, where both feature and spatial probability are known to affect detection accuracy and reaction times. However, little has been done by way of comparing these effects. Are probability manipulations on space and features distinct? In a series of five experiments, we systematically varied spatial probability and feature probability along two dimensions (orientation or color). In addition, we decomposed response times into initiation and movement components. <span class="hlt">Targets</span> appearing at the probable location were reported more quickly and more accurately regardless of whether the report was based on orientation or color. On the other hand, when either color probability or orientation probability was manipulated, response time and accuracy improvements were specific for that probable feature dimension. Decomposition of the response time benefits demonstrated that spatial probability only affected initiation times, whereas manipulations of feature probability affected both initiation and movement times. As detection was made more difficult, the two effects further diverged, with spatial probability disproportionally affecting initiation times and feature probability disproportionately affecting accuracy. In conclusion, all manipulations of probability, whether spatial or featural, affect detection. However, only feature probability affects perceptual precision, and precision effects are specific to the probable attribute.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25074701','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25074701"><span>Effects of pistachio by-<span class="hlt">products</span> on digestibility, milk <span class="hlt">production</span>, milk fatty acid <span class="hlt">profile</span> and blood metabolites in Saanen dairy goats.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sedighi-Vesagh, R; Naserian, A A; Ghaffari, M H; Petit, H V</p> <p>2015-08-01</p> <p>The objective of this study was to investigate the effects of pistachio by-<span class="hlt">products</span> (PBP) on nutrient digestibility, blood metabolites and milk fatty acid (FA) <span class="hlt">profile</span> in Saanen dairy goats. Nine multiparous lactating Saanen goats (on day 90 post-partum, 45 ± 2/kg BW) were randomly assigned to a 3 × 3 Latin square design with three treatment diets: 1) control diet (alfalfa hay based), 2) 32% PBP and 3) 32% PBP + polyethylene glycol (PEG-4000; 1 g/kg dry matter). Each period lasted 21 days, including 14 day for treatment adaptation and 7 day for data collection. Pistachio by-<span class="hlt">products</span> significantly decreased (p < 0.01) crude protein (CP) digestibility compared with the control diet (64.4% vs. 58.7%), but PEG addition did not differ for CP digestibility of goats fed 32% PBP + PEG and those fed the two other diets. The digestibility of NDF tended (p = 0.06) to decrease for goats fed PBP compared with those fed the control diet. Yields of milk and 4% fat-corrected milk were not affected by dietary treatments. Compared with the control diet, PBP supplementation appreciably changed the proportions of almost all the milk FA measured; the main effects were decreases (p < 0.01) in FA from 8:0 to 16:0 and increases (p < 0.01) proportions of cis-9, trans-11 18:2 and trans-11 18:1, monounsaturated FA, polyunsaturated FA and long-chain FA. The saturated FA, short-chain FA and medium-chain FA proportions were lower (p < 0.01) in goats fed the two PBP supplemented diet than in those fed the control diet and PEG addition led to intermediate proportions of saturated FA, unsaturated and monounsaturated FA. Inclusion of PBP in the diet decreased (p < 0.01) plasma concentrations of glucose and urea nitrogen compared with the control diet. It was concluded that PBP can be used as forage in the diet of dairy goats without interfering with milk yield. Inclusion of 32% PBP in the diet of dairy goats had beneficial effects on milk FA <span class="hlt">profile</span> but PEG addition to PBP</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4337502','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4337502"><span>Toward a magic or imaginary bullet? Ligands for drug <span class="hlt">targeting</span> to cancer cells: principles, hopes, and challenges</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Toporkiewicz, Monika; Meissner, Justyna; Matusewicz, Lucyna; Czogalla, Aleksander; Sikorski, Aleksander F</p> <p>2015-01-01</p> <p>There are many problems directly correlated with the systemic administration of drugs and how they reach their <span class="hlt">target</span> site. <span class="hlt">Targeting</span> promises to be a hopeful strategy as an improved means of drug delivery, with reduced toxicity and minimal adverse side effects. <span class="hlt">Targeting</span> exploits the high affinity of cell-surface-<span class="hlt">targeted</span> ligands, either directly or as carriers for a drug, for specific retention and uptake by the <span class="hlt">targeted</span> diseased cells. One of the most important parameters which should be taken into consideration in the selection of an appropriate ligand for <span class="hlt">targeting</span> is the binding affinity (KD). In this review we focus on the importance of binding affinities of monoclonal antibodies, antibody derivatives, peptides, aptamers, DARPins, and small <span class="hlt">targeting</span> molecules in the process of selection of the most suitable ligand for <span class="hlt">targeting</span> of nanoparticles. In order to provide a critical comparison between these various options, we have also assessed each technology format across a range of parameters such as molecular size, immunogenicity, costs of <span class="hlt">production</span>, clinical <span class="hlt">profiles</span>, and examples of the level of selectivity and toxicity of each. Wherever possible, we have also assessed how incorporating such a <span class="hlt">targeted</span> approach compares with, or is superior to, original treatments. PMID:25733832</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20607445','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20607445"><span>Evaluation of <span class="hlt">target</span> efficiencies for solid-liquid separation steps in biofuels <span class="hlt">production</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kochergin, Vadim; Miller, Keith</p> <p>2011-01-01</p> <p>Development of liquid biofuels has entered a new phase of large scale pilot demonstration. A number of plants that are in operation or under construction face the task of addressing the engineering challenges of creating a viable plant design, scaling up and optimizing various unit operations. It is well-known that separation technologies account for 50-70% of both capital and operating cost. Additionally, reduction of environmental impact creates technological challenges that increase project cost without adding to the bottom line. Different technologies vary in terms of selection of unit operations; however, solid-liquid separations are likely to be a major contributor to the overall project cost. Despite the differences in pretreatment approaches, similar challenges arise for solid-liquid separation unit operations. A typical process for ethanol <span class="hlt">production</span> from biomass includes several solid-liquid separation steps, depending on which particular stream is <span class="hlt">targeted</span> for downstream processing. The nature of biomass-derived materials makes it either difficult or uneconomical to accomplish complete separation in a single step. Therefore, setting realistic efficiency <span class="hlt">targets</span> for solid-liquid separations is an important task that influences overall process recovery and economics. Experimental data will be presented showing typical characteristics for pretreated cane bagasse at various stages of processing into cellulosic ethanol. Results of generic material balance calculations will be presented to illustrate the influence of separation <span class="hlt">target</span> efficiencies on overall process recoveries and characteristics of waste streams.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26823078','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26823078"><span>Prioritization of anti-malarial hits from nature: chemo-informatic <span class="hlt">profiling</span> of natural <span class="hlt">products</span> with in vitro antiplasmodial activities and currently registered anti-malarial drugs.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Egieyeh, Samuel Ayodele; Syce, James; Malan, Sarel F; Christoffels, Alan</p> <p>2016-01-29</p> <p>A large number of natural <span class="hlt">products</span> have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural <span class="hlt">products</span> with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic <span class="hlt">profiling</span> of these natural <span class="hlt">products</span> were conducted and compared to currently registered anti-malarial drugs (CRAD). Natural <span class="hlt">products</span> with in vitro antiplasmodial activities (NAA) were compiled from various sources. These natural <span class="hlt">products</span> were sub-divided into four groups based on inhibitory concentration (IC50). Key molecular descriptors and physicochemical properties were computed for these compounds and analysis of variance used to assess statistical significance amongst the sets of compounds. Molecular similarity analysis, estimation of drug-likeness, in silico pharmacokinetic <span class="hlt">profiling</span>, and exploration of structure-activity landscape were also carried out on these sets of compounds. A total of 1040 natural <span class="hlt">products</span> were selected and a total of 13 molecular descriptors were analysed. Significant differences were observed among the sub-groups of NAA and CRAD for at least 11 of the molecular descriptors, including number of hydrogen bond donors and acceptors, molecular weight, polar and hydrophobic surface areas, chiral centres, oxygen and nitrogen atoms, and shape index. The remaining molecular descriptors, including clogP, number of rotatable bonds and number of aromatic rings, did not show any significant difference when comparing the two compound sets. Molecular similarity and chemical space analysis identified natural <span class="hlt">products</span> that were structurally diverse from CRAD. Prediction of the pharmacokinetic properties and drug-likeness of these natural <span class="hlt">products</span> identified over 50% with desirable drug-like properties. Nearly 70% of all natural <span class="hlt">products</span> were identified as potentially promiscuous compounds. Structure-activity landscape analysis highlighted compound pairs that</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29220658','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29220658"><span>Multi-omic Mitoprotease <span class="hlt">Profiling</span> Defines a Role for Oct1p in Coenzyme Q <span class="hlt">Production</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Veling, Mike T; Reidenbach, Andrew G; Freiberger, Elyse C; Kwiecien, Nicholas W; Hutchins, Paul D; Drahnak, Michael J; Jochem, Adam; Ulbrich, Arne; Rush, Matthew J P; Russell, Jason D; Coon, Joshua J; Pagliarini, David J</p> <p>2017-12-07</p> <p>Mitoproteases are becoming recognized as key regulators of diverse mitochondrial functions, although their direct substrates are often difficult to discern. Through multi-omic <span class="hlt">profiling</span> of diverse Saccharomyces cerevisiae mitoprotease deletion strains, we predicted numerous associations between mitoproteases and distinct mitochondrial processes. These include a strong association between the mitochondrial matrix octapeptidase Oct1p and coenzyme Q (CoQ) biosynthesis-a pathway essential for mitochondrial respiration. Through Edman sequencing and in vitro and in vivo biochemistry, we demonstrated that Oct1p directly processes the N terminus of the CoQ-related methyltransferase, Coq5p, which markedly improves its stability. A single mutation to the Oct1p recognition motif in Coq5p disrupted its processing in vivo, leading to CoQ deficiency and respiratory incompetence. This work defines the Oct1p processing of Coq5p as an essential post-translational event for proper CoQ <span class="hlt">production</span>. Additionally, our data visualization tool enables efficient exploration of mitoprotease <span class="hlt">profiles</span> that can serve as the basis for future mechanistic investigations. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1171945','SCIGOV-DOEDE'); return false;" href="https://www.osti.gov/servlets/purl/1171945"><span>Tropical Cloud Properties and Radiative Heating <span class="hlt">Profiles</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/dataexplorer">DOE Data Explorer</a></p> <p>Mather, James</p> <p>2008-01-15</p> <p>We have generated a suite of <span class="hlt">products</span> that includes merged soundings, cloud microphysics, and radiative fluxes and heating <span class="hlt">profiles</span>. The cloud microphysics is strongly based on the ARM Microbase value added <span class="hlt">product</span> (Miller et al., 2003). We have made a few changes to the microbase parameterizations to address issues we observed in our initial analysis of the tropical data. The merged sounding <span class="hlt">product</span> is not directly related to the <span class="hlt">product</span> developed by ARM but is similar in that it uses the microwave radiometer to scale the radiosonde column water vapor. The radiative fluxes also differ from the ARM BBHRP (Broadband Heating Rate <span class="hlt">Profile</span>) <span class="hlt">product</span> in terms of the radiative transfer model and the sampling interval.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20691087','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20691087"><span>Chemical-genetic <span class="hlt">profile</span> analysis of five inhibitory compounds in yeast.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Alamgir, Md; Erukova, Veronika; Jessulat, Matthew; Azizi, Ali; Golshani, Ashkan</p> <p>2010-08-06</p> <p>Chemical-genetic <span class="hlt">profiling</span> of inhibitory compounds can lead to identification of their modes of action. These <span class="hlt">profiles</span> can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s). Colony size reduction was used to investigate the chemical-genetic <span class="hlt">profile</span> of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds <span class="hlt">target</span> the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall <span class="hlt">profiles</span> of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these <span class="hlt">profiles</span>. Further investigations were carried out to assess the activity of three <span class="hlt">profiled</span> genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays. Chemical-genetic <span class="hlt">profiles</span> provide insight into the molecular mechanism(s) of the examined compounds by elucidating their potential primary and secondary cellular <span class="hlt">target</span> sites. Our follow-up investigations into the activity of three <span class="hlt">profiled</span> genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5408231','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5408231"><span>Establishing the Secondary Metabolite <span class="hlt">Profile</span> of the Marine Fungus: Tolypocladium geodes sp. MF458 and Subsequent Optimisation of Bioactive Secondary Metabolite <span class="hlt">Production</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kebede, Bethlehem; Wrigley, Stephen K.; Prashar, Anjali; Rahlff, Janina; Wolf, Markus; Reinshagen, Jeanette; Gribbon, Philip; Imhoff, Johannes F.; Silber, Johanna; Labes, Antje; Ellinger, Bernhard</p> <p>2017-01-01</p> <p>As part of an international research project, the marine fungal strain collection of the Helmholtz Centre for Ocean Research (GEOMAR) research centre was analysed for secondary metabolite <span class="hlt">profiles</span> associated with anticancer activity. Strain MF458 was identified as Tolypocladium geodes, by internal transcribed spacer region (ITS) sequence similarity and its natural <span class="hlt">product</span> <span class="hlt">production</span> <span class="hlt">profile</span>. By using five different media in two conditions and two time points, we were able to identify eight natural <span class="hlt">products</span> produced by MF458. As well as cyclosporin A (1), efrapeptin D (2), pyridoxatin (3), terricolin A (4), malettinins B and E (5 and 6), and tolypocladenols A1/A2 (8), we identified a new secondary metabolite which we termed tolypocladenol C (7). All compounds were analysed for their anticancer potential using a selection of the NCI60 cancer cell line panel, with malettinins B and E (5 and 6) being the most promising candidates. In order to obtain sufficient quantities of these compounds to start preclinical development, their <span class="hlt">production</span> was transferred from a static flask culture to a stirred tank reactor, and fermentation medium development resulted in a nearly eight-fold increase in compound <span class="hlt">production</span>. The strain MF458 is therefore a producer of a number of interesting and new secondary metabolites and their <span class="hlt">production</span> levels can be readily improved to achieve higher yields. PMID:28333084</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23110515','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23110515"><span>Dengue vector management using insecticide treated materials and <span class="hlt">targeted</span> interventions on <span class="hlt">productive</span> breeding-sites in Guatemala.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rizzo, Nidia; Gramajo, Rodrigo; Escobar, Maria Cabrera; Arana, Byron; Kroeger, Axel; Manrique-Saide, Pablo; Petzold, Max</p> <p>2012-10-30</p> <p>In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combination with appropriate <span class="hlt">targeted</span> interventions of the most <span class="hlt">productive</span> vector breeding-sites. The study was conducted as a cluster randomized community trial using "reduction of the vector population" as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods) and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal <span class="hlt">productivity</span>, Stegomyia indices) at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material) and 6 weeks after the second intervention (combination of treated materials and other suitable interventions <span class="hlt">targeting</span> <span class="hlt">productive</span> breeding-sites i.e larviciding with Temephos, elimination etc.). The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected. At baseline (during the dry season) a variety of <span class="hlt">productive</span> container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae). After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed) in 970 study households, tropical rains occurred in the area and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3533994','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3533994"><span>Dengue vector management using insecticide treated materials and <span class="hlt">targeted</span> interventions on <span class="hlt">productive</span> breeding-sites in Guatemala</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2012-01-01</p> <p>Background In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combination with appropriate <span class="hlt">targeted</span> interventions of the most <span class="hlt">productive</span> vector breeding-sites. Methods The study was conducted as a cluster randomized community trial using “reduction of the vector population” as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods) and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal <span class="hlt">productivity</span>, Stegomyia indices) at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material) and 6 weeks after the second intervention (combination of treated materials and other suitable interventions <span class="hlt">targeting</span> <span class="hlt">productive</span> breeding-sites i.e larviciding with Temephos, elimination etc.). The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected. Results At baseline (during the dry season) a variety of <span class="hlt">productive</span> container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae). After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed) in 970 study households, tropical</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018AMT....11...17H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018AMT....11...17H"><span>Validation of 10-year SAO OMI ozone <span class="hlt">profile</span> (PROFOZ) <span class="hlt">product</span> using Aura MLS measurements</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Huang, Guanyu; Liu, Xiong; Chance, Kelly; Yang, Kai; Cai, Zhaonan</p> <p>2018-01-01</p> <p>We validate the Ozone Monitoring Instrument (OMI) ozone <span class="hlt">profile</span> (PROFOZ v0.9.3) <span class="hlt">product</span> including ozone <span class="hlt">profiles</span> between 0.22 and 261 hPa and stratospheric ozone columns (SOCs) down to 100, 215, and 261 hPa from October 2004 through December 2014 retrieved by the Smithsonian Astrophysical Observatory (SAO) algorithm against the latest Microwave Limb Sound (MLS) v4.2x data. We also evaluate the effects of OMI row anomaly (RA) on the retrieval by dividing the data set into before and after the occurrence of serious RA, i.e., pre-RA (2004-2008) and post-RA (2009-2014). During the pre-RA period, OMI ozone <span class="hlt">profiles</span> agree very well with MLS data. After applying OMI averaging kernels to MLS data, the global mean biases (MBs) are within 3 % between 0.22 and 100 hPa, negative biases are within 3-9 % for lower layers, and the standard deviations (SDs) are 3.5-5 % from 1 to 40 hPa, 6-10 % for upper layers, and 5-20 % for lower layers. OMI shows biases dependent on latitude and solar zenith angle (SZA), but MBs and SDs are mostly within 10 % except for low and high altitudes of high latitudes and SZAs. Compared to the retrievals during the pre-RA period, OMI retrievals during the post-RA period degrade slightly between 5 and 261 hPa with MBs and SDs typically larger by 2-5 %, and degrade much more for pressure less than ˜ 5 hPa, with larger MBs by up to 8 % and SDs by up to 15 %, where the MBs are larger by 10-15 % south of 40° N due to the blockage effect of RA and smaller by 15-20 % north of 40° N due to the solar contamination effect of RA. The much worse comparisons at high altitudes indicate the UV1 channel of pixels that are not flagged as RA is still affected by the RA. During the pre-RA period, OMI SOCs show very good agreement with MLS data with global mean MBs within 0.6 % and SDs of 1.9 % for SOCs down to 215 and 261 hPa and of 2.30 % for SOC down to 100 hPa. Despite clearly worse ozone <span class="hlt">profile</span> comparisons during the post-RA period, OMI SOCs only slightly degrade</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29617986','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29617986"><span>Fermentation <span class="hlt">products</span> in the cystic fibrosis airways induce aggregation and dormancy-associated expression <span class="hlt">profiles</span> in a CF clinical isolate of Pseudomonas aeruginosa.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Phan, Joann; Gallagher, Tara; Oliver, Andrew; England, Whitney E; Whiteson, Katrine</p> <p>2018-05-01</p> <p>Pseudomonas aeruginosa is a well-known dominant opportunistic pathogen in cystic fibrosis (CF) with a wide range of metabolic capacities. However, P. aeruginosa does not colonize the airways alone, and benefits from the metabolic <span class="hlt">products</span> of neighboring cells-especially volatile molecules that can travel between different parts of the airways easily. Here, we present a study that investigates the metabolic, gene expression <span class="hlt">profiles</span> and phenotypic responses of a P. aeruginosa clinical isolate to fermentation <span class="hlt">products</span> lactic acid and 2,3-butanediol, metabolites that are produced by facultative anaerobic members of the CF polymicrobial community and potential biomarkers of disease progression. Although previous studies have successfully investigated the metabolic and transcriptional <span class="hlt">profiles</span> of P. aeruginosa, most have used common lab reference strains that may differ in important ways from clinical isolates. Using transcriptomics and metabolomics with gas chromatography time of flight mass spectrometry, we observe that fermentation <span class="hlt">products</span> induce pyocyanin <span class="hlt">production</span> along with the expression of genes involved in P. aeruginosa amino acid utilization, dormancy and aggregative or biofilm modes of growth. These findings have important implications for how interactions within the diverse CF microbial community influence microbial physiology, with potential clinical consequences.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_24 --> <div id="page_25" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="481"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5928460','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5928460"><span>Fermentation <span class="hlt">products</span> in the cystic fibrosis airways induce aggregation and dormancy-associated expression <span class="hlt">profiles</span> in a CF clinical isolate of Pseudomonas aeruginosa</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Phan, Joann; Gallagher, Tara; Oliver, Andrew; England, Whitney E; Whiteson, Katrine</p> <p>2018-01-01</p> <p>Abstract Pseudomonas aeruginosa is a well-known dominant opportunistic pathogen in cystic fibrosis (CF) with a wide range of metabolic capacities. However, P. aeruginosa does not colonize the airways alone, and benefits from the metabolic <span class="hlt">products</span> of neighboring cells—especially volatile molecules that can travel between different parts of the airways easily. Here, we present a study that investigates the metabolic, gene expression <span class="hlt">profiles</span> and phenotypic responses of a P. aeruginosa clinical isolate to fermentation <span class="hlt">products</span> lactic acid and 2,3-butanediol, metabolites that are produced by facultative anaerobic members of the CF polymicrobial community and potential biomarkers of disease progression. Although previous studies have successfully investigated the metabolic and transcriptional <span class="hlt">profiles</span> of P. aeruginosa, most have used common lab reference strains that may differ in important ways from clinical isolates. Using transcriptomics and metabolomics with gas chromatography time of flight mass spectrometry, we observe that fermentation <span class="hlt">products</span> induce pyocyanin <span class="hlt">production</span> along with the expression of genes involved in P. aeruginosa amino acid utilization, dormancy and aggregative or biofilm modes of growth. These findings have important implications for how interactions within the diverse CF microbial community influence microbial physiology, with potential clinical consequences. PMID:29617986</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/7323028','DOE-PATENT-XML'); return false;" href="https://www.osti.gov/biblio/7323028"><span>Multiple shell fusion <span class="hlt">targets</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/doepatents">DOEpatents</a></p> <p>Lindl, J.D.; Bangerter, R.O.</p> <p>1975-10-31</p> <p>Multiple shell fusion <span class="hlt">targets</span> for use with electron beam and ion beam implosion systems are described. The multiple shell <span class="hlt">targets</span> are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The <span class="hlt">targets</span> use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power <span class="hlt">profile</span> and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell <span class="hlt">target</span> can be accomplished.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017AMT....10.1511L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017AMT....10.1511L"><span>Merged ozone <span class="hlt">profiles</span> from four MIPAS processors</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Laeng, Alexandra; von Clarmann, Thomas; Stiller, Gabriele; Dinelli, Bianca Maria; Dudhia, Anu; Raspollini, Piera; Glatthor, Norbert; Grabowski, Udo; Sofieva, Viktoria; Froidevaux, Lucien; Walker, Kaley A.; Zehner, Claus</p> <p>2017-04-01</p> <p>The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) was an infrared (IR) limb emission spectrometer on the Envisat platform. Currently, there are four MIPAS ozone data <span class="hlt">products</span>, including the operational Level-2 ozone <span class="hlt">product</span> processed at ESA, with the scientific prototype processor being operated at IFAC Florence, and three independent research <span class="hlt">products</span> developed by the Istituto di Fisica Applicata Nello Carrara (ISAC-CNR)/University of Bologna, Oxford University, and the Karlsruhe Institute of Technology-Institute of Meteorology and Climate Research/Instituto de Astrofísica de Andalucía (KIT-IMK/IAA). Here we present a dataset of ozone vertical <span class="hlt">profiles</span> obtained by merging ozone retrievals from four independent Level-2 MIPAS processors. We also discuss the advantages and the shortcomings of this merged <span class="hlt">product</span>. As the four processors retrieve ozone in different parts of the spectra (microwindows), the source measurements can be considered as nearly independent with respect to measurement noise. Hence, the information content of the merged <span class="hlt">product</span> is greater and the precision is better than those of any parent (source) dataset. The merging is performed on a <span class="hlt">profile</span> per <span class="hlt">profile</span> basis. Parent ozone <span class="hlt">profiles</span> are weighted based on the corresponding error covariance matrices; the error correlations between different <span class="hlt">profile</span> levels are taken into account. The intercorrelations between the processors' errors are evaluated statistically and are used in the merging. The height range of the merged <span class="hlt">product</span> is 20-55 km, and error covariance matrices are provided as diagnostics. Validation of the merged dataset is performed by comparison with ozone <span class="hlt">profiles</span> from ACE-FTS (Atmospheric Chemistry Experiment-Fourier Transform Spectrometer) and MLS (Microwave Limb Sounder). Even though the merging is not supposed to remove the biases of the parent datasets, around the ozone volume mixing ratio peak the merged <span class="hlt">product</span> is found to have a smaller (up to 0.1 ppmv</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018PPN....49...75P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018PPN....49...75P"><span><span class="hlt">Target</span> development for 67Cu, 82Sr radionuclide <span class="hlt">production</span> at the RIC-80 facility</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Panteleev, V. N.; Barzakh, A. E.; Batist, L. Kh.; Fedorov, D. V.; Ivanov, V. S.; Krotov, S. A.; Molkanov, P. L.; Moroz, F. V.; Orlov, S. Yu.; Volkov, Yu. M.</p> <p>2018-01-01</p> <p>A high-current cyclotron C-80 capable of producing 40-80 MeV proton beams with a current of up to 200 μA has been constructed and commissioned at PNPI (Petersburg Nuclear Physics Institute). One of the main goals of cyclotron C-80 is the <span class="hlt">production</span> of a wide spectrum of medical radionuclides for diagnostics and therapy. To date, the project development of a radioisotope facility RIC-80 (radioisotopes at cyclotron C-80) has been completed. The feature of the project is the use of a mass-separator combined with the ion-<span class="hlt">target</span> device for obtaining ion beams of radioisotopes with a high purity of separation that is especially important for medical applications. The first results of a new high-temperature method for extracting 82Sr and 67Cu radioisotopes from irradiated <span class="hlt">targets</span> have been presented.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014APS..DNP.MH003K','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014APS..DNP.MH003K"><span><span class="hlt">Production</span> of 64Cu and 67Cu radiopharmaceuticals using zinc <span class="hlt">target</span> irradiated with accelerator neutrons</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Kawabata, Masako; Hashimoto, Kazuyuki; Saeki, Hideya; Sato, Nozomi; Motoishi, Shoji; Nagai, Yasuki</p> <p>2014-09-01</p> <p>Copper radioisotopes have gained a lot of attention in radiopharmaceuticals owing to their unique decay characteristics. The longest half-life β emitter, 67Cu, is thought to be suitable for <span class="hlt">targeted</span> radio-immunotherapy. Adequate <span class="hlt">production</span> of 67Cu to meet the demands of clinical studies has not been fully established. Another attractive copper isotope, 64Cu has possible applications as a diagnostic imaging tracer combined with a therapeutic effect. This work proposes a <span class="hlt">production</span> method using accelerator neutrons in which two copper radioisotopes can be produced: 1) 68Zn(n,x)67Cu and 2) 64Zn(n,p)64Cu using ~14 MeV neutrons generated by natC(d, n) reaction, both from natural or enriched zinc oxides. The generated 64,67Cu were separated from the <span class="hlt">target</span> zinc oxide using a chelating and an anion exchange columns and were labelled with two widely studied chelators where the labelling efficiency was found to be acceptably good. The major advantage of this method is that a significant amount of 64,67Cu with a very few impurity radionuclides are produced which also makes the separation procedure simple. Provided an accelerator supplying an Ed = ~ 40 MeV, a wide application of 64,67Cu based drugs in nuclear medicine is feasible in the near future. We will present the characteristics of this <span class="hlt">production</span> method using accelerator neutrons including the chemical separation processes.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://proteomics.cancer.gov/news_and_announcements/reminder-nci-requests-cancer-targets-monoclonal-antibody-production-and','NCI'); return false;" href="https://proteomics.cancer.gov/news_and_announcements/reminder-nci-requests-cancer-targets-monoclonal-antibody-production-and"><span>Reminder: NCI Requests Cancer <span class="hlt">Targets</span> for Monoclonal Antibody <span class="hlt">Production</span> and Characterization | Office of Cancer Clinical Proteomics Research</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>In an effort to improve rigor and reproducibility, the National Cancer Institute (NCI) Antibody Characterization Program requests cancer-related protein <span class="hlt">targets</span> for monoclonal antibody <span class="hlt">production</span> and distribution to the scientific community. The program from The Office of Cancer Clinical Proteomics Research provides well-characterized</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018AIPC.1962c0011M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018AIPC.1962c0011M"><span><span class="hlt">Production</span> of 9Be <span class="hlt">targets</span> for nuclear physics experiments</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Marín-Lámbarri, D. J.; Kheswa, N. Y.</p> <p>2018-05-01</p> <p>Self-supporting beryllium (9Be) <span class="hlt">targets</span> were produced by mechanical rolling method in which a double pack technique was implemented. <span class="hlt">Targets</span> were used for the investigation of the low-lying excitation energy region in 9B through the 9Be(3He,t)9B reaction at the K600 spectrometer, at iThemba LABS facility. Beryllium is a semi-metal in nature and this makes it hard to deform by rolling or vacuum evaporate as a self-supporting <span class="hlt">target</span>. Therefore heat treatment was needed to avoid brittleness and breakage of the material during rolling process. A description is given on how beryllium <span class="hlt">targets</span> were manufactured.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25379806','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25379806"><span>Development, optimization and characterization of glycyrrhetinic acid-chitosan nanoparticles of atorvastatin for liver <span class="hlt">targeting</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rohilla, Raman; Garg, Tarun; Bariwal, Jitender; Goyal, Amit K; Rath, Goutam</p> <p>2016-09-01</p> <p>Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-<span class="hlt">targeted</span> carrier for drug delivery. In this study, nanoparticles were prepared by ionic gelation process, and glycyrrhetinic acid act as the <span class="hlt">targeting</span> ligand. The structure of the <span class="hlt">product</span> was confirmed by IR and NMR techniques. The main aim of this study was to deliver atorvastatin directly to the liver by using same conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high dose. Characterization of the developed formulation was performed by differential scanning calorimetry, particle size measurements and cellular uptake studies. Release <span class="hlt">profile</span>, pharmacokinetics studies and organ distribution studies showed that developed formulation shows a relative higher liver uptake. The optimized formulation showed increased plasma concentration than the CTS nanoparticles as well as plain drug and the accumulation in the liver was nearly 2.59 times more than that of obtained with the CTS nanoparticles. Pharmaceutical and pharmacological indicators suggested that the proposed strategy can be successfully utilized for liver <span class="hlt">targeting</span> of therapeutics.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4521122','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4521122"><span>Cohort <span class="hlt">Profile</span>: The Applied Research Group for Kids (<span class="hlt">TARGet</span> Kids!)</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Carsley, Sarah; Borkhoff, Cornelia M; Maguire, Jonathon L; Birken, Catherine S; Khovratovich, Marina; McCrindle, Brian; Macarthur, Colin; Parkin, Patricia C</p> <p>2015-01-01</p> <p>The Applied Research Group for Kids (<span class="hlt">TARGet</span> Kids!) is an ongoing open longitudinal cohort study enrolling healthy children (from birth to 5 years of age) and following them into adolescence. The aim of the <span class="hlt">TARGet</span> Kids! cohort is to link early life exposures to health problems including obesity, micronutrient deficiencies and developmental problems. The overarching goal is to improve the health of Canadians by optimizing growth and developmental trajectories through preventive interventions in early childhood. <span class="hlt">TARGet</span> Kids!, the only child health research network embedded in primary care practices in Canada, leverages the unique relationship between children and families and their trusted primary care practitioners, with whom they have at least seven health supervision visits in the first 5 years of life. Children are enrolled during regularly scheduled well-child visits. To date, we have enrolled 5062 children. In addition to demographic information, we collect physical measurements (e.g. height, weight), lifestyle factors (nutrition, screen time and physical activity), child behaviour and developmental screening and a blood sample (providing measures of cardiometabolic, iron and vitamin D status, and trace metals). All data are collected at each well-child visit: twice a year until age 2 and every year until age 10. Information can be found at: http://www.targetkids.ca/contact-us/. PMID:24982016</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017E%26ES...82a2061X','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017E%26ES...82a2061X"><span>Chemical water shutoff <span class="hlt">profile</span> research status and development trends</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Xu, L. T.</p> <p>2017-08-01</p> <p>Excess water <span class="hlt">production</span> is now a common problem encountered in almost every water flooding mature oilfield. The exploitation of oil field is faced with great challenge because of the decrease of oil field <span class="hlt">production</span>. For the development of high water cut rare the status quo chemical water shutoff <span class="hlt">profile</span> control technology is an important solution to solve this problem. Oilfield chemical water shutoff has important application prospects. This paper analyzes the water shutoff <span class="hlt">profile</span> control and water shutoff <span class="hlt">profile</span> control agent currently oilfield applications, moreover the use and development of blocking agent <span class="hlt">profile</span> technology is to improve reservoir recovery and propose solutions. With the constant increase in water cut, <span class="hlt">profile</span> technology should be simple, efficient, practical and <span class="hlt">profile</span> control agent of development should be economic, environmental, and long period</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015ISPAr.XL7.1475S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015ISPAr.XL7.1475S"><span>Technology <span class="hlt">targeting</span> for sustainable intensification of crop <span class="hlt">production</span> in the Delta region of Bangladesh</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Schulthess, U.; Krupnik, T. J.; Ahmed, Z. U.; McDonald, A. J.</p> <p>2015-04-01</p> <p>Remote sensing data are nowadays being acquired within short intervals and made available at a low cost or for free. This opens up opportunities for new remote sensing applications, such as the characterization of entire regions to identify most suitable areas for technology <span class="hlt">targeting</span>. Increasing population growth and changing dietary habits in South Asia call for higher cereal <span class="hlt">production</span> to ensure future food security. In the Delta area of Bangladesh, surface water is considered to be available in quantities large enough to support intensification by adding an irrigated dry season crop. Fuel-efficient, low lift axial flow pumps have shown to be suitable to carry water to fields that are within a buffer of four hundred meters of the rivers. However, information on how and where to <span class="hlt">target</span> surface water irrigation efforts is currently lacking. We describe the opportunities and constraints encountered in developing a procedure to identify cropland for which axial flow pumps could be successfully deployed upon in a 43'000 km2 area. First, we isolated cropland and waterways using Landsat 5 and 7 scenes using image segmentation followed by classification with the random forest algorithm. Based on Landsat 7 and 8 scenes, we extracted maximum dry season enhanced vegetation index (EVI) values, which we classified into fallow, low-, and high-intensity cropland for the last three years. Last, we investigated the potential for surface water irrigation on fallow and low-intensity land by applying a cropping risk matrix to address the twin threats of soil and water salinity. Our analysis indicates that there are at least 20,000 ha of fallow land under the low-risk category, while more than 100,000 ha of low-intensity cropland can be brought into intensified <span class="hlt">production</span>. This information will aid in technology <span class="hlt">targeting</span> for the efficient deployment of surface water irrigation as a tool for intensification.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/1995OptCo.117..485L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/1995OptCo.117..485L"><span><span class="hlt">Production</span> of high energy, uniform focal <span class="hlt">profiles</span> with the Nike laser</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Lehecka, T.; Lehmberg, R. H.; Deniz, A. V.; Gerber, K. A.; Obenschain, S. P.; Pawley, C. J.; Pronko, M. S.; Sullivan, C. A.</p> <p>1995-02-01</p> <p>Nike, a KrF laser facility at the Naval Research Laboratory, is designed to produce high intensity, ultra-uniform focal <span class="hlt">profiles</span> for experiments relating to direct drive inertial confinement fusion. We present measurements of focal <span class="hlt">profiles</span> through the next-to-last amplifier, a 20 × 20 cm 2 aperture electron beam pumped amplifier capable of producing more than 120 J of output in a 120 ns pulse. Using echelon free induced spatial incoherence beam smoothing this system has produced focal <span class="hlt">profiles</span> with less than 2% tilt and curvature and less than 2% rms variation from a flat top distribution.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20102203','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20102203"><span>Identification of the botanical origin of pine nuts found in food <span class="hlt">products</span> by gas-liquid chromatography analysis of fatty acid <span class="hlt">profile</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Destaillats, Frédéric; Cruz-Hernandez, Cristina; Giuffrida, Francesca; Dionisi, Fabiola</p> <p>2010-02-24</p> <p>Pine nuts are traditionally used in various part of the world for the preparation of desserts or sauces or in salads. Local <span class="hlt">production</span> is not sufficient to cope with the high demand of pine nuts around the world, and countries such as China or Pakistan are exporting much of their <span class="hlt">production</span> to Western countries. Almost all the nuts that are traditionally consumed belong to the Pinus genus, but over the past years, the number of consumer complaints following consumption of commercial pine nuts increased. Some consumers experienced taste disturbance lasting for up to two weeks after consumption. Food safety agencies raised some concerns regarding pine nuts imported from Asia and their association with taste disturbance. However, even though a formal association has not been found to date, the Pinus genus comprises species that are not classified as edible and could be eventually used to adulterate edible species. Pinus spp. seed lipids are known to contain very specific polyunsaturated fatty acids know as Delta5-olefinic acids. Seed fatty acid <span class="hlt">profile</span> of conifers had been used in the past as a taxonomic marker, and in the present study to identify the botanical origin of pine nut in nine commercial <span class="hlt">products</span>. Fast gas-liquid chromatography (GLC) was used to resolve the complete fatty acid <span class="hlt">profile</span> of Pinus spp. samples in less than 5 min. A diagnostic index based on the relative levels of the main fatty acids including distinctive Delta5-olefinic acids was used to identify botanical origins. Results revealed the occurrence of the following Pinus spp. in commercial <span class="hlt">products</span>: P. pinea, P. koraiensis, P. gerardiana, P. armandii and P. massoniana. The later two species, known as Chinese white pine and Chinese red pine, are only cultivated in China and are not listed as common source of edible pine nuts by the Food and Agriculture Organization (FAO). The present study shows that the botanical origin of pine nuts can be identified in <span class="hlt">products</span> based on the fatty acid <span class="hlt">profile</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22313117','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22313117"><span>Protein <span class="hlt">profiling</span> in potato (Solanum tuberosum L.) leaf tissues by differential centrifugation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lim, Sanghyun; Chisholm, Kenneth; Coffin, Robert H; Peters, Rick D; Al-Mughrabi, Khalil I; Wang-Pruski, Gefu; Pinto, Devanand M</p> <p>2012-04-06</p> <p>Foliar diseases, such as late blight, result in serious threats to potato <span class="hlt">production</span>. As such, potato leaf tissue becomes an important substrate to study biological processes, such as plant defense responses to infection. Nonetheless, the potato leaf proteome remains poorly characterized. Here, we report protein <span class="hlt">profiling</span> of potato leaf tissues using a modified differential centrifugation approach to separate the leaf tissues into cell wall and cytoplasmic fractions. This method helps to increase the number of identified proteins, including <span class="hlt">targeted</span> putative cell wall proteins. The method allowed for the identification of 1484 nonredundant potato leaf proteins, of which 364 and 447 were reproducibly identified proteins in the cell wall and cytoplasmic fractions, respectively. Reproducibly identified proteins corresponded to over 70% of proteins identified in each replicate. A diverse range of proteins was identified based on their theoretical pI values, molecular masses, functional classification, and biological processes. Such a protein extraction method is effective for the establishment of a highly qualified proteome <span class="hlt">profile</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017AIPC.1845b0001A','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017AIPC.1845b0001A"><span>Cyclotron <span class="hlt">production</span> of Ga-68 for human use from liquid <span class="hlt">targets</span>: From theory to practice</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Alves, F.; Alves, V. H.; Neves, A. C. B.; do Carmo, S. J. C.; Nactergal, B.; Hellas, V.; Kral, E.; Gonçalves-Gameiro, C.; Abrunhosa, A. J.</p> <p>2017-05-01</p> <p>A fully automated system for the <span class="hlt">production</span> of 68Ga based on commercially available cyclotron liquid <span class="hlt">target</span> and synthesis modules is described. A solution containing enriched 68Zn dissolved in a nitric solution is irradiated in a Cyclone 18/9 IBA cyclotron leading to the <span class="hlt">production</span> of up to about 25 GBq of 68Ga. The irradiated solution is transferred to a Synthera synthesis module in which 68Ga is separated and purified with a yield superior to 85 % and where further labelling is achieved with yields no inferior to 70 %. The developed and implemented method presents an improved approach for the <span class="hlt">production</span> of 68Ga-radiopharmaceuticals suitable for human use, in a process that takes less than 2 hours. This technique represents an economically viable alternative to 68Ge/68Ga generators with improved characteristics.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015PMB....60..931D','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015PMB....60..931D"><span><span class="hlt">Production</span> of medical isotopes from a thorium <span class="hlt">target</span> irradiated by light charged particles up to 70 MeV</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Duchemin, C.; Guertin, A.; Haddad, F.; Michel, N.; Métivier, V.</p> <p>2015-02-01</p> <p>The irradiation of a thorium <span class="hlt">target</span> by light charged particles (protons and deuterons) leads to the <span class="hlt">production</span> of several isotopes of medical interest. Direct nuclear reaction allows the <span class="hlt">production</span> of Protactinium-230 which decays to Uranium-230 the mother nucleus of Thorium-226, a promising isotope for alpha radionuclide therapy. The fission of Thorium-232 produces fragments of interest like Molybdenum-99, Iodine-131 and Cadmium-115g. We focus our study on the <span class="hlt">production</span> of these isotopes, performing new cross section measurements and calculating <span class="hlt">production</span> yields. Our new sets of data are compared with the literature and the last version of the TALYS code.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25574934','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25574934"><span><span class="hlt">Production</span> of medical isotopes from a thorium <span class="hlt">target</span> irradiated by light charged particles up to 70 MeV.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Duchemin, C; Guertin, A; Haddad, F; Michel, N; Métivier, V</p> <p>2015-02-07</p> <p>The irradiation of a thorium <span class="hlt">target</span> by light charged particles (protons and deuterons) leads to the <span class="hlt">production</span> of several isotopes of medical interest. Direct nuclear reaction allows the <span class="hlt">production</span> of Protactinium-230 which decays to Uranium-230 the mother nucleus of Thorium-226, a promising isotope for alpha radionuclide therapy. The fission of Thorium-232 produces fragments of interest like Molybdenum-99, Iodine-131 and Cadmium-115g. We focus our study on the <span class="hlt">production</span> of these isotopes, performing new cross section measurements and calculating <span class="hlt">production</span> yields. Our new sets of data are compared with the literature and the last version of the TALYS code.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018NIMPA.889..113F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018NIMPA.889..113F"><span>Two-dimensional beam <span class="hlt">profiles</span> and one-dimensional projections</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Findlay, D. J. S.; Jones, B.; Adams, D. J.</p> <p>2018-05-01</p> <p>One-dimensional projections of improved two-dimensional representations of transverse <span class="hlt">profiles</span> of particle beams are proposed for fitting to data from harp-type monitors measuring beam <span class="hlt">profiles</span> on particle accelerators. Composite distributions, with tails smoothly matched on to a central (inverted) parabola, are shown to give noticeably better fits than single gaussian and single parabolic distributions to data from harp-type beam <span class="hlt">profile</span> monitors all along the proton beam transport lines to the two <span class="hlt">target</span> stations on the ISIS Spallation Neutron Source. Some implications for inferring beam current densities on the beam axis are noted.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1029662-shielding-experiments-jasmin-collaboration-fermilab-ii-radioactivity-measurement-induced-secondary-particles-from-anti-proton-production-target','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1029662-shielding-experiments-jasmin-collaboration-fermilab-ii-radioactivity-measurement-induced-secondary-particles-from-anti-proton-production-target"><span>Shielding experiments by the JASMIN Collaboration at Fermilab (II) - radioactivity measurement induced by secondary particles from the anti-proton <span class="hlt">production</span> <span class="hlt">target</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Hiroshi, Yashima; Norihiro, Matsuda; Yoshimi, Kasugai; ...</p> <p>2011-08-01</p> <p>The JASMIN Collaboration has performed an experiment to conduct measurements of nuclear reaction rates around the anti-proton <span class="hlt">production</span> (Pbar) <span class="hlt">target</span> at the Fermi National Accelerator Laboratory (FNAL). At the Pbar <span class="hlt">target</span> station, the <span class="hlt">target</span>, consisting of an Inconel 600 cylinder, was irradiated by a 120 GeV/c proton beam from the FNAL Main Injector. The beam intensity was 3.6 x 10 12 protons per second. The samples of Al, Nb, Cu, and Au were placed near the <span class="hlt">target</span> to investigate the spatial and energy distribution of secondary particles emitted from it. After irradiation, the induced activities of the samples were measuredmore » by studying their gamma ray spectra using HPGe detectors. The <span class="hlt">production</span> rates of 30 nuclides induced in Al, Nb, Cu, Au samples were obtained. These rates increase for samples placed in a forward (small angle) position relative to the <span class="hlt">target</span>. The angular dependence of these reaction rates becomes larger for increasing threshold energy. These experimental results are compared with Monte Carlo calculations. The calculated results generally agree with the experimental results to within a factor of 2 to 3.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1009184','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/1009184"><span>Shielding experiments by the JASMIN collaboration at Fermilab (II) - Radioactivity measurement induced by secondary particles from the anti-proton <span class="hlt">production</span> <span class="hlt">target</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Yashima, Hiroshi; /Kyoto U., KURRI; Matsuda, Norihiro</p> <p>2011-01-01</p> <p>The JASMIN Collaboration has performed an experiment to conduct measurements of nuclear reaction rates around the anti-proton <span class="hlt">production</span> (Pbar) <span class="hlt">target</span> at the Fermi National Accelerator Laboratory (FNAL). At the Pbar <span class="hlt">target</span> station, the <span class="hlt">target</span>, consisting an Inconel 600 cylinder, was irradiated by a 120 GeV/c proton beam from the FNAL Main Injector. The beam intensity was 3.6 x 10{sub 12} protons per second. Samples of Al, Nb, Cu, and Au were placed near the <span class="hlt">target</span> to investigate the spatial and energy distribution of secondary particles emitted from it. After irradiation, the induced activities of the samples were measured by studyingmore » their gamma ray spectra using HPGe detectors. The <span class="hlt">production</span> rates of 30 nuclides induced in Al, Nb, Cu, Au samples were obtained. These rates increase for samples placed in a forward (small angle) position relative to the <span class="hlt">target</span>. The angular dependence of these reaction rates becomes larger for increasing threshold energy. These experimental results are compared with Monte Carlo calculations. The calculated results generally agree with the experimental results to within a factor of 2 to 3.« less</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_25 --> <div class="footer-extlink text-muted" style="margin-bottom:1rem; text-align:center;">Some links on this page may take you to non-federal websites. 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