Science.gov

Sample records for biological product deviation

  1. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at...

  2. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at...

  3. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at...

  4. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at...

  5. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 803 of this chapter; (ii) Persons who manufacture blood and blood components, including licensed manufacturers, unlicensed registered blood establishments, and transfusion services, do not report biological...; (iii) Persons who manufacture Source Plasma or any other blood component and use that Source Plasma...

  6. 21 CFR 606.171 - Reporting of product deviations by licensed manufacturers, unlicensed registered blood...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Reporting of product deviations by licensed... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS Records and Reports §...

  7. 21 CFR 606.171 - Reporting of product deviations by licensed manufacturers, unlicensed registered blood...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... manufacturers, unlicensed registered blood establishments, and transfusion services. 606.171 Section 606.171...) BIOLOGICS CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS Records and Reports § 606.171 Reporting of product deviations by licensed manufacturers, unlicensed registered blood establishments,...

  8. 21 CFR 606.171 - Reporting of product deviations by licensed manufacturers, unlicensed registered blood...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... manufacturers, unlicensed registered blood establishments, and transfusion services. 606.171 Section 606.171...) BIOLOGICS CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS Records and Reports § 606.171 Reporting of product deviations by licensed manufacturers, unlicensed registered blood establishments,...

  9. 21 CFR 606.171 - Reporting of product deviations by licensed manufacturers, unlicensed registered blood...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... manufacturers, unlicensed registered blood establishments, and transfusion services. 606.171 Section 606.171...) BIOLOGICS CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD COMPONENTS Records and Reports § 606.171 Reporting of product deviations by licensed manufacturers, unlicensed registered blood establishments,...

  10. Biological hydrogen production

    SciTech Connect

    Benemann, J.R.

    1995-11-01

    Biological hydrogen production can be accomplished by either thermochemical (gasification) conversion of woody biomass and agricultural residues or by microbiological processes that yield hydrogen gas from organic wastes or water. Biomass gasification is a well established technology; however, the synthesis gas produced, a mixture of CO and H{sub 2}, requires a shift reaction to convert the CO to H{sub 2}. Microbiological processes can carry out this reaction more efficiently than conventional catalysts, and may be more appropriate for the relatively small-scale of biomass gasification processes. Development of a microbial shift reaction may be a near-term practical application of microbial hydrogen production.

  11. 40 CFR 63.2990 - Can I conduct short-term experimental production runs that cause parameters to deviate from...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... production runs that cause parameters to deviate from operating limits? 63.2990 Section 63.2990 Protection of... Plan § 63.2990 Can I conduct short-term experimental production runs that cause parameters to deviate... production runs during which your operating parameters deviate from the operating limits. Experimental...

  12. 40 CFR 63.2990 - Can I conduct short-term experimental production runs that cause parameters to deviate from...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... production runs that cause parameters to deviate from operating limits? 63.2990 Section 63.2990 Protection of... Plan § 63.2990 Can I conduct short-term experimental production runs that cause parameters to deviate... production runs during which your operating parameters deviate from the operating limits. Experimental...

  13. 40 CFR 63.2990 - Can I conduct short-term experimental production runs that cause parameters to deviate from...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... production runs that cause parameters to deviate from operating limits? 63.2990 Section 63.2990 Protection of... Plan § 63.2990 Can I conduct short-term experimental production runs that cause parameters to deviate... production runs during which your operating parameters deviate from the operating limits. Experimental...

  14. 21 CFR 606.171 - Reporting of product deviations by licensed manufacturers, unlicensed registered blood...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Reporting of product deviations by licensed manufacturers, unlicensed registered blood establishments, and transfusion services. 606.171 Section 606.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  15. 40 CFR 63.2990 - Can I conduct short-term experimental production runs that cause parameters to deviate from...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... production runs that cause parameters to deviate from operating limits? 63.2990 Section 63.2990 Protection of... I conduct short-term experimental production runs that cause parameters to deviate from operating limits? With the approval of the Administrator, you may conduct short-term experimental production...

  16. 40 CFR 63.2990 - Can I conduct short-term experimental production runs that cause parameters to deviate from...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... production runs that cause parameters to deviate from operating limits? 63.2990 Section 63.2990 Protection of... I conduct short-term experimental production runs that cause parameters to deviate from operating limits? With the approval of the Administrator, you may conduct short-term experimental production...

  17. Plankton Production Biology

    DTIC Science & Technology

    2010-09-30

    studied. The book by Sazhina provides illustrated keys for all stages of the nauplii ( copepod larvae) of 85 species common in the oceans and is the...has to take precedence. 6 3. Sazhina’s (1985) keys for copepod nauplii still are the only ones anywhere. They will permit the study of stage...specific population dynamics (growth rate, production, mortality) of copepod larvae in mixed populations. TRANSITIONS The world’s oceanographic

  18. Biological Processes for Hydrogen Production.

    PubMed

    van Niel, Ed W J

    Methane is produced usually from organic waste in a straightforward anaerobic digestion process. However, hydrogen production is technically more challenging as more stages are needed to convert all biomass to hydrogen because of thermodynamic constraints. Nevertheless, the benefit of hydrogen is that it can be produced, both biologically and thermochemically, in more than one way from either organic compounds or water. Research in biological hydrogen production is booming, as reflected by the myriad of recently published reviews on the topic. This overview is written from the perspective of how to transfer as much energy as possible from the feedstock into the gaseous products hydrogen, and to a lesser extent, methane. The status and remaining challenges of all the biological processes are concisely discussed.

  19. A methyl-deviator epigenotype of estrogen receptor-positive breast carcinoma is associated with malignant biology.

    PubMed

    Killian, J Keith; Bilke, Sven; Davis, Sean; Walker, Robert L; Jaeger, Erich; Killian, M Scott; Waterfall, Joshua J; Bibikova, Marina; Fan, Jian-Bing; Smith, William I; Meltzer, Paul S

    2011-07-01

    We broadly profiled DNA methylation in breast cancers (n = 351) and benign parenchyma (n = 47) for correspondence with disease phenotype, using FFPE diagnostic surgical pathology specimens. Exploratory analysis revealed a distinctive primary invasive carcinoma subclass featuring extreme global methylation deviation. Subsequently, we tested the correlation between methylation remodeling pervasiveness and malignant biological features. A methyl deviation index (MDI) was calculated for each lesion relative to terminal ductal-lobular unit baseline, and group comparisons revealed that high-grade and short-survival estrogen receptor-positive (ER(+)) cancers manifest a significantly higher MDI than low-grade and long-survival ER(+) cancers. In contrast, ER(-) cancers display a significantly lower MDI, revealing a striking epigenomic distinction between cancer hormone receptor subtypes. Kaplan-Meier survival curves of MDI-based risk classes showed significant divergence between low- and high-risk groups. MDI showed superior prognostic performance to crude methylation levels, and MDI retained prognostic significance (P < 0.01) in Cox multivariate analysis, including clinical stage and pathological grade. Most MDI targets individually are significant markers of ER(+) cancer survival. Lymphoid and mesenchymal indexes were not substantially different between ER(+) and ER(-) groups and do not explain MDI dichotomy. However, the mesenchymal index was associated with ER(+) cancer survival, and a high lymphoid index was associated with medullary carcinoma. Finally, a comparison between metastases and primary tumors suggests methylation patterns are established early and maintained through disease progression for both ER(+) and ER(-) tumors.

  20. A Methyl-Deviator Epigenotype of Estrogen Receptor–Positive Breast Carcinoma Is Associated with Malignant Biology

    PubMed Central

    Killian, J.. Keith; Bilke, Sven; Davis, Sean; Walker, Robert L.; Jaeger, Erich; Killian, M. Scott; Waterfall, Joshua J.; Bibikova, Marina; Fan, Jian-Bing; Smith, William I.; Meltzer, Paul S.

    2011-01-01

    We broadly profiled DNA methylation in breast cancers (n = 351) and benign parenchyma (n = 47) for correspondence with disease phenotype, using FFPE diagnostic surgical pathology specimens. Exploratory analysis revealed a distinctive primary invasive carcinoma subclass featuring extreme global methylation deviation. Subsequently, we tested the correlation between methylation remodeling pervasiveness and malignant biological features. A methyl deviation index (MDI) was calculated for each lesion relative to terminal ductal-lobular unit baseline, and group comparisons revealed that high-grade and short-survival estrogen receptor–positive (ER+) cancers manifest a significantly higher MDI than low-grade and long-survival ER+ cancers. In contrast, ER− cancers display a significantly lower MDI, revealing a striking epigenomic distinction between cancer hormone receptor subtypes. Kaplan-Meier survival curves of MDI-based risk classes showed significant divergence between low- and high-risk groups. MDI showed superior prognostic performance to crude methylation levels, and MDI retained prognostic significance (P < 0.01) in Cox multivariate analysis, including clinical stage and pathological grade. Most MDI targets individually are significant markers of ER+ cancer survival. Lymphoid and mesenchymal indexes were not substantially different between ER+ and ER− groups and do not explain MDI dichotomy. However, the mesenchymal index was associated with ER+ cancer survival, and a high lymphoid index was associated with medullary carcinoma. Finally, a comparison between metastases and primary tumors suggests methylation patterns are established early and maintained through disease progression for both ER+ and ER− tumors. PMID:21641572

  1. Heterogeneity-induced large deviations in activity and (in some cases) entropy production

    NASA Astrophysics Data System (ADS)

    Gingrich, Todd R.; Vaikuntanathan, Suriyanarayanan; Geissler, Phillip L.

    2014-10-01

    We solve a simple model that supports a dynamic phase transition and show conditions for the existence of the transition. Using methods of large deviation theory we analytically compute the probability distribution for activity and entropy production rates of the trajectories on a large ring with a single heterogeneous link. The corresponding joint rate function demonstrates two dynamical phases—one localized and the other delocalized, but the marginal rate functions do not always exhibit the underlying transition. Symmetries in dynamic order parameters influence the observation of a transition, such that distributions for certain dynamic order parameters need not reveal an underlying dynamical bistability. Solution of our model system furthermore yields the form of the effective Markov transition matrices that generate dynamics in which the two dynamical phases are at coexistence. We discuss the implications of the transition for the response of bacterial cells to antibiotic treatment, arguing that even simple models of a cell cycle lacking an explicit bistability in configuration space will exhibit a bistability of dynamical phases.

  2. Synthetic Biology Guides Biofuel Production

    PubMed Central

    Connor, Michael R.; Atsumi, Shota

    2010-01-01

    The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges. PMID:20827393

  3. 9 CFR 317.7 - Products for foreign commerce; printing labels in foreign language permissible; other deviations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...; printing labels in foreign language permissible; other deviations. 317.7 Section 317.7 Animals and Animal... DEVICES, AND CONTAINERS General § 317.7 Products for foreign commerce; printing labels in foreign language... printed in a foreign language and may show the statement of the quantity of contents in accordance...

  4. 9 CFR 317.7 - Products for foreign commerce; printing labels in foreign language permissible; other deviations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...; printing labels in foreign language permissible; other deviations. 317.7 Section 317.7 Animals and Animal... DEVICES, AND CONTAINERS General § 317.7 Products for foreign commerce; printing labels in foreign language... printed in a foreign language and may show the statement of the quantity of contents in accordance...

  5. 9 CFR 317.7 - Products for foreign commerce; printing labels in foreign language permissible; other deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...; printing labels in foreign language permissible; other deviations. 317.7 Section 317.7 Animals and Animal... DEVICES, AND CONTAINERS General § 317.7 Products for foreign commerce; printing labels in foreign language... printed in a foreign language and may show the statement of the quantity of contents in accordance...

  6. 9 CFR 317.7 - Products for foreign commerce; printing labels in foreign language permissible; other deviations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...; printing labels in foreign language permissible; other deviations. 317.7 Section 317.7 Animals and Animal... DEVICES, AND CONTAINERS General § 317.7 Products for foreign commerce; printing labels in foreign language... printed in a foreign language and may show the statement of the quantity of contents in accordance...

  7. 9 CFR 317.7 - Products for foreign commerce; printing labels in foreign language permissible; other deviations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...; printing labels in foreign language permissible; other deviations. 317.7 Section 317.7 Animals and Animal... DEVICES, AND CONTAINERS General § 317.7 Products for foreign commerce; printing labels in foreign language... printed in a foreign language and may show the statement of the quantity of contents in accordance...

  8. Biological production of products from waste gases

    DOEpatents

    Gaddy, James L.

    2002-01-22

    A method and apparatus are designed for converting waste gases from industrial processes such as oil refining, and carbon black, coke, ammonia, and methanol production, into useful products. The method includes introducing the waste gases into a bioreactor where they are fermented to various products, such as organic acids, alcohols, hydrogen, single cell protein, and salts of organic acids by anaerobic bacteria within the bioreactor. These valuable end products are then recovered, separated and purified.

  9. Synthetic biology advances for pharmaceutical production

    PubMed Central

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

  10. Synthetic biology advances for pharmaceutical production.

    PubMed

    Breitling, Rainer; Takano, Eriko

    2015-12-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems.

  11. Biologically active proteins from natural product extracts.

    PubMed

    O'Keefe, B R

    2001-10-01

    The term "biologically active proteins" is almost redundant. All proteins produced by living creatures are, by their very nature, biologically active to some extent in their homologous species. In this review, a subset of these proteins will be discussed that are biologically active in heterologous systems. The isolation and characterization of novel proteins from natural product extracts including those derived from microorganisms, plants, insects, terrestrial vertebrates, and marine organisms will be reviewed and grouped into several distinct classes based on their biological activity and their structure.

  12. Biological production of organic compounds

    DOEpatents

    Yu, Jianping; Paddock, Troy; Carrieri, Damian; Maness, Pin-Ching; Seibert, Michael

    2016-04-12

    Strains of cyanobacteria that produce high levels of alpha ketoglutarate (AKG) and pyruvate are disclosed herein. Methods of culturing these cyanobacteria to produce AKG or pyruvate and recover AKG or pyruvate from the culture are also described herein. Nucleic acid sequences encoding polypeptides that function as ethylene-forming enzymes and their use in the production of ethylene are further disclosed herein. These nucleic acids may be expressed in hosts such as cyanobacteria, which in turn may be cultured to produce ethylene.

  13. Biological engineering for sustainable biomass production

    SciTech Connect

    Shen, S.

    1986-09-01

    A new discipline has evolved in efforts to engineer photosynthetic production systems that produce biomass feedstocks efficiently, economically and with minimal adverse environmental impact. In this talk an overview is given of how biological engineering systems are designed to produce energy and novel material products within the framework of existing market infrastructure. Practical examples of biological engineering systems which employ components based on genetic engineering, species propagation, modern agricultural techniques, chemical engineering, and mechanical engineering are analyzed for worldwide materials application and environmental conservation. 9 refs., 6 figs.

  14. Systems biology solutions for biochemical production challenges.

    PubMed

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

    2017-03-16

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals.

  15. Synthetic Biological Approaches to Natural Product Biosynthesis

    PubMed Central

    Winter, Jaclyn M; Tang, Yi

    2012-01-01

    Small molecules produced in Nature continue to be an inspiration for the development of new therapeutic agents. These natural products possess exquisite chemical diversity, which gives rise to their wide range of biological activities. In their host organism, natural products are assembled and modified by dedicated biosynthetic pathways that Nature has meticulously developed. Often times, the complex structures or chemical modifications instated by these pathways are difficult to replicate using traditional synthetic methods. An alternative approach for creating or enhancing the structural variation of natural products is through combinatorial biosynthesis. By rationally reprogramming and manipulating the biosynthetic machinery responsible for their production, unnatural metabolites that were otherwise inaccessible can be obtained. Additionally, new chemical structures can be synthesized or derivatized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed unnatural metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds. PMID:22221832

  16. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL... products which are neither composed of nor prepared with organisms or antigens used in biologicals...

  17. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL... products which are neither composed of nor prepared with organisms or antigens used in biologicals...

  18. Systems Biology of Microbial Exopolysaccharides Production

    PubMed Central

    Ates, Ozlem

    2015-01-01

    Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran. PMID:26734603

  19. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1992-12-01

    Due to the abundant supply of coal in the United States, significant research efforts have occurred over the past 15 years concerning the conversion of coal to liquid fuels. Researchers at the University of Arkansas have concentrated on a biological approach to coal liquefaction, starting with coal-derived synthesis gas as the raw material. Synthesis gas, a mixture of CO, H[sub 2], CO[sub 2], CH[sub 4] and sulfur gases, is first produced using traditional gasification techniques. The CO, CO[sub 2] and H[sub 2] are then converted to ethanol using a bacterial culture of Clostridium 1jungdahlii. Ethanol is the desired product if the resultant product stream is to be used as a liquid fuel. However, under normal operating conditions, the wild strain'' produces acetate in favor of ethanol in conjunction with growth in a 20:1 molar ratio. Research was performed to determine the conditions necessary to maximize not only the ratio of ethanol to acetate, but also to maximize the concentration of ethanol resulting in the product stream.

  20. Chemical and biological production of cyclotides

    PubMed Central

    Li, Yilong; Bi, Tao; Camarero, Julio A.

    2016-01-01

    Cyclotides are fascinating naturally occurring micro-proteins (≈30 residues long) present in several plant families, and display various biological properties such as protease inhibitory, anti-microbial, insecticidal, cytotoxic, anti-HIV and hormone-like activities. Cyclotides share a unique head-to-tail circular knotted topology of three disulfide bridges, with one disulfide penetrating through a macrocycle formed by the two other disulfides and interconnecting peptide backbones, forming what is called a cystine knot topology. This cyclic cystine knot (CCK) framework gives the cyclotides exceptional rigidity, resistance to thermal and chemical denaturation, and enzymatic stability against degradation. Interestingly, cyclotides have been shown to be orally bioavailable, and other cyclotides have been shown to cross the cell membranes. Moreover, recent reports have also shown that engineered cyclotides can be efficiently used to target extracellular and intracellular protein-protein interactions, therefore making cyclotides ideal tools for drug development to selectively target protein-protein interactions. In this work we will review all the available methods for production of these interesting proteins using chemical or biological methods. PMID:27064329

  1. Biological response modifiers: interferons, interleukins, recombinant products, liposomal products.

    PubMed

    Kruth, S A

    1998-03-01

    The concept of enhancing the normal immune response against infections and neoplasms has been considered for decades. The administration of various natural and synthetic products to simulate systemic infections has largely given over to the idea that specific cytokines can be used effectively when administered systemically. Interferons, interleukins, and hematopoietic growth factors may offer substantial clinical benefit in chronic viral infections, and cancers such as osteosarcoma, melanoma, and lymphosarcoma. Erythropoietin has been shown to have great utility in the management of chronic renal failure. At this point in time, only recombinant products derived from humans are commercially available, and they are expensive and not licensed for use in companion animals. Nevertheless, these products may have significant clinical impact on several highly fatal disorders of dogs and cats. When administered systemically, cytokines perturb complex regulatory pathways, and serious side effects may occur. Innovative delivery methods, such as liposomes, gene therapy, and even oral administration may increase the therapeutic index of these molecules. Biological response modification, cytokine biology, and associated delivery systems are rapidly changing fields, and the small animal veterinarian will need to watch for significant advances in these areas over the next several years.

  2. Regulatory considerations for raw materials used in biological products.

    PubMed

    Khan, A S

    2010-01-01

    Raw materials are critical components of product manufacture; these include source materials such as cell substrates, tissues, and biological fluids required for product manufacture, as well as biological materials required for cell growth, propagation, differentiation, and selection. Adventitious viruses are a major safety concern in biological raw materials. This paper discusses the specific concerns related to different types of biological materials and presents the Center for Biologics Evaluation and Research's perspective on the qualification and management of raw materials for purposes of developing a safety program for the manufacture of biological products.

  3. Monascus secondary metabolites: production and biological activity.

    PubMed

    Patakova, Petra

    2013-02-01

    The genus Monascus, comprising nine species, can reproduce either vegetatively with filaments and conidia or sexually by the formation of ascospores. The most well-known species of genus Monascus, namely, M. purpureus, M. ruber and M. pilosus, are often used for rice fermentation to produce red yeast rice, a special product used either for food coloring or as a food supplement with positive effects on human health. The colored appearance (red, orange or yellow) of Monascus-fermented substrates is produced by a mixture of oligoketide pigments that are synthesized by a combination of polyketide and fatty acid synthases. The major pigments consist of pairs of yellow (ankaflavin and monascin), orange (rubropunctatin and monascorubrin) and red (rubropunctamine and monascorubramine) compounds; however, more than 20 other colored products have recently been isolated from fermented rice or culture media. In addition to pigments, a group of monacolin substances and the mycotoxin citrinin can be produced by Monascus. Various non-specific biological activities (antimicrobial, antitumor, immunomodulative and others) of these pigmented compounds are, at least partly, ascribed to their reaction with amino group-containing compounds, i.e. amino acids, proteins or nucleic acids. Monacolins, in the form of β-hydroxy acids, inhibit hydroxymethylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis in animals and humans.

  4. Biological treatment of shrimp production wastewater.

    PubMed

    Boopathy, Raj

    2009-07-01

    Over the last few decades, there has been an increase in consumer demand for shrimp, which has resulted in its worldwide aquaculture production. In the United States, the stringent enforcement of environmental regulations encourages shrimp farmers to develop new technologies, such as recirculating raceway systems. This is a zero-water exchange system capable of producing high-density shrimp yields. The system also produces wastewater characterized by high levels of ammonia, nitrate, nitrite, and organic carbon, which make waste management costs prohibitive. Shrimp farmers have a great need for a waste management method that is effective and economical. One such method is the sequencing batch reactor (SBR). A SBR is a variation of the activated sludge biological treatment process. This process uses multiple steps in the same reactor to take the place of multiple reactors in a conventional treatment system. The SBR accomplishes equalization, aeration, and clarification in a timed sequence in a single reactor system. This is achieved through reactor operation in sequences, which includes fill, react, settle, decant, and idle. A laboratory scale SBR was successfully operated using shrimp aquaculture wastewater. The wastewater contained high concentrations of carbon and nitrogen. By operating the reactors sequentially, namely, aerobic and anoxic modes, nitrification and denitrification were achieved as well as removal of carbon. Ammonia in the waste was nitrified within 4 days. The denitrification of nitrate was achieved by the anoxic process, and 100% removal of nitrate was observed within 15 days of reactor operation.

  5. Biosynthesis of therapeutic natural products using synthetic biology.

    PubMed

    Awan, Ali R; Shaw, William M; Ellis, Tom

    2016-10-01

    Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production.

  6. [Application of systems biology and synthetic biology in strain improvement for biofuel production].

    PubMed

    Zhao, Xinqing; Bai, Fengwu; Li, Yin

    2010-07-01

    Biofuels are renewable and environmentally friendly, but high production cost makes them economically not competitive, and the development of robust strains is thus one of the prerequisites. In this article, strain improvement studies based on the information from systems biology studies are reviewed, with a focus on their applications on stress tolerance improvement. Furthermore, the contribution of systems biology, synthetic biology and metabolic engineering in strain development for biofuel production is discussed, with an expectation for developing more robust strains for biofuel production.

  7. Design control considerations for biologic-device combination products.

    PubMed

    Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

    2017-01-11

    Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting

  8. Biological control and sustainable food production.

    PubMed

    Bale, J S; van Lenteren, J C; Bigler, F

    2008-02-27

    The use of biological control for the management of pest insects pre-dates the modern pesticide era. The first major successes in biological control occurred with exotic pests controlled by natural enemy species collected from the country or area of origin of the pest (classical control). Augmentative control has been successfully applied against a range of open-field and greenhouse pests, and conservation biological control schemes have been developed with indigenous predators and parasitoids. The cost-benefit ratio for classical biological control is highly favourable (1:250) and for augmentative control is similar to that of insecticides (1:2-1:5), with much lower development costs. Over the past 120 years, more than 5000 introductions of approximately 2000 non-native control agents have been made against arthropod pests in 196 countries or islands with remarkably few environmental problems. Biological control is a key component of a 'systems approach' to integrated pest management, to counteract insecticide-resistant pests, withdrawal of chemicals and minimize the usage of pesticides. Current studies indicate that genetically modified insect-resistant Bt crops may have no adverse effects on the activity or function of predators or parasitoids used in biological control. The introduction of rational approaches for the environmental risk assessment of non-native control agents is an essential step in the wider application of biological control, but future success is strongly dependent on a greater level of investment in research and development by governments and related organizations that are committed to a reduced reliance on chemical control.

  9. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Packaging biological products. 112.6 Section 112.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  10. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Packaging biological products. 112.6 Section 112.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  11. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  12. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  13. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Biological products; exemption. 106.1 Section 106.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR...

  14. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Biological products; exemption. 106.1 Section 106.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR...

  15. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Biological products; exemption. 106.1 Section 106.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR...

  16. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Biological products and related terms. 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  17. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Packaging biological products. 112.6 Section 112.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  18. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Inspections of biological products. 115.2 Section 115.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  19. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Biological products; exemption. 106.1 Section 106.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR...

  20. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Packaging biological products. 112.6 Section 112.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  1. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Sampling of biological products. 113.3 Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD...

  2. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false U.S. Veterinary Biological Product... BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a) Authorization to produce each biological product shall be specified on a U.S. Veterinary Biological Product License, issued by...

  3. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... animals, Provided, that, the Administrator determines that the conditions under which the experiment is to... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Shipment of experimental biological products. 103.3 Section 103.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

  4. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... submitted to the Administrator. Research facilities that are entirely separate and apart from...

  5. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    A batch kinetic study involving Clostridium lungdahlii in a mineral medium was carried out in order to provide baseline data for the effects of nutrients on product ratio and kinetics. The use of this minimal medium containing vitamins, minerals, select amino acids and salts showed both a lower maximum specific growth rate and a lower maximum specific uptake rate than found when using a complex medium supplemented with 0.01% yeast extract. At the same time, the product ratio was improved slightly in favor of ethanol over acetate. Future experiments will measure the effects of ammonia and phosphate limitation on product ratio and process kinetics.

  6. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    Previous results have shown that the medium pH, the composition of the medium and concentration of medium constituents significantly affect the ratio of ethanol to acetate in the product stream when fermenting CO, CO{sub 2} and H{sub 2} in synthesis gas to products by Clostridium ljungdahlii. An additional batch study was carried out varying the agitation rate at pH 4, 4.5 and 5.0. It was speculated that increased agitation rates in combination with low pH might result in increased ethanol production while, at the same time, yielding higher cell concentrations which could eventually result in higher ethanol concentrations.

  7. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1991-01-01

    Previously studies have shown the importance of both medium composition and concentration and medium pH on ethanol production of Clostridium ljungdahlii in fermenting CO, CO{sub 2} and H{sub 2} in synthesis gas. Four additional batch experiments involving medium composition and concentration were carried out in modified basal medium without yeast extract at pH 4.0. These experiments indicate that basal medium with only small amounts of B-vitamins can yield significant cell growth while yielding ethanol as the major product. Product ratios as high as 11.0 g ethanol per g acetate were obtained with half strength B-vitamins. Further experiments indicates that Ca-pantothenate may be necessary for the growth of C. ljungdahlii and that growth and ethanol production can occur simultaneously.

  8. Biological Activity of Recently Discovered Halogenated Marine Natural Products

    PubMed Central

    Gribble, Gordon W.

    2015-01-01

    This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included. PMID:26133553

  9. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... United States veterinary license number or a United States veterinary permit number or other mark...) When notified to stop distribution and sale of a serial or subserial of a veterinary biological product by the Secretary, veterinary biologics licensees or permittees shall: (1) Stop the...

  10. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1992-01-01

    Research is continuing in an attempt to increase both the ethanol concentration and product ratio using C. ljungdahlii. The purpose of this report is to present data utilizing a medium prepared especially for C. ljungdahlii. Medium development studies are presented, as well as reactor studies with the new medium in batch reactors. CSTRs and CSTRs with cell recycle. The use of this new medium has resulted in significant improvements in cell concentration, ethanol concentration and product ratio.

  11. Biological production of ethanol fom coal

    SciTech Connect

    Not Available

    1992-05-01

    Research is continuing in an attempt to increase both the ethanol concentration and product ratio using C. ljungdahlii. The purpose of this report is to present data (acetate to ethanol) utilizing a medium prepared especially for C. ljungdahlii. Medium development studies are presented, as well as reactor studies with the new medium in batch reactors. Continuous stirred tank reactor (CSTR) with cell recycle. The use of this new medium has resulted in significant improvements in cell concentration, ethanol concentration and product ratio.

  12. Production of hydrogen using an anaerobic biological process

    SciTech Connect

    Kramer, Robert; Pelter, Libbie S.; Patterson, John A.

    2016-11-29

    Various embodiments of the present invention pertain to methods for biological production of hydrogen. More specifically, embodiments of the present invention pertain to a modular energy system and related methods for producing hydrogen using organic waste as a feed stock.

  13. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    Previous results have shown that the yeast extract concentration and the medium pH significantly affect the ratio of ethanol to acetate in the product stream when fermenting CO, CO{sub 2} and H{sub 2} in synthesis gas to products by Clostridium ljungdahlii. Further experimentation has demonstrated the impact of eliminating yeast extract from the medium (except for the slight quantity transferred with the inoculm), especially when coupled with low pH. An ethanol to acetate product ratio of 4.0 was obtained at pH 4.5 without yeast extract present in the medium when using culture previously exposed to growth-limiting H{sub 2}S. The product ratio was 2.0 at pH 4.0 (nearly three times the value of pH 4.5 and nine times the value of pH 5.0) without yeast extract present in the media when using the standard (unexposed) culture.

  14. Biological production of liquid fuels from biomass

    SciTech Connect

    1982-01-01

    A scheme for the production of liquid fuels from renewable resources such as poplar wood and lignocellulosic wastes from a refuse hydropulper was investigated. The particular scheme being studied involves the conversion of a cellulosic residue, resulting from a solvent delignified lignocellulosic feed, into either high concentration sugar syrups or into ethyl and/or butyl alcohol. The construction of a pilot apparatus for solvent delignifying 150 g samples of lignocellulosic feeds was completed. Also, an analysis method for characterizing the delignified product has been selected and tested. This is a method recommended in the Forage Fiber Handbook. Delignified samples are now being prepared and tested for their extent of delignification and susceptibility to enzyme hydrolysis. Work is continuing on characterizing the cellulase and cellobiase enzyme systems derived from the YX strain of Thermomonospora.

  15. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    The fermentation pH has been observed to be the key parameter affecting the ratio of ethanol to acetate produced by Clostridium ljungdahlii. The effects of controlled pH on cell growth and product formation by C. ljungdahlii were measured. It was found that cell concentration and acetate concentration increased with pH, while the ethanol concentration was highest at the lower pH. The molar product ratio of ethanol to acetate was 0.74 at pH 4.0, 0.39 at pH 4.5 and 0.12 at pH 5.0. Future experiments will concentrate on studying other important parameters such as agitation rate and nutrients concentrations with controlled pH as a preclude to continuous reactor studies.

  16. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1991-01-01

    Research is continuing in attempting to increase both the ethanol concentration and product ratio from the C. ljungdahlii fermentation. Both batch and continuous reactors are being used for this purpose. The purpose of this report is four-fold. First, the data presented in PETC Report No. 2-4-91 (June--September 1991) are analyzed and interpreted using normalized specific growth and production rates. This technique eliminates experimental variation due to the differences in inoculum history. Secondly, the effects of the sulfur gases H{sub 2}S and COS on the performance of C. ljungdahlii are presented and discussed. Although these are preliminary results, they illustrate the tolerance of the bacterium to low levels of sulfur gases. Thirdly, the results of continuous stirred tank reactor studies are presented, where cell and product concentrations are shown as a function of agitation rate and gas flow rate. Finally, additional data are presented showing the performance of C. ljungdahlii in a CSTR with cell recycle.

  17. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... market by a Animal and Plant Health Inspection Service representative. (a) Either an employee of the... biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant...

  18. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... market by a Animal and Plant Health Inspection Service representative. (a) Either an employee of the... biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant...

  19. Role of natural product diversity in chemical biology.

    PubMed

    Hong, Jiyong

    2011-06-01

    Through the natural selection process, natural products possess a unique and vast chemical diversity and have been evolved for optimal interactions with biological macromolecules. Owing to their diversity, target affinity, and specificity, natural products have demonstrated enormous potential as modulators of biomolecular function, been an essential source for drug discovery, and provided design principles for combinatorial library development.

  20. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... market by a Animal and Plant Health Inspection Service representative. (a) Either an employee of the... biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant...

  1. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... market by a Animal and Plant Health Inspection Service representative. (a) Either an employee of the... biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant...

  2. Neurotrophic Natural Products: Chemistry and Biology

    PubMed Central

    Xu, Jing; Lacoske, Michelle H.

    2014-01-01

    Neurodegenerative diseases and spinal cord injury affect approximately 50 million people worldwide, bringing the total healthcare cost to over 600 billion dollars per year. Nervous system growth factors, that is, neurotrophins, are a potential solution to these disorders, since they could promote nerve regeneration. An average of 500 publications per year attests to the significance of neurotrophins in biomedical sciences and underlines their potential for therapeutic applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins severely restricts their clinical use. On the other hand, small molecules that modulate neurotrophic activity offer a promising therapeutic approach against neurological disorders. Nature has provided an impressive array of natural products that have potent neurotrophic activities. This Review highlights the current synthetic strategies toward these compounds and summarizes their ability to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic natural products could be used not only as starting points in drug design but also as tools to study the next frontier in biomedical sciences: the brain activity map project. PMID:24353244

  3. Improvement of FK506 production by synthetic biology approaches.

    PubMed

    Fu, Li-Feng; Tao, Yang; Jin, Mei-Ying; Jiang, Hui

    2016-12-01

    Synthetic biology has been applied to direct improvement of valuable metabolite productions. Tacrolimus (FK506), a clinically used immunosuppressive agent isolated from many Streptomyces, is produced by fermentation in industry. Here we chose FK506 as an example to review recent progress in improving FK506 production, including enhancing transcription levels of biosynthetic genes, accelerating post-translational modification levels of biosynthetic enzymes, increasing activities of rate limiting enzymes, and rational supplement of limited precursors. FK506 production was increased from 25 % to sevenfold by these synthetic biology approaches.

  4. The Interstellar Production of Biologically Important Organics

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.; Bernstein, Max P.; Dworkin, Jason; Allamandola, Louis J.

    2000-01-01

    One of the primary tasks of the Astrochemistry Laboratory at Ames Research Center is to use laboratory simulations to study the chemical processes that occur in dense interstellar clouds. Since new stars are formed in these clouds, their materials may be responsible for the delivery of organics to new habitable planets and may play important roles in the origin of life. These clouds are extremely cold (less than 50 kelvin), and most of the volatiles in these clouds are condensed onto dust grains as thin ice mantles. These ices are exposed to cosmic rays and ultraviolet (UV) photons that break chemical bonds and result in the production of complex molecules when the ices are warmed (as they would be when incorporated into a star-forming region). Using cryovacuum systems and UV lamps, this study simulates the conditions of these clouds and studies the resulting chemistry. Some of the areas of progress made in 1999 are described below. It shows some of the types of molecules that may be formed in the interstellar medium. Laboratory simulations have already confirmed that many of these compounds are made under these conditions.

  5. Systems Biology Approaches to Understand Natural Products Biosynthesis.

    PubMed

    Licona-Cassani, Cuauhtemoc; Cruz-Morales, Pablo; Manteca, Angel; Barona-Gomez, Francisco; Nielsen, Lars K; Marcellin, Esteban

    2015-01-01

    Actinomycetes populate soils and aquatic sediments that impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams, and terpenes are well-known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed toward a shift in the exploitation of actinomycete's biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation, and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets.

  6. Milk kefir: composition, microbial cultures, biological activities, and related products

    PubMed Central

    Prado, Maria R.; Blandón, Lina Marcela; Vandenberghe, Luciana P. S.; Rodrigues, Cristine; Castro, Guillermo R.; Thomaz-Soccol, Vanete; Soccol, Carlos R.

    2015-01-01

    In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance. PMID:26579086

  7. Assessment of biological Hydrogen production processes: A review

    NASA Astrophysics Data System (ADS)

    Najafpour, G. D.; Shahavi, M. H.; Neshat, S. A.

    2016-06-01

    Energy crisis created a special attention on renewable energy sources. Among these sources; hydrogen through biological processes is well-known as the most suitable and renewable energy sources. In terms of process yield, hydrogen production from various sources was evaluated. A summary of microorganisms as potential hydrogen producers discussed along with advantages and disadvantages of several bioprocesses. The pathway of photo-synthetic and dark fermentative organisms was discussed. In fact, the active enzymes involved in performance of biological processes for hydrogen generation were identified and their special functionalities were discussed. The influential factors affecting on hydrogen production were known as enzymes assisting liberation specific enzymes such as nitrogenase, hydrogenase and uptake hydrogenase. These enzymes were quite effective in reduction of proton and form active molecular hydrogen. Several types of photosynthetic systems were evaluated with intension of maximum hydrogen productivities. In addition dark fermentative and light intensities on hydrogen productions were evaluated. The hydrogen productivities of efficient hydrogen producing strains were evaluated.

  8. Yeast synthetic biology toolbox and applications for biofuel production.

    PubMed

    Tsai, Ching-Sung; Kwak, Suryang; Turner, Timothy L; Jin, Yong-Su

    2015-02-01

    Yeasts are efficient biofuel producers with numerous advantages outcompeting bacterial counterparts. While most synthetic biology tools have been developed and customized for bacteria especially for Escherichia coli, yeast synthetic biological tools have been exploited for improving yeast to produce fuels and chemicals from renewable biomass. Here we review the current status of synthetic biological tools and their applications for biofuel production, focusing on the model strain Saccharomyces cerevisiae We describe assembly techniques that have been developed for constructing genes, pathways, and genomes in yeast. Moreover, we discuss synthetic parts for allowing precise control of gene expression at both transcriptional and translational levels. Applications of these synthetic biological approaches have led to identification of effective gene targets that are responsible for desirable traits, such as cellulosic sugar utilization, advanced biofuel production, and enhanced tolerance against toxic products for biofuel production from renewable biomass. Although an array of synthetic biology tools and devices are available, we observed some gaps existing in tool development to achieve industrial utilization. Looking forward, future tool development should focus on industrial cultivation conditions utilizing industrial strains.

  9. Natural product synthesis at the interface of chemistry and biology

    PubMed Central

    2014-01-01

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. PMID:25043880

  10. Natural product synthesis at the interface of chemistry and biology.

    PubMed

    Hong, Jiyong

    2014-08-11

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences.

  11. Caudal septal deviation.

    PubMed

    Haack, Jason; Papel, Ira D

    2009-06-01

    The nasal septum is a structure poorly understood and appreciated by the lay public and the nonotolaryngologist--head and neck surgeon alike. Deviation of the caudal portion of the nasal septum may result in nasal obstruction, a crooked nose, and columellar irregularities. The correction of a severely deviated caudal septum is one of the most difficult challenges of the otolaryngologist and facial plastic surgeon. A variety of options are available for correction of mild, to the most severe, deflections. This condition, as with all challenges in medicine, should not be a one size fits all or one surgery fits all situation. The skilled surgeon should understand the multiple options available for surgical correction and tailor fit the procedure to the deformity.

  12. Analyzing Vehicle Operator Deviations

    DTIC Science & Technology

    2008-07-01

    related to vehicle operator deviations ( VODs ). VODs occur when a vehicle enters the airport movement area without ATC approval. We developed a VOD ...prediction model to help understand the human factors causes associated with different types of VODs . We then examined the validity of the model, using...the data that we needed was missing due to incomplete reporting of the human factors associated with a given VOD . To aid in the development of a

  13. Continuous downstream processing for high value biological products: A Review.

    PubMed

    Zydney, Andrew L

    2016-03-01

    There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations.

  14. Irradiation of advanced health care products - Tissues and biologics

    NASA Astrophysics Data System (ADS)

    Winters, Martell

    2014-12-01

    Radiation sterilization of tissues and biologics has become more common in recent years. As a result it has become critical to understand how to adapt the typical test methods and validation approaches to a tissue or biological product scenario. Also data evaluation sometimes becomes more critical than with traditional medical devices because for many tissues and biologics a low radiation dose is required. It is the intent behind this paper to provide information on adapting bioburden tests used in radiation validations such that the data can be most effectively used on tissues and biologics. In addition challenges with data evaluation are discussed, particularly the use of less-than values for bioburden results in radiation validation studies.

  15. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL... control of the Department in the prevention, control or eradication of animal diseases in connection with (a) an official USDA program; or (b) an emergency animal disease situation, or (c) a...

  16. Natural products with health benefits from marine biological resources

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ocean is the cradle of lives, which provides a diverse array of intriguing natural products that has captured scientists’ attention in the past few decades due to their significant and extremely potent biological activities. In addition to being rich sources for pharmaceutical drugs, marine nat...

  17. PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    EPA Science Inventory

    PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    Miroslav Styblo1,2,*, Zuzana Drobna1, Felecia S. Walton1, Ilona Jaspers1,2, Shan Lin3,
    Stephen B. Waters3, David J. Thomas4

    1Department of Pediatrics, 2Center for Environmental Medicine an...

  18. Microbial Production of Isoprenoids Enabled by Synthetic Biology

    PubMed Central

    Immethun, Cheryl M.; Hoynes-O’Connor, Allison G.; Balassy, Andrea; Moon, Tae Seok

    2013-01-01

    Microorganisms transform inexpensive carbon sources into highly functionalized compounds without toxic by-product generation or significant energy consumption. By redesigning the natural biosynthetic pathways in an industrially suited host, microbial cell factories can produce complex compounds for a variety of industries. Isoprenoids include many medically important compounds such as antioxidants and anticancer and antimalarial drugs, all of which have been produced microbially. While a biosynthetic pathway could be simply transferred to the production host, the titers would become economically feasible when it is rationally designed, built, and optimized through synthetic biology tools. These tools have been implemented by a number of research groups, with new tools pledging further improvements in yields and expansion to new medically relevant compounds. This review focuses on the microbial production of isoprenoids for the health industry and the advancements though synthetic biology. PMID:23577007

  19. Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care

    PubMed Central

    Perez-Pinera, Pablo; Han, Ningren; Cleto, Sara; Cao, Jicong; Purcell, Oliver; Shah, Kartik A.; Lee, Kevin; Ram, Rajeev; Lu, Timothy K.

    2016-01-01

    Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care. PMID:27470089

  20. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

    PubMed Central

    Crane, Erika A.

    2016-01-01

    Abstract Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products. PMID:26833854

  1. Systems Biology of Recombinant Protein Production in Bacillus megaterium

    NASA Astrophysics Data System (ADS)

    Biedendieck, Rebekka; Bunk, Boyke; Fürch, Tobias; Franco-Lara, Ezequiel; Jahn, Martina; Jahn, Dieter

    Over the last two decades the Gram-positive bacterium Bacillus megaterium was systematically developed to a useful alternative protein production host. Multiple vector systems for high yield intra- and extracellular protein production were constructed. Strong inducible promoters were combined with DNA sequences for optimised ribosome binding sites, various leader peptides for protein export and N- as well as C-terminal affinity tags for affinity chromatographic purification of the desired protein. High cell density cultivation and recombinant protein production were successfully tested. For further system biology based control and optimisation of the production process the genomes of two B. megaterium strains were completely elucidated, DNA arrays designed, proteome, fluxome and metabolome analyses performed and all data integrated using the bioinformatics platform MEGABAC. Now, solid theoretical and experimental bases for primary modeling attempts of the production process are available.

  2. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis.

    PubMed

    Crane, Erika A; Gademann, Karl

    2016-03-14

    Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody-drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.

  3. Systems Biology Approaches to Understand Natural Products Biosynthesis

    PubMed Central

    Licona-Cassani, Cuauhtemoc; Cruz-Morales, Pablo; Manteca, Angel; Barona-Gomez, Francisco; Nielsen, Lars K.; Marcellin, Esteban

    2015-01-01

    Actinomycetes populate soils and aquatic sediments that impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams, and terpenes are well-known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed toward a shift in the exploitation of actinomycete’s biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation, and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets. PMID:26697425

  4. Current advances in biological production of propionic acid.

    PubMed

    Eş, Ismail; Khaneghah, Amin Mousavi; Hashemi, Seyed Mohammad Bagher; Koubaa, Mohamed

    2017-02-01

    Propionic acid and its derivatives are considered "Generally Recognized As Safe" food additives and are generally used as an anti-microbial and anti-inflammatory agent, herbicide, and artificial flavor in diverse industrial applications. It is produced via biological pathways using Propionibacterium and some anaerobic bacteria. However, its commercial chemical synthesis from the petroleum-based feedstock is the conventional production process bit results in some environmental issues. Novel biological approaches using microorganisms and renewable biomass have attracted considerable recent attention due to economic advantages as well as great adaptation with the green technology. This review provides a comprehensive overview of important biotechnological aspects of propionic acid production using recent technologies such as employment of co-culture, genetic and metabolic engineering, immobilization technique and efficient bioreactor systems.

  5. Formate Formation and Formate Conversion in Biological Fuels Production

    PubMed Central

    Crable, Bryan R.; Plugge, Caroline M.; McInerney, Michael J.; Stams, Alfons J. M.

    2011-01-01

    Biomethanation is a mature technology for fuel production. Fourth generation biofuels research will focus on sequestering CO2 and providing carbon-neutral or carbon-negative strategies to cope with dwindling fossil fuel supplies and environmental impact. Formate is an important intermediate in the methanogenic breakdown of complex organic material and serves as an important precursor for biological fuels production in the form of methane, hydrogen, and potentially methanol. Formate is produced by either CoA-dependent cleavage of pyruvate or enzymatic reduction of CO2 in an NADH- or ferredoxin-dependent manner. Formate is consumed through oxidation to CO2 and H2 or can be further reduced via the Wood-Ljungdahl pathway for carbon fixation or industrially for the production of methanol. Here, we review the enzymes involved in the interconversion of formate and discuss potential applications for biofuels production. PMID:21687599

  6. Evolution of approaches to viral safety issues for biological products.

    PubMed

    Lubiniecki, Anthony S

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Approaches to viral safety issues for biological products have evolved during the past 50+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin products. But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-1 to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contamination due to human viruses and purification technologies to physically remove and inactivate adventitious and endogenous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viral clearance for safety of biotechnology products. These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has

  7. Intensification of tropical Pacific biological productivity due to volcanic eruptions

    NASA Astrophysics Data System (ADS)

    Chikamoto, Megumi O.; Timmermann, Axel; Yoshimori, Masakazu; Lehner, Flavio; Laurian, Audine; Abe-Ouchi, Ayako; Mouchet, Anne; Joos, Fortunat; Raible, Christoph C.; Cobb, Kim M.

    2016-02-01

    Major volcanic eruptions generate widespread ocean cooling, which reduces upper ocean stratification. This effect has the potential to increase nutrient delivery into the euphotic zone and boost biological productivity. Using externally forced last millennium simulations of three climate/Earth System models (Model for Interdisciplinary Research On Climate (MIROC), Community Earth System Model (CESM), and LOch-Vecode-Ecbilt-CLio-agIsm Model (LOVECLIM)), we test the hypothesis that large volcanic eruptions intensify nutrient-driven export production. It is found that strong volcanic radiative forcing enhances the likelihood of eastern Pacific El Niño-like warming in CESM and LOVECLIM. This leads to an initial reduction of nutrients and export production in the eastern equatorial Pacific. However, this initial response reverses after about 3 years in association with La Niña cooling. The resulting delayed enhancement of biological production resembles the multiyear response in MIROC. The model simulations show that volcanic impacts on tropical Pacific dynamics and biogeochemistry persist for several years, thus providing a new source for potential multiyear ecosystem predictability.

  8. Molecular biology in studies of oceanic primary production

    SciTech Connect

    LaRoche, J.; Falkowski, P.G.; Geider, R.

    1992-07-01

    Remote sensing and the use of moored in situ instrumentation has greatly improved our ability to measure phytoplankton chlorophyll and photosynthesis on global scales with high temporal resolution. However, the interpretation of these measurements and their significance with respect to the biogeochemical cycling of carbon relies on their relationship with physiological and biochemical processes in phytoplankton. For example, the use of satellite images of surface chlorophyll to estimate primary production is often based on the functional relationship between photosynthesis and irradiance. A variety of environmental factors such as light, temperature, nutrient availability affect the photosynthesis/irradiance (P vs I) relationship in phytoplankton. We present three examples showing how molecular biology can be used to provide basic insight into the factors controlling primary productivity at three different levels of complexity: 1. Studies of light intensity regulation in unicellular alga show how molecular biology can help understand the processing of environmental cues leading to the regulation of photosynthetic gene expression. 2. Probing of the photosynthetic apparatus using molecular techniques can be used to test existing mechanistic models derived from the interpretation of physiological and biophysical measurements. 3. Exploratory work on the expression of specific proteins during nutrient-limited growth of phytoplankton may lead to the identification and production of molecular probes for field studies.

  9. Molecular biology in studies of oceanic primary production

    SciTech Connect

    LaRoche, J.; Falkowski, P.G. ); Geider, R. . Coll. of Marine Studies)

    1992-01-01

    Remote sensing and the use of moored in situ instrumentation has greatly improved our ability to measure phytoplankton chlorophyll and photosynthesis on global scales with high temporal resolution. However, the interpretation of these measurements and their significance with respect to the biogeochemical cycling of carbon relies on their relationship with physiological and biochemical processes in phytoplankton. For example, the use of satellite images of surface chlorophyll to estimate primary production is often based on the functional relationship between photosynthesis and irradiance. A variety of environmental factors such as light, temperature, nutrient availability affect the photosynthesis/irradiance (P vs I) relationship in phytoplankton. We present three examples showing how molecular biology can be used to provide basic insight into the factors controlling primary productivity at three different levels of complexity: 1. Studies of light intensity regulation in unicellular alga show how molecular biology can help understand the processing of environmental cues leading to the regulation of photosynthetic gene expression. 2. Probing of the photosynthetic apparatus using molecular techniques can be used to test existing mechanistic models derived from the interpretation of physiological and biophysical measurements. 3. Exploratory work on the expression of specific proteins during nutrient-limited growth of phytoplankton may lead to the identification and production of molecular probes for field studies.

  10. Isoleukotrienes are biologically active free radical products of lipid peroxidation.

    PubMed

    Harrison, K A; Murphy, R C

    1995-07-21

    The free radical oxidation of arachidonic acid esterified to glycerophospholipids is known to generate complex metabolites, termed isoprostanes, that share structural features of prostaglandins derived from prostaglandin H2 synthase. Furthermore, certain isoprostanes have been found to exert biological activity through endogenous receptors on cell surfaces. Using mass spectrometry and ancillary techniques, the free radical oxidation of 1-hexadecanoyl-2-arachidonoyl-glycerophosphocholine was studied in the search for products of arachidonic acid isomeric to the leukotrienes that are derived from 5-lipoxygenase-catalyzed metabolism of arachidonic acid. Several conjugated triene metabolites were chromatographically separated from known 5-lipoxygenase products and structures characterized as 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid esterified to the glycerophosphocholine backbone. We have termed these products as B4-isoleukotrienes. Following saponification some, but not all, B4-isoleukotrienes were found to exert biological activity in elevating intracellular calcium in Indo-1-loaded human polymorphonuclear leukocytes. This activity could be blocked by a leukotriene B4 receptor antagonist. An EC50 of approximately 30 nM was determined for one unique B4-isoleukotriene with a relative retention index of 2.54. We have shown that free radical processes can lead to the formation of biologically active isoleukotrienes in glycerophosphocholine liposomes, and we propose that B4-isoleukotrienes may also be formed in membrane glycerophospholipids as a result of lipid peroxidation during tissue injury. Such B4-isoleukotrienes could then mediate events of tissue damage through activation of leukotriene B4 receptors on target cells.

  11. Natural products as a resource for biologically active compounds

    SciTech Connect

    Hanke, F.J.

    1986-01-01

    The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod)/sub 3/ is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous /sup 13/C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the /sup 1/H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants.

  12. Systems biological approaches towards understanding cellulase production by Trichoderma reesei.

    PubMed

    Kubicek, Christian P

    2013-01-20

    Recent progress and improvement in "-omics" technologies has made it possible to study the physiology of organisms by integrated and genome-wide approaches. This bears the advantage that the global response, rather than isolated pathways and circuits within an organism, can be investigated ("systems biology"). The sequencing of the genome of Trichoderma reesei (teleomorph Hypocrea jecorina), a fungus that serves as a major producer of biomass-degrading enzymes for the use of renewable lignocellulosic material towards production of biofuels and biorefineries, has offered the possibility to study this organism and its enzyme production on a genome wide scale. In this review, I will highlight the use of genomics, transcriptomics, proteomics and metabolomics towards an improved and novel understanding of the biochemical processes that involve in the massive overproduction of secreted proteins.

  13. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights... Calculation of patent term extension for a veterinary biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a veterinary biological product is eligible for extension, the...

  14. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded... for the reclassification of all biological products that have been classified into Category IIIA....

  15. Biological standards: problems in large-scale production.

    PubMed

    Campbell, P J

    1976-10-01

    A biological standard usually consists of a batch of perhaps several thousand ampoules. In defining a batch of ampoules to be a standard, we are in essence making a number of fundamental claims: (1) That in terms of content, (mass and potency) each individual ampoule is identical to every other amoule in the batch. (2) That in the course of preparation of the standard, the contents of each ampoule have been treated in exactly the same way and held for the same length of time under the same conditions, (i.e. all the ampoules of the standard have been treated as one single batch, each stage of processing being carried out under constant conditions in one complete working session, however long). (3) That the stability or instability of the biological activity of the contents of each ampoule of the batch is identical to every other ampoule (i.e. that moisture, oxygen, light, raised temperature--all factors which cause deterioration of biological activity--have been exculuded to the same degree in each and every ampoule in the batch, so that each ampoule of the standard is equally stable or unstable). It is quite a difficult task to meet these criteria even in a small number of ampoules at the bench. It becomes a very demanding exercise to achieve the same results in 4,000 ampoules--the normal batch size at NIBSC. Details of the methods used at NIBSC for the production of large batches of ampoules of biological standards have already been published (Campbell, 1974). The author of the papers will take the opportunity to develop various aspects of the published detail.

  16. An overview of biological production of L-theanine.

    PubMed

    Mu, Wanmeng; Zhang, Tao; Jiang, Bo

    2015-01-01

    L-Theanine (γ-glutamylethylamide) is a unique non-protein amino acid that is naturally found in tea plants. It contributes to the umami taste and unique flavor to green tea infusion, and thus its content in tea leaves highly impacts the tea quality and price. In addition to the graceful taste, it has been proved to have many beneficial physiological effects, especially promoting relaxation and improving concentration and learning ability. Based on these promising advantages, L-theanine has been commercially developed as a valuable ingredient for use in food and beverages to improve and/or maintain human health. L-Theanine can be obtained by chemical synthesis or isolation from tea, while chemical synthesis of L-theanine is hard to be accepted by consumers and is not allowed to use in food industry, and isolation of L-theanine in high purity generally involves time-consuming, cost-ineffective, and complicated operational processes. Accordingly, the biological production of L-theanine has recently attracted much attention. Four kinds of bacterial enzymes, including L-glutamine synthetase, γ-glutamylmethylamide synthetase, γ-glutamyltranspeptidase, and L-glutaminase, have been characterized to have L-theanine-producing ability. Herein, an overview of recent studies on the biological production of L-theanine was presented.

  17. Biological evaluation of nanosilver incorporated cellulose pulp for hygiene products.

    PubMed

    Kavitha Sankar, P C; Ramakrishnan, Reshmi; Rosemary, M J

    2016-04-01

    Cellulose pulp has a visible market share in personal hygiene products such as sanitary napkins and baby diapers. However it offers good surface for growth of microorganisms. Huge amount of research is going on in developing hygiene products that do not initiate microbial growth. The objective of the present work is to produce antibacterial cellulose pulp by depositing silver nanopowder on the cellulose fiber. The silver nanoparticles used were of less than 100 nm in size and were characterised using transmission electron microscopy and X-ray powder diffraction studies. Antibacterial activity of the functionalized cellulose pulp was proved by JIS L 1902 method. The in-vitro cytotoxicity, in-vivo vaginal irritation and intracutaneous reactivity studies were done with silver nanopowder incorporated cellulose pulp for introducing a new value added product to the market. Cytotoxicity evaluation suggested that the silver nanoparticle incorporated cellulose pulp is non-cytotoxic. No irritation and skin sensitization were identified in animals tested with specific extracts prepared from the test material in the in-vivo experiments. The results indicated that the silver nanopowder incorporated cellulose pulp meets the requirements of the standard practices recommended for evaluating the biological reactivity and has good biocompatibility, hence can be classified as a safe hygiene product.

  18. Suitability of Gray Water for Hydroponic Crop Production Following Biological and Physical Chemical and Biological Subsystems

    NASA Technical Reports Server (NTRS)

    Bubenheim, David L.; Harper, Lynn D.; Wignarajah, Kanapathipillai; Greene, Catherine

    1994-01-01

    The water present in waste streams from a human habitat must be recycled in Controlled Ecological Life Support Systems (CELSS) to limit resupply needs and attain self-sufficiency. Plants play an important role in providing food, regenerating air, and producing purified water via transpiration. However, we have shown that the surfactants present in hygiene waste water have acute toxic effects on plant growth (Bubenheim et al. 1994; Greene et al., 1994). These phytotoxic affects can be mitigated by allowing the microbial population on the root surface to degrade the surfactant, however, a significant suppression (several days) in crop performance is experienced prior to reaching sub-toxic surfactant levels and plant recovery. An effective alternative is to stabilize the microbial population responsible for degradation of the surfactant on an aerobic bioreactor and process the waste water prior to utilization in the hydroponic solution (Wisniewski and Bubenheim, 1993). A sensitive bioassay indicates that the surfactant phytotoxicity is suppressed by more than 90% within 5 hours of introduction of the gray water to the bioreactor; processing for more than 12 hours degrades more than 99% of the phytotoxin. Vapor Compression Distillation (VCD) is a physical / chemical method for water purification which employees sequential distillation steps to separate water from solids and to volatilize contaminants. The solids from the waste water are concentrated in a brine and the pure product water (70 - 90% of the total waste water volume depending on operating conditions) retains non of the phytotoxic effects. Results of the bioassay were used to guide evaluations of the suitability of recovered gray water following biological and VCD processing for hydroponic lettuce production in controlled environments. Lettuce crops were grown for 28 days with 100% of the input water supplied with recovered water from the biological processor or VCD. When compared with the growth of plants

  19. 9 CFR 318.308 - Deviations in processing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY...) Deviations in processing (or process deviations) must be handled according to: (1)(i) A HACCP plan for canned...) of this section. (c) (d) Procedures for handling process deviations where the HACCP plan...

  20. Biological hydrogen production by dark fermentation: challenges and prospects towards scaled-up production.

    PubMed

    RenNanqi; GuoWanqian; LiuBingfeng; CaoGuangli; DingJie

    2011-06-01

    Among different technologies of hydrogen production, bio-hydrogen production exhibits perhaps the greatest potential to replace fossil fuels. Based on recent research on dark fermentative hydrogen production, this article reviews the following aspects towards scaled-up application of this technology: bioreactor development and parameter optimization, process modeling and simulation, exploitation of cheaper raw materials and combining dark-fermentation with photo-fermentation. Bioreactors are necessary for dark-fermentation hydrogen production, so the design of reactor type and optimization of parameters are essential. Process modeling and simulation can help engineers design and optimize large-scale systems and operations. Use of cheaper raw materials will surely accelerate the pace of scaled-up production of biological hydrogen. And finally, combining dark-fermentation with photo-fermentation holds considerable promise, and has successfully achieved maximum overall hydrogen yield from a single substrate. Future development of bio-hydrogen production will also be discussed.

  1. Is biological productivity enhanced at the New England shelfbreak front?

    NASA Astrophysics Data System (ADS)

    Zhang, Weifeng G.; McGillicuddy, Dennis J.; Gawarkiewicz, Glen G.

    2013-01-01

    A two-dimensional (cross-shelf) numerical model of the mean seasonal circulation offshore of southern New England predicts upwelling at the shelfbreak front. Expected ramifications of this upwelling include enhancement of nutrient supply, phytoplankton biomass, and productivity. However, seasonal climatologies of chlorophyll based on both in situ data and satellite observations show no mean enhancement at the front. We investigate this apparent discrepancy with a four-component planktonic ecosystem model coupled to the two-dimensional physical model. Nutrient fields are restored to climatological values at depth, and upper ocean values evolve freely according to physical and biological forcing. Vertical diffusivity is based on seasonally averaged surface and bottom mixed layer depths compiled from in situ observations. The model reproduces the general pattern of the observed cross-shelf and seasonal variations of the chlorophyll distribution. It predicts a local enhancement of phytoplankton productivity at the shelfbreak in spring and summer as a result of the persistently upwelled nutrient-rich slope water. In the model, zooplankton grazing prevents accumulation of phytoplankton biomass at the site of the upwelling. The predicted enhancement of primary productivity (but not phytoplankton biomass) at the shelfbreak constitutes a hypothesis that could be tested in the future with suitable measurements from regional long-term observatories, such as the Ocean Observatories Initiative Pioneer Array.

  2. Systems biology of recombinant protein production using Bacillus megaterium.

    PubMed

    Biedendieck, Rebekka; Borgmeier, Claudia; Bunk, Boyke; Stammen, Simon; Scherling, Christian; Meinhardt, Friedhelm; Wittmann, Christoph; Jahn, Dieter

    2011-01-01

    The Gram-negative bacterium Escherichia coli is the most widely used production host for recombinant proteins in both academia and industry. The Gram-positive bacterium Bacillus megaterium represents an increasingly used alternative for high yield intra- and extracellular protein synthesis. During the past two decades, multiple tools including gene expression plasmids and production strains have been developed. Introduction of free replicating and integrative plasmids into B. megaterium is possible via protoplasts transformation or transconjugation. Using His(6)- and StrepII affinity tags, the intra- or extracellular produced proteins can easily be purified in one-step procedures. Different gene expression systems based on the xylose controlled promoter P(xylA) and various phage RNA polymerase (T7, SP6, K1E) driven systems enable B. megaterium to produce up to 1.25g of recombinant protein per liter. Biomass concentrations of up to 80g/l can be achieved by high cell density cultivations in bioreactors. Gene knockouts and gene replacements in B. megaterium are possible via an optimized gene disruption system. For a safe application in industry, sporulation and protease-deficient as well as UV-sensitive mutants are available. With the help of the recently published B. megaterium genome sequence, it is possible to characterize bottle necks in the protein production process via systems biology approaches based on transcriptome, proteome, metabolome, and fluxome data. The bioinformatical platform (Megabac, http://www.megabac.tu-bs.de) integrates obtained theoretical and experimental data.

  3. Biological production of ethanol from coal. Final report

    SciTech Connect

    Not Available

    1992-12-01

    Due to the abundant supply of coal in the United States, significant research efforts have occurred over the past 15 years concerning the conversion of coal to liquid fuels. Researchers at the University of Arkansas have concentrated on a biological approach to coal liquefaction, starting with coal-derived synthesis gas as the raw material. Synthesis gas, a mixture of CO, H{sub 2}, CO{sub 2}, CH{sub 4} and sulfur gases, is first produced using traditional gasification techniques. The CO, CO{sub 2} and H{sub 2} are then converted to ethanol using a bacterial culture of Clostridium 1jungdahlii. Ethanol is the desired product if the resultant product stream is to be used as a liquid fuel. However, under normal operating conditions, the ``wild strain`` produces acetate in favor of ethanol in conjunction with growth in a 20:1 molar ratio. Research was performed to determine the conditions necessary to maximize not only the ratio of ethanol to acetate, but also to maximize the concentration of ethanol resulting in the product stream.

  4. Production and biological activities of yellow pigments from Monascus fungi.

    PubMed

    Chen, Gong; Wu, Zhenqiang

    2016-08-01

    Monascus yellow pigments (MYPs), are azaphilone compounds and one of the three main components of total Monascus pigments (MPs). Thirty-five hydrophilic or hydrophobic MYPs have been identified, with the majority being hydrophobic. Apart from screening special Monascus strains, some advanced approaches, such as extractive and high-cell-density fermentations, have been applied for developing or producing new MYPs, especially extracellular hydrophilic MYPs. The outstanding performance of MYPs in terms of resistance to photodegradation, as well as tolerance for temperature and pH, give natural MYPs reasonable prospects, compared with the orange and red MPs, for practical use in the present and future. Meanwhile, MYPs have shown promising potential for applications in the food and pharmaceutical industries based on their described bioactivities. This review briefly summarizes the reports to date on chemical structures, biological activities, biosynthetic pathways, production technologies, and physicochemical performances of MYPs. The existing problems for MYPs are discussed and research prospects proposed.

  5. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL... live organisms. Safeguards as herein provided shall be established by the research investigator...

  6. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND... PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL... live organisms. Safeguards as herein provided shall be established by the research investigator...

  7. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... serial or subserial of a veterinary biological product under the provisions of paragraph (a) or (b) of this section, veterinary biologics licensees or permittees shall: (1) Stop the preparation... veterinary biological product pending further instructions from APHIS. (2) Immediately, but no later than...

  8. 76 FR 13646 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. In...

  9. 76 FR 52668 - Vaccines and Related Biological Products Advisory Committee; Amendment of Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... Administration (FDA) is announcing an amendment to the notice of meeting of the Vaccines and Related Biological... announced that a meeting of the Vaccines and Related Biological Products Advisory Committee would be held...

  10. 77 FR 3780 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological..., Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics...

  11. Hormones in international meat production: biological, sociological and consumer issues.

    PubMed

    Galbraith, Hugh

    2002-12-01

    Beef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds ('hormones') to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17beta and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17beta as a carcinogen in certain tissues. Now subject to a 'permanent' EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate

  12. Review: production, characterization, and testing of banked mammalian cell substrates used to produce biological products.

    PubMed

    Schiff, Leonard J

    2005-01-01

    A critical component in controlling the production of biological products derived from human and animal cell lines is the characterization and testing of banked cell substrates. The objective is to confirm the identity, purity, and suitability of these cells for manufacturing use. Quality concerns for biological products derived from cell lines originate from the presence of cellular and adventitious contaminants. Well-characterized cell banks not only permit a consistent source of production cells throughout the life of a product but also decrease the likelihood of contamination by other cell lines and adventitious agents. An important part of qualifying a cell line is choosing the appropriate testing for the presence of adventitious contaminants. The qualification of cell banks includes tests for cell identity and endogenous and adventitious microbial contaminants (bacteria, fungi, mycoplasmas, and viruses). For cells producing recombinant deoxyribonucleic acid-derived products, analysis of the expression construct at the nucleic acid level (genetic stability) is also a primary concern. The strategy for designing a safety-testing program for banked cells should be based on sound scientific principles and current regulatory guidance.

  13. Competency development in antibody production in cancer cell biology

    SciTech Connect

    Park, M.S.

    1998-12-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The main objective of this project was to develop a rapid recombinant antibody production technology. To achieve the objective, the authors employed (1) production of recombinant antigens that are important for cell cycle regulation and DNA repair, (2) immunization and specific selection of antibody-producing lymphocytes using the flow cytometry and magnetic bead capturing procedure, (3) construction of single chain antibody library, (4) development of recombinant vectors that target, express, and regulate the expression of intracellular antibodies, and (5) specific inhibition of tumor cell growth in tissue culture. The authors have accomplished (1) optimization of a selection procedure to isolate antigen-specific lymphocytes, (2) optimization of the construction of a single-chain antibody library, and (3) development of a new antibody expression vector for intracellular immunization. The future direction of this research is to continue to test the potential use of the intracellular immunization procedure as a tool to study functions of biological molecules and as an immuno-cancer therapy procedure to inhibit the growth of cancer cells.

  14. Biological removal of cationic fission products from nuclear wastewater.

    PubMed

    Ngwenya, N; Chirwa, E M N

    2011-01-01

    Nuclear energy is becoming a preferred energy source amidst rising concerns over the impacts of fossil fuel based energy on global warming and climate change. However, the radioactive waste generated during nuclear power generation contains harmful long-lived fission products such as strontium (Sr). In this study, cationic strontium uptake from solution by microbial cultures obtained from mine wastewater is evaluated. A high strontium removal capacity (q(max)) with maximum loading of 444 mg/g biomass was achieved by a mixed sulphate reducing bacteria (SRB) culture. Sr removal in SRB was facilitated by cell surface based electrostatic interactions with the formation of weak ionic bonds, as 68% of the adsorbed Sr(2+) was easily desorbed from the biomass in an ion exchange reaction with MgCl₂. To a lesser extent, precipitation reactions were also found to account for the removal of Sr from aqueous solution as about 3% of the sorbed Sr was precipitated due to the presence of chemical ligands while the remainder occurred as an immobile fraction. Further analysis of the Sr-loaded SRB biomass by scanning electron microscopy (SEM) coupled to energy dispersive X-ray (EDX) confirmed extracellular Sr(2+) precipitation as a result of chemical interaction. In summary, the obtained results demonstrate the prospects of using biological technologies for the remediation of industrial wastewaters contaminated by fission products.

  15. Biological conversion of pyrolytic products to ethanol and lipids

    NASA Astrophysics Data System (ADS)

    Lian, Jieni

    Pyrolysis is a promising technology that can convert up to 75 % of lignocellulosic biomass into crude bio-oil. However, due to the complex chemical compositions of bio-oil, its further refining into fuels and high value chemicals faces great challenges. This dissertation research proposed new technologies for biological conversion of pyrolytic products derived from cellulose and hemicellulose, such as anhydrosugars and carbolic acids to fuels and chemicals. First, the pyrolytic anhydrosugars (chiefly levoglucosan (LG)) were hydrolysed into glucose followed by neutralization, detoxification and fermentation to produce ethanol by ethanogenetic yeast and lipids by oleaginous yeasts. Second, a novel process for the conversion of C1-C4 pyrolytic products to lipid with oleaginous yeasts was investigated. Third, oleaginous yeasts that can directly convert LG to lipids were studied and a recombined yeast with LG kinase was constructed for the direct convertion of LG into lipids. This allowed a reduction of existing process for LG fermentation from four steps into two steps and eliminated the need for acids and bases as well as the disposal of chemicals. The development of genetic modified organisms with LG kinase opens a promising avenue for the direct LG fermentation to produce a wide range of fuels and chemicals. The simplification of LG utilization process would enhance the economic viability of this technology.

  16. Fundamental hair follicle biology and fine fibre production in animals.

    PubMed

    Galbraith, H

    2010-09-01

    Hair 'fine' fibre is an important commercial product of farmed and certain wild animal species. The fibre is produced in follicles embedded in skin. These have properties in common with other tissues of the integument and have importance in determining yield and quality of fibre. Means of understanding and improving these characteristics are informed by knowledge of integumental and follicle biology. This paper reviews contemporary information that identifies the major fibre-producing species and their production characteristic. It surveys knowledge describing fundamental biology of the integument and considers information derived for the hair follicle from studies on a number of species including genetically modified mice. It identifies the composition of the follicle and describes components and interrelationships between epidermal hair-fibre producing epidermis and fibroblast- and connective tissue-containing dermis. The structure of different primary and secondary follicle types, and associated structures, are described. Focus is given to the alterations in anatomy and in behaviour from active to inactive state, which occurs during the hair follicle cycle. Information is provided on the anatomical substructures (hair medulla, cortex, cuticles and supporting sheaths and dermal papilla), cellular and extracellular composition, and adhesion and chemical signalling systems, which regulate development from the early embryo to post-natal state and subsequent cycling. Such signalling involves the dermis and its specialist fibroblasts, which secrete signalling molecules, which along with those from local epidermis and systemic sources, largely determine structure and function of epidermal cells. Such chemical signalling typically includes endocrine-, paracrine-, autocrine- and juxtacrine-acting molecules and interactions with their receptors located on cell membranes or intracellularly with transduction of message mediated by transcription factors at gene level

  17. Biological risks associated with consumption of reptile products.

    PubMed

    Magnino, Simone; Colin, Pierre; Dei-Cas, Eduardo; Madsen, Mogens; McLauchlin, Jim; Nöckler, Karsten; Maradona, Miguel Prieto; Tsigarida, Eirini; Vanopdenbosch, Emmanuel; Van Peteghem, Carlos

    2009-09-15

    The consumption of a wide variety of species of reptiles caught from the wild has been an important source of protein for humans world-wide for millennia. Terrapins, snakes, lizards, crocodiles and iguanas are now farmed and the consumption and trade of their meat and other edible products have recently increased in some areas of the world. Biological risks associated with the consumption of products from both farmed and wild reptile meat and eggs include infections caused by bacteria (Salmonella spp., Vibrio spp.), parasites (Spirometra, Trichinella, Gnathostoma, pentastomids), as well as intoxications by biotoxins. For crocodiles, Salmonella spp. constitute a significant public health risk due to the high intestinal carrier rate which is reflected in an equally high contamination rate in their fresh and frozen meat. There is a lack of information about the presence of Salmonella spp. in meat from other edible reptilians, though captive reptiles used as pets (lizards or turtles) are frequently carriers of these bacteria in Europe. Parasitic protozoa in reptiles represent a negligible risk for public health compared to parasitic metazoans, of which trichinellosis, pentastomiasis, gnathostomiasis and sparganosis can be acquired through consumption of contaminated crocodile, monitor lizard, turtle and snake meat, respectively. Other reptiles, although found to harbour the above parasites, have not been implicated with their transmission to humans. Freezing treatment inactivates Spirometra and Trichinella in crocodile meat, while the effectiveness of freezing of other reptilian meat is unknown. Biotoxins that accumulate in the flesh of sea turtles may cause chelonitoxism, a type of food poisoning with a high mortality rate in humans. Infections by fungi, including yeasts, and viruses widely occur in reptiles but have not been linked to a human health risk through the contamination of their meat. Currently there are no indications that natural transmissible spongiform

  18. Sustainable production of biologically active molecules of marine based origin.

    PubMed

    Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

    2013-09-25

    The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules.

  19. Maximizing overall liking results in a superior product to minimizing deviations from ideal ratings: an optimization case study with coffee-flavored milk.

    PubMed

    Li, Bangde; Hayes, John E; Ziegler, Gregory R

    2015-06-01

    In just-about-right (JAR) scaling and ideal scaling, attribute delta (i.e., "Too Little" or "Too Much") reflects a subject's dissatisfaction level for an attribute relative to their hypothetical ideal. Dissatisfaction (attribute delta) is a different construct from consumer acceptability, operationalized as liking. Therefore, we hypothesized minimizing dissatisfaction and maximizing liking would yield different optimal formulations. The objective of this research was to compare product optimization strategies, i.e. maximizing liking vis-à-vis minimizing dissatisfaction. Coffee-flavored dairy beverages (n = 20) were formulated using a fractional mixture design that constrained the proportions of coffee extract, milk, sucrose, and water. Participants (n = 388) were randomly assigned to one of three research conditions, where they evaluated 4 of the 20 samples using an incomplete block design. Samples were rated for overall liking and for intensity of the attributes sweetness, milk flavor, thickness and coffee flavor. Where appropriate, measures of overall product quality (Ideal_Delta and JAR_Delta) were calculated as the sum of the absolute values of the four attribute deltas. Optimal formulations were estimated by: a) maximizing liking; b) minimizing Ideal_Delta; or c) minimizing JAR_Delta. A validation study was conducted to evaluate product optimization models. Participants indicated a preference for a coffee-flavored dairy beverage with more coffee extract and less milk and sucrose in the dissatisfaction model compared to the formula obtained by maximizing liking. That is, when liking was optimized, participants generally liked a weaker, milkier and sweeter coffee-flavored dairy beverage. Predicted liking scores were validated in a subsequent experiment, and the optimal product formulated to maximize liking was significantly preferred to that formulated to minimize dissatisfaction by a paired preference test. These findings are consistent with the view that JAR

  20. Maximizing overall liking results in a superior product to minimizing deviations from ideal ratings: an optimization case study with coffee-flavored milk

    PubMed Central

    Li, Bangde; Hayes, John E.; Ziegler, Gregory R.

    2015-01-01

    In just-about-right (JAR) scaling and ideal scaling, attribute delta (i.e., “Too Little” or “Too Much”) reflects a subject’s dissatisfaction level for an attribute relative to their hypothetical ideal. Dissatisfaction (attribute delta) is a different construct from consumer acceptability, operationalized as liking. Therefore, we hypothesized minimizing dissatisfaction and maximizing liking would yield different optimal formulations. The objective of this research was to compare product optimization strategies, i.e. maximizing liking vis-à-vis minimizing dissatisfaction. Coffee-flavored dairy beverages (n = 20) were formulated using a fractional mixture design that constrained the proportions of coffee extract, milk, sucrose, and water. Participants (n = 388) were randomly assigned to one of three research conditions, where they evaluated 4 of the 20 samples using an incomplete block design. Samples were rated for overall liking and for intensity of the attributes sweetness, milk flavor, thickness and coffee flavor. Where appropriate, measures of overall product quality (Ideal_Delta and JAR_Delta) were calculated as the sum of the absolute values of the four attribute deltas. Optimal formulations were estimated by: a) maximizing liking; b) minimizing Ideal_Delta; or c) minimizing JAR_Delta. A validation study was conducted to evaluate product optimization models. Participants indicated a preference for a coffee-flavored dairy beverage with more coffee extract and less milk and sucrose in the dissatisfaction model compared to the formula obtained by maximizing liking. That is, when liking was optimized, participants generally liked a weaker, milkier and sweeter coffee-flavored dairy beverage. Predicted liking scores were validated in a subsequent experiment, and the optimal product formulated to maximize liking was significantly preferred to that formulated to minimize dissatisfaction by a paired preference test. These findings are consistent with the view

  1. Presence and biological activity of antibiotics used in fuel ethanol and corn co-product production.

    PubMed

    Compart, D M Paulus; Carlson, A M; Crawford, G I; Fink, R C; Diez-Gonzalez, F; Dicostanzo, A; Shurson, G C

    2013-05-01

    Antibiotics are used in ethanol production to control bacteria from competing with yeast for nutrients during starch fermentation. However, there is no published scientific information on whether antibiotic residues are present in distillers grains (DG), co-products from ethanol production, or whether they retain their biological activity. Therefore, the objectives of this study were to quantify concentrations of various antibiotic residues in DG and determine whether residues were biologically active. Twenty distillers wet grains and 20 distillers dried grains samples were collected quarterly from 9 states and 43 ethanol plants in the United States. Samples were analyzed for DM, CP, NDF, crude fat, S, P, and pH to describe the nutritional characteristics of the samples evaluated. Samples were also analyzed for the presence of erythromycin, penicillin G, tetracycline, tylosin, and virginiamycin M1, using liquid chromatography and mass spectrometry. Additionally, virginiamycin residues were determined, using a U.S. Food and Drug Administration-approved bioassay method. Samples were extracted and further analyzed for biological activity by exposing the sample extracts to 10(4) to 10(7) CFU/mL concentrations of sentinel bacterial strains Escherichia coli ATCC 8739 and Listeria monocytogenes ATCC 19115. Extracts that inhibited bacterial growth were considered to have biological activity. Physiochemical characteristics varied among samples but were consistent with previous findings. Thirteen percent of all samples contained low (≤1.12 mg/kg) antibiotic concentrations. Only 1 sample extract inhibited growth of Escherichia coli at 10(4) CFU/mL, but this sample contained no detectable concentrations of antibiotic residues. No extracts inhibited Listeria monocytogenes growth. These data indicate that the likelihood of detectable concentrations of antibiotic residues in DG is low; and if detected, they are found in very low concentrations. The inhibition in only 1 DG

  2. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  3. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  4. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  5. 78 FR 78796 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... Applications Proposing Labeling Changes for Approved Drugs and Biological Products; Correction and Extension of... holders of an approved drug or biological product to change the product labeling to reflect certain types of newly acquired information in advance of FDA's review of the change. The proposed rule...

  6. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological product imported for research and evaluation under a permit issued in accordance with § 104.4, with...

  7. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PACKAGING AND LABELING § 112.9 Biological products imported for research and evaluation. A biological product imported for research and evaluation under a permit issued in accordance with § 104.4, with...

  8. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  9. 9 CFR 113.51 - Requirements for primary cells used for production of biologics.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Requirements for primary cells used... VECTORS STANDARD REQUIREMENTS Ingredient Requirements § 113.51 Requirements for primary cells used for production of biologics. Primary cells used to prepare biological products shall be derived from...

  10. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR... be mixed thoroughly in a single container. During bottling operations, the product shall...

  11. 9 CFR 318.308 - Deviations in processing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... deviation file. The establishment shall maintain full records regarding the handling of each deviation. Such records shall include, at a minimum, the appropriate processing and production records, a full description... establishment shall: (i) Immediately reprocess the product using the full process schedule; or (ii) Use...

  12. 9 CFR 318.308 - Deviations in processing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... deviation file. The establishment shall maintain full records regarding the handling of each deviation. Such records shall include, at a minimum, the appropriate processing and production records, a full description... establishment shall: (i) Immediately reprocess the product using the full process schedule; or (ii) Use...

  13. 75 FR 47605 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological..., Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. FDA intends...

  14. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...-Serum-Toxin Act, of any biological product by any person holding a license or permit may be dangerous...

  15. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...-Serum-Toxin Act, of any biological product by any person holding a license or permit may be dangerous...

  16. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...-Serum-Toxin Act, of any biological product by any person holding a license or permit may be dangerous...

  17. Development of biological platform for the autotrophic production of biofuels

    NASA Astrophysics Data System (ADS)

    Khan, Nymul

    The research described herein is aimed at developing an advanced biofuel platform that has the potential to surpass the natural rate of solar energy capture and CO2 fixation. The underlying concept is to use the electricity from a renewable source, such as wind or solar, to capture CO 2 via a biological agent, such as a microbe, into liquid fuels that can be used for the transportation sector. In addition to being renewable, the higher rate of energy capture by photovoltaic cells than natural photosynthesis is expected to facilitate higher rate of liquid fuel production than traditional biofuel processes. The envisioned platform is part of ARPA-E's (Advanced Research Projects Agency - Energy) Electrofuels initiative which aims at supplementing the country's petroleum based fuel production with renewable liquid fuels that can integrate easily with the existing refining and distribution infrastructure (http://arpae. energy.gov/ProgramsProjects/Electrofuels.aspx). The Electrofuels initiative aimed to develop liquid biofuels that avoid the issues encountered in the current generation of biofuels: (1) the reliance of biomass-derived technologies on the inefficient process of photosynthesis, (2) the relatively energy- and resource-intensive nature of agronomic processes, and (3) the occupation of large areas of arable land for feedstock production. The process proceeds by the capture of solar energy into electrical energy via photovoltaic cells, using the generated electricity to split water into molecular hydrogen (H2) and oxygen (O2), and feeding these gases, along with carbon dioxide (CO2) emitted from point sources such as a biomass or coal-fired power plant, to a microbial bioprocessing platform. The proposed microbial bioprocessing platform leverages a chemolithoautotrophic microorganism (Rhodobacter capsulatus or Ralstonia eutropha) naturally able to utilize these gases as growth substrates, and genetically modified to produce a triterpene hydrocarbon fuel

  18. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL... case of products containing live organisms, when they are deemed necessary or advisable by...

  19. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL... case of products containing live organisms, when they are deemed necessary or advisable by...

  20. 78 FR 20663 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... DNA Viruses, Division of Viral Products, Office of Vaccines Research and Review, Center for...

  1. 76 FR 3639 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... selection of strains to be included in the influenza virus vaccine for the 2011-2012 influenza season....

  2. 78 FR 60884 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... of Retroviruses and Laboratory of Immunoregulation, Division of Viral Products, Office of...

  3. 76 FR 44016 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological..., Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review,...

  4. 78 FR 5465 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... strains to be included in the influenza virus vaccine for the 2013- 2014 influenza season. FDA intends...

  5. 75 FR 2876 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... selection of strains to be included in the influenza virus vaccine for the 2010 - 2011 influenza season....

  6. 77 FR 42319 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-18

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... lines derived from human tumors for vaccine manufacture. FDA intends to make background...

  7. 76 FR 55397 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... the Laboratory of Method Development, Division of Viral Products, Office of Vaccines Research...

  8. 75 FR 17929 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... circovirus type 1 (PCV 1) in Rotarix, a U.S. licensed vaccine manufactured by GlaxoSmithKline and...

  9. 77 FR 63839 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... immunogenicity of an Influenza A (H5N1) Virus Monovalent Vaccine manufactured by GlaxoSmithKline. On November...

  10. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (b) To obtain marketing approval for radioactive biological products for human use, as defined...

  11. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (b) To obtain marketing approval for radioactive biological products for human use, as defined...

  12. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (b) To obtain marketing approval for radioactive biological products for human use, as defined...

  13. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (b) To obtain marketing approval for radioactive biological products for human use, as defined...

  14. 77 FR 30887 - Amendments to Sterility Test Requirements for Biological Products; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ...The Food and Drug Administration (FDA) is correcting a final rule that appeared in the Federal Register of May 3, 2012. (77 FR 26162). The final rule provides manufacturers of biological products greater flexibility, as appropriate, and encourages use of the most appropriate and state-of-the-art test methods for assuring the safety of biological products. The rule was published with an......

  15. Large deviations in Taylor dispersion

    NASA Astrophysics Data System (ADS)

    Kahlen, Marcel; Engel, Andreas; Van den Broeck, Christian

    2017-01-01

    We establish a link between the phenomenon of Taylor dispersion and the theory of empirical distributions. Using this connection, we derive, upon applying the theory of large deviations, an alternative and much more precise description of the long-time regime for Taylor dispersion.

  16. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Biological products imported for research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  17. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false U.S. Veterinary Biological Product License. 102.5 Section 102.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES...

  18. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false U.S. Veterinary Biological Product License. 102.5 Section 102.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES...

  19. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false U.S. Veterinary Biological Product License. 102.5 Section 102.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS LICENSES...

  20. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Biological products imported for research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  1. 9 CFR 112.9 - Biological products imported for research and evaluation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Biological products imported for research and evaluation. 112.9 Section 112.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  2. Advancement in bioprocess technology: parallels between microbial natural products and cell culture biologics.

    PubMed

    Bandyopadhyay, Arpan A; Khetan, Anurag; Malmberg, Li-Hong; Zhou, Weichang; Hu, Wei-Shou

    2017-02-09

    The emergence of natural products and industrial microbiology nearly eight decades ago propelled an era of bioprocess innovation. Half a century later, recombinant protein technology spurred the tremendous growth of biologics and added mammalian cells to the forefront of industrial producing cells in terms of the value of products generated. This review highlights the process technology of natural products and protein biologics. Despite the separation in time, there is a remarkable similarity in their progression. As the new generation of therapeutics for gene and cell therapy emerges, its process technology development can take inspiration from that of natural products and biologics.

  3. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... products for mass administration (including but not limited to administration through drinking water and... if seal is broken.” (d) Diluent for the following products need not be packaged with the...

  4. International reference preparations for standardization of biological medicinal products.

    PubMed

    Minor, P

    2014-10-01

    International standards are prepared as materials assigned an arbitrary unitage for a biological activity by the Expert Committee on Biological Standardization of the World Health Organization. Working reference materials are calibrated against international standards giving a common unit of measurement between laboratories. The references are assessed by a collaborative study including all relevant assays rather than by a single reference method as in the SI (Le Système international d'unités) system and the unitage assigned is an arbitrary value derived from a consensus of all valid methods. The process has proved valuable in assaying the activity of therapeutic biological medicines and in standardizing certain types of diagnostics. Issues arise with maintaining the unit when the primary reference must be replaced and to some extent in assessing the commutability of the reference with real life analytes.

  5. Biological production of ethanol from waste gases with Clostridium ljungdahlii

    DOEpatents

    Gaddy, James L.

    2000-01-01

    A method and apparatus for converting waste gases from industrial processes such as oil refining, carbon black, coke, ammonia, and methanol production, into useful products is disclosed. The method includes introducing the waste gases into a bioreactor where they are fermented to various product, such as organic acids, alcohols H.sub.2, SCP, and salts of organic acids by anaerobic bacteria within the bioreactor. These valuable end products are then recovered, separated and purified.

  6. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., the harvest date shall be the date blood or tissues are collected for production or the date cultures..., representing a whole culture or a concentrate thereof, with or without the unevaluated growth products, which... toxin or toxic growth product, which has resulted from the growth of bacterial organisms in a...

  7. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., the harvest date shall be the date blood or tissues are collected for production or the date cultures..., representing a whole culture or a concentrate thereof, with or without the unevaluated growth products, which... toxin or toxic growth product, which has resulted from the growth of bacterial organisms in a...

  8. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Product Code Number. A number assigned by Animal and Plant Health Inspection Service to each type of..., the harvest date shall be the date blood or tissues are collected for production or the date cultures... cellular antigens and shall stimulate the development of antitoxin; or (2) A combination product in...

  9. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Product Code Number. A number assigned by Animal and Plant Health Inspection Service to each type of..., the harvest date shall be the date blood or tissues are collected for production or the date cultures... cellular antigens and shall stimulate the development of antitoxin; or (2) A combination product in...

  10. Synthetic biology for microbial production of lipid-based biofuels.

    PubMed

    d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

    2015-12-01

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing.

  11. Management of paretic vertical deviations.

    PubMed

    Archer, Steven M

    2011-01-01

    Paretic vertical deviations are characterized by complex patterns of incomitance that make them some of the most challenging strabismus problems to treat. Optimum results are obtained by performing surgery on those muscles, selected from among the eight cyclovertical muscles in the two eyes, that minimize the incomitance. In superior oblique paresis the additional factors of torticollis and torsion need to be addressed and aberrant regeneration can alter the surgical plan in third nerve paresis.

  12. Large Deviations for Random Trees

    PubMed Central

    Heitsch, Christine

    2010-01-01

    We consider large random trees under Gibbs distributions and prove a Large Deviation Principle (LDP) for the distribution of degrees of vertices of the tree. The LDP rate function is given explicitly. An immediate consequence is a Law of Large Numbers for the distribution of vertex degrees in a large random tree. Our motivation for this study comes from the analysis of RNA secondary structures. PMID:20216937

  13. Importance of systems biology in engineering microbes for biofuel production

    SciTech Connect

    Mukhopadhyay, Aindrila; Redding, Alyssa M.; Rutherford, Becky J.; Keasling, Jay D.

    2009-12-02

    Microorganisms have been rich sources for natural products, some of which have found use as fuels, commodity chemicals, specialty chemicals, polymers, and drugs, to name a few. The recent interest in production of transportation fuels from renewable resources has catalyzed numerous research endeavors that focus on developing microbial systems for production of such natural products. Eliminating bottlenecks in microbial metabolic pathways and alleviating the stresses due to production of these chemicals are crucial in the generation of robust and efficient production hosts. The use of systems-level studies makes it possible to comprehensively understand the impact of pathway engineering within the context of the entire host metabolism, to diagnose stresses due to product synthesis, and provides the rationale to cost-effectively engineer optimal industrial microorganisms.

  14. Recombinant biologic products versus nutraceuticals from plants - a regulatory choice?

    PubMed

    Drake, Pascal M W; Szeto, Tim H; Paul, Mathew J; Teh, Audrey Y-H; Ma, Julian K-C

    2017-01-01

    Biotechnology has transformed the potential for plants to be a manufacturing source of pharmaceutical compounds. Now, with transgenic and transient expression techniques, virtually any biologic, including vaccines and therapeutics, could be manufactured in plants. However, uncertainty over the regulatory path for such new pharmaceuticals has been a deterrent. Consideration has been given to using alternative regulatory paths, including those for nutraceuticals or cosmetic agents. This review will consider these possibilities, and discuss the difficulties in establishing regulatory guidelines for new pharmaceutical manufacturing technologies.

  15. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... products. 103.3 Section 103.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... permit and encourage research, a person may be authorized by the Administrator to ship unlicensed..., recommendations for use, and results of preliminary research work; (d) Two copies of labels or label...

  16. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... products. 103.3 Section 103.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... permit and encourage research, a person may be authorized by the Administrator to ship unlicensed..., recommendations for use, and results of preliminary research work; (d) Two copies of labels or label...

  17. Strategies for optimizing algal biology for enhanced biomass production

    SciTech Connect

    Barry, Amanda N.; Starkenburg, Shawn R.; Sayre, Richard T.

    2015-02-02

    One of the most environmentally sustainable ways to produce high-energy density (oils) feed stocks for the production of liquid transportation fuels is from biomass. Photosynthetic carbon capture combined with biomass combustion (point source) and subsequent carbon capture and sequestration has also been proposed in the intergovernmental panel on climate change report as one of the most effective and economical strategies to remediate atmospheric greenhouse gases. To maximize photosynthetic carbon capture efficiency and energy-return-on-investment, we must develop biomass production systems that achieve the greatest yields with the lowest inputs. Numerous studies have demonstrated that microalgae have among the greatest potentials for biomass production. This is in part due to the fact that all alga cells are photoautotrophic, they have active carbon concentrating mechanisms to increase photosynthetic productivity, and all the biomass is harvestable unlike plants. All photosynthetic organisms, however, convert only a fraction of the solar energy they capture into chemical energy (reduced carbon or biomass). To increase aerial carbon capture rates and biomass productivity, it will be necessary to identify the most robust algal strains and increase their biomass production efficiency often by genetic manipulation. We review recent large-scale efforts to identify the best biomass producing strains and metabolic engineering strategies to improve aerial productivity. In addition, these strategies include optimization of photosynthetic light-harvesting antenna size to increase energy capture and conversion efficiency and the potential development of advanced molecular breeding techniques. To date, these strategies have resulted in up to twofold increases in biomass productivity.

  18. Biology Needs a Modern Assessment System for Professional Productivity

    ERIC Educational Resources Information Center

    McDade, Lucinda A.; Maddison, David R.; Guralnick, Robert; Piwowar, Heather A.; Jameson, Mary Liz; Helgen, Kristofer M.; Herendeen, Patrick S.; Hill, Andrew; Vis, Morgan L.

    2011-01-01

    Stimulated in large part by the advent of the Internet, research productivity in many academic disciplines has changed dramatically over the last two decades. However, the assessment system that governs professional success has not kept pace, creating a mismatch between modes of scholarly productivity and academic assessment criteria. In this…

  19. 9 CFR 113.52 - Requirements for cell lines used for production of biologics.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Requirements for cell lines used for... STANDARD REQUIREMENTS Ingredient Requirements § 113.52 Requirements for cell lines used for production of... cell line used to prepare a biological product shall be tested as prescribed in this section. A...

  20. 9 CFR 113.52 - Requirements for cell lines used for production of biologics.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Requirements for cell lines used for... STANDARD REQUIREMENTS Ingredient Requirements § 113.52 Requirements for cell lines used for production of... cell line used to prepare a biological product shall be tested as prescribed in this section. A...

  1. 9 CFR 113.52 - Requirements for cell lines used for production of biologics.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Requirements for cell lines used for... STANDARD REQUIREMENTS Ingredient Requirements § 113.52 Requirements for cell lines used for production of... cell line used to prepare a biological product shall be tested as prescribed in this section. A...

  2. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Disposition of animals administered experimental biological products or live organisms. 103.2 Section 103.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND...

  3. 9 CFR 113.52 - Requirements for cell lines used for production of biologics.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Requirements for cell lines used for... STANDARD REQUIREMENTS Ingredient Requirements § 113.52 Requirements for cell lines used for production of... cell line used to prepare a biological product shall be tested as prescribed in this section. A...

  4. 9 CFR 113.52 - Requirements for cell lines used for production of biologics.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Requirements for cell lines used for... STANDARD REQUIREMENTS Ingredient Requirements § 113.52 Requirements for cell lines used for production of... cell line used to prepare a biological product shall be tested as prescribed in this section. A...

  5. Synoptic events force biological productivity in Patagonian fjord ecosystems

    NASA Astrophysics Data System (ADS)

    Daneri, Giovanni

    2016-04-01

    The annual cycle of primary productivity of the Patagonian fjords has, to date, been described as a two phase system consisting of a short non productive winter phase (during June and July) and a productive phase extending from late winter (August) to autumn (May). Low levels of primary production, phytoplankton biomass and high concentrations of surface nutrients have been described as characterizing winter conditions while pulsed productivity events typifies the productivity pattern during the extended productive season. Pulsed productivity events characterize coastal waters where inorganic nutrients in surface layers are replenished following periods of intensive utilization by autotrophs. Freshwater input in Patagonian fjords in southern Chile (41-55°S) results in one of the largest estuarine regions worldwide. Here strong haline water column stratification prevents nutrient mixing to the surface layers thus potentially shutting off algal production. Our working hypothesis considered that in order to reconcile the observed pulsed productivity pattern, periodic breaking (associated to surface nutrient replenishment) and re-establishment of estuarine conditions (associated to water column stratification) would be required. Up to now however our understanding of the physical processes that control water column conditions in the Patagonian fjord area has been extremely limited. Here we present evidence linking the passage of synoptic low pressure fronts to pulsed productivity events in the Patagonian fjord area. These front controls and influence local processes of interaction between the fjord and the atmosphere generating a rapid water column response. In the specific case of the Puyuhuapi fjord we have been able to show that such synoptic fronts induce surface flow reversal and water column mixing. Phytoplankton blooming occurs after the passage of the synoptic front once calmer conditions prevail and estuarine conditions are re established. The occurrence of

  6. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS INSPECTIONS... excuse any person from compliance with the Virus-Serum-Toxin Act. (Approved by the Office of...

  7. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS INSPECTIONS... excuse any person from compliance with the Virus-Serum-Toxin Act. (Approved by the Office of...

  8. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS INSPECTIONS... excuse any person from compliance with the Virus-Serum-Toxin Act. (Approved by the Office of...

  9. Intended use of reference products & WHO International Standards/Reference Reagents in the development of similar biological products (biosimilars).

    PubMed

    Thorpe, Robin; Wadhwa, Meenu

    2011-09-01

    Reference Products and WHO International Standards/Reference Reagents have roles to play in the development and characterization of similar biological products (SBPs). However, these roles are distinct and non-interchangeable. The uses of these materials and their limitations are considered in this paper.

  10. 77 FR 47397 - Request for Nominations of Specific Drug/Biologic Product(s) That Could Be Brought Before the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-08

    ... HUMAN SERVICES Food and Drug Administration Request for Nominations of Specific Drug/Biologic Product(s) That Could Be Brought Before the Food and Drug Administration's Pediatric Subcommittee of the Oncologic Drugs Advisory Committee AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for...

  11. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... biological product. IV. Animal safety data. A. Individual active components. 1. Controlled studies. 2. Partially controlled or uncontrolled studies. B. Combinations of the individual active components. 1. Controlled studies. 2. Partially controlled or uncontrolled studies. C. Finished biological product....

  12. 75 FR 59729 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... for protective antigen-based anthrax vaccines for a post-exposure prophylaxis indication using...

  13. Strategies for optimizing algal biology for enhanced biomass production

    DOE PAGES

    Barry, Amanda N.; Starkenburg, Shawn R.; Sayre, Richard T.

    2015-02-02

    One of the most environmentally sustainable ways to produce high-energy density (oils) feed stocks for the production of liquid transportation fuels is from biomass. Photosynthetic carbon capture combined with biomass combustion (point source) and subsequent carbon capture and sequestration has also been proposed in the intergovernmental panel on climate change report as one of the most effective and economical strategies to remediate atmospheric greenhouse gases. To maximize photosynthetic carbon capture efficiency and energy-return-on-investment, we must develop biomass production systems that achieve the greatest yields with the lowest inputs. Numerous studies have demonstrated that microalgae have among the greatest potentials formore » biomass production. This is in part due to the fact that all alga cells are photoautotrophic, they have active carbon concentrating mechanisms to increase photosynthetic productivity, and all the biomass is harvestable unlike plants. All photosynthetic organisms, however, convert only a fraction of the solar energy they capture into chemical energy (reduced carbon or biomass). To increase aerial carbon capture rates and biomass productivity, it will be necessary to identify the most robust algal strains and increase their biomass production efficiency often by genetic manipulation. We review recent large-scale efforts to identify the best biomass producing strains and metabolic engineering strategies to improve aerial productivity. In addition, these strategies include optimization of photosynthetic light-harvesting antenna size to increase energy capture and conversion efficiency and the potential development of advanced molecular breeding techniques. To date, these strategies have resulted in up to twofold increases in biomass productivity.« less

  14. Large deviations and portfolio optimization

    NASA Astrophysics Data System (ADS)

    Sornette, Didier

    Risk control and optimal diversification constitute a major focus in the finance and insurance industries as well as, more or less consciously, in our everyday life. We present a discussion of the characterization of risks and of the optimization of portfolios that starts from a simple illustrative model and ends by a general functional integral formulation. A major item is that risk, usually thought of as one-dimensional in the conventional mean-variance approach, has to be addressed by the full distribution of losses. Furthermore, the time-horizon of the investment is shown to play a major role. We show the importance of accounting for large fluctuations and use the theory of Cramér for large deviations in this context. We first treat a simple model with a single risky asset that exemplifies the distinction between the average return and the typical return and the role of large deviations in multiplicative processes, and the different optimal strategies for the investors depending on their size. We then analyze the case of assets whose price variations are distributed according to exponential laws, a situation that is found to describe daily price variations reasonably well. Several portfolio optimization strategies are presented that aim at controlling large risks. We end by extending the standard mean-variance portfolio optimization theory, first within the quasi-Gaussian approximation and then using a general formulation for non-Gaussian correlated assets in terms of the formalism of functional integrals developed in the field theory of critical phenomena.

  15. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS... live organisms. Safeguards as herein provided shall be established by the research investigator or research sponsor to control disposition of all animals administered experimental biological products...

  16. 9 CFR 103.2 - Disposition of animals administered experimental biological products or live organisms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS... live organisms. Safeguards as herein provided shall be established by the research investigator or research sponsor to control disposition of all animals administered experimental biological products...

  17. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS General Provisions § 310.4 Biologics; products subject to license control. (a) If a drug has an...

  18. The Analysis of Cyanide and Its Breakdown Products in Biological Samples

    DTIC Science & Technology

    2010-01-01

    Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE The Analysis of Cyanide and Its Breakdown Products in Biological Samples 5a. CONTRACT... cyanide , thiocyanate, 2-amino-2-thiazoline-4-carboxylic acid (ATCA), chemical warfare agent, exposure, toxicology, analytical methods 16. SECURITY...ISSN: 1040-8347 print / 1547-6510 online DOI: 10.1080/10408340903535315 The Analysis of Cyanide and its Breakdown Products in Biological Samples Brian A

  19. Biological Methanol Production by a Type II Methanotroph Methylocystis bryophila.

    PubMed

    Patel, Sanjay K S; Mardina, Primata; Kim, Sang-Yong; Lee, Jung-Kul; Kim, In-Won

    2016-04-28

    Methane (CH₄) is the most abundant component in natural gas. To reduce its harmful environmental effect as a greenhouse gas, CH₄ can be utilized as a low-cost feed for the synthesis of methanol by methanotrophs. In this study, several methanotrophs were examined for their ability to produce methanol from CH₄; including Methylocella silvestris, Methylocystis bryophila, Methyloferula stellata, and Methylomonas methanica. Among these methanotrophs, M. bryophila exhibited the highest methanol production. The optimum process parameters aided in significant enhancement of methanol production up to 4.63 mM. Maximum methanol production was observed at pH 6.8, 30°C, 175 rpm, 100 mM phosphate buffer, 50 mM MgCl₂ as a methanol dehydrogenase inhibitor, 50% CH₄ concentration, 24 h of incubation, and 9 mg of dry cell mass ml(-1) inoculum load, respectively. Optimization of the process parameters, screening of methanol dehydrogenase inhibitors, and supplementation with formate resulted in significant improvements in methanol production using M. bryophila. This report suggests, for the first time, the potential of using M. bryophila for industrial methanol production from CH₄.

  20. 48 CFR 3401.404 - Class deviations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Class deviations. 3401.404 Section 3401.404 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.404 Class deviations. A class deviation from...

  1. 48 CFR 3401.404 - Class deviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Class deviations. 3401.404 Section 3401.404 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.404 Class deviations. A class deviation from...

  2. 48 CFR 3401.404 - Class deviations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Class deviations. 3401.404 Section 3401.404 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.404 Class deviations. A class deviation from...

  3. 48 CFR 3401.404 - Class deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Class deviations. 3401.404 Section 3401.404 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.404 Class deviations. A class deviation from...

  4. 48 CFR 3401.404 - Class deviations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Class deviations. 3401.404 Section 3401.404 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.404 Class deviations. A class deviation from...

  5. Synthetic biology tools for bioprospecting of natural products in eukaryotes.

    PubMed

    Unkles, Shiela E; Valiante, Vito; Mattern, Derek J; Brakhage, Axel A

    2014-04-24

    Filamentous fungi have the capacity to produce a battery of natural products of often unknown function, synthesized by complex metabolic pathways. Unfortunately, most of these pathways appear silent, many in intractable organisms, and their products consequently unidentified. One basic challenge is the difficulty of expressing a biosynthesis pathway for a complex natural product in a heterologous eukaryotic host. Here, we provide a proof-of concept solution to this challenge and describe how the entire penicillin biosynthesis pathway can be expressed in a heterologous host. The method takes advantage of a combination of improved yeast in vivo cloning technology, generation of polycistronic mRNA for the gene cluster under study, and an amenable and easily manipulated fungal host, i.e., Aspergillus nidulans. We achieve expression from a single promoter of the pathway genes to yield a large polycistronic mRNA by using viral 2A peptide sequences to direct successful cotranslational cleavage of pathway enzymes.

  6. Systems-Level Synthetic Biology for Advanced Biofuel Production

    SciTech Connect

    Ruffing, Anne; Jensen, Travis J.; Strickland, Lucas Marshall; Meserole, Stephen; Tallant, David

    2015-03-01

    Cyanobacteria have been shown to be capable of producing a variety of advanced biofuels; however, product yields remain well below those necessary for large scale production. New genetic tools and high throughput metabolic engineering techniques are needed to optimize cyanobacterial metabolisms for enhanced biofuel production. Towards this goal, this project advances the development of a multiple promoter replacement technique for systems-level optimization of gene expression in a model cyanobacterial host: Synechococcus sp. PCC 7002. To realize this multiple-target approach, key capabilities were developed, including a high throughput detection method for advanced biofuels, enhanced transformation efficiency, and genetic tools for Synechococcus sp. PCC 7002. Moreover, several additional obstacles were identified for realization of this multiple promoter replacement technique. The techniques and tools developed in this project will help to enable future efforts in the advancement of cyanobacterial biofuels.

  7. Perspectives and advances of biological H2 production in microorganisms.

    PubMed

    Rupprecht, Jens; Hankamer, Ben; Mussgnug, Jan H; Ananyev, Gennady; Dismukes, Charles; Kruse, Olaf

    2006-09-01

    The rapid development of clean fuels for the future is a critically important global challenge for two main reasons. First, new fuels are needed to supplement and ultimately replace depleting oil reserves. Second, fuels capable of zero CO2 emissions are needed to slow the impact of global warming. This review summarizes the development of solar powered bio-H2 production processes based on the conversion of photosynthetic products by fermentative bacteria, as well as using photoheterotrophic and photoautrophic organisms. The use of advanced bioreactor systems and their potential and limitations in terms of process design, efficiency, and cost are also briefly reviewed.

  8. Combination biological and microwave treatments of used rubber products

    DOEpatents

    Fliermans, Carl B.; Wicks, George G.

    2002-01-01

    A process and resulting product is provided in which a vulcanized solid particulate, such as vulcanized crumb rubber, has select chemical bonds altered by biotreatment with thermophillic microorganisms selected from natural isolates from hot sulfur springs. Following the biotreatment, microwave radiation is used to further treat the surface and to treat the bulk interior of the crumb rubber. The resulting combined treatments render the treated crumb rubber more suitable for use in new rubber formulations. As a result, larger loading levels and sizes of the treated crumb rubber can be used in new rubber mixtures and good properties obtained from the new recycled products.

  9. Similar biological medicinal products containing recombinant human growth hormone: European regulation.

    PubMed

    Pavlovic, Mira; Girardin, Elizabeth; Kapetanovic, Liliana; Ho, Kowid; Trouvin, Jean-Hugues

    2008-01-01

    The concept of similar biological medicinal products ('biosimilar' medicinal products) allows pharmaceutical companies to develop products based on an abridged dossier once the marketing protection of the 'reference' biological medicinal product has expired. A biosimilar medicinal product can be granted a marketing authorization provided that its similarity to a reference product is established in terms of quality, safety and efficacy (step-wise comparability exercise). A decision to launch a biosimilar medicinal product on the market is taken if it has a similar efficacy and comparable or better (less) immunogenicity than the chosen reference biological medicinal product. However, this decision is based on limited data and the comparability program may detect substantial differences in immunogenicity profiles but is likely incapable of detecting rare events. This is why clinical experience, through clinical trials and extensive pharmacovigilance programs, remains the most reliable way to assess the immunogenicity and tolerance profile of recombinant therapeutic proteins. Substitution of one biological medicinal product by a biosimilar medicinal product is not currently recommended before long-term clinical efficacy and safety have been acquired in all relevant populations. Here we review recent regulatory guidelines provided by EMEA and comment on the marketing authorizations and risk management plans of two recently approved biosimilar somatropins.

  10. Bovine mammary stem cells: Cell biology meets production agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  11. DISINFECTION BY-PRODUCT CONTROL THROUGH BIOLOGICAL FILTRATION

    EPA Science Inventory

    Disinfection by-product (DBP) control through biofiltration is defined as the removal of DBP precursor mateterial (PM) by bacteria attached to the filte nedia. The PM consists of dissolved organic matter (DOM) and is utilized by the filter bacteria as a substrate for cell mainten...

  12. Improvements in fermentative biological hydrogen production through metabolic engineering.

    PubMed

    Hallenbeck, Patrick C; Ghosh, Dipankar

    2012-03-01

    Replacement of fossil fuels with alternative energies is increasingly imperative in light of impending climate change and fossil fuel shortages. Biohydrogen has several potential advantages over other biofuels. Dark fermentation as a means of producing biohydrogen is attractive since a variety of readily available waste streams can be used. However, at present its practical application is prevented by the low yields obtained. Here the basic metabolisms leading to hydrogen production are outlined and current research to increase yields, either through modification of existing pathways, or by metabolic engineering to create new, higher yielding, pathways, is discussed. Inactivation of competing reactions and manipulation of culture conditions has lead to higher hydrogen yields, near those predicted by metabolic schemes. However, to be useful, hydrogen production must be increased beyond present limits. Several possibilities for surpassing those limits using metabolic engineering are presented.

  13. Time-ordered product expansions for computational stochastic system biology.

    PubMed

    Mjolsness, Eric

    2013-06-01

    The time-ordered product framework of quantum field theory can also be used to understand salient phenomena in stochastic biochemical networks. It is used here to derive Gillespie's stochastic simulation algorithm (SSA) for chemical reaction networks; consequently, the SSA can be interpreted in terms of Feynman diagrams. It is also used here to derive other, more general simulation and parameter-learning algorithms including simulation algorithms for networks of stochastic reaction-like processes operating on parameterized objects, and also hybrid stochastic reaction/differential equation models in which systems of ordinary differential equations evolve the parameters of objects that can also undergo stochastic reactions. Thus, the time-ordered product expansion can be used systematically to derive simulation and parameter-fitting algorithms for stochastic systems.

  14. Biological Utilization of Wood for Production of Chemicals and Foodstuffs.

    DTIC Science & Technology

    1981-03-01

    throughout the country for methionine. Rose (126) has shown dairy cows concluded that: (a) torula feeding trials. Feeding tests were that methionine should...correction for methionine in the and (b) the dried yeast is equal to cows , beef cattle, sheep, swine, and yeasts. An excess of methionine was soybean meal...168): peared to be preferred slightly by mo!asses. Wood molasses was con- dairy cows in production. cluded to be comparable to cane Ration Weight gain

  15. Biological Hydrogen Production Using Chloroform-treated Methanogenic Granules

    NASA Astrophysics Data System (ADS)

    Hu, Bo; Chen, Shulin

    In fermentative hydrogen production, the low-hydrogen-producing bacteria retention rate limits the suspended growth reactor productivity because of the long hydraulic retention time (HRT) required to maintain adequate bacteria population. Traditional bacteria immobilization methods such as calcium alginate entrapment have many application limitations in hydrogen fermentation, including limited duration time, bacteria leakage, cost, and so on. The use of chloroform-treated anaerobic granular sludge as immobilized hydrogen-producing bacteria in an immobilized hydrogen culture may be able to overcome the limitations of traditional immobilization methods. This paper reports the findings on the performance of fed-batch cultures and continuous cultures inoculated with chloroform-treated granules. The chloroform-treated granules were able to be reused over four fed-batch cultures, with pH adjustment. The upflow reactor packed with chloroform-treated granules was studied, and the HRT of the upflow reactor was found to be as low as 4 h without any decrease in hydrogen production yield. Initial pH and glucose concentration of the culture medium significantly influenced the performance of the reactor. The optimum initial pH of the culture medium was neutral, and the optimum glucose concentration of the culture medium was below 20 g chemical oxygen demand/L at HRT 4 h. This study also investigated the possibility of integrating immobilized hydrogen fermentation using chloroform-treated granules with immobilized methane production using untreated granular sludge. The results showed that the integrated batch cultures produced 1.01 mol hydrogen and 2 mol methane per mol glucose. Treating the methanogenic granules with chloroform and then using the treated granules as immobilized hydrogen-producing sludge demonstrated advantages over other immobilization methods because the treated granules provide hydrogen-producing bacteria with a protective niche, a long duration of an active

  16. Production and flocculating performance of sludge bioflocculant from biological sludge.

    PubMed

    Zhang, Xiuhong; Sun, Jie; Liu, Xiuxiu; Zhou, Jiti

    2013-10-01

    Excess biological sludge was utilized to prepared bioflocculant with hydrochloric acid. The prepared crude bioflocculant was purified and fractionally precipitated to attain four purified sludge bioflocculant defined as PSB1-4. The PSB-2 has higher flocculating rate for kaolin suspension than others. When the pH of the flocculation system ranged from 4.0 to 11.0 the flocculating rates of PSB-2 were over 96.0%. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectra showed that amino and hydroxyl groups were present in the bioflocculant molecules. More amine group existed in the bioflocculant PSB-2 relatively. The amino group was believed to play an important role in flocculation. The experiment of zeta potential measuring indicated that the charge neutralization contributed to flocculation process. Flocculating mechanism investigation reveals that the sludge bioflocculant caused kaolin suspension instability by means of charge neutralization firstly and then promoted the aggregation of suspension particles by adsorption and bridge.

  17. 21 CFR 510.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed in full conformance with the animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21 U.S.C. 151 et seq. )...

  18. 21 CFR 510.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed in full conformance with the animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21 U.S.C. 151 et seq. )...

  19. 78 FR 65904 - Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ...(D) Immune Globulin and Hepatitis B Immune Globulin; Coagulation Factor VIIa (Recombinant); and..., or mitigate shortages of these products. b. Vaccines. We are proposing to apply section 506C of the FD&C Act to all biological products, including vaccines. Under section 506C(i)(3)(B) of the FD&C...

  20. Pharmacogenomic Biomarkers: an FDA Perspective on Utilization in Biological Product Labeling.

    PubMed

    Schuck, Robert N; Grillo, Joseph A

    2016-05-01

    Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities. Since pharmacogenomic biomarker information can help inform drug dosing, efficacy, and safety, pharmacogenomic data are critically reviewed by FDA staff to ensure effective use of pharmacogenomic strategies in drug development and appropriate incorporation into product labels. Pharmacogenomic information may be provided in drug or biological product labeling to inform health care providers about the impact of genotype on response to a drug through description of relevant genomic markers, functional effects of genomic variants, dosing recommendations based on genotype, and other applicable genomic information. The format and content of labeling for biologic drugs will generally follow that of small molecule drugs; however, there are notable differences in pharmacogenomic information that might be considered useful for biologic drugs in comparison to small molecule drugs. Furthermore, the rapid entry of biologic drugs for treatment of rare genetic diseases and molecularly defined subsets of common diseases will likely lead to increased use of pharmacogenomic information in biologic drug labels in the near future. In this review, we outline the general principles of therapeutic product labeling and discuss the utilization of pharmacogenomic information in biologic drug labels.

  1. Metabolic engineering for production of biorenewable fuels and chemicals: contributions of synthetic biology.

    PubMed

    Jarboe, Laura R; Zhang, Xueli; Wang, Xuan; Moore, Jonathan C; Shanmugam, K T; Ingram, Lonnie O

    2010-01-01

    Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use of metabolic engineering and synthetic biology in biocatalyst engineering for biorenewable fuels and chemicals production, such as ethanol, butanol, acetate, lactate, succinate, alanine, and xylitol. We also examine the existing challenges in this area and discuss strategies for improving biocatalyst tolerance to chemical inhibitors.

  2. Metabolic Engineering for Production of Biorenewable Fuels and Chemicals: Contributions of Synthetic Biology

    PubMed Central

    Jarboe, Laura R.; Zhang, Xueli; Wang, Xuan; Moore, Jonathan C.; Shanmugam, K. T.; Ingram, Lonnie O.

    2010-01-01

    Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use of metabolic engineering and synthetic biology in biocatalyst engineering for biorenewable fuels and chemicals production, such as ethanol, butanol, acetate, lactate, succinate, alanine, and xylitol. We also examine the existing challenges in this area and discuss strategies for improving biocatalyst tolerance to chemical inhibitors. PMID:20414363

  3. Models of risk assessments for biologicals or related products in the European Union.

    PubMed

    Moos, M

    1995-12-01

    In the context of veterinary biologicals, environmental risk assessment means the evaluation of the risk to human health and the environment (which includes plants and animals) connected with the release of such products. The following categories or types of veterinary biologicals can be distinguished: non-genetically modified organisms (non-GMOs) (inactivated/live) GMOs (inactivated/live) carrier products related products (e.g. non-specific "inducers'). Suitable models used in risk assessment for these products should aim to identify all possible adverse effects. A good working model should lead, at least, to a qualitative judgement on the environmental risk of the biological product (e.g. negligible, low, medium, severe, unacceptable). Quantifiable outcomes are rare; therefore, the producer of a biological product and the European control authorities should accept only models which are based on testable points and which are relevant to the type of product and its instructions for use. In view of animal welfare aspects, models working without animals should be preferred. In recent years, some of these methods have been integrated into safety tests described in European Union Directives and in monographs of the European Pharmacopoeia. By reviewing vaccine/registration problems (e.g. Aujeszky's disease live vaccine for pigs, and vaccinia-vectored rabies vaccine), several models used in risk assessment are demonstrated and discussed.

  4. The Production Processes and Biological Effects of Intravenous Immunoglobulin

    PubMed Central

    Barahona Afonso, Ana Filipa; João, Cristina Maria Pires

    2016-01-01

    Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it can stimulate certain sub-populations of T cells with effects on T cell proliferation, survival and function in situations of lymphopenia. These results present a novel and considerable impact of intravenous immunoglobulin (IVIg) treatment in situations of severe lymphopenia, a situation that can occur in cancer patients after chemo and radiotherapy treatments. In this review paper the established and experimental role of polyclonal immunoglobulin will be presented and discussed as well as the manufacturing processes involved in their production. PMID:27005671

  5. Fermentative production of butanol: Perspectives on synthetic biology.

    PubMed

    Nanda, Sonil; Golemi-Kotra, Dasantila; McDermott, John C; Dalai, Ajay K; Gökalp, Iskender; Kozinski, Janusz A

    2017-03-09

    Apprehensions relating to global warming, climate change, pollution, rising energy demands as well as fluctuating crude oil prices and supply are leading to a shift in global interest to find suitable alternatives to fossil fuels. This review aims to highlight the many different facets of butanol as an advanced next-generation transportation biofuel. Butanol has fuel properties almost on a par with gasoline, such as high energy content, low vapor pressure, non-hygroscopic nature, less volatility, flexible fuel blends and high octane number. The paper reviews some recent advances in acetone-butanol-ethanol fermentation with special emphasis on the primary challenges encountered in butanol fermentation, including butanol toxicity, solvent intolerance and bacteriophage contamination. The mechanisms for butanol recovery techniques have been covered along with their benefits and limitations. A comprehensive discussion of genetic and metabolic engineering of butanol-producing microorganisms is made for the prospective development of industrially-relevant strains that can overcome the technical challenges involved in efficient butanol production.

  6. Occurrence, pathways and implications of biological production of reactive oxygen species in natural waters

    NASA Astrophysics Data System (ADS)

    Zhang, T.; Hansel, C. M.; Voelker, B. M.; Lamborg, C. H.

    2014-12-01

    Reactive oxygen species (ROS), such as superoxide (O2-) and hydrogen peroxide (H2O2) play a critical role in the redox cycling of both toxic (e.g., Hg) and nutrient (e.g., Fe) metals. Despite the discovery of extracellular ROS production in various microbial cultures, including fungi, algae and bacteria, photo-dependent processes are generally considered as the predominant source of ROS in natural waters. Here we show that biological production of ROS is ubiquitous and occurs at a significant rate in freshwater and brackish water environments. Water samples were collected from three freshwater and one brackish water ponds in Cape Cod, Massachusetts, USA, periodically from 2012 to 2014. Production of O2- and H2O2 were measured in dark incubations of natural water using a chemiluminescent and a colorimetric probe, respectively. Rates of biological ROS production were obtained by comparing unfiltered with 0.2-μm filtered samples. The role of biological activity in ROS production was confirmed by the cessation of ROS production upon addition of formaldehyde. In surface water, production rates of O2- ranged from undetectable to 96.0 ± 30.0 nmol L-1 h-1, and production rates of H2O2 varied between 9.9 ± 1.3 nmol L-1 h-1 and 145.6 ± 11.2 nmol L-1 h-1. The maximum production rates of both ROS were observed in mid-summer 2013, which coincides with peak biological activity. ROS production in the water from aphotic zone was greater than in the water from photic zone. Thus, non-light dependent biological processes are likely the major contributors to ROS production in this system. Moreover, O2- production appeared to be enhanced by NADH and inhibited by proteinase-K, suggesting the possible involvement of NADH oxidoreductases in this process. The potential role of different microbial communities in ROS production, and the implications of biological ROS production for mercury speciation will also be discussed.

  7. 10 CFR 961.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Deviations. 961.4 Section 961.4 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.4 Deviations. Requests for authority to deviate from this part shall be submitted in writing...

  8. 10 CFR 961.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Deviations. 961.4 Section 961.4 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.4 Deviations. Requests for authority to deviate from this part shall be submitted in writing...

  9. 10 CFR 961.4 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Deviations. 961.4 Section 961.4 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.4 Deviations. Requests for authority to deviate from this part shall be submitted in writing...

  10. 10 CFR 961.4 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Deviations. 961.4 Section 961.4 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.4 Deviations. Requests for authority to deviate from this part shall be submitted in writing...

  11. 14 CFR 1260.7 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Deviations. 1260.7 Section 1260.7 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General § 1260.7 Deviations. (a) A deviation is required for any of the following: (1) When a...

  12. 14 CFR 1260.7 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Deviations. 1260.7 Section 1260.7 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General § 1260.7 Deviations. (a) A deviation is required for any of the following: (1) When a...

  13. 14 CFR 1260.7 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Deviations. 1260.7 Section 1260.7 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General § 1260.7 Deviations. (a) A deviation is required for any of the following: (1) When a...

  14. 14 CFR § 1260.7 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Deviations. § 1260.7 Section § 1260.7 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General § 1260.7 Deviations. (a) A deviation is required for any of the following: (1) When a...

  15. 14 CFR 1260.7 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Deviations. 1260.7 Section 1260.7 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General § 1260.7 Deviations. (a) A deviation is required for any of the following: (1) When a...

  16. Introducing the Mean Absolute Deviation "Effect" Size

    ERIC Educational Resources Information Center

    Gorard, Stephen

    2015-01-01

    This paper revisits the use of effect sizes in the analysis of experimental and similar results, and reminds readers of the relative advantages of the mean absolute deviation as a measure of variation, as opposed to the more complex standard deviation. The mean absolute deviation is easier to use and understand, and more tolerant of extreme…

  17. 10 CFR 602.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Deviations. 602.4 Section 602.4 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS EPIDEMIOLOGY AND OTHER HEALTH STUDIES FINANCIAL ASSISTANCE PROGRAM § 602.4 Deviations. (a) Single-case deviations from this part may be authorized in writing by...

  18. 48 CFR 3401.403 - Individual deviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Individual deviations. 3401.403 Section 3401.403 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.403 Individual deviations. An...

  19. 48 CFR 3401.403 - Individual deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Individual deviations. 3401.403 Section 3401.403 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.403 Individual deviations. An...

  20. 48 CFR 3401.403 - Individual deviations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Individual deviations. 3401.403 Section 3401.403 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.403 Individual deviations. An...

  1. 48 CFR 3401.403 - Individual deviations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Individual deviations. 3401.403 Section 3401.403 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.403 Individual deviations. An...

  2. 48 CFR 3401.403 - Individual deviations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Individual deviations. 3401.403 Section 3401.403 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.403 Individual deviations. An...

  3. 10 CFR 602.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Deviations. 602.4 Section 602.4 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS EPIDEMIOLOGY AND OTHER HEALTH STUDIES FINANCIAL ASSISTANCE PROGRAM § 602.4 Deviations. (a) Single-case deviations from this part may be authorized in writing by...

  4. 10 CFR 961.4 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Deviations. 961.4 Section 961.4 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.4 Deviations. Requests for authority to deviate from this part shall be submitted in writing...

  5. 48 CFR 2801.404 - Class deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Class deviations. 2801.404 Section 2801.404 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE General DEPARTMENT OF JUSTICE ACQUISITION REGULATIONS SYSTEM Deviations From the FAR and JAR 2801.404 Class deviations....

  6. 48 CFR 2901.404 - Class deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Class deviations. 2901.404 Section 2901.404 Federal Acquisition Regulations System DEPARTMENT OF LABOR GENERAL DEPARTMENT OF LABOR ACQUISITION REGULATION SYSTEM Deviations From the FAR and DOLAR 2901.404 Class deviations. (a) The...

  7. Recent advances in endophytic exopolysaccharides: Production, structural characterization, physiological role and biological activity.

    PubMed

    Liu, Jun; Wang, Xingchi; Pu, Huimin; Liu, Shuang; Kan, Juan; Jin, Changhai

    2017-02-10

    Endophytes are microorganisms that colonize living, internal tissues of plants without causing any immediate, overt negative effects. In recent years, both endophytic bacteria and fungi have been demonstrated to be excellent exopolysaccharides (EPS) producers. This review focuses on the recent advances in EPS produced by endophytes, including its production, isolation and purification, structural characterization, physiological role and biological activity. In general, EPS production is influenced by media components and cultivation conditions. The structures of purified EPS range from linear homopolysaccharides to highly branched heteropolysaccharides. These structurally novel EPS not only play important roles in plant-endophyte interactions; but also exhibit several biological functions, such as antioxidant, antitumor, anti-inflammatory, anti-allergic and prebiotic activities. In order to utilize endophytic EPS on an industrial scale, both yield and productivity enhancement strategies are required at several levels. Besides, the exact mechanisms on the physiological roles and biological functions of EPS should be elucidated in future.

  8. Effects of variable winds on biological productivity on continental shelves in coastal upwelling systems

    NASA Astrophysics Data System (ADS)

    Botsford, Louis W.; Lawrence, Cathryn A.; Dever, Edward P.; Hastings, Alan; Largier, John

    2006-12-01

    The production and distribution of biological material in wind-driven coastal upwelling systems are of global importance, yet they remain poorly understood. Production is frequently presumed to be proportional to upwelling rate, yet high winds can lead to advective losses from continental shelves, where many species at higher trophic levels reside. An idealized mixed-layer conveyor (MLC) model of biological production from constant upwelling winds demonstrated previously that the amount of new production available to shelf species increased with upwelling at low winds, but declined at high winds [Botsford, L.W., Lawrence, C.A., Dever, E.P., Hastings, A., Largier, J., 2003. Wind strength and biological productivity in upwelling systems: an idealized study. Fisheries Oceanography 12, 245-259]. Here we analyze the response of this model to time-varying winds for parameter values and observed winds from the Wind Events and Shelf Transport (WEST) study region. We compare this response to the conventional view that the results of upwelling are proportional to upwelled volume. Most new production per volume upwelled available to shelf species occurs following rapid increases in shelf transit time due to decreases in wind (i.e. relaxations). However, on synoptic, event time-scales shelf production is positively correlated with upwelling rate. This is primarily due to the effect of synchronous periods of low values in these time series, paradoxically due to wind relaxations. On inter-annual time-scales, computing model production from wind forcing from 20 previous years shows that these synchronous periods of low values have little effect on correlations between upwelling and production. Comparison of model production from 20 years of wind data over a range of shelf widths shows that upwelling rate will predict biological production well only in locations where cross-shelf transit times are greater than the time required for phytoplankton or zooplankton production. For

  9. Interventions for dissociated vertical deviation

    PubMed Central

    Hatt, Sarah R; Wang, Xue; Holmes, Jonathan M

    2015-01-01

    Background The term “strabismus” describes misalignment of the eyes. One or both eyes may deviate inward, outward, upward, or downward. Dissociated vertical deviation (DVD) is a well-recognized type of upward drifting of one or both eyes, which can occur in children or adults. DVD often develops in the context of infantile- or childhood-onset horizontal strabismus, either esotropia (inward-turning) or exotropia (outward-turning). For some individuals, DVD remains controlled and can only be detected during clinical testing. For others, DVD becomes spontaneously “manifest” and the eye drifts up of its own accord. Spontaneously manifest DVD can be difficult to control and often causes psychosocial concerns. Traditionally, DVD has been thought to be asymptomatic, although some individuals have double vision. More recently it has been suggested that individuals with DVD may also suffer from eyestrain. Treatment for DVD may be sought either due to psychosocial concerns or because of these symptoms. The standard treatment for DVD is a surgical procedure; non-surgical treatments are offered less commonly. Although there are many studies evaluating different management options for the correction of DVD, a lack of clarity remains regarding which treatments are most effective. Objectives The objective of this review was to determine the effectiveness and safety of various surgical and non-surgical interventions in randomized controlled trials of participants with DVD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), PubMed (1948 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to August 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 3

  10. Bioinformatics for the synthetic biology of natural products: integrating across the Design–Build–Test cycle

    PubMed Central

    Currin, Andrew; Jervis, Adrian J.; Rattray, Nicholas J. W.; Swainston, Neil; Yan, Cunyu; Breitling, Rainer

    2016-01-01

    Covering: 2000 to 2016 Progress in synthetic biology is enabled by powerful bioinformatics tools allowing the integration of the design, build and test stages of the biological engineering cycle. In this review we illustrate how this integration can be achieved, with a particular focus on natural products discovery and production. Bioinformatics tools for the DESIGN and BUILD stages include tools for the selection, synthesis, assembly and optimization of parts (enzymes and regulatory elements), devices (pathways) and systems (chassis). TEST tools include those for screening, identification and quantification of metabolites for rapid prototyping. The main advantages and limitations of these tools as well as their interoperability capabilities are highlighted. PMID:27185383

  11. The Standard Deviation of Launch Vehicle Environments

    NASA Technical Reports Server (NTRS)

    Yunis, Isam

    2005-01-01

    Statistical analysis is used in the development of the launch vehicle environments of acoustics, vibrations, and shock. The standard deviation of these environments is critical to accurate statistical extrema. However, often very little data exists to define the standard deviation and it is better to use a typical standard deviation than one derived from a few measurements. This paper uses Space Shuttle and expendable launch vehicle flight data to define a typical standard deviation for acoustics and vibrations. The results suggest that 3dB is a conservative and reasonable standard deviation for the source environment and the payload environment.

  12. 9 CFR 381.308 - Deviations in processing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY...) must be handled according to: (1)(i) A HACCP plan for canned product that addresses hazards associated... (d) of this section. (c) (d) Procedures for handling process deviations where the HACCP plan...

  13. 9 CFR 381.308 - Deviations in processing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... shall maintain full records regarding the handling of each deviation. Such records shall include, at a minimum, the appropriate processing and production records, a full description of the corrective actions... establishment shall: (i) Immediately reprocess the product using the full process schedule; or, (ii) Use...

  14. 9 CFR 381.308 - Deviations in processing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... shall maintain full records regarding the handling of each deviation. Such records shall include, at a minimum, the appropriate processing and production records, a full description of the corrective actions... establishment shall: (i) Immediately reprocess the product using the full process schedule; or, (ii) Use...

  15. A probabilistic model for risk assessment of residual host cell DNA in biological products.

    PubMed

    Yang, Harry; Zhang, Lanju; Galinski, Mark

    2010-04-26

    Biological products such as viral vaccines manufactured in cells contain residual DNA derived from host cell substrates used in production. It is theoretically possible that the residual DNA could transmit activated oncogenes and/or latent infectious viral genomes to subjects receiving the product, and induce oncogenic or infective events. A probabilistic model to estimate the risks due to residual DNA is proposed. The model takes account of enzyme inactivation process. It allows for more accurate risk assessment when compared to methods currently in use. An application of the method to determine safety factor of a vaccine product is provided.

  16. Ocean glider observations of iceberg-enhanced biological production in the northwestern Weddell Sea

    NASA Astrophysics Data System (ADS)

    Biddle, Louise C.; Kaiser, Jan; Heywood, Karen J.; Thompson, Andrew F.; Jenkins, Adrian

    2015-01-01

    Icebergs affect local biological production around Antarctica. We used an ocean glider to observe the effects of a large iceberg that was advected by the Antarctic Slope Current along the continental slope in the northwestern Weddell Sea in early 2012. The high-resolution glider data reveal a pronounced effect of the iceberg on ocean properties, with oxygen concentrations of (13 ± 4) μmol kg-1 higher than levels in surrounding waters, which are most likely due to positive net community production. This response was confined to three areas of water in the direct vicinity of the iceberg track, each no larger than 2 km2. Our findings suggest that icebergs have an impact on Antarctic production presumably through local micronutrient injections, on a scale smaller than typical satellite observations of biological production in the Southern Ocean.

  17. New approaches to estimation of peat deposits for production of biologically active compounds

    NASA Astrophysics Data System (ADS)

    Stepchenko, L. M.; Yurchenko, V. I.; Krasnik, V. G.; Syedykh, N. J.

    2009-04-01

    It is known, that biologically active preparations from peat increase animals productivity as well as resistance against stress-factors and have adaptogeneous, antioxidant, immunomodulative properties. Optymal choice of peat deposits for the production of biologically active preparations supposes the detailed comparative analysis of peat properties from different deposits. For this the cadastre of peat of Ukraine is developed in the humic substances laboratory named after prof. Khristeva L.A. (Dnipropetrovsk Agrarian University, Ukraine). It based on the research of its physical and chemical properties, toxicity and biological activity, and called Biocadastre. The Biocadastre is based on the set of parameters, including the descriptions of physical and chemical properties (active acidity, degree of decomposition, botanical composition etc.), toxicity estimation (by parabyotyc, infusorial, inhibitor and other tests), biological activity indexes (growth-promoting, antioxidative, adaptogeneous, immunomodulative antistress and other actions). The blocks of Biocadastre indexes are differentiated, taking into account their use for creation the preparations for vegetable, animals and microorganisms. The Biocadastre will allow to choose the peat deposits, most suitable for the production of different biologically active preparations, both wide directed and narrow spectrum of action, depending on application fields (medicine, agriculture, veterinary medicine, microbiological industry, balneology, cosmetology).

  18. Synthetic biology: tools to design microbes for the production of chemicals and fuels.

    PubMed

    Seo, Sang Woo; Yang, Jina; Min, Byung Eun; Jang, Sungho; Lim, Jae Hyung; Lim, Hyun Gyu; Kim, Seong Cheol; Kim, Se Yeon; Jeong, Jun Hong; Jung, Gyoo Yeol

    2013-11-01

    The engineering of biological systems to achieve specific purposes requires design tools that function in a predictable and quantitative manner. Recent advances in the field of synthetic biology, particularly in the programmable control of gene expression at multiple levels of regulation, have increased our ability to efficiently design and optimize biological systems to perform designed tasks. Furthermore, implementation of these designs in biological systems highlights the potential of using these tools to build microbial cell factories for the production of chemicals and fuels. In this paper, we review current developments in the design of tools for controlling gene expression at transcriptional, post-transcriptional and post-translational levels, and consider potential applications of these tools.

  19. Production, Isotopic Composition, and Atmospheric Fate of Biologically Produced Nitrous Oxide

    NASA Astrophysics Data System (ADS)

    Stein, Lisa Y.

    The anthropogenic production of greenhouse gases and their consequent effects on global climate have garnered international attention for years. A remaining challenge facing scientists is to unambiguously quantify both sources and sinks of targeted gases. Microbiological metabolism accounts for the largest source of nitrous oxide (N2O), mostly due to global conversion of land for agriculture and massive usage of nitrogen-based fertilizers. A most powerful method for characterizing the sources of N2O lies in its multi-isotope signature. This review summarizes mechanisms that lead to biological N2O production and how discriminate placement of 15N into molecules of N2O occurs. Through direct measurements and atmospheric modeling, we can now place a constraint on the isotopic composition of biological sources of N2O and trace its fate in the atmosphere. This powerful interdisciplinary combination of biology and atmospheric chemistry is rapidly advancing the closure of the global N2O budget.

  20. 76 FR 79203 - Prospective Grant of Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... Biological Products for Swine Influenza Vaccines AGENCY: National Institutes of Health, Public Health Service... methods of use as Veterinary Influenza Vaccines. Sustained outbreaks of highly pathogenic influenza in animals increase the risk of reassortment and adaption to humans. This technology describes DNA...

  1. 9 CFR 105.3 - Notices re: worthless, contaminated, dangerous, or harmful biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... veterinary biological product at each location in the distribution channel known to the manufacturer... licensee to stop distribution and sale of the serial. (c) When notified to stop distribution and sale of a..., distribution, sale, barter, exchange, shipment, or importation of the affected serial(s) or subserial(s) of...

  2. 76 FR 66235 - Bar Code Technologies for Drugs and Biological Products; Retrospective Review Under Executive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-26

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 201 and 610 Bar Code Technologies for Drugs and Biological Products; Retrospective Review Under Executive Order 13563; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and...

  3. 75 FR 61497 - Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    .... Most biological products are produced in a living system such as a microorganism, or plant or animal...-mail address; and a phone number. III. Attendance and Registration The FDA Conference Center at the..., and phone number. Those without e-mail access may register by contacting Sandra Benton (see...

  4. Do biological medicinal products pose a risk to the environment?: a current view on ecopharmacovigilance.

    PubMed

    Kühler, Thomas C; Andersson, Mikael; Carlin, Gunnar; Johnsson, Ann; Akerblom, Lennart

    2009-01-01

    The occurrence of active pharmaceutical substances in the environment is of growing concern. The vast majority of the compounds in question are of low molecular weight, intended for oral use and designed to tolerate, for example, the digestive enzymes in the upper alimentary tract, the harsh milieus found in the acidic stomach, or the microbe rich intestine. Accordingly, these xenobiotic compounds may, due to their inherent biological activity, constitute a risk to the environment. Biological medicinal products, for example recombinant human insulin or monoclonal antibodies, however, are different. They are primarily made up of oligomers or polymers of amino acids, sugars or nucleotides and are thus readily metabolized. They are therefore generally not considered to pose any risk to the environment. Certain classes of biological medicinal products, however, are associated with specific safety issues. Genetically modified organisms as vectors in vaccines or in gene therapy products have attracted much attention in this regard. Issues include the degree of attenuation of the live recombinant vaccine, replication restrictions of the vaccine vector, alteration of the host and tissue tropism of the vector, the possibility of reversion to virulence, and risk to the ecosystem. In this review we discuss the fate and the potential environmental impact of biological medicinal products following clinical use from an ecopharmacovigilance point of view, and review relevant policy documents and regulatory statements.

  5. A downstream process for production of a viable and stable Bacillus cereus aquaculture biological agent.

    PubMed

    Lalloo, Rajesh; Maharajh, Dheepak; Görgens, Johann; Gardiner, Neil

    2010-03-01

    Biological products offer advantages over chemotherapeutics in aquaculture. Adoption in commercial application is lacking due to limitations in process and product development that address key end user product requirements such as cost, efficacy, shelf life and convenience. In previous studies, we have reported on the efficacy, physiological robustness and low-cost spore production of a Bacillus cereus isolate (NRRL 100132). This study examines the development of suitable spore recovery, drying, formulation and tablet production from the fermentation product. Key criteria used for such downstream process unit evaluation included spore viability, recovery, spore balance, spore re-germination, product intermediate stability, end product stability and efficacy. A process flow sheet comprising vertical tube centrifugation, fluidised bed agglomeration and tablet pressing yielded a suitable product. The formulation included corn steep liquor and glucose to enhance subsequent spore regermination. Viable spore recovery and spore balance closure across each of the process units was high (>70% and >99% respectively), with improvement in recovery possible by adoption of continuous processing at large scale. Spore regermination was 97%, whilst a product half-life in excess of 5 years was estimated based on thermal resistance curves. The process resulted in a commercially attractive product and suitable variable cost of production.

  6. Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity

    PubMed Central

    Turner, David P.

    2015-01-01

    Low income, poor diet, obesity and a lack of exercise are inter-related lifestyle factors that can profoundly alter our biological make-up to increase cancer risk, growth and development. We recently reported a potential mechanistic link between carbohydrate derived metabolites and cancer which may provide a biological consequence of lifestyle that can directly impact tumor biology. Advanced glycation end-products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism. Failure to remove these highly reactive metabolites can lead to protein damage, aberrant cell signaling, increased stress responses, and decreased genetic fidelity. Critically, AGE accumulation is also directly affected by our lifestyle choices and shows a race specific, tumor dependent pattern of accumulation in cancer patients. This review will discuss the contribution of AGEs to the cancer phenotype with a particular emphasis on their biological links with the socioeconomic and environmental risk factors that drive cancer disparity. Given the potential benefits of lifestyle changes and the potential biological role of AGEs in promoting cancer, opportunities exist for collaborations impacting basic, translational, epidemiological and cancer prevention initiatives. PMID:25920350

  7. Integrated catalytic wet air oxidation and biological treatment of wastewater from Vitamin B 6 production

    NASA Astrophysics Data System (ADS)

    Kang, Jianxiong; Zhan, Wei; Li, Daosheng; Wang, Xiaocong; Song, Jing; Liu, Dongqi

    This study investigated the feasibility of coupling a catalytic wet air oxidation (CWAO), with CuO/Al 2O 3 as catalyst, and an anaerobic/aerobic biological process to treat wastewater from Vitamin B 6 production. Results showed that the CWAO enhanced the biodegradability (BOD 5/COD) from 0.10 to 0.80. The oxidized effluents with COD of 10,000 mg l -1 was subjected to subsequent continuous anaerobic/aerobic oxidation, and 99.3% of total COD removal was achieved. The quality of the effluent obtained met the discharge standards of water pollutants for pharmaceutical industry Chemical Synthesis Products Category (GB21904-2008), and thereby it implies that the integrated CWAO and anaerobic/aerobic biological treatment may offer a promising process to treat wastewater from Vitamin B 6 production.

  8. What controls biological productivity in coastal upwelling systems? Insights from a comparative modeling study

    NASA Astrophysics Data System (ADS)

    Lachkar, Z.; Gruber, N.

    2011-06-01

    The magnitude of the biological productivity in Eastern Boundary Upwelling Systems (EBUS) is traditionally viewed as directly reflecting the upwelling intensity. Yet, different EBUS show different sensitivities of productivity to upwelling-favorable winds (Carr and Kearns, 2003). Here, using a comparative modeling study of the California Current System (California CS) and Canary Current System (Canary CS), we show how physical and environmental factors, such as light, temperature and cross-shore circulation modulate the response of biological productivity to upwelling strength. To this end, we made a series of eddy-resolving simulations of the California CS and Canary CS using the Regional Ocean Modeling System (ROMS), coupled to a nitrogen based Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD) ecosystem model. We find the nutrient content of the euphotic zone to be 20 % smaller in the Canary CS relative to the California CS. Yet, the biological productivity is 50 % smaller in the latter. This is due to: (1) a faster nutrient-replete growth in the Canary CS relative to the California CS, related to a more favorable light and temperature conditions in the Canary CS, and (2) the longer nearshore water residence times in the Canary CS which lead to larger buildup of biomass in the upwelling zone, thereby enhancing the productivity. The longer residence times in the Canary CS appear to be associated with the wider continental shelves and the lower eddy activity characterizing this upwelling system. This results in a weaker offshore export of nutrients and organic matter, thereby increasing local nutrient recycling and enhancing the coupling between new and export production in the Northwest African system. Our results suggest that climate change induced perturbations such as upwelling favorable wind intensification might lead to contrasting biological responses in the California CS and the Canary CS, with major implications for the biogeochemical cycles and fisheries

  9. New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation.

    PubMed

    Baud, Matthias G J; Leiser, Thomas; Meyer-Almes, Franz-Josef; Fuchter, Matthew J

    2011-02-07

    New synthetic routes towards the natural product psammaplin A were developed with the particular view to preparing diverse analogues for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A analogues not accessible via currently reported methods. Preliminary biological studies revealed these compounds to be the most potent non peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our synthetic analogues show class I selectivity in vitro, an important feature for the design and synthesis of future isoform selective inhibitors.

  10. From systems biology to fuel--Chlamydomonas reinhardtii as a model for a systems biology approach to improve biohydrogen production.

    PubMed

    Rupprecht, Jens

    2009-06-01

    With economic wealth the need for energy is rising. Hence we are facing two problems: to satisfy the increasing energy demand and concomitantly deliver emission-free energy to avoid global warming. The process of photosynthesis offers a natural and highly efficient method to produce emission-neutral biofuels. However, using higher plants for such purposes causes several problems which are difficult to overcome and includes competition with food producing agriculture in terms of arable land, the need for fresh water, low process efficiency and the application of energy-intensive fertilizer in order to enhance growth performance. Photosynthetic microorganisms and, in particular, microalgae offer an alternative approach. In this case production sites in photo-bioreactors can be located on cheap, rural land and the organisms can be cultured in sea water rather than fresh water. However microorganisms are not naturally adapted as efficient producers of biofuels. Due to the complex regulatory network and mutual interaction of physiological processes and organelles, identifying the optimal production strategy is impossible without a greater understanding of the complex interplay of all cellular processes. Systems biology has emerged recently as a discipline to gain an understanding of these networks and their translation into a mathematical in silico model. An in silico model allows simulating optimization steps and, therefore, provides a useful method to identify targets for directed genetic/physiological modification to optimize the system for a biotechnological approach.

  11. Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels.

    PubMed

    Lee, Sung Kuk; Chou, Howard; Ham, Timothy S; Lee, Taek Soon; Keasling, Jay D

    2008-12-01

    The ability to generate microorganisms that can produce biofuels similar to petroleum-based transportation fuels would allow the use of existing engines and infrastructure and would save an enormous amount of capital required for replacing the current infrastructure to accommodate biofuels that have properties significantly different from petroleum-based fuels. Several groups have demonstrated the feasibility of manipulating microbes to produce molecules similar to petroleum-derived products, albeit at relatively low productivity (e.g. maximum butanol production is around 20 g/L). For cost-effective production of biofuels, the fuel-producing hosts and pathways must be engineered and optimized. Advances in metabolic engineering and synthetic biology will provide new tools for metabolic engineers to better understand how to rewire the cell in order to create the desired phenotypes for the production of economically viable biofuels.

  12. Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels

    SciTech Connect

    Kuk Lee, Sung; Chou, Howard; Ham, Timothy S.; Soon Lee, Taek; Keasling, Jay D.

    2009-12-02

    The ability to generate microorganisms that can produce biofuels similar to petroleum-based transportation fuels would allow the use of existing engines and infrastructure and would save an enormous amount of capital required for replacing the current infrastructure to accommodate biofuels that have properties significantly different from petroleum-based fuels. Several groups have demonstrated the feasibility of manipulating microbes to produce molecules similar to petroleum-derived products, albeit at relatively low productivity (e.g. maximum butanol production is around 20 g/L). For cost-effective production of biofuels, the fuel-producing hosts and pathways must be engineered and optimized. Advances in metabolic engineering and synthetic biology will provide new tools for metabolic engineers to better understand how to rewire the cell in order to create the desired phenotypes for the production of economically viable biofuels.

  13. 10 CFR 609.18 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Deviations. 609.18 Section 609.18 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS LOAN GUARANTEES FOR PROJECTS THAT EMPLOY INNOVATIVE TECHNOLOGIES § 609.18 Deviations. To the extent that such requirements are not specified by the Act or...

  14. 34 CFR 74.4 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Deviations. 74.4 Section 74.4 Education Office of the Secretary, Department of Education ADMINISTRATION OF GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 74.4 Deviations. The Secretary,...

  15. 34 CFR 74.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Deviations. 74.4 Section 74.4 Education Office of the Secretary, Department of Education ADMINISTRATION OF GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 74.4 Deviations. The Secretary,...

  16. 34 CFR 74.4 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Deviations. 74.4 Section 74.4 Education Office of the Secretary, Department of Education ADMINISTRATION OF GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 74.4 Deviations. The Secretary,...

  17. 34 CFR 74.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Deviations. 74.4 Section 74.4 Education Office of the Secretary, Department of Education ADMINISTRATION OF GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 74.4 Deviations. The Secretary,...

  18. 34 CFR 74.4 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Deviations. 74.4 Section 74.4 Education Office of the Secretary, Department of Education ADMINISTRATION OF GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 74.4 Deviations. The Secretary,...

  19. Alternating Skew Deviation from Traumatic Intracranial Hypotension

    PubMed Central

    Moster, Stephen J.; Moster, Mark L.

    2014-01-01

    Abstract A 56-year-old woman developed progressive headache, mental status changes, and diplopia after trauma. She was diagnosed with alternating skew deviation caused by intracranial hypotension. This is the first case of alternating skew deviation reported from intracranial hypotension and perhaps a differential pressure between intracranial and intraspinal spaces plays a role in the development of these findings. PMID:27928294

  20. 22 CFR 518.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Deviations. 518.4 Section 518.4 Foreign Relations BROADCASTING BOARD OF GOVERNORS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 518.4 Deviations....

  1. 22 CFR 518.4 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Deviations. 518.4 Section 518.4 Foreign Relations BROADCASTING BOARD OF GOVERNORS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 518.4 Deviations....

  2. 22 CFR 145.4 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Deviations. 145.4 Section 145.4 Foreign Relations DEPARTMENT OF STATE CIVIL RIGHTS GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 145.4 Deviations. The Office of Management...

  3. 22 CFR 145.4 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Deviations. 145.4 Section 145.4 Foreign Relations DEPARTMENT OF STATE CIVIL RIGHTS GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 145.4 Deviations. The Office of Management...

  4. 22 CFR 145.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Deviations. 145.4 Section 145.4 Foreign Relations DEPARTMENT OF STATE CIVIL RIGHTS GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 145.4 Deviations. The Office of Management...

  5. 22 CFR 518.4 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Deviations. 518.4 Section 518.4 Foreign Relations BROADCASTING BOARD OF GOVERNORS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 518.4 Deviations....

  6. 22 CFR 518.4 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Deviations. 518.4 Section 518.4 Foreign Relations BROADCASTING BOARD OF GOVERNORS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 518.4 Deviations....

  7. 22 CFR 145.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Deviations. 145.4 Section 145.4 Foreign Relations DEPARTMENT OF STATE CIVIL RIGHTS GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 145.4 Deviations. The Office of Management...

  8. 48 CFR 1480.403 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... authorize a deviation for an IA acquisition: For a proposed contract action . . . The following official may authorize a deviation . . . Exceeding $25,000 but not exceeding $550,000 The CCO (or the IA Procurement Chief, absent a CCO). Exceeding $550,000 but not exceeding $11.5 million IA Competition...

  9. 48 CFR 2001.403 - Individual deviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Individual deviations. 2001.403 Section 2001.403 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR...

  10. 48 CFR 2001.403 - Individual deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Individual deviations. 2001.403 Section 2001.403 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR...

  11. 48 CFR 2001.403 - Individual deviations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Individual deviations. 2001.403 Section 2001.403 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR...

  12. 48 CFR 2001.404 - Class deviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Class deviations. 2001.404 Section 2001.404 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR 2001.404...

  13. 48 CFR 2001.403 - Individual deviations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Individual deviations. 2001.403 Section 2001.403 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR...

  14. 48 CFR 2001.404 - Class deviations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Class deviations. 2001.404 Section 2001.404 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR 2001.404...

  15. 48 CFR 2001.404 - Class deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Class deviations. 2001.404 Section 2001.404 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR 2001.404...

  16. 48 CFR 2001.403 - Individual deviations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Individual deviations. 2001.403 Section 2001.403 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR...

  17. 48 CFR 2001.404 - Class deviations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Class deviations. 2001.404 Section 2001.404 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR 2001.404...

  18. 48 CFR 2001.404 - Class deviations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Class deviations. 2001.404 Section 2001.404 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Deviations From the FAR and the NRCAR 2001.404...

  19. 20 CFR 435.4 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Deviations. 435.4 Section 435.4 Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH... General § 435.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for classes...

  20. 20 CFR 435.4 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Deviations. 435.4 Section 435.4 Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH... General § 435.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for classes...

  1. 20 CFR 435.4 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Deviations. 435.4 Section 435.4 Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH... General § 435.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for classes...

  2. 20 CFR 435.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Deviations. 435.4 Section 435.4 Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH... General § 435.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for classes...

  3. 20 CFR 435.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deviations. 435.4 Section 435.4 Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH... General § 435.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for classes...

  4. 10 CFR 800.204 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Deviations. 800.204 Section 800.204 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE Loans § 800.204 Deviations. (a) To the extent consistent with the Act, relevant...

  5. 10 CFR 800.204 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Deviations. 800.204 Section 800.204 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE Loans § 800.204 Deviations. (a) To the extent consistent with the Act, relevant...

  6. 10 CFR 800.204 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Deviations. 800.204 Section 800.204 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE Loans § 800.204 Deviations. (a) To the extent consistent with the Act, relevant...

  7. 10 CFR 800.204 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Deviations. 800.204 Section 800.204 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE Loans § 800.204 Deviations. (a) To the extent consistent with the Act, relevant...

  8. 10 CFR 800.204 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Deviations. 800.204 Section 800.204 Energy DEPARTMENT OF ENERGY LOANS FOR BID OR PROPOSAL PREPARATION BY MINORITY BUSINESS ENTERPRISES SEEKING DOE CONTRACTS AND ASSISTANCE Loans § 800.204 Deviations. (a) To the extent consistent with the Act, relevant...

  9. 48 CFR 1401.404 - Class deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Class deviations. 1401.404 Section 1401.404 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL DEPARTMENT OF THE INTERIOR ACQUISITION REGULATION SYSTEM Deviations from the FAR and DIAR 1401.404 Class...

  10. 48 CFR 3001.404 - Class deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Class deviations. 3001.404 Section 3001.404 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM Deviations from the FAR and...

  11. A PCR detection method for testing Mycoplasma contamination of veterinary vaccines and biological products.

    PubMed

    Ingebritson, A L; Gibbs, C P; Tong, C; Srinivas, G B

    2015-02-01

    A rapid test method was developed for detecting mycoplasma contamination in veterinary biological products. The method reduces testing time by 2 weeks and shows comparable sensitivity to the current agar-based detection model. The primary goals for the development of the test were to reduce the testing time, incorporate a method that was easily adaptable across the veterinary biologics industry and reduce the subjective interpretation of results. We found that biological enrichment is necessary to maintain sensitivity of the detection method when compared to the standard culture-based test and that periodic sampling of enrichment cultures is essential to detect a wide variety of mycoplasma species that may be present as contaminants. The PCR detection method is comparable to the agar-based model and can reduce the overall testing time by up to 14 days.

  12. Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects.

    PubMed

    Dziuba, Bartłomiej; Dziuba, Marta

    2014-01-01

    Proteins are one of the primary components of the food, both in terms of nutrition and function. They are main source of amino acids, essential for synthesis of proteins, and also source of energy. Additionally, many proteins exhibit specific biological activities, which may have effect on functional or pro-health properties of food products. These proteins and their hydrolysis products, peptides, may influence the properties of food and human organism. The number of commercially available food products containing bioactive peptides is very low, apart from that milk proteins are their rich source. It could be supposed that number of available products with declared activity will rise in near future because of observed strong uptrend on interest in such products. Molecular and biological properties of milk proteins, as precursors of bioactive peptides was characterised in the work. Therefore, the strategy of research and obtaining of such peptides both in laboratory and industrial scale, as well as the range of their commercial application, was presented. Several examples of research efforts presenting high potential to develop new products containing bioactive peptides from milk proteins and predetermined as nutraceuticals was described.

  13. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  14. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  15. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  16. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  17. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug,...

  18. 21 CFR 211.100 - Written procedures; deviations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Written procedures; deviations. 211.100 Section 211.100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Production...

  19. 21 CFR 114.89 - Deviations from scheduled processes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Deviations from scheduled processes. 114.89 Section 114.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION ACIDIFIED FOODS Production and Process Controls § 114.89...

  20. 21 CFR 114.89 - Deviations from scheduled processes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Deviations from scheduled processes. 114.89 Section 114.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION ACIDIFIED FOODS Production and Process Controls § 114.89...

  1. 21 CFR 114.89 - Deviations from scheduled processes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Deviations from scheduled processes. 114.89 Section 114.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION ACIDIFIED FOODS Production and Process Controls § 114.89...

  2. 21 CFR 114.89 - Deviations from scheduled processes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Deviations from scheduled processes. 114.89 Section 114.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION ACIDIFIED FOODS Production and Process Controls § 114.89...

  3. 21 CFR 114.89 - Deviations from scheduled processes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Deviations from scheduled processes. 114.89 Section 114.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION ACIDIFIED FOODS Production and Process Controls § 114.89...

  4. Meiosis and its deviations in polyploid animals.

    PubMed

    Stenberg, P; Saura, A

    2013-01-01

    We review the different modes of meiosis and its deviations encountered in polyploid animals. Bisexual reproduction involving normal meiosis occurs in some allopolyploid frogs with variable degrees of polyploidy. Aberrant modes of bisexual reproduction include gynogenesis, where a sperm stimulates the egg to develop. The sperm may enter the egg but there is no fertilization and syngamy. In hybridogenesis, a genome is eliminated to produce haploid or diploid eggs or sperm. Ploidy can be elevated by fertilization with a haploid sperm in meiotic hybridogenesis, which elevates the ploidy of hybrid offspring such that they produce diploid gametes. Polyploids are then produced in the next generation. In kleptogenesis, females acquire full or partial genomes from their partners. In pre-equalizing hybrid meiosis, one genome is transmitted in the Mendelian fashion, while the other is transmitted clonally. Parthenogenetic animals have a very wide range of mechanisms for restoring or maintaining the mother's ploidy level, including gamete duplication, terminal fusion, central fusion, fusion of the first polar nucleus with the product of the first division, and premeiotic duplication followed by a normal meiosis. In apomictic parthenogenesis, meiosis is replaced by what is effectively mitotic cell division. The above modes have different evolutionary consequences, which are discussed. See also the sister article by Grandont et al. in this themed issue.

  5. Characterization of persistent colors and decolorization of effluent from biologically treated cellulosic ethanol production wastewater.

    PubMed

    Shan, Lili; Liu, Junfeng; Yu, Yanling; Ambuchi, John J; Feng, Yujie

    2016-05-01

    The high chroma of cellulosic ethanol production wastewater poses a serious environmental concern; however, color-causing compounds are still not fully clear. The characteristics of the color compounds and decolorization of biologically treated effluent by electro-catalytic oxidation were investigated in this study. Excitation-emission matrix (EEM), fourier transform infrared spectrometer (FTIR), UV-Vis spectra, and ultrafiltration (UF) fractionation were used to analyze color compounds. High chroma of wastewater largely comes from humic materials, which exhibited great fluorescence proportion (67.1 %) in the biologically treated effluent. Additionally, the color compounds were mainly distributed in the molecular weight fractions with 3-10 and 10-30 kDa, which contributed 53.5 and 34.6 % of the wastewater color, respectively. Further decolorization of biologically treated effluent by electro-catalytic oxidation was investigated, and 98.3 % of color removal accompanied with 97.3 % reduction of humic acid-like matter was achieved after 180 min. The results presented herein will facilitate the development of a well decolorization for cellulosic ethanol production wastewater and better understanding of the biological fermentation.

  6. Application of synthetic biology for production of chemicals in yeast Saccharomyces cerevisiae.

    PubMed

    Li, Mingji; Borodina, Irina

    2015-02-01

    Synthetic biology and metabolic engineering enable generation of novel cell factories that efficiently convert renewable feedstocks into biofuels, bulk, and fine chemicals, thus creating the basis for biosustainable economy independent on fossil resources. While over a hundred proof-of-concept chemicals have been made in yeast, only a very small fraction of those has reached commercial-scale production so far. The limiting factor is the high research cost associated with the development of a robust cell factory that can produce the desired chemical at high titer, rate, and yield. Synthetic biology has the potential to bring down this cost by improving our ability to predictably engineer biological systems. This review highlights synthetic biology applications for design, assembly, and optimization of non-native biochemical pathways in baker's yeast Saccharomyces cerevisiae We describe computational tools for the prediction of biochemical pathways, molecular biology methods for assembly of DNA parts into pathways, and for introducing the pathways into the host, and finally approaches for optimizing performance of the introduced pathways.

  7. Evaluating and Reporting the Immunogenicity Impacts for Biological Products--a Clinical Pharmacology Perspective.

    PubMed

    Wang, Yow-Ming C; Wang, Jie; Hon, Yuen Yi; Zhou, Lin; Fang, Lanyan; Ahn, Hae Young

    2016-03-01

    Immunogenicity assessment is important for biological products due to potential impacts of immunogenicity on safety and efficacy. We reviewed the prescribing information and the FDA's clinical pharmacology review of 121 approved biological products for evaluating and reporting of immunogenicity data. Of the 121 products, 89% (n = 108) reported the incidence of immunogenicity and 49% (n = 59) reported immunogenicity impact on efficacy. However, only 26% (n = 31) reported whether the immunogenicity affected pharmacokinetics. A subset of 16 products reported effects of anti-drug antibodies (ADA) on both systemic clearance and efficacy; 8 of 16 products had increased systemic clearance coinciding with reduced efficacy, and 6 of 16 products had no changes in either clearance or efficacy. Factors contributing to infrequent reporting of the ADA effect on exposure and methods for determining the effect of ADA on exposure are summarized. Measuring ADA and drug concentrations concurrently over time enables the evaluation of ADA impact on pharmacokinetics. Within-subject comparison of concentration data (before vs. after ADA formation) is a useful alternative to between-subject (ADA+ vs. ADA-) comparison when sample size is limited or when the majority of subjects developed ADA. The biological complexity of immune responses presents challenges to quantifying the ADA impact on pharmacokinetics using model-based methods. Our findings support that pharmacokinetic exposure is more sensitive than efficacy endpoints for evaluating ADA effects. A decrease in drug concentration due to formation of ADA during treatment can serve as an early indicator for potential reduced efficacy occurring at a later time.

  8. Activity and biological effects of neem products against arthropods of medical and veterinary importance.

    PubMed

    Mulla, M S; Su, T

    1999-06-01

    Botanical insecticides are relatively safe and degradable, and are readily available sources of biopesticides. The most prominent phytochemical pesticides in recent years are those derived from neem trees, which have been studied extensively in the fields of entomology and phytochemistry, and have uses for medicinal and cosmetic purposes. The neem products have been obtained from several species of neem trees in the family Meliaceae. Six species in this family have been the subject of botanical pesticide research. They are Azadirachta indica A. Juss, Azadirachta excelsa Jack, Azadirachta siamens Valeton, Melia azedarach L., Melia toosendan Sieb. and Zucc., and Melia volkensii Gürke. The Meliaceae, especially A. indica (Indian neem tree), contains at least 35 biologically active principles. Azadirachtin is the predominant insecticidal active ingredient in the seed, leaves, and other parts of the neem tree. Azadirachtin and other compounds in neem products exhibit various modes of action against insects such as antifeedancy, growth regulation, fecundity suppression and sterilization, oviposition repellency or attractancy, changes in biological fitness, and blocking development of vector-borne pathogens. Some of these bioactivity parameters of neem products have been investigated at least in some species of insects of medical and veterinary importance, such as mosquitoes, flies, triatomines, cockroaches, fleas, lice, and others. Here we review, synthesize, and analyze published information on the activity, modes of action, and other biological effects of neem products against arthropods of medical and veterinary importance. The amount of information on the activity, use, and application of neem products for the control of disease vectors and human and animal pests is limited. Additional research is needed to determine the potential usefulness of neem products in vector control programs.

  9. The potential of plants as a system for the development and production of human biologics

    PubMed Central

    Chen, Qiang; Davis, Keith R.

    2016-01-01

    The growing promise of plant-made biologics is highlighted by the success story of ZMapp™ as a potentially life-saving drug during the Ebola outbreak of 2014-2016. Current plant expression platforms offer features beyond the traditional advantages of low cost, high scalability, increased safety, and eukaryotic protein modification. Novel transient expression vectors have been developed that allow the production of vaccines and therapeutics at unprecedented speed to control potential pandemics or bioterrorism attacks. Plant-host engineering provides a method for producing proteins with unique and uniform mammalian post-translational modifications, providing opportunities to develop biologics with increased efficacy relative to their mammalian cell-produced counterparts. Recent demonstrations that plant-made proteins can function as biocontrol agents of foodborne pathogens further exemplify the potential utility of plant-based protein production. However, resolving the technical and regulatory challenges of commercial-scale production, garnering acceptance from large pharmaceutical companies, and obtaining U.S. Food and Drug Administration approval for several major classes of biologics are essential steps to fulfilling the untapped potential of this technology. PMID:27274814

  10. Connecting marine productivity to sea-spray via microscale biological processes: phytoplancton demise and viral infection

    NASA Astrophysics Data System (ADS)

    Facchini, C.; O'Dowd, C. D. D.; Danovaro, R.

    2015-12-01

    The processes that link phytoplankton biomass and productivity to the organic matter enrichment in sea spray aerosol are far from being elucidated and modelling predictions remain highly uncertain at the moment. While some studies have asserted that the enrichment of OM in sea spray aerosol is independent on marine productivity, others, have shown significant correlation with phytoplankton biomass and productivity (Chl-a retrieved by satellites). We present here new results illustrating a clear link between OM mass-fraction enrichment in sea spray (OMss) and both phytoplankton-biomass and Net Primary Productivity (NPP). We suggest that the OM enrichment of sea spray through the demise of the bloom, driven by nanoscale biological processes (such as viral infections), which determine the release of celldebris, exudates and other colloidal material. This OM, through processes, leads to enrichment in sea-spray, thus demonstrating an important coupling between biologically-drive plankton bloom termination, marine productivity and sea-spraymodification with potentially significant climate impacts.

  11. Potential of chicken by-products as sources of useful biological resources.

    PubMed

    Lasekan, Adeseye; Abu Bakar, Fatimah; Hashim, Dzulkifly

    2013-03-01

    By-products from different animal sources are currently being utilised for beneficial purposes. Chicken processing plants all over the world generate large amount of solid by-products in form of heads, legs, bones, viscera and feather. These wastes are often processed into livestock feed, fertilizers and pet foods or totally discarded. Inappropriate disposal of these wastes causes environmental pollution, diseases and loss of useful biological resources like protein, enzymes and lipids. Utilisation methods that make use of these biological components for producing value added products rather than the direct use of the actual waste material might be another viable option for dealing with these wastes. This line of thought has consequently led to researches on these wastes as sources of protein hydrolysates, enzymes and polyunsaturated fatty acids. Due to the multi-applications of protein hydrolysates in various branches of science and industry, and the large body of literature reporting the conversion of animal wastes to hydrolysates, a large section of this review was devoted to this subject. Thus, this review reports the known functional and bioactive properties of hydrolysates derived from chicken by-products as well their utilisation as source of peptone in microbiological media. Methods of producing these hydrolysates including their microbiological safety are discussed. Based on the few references available in the literature, the potential of some chicken by-product as sources of proteases and polyunsaturated fatty acids are pointed out along with some other future applications.

  12. Potential of chicken by-products as sources of useful biological resources

    SciTech Connect

    Lasekan, Adeseye; Abu Bakar, Fatimah; Hashim, Dzulkifly

    2013-03-15

    By-products from different animal sources are currently being utilised for beneficial purposes. Chicken processing plants all over the world generate large amount of solid by-products in form of heads, legs, bones, viscera and feather. These wastes are often processed into livestock feed, fertilizers and pet foods or totally discarded. Inappropriate disposal of these wastes causes environmental pollution, diseases and loss of useful biological resources like protein, enzymes and lipids. Utilisation methods that make use of these biological components for producing value added products rather than the direct use of the actual waste material might be another viable option for dealing with these wastes. This line of thought has consequently led to researches on these wastes as sources of protein hydrolysates, enzymes and polyunsaturated fatty acids. Due to the multi-applications of protein hydrolysates in various branches of science and industry, and the large body of literature reporting the conversion of animal wastes to hydrolysates, a large section of this review was devoted to this subject. Thus, this review reports the known functional and bioactive properties of hydrolysates derived from chicken by-products as well their utilisation as source of peptone in microbiological media. Methods of producing these hydrolysates including their microbiological safety are discussed. Based on the few references available in the literature, the potential of some chicken by-product as sources of proteases and polyunsaturated fatty acids are pointed out along with some other future applications.

  13. Microbial production of amino acids and derived chemicals: synthetic biology approaches to strain development.

    PubMed

    Wendisch, Volker F

    2014-12-01

    Amino acids are produced at the multi-million-ton-scale with fermentative production of l-glutamate and l-lysine alone being estimated to amount to more than five million tons in the year 2013. Metabolic engineering constantly improves productivities of amino acid producing strains, mainly Corynebacterium glutamicum and Escherichia coli strains. Classical mutagenesis and screening have been accelerated by combination with intracellular metabolite sensing. Synthetic biology approaches have allowed access to new carbon sources to realize a flexible feedstock concept. Moreover, new pathways for amino acid production as well as fermentative production of non-native compounds derived from amino acids or their metabolic precursors were developed. These include dipeptides, α,ω-diamines, α,ω-diacids, keto acids, acetylated amino acids and ω-amino acids.

  14. Methods for genetic optimization of biocatalysts for biofuel production from dairy waste through synthetic biology.

    PubMed

    Pasotti, Lorenzo; Zucca, Susanna; Casanova, Michela; Politi, Nicolo; Massaiu, Ilaria; Mazzini, Giuliano; Micoli, Giuseppina; Calvio, Cinzia; Cusella De Angelis, Maria Gabriella; Magni, Paolo

    2015-08-01

    Whey is an abundant by-product of cheese production process and it is considered a special waste due to its high nutritional load and hypertrophic potential. Technologies for whey valorization are available. They can convert such waste into high-value products, like whey proteins. However, the remaining liquid (called permeate) is still considered as a polluting waste due to its high lactose concentration. The alcoholic fermentation of lactose into ethanol will simultaneously achieve two important goals: safe disposal of a pollutant waste and green energy production. This methodology paper illustrates the workflow carried out to design and realize an optimized microorganism that can efficiently perform the lactose-to-ethanol conversion, engineered via synthetic biology experimental and computational approaches.

  15. Development of GRAS strains for nutraceutical production using systems and synthetic biology approaches: advances and prospects.

    PubMed

    Liu, Long; Guan, Ningzi; Li, Jianghua; Shin, Hyun-Dong; Du, Guocheng; Chen, Jian

    2017-03-01

    Nutraceuticals are food substances with medical and health benefits for humans. Limited by complicated procedures, high cost, low yield, insufficient raw materials, resource waste, and environment pollution, chemical synthesis and extraction are being replaced by microbial synthesis of nutraceuticals. Many microbial strains that are generally regarded as safe (GRAS) have been identified and developed for the synthesis of nutraceuticals, and significant nutraceutical production by these strains has been achieved. In this review, we systematically summarize recent advances in nutraceutical research in terms of physiological effects on health, potential applications, drawbacks of traditional production processes, characteristics of production strains, and progress in microbial fermentation. Recent advances in systems and synthetic biology techniques have enabled comprehensive understanding of GRAS strains and its wider applications. Thus, these microbial strains are promising cell factories for the commercial production of nutraceuticals.

  16. Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals.

    PubMed

    Jullesson, David; David, Florian; Pfleger, Brian; Nielsen, Jens

    2015-11-15

    Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through metabolic engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine chemicals that have reached the market, key metabolic engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes.

  17. Techno-economic evaluation of a two-step biological process for hydrogen production.

    PubMed

    Ljunggren, Mattias; Zacchi, Guido

    2010-01-01

    An integrated biological process for the production of hydrogen based on thermophilic and photo-heterotrophic fermentation was evaluated from a technical and economic standpoint. Besides the two fermentation steps the process also includes pretreatment of the raw material (potato steam peels) and purification of hydrogen using amine absorption. The study aimed neither at determining the absolute cost of biohydrogen nor at an economic optimization of the production process, but rather at studying the effects of different parameters on the production costs of biohydrogen as a guideline for future improvements. The effect of the key parameters, hydrogen productivity and yield and substrate concentration in the two fermentations on the cost of the hydrogen produced was studied. The selection of the process conditions was based mainly on laboratory data. The process was simulated by use of the software Aspen Plus and the capital costs were estimated using the program Aspen Icarus Process Evaluator. The study shows that the photo-fermentation is the main contributor to the hydrogen production cost mainly because of the cost of plastic tubing, for the photo-fermentors, which represents 40.5% of the hydrogen production cost. The costs of the capital investment and chemicals were also notable contributors to the hydrogen production cost. Major economic improvements could be achieved by increasing the productivity of the two fermentation steps on a medium-term to long-term scale.

  18. Eddy-mediated biological productivity in the Bay of Bengal during fall and spring intermonsoons

    NASA Astrophysics Data System (ADS)

    Prasanna Kumar, S.; Nuncio, M.; Ramaiah, N.; Sardesai, S.; Narvekar, Jayu; Fernandes, Veronica; Paul, Jane T.

    2007-09-01

    The signature of cold-core eddies and their role in altering the biological productivity of the Bay of Bengal was examined using two recent sets of hydrographic data collected along the central and western Bay of Bengal during fall (14 September-12 October, 2002) and spring (12 April-7 May, 2003) intermonsoons under the Bay of Bengal process studies (BOBPS) programme. Based on the thermohaline structure and the satellite-derived sea-level anomaly maps nine cyclonic eddies were identified. Out of this, four cyclonic eddies—two each along the central Bay and along the western boundary—occurred during fall intermonsoon 2002, while five occurred—three along the central Bay and two along the western boundary—during spring intermonsoon. The eddy depressed the temperature, which varied from 3 °C to 7 °C at 120 m depth. Maximum depression of temperature was associated with spring-time eddies in the northern Bay, where subsurface stability was low. The reduced water column stability in spring leads to greater eddy-pumping, thereby cooling the water to a greater extent. However, the cyclonic eddies were unable to break the stratification of the top 20 m layer, thereby curtailing their effects below this depth during both seasons. Eddy-pumping not only cooled the water column but also enhanced the nutrient concentrations. This in turn increased the biological productivity of the Bay to 1{1}/{2}-2 times. In addition, the subsurface chlorophyll maximum (SCM), which is generally located between 40 and 70 m in fall and 60 and 90 m in spring intermonsoons, shallowed under the influence of the eddies and also enhanced the chlorophyll concentration in the SCM to more than double. Thus, eddy-pumping of nutrients controls the biological productivity of the Bay of Bengal during both the seasons. In the fall intermonsoon, however, the riverine input of nutrients and sediments in the northern Bay also plays a role in altering the biological productivity. This has an overall

  19. 38 CFR 49.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... NON-PROFIT ORGANIZATIONS General § 49.4 Deviations. The Office of Management and Budget (OMB) may..., which are statutory. Exceptions on a case-by-case basis may also be made by Federal awarding...

  20. 32 CFR 32.4 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... class deviations. (1) For classes of awards other than small awards, the Director of Defense Research... part: (i) With the written concurrence of the Office of the Management and Budget (OMB). The DDR&E,...

  1. 32 CFR 32.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... class deviations. (1) For classes of awards other than small awards, the Director of Defense Research... part: (i) With the written concurrence of the Office of the Management and Budget (OMB). The DDR&E,...

  2. 48 CFR 201.403 - Individual deviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... 2341(2)), or with United Nations or NATO organizations; and (ii) Such governments or organizations will...). (2) Contracting officers outside the United States may deviate from prescribed nonstatutory FAR...

  3. Biological Pretreatment of Rubberwood with Ceriporiopsis subvermispora for Enzymatic Hydrolysis and Bioethanol Production

    PubMed Central

    Nazarpour, Forough; Abdullah, Dzulkefly Kuang; Abdullah, Norhafizah; Motedayen, Nazila; Zamiri, Reza

    2013-01-01

    Rubberwood (Hevea brasiliensis), a potential raw material for bioethanol production due to its high cellulose content, was used as a novel feedstock for enzymatic hydrolysis and bioethanol production using biological pretreatment. To improve ethanol production, rubberwood was pretreated with white rot fungus Ceriporiopsis subvermispora to increase fermentation efficiency. The effects of particle size of rubberwood (1 mm, 0.5 mm, and 0.25 mm) and pretreatment time on the biological pretreatment were first determined by chemical analysis and X-ray diffraction and their best condition obtained with 1 mm particle size and 90 days pretreatment. Further morphological study on rubberwood with 1 mm particle size pretreated by fungus was performed by FT-IR spectra analysis and SEM observation and the result indicated the ability of this fungus for pretreatment. A study on enzymatic hydrolysis resulted in an increased sugar yield of 27.67% as compared with untreated rubberwood (2.88%). The maximum ethanol concentration and yield were 17.9 g/L and 53% yield, respectively, after 120 hours. The results obtained demonstrate that rubberwood pretreated by C. subvermispora can be used as an alternative material for the enzymatic hydrolysis and bioethanol production. PMID:24167813

  4. Fate of phosphorus from biological aerobic treatment of pig slurry. By-products characterization and recovery.

    PubMed

    Daumer, M L; Beline, F; Guiziou, F

    2003-11-01

    The fate of phosphorus distribution in the products obtained from biological aerobic treatment of pig slurry, e.g. separated solids, liquid effluent and sludge, was monitored in three different farm-scale units. Samples of raw slurry, solid products, aerated slurry, liquid effluent and sludge were characterised and analysed for their concentration in total phosphorus, nitrogen content and heavy metals (Cu and Zn). At each treatment stage, nitrogen, phosphorus and heavy metals mass balance between input and output was established. Moreover, liquid products were characterised and analysed both for their total and dissolved ortho-phosphate content. Separated solids, sludge and liquid effluent represented 5%, 15-40% and 75-83% of the mass of the raw slurry, respectively. A mechanical separation step prior to aeration allowed the export of 25-30% of total phosphorus for further use as organic fertiliser. A large amount of total phosphorus (e.g. 60-70%) was located in sludge while phosphorus remaining in liquid effluent was about 15-25%. Raw slurry separation and sufficient aeration allowed phosphorus to concentrate in the sludge. Insufficient aeration resulted in the release of phosphorus as dissolved ortho-phosphate within the liquid effluent. Finally, relevance of the agronomic use of the products was discussed and improvements of biological aerobic treatment to enhance phosphorus removal and/or recovery were considered.

  5. Modeling the impact of tidal flows on the biological productivity of the Alboran Sea

    NASA Astrophysics Data System (ADS)

    Sánchez-Garrido, José C.; Naranjo, C.; Macías, D.; García-Lafuente, J.; Oguz, T.

    2015-11-01

    The control of phytoplankton production by tidal forcing in the Alboran Sea is investigated with a high-resolution ocean circulation model coupled to an ecosystem model. The aim of the modeling efforts was to elucidate the role of tides in sustaining the high biological productivity of the Alboran Sea, as compared with the rest of the Mediterranean subbasins. It is shown that tidal forcing accounts for an increase of phytoplankton biomass and primary productivity in the basin of about 40% with respect to a nontidal circulation, and about 60% in the western Alboran Sea alone. The tidal dynamics of the Strait of Gibraltar is shown to be the primary factor in determining the enhancement of productivity, pumping nutrients from depth to the photic zone in the Alboran Sea. Model results indicate that the biological implications of the propagating internal tides are small. These results imply that nutrient transports through the Strait of Gibraltar have to be parametrized in ocean models that do not resolve tides in order to properly represent the biochemical budgets of the Alboran Sea.

  6. Role of Extracorporeal Septoplasty in Deviated Noses.

    PubMed

    Ghaisas, Virendra; Parab, Sapna Ramkrishna

    2015-09-01

    Severe gross septal deviations present big surgical challenges for operating surgeon. Septal deviations has direct effect on aesthetic and functional part of nose. Correcting septal deviations during rhinoplasty is basic procedure. Extreme deviations of septum especially on dorsal and caudal end of cartilaginous septum are difficult to treat. The classical septoplasty approach becomes unsuitable for such severe deviations. Gubisch has first reported in 1995 about extracorporeal septoplasty. To report the experience of Extracorporeal septoplasty and the complication rates with the technique. Retrospective study of 112 patients who underwent extracorporeal septoplasty in primary rhinoplasty from May 2009 to June 2014. Patient's pre and postoperatively evaluation was done by photographs, nasal endoscopy and subjective by symptoms evaluation satisfaction scale 6 and 12 months postoperatively. Nasal endoscopy revealed significant improvement in nasal airway and nasal valve and subjective evaluation satisfaction score was very encouraging. Complications like septal perforation, bleeding, aesthetic complications were minimal (9 %) On basis of results obtained, shows that this technique, increases patients nasal airway and aesthetic look of the patients. Irrespective of extreme nasal deviations.

  7. Meat Production in a Feedlot System of Zebu—Holstein Steers and Heifers with Dairy Genetics: Productive and Biological Analyses

    PubMed Central

    Menezes, Gustavo Chamon de Castro; Valadares Filho, Sebastião de Campos; Ruas, José Reinaldo Mendes; Detmann, Edenio; Menezes, Arismar de Castro; Zanett, Diego; Mariz, Lays Débora Silva; Rennó, Luciana Navajas; da Silva Junior, Jarbas Miguel

    2014-01-01

    The aim of this study was to evaluate the productive and biological efficiency of steers and heifers from dairy genetics in a feedlot system in terms of meat production. Twenty-four steers and 24 heifers at 10 monthes of age, (3/4) Zebu × (1/4) Holstein were utilized. They were distributed over four feedlot times, 30, 60, 90, and 120 days with four replications for each sex, and were slaughtered at the end of each period. The productive and biological analyses were performed through comparative slaughter to determine the body composition. Heifers presented with greater intakes (P < 0.05) of dry matter in grams per kg of body weight. Steers presented with a greater (P < 0.05) final empty body weight, carcass gain, cold carcass weight, and meat proportion in the carcass; however, heifers presented with a greater subcutaneous fat thickness (P < 0.05) and, consequently, a greater (P < 0.05) fat proportion in the carcass. We conclude that steers are more efficient in their productive performance than heifers in a feedlot. For the finishing carcass fat cover, heifers need 90 days in the feedlot. The net energy requirements for maintenance are 67 kcal/EBW0.75/d, and the net requirements of energy (NEg) and protein (NPg) for gain can be estimated by the following equations: NEg(Mcal/d) = 0.067 × EBW0.75 × EBG1.095 and NPg = 162 × EBG − 5.62 × RE for the two sexes. PMID:25574483

  8. HPLC study of oxidation products of hydroethidine in chemical and biological systems: Ramifications in superoxide measurements

    PubMed Central

    Zielonka, Jacek; Hardy, Micael; Kalyanaraman, B.

    2012-01-01

    Methods for detection and quantitation of hydroethidine (HE) and its oxidation products by HPLC analysis are described. Synthetic methods for preparations of authentic standards (2-hydroxyethidium and diethidium) are provided. Potential applications of the HPLC methods to chemical and biological systems are discussed. Specific examples of chromatograms obtained using UV-Vis absorption, fluorescence, electrochemical and mass spectrometry detectors are provided. The development of a dual electrochemical and fluorescence detection methodology and its applications are described. The HPLC-based method enables analyses of HE and its oxidation products such as ethidium and the dimeric products of HE. Ramifications of HPLC measurements of HE and its oxidation products in the detection and quantitation of 2-hydroxyethidium, the diagnostic marker product of superoxide and HE, in the intracellular milieu are discussed. Similarly, mitochondria-targeted HE conjugated to a triphenylphosphonium group (Mito-HE or Mito-SOX) also forms oxidation products (dimers of Mito-HE and Mito-E+) that can affect the detection and quantitation of 2-hydroxy-mito-ethidium, the diagnostic marker product of Mito-HE and superoxide in mitochondria. PMID:19026738

  9. Mass and energy balance constraints on the biological production of chemicals from coal

    SciTech Connect

    Andrews, G.

    1990-01-01

    Several organic chemicals, including methane and ethanol, may be produced by the bioprocessing of coal. This may be done either by direct microbial attack on the coal, or indirectly by the bioprocessing of solubilized coal. As in chemical liquefaction and gasification, the relative amounts of the various products that can be produced are severely constrained by mass and energy balance considerations. The main differences in biological processing are that water is a ubiquitous reactant, carbon dioxide a common product, and that some of the carbon and nitrogen in the coal may go to the synthesis of new biomass rather than products. The conventional biotechnological yield analysis applied to coal processing has several interesting consequences. The mass balance reduces to a balance of available electrons, and coal has a similar oxidation/reduction state to both carbohydrates and biomass. This makes high product yields feasible particularly under anaerobic conditions, although leaving open the question of whether the relevant hydrolase enzymes exist. Recommendations are made on products, and combinations of two products, that may be made with high yields and economic return. The energy balance provides little extra information. A general intracellular energy balance can be written in terms of the production and consumption of ATP, but much of the necessary information on the metabolic pathways is currently not available for coal processing microorganisms. 9 refs., 2 figs., 2 tabs.

  10. The biological pump in the Costa Rica Dome: an open-ocean upwelling system with high new production and low export

    PubMed Central

    Stukel, Michael R.; Benitez-Nelson, Claudia R.; Décima, Moira; Taylor, Andrew G.; Buchwald, Carolyn; Landry, Michael R.

    2016-01-01

    The Costa Rica Dome is a picophytoplankton-dominated, open-ocean upwelling system in the Eastern Tropical Pacific that overlies the ocean's largest oxygen minimum zone. To investigate the efficiency of the biological pump in this unique area, we used shallow (90–150 m) drifting sediment traps and 234Th:238U deficiency measurements to determine export fluxes of carbon, nitrogen and phosphorus in sinking particles. Simultaneous measurements of nitrate uptake and shallow water nitrification allowed us to assess the equilibrium balance of new and export production over a monthly timescale. While f-ratios (new:total production) were reasonably high (0.36 ± 0.12, mean ± standard deviation), export efficiencies were considerably lower. Sediment traps suggested e-ratios (export/14C-primary production) at 90–100 m ranging from 0.053 to 0.067. ThE-ratios (234Th disequilibrium-derived export) ranged from 0.038 to 0.088. C:N and N:P stoichiometries of sinking material were both greater than canonical (Redfield) ratios or measured C:N of suspended particulates, and they increased with depth, suggesting that both nitrogen and phosphorus were preferentially remineralized from sinking particles. Our results are consistent with an ecosystem in which mesozooplankton play a major role in energy transfer to higher trophic levels but are relatively inefficient in mediating vertical carbon flux to depth, leading to an imbalance between new production and sinking flux. PMID:27275035

  11. Recent advances in food biopeptides: production, biological functionalities and therapeutic applications.

    PubMed

    Saadi, Sami; Saari, Nazamid; Anwar, Farooq; Hamid, Azizah Abdul; Mohd Ghazali, Hasanah

    2015-01-01

    The growing momentum of several common life-style diseases such as myocardial infarction, cardiovascular disorders, stroke, hypertension, diabetes, and atherosclerosis has become a serious global concern. Recent developments in the field of proteomics offering promising solutions to solving such health problems stimulates the uses of biopeptides as one of the therapeutic agents to alleviate disease-related risk factors. Functional peptides are typically produced from protein via enzymatic hydrolysis under in vitro or in vivo conditions using different kinds of proteolytic enzymes. An array of biological activities, including antioxidative, antihypertensive, antidiabetic and immunomodulating has been ascribed to different types of biopeptides derived from various food sources. In fact, biopeptides are nutritionally and functionally important for regulating some physiological functions in the body; however, these are yet to be extensively addressed with regard to their production through advance strategies, mechanisms of action and multiple biological functionalities. This review mainly focuses on recent biotechnological advances that are being made in the field of production in addition to covering the mode of action and biological activities, medicinal health functions and therapeutic applications of biopeptides. State-of-the-art strategies that can ameliorate the efficacy, bioavailability, and functionality of biopeptides along with their future prospects are likewise discussed.

  12. A review of biological delignification and detoxification methods for lignocellulosic bioethanol production.

    PubMed

    Moreno, Antonio D; Ibarra, David; Alvira, Pablo; Tomás-Pejó, Elia; Ballesteros, Mercedes

    2015-01-01

    Future biorefineries will integrate biomass conversion processes to produce fuels, power, heat and value-added chemicals. Due to its low price and wide distribution, lignocellulosic biomass is expected to play an important role toward this goal. Regarding renewable biofuel production, bioethanol from lignocellulosic feedstocks is considered the most feasible option for fossil fuels replacement since these raw materials do not compete with food or feed crops. In the overall process, lignin, the natural barrier of the lignocellulosic biomass, represents an important limiting factor in biomass digestibility. In order to reduce the recalcitrant structure of lignocellulose, biological pretreatments have been promoted as sustainable and environmentally friendly alternatives to traditional physico-chemical technologies, which are expensive and pollute the environment. These approaches include the use of diverse white-rot fungi and/or ligninolytic enzymes, which disrupt lignin polymers and facilitate the bioconversion of the sugar fraction into ethanol. As there is still no suitable biological pretreatment technology ready to scale up in an industrial context, white-rot fungi and/or ligninolytic enzymes have also been proposed to overcome, in a separated or in situ biodetoxification step, the effect of the inhibitors produced by non-biological pretreatments. The present work reviews the latest studies regarding the application of different microorganisms or enzymes as useful and environmentally friendly delignification and detoxification technologies for lignocellulosic biofuel production. This review also points out the main challenges and possible ways to make these technologies a reality for the bioethanol industry.

  13. Gamma irradiation induced disintegration of waste activated sludge for biological hydrogen production

    NASA Astrophysics Data System (ADS)

    Yin, Yanan; Wang, Jianlong

    2016-04-01

    In this paper, gamma irradiation was applied for the disintegration and dissolution of waste activated sludge produced during the biological wastewater treatment, and the solubilized sludge was used as substrate for bio-hydrogen production. The experimental results showed that the solubilization of waste activated sludge was 53.7% at 20 kGy and pH=12, and the SCOD, polysaccharides, protein, TN and TP contents in the irradiated sludge solutions was 3789.6 mg/L, 268.3 mg/L, 1881.5 mg/L, 132.3 mg/L and 80.4 mg/L, respectively. The irradiated sludge was used for fermentative hydrogen production, and the hydrogen yield was 10.5±0.7 mL/g SCODconsumed. It can be concluded that the irradiated waste activated sludge could be used as a low-cost substrate for fermentative hydrogen production.

  14. Extracellular production of an intact and biologically active human growth hormone by the Bacillus brevis system.

    PubMed

    Kajino, T; Saito, Y; Asami, O; Yamada, Y; Hirai, M; Udata, S

    1997-10-01

    The characteristic features of the Bacillus brevis system are very high productivity of heterologous proteins and very low extracellular protease activity. However, degradation of some heterologous proteins, especially mammalian proteins, can be observed and resulted in a lowering of protein productivity. By using a mutant expressing low levels of proteases and the addition of EDTA to the medium, intact human growth hormone (hGH) was successfully produced with the B. brevis system. Signal peptide modification with higher basicity in the amino terminal region and higher hydrophobicity in the middle region brought about a twelve-fold increase in hGH production. The hGH yield was further elevated to 240 mg L-1 by optimization of culture conditions. Thus, biologically active and mature hGH can be efficiently produced directly in the medium with the B. brevis system.

  15. Biological butanol production from microalgae-based biodiesel residues by Clostridium acetobutylicum.

    PubMed

    Cheng, Hai-Hsuan; Whang, Liang-Ming; Chan, Kun-Chi; Chung, Man-Chien; Wu, Shu-Hsien; Liu, Cheng-Pin; Tien, Shih-Yuan; Chen, Shan-Yuan; Chang, Jo-Shu; Lee, Wen-Jhy

    2015-05-01

    This study conducted batch experiments to evaluate the potential of butanol production from microalgae biodiesel residues by Clostridium acetobutylicum. The results indicated that with 90 g/L of glucose as the sole substrate the highest butanol yield of 0.2 g/g-glucose was found, but the addition of butyrate significantly enhanced the butanol yield. The highest butanol yield of 0.4 g/g-glucose was found with 60 g/L of glucose and 18 g/L of butyrate. Using microalgae biodiesel residues as substrate, C. acetobutylicum produced 3.86 g/L of butanol and achieved butanol yield of 0.13 g/g-carbohydrate via ABE fermentation, but the results indicated that approximately one third of carbohydrate was not utilized by C. acetobutylicum. Biological butanol production from microalgae biodiesel residues can be possible, but further research on fermentation strategies are required to improve production yield.

  16. Alien Biochemistries and Their Metabolic By-Products. Lessons from Synthetic Biology

    NASA Astrophysics Data System (ADS)

    Benner, S.

    2014-03-01

    While the metabolisms of terran organisms are accessible for study and their byproducts are, for the most part, well known, the "diversity" of terran biology arises (as far as we know) from a single common ancestor, represents only a small fraction of possible chemical difersity, and may reflect only a fraction of the possible chemical diversity that might support Darwinian evolution [1]. This talk will consider laboratory experiments on origins [2] and synthetic biology [3], asking how they might inform us about alternative biochemistries, and whether we have any chance of observing remotely their by-products, recognizing the uncertanties in both our models for "weird life" and our models of abiotic processes in incompletely defined planetary environments.

  17. Enzyme and metabolic engineering for the production of novel biopolymers: crossover of biological and chemical processes.

    PubMed

    Matsumoto, Ken'ichiro; Taguchi, Seiichi

    2013-12-01

    The development of synthetic biology has transformed microbes into useful factories for producing valuable polymers and/or their precursors from renewable biomass. Recent progress at the interface of chemistry and biology has enabled the production of a variety of new biopolymers with properties that substantially differ from their petroleum-derived counterparts. This review touches on recent trials and achievements in the field of biopolymer synthesis, including chemo-enzymatically synthesized aliphatic polyesters, wholly biosynthesized lactate-based polyesters, polyhydroxyalkanoates and other unusual bacterially synthesized polyesters. The expanding diversities in structure and the material properties of biopolymers are key for exploring practical applications. The enzyme and metabolic engineering approaches toward this goal are discussed by shedding light on the successful case studies.

  18. Innovation in biological production and upgrading of methane and hydrogen for use as gaseous transport biofuel.

    PubMed

    Xia, Ao; Cheng, Jun; Murphy, Jerry D

    2016-01-01

    Biofuels derived from biomass will play a major role in future renewable energy supplies in transport. Gaseous biofuels have superior energy balances, offer greater greenhouse gas emission reductions and produce lower pollutant emissions than liquid biofuels. Biogas derived through fermentation of wet organic substrates will play a major role in future transport systems. Biogas (which is composed of approximately 60% methane/hydrogen and 40% carbon dioxide) requires an upgrading process to reduce the carbon dioxide content to less than 3% before it is used as compressed gas in transport. This paper reviews recent developments in fermentative biogas production and upgrading as a transport fuel. Third generation gaseous biofuels may be generated using marine-based algae via two-stage fermentation, cogenerating hydrogen and methane. Alternative biological upgrading techniques, such as biological methanation and microalgal biogas upgrading, have the potential to simultaneously upgrade biogas, increase gaseous biofuel yield and reduce carbon dioxide emission.

  19. Biologically active amines in fermented and non-fermented commercial soybean products from the Spanish market.

    PubMed

    Toro-Funes, N; Bosch-Fuste, J; Latorre-Moratalla, M L; Veciana-Nogués, M T; Vidal-Carou, M C

    2015-04-15

    Biologically active amines were determined in commercial soybean products. The antioxidant polyamines were found in both non-fermented and fermented soybean products. Natto and tempeh showed the highest content of polyamines (75-124 and 11-24 mg/kg of spermidine and spermine, respectively). On the other hand, the bacterial-related biogenic amines, tyramine, histamine, tryptamine and β-phenylethylamine, were detected in practically all fermented products with a high variability. The highest contents were found in sufu, tamari and soybean paste. Extremely high tyramine and histamine contents, 1700 and 700 mg/kg, respectively, found in some sufu samples could be unhealthy. However, biogenic amines observed in the other soybean products should not be a risk for healthy consumers. However, individuals who take monoamine and diamine oxidase inhibitors drugs should be strongly recommended to avoid this kind of products in order to suffer no adverse health effects. These biogenic amines were not detected in non-fermented soybean products.

  20. A cell-free expression and purification process for rapid production of protein biologics.

    PubMed

    Sullivan, Challise J; Pendleton, Erik D; Sasmor, Henri H; Hicks, William L; Farnum, John B; Muto, Machiko; Amendt, Eric M; Schoborg, Jennifer A; Martin, Rey W; Clark, Lauren G; Anderson, Mark J; Choudhury, Alaksh; Fior, Raffaella; Lo, Yu-Hwa; Griffey, Richard H; Chappell, Stephen A; Jewett, Michael C; Mauro, Vincent P; Dresios, John

    2016-02-01

    Cell-free protein synthesis has emerged as a powerful technology for rapid and efficient protein production. Cell-free methods are also amenable to automation and such systems have been extensively used for high-throughput protein production and screening; however, current fluidic systems are not adequate for manufacturing protein biopharmaceuticals. In this work, we report on the initial development of a fluidic process for rapid end-to-end production of recombinant protein biologics. This process incorporates a bioreactor module that can be used with eukaryotic or prokaryotic lysates that are programmed for combined transcription/translation of an engineered DNA template encoding for specific protein targets. Purification of the cell-free expressed product occurs through a series of protein separation modules that are configurable for process-specific isolation of different proteins. Using this approach, we demonstrate production of two bioactive human protein therapeutics, erythropoietin and granulocyte-macrophage colony-stimulating factor, in yeast and bacterial extracts, respectively, each within 24 hours. This process is flexible, scalable and amenable to automation for rapid production at the point-of-need of proteins with significant pharmaceutical, medical, or biotechnological value.

  1. Biological Oxygen Productivity Over The Last Glacial Termination From Triple Oxygen Isotope Measurements

    NASA Astrophysics Data System (ADS)

    Blunier, T.; Bender, M. L.; Hendricks, M. B.

    The atmospheric oxygen isotope signature of O2 is linked to the oxygen signature of seawater through photosynthesis and respiration. Fractionation during these pro- cesses is mass dependent affecting 17O about half as much as 18O. A mass indepen- dent fractionation process takes place during isotope exchange between O2 and CO2 in the stratosphere (Thiemens, 1999; Luz et al., 1999). The magnitude of the mass- independent anomaly in the triple isotope composition of O2 depends on relative rates of biological O2 cycling and photochemical reactions in the stratosphere. Variations of this anomaly thus allows us to estimate changes of mass dependent O2 production by photosynthesis versus mass independent O2-CO2 exchange in the stratosphere. We reconstruct total oxygen productivity for the past from 17O and 18O measure- ments of O2 trapped in ice cores. With a box model we estimate that the total biogenic productivity was only 76-83 % of today for the glacial and was probably still lower than today during the glacial-interglacial transition and the early Holocene. In principle we can calculate the oxygen flux from the ocean biosphere if we know the oxygen flux from the land biosphere. Calculated ocean production is very sensitive to the estimate of land biosphere production. The latter term remains uncertain, however, and we can presently only constrain glacial ocean production to 88 to 140 % of the present value.

  2. Models for the biological production of glycerol and biosurfactants from potato-processing industry residuals

    SciTech Connect

    Polman, K.; Bala, G.A.; St. Clair, P.

    1995-12-31

    The fermentative production of valuable chemicals from biomass-derived substrates (e.g., glucose) represents the historical essence of industrial biotechnology. In the past, the capabilities of microorganisms to produce useful chemicals have been, at best, sporadically utilized. The primary products produced biotechnologically today are antibiotics and ethanol (for fuel and beverage uses). Many years ago, glycerol (also known as glycerin or glycerine) was produced at an industrial scale by fermentative means. Such production was stimulated by increased demand for glycerol and diversion of petroleum resources during wartime. Biotechnological production of glycerol ceased during peacetime, because the undeveloped and inefficient biotechnological processes that were used could not compete with inexpensive petroleum and natural feedstocks and the efficient and well developed methods by which to convert them to commodity chemicals. Industrial glycerol production by biological conversion of sugar has not occurred since that time. However, several factors, including the historical uncertainty of petroleum price and supply, the demand for environmentally safe industrial processes, and the vast development and improvement of bioprocess technology, suggest that the time for taking advantage of bioprocesses that produce marketable chemicals is near. Glycerol is a good candidate for such a chemical, because it is biologically produced from glucose in good yield (0.5 g glycerol/g glucose), the market is very large (> 140 million kg consumed/yr in the US), and future market growth is predicted to be good because of the widespread usage of glycerol and its historically strong market. Based on this, recent research has involved developing patentable technologies for the conversion of corn starch to glycerol; these efforts have progressed to the pilot plant scale.

  3. Standard Preparations, Limits of Potency, and Dating Period Limitations for Biological Products. Direct final rule.

    PubMed

    2016-05-04

    The Food and Drug Administration (FDA or Agency or we) is amending the general biological products standards relating to dating periods and also removing certain standards relating to standard preparations and limits of potency. FDA is taking this action to update outdated requirements, and accommodate new and evolving technology and testing capabilities, without diminishing public health protections. This action is part of FDA's retrospective review of its regulations in response to an Executive order. FDA is issuing these amendments directly as a final rule because the Agency believes they are noncontroversial and FDA anticipates no significant adverse comments.

  4. Online Deviation Detection for Medical Processes

    PubMed Central

    Christov, Stefan C.; Avrunin, George S.; Clarke, Lori A.

    2014-01-01

    Human errors are a major concern in many medical processes. To help address this problem, we are investigating an approach for automatically detecting when performers of a medical process deviate from the acceptable ways of performing that process as specified by a detailed process model. Such deviations could represent errors and, thus, detecting and reporting deviations as they occur could help catch errors before harm is done. In this paper, we identify important issues related to the feasibility of the proposed approach and empirically evaluate the approach for two medical procedures, chemotherapy and blood transfusion. For the evaluation, we use the process models to generate sample process executions that we then seed with synthetic errors. The process models describe the coordination of activities of different process performers in normal, as well as in exceptional situations. The evaluation results suggest that the proposed approach could be applied in clinical settings to help catch errors before harm is done. PMID:25954343

  5. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... biological product. IV. Animal safety data. A. Individual active components. 1. Controlled studies. 2... investigation, and that an alternative method of investigation is adequate to substantiate effectiveness. Alternate methods, such as serological response evaluation in clinical studies and appropriate animal...

  6. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... biological product. IV. Animal safety data. A. Individual active components. 1. Controlled studies. 2... investigation, and that an alternative method of investigation is adequate to substantiate effectiveness. Alternate methods, such as serological response evaluation in clinical studies and appropriate animal...

  7. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... biological product. IV. Animal safety data. A. Individual active components. 1. Controlled studies. 2... investigation, and that an alternative method of investigation is adequate to substantiate effectiveness. Alternate methods, such as serological response evaluation in clinical studies and appropriate animal...

  8. Formation of ring-opened and rearranged products of guanine: mechanisms and biological significance.

    PubMed

    Jena, N R; Mishra, P C

    2012-07-01

    DNA damage by endogenous and exogenous agents is a serious concern, as the damaged products can affect genome integrity severely. Damage to DNA may arise from various factors such as DNA base modifications, strand break, inter- and intrastrand crosslinks, and DNA-protein crosslinks. Among these factors, DNA base modification is a common and important form of DNA damage that has been implicated in mutagenesis, carcinogenesis, and many other pathological conditions. Among the four DNA bases, guanine (G) has the smallest oxidation potential, because of which it is frequently modified by reactive species, giving rise to a plethora of lethal lesions. Similarly, 8-oxo-7,8-dihydroguanine (8-oxoG), an oxidatively damaged guanine lesion, also undergoes various degradation reactions giving rise to several mutagenic species. The various products formed from reactions of G or 8-oxoG with different reactive species are mainly 2,6-diamino-4-oxo-5-formamidopyrimidine, 2,5-diamino-4H-imidazolone, 2,2,4-triamino-5-(2H)-oxazolone, 5-guanidino-4-nitroimidazole, guanidinohydantoin, spiroiminodihydantoin, cyanuric acid, parabanic acid, oxaluric acid, and urea, among others. These products are formed from either ring opening or ring opening and subsequent rearrangement. The main aim of this review is to provide a comprehensive overview of various possible reactions and the mechanisms involved, after which these ring-opened and rearranged products of guanine would be formed in DNA. The biological significance of oxidatively damaged products of G is also discussed.

  9. [The pharmaceutical company Choay: an history linked to research and commercialization of biological products].

    PubMed

    Bonnemain, Bruno

    2015-12-01

    Eugène Choay, when he created his own company in 1911, had already a large experience in pharmaceutical industry obtained with Maison Frère where he discovered the famous Dentol, well known thank to Poulbot's publicity drawings for this product. But, convinced of the future of biological products and Opotherapy, he decided to invest himself in this area with a totally new process for cold desiccation of organs. The success will be there and several pharmacists from Choay family will take care of the company and bring it to the top of its specialty in Opotherapy. At the beginning of the 1970's, Choay in in full development and has the products, the sites and the human resources for the future. In 1975, 4 therapeutic areas are covered by Choay's products: coagulation, inflammation, dermatology and hepatology. After more than 65 years of independence, Choay group will be finally bought partially and then totally by Sanofi. With the support of Sanofi, Choay created, in 1981, their US subsidiary called Choay Laboratories Inc;, after the NDA approval of sub-cutaneous Calciparine by the FDA. In 1985 Fraxiparine, a low molecular weight heparin discovered by Jean Choay's team, is lauched on the market. All these developments represent an outstanding record a longevity which indicates how perceptive was Eugène Choay and his successors when choosing to invest totally in the therapeutic use of hormones and products acting on coagulation factors.

  10. Suppressing and enhancing effects of mesoscale dynamics on biological production in the Mozambique Channel

    NASA Astrophysics Data System (ADS)

    José, Y. S.; Penven, P.; Aumont, O.; Machu, E.; Moloney, C. L.; Shillington, F.; Maury, O.

    2016-06-01

    We used a coupled physical-biogeochemical model to investigate how the strong eddy activity typical of the Mozambique Channel affects biological production. A numerical experiment was carried out, in which mesoscale dynamics were suppressed by cancelling the nonlinear terms for horizontal momentum in the Naviers-Stokes equation. Mesoscale dynamics were found to be responsible for (1) increased offshore production in the Mozambique Channel as a result of net eddy-induced offshore transport of nutrient-rich coastal waters; (2) decreased shelf production along the central Mozambican and south-west Madagascar coast caused by a reduction in nutrient availability related to the net eddy-induced lateral transport of nutrients; (3) increased coastal production along the northern Mozambican coast caused by eddy-induced nutrient supply. The model results also showed an intensification and shallowing of the subsurface production, related to increased upper layer nutrient concentrations caused by eddy activity. In addition, by driving the detachment of the East Madagascar Current at the southern tip of the island, inertial processes intensify the southern Madagascar upwelling and causes offshore diffusion of the upwelled waters. These results emphasize the complex role played by eddy activity and, more generally, inertial processes on marine ecosystems in this region.

  11. High-density spore production of a B. cereus aquaculture biological agent by nutrient supplementation.

    PubMed

    Lalloo, Rajesh; Maharajh, Dheepak; Görgens, Johann; Gardiner, Neil; Görgens, J F

    2009-05-01

    Previous studies have demonstrated the efficacy of our Bacillus cereus isolate (NRRL 100132) in reducing concentrations of nitrogenous wastes and inhibiting growth of fish pathogens. In vivo efficacy and tolerance to a range of physiological conditions in systems used to rear Cyprinus carpio make this isolate an excellent candidate for aquaculture applications. Production cost is an important consideration in development of commercially relevant biological products, and this study examines the optimization of nutrient supplementation, which has an impact on high-density production of spores by fermentation. Corn steep liquor (CSL) was identified as a lower cost and more effective nutrient source in comparison to conventional nutrient substrates, in particular yeast extract and nutrient broth. The improved sporulation performance of B. cereus could be related to the increased availability of free amino acids, carbohydrates, and minerals in CSL, which had a positive effect on sporulation efficiency. The impact of nutrient concentration on spore yield and productivity was modeled to develop a tool for optimization of nutrient concentration in fermentation. An excellent fit of the model was confirmed in laboratory fermentation studies. A cost comparison revealed that production using liquid phytase and ultrafiltered-treated CSL was less expensive than spray-dried CSL and supported cultivation of B. cereus spores at densities higher than 1 x 10(10) CFU ml(-1).

  12. An integrated cell-free metabolic platform for protein production and synthetic biology

    PubMed Central

    Jewett, Michael C; Calhoun, Kara A; Voloshin, Alexei; Wuu, Jessica J; Swartz, James R

    2008-01-01

    Cell-free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell-free systems, however, have been limited by their inability to co-activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell-free platform designed to activate natural metabolism, the Cytomim system. We reveal that central catabolism, oxidative phosphorylation, and protein synthesis can be co-activated in a single reaction system. Never before have these complex systems been shown to be simultaneously activated without living cells. The Cytomim system therefore promises to provide the metabolic foundation for diverse ab initio cell-free synthetic biology projects. In addition, we describe an improved Cytomim system with enhanced protein synthesis yields (up to 1200 mg/l in 2 h) and lower costs to facilitate production of protein therapeutics and biochemicals that are difficult to make in vivo because of their toxicity, complexity, or unusual cofactor requirements. PMID:18854819

  13. 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

  14. Connecting marine productivity to sea-spray via nanoscale biological processes: Phytoplankton Dance or Death Disco?

    PubMed Central

    O’Dowd, Colin; Ceburnis, Darius; Ovadnevaite, Jurgita; Bialek, Jakub; Stengel, Dagmar B.; Zacharias, Merry; Nitschke, Udo; Connan, Solene; Rinaldi, Matteo; Fuzzi, Sandro; Decesari, Stefano; Cristina Facchini, Maria; Marullo, Salvatore; Santoleri, Rosalia; Dell’Anno, Antonio; Corinaldesi, Cinzia; Tangherlini, Michael; Danovaro, Roberto

    2015-01-01

    Bursting bubbles at the ocean-surface produce airborne salt-water spray-droplets, in turn, forming climate-cooling marine haze and cloud layers. The reflectance and ultimate cooling effect of these layers is determined by the spray’s water-uptake properties that are modified through entrainment of ocean-surface organic matter (OM) into the airborne droplets. We present new results illustrating a clear dependence of OM mass-fraction enrichment in sea spray (OMss) on both phytoplankton-biomass, determined from Chlorophyll-a (Chl-a) and Net Primary Productivity (NPP). The correlation coefficient for OMss as a function of Chl-a increased form 0.67 on a daily timescale to 0.85 on a monthly timescale. An even stronger correlation was found as a function of NPP, increasing to 0.93 on a monthly timescale. We suggest the observed dependence is through the demise of the bloom, driven by nanoscale biological processes (such as viral infections), releasing large quantities of transferable OM comprising cell debris, exudates and other colloidal materials. This OM, through aggregation processes, leads to enrichment in sea-spray, thus demonstrating an important coupling between biologically-driven plankton bloom termination, marine productivity and sea-spray modification with potentially significant climate impacts. PMID:26464099

  15. Connecting marine productivity to sea-spray via nanoscale biological processes: Phytoplankton Dance or Death Disco?

    PubMed

    O'Dowd, Colin; Ceburnis, Darius; Ovadnevaite, Jurgita; Bialek, Jakub; Stengel, Dagmar B; Zacharias, Merry; Nitschke, Udo; Connan, Solene; Rinaldi, Matteo; Fuzzi, Sandro; Decesari, Stefano; Facchini, Maria Cristina; Marullo, Salvatore; Santoleri, Rosalia; Dell'Anno, Antonio; Corinaldesi, Cinzia; Tangherlini, Michael; Danovaro, Roberto

    2015-10-14

    Bursting bubbles at the ocean-surface produce airborne salt-water spray-droplets, in turn, forming climate-cooling marine haze and cloud layers. The reflectance and ultimate cooling effect of these layers is determined by the spray's water-uptake properties that are modified through entrainment of ocean-surface organic matter (OM) into the airborne droplets. We present new results illustrating a clear dependence of OM mass-fraction enrichment in sea spray (OMss) on both phytoplankton-biomass, determined from Chlorophyll-a (Chl-a) and Net Primary Productivity (NPP). The correlation coefficient for OMss as a function of Chl-a increased form 0.67 on a daily timescale to 0.85 on a monthly timescale. An even stronger correlation was found as a function of NPP, increasing to 0.93 on a monthly timescale. We suggest the observed dependence is through the demise of the bloom, driven by nanoscale biological processes (such as viral infections), releasing large quantities of transferable OM comprising cell debris, exudates and other colloidal materials. This OM, through aggregation processes, leads to enrichment in sea-spray, thus demonstrating an important coupling between biologically-driven plankton bloom termination, marine productivity and sea-spray modification with potentially significant climate impacts.

  16. Effect of Methanethiol Concentration on Sulfur Production in Biological Desulfurization Systems under Haloalkaline Conditions.

    PubMed

    Roman, Pawel; Veltman, René; Bijmans, Martijn F M; Keesman, Karel J; Janssen, Albert J H

    2015-08-04

    Bioremoval of H2S from gas streams became popular in recent years because of high process efficiency and low operational costs. To expand the scope of these processes to gas streams containing volatile organic sulfur compounds, like thiols, it is necessary to provide new insights into their impact on overall biodesulfurization process. Published data on the effect of thiols on biodesulfurization processes are scarce. In this study, we investigated the effect of methanethiol on the selectivity for sulfur production in a bioreactor integrated with a gas absorber. This is the first time that the inhibition of biological sulfur formation by methanethiol is investigated. In our reactor system, inhibition of sulfur production started to occur at a methanethiol loading rate of 0.3 mmol L(-1) d(-1). The experimental results were also described by a mathematical model that includes recent findings on the mode of biomass inhibition by methanethiol. We also found that the negative effect of methanethiol can be mitigated by lowering the salinity of the bioreactor medium. Furthermore, we developed a novel approach to measure the biological activity by sulfide measurements using UV-spectrophotometry. On the basis of this measurement method, it is possible to accurately estimate the unknown kinetic parameters in the mathematical model.

  17. The Pig PeptideAtlas: a resource for systems biology in animal production and biomedicine

    PubMed Central

    Hesselager, Marianne O.; Codrea, Marius C.; Sun, Zhi; Deutsch, Eric W.; Bennike, Tue B.; Stensballe, Allan; Bundgaard, Louise; Moritz, Robert L.; Bendixen, Emøke

    2016-01-01

    Biological research of Sus scrofa, the domestic pig, is of immediate relevance for food production sciences, and for developing pig as a model organism for human biomedical research. Publicly available data repositories play a fundamental role for all biological sciences, and protein data repositories are in particular essential for the successful development of new proteomic methods. Cumulative proteome data repositories, including the PeptideAtlas, provide the means for targeted proteomics, system wide observations, and cross species observational studies, but pigs have so far been underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within the veterinary proteomics domain, and this manuscript demonstrates how the expression of isoform-unique peptides can be observed across distinct tissues and body fluids. The Pig PeptideAtlas is a unique resource for use in animal proteome research, particularly biomarker discovery and for preliminary design of SRM assays, which are equally important for progress in research that supports farm animal production and veterinary health, as for developing pig models with relevance to human health research. PMID:26699206

  18. Huitlacoche (Ustilago maydis) as a food source--biology, composition, and production.

    PubMed

    Valverde, M E; Paredes-López, O; Pataky, J K; Guevara-Lara, F

    1995-01-01

    Huitlacoche is the ethnic name applied to the young fruiting bodies (galls) of the fungus Ustilago maydis, which causes common smut of maize (Zea mays L). Biologists and agronomists have historically used U. maydis as a model to study a wide array of genetic, physiological, ecological, and phytopathological phenomena. In Mexico and other Latin American countries, huitlacoche has been used traditionally as human food, being highly regarded as an interesting dish or condiment. The food potential of huitlacoche is described here in terms of its chemical composition, which includes carbohydrates, proteins, fats, vitamins, and minerals. In addition, essential amino acids (especially lysine) and fatty acids (linoleate) are present in huitlacoche in considerable levels, adding to its nutritional attributes. The feasibility of growing U. maydis in submerged agitated culture has yielded a variety of fermentation products, including essential amino acids, proteins, vitamins, and flavorings, among others. Recent interest in developing huitlacoche as a cash crop has come from increasing acceptance by the North American public, who prize it as a new delicacy. However, research efforts are still needed to determine the biological factors involved in the establishment of U. maydis as a pathogen on the maize plant. This review deals with the role of huitlacoche as a food source, implicating the biological components that will determine the development of technologies for large scale production.

  19. Connecting marine productivity to sea-spray via nanoscale biological processes: Phytoplankton Dance or Death Disco?

    NASA Astrophysics Data System (ADS)

    O'Dowd, Colin; Ceburnis, Darius; Ovadnevaite, Jurgita; Bialek, Jakub; Stengel, Dagmar B.; Zacharias, Merry; Nitschke, Udo; Connan, Solene; Rinaldi, Matteo; Fuzzi, Sandro; Decesari, Stefano; Cristina Facchini, Maria; Marullo, Salvatore; Santoleri, Rosalia; Dell'Anno, Antonio; Corinaldesi, Cinzia; Tangherlini, Michael; Danovaro, Roberto

    2015-10-01

    Bursting bubbles at the ocean-surface produce airborne salt-water spray-droplets, in turn, forming climate-cooling marine haze and cloud layers. The reflectance and ultimate cooling effect of these layers is determined by the spray’s water-uptake properties that are modified through entrainment of ocean-surface organic matter (OM) into the airborne droplets. We present new results illustrating a clear dependence of OM mass-fraction enrichment in sea spray (OMss) on both phytoplankton-biomass, determined from Chlorophyll-a (Chl-a) and Net Primary Productivity (NPP). The correlation coefficient for OMss as a function of Chl-a increased form 0.67 on a daily timescale to 0.85 on a monthly timescale. An even stronger correlation was found as a function of NPP, increasing to 0.93 on a monthly timescale. We suggest the observed dependence is through the demise of the bloom, driven by nanoscale biological processes (such as viral infections), releasing large quantities of transferable OM comprising cell debris, exudates and other colloidal materials. This OM, through aggregation processes, leads to enrichment in sea-spray, thus demonstrating an important coupling between biologically-driven plankton bloom termination, marine productivity and sea-spray modification with potentially significant climate impacts.

  20. Biological treatment of wastewater discharged from biodiesel fuel production plant with alkali-catalyzed transesterification.

    PubMed

    Suehara, Ken-ichiro; Kawamoto, Yoshihiro; Fujii, Eiko; Kohda, Jiro; Nakano, Yasuhisa; Yano, Takuo

    2005-10-01

    The biological treatment of wastewater discharged from a biodiesel fuel (BDF) production plant conducting alkali catalysis transesterification was investigated. BDF wastewater has a high pH and high hexane-extracted oil and low nitrogen concentrations, and inhibits the growth of microorganisms. The biological treatment of BDF wastewater is difficult because the composition of such wastewater is not suitable for microbial growth. To apply the microbiological treatment of BDF wastewater using an oil degradable yeast, Rhodotorula mucilaginosa, the pH was adjusted to 6.8 and several nutrients such as a nitrogen source (ammonium sulfate, ammonium chloride or urea), yeast extract, KH2PO4 and MgSO4.7H2O were added to the wastewater. The optimal initial concentration of yeast extract was 1 g/l and the optimal C/N ratio was between 17 and 68 when using urea as a nitrogen source. A growth inhibitor was also present in the BDF wastewater, and this growth inhibitor could be detected by measuring the solid content in an aqueous phase after the hexane extraction of the wastewater. Microorganisms could not grow at solid contents higher than 2.14 g/l in the wastewater. To avoid the growth inhibition, the BDF wastewater was diluted with the same volume of water. Oil degradation in the diluted BDF wastewater was observed and the best result was obtained under the determined optimal conditions. This treatment system is simple because no controllers, except for a temperature, are necessary. These results suggest that the biological treatment system developed for BDF wastewater is useful for small-scale BDF production plants.

  1. 41 CFR 109-1.5304 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... High Risk Personal Property § 109-1.5304 Deviations. (a) Life cycle control determinations. When the HFO approves a contractor program containing controls, other than life cycle control consistent with... Secretary for Procurement and Assistance Management. A HFO's decision not to provide life-cycle...

  2. 41 CFR 109-1.5304 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... High Risk Personal Property § 109-1.5304 Deviations. (a) Life cycle control determinations. When the HFO approves a contractor program containing controls, other than life cycle control consistent with... Secretary for Procurement and Assistance Management. A HFO's decision not to provide life-cycle...

  3. 2 CFR 170.115 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 2 Grants and Agreements 1 2013-01-01 2013-01-01 false Deviations. 170.115 Section 170.115 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS NATIONAL POLICY REQUIREMENTS...

  4. 2 CFR 170.115 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Deviations. 170.115 Section 170.115 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS Reserved REPORTING SUBAWARD AND...

  5. 2 CFR 25.115 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Deviations. 25.115 Section 25.115 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS Reserved UNIVERSAL IDENTIFIER AND CENTRAL...

  6. 2 CFR 25.115 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 2 Grants and Agreements 1 2013-01-01 2013-01-01 false Deviations. 25.115 Section 25.115 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS PRE-AWARD RESPONSIBILITIES UNIVERSAL IDENTIFIER AND...

  7. 2 CFR 25.115 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 2 Grants and Agreements 1 2012-01-01 2012-01-01 false Deviations. 25.115 Section 25.115 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS PRE-AWARD RESPONSIBILITIES UNIVERSAL IDENTIFIER AND...

  8. 2 CFR 170.115 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 2 Grants and Agreements 1 2012-01-01 2012-01-01 false Deviations. 170.115 Section 170.115 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS NATIONAL POLICY REQUIREMENTS...

  9. Manifestations of Deviation in the Adolescent Subculture

    ERIC Educational Resources Information Center

    Sobkin, V. S.; Abrosimova, Z. B.; Adamchuk, D. V.; Baranova, E. V.

    2005-01-01

    In this article the authors look at questions relating to school students' attitudes toward types of deviation such as smoking and the use of alcohol and narcotics. The empirical material is divided into the following topics: how widespread these forms of behavior are; motives that cause adolescents to start smoking, using alcohol, and taking…

  10. 2 CFR 25.115 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false Deviations. 25.115 Section 25.115 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS Pre-award responsibilities UNIVERSAL IDENTIFIER AND...

  11. 2 CFR 170.115 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false Deviations. 170.115 Section 170.115 Grants and Agreements Office of Management and Budget Guidance for Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS REPORTING SUBAWARD AND...

  12. 15 CFR 14.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORGANIZATIONS General § 14.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for.... Exceptions on a case-by-case basis may also be made by the Assistant Secretary. An exception made on a case-by-case basis will apply to a single award....

  13. 22 CFR 226.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ORGANIZATIONS General § 226.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for... awarding small awards, except for those requirements which are statutory. Exceptions on a case-by-case basis may also be made by the USAID Deputy Assistant Administrator for Management....

  14. 49 CFR 19.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Deviations. 19.4 Section 19.4 Transportation Office of the Secretary of Transportation UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General §...

  15. 49 CFR 19.4 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Deviations. 19.4 Section 19.4 Transportation Office of the Secretary of Transportation UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General §...

  16. 48 CFR 1480.403 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... officials may authorize a deviation for an IA acquisition: For a proposed contract action . . . The... the IA Procurement Chief, absent a CCO). Exceeding $550,000 but not exceeding $11.5 million IA... solicitation when IA makes the following determinations and the appropriate official takes the...

  17. 7 CFR 2502.3 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Deviations. 2502.3 Section 2502.3 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ADVOCACY AND OUTREACH, DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM General Information § 2502.3...

  18. 40 CFR 30.4 - Deviations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Deviations. 30.4 Section 30.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND...

  19. 40 CFR 30.4 - Deviations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Deviations. 30.4 Section 30.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND...

  20. 40 CFR 30.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Deviations. 30.4 Section 30.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND...

  1. 40 CFR 30.4 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Deviations. 30.4 Section 30.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND...

  2. 40 CFR 30.4 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Deviations. 30.4 Section 30.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND...

  3. Bodily Deviations and Body Image in Adolescence

    ERIC Educational Resources Information Center

    Vilhjalmsson, Runar; Kristjansdottir, Gudrun; Ward, Dianne S.

    2012-01-01

    Adolescents with unusually sized or shaped bodies may experience ridicule, rejection, or exclusion based on their negatively valued bodily characteristics. Such experiences can have negative consequences for a person's image and evaluation of self. This study focuses on the relationship between bodily deviations and body image and is based on a…

  4. Use of biologically reclaimed minerals for continuous hydroponic potato production in a CELSS

    NASA Astrophysics Data System (ADS)

    Mackowiak, C. L.; Wheeler, R. M.; Stutte, G. W.; Yorio, N. C.; Sager, J. C.

    1997-01-01

    Plant-derived nutrients were successfully recycled in a Controlled Ecological Life Support System (CELSS) using biological methods. The majority of the essential nutrients were recovered by microbiologically treating the plant biomass in an aerobic bioreactor. Liquid effluent containing the nutrients was then returned to the biomass production component via a recirculating hydroponic system. Potato (Solanum tuberosum L.) cv. Norland plants were grown on those nutrients in either a batch production mode (same age plants on a nutrient solution) or a staggered production mode (4 different ages of plants on a nutrient solution). The study continued over a period of 418 days, within NASA Breadboard Project's Biomass Production Chamber at the Kennedy Space Center. During this period, four consecutive batch cycles (104-day harvests) and 13 consecutive staggered cycles (26-day harvests) were completed using reclaimed minerals and compared to plants grown with standard nutrient solutions. All nutrient solutions were continually recirculated during the entire 418 day study. In general, tuber yields with reclaimed minerals were within 10% of control solutions. Contaminants, such as sodium and recalcitrant organics tended to increase over time in solutions containing reclaimed minerals, however tuber composition was comparable to tubers grown in the control solutions.

  5. Biological oxygen productivity during the last 60,000 years from triple oxygen isotope measurements

    NASA Astrophysics Data System (ADS)

    Blunier, Thomas; Barnett, Bruce; Bender, Michael L.; Hendricks, Melissa B.

    2002-07-01

    The oxygen isotope signature of atmospheric O2 is linked to the isotopic signature of seawater (H2O) through photosynthesis and respiration. Fractionation during these processes is mass dependent, affecting δ17O about half as much as δ18O. An ``anomalous'' fractionation process, which changes δ17O and δ18O of O2 about equally, takes place during isotope exchange between O2 and CO2 in the stratosphere. The relative rates of biologic O2 production and stratospheric processing determine the relationship between δ17O and δ18O of O2 in the atmosphere. Variations of this relationship thus allow us to estimate changes in the rate of mass-dependent O2 production by photosynthesis versus the rate of O2-CO2 exchange in the stratosphere with about equal fractionations of δ17O and δ18O. In this study we reconstruct total oxygen productivity for the last glacial, the last glacial termination, and the early Holocene from the triple isotope composition of atmospheric oxygen trapped in ice cores. With a box model we estimate that total biogenic productivity was only ~76-83% of today for the glacial and was probably lower than today during the glacial-interglacial transition and the early Holocene. Depending on how reduced the oxygen flux from the land biosphere was during the glacial, the oxygen flux from the glacial ocean biosphere was 88-140% of its present value.

  6. The great 2012 Arctic Ocean summer cyclone enhanced biological productivity on the shelves.

    PubMed

    Zhang, Jinlun; Ashjian, Carin; Campbell, Robert; Hill, Victoria; Spitz, Yvette H; Steele, Michael

    2014-01-01

    [1] A coupled biophysical model is used to examine the impact of the great Arctic cyclone of early August 2012 on the marine planktonic ecosystem in the Pacific sector of the Arctic Ocean (PSA). Model results indicate that the cyclone influences the marine planktonic ecosystem by enhancing productivity on the shelves of the Chukchi, East Siberian, and Laptev seas during the storm. Although the cyclone's passage in the PSA lasted only a few days, the simulated biological effects on the shelves last 1 month or longer. At some locations on the shelves, primary productivity (PP) increases by up to 90% and phytoplankton biomass by up to 40% in the wake of the cyclone. The increase in zooplankton biomass is up to 18% on 31 August and remains 10% on 15 September, more than 1 month after the storm. In the central PSA, however, model simulations indicate a decrease in PP and plankton biomass. The biological gain on the shelves and loss in the central PSA are linked to two factors. (1) The cyclone enhances mixing in the upper ocean, which increases nutrient availability in the surface waters of the shelves; enhanced mixing in the central PSA does not increase productivity because nutrients there are mostly depleted through summer draw down by the time of the cyclone's passage. (2) The cyclone also induces divergence, resulting from the cyclone's low-pressure system that drives cyclonic sea ice and upper ocean circulation, which transports more plankton biomass onto the shelves from the central PSA. The simulated biological gain on the shelves is greater than the loss in the central PSA, and therefore, the production on average over the entire PSA is increased by the cyclone. Because the gain on the shelves is offset by the loss in the central PSA, the average increase over the entire PSA is moderate and lasts only about 10 days. The generally positive impact of cyclones on the marine ecosystem in the Arctic, particularly on the shelves, is likely to grow with increasing

  7. Determination of production biology of cladocera in a reservoir receiving hyperthermal effluents from a nuclear production reactor. [Par Pond

    SciTech Connect

    Vigerstad, T J

    1980-01-01

    The effects on zooplankton of residence in a cooling reservoir receiving hyperthermal effluents directly from a nuclear-production-reactor were studied. Rates of cladoceran population production were compared at two stations in the winter and summer of 1976 on Par Pond located on the Savannah River Plant, Aiken, SC. One station was located in an area of the reservoir directly receiving hyperthermal effluent (Station MAS) and the second was located about 4 km away in an area where surface temperatures were normal for reservoirs in the general geographical region (Station CAS). A non-parametric comparison between stations of standing stock and fecundity data for Bosmina longirostris, taken for the egg ratio model, was used to observe potential hyperthermal effluent effects. There was a statistically higher incidence of deformed eggs in the Bosmina population at Station MAS in the summer. Bosmina standing stock underwent two large oscillations in the winter and three large oscillations in the summer at Station MAS compared with two in the winter and one in the summer at Station CAS. These results are consistent with almost all other Par Pond studies which have found the two stations to be essentially similar in spectra composition but with some statistically significant differences in various aspects of the biology of the species.

  8. A novel biologic activity of thrombin: stimulation of monocyte chemotactic protein production

    PubMed Central

    1994-01-01

    Thrombin is a serine protease that is released at sites of vascular injury and exerts a variety of biologic effects on different cell types. Thrombin is postulated to play a role in the pathogenesis of a number of diseases including atherosclerosis, since it activates vascular smooth muscle and endothelial cells. Thrombin mediates these effects through a specific receptor that is upregulated in vascular cells in atherosclerosis. Atherosclerosis and glomerulosclerosis are characterized by the presence of monocyte-macrophages in the lesions. Monocyte chemotactic protein (MCP-1) is believed to be an important mediator of monocyte recruitment to the tissue and can be induced in a broad variety of cells including mesangial cells. We studied the effect of thrombin on MCP-1 production and gene expression in well- characterized human mesangial cells, vascular pericytes that play a central role in fibrosis of the glomerular microvascular bed. alpha thrombin stimulates MCP-1 production and gene expression in mesangial cells in a dose- and time-dependent manner. Experiments with diisopropylfluorophosphate thrombin and gamma thrombin demonstrate that this thrombin effect requires both receptor binding as well as catalytic activity, features consistent with the known properties of the recently characterized and cloned thrombin receptor. Moreover, a human thrombin receptor activating peptide (TRAP1-7) also stimulates MCP-1 production. Northern blot analysis demonstrated that mesangial cells express an mRNA transcript that hybridizes with labeled human thrombin receptor cDNA. These data describe a novel biologic activity of thrombin and suggest an additional mechanism by which this coagulation factor may participate in the progression of glomerulosclerosis, and by analogy, atherosclerosis. PMID:8163952

  9. Linking Physical Dynamics and Biological Productivity in a Coastal Mesoscale Eddy

    NASA Astrophysics Data System (ADS)

    Simons, R. D.; Nishimoto, M. M.; Washburn, L.; Brown, K. S.; Siegel, D. A.

    2014-12-01

    The Santa Barbara Channel (SBC) eddy is a cyclonic mesoscale eddy located off the coast of Southern California, USA. In the summer of 1998 and 1999, the SBC eddy was surveyed for juvenile fishes. In 1998, very high numbers of juvenile fishes were observed within the eddy, but not in 1999. The ocean conditions that contributed to the differences in fish abundances inside the eddy were investigated with three-dimensional numerical modeling. The physical dynamics of the SBC eddy, which included eddy size, three-dimensional rotational structure, and isopycnal uplift, were evaluated using a three-dimensional Regional Ocean Modeling System (ROMS). The retention ability of the eddy was quantified using a three-dimensional particle tracking model driven by the ROMS. The physical dynamics and particle retention of the SBC eddy were found to differ significantly in 1998 and 1999. In 1998, when the SBC eddy was rotating at a steady rate spatially and temporally and cycling consistently in and out of solid-body rotation, the particle retention was high and the isopycnal uplift sustained. However in 1999, when the SBC eddy was rotating unsteadily in space and time and did not have periods of solid-body rotation, the particle retention was low and the isopycnal uplift unstable. We theorize that the steady symmetric rotation of the eddy in 1998 had two important impacts on the biological productivity inside the eddy. First, it provided a prolonged period of cold nutrient rich water uplifting into the euphotic zone, which stimulated productivity and consequently attracted zooplankton. Second, it allowed the zooplankton, prey for the juvenile fish, to be retained inside the eddy, which attracted the juvenile fish. We conclude that biological productivity inside mesoscale eddies may be linked to the stability of its three-dimensional rotational structure and consequently its ability to retain particles.

  10. Biological detoxification of fungal toxins and its use in plant breeding, feed and food production.

    PubMed

    Karlovsky, P

    1999-01-01

    Enzymatic inactivation of fungal toxins is an attractive strategy for the decontamination of agricultural commodities and for the protection of crops from phytotoxic effects of fungal metabolites. This review summarizes research on the biological detoxification of fungal toxins by microorganisms and plants and its practical applications. Some mycotoxins are detoxified during ensiling and other fermentation processes (aflatoxins, alternariol, mycophenolic acid, patulin, PR toxin) while others are transformed into toxic products or survive fermentation unchanged. Plants can detoxify fomannoxin, fusaric acid, HC-toxin, ochratoxin A and oxalate but the degradation of deoxynivalenol has yet to be proven. Microflora of the digestive tract of vertebrates and invertebrates exhibit detoxification activities towards aflatoxins, ochratoxin A, oxalate and trichothecenes. Some toxin-producing fungi are able to degrade or transform their own products under suitable conditions. Pure cultures of bacteria and fungi which detoxify mycotoxins have been isolated from complex microbial populations by screening and enrichment culture techniques. Genes responsible for some of the detoxification activities have been cloned and expressed in heterologous hosts. The detoxification of aflatoxins, cercosporin, fumonisins, fusaric acid, ochratoxin A, oxalic acid, patulin, trichothecenes and zearalenone by pure cultures is reviewed. Finally, current application of these results in food and feed production and plant breeding is summarized and expected future developments are outlined.

  11. Production of Biologically Active Cecropin A Peptide in Rice Seed Oil Bodies

    PubMed Central

    Izquierdo, Esther; Campo, Sonia; Badosa, Esther; Rossignol, Michel; Montesinos, Emilio; San Segundo, Blanca; Coca, María

    2016-01-01

    Cecropin A is a natural antimicrobial peptide that exhibits fast and potent activity against a broad spectrum of pathogens and neoplastic cells, and that has important biotechnological applications. However, cecropin A exploitation, as for other antimicrobial peptides, is limited by their production and purification costs. Here, we report the efficient production of this bioactive peptide in rice bran using the rice oleosin 18 as a carrier protein. High cecropin A levels were reached in rice seeds driving the expression of the chimeric gene by the strong embryo-specific oleosin 18 own promoter, and targeting the peptide to the oil body organelle as an oleosin 18-cecropin A fusion protein. The accumulation of cecropin A in oil bodies had no deleterious effects on seed viability and seedling growth, as well as on seed yield. We also show that biologically active cecropin A can be easily purified from the transgenic rice seeds by homogenization and simple flotation centrifugation methods. Our results demonstrate that the oleosin fusion technology is suitable for the production of cecropin A in rice seeds, which can potentially be extended to other antimicrobial peptides to assist their exploitation. PMID:26760761

  12. In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector

    PubMed Central

    Li, Yi; Beitelshees, Marie; Fang, Lei; Hill, Andrew; Ahmadi, Mahmoud Kamal; Chen, Mingfu; Davidson, Bruce A.; Knight, Paul; Smith, Randall J.; Andreadis, Stelios T.; Hakansson, Anders P.; Jones, Charles H.; Pfeifer, Blaine A.

    2016-01-01

    The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector. PMID:27419235

  13. Characterization of soluble microbial products in a drinking water biological aerated filter.

    PubMed

    Kang, Jia; Ma, Teng-Fei; Zhang, Peng; Gao, Xu; Chen, You-Peng

    2016-05-01

    Utilization-associated products (UAPs) and biomass-associated products (BAPs) were quantified separately in this study to characterize soluble microbial products (SMPs) in a drinking water lab-scale biological aerated filter (BAF), and their basic characteristics were explored using gel filtration chromatography and three-dimensional excitation-emission matrix (3D-EEM) spectrophotometry with fluorescence regional integration analysis and parallel factor model. UAPs were observed increased with the increase of filter media depth and accumulated after BAF treatment, whereas BAPs were basically constant. 3D-EEM spectroscopy analysis result showed that tryptophan and protein-like compounds were the main components of UAPs and BAPs, and fulvic-acid-like substance was a major component of BAPs, rather than UAPs. In terms of molecular weight (MW) distribution, UAP MW presented a bimodal distribution in the range of 1-5 and >10 kDa, while BAP MW exhibited unimodal distribution with MW >20 kDa fraction accounting for more than 90 %. The macromolecules of UAPs accumulated after BAF treatment. This study provides theoretical support for in-depth study of SMP characteristics.

  14. Production of Biologically Active Cecropin A Peptide in Rice Seed Oil Bodies.

    PubMed

    Montesinos, Laura; Bundó, Mireia; Izquierdo, Esther; Campo, Sonia; Badosa, Esther; Rossignol, Michel; Montesinos, Emilio; San Segundo, Blanca; Coca, María

    2016-01-01

    Cecropin A is a natural antimicrobial peptide that exhibits fast and potent activity against a broad spectrum of pathogens and neoplastic cells, and that has important biotechnological applications. However, cecropin A exploitation, as for other antimicrobial peptides, is limited by their production and purification costs. Here, we report the efficient production of this bioactive peptide in rice bran using the rice oleosin 18 as a carrier protein. High cecropin A levels were reached in rice seeds driving the expression of the chimeric gene by the strong embryo-specific oleosin 18 own promoter, and targeting the peptide to the oil body organelle as an oleosin 18-cecropin A fusion protein. The accumulation of cecropin A in oil bodies had no deleterious effects on seed viability and seedling growth, as well as on seed yield. We also show that biologically active cecropin A can be easily purified from the transgenic rice seeds by homogenization and simple flotation centrifugation methods. Our results demonstrate that the oleosin fusion technology is suitable for the production of cecropin A in rice seeds, which can potentially be extended to other antimicrobial peptides to assist their exploitation.

  15. Deviations from LTE in a stellar atmosphere

    NASA Technical Reports Server (NTRS)

    Kalkofen, W.; Klein, R. I.; Stein, R. F.

    1979-01-01

    Deviations for LTE are investigated in an atmosphere of hydrogen atoms with one bound level, satisfying the equations of radiative, hydrostatic, and statistical equilibrium. The departure coefficient and the kinetic temperature as functions of the frequency dependence of the radiative cross section are studied analytically and numerically. Near the outer boundary of the atmosphere, the departure coefficient is smaller than unity when the radiative cross section grows with frequency faster than with the square of frequency; it exceeds unity otherwise. Far from the boundary the departure coefficient tends to exceed unity for any frequency dependence of the radiative cross section. Overpopulation always implies that the kinetic temperature in the statistical-equilibrium atmosphere is higher than the temperature in the corresponding LTE atmosphere. Upper and lower bounds on the kinetic temperature are given for an atmosphere with deviations from LTE only in the optically shallow layers when the emergent intensity can be described by a radiation temperature.

  16. Applying complex models to poultry production in the future--economics and biology.

    PubMed

    Talpaz, H; Cohen, M; Fancher, B; Halley, J

    2013-09-01

    The ability to determine the optimal broiler feed nutrient density that maximizes margin over feeding cost (MOFC) has obvious economic value. To determine optimal feed nutrient density, one must consider ingredient prices, meat values, the product mix being marketed, and the projected biological performance. A series of 8 feeding trials was conducted to estimate biological responses to changes in ME and amino acid (AA) density. Eight different genotypes of sex-separate reared broilers were fed diets varying in ME (2,723-3,386 kcal of ME/kg) and AA (0.89-1.65% digestible lysine with all essential AA acids being indexed to lysine) levels. Broilers were processed to determine carcass component yield at many different BW (1.09-4.70 kg). Trial data generated were used in model constructed to discover the dietary levels of ME and AA that maximize MOFC on a per broiler or per broiler annualized basis (bird × number of cycles/year). The model was designed to estimate the effects of dietary nutrient concentration on broiler live weight, feed conversion, mortality, and carcass component yield. Estimated coefficients from the step-wise regression process are subsequently used to predict the optimal ME and AA concentrations that maximize MOFC. The effects of changing feed or meat prices across a wide spectrum on optimal ME and AA levels can be evaluated via parametric analysis. The model can rapidly compare both biological and economic implications of changing from current practice to the simulated optimal solution. The model can be exploited to enhance decision making under volatile market conditions.

  17. Versatile method for production and controlled polymer-immobilization of biologically active recombinant proteins.

    PubMed

    Allard, Laure; Cheynet, Valérie; Oriol, Guy; Mandrand, Bernard; Delair, Thierry; Mallet, François

    2002-11-05

    The immobilization of a protein by covalent attachment to a support matrix should involve only functional groups of the protein that are not essential for its biological activity. A general strategy for obtaining recombinant proteins designed for oriented covalent grafting onto copolymers was investigated. The rationale involves the definition of seven p24-derived recombinant proteins as fused to either distant or adjacent tags comprising primary amine rich tag consisting of six contiguous lysines suitable for oriented covalent immobilization and a hexa-histidine tag suitable for metal chelate affinity purification. High-level expression, efficient affinity purification, and coupling yields onto maleic anhydride-alt-methyl vinyl ether copolymers higher than 95% were obtained for all proteins. Afterwards, an investigation of the biological features of the immobilized vs. nonimmobilized protein onto the copolymer allowed us to select one bioconjugate which was used in a diagnostic context, i.e., as a capture antigen in an ELISA format test. Sera from 107 HIV-seropositive individuals at various stages of HIV infection, including two seroconversion panels and 104 healthy HIV-seronegative controls, were tested using either RH24 or RK24H-copolymer coated onto the microtiter plate. These assays showed that the use of such a protein-copolymer bioconjugate allowed detection of lower antibody titers than the RH24 protein, illustrating the potential of applications of such doubly tagged proteins. Thus, a set of expression vectors was designed containing four different combinations of hexa-lysine and hexa-histidine tags and a multiple cloning site, allowing the production of different recombinant fusion proteins suitable for biological reactivity conservation after immobilization.

  18. Biological products for the treatment of psoriasis: therapeutic targets, pharmacodynamics and disease-drug-drug interaction implications.

    PubMed

    Wang, Jie; Wang, Yow-Ming C; Ahn, Hae-Young

    2014-09-01

    Psoriasis is a chronic inflammatory skin disease condition that involves altered expression of a broad spectrum of proinflammatory cytokines which are associated with activation of T cells and proliferation of keratinocytes. Currently approved biological products for psoriasis treatment fall into two main classes: cytokine modulators and biologics targeting T cells. In psoriatic patients, elevated levels of proinflammatory cytokines are observed. Elevated proinflammatory cytokines can suppress some cytochrome P450 (CYP) enzymes, and the treatment of psoriasis with biological products can reduce proinflammatory cytokine levels. Therefore, the exposure of CYP substrate drugs is anticipated to be affected by the psoriasis disease resulting in a higher exposure than in healthy state (named disease-drug interaction) as well as by the biological treatments due to disease improvements resulting in a decrease in exposure (named disease-drug-drug interaction, disease-DDI). However, the quantitative impact on CYP substrate exposure due to disease or due to treatment with biological products remains to be evaluated. The objective of the current review is to provide an overview of the therapeutic targets and cytokine-related pharmacodynamic effects of biological products in psoriasis treatment with a particular focus on their implications for disease-DDI. The clinical study design considerations for psoriasis disease-DDI evaluation are also discussed.

  19. Optimisation of the biological pretreatment of wheat straw with white-rot fungi for ethanol production.

    PubMed

    López-Abelairas, M; Álvarez Pallín, M; Salvachúa, D; Lú-Chau, T; Martínez, M J; Lema, J M

    2013-09-01

    The biological pretreatment of lignocellulosic biomass for the production of bioethanol is an environmentally friendly alternative to the most frequently used process, steam explosion (SE). However, this pretreatment can still not be industrially implemented due to long incubation times. The main objective of this work was to test the viability of and optimise the biological pretreatment of lignocellulosic biomass, which uses ligninolytic fungi (Pleurotus eryngii and Irpex lacteus) in a solid-state fermentation of sterilised wheat straw complemented with a mild alkali treatment. In this study, the most important parameters of the mechanical and thermal substrate conditioning processes and the most important parameters of the fungal fermentation process were optimised to improve sugar recovery. The largest digestibilities were achieved with fermentation with I. lacteus under optimised conditions, under which cellulose and hemicellulose digestibility increased after 21 days of pretreatment from 16 to 100 % and 12 to 87 %, respectively. The maximum glucose yield (84 %) of cellulose available in raw material was obtained after only 14 days of pretreatment with an overall ethanol yield of 74 % of the theoretical value, which is similar to that reached with SE.

  20. Production of feline leukemia inhibitory factor with biological activity in Escherichia coli.

    PubMed

    Kanegi, R; Hatoya, S; Tsujimoto, Y; Takenaka, S; Nishimura, T; Wijewardana, V; Sugiura, K; Takahashi, M; Kawate, N; Tamada, H; Inaba, T

    2016-07-15

    Leukemia inhibitory factor (LIF) is a cytokine which is essential for oocyte and embryo development, embryonic stem cell, and induced pluripotent stem cell maintenance. Leukemia inhibitory factor improves the maturation of oocytes in the human and the mouse. However, feline LIF (fLIF) cloning and effects on oocytes during IVM have not been reported. Thus, we cloned complete cDNA of fLIF and examined its biological activity and effects on oocytes during IVM in the domestic cat. The aminoacid sequence of fLIF revealed a homology of 81% or 92% with that of mouse or human. The fLIF produced by pCold TF DNA in Escherichia coli was readily soluble and after purification showed bioactivity in maintaining the undifferentiated state of mouse embryonic stem cells and enhancing the proliferation of human erythrocyte leukemia cells. Furthermore, 10- and 100-ng/mL fLIF induced cumulus expansion with or without FSH and EGF (P < 0.05). The rate of metaphase II oocytes was also improved with 100-ng/mL fLIF (P < 0.05). We therefore confirmed the successful production for the first time of biologically active fLIF and revealed its effects on oocytes during IVM in the domestic cat. Feline LIF will further improve reproduction and stem cell research in the feline family.

  1. Synthetic biology for production of natural and new-to-nature terpenoids in photosynthetic organisms.

    PubMed

    Arendt, Philipp; Pollier, Jacob; Callewaert, Nico; Goossens, Alain

    2016-07-01

    With tens of thousands of characterized members, terpenoids constitute the largest class of natural compounds that are synthesized by all living organisms. Several terpenoids play primary roles in the maintenance of cell membrane fluidity, as pigments or as phytohormones, but most of them function as specialized metabolites that are involved in plant resistance to herbivores or plant-environment interactions. Terpenoids are an essential component of human nutrition, and many are economically important pharmaceuticals, aromatics and potential next-generation biofuels. Because of the often low abundance in their natural source, as well as the demand for novel terpenoid structures with new or improved bioactivities, terpenoid biosynthesis has become a prime target for metabolic engineering and synthetic biology projects. In this review we focus on the creation of new-to-nature or tailor-made plant-derived terpenoids in photosynthetic organisms, in particular by means of combinatorial biosynthesis and the activation of silent metabolism. We reflect on the characteristics of different potential photosynthetic host organisms and recent advances in synthetic biology and discuss their utility for the (heterologous) production of (novel) terpenoids.

  2. Removal of anaerobic soluble microbial products in a biological activated carbon reactor.

    PubMed

    Dong, Xiaojing; Zhou, Weili; He, Shengbing

    2013-09-01

    The soluble microbial products (SMP) in the biological treatment effluent are generally of great amount and are poorly biodegradable. Focusing on the biodegradation of anaerobic SMP, the biological activated carbon (BAC) was introduced into the anaerobic system. The experiments were conducted in two identical lab-scale up-flow anaerobic sludge blanket (UASB) reactors. The high strength organics were degraded in the first UASB reactor (UASB1) and the second UASB (UASB2, i.e., BAC) functioned as a polishing step to remove SMP produced in UASB1. The results showed that 90% of the SMP could be removed before granular activated carbon was saturated. After the saturation, the SMP removal decreased to 60% on the average. Analysis of granular activated carbon adsorption revealed that the main role of SMP removal in BAC reactor was biodegradation. A strain of SMP-degrading bacteria, which was found highly similar to Klebsiella sp., was isolated, enriched and inoculated back to the BAC reactor. When the influent chemical oxygen demand (COD) was 10,000 mg/L and the organic loading rate achieved 10 kg COD/(m3 x day), the effluent from the BAC reactor could meet the discharge standard without further treatment. Anaerobic BAC reactor inoculated with the isolated Klebsiella was proved to be an effective, cheap and easy technical treatment approach for the removal of SMP in the treatment of easily-degradable wastewater with COD lower than 10,000 mg/L.

  3. Note onset deviations as musical piece signatures.

    PubMed

    Serrà, Joan; Özaslan, Tan Hakan; Arcos, Josep Lluis

    2013-01-01

    A competent interpretation of a musical composition presents several non-explicit departures from the written score. Timing variations are perhaps the most important ones: they are fundamental for expressive performance and a key ingredient for conferring a human-like quality to machine-based music renditions. However, the nature of such variations is still an open research question, with diverse theories that indicate a multi-dimensional phenomenon. In the present study, we consider event-shift timing variations and show that sequences of note onset deviations are robust and reliable predictors of the musical piece being played, irrespective of the performer. In fact, our results suggest that only a few consecutive onset deviations are already enough to identify a musical composition with statistically significant accuracy. We consider a mid-size collection of commercial recordings of classical guitar pieces and follow a quantitative approach based on the combination of standard statistical tools and machine learning techniques with the semi-automatic estimation of onset deviations. Besides the reported results, we believe that the considered materials and the methodology followed widen the testing ground for studying musical timing and could open new perspectives in related research fields.

  4. Note Onset Deviations as Musical Piece Signatures

    PubMed Central

    Serrà, Joan; Özaslan, Tan Hakan; Arcos, Josep Lluis

    2013-01-01

    A competent interpretation of a musical composition presents several non-explicit departures from the written score. Timing variations are perhaps the most important ones: they are fundamental for expressive performance and a key ingredient for conferring a human-like quality to machine-based music renditions. However, the nature of such variations is still an open research question, with diverse theories that indicate a multi-dimensional phenomenon. In the present study, we consider event-shift timing variations and show that sequences of note onset deviations are robust and reliable predictors of the musical piece being played, irrespective of the performer. In fact, our results suggest that only a few consecutive onset deviations are already enough to identify a musical composition with statistically significant accuracy. We consider a mid-size collection of commercial recordings of classical guitar pieces and follow a quantitative approach based on the combination of standard statistical tools and machine learning techniques with the semi-automatic estimation of onset deviations. Besides the reported results, we believe that the considered materials and the methodology followed widen the testing ground for studying musical timing and could open new perspectives in related research fields. PMID:23935971

  5. On large deviations for ensembles of distributions

    SciTech Connect

    Khrychev, D A

    2013-11-30

    The paper is concerned with the large deviations problem in the Freidlin-Wentzell formulation without the assumption of the uniqueness of the solution to the equation involving white noise. In other words, it is assumed that for each ε>0 the nonempty set P{sub ε} of weak solutions is not necessarily a singleton. Analogues of a number of concepts in the theory of large deviations are introduced for the set (P{sub ε}, ε>0), hereafter referred to as an ensemble of distributions. The ensembles of weak solutions of an n-dimensional stochastic Navier-Stokes system and stochastic wave equation with power-law nonlinearity are shown to be uniformly exponentially tight. An idempotent Wiener process in a Hilbert space and idempotent partial differential equations are defined. The accumulation points in the sense of large deviations of the ensembles in question are shown to be weak solutions of the corresponding idempotent equations. Bibliography: 14 titles.

  6. Constrained Least Absolute Deviation Neural Networks

    PubMed Central

    Wang, Zhishun; Peterson, Bradley S.

    2008-01-01

    It is well known that least absolute deviation (LAD) criterion or L1-norm used for estimation of parameters is characterized by robustness, i.e., the estimated parameters are totally resistant (insensitive) to large changes in the sampled data. This is an extremely useful feature, especially, when the sampled data are known to be contaminated by occasionally occurring outliers or by spiky noise. In our previous works, we have proposed the least absolute deviation neural network (LADNN) to solve unconstrained LAD problems. The theoretical proofs and numerical simulations have shown that the LADNN is Lyapunov-stable and it can globally converge to the exact solution to a given unconstrained LAD problem. We have also demonstrated its excellent application value in time-delay estimation. More generally, a practical LAD application problem may contain some linear constraints, such as a set of equalities and/or inequalities, which is called constrained LAD problem, whereas the unconstrained LAD can be considered as a special form of the constrained LAD. In this paper, we present a new neural network called constrained least absolute deviation neural network (CLADNN) to solve general constrained LAD problems. Theoretical proofs and numerical simulations demonstrate that the proposed CLADNN is Lyapunov stable and globally converges to the exact solution to a given constrained LAD problem, independent of initial values. The numerical simulations have also illustrated that the proposed CLADNN can be used to robustly estimate parameters for nonlinear curve fitting, which is extensively used in signal and image processing. PMID:18269958

  7. Postmarketing safety reports for human drug and biological products; electronic submission requirements. Final rule.

    PubMed

    2014-06-10

    The Food and Drug Administration (FDA or we) is amending its postmarketing safety reporting regulations for human drug and biological products to require that persons subject to mandatory reporting requirements submit safety reports in an electronic format that FDA can process, review, and archive. FDA is taking this action to improve the Agency's systems for collecting and analyzing postmarketing safety reports. The change will help the Agency to more rapidly review postmarketing safety reports, identify emerging safety problems, and disseminate safety information in support of FDA's public health mission. In addition, the amendments will be a key element in harmonizing FDA's postmarketing safety reporting regulations with international standards for the electronic submission of safety information.

  8. [Fundamentals of interferon system function in pathology and molecular biological peculiarities of interferon production].

    PubMed

    Spivak, M Ia; Didenko, L F; Lazarenko, L M; Zholobak, N M

    2008-01-01

    Molecular biological peculiarities of interferon system function in PV-infected persons have been found. It is evident that the interferon production, anti-inflammatory cytokines and their receptors and also defensines play an important role in the mechanism of virus interaction with sensitive cells of macroorganism with development of pathological process. The new conception of expediency for the use of interferons and their inducers as the polyfunctional regulators with a broad spectrum of activity for the treatment of PV-infected patients was suggested. Patents for the method of treatment of PV-infected patients were obtained. New inducers of interferon as well as recombinant IFN-alpha-2b was developed. Our results were introduced in the medical practice.

  9. Advances in microalgae engineering and synthetic biology applications for biofuel production.

    PubMed

    Gimpel, Javier A; Specht, Elizabeth A; Georgianna, D Ryan; Mayfield, Stephen P

    2013-06-01

    Among the technologies being examined to produce renewable fuels, microalgae are viewed by many in the scientific community as having the greatest potential to become economically viable. Algae are capable of producing greater than 50,000 kg/acre/year of biomass [1]. Additionally, most algae naturally accumulate energy-dense oils that can easily be converted into transportation fuels. To reach economic parity with fossil fuels there are still several challenges. These include identifying crop protection strategies, improving harvesting and oil extraction processes, and increasing biomass productivity and oil content. All of these challenges can be impacted by genetic, molecular, and ultimately synthetic biology techniques, and all of these technologies are being deployed to enable algal biofuels to become economically competitive with fossil fuels.

  10. Photolysis of water for H2 production with the use of biological and artificial catalysts

    NASA Astrophysics Data System (ADS)

    Hall, D. O.; Adams, M. W. W.; Morris, P.; Rao, K. K.

    1980-02-01

    An aqueous mixture of chloroplasts, hydrogenase and electron transfer catalyst on illumination liberates H2, the source of the H atoms being water. The rate and duration of H2 production from such a system depends on the stability of chloroplast and hydrogenase activities in light and oxygen. Both chloroplasts and hydrogenases can be stabilized to a certain degree by immobilization in gels or by incubation in bovine serum albumin. Natural electron carriers of hydrogenases are ferredoxin, cytochrome c3 and NAD. Viologen dyes and synthetic iron-sulphur particles (Jeevanu) can substitute for the biological carriers. Methyl viologen, photoreduced in the presence of chloroplasts, can liberate H2 in combination with Pt (Adam's catalyst). An aqueous solution of proflavine can be photoreduced in the presence of organic electron donors such as EDTA, cysteine, dithiothreitol, etc.; the reduced proflavine can subsequently liberate H2 with MV-Pt, MV-hydrogenase, ferredoxin-hydrogenase or cytochrome-hydrogenase systems.

  11. Carboxyethylpyrroles: From Hypothesis to the Discovery of Biologically Active Natural Products.

    PubMed

    Salomon, Robert G

    2017-01-17

    Our research on the roles of lipid oxidation in human disease is guided by chemical intuition. For example, we postulated that 2-(ω-carboxyethyl)pyrrole (CEP) derivatives of primary amines would be produced through covalent adduction of a γ-hydroxyalkenal generated, in turn, through oxidative fragmentation of docosahexaenoates. Our studies confirmed the natural occurrence of this chemistry, and the biological activities of these natural products and their extensive involvements in human physiology (wound healing) and pathology (age-related macular degeneration, autism, atherosclerosis, sickle cell disease, and tumor growth) continue to emerge. This perspective recounts these discoveries and proposes new frontiers where further developments are likely. Perhaps more significantly, it depicts an effective chemistry-based approach to the discovery of novel biochemistry.

  12. Discharge of pharmaceutical products (PPs) through a conventional biological sewage treatment plant: MECs vs PECs?

    PubMed

    Coetsier, C M; Spinelli, S; Lin, L; Roig, B; Touraud, E

    2009-07-01

    Pharmaceuticals for human use are consumed in significant quantities and their occurrence in aquatic systems has been reported by a number of authors. In the context of environmental risk assessment, there is an increasing interest in evaluating the discharge of pharmaceutical products to surface waters through sewage treatment plants (STP). This case study was carried out on a conventional biological treatment plant (Alès, France) and focused on a set of eleven drugs representing the main therapeutic classes. Measured environmental concentrations (MECs) range from the low ng L(-1) to 1.5 microg L(-1) in effluent and up to few hundred ng L(-1) in receiving surface waters. There is a good agreement between MEC and predicted environmental concentration (PEC) values for seven of the eleven investigated drugs in STP effluent. There is not such a good match between PEC and MEC values in surface waters, and this highlights the limits of this approach, at the local scale.

  13. New approach on trace analysis of triclosan in personal care products, biological and environmental matrices.

    PubMed

    Silva, Ana Rita M; Nogueira, J M F

    2008-02-15

    Stir bar sorptive extraction and liquid desorption followed by high performance liquid chromatography with diode array detection (SBSE-LD-LC-DAD) is proposed for the determination of triclosan in personal care products, biological and environmental matrices, which is included in the priority lists, set by several international regulatory organizations. Instrumental conditions and experimental parameters that affecting SBSE-LD efficiency are fully discussed. Throughout systematic assays on 25 mL water samples spiked at the 10.0 microg L(-1) level, it had been established that stir bars coated with 126 microL of polydimethylsiloxane, an equilibrium time of 1h (1000 rpm) and acetonitrile under sonification (60 min) as back-extraction solvent, allowed the best analytical performance to determine triclosan in water matrices. From the data obtained, good recovery and remarkable repeatability were attained, providing experimental average yields (78.5+/-2.2%), although slightly lower than the theoretical equilibrium (99.7%) described by the octanol-water partition coefficients (K(PDMS/W)0.9992) from 0.4 to 108.0 microg L(-1). The application of the present method to determine triclosan in real matrices such as commercial toothpaste, saliva and urban wastewater samples, allowed appropriate selectivity, high sensitivity and accuracy using the standard addition methodology. The proposed method showed to be feasible and sensitive with a low-sample volume requirement to monitor triclosan in personal care products, biological and environmental matrices at the trace level, in compliance with international regulatory directives.

  14. Constraining geochemistry and biological primary productivity in hydrothermal systems via in situ mass spectrometric geochemical mapping

    NASA Astrophysics Data System (ADS)

    Vidoudez, Charles; Marcon, Yann; Bach, Wolfgang; Lebris, Nadine; Dubilier, Nicole; Girguis, Peter

    2014-05-01

    Hydrothermal vent ecosystems are biological hot spots, supported by chemoautotrophic primary productivity and achieving densities comparable to rainforests. Nevertheless, our understanding of the geochemical factors that govern the distribution of animals and microbes within vents is limited. It is well known that vent endemic organisms are found in specific vent "microenvironments", and that these microenvironments are distributed -coarsely speaking- in predictable patterns within a vent field. However, the relative differences in activity among these faunal patches, and their role in influencing geochemical flux remains largely unknown due to historical limitations in our ability to sample and quantify geochemical constituents with fine spatial resolution. In particular, the distribution of biologically important volatiles around vent fields is poorly constrained, as is the degree to which their distribution influences the destiny and distribution of organisms. To characterize the relationship between the distribution of volatiles, chemosynthetic microbes, and chemosynthetic symbioses, we generated detailed geo-referenced maps of methane, hydrogen sulfide, carbon dioxide and oxygen (four of the key volatiles that are both vent- and seawater derived) using an in situ mass spectrometer (ISMS). We characterized these concentrations in over 130 spots across three vent sites associated with the mid-Atlantic ridge in the Menez Gwen vent field. We quantified gases in sites ranging from hot fluids to mussel beds, and found notable relationships between the distribution and consumption of hydrogen sulfide and methane and the animal and microbial communities. Finally, we also developed a metabolic energy "map", which enables us to constrain both the potential energy that is available to these communities as well as the extent to which it is being used, and places constraints on the extent of primary production that can be supported by the realized use of these volatiles.

  15. Physical influence on biological production along the western shelf of Madagascar

    NASA Astrophysics Data System (ADS)

    Pripp, T.; Gammelsrød, T.; Krakstad, J. O.

    2014-02-01

    In September 2009, the R.V. Dr. Fridtjof Nansen surveyed the western coast of Madagascar. Environmental parameters of temperature, salinity, fluorescence and oxygen were profiled with a CTD probe and continuously underway at 5 m utilising a thermosalinograph equipped with a fluorescence sensor. A ship mounted Acoustic Doppler Current Profiler (ADCP) provided current profiles down to 250 m, while estimates of biomass were obtained from acoustics and trawling was used for species identification. In addition, visual whale observations were conducted. The survey revealed three areas that were identified as upwelling regions, namely the Southern Coast (26°S), offshore from Cap St. André (16°S) and near Nosy Be Island (13°S). In these upwelling regions, acoustic estimates, trawling and whale observations indicated high biological productivity. The total acoustic estimate for the whole western coast was as low as 62 000 t, typical for tropical waters. In addition to the upwelling areas, high biological productivity was also found outside river mouths. Ship born wind measurements, as well as re-analysed wind fields, indicated that the southern coast upwelling cell was wind-driven and had a larger extent than reported earlier. The wind conditions were not favourable for upwelling in the two northernmost upwelling cells. Here the ADCP showed high bottom velocities (>1 m s-1) oriented northeast. These currents were probably forced by the migrating eddies in the area as indicated by the remotely sensed Sea Level Anomaly (SLA). Such currents induce bottom friction layer transport oriented towards the coast, thus driving upwelling, although not necessarily penetrating all the way to the surface layer as was the case near Cap St. André.

  16. The contribution of oxazolidinone frame to the biological activity of pharmaceutical drugs and natural products.

    PubMed

    Zappia, Giovanni; Menendez, Pilar; Monache, Giuliano Delle; Misiti, Domenico; Nevola, Laura; Botta, Bruno

    2007-04-01

    The development of resistance by the antibiotics in the Gram-positive pathogenic bacteria over the last twenty years and continuing today has created a need for new antibiotic classes, which may be unaffected by existing bacterial resistance. The oxazolidin-2-ones represent not only a new class with a novel mechanism of action, but also satisfy the requirement for overcoming the resistance mechanisms. Both linezolid and eperozolid, the first chemical candidates, arose from the piperazine subclass, with the first one being chosen further development because of its enhanced pharmacokinetic properties. The main attractive traits of the oxazolidinone series has encouraged further work in the area, and the patent literature reveals that extensive chemical investigation is currently being made. The unexpected early resistance development emphasizes the need for further exploration of features of the oxazolidinone to eliminate these deficiencies. Recently, several changes, involving the C5 side chain as well the N-phenyl heterocyclic ring, give promise for such improvement. Oxazolidinone antibacterial agents comprise also ketolides, derivatives of macrolides, such as erythromycin A, with a newly formed carbamate cycle, with a largely unexplored potential. The oxazolidinone nucleus does not appear only in the structures of antimicrobial drugs, but a number of biological activities are connected with frameworks including the oxazolidinone ring. A partial list of these activities comprises enzyme inhibitors, agonists and antagonists, with a particular citation for a new generation of selective monoamino oxidase inhibitors (befloxatone). The oxazolidinone moiety was found in the structure of few biologically active natural products, such as (-)-cytoxazone and streptazolin. Moreover, in some cases the oxazolidinone ring has been chosen for the preparation of isosteric aza analogues of natural compounds (podophyllotoxin, pilocarpine) that can be more easily synthesised and more

  17. Modelling the impact of variations in ice sheet runoff on fjord and coastal biological productivity over annual to decadal timescales

    NASA Astrophysics Data System (ADS)

    Sole, A. J.; Cowton, T. R.

    2015-12-01

    Each summer, vast quantities of surface-derived ice sheet meltwater runs off from the Greenland Ice Sheet. Much of this runoff is injected into glaciated fjords at depth beneath marine-terminating glaciers. Due to its low relative density, the runoff rises as a buoyant plume up the glaciers' calving fronts, entraining deep fjord water as it does so. This deep, ambient water tends to be relatively rich in nutrients and so the runoff plumes act to fertilise the surface layers of the fjord, leading to an observed late season spike in biological productivity in the fjord's surface layers. Although surface melting and runoff from the Greenland Ice Sheet are predicted to increase significantly in the coming years and decades, the potential effect of this on fjord and coastal biological productivity is yet to be quantified. Here we present simulations of fjord circulation and biological productivity using the Massachusetts Institute of Technology general circulation model (MITgcm), and a new coupled representation of buoyant runoff plumes which enables decadal time period experiments of large three dimensional fjords. We investigate the effect on biological productivity of varying ice sheet runoff, ocean properties, near-surface winds and fjord geometry and bathymetry. We find that variations in ice sheet runoff are particularly important for biological productivity because the rate of discharge controls the depth at which the plumes reach neutral buoyancy and therefore whether the nutrient-rich deep water is delivered to the photic zone.

  18. Biological Production of Methane from Lunar Mission Solid Waste: An Initial Feasibility Assessment

    NASA Astrophysics Data System (ADS)

    Strayer, Richard; Garland, Jay; Janine, Captain

    A preliminary assessment was made of the potential for biological production of methane from solid waste generated during an early planetary base mission to the moon. This analysis includes: 1) estimation of the amount of biodegradable solid waste generated, 2) background on the potential biodegradability of plastics given their significance in solid wastes, and 3) calculation of potential methane production from the estimate of biodegradable waste. The completed analysis will also include the feasibility of biological methane production costs associated with the biological processing of the solid waste. NASA workshops and Advanced Life Support documentation have estimated the projected amount of solid wastes generated for specific space missions. From one workshop, waste estimates were made for a 180 day transit mission to Mars. The amount of plastic packaging material was not specified, but our visual examination of trash returned from stocktickerSTS missions indicated a large percentage would be plastic film. This plastic, which is not biodegradable, would amount to 1.526 kgdw crew-1 d-1 or 6.10 kgdw d-1 for a crew of 4. Over a mission of 10 days this would amount to 61 kgdw of plastics and for an 180 day lunar surface habitation it would be nearly 1100 kgdw . Approx. 24 % of this waste estimate would be biodegradable (human fecal waste, food waste, and paper), but if plastic packaging was replaced with biodegradable plastic, then 91% would be biodegradable. Plastics are man-made long chain polymeric molecules, and can be divided into two main groups; thermoplastics and thermoset plastics. Thermoplastics comprise over 90% of total plastic use in the placecountry-regionUnited States and are derived from polymerization of olefins via breakage of the double bond and subsequent formation of additional carbon to carbon bonds. The resulting sole-carbon chain polymers are highly resistant to biodegradation and hydrolytic cleavage. Common thermoplastics include low

  19. Potential impact of synthetic biology on the development of microbial systems for the production of renewable fuels and chemicals.

    PubMed

    Picataggio, Stephen

    2009-06-01

    Synthetic biology leverages advances in computational biology, molecular biology, protein engineering, and systems biology to design, synthesize, and assemble genetic elements for manipulating cell phenotypes. This emerging field is founded on a vast amount of gene sequence data available in public databases and our ability to rapidly and inexpensively synthesize DNA fragments of sufficient length to encode full-length genes, enzymes, metabolic pathways, and even entire genomes. Several thousand genetic elements encoding enzymes, reporters, repressors, activators, promoters, terminators, ribosome binding sites, signaling devices, and measurement systems are now available for engineering microbes. In addition to facilitating rational design, these new tools allow us to create and harness genetic diversity in combinatorial approaches to rapidly optimize metabolic pathways. As such, synthetic biology holds great promise for accelerating the development of microbial systems for the production of renewable fuels and chemicals.

  20. Current strategies for protein production and purification enabling membrane protein structural biology.

    PubMed

    Pandey, Aditya; Shin, Kyungsoo; Patterson, Robin E; Liu, Xiang-Qin; Rainey, Jan K

    2016-12-01

    Membrane proteins are still heavily under-represented in the protein data bank (PDB), owing to multiple bottlenecks. The typical low abundance of membrane proteins in their natural hosts makes it necessary to overexpress these proteins either in heterologous systems or through in vitro translation/cell-free expression. Heterologous expression of proteins, in turn, leads to multiple obstacles, owing to the unpredictability of compatibility of the target protein for expression in a given host. The highly hydrophobic and (or) amphipathic nature of membrane proteins also leads to challenges in producing a homogeneous, stable, and pure sample for structural studies. Circumventing these hurdles has become possible through the introduction of novel protein production protocols; efficient protein isolation and sample preparation methods; and, improvement in hardware and software for structural characterization. Combined, these advances have made the past 10-15 years very exciting and eventful for the field of membrane protein structural biology, with an exponential growth in the number of solved membrane protein structures. In this review, we focus on both the advances and diversity of protein production and purification methods that have allowed this growth in structural knowledge of membrane proteins through X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM).

  1. Preparation and biological activity of four epiprogoitrin myrosinase-derived products.

    PubMed

    Galletti, S; Bernardi, R; Leoni, O; Rollin, P; Palmieri, S

    2001-01-01

    (5R)-5-Vinyl-1,3-oxazolidine-2-thione, (2S)-1-cyano-2-hydroxy-3-butene, and two diastereoisomeric erythro-(2S)- and threo-(2S)-1-cyano-2-hydroxy-3,4-epithiobutanes were prepared in pure form starting from (2S)-2-hydroxybut-3-enyl glucosinolate (epiprogoitrin). This glucosinolate was isolated in almost pure form using ripe seeds of Crambe abyssinica and then hydrolyzed under different conditions. The hydrolysis was carried out using either myrosinase immobilized on nylon, to produce (5R)-5-vinyl-1,3-oxazolidine-2-thione, or the endogenous myrosinase contained in defatted crambe meals, to produce the other epiprogoitrin-derived products. After purification and physicochemical characterization, all four myrosinase degradation products were tested for their biological activity. A bioassay on Lactuca sativa was chosen as a simple test to determine their apparent action on living tissues. (5R)-5-Vinyl-1,3-oxazolidine-2-thione negatively affected mainly root growth, whereas (2S)-1-cyano-2-hydroxy-3-butene affected the early phase of germination, and both (2S)-1-cyano-2-hydroxy-3,4-epithiobutane diastereoisomers appeared to negatively affect both germination and root growth at doses 5-10 times lower than those of (2S)-1-cyano-2-hydroxy-3-butene or (5R)-5-vinyl-1,3-oxazolidine-2-thione.

  2. Self in vivo production of a synthetic biological drug CTLA4Ig using a minicircle vector.

    PubMed

    Rim, Yeri Alice; Yi, Hyoju; Kim, Youngkyun; Park, Narae; Jung, Hyerin; Kim, Juryun; Jung, Seung Min; Park, Sung-Hwan; Ju, Ji Hyeon

    2014-11-06

    Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA4Ig, abatacept) is a B7/CD28 costimulation inhibitor that can ward off the immune response by preventing the activation of naïve T cells. This therapeutic agent is administered to patients with autoimmune diseases such as rheumatoid arthritis. Its antiarthritic efficacy is satisfactory, but the limitations are the necessity for frequent injection and high cost. Minicircles can robustly express the target molecule and excrete it outside the cell as an indirect method to produce the protein of interest in vivo. We inserted the sequence of abatacept into the minicircle vector, and by successful in vivo injection the host was able to produce the synthetic protein drug. Intravenous infusion of the minicircle induced spontaneous production of CTLA4Ig in mice with collagen-induced arthritis. Self-produced CTLA4Ig significantly decreased the symptoms of arthritis. Injection of minicircle CTLA4Ig regulated Foxp3(+) T cells and Th17 cells. Parental and mock vectors did not ameliorate arthritis or modify the T cell population. We have developed a new concept of spontaneous protein drug delivery using a minicircle vector. Self in vivo production of a synthetic protein drug may be useful when biological drugs cannot be injected because of manufacturing or practical problems.

  3. Self in vivo production of a synthetic biological drug CTLA4Ig using a minicircle vector

    PubMed Central

    Rim, Yeri Alice; Yi, Hyoju; Kim, Youngkyun; Park, Narae; Jung, Hyerin; Kim, Juryun; Jung, Seung Min; Park, Sung-Hwan; Ju, Ji Hyeon

    2014-01-01

    Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA4Ig, abatacept) is a B7/CD28 costimulation inhibitor that can ward off the immune response by preventing the activation of naïve T cells. This therapeutic agent is administered to patients with autoimmune diseases such as rheumatoid arthritis. Its antiarthritic efficacy is satisfactory, but the limitations are the necessity for frequent injection and high cost. Minicircles can robustly express the target molecule and excrete it outside the cell as an indirect method to produce the protein of interest in vivo. We inserted the sequence of abatacept into the minicircle vector, and by successful in vivo injection the host was able to produce the synthetic protein drug. Intravenous infusion of the minicircle induced spontaneous production of CTLA4Ig in mice with collagen-induced arthritis. Self-produced CTLA4Ig significantly decreased the symptoms of arthritis. Injection of minicircle CTLA4Ig regulated Foxp3+ T cells and Th17 cells. Parental and mock vectors did not ameliorate arthritis or modify the T cell population. We have developed a new concept of spontaneous protein drug delivery using a minicircle vector. Self in vivo production of a synthetic protein drug may be useful when biological drugs cannot be injected because of manufacturing or practical problems. PMID:25374010

  4. Biological Pretreatment of Chicken Feather and Biogas Production from Total Broth.

    PubMed

    Patinvoh, Regina J; Feuk-Lagerstedt, Elisabeth; Lundin, Magnus; Sárvári Horváth, Ilona; Taherzadeh, Mohammad J

    2016-12-01

    Chicken feathers are available in large quantities around the world causing environmental challenges. The feathers are composed of keratin that is a recalcitrant protein and is hard to degrade. In this work, chicken feathers were aerobically pretreated for 2-8 days at total solid concentrations of 5, 10, and 20 % by Bacillus sp. C4, a bacterium that produces both α- and β-keratinases. Then, the liquid fraction (feather hydrolysate) as well as the total broth (liquid and solid fraction of pretreated feathers) was used as substrates for biogas production using anaerobic sludge or bacteria granules as inoculum. The biological pretreatment of feather waste was productive; about 75 % of feather was converted to soluble crude protein after 8 days of degradation at initial feather concentration of 5 %. Bacteria granules performed better during anaerobic digestion of untreated feathers, resulting in approximately two times more methane yield (i.e., 199 mlCH4/gVS compared to 105 mlCH4/gVS when sludge was used). Pretreatment improved methane yield by 292 and 105 % when sludge and granules were used on the hydrolysate. Bacteria granules worked effectively on the total broth, yielded 445 mlCH4/gVS methane, which is 124 % more than that obtained with the same type of inoculum from untreated feather.

  5. Human chorionic gonadotropin: Different glycoforms and biological activity depending on its source of production.

    PubMed

    Fournier, Thierry

    2016-06-01

    Human chorionic gonadotropin (hCG) is the first hormonal message from the placenta to the mother. It is detectable in maternal blood two days after implantation and behaves like a super LH agonist stimulating progesterone secretion by the corpus luteum. In addition to maintaining the production of progesterone until the placenta itself produces it, hCG also has a role in myometrial quiescence and local immune tolerance. Specific to humans, hCG is a complex glycoprotein composed of two highly glycosylated subunits. The α-subunit is identical to the pituitary gonadotropin hormones (LH, FSH, TSH), contains two N-glycosylation sites, and is encoded by a single gene (CGA). By contrast, the β-subunits are distinct for each hormones and confer both receptor and biological specificity, although LH and hCG bind to the same receptor (LH/CG-R). The hCG ß-subunit is encoded by a cluster of genes (CGB) and contains two sites of N-glycosylation and four sites of O-glycosylation. The hCG glycosylation state varies with the stage of pregnancy, its source of production and in the pathology. It is well established that hCG is mainly secreted into maternal blood, where it peaks at 8-10weeks of gestation (WG), by the syncytiotrophoblast (ST), which represents the endocrine tissue of the human placenta. The invasive extravillous trophoblast (iEVT) also secretes hCG, and in particular hyperglycosylated forms of hCG (hCG-H) also produced by choriocarcinoma cells. In maternal blood, hCG-H is elevated during early first trimester corresponding to the trophoblastic cell invasion process and then decreases. In addition to its endocrine role, hCG has autocrine and paracrine roles. It promotes formation of the ST and angiogenesis through LH/CG-R but has no effect on trophoblast invasion in vitro. By contrast, hCG-H stimulates trophoblast invasion and angiogenesis by interacting with the TGFß receptor in a LH/CG-R independent signalling pathway. hCG is largely used in antenatal screening

  6. WebBio, a web-based management and analysis system for patient data of biological products in hospital.

    PubMed

    Lu, Ying-Hao; Kuo, Chen-Chun; Huang, Yaw-Bin

    2011-08-01

    We selected HTML, PHP and JavaScript as the programming languages to build "WebBio", a web-based system for patient data of biological products and used MySQL as database. WebBio is based on the PHP-MySQL suite and is run by Apache server on Linux machine. WebBio provides the functions of data management, searching function and data analysis for 20 kinds of biological products (plasma expanders, human immunoglobulin and hematological products). There are two particular features in WebBio: (1) pharmacists can rapidly find out whose patients used contaminated products for medication safety, and (2) the statistics charts for a specific product can be automatically generated to reduce pharmacist's work loading. WebBio has successfully turned traditional paper work into web-based data management.

  7. Measuring and Plotting Surface-Contour Deviations

    NASA Technical Reports Server (NTRS)

    Aragon, Lino A.; Shuck, Thomas; Crockett, Leroy K.

    1987-01-01

    Hand-held device measures deviation of contour of surface from desired contour and provides output to x-y plotter. Carriage on device rolled along track representing desired contour, while spring-loaded stylus on device deflects perpendicularly to track to follow surface. Operator moves carriage of contour-measuring device on beamlike track. Stylus on carriage traces contour of surface above it. Carriage of measuring device holds transducer measuring cross-track displacement of surface from desired contour, and multiple-turn potentiometer measuring position along track.

  8. Meiosis and its deviations in polyploid plants.

    PubMed

    Grandont, L; Jenczewski, E; Lloyd, A

    2013-01-01

    Meiosis is a fundamental process in all sexual organisms that ensures fertility and genome stability and creates genetic diversity. For each of these outcomes, the exclusive formation of crossovers between homologous chromosomes is needed. This is more difficult to achieve in polyploid species which have more than 2 sets of chromosomes able to recombine. In this review, we describe how meiosis and meiotic recombination 'deviate' in polyploid plants compared to diploids, and give an overview of current knowledge on how they are regulated. See also the sister article focusing on animals by Stenberg and Saura in this themed issue.

  9. Penile ossification and acquired penile deviation.

    PubMed

    Vahlensieck, W K; Schaefer, H E; Westenfelder, M

    1995-01-01

    We report on 3 patients with penile deviation during erection caused by ossification in the corpora cavernosa. In each case hard plaques could be palpated. These indurations were removed through a dorsal longitudinal incision. Histologically, solid bone was demonstrable. Two patients were able to resume normal sexual intercourse, but one became impotent following postoperative cavernitis. Penile ossification is rare in man, and its etiology is unknown. It bears no relationship to the os penis normally present in many other mammals. Diagnosis is best made by palpation and X-ray examination. The treatment of choice for symptomatic ossification is surgical excision.

  10. Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance.

    PubMed

    Nicolaou, K C; Hale, Christopher R H; Nilewski, Christian; Ioannidou, Heraklidia A

    2012-08-07

    The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon. Although the early beginnings of organic synthesis came about serendipitously, organic chemists quickly recognized its potential and moved decisively to advance and exploit it in myriad ways for the benefit of mankind. Indeed, from the early days of the synthesis of urea and the construction of the first carbon-carbon bond, the art of organic synthesis improved to impressively high levels of sophistication. Through its practice, today chemists can synthesize organic molecules--natural and designed--of all types of structural motifs and for all intents and purposes. The endeavor of constructing natural products--the organic molecules of nature--is justly called both a creative art and an exact science. Often called simply total synthesis, the replication of nature's molecules in the laboratory reflects and symbolizes the state of the art of synthesis in general. In the last few decades a surge in total synthesis endeavors around the world led to a remarkable collection of achievements that covers a wide ranging landscape of molecular complexity and diversity. In this article, we present highlights of some of our contributions in the field of total synthesis of natural products of biological and medicinal importance. For perspective, we also provide a listing of selected examples of additional natural products synthesized in other laboratories around the world over the last few years.

  11. [Total Synthesis of Biologically Active Natural Products toward Elucidation of the Mode of Action].

    PubMed

    Yoshida, Masahito

    2015-01-01

    Total synthesis of biologically active cyclodepsipeptide destruxin E using solid- and solution-phase synthesis is described. The solid-phase synthesis of destruxin E was initially investigated for the efficient synthesis of destruxin analogues. Peptide elongation from polymer-supported β-alanine was efficiently performed using DIC/HOBt or PyBroP/DIEA, and subsequent cleavage from the polymer-support under weakly acidic conditions furnished a cyclization precursor in moderate yield. Macrolactonization of the cyclization precursor was smoothly performed using 2-methyl-6-nitrobenzoic anhydride (MNBA)/4-(dimethylamino)pyridine N-oxide (DMAPO) to afford macrolactone in moderate yield. Finally, formation of the epoxide in the side chain via three steps provided destruxin E, and the stereochemistry of the epoxide was determined to be S. Its diastereomer, epi-destruxin E, was also synthesized in the same manner used to synthesize the natural product. The stereochemistry of the epoxide was critical for the V-ATPase inhibition; natural product destruxin E exhibited 10-fold more potent V-ATPase inhibition than epi-destruxin E. Next, the scalable synthesis of destruxin E for in vivo study was also performed via solution-phase synthesis. The scalable synthesis of a key component, (S)-HA-Pro-OH, was achieved using osmium-catalyzed diastereoselective dihydroxylation with (DHQD)2PHAL as a chiral ligand; peptide synthesis using Cbz-protected amino acid derivatives furnished the cyclization precursor on a gram-scale. Macrolactonization smoothly provided the macrolactone without forming a dimerized product, even at 6 mM, and the synthesis of destruxin E was achieved via three steps on a gram scale in high purity (>98%).

  12. Nutrient availability affects pigment production but not growth in lichens of biological soil crusts

    USGS Publications Warehouse

    Bowker, M.A.; Koch, G.W.; Belnap, J.; Johnson, N.C.

    2008-01-01

    Recent research suggests that micronutrients such as Mn may limit growth of slow-growing biological soil crusts (BSCs) in some of the drylands of the world. These soil surface communities contribute strongly to arid ecosystem function and are easily degraded, creating a need for new restoration tools. The possibility that Mn fertilization could be used as a restoration tool for BSCs has not been tested previously. We used microcosms in a controlled greenhouse setting to investigate the hypothesis that Mn may limit photosynthesis and consequently growth in Collema tenax, a dominant N-fixing lichen found in BSCs worldwide. We found no evidence to support our hypothesis; furthermore, addition of other nutrients (primarily P, K, and Zn) had a suppressive effect on gross photosynthesis (P = 0.05). We also monitored the growth and physiological status of our microcosms and found that other nutrients increased the production of scytonemin, an important sunscreen pigment, but only when not added with Mn (P = 0.01). A structural equation model indicated that this effect was independent of any photosynthesis-related variable. We propose two alternative hypotheses to account for this pattern: (1) Mn suppresses processes needed to produce scytonemin; and (2) Mn is required to suppress scytonemin production at low light, when it is an unnecessary photosynthate sink. Although Mn fertilization does not appear likely to increase photosynthesis or growth of Collema, it could have a role in survivorship during environmentally stressful periods due to modification of scytonemin production. Thus, Mn enrichment should be studied further for its potential to facilitate BSC rehabilitation. ?? 2008 Elsevier Ltd.

  13. Conference Report: ESF-COST High-Level Research Conference Natural Products Chemistry, Biology and Medicine III.

    PubMed

    Catino, Arthur

    2010-12-01

    Natural Products Chemistry, Biology and Medicine III was the third conference in a series of events sponsored by the European Science Foundation (ESF) and the European Cooperation in the field of Scientific and Technical Research (COST). Scientists came together from within and outside the EU to present cutting-edge developments in chemical synthesis. Research areas included the synthesis of natural products, methods development, isolation/structural elucidation and chemical biology. As our capacity to produce new chemotherapeutic agents relies on chemical synthesis, this year's conference has never been so timely. This report highlights several of the scientific contributions presented during the meeting.

  14. (/sup 125/I)diiodoinsulins. Binding affinities, biologic potencies, and properties of their decay products

    SciTech Connect

    Perez Maceda, B.; Linde, S.; Sonne, O.; Gliemann, J.

    1982-07-01

    Insulin was iodinated with 0.3-0.4 mol /sup 125/I/mol insulin using the lactoperoxidase method. About one-third of the radioactivity incorporated into insulin was in diiodoinsulins and about 40% of these molecules contained diiodotyrosine in residue 14 of the A chain. Most of the remaining molecules contained one A14-monoiodotyrosine and one monoiodotyrosine in either position A19, B16, or B26. The binding affinity and biologic potency of this heterogeneous diiodoinsulin preparation was not significantly different from that of A14-(/sup 125/I)monoiodoinsulin in rat adipocytes, whereas it was slightly reduced in hepatocytes and IM-9 lymphocytes. From the iodine distribution and previous data on the binding affinity of each of the four monoiodoinsulin isomers it was calculated that A14-diiodotyrosine-insulin possesses full binding affinity and biologic potency in adipocytes. Diiodoinsulins isolated from another iodoinsulin preparation (iodate method) contained 58% A19-diiodotyrosine-insulin, and most remaining molecules contained one A19-monoiodotyrosine. The binding affinity of this mixed diiodoinsulin preparation was approximately one-fourth of that of A14-monoiodoinsulin in adipocytes, IM-9 lymphocytes, and hepatocytes. It was calculated that A19-diiodotyrosine-insulin is nearly devoid of binding affinity. The diiodoinsulins (lactoperoxidase method) decayed to iodide (probably from diiodotyrosine-insulin) or to polymers with little specific but a markedly increased nonspecific binding. In addition, the polymers had a marked tendency to adsorb to cellulose acetate filters. Conclusions: 1. The binding affinities of diiodoinsulins range from very low values to values at least as high as that of insulin depending on the positions of the iodine moieties. 2. The relative binding affinities vary among tissues. 3. Polymeric decay products give high nonspecific binding.

  15. Perception via the Deviated Eye in Strabismus

    PubMed Central

    Economides, John R.; Adams, Daniel L.; Horton, Jonathan C.

    2012-01-01

    Misalignment of the eyes can lead to double vision and visual confusion. However, these sensations are rare when strabismus is acquired early in life, because the extra image is suppressed. To explore the mechanism of perceptual suppression in strabismus, the visual fields were mapped binocularly in 14 human subjects with exotropia. Subjects wore red/blue filter glasses to permit dichoptic stimulation while fixating a central target on a tangent screen. A purple stimulus was flashed at a peripheral location; its reported color (“red” or “blue”) revealed which eye’s image was perceived at that locus. The maps showed a vertical border between the center of gaze for each eye, splitting the visual field into two separate regions. In each region, perception was mediated by only one eye, with suppression of the other eye. Unexpectedly, stimuli falling on the fovea of the deviated eye were seen in all subjects. However, they were perceived in a location shifted by the angle of ocular deviation. This plasticity in the coding of visual direction allows accurate localization of objects everywhere in the visual scene, despite the presence of strabismus. PMID:22836262

  16. Tunability versus deviation sensitivity in a nonlinear vortex oscillator

    NASA Astrophysics Data System (ADS)

    Martin, S. Y.; Thirion, C.; Hoarau, C.; Baraduc, C.; Diény, B.

    2013-07-01

    Frequency modulation experiments were performed on a spin torque vortex oscillator for a wide range of modulation frequencies, up to 10% of the oscillator frequency. A thorough analysis of the intermodulation products shows that the key parameter that describes these experiments is the deviation sensitivity, which is the dynamical frequency-current dependence. It differs significantly from the oscillator tunability discussed so far in the context of spin-transfer oscillators. The essential difference between these two concepts is related to the response time of the vortex oscillator, driven either in quasisteady state or in a transient regime.

  17. Mass-production of the arundo wasp and other insects for biological weed control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mass-rearing is underutilized in biological weed control, despite the wealth of biological information available for insects that have been released and the utility of inoculative releases using large numbers of insects to maximize establishment. Mass-rearing is particularly uncommon for biological...

  18. Regulatory and information support for evaluation of biological productivity of Ukrainian forests and climate change

    NASA Astrophysics Data System (ADS)

    Lakyda, Petro; Vasylyshyn, Roman; Lakyda, Ivan

    2013-04-01

    Stabilization and preservation of the planet's climate system today is regarded as one of the most important global political-economic, environmental and social problems of mankind. Rising concentration of carbon dioxide in the planet's atmosphere due to anthropogenic impact is the main reason leading to global climate change. Due to the above mentioned, social demands on forests are changing their biosphere role and function of natural sink of greenhouse gases becomes top priority. It is known that one of the most essential components of biological productivity of forests is their live biomass. Absorption, long-term sequestration of carbon and generation of oxygen are secured by its components. System research of its parametric structure and development of regulatory and reference information for assessment of aboveground live biomass components of trees and stands of the main forest-forming tree species in Ukraine began over twenty-five years ago at the department of forest mensuration and forest inventory of National University of Life and Environmental Sciences of Ukraine, involving staff from other research institutions. Today, regulatory and reference materials for evaluation of parametric structure of live biomass are developed for trees of the following major forest-forming tree species of Ukraine: Scots pine of natural and artificial origin, Crimean pine, Norway spruce, silver fir, pedunculate oak, European beech, hornbeam, ash, common birch, aspen and black alder (P.I. Lakyda et al., 2011). An ongoing process on development of similar regulatory and reference materials for forest stands of the abovementioned forest-forming tree species of Ukraine is secured by scientists of departments of forest management, and forest mensuration and forest inventory. The total experimental research base is 609 temporary sample plots, where 4880 model trees were processed, including 3195 model trees with estimates of live biomass components. Laboratory studies conducted

  19. Impact of sea-ice biology on overall primary production in a biophysical model of the pan-Arctic Ocean

    NASA Astrophysics Data System (ADS)

    Dupont, Frédéric

    2012-08-01

    The contribution of sea-ice biology and impact of Arctic warming on overall primary production in a Pan-Arctic ocean model are investigated in a 57 year (1950-2006) simulation at coarse resolution using a simple ecosystem model. The ice biology model formally represents the growth and aggregation of micro algae into an ice-water interface, nearly undisturbed by surface mixed layer dynamics. The importance of this so-called ‘ice-algae’ stems from their significant contribution to the total primary production (up to 50% depending on the locations, according to observations described in Gosselin et al. (1997). Simple 1D tests reveal that, depending on their initial biomass and light availability, ice algae can affect the temporal variation of surface nutrients, while they marginally impact the total primary production, or the long term position of the nutricline. The sea-ice primary production is found in the model to be as high as 40% of the total primary production depending on the location and 7.5% for the whole Arctic. The modeled primary production of the ocean is negatively correlated to the September ice cover whereas the production in the ice is more weakly positively correlated. Because of the negative correlation between sea ice cover and pelagic primary production, the short term response to the continuing ice decline will be an increased total production as seen in the model, while the ice algae production would decline.

  20. Spectral relative standard deviation: a practical benchmark in metabolomics.

    PubMed

    Parsons, Helen M; Ekman, Drew R; Collette, Timothy W; Viant, Mark R

    2009-03-01

    Metabolomics datasets, by definition, comprise of measurements of large numbers of metabolites. Both technical (analytical) and biological factors will induce variation within these measurements that is not consistent across all metabolites. Consequently, criteria are required to assess the reproducibility of metabolomics datasets that are derived from all the detected metabolites. Here we calculate spectrum-wide relative standard deviations (RSDs; also termed coefficient of variation, CV) for ten metabolomics datasets, spanning a variety of sample types from mammals, fish, invertebrates and a cell line, and display them succinctly as boxplots. We demonstrate multiple applications of spectral RSDs for characterising technical as well as inter-individual biological variation: for optimising metabolite extractions, comparing analytical techniques, investigating matrix effects, and comparing biofluids and tissue extracts from single and multiple species for optimising experimental design. Technical variation within metabolomics datasets, recorded using one- and two-dimensional NMR and mass spectrometry, ranges from 1.6 to 20.6% (reported as the median spectral RSD). Inter-individual biological variation is typically larger, ranging from as low as 7.2% for tissue extracts from laboratory-housed rats to 58.4% for fish plasma. In addition, for some of the datasets we confirm that the spectral RSD values are largely invariant across different spectral processing methods, such as baseline correction, normalisation and binning resolution. In conclusion, we propose spectral RSDs and their median values contained herein as practical benchmarks for metabolomics studies.

  1. Production of anthraquinones, phenolic compounds and biological activities from hairy root cultures of Polygonum multiflorum Thunb.

    PubMed

    Thiruvengadam, Muthu; Praveen, Nagella; Kim, Eun-Hye; Kim, Seung-Hyun; Chung, Ill-Min

    2014-05-01

    report for the production of anthraquinones (emodin and physcion), phenolic compounds and biological activities from hairy root cultures of P. multiflorum.

  2. Simultaneous determination of polar pharmaceuticals and personal care products in biological organs and tissues.

    PubMed

    Tanoue, Rumi; Nomiyama, Kei; Nakamura, Haruna; Hayashi, Terutake; Kim, Joon-Woo; Isobe, Tomohiko; Shinohara, Ryota; Tanabe, Shinsuke

    2014-08-15

    In the present study, a sensitive and accurate isotope dilution method was developed for the simultaneous determination of 17 polar pharmaceutical and personal care product (PPCP) residues (logKow=1.40-5.74), including 14 pharmaceuticals and 3 personal care products, in biological organs and tissues. The proposed method involved enzymatic hydrolysis, followed by sequential clean-up using silica gel chromatography and gel permeation chromatography, and analysis via ultra-high-performance liquid chromatography with tandem mass spectrometry. This method yielded acceptable absolute recoveries (48-88%) and internal standard-corrected recoveries (90-130%) for 17 PPCPs. Method detection limits were between 0.0092 and 3.2ngg(-1) wet weight, and the limits of quantification were between 0.020 and 8.7ngg(-1) wet weight. The method can be used to readily detect the target compounds at trace levels while minimizing the required sample volume. The developed method was applied to the determination of 17 PPCPs in the liver and kidney of 17 birds collected from Japan and also in the plasma, liver, and brain of 7 cyprinoid fish from an effluent-dominated stream in Japan. Triclosan was detected in 5 of 11 fish-eating birds but not in non-fish-eating birds, suggesting the contamination of prey fish by the chemical. Non-steroidal anti-inflammatory drugs, antibacterial agents, and psychotropic agents were frequently detected in the fish tissues. In addition, 7 of the target compounds were found in fish brain. The median brain/plasma ratios of the psychotropic agents ranged from 1.6 (carbamazepine) to 12 (diphenhydramine), indicating high transportability to fish brain.

  3. Constructing Molecular Complexity and Diversity: Total Synthesis of Natural Products of Biological and Medicinal Importance

    PubMed Central

    Nicolaou, K. C.; Hale, Christopher R. H.; Nilewski, Christian; Ioannidou, Heraklidia A.

    2012-01-01

    The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon. Although the early beginnings of organic synthesis came about serendipitously, organic chemists quickly recognized its potential and moved decisively to advance and exploit it in myriad ways for the benefit of mankind. Indeed, from the early days of the synthesis of urea and the construction of the first carbon-carbon bond, the art of organic synthesis improved to impressively high levels of sophistication. Through its practice, today chemists can synthesize organic molecules—natural and designed—of all types of structural motifs and for all intents and purposes. The endeavor of constructing natural products—the organic molecules of nature—is justly called both a creative art and an exact science. Often called simply total synthesis, the replication of nature’s molecules in the laboratory reflects and symbolizes the state of the art of synthesis in general. In the last few decades a surge in total synthesis endeavors around the world led to a remarkable collection of achievements that covers a wide ranging landscape of molecular complexity and diversity. In this article, we present highlights of some of our contributions in the field of total synthesis of natural products of biological and medicinal importance. For perspective, we also provide a listing of selected examples of additional natural products synthesized in other laboratories around the world over the last few years. PMID:22743704

  4. Recovery of Phenolic Acid and Enzyme Production from Corn Silage Biologically Treated by Trametes versicolor.

    PubMed

    Bucić-Kojić, Ana; Šelo, Gordana; Zelić, Bruno; Planinić, Mirela; Tišma, Marina

    2017-03-01

    Corn silage is used as high-energy forage for dairy cows and more recently for biogas production in a process of anaerobic co-digestion with cow manure. In this work, fresh corn silage after the harvest was used as a substrate in solid-state fermentations with T. versicolor with the aim of phenolic acid recovery and enzyme (laccase and manganese peroxidase) production. During 20 days of fermentation, 10.4-, 3.4-, 3.0-, and 1.8-fold increments in extraction yield of syringic acid, vanillic acid, p-hydroxybenzoic acid, and caffeic acid, respectively, were reached when compared to biologically untreated corn silage. Maximal laccase activity was gained on the 4th day of fermentation (V.A. = 180.2 U/dm(3)), and manganese peroxidase activity was obtained after the 3rd day of fermentation (V.A. = 30.1 U/dm(3)). The addition of copper(II) sulfate as inducer during solid state fermentation resulted in 8.5- and 7-fold enhancement of laccase and manganese peroxidase activities, respectively. Furthermore, the influence of pH and temperature on enzyme activities was investigated. Maximal activity of laccase was obtained at T = 50 °C and pH = 3.0, while manganese peroxidase is active at temperature range T = 45-70 °C with the maximal activity at pH = 4.5.

  5. Spotting deviations from R2 inflation

    NASA Astrophysics Data System (ADS)

    de la Cruz-Dombriz, Álvaro; Elizalde, Emilio; Odintsov, Sergei D.; Sáez-Gómez, Diego

    2016-05-01

    We discuss the soundness of inflationary scenarios in theories beyond the Starobinsky model, namely a class of theories described by arbitrary functions of the Ricci scalar and the K-essence field. We discuss the pathologies associated with higher-order equations of motion which will be shown to constrain the stability of this class of theories. We provide a general framework to calculate the slow-roll parameters and the corresponding mappings to the theory parameters. For paradigmatic gravitational models within the class of theories under consideration we illustrate the power of the Planck/Bicep2 latest results to constrain such gravitational Lagrangians. Finally, bounds for potential deviations from Starobinsky-like inflation are derived.

  6. Testing for phylogenetic signal in biological traits: the ubiquity of cross-product statistics.

    PubMed

    Pavoine, Sandrine; Ricotta, Carlo

    2013-03-01

    To evaluate rates of evolution, to establish tests of correlation between two traits, or to investigate to what degree the phylogeny of a species assemblage is predictive of a trait value so-called tests for phylogenetic signal are used. Being based on different approaches, these tests are generally thought to possess quite different statistical performances. In this article, we show that the Blomberg et al. K and K*, the Abouheif index, the Moran's I, and the Mantel correlation are all based on a cross-product statistic, and are thus all related to each other when they are associated to a permutation test of phylogenetic signal. What changes is only the way phylogenetic and trait similarities (or dissimilarities) among the tips of a phylogeny are computed. The definitions of the phylogenetic and trait-based (dis)similarities among tips thus determines the performance of the tests. We shortly discuss the biological and statistical consequences (in terms of power and type I error of the tests) of the observed relatedness among the statistics that allow tests for phylogenetic signal. Blomberg et al. K* statistic appears as one on the most efficient approaches to test for phylogenetic signal. When branch lengths are not available or not accurate, Abouheif's Cmean statistic is a powerful alternative to K*.

  7. A recyclable protein resource derived from cauliflower by-products: Potential biological activities of protein hydrolysates.

    PubMed

    Xu, Yang; Li, Yuting; Bao, Tao; Zheng, Xiaodong; Chen, Wei; Wang, Jianxu

    2017-04-15

    Cauliflower by-products (CBP) are rich in leaf protein. Every year tons of CBP will lead to environmental pollution. Therefore, this study was conducted to extract leaf protein from CBP and investigate its biological activities. Our results showed that the optimal extraction parameters were: a liquid to solid ratio of 4mL/g, a pH of 11, an ultrasonic extraction lasting 15min, and at an applied power of 175W. Under these optimized conditions, 12.066g of soluble leaf protein (SLP) was obtained from 1000g of CBP and its extraction yield was 53.07%. The obtained SLP was further hydrolysed by Alcalase and the SLP hydrolysate (SLPH) showed a potent angiotensin I-converting enzyme (ACE) inhibitory activity with an IC50 value of 138.545μg/mL in vitro. In addition, SLPH promoted the glucose consumption and enhanced the glycogen content in HepG2 cells. Overall, our results suggested that CBP may be recycled for designing future functional foods.

  8. A biological/chemical process for reduced waste and energy consumption: caprolactam production. Final report

    SciTech Connect

    1996-05-01

    A biological/chemical process for converting cyclohexane into caprolactam was investigated: microorganisms in a bioreactor would be used to convert cyclohexane into caprolactone followed by chemical synthesis of caprolactam using ammonia. Four microorganisms were isolated from natural soil and water, that can utilize cyclohexane as a sole source of C and energy for growth. They were shown to have the correct metabolic intermediates and enzymes to convert cyclohexane into cyclohexanol, cyclohexanone, and caprolactone. Genetic techniques to create and select for caprolactone hydrolase negative-mutants were developed; those are used to convert cyclohexane into caprolactone but, because of the block, are unable to metabolize the caprolactone further. Because of a new nylon carpet reycle process and the long time frame for a totally new bioprocess, a limited study was done to evaluate whether a simplified bioprocess to convert cyclohexanol into cyclohexanone or caprolactone was feasible; growth rates and key enzyme levels were measured in a collection of microorganisms that metabolize cyclohexanol to determine if the bioactivity is high enough to support an economical cyclohexanol bioprocess. Although these microorganisms had sufficient bioactivity, they could tolerate only low levels (<1%) of cyclohexanol and thus are not suitable for developing a cost effective bioprocess because of the high cost of dilute product recovery.

  9. Production, purification and biological characterization of mono-PEGylated anti-IL-17A antibody fragments.

    PubMed

    Koussoroplis, Salome-Juliette; Heywood, Sam; Uyttenhove, Catherine; Barilly, Céline; Van Snick, Jacques; Vanbever, Rita

    2013-09-15

    The aim of this study was to maximize the yield of the production of mono-PEGylated anti-interleukin-17A (anti-IL-17A) antibody fragments using large (≥ 20 kDa) polyethylene glycol (PEG) chains. Particular attention was paid to selectively yield mono-PEGylated species to maintain the maximum possible functionality and to simplify the purification. Neutralization of IL-17A by antibody constructs might find application for the treatment of bronchial hyperreactivity. Amino-directed and sulfhydryl-directed PEGylation of the native antibody fragments were compared. The former was selected as it produced the most interesting construct in terms of yield and preservation of biological activity. In particular, the F(ab')2-PEG conjugate with one 40 kDa branched PEG prepared in this study was produced at a 42% yield. The conjugate presented only a slight decrease in its binding activity and in its in vitro inhibitory potency offering interesting perspectives for in vivo studies.

  10. Biological Denitrification of High Nitrate Processing Wastewaters from Explosives Production Plant.

    PubMed

    Cyplik, Paweł; Marecik, Roman; Piotrowska-Cyplik, Agnieszka; Olejnik, Anna; Drożdżyńska, Agnieszka; Chrzanowski, Lukasz

    2012-05-01

    Wastewater samples originating from an explosives production plant (3,000 mg N l(-1) nitrate, 4.8 mg l(-1) nitroglycerin, 1.9 mg l(-1) nitroglycol and 1,200 mg l(-1) chemical oxygen demand) were subjected to biological purification. An attempt to completely remove nitrate and to decrease the chemical oxygen demand was carried out under anaerobic conditions. A soil isolated microbial consortium capable of biodegrading various organic compounds and reduce nitrate to atmospheric nitrogen under anaerobic conditions was used. Complete removal of nitrates with simultaneous elimination of nitroglycerin and ethylene glycol dinitrate (nitroglycol) was achieved as a result of the conducted research. Specific nitrate reduction rate was estimated at 12.3 mg N g(-1) VSS h(-1). Toxicity of wastewater samples during the denitrification process was studied by measuring the activity of dehydrogenases in the activated sludge. Mutagenicity was determined by employing the Ames test. The maximum mutagenic activity did not exceed 0.5. The obtained results suggest that the studied wastewater samples did not exhibit mutagenic properties.

  11. Effect of salinity on N₂O production during shortcut biological nitrogen removal from landfill leachate.

    PubMed

    Liu, Mu; Liu, Tiantian; Peng, Yongzhen; Wang, Shuying; Xiao, Han

    2014-05-01

    Three identical SBR adapted to different salinity were applied to investigate the characteristics of the treatment performance and N2O production [Formula: see text] during shortcut biological nitrogen removal from landfill leachate under various operating parameters. Increase of salinity might deteriorate the activity of the microorganisms leading to the increase of [Formula: see text] , however, the system could be gradually adapted to the inhibition and alleviate the detrimental effect to some extent. The system acclimated to high salinity provided better performance under high salinity shock and a lower possibility of [Formula: see text] , while a sudden decrease in salinity can cause a temporary increase in [Formula: see text] . High salinity strengthened the influence of high ammonia nitrogen concentration and low DO concentration on [Formula: see text] while the strengthening effect was unconspicuous at high DO concentration. The anoxic phase did not produce a significant amount of N2O even at the lowest C/N ratio of 0.5 and was less susceptible to salinity. Characterization of the biomass composition using fluorescence in situ hybridization analysis confirmed that the relative proportion of Nitrosomonas europaea was increased with the increase of the salinity, which may be an important factor for the strengthening effect of salinity on [Formula: see text] .

  12. Animal protein production modules in biological life support systems: Novel combined aquaculture techniques based on the closed equilibrated biological aquatic system (C.E.B.A.S.)

    NASA Astrophysics Data System (ADS)

    Blüm, V.; Andriske, M.; Kreuzberg, K.; Schreibman, M. P.

    Based on the experiences made with the Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) which was primarily deveoloped for long-term and multi-generation experiments with aquatic animals and plants in a space station highly effective fresh water recycling modules were elaborated utilizing a combination of ammonia oxidizing bacteria filters and higher plants. These exhibit a high effectivity to eliminate phosphate and anorganic nitrogen compounds and arc. in addidition. able to contribute to the oxygen supply of the aquatic animals. The C.E.B.A.S. filter system is able to keep a closed artificial aquatic ecosystem containing teleost fishes and water snails biologically stable for several month and to eliminate waste products deriving from degraded dead fishes without a decrease of the oxygen concentration down to less than 3.5 mg/l at 25 °C. More advanced C.E.B.A.S. filter systems, the BIOCURE filters, were also developed for utilization in semiintensive and intensive aquaculture systems for fishes. In fact such combined animal-plant aquaculture systems represent highly effective productions sites for human food if proper plant and fish species are selected The present papers elucidates ways to novel aquaculture systems in which herbivorous fishes are raised by feeding them with plant biomass produced in the BIOCURE filters and presents the scheme of a modification which utilizes a plant species suitable also for human nutrition. Special attention is paid to the benefits of closed aquaculture system modules which may be integrated into bioregenerative life support systems of a higher complexity for, e. g.. lunar or planetary bases including some psychologiccal aspects of the introduction of animal protein production into plant-based life support systems. Moreover, the basic reproductive biological problems of aquatic animal breeding under reduced gravity are explained leading to a disposition of essential research programs in this context.

  13. Biological feedbacks dominate environmental sensitivity of net biomass production in temperate and boreal North American forests

    NASA Astrophysics Data System (ADS)

    Hember, R. A.; Kurz, W. A.; Coops, N.; Boisvenue, C.; Metsaranta, J. M.

    2012-12-01

    Considerable uncertainty remains in how environmental changes are impacting forest biomass dynamics. Here, we analyze a large sample of permanent sample plots and tree-ring chronologies from temperate and boreal forests across North America to empirically derive environmental sensitivity and constrain ecophysiological model simulations of biomass growth (G) and mortality (M). We argue that observed cross-site variation of G for common forest types reflects a combination of genetic differentiation and equilibrium sensitivity to environmental conditions. Growth of all tested tree species exhibited greater than expected exponential sensitivity to temperature and widely varying responses to water deficits. A high degree of persistence in temporal responses of G to environmental change, evident in both tree-ring chronologies and models, suggests that high estimates of equilibrium sensitivity derived from cross-site variation may be attributed to biological feedbacks (e.g., leaf area expansion) that delay and amplify environmental sensitivity above levels more often inferred from short-term transient variation. Long-term plots and tree-ring chronologies in western North America suggest that environmental changes contributed to significant enhancement of G over the 20th century. Increases in M above background levels were triggered by a critical level of modelled actual evapotranspiration (ETa). Leaf area expansion and consequent positive trends in transpiration were the primary factors causing stands to exceed critical levels of ETa. Positive dependence of M on transpiration led us to propose that hydraulic failure may be the primary mechanism causing drought-induced regular mortality and that recent trends may reflect a negative feedback response to 20th century growth enhancement that allowed biomass to build up to levels that were eventually unsustainable through the 1980's and 90's droughts. The effect of the mortality feedback on net biomass production (ΔB) is

  14. Exploratory research on bioactive natural products with a focus on biological phenomena.

    PubMed

    Uemura, Daisuke

    2010-01-01

    The discovery of new basic compounds holds the key for advancing material sciences. We have focused on the identification and characterization of natural key compounds that control biologically and physiologically intriguing phenomena. The discovery of new bioactive molecules, facilitated by a deeper understanding of nature, should advance our knowledge of biological processes and lead to new strategies to treat disease. The structure and function of natural compounds are sometimes unexpectedly original. Based on our past experience and results, we have carried out research to find new directions for compound exploration by directly learning from dynamic biological phenomena in the field, and have succeeded in creating a new research field in biological molecular sciences.

  15. Large deviation analysis of a simple information engine.

    PubMed

    Maitland, Michael; Grosskinsky, Stefan; Harris, Rosemary J

    2015-11-01

    Information thermodynamics provides a framework for studying the effect of feedback loops on entropy production. It has enabled the understanding of novel thermodynamic systems such as the information engine, which can be seen as a modern version of "Maxwell's Dæmon," whereby a feedback controller processes information gained by measurements in order to extract work. Here, we analyze a simple model of such an engine that uses feedback control based on measurements to obtain negative entropy production. We focus on the distribution and fluctuations of the information obtained by the feedback controller. Significantly, our model allows an analytic treatment for a two-state system with exact calculation of the large deviation rate function. These results suggest an approximate technique for larger systems, which is corroborated by simulation data.

  16. Large deviation analysis of a simple information engine

    NASA Astrophysics Data System (ADS)

    Maitland, Michael; Grosskinsky, Stefan; Harris, Rosemary J.

    2015-11-01

    Information thermodynamics provides a framework for studying the effect of feedback loops on entropy production. It has enabled the understanding of novel thermodynamic systems such as the information engine, which can be seen as a modern version of "Maxwell's Dæmon," whereby a feedback controller processes information gained by measurements in order to extract work. Here, we analyze a simple model of such an engine that uses feedback control based on measurements to obtain negative entropy production. We focus on the distribution and fluctuations of the information obtained by the feedback controller. Significantly, our model allows an analytic treatment for a two-state system with exact calculation of the large deviation rate function. These results suggest an approximate technique for larger systems, which is corroborated by simulation data.

  17. Correlation of Arsenic Levels in Smokeless Tobacco Products and Biological Samples of Oral Cancer Patients and Control Consumers.

    PubMed

    Arain, Sadaf S; Kazi, Tasneem G; Afridi, Hassan I; Talpur, Farah N; Kazi, Atif G; Brahman, Kapil D; Naeemullah; Panhwar, Abdul H; Kamboh, Muhammad A

    2015-12-01

    It has been extensively reported that chewing of smokeless tobacco (SLT) can lead to cancers of oral cavity. In present study, the relationship between arsenic (As) exposure via chewing/inhaling different SLT products in oral cancer patients have or/not consumed SLT products was studied. The As in different types of SLT products (gutkha, mainpuri, and snuff) and biological (scalp hair and blood) samples of different types of oral cancer patients and controls were analyzed. Both controls and oral cancer patients have same age group (ranged 30-60 years), socio-economic status, localities, and dietary habits. The concentrations of As in SLT products and biological samples were measured by electrothermal atomic absorption spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked by certified reference materials. The resulted data of present study indicates that the concentration of As was significantly higher in scalp hair and blood samples of oral cancer patients than those of controls (p<0.001). It was also observed that the values of As were two- to threefolds higher in biological samples of controls subjects, consuming SLT products as compared to those have none of these habits (p>0.01). The intake of As via consuming different SLT may have synergistic effects, in addition to other risk factors associated with oral cancer.

  18. Propolis: A Complex Natural Product with a Plethora of Biological Activities That Can Be Explored for Drug Development

    PubMed Central

    Silva-Carvalho, Ricardo; Baltazar, Fátima; Almeida-Aguiar, Cristina

    2015-01-01

    The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins. PMID:26106433

  19. Propolis: A Complex Natural Product with a Plethora of Biological Activities That Can Be Explored for Drug Development.

    PubMed

    Silva-Carvalho, Ricardo; Baltazar, Fátima; Almeida-Aguiar, Cristina

    2015-01-01

    The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins.

  20. Evaluation of growth based rapid microbiological methods for sterility testing of vaccines and other biological products.

    PubMed

    Parveen, Seema; Kaur, Simleen; David, Selwyn A Wilson; Kenney, James L; McCormick, William M; Gupta, Rajesh K

    2011-10-19

    Most biological products, including vaccines, administered by the parenteral route are required to be tested for sterility at the final container and also at various stages during manufacture. The sterility testing method described in the Code of Federal Regulations (21 CFR 610.12) and the United States Pharmacopoeia (USP, Chapter <71>) is based on the observation of turbidity in liquid culture media due to growth of potential contaminants. We evaluated rapid microbiological methods (RMM) based on detection of growth 1) by adenosine triphosphate (ATP) bioluminescence technology (Rapid Milliflex(®) Detection System [RMDS]), and 2) by CO(2) monitoring technologies (BacT/Alert and the BACTEC systems), as alternate sterility methods. Microorganisms representing Gram negative, Gram positive, aerobic, anaerobic, spore forming, slow growing bacteria, yeast, and fungi were prepared in aliquots of Fluid A or a biological matrix (including inactivated influenza vaccines) to contain approximately 0.1, 1, 10 and 100 colony forming units (CFU) in an inoculum of 10 ml. These preparations were inoculated to the specific media required for the various methods: 1) fluid thioglycollate medium (FTM) and tryptic soy broth (TSB) of the compendial sterility method (both membrane filtration and direct inoculation); 2) tryptic soy agar (TSA), Sabouraud dextrose agar (SDA) and Schaedler blood agar (SBA) of the RMDS; 3) iAST and iNST media of the BacT/Alert system and 4) Standard 10 Aerobic/F and Standard Anaerobic/F media of the BACTEC system. RMDS was significantly more sensitive in detecting various microorganisms at 0.1CFU than the compendial methods (p<0.05), whereas the compendial membrane filtration method was significantly more sensitive than the BACTEC and BacT/Alert methods (p<0.05). RMDS detected all microorganisms significantly faster than the compendial method (p<0.05). BacT/Alert and BACTEC methods detected most microorganisms significantly faster than the compendial method