Secured network sensor-based defense system

NASA Astrophysics Data System (ADS)

Wei, Sixiao; Shen, Dan; Ge, Linqiang; Yu, Wei; Blasch, Erik P.; Pham, Khanh D.; Chen, Genshe

2015-05-01

Network sensor-based defense (NSD) systems have been widely used to defend against cyber threats. Nonetheless, if the adversary finds ways to identify the location of monitor sensors, the effectiveness of NSD systems can be reduced. In this paper, we propose both temporal and spatial perturbation based defense mechanisms to secure NSD systems and make the monitor sensor invisible to the adversary. The temporal-perturbation based defense manipulates the timing information of published data so that the probability of successfully recognizing monitor sensors can be reduced. The spatial-perturbation based defense dynamically redeploys monitor sensors in the network so that the adversary cannot obtain the complete information to recognize all of the monitor sensors. We carried out experiments using real-world traffic traces to evaluate the effectiveness of our proposed defense mechanisms. Our data shows that our proposed defense mechanisms can reduce the attack accuracy of recognizing detection sensors.

Components of the cellular defense and detoxification system of the common cuttlefish Sepia officinalis (Mollusca, Cephalopoda).

PubMed

Beuerlein, Knut; Löhr, Sandra; Westermann, Bettina; Ruth, Peter; Schipp, Rudolf

2002-12-01

Endocytotic-active cells in the branchial heart complex of Sepia officinalis were studied by in situ injection of different types of xenobiotics and by in vitro perfusion of the organ complex with a bacterial suspension. The rhogocytes (ovoid cells) ingest particles of all tested sizes by endocytosis and phagocytosis. The hemocytes of the circulating blood and the adhesive hemocytes in the wall of the branchial heart incorporate all tested kinds of foreign materials, including bacterial cells due to phagocytosis achieved by the triangular mesenchymatic cells. The ultrastructural findings also give strong evidence that the triangular mesenchymatic cells are fixed hemocytes that have migrated into the branchial heart tissue. The ingestion and digestion of allogeneic substances and bacteria or their debris by rhogocytes and/or all (forms of) hemocytes suggests the involvement of these either fixed or mobile endocytotic-active cells in the defense and detoxification system of cephalopods.

Comparative genomics of defense systems in archaea and bacteria

PubMed Central

Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.

2013-01-01

Our knowledge of prokaryotic defense systems has vastly expanded as the result of comparative genomic analysis, followed by experimental validation. This expansion is both quantitative, including the discovery of diverse new examples of known types of defense systems, such as restriction-modification or toxin-antitoxin systems, and qualitative, including the discovery of fundamentally new defense mechanisms, such as the CRISPR-Cas immunity system. Large-scale statistical analysis reveals that the distribution of different defense systems in bacterial and archaeal taxa is non-uniform, with four groups of organisms distinguishable with respect to the overall abundance and the balance between specific types of defense systems. The genes encoding defense system components in bacterial and archaea typically cluster in defense islands. In addition to genes encoding known defense systems, these islands contain numerous uncharacterized genes, which are candidates for new types of defense systems. The tight association of the genes encoding immunity systems and dormancy- or cell death-inducing defense systems in prokaryotic genomes suggests that these two major types of defense are functionally coupled, providing for effective protection at the population level. PMID:23470997

Missile Defense: Ballistic Missile Defense System Testing Delays Affect Delivery of Capabilities

DTIC Science & Technology

2016-04-28

Page 1 GAO- 16 -339R Ballistic Missile Defense 441 G St. N.W. Washington, DC 20548 April 28, 2016 Congressional Committees Missile Defense...Ballistic Missile Defense System Testing Delays Affect Delivery of Capabilities For over half a century , the Department of Defense (DOD) has been...81, § 232 (a) (2011). 2 GAO- 16 -339R Ballistic Missile Defense baselines, we analyzed the testing goals for selected elements, which are

Department of Defense Healthcare Management System Modernization (DHMSM)

DTIC Science & Technology

2016-03-01

2016 Major Automated Information System Annual Report Department of Defense Healthcare Management System Modernization (DHMSM) Defense...DSN Fax: Date Assigned: November 16, 2015 Program Information Program Name Department of Defense Healthcare Management System Modernization...DHMSM) DoD Component DoD The acquiring DoD Component is Program Executive Office (PEO) Department of Defense (DoD) Healthcare Management Systems (DHMS

Defense Islands in Bacterial and Archaeal Genomes and Prediction of Novel Defense Systems ▿†‡

PubMed Central

Makarova, Kira S.; Wolf, Yuri I.; Snir, Sagi; Koonin, Eugene V.

2011-01-01

The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic “sinks” that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands. PMID:21908672

Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring

PubMed Central

Vallaster, Markus P; Kukreja, Shweta; Bing, Xin Y; Ngolab, Jennifer; Zhao-Shea, Rubing; Gardner, Paul D; Tapper, Andrew R; Rando, Oliver J

2017-01-01

Paternal environmental conditions can influence phenotypes in future generations, but it is unclear whether offspring phenotypes represent specific responses to particular aspects of the paternal exposure history, or a generic response to paternal ‘quality of life’. Here, we establish a paternal effect model based on nicotine exposure in mice, enabling pharmacological interrogation of the specificity of the offspring response. Paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in male offspring. This effect manifested as increased survival following injection of toxic levels of either nicotine or cocaine, accompanied by hepatic upregulation of xenobiotic processing genes, and enhanced drug clearance. Surprisingly, this protective effect could also be induced by a nicotinic receptor antagonist, suggesting that xenobiotic exposure, rather than nicotinic receptor signaling, is responsible for programming offspring drug resistance. Thus, paternal drug exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics. DOI: http://dx.doi.org/10.7554/eLife.24771.001 PMID:28196335

Xenobiotic Transporter Expression along the Male Genital Tract1

PubMed Central

Klein, David M.; Wright, Stephen H.; Cherrington, Nathan J.

2015-01-01

The male genital tract plays an important role in protecting sperm by forming a distinct compartment separate from the body which limits exposure to potentially toxic substrates. Transporters along this tract can influence the distribution of xenobiotics into the male genital tract through efflux back into the blood or facilitating the accumulation of toxicants. The aim of this study was to quantitatively determine the constitutive mRNA expression of 30 xenobiotic transporters in caput and cauda regions of the epididymis, vas deferens, prostate, and seminal vesicles from adult Sprague-Dawley rats. The epididymis was found to express at least moderate levels of 18 transporters, vas deferens 15, seminal vesicles 23, and prostate 18. Constitutive expression of these xenobiotic transporters in the male genital tract may provide insight into the xenobiotics that can potentially be transported into these tissues and may provide the molecular mechanism for site specific toxicity of select agents. PMID:24814985

Laboratory procedure for estimating residue dynamics of xenobiotic contaminants in a freshwater food chain

USGS Publications Warehouse

Johnson, B. Thomas

1980-01-01

A laboratory method of measuring the accumulation, transfer, elimination, and degradation of xenobiotic contaminants is described for organisms in a freshwater food chain (microorganisms, filter-feeder, and fish). A flow-through diluter-system, 14C-labeled contaminants, gas and thin-layer chromatography, autoradiography, and liquid scintillation spectrometry are used in making residue determinations. Accumulation factors and various index values are developed for measuring and estimating potential accumulation of xenobiotic contaminants by aquatic organisms. The laboratory procedure is economical, simple, reproducible, and ecologically relevant.

Genomic analysis of the aging rodent and human liver: impact on xenobiotic metabolism

EPA Science Inventory

Metabolic homeostasis of the organism is maintained by the liver’s ability to detoxify and eliminate xenobiotics. This is accomplished, in part, by xenobiotic metabolizing enzymes (XMEs), which metabolize xenobiotics and determine whether exposure will result in toxicity. Some ev...

Evolutionary Genomics of Defense Systems in Archaea and Bacteria*

PubMed Central

Koonin, Eugene V.; Makarova, Kira S.; Wolf, Yuri I.

2018-01-01

Evolution of bacteria and archaea involves an incessant arms race against an enormous diversity of genetic parasites. Accordingly, a substantial fraction of the genes in most bacteria and archaea are dedicated to antiparasite defense. The functions of these defense systems follow several distinct strategies, including innate immunity; adaptive immunity; and dormancy induction, or programmed cell death. Recent comparative genomic studies taking advantage of the expanding database of microbial genomes and metagenomes, combined with direct experiments, resulted in the discovery of several previously unknown defense systems, including innate immunity centered on Argonaute proteins, bacteriophage exclusion, and new types of CRISPR-Cas systems of adaptive immunity. Some general principles of function and evolution of defense systems are starting to crystallize, in particular, extensive gain and loss of defense genes during the evolution of prokaryotes; formation of genomic defense islands; evolutionary connections between mobile genetic elements and defense, whereby genes of mobile elements are repeatedly recruited for defense functions; the partially selfish and addictive behavior of the defense systems; and coupling between immunity and dormancy induction/programmed cell death. PMID:28657885

Spatio-temporal Model of Xenobiotic Distribution and Metabolism in an in Silico Mouse Liver Lobule

NASA Astrophysics Data System (ADS)

Fu, Xiao; Sluka, James; Clendenon, Sherry; Glazier, James; Ryan, Jennifer; Dunn, Kenneth; Wang, Zemin; Klaunig, James

Our study aims to construct a structurally plausible in silico model of a mouse liver lobule to simulate the transport of xenobiotics and the production of their metabolites. We use a physiologically-based model to calculate blood-flow rates in a network of mouse liver sinusoids and simulate transport, uptake and biotransformation of xenobiotics within the in silico lobule. Using our base model, we then explore the effects of variations of compound-specific (diffusion, transport and metabolism) and compound-independent (temporal alteration of blood flow pattern) parameters, and examine their influence on the distribution of xenobiotics and metabolites. Our simulations show that the transport mechanism (diffusive and transporter-mediated) of xenobiotics and blood flow both impact the regional distribution of xenobiotics in a mouse hepatic lobule. Furthermore, differential expression of metabolic enzymes along each sinusoid's portal to central axis, together with differential cellular availability of xenobiotics, induce non-uniform production of metabolites. Thus, the heterogeneity of the biochemical and biophysical properties of xenobiotics, along with the complexity of blood flow, result in different exposures to xenobiotics for hepatocytes at different lobular locations. We acknowledge support from National Institute of Health GM 077138 and GM 111243.

In silico identification and construction of microbial gene clusters associated with biodegradation of xenobiotic compounds.

PubMed

Awasthi, Garima; Kumari, Anjani; Pant, Aditya Bhushan; Srivastava, Prachi

2018-01-01

Chemical substances not showing any importance in existence of biological systems and causing serious health hazards may be designated as Xenobiotic compound. Elimination or degradation of these unwanted substances is a major issue of concern for current time research. Process of biodegradation is a very important aspect of current research as discussed in current manuscript. Current study focuses on the detailed mining of data for the construction of microbial consortia for wide range of xenobiotics compounds. Intensive literature search was done for the construction of this library. Desired data was retrieved from NCBI in fasta format. Data was analysed through homology approaches by using BLAST. This homology based searched enriched with a great vision that not only bacterial population but many other cheap and potential sources are available for different xenobiotic degradation. Though it was focused that bacterial population covers a major part of biodegradation which is near about 90.6% but algae and fungi are also showing promising future in degradation of some important xenobiotic compounds. Analysis of data reveals that Pseudomonas putida has potential for degrading maximum compounds. Establishment of correlation through cluster analysis signifies that Pseudomonas putida, Aspergillus niger and Skeletonema costatum can have combined traits that can be used in finding out actual evolutionary relationship between these species. These findings may also givea new outcome in terms of much cheaper and eco-friendly source in the area of biodegradation of specified xenobiotic compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microbial Genomics: The Expanding Universe of Bacterial Defense Systems.

PubMed

Forsberg, Kevin J; Malik, Harmit S

2018-04-23

Bacteria protect themselves against infection using multiple defensive systems that move by horizontal gene transfer and accumulate in genomic 'defense islands'. A recent study exploited these features to uncover ten novel defense systems, substantially expanding the catalog of bacterial defense systems and predicting the discovery of many more. Copyright © 2018 Elsevier Ltd. All rights reserved.

Protecting Networks Via Automated Defense of Cyber Systems

DTIC Science & Technology

2016-09-01

autonomics, and artificial intelligence . Our conclusion is that automation is the future of cyber defense, and that advances are being made in each of...SUBJECT TERMS Internet of Things, autonomics, sensors, artificial intelligence , cyber defense, active cyber defense, automated indicator sharing...called Automated Defense of Cyber Systems, built upon three core technological components: sensors, autonomics, and artificial intelligence . Our

Back to the future: transgenerational transmission of xenobiotic-induced epigenetic remodeling

PubMed Central

Jiménez-Chillarón, Josep C; Nijland, Mark J; Ascensão, António A; Sardão, Vilma A; Magalhães, José; Hitchler, Michael J; Domann, Frederick E; Oliveira, Paulo J

2015-01-01

Epigenetics, or regulation of gene expression independent of DNA sequence, is the missing link between genotype and phenotype. Epigenetic memory, mediated by histone and DNA modifications, is controlled by a set of specialized enzymes, metabolite availability, and signaling pathways. A mostly unstudied subject is how sub-toxic exposure to several xenobiotics during specific developmental stages can alter the epigenome and contribute to the development of disease phenotypes later in life. Furthermore, it has been shown that exposure to low-dose xenobiotics can also result in further epigenetic remodeling in the germ line and contribute to increase disease risk in the next generation (multigenerational and transgenerational effects). We here offer a perspective on current but still incomplete knowledge of xenobiotic-induced epigenetic alterations, and their possible transgenerational transmission. We also propose several molecular mechanisms by which the epigenetic landscape may be altered by environmental xenobiotics and hypothesize how diet and physical activity may counteract epigenetic alterations. PMID:25774863

Modulation of expression and activity of intestinal multidrug resistance-associated protein 2 by xenobiotics

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

Tocchetti, Guillermo Nicolás

The multidrug resistance-associated protein 2 (MRP2/ABCC2) is a transporter that belongs to the ATP-binding cassette (ABC) superfamily. In the intestine, it is localized to the apical membrane of the enterocyte and plays a key role in limiting the absorption of xenobiotics incorporated orally. MRP2 may also play a role in systemic clearance of xenobiotics available from the serosal side of the intestine. MRP2 transports a wide range of substrates, mainly organic anions conjugated with glucuronic acid, glutathione and sulfate and its expression can be modulated by xenobiotics at transcriptional- and post-transcriptional levels. Transcriptional regulation is usually mediated by a groupmore » of nuclear receptors. The pregnane X receptor (PXR) is a major member of this group. Relevant drugs described to up-regulate intestinal MRP2 via PXR are rifampicin, spironolactone and carbamazepine, among others. The constitutive androstane receptor (CAR, NR1I3) was also reported to modulate MRP2 expression, phenobarbital being a typical activator. Dietary compounds, including micronutrients and other natural products, are also capable of regulating intestinal MRP2 expression transcriptionally. We have given them particular attention since the composition of the food ingested daily is not necessarily supervised and may result in interactions with therapeutic drugs. Post-transcriptional regulation of MRP2 activity by xenobiotics, e.g. as a consequence of inhibitory actions, is also described in this review. Unfortunately, only few studies report on drug-drug or nutrient-drug interactions as a consequence of modulation of intestinal MRP2 activity by xenobiotics. Future clinical studies are expected to identify additional interactions resulting in changes in efficacy or safety of therapeutic drugs. - Highlights: • Intestinal MRP2 (ABCC2) expression and activity can be regulated by xenobiotics. • PXR and CAR are major MRP2 modulators through a transcriptional mechanism. �

Structure-activity relationships for xenobiotic transport substrates and inhibitory ligands of P-glycoprotein.

PubMed Central

Bain, L J; McLachlan, J B; LeBlanc, G A

1997-01-01

The multixenobiotic resistance phenotype is characterized by the reduced accumulation of xenobiotics by cells or organisms due to increased efflux of the compounds by P-glycoprotein (P-gp) or related transporters. An extensive xenobiotic database, consisting primarily of pesticides, was utilized in this study to identify molecular characteristics that render a xenobiotic susceptible to transport by or inhibition of P-gp. Transport substrates were differentiated by several molecular size/shape parameters, lipophilicity, and hydrogen bonding potential. Electrostatic features differentiated inhibitory ligands from compounds not catagorized as transport substrates and that did no interact with P-gp. A two-tiered system was developed using the derived structure-activity relationships to identify P-gp transport substrates and inhibitory ligands. Prediction accuracy of the approach was 82%. We then validated the system using six additional pesticides of which tow were predicted to be P-gp inhibitors and four were predicted to be noninteractors, based upon the structure-activity analyses. Experimental determinations using cells transfected with the human MDR1 gene demonstrated that five of the six pesticides were properly catagorized by the structure-activity analyses (83% accuracy). Finally, structure-activity analyses revealed that among P-gp inhibitors, relative inhibitory potency can be predicted based upon the surface area or volume of the compound. These results demonstrate that P-gp transport substrates and inhibitory ligands can be distinguished using molecular characteristics. Molecular characteristics of transport substrates suggest that P-gp may function in the elimination of hydroxylated metabolites of xenobiotics. Images Figure 1. A Figure 1. B Figure 1. C Figure 1. D Figure 1. E Figure 1. F Figure 1. G Figure 1. H Figure 2. Figure 2. Figure 2. Figure 2. Figure 2. Figure 2. Figure 3. A Figure 3. B PMID:9347896

Detection technique of targets for missile defense system

NASA Astrophysics Data System (ADS)

Guo, Hua-ling; Deng, Jia-hao; Cai, Ke-rong

2009-11-01

Ballistic missile defense system (BMDS) is a weapon system for intercepting enemy ballistic missiles. It includes ballistic-missile warning system, target discrimination system, anti-ballistic-missile guidance systems, and command-control communication system. Infrared imaging detection and laser imaging detection are widely used in BMDS for surveillance, target detection, target tracking, and target discrimination. Based on a comprehensive review of the application of target-detection techniques in the missile defense system, including infrared focal plane arrays (IRFPA), ground-based radar detection technology, 3-dimensional imaging laser radar with a photon counting avalanche photodiode (APD) arrays and microchip laser, this paper focuses on the infrared and laser imaging detection techniques in missile defense system, as well as the trends for their future development.

Systematic discovery of antiphage defense systems in the microbial pangenome.

PubMed

Doron, Shany; Melamed, Sarah; Ofir, Gal; Leavitt, Azita; Lopatina, Anna; Keren, Mai; Amitai, Gil; Sorek, Rotem

2018-03-02

The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Sandia National Laboratories: National Security Missions: Defense Systems

Science.gov Websites

; Technology Defense Systems & Assessments About Defense Systems & Assessments Program Areas Robotics R&D 100 Awards Laboratory Directed Research & Development Technology Deployment Centers Audit Sandia's Economic Impact Licensing & Technology Transfer Browse Technology Portfolios

DEFENSE MEDICAL SURVEILLANCE SYSTEM (DMSS)

EPA Science Inventory

AMSA operates the Defense Medical Surveillance System (DMSS), an executive information system whose database contains up-to-date and historical data on diseases and medical events (e.g., hospitalizations, ambulatory visits, reportable diseases, HIV tests, acute respiratory diseas...

Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination.

PubMed

Benachour, Nora; Moslemi, Safa; Sipahutar, Herbert; Seralini, Gilles-Eric

2007-07-15

Xenobiotics may cause long-term adverse effects in humans, especially at the embryonic level, raising questions about their levels of exposure, combined effects, and crucial endpoints. We are interested in the possible interactions between xenobiotic endocrine disrupters, cellular viability and androgen metabolism. Accordingly, we tested aroclor 1254 (A1254), atrazine (AZ), o,p'-DDT, vinclozolin (VZ), p,p'-DDE, bisphenol A (BPA), chlordecone (CD), nonylphenol (NP), tributylin oxide (TBTO), and diethylstilbestrol (DES) for cellular toxicity against human embryonic 293 cells, and activity against cellular aromatase, but also on placental microsomes and on the purified equine enzyme. Cellular viability was affected in 24 h by all the xenobiotics with a threshold at 50 microM (except for TBTO and DES, 10 microM threshold), and aromatase was inhibited at non-toxic doses. In combination synergism was observed reducing the threshold values of toxicity to 4-10 microM, and aromatase activity by 50% in some cases. In placental microsomes the most active xenobiotics rapidly inhibited microsomal aromatase in a manner independent of NADPH metabolism. Prolonged exposures to low doses in cells generally amplified by 50 times aromatase inhibition. These xenobiotics may act by inhibition of the active site or by allosteric effects on the enzyme. Bioaccumulation is a feature of some xenobiotics, especially chlordecone, DDT and DDE, and low level chronic exposures can also affect cell signaling mechanisms. This new information about the mechanism of action of these xenobiotics will assist in improved molecular design with a view to providing safer compounds for use in the (human) environment.

Plant defense compounds: systems approaches to metabolic analysis.

PubMed

Kliebenstein, Daniel J

2012-01-01

Systems biology attempts to answer biological questions by integrating across diverse genomic data sets. With the increasing ability to conduct genomics experiments, this integrative approach is being rapidly applied across numerous biological research communities. One of these research communities investigates how plants utilize secondary metabolites or defense metabolites to defend against attack by pathogens and other biotic organisms. This use of systems biology to integrate across transcriptomics, metabolomics, and genomics is significantly enhancing the rate of discovery of genes, metabolites, and bioactivities for plant defense compounds as well as extending our knowledge of how these compounds are regulated. Plant defense compounds are also providing a unique proving platform to develop new approaches that enhance the ability to conduct systems biology with existing and previously unforseen genomics data sets. This review attempts to illustrate both how systems biology is helping the study of plant defense compounds and vice versa.

75 FR 65439 - Defense Federal Acquisition Regulation Supplement; Electronic Subcontracting Reporting System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 219 and 252 [DFARS Case... System AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Interim rule... Supplement (DFARS) to conform to the Federal Acquisition Regulation (FAR) by providing Department of Defense...

Coordinated Changes in Xenobiotic Metabolizing Enzyme Gene Expression in Aging Male Rats

EPA Science Inventory

In order to gain better insight on aging and susceptibility, we characterized the expression of xenobiotic metabolizing enzymes (XMEs) from the livers of rats to evaluate the change in capacity to respond to xenobiotics across the adult lifespan. Gene expression profiles for XMEs...

Intelligent systems for strategic power infrastructure defense

NASA Astrophysics Data System (ADS)

Jung, Ju-Hwan

A fault or disturbance in a power system can be severe due to the sources of vulnerability such as human errors, protection and control system failures, a failure of communication networks to deliver critical control signals, and market and load uncertainties. There have been several catastrophic failures resulting from disturbances involving the sources of vulnerability while power systems are designed to withstand disturbances or faults. To avoid catastrophic failures or minimize the impact of a disturbance(s), the state of the power system has to be analyzed correctly and preventive or corrective self-healing control actions have to be deployed. This dissertation addresses two aspects of power systems: Defense system and diagnosis, both concerned with the power system analysis and operation during events involving faults or disturbances. This study is intended to develop a defense system that is able to assess power system vulnerability and to perform self-healing control actions based on the system-wide analysis. In order to meet the requirements of the system-wide analysis, the defense system is designed with multi-agent system technologies. Since power systems are dynamic and uncertain the self-healing control actions need to be adaptive. This study applies the reinforcement learning technique to provide a theoretical basis for adaptation. One of the important issues in adaptation is the convergence of the learning algorithm. An appropriate convergence criterion is derived and an application with a load-shedding scheme is demonstrated in this study. This dissertation also demonstrates the feasibility of the defense system and self-healing control actions through multi-agent system technologies. The other subject of this research is to investigate the methodology for on-line fault diagnosis using the information from Sequence-of-Events Recorders (SER). The proposed multiple-hypothesis analysis generates one or more hypothetical fault scenarios to interpret the

Reconstruction of the evolution of microbial defense systems.

PubMed

Puigbò, Pere; Makarova, Kira S; Kristensen, David M; Wolf, Yuri I; Koonin, Eugene V

2017-04-04

Evolution of bacterial and archaeal genomes is a highly dynamic process that involves intensive loss of genes as well as gene gain via horizontal transfer, with a lesser contribution from gene duplication. The rates of these processes can be estimated by comparing genomes that are linked by an evolutionary tree. These estimated rates of genome dynamics events substantially differ for different functional classes of genes. The genes involved in defense against viruses and other invading DNA are among those that are gained and lost at the highest rates. We employed a stochastic birth-and-death model to obtain maximum likelihood estimates of the rates of gain and loss of defense genes in 35 groups of closely related bacterial genomes and one group of archaeal genomes. We find that on average, the defense genes experience 1.4 fold higher flux than the rest of microbial genes. This excessive flux of defense genes over the genomic mean is consistent across diverse microbial groups. The few exceptions include intracellular parasites with small, degraded genomes that possess few defense systems which are more stable than in other microbes. Generally, defense genes follow the previously established pattern of genome dynamics, with gene family loss being about 3 times more common than gain and an order of magnitude more common than expansion or contraction of gene families. Case by case analysis of the evolutionary dynamics of defense genes indicates frequent multiple events in the same locus and widespread involvement of mobile elements in the gain and loss of defense genes. Evolution of microbial defense systems is highly dynamic but, notwithstanding the host-parasite arms race, generally follows the same trends that have been established for the rest of the genes. Apart from the paucity and the low flux of defense genes in parasitic bacteria with deteriorating genomes, there is no clear connection between the evolutionary regime of defense systems and microbial life style.

The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?

PubMed

Park, Yeong-Chul; Lee, Sundong; Cho, Myung-Haing

2014-09-01

Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems.

The biochemistry and molecular biology of xenobiotic polymer degradation by microorganisms.

PubMed

Kawai, Fusako

2010-01-01

Research on microbial degradation of xenobiotic polymers has been underway for more than 40 years. It has exploited a new field not only in applied microbiology but also in environmental microbiology, and has greatly contributed to polymer science by initiating the design of biodegradable polymers. Owing to the development of analytical tools and technology, molecular biological and biochemical advances have made it possible to prospect for degrading microorganisms in the environment and to determine the mechanisms involved in biodegradation when xenobiotic polymers are introduced into the environment and are exposed to microbial attack. In this review, the molecular biological and biochemical aspects of the microbial degradation of xenobiotic polymers are summarized, and possible applications of potent microorganisms, enzymes, and genes in environmental biotechnology are suggested.

Xenobiotics: How the Environment Changes Your Body

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

Baker, Erin

Erin Baker studies how substances foreign to your body affect your health. To do so, her team at PNNL developed a rapid way to separate and study both xenobiotics and endogenous molecules using ion mobility.

Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.

PubMed

Garza-Lombó, Carla; Posadas, Yanahi; Quintanar, Liliana; Gonsebatt, María E; Franco, Rodrigo

2018-06-20

Essential metals such as copper, iron, manganese, and zinc play a role as cofactors in the activity of a wide range of processes involved in cellular homeostasis and survival, as well as during organ and tissue development. Throughout our life span, humans are also exposed to xenobiotic metals from natural and anthropogenic sources, including aluminum, arsenic, cadmium, lead, and mercury. It is well recognized that alterations in the homeostasis of essential metals and an increased environmental/occupational exposure to xenobiotic metals are linked to several neurological disorders, including neurodegeneration and neurodevelopmental alterations. Recent Advances: The redox activity of essential metals is key for neuronal homeostasis and brain function. Alterations in redox homeostasis and signaling are central to the pathological consequences of dysfunctional metal ion homeostasis and increased exposure to xenobiotic metals. Both redox-active and redox-inactive metals trigger oxidative stress and damage in the central nervous system, and the exact mechanisms involved are starting to become delineated. In this review, we aim to appraise the role of essential metals in determining the redox balance in the brain and the mechanisms by which alterations in the homeostasis of essential metals and exposure to xenobiotic metals disturb the cellular redox balance and signaling. We focus on recent literature regarding their transport, metabolism, and mechanisms of toxicity in neural systems. Delineating the specific mechanisms by which metals alter redox homeostasis is key to understand the pathological processes that convey chronic neuronal dysfunction in neurodegenerative and neurodevelopmental disorders. Antioxid. Redox Signal. 28, 1669-1703.

PROXIMAL: a method for Prediction of Xenobiotic Metabolism.

PubMed

Yousofshahi, Mona; Manteiga, Sara; Wu, Charmian; Lee, Kyongbum; Hassoun, Soha

2015-12-22

Contamination of the environment with bioactive chemicals has emerged as a potential public health risk. These substances that may cause distress or disease in humans can be found in air, water and food supplies. An open question is whether these chemicals transform into potentially more active or toxic derivatives via xenobiotic metabolizing enzymes expressed in the body. We present a new prediction tool, which we call PROXIMAL (Prediction of Xenobiotic Metabolism) for identifying possible transformation products of xenobiotic chemicals in the liver. Using reaction data from DrugBank and KEGG, PROXIMAL builds look-up tables that catalog the sites and types of structural modifications performed by Phase I and Phase II enzymes. Given a compound of interest, PROXIMAL searches for substructures that match the sites cataloged in the look-up tables, applies the corresponding modifications to generate a panel of possible transformation products, and ranks the products based on the activity and abundance of the enzymes involved. PROXIMAL generates transformations that are specific for the chemical of interest by analyzing the chemical's substructures. We evaluate the accuracy of PROXIMAL's predictions through case studies on two environmental chemicals with suspected endocrine disrupting activity, bisphenol A (BPA) and 4-chlorobiphenyl (PCB3). Comparisons with published reports confirm 5 out of 7 and 17 out of 26 of the predicted derivatives for BPA and PCB3, respectively. We also compare biotransformation predictions generated by PROXIMAL with those generated by METEOR and Metaprint2D-react, two other prediction tools. PROXIMAL can predict transformations of chemicals that contain substructures recognizable by human liver enzymes. It also has the ability to rank the predicted metabolites based on the activity and abundance of enzymes involved in xenobiotic transformation.

An Analysis of Turkey’s Defense Systems Acquisition Policy

DTIC Science & Technology

2009-03-01

i NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA MBA PROFESSIONAL REPORT An Analysis of Turkey’s Defense Systems Acquisition...2009 3. REPORT TYPE AND DATES COVERED MBA THESIS 4. TITLE AND SUBTITLE An Analysis of Turkey’s Defense Systems Acquisition Policy 6. AUTHOR(S...DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) The purpose of this MBA thesis is to analyze Turkey’s defense systems acquisition policy and

The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a “Central Dogma” for Toxic Mechanisms?

PubMed Central

Lee, Sundong; Cho, Myung-Haing

2014-01-01

Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems. PMID:25343011

Depth Perception and Defensive System Activation in a 3-D Environment

PubMed Central

Combe, Emmanuelle; Fujii, Naotaka

2011-01-01

To survive, animals must be able to react appropriately (in temporal and behavioral terms) when facing a threat. One of the essential parameters considered by the defensive system is the distance of the threat, the “defensive distance.” In this study, we investigate the visual depth cues that could be considered as an alarm cue for the activation of the defensive system. For this purpose, we performed an active-escape pain task in a virtual three-dimensional environment. In two experiments, we manipulated the nature and consistency of different depth cues: vergence, linear perspective, and angular size. By measuring skin conductance responses, we characterized the situations that activated the defensive system. We show that the angular size of the predator was sufficient information to trigger responses from the defensive system, but we also demonstrate that vergence, which can delay the emotional response in inconsistent situations, is also a highly reliable cue for the activation of the defensive system. PMID:21941515

The Evolution of the Contract Type Used in Defense Acquisition with a Focus on Major Defense Weapon Systems

DTIC Science & Technology

2012-09-01

III. THE DEFENSE MARKETPLACE A. DEFENSE INDUSTRY OVERVIEW The market of the defense industry in the United States is different than the commercial...marketplace in a number of respects. Lorell, Lowell, Kennedy, and Levaux (2000) defined the uniqueness of the U.S. defense market in two ways. First...the U.S. defense market for weapon systems is characterized by a single buyer (Lorell et al., 2000, p. 13). “The second distinguishing feature of

Symposium overview: alterations in cytokine receptors by xenobiotics.

PubMed

Cohen, M D; Schook, L B; Oppenheim, J J; Freed, B M; Rodgers, K E

1999-04-01

A symposium entitled Alterations in Cytokine Receptors by Xenobiotics was held at the 37th Annual Meeting of the Society of Toxicology (SOT) in Seattle, Washington. The symposium was sponsored by the Immunotoxicology Specialty Section of SOT and was designed to present information on the effect of several different classes of xenobiotics on various aspects of receptor function (i.e., post-receptor signal transduction of receptor expression), or the involvement of cytokine receptors in the action of the toxicant under consideration. This symposium brought together scientists in the area of receptor immunobiology whose expertise in receptor modulation encompassed those major signaling agents involved in the normal immune response, i.e., proinflammatory cytokines, chemokines, interleukins, and interferons. The following is a summary of each of the individual presentations.

Pregnane xenobiotic receptor in cancer pathogenesis and therapeutic response

PubMed Central

Pondugula, Satyanarayana R.; Mani, Sridhar

2012-01-01

Pregnane xenobiotic receptor (PXR) is an orphan nuclear receptor that regulates the metabolism of endobiotics and xenobiotics. PXR is promiscuous and unique in that it is activated by a diverse group of xenochemicals, including therapeutic anticancer drugs and naturally-occurring endocrine disruptors. PXR has been predominantly studied to understand its regulatory role in xenobiotic clearance in liver and intestine via induction of drug metabolizing enzymes and drug transporters. PXR, however, is widely expressed and has functional implications in other normal and malignant tissues, including breast, prostate, ovary, endometrium and bone. The differential expression of PXR and its target genes in cancer tissues has been suggested to determine the prognosis of chemotherapeutic outcome. In addition, the emerging evidence points to the implications of PXR in regulating apoptotic and antiapoptotic as well as growth factor signaling that promote tumor proliferation and metastasis. In this review, we highlight the recent progress made in understanding the role of PXR in cancer, discuss the future directions to further understand the mechanistic role of PXR in cancer, and conclude with the need to identify novel selective PXR modulators. PMID:22939994

Xenobiotics enhance laccase activity in alkali-tolerant γ-proteobacterium JB.

PubMed

Singh, Gursharan; Batish, Mona; Sharma, Prince; Capalash, Neena

2009-01-01

Various genotoxic textile dyes, xenobiotics, substrates (10 µM) and agrochemicals (100 µg/ml) were tested for enhancement of alkalophilic laccase activity in γ-proteobacterium JB. Neutral Red, Indigo Carmine, Naphthol Base Bordears and Sulphast Ruby dyes increased the activity by 3.7, 2.7, 2.6 and 2.3 fold respectively. Xenobiotics/substrates like p-toluidine, 8-hydroxyquinoline and anthracine increased it by 3.4, 2.8 and 2.3 fold respectively. Atrazine and trycyclozole pesticides enhanced the activity by 1.95 and 1.5 fold respectively.

Xenobiotics enhance laccase activity in alkali-tolerant γ-proteobacterium JB

PubMed Central

Singh, Gursharan; Batish, Mona; Sharma, Prince; Capalash, Neena

2009-01-01

Various genotoxic textile dyes, xenobiotics, substrates (10 µM) and agrochemicals (100 µg/ml) were tested for enhancement of alkalophilic laccase activity in γ-proteobacterium JB. Neutral Red, Indigo Carmine, Naphthol Base Bordears and Sulphast Ruby dyes increased the activity by 3.7, 2.7, 2.6 and 2.3 fold respectively. Xenobiotics/substrates like p-toluidine, 8-hydroxyquinoline and anthracine increased it by 3.4, 2.8 and 2.3 fold respectively. Atrazine and trycyclozole pesticides enhanced the activity by 1.95 and 1.5 fold respectively. PMID:24031313

Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling

PubMed Central

Ochsner, Scott A.; Tsimelzon, Anna; Dong, Jianrong; Coarfa, Cristian

2016-01-01

The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities. PMID:27409825

Research Resource: A Reference Transcriptome for Constitutive Androstane Receptor and Pregnane X Receptor Xenobiotic Signaling.

PubMed

Ochsner, Scott A; Tsimelzon, Anna; Dong, Jianrong; Coarfa, Cristian; McKenna, Neil J

2016-08-01

The pregnane X receptor (PXR) (PXR/NR1I3) and constitutive androstane receptor (CAR) (CAR/NR1I2) members of the nuclear receptor (NR) superfamily of ligand-regulated transcription factors are well-characterized mediators of xenobiotic and endocrine-disrupting chemical signaling. The Nuclear Receptor Signaling Atlas maintains a growing library of transcriptomic datasets involving perturbations of NR signaling pathways, many of which involve perturbations relevant to PXR and CAR xenobiotic signaling. Here, we generated a reference transcriptome based on the frequency of differential expression of genes across 159 experiments compiled from 22 datasets involving perturbations of CAR and PXR signaling pathways. In addition to the anticipated overrepresentation in the reference transcriptome of genes encoding components of the xenobiotic stress response, the ranking of genes involved in carbohydrate metabolism and gonadotropin action sheds mechanistic light on the suspected role of xenobiotics in metabolic syndrome and reproductive disorders. Gene Set Enrichment Analysis showed that although acetaminophen, chlorpromazine, and phenobarbital impacted many similar gene sets, differences in direction of regulation were evident in a variety of processes. Strikingly, gene sets representing genes linked to Parkinson's, Huntington's, and Alzheimer's diseases were enriched in all 3 transcriptomes. The reference xenobiotic transcriptome will be supplemented with additional future datasets to provide the community with a continually updated reference transcriptomic dataset for CAR- and PXR-mediated xenobiotic signaling. Our study demonstrates how aggregating and annotating transcriptomic datasets, and making them available for routine data mining, facilitates research into the mechanisms by which xenobiotics and endocrine-disrupting chemicals subvert conventional NR signaling modalities.

GENE EXPRESSION PROFILING IN AGING RATS AND MICE REVEALS CHANGES IN XENOBIOTIC METABOLISM GENES

EPA Science Inventory

Detoxification and elimination of xenobiotics are major functions of the liver and is important in maintaining the metabolic homeostasis of the organism. The degree to which aging affects hepatic metabolism is not known. The expression of xenobiotic metabolizing enzymes (XMEs), i...

Defense system shortcuts and limits of scope.

PubMed

Rewald, E; Francischetti, M M

2000-10-01

Defense, as a key factor of life, shares the biological tendencies of simplicity and energy saving. We propose that, like the mind, defense tends to rely on shortcuts via immune memes. Also, response repetition may induce the formation of virtual 'modules' [toolkits] to simplify and perfect performance. Engaged modules may expand by proliferating or by capturing immune components from the 'dormant' and even perhaps from active ones. With regard to recovery and/or survival, complexity of the integrated defense system (IDS) (1) requires to be inside of what we call the 'functional window'. In contrast to the physiological and common disease repair, energy is squandered when IDS perceives real danger. Our concern is the uncertain transition to conditions that do not fit into the IDS routine and, even worse, that are outside the functional window where the system is lacking. Copyright 2000 Harcourt Publishers Ltd.

Current knowledge of detoxification mechanisms of xenobiotic in honey bees.

PubMed

Gong, Youhui; Diao, Qingyun

2017-01-01

The western honey bee Apis mellifera is the most important managed pollinator species in the world. Multiple factors have been implicated as potential causes or factors contributing to colony collapse disorder, including honey bee pathogens and nutritional deficiencies as well as exposure to pesticides. Honey bees' genome is characterized by a paucity of genes associated with detoxification, which makes them vulnerable to specific pesticides, especially to combinations of pesticides in real field environments. Many studies have investigated the mechanisms involved in detoxification of xenobiotics/pesticides in honey bees, from primal enzyme assays or toxicity bioassays to characterization of transcript gene expression and protein expression in response to xenobiotics/insecticides by using a global transcriptomic or proteomic approach, and even to functional characterizations. The global transcriptomic and proteomic approach allowed us to learn that detoxification mechanisms in honey bees involve multiple genes and pathways along with changes in energy metabolism and cellular stress response. P450 genes, is highly implicated in the direct detoxification of xenobiotics/insecticides in honey bees and their expression can be regulated by honey/pollen constitutes, resulting in the tolerance of honey bees to other xenobiotics or insecticides. P450s is also a key detoxification enzyme that mediate synergism interaction between acaricides/insecticides and fungicides through inhibition P450 activity by fungicides or competition for detoxification enzymes between acaricides. With the wide use of insecticides in agriculture, understanding the detoxification mechanism of insecticides in honey bees and how honeybees fight with the xenobiotis or insecticides to survive in the changing environment will finally benefit honeybees' management.

Removal of xenobiotics from effluent discharge by adsorption on zeolite and expanded clay: an alternative to activated carbon?

PubMed

Tahar, A; Choubert, J M; Miège, C; Esperanza, M; Le Menach, K; Budzinski, H; Wisniewski, C; Coquery, M

2014-04-01

Xenobiotics such as pesticides and pharmaceuticals are an increasingly large problem in aquatic environments. A fixed-bed adsorption filter, used as tertiary stage of sewage treatment, could be a solution to decrease xenobiotics concentrations in wastewater treatment plants (WWTPs) effluent. The adsorption efficiency of two mineral adsorbent materials (expanded clay (EC) and zeolite (ZE)), both seen as a possible alternative to activated carbon (AC), was evaluated in batch tests. Experiments involving secondary treated domestic wastewater spiked with a cocktail of ten xenobiotics (eight pharmaceuticals and two pesticides) known to be poorly eliminated in conventional biological process were carried out. Removal efficiencies and partitions coefficients were calculated for two levels of initial xenobiotic concentration, i.e, concentrations lower to 10 μg/L and concentrations ranged from 100 to 1,000 μg/L. While AC was the most efficient adsorbent material, both alternative adsorbent materials showed good adsorption efficiencies for all ten xenobiotics (from 50 to 100 % depending on the xenobiotic/adsorbent material pair). For all the targeted xenobiotics, at lower concentrations, EC presented the best adsorption potential with higher partition coefficients, confirming the results in terms of removal efficiencies. Nevertheless, Zeolite presents virtually the same adsorption potential for both high and low xenobiotics concentrations to be treated. According to this first batch investigation, ZE and EC could be used as alternative absorbent materials to AC in WWTP.

Computer-aided prediction of xenobiotic metabolism in the human body

NASA Astrophysics Data System (ADS)

Bezhentsev, V. M.; Tarasova, O. A.; Dmitriev, A. V.; Rudik, A. V.; Lagunin, A. A.; Filimonov, D. A.; Poroikov, V. V.

2016-08-01

The review describes the major databases containing information about the metabolism of xenobiotics, including data on drug metabolism, metabolic enzymes, schemes of biotransformation and the structures of some substrates and metabolites. Computational approaches used to predict the interaction of xenobiotics with metabolic enzymes, prediction of metabolic sites in the molecule, generation of structures of potential metabolites for subsequent evaluation of their properties are considered. The advantages and limitations of various computational methods for metabolism prediction and the prospects for their applications to improve the safety and efficacy of new drugs are discussed. Bibliography — 165 references.

An activated sludge modeling framework for xenobiotic trace chemicals (ASM-X): assessment of diclofenac and carbamazepine.

PubMed

Plósz, Benedek Gy; Langford, Katherine H; Thomas, Kevin V

2012-11-01

Conventional models for predicting the fate of xenobiotic organic trace chemicals, identified, and calibrated using data obtained in batch experiments spiked with reference substances, can be limited in predicting xenobiotic removal in wastewater treatment plants (WWTPs). At stake is the level of model complexity required to adequately describe a general theory of xenobiotic removal in WWTPs. In this article, we assess the factors that influence the removal of diclofenac and carbamazepine in activated sludge, and evaluate the complexity required for the model to effectively predict their removal. The results are generalized to previously published cases. Batch experimental results, obtained under anoxic and aerobic conditions, were used to identify extensions to, and to estimate parameter values of the activated sludge modeling framework for Xenobiotic trace chemicals (ASM-X). Measurement and simulation results obtained in the batch experiments, spiked with the diclofenac and carbamazepine content of preclarified municipal wastewater shows comparably high biotransformation rates in the presence of growth substrates. Forward dynamic simulations were performed using full-scale data obtained from Bekkelaget WWTP (Oslo, Norway) to evaluate the model and to estimate the level of re-transformable xenobiotics present in the influent. The results obtained in this study demonstrate that xenobiotic loading conditions can significantly influence the removal capacity of WWTPs. We show that the trace chemical retransformation in upstream sewer pipes can introduce considerable error in assessing the removal efficiency of a WWTP, based only on parent compound concentration measurements. The combination of our data with those from the literature shows that solids retention time (SRT) can enhance the biotransformation of diclofenac, which was not the case for carbamazepine. Model approximation of the xenobiotic concentration, detected in the solid phase, suggest that between

The Science and Technology of the US National Missile Defense System

NASA Astrophysics Data System (ADS)

Postol, Theodore A.

2010-03-01

The National Missile Defense System utilizes UHF and X-band radars for search, track and discrimination, and interceptors that use long-wave infrared sensors to identify and home on attacking warheads. The radars and infrared sensors in the missile defense system perform at near the theoretical limits predicted by physics. However, in spite of the fantastic technical advances in sensor technology, signal processing, and computational support functions, the National Missile Defense System cannot be expected to ever work in realistic combat environments. This talk will describe why these impressive technologies can never deliver on the promise of a credible defense against long-range ballistic missiles.

Defense Enterprise Accounting and Management System-Increment 1 (DEAMS Inc 1)

DTIC Science & Technology

2016-03-01

information accurately and in conformance with Generally Accepted Accounting Principles , to comply with Congressional requirements of the Chief Financial ...2016 Major Automated Information System Annual Report Defense Enterprise Accounting and Management System-Increment 1 (DEAMS Inc 1) Defense...Phone: 937-257-2714 Fax: DSN Phone: 787-2714 DSN Fax: Date Assigned: August 17, 2015 Program Information Program Name Defense Enterprise Accounting

Two horizontally transferred xenobiotic resistance gene clusters associated with detoxification of benzoxazolinones by Fusarium species

USDA-ARS?s Scientific Manuscript database

Microbes encounter a broad spectrum of chemical compounds in their diverse environments. These xenobiotics may negatively impact growth or cause death. To counter such adverse effects, many microbes possess metabolic strategies to detoxify and biotransform xenobiotics. Fusarium verticillioides is a ...

Nontargeted analysis of the urine nonpolar sulfateome: a pathway to the nonpolar xenobiotic exposome

PubMed Central

Yao, Yuanyuan; Wang, Poguang; Shao, Gang; Anzalota Del Toro, Liza V.; Codero, Jose; Giese, Roger W.

2016-01-01

RATIONALE Testing the urine nonpolar sulfateome can enable discovery of xenobiotics that are most likely to be bioactive. This is based on the fact that nonpolar xenobiotics are more likely to enter cells where they tend to undergo metabolism, in part, to sulfates that are then largely excreted into the urine. METHODS The following sequence of steps, with conditions that achieve high reproducibility, was applied to large human urine samples: (1) competitive nonpolar extraction with a porous extraction paddle; (2) weak anion exchange extraction with strong organic washing; and (3) UHPLC/negative ion-MALDI-TOF/TOF-MS with recording of ions with S/N ≥ 20 that yielded M-1-80 (loss of SO3) or m/z 97 (HSO4−) upon fragmentation. RESULTS From a collection of urine samples from six pregnant women, the masses of 1129 putative sulfates were measured. Three lists of candidate compounds (preliminary hits) from these masses were formed by searching METLIN, especially via MATLAB, yielding putative xenobiotic contaminants (35 compounds), steroids (122), and flavonoids (1582). CONCLUSION A new way to reveal some of the nonpolar xenobiotic exposome has been developed that applies to urine samples. The value of the method is to suggest xenobiotics for subsequent targeted analysis in the population of people under study, in order to relate the environment to health and disease. PMID:27557133

Generation Z: Adolescent Xenobiotic Abuse in the 21st Century.

PubMed

Eggleston, William; Stork, Christine

2015-12-01

NMDA receptor antagonists include the prescription medication ketamine, the illicit xenobiotics PCP, MXE, and other novel PCP analogs, and the OTC medication DXM. The NMDA receptor antagonist most commonly abused by adolescents in the United States is DXM. These xenobiotics cause dissociative effects by non-competitively inhibiting the action of glutamate at the NMDA receptor. Additionally, these agents modulate the actions of monoamine neurotransmitters, agonize opioid receptors, and inhibit nitric oxide synthase. Patients typically present with sympathomimetic and neuropsychiatric clinical manifestations after abuse of NMDA receptor antagonists. Treatment is generally symptomatic and supportive. Interventions include benzodiazepines, propofol, fluids, antiemetics, aggressive cooling, and respiratory support.

Review and evaluation of the effects of xenobiotic chemicals on microorganisms in soil. [139 references

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

Hicks, R.J.; Van Voris, P.

1988-02-01

The primary objective was to review and evaluate the relevance and quality of existing xenobiotic data bases and test methods for evaluating direct and indirect effects (both adverse and beneficial) of xenobiotics on the soil microbial community; direct and indirect effects of the soil microbial community on xenobiotics; and adequacy of test methods used to evaluate these effects and interactions. Xenobiotic chemicals are defined here as those compounds, both organic and inorganic, produced by man and introduced into the environment at concentrations that cause undesirable effects. Because soil serves as the main repository for many of these chemicals, it thereforemore » has a major role in determining their ultimate fate. Once released, the distribution of xenobiotics between environmental compartments depends on the chemodynamic properties of the compounds, the physicochemical properties of the soils, and the transfer between soil-water and soil-air interfaces and across biological membranes. Abiotic and biotic processes can transform the chemical compound, thus altering its chemical state and, subsequently, its toxicity and reactivity. Ideally, the conversion is to carbon dioxide, water, and mineral elements, or at least, to some harmless substance. However, intermediate transformation products, which can become toxic pollutants in their own right, can sometimes be formed. 139 refs., 6 figs., 11 tabs.« less

Xenobiotics removal by adsorption in the context of tertiary treatment: a mini review.

PubMed

Tahar, Alexandre; Choubert, Jean-Marc; Coquery, Marina

2013-08-01

Many xenobiotics, including several pharmaceuticals and pesticides, are poorly treated in domestic wastewater treatment plants. Adsorption processes, such as with activated carbons, could be a solution to curb their discharge into the aquatic environment. As adsorbent-like activated carbon is known to be expensive, identifying promising alternative adsorbent materials is a key challenge for efficient yet affordable xenobiotic removal from wastewaters. As part of the effort to address this challenge, we surveyed the literature on pharmaceutical and pesticide xenobiotics and built a database compiling data from 38 scientific publications covering 65 xenobiotics and 58 materials. Special focus was given to the relevance and comparability of the data to the characteristics of the adsorbent materials used and to the operating conditions of the batch tests inventoried. This paper gives an in-depth overview of the adsorption capacities of various adsorbents. The little data on alternative adsorbent materials, especially for the adsorption of pharmaceuticals, makes it difficult to single out any one activated carbon alternative capable of adsorbing pesticides and pharmaceuticals at the tertiary stage of treatment. There is a pressing need for further lab-scale experiments to investigate the tertiary treatment of discharged effluents. We conclude with recommendations on how future data should best be used and interpreted.

DEFENSE RTD&E ONLINE SYSTEM (DROLS)

EPA Science Inventory

Web Enabled DROLS (WED) is a free subscription service available to registered users that provides online access to DTIC's Technical Reports and Research Summaries Databases. It replaces the former unclassified dial-up access to DROLS, DTIC's Defense RDT&E Online System. The Defe...

Biomarkers of oxidative damage and antioxidant defense capacity in Caiman latirostris blood.

PubMed

Poletta, Gisela L; Simoniello, María Fernanda; Mudry, Marta D

2016-01-01

Several xenobiotics, and among them pesticides, can produce oxidative stress, providing a mechanistic basis for their observed toxicity. Chronic oxidative stress induces deleterious modifications to DNA, lipids and proteins that are used as effective biomarkers to study pollutant-mediated oxidative stress. No previous report existed on the application of oxidative damage and antioxidant defense biomarkers in Caiman latirostris blood, while few studies reported in other crocodilians were done in organs or muscles of dead animals. The aim of this study was to characterize a new set of oxidative stress biomarkers in C. latirostris blood, through the modification of conventional techniques: 1) damage to lipids by thiobarbituric acid reactive substances (TBARS), 2) damage to DNA by comet assay modified with the enzymes FPG and Endo III, and 3) antioxidant defenses: catalase, superoxide dismutase and glutathione; in order to apply them in future biomonitoring studies. We successfully adapted standard procedures for CAT, SOD, GSH and TBARS determination in C. latirostris blood. Calibration curves for FPG and Endo III showed that the three dilutions tested were appropriate to conduct the modified comet assay for the detection of oxidized bases in C. latirostris erythrocytes. One hour of incubation allowed a complete repair of the damage generated. The incorporation of these biomarkers in biomonitoring studies of caiman populations exposed to xenobiotics is highly important considering that this species has recovered from a serious endangered state through the implementation of sustainable use programs in Argentina, and represents nowadays a relevant economic resource for many human communities. Copyright © 2015 Elsevier Inc. All rights reserved.

75 FR 32635 - Defense Acquisition Regulations System; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... Regulations System; Defense Federal Acquisition Regulation Supplement; Balance of Payments Program Exemption... implement the exemption from the Balance of Payments Program for construction material that is commercial... is proposing to amend the DFARS to implement in the clauses at 252.225-7044, Balance of Payments...

75 FR 71560 - Defense Federal Acquisition Regulation Supplement; Cost and Software Data Reporting System (DFARS...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 215, 234, 242, and 252... System (DFARS Case 2008-D027) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD... 1921-2, Progress Curve Report Comment: A respondent noted that DD Form 1921-2 Progress Curve Report...

75 FR 3178 - Defense Federal Acquisition Regulation Supplement; Lead System Integrators

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... Government procurement. Amy G. Williams, Editor, Defense Acquisition Regulations System. 0 Accordingly, the..., without change, an interim rule amending the Defense Federal Acquisition Regulation Supplement (DFARS) to... limitations on the award of new contracts for lead system integrator functions in the acquisition of major DoD...

System justification and the defense of committed relationship ideology.

PubMed

Day, Martin V; Kay, Aaron C; Holmes, John G; Napier, Jaime L

2011-08-01

A consequential ideology in Western society is the uncontested belief that a committed relationship is the most important adult relationship and that almost all people want to marry or seriously couple (DePaulo & Morris, 2005). In the present article, we investigated the extent to which the system justification motive may contribute to the adoption of this ideology. In Studies 1 and 2, we examined whether a heightened motive to maintain the status quo would increase defense of committed relationship values. In Study 3, we examined the reverse association, that is, whether a threat to committed relationship ideology would also affect sociopolitical system endorsement. As past research has found that the justification of political systems depends upon how much these systems are perceived as controlling, in Study 4 we tested whether the defense of the system of committed relationships would also increase when framed as controlling. Results from Studies 1-4 were consistent with our hypotheses, but only for men. In Study 5, using cross-cultural data, we sought to replicate these findings correlationally and probe for a cause of the gender effect. Results from more than 33,000 respondents indicated a relationship (for men) between defense of the sociopolitical system and defense of marriage in countries where the traditional advantages of men over women were most threatened. In Studies 6 and 7, we investigated when this gender difference disappears. Results revealed that when we measured (Study 6) or manipulated (Study 7) personal relationship identity rather than relationship ideology, effects also emerge for women.

Study on combat effectiveness of air defense missile weapon system based on queuing theory

NASA Astrophysics Data System (ADS)

Zhao, Z. Q.; Hao, J. X.; Li, L. J.

2017-01-01

Queuing Theory is a method to analyze the combat effectiveness of air defense missile weapon system. The model of service probability based on the queuing theory was constructed, and applied to analyzing the combat effectiveness of "Sidewinder" and "Tor-M1" air defense missile weapon system. Finally aimed at different targets densities, the combat effectiveness of different combat units of two types' defense missile weapon system is calculated. This method can be used to analyze the usefulness of air defense missile weapon system.

Xenobiotic-induced apoptosis: significance and potential application as a general biomarker of response

USGS Publications Warehouse

Sweet, Leonard I.; Passino-Reader, Dora R.; Meier, Peter G.; Omann, Geneva M.

1999-01-01

The process of apoptosis, often coined programmed cell death, involves cell injury induced by a variety of stimuli including xenobiotics and is morphologically, biochemically, and physiologically distinct from necrosis. Apoptotic death is characterized by cellular changes such as cytoplasm shrinkage, chromatin condensation, and plasma membrane asymmetry. This form of cell suicide is appealing as a general biomarker of response in that it is expressed in multiple cell systems (e.g. immune, neuronal, hepatal, intestinal, dermal, reproductive), is conserved phylogenetically (e.g. fish, rodents, birds, sheep, amphibians, roundworms, plants, humans), is modulated by environmentally relevant levels of chemical contaminants, and indicates a state of stress of the organism. Further, apoptosis is useful as a biomarker as it serves as a molecular control point and hence may provide mechanistic information on xenobiotic stress. Studies reviewed here suggest that apoptosis is a sensitive and early indicator of acute and chronic chemical stress, loss of cellular function and structure, and organismal health. Examples are provided of the application of this methodology in studies of health of lake trout (Salvelinus namaycush) in the Laurentian Great Lakes.

Defense Systems Management Review. Volume I, Number 4. Autumn 1977

DTIC Science & Technology

1977-10-03

quarterly by the Defense Systems Management College, Fort Belvoir, VA 22060. Publication of the Review was approved by OASD(PA) May 18 1976. The views...Two copies of reprinted material should be forwarded to the Editor. Distribution of this publication is controlled. Inquiries concerning...DESTBIBUTION STATEMENT A Approved for public release; ■Distribution Unlimited in DEFENSE SYSTEMS MANAGEMENT REVIEW PURPOSE The purpose of the

Xenobiotic effects on intestinal stem cell proliferation in adult honey bee (Apis mellifera L) workers.

PubMed

Forkpah, Cordelia; Dixon, Luke R; Fahrbach, Susan E; Rueppell, Olav

2014-01-01

The causes of the current global decline in honey bee health are unknown. One major group of hypotheses invokes the pesticides and other xenobiotics to which this important pollinator species is often exposed. Most studies have focused on mortality or behavioral deficiencies in exposed honey bees while neglecting other biological functions and target organs. The midgut epithelium of honey bees presents an important interface between the insect and its environment. It is maintained by proliferation of intestinal stem cells throughout the adult life of honey bees. We used caged honey bees to test multiple xenobiotics for effects on the replicative activity of the intestinal stem cells under laboratory conditions. Most of the tested compounds did not alter the replicative activity of intestinal stem cells. However, colchicine, methoxyfenozide, tetracycline, and a combination of coumaphos and tau-fluvalinate significantly affected proliferation rate. All substances except methoxyfenozide decreased proliferation rate. Thus, the results indicate that some xenobiotics frequently used in apiculture and known to accumulate in honey bee hives may have hitherto unknown physiological effects. The nutritional status and the susceptibility to pathogens of honey bees could be compromised by the impacts of xenobiotics on the maintenance of the midgut epithelium. This study contributes to a growing body of evidence that more comprehensive testing of xenobiotics may be required before novel or existing compounds can be considered safe for honey bees and other non-target species.

Xenobiotic Effects on Intestinal Stem Cell Proliferation in Adult Honey Bee (Apis mellifera L) Workers

PubMed Central

Forkpah, Cordelia; Dixon, Luke R.; Fahrbach, Susan E.; Rueppell, Olav

2014-01-01

The causes of the current global decline in honey bee health are unknown. One major group of hypotheses invokes the pesticides and other xenobiotics to which this important pollinator species is often exposed. Most studies have focused on mortality or behavioral deficiencies in exposed honey bees while neglecting other biological functions and target organs. The midgut epithelium of honey bees presents an important interface between the insect and its environment. It is maintained by proliferation of intestinal stem cells throughout the adult life of honey bees. We used caged honey bees to test multiple xenobiotics for effects on the replicative activity of the intestinal stem cells under laboratory conditions. Most of the tested compounds did not alter the replicative activity of intestinal stem cells. However, colchicine, methoxyfenozide, tetracycline, and a combination of coumaphos and tau-fluvalinate significantly affected proliferation rate. All substances except methoxyfenozide decreased proliferation rate. Thus, the results indicate that some xenobiotics frequently used in apiculture and known to accumulate in honey bee hives may have hitherto unknown physiological effects. The nutritional status and the susceptibility to pathogens of honey bees could be compromised by the impacts of xenobiotics on the maintenance of the midgut epithelium. This study contributes to a growing body of evidence that more comprehensive testing of xenobiotics may be required before novel or existing compounds can be considered safe for honey bees and other non-target species. PMID:24608542

32 CFR 21.200 - What is the Defense Grant and Agreement Regulatory System (DGARS)?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false What is the Defense Grant and Agreement Regulatory System (DGARS)? 21.200 Section 21.200 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Defense...

32 CFR 21.200 - What is the Defense Grant and Agreement Regulatory System (DGARS)?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false What is the Defense Grant and Agreement Regulatory System (DGARS)? 21.200 Section 21.200 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Defense...

32 CFR 21.200 - What is the Defense Grant and Agreement Regulatory System (DGARS)?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false What is the Defense Grant and Agreement Regulatory System (DGARS)? 21.200 Section 21.200 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Defense...

32 CFR 21.200 - What is the Defense Grant and Agreement Regulatory System (DGARS)?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false What is the Defense Grant and Agreement Regulatory System (DGARS)? 21.200 Section 21.200 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Defense...

32 CFR 21.200 - What is the Defense Grant and Agreement Regulatory System (DGARS)?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false What is the Defense Grant and Agreement Regulatory System (DGARS)? 21.200 Section 21.200 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Defense...

Influence of xenobiotics on the microbiological and agrochemical parameters of soddy-podzolic soil

NASA Astrophysics Data System (ADS)

Vakkerov-Kouzova, N. D.

2010-08-01

We studied the influence of various chemical compounds, i.e., azobenzene (an insecticide and acaricide), nitrification inhibitors (DCD, dicyandiamide and DMPP, and 3,4-dimetylpyrazolphosphate), and inhibitors of urease activity (HQ-hydroquinone), on the agrochemical and microbiological parameters of a soddy-podzolic soil. It is proved that these xenobiotics are able to influence the agrochemical parameters (the pH and the content of NO{3/-} and NH{4/+}, the microbial activity (the basal respiration, the microbial mass carbon, and the microbial quotient), and the number of bacteria of different physiological groups in soddypodzolic soil. The influence of the xenobiotics was preserved for some time, which testified to their persistence in the soil. Upon cultivating the soil microorganisms in different media, the growth of the heterotrophic bacteria was inhibited, the radial growth velocity was slowed down, and the sporogenesis of the micromycetes was retarded. The toxic effect of the xenobiotics was higher with their increasing concentrations.

Semantic Web and Inferencing Technologies for Department of Defense Systems

DTIC Science & Technology

2014-10-01

contact report for a specific type of aircraft . Intra-domain-specific metadata in the threat data domain might be used to categorize the contact...DEFENSE SYSTEMS by Duane Davis October 2014 Approved for public release; distribution is unlimited Prepared for: The NPS Center for Multi-INT...TITLE AND SUBTITLE Semantic Web and Inferencing Technologies for Department of Defense Systems 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

Defense Occupational and Environmental Health Readiness System (DOEHRS) Guidance

DTIC Science & Technology

2009-07-01

TERMS Defense Occupational and Environmental Health Reporting System (DOEHRS), Industrial Hygiene, Environmental Health, Information Management System Hygiene...Information System (AF EMIS), the Air Force Enterprise Environmental, Safety, and Occupational Health Information Management System (EESOH MIS), or the

Free Radical Mechanisms of Xenobiotic Mammalian Cytotoxicities

DTIC Science & Technology

1991-06-30

injury process was mediated through biotransformation of the halocarbons to a free radical intermediate, similar to what happens in the liver . However...peroxidation) of antioxidant agents - is not limited to the liver , but also occurs in vascular cells as well. Unlike the liver , where most of the injury is...frequent mechanism of xenobiotic liver toxicity is biotransformation by cytochrome P,5o-enzymes to toxic free radical intermediates. The primary objective

Free Radical Mechanisms of Xenobiotic Mammalian Cytotoxicities

DTIC Science & Technology

1988-10-31

cytochrome P450 is small compared to that of the liver (about 0.1%), cardiovascular tissues may be more susceptible to oxidative injury because of the... injury participates in the pathogenic mechanisms of many lipophilic xenobiotic compounds). The most dramatic finding is our demonstration that five...UPID PEROXIDATION BETTER THAN THE INITIAL RADICAL OR HYDROPEROXIDE. INDIRECT IRP EFFECTS ON FREE RADICAL MEMBRANE INJURY : 4) POISONING OF THE ELECTRON

Prophage-mediated defense against viral attack and viral counter-defense

PubMed Central

Dedrick, Rebekah M.; Jacobs-Sera, Deborah; Guerrero Bustamante, Carlos A.; Garlena, Rebecca A.; Mavrich, Travis N.; Pope, Welkin H.; Reyes, Juan C Cervantes; Russell, Daniel A.; Adair, Tamarah; Alvey, Richard; Bonilla, J. Alfred; Bricker, Jerald S.; Brown, Bryony R.; Byrnes, Deanna; Cresawn, Steven G.; Davis, William B.; Dickson, Leon A.; Edgington, Nicholas P.; Findley, Ann M.; Golebiewska, Urszula; Grose, Julianne H.; Hayes, Cory F.; Hughes, Lee E.; Hutchison, Keith W.; Isern, Sharon; Johnson, Allison A.; Kenna, Margaret A.; Klyczek, Karen K.; Mageeney, Catherine M.; Michael, Scott F.; Molloy, Sally D.; Montgomery, Matthew T.; Neitzel, James; Page, Shallee T.; Pizzorno, Marie C.; Poxleitner, Marianne K.; Rinehart, Claire A.; Robinson, Courtney J.; Rubin, Michael R.; Teyim, Joseph N.; Vazquez, Edwin; Ware, Vassie C.; Washington, Jacqueline; Hatfull, Graham F.

2017-01-01

Temperate phages are common and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses infecting mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity, and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages reveals at least five distinct prophage-expressed viral defense systems that interfere with infection of lytic and temperate phages that are either closely-related (homotypic defense) or unrelated (heterotypic defense). Target specificity is unpredictable, ranging from a single target phage to one-third of those tested. The defense systems include a single-subunit restriction system, a heterotypic exclusion system, and a predicted (p)ppGpp synthetase, which blocks lytic phage growth, promotes bacterial survival, and enables efficient lysogeny. The predicted (p)ppGpp synthetase coded by the Phrann prophage defends against phage Tweety infection, but Tweety codes for a tetrapeptide repeat protein, gp54, that acts as a highly effective counter-defense system. Prophage-mediated viral defense offers an efficient mechanism for bacterial success in host-virus dynamics, and counter-defense promotes phage co-evolution. PMID:28067906

Development of an ATP measurement method suitable for xenobiotic treatment activated sludge biomass.

PubMed

Nguyen, Lan Huong; Chong, Nyuk-Min

2015-09-01

Activated sludge consumes a large amount of energy to degrade a xenobiotic organic compound. By tracking the energy inventory of activated sludge biomass during the sludge's degradation of a xenobiotic, any disadvantageous effect on the sludge's performance caused by energy deficiency can be observed. The purpose of this study was to develop a reliable and accurate method for measuring the ATP contents of activated sludge cells that were to degrade a xenobiotic organic. Cell disruption and cellular ATP extraction were performed by a protocol with which xenobiotic degrading activated sludge biomass was washed with SDS, treated by Tris and TCA, and followed by bead blasting. The suspension of disrupted cells was filtered before the filtrate was injected into HPLC that was set at optimal conditions to measure the ATP concentration therein. This extraction protocol and HPLC measurement of ATP was evaluated for its linearity, limits of detection, and reproducibility. Evaluation test results reported a R(2) of 0.999 of linear fit of ATP concentration versus activated sludge concentration, a LOD=0.00045mg/L, a LOQ=0.0015mg/L for HPLC measurement of ATP, a MDL=0.46mg/g SS for ATP extraction protocol, and a recovery efficiency of 96.4±2%. This method of ATP measurement was simple, rapid, reliable, and was unburdened of some limitations other methods may have. Copyright © 2015 Elsevier B.V. All rights reserved.

Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers.

PubMed

Efferth, Thomas; Volm, Manfred

2017-07-01

The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR). Hence ABC-transporters may have opposing effects for organismic health reaching from harmful in MDR of tumors to beneficial for maintenance of health in MXR. While their inhibition by specific inhibitors may improve treatment success in oncology and avoid carcinogenesis, blocking of ABC-transporter-driven efflux by environmental pollutants leads to ecotoxicological consequences in marine biotopes. Poisoned seafood may enter the food-chain and cause intoxications in human beings. As exemplified with ABC-transporters, joining forces in interdisciplinary research may, therefore, be a wise strategy to fight problems in human medicine and environmental sciences.

Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood

PubMed Central

Llobet, Laura; Toivonen, Janne M.; Montoya, Julio; Ruiz-Pesini, Eduardo; López-Gallardo, Ester

2015-01-01

ABSTRACT Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chemical compounds used in medicine, agriculture or other human activities affect oxidative phosphorylation function. Therefore, these xenobiotics could alter adipogenesis. We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system. The tested concentrations have been previously reported in human blood. Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion. By contrast, the environmental chemical pollutant tributyltin chloride, which inhibits the ATP synthase of the oxidative phosphorylation system, can promote adipocyte differentiation and leptin secretion, leading to obesity and metabolic syndrome as postulated by the obesogen hypothesis. PMID:26398948

Xenobiotic-metabolizing enzymes in plants and their role in uptake and biotransformation of veterinary drugs in the environment.

PubMed

Bártíková, Hana; Skálová, Lenka; Stuchlíková, Lucie; Vokřál, Ivan; Vaněk, Tomáš; Podlipná, Radka

2015-08-01

Many various xenobiotics permanently enter plants and represent potential danger for their organism. For that reason, plants have evolved extremely sophisticated detoxification systems including a battery of xenobiotic-metabolizing enzymes. Some of them are similar to those in humans and animals, but there are several plant-specific ones. This review briefly introduces xenobiotic-metabolizing enzymes in plants and summarizes present information about their action toward veterinary drugs. Veterinary drugs are used worldwide to treat diseases and protect animal health. However, veterinary drugs are also unwantedly introduced into environment mostly via animal excrements, they persist in the environment for a long time and may impact on the non-target organisms. Plants are able to uptake, transform the veterinary drugs to non- or less-toxic compounds and store them in the vacuoles and cell walls. This ability may protect not only plant themselves but also other organisms, predominantly invertebrates and wild herbivores. The aim of this review is to emphasize the importance of plants in detoxification of veterinary drugs in the environment. The results of studies, which dealt with transport and biotransformation of veterinary drugs in plants, are summarized and evaluated. In conclusion, the risks and consequences of veterinary drugs in the environment and the possibilities of phytoremediation technologies are considered and future perspectives are outlined.

Defense Primer: The National Defense Budget Function (050)

DTIC Science & Technology

2017-03-17

in parenthesis). This defense primer addresses the National Defense Budget (050), which is frequently used to explain trends in military spending...but which also includes some activities not conducted by the Department of Defense. What Is the Purpose of the Budget Function System? The budget

Do Candida spp. "read" Nietzsche? Can xenobiotics modulate their aggressiveness? Proposition that chemicals may interfere in their virulence attributes.

PubMed

Rosa, Edvaldo Antonio Ribeiro

2012-01-01

As well as the host, opportunist Candida spp. enface all sorts of exogenous chemicals, so-called xenobiotics. It is plausible that xenobiotics exert some effects on such microorganisms; among them, the modulation of virulence attributes.

Harnessing the Prokaryotic Adaptive Immune System as a Eukaryotic Antiviral Defense

PubMed Central

Price, Aryn A.; Grakoui, Arash; Weiss, David S.

2016-01-01

Clustered, regularly interspaced, short palindromic repeats - CRISPR associated (CRISPR-Cas) systems are sequence specific RNA-directed endonuclease complexes that bind and cleave nucleic acids. These systems evolved within prokaryotes as adaptive immune defenses to target and degrade nucleic acids derived from bacteriophages and other foreign genetic elements. The antiviral function of these systems has now been exploited to combat eukaryotic viruses throughout the viral life cycle. Here we discuss current advances in CRISPR-Cas9 technology as a eukaryotic antiviral defense. PMID:26852268

Disposition of xenobiotic chemicals and metabolites in marine organisms.

PubMed Central

Varanasi, U; Stein, J E

1991-01-01

Studies with several bottom fish species from urban waterways show that of the identified xenobiotic chemicals in bottom sediments, polycylic aromatic hydrocarbons (PAHs) are the most strongly associated with the prevalence of liver lesions, including neoplasms. Accordingly, there is concern about the transfer of contaminants, such as PAHs, from aquatic species to humans. Because PAHs exert their toxicity only after being biotransformed, increasing attention has been focused on the ability of aquatic organisms to metabolize these chemicals. Overall, the results of both laboratory and field studies show that generally low levels (nanograms per gram wet weight) of a few low molecular weight PAHs may be present in edible tissue of fish from contaminated areas and that high molecular weight PAHs, such as the carcinogen benzo(a)pyrene, will rarely be detected because of extensive metabolism. Additionally, the results from a few studies suggest that even though interactions between xenobiotics can affect both biochemical and physiological systems to alter the disposition of PAHs in fish, these interactions do not markedly change the relative proportions of metabolites to parent PAH in tissues. Thus, these studies clearly demonstrate that to obtain some insight into the questions of whether there is any risk to human health from consuming fish and crustaceans from urban areas, techniques must be developed that measure metabolites of carcinogens, such as PAHs, in edible tissue. Initial attempts may focus on semiquantitative methods that permit rapid assessment of the level of metabolites in edible tissues of fish and crustaceans from many urban areas.(ABSTRACT TRUNCATED AT 250 WORDS) Images FIGURE 4. FIGURE 4. FIGURE 4. PMID:2050086

Tracing the evolution of degraders in activated sludge during the sludge’s acclimation to a xenobiotic organic

NASA Astrophysics Data System (ADS)

Chong, N. M.; Fan, C. H.; Yang, Y. C.

2017-01-01

The molecular biology method of high-throughput pyrosequencing was employed to examine the change of activated sludge community structures during the process in which activated sludge was acclimated to and degraded a target xenobiotic. The sample xenobiotic organic compound used as the activated sludge acclimation target was the herbicide 2,4-dichlorphenoxyacetic acid (2,4-D). Indigenous activated sludge microorganisms were acclimated to 2,4-D as the sole carbon source in both the batch and the continuous-flow reaction modes. Sludge masses at multiple time points during the course of acclimation were subjected to pyrosequencing targeting the microorganisms’ 16S rRNA genes. With the bacterial 16S rRNA sequencing results the genera that increased in abundance were checked with degradative pathway databases or literature to confirm that they are commonly seen as potent degraders of 2,4-D. From this systematic examination of degrader changes at time points during activated sludge acclimation and degradation of the target xenobiotic, the trend of degrader evolution in activated sludge over the sludge’s acclimation process to a xenobiotic was traced.

Alaskan Air Defense and Early Warning Systems Clear Air ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Alaskan Air Defense and Early Warning Systems - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress.

PubMed

Wages, Phillip A; Cheng, Wan-Yun; Gibbs-Flournoy, Eugene; Samet, James M

2016-12-01

Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes. The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies. Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress. Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Published by Elsevier B.V.

77 FR 30361 - Defense Federal Acquisition Regulation Supplement; Defense Trade Cooperation Treaty With the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

... DEPARTMENT OF DEFENSE Defense Acquisitions Regulations System 48 CFR Parts 225 and 252 RIN 0750... United Kingdom (DFARS 2012-D034) AGENCY: Defense Acquisition Regulations System; Department of Defense... Acquisition Regulations System, Attn: (Insert case manager's name), OUSD (AT&L) DPAP/DARS, Room 3B855, 3060...

Defense Logistics Standard Systems Functional Requirements.

DTIC Science & Technology

1987-03-01

Artificial Intelligence - the development of a machine capability to perform functions normally concerned with human intelligence, such as learning , adapting...Basic Data Base Machine Configurations .... ......... D- 18 xx ~ ?f~~~vX PART I: MODELS - DEFENSE LOGISTICS STANDARD SYSTEMS FUNCTIONAL REQUIREMENTS...On-line, Interactive Access. Integrating user input and machine output in a dynamic, real-time, give-and- take process is considered the optimum mode

Knockout of cytochrome P450 3A yields new mouse models for understanding xenobiotic metabolism

PubMed Central

van Herwaarden, Antonius E.; Wagenaar, Els; van der Kruijssen, Cornelia M.M.; van Waterschoot, Robert A.B.; Smit, Johan W.; Song, Ji-Ying; van der Valk, Martin A.; van Tellingen, Olaf; van der Hoorn, José W.A.; Rosing, Hilde; Beijnen, Jos H.; Schinkel, Alfred H.

2007-01-01

Cytochrome P450 3A (CYP3A) enzymes constitute an important detoxification system that contributes to primary metabolism of more than half of all prescribed medications. To investigate the physiological and pharmacological roles of CYP3A, we generated Cyp3a-knockout (Cyp3a–/–) mice lacking all functional Cyp3a genes. Cyp3a–/– mice were viable, fertile, and without marked physiological abnormalities. However, these mice exhibited severely impaired detoxification capacity when exposed to the chemotherapeutic agent docetaxel, displaying higher exposure levels in response to both oral and intravenous administration. These mice also demonstrated increased sensitivity to docetaxel toxicity, suggesting a primary role for Cyp3a in xenobiotic detoxification. To determine the relative importance of intestinal versus hepatic Cyp3a in first-pass metabolism, we generated transgenic Cyp3a–/– mice expressing human CYP3A4 in either the intestine or the liver. Expression of CYP3A4 in the intestine dramatically decreased absorption of docetaxel into the bloodstream, while hepatic expression aided systemic docetaxel clearance. These results suggest that CYP3A expression determines impairment of drug absorption and efficient systemic clearance in a tissue-specific manner. The genetic models used in this study provide powerful tools to further study CYP3A-mediated xenobiotic metabolism, as well as interactions between CYP3A and other detoxification systems. PMID:17975676

32 CFR 37.1025 - Must I report information to the Defense Assistance Awards Data System?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Must I report information to the Defense Assistance Awards Data System? 37.1025 Section 37.1025 National Defense Department of Defense OFFICE OF THE... Award Reporting Information About the Award § 37.1025 Must I report information to the Defense...

32 CFR 37.1025 - Must I report information to the Defense Assistance Awards Data System?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Must I report information to the Defense Assistance Awards Data System? 37.1025 Section 37.1025 National Defense Department of Defense OFFICE OF THE... Award Reporting Information About the Award § 37.1025 Must I report information to the Defense...

32 CFR 37.1025 - Must I report information to the Defense Assistance Awards Data System?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Must I report information to the Defense Assistance Awards Data System? 37.1025 Section 37.1025 National Defense Department of Defense OFFICE OF THE... Award Reporting Information About the Award § 37.1025 Must I report information to the Defense...

32 CFR 37.1025 - Must I report information to the Defense Assistance Awards Data System?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Must I report information to the Defense Assistance Awards Data System? 37.1025 Section 37.1025 National Defense Department of Defense OFFICE OF THE... Award Reporting Information About the Award § 37.1025 Must I report information to the Defense...

32 CFR 37.1025 - Must I report information to the Defense Assistance Awards Data System?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Must I report information to the Defense Assistance Awards Data System? 37.1025 Section 37.1025 National Defense Department of Defense OFFICE OF THE... Award Reporting Information About the Award § 37.1025 Must I report information to the Defense...

The Missile Defense Agency's space tracking and surveillance system

NASA Astrophysics Data System (ADS)

Watson, John; Zondervan, Keith

2008-10-01

The Ballistic Missile Defense System (BMDS) is a layered system incorporating elements in space. In addition to missile warning systems at geosynchronous altitudes, an operational BMDS will include a low Earth orbit (LEO) system-the Space Tracking and Surveillance System (STSS). It will use infrared sensing technologies synergistically with the Space Based Infrared Systems (SBIRS) and will provide a seamless adjunct to radars and sensors on the ground and in airborne platforms. STSS is being designed for a future operational capability to defend against evolving threats. STSS development is divided into phases, commencing with a two-satellite demonstration constellation scheduled for launch in 2008. The demonstration satellites will conduct a menu of tests and experiments to prove the system concept, including the ground segment. They will have limited operational capability within the integrated BMDS. Data from the demonstration satellites will be received and processed by the Missile Defense Space Experiment Center (MDSEC), a part of the Missile Defense Integration and Operations Center (MDIOC). MDA launched in 2007 into LEO a satellite (NFIRE) designed to make near-field multispectral measurements of boosting targets and to demonstrate laser communication, the latter in conjunction with the German satellite TerraSAR-X. The gimbaled, lightweight laser terminal has demonstrated on orbit a 5.5 gbps rate in both directions. The filter passbands of NFIRE are similar to the STSS demonstrator track sensor. While providing useful phenomenology during its time on orbit, NFIRE will also serve as a pathfinder in the development of STSS operations procedures.

Evolution of System Safety at NASA as Related to Defense-in-Depth

NASA Technical Reports Server (NTRS)

Dezfuli, Homayoon

2015-01-01

Presentation given at the Defense-in-Depth Inter-Agency Workshop on August 26, 2015 in Rockville, MD by Homayoon Dezfuli. The presentation addresses the evolution of system safety at NASA as related to Defense-in-Depth.

The Therapeutic Role of Xenobiotic Nuclear Receptors against Metabolic Syndrome.

PubMed

Pu, Shuqi; Wu, Xiaojie; Yang, Xiaoying; Zhang, Yunzhan; Dai, Yunkai; Zhang, Yueling; Wu, Xiaoting; Liu, Yan; Cui, Xiaona; Jin, Haiyong; Cao, Jianhong; Li, Ruliu; Cai, Jiazhong; Cao, Qizhi; Hu, Ling; Gao, Yong

2018-06-10

Xenobiotic nuclear receptors (XNRs) are nuclear receptors that characterized by coordinately regulating the expression of genes encoding drug-metabolizing enzymes and transporters to essentially eliminate and detoxify xenobiotics and endobiotics from the body, including the peroxisome proliferator-activated receptor (PPAR), the farnesoid X receptor (FXR), the liver X receptor (LXR), the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Heretofore, increasing evidences have suggested that these five XNRs are not only involved in the regulation of xeno-/endo-biotics detoxication but also the development of human diseases, such as cancer, obesity and diabetes. PPAR, FXR, LXR, PXR and CAR, as the receptors for numerous natural or synthetic compounds may be the most effective therapeutic targets in the treatment of metabolic diseases. In this review, we will focus on these five XNRs and their recently discovered functions in diabetes and its complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Risk Assessment Using The Homeland-Defense Operational Planning System (HOPS)

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

Price, D E; Durling, R L

2005-10-10

The Homeland-Defense Operational Planning System (HOPS), is a new operational planning tool leveraging Lawrence Livermore National Laboratory's expertise in weapons systems and in sparse information analysis to support the defense of the U.S. homeland. HOPS provides planners with a basis to make decisions to protect against acts of terrorism, focusing on the defense of facilities critical to U.S. infrastructure. Criticality of facilities, structures, and systems is evaluated on a composite matrix of specific projected casualty, economic, and sociopolitical impact bins. Based on these criteria, significant unidentified vulnerabilities are identified and secured. To provide insight into potential successes by malevolent actors,more » HOPS analysts strive to base their efforts mainly on unclassified open-source data. However, more cooperation is needed between HOPS analysts and facility representatives to provide an advantage to those whose task is to defend these facilities. Evaluated facilities include: refineries, major ports, nuclear power plants and other nuclear licensees, dams, government installations, convention centers, sports stadiums, tourist venues, and public and freight transportation systems. A generalized summary of analyses of U.S. infrastructure facilities will be presented.« less

Regulation of hepatic ABCC transporters by xenobiotics and in disease states

PubMed Central

Gu, Xinsheng; Manautou, Jose E.

2015-01-01

The subfamily of ABCC transporters consists of 13 members in mammals, including the multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and the cystic fibrosis transmembrane conductance regulator (CFTR). These proteins play roles in chemical detoxification, disposition, and normal cell physiology. ABCC transporters are expressed differentially in the liver and are regulated at the transcription and translation level. Their expression and function are also controlled by post-translational modification and membrane-trafficking events. These processes are tightly regulated. Information about alterations in the expression of hepatobiliary ABCC transporters could provide important insights into the pathogenesis of diseases and disposition of xenobiotics. In this review, we describe the regulation of hepatic ABCC transporters in humans and rodents by a variety of xenobiotics, under disease states and in genetically modified animal models deficient in transcription factors, transporters, and cell-signaling molecules. PMID:20233023

Cytochrome P450 peroxidase/peroxygenase mediated xenobiotic metabolic activation and cytotoxicity in isolated hepatocytes.

PubMed

Anari, M R; Khan, S; Liu, Z C; O'Brien, P J

1995-12-01

Cytochrome P450 (P450) can utilize organic hydroperoxides and peracids to support hydroxylation and dealkylation of various P450 substrates. However, the biological significance of this P450 peroxygenase/peroxidase activity in the bioactivation of xenobiotics in intact cells has not been demonstrated. We have shown that tert-butyl hydroperoxide (tBHP) markedly enhances 3-20-fold the cytotoxicity of various aromatic hydrocarbons and their phenolic metabolites. The tBHP-enhanced hepatocyte cytotoxicity of 4-nitroanisole (4-NA) and 4-hydroxyanisole (4-HA) was also accompanied by an increase in the hepatocyte O-demethylation of 4-NA and 4-HA up to 7.5- and 21-fold, respectively. Hepatocyte GSH conjugation by 4-HA was also markedly increased by tBHP. An LC/MS analysis of the GSH conjugates identified hydroquinone-GSH and 4-methoxy-catechol:GSH conjugates as the predominant adducts. Pretreatment of hepatocytes with P450 inhibitors, e.g., phenylimidazole, prevented tBHP-enhanced 4-HA metabolism, GSH depletion, and cytotoxicity. In conclusion, hydroperoxides can therefore be used by intact cells to support the bioactivation of xenobiotics through the P450 peroxidase/peroxygenase system.

Jasmonic acid and salicylic acid activate a common defense system in rice.

PubMed

Tamaoki, Daisuke; Seo, Shigemi; Yamada, Shoko; Kano, Akihito; Miyamoto, Ayumi; Shishido, Hodaka; Miyoshi, Seika; Taniguchi, Shiduku; Akimitsu, Kazuya; Gomi, Kenji

2013-06-01

Jasmonic acid (JA) and salicylic acid (SA) play important roles in plant defense systems. JA and SA signaling pathways interact antagonistically in dicotyledonous plants, but, the status of crosstalk between JA and SA signaling is unknown in monocots. Our rice microarray analysis showed that more than half of the genes upregulated by the SA analog BTH are also upregulated by JA, suggesting that a major portion of the SA-upregulated genes are regulated by JA-dependent signaling in rice. A common defense system that is activated by both JA and SA is thus proposed which plays an important role in pathogen defense responses in rice.

Disposition of xenobiotic chemicals and metabolites in marine organisms

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

Varanasi, U.; Stein, J.E.

1991-01-01

Studies with several bottom fish species from urban waterways show that of the identified xenobiotic chemicals in bottom sediments, polycyclic aromatic hydrocarbons (PAHs) are the most strongly associated with the prevalence of liver lesions, including neoplasms. Accordingly, there is concern about the transfer of contaminants, such as PAHs, from aquatic species to humans. Because PAHs exert their toxicity only after being biotransformed, increasing attention has been focused on the ability of aquatic organisms to metabolize these chemicals. Overall, the results of both laboratory and field studies show that generally low levels of a few low molecular weight PAHs may bemore » present in edible tissue of fish from contaminated areas and that high molecular weight PAHs, such as the carcinogen benzo(a)pyrene, will rarely be detected because of extensive metabolism. Additionally, the results from a few studies suggest that even though interactions between xenobiotics can affect both biochemical and physiological systems to alter the disposition of PAHs in fish, these interactions do not markedly change the relative proportions of metabolites to parent PAH in tissues. Thus, these studies clearly demonstrate that to obtain some insight into the questions of whether there is any risk to human health from consuming fish and crustaceans from urban areas, techniques must be developed that measure metabolites of carcinogens, such as PAHs, in edible tissue. Initial attempts may focus on semiquantitative methods that permit rapid assessment of the level of metabolites in edible tissues of fish and crustaceans from many urban areas. Based on information from such screening studies, further refinement in methodology leading to identification of specific compounds may be needed because certain metabolites may not be as toxic or carcinogenic as others.« less

Towards an integrated defense system for cyber security situation awareness experiment

NASA Astrophysics Data System (ADS)

Zhang, Hanlin; Wei, Sixiao; Ge, Linqiang; Shen, Dan; Yu, Wei; Blasch, Erik P.; Pham, Khanh D.; Chen, Genshe

2015-05-01

In this paper, an implemented defense system is demonstrated to carry out cyber security situation awareness. The developed system consists of distributed passive and active network sensors designed to effectively capture suspicious information associated with cyber threats, effective detection schemes to accurately distinguish attacks, and network actors to rapidly mitigate attacks. Based on the collected data from network sensors, image-based and signals-based detection schemes are implemented to detect attacks. To further mitigate attacks, deployed dynamic firewalls on hosts dynamically update detection information reported from the detection schemes and block attacks. The experimental results show the effectiveness of the proposed system. A future plan to design an effective defense system is also discussed based on system theory.

GENE EXPRESSION PROFILING OF XENOBIOTIC METABOLIZING ENZYMES (XMES) THROUGH THE LIFE STAGES OF THE MALE C57BL/6 MOUSE

EPA Science Inventory

In the presence of foreign compounds, metabolic homeostasis of the organism is maintained by the liver's ability to detoxify and eliminate these xenobiotics. This is accomplished, in part, by the expression of XMEs, which metabolize xenobiotics and determine whether exposure will...

Systemic bacterial infection and immune defense phenotypes in Drosophila melanogaster.

PubMed

Khalil, Sarah; Jacobson, Eliana; Chambers, Moria C; Lazzaro, Brian P

2015-05-13

The fruit fly Drosophila melanogaster is one of the premier model organisms for studying the function and evolution of immune defense. Many aspects of innate immunity are conserved between insects and mammals, and since Drosophila can readily be genetically and experimentally manipulated, they are powerful for studying immune system function and the physiological consequences of disease. The procedure demonstrated here allows infection of flies by introduction of bacteria directly into the body cavity, bypassing epithelial barriers and more passive forms of defense and allowing focus on systemic infection. The procedure includes protocols for the measuring rates of host mortality, systemic pathogen load, and degree of induction of the host immune system. This infection procedure is inexpensive, robust and quantitatively repeatable, and can be used in studies of functional genetics, evolutionary life history, and physiology.

System Support/Sustainment Plan Platform for the Defense Enterprise Accounting Management System (DEAMS)

DTIC Science & Technology

2006-12-01

warfighters requirements and identifies system performance short-comings over its life cycle. 15. NUMBER OF PAGES 89 14. SUBJECT TERMS Information...the system performs to warfighters requirements and identifies system performance short-comings over its life cycle. vi...3 II. DEFENSE ACQUISITION LIFE CYCLE CURRENT STAGE ANALYSIS.......5 A. INTRODUCTION

Strategic Defense Initiative: Splendid Defense or Pipe Dream? Headline Series No. 275.

ERIC Educational Resources Information Center

Armstrong, Scott; Grier, Peter

This pamphlet presents a discussion of the various components of President Reagan's Strategic Defense Initiative (SDI) including the problem of pulling together various new technologies into an effective defensive system and the politics of the so-called "star wars" system. An important part of the defense initiative is the…

The natural defense system and the normative self model

PubMed Central

Kourilsky, Philippe

2016-01-01

Infectious agents are not the only agressors, and the immune system is not the sole defender of the organism. In an enlarged perspective, the ‘normative self model’ postulates that a ‘natural defense system’ protects man and other complex organisms against the environmental and internal hazards of life, including infections and cancers. It involves multiple error detection and correction mechanisms that confer robustness to the body at all levels of its organization. According to the model, the self relies on a set of physiological norms, and NONself (meaning : Non Obedient to the Norms of the self) is anything ‘off-norms’. The natural defense system comprises a set of ‘civil defenses’ (to which all cells in organs and tissues contribute), and a ‘professional army ‘, made of a smaller set of mobile cells. Mobile and non mobile cells differ in their tuning abilities. Tuning extends the recognition capabilities of NONself by the mobile cells, which increase their defensive function. To prevent them to drift, which would compromise self/NONself discrimination, the more plastic mobile cells need to periodically refer to the more stable non mobile cells to keep within physiological standards. PMID:27303629

Multiple operating system rotation environment moving target defense

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

Evans, Nathaniel; Thompson, Michael

Systems and methods for providing a multiple operating system rotation environment ("MORE") moving target defense ("MTD") computing system are described. The MORE-MTD system provides enhanced computer system security through a rotation of multiple operating systems. The MORE-MTD system increases attacker uncertainty, increases the cost of attacking the system, reduces the likelihood of an attacker locating a vulnerability, and reduces the exposure time of any located vulnerability. The MORE-MTD environment is effectuated by rotation of the operating systems at a given interval. The rotating operating systems create a consistently changing attack surface for remote attackers.

Non-targeted, high resolution mass spectrometry strategy for simultaneous monitoring of xenobiotics and endogenous compounds in green sea turtles on the Great Barrier Reef.

PubMed

Heffernan, Amy L; Gómez-Ramos, Maria M; Gaus, Caroline; Vijayasarathy, Soumini; Bell, Ian; Hof, Christine; Mueller, Jochen F; Gómez-Ramos, Maria J

2017-12-01

Chemical contamination poses a threat to ecosystem, biota and human health, and identifying these hazards is a complex challenge. Traditional hazard identification relies on a priori-defined targets of limited chemical scope, and is generally inappropriate for exploratory studies such as explaining toxicological effects in environmental systems. Here we present a non-target high resolution mass spectrometry environmental monitoring study with multivariate statistical analysis to simultaneously detect biomarkers of exposure (e.g. xenobiotics) and biomarkers of effect in whole turtle blood. Borrowing the concept from clinical chemistry, a case-control sampling approach was used to investigate the potential influence of xenobiotics of anthropogenic origin on free-ranging green sea turtles (Chelonia mydas) from a remote, offshore 'control' site; and two coastal 'case' sites influenced by urban/industrial and agricultural activities, respectively, on the Great Barrier Reef in North Queensland, Australia. Multiple biomarkers of exposure, including sulfonic acids (n=9), a carbamate insecticide metabolite, and other industrial chemicals; and five biomarkers of effect (lipid peroxidation products), were detected in case sites. Additionally, two endogenous biomarkers of neuroinflammation and oxidative stress were identified, and showed moderate-to-strong correlations with clinical measures of inflammation and liver dysfunction. Our data filtering strategy overcomes limitations of traditional a priori selection of target compounds, and adds to the limited environmental xenobiotic metabolomics literature. To our knowledge this is the first case-control study of xenobiotics in marine megafauna, and demonstrates the utility of green sea turtles to link internal and external exposure, to explain potential toxicological effects in environmental systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Operation of the Defense Acquisition System

DTIC Science & Technology

2008-12-08

United States Code (l) DoD Directive 8320.02, “Data Sharing in a Net-Centric Department of Defense,” December 2, 2004 (m) DoD Instruction 5200.39...2004 (t) ISO 15418-1999- “EAN/ UCC Application Identifiers and Fact Data Identifiers and Maintenance” (u) ISO 15434-1999 – “Transfer Syntax for High...Acquisition Knowledge Sharing System7 (y) Section 644 of title 15, United States Code, “Procurement strategies; contract bundling” (z) Public Law 101-576

Optimized laser-induced breakdown spectroscopy for determination of xenobiotic silver in monosodium glutamate and its verification using ICP-AES.

PubMed

Rehan, I; Gondal, M A; Rehan, K

2018-04-20

Laser-induced breakdown spectroscopy (LIBS) was applied as a potential tool for the determination of xenobiotic metal in monosodium glutamate (MSG). In order to achieve a high-sensitivity LIBS system required to determine trace amounts of metallic silver in MSG and to attain the best detection limit, the parameters used in our experiment (impact of focusing laser energy on the intensity of LIBS emission signals, the influence of focusing lens distance on the intensity of LIBS signals, and time responses of the plasma emissions) were optimized. The spectra of MSG were obtained in air using a suitable detector with an optical resolution of 0.06 nm, covering a spectral region from 220 to 720 nm. Along with the detection of xenobiotic silver, other elements such as Ca, Mg, S, and Na were also detected in MSG. To determine the concentration of xenobiotic silver in MSG, the calibration curve was plotted by preparing standard samples having different silver abundances in an MSG matrix. The LIBS results of each sample were cross-verified by analyzing with a standard analytical technique such as inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Both (LIBS and ICP-AES) results were in mutual agreement. The limit of detection of the LIBS setup was found to be 0.57 ppm for silver present in MSG samples.

Oxidation and adduct formation of xenobiotics in a microfluidic electrochemical cell with boron doped diamond electrodes and an integrated passive gradient rotation mixer.

PubMed

van den Brink, Floris T G; Wigger, Tina; Ma, Liwei; Odijk, Mathieu; Olthuis, Wouter; Karst, Uwe; van den Berg, Albert

2016-10-05

Reactive xenobiotic metabolites and their adduct formation with biomolecules such as proteins are important to study as they can be detrimental to human health. Here, we present a microfluidic electrochemical cell with integrated micromixer to study phase I and phase II metabolism as well as protein adduct formation of xenobiotics in a purely instrumental approach. The newly developed microfluidic device enables both the generation of reactive metabolites through electrochemical oxidation and subsequent adduct formation with biomolecules in a chemical microreactor. This allows us to study the detoxification of reactive species with glutathione and to predict potential toxicity of xenobiotics as a result of protein modification. Efficient mixing in microfluidic systems is a slow process due to the typically laminar flow conditions in shallow channels. Therefore, a passive gradient rotation micromixer has been designed that is capable of mixing liquids efficiently in a 790 pL volume within tens of milliseconds. The mixing principle relies on turning the concentration gradient that is initially established by bringing together two streams of liquid, to take advantage of the short diffusion distances in the shallow microchannels of thin-layer flow cells. The mixer is located immediately downstream of the working electrode of an electrochemical cell with integrated boron doped diamond electrodes. In conjunction with mass spectrometry, the two microreactors integrated in a single device provide a powerful tool to study the metabolism and toxicity of xenobiotics, which was demonstrated by the investigation of the model compound 1-hydroxypyrene.

Defense on the Move: Ant-Based Cyber Defense

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

Fink, Glenn A.; Haack, Jereme N.; McKinnon, Archibald D.

Many common cyber defenses (like firewalls and IDS) are as static as trench warfare allowing the attacker freedom to probe them at will. The concept of Moving Target Defense (MTD) adds dynamism to the defender side, but puts the systems to be defended themselves in motion, potentially at great cost to the defender. An alternative approach is a mobile resilient defense that removes attackers’ ability to rely on prior experience without requiring motion in the protected infrastructure itself. The defensive technology absorbs most of the cost of motion, is resilient to attack, and is unpredictable to attackers. The Ant-Based Cybermore » Defense (ABCD) is a mobile resilient defense providing a set of roaming, bio-inspired, digital-ant agents working with stationary agents in a hierarchy headed by a human supervisor. The ABCD approach provides a resilient, extensible, and flexible defense that can scale to large, multi-enterprise infrastructures like the smart electric grid.« less

Effects of Brown Rice and White Rice on Expression of Xenobiotic Metabolism Genes in Type 2 Diabetic Rats

PubMed Central

Imam, Mustapha Umar; Ismail, Maznah

2012-01-01

Xenobiotics constantly influence biological systems through several means of interaction. These interactions are disturbed in type 2 diabetes, with implications for disease outcome. We aimed to study the implications of such disturbances on type 2 diabetes and rice consumption, the results of which could affect management of the disease in developing countries. In a type 2 diabetic rat model induced through a combination of high fat diet and low dose streptozotocin injection, up-regulation of xenobiotic metabolism genes in the diabetic untreated group was observed. Xenobiotic metabolism genes were upregulated more in the white rice (WR) group than the diabetic untreated group while the brown rice (BR) group showed significantly lower expression values, though not as effective as metformin, which gave values closer to the normal non-diabetic group. The fold changes in expression in the WR group compared to the BR group for Cyp2D4, Cyp3A1, Cyp4A1, Cyp2B1, Cyp2E1, Cyp2C11, UGT2B1, ALDH1A1 and Cyp2C6 were 2.6, 2, 1.5, 4, 2.8, 1.5, 1.8, 3 and 5, respectively. Our results suggest that WR may upregulate these genes in type 2 diabetes more than BR, potentially causing faster drug metabolism, less drug efficacy and more toxicity. These results may have profound implications for rice eating populations, constituting half the world’s population. PMID:22942722

Coordinated changes in xenobiotic metabolizing enzyme (XME) gene expression through the life stages of the male C57BL/6 mouse

EPA Science Inventory

Metabolic homeostasis of the organism is maintained by the liver's ability to detoxify and eliminate xenobiotics. This is accomplished, in part, by the expression of XMEs, which metabolize xenobiotics and determine whether exposure will result in toxicity. Some evidence indicates...

77 FR 11367 - Defense Federal Acquisition Regulation Supplement; Extension of the Department of Defense Mentor...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 219 and Appendix I to Chapter 2 RIN 0750-AH59 Defense Federal Acquisition Regulation Supplement; Extension of the Department of... Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is issuing this final rule...

Live-cell Imaging Approaches for the Investigation of Xenobiotic-Induced Oxidant Stress

EPA Science Inventory

BACKGROUND: Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular t...

Detoxification function of the Arabidopsis sulphotransferase AtSOT12 by sulphonation of xenobiotics.

PubMed

Chen, Jinhua; Gao, Liqiong; Baek, Dongwon; Liu, Chunlin; Ruan, Ying; Shi, Huazhong

2015-08-01

Cytosolic sulphotransferases have been implicated in inactivation of endogenous steroid hormones and detoxification of xenobiotics in human and animals. Yet, the function of plant sulphotransferases in xenobiotic sulphonation and detoxification has not been reported. In this study, we show that the Arabidopsis sulphotransferase AtSOT12 could sulphonate the bacterial-produced toxin cycloheximide. Loss-of-function mutant sot12 exhibited hypersensitive phenotype to cycloheximide, and expression of AtSOT12 protein in yeast cells conferred resistance to this toxic compound. AtSOT12 exhibited broad specificity and could sulphonate a variety of xenobiotics including phenolic and polycyclic compounds. Enzyme kinetics analysis indicated that AtSOT12 has different selectivity for simple phenolics with different side chains, and the position of the side chain in the simple phenolic compounds affects substrate binding affinity and catalytic efficiency. We proposed that the broad specificity and induced production of AtSOT12 may have rendered this enzyme to not only modify endogenous molecules such as salicylic acid as we previously reported, but also sulphonate pathogen-produced toxic small molecules to protect them from infection. Sulphonation of small molecules in plants may constitute a rapid way to inactivate or change the physiochemical properties of biologically active molecules that could have profound effects on plant growth, development and defence. © 2015 John Wiley & Sons Ltd.

A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance.

PubMed

McNaughton, Neil; Corr, Philip J

2004-05-01

We present in this paper a picture of the neural systems controlling defense that updates and simplifies Gray's "Neuropsychology of Anxiety". It is based on two behavioural dimensions: 'defensive distance' as defined by the Blanchards and 'defensive direction'. Defensive direction is a categorical dimension with avoidance of threat corresponding to fear and approach to threat corresponding to anxiety. These two psychological dimensions are mapped to underlying neural dimensions. Defensive distance is mapped to neural level, with the shortest defensive distances involving the lowest neural level (periaqueductal grey) and the largest defensive distances the highest neural level (prefrontal cortex). Defensive direction is mapped to separate parallel streams that run across these levels. A significant departure from prior models is the proposal that both fear and anxiety are represented at all levels. The theory is presented in a simplified form that does not incorporate the interactions that must occur between non-adjacent levels of the system. It also requires expansion to include the dimension of escapability of threat. Our current development and these proposed future extensions do not change the core concepts originally proposed by Gray and, we argue, demonstrate their enduring value.

An operational computer program to control Self Defense Surface Missile System operations

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

Roe, C.L.

1991-12-01

An account is given of the system architecture and operational protocols of the NATO Seasparrow Surface Missile System (NSSMS) Operational Computer Program (OCP) which has been developed, and is being deployed multinationally, to respond against antiship missiles. Flowcharts are presented for the target detection and tracking, control, and engagement phases of the Self Defense Surface Missile System that is controlled by the OCP. USN and other NATO vessels will carry the NSSMS well into the next century; the OCP presently described will be deployed in the course of 1992 to enhance the self-defense capabilities of the NSSMS-equipped fleet. 8 refs.

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

EPA Science Inventory

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

Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress☆,☆☆

PubMed Central

Wages, Phillip A.; Cheng, Wan-Yun; Gibbs-Flournoy, Eugene; Samet, James M.

2017-01-01

Background Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes. Scope of review The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies. Major conclusions Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress. General significance Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. PMID:27208426

Behavioral responses of honey bees (Apis mellifera) to natural and synthetic xenobiotics in food.

PubMed

Liao, Ling-Hsiu; Wu, Wen-Yen; Berenbaum, May R

2017-11-21

While the natural foods of the western honey bee (Apis mellifera) contain diverse phytochemicals, in contemporary agroecosystems honey bees also encounter pesticides as floral tissue contaminants. Whereas some ubiquitous phytochemicals in bee foods up-regulate detoxification and immunity genes, thereby benefiting nestmates, many agrochemical pesticides adversely affect bee health even at sublethal levels. How honey bees assess xenobiotic risk to nestmates as they forage is poorly understood. Accordingly, we tested nine phytochemicals ubiquitous in nectar, pollen, or propolis, as well as five synthetic xenobiotics that frequently contaminate hives-two herbicides (atrazine and glyphosate) and three fungicides (boscalid, chlorothalonil, and prochloraz). In semi-field free-flight experiments, bees were offered a choice between paired sugar water feeders amended with either a xenobiotic or solvent only (control). Among the phytochemicals, foragers consistently preferred quercetin at all five concentrations tested, as evidenced by both visitation frequency and consumption rates. This preference may reflect the long evolutionary association between honey bees and floral tissues. Of pesticides eliciting a response, bees displayed a preference at specific concentrations for glyphosate and chlorothalonil. This paradoxical preference may account for the frequency with which these pesticides occur as hive contaminants and suggests that they present a greater risk factor for honey bee health than previously suspected.

Avian species differences in the intestinal absorption of xenobiotics (PCB, dieldrin, Hg2+)

USGS Publications Warehouse

Serafin, J.A.

1984-01-01

1. Intestinal absorption of a polychlorinated biphenyl, dieldrin, and mercury (from HgCl2) was measured in adult Northern bobwhites, Eastern screech owls, American kestrels, black-crowned night-herons and mallards in vivo by an in situ luminal perfusion technique.2. Bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards.3. Mallards absorbed less dieldrin and mercury than black-crowned night-herons.4. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards.5. Pronounced differences in xenobiotic absorption rates between bobwhites, screech owls and kestrels on the one hand, and black-crowned night-herons and mallards on the other, raise the possibility that absorptive ability may be associated with the phylogenetic classification of birds.

[Hypothetical link between endometriosis and xenobiotics-associated genetically modified food].

PubMed

Aris, A; Paris, K

2010-12-01

Endometriosis is an oestrogen-dependent inflammatory disease affecting 10 % of reproductive-aged women. Often accompanied by chronic pelvic pain and infertility, endometriosis rigorously interferes with women's quality of life. Although the pathophysiology of endometriosis remains unclear, a growing body of evidence points to the implication of environmental toxicants. Over the last decade, an increase in the incidence of endometriosis has been reported and coincides with the introduction of genetically modified foods in our diet. Even though assessments of genetically modified food risk have not indicated any hazard on human health, xenobiotics-associated genetically modified food, such as pesticides residues and xenoproteins, could be harmful in the long-term. The "low-dose hypothesis", accumulation and biotransformation of pesticides-associated genetically modified food and the multiplied toxicity of pesticides-formulation adjuvants support this hypothesis. This review summarizes toxic effects (in vitro and on animal models) of some xenobiotics-associated genetically modified food, such as glyphosate and Cry1Ab protein, and extrapolates on their potential role in the pathophysiology of endometriosis. Their roles as immune toxicants, pro-oxidants, endocrine disruptors and epigenetic modulators are discussed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Correlation of the lipophilicity of xenobiotics with their synergistic effects on DNA synthesis in human fibroblasts.

PubMed

Jacobi, H; Leier, G; Witte, I

1996-04-01

The binary combination effects of DNA synthesis of human fibroblasts were investigated using 2,4-D with 15 xenobiotics of different chemical substance classes. Results were compared with previous investigations on cell growth. Each of the 15 chemicals tested at their no effect concentrations (NOEC's) increased the effects of 2,4-D on DNA synthesis. Thereby, the EC20 value of 2,4-D was reduced by approximately 40% in the combinations. The NOEC's of the xenobiotics used in the combinations varied by a factor of 1,600 and depended strongly on the lipophilicity of the agents combined with 2,4-D. A significant statistical correlation of r = 0.90 was found between the NOEC's of the 15 combined xenobiotics and their lipophilicity. The combination effects on DNA synthesis were similar to those on cell growth. The regression lines of the relationship between the NOEC's and lipophilicity in both assays showed only slight differences in the slopes. This is an additional confirmation of our hypothesis on a facilitated uptake of 2,4-D in the binary combinations.

75 FR 32639 - Defense Federal Acquisition Regulation Supplement; Limitations on Procurements With Non-Defense...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... elements of the Department of Homeland Security concerned with the analysis of intelligence information... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 217 RIN 0750-AG67 Defense Federal Acquisition Regulation Supplement; Limitations on Procurements With Non-Defense Agencies (DFARS...

Department of Defense (DOD) Automated Biometric Identification System (ABIS) Version 1.2: Initial Operational Test and Evaluation Report

DTIC Science & Technology

2015-05-01

Director, Operational Test and Evaluation Department of Defense (DOD) Automated Biometric Identification System (ABIS) Version 1.2 Initial...Operational Test and Evaluation Report May 2015 This report on the Department of Defense (DOD) Automated Biometric Identification System...COVERED - 4. TITLE AND SUBTITLE Department of Defense (DOD) Automated Biometric Identification System (ABIS) Version 1.2 Initial Operational Test

It’s War Out There: Fighting for life with xenobiotic degrading enzymes

USDA-ARS?s Scientific Manuscript database

It’s War Out There: Fighting for life with xenobiotic degrading enzymes Beta-lactamase enzymes are well studied because of their tremendous impact on medicine. Their prominent role is in resistance to beta-lactam (four membered lactam ring) antibiotics including the first and most famous fungally d...

Estimation of maximum transdermal flux of nonionized xenobiotics from basic physicochemical determinants

PubMed Central

Milewski, Mikolaj; Stinchcomb, Audra L.

2012-01-01

An ability to estimate the maximum flux of a xenobiotic across skin is desirable both from the perspective of drug delivery and toxicology. While there is an abundance of mathematical models describing the estimation of drug permeability coefficients, there are relatively few that focus on the maximum flux. This article reports and evaluates a simple and easy-to-use predictive model for the estimation of maximum transdermal flux of xenobiotics based on three common molecular descriptors: logarithm of octanol-water partition coefficient, molecular weight and melting point. The use of all three can be justified on the theoretical basis of their influence on the solute aqueous solubility and the partitioning into the stratum corneum lipid domain. The model explains 81% of the variability in the permeation dataset comprised of 208 entries and can be used to obtain a quick estimate of maximum transdermal flux when experimental data is not readily available. PMID:22702370

Use of the Homeland-Defense Operational Planning System (HOPS) for Emergency Management

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

Durling, Jr., R L; Price, D E

2005-12-16

The Homeland-Defense Operational Planning System (HOPS), is a new operational planning tool leveraging Lawrence Livermore National Laboratory's expertise in weapons systems and in sparse information analysis to support the defense of the U.S. homeland. HOPS provides planners with a basis to make decisions to protect against acts of terrorism, focusing on the defense of facilities critical to U.S. infrastructure. Criticality of facilities, structures, and systems is evaluated on a composite matrix of specific projected casualty, economic, and sociopolitical impact bins. Based on these criteria, significant unidentified vulnerabilities are identified and secured. To provide insight into potential successes by malevolent actors,more » HOPS analysts strive to base their efforts mainly on unclassified open-source data. However, more cooperation is needed between HOPS analysts and facility representatives to provide an advantage to those whose task is to defend these facilities. Evaluated facilities include: refineries, major ports, nuclear power plants and other nuclear licensees, dams, government installations, convention centers, sports stadiums, tourist venues, and public and freight transportation systems. A generalized summary of analyses of U.S. infrastructure facilities will be presented.« less

Impact of Defense Industry Mergers on The Cost of Military Weapons Systems

DTIC Science & Technology

2007-12-01

over the last 16 years . This thesis reports the impact of these defense related mergers on the cost of military weapons systems. The Selected...the requirements for the degree of MASTER OF BUSINESS ADMINISTRATION from the NAVAL POSTGRADUATE SCHOOL December 2007 Author...Graduate School of Business and Public Policy iv THIS PAGE INTENTIONALLY LEFT BLANK v ABSTRACT The United States defense industry has been in a

Xenobiotics and loss of cell adhesion drive distinct transcriptional outcomes by aryl hydrocarbon receptor signaling.

PubMed

Hao, Nan; Lee, Kian Leong; Furness, Sebastian G B; Bosdotter, Cecilia; Poellinger, Lorenz; Whitelaw, Murray L

2012-12-01

The aryl hydrocarbon receptor (AhR) is a signal-regulated transcription factor, which is canonically activated by the direct binding of xenobiotics. In addition, switching cells from adherent to suspension culture also activates the AhR, representing a nonxenobiotic, physiological activation of AhR signaling. Here, we show that the AhR is recruited to target gene enhancers in both ligand [isopropyl-2-(1,3-dithietane-2-ylidene)-2-[N-(4-methylthiazol-2-yl)carbamoyl]acetate (YH439)]-treated and suspension cells, suggesting a common mechanism of target gene induction between these two routes of AhR activation. However, gene expression profiles critically differ between xenobiotic- and suspension-activated AhR signaling. Por and Cldnd1 were regulated predominantly by ligand treatments, whereas, in contrast, ApoER2 and Ganc were regulated predominantly by the suspension condition. Classic xenobiotic-metabolizing AhR targets such as Cyp1a1, Cyp1b1, and Nqo1 were regulated by both ligand and suspension conditions. Temporal expression patterns of AhR target genes were also found to vary, with examples of transient activation, transient repression, or sustained alterations in expression. Furthermore, sequence analysis coupled with chromatin immunoprecipitation assays and reporter gene analysis identified a functional xenobiotic response element (XRE) in the intron 1 of the mouse Tiparp gene, which was also bound by hypoxia-inducible factor-1α during hypoxia and features a concatemer of four XRE cores (GCGTG). Our data suggest that this XRE concatemer site concurrently regulates the expression of both the Tiparp gene and its cis antisense noncoding RNA after ligand- or suspension-induced AhR activation. This work provides novel insights into how AhR signaling drives different transcriptional programs via the ligand versus suspension modes of activation.

P-glycoprotein Inhibition by the Agricultural Pesticide Propiconazole and Its Hydroxylated Metabolites: Implications for Pesticide-Drug Interactions.

EPA Science Inventory

The human efflux transporter P-glycoprotein (P-gp; MDR1) functions an important cellular defense system against a variety of xenobiotics; however, little information exists on whether environmental chemicals interact with P-gp. Conazoles provide a unique challenge to exposure ass...

P-glycoprotein Inhibition by the Agricultural Pesticide Propiconazole and Its Hydroxylated Metabolites: Implications for Pesticide-Drug Interactions

EPA Science Inventory

The human efflux transporter P-glycoprotein (P-gp, MDR1) functions an important cellular defense system against a variety of xenobiotics; however, little information exists on whether environmental chemicals interact with P-gp. Conazoles provide a unique challenge to exposure ass...

Evaluation of the DEIMS (Defense Economic Impact Modeling System) System.

DTIC Science & Technology

1984-07-01

AOORESS(H d~fereet m Caii~dl Offiee) IS. SECURITY CLASS. (of Wd e~w Vr OUSDRE (DoD-IDA Management Office) UCASFE 1801 N. Beauregard Street UCASFE...Defense Spending Mr. Paul Dickens, PA&E Labor Demand - Dr. David Blond Conclusion - Dr. David L. Mdicol 11:00 Break SESSION III - IMPACT OF DEFENSE...presented highlights of the industrial and labor impact of defense spending during. . 1985-89. Mr. Paul Dickens then analysed trends in the I- .""L- " ’•L

Combat Identification Systems COMO Integrated Air Defense Model Evaluation (CISE) Study

DTIC Science & Technology

1989-02-01

use K or IR , whichever one applies) E-6 CAA-SR-89- 3 Subroutine PDECLR 1/21/88 Before label 1000 Insert: IF (IR.GT.10) IR a 10 These changes were made...Internal Distribution: Unclassified Library 2 F-2 CAA-SR-89- 3 GLOSSARY 1. ABBREVIATIONS, ACRONYMS, AND SHORT TERMS ADM2 Air Defense Models Modification...STUDY REPORT ’ , CAA-Sn-89- 3 i , .- CD o COMBAT IDENTIFICATION SYSTEMS N COMO INTEGRATED AIR DEFENSE MODEL EVALUATION (CISE) STUDY FEBRUARY 1989

Combination of microautoradiography and fluorescence in situ hybridization for identification of microorganisms degrading xenobiotic contaminants.

PubMed

Yang, Yanru; Zarda, Annatina; Zeyer, Josef

2003-12-01

One of the central topics in environmental bioremediation research is to identify microorganisms that are capable of degrading the contaminants of interest. Here we report application of combined microautoradiography (MAR) and fluorescence in situ hybridization (FISH). The method has previously been used in a number of systems; however, here we demonstrate its feasibility in studying the degradation of xenobiotic compounds. With a model system (coculture of Pseudomonas putida B2 and Sphingomonas stygia incubated with [14C] o-nitrophenol), combination of MAR and FISH was shown to be able to successfully identify the microorganisms degrading o-nitrophenol. Compared with the conventional techniques, MAR-FISH allows fast and accurate identification of the microorganisms involved in environmental contaminant degradation.

Issues With Access to Acquisition Data and Information in the Department of Defense: Doing Data Right in Weapon System Acquisition

DTIC Science & Technology

2016-04-30

Defense: Doing Data Right in Weapon System Acquisition Nancy Moore, Senior Management Scientist, RAND Megan McKernan, Defense Research Analyst...Access to Acquisition Data & Information in the Department of Defense: Doing Data Right in Weapon System Acquisition Nancy Moore, Senior Management...With Access to Acquisition Data and Information in the Department of Defense: Doing Data Right in Weapon System Acquisition Nancy Y. Moore—is a

Defensive weapons and defense signals in plants: some metabolites serve both roles.

PubMed

Maag, Daniel; Erb, Matthias; Köllner, Tobias G; Gershenzon, Jonathan

2015-02-01

The defense of plants against herbivores and pathogens involves the participation of an enormous range of different metabolites, some of which act directly as defensive weapons against enemies (toxins or deterrents) and some of which act as components of the complex internal signaling network that insures that defense is timed to enemy attack. Recent work reveals a surprising trend: The same compounds may act as both weapons and signals of defense. For example, two groups of well-studied defensive weapons, glucosinolates and benzoxazinoids, trigger the accumulation of the protective polysaccharide callose as a barrier against aphids and pathogens. In the other direction, several hormones acting in defense signaling (and their precursors and products) exhibit activity as weapons against pathogens. Knowing which compounds are defensive weapons, which are defensive signals and which are both is vital for understanding the functioning of plant defense systems. © 2015 WILEY Periodicals, Inc.

Hepatic Xenobiotic Metabolizing Enzyme Gene Expression Through the Life Stages of the Mouse

EPA Science Inventory

BACKGROUND: Differences in responses to environmental chemicals and drugs between life stages are likely due in part to differences in the expression of xenobiotic metabolizing enzymes and transporters (XMETs). No comprehensive analysis of the mRNA expression of XMETs has been ca...

Acquisition Planning at the Defense Communications Agency.

DTIC Science & Technology

1984-04-01

guidelines for interaction are developed under the leadership of DCA agencywide integrators with the participation of personnel from DCA, the Services...Communications System DCSO - Defense Communications System Organizatin . DDN - Defense Data Network DEC - Decision Making DG - Defense Guidance DIA - Defense

A Locus Encoding Variable Defense Systems against Invading DNA Identified in Streptococcus suis

PubMed Central

Okura, Masatoshi; Nozawa, Takashi; Watanabe, Takayasu; Murase, Kazunori; Nakagawa, Ichiro; Takamatsu, Daisuke; Osaki, Makoto; Sekizaki, Tsutomu; Gottschalk, Marcelo; Hamada, Shigeyuki

2017-01-01

Streptococcus suis, an important zoonotic pathogen, is known to have an open pan-genome and to develop a competent state. In S. suis, limited genetic lineages are suggested to be associated with zoonosis. However, little is known about the evolution of diversified lineages and their respective phenotypic or ecological characteristics. In this study, we performed comparative genome analyses of S. suis, with a focus on the competence genes, mobile genetic elements, and genetic elements related to various defense systems against exogenous DNAs (defense elements) that are associated with gene gain/loss/exchange mediated by horizontal DNA movements and their restrictions. Our genome analyses revealed a conserved competence-inducing peptide type (pherotype) of the competence system and large-scale genome rearrangements in certain clusters based on the genome phylogeny of 58 S. suis strains. Moreover, the profiles of the defense elements were similar or identical to each other among the strains belonging to the same genomic clusters. Our findings suggest that these genetic characteristics of each cluster might exert specific effects on the phenotypic or ecological differences between the clusters. We also found certain loci that shift several types of defense elements in S. suis. Of note, one of these loci is a previously unrecognized variable region in bacteria, at which strains of distinct clusters code for different and various defense elements. This locus might represent a novel defense mechanism that has evolved through an arms race between bacteria and invading DNAs, mediated by mobile genetic elements and genetic competence. PMID:28379509

Comparative investigation of the xenobiotic metabolizing arylamine N-acetyltransferase enzyme family among fungi

USDA-ARS?s Scientific Manuscript database

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes well-characterized in several bacteria and higher eukaryotes. The role of NATs in fungal biology has only recently been investigated. The NAT1 gene of Gibberella moniliformis was the first NAT cloned and characterized from fun...

Comparative genomic and phylogenetic investigation of the xenobiotic metabolizing arylamine N-acetyltransferase enzyme family

USDA-ARS?s Scientific Manuscript database

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes characterized in several bacteria and eukaryotic organisms. We report a comprehensive phylogenetic analysis employing an exhaustive dataset of NAT-homologous sequences recovered through inspection of 2445 genomes. We describe ...

Do heavy metals and metalloids influence the detoxification of organic xenobiotics in plants?

PubMed

Schröder, Peter; Lyubenova, Lyudmila; Huber, Christian

2009-11-01

80 microM arsenic alone doubled GSSG values. Based on these results, further experiments were performed in whole plants of cattail and reed, using cadmium in Phragmites and cadmium and arsenic in Typha as inducers of stress. In Phragmites australis, GST activities for CDNB and DCNB were significantly reduced after short-term Cd exposure (24 h). In the same samples, all antioxidant enzymes increased with rising heavy metal concentrations. Typha latifolia rhizome incubation with Cd and As leads to an increase in glutathione reductase and total peroxidase activity and to a decrease in ascorbate peroxidase activity. Measurements of the same enzymes in leaves of the same plants show increased GR activities, but no change in peroxidases. GST conjugation for CDNB was depressed in both cattail rhizomes and leaves treated with Cd. After As application increased, DCNB enzyme activities were detected. T. latifolia and P. australis are powerful species for phytoremediation because they penetrate a large volume of soil with their extensive root and rhizome systems. However, an effective remediation process will depend on active detoxifying enzymes, and also on the availability of conjugation partners, e.g. glutathione and its analogues. Species-specific differences seem to exist between the regulations of primary defence enzymes like SOD, catalase, peroxidases, whereas others prefer to induce the glutathione-dependent enzymes. As long as the pollutant mix encountered is simple and dominated by heavy metals, plant defence might be sufficient. When pollution plumes contain heavy metals and organic xenobiotics at the same time, this means that part of the detoxification capacity, at least of glutathione-conjugating reactions, is withdrawn from the heavy metal front to serve other purposes. In fact, glutathione S-transferases show strong reactions in stressed plants or in the presence of heavy metals. The spruce cell culture was a perfect model system to study short-term responses on

Monobromobimane occupies a distinct xenobiotic substrate site in glutathione S-transferase π

PubMed Central

Ralat, Luis A.; Colman, Roberta F.

2003-01-01

Monobromobimane (mBBr), functions as a substrate of porcine glutathione S-transferase π (GST π): The enzyme catalyzes the reaction of mBBr with glutathione. S-(Hydroxyethyl)bimane, a nonreactive analog of monobromobimane, acts as a competitive inhibitor with respect to mBBr as substrate but does not affect the reaction of GST π with another substrate, 1-chloro-2,4-dinitrobenzene (CDNB). In the absence of glutathione, monobromobimane inactivates GST π at pH 7.0 and 25°C as assayed using mBBr as substrate, with a lesser effect on the enzyme’s use of CDNB as substrate. These results indicate that the sites occupied by CDNB and mBBr are not identical. Inactivation is proportional to the incorporation of 2 moles of bimane/mole of subunit. Modification of GST π with mBBr does not interfere with its binding of 8-anilino-1-naphthalene sulfonate, indicating that this hydrophobic site is not the target of monobromobimane. S-Methylglutathione and S-(hydroxyethyl)bimane each yield partial protection against inactivation and decrease reagent incorporation, while glutathionyl-bimane protects completely against inactivation. Peptide analysis after trypsin digestion indicates that mBBr modifies Cys45 and Cys99 equally. Modification of Cys45 is reduced in the presence of S-methylglutathione, indicating that this residue is at or near the glutathione binding region. In contrast, modification of Cys99 is reduced in the presence of S-(hydroxyethyl)bimane, suggesting that this residue is at or near the mBBr xenobiotic substrate binding site. Modification of Cys99 can best be understood by reaction with monobromobimane while it is bound to its xenobiotic substrate site in an alternate orientation. These results support the concept that glutathione S-transferase accomplishes its ability to react with a diversity of substrates in part by harboring distinct xenobiotic substrate sites. PMID:14573868

Monobromobimane occupies a distinct xenobiotic substrate site in glutathione S-transferase pi.

PubMed

Ralat, Luis A; Colman, Roberta F

2003-11-01

Monobromobimane (mBBr), functions as a substrate of porcine glutathione S-transferase pi (GST pi): The enzyme catalyzes the reaction of mBBr with glutathione. S-(Hydroxyethyl)bimane, a nonreactive analog of monobromobimane, acts as a competitive inhibitor with respect to mBBr as substrate but does not affect the reaction of GST pi with another substrate, 1-chloro-2,4-dinitrobenzene (CDNB). In the absence of glutathione, monobromobimane inactivates GST pi at pH 7.0 and 25 degrees C as assayed using mBBr as substrate, with a lesser effect on the enzyme's use of CDNB as substrate. These results indicate that the sites occupied by CDNB and mBBr are not identical. Inactivation is proportional to the incorporation of 2 moles of bimane/mole of subunit. Modification of GST pi with mBBr does not interfere with its binding of 8-anilino-1-naphthalene sulfonate, indicating that this hydrophobic site is not the target of monobromobimane. S-Methylglutathione and S-(hydroxyethyl)bimane each yield partial protection against inactivation and decrease reagent incorporation, while glutathionyl-bimane protects completely against inactivation. Peptide analysis after trypsin digestion indicates that mBBr modifies Cys45 and Cys99 equally. Modification of Cys45 is reduced in the presence of S-methylglutathione, indicating that this residue is at or near the glutathione binding region. In contrast, modification of Cys99 is reduced in the presence of S-(hydroxyethyl)bimane, suggesting that this residue is at or near the mBBr xenobiotic substrate binding site. Modification of Cys99 can best be understood by reaction with monobromobimane while it is bound to its xenobiotic substrate site in an alternate orientation. These results support the concept that glutathione S-transferase accomplishes its ability to react with a diversity of substrates in part by harboring distinct xenobiotic substrate sites.

The Gulf War's impact on ballistic missile defense systems

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

Likourezos, G.

1993-01-01

During Desert Storm the United States and its allies had an overwhelming advantage over the Iraqi armed forces. Nonetheless, the Iraqis managed to strike Israel and Saudi Arabia with Scud missiles. Because of the changing political climate and the expanding transfer of technology among nations, there is great concern by the US Government about missile proliferation and the ability of any country to obtain weapons of mass destruction. The US Government tried to downplay this concern for many years until the recent events in the Middle East affirmed its seriousness. The truth is that every year countries once thought tomore » pose no international threat are acquiring biological, chemical, and nuclear weapons. Moreover, state-sponsored terrorist organizations could conceivably acquire these weapons in the future. In response to these concerns and in light of the lessons learned from the Gulf War, President George Bush in January 1991 redirected the SDI Program to concentrate on providing protection from limited ballistic missile strikes, rather than from an all-out nuclear missile attack by the Soviet Union. The Patriot air defense system, after knocking out Iraqi Scuds in the Gulf War with a near perfect record, appears for now to be the working model for the development of advanced ballistic missile defense systems - direct-kill missiles and projectiles instead of laser and particle beams. Even though the Patriot's use in Desert Storm has been argued by some to have been militarily insignificant, it has managed to change the viewpoint of many political and scientific leaders into believing that ballistic missile defense systems are needed to defend peaceful population centers and military installations from missile strikes like the ones on Israel and Saudi Arabia. 18 refs.« less

Passive automatic anti-piracy defense system of ships

NASA Astrophysics Data System (ADS)

Szustakowski, M.; Życzkowski, M.; Ciurapiński, W.; Karol, M.; Kastek, M.; Stachowiak, R.; Markowski, P.

2013-10-01

The article describes the technological solution for ship self-defense against pirate attacks. The paper presents the design solutions in the field of direct physical protection. All the solutions are connected with the latest optoelectronic and microwave systems and sensors to detect, recognize and the threat posed by pirates. In particular, tests of effectiveness and the detection-range of technology demonstrator developed by a team of authors were carried out.

Defense Intelligence: Additional Steps Could Better Integrate Intelligence Input into DODs Acquisition of Major Weapon Systems

DTIC Science & Technology

2016-11-01

DEFENSE INTELLIGENCE Additional Steps Could Better Integrate Intelligence Input into DOD’s Acquisition of Major Weapon...States Government Accountability Office Highlights of GAO-17-10, a report to congressional committees November 2016 DEFENSE INTELLIGENCE ...Additional Steps Could Better Integrate Intelligence Input into DOD’s Acquisition of Major Weapon Systems What GAO Found The Department of Defense (DOD

Cryptic indole hydroxylation by a non-canonical terpenoid cyclase parallels bacterial xenobiotic detoxification

NASA Astrophysics Data System (ADS)

Kugel, Susann; Baunach, Martin; Baer, Philipp; Ishida-Ito, Mie; Sundaram, Srividhya; Xu, Zhongli; Groll, Michael; Hertweck, Christian

2017-06-01

Terpenoid natural products comprise a wide range of molecular architectures that typically result from C-C bond formations catalysed by classical type I/II terpene cyclases. However, the molecular diversity of biologically active terpenoids is substantially increased by fully unrelated, non-canonical terpenoid cyclases. Their evolutionary origin has remained enigmatic. Here we report the in vitro reconstitution of an unusual flavin-dependent bacterial indoloterpenoid cyclase, XiaF, together with a designated flavoenzyme-reductase (XiaP) that mediates a key step in xiamycin biosynthesis. The crystal structure of XiaF with bound FADH2 (at 2.4 Å resolution) and phylogenetic analyses reveal that XiaF is, surprisingly, most closely related to xenobiotic-degrading enzymes. Biotransformation assays show that XiaF is a designated indole hydroxylase that can be used for the production of indigo and indirubin. We unveil a cryptic hydroxylation step that sets the basis for terpenoid cyclization and suggest that the cyclase has evolved from xenobiotics detoxification enzymes.

Information Management Principles Applied to the Ballistic Missile Defense System

DTIC Science & Technology

2007-03-01

of a BMDS. From this, the Army produced the Nike -Zeus system comprised of four radars, the Zeus missile, and a computer fire control system (General...made the Nike -Zeus our first National Missile Defense (NMD) system named Sentinel. The architecture was to cover 14 locations, 10 of which were...1999). Additionally, there are cultural impacts (Gordon & Gordon, 1999). A company choosing an Apple OS may have to wage a big fight against the

The Jasmonate Pathway Is a Key Player in Systemically Induced Defense against Root Knot Nematodes in Rice1[C

PubMed Central

Nahar, Kamrun; Kyndt, Tina; De Vleesschauwer, David; Höfte, Monica; Gheysen, Godelieve

2011-01-01

Complex defense signaling pathways, controlled by different hormones, are involved in the reaction of plants to a wide range of biotic and abiotic stress factors. We studied the ability of salicylic acid, jasmonate (JA), and ethylene (ET) to induce systemic defense in rice (Oryza sativa) against the root knot nematode Meloidogyne graminicola. Exogenous ET (ethephon) and JA (methyl jasmonate) supply on the shoots induced a strong systemic defense response in the roots, exemplified by a major up-regulation of pathogenesis-related genes OsPR1a and OsPR1b, while the salicylic acid analog BTH (benzo-1,2,3-thiadiazole-7-carbothioic acid S-methyl ester) was a less potent systemic defense inducer from shoot to root. Experiments with JA biosynthesis mutants and ET-insensitive transgenics showed that ET-induced defense requires an intact JA pathway, while JA-induced defense was still functional when ET signaling was impaired. Pharmacological inhibition of JA and ET biosynthesis confirmed that JA biosynthesis is needed for ET-induced systemic defense, and quantitative real-time reverse transcription-polymerase chain reaction data revealed that ET application onto the shoots strongly activates JA biosynthesis and signaling genes in the roots. All data provided in this study point to the JA pathway to play a pivotal role in rice defense against root knot nematodes. The expression of defense-related genes was monitored in root galls caused by M. graminicola. Different analyzed defense genes were attenuated in root galls caused by the nematode at early time points after infection. However, when the exogenous defense inducers ethephon and methyl jasmonate were supplied to the plant, the nematode was less effective in counteracting root defense pathways, hence making the plant more resistant to nematode infection. PMID:21715672

48 CFR 225.7902 - Defense Trade Cooperation Treaties.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Defense Trade Cooperation Treaties. 225.7902 Section 225.7902 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION EXPORT CONTROL 225.7902 Defense Trade Cooperation Treaties. This...

48 CFR 225.7902 - Defense Trade Cooperation Treaties.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Defense Trade Cooperation Treaties. 225.7902 Section 225.7902 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION EXPORT CONTROL 225.7902 Defense Trade Cooperation Treaties. This...

A host defense role for a natural antiviral substance in the nervous system.

PubMed

Baron, S; Chopra, A K; Coppenhaver, D H; Gelman, B B; Poast, J; Singh, I P

1998-05-15

The pathogenesis of virus infections of the nervous system (NS) is regulated by host defenses. The defensive role of a major constitutive antiviral substance was studied by determining its distribution in the human nervous system, its concentration and the ability of this viral inhibitor to protect mice against viral infection. The 4000 kDa inhibitor complex in the human nervous system was detected in brain gray and white matter, spinal cord, and sciatic nerve but not in human cerebrospinal fluid. The inhibitor was found in the extracellular medium incubated with minced murine brain. The inhibitory titer ranged from approximately 50 to 200 antiviral units per gram against polio 1, Semliki Forest, Banzi, mengo, Newcastle disease and herpes simplex 1 viruses. The inhibitor is composed of lipid and essential protein and carbohydrate moieties as determined by enzymatic inactivation. Protection of inhibitor-treated mice was demonstrated against both an alphavirus and a picornavirus. Thus a natural defensive role for the broadly antiviral inhibitor is suggested by its constitutively high concentration, wide distribution in nervous system tissues, presence in extracellular fluid and its ability to provide protection in infected mice.

Intermolecular Forces as a Key to Understanding the Environmental Fate of Organic Xenobiotics

ERIC Educational Resources Information Center

Casey, Ryan E.; Pittman, Faith A.

2005-01-01

A module that can be incorporated into chemistry or environmental science classes at the high school or undergraduate level is described. The module is divided into a series of segments, each of which incorporates several concepts and results in students making significant predictions about the behavior of organic xenobiotics.

Density-dependent adjustment of inducible defenses.

PubMed

Tollrian, Ralph; Duggen, Sonja; Weiss, Linda C; Laforsch, Christian; Kopp, Michael

2015-08-03

Predation is a major factor driving evolution, and organisms have evolved adaptations increasing their survival chances. However, most defenses incur trade-offs between benefits and costs. Many organisms save costs by employing inducible defenses as responses to fluctuating predation risk. The level of defense often increases with predator densities. However, individual predation risk should not only depend on predator density but also on the density of conspecifics. If the predator has a saturating functional response one would predict a negative correlation between prey density and individual predation risk and hence defense expression. Here, we tested this hypothesis using six model systems, covering a taxonomic range from protozoa to rotifers and crustaceans. In all six systems, we found that the level of defense expression increased with predator density but decreased with prey density. In one of our systems, i.e. in Daphnia, we further show that the response to prey density is triggered by a chemical cue released by conspecifics and congeners. Our results indicate that organisms adjust the degree of defense to the acute predation risk, rather than merely to predators' densities. Our study suggests that density-dependent defense expression reflects accurate predation-risk assessment and is a general principle in many inducible-defense systems.

Density-dependent adjustment of inducible defenses

PubMed Central

Tollrian, Ralph; Duggen, Sonja; Weiss, Linda C.; Laforsch, Christian; Kopp, Michael

2015-01-01

Predation is a major factor driving evolution, and organisms have evolved adaptations increasing their survival chances. However, most defenses incur trade-offs between benefits and costs. Many organisms save costs by employing inducible defenses as responses to fluctuating predation risk. The level of defense often increases with predator densities. However, individual predation risk should not only depend on predator density but also on the density of conspecifics. If the predator has a saturating functional response one would predict a negative correlation between prey density and individual predation risk and hence defense expression. Here, we tested this hypothesis using six model systems, covering a taxonomic range from protozoa to rotifers and crustaceans. In all six systems, we found that the level of defense expression increased with predator density but decreased with prey density. In one of our systems, i.e. in Daphnia, we further show that the response to prey density is triggered by a chemical cue released by conspecifics and congeners. Our results indicate that organisms adjust the degree of defense to the acute predation risk, rather than merely to predators’ densities. Our study suggests that density-dependent defense expression reflects accurate predation-risk assessment and is a general principle in many inducible-defense systems. PMID:26235428

Patriot/Medium Extended Air Defense System Combined Aggregate Program (Patriot/MEADS CAP)

DTIC Science & Technology

2013-12-01

States, Germany, and Italy to replace the U.S. Patriot air defense systems, Patriot and Hawk systems in Germany, and the Nike system in Italy. The MEADS...Appropriation: RDT&E Contract Name Design & Development Contractor MEADS International Inc . Contractor Location 5600 W Sand Lake Road Orlando, FL 32819

Virtual Screening as a Strategy for the Identification of Xenobiotics Disrupting Corticosteroid Action

PubMed Central

Praxmarer, Lukas; Chantong, Boonrat; Cereghetti, Diego; Winiger, Rahel; Schuster, Daniela; Odermatt, Alex

2012-01-01

Background Impaired corticosteroid action caused by genetic and environmental influence, including exposure to hazardous xenobiotics, contributes to the development and progression of metabolic diseases, cardiovascular complications and immune disorders. Novel strategies are thus needed for identifying xenobiotics that interfere with corticosteroid homeostasis. 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) and mineralocorticoid receptors (MR) are major regulators of corticosteroid action. 11β-HSD2 converts the active glucocorticoid cortisol to the inactive cortisone and protects MR from activation by glucocorticoids. 11β-HSD2 has also an essential role in the placenta to protect the fetus from high maternal cortisol concentrations. Methods and Principal Findings We employed a previously constructed 3D-structural library of chemicals with proven and suspected endocrine disrupting effects for virtual screening using a chemical feature-based 11β-HSD pharmacophore. We tested several in silico predicted chemicals in a 11β-HSD2 bioassay. The identified antibiotic lasalocid and the silane-coupling agent AB110873 were found to concentration-dependently inhibit 11β-HSD2. Moreover, the silane AB110873 was shown to activate MR and stimulate mitochondrial ROS generation and the production of the proinflammatory cytokine interleukin-6 (IL-6). Finally, we constructed a MR pharmacophore, which successfully identified the silane AB110873. Conclusions Screening of virtual chemical structure libraries can facilitate the identification of xenobiotics inhibiting 11β-HSD2 and/or activating MR. Lasalocid and AB110873 belong to new classes of 11β-HSD2 inhibitors. The silane AB110873 represents to the best of our knowledge the first industrial chemical shown to activate MR. Furthermore, the MR pharmacophore can now be used for future screening purposes. PMID:23056542

Role of resveratrol in regulation of cellular defense systems against oxidative stress.

PubMed

Truong, Van-Long; Jun, Mira; Jeong, Woo-Sik

2018-01-01

Resveratrol, a natural polyphenolic compound, is found in various kinds of fruits, plants, and their commercial products such as red wine. It has been demonstrated to exhibit a variety of health-promoting effects including prevention and/or treatment of cardiovascular diseases, inflammation, diabetes, neurodegeneration, aging, and cancer. Cellular defensive properties of resveratrol can be explained through its ability of either directly neutralizing reactive oxygen species/reactive nitrogen species (ROS/RNS) or indirectly upregulating the expression of cellular defensive genes. As a direct antioxidant agent, resveratrol scavenges diverse ROS/RNS as well as secondary organic radicals with mechanisms of hydrogen atom transfer and sequential proton loss electron transfer, thereby protecting cellular biomolecules from oxidative damage. Resveratrol also enhances the expression of various antioxidant defensive enzymes such as heme oxygenase 1, catalase, glutathione peroxidase, and superoxide dismutase as well as the induction of glutathione level responsible for maintaining the cellular redox balance. Such defenses could be achieved by regulating various signaling pathways including sirtuin 1, nuclear factor-erythroid 2-related factor 2 and nuclear factor κB. This review provides current understanding and information on the role of resveratrol in cellular defense system against oxidative stress. © 2017 BioFactors, 44(1):36-49, 2018. © 2017 International Union of Biochemistry and Molecular Biology.

DEVELOPMENT OF MOLECULAR INDICATORS OF EXPOSURE TO ENDOCRINE DISRUPTING COMPOUNDS, PESTICIDES & OTHER XENOBIOTIC AGENTS

EPA Science Inventory

A great deal of uncertainty exists regarding the extent to which humans and wildlife are exposed to chemical stressors in aquatic resources. Scientific literature is replete with studies of xenobiotics in surface waters, including a recent national USGS survey of endocrine disrup...

Bayesian performance metrics and small system integration in recent homeland security and defense applications

NASA Astrophysics Data System (ADS)

Jannson, Tomasz; Kostrzewski, Andrew; Patton, Edward; Pradhan, Ranjit; Shih, Min-Yi; Walter, Kevin; Savant, Gajendra; Shie, Rick; Forrester, Thomas

2010-04-01

In this paper, Bayesian inference is applied to performance metrics definition of the important class of recent Homeland Security and defense systems called binary sensors, including both (internal) system performance and (external) CONOPS. The medical analogy is used to define the PPV (Positive Predictive Value), the basic Bayesian metrics parameter of the binary sensors. Also, Small System Integration (SSI) is discussed in the context of recent Homeland Security and defense applications, emphasizing a highly multi-technological approach, within the broad range of clusters ("nexus") of electronics, optics, X-ray physics, γ-ray physics, and other disciplines.

Investigation of runoff generation from anthropogenic sources with dissolved xenobiotics

NASA Astrophysics Data System (ADS)

Krein, A.; Pailler, J.; Guignard, C.; Iffly, J.; Pfister, L.; Hoffmann, L.

2009-04-01

In the experimental Mess basin (35 km2, Luxembourg) dissolved xenobiotics in surface water are used to study the influences of anthropogenic sources like separated sewer systems on runoff generation. Emerging contaminants like pharmaceuticals are of growing interest because of their use in large quantities in human and veterinary medicine. The amounts reaching surface waters depend on rainfall patterns, hydraulic conditions, consumption, metabolism, degradation, and disposal. The behaviour of endocrine disruptors including pharmaceuticals in the aquatic environment is widely unknown. The twelve molecules analyzed belong to three families: the estrogens, the antibiotics (sulfonamides, tetracyclines), and the painkillers (ibuprofen, diclofenac). Xenobiotics can be used as potential environmental tracers for untreated sewerage. Our results show that the concentrations are highly variable during flood events. The highest concentrations are reached in the first flush period, mainly during the rising limb of the flood hydrographs. As a result of the kinematic wave effect the concentration peak occurs in some cases a few hours after the discharge maximum. In floodwater (eleven floods, 66 samples) the highest concentrations were measured for ibuprofen (g/l range), estrone, and diclofenac (all ng/l range). From the tetracycline group, essentially tetracycline itself is of relevance, while the sulfonamides are mainly represented by sulfamethoxazole (all in ng/l range). In the Mess River the pharmaceuticals fluxes during flood events proved to be influenced by hydrological conditions. Different pharmaceuticals showed their concentration peaks during different times of a flood event. An example is the estrone peak that - during summer flash floods - often occurred one to two hours prior to the largest concentrations of the painkillers. This suggests for more sources than the sole storm drainage through the spillway of the single sewage water treatment plant, different

Systemic responses to inhaled ozone in mice: cachexia and down-regulation of liver xenobiotic metabolizing genes

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

Last, Jerold A.; Gohil, Kishorchandra; Mathrani, Vivek C.

2005-10-15

Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkersmore » of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-{kappa}B in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, including genes related to lipid and fatty acid metabolism, and to carbohydrate metabolism in this tissue, consistent with a systemic cachexic response. Several interferon-dependent genes were down-regulated in the liver, suggesting a possible role for interferon as a signaling molecule between lung and liver. In addition, transcription of several mRNAs encoding enzymes of xenobiotic metabolism in the livers of mice exposed to ozone was decreased, suggesting cytokine-mediated suppression of cytochrome P450 expression. This finding may explain a previously controversial report from other investigators more than 20 years ago of prolongation of pentobarbital sleeping time in mice exposed to ozone.« less

Systemic responses to inhaled ozone in mice: cachexia and down-regulation of liver xenobiotic metabolizing genes.

PubMed

Last, Jerold A; Gohil, Kishorchandra; Mathrani, Vivek C; Kenyon, Nicholas J

2005-10-15

Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-kappaB in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, including genes related to lipid and fatty acid metabolism, and to carbohydrate metabolism in this tissue, consistent with a systemic cachexic response. Several interferon-dependent genes were down-regulated in the liver, suggesting a possible role for interferon as a signaling molecule between lung and liver. In addition, transcription of several mRNAs encoding enzymes of xenobiotic metabolism in the livers of mice exposed to ozone was decreased, suggesting cytokine-mediated suppression of cytochrome P450 expression. This finding may explain a previously controversial report from other investigators more than 20 years ago of prolongation of pentobarbital sleeping time in mice exposed to ozone.

Codifying Information Assurance Controls for Department of Defense (DoD) Supervisory Control and Data Acquisition (SCADA) Systems

DTIC Science & Technology

2010-03-01

CODIFYING INFORMATION ASSURANCE CONTROLS FOR DEPARTMENT OF DEFENSE (DOD) SUPERVISORY CONTROL AND DATA...Force, Department of Defense, or the U.S. Government. AFIT/GCO/ENG/10-13 CODIFYING INFORMATION ASSURANCE CONTROLS FOR DEPARTMENT OF...DEFENSE (DOD) SUPERVISORY CONTROL AND DATA ACQUISITION (SCADA) SYSTEMS THESIS Presented to the Faculty Department of Electrical and Computer

2015 Assessment of the Ballistic Missile Defense System (BMDS)

DTIC Science & Technology

2016-04-01

performance and test adequacy of the BMDS, its four autonomous BMDS systems, and its sensor/command and control architecture. The four autonomous BMDS...Patriot. The Command and Control , Battle Management, and Communications (C2BMC) element anchors the sensor/command and control architecture. This...Warfare operations against a cruise missile surrogate. Ground-based Midcourse Defense (GMD). GMD has demonstrated capability against small

Passive rGE or developmental gene-environment cascade? An investigation of the role of xenobiotic metabolism genes in the association between smoke exposure during pregnancy and child birth weight

PubMed Central

Marceau, Kristine; Palmer, Rohan H.C.; Neiderhiser, Jenae M.; Smith, Taylor F.; McGeary, John E.; Knopik, Valerie S.

2016-01-01

There is considerable evidence that smoke exposure during pregnancy (SDP) environmentally influences birth weight after controlling for genetic influences and maternal characteristics. However, maternal smoking during pregnancy – the behavior that leads to smoke exposure during pregnancy – is also genetically-influenced, indicating the potential role of passive gene-environment correlation. An alternative to passive gene-SDP correlation is a cascading effect whereby maternal and child genetic influences are causally linked to prenatal exposures, which then have an ‘environmental’ effect on the development of the child’s biology and behavior. We describe and demonstrate a conceptual framework for disentangling passive rGE from this cascading GE effect using a systems-based polygenic scoring approach comprised of genes shown to be important in the xenobiotic (substances foreign to the body) metabolism pathway. Data were drawn from 5,044 families from the Avon Longitudinal Study of Parents and Children with information on maternal SDP, birth weight, and genetic polymorphisms in the xenobiotic pathway. Within a k-fold cross-validation approach (k=5), we created weighted maternal and child polygenic scores using 18 polymorphisms from 10 genes that have been implicated in the xenobiotic metabolism pathway. Mothers and children shared variation in xenobiotic metabolism genes. Amongst mothers who smoked during pregnancy, neither maternal nor child xenobiotic metabolism polygenic scores were associated with a higher likelihood of smoke exposure during pregnancy, or the severity of smoke exposure during pregnancy (and therefore, neither proposed mechanism was supported), or with child birth weight. SDP was consistently associated with lower child birth weight controlling for the polygenic scores, maternal educational attainment, social class, psychiatric problems, and age. Limitations of the study design and the potential of the framework using other designs are

The Impact of Environmental Regulation on Defense System Acquisition Management

DTIC Science & Technology

1976-05-01

producer, had been the sole source for the fuel. The process of manufacturing the fuel also produced a toxic ~arcinogenic byproduct. This condition caused...minimized. Could the design be quieter? Does the maintenance of the system require environmentally sensitive equipment, processes , or material? For ... Of particular interest to this report is the effect of such regulation on the defense system acquisition process . There is a direct impact on the

Multi-Objective Optimization of System Capability Satisficing in Defense Acquisition

DTIC Science & Technology

2012-01-01

of System Capability Satisficing in Defense Acquisition 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Stevens Institute of Technology,School of Systems...Report (SAR) 18. NUMBER OF PAGES 27 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT

77 FR 11355 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... the interim rule. Contractor business systems and internal controls are the first line of defense... contractor's accounting system shall provide for management reviews or internal audits of the contractor's... controls as part of any evaluation as to the reliability of information produced by a business system(s...

GENE EXPRESSION PROFILING OF XENOBIOTIC METABOLIZING ENZYMES (XMES) IN THE AGING MALE FISHER RAT

EPA Science Inventory

Detoxification and elimination of xenobiotics is a major function of the liver and is important in maintaining the metabolic homeostasis of the organism. The degree to which aging affects hepatic metabolism is not known. The expression of XMEs, in part, determines the fate of the...

75 FR 32416 - Defense Science Board

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... DEPARTMENT OF DEFENSE Office of the Secretary Defense Science Board AGENCY: Department of Defense (DoD). ACTION: Notice of advisory committee meeting. SUMMARY: The Defense Science Board Task Force on the Survivability of DoD Systems and Assets to Electromagnetic Pulse (EMP) and other Nuclear Weapons...

Report on Defense Business Operations to the Congressional Defense Committees

DTIC Science & Technology

2009-03-15

7 . PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Department of Defense,Business Information Agency,Washington,DC 8. PERFORMING ORGANIZATION...Defense Business Transformation 7 Table 2-2: System Modernizations and Initiatives by Business Enterprise Priority* Personnel Visibility...and people to ensure reliable and accurate delivery of acceptable goods and services. The procurement functional area establishes requirements for

Silverleaf whitefly induces salicylic acid defenses and suppresses effectual jasmonic acid defenses.

PubMed

Zarate, Sonia I; Kempema, Louisa A; Walling, Linda L

2007-02-01

The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF.

Xenobiotic metabolism in human skin and 3D human skin reconstructs: a review.

PubMed

Gibbs, Sue; van de Sandt, Johannes J M; Merk, Hans F; Lockley, David J; Pendlington, Ruth U; Pease, Camilla K

2007-12-01

In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential target organ for adverse health effects. Occupational, accidental or intended-use exposure to toxic chemicals could result in acute or delayed injury to the skin (e.g. inflammation, allergy, cancer). Skin metabolism may play a role in the manifestation or amelioration of adverse effects via the topical route. Today, we have robust testing strategies to assess the potential for local skin toxicity of chemical exposure. Such methods (e.g. the local lymph node assay for assessing skin sensitisation; skin painting carcinogenicity studies) incorporate skin metabolism implicitly in the in vivo model system used. In light of recent European legislation (i.e. 7(th) Amendment to the Cosmetics Directive and Registration Evaluation and Authorisation of existing Chemicals (REACH)), non-animal approaches will be required to reduce and replace animal experiments for chemical risk assessment. It is expected that new models and approaches will need to account for skin metabolism explicitly, as the mechanisms of adverse effects in the skin are deconvoluted. 3D skin models have been proposed as a tool to use in new in vitro alternative approaches. In order to be able to use 3D skin models in this context, we need to understand their metabolic competency in relation to xenobiotic biotransformation and whether functional activity is representative of that seen in human skin.

Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas.

PubMed

Fairchild, C R; Ivy, S P; Rushmore, T; Lee, G; Koo, P; Goldsmith, M E; Myers, C E; Farber, E; Cowan, K H

1987-11-01

We have previously reported the isolation of a human breast cancer cell line resistant to doxorubicin (adriamycin; AdrR MCF-7 cells) that has also developed the phenotype of multidrug resistance (MDR). MDR in this cell line is associated with increased expression of mdr (P glycoprotein) gene sequences. The development of MDR in AdrR MCF-7 cells is also associated with changes in the expression of several phase I and phase II drug-detoxifying enzymes. These changes are remarkably similar to those associated with development of xenobiotic resistance in rat hyperplastic liver nodules, a well-studied model system of chemical carcinogenesis. Using an mdr-encoded cDNA sequence isolated from AdrR MCF-7 cells, we have examined the expression of mdr sequences in rat livers under a variety of experimental conditions. The expression of mdr increased 3-fold in regenerating liver. It was also elevated (3- to 12-fold) in several different samples of rat hyperplastic nodules and in four of five hepatomas that developed in this system. This suggests that overexpression of mdr, a gene previously associated with resistance to antineoplastic agents, may also be involved in the development of resistance to xenobiotics in rat hyperplastic nodules. In addition, although the acute administration of 2-acetylaminofluorene induced an 8-fold increase in hepatic mdr-encoded RNA, performance of a partial hepatectomy either before or after administration of 2-acetylaminofluorene resulted in a greater than 80-fold increase in mdr gene expression over that in normal untreated livers. This represents an important in vivo model system in which to study the acute regulation of this drug resistance gene.

Evolution of RNA- and DNA-guided antivirus defense systems in prokaryotes and eukaryotes: common ancestry vs convergence.

PubMed

Koonin, Eugene V

2017-02-10

Complementarity between nucleic acid molecules is central to biological information transfer processes. Apart from the basal processes of replication, transcription and translation, complementarity is also employed by multiple defense and regulatory systems. All cellular life forms possess defense systems against viruses and mobile genetic elements, and in most of them some of the defense mechanisms involve small guide RNAs or DNAs that recognize parasite genomes and trigger their inactivation. The nucleic acid-guided defense systems include prokaryotic Argonaute (pAgo)-centered innate immunity and CRISPR-Cas adaptive immunity as well as diverse branches of RNA interference (RNAi) in eukaryotes. The archaeal pAgo machinery is the direct ancestor of eukaryotic RNAi that, however, acquired additional components, such as Dicer, and enormously diversified through multiple duplications. In contrast, eukaryotes lack any heritage of the CRISPR-Cas systems, conceivably, due to the cellular toxicity of some Cas proteins that would get activated as a result of operon disruption in eukaryotes. The adaptive immunity function in eukaryotes is taken over partly by the PIWI RNA branch of RNAi and partly by protein-based immunity. In this review, I briefly discuss the interplay between homology and analogy in the evolution of RNA- and DNA-guided immunity, and attempt to formulate some general evolutionary principles for this ancient class of defense systems. This article was reviewed by Mikhail Gelfand and Bojan Zagrovic.

76 FR 28855 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-18

... business systems and internal controls are the first line of defense against waste, fraud, and abuse. Weak control systems increase the risk of unallowable and unreasonable costs on Government contracts. To...'s accounting system rather than the adequacy of the contractor's control environment and overall...

Interoperability In Multi-Layered Active Defense:The Need For Commonality And Robustness Between Active Defense Weapon Systems

DTIC Science & Technology

2016-02-16

into areas where there is no access to maritime platforms. Sea-based interceptor platforms have the ability to intercept targets at each stage of the...argues that the most efficient concept for integrating active defense weapon systems is a multi- layered architecture with redundant intercept ...faster data transfer and will prevent data loss. The need for almost 100% interception successes is increasing as the threat becomes more

Department of Defense Systems Engineering FY 2012 Annual Report

DTIC Science & Technology

2013-03-01

by the Utility Helicopter PMO, is utilizing the latest Defense Acquisition Guidelines and previously approved PEO AVN SEP examples to develop all...efforts. As a whole, all of PEO AVN Program Management Offices understand the importance of systems engineering. They stress the continued use of...established SE guidelines, practices and procedures throughout our acquisition processes. PEO AVN , working with the AMRDEC SE Division, has

High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities

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

Sadler, Natalie C.; Webb-Robertson, Bobbie-Jo M.; Clauss, Therese R.

Cytochrome P450 monooxygenases (P450) are key to the metabolism of myriad endogenous chemicals and xenobiotics, including the majority of therapeutic drugs. Dysregulated P450 activities can lead to altered drug metabolism and toxicity, oxidative stress, and inflammation; all physiological states frequently charged as the impetus for various chronic pathologies. We characterized the impact of common xenobiotic exposures, specifically high-fat diet and active or passive cigarette smoke, on the functional capacity of hepatic and pulmonary P450s. We employed an activity-based protein profiling approach to characterize the identity and activity level of measured individual P450 isoforms. Our results confirm expectations of significant alterationsmore » in pulmonary P450s due to cigarette smoke, but now reveal the repressive impact of high-fat diet-induced obesity on many hepatic P450s activities, and the dynamic alterations due to concomitant diet and smoke exposures on liver and lung P450 activities impacting drug metabolism and pathways of inflammation.« less

Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses.

PubMed

Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E

2009-06-15

Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

78 FR 41331 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-10

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 225 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is making technical amendment to the Defense...

Uncertainties in building a strategic defense.

PubMed

Zraket, C A

1987-03-27

Building a strategic defense against nuclear ballistic missiles involves complex and uncertain functional, spatial, and temporal relations. Such a defensive system would evolve and grow over decades. It is too complex, dynamic, and interactive to be fully understood initially by design, analysis, and experiments. Uncertainties exist in the formulation of requirements and in the research and design of a defense architecture that can be implemented incrementally and be fully tested to operate reliably. The analysis and measurement of system survivability, performance, and cost-effectiveness are critical to this process. Similar complexities exist for an adversary's system that would suppress or use countermeasures against a missile defense. Problems and opportunities posed by these relations are described, with emphasis on the unique characteristics and vulnerabilities of space-based systems.

Impact of Contract Bundling and Consolidation on Defense Acquisition System and Defense Industrial Base: The Case of the U.S. Department of the Navy

DTIC Science & Technology

2012-04-27

Department of the Navy 27 April 2012 by Max V. Kidalov, J.D., LL.M., Assistant Professor Graduate School of Business & Public Policy Naval...Consolidation on Defense Acquisition System and Defense Industrial Base: The Case of the U.S. Department of the Navy 5a. CONTRACT NUMBER 5b. GRANT...examining Department of the Navy (DoN) bundled and consolidated contracts for fiscal year (FY) 2010, the record year for bundling and consolidation in

Ecologically Appropriate Xenobiotics Induce Cytochrome P450s in Apis mellifera

PubMed Central

Johnson, Reed M.; Mao, Wenfu; Pollock, Henry S.; Niu, Guodong; Schuler, Mary A.; Berenbaum, May R.

2012-01-01

Background Honey bees are exposed to phytochemicals through the nectar, pollen and propolis consumed to sustain the colony. They may also encounter mycotoxins produced by Aspergillus fungi infesting pollen in beebread. Moreover, bees are exposed to agricultural pesticides, particularly in-hive acaricides used against the parasite Varroa destructor. They cope with these and other xenobiotics primarily through enzymatic detoxificative processes, but the regulation of detoxificative enzymes in honey bees remains largely unexplored. Methodology/Principal Findings We used several approaches to ascertain effects of dietary toxins on bee susceptibility to synthetic and natural xenobiotics, including the acaricide tau-fluvalinate, the agricultural pesticide imidacloprid, and the naturally occurring mycotoxin aflatoxin. We administered potential inducers of cytochrome P450 enzymes, the principal biochemical system for Phase 1 detoxification in insects, to investigate how detoxification is regulated. The drug phenobarbital induces P450s in many insects, yet feeding bees with phenobarbital had no effect on the toxicity of tau-fluvalinate, a pesticide known to be detoxified by bee P450s. Similarly, no P450 induction, as measured by tau-fluvalinate tolerance, occurred in bees fed xanthotoxin, salicylic acid, or indole-3-carbinol, all of which induce P450s in other insects. Only quercetin, a common pollen and honey constituent, reduced tau-fluvalinate toxicity. In microarray comparisons no change in detoxificative gene expression was detected in phenobarbital-treated bees. However, northern blot analyses of guts of bees fed extracts of honey, pollen and propolis showed elevated expression of three CYP6AS P450 genes. Diet did not influence tau-fluvalinate or imidacloprid toxicity in bioassays; however, aflatoxin toxicity was higher in bees consuming sucrose or high-fructose corn syrup than in bees consuming honey. Conclusions/Significance These results suggest that regulation of

75 FR 76692 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-09

..., and 252 RIN 0750-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems--Definition... for Business Systems--Definition and Administration (DFARS Case 2009-D038) in the Federal Register on... improve the effectiveness of DoD oversight of contractor business systems. The comment period is being...

75 FR 2457 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-15

... INFORMATION: A. Background Contractor business systems and internal controls are the first line of defense against waste, fraud, and abuse. Weak control systems increase the risk of unallowable and unreasonable... Office of Management and Budget (OMB) as follows: (1) Accounting Systems--OMB Clearance 9000-0011; (2...

Control Systems Cyber Security:Defense in Depth Strategies

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

David Kuipers; Mark Fabro

2006-05-01

Information infrastructures across many public and private domains share several common attributes regarding IT deployments and data communications. This is particularly true in the control systems domain. A majority of the systems use robust architectures to enhance business and reduce costs by increasing the integration of external, business, and control system networks. However, multi-network integration strategies often lead to vulnerabilities that greatly reduce the security of an organization, and can expose mission-critical control systems to cyber threats. This document provides guidance and direction for developing ‘defense-in-depth’ strategies for organizations that use control system networks while maintaining a multi-tier information architecturemore » that requires: Maintenance of various field devices, telemetry collection, and/or industrial-level process systems Access to facilities via remote data link or modem Public facing services for customer or corporate operations A robust business environment that requires connections among the control system domain, the external Internet, and other peer organizations.« less

Control Systems Cyber Security: Defense-in-Depth Strategies

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

Mark Fabro

2007-10-01

Information infrastructures across many public and private domains share several common attributes regarding IT deployments and data communications. This is particularly true in the control systems domain. A majority of the systems use robust architectures to enhance business and reduce costs by increasing the integration of external, business, and control system networks. However, multi-network integration strategies often lead to vulnerabilities that greatly reduce the security of an organization, and can expose mission-critical control systems to cyber threats. This document provides guidance and direction for developing ‘defense-in-depth’ strategies for organizations that use control system networks while maintaining a multi-tier information architecturemore » that requires: • Maintenance of various field devices, telemetry collection, and/or industrial-level process systems • Access to facilities via remote data link or modem • Public facing services for customer or corporate operations • A robust business environment that requires connections among the control system domain, the external Internet, and other peer organizations.« less

Strategic Missile Defense & Nuclear Deterrence

NASA Astrophysics Data System (ADS)

Grego, Laura

The United States has pursued defenses against nuclear-armed long-range ballistic missiles since at least the 1950s. At the same time, concerns that missile defenses could undermine nuclear deterrence and potentially spark an arms race led the United States and Soviet Union to negotiate limits on these systems. The 1972 Anti-Ballistic Missile Treaty constrained strategic missile defenses for thirty years. After abandoning the treaty in 2002, President George W. Bush began fielding the Ground-based Midcourse Defense (GMD) homeland missile defense system on an extremely aggressive schedule, nominally to respond to threats from North Korea and Iran. Today, nearly fifteen years after its initial deployment, the potential and the limits of this homeland missile defense are apparent. Its test record is poor and it has no demonstrated ability to stop an incoming missile under real-world conditions. No credible strategy is in place to solve the issue of discriminating countermeasures. Insufficient oversight has not only exacerbated the GMD system's problems, but has obscured their full extent, which could encourage politicians and military leaders to make decisions that actually increase the risk of a missile attack against the United States. These are not the only costs. Both Russia and China have repeatedly expressed concerns that U.S. missile defenses adversely affect their own strategic capabilities and interests, particularly taken in light of the substantial US nuclear forces. This in turn affects these countries' nuclear modernization priorities. This talk will provide a technical overview of the US strategic missile defense system, and how it relates to deterrence against non-peer adversaries as well as how it affects deterrence with Russia and China and the long-term prospects for nuclear reductions

Analysis of System Training Impact for Major Defense Acquisition Programs (MDAPs): Training Systems Acquisition

DTIC Science & Technology

2012-07-01

Background The Patriot system began because of the need to replace an aging and limited air defense system in the 1970s, the Nike -Hercules, and...1980s by Bolt, Beranek & Newman Inc . that overlaid student performance and expert solutions in a real-time simulation, with feedback from an...Interaction and Interface Design Team at Aptima, Inc . In this role she managed and led the work-centered development of a variety of military and

Differential Regulation of CYP3A4 and CYP3A5 and Its Implication in Drug Discovery

PubMed Central

Lolodi, Ogheneochukome; Wang, Yue-Ming; Wright, William C.; Chen, Taosheng

2017-01-01

Cancer cells use several mechanisms to resist the cytotoxic effects of drugs, resulting in tumor progression and invasion. One such mechanism capitalizes on the body’s natural defense against xenobiotics by increasing the rate of xenobiotic efflux and metabolic inactivation. Xenobiotic metabolism typically involves conversion of parent molecules to more soluble and easily excreted derivatives in reactions catalyzed by Phase I and Phase II drug metabolizing enzymes. Recent reports indicate that components of the xenobiotic response system are upregulated in some diseases, including many cancers. Such components include the pregnane X receptor (PXR) and the cytochrome P450 (CYP) 3A4 and 3A5 enzymes. The CYP3A enzymes are a subset of the numerous enzymes that are transcriptionally activated following the interaction of PXR and many ligands. Intense research is ongoing to understand the functional ramifications of aberrant expression of these components in diseased states with the goal of designing novel drugs that can selectively target them. PMID:28558634

Program Manager: The Journal of the Defense Systems Management College. Volume 15, Number 4, July-August 1986.

DTIC Science & Technology

1986-08-01

Architect, troi systems, CAD CAM, and com- functional analysis , synthesis, and National Bureau of Standards, mon engineering data bases will be the trade...Recurrent analysis of a management these s h e m evolutionary chain of data processing problem combining real data and ponents of defense support system...at the Defense first constructed his support simulator Systems Management College, the by assembling appropriate analysis Data Storage and Retrieval

Changes in the glucosinolate-myrosinase defense system in Brassica juncea cotyledons during seedling development.

PubMed

Wallace, S K; Eigenbrode, Sanford D

2002-02-01

Optimal defense theory (ODT) predicts that plant defenses will be allocated to plant organs and tissues in proportion to their relative fitness values and susceptibilities to attack. This study was designed to test ODT predictions on the myrosinase-glucosinolate defense system in Brassica juncea by examining the relationships between the fitness value of B. juncea cotyledons and the levels and effectiveness of cotyledon defenses. Specifically, we estimated fitness value of cotyledons during plant development by measuring plant growth and seed production after cotyledon damage or removal at successive seedling ages. Cotyledon removal within five days of emergence had a significant impact on growth and seed production, but cotyledon removal at later stages did not. Consistent with ODT, glucosinolate and myrosinase levels in cotyledons also declined with seedling age, as did relative defenses against a generalist herbivore, Spodoptera eridania, as estimated by bioassay. Declines in glucosinolates were as predicted by a passive, allometric dilution model based on cotyledon expansion. Declines in myrosinase activity were significantly more gradual than predicted by allometric dilution, suggesting active retention of myrosinase activity as young cotyledons expand.

Cross-induction of detoxification genes by environmental xenobiotics and insecticides in the mosquito Aedes aegypti: impact on larval tolerance to chemical insecticides.

PubMed

Poupardin, Rodolphe; Reynaud, Stéphane; Strode, Clare; Ranson, Hilary; Vontas, John; David, Jean-Philippe

2008-05-01

The effect of exposure of Aedes aegypti larvae to sub-lethal doses of the pyrethroid insecticide permethrin, the organophosphate temephos, the herbicide atrazine, the polycyclic aromatic hydrocarbon fluoranthene and the heavy metal copper on their subsequent tolerance to insecticides, detoxification enzyme activities and expression of detoxification genes was investigated. Bioassays revealed a moderate increase in larval tolerance to permethrin following exposure to fluoranthene and copper while larval tolerance to temephos increased moderately after exposure to atrazine, copper and permethrin. Cytochrome P450 monooxygenases activities were induced in larvae exposed to permethrin, fluoranthene and copper while glutathione S-transferase activities were induced after exposure to fluoranthene and repressed after exposure to copper. Microarray screening of the expression patterns of all detoxification genes following exposure to each xenobiotic with the Aedes Detox Chip identified multiple genes induced by xenobiotics and insecticides. Further expression studies using real-time quantitative PCR confirmed the induction of multiple CYP genes and one carboxylesterase gene by insecticides and xenobiotics. Overall, this study reveals the potential of xenobiotics found in polluted mosquito breeding sites to affect their tolerance to insecticides, possibly through the cross-induction of particular detoxification genes. Molecular mechanisms involved and impact on mosquito control strategies are discussed.

Targeting xenobiotic receptors PXR and CAR in human diseases

PubMed Central

Banerjee, Monimoy; Robbins, Delira; Chen, Taosheng

2014-01-01

Nuclear receptors such as the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are xenobiotic receptors regulating not only drug metabolism and disposition but also various human diseases such as cancer, diabetes, inflammatory disease, metabolic disease and liver diseases, suggesting that PXR and CAR are promising targets for drug discovery. Consequently, there is an urgent need to discover and develop small molecules that target these PXR- and/or CAR-mediated human-disease-related pathways for relevant therapeutic applications. This review proposes approaches to target PXR and CAR, either individually or simultaneously, in the context of various human diseases, taking into consideration the structural differences between PXR and CAR. PMID:25463033

Phylogenetic and biological investigation of the xenobiotic metabolizing arylamine N-acetyltransferase enzyme family among fungi

USDA-ARS?s Scientific Manuscript database

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes well-characterized in several bacteria and eukaryotic organisms. The role of NATs in fungal biology has only recently been investigated. The NAT1 (FDB2) gene of Fusarium verticillioides was the first NAT cloned and character...

Silymarin Ameliorates Oxidative Stress and Enhances Antioxidant Defense System Capacity in Cadmium-Treated Mice.

PubMed

Farjad, Elham; Momeni, Hamid Reza

2018-10-01

Cadmium is an environmental pollutant which induces oxidative stress while silymarin as an antioxidant is able to scavenge free radicals. The aim of the present study was to investigate the effect of silymarin on oxidative stress markers and antioxidant defense system capacity in mice treated with cadmium chloride. In this experimental study, adult mice were divided into four groups as follow: i. Control, ii. Cadmium chloride (5 mg/kg b.w., s.c.), iii. Silymarin+cadmium chloride, and iv. Silymarin (100 mg/kg b.w., i.p.). Mice were treated with cadmium chloride for 24 hours and silymarin was administered 24 hours before the cadmium. Blood samples were then collected from the experimental groups and their sera were prepared. To investigate oxidative stress markers in the serum, the amount of malondialdehyde (MDA) and thiol groups (-SH) were evaluated. To measure the total antioxidant power in the serum, Ferric Reducing/ Antioxidant Power (FRAP) method was used. In addition, the activity of enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) was assessed to evaluate serum antioxidant defense power. In the cadmium-treated group, the amount of MDA significantly increased as compared to the control group. In silymarin+cadmium group, silymarin significantly ameliorated the level of MDA compared to the cadmium group. In addition, cadmium significantly reduced serum FRAP, the activity of antioxidant defense system enzymes and thiol groups compared to the control. In silymarin+cadmium group, silymarin could significantly reverse the reduction of these markers compared to the cadmium group. Administration of silymarin alone caused a significant increase in serum FRAP, the activity of antioxidant defense system enzymes and thiol groups compared to the control group. Silymarin as a powerful antioxidant reverses the toxic effect of cadmium on the serum levels of lipid peroxidation, total antioxidant power, antioxidant defense system

An Exploratory Analysis of the U.S. System of Major Defense Acquisition Utilizing the CLIOS Process

DTIC Science & Technology

2009-09-01

SPENDING COUNTRIES .............................................20 1. The United States’ Defense Acquisition System..............................21 2...Improvement Initiatives ...............................................................20 Table 4. The Top 15 Military Spender Countries in 2008...other top military spending countries . It will end with a review of the major defense acquisition literature. This literature review will focus on

78 FR 13543 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-28

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 201, 204, 215, 225, 227, 242, 245, and 252 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is...

78 FR 12294 - Proposed Information Collection; Comment Request; Defense Priorities and Allocations System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

... Request; Defense Priorities and Allocations System AGENCY: Bureau of Industry and Security, Commerce...: Direct all written comments to Jennifer Jessup, Departmental Paperwork Clearance Officer, Department of... Priorities and Allocations System regulation (15 CFR part 700) must retain the records for at least 3 years...

75 FR 12173 - Proposed Information Collection; Comment Request; Defense Priorities and Allocations System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

... Allocations System regulation (15 CFR part 700) must retain the records for at least 3 years. II. Method of... Request; Defense Priorities and Allocations System AGENCY: Bureau of Industry and Security, Commerce...: Direct all written comments to Diana Hynek, Departmental Paperwork Clearance Officer, Department of...

Restricted emigration, system inescapability, and defense of the status quo: system-justifying consequences of restricted exit opportunities.

PubMed

Laurin, Kristin; Shepherd, Steven; Kay, Aaron C

2010-08-01

The freedom to emigrate at will from a geographic location is an internationally recognized human right. However, this right is systematically violated by restrictive migration policies. In three experiments, we explored the psychological consequences of violating the right to mobility. Our results suggest that, ironically, restricted freedom of movement can lead to increased system justification (i.e., increased support of the status quo). In Study 1, we found that participants who read that their country was difficult to leave became stronger defenders of their system's legitimacy than before, even in domains unrelated to emigration policy (e.g., gender relations). In Study 2, we demonstrated that this increased system defense was the result of a motivated process. In Study 3, we broadened the scope of this psychological phenomenon by conceptually replicating it using a different system (participants' university) and measure of system defense. The importance of these two findings-the first experimental demonstration of the psychological consequences of restrictive emigration policies and the introduction of a novel psychological phenomenon-is discussed.

Application of System and Integration Readiness Levels to Department of Defense Research and Development

DTIC Science & Technology

2016-07-01

etc., and all of the IRL1n rather than a technology-centric approach that included TR L1 with all its interfaces. The inter- face -centric approach...Acquisition Research Journal , 23(3), In Print. The average of the SRL vector, equation (4), describes how mature the sys- tem is. The Sauser approach...Application of System and Integration Readiness Levels to Department of Defense Research and Development. Defense Acquisition Research Journal , 23(3), In

Pregnane X Receptor Regulates Pathogen-Induced Inflammation and Host Defense against an Intracellular Bacterial Infection through Toll-like Receptor 4.

PubMed

Qiu, Zhijuan; Cervantes, Jorge L; Cicek, Basak B; Mukherjee, Subhajit; Venkatesh, Madhukumar; Maher, Leigh A; Salazar, Juan C; Mani, Sridhar; Khanna, Kamal M

2016-08-23

The nuclear pregnane X receptor (PXR) plays a central role in regulating xenobiotic metabolism. We now report a novel role for PXR as a critical negative regulator of innate immunity after infection. Pxr(-/-) mice exhibited remarkably elevated pro-inflammatory cytokine and chemokine production following infection with Listeria monocytogenes (Lm). Despite the more robust innate immune response, Pxr(-/-) mice were highly susceptible to Lm infection. Surprisingly, disruption of the Toll-like receptor 4 (TLR4) but not TLR2 signaling restored the inflammation to normal levels and the ability to clear Lm in Pxr(-/-) mice. Mechanistically, the heightened inflammation in Pxr(-/-) mice resulted in the death of inflammatory monocytes that led to the enhanced susceptibility to Lm infection. These data demonstrated that PXR regulated pathogen-induced inflammation and host defense against Lm infection through modulating the TLR4 pathway. In summary, we discovered an apical role for PXR in regulating innate immunity. In addition, we uncovered a remarkable negative impact of the TLR4 pathway in controlling the quality of the inflammatory response and host defense against a gram-positive bacterial infection.

Proteomic analysis of drought resistance in crabapple seedlings primed by the xenobiotic Beta-aminobutyric acid

USDA-ARS?s Scientific Manuscript database

In a variety of annual crops and model plants, the xenobiotic DL-Beta-aminobutyric acid (BABA) has been shown to enhance disease resistance and increase salt, drought and thermotolerance. BABA does not activate stress genes directly, but sensitizes plants to respond more quickly and strongly to biot...

System Requirements Analysis and Technological Support for the Ballistic Missile Defense System (BMDS) - FY07 Progress Report

DTIC Science & Technology

2007-07-01

Systems , Boeing-led Airborne Laser Team Actively Tracks Airborne Target, Compensates for Atmospheric Turbulence and Fires Sur- rogate High-Energy Laser...7100 System Requirements Analysis and Technological Support for the Ballistic Missile Defense System (BMDS) FY07 Progress Report By...Office of Management and Budget , Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE July

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review.

PubMed

Bévalot, Fabien; Cartiser, Nathalie; Bottinelli, Charline; Fanton, Laurent; Guitton, Jérôme

2016-01-01

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

Metagenomic analysis of the pinewood nematode microbiome reveals a symbiotic relationship critical for xenobiotics degradation

PubMed Central

Cheng, Xin-Yue; Tian, Xue-Liang; Wang, Yun-Sheng; Lin, Ren-Miao; Mao, Zhen-Chuan; Chen, Nansheng; Xie, Bing-Yan

2013-01-01

Our recent research revealed that pinewood nematode (PWN) possesses few genes encoding enzymes for degrading α-pinene, which is the main compound in pine resin. In this study, we examined the role of PWN microbiome in xenobiotics detoxification by metagenomic and bacteria culture analyses. Functional annotation of metagenomes illustrated that benzoate degradation and its related metabolisms may provide the main metabolic pathways for xenobiotics detoxification in the microbiome, which is obviously different from that in PWN that uses cytochrome P450 metabolism as the main pathway for detoxification. The metabolic pathway of degrading α-pinene is complete in microbiome, but incomplete in PWN genome. Experimental analysis demonstrated that most of tested cultivable bacteria can not only survive the stress of 0.4% α-pinene, but also utilize α-pinene as carbon source for their growth. Our results indicate that PWN and its microbiome have established a potentially mutualistic symbiotic relationship with complementary pathways in detoxification metabolism. PMID:23694939

Defense Planning in the Ministry of Defense of Ukraine: Decade of Attempts and Mistakes

DTIC Science & Technology

2015-06-01

Defense. (University of California Press, Berkeley and Los Angeles , 1967). 22 but due to the Soviet Union basis system, it is not as efficient in...Making for Defense. University of California Press, Berkeley and Los Angeles , 1967. Hitch, Charles Johnston and Roland N. McKean. The Economics of...loss of defense is not an instantaneous phenomenon. This phenomenon has led to human disorder, blind and continuous personnel downsizing, reform of the

COMPARISON OF MICROBIAL TRANSFORMATION RATE COEFFICIENTS OF XENOBIOTIC CHEMICALS BETWEEN FIELD-COLLECTED AND LABORATORY MICROCOSM MICROBIOTA

EPA Science Inventory

Two second-order transformation rate coefficients--kb, based on total plate counts, and kA, based on periphyton-colonized surface areas--were used to compare xenobiotic chemical transformation by laboratory-developed (microcosm) and by field-collected microbiota. Similarity of tr...

Defense.gov Special Report: Defense Intelligence

Science.gov Websites

Department of Defense Submit Search Defense intelligence is critical to the Defense Department's role in and conduct successful military and security operations that protect America. Defense Intelligence News Story Intelligence Chief Describes 'Pervasive Uncertainty' of Worldwide Threats "

76 FR 27274 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 225 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System... Federal Acquisition Regulation Supplement (DFARS) to direct contracting officers to additional guidance on...

Defense Acquisitions. Missile Defense Agency Fields Initial Capability but Falls Short of Original Goals

DTIC Science & Technology

2006-03-01

Implementation Plan MAP Missile Defense System Assurance Provisions MDA Missile Defense System NASA National Aeronautics and Space Administration NFIRE ...fourth element, KEI, also delayed some activities related to its Near Field Infrared Experiment ( NFIRE ), which is being conducted to gather data on the...to complete a number of tasks that would have enabled it to conduct the NFIRE experiment. The experiment places sensors aboard a satellite that

78 FR 67133 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-08

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [Docket Number DARS-2013-0038] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Publicizing Contract Actions AGENCY: Defense Acquisition Regulation System, Department of Defense (DoD). ACTION: Notice and...

76 FR 72916 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0454] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Administrative Matters AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice; request for...

78 FR 70294 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [Docket Number DARS 2013-0046] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Administrative Matters AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice and request...

Cost of space-based laser ballistic missile defense.

PubMed

Field, G; Spergel, D

1986-03-21

Orbiting platforms carrying infrared lasers have been proposed as weapons forming the first tier of a ballistic missile defense system under the President's Strategic Defense Initiative. As each laser platform can destroy a limited number of missiles, one of several methods of countering such a system is to increase the number of offensive missiles. Hence it is important to know whether the cost-exchange ratio, defined as the ratio of the cost to the defense of destroying a missile to the cost to the offense of deploying an additional missile, is greater or less than 1. Although the technology to be used in a ballistic missile defense system is still extremely uncertain, it is useful to examine methods for calculating the cost-exchange ratio. As an example, the cost of an orbiting infrared laser ballistic missile defense system employed against intercontinental ballistic missiles launched simultaneously from a small area is compared to the cost of additional offensive missiles. If one adopts lower limits to the costs for the defense and upper limits to the costs for the offense, the cost-exchange ratio comes out substantially greater than 1. If these estimates are confirmed, such a ballistic missile defense system would be unable to maintain its effectiveness at less cost than it would take to proliferate the ballistic missiles necessary to overcome it and would therefore not satisfy the President's requirements for an effective strategic defense. Although the method is illustrated by applying it to a space-based infrared laser system, it should be straightforward to apply it to other proposed systems.

Update on nandrolone and norsteroids: how endogenous or xenobiotic are these substances?

PubMed

Bricout, V; Wright, F

2004-06-01

Norsteroids are xenobiotics with androgenic and anabolic properties known since as far back as the 1930s. In doping controls, the use of the banned xenobiotic norsteroids is detected in the competitor's urines by the measurement of norandrosterone (19-NA) and noretiocholanolone (19-NE), which are the main metabolites for nandrolone (NT) and most norsteroids with anabolic properties. In 1996, the IOC subcommission "Doping and Biochemistry of Sport" informed the Heads of the "IOC Accredited Laboratories" that the recommended cut-off limit for reporting an offence was to be 1-2 ng ml(-1) urine for either 19-NA or 19-NE. We will discuss how technical progress in gas chromatography coupled to high-resolution mass spectrometry permitted a dramatic increase in sensitivity with a detection limit of 1 pg ml(-1) urine, or less, and an assay limit of 20-50 pg ml(-1) urine, for either 19-NA or 19-NE. As a paradox, norsteroids have been known for decades as not only xenobiotics but also obligatory endogenous intermediates in the biosynthesis of estrogens from androgens in all species, man included. It is this biochemical observation which fed the active scientific and medical controversy initiated in 1998 over the possibly endogenous production of nandrolone and metabolites well over the new IOC's recommended cut-off limit of 2 ng ml(-1) urine. Notwithstanding the particular technical difficulties attached, we will provide data and discuss the minute endogenous levels detected and measured in man either at rest, after performance or training and compare them to the relatively high levels reported in male athlete's doping controls today. We will also discuss data on the pharmacological effects of some contraceptive therapies containing norsteroids in women. In view of the well-documented noxious effects repeatedly observed after anabolic steroid misuse, the confirmation and implementation of technically proven procedures for reporting norsteroid abuse in sports seems an

Systemic acquired resistance: turning local infection into global defense.

PubMed

Fu, Zheng Qing; Dong, Xinnian

2013-01-01

Systemic acquired resistance (SAR) is an induced immune mechanism in plants. Unlike vertebrate adaptive immunity, SAR is broad spectrum, with no specificity to the initial infection. An avirulent pathogen causing local programmed cell death can induce SAR through generation of mobile signals, accumulation of the defense hormone salicylic acid, and secretion of the antimicrobial PR (pathogenesis-related) proteins. Consequently, the rest of the plant is protected from secondary infection for a period of weeks to months. SAR can even be passed on to progeny through epigenetic regulation. The Arabidopsis NPR1 (nonexpresser of PR genes 1) protein is a master regulator of SAR. Recent study has shown that salicylic acid directly binds to the NPR1 adaptor proteins NPR3 and NPR4, regulates their interactions with NPR1, and controls NPR1 protein stability. However, how NPR1 interacts with TGA transcription factors to activate defense gene expression is still not well understood. In addition, redox regulators, the mediator complex, WRKY transcription factors, endoplasmic reticulum-resident proteins, and DNA repair proteins play critical roles in SAR.

Factors Influencing the Effectiveness of Systems Engineering Training and Education in the Department of Defense

DTIC Science & Technology

2011-04-30

learning. Recommendations are also presented for additional research into a more effective systems engineering andragogy . 15. SUBJECT TERMS 16...into a more effective systems engineering andragogy . Purpose Competency-based training for defense acquisition workers in the systems engineering

Variation in plant defense suppresses herbivore performance

USGS Publications Warehouse

Pearse, Ian; Paul, Ryan; Ode, Paul J.

2018-01-01

Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging.

Defense Workforce Training Programs.

ERIC Educational Resources Information Center

Fletcher, J. D.; And Others

This report discusses the amount and kinds of Department of Defense (DoD) interactive courseware (ICW) programs that are candidates for transfer to the private sector. Candidates for transfer were identified through an analysis of the Defense Instructional Technology Information System (DITIS). Out of 4,644 ICW programs that have been reported to…

An in vitro bioassay for xenobiotics using the SXR-driven human CYP3A4/lacZ reporter gene.

PubMed

Lee, Mi R; Kim, Yeon J; Hwang, Dae Y; Kang, Tae S; Hwang, Jin H; Lim, Chae H; Kang, Hyung K; Goo, Jun S; Lim, Hwa J; Ahn, Kwang S; Cho, Jung S; Chae, Kap R; Kim, Yong K

2003-01-01

The dose and time effect of nine xenobiotics, including 17beta-estradiol, corticosterone, dexamethasone, progesterone, nifedipine, bisphenol A, rifampicin, methamphetamine, and nicotine were investigated, in vitro, using human steroid and xenobiotics receptor (SXR)-binding sites on the human CYP3A4 promoter, which can enhance the linked lacZ reporter gene transcription. To test this, liver-specific SAP (human serum amyloid P component)-SXR (SAP/SXR) and human CYP3A4 promoter-regulated lacZ (hCYP3A4/lacZ) constructs were transiently transfected into HepG2 and NIH3T3 cells to compare the xenobiotic responsiveness between human and nonhuman cell lines. In the HepG2 cells, rifampicin, followed by corticosterone, nicotine, methamphetamine, and dexamethasone, exhibited enhanced levels of the lacZ transcript, whereas those of bisphenol A and nifedipine were found to be reduced. No significant responses were observed with 17beta-estradiol or progesterone. In addition, 17beta-estradiol and progesterone did not change the levels of the lacZ transcripts in the HepG2 cells, but did induce significant increases in the transcripts of the NIH3T3 cells. Treatment with corticosterone and dexamethasone, which were highly expressed in the HepG2 cells, did not affect the levels of the lacZ transcript in NIH3T3 cells. These results show that lacZ transcripts can be measured, rapidly and reproducibly, using reverse transcriptase-polymerase chain reaction (RT-PCR) based on the expression of the hCYP3A4/lacZ reporter gene, and was mediated by the SXR. Thus, this in vitro reporter gene bioassay is useful for measuring xenobiotic activities, and is a means to a better relevant bioassay, using human cells, human genes and human promoters, in order to get a closer look at actual human exposure.

A single amino acid controls the functional switch of human constitutive androstane receptor (CAR) 1 to the xenobiotic-sensitive splicing variant CAR3.

PubMed

Chen, Tao; Tompkins, Leslie M; Li, Linhao; Li, Haishan; Kim, Gregory; Zheng, Yuxin; Wang, Hongbing

2010-01-01

The constitutive androstane receptor (CAR) is constitutively activated in immortalized cell lines independent of xenobiotic stimuli. This feature of CAR has limited its use as a sensor for xenobiotic-induced expression of drug-metabolizing enzymes. Recent reports, however, reveal that a splicing variant of human CAR (hCAR3), which contains an insertion of five amino acids (APYLT), exhibits low basal but xenobiotic-inducible activities in cell-based reporter assays. Nonetheless, the underlying mechanisms of this functional shift are not well understood. We have now generated chimeric constructs containing various residues of the five amino acids of hCAR3 and examined their response to typical hCAR activators. Our results showed that the retention of alanine (hCAR1+A) alone is sufficient to confer the constitutively activated hCAR1 to the xenobiotic-sensitive hCAR3. It is noteworthy that hCAR1+A was significantly activated by a series of known hCAR activators, and displayed activation superior to that of hCAR3. Moreover, intracellular localization assays revealed that hCAR1+A exhibits nuclear accumulation upon 6-(4-chlorophenyl) imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime (CITCO) treatment in COS1 cells, which differs from the spontaneous nuclear distribution of hCAR1 and the nontranslocatable hCAR3. Mammalian two-hybrid and glutathione S-transferase pull-down assays further demonstrated that hCAR1+A interacts with the coactivator SRC-1 and GRIP-1 at low level before activation, while at significantly enhanced level in the presence of CITCO. Thus, the alanine residue in the insertion of hCAR3 seems in charge of the xenobiotic response of hCAR3 through direct and indirect mechanisms. Activation of hCAR1+A may represent a sensitive avenue for the identification of hCAR activators.

A Single Amino Acid Controls the Functional Switch of Human Constitutive Androstane Receptor (CAR) 1 to the Xenobiotic-Sensitive Splicing Variant CAR3

PubMed Central

Chen, Tao; Tompkins, Leslie M.; Li, Linhao; Li, Haishan; Kim, Gregory; Zheng, Yuxin

2010-01-01

The constitutive androstane receptor (CAR) is constitutively activated in immortalized cell lines independent of xenobiotic stimuli. This feature of CAR has limited its use as a sensor for xenobiotic-induced expression of drug-metabolizing enzymes. Recent reports, however, reveal that a splicing variant of human CAR (hCAR3), which contains an insertion of five amino acids (APYLT), exhibits low basal but xenobiotic-inducible activities in cell-based reporter assays. Nonetheless, the underlying mechanisms of this functional shift are not well understood. We have now generated chimeric constructs containing various residues of the five amino acids of hCAR3 and examined their response to typical hCAR activators. Our results showed that the retention of alanine (hCAR1+A) alone is sufficient to confer the constitutively activated hCAR1 to the xenobiotic-sensitive hCAR3. It is noteworthy that hCAR1+A was significantly activated by a series of known hCAR activators, and displayed activation superior to that of hCAR3. Moreover, intracellular localization assays revealed that hCAR1+A exhibits nuclear accumulation upon 6-(4-chlorophenyl) imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime (CITCO) treatment in COS1 cells, which differs from the spontaneous nuclear distribution of hCAR1 and the nontranslocatable hCAR3. Mammalian two-hybrid and glutathione S-transferase pull-down assays further demonstrated that hCAR1+A interacts with the coactivator SRC-1 and GRIP-1 at low level before activation, while at significantly enhanced level in the presence of CITCO. Thus, the alanine residue in the insertion of hCAR3 seems in charge of the xenobiotic response of hCAR3 through direct and indirect mechanisms. Activation of hCAR1+A may represent a sensitive avenue for the identification of hCAR activators. PMID:19820207

Defense Logistics Agency Did Not Obtain Fair and Reasonable Prices From Meggitt Aircraft Braking Systems for Sole-Source Commercial Spare Parts (REDACTED)

DTIC Science & Technology

2015-05-08

Defense Logistics Agency Did Not Obtain Fair and Reasonable Prices From Meggitt Aircraft Braking Systems for Sole-Source Commercial Spare Parts...Defense Logistics Agency Did Not Obtain Fair and Reasonable Prices From Meggitt Aircraft Braking Systems for Sole-Source Commercial Spare Parts...D000AH-0180.000) │ i Results in Brief Defense Logistics Agency Did Not Obtain Fair and Reasonable Prices From Meggitt Aircraft Braking Systems for

Program Manager: Journal of the Defense Systems Management College, Volume 21, Number 3, May-June 1992

DTIC Science & Technology

1992-05-01

one manager -to-player inter- coaching styles are being used in tions do best with structured and actions, which diminish as each these outside...May-june 1992’ MANAGER Journal of the Defense Systems Management College Program management ,teI hIN be pl~ vrb~c aeese and sole; its 92-19864 92 7...23 l 9~3 PROGRAM MANAGER Journal of the Defense Systems Management College Vol. XXI, No. 3, DSMC 108 2 8 Is There Going to Be a High- Rebuilding the

76 FR 36905 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Taxes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-23

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Taxes AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). [[Page 36906

Dectin-1 plays an important role in host defense against systemic Candida glabrata infection.

PubMed

Chen, Si Min; Shen, Hui; Zhang, Teng; Huang, Xin; Liu, Xiao Qi; Guo, Shi Yu; Zhao, Jing Jun; Wang, Chun Fang; Yan, Lan; Xu, Guo Tong; Jiang, Yuan Ying; An, Mao Mao

2017-11-17

Candida glabrata is the second most common pathogen of severe candidiasis in immunocompromised hosts, following C. albicans. Although C. glabrata and C. albicans belong to the same genus, they are phylogenetically distinct. C-type lectin receptors (CLRs), acting as pattern-recognition receptors (PRRs), play critical roles in host defense against C. albicans infections. However, our understanding of the specific roles of CLRs in host defense against C. glabrata is limited. Here, we explored the potential roles of the C-type lectins Dectin-1 and Dectin-2 in host defense against C. glabrata. We found that both Dectin-1-deficient mice (Dectin-1 -/- ) and Dectin-2-deficient mice (Dectin-2 -/- ) are more susceptible to C. glabrata infection. Dectin-1confers host higher sensitivity for sensing C. glabrata infections, while the effect of Dectin-2 in the host defense against C. glabrata is infection dose dependent. Dectin-1 is required for host myeloid cells recognition, killing of C. glabrata, and development of subsequent Th1 and Th17 cell-mediated adaptive immune response. Significantly impaired inflammatory responses such as inflammatory cells recruitment and cytokines release that were induced by C. glabrata were manifested in Dectin-1-deficient mice. Together, our study demonstrates that Dectin-1 plays an important role in host defense against systemic Candida glabrata infections, indicating a previous unknown control mechanism for this particular type of infection in host. Our study, therefore, provides new insights into the host defense against C. glabrata.

External Quality Control Review of the Defense Information Systems Agency Audit Organization

DTIC Science & Technology

2012-08-07

We are providing this report for your information and use. We have reviewed the system of quality control for the audit organization of the Defense...audit organization encompasses the audit organization’s leadership, emphasis on performing high quality work, and policies and procedures established

Plant Defense against Insect Herbivores

PubMed Central

Fürstenberg-Hägg, Joel; Zagrobelny, Mika; Bak, Søren

2013-01-01

Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce several internal signals from the wounded tissues, including calcium ion fluxes, phosphorylation cascades and systemic- and jasmonate signaling. These are perceived in undamaged tissues, which thereafter reinforce their defense by producing different, mostly low molecular weight, defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects have adapted to resist plant defenses, and in some cases even sequester the compounds and reuse them in their own defense. Both plant defense and insect adaptation involve metabolic costs, so most plant-insect interactions reach a stand-off, where both host and herbivore survive although their development is suboptimal. PMID:23681010

Cost of space-based laser ballistic missile defense

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

Field, G.; Spergel, D.

1986-03-21

Orbiting platforms carrying infrared lasers have been proposed as weapons forming the first tier of a ballistic missile defense system under the President's Strategic Defense Initiative. As each laser platform can destroy a limited number of missiles, one of several methods of countering such a system is to increase the number of offensive missiles. Hence it is important to know whether the cost-exchange ratio, defined as the ratio of the cost to the defense of destroying a missile to the cost to the offense of deploying an additional missile, is greater or less than 1. Although the technology to bemore » used in a ballistic missile defense system is still extremely uncertain, it is useful to examine methods for calculating the cost-exchange ration. As an example, the cost of an orbiting infrared laser ballistic missile defense system employed against intercontinental ballistic missiles launched simultaneously from a small area is compared to the cost of additional offensive missiles. If one adopts lower limits to the costs for the defense and upper limits to the costs for the offense, the cost-exchange ratio comes out substantially greater than 1. If these estimates are confirmed, such a ballistic missile defense system would be unable to maintain its effectiveness at less cost than it would take to proliferate the ballistic missiles necessary to overcome it and would therefore not satisfy the President's requirements for an effective strategic defense. Although the method is illustrated by applying it to a space-based infrared laser system, it should be straightforward to apply it to other proposed systems. 28 references, 2 tables.« less

Visualization of the Drosophila dKeap1-CncC interaction on chromatin illumines cooperative, xenobiotic-specific gene activation

PubMed Central

Deng, Huai; Kerppola, Tom K.

2014-01-01

Interactions among transcription factors control their physiological functions by regulating their binding specificities and transcriptional activities. We implement a strategy to visualize directly the genomic loci that are bound by multi-protein complexes in single cells in Drosophila. This method is based on bimolecular fluorescence complementation (BiFC) analysis of protein interactions on polytene chromosomes. Drosophila Keap1 (dKeap1)-CncC complexes localized to the nucleus and bound chromatin loci that were not bound preferentially by dKeap1 or CncC when they were expressed separately. dKeap1 and CncC binding at these loci was enhanced by phenobarbital, but not by tert-butylhydroquinone (tBHQ) or paraquat. Endogenous dKeap1 and CncC activated transcription of the Jheh (Jheh1, Jheh2, Jheh3) and dKeap1 genes at these loci, whereas CncC alone activated other xenobiotic response genes. Ectopic dKeap1 expression increased CncC binding at the Jheh and dKeap1 gene loci and activated their transcription, whereas dKeap1 inhibited CncC binding at other xenobiotic response gene loci and suppressed their transcription. The combinatorial chromatin-binding specificities and transcriptional activities of dKeap1-CncC complexes mediated the selective activation of different sets of genes by different xenobiotic compounds, in part through feed-forward activation of dKeap1 transcription. PMID:25063457

ADAPTATION OF AQUIFER MICROBIAL COMMUNITIES TO THE BIODEGRADATION OF XENOBIOTIC COMPOUNDS: INFLUENCE OF SUBSTRATE CONCENTRATION AND PREEXPOSURE

EPA Science Inventory

Studies were conducted to examine the adaptation response of aquifer microbial communities to xenobiotic compounds and the influence of chemical preexposure in the laboratory and in situ on adaptation. Adaptation and biodegradation were assessed as mineralization and cellular inc...

Joint Land Attack Cruise Missile Defense Elevated Netted Sensor System Not Ready for Production Decision (REDACTED)

DTIC Science & Technology

2012-09-07

Average Procurement Unit Cost CMDS Cruise Missile Defense Systems CPD Capability Production Document EMD Engineering and Manufacturing...Defense for Acquisition, Technology and Logistics also determined that continuing test and evaluation of the two JLENS Engineering and Manufacturing...Program (Category ID) that was established in January 1996 and, during the audit, was in the Engineering and Manufacturing Development (EMD) phase of

Silverleaf Whitefly Induces Salicylic Acid Defenses and Suppresses Effectual Jasmonic Acid Defenses1[W][OA

PubMed Central

Zarate, Sonia I.; Kempema, Louisa A.; Walling, Linda L.

2007-01-01

The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF. PMID:17189328

Photovoltaics in the Department of Defense

NASA Astrophysics Data System (ADS)

Chapman, Richard N.

1997-02-01

This paper documents the history of photovoltaic use within the Department of Defense leading up to the installation of 2.1 MW of photovoltaics underway today. This history describes the evolution of the Department of Defense's Tri-Service Photovoltaic Review Committee and the committee's strategic plan to realize photovoltaic's full potential through outreach, conditioning of the federal procurement system, and specific project development. The Photovoltaic Review Committee estimates photovoltaic's potential at nearly 4,000 MW, of which about 700 MW are considered to be cost-effective at today's prices. The paper describes photovoltaic's potential within the Department of Defense, the status and features of the 2.1-MW worth of photovoltaic systems under installation, and how these systems are selected and implemented. The paper also documents support provided to the Department of Defense by the Department of Energy dating back to the late 70s.

Self-Assembly of Multi-nanozymes to Mimic an Intracellular Antioxidant Defense System.

PubMed

Huang, Yanyan; Liu, Zhen; Liu, Chaoqun; Ju, Enguo; Zhang, Yan; Ren, Jinsong; Qu, Xiaogang

2016-06-01

In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2 O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2 O5 @pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variation in Plant Defense Suppresses Herbivore Performance.

PubMed

Pearse, Ian S; Paul, Ryan; Ode, Paul J

2018-06-18

Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory [1, 2]. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores [3, 4]. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory [5]. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging. Published by Elsevier Ltd.

Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells.

PubMed

Liao, Hsin-Kai; Gu, Ying; Diaz, Arturo; Marlett, John; Takahashi, Yuta; Li, Mo; Suzuki, Keiichiro; Xu, Ruo; Hishida, Tomoaki; Chang, Chan-Jung; Esteban, Concepcion Rodriguez; Young, John; Izpisua Belmonte, Juan Carlos

2015-03-10

To combat hostile viruses, bacteria and archaea have evolved a unique antiviral defense system composed of clustered regularly interspaced short palindromic repeats (CRISPRs), together with CRISPR-associated genes (Cas). The CRISPR/Cas9 system develops an adaptive immune resistance to foreign plasmids and viruses by creating site-specific DNA double-stranded breaks (DSBs). Here we adapt the CRISPR/Cas9 system to human cells for intracellular defense against foreign DNA and viruses. Using HIV-1 infection as a model, our results demonstrate that the CRISPR/Cas9 system disrupts latently integrated viral genome and provides long-term adaptive defense against new viral infection, expression and replication in human cells. We show that engineered human-induced pluripotent stem cells stably expressing HIV-targeted CRISPR/Cas9 can be efficiently differentiated into HIV reservoir cell types and maintain their resistance to HIV-1 challenge. These results unveil the potential of the CRISPR/Cas9 system as a new therapeutic strategy against viral infections.

Department of Defense Chemical and Biological Defense Program. Annual Report to Congress

DTIC Science & Technology

2008-05-01

defense system acquisition costs through collaboration in the areas of development, production , and support, and to enhance interoperability with...security area leverages S&T efforts of the other product areas. Where unmet requirements are identified and where S&T is required to meet cost ...Defense Program Inventory Requirements The industrial base, which has scaled down since the end of the Cold War, has stabilized. Ongoing military

78 FR 68830 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Service...

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2013-11-15

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78 FR 68829 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

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2013-11-15

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2010-08-06

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Relationships between U.S. Naval Observatory, LORAN-C and the Defense Satellite Communication System

NASA Technical Reports Server (NTRS)

Charron, L. G.

1982-01-01

The methods used in forming time scales for distant sites monitoring LORAN-C are addressed. The time transfers obtained via the defense satellite communication system (DSCS) and the data provided by this system used to calibrate these remote time scales are emphasized. The errors involved are discussed.

Development of System Architecture to Investigate the Impact of Integrated Air and Missile Defense in a Distributed Lethality Environment

DTIC Science & Technology

2017-12-01

SYSTEM ARCHITECTURE TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT by Justin K. Davis...TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT 5. FUNDING NUMBERS 6. AUTHOR(S) Justin K...ARCHITECTURE TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT Justin K. Davis Lieutenant

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2013-11-08

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75 FR 45104 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

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2010-08-02

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Development of an invitro technique to use mouse embryonic stem cell in evaluating effects of xenobiotics

EPA Science Inventory

Our goal has been to develop a high-throughput, in vitro technique for evaluating the effects of xenobiotics using mouse embryonic stem cells (mESCs). We began with the Embryonic Stem Cell Test (EST), which is used to predict the embryotoxic potential of a test compound by combin...

Stochastic model for threat assessment in multi-sensor defense system

NASA Astrophysics Data System (ADS)

Wang, Yongcheng; Wang, Hongfei; Jiang, Changsheng

2007-11-01

This paper puts forward a stochastic model for target detecting and tracking in multi-sensor defense systems and applies the Lanchester differential equations to threat assessment in combat. The two different modes of targets tracking and their respective Lanchester differential equations are analyzed and established. By use of these equations, we could briefly estimate the loss of each combat side and accordingly get the threat estimation results, given the situation analysis is accomplished.

A Liver-Centric Multiscale Modeling Framework for Xenobiotics.

PubMed

Sluka, James P; Fu, Xiao; Swat, Maciej; Belmonte, Julio M; Cosmanescu, Alin; Clendenon, Sherry G; Wambaugh, John F; Glazier, James A

2016-01-01

We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK) modeling of acetaminophen uptake and distribution at the whole body level, cell and blood flow modeling at the tissue/organ level and metabolism at the sub-cellular level. We have used standard modeling modalities at each of the three scales. In particular, we have used the Systems Biology Markup Language (SBML) to create both the whole-body and sub-cellular scales. Our modeling approach allows us to run the individual sub-models separately and allows us to easily exchange models at a particular scale without the need to extensively rework the sub-models at other scales. In addition, the use of SBML greatly facilitates the inclusion of biological annotations directly in the model code. The model was calibrated using human in vivo data for acetaminophen and its sulfate and glucuronate metabolites. We then carried out extensive parameter sensitivity studies including the pairwise interaction of parameters. We also simulated population variation of exposure and sensitivity to acetaminophen. Our modeling framework can be extended to the prediction of liver toxicity following acetaminophen overdose, or used as a general purpose pharmacokinetic model for xenobiotics.

A Liver-Centric Multiscale Modeling Framework for Xenobiotics

PubMed Central

Swat, Maciej; Cosmanescu, Alin; Clendenon, Sherry G.; Wambaugh, John F.; Glazier, James A.

2016-01-01

We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK) modeling of acetaminophen uptake and distribution at the whole body level, cell and blood flow modeling at the tissue/organ level and metabolism at the sub-cellular level. We have used standard modeling modalities at each of the three scales. In particular, we have used the Systems Biology Markup Language (SBML) to create both the whole-body and sub-cellular scales. Our modeling approach allows us to run the individual sub-models separately and allows us to easily exchange models at a particular scale without the need to extensively rework the sub-models at other scales. In addition, the use of SBML greatly facilitates the inclusion of biological annotations directly in the model code. The model was calibrated using human in vivo data for acetaminophen and its sulfate and glucuronate metabolites. We then carried out extensive parameter sensitivity studies including the pairwise interaction of parameters. We also simulated population variation of exposure and sensitivity to acetaminophen. Our modeling framework can be extended to the prediction of liver toxicity following acetaminophen overdose, or used as a general purpose pharmacokinetic model for xenobiotics. PMID:27636091

Systemic Adenosine Triphosphate Impairs Neutrophil Chemotaxis and Host Defense in Sepsis.

PubMed

Li, Xiaoou; Kondo, Yutaka; Bao, Yi; Staudenmaier, Laura; Lee, Albert; Zhang, Jingping; Ledderose, Carola; Junger, Wolfgang G

2017-01-01

Sepsis remains an unresolved clinical problem. Therapeutic strategies focusing on inhibition of neutrophils (polymorphonuclear neutrophils) have failed, which indicates that a more detailed understanding of the underlying pathophysiology of sepsis is required. Polymorphonuclear neutrophil activation and chemotaxis require cellular adenosine triphosphate release via pannexin-1 channels that fuel autocrine feedback via purinergic receptors. In the current study, we examined the roles of endogenous and systemic adenosine triphosphate on polymorphonuclear neutrophil activation and host defense in sepsis. Prospective randomized animal investigation and in vitro studies. Preclinical academic research laboratory. Wild-type C57BL/6 mice, pannexin-1 knockout mice, and healthy human subjects used to obtain polymorphonuclear neutrophils for in vitro studies. Wild-type and pannexin-1 knockout mice were treated with suramin or apyrase to block the endogenous or systemic effects of adenosine triphosphate. Mice were subjected to cecal ligation and puncture and polymorphonuclear neutrophil activation (CD11b integrin expression), organ (liver) injury (plasma aspartate aminotransferase), bacterial spread, and survival were monitored. Human polymorphonuclear neutrophils were used to study the effect of systemic adenosine triphosphate and apyrase on chemotaxis. Inhibiting endogenous adenosine triphosphate reduced polymorphonuclear neutrophil activation and organ injury, but increased the spread of bacteria and mortality in sepsis. By contrast, removal of systemic adenosine triphosphate improved bacterial clearance and survival in sepsis by improving polymorphonuclear neutrophil chemotaxis. Systemic adenosine triphosphate impairs polymorphonuclear neutrophil functions by disrupting the endogenous purinergic signaling mechanisms that regulate cell activation and chemotaxis. Removal of systemic adenosine triphosphate improves polymorphonuclear neutrophil function and host defenses

Homologues of xenobiotic metabolizing N-acetyltransferases in plant-associated fungi: Novel functions for an old enzyme family

USDA-ARS?s Scientific Manuscript database

Plant-pathogenic fungi and their hosts engage in chemical warfare, attacking each other with toxic products of secondary metabolism and defending themselves via an arsenal of xenobiotic metabolizing enzymes. One such enzyme is homologous to arylamine N-acetyltransferase (NAT) and has been identified...

Testicular defense systems: immune privilege and innate immunity

PubMed Central

Zhao, Shutao; Zhu, Weiwei; Xue, Shepu; Han, Daishu

2014-01-01

The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation. PMID:24954222

Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.

PubMed

Gabrinetti, Paul A; Özler, Sule

2014-10-01

In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system.

75 FR 9114 - Defense Federal Acquisition Regulation Supplement; Additional Requirements Applicable to...

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2010-03-01

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2010-06-11

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75 FR 78619 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

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2010-12-16

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22 CFR 130.4 - Defense articles and defense services.

Code of Federal Regulations, 2012 CFR

2012-04-01

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22 CFR 130.4 - Defense articles and defense services.

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2013-04-01

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22 CFR 130.4 - Defense articles and defense services.

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2010-04-01

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22 CFR 130.4 - Defense articles and defense services.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Defense articles and defense services. 130.4 Section 130.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS POLITICAL CONTRIBUTIONS, FEES AND COMMISSIONS § 130.4 Defense articles and defense services. Defense articles and defense...

75 FR 48278 - Defense Federal Acquisition Regulation Supplement; Excessive Pass-Through Charges

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2010-08-10

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Feasibility Study for a Computerized Serials Control System in the Defense Communications Agency Technical and Management Information Center.

DTIC Science & Technology

1984-06-20

AD-A162 ±88 FEASIBILITY STUDY FOR A COMPUTERIZED SERIALS CONTROL 1/1 SYSTEM IN THE DEFENS (U) DEFENSE COMMUNICATIONS AGENCY WASHINGTON DC TECHNICAL...NATIONAL BUREAU OF STANDARDS- 1963-A 0FEASIBILITY STUDY FOR A COMPUTERIZED SERIALS CONTROL SYSTEM IN THE DEFENSE COMMUNICATIONS 0AGENCY TECHNICAL AND...ABSTRACT 21. ABSTRACT SECURITY CLASSIFICATION UNCLASSIFIED/UNLIMITED R1 SAME AS RPT. 0 DTIC USERS 0 UNCLASSIFIED 22&. NAME OF RESPONSIBLE INDIVIDUAL 22b

EFFECT OF PREGNANE XENOBIOTIC RECEPTOR ACTIVATION ON INFLAMMATORY BOWEL DISEASE TREATED WITH RIFAXIMIN.

PubMed

Wan, Y C; Li, T; Han, Y-D; Zhang, H-Y; Lin, H; Zhang, B

2015-01-01

The causes and pathogenesis of Inflammatory Bowel Disease (IBD) are still not clearly understood. This study aims to prove the important role of rifaximin played in inflammatory reaction caused by abnormity of the intestinal mucosal immune system. Intestinal microflora can greatly promote and maintain the inflammatory reaction of IBD, therefore, antibiotics can be used to treat IBD. Rifaximin is a medicine usually used for local intestinal infection. Many clinical and basic studies have shown that both a single application of rifaximin and the joint application with other medicines could achieve a good efficacy. This paper studied the activation of Pregnane Xenobiotic Receptor (PXR) in treating IBD with rifaximin and analyzed its efficacy in IBD when PXR was involved in the transport of medicine and metabolism. The results prove that rifaximin can not only serve as an anti-microbial drug, but can activate PXR and actually weaken the reaction of IBD. Thus it is safe to say that rifaximin has great potential in treating IBD.

Comparative genomic, phylogenetic, and functional investigation of the xenobiotic metabolizing arylamine N-acetyltransferase enzyme family among fungi

USDA-ARS?s Scientific Manuscript database

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes well-characterized in several bacteria and higher eukaryotes. The role of NATs in fungal biology has only recently been investigated (Glenn and Bacon, 2009; Glenn et al., 2010). The NAT1 gene of Gibberella moniliformis was the...

77 FR 58817 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

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2012-09-24

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0321... Financing AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice and... . Paper copies are available from Mr. Mark Gomersall, OUSD(AT&L) DPAP/DARS, Room 3B855, 3060 Defense...

Modulation of xenobiotic biotransformation system and hormonal responses in Atlantic salmon (Salmo salar) after exposure to tributyltin (TBT).

PubMed

Mortensen, Anne Skjetne; Arukwe, Augustine

2007-04-01

Multiple biological effects of tributyltin (TBT) on juvenile salmon have been investigated. Fish were exposed for 7 days to waterborne TBT at nominal concentrations of 50 and 250 microg/L dissolved in dimethyl sulfoxide (DMSO). Hepatic samples were analyzed for gene expression patterns in the hormonal and xenobiotic biotransformation pathways using validated real-time PCR method. Immunochemical and several cytochrome P450 (CYP)-mediated enzyme activity (ethoxyresorufin: EROD, benzyloxyresorufin: BROD, methoxyresorufin: MROD and pentoxyresorufin: PROD) assays were analyzed. Our data show that TBT produced concentration-specific decrease of estrogen receptor-alpha (ERalpha), vitellogenin (Vtg), zona radiata protein (Zr-protein) and increase of estrogen receptor-beta (ERbeta) and androgen receptor-beta (ARbeta) in the hormonal pathway. In the xenobiotic biotransformation pathway, TBT produced apparent increase and decrease at respective low and high concentration, on aryl hydrocarbon receptor-alpha (AhRalpha), AhR nuclear translocator (ARNT) and AhR repressor (AhRR) mRNA. The expression of CYP1A1 and GST showed a TBT concentration-dependent decrease. The AhRbeta, CYP3A and uridine diphosphoglucuronosyl transferase (UGT) mRNA expressions were significantly induced after exposure to TBT. Immunochemical analysis of CYP3A and CYP1A1 protein levels confirmed the TBT effects observed at the transcriptional levels. The effect of TBT on the biotransformation enzyme gene expressions partially co-related but did not directly parallel enzyme activity levels for EROD, BROD, MROD and PROD. In general, these findings confirm previous reports on the endocrine effects of TBT, in addition to effects on hepatic CYP1A isoenzyme at the transcriptional level that transcends to protein and enzymatic levels. The induced expression patterns of CYP3A and UGT mRNA after TBT exposure, suggest the involvement of CYP3A and UGT in TBT metabolism in fish. The effect of TBT on CYP3A is proposed to

Adaptation to environmental stress in Daphnia magna simultaneously exposed to a xenobiotic.

PubMed

Coors, Anja; Hammers-Wirtz, Monika; Ratte, Hans Toni

2004-07-01

In standardized ecotoxicological testing chemicals are investigated under optimal conditions for the test organisms despite the fact that environmental factors such as predation pressure and food availability are important parameters regulating natural populations. Food limitation and predator presence can induce shifts in life-history traits in various Daphnia species, especially trade-offs in reproductive biomass allocation. These adaptive responses are thought to ensure survival of the population in a highly variable environment. A xenobiotic dispersant (used in textile dyeing processes) also shifted the biomass allocation of Daphnia magna. To assess whether the dispersant could hinder D. magna adaptation to varying environmental conditions, we conducted experiments with food level and presence of Chaoborus larvae as environmental factors and simultaneous exposure to the dispersant. At low food level and in presence of the predator, D. magna produced fewer but larger sized neonates, regardless of dispersant exposure. The dispersant shifted biomass allocation towards more but smaller sized offspring in all experiments. However, the adaptive response to the environmental factors and the dispersant effect cancelled each other out in that they induced independently from each other opposite shifts in biomass allocation. In summary, the dispersant exposure resulted not in an inhibition of the adaptive response but in a reduction of the value of the response. Our study with this model substance demonstrates that xenobiotics can affect the adaptation of organisms to environmental stress which can result in effects likely to be overlooked in standardized testing.

Integrated Air and Missile Defense (IAMD)

DTIC Science & Technology

2015-12-01

equal to or greater than the effectiveness levels of fielded TBM and CM/ABT defense systems. Common Command and Control The Army IAMD SoS common C2...externally developed sensors and shooters to provide an effective IAMD capability. The IAMD program will allow transformation to a network-centric system of...systems capability, also referred to as "Plug and Fight", that integrates all Air and Missile Defense (AMD) sensors, weapons, and mission control

Radiological Defense. Planning and Operations Guide. Revised.

ERIC Educational Resources Information Center

Office of Civil Defense (DOD), Washington, DC.

This guide is a reprint of published and draft materials from the Federal Civil Defense Guide. This guide is intended to assist the student in planning, developing, implementing and operating a local, county, or state radiological defense (RADEF) system. The state and local radiological defense program objectives are to create an effective and…

76 FR 20336 - Defense Audit Advisory Committee (DAAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-12

... DEPARTMENT OF DEFENSE Office of the Secretary Defense Audit Advisory Committee (DAAC) AGENCY... following Federal advisory committee meeting of the Defense Audit Advisory Committee will be held. DATES... management to include financial reporting processes, systems of internal controls, audit processes, and...

76 FR 52131 - Defense Federal Acquisition Regulation Supplement; Nonavailability Exception for Procurement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... Vol. 76 Friday, No. 161 August 19, 2011 Part III Department of Defense Defense Acquisition Regulations System 48 CFR Parts 201, 209, 216, et al. Defense Federal Acquisition Regulation Supplements... DEFENSE Defense Acquisition Regulations System 48 CFR Part 225 RIN 0750-AH17 Defense Federal Acquisition...

Macroevolutionary patterns of glucosinolate defense and tests of defense-escalation and resource availability hypotheses.

PubMed

Cacho, N Ivalú; Kliebenstein, Daniel J; Strauss, Sharon Y

2015-11-01

We explored macroevolutionary patterns of plant chemical defense in Streptanthus (Brassicaceae), tested for evolutionary escalation of defense, as predicted by Ehrlich and Raven's plant-herbivore coevolutionary arms-race hypothesis, and tested whether species inhabiting low-resource or harsh environments invest more in defense, as predicted by the resource availability hypothesis (RAH). We conducted phylogenetically explicit analyses using glucosinolate profiles, soil nutrient analyses, and microhabitat bareness estimates across 30 species of Streptanthus inhabiting varied environments and soils. We found weak to moderate phylogenetic signal in glucosinolate classes and no signal in total glucosinolate production; a trend toward evolutionary de-escalation in the numbers and diversity of glucosinolates, accompanied by an evolutionary increase in the proportion of aliphatic glucosinolates; some support for the RAH relative to soil macronutrients, but not relative to serpentine soil use; and that the number of glucosinolates increases with microhabitat bareness, which is associated with increased herbivory and drought. Weak phylogenetic signal in chemical defense has been observed in other plant systems. A more holistic approach incorporating other forms of defense might be necessary to confidently reject escalation of defense. That defense increases with microhabitat bareness supports the hypothesis that habitat bareness is an underappreciated selective force on plants in harsh environments. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Natural allelic variations of xenobiotic-metabolizing enzymes affect sexual dimorphism in Oryzias latipes.

PubMed

Katsumura, Takafumi; Oda, Shoji; Nakagome, Shigeki; Hanihara, Tsunehiko; Kataoka, Hiroshi; Mitani, Hiroshi; Kawamura, Shoji; Oota, Hiroki

2014-12-22

Sexual dimorphisms, which are phenotypic differences between males and females, are driven by sexual selection. Interestingly, sexually selected traits show geographical variations within species despite strong directional selective pressures. This paradox has eluded many evolutionary biologists for some time, and several models have been proposed (e.g. 'indicator model' and 'trade-off model'). However, disentangling which of these theories explains empirical patterns remains difficult, because genetic polymorphisms that cause variation in sexual differences are still unknown. In this study, we show that polymorphisms in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolizing enzyme, are associated with geographical differences in sexual dimorphism in the anal fin morphology of medaka fish (Oryzias latipes). Biochemical assays and genetic cross experiments show that high- and low-activity CYP1B1 alleles enhanced and declined sex differences in anal fin shapes, respectively. Behavioural and phylogenetic analyses suggest maintenance of the high-activity allele by sexual selection, whereas the low-activity allele possibly has experienced positive selection due to by-product effects of CYP1B1 in inferred ancestral populations. The present data can elucidate evolutionary mechanisms behind genetic variations in sexual dimorphism and indicate trade-off interactions between two distinct mechanisms acting on the two alleles with pleiotropic effects of xenobiotic-metabolizing enzymes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Development of the Defense Documentation Center Remote On-Line Retrieval System - Past, Present and Future.

ERIC Educational Resources Information Center

Bennertz, Richard K.

The document highlights in nontechnical language the development of the Defense Documentation Center (DDC) Remote On-Line Retrieval System from its inception in 1967 to what is planned. It describes in detail the current operating system, equipment configuration and associated costs, user training and system evaluation and may be of value to other…

76 FR 50461 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Types of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0259] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Types of Contracts AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Notice and request...

76 FR 71558 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Requests...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [Docket No. DARS 2011-0069-0002] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Requests for Equitable Adjustment (OMB Control Number 0704-0397) AGENCY: Defense Acquisition Regulations System, Department of...

75 FR 32122 - Revisions to Defense Priorities and Allocations System Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-07

...This proposed rule would reorganize and clarify existing standards and procedures by which the Bureau of Industry and Security (BIS) may require that certain contracts or orders that promote the national defense be given priority over other contracts or orders. This rule also sets new standards and procedures by which BIS may allocate materials, services and facilities to promote the national defense. BIS is publishing this rule to comply with a requirement of the Defense Production Act Reauthorization of 2009 to publish regulations providing standards and procedures for prioritization of contracts and orders and for allocation of materials, services and facilities to promote the national defense.

Cost Effective Regional Ballistic Missile Defense

DTIC Science & Technology

2016-02-16

deploying advanced air defense systems18, such as the Russian S-300 and S-500, and concealing them in hardened, camouflaged sites, such as extensive... Russian objections to the European Phased Adaptive Approach (EPAA) and fund homeland defense priorities.39 Furthermore, the PTSS system was also... Theatre Ballistic Missile Defence Capability Becomes Operational,” Jane’s Missiles & Rockets, 1 February 2011. 55 Joseph W. Kirschbaum, REGIONAL MISSILE

78 FR 18877 - Defense Federal Acquisition Regulation Supplement; Specialty Metals-Definition of “Produce...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 252 RIN 0750-AH78 Defense...-D041) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is issuing a final rule amending the Defense Federal Acquisition Regulation Supplement (DFARS...

The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism

PubMed Central

Spanogiannopoulos, Peter; Bess, Elizabeth N.; Carmody, Rachel N.; Turnbaugh, Peter J.

2016-01-01

Although the significance of human genetic polymorphisms in therapeutic outcomes is well established, the importance of our “second genome” (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that shed light on the mechanisms linking the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and the development of a next generation of therapeutics based on or targeted at the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within. PMID:26972811

78 FR 33994 - Defense Federal Acquisition Regulation Supplement; Government Support Contractor Access to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 252 RIN Number 0750-AG38 Defense Federal Acquisition Regulation Supplement; Government Support Contractor Access to Technical Data (DFARS 2009-D031); Correction AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD...

77 FR 52254 - Defense Federal Acquisition Regulation Supplement: Reporting of Government-Furnished Property...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 211, 212, and 252 RIN... (DFARS Case 2012-D001) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD... requirements of the current clause, which requires Defense contractors to report (primarily) Government...

78 FR 48397 - Defense Federal Acquisition Regulation Supplement: Clauses With Alternates-Transportation (DFARS...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 212, 216, 247, and 252...--Transportation (DFARS Case 2012-D057) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD... manufacture, fabrication, or assembly by the Contractor or any subcontractor. (2) ``Department of Defense...

Optimal defense strategies in an idealized microbial food web under trade-off between competition and defense.

PubMed

Våge, Selina; Storesund, Julia E; Giske, Jarl; Thingstad, T Frede

2014-01-01

Trophic mechanisms that can generate biodiversity in food webs include bottom-up (growth rate regulating) and top-down (biomass regulating) factors. The top-down control has traditionally been analyzed using the concepts of "Keystone Predation" (KP) and "Killing-the-Winner" (KtW), predominately occuring in discussions of macro- and micro-biological ecology, respectively. Here we combine the classical diamond-shaped food web structure frequently discussed in KP analyses and the KtW concept by introducing a defense strategist capable of partial defense. A formalized description of a trade-off between the defense-strategist's competitive and defensive ability is included. The analysis reveals a complex topology of the steady state solution with strong relationships between food web structure and the combination of trade-off, defense strategy and the system's nutrient content. Among the results is a difference in defense strategies corresponding to maximum biomass, production, or net growth rate of invading individuals. The analysis thus summons awareness that biomass or production, parameters typically measured in field studies to infer success of particular biota, are not directly acted upon by natural selection. Under coexistence with a competition specialist, a balance of competitive and defensive ability of the defense strategist was found to be evolutionarily stable, whereas stronger defense was optimal under increased nutrient levels in the absence of the pure competition specialist. The findings of success of different defense strategies are discussed with respect to SAR11, a highly successful bacterial clade in the pelagic ocean.

Removal of Antibiotics in Biological Wastewater Treatment Systems-A Critical Assessment Using the Activated Sludge Modeling Framework for Xenobiotics (ASM-X).

PubMed

Polesel, Fabio; Andersen, Henrik R; Trapp, Stefan; Plósz, Benedek Gy

2016-10-04

Many scientific studies present removal efficiencies for pharmaceuticals in laboratory-, pilot-, and full-scale wastewater treatment plants, based on observations that may be impacted by theoretical and methodological approaches used. In this Critical Review, we evaluated factors influencing observed removal efficiencies of three antibiotics (sulfamethoxazole, ciprofloxacin, tetracycline) in pilot- and full-scale biological treatment systems. Factors assessed include (i) retransformation to parent pharmaceuticals from e.g., conjugated metabolites and analogues, (ii) solid retention time (SRT), (iii) fractions sorbed onto solids, and (iv) dynamics in influent and effluent loading. A recently developed methodology was used, relying on the comparison of removal efficiency predictions (obtained with the Activated Sludge Model for Xenobiotics (ASM-X)) with representative measured data from literature. By applying this methodology, we demonstrated that (a) the elimination of sulfamethoxazole may be significantly underestimated when not considering retransformation from conjugated metabolites, depending on the type (urban or hospital) and size of upstream catchments; (b) operation at extended SRT may enhance antibiotic removal, as shown for sulfamethoxazole; (c) not accounting for fractions sorbed in influent and effluent solids may cause slight underestimation of ciprofloxacin removal efficiency. Using tetracycline as example substance, we ultimately evaluated implications of effluent dynamics and retransformation on environmental exposure and risk prediction.

Racial disparity in survival from early breast cancer in the department of defense healthcare system.

PubMed

Rizzo, Julie A; Sherman, William E; Arciero, Cletus A

2015-06-01

Racial disparity is often identified as a factor in survival from breast cancer in the United States. Current data regarding survival in patients treated in the Department of Defense Military Healthcare System is lacking. The Department of Defense Automated Central Tumor Registry (ACTUR) was queried for all women diagnosed with Stage I or II breast cancer from January 1, 1996 through December 31, 2008. Statistical analyses evaluated demographics, surgical treatment, tumor stage, and survival rates. There were 8,890 patients meeting inclusion criteria. Patients who were younger, Asian American (versus white or black), lower T and/or N stage had significantly improved survival rates. Interestingly, white and black patients demonstrated similar survival in this study. Patients with a longer period of time between diagnosis and treatment had no decrement in survival. As would be expected, patients with a longer recurrence free period enjoyed longer survival. Survival from early stage breast cancer is equivalent between white and black patients in the Department of Defense Healthcare System. This finding is contrary to reports from our civilian counterparts and may be indicative of improved access to care and overall improved cancer surveillance. © 2015 Wiley Periodicals, Inc.

A Global Genomic and Genetic Strategy to Predict Pathway Activation of Xenobiotic Responsive Transcription Factors in the Mouse Liver

EPA Science Inventory

Many drugs and environmentally-relevant chemicals activate xenobiotic-responsive transcription factors(TF). Identification of target genes of these factors would be useful in predicting pathway activation in in vitro chemical screening. Starting with a large compendium of Affymet...

Program Manager: Journal of the Defense Systems Management College. Volume 19, Number 5, September-October 1990

DTIC Science & Technology

1990-10-01

International Defense Cooperation Agreements; Quality Force Deployment; How Contractors See Systems Acquisition; DOD Metric Transition Plans and Actions; Proposals for Innovation In Service Quality . (sdw)

Review of defense display research programs

NASA Astrophysics Data System (ADS)

Tulis, Robert W.; Hopper, Darrel G.; Morton, David C.; Shashidhar, Ranganathan

2001-09-01

Display research has comprised a substantial portion of the defense investment in new technology for national security for the past 13 years. These investments have been made by the separate service departments and, especially, via several Defense Research Projects Agency (DARPA) programs, known collectively as the High Definition Systems (HDS) Program (which ended in 2001) and via the Office of the Secretary of Defense (OSD) Defense Production Act (DPA) Title III Program (efforts ended in 2000). Using input from the Army, Navy, and Air Force to focus research and identify insertion opportunities, DARPA and the Title III Program Office have made investments to develop the national technology base and manufacturing infrastructure necessary to meet the twin challenge of providing affordable displays in current systems and enabling the DoD strategy of winning future conflicts by getting more information to all participants during the battle. These completed DARPA and DPA research and infrastructure programs are reviewed. Service investments have been and are being made to transition display technology; examples are described. Display science and technology (S&T) visions are documented for each service to assist the identification of areas meriting consideration for future defense research.

48 CFR 228.102-70 - Defense Environmental Restoration Program construction contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Restoration Program construction contracts. 228.102-70 Section 228.102-70 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds 228.102-70 Defense Environmental Restoration Program construction contracts...

A Txnrd1-dependent metabolic switch alters hepatic lipogenesis, glycogen storage, and detoxification

PubMed Central

Iverson, Sonya V.; Eriksson, Sofi; Xu, Jianqiang; Prigge, Justin R.; Talago, Emily A.; Meade, Tesia A.; Meade, Erin S.; Capecchi, Mario R.; Arnér, Elias S.J.; Schmidt, Edward E.

2013-01-01

Besides helping to maintain a reducing intracellular environment, the thioredoxin (Trx) system impacts bioenergetics and drug-metabolism. We show that hepatocyte-specific disruption of Txnrd1, encoding Trx reductase-1 (TrxR1), causes a metabolic switch in which lipogenic genes are repressed and periportal hepatocytes become engorged with glycogen. These livers also overexpress machinery for biosynthesis of glutathione and conversion of glycogen into UDP-glucuronate; they stockpile glutathione-S-transferases and UDP-glucuronyl-transferases; and they overexpress xenobiotic exporters. This realigned metabolic profile suggested that the mutant hepatocytes might be preconditioned to more effectively detoxify certain xenobiotic challenges. Hepatocytes convert the pro-toxin acetaminophen (APAP, paracetamol) into cytotoxic N-acetyl-p-benzoquinone imine (NAPQI). APAP defenses include glucuronidation of APAP or glutathionylation of NAPQI, allowing removal by xenobiotic exporters. We found that NAPQI directly inactivates TrxR1, yet Txnrd1-null livers were resistant to APAP-induced hepatotoxicity. Txnrd1-null livers did not have more effective gene expression responses to APAP challenge; however their constitutive metabolic state supported more robust GSH biosynthesis-, glutathionylation-, and glucuronidation-systems. Following APAP challenge, this effectively sustained the GSH system and attenuated damage. PMID:23743293

The species recognition system: a new corollary for the human fetoembryonic defense system hypothesis.

PubMed

Clark, G F; Dell, A; Morris, H R; Patankar, M S; Easton, R L

2001-01-01

We have previously suggested that the human fetus is protected during human development by a system of both soluble and cell surface associated glycoconjugates that utilize their carbohydrate sequences as functional groups to enable them to evoke tolerance. The proposed model has been referred to as the human fetoembryonic defense system hypothesis (hu-FEDS). In this paradigm, it has previously been proposed that similar oligosaccharides are used to mediate crucial recognition events required during both human sperm-egg binding and immune-inflammatory cell interactions. This vertical integration suggested to us that the sperm-egg binding itself is related to universal recognition events that occur between immune and inflammatory cells, except that in this case recognition of 'species' rather than recognition of 'self' is being manifested. In this paper, we have designated this component of hu-FEDS as the species recognition system (SRS). We propose that the SRS is an integral component of the hu-FEDS used to enable sperm-egg recognition and protection of the gametes from potential immune responses. Recent structural data indicates that the glycan sequences implicated in mediating murine gamete recognition are also expressed on CD45 in activated murine T lymphocytes and cytotoxic T lymphocytes. This overlap supports our contention that there is an overlap between the immune and gamete recognition systems. Therefore the hu-FEDS paradigm may be a subset of a larger model that also applies to other placental mammals. We therefore propose that the hu-FEDS model for protection should in the future be referred to as the eutherian fetoembryonic defense system hypothesis (eu-FEDS) to account for this extension. The possibility exists that the SRS component of eu-FEDS could predate eutherians and extend to all sexually reproducing organisms. Future investigation of the interactions between the immune and gamete recognition system will be required to determine the degree of

76 FR 64885 - Defense Federal Acquisition Regulation Supplement: Reporting of Government-Furnished Property...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... property accounting system of record, and the Army requires GFP to be recorded in DPAS as well. Response... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 211 and 252 RIN 0750... (DFARS Case 2012-D001) AGENCIES: Defense Acquisition Regulations System, Department of Defense (DoD...

77 FR 30366 - Defense Federal Acquisition Regulation Supplement: Contingency Contract Closeout (DFARS Case 2012...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 204 RIN 0750-AH71 Defense...: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is issuing a final rule amending the Defense Federal Acquisition Regulation Supplement (DFARS) to require...

The Dwight D. Eisenhower National System of Interstate and Defense Highways: The Road to Success?

ERIC Educational Resources Information Center

Blas, Elisheva

2010-01-01

The Dwight D. Eisenhower National System of Interstate and Defense Highways was an innovation that changed America. The highway system, the greatest public works project in American history, made travel faster, easier, and safer. However, there were serious negative effects of the highways; they hindered the growth of cities, destroyed…

Defense Health Care: DOD Chiropractor Wage Rates

DTIC Science & Technology

2013-03-14

Page 2 Introduction • In 2000, Congress mandated that the Department of Defense (DOD) develop a plan to provide chiropractic care as a permanent...part of the Defense Health Program. • Prior to the establishment of DOD’s chiropractic program, Congress directed DOD to conduct demonstration...projects to evaluate the feasibility and advisability of expanding DOD’s health system to include chiropractic care. • The National Defense

Defense Agencies Initiative Increment 2 (DAI Inc 2)

DTIC Science & Technology

2016-03-01

2016 Major Automated Information System Annual Report Defense Agencies Initiative Increment 2 (DAI Inc 2) Defense Acquisition Management...Automated Information System MAIS OE - MAIS Original Estimate MAR – MAIS Annual Report MDA - Milestone Decision Authority MDD - Materiel Development...management systems supporting diverse operational functions and the warfighter in decision making and financial reporting . These disparate, non

Second Line of Defense Virtual Private Network Guidance for Deployed and New CAS Systems

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

Singh, Surya V.; Thronas, Aaron I.

2010-01-01

This paper discusses the importance of remote access via virtual private network (VPN) for the Second Line of Defense (SLD) Central Alarm System (CAS) sites, the requirements for maintaining secure channels while using VPN and implementation requirements for current and future sites.

75 FR 20825 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DoD Pilot...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-21

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0332] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DoD Pilot Mentor-Protege Program AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION...

A Compilation of In Vitro Rate and Affinity Values for Xenobiotic Biotransformation in Fish, Measured Under Physiological Conditions

EPA Science Inventory

This manuscript presents a summary of in vitro rate and affinity data for xenobiotic biotransformation enzymes in fish...One potential use of this data summary is to support in vitro to in vivo metabolism extrapolations which can be used as inputs to chemical kinetic models for f...

The Chemically Inducible Plant Cytochrome P450 CYP76B1 Actively Metabolizes Phenylureas and Other Xenobiotics1

PubMed Central

Robineau, Tiburce; Batard, Yannick; Nedelkina, Svetlana; Cabello-Hurtado, Francisco; LeRet, Monique; Sorokine, Odile; Didierjean, Luc; Werck-Reichhart, Danièle

1998-01-01

Cytochrome P450s (P450s) constitute one of the major classes of enzymes that are responsible for detoxification of exogenous molecules both in animals and plants. On the basis of its inducibility by exogenous chemicals, we recently isolated a new plant P450, CYP76B1, from Jerusalem artichoke (Helianthus tuberosus) and showed that it was capable of dealkylating a model xenobiotic compound, 7-ethoxycoumarin. In the present paper we show that CYP76B1 is more strongly induced by foreign compounds than other P450s isolated from the same plant, and metabolizes with high efficiency a wide range of xenobiotics, including alkoxycoumarins, alkoxyresorufins, and several herbicides of the class of phenylureas. CYP76B1 catalyzes the double N-dealkylation of phenylureas with turnover rates comparable to those reported for physiological substrates and produces nonphytotoxic compounds. Potential uses for CYP76B1 thus include control of herbicide tolerance and selectivity, as well as soil and groundwater bioremediation. PMID:9808750

Modular Open System Architecture for Reducing Contamination Risk in the Space and Missile Defense Supply Chain

NASA Technical Reports Server (NTRS)

Seasly, Elaine

2015-01-01

To combat contamination of physical assets and provide reliable data to decision makers in the space and missile defense community, a modular open system architecture for creation of contamination models and standards is proposed. Predictive tools for quantifying the effects of contamination can be calibrated from NASA data of long-term orbiting assets. This data can then be extrapolated to missile defense predictive models. By utilizing a modular open system architecture, sensitive data can be de-coupled and protected while benefitting from open source data of calibrated models. This system architecture will include modules that will allow the designer to trade the effects of baseline performance against the lifecycle degradation due to contamination while modeling the lifecycle costs of alternative designs. In this way, each member of the supply chain becomes an informed and active participant in managing contamination risk early in the system lifecycle.

Sulforaphane protects Microcystin-LR-induced toxicity through activation of the Nrf2-mediated defensive response

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

Gan Nanqin; Mi Lixin; Sun Xiaoyun

2010-09-01

Microcystins (MCs), a cyclic heptapeptide hepatotoxins, are mainly produced by the bloom-forming cyanobacerium Microcystis, which has become an environmental hazard worldwide. Long term consumption of MC-contaminated water may induce liver damage, liver cancer, and even human death. Therefore, in addition to removal of MCs in drinking water, novel strategies that prevent health damages are urgently needed. Sulforaphane (SFN), a natural-occurring isothiocyanate from cruciferous vegetables, has been reported to reduce and eliminate toxicities from xenobiotics and carcinogens. The purpose of the present study was to provide mechanistic insights into the SFN-induced antioxidative defense system against MC-LR-induced cytotoxicity. We performed cell viabilitymore » assays, including MTS assay, colony formation assay and apoptotic cell sorting, to study MC-LR-induced cellular damage and the protective effects by SFN. The results showed that SFN protected MC-LR-induced damages at a nontoxic and physiological relevant dose in HepG2, BRL-3A and NIH 3 T3 cells. The protection was Nrf2-mediated as evident by transactivation of Nrf2 and activation of its downstream genes, including NQO1 and HO-1, and elevated intracellular GSH level. Results of our studies indicate that pretreatment of cells with 10 {mu}M SFN for 12 h significantly protected cells from MC-LR-induced damage. SFN-induced protective response was mediated through Nrf2 pathway.« less

Selection of Reference Genes for Expression Studies of Xenobiotic Adaptation in Tetranychus urticae.

PubMed

Morales, Mariany Ashanty; Mendoza, Bianca Marie; Lavine, Laura Corley; Lavine, Mark Daniel; Walsh, Douglas Bruce; Zhu, Fang

2016-01-01

Quantitative real-time PCR (qRT-PCR) is an extensively used, high-throughput method to analyze transcriptional expression of genes of interest. An appropriate normalization strategy with reliable reference genes is required for calculating gene expression across diverse experimental conditions. In this study, we aim to identify the most stable reference genes for expression studies of xenobiotic adaptation in Tetranychus urticae, an extremely polyphagous herbivore causing significant yield reduction of agriculture. We chose eight commonly used housekeeping genes as candidates. The qRT-PCR expression data for these genes were evaluated from seven populations: a susceptible and three acaricide resistant populations feeding on lima beans, and three other susceptible populations which had been shifted host from lima beans to three other plant species. The stability of the candidate reference genes was then assessed using four different algorithms (comparative ΔCt method, geNorm, NormFinder, and BestKeeper). Additionally, we used an online web-based tool (RefFinder) to assign an overall final rank for each candidate gene. Our study found that CycA and Rp49 are best for investigating gene expression in acaricide susceptible and resistant populations. GAPDH, Rp49, and Rpl18 are best for host plant shift studies. And GAPDH and Rp49 were the most stable reference genes when investigating gene expression under changes in both experimental conditions. These results will facilitate research in revealing molecular mechanisms underlying the xenobiotic adaptation of this notorious agricultural pest.

Selection of Reference Genes for Expression Studies of Xenobiotic Adaptation in Tetranychus urticae

PubMed Central

Morales, Mariany Ashanty; Mendoza, Bianca Marie; Lavine, Laura Corley; Lavine, Mark Daniel; Walsh, Douglas Bruce; Zhu, Fang

2016-01-01

Quantitative real-time PCR (qRT-PCR) is an extensively used, high-throughput method to analyze transcriptional expression of genes of interest. An appropriate normalization strategy with reliable reference genes is required for calculating gene expression across diverse experimental conditions. In this study, we aim to identify the most stable reference genes for expression studies of xenobiotic adaptation in Tetranychus urticae, an extremely polyphagous herbivore causing significant yield reduction of agriculture. We chose eight commonly used housekeeping genes as candidates. The qRT-PCR expression data for these genes were evaluated from seven populations: a susceptible and three acaricide resistant populations feeding on lima beans, and three other susceptible populations which had been shifted host from lima beans to three other plant species. The stability of the candidate reference genes was then assessed using four different algorithms (comparative ΔCt method, geNorm, NormFinder, and BestKeeper). Additionally, we used an online web-based tool (RefFinder) to assign an overall final rank for each candidate gene. Our study found that CycA and Rp49 are best for investigating gene expression in acaricide susceptible and resistant populations. GAPDH, Rp49, and Rpl18 are best for host plant shift studies. And GAPDH and Rp49 were the most stable reference genes when investigating gene expression under changes in both experimental conditions. These results will facilitate research in revealing molecular mechanisms underlying the xenobiotic adaptation of this notorious agricultural pest. PMID:27570487

Role of plant β-glucosidases in the dual defense system of iridoid glycosides and their hydrolyzing enzymes in Plantago lanceolata and Plantago major.

PubMed

Pankoke, Helga; Buschmann, Torsten; Müller, Caroline

2013-10-01

The typical defense compounds of Plantaginaceae are the iridoid glycosides, which retard growth and/or enhance mortality of non-adapted herbivores. In plants, glycosidic defense compounds and hydrolytic enzymes often form a dual defense system, in which the glycosides are activated by the enzymes to exert biological effects. Yet, little is known about the activating enzymes in iridoid glycoside-containing plants. To examine the role of plant-derived β-glucosidases in the dual defense system of two common plantain species, Plantago lanceolata and Plantago major, we determined the concentration of iridoid glycosides as well as the β-glucosidase activity in leaves of different age. To investigate the presence of other leaf metabolites potentially involved in plant defense, we used a metabolic fingerprinting approach with ultra-high performance liquid chromatography coupled with time-of-flight-mass spectrometry. According to the optimal defense hypothesis, more valuable parts such as young leaves should be better protected than less valuable parts. Therefore, we expected that both, the concentrations of defense compounds as well as the β-glucosidase activity, should be highest in younger leaves and decrease with increasing leaf age. Both species possessed β-glucosidase activity, which hydrolyzed aucubin, one of the two most abundant iridoid glycosides in both plant species, with high activity. In line with the optimal defense hypothesis, the β-glucosidase activity in both Plantago species as well as the concentration of defense-related metabolites such as iridoid glycosides correlated negatively to leaf age. When leaf extracts were incubated with bovine serum albumin and aucubin, SDS-PAGE revealed a protein-denaturing effect of the leaf extracts of both plantain species, suggesting that iridoid glycosides and plant β-glucosidase interact in a dual defense system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimal Defense Strategies in an Idealized Microbial Food Web under Trade-Off between Competition and Defense

PubMed Central

Våge, Selina; Storesund, Julia E.; Giske, Jarl; Thingstad, T. Frede

2014-01-01

Trophic mechanisms that can generate biodiversity in food webs include bottom-up (growth rate regulating) and top-down (biomass regulating) factors. The top-down control has traditionally been analyzed using the concepts of “Keystone Predation” (KP) and “Killing-the-Winner” (KtW), predominately occuring in discussions of macro- and micro-biological ecology, respectively. Here we combine the classical diamond-shaped food web structure frequently discussed in KP analyses and the KtW concept by introducing a defense strategist capable of partial defense. A formalized description of a trade-off between the defense-strategist's competitive and defensive ability is included. The analysis reveals a complex topology of the steady state solution with strong relationships between food web structure and the combination of trade-off, defense strategy and the system's nutrient content. Among the results is a difference in defense strategies corresponding to maximum biomass, production, or net growth rate of invading individuals. The analysis thus summons awareness that biomass or production, parameters typically measured in field studies to infer success of particular biota, are not directly acted upon by natural selection. Under coexistence with a competition specialist, a balance of competitive and defensive ability of the defense strategist was found to be evolutionarily stable, whereas stronger defense was optimal under increased nutrient levels in the absence of the pure competition specialist. The findings of success of different defense strategies are discussed with respect to SAR11, a highly successful bacterial clade in the pelagic ocean. PMID:24999739

Directed Energy Technology Working Group Report (IDA/OSD R&M (Institute for Defense Analyses/Office of the Secretary of Defense Reliability and Maintainability) Study).

DTIC Science & Technology

1983-08-01

Missile (SLBM) Defense Scenario ............................................ B-1 C Space-Based Anti-Ballistic Missile ( ABM ) Defense Scenario...Ballistic Missile (SLBM) Defense Scenario, and at Strategic Space-Based Anti-Ballistic Missile ( ABM ) Defense Scenario. These case studies are provided...of flight. 3.5.3 Spaced-Based ABM Defense Scenario In this scenario, an orbiting battle station is operating as an element of GBMD System, and it is

Daphnia HR96 is a Promiscuous Xenobiotic and Endobiotic Nuclear Receptor

PubMed Central

Karimullina, Elina; Li, Yangchun; Ginjupalli, Gautam; Baldwin, William S.

2012-01-01

Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics. PMID:22466357

Soviet Assessments of North American Air Defense

DTIC Science & Technology

1986-06-01

whether they represented misunderstandings or errors on the Soviet part, or unique Soviet perspectives and biases. Finally, articles on Soviet strategy...and what reactions do these assessments prompt? First, most articles on U.S. continental air defenses were found in the journal of the Air Defense...Soviet assessments of U.S. air defense control systems with articles in Military Thought. Some of these themes are: - The importance of centralized

Characterization of the Impact of Life Stage on Xenobiotic Metabolizing Enzyme Expression and Gene -Chemical Interactions in the Liver

EPA Science Inventory

Differences in responses to environmental chemicals and drugs between life stages are likely due in part to differences in the expression of xenobiotic metabolizing enzymes and transporters (XMETs). We have carried out a comprehensive analysis of the mRNA expression of XMETs thro...

75 FR 40714 - Defense Federal Acquisition Regulation Supplement; Publication of Notification of Bundling of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-13

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 205 and 210 Defense Federal Acquisition Regulation Supplement; Publication of Notification of Bundling of Contracts of the Department of Defense (DFARS Case 2009-D033) AGENCY: Defense Acquisition Regulations System, Department of...

75 FR 33752 - Defense Federal Acquisition Regulation Supplement; Organizational Conflicts of Interest in Major...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 202, 203, 212, and 252 [DFARS Case 2009-D015] RIN 0750-AG63 Defense Federal Acquisition Regulation Supplement; Organizational Conflicts of Interest in Major Defense Acquisition Programs AGENCY: Defense Acquisition Regulations System...

Xenobiotic Compounds Degradation by Heterologous Expression of a Trametes sanguineus Laccase in Trichoderma atroviride

PubMed Central

Balcázar-López, Edgar; Méndez-Lorenzo, Luz Helena; Batista-García, Ramón Alberto; Esquivel-Naranjo, Ulises; Ayala, Marcela; Kumar, Vaidyanathan Vinoth; Savary, Olivier; Cabana, Hubert; Herrera-Estrella, Alfredo; Folch-Mallol, Jorge Luis

2016-01-01

Fungal laccases are enzymes that have been studied because of their ability to decolorize and detoxify effluents; they are also used in paper bleaching, synthesis of polymers, bioremediation, etc. In this work we were able to express a laccase from Trametes (Pycnoporus) sanguineus in the filamentous fungus Trichoderma atroviride. For this purpose, a transformation vector was designed to integrate the gene of interest in an intergenic locus near the blu17 terminator region. Although monosporic selection was still necessary, stable integration at the desired locus was achieved. The native signal peptide from T. sanguineus laccase was successful to secrete the recombinant protein into the culture medium. The purified, heterologously expressed laccase maintained similar properties to those observed in the native enzyme (Km and kcat and kcat/km values for ABTS, thermostability, substrate range, pH optimum, etc). To determine the bioremediation potential of this modified strain, the laccase-overexpressing Trichoderma strain was used to remove xenobiotic compounds. Phenolic compounds present in industrial wastewater and bisphenol A (an endocrine disruptor) from the culture medium were more efficiently removed by this modified strain than with the wild type. In addition, the heterologously expressed laccase was able to decolorize different dyes as well as remove benzo[α]pyrene and phenanthrene in vitro, showing its potential for xenobiotic compound degradation. PMID:26849129

Anti-CRISPR proteins: Counterattack of phages on bacterial defense (CRISPR/Cas) system.

PubMed

Chaudhary, Kulbhushan; Chattopadhyay, Anirudha; Pratap, Dharmendra

2018-01-01

Since the dawn of life there is a never ending strife between bacteria and phages. Both are perpetually changing their strategies to take over each other. CRISPR/Cas is the most widespread defense system used by bacteria against mobile genetic elements (MGEs) such as phages, cojugative palsmids, transoposons, and pathogenicity islands. This system utilizes small guide RNA molecules to protect against phages infection and invasion by MGEs. Phages circumvent to these antiviral barriers by point mutation in PAM (protospacer-adjacent motif) sequence, genome rearrangements and by using anti-CRISPR proteins. © 2017 Wiley Periodicals, Inc.

High-throughput metagenomic analysis of petroleum-contaminated soil microbiome reveals the versatility in xenobiotic aromatics metabolism.

PubMed

Bao, Yun-Juan; Xu, Zixiang; Li, Yang; Yao, Zhi; Sun, Jibin; Song, Hui

2017-06-01

The soil with petroleum contamination is one of the most studied soil ecosystems due to its rich microorganisms for hydrocarbon degradation and broad applications in bioremediation. However, our understanding of the genomic properties and functional traits of the soil microbiome is limited. In this study, we used high-throughput metagenomic sequencing to comprehensively study the microbial community from petroleum-contaminated soils near Tianjin Dagang oilfield in eastern China. The analysis reveals that the soil metagenome is characterized by high level of community diversity and metabolic versatility. The metageome community is predominated by γ-Proteobacteria and α-Proteobacteria, which are key players for petroleum hydrocarbon degradation. The functional study demonstrates over-represented enzyme groups and pathways involved in degradation of a broad set of xenobiotic aromatic compounds, including toluene, xylene, chlorobenzoate, aminobenzoate, DDT, methylnaphthalene, and bisphenol. A composite metabolic network is proposed for the identified pathways, thus consolidating our identification of the pathways. The overall data demonstrated the great potential of the studied soil microbiome in the xenobiotic aromatics degradation. The results not only establish a rich reservoir for novel enzyme discovery but also provide putative applications in bioremediation. Copyright © 2016. Published by Elsevier B.V.

Classification and modelling of non-extractable residue (NER) formation from xenobiotics in soil - a synthesis

NASA Astrophysics Data System (ADS)

Kaestner, Matthias; Nowak, Karolina; Miltner, Anja; Trapp, Stefan; Schaeffer, Andreas

2014-05-01

This presentation provides a comprehensive overview about the formation of non-extractable residues (NER) from organic pesticides and contaminants in soil and tries classifying the different types. Anthropogenic organic chemicals are deliberately (e.g. pesticides) or unintentionally (e.g. polyaromatic hydrocarbons [PAH], chlorinated solvents, pharmaceuticals) released in major amounts to nearly all compartments of the environment. Soils and sediments as complex matrices provide a wide variety of binding sites and are the major sinks for these compounds. Many of the xenobiotics entering soil undergo turnover processes and can be volatilised, leached to the groundwater, degraded by microorganisms or taken up and enriched by living organisms. Xenobiotic NER may be derived from parent compounds and primary metabolites that are sequestered (sorbed or entrapped) within the soil organic matter (type I NER) or can be covalently bound (type II NER). Especially type I NER may pose a considerably environmental risk of potential release. However, NER resulting from productive biodegradation, which means the conversion of carbon (or nitrogen) from the compounds into microbial biomass molecules during microbial degradation (type III, bioNER), do not pose any risk. Experimental and analytical approaches to clearly distinguish between the types are provided and a model to prospectively estimate their fate in soil is proposed.

76 FR 23504 - Defense Federal Acquisition Regulation Supplement; Definition of Multiple-Award Contract (DFARS...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 207 RIN 0750-AH12 Defense Federal Acquisition Regulation Supplement; Definition of Multiple-Award Contract (DFARS Case 2011-D016) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY...

76 FR 32843 - Defense Federal Acquisition Regulation Supplement; Fire-Resistant Fiber for Production of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 225 RIN 0750-AH22 Defense Federal Acquisition Regulation Supplement; Fire-Resistant Fiber for Production of Military Uniforms (DFARS Case 2011-D021) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION...

Molecular cloning of a family of xenobiotic-inducible drosophilid cytochrome P450s: Evidence for involvement in host-plant allelochemical resistance

PubMed Central

Danielson, Phillip B.; MacIntyre, Ross J.; Fogleman, James C.

1997-01-01

Cytochrome P450s constitute a superfamily of genes encoding mostly microsomal hemoproteins that play a dominant role in the metabolism of a wide variety of both endogenous and foreign compounds. In insects, xenobiotic metabolism (i.e., metabolism of insecticides and toxic natural plant compounds) is known to involve members of the CYP6 family of cytochrome P450s. Use of a 3′ RACE (rapid amplification of cDNA ends) strategy with a degenerate primer based on the conserved cytochrome P450 heme-binding decapeptide loop resulted in the amplification of four cDNA sequences representing another family of cytochrome P450 genes (CYP28) from two species of isoquinoline alkaloid-resistant Drosophila and the cosmopolitan species Drosophila hydei. The CYP28 family forms a monophyletic clade with strong regional homologies to the vertebrate CYP3 family and the insect CYP6 family (both of which are involved in xenobiotic metabolism) and to the insect CYP9 family (of unknown function). Induction of mRNA levels for three of the CYP28 cytochrome P450s by toxic host-plant allelochemicals (up to 11.5-fold) and phenobarbital (up to 49-fold) corroborates previous in vitro metabolism studies and suggests a potentially important role for the CYP28 family in determining patterns of insect–host-plant relationships through xenobiotic detoxification. PMID:9380713

Environmental Factors and Bioremediation of Xenobiotics Using White Rot Fungi

PubMed Central

Fragoeiro, Silvia; Bastos, Catarina

2010-01-01

This review provides background information on the importance of bioremediation approaches. It describes the roles of fungi, specifically white rot fungi, and their extracellular enzymes, laccases, ligninases, and peroxidises, in the degradation of xenobiotic compounds such as single and mixtures of pesticides. We discuss the importance of abiotic factors such as water potential, temperature, and pH stress when considering an environmental screening approach, and examples are provided of the differential effect of white rot fungi on the degradation of single and mixtures of pesticides using fungi such as Trametes versicolor and Phanerochaete chrysosporium. We also explore the formulation and delivery of fungal bioremedial inoculants to terrestrial ecosystems as well as the use of spent mushroom compost as an approach. Future areas for research and potential exploitation of new techniques are also considered. PMID:23956663

Protease inhibitor (PI) mediated defense in leaves and flowers of pigeonpea (protease inhibitor mediated defense in pigeonpea).

PubMed

Padul, Manohar V; Tak, Rajesh D; Kachole, Manvendra S

2012-03-01

More than 200 insect pests are found growing on pigeonpea. Insects lay eggs, attack and feed on leaves, flowers and developing pods. Plants have developed elaborate defenses against these insect pests. The present work evaluates protease inhibitor (PI) based defense of pigeonpea in leaves and flowers. PIs in the extracts of these tender tissues were detected by using gel X-ray film contact print method. Up to three PIs (PI-3, PI-4 and PI-5) were detected in these tissues as against nine (PI-1-PI-9) in mature seeds. PI-3 is the major component of these tissues. Mechanical wounding, insect chewing, fungal pathogenesis and application of salicylic acid induced PIs in pigeonpea in these tissues. Induction was found to be local as well as systemic but local response was stronger than systemic response. During both local and systemic induction, PI-3 appeared first. In spite of the presence and induction of PIs in these tender tissues and seeds farmers continue to suffer yield loses. This is due to the weak expression of PIs. However the ability of the plant to respond to external stimuli by producing defense proteins does not seem to be compromised. This study therefore indicates that PIs are components of both constitutive and inducible defense and provide a ground for designing stronger inducible defense (PIs or other insect toxin based) in pigeonpea. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Characteristics of a newly isolated fungus Geotrichum candidum Dec 1 with broad degradation spectrum of xenobiotic compounds.

PubMed

Shoda, M

2003-01-01

A newly isolated fungus, Geotrichum candidum Dec 1 (abbreviated as Dec 1), was found to have the ability to degrade many xenobiotic compounds such as synthetic dyes, food coloring agents, molasses, organic halogens, lignin and kraft pulp effluents. The broad spectrum of the degradation of these compounds are associated mainly with peroxidases produced by the fungus.

Report to Congress on the Strategic Defense Initiative, 1992

DTIC Science & Technology

1992-07-01

1.4.3 Shared View on Defenses .............................................................. 1-6 1.5 U.S. Contribution to a Global Defense System...including, in our view , that such defenses would not threaten existing deterrents--and the willingness of the U.S. to extend protection to allies...representing the central government as well as several Republics, the presentation was positively received. 1.4.3 Shared View on Defenses President

77 FR 76938 - Defense Federal Acquisition Regulation Supplement: Contracting Activity Updates (DFARS Case 2012...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-31

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 202 RIN 0750-AH81 Defense...: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is... has either a significant effect beyond the internal operating procedures of the agency issuing the...

Comparison of Intracellular "Ca. Endomicrobium Trichonymphae" Genomovars Illuminates the Requirement and Decay of Defense Systems against Foreign DNA.

PubMed

Izawa, Kazuki; Kuwahara, Hirokazu; Kihara, Kumiko; Yuki, Masahiro; Lo, Nathan; Itoh, Takehiko; Ohkuma, Moriya; Hongoh, Yuichi

2016-10-13

"Candidatus Endomicrobium trichonymphae" (Bacteria; Elusimicrobia) is an obligate intracellular symbiont of the cellulolytic protist genus Trichonympha in the termite gut. A previous genome analysis of "Ca Endomicrobium trichonymphae" phylotype Rs-D17 (genomovar Ri2008), obtained from a Trichonympha agilis cell in the gut of the termite Reticulitermes speratus, revealed that its genome is small (1.1 Mb) and contains many pseudogenes; it is in the course of reductive genome evolution. Here we report the complete genome sequence of another Rs-D17 genomovar, Ti2015, obtained from a different T. agilis cell present in an R. speratus gut. These two genomovars share most intact protein-coding genes and pseudogenes, showing 98.6% chromosome sequence similarity. However, characteristic differences were found in their defense systems, which comprised restriction-modification and CRISPR/Cas systems. The repertoire of intact restriction-modification systems differed between the genomovars, and two of the three CRISPR/Cas loci in genomovar Ri2008 are pseudogenized or missing in genomovar Ti2015. These results suggest relaxed selection pressure for maintaining these defense systems. Nevertheless, the remaining CRISPR/Cas system in each genomovar appears to be active; none of the "spacer" sequences (112 in Ri2008 and 128 in Ti2015) were shared whereas the "repeat" sequences were identical. Furthermore, we obtained draft genomes of three additional endosymbiotic Endomicrobium phylotypes from different host protist species, and discovered multiple, intact CRISPR/Cas systems in each genome. Collectively, unlike bacteriome endosymbionts in insects, the Endomicrobium endosymbionts of termite-gut protists appear to require defense against foreign DNA, although the required level of defense has likely been reduced during their intracellular lives. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

75 FR 59102 - Defense Federal Acquisition Regulation Supplement; Part 204, Administrative Matters

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... indexing methodology across DoD. This technical amendment adds language to the Defense Federal Acquisition... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 204 Defense Federal Acquisition Regulation Supplement; Part 204, Administrative Matters AGENCY: Defense Acquisition Regulations...

78 FR 63462 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [Docket Number DARS-2013-0035] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Organizational Conflict..., Department of Defense (DoD). ACTION: Notice and request for comments regarding a proposed extension of an...

Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver.

PubMed

Cavin, C; Marin-Kuan, M; Langouët, S; Bezençon, C; Guignard, G; Verguet, C; Piguet, D; Holzhäuser, D; Cornaz, R; Schilter, B

2008-04-01

Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB1). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB1-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB1 genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB1. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses.

76 FR 52139 - Defense Federal Acquisition Regulation Supplement; Government; Property (DFARS Case 2009-D008)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 201, 245, and 252 RIN...-D008) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule... Department of Defense as ineligible, debarred, or suspended from defense contracts; or (iv) Subject to denial...

Improving the Defense Acquisition System and Reducing System Costs

DTIC Science & Technology

1981-03-30

The need for this specific commitment results from the competition among the conflicting objectives of high perform- ance, lower cost, shorter... conflict with initiatives to improve reliability and support. Whereas the fastest acquisition approach involves initiating production prxor to...their Individual thrusts result in confusion on the part of OASD who tries to implement conflicting programs, and of defense contractors performing

The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early Defense Responses to Effectively Nodulate Soybean.

PubMed

Jiménez-Guerrero, Irene; Pérez-Montaño, Francisco; Monreal, José Antonio; Preston, Gail M; Fones, Helen; Vioque, Blanca; Ollero, Francisco Javier; López-Baena, Francisco Javier

2015-07-01

Plants that interact with pathogenic bacteria in their natural environments have developed barriers to block or contain the infection. Phytopathogenic bacteria have evolved mechanisms to subvert these defenses and promote infection. Thus, the type 3 secretion system (T3SS) delivers bacterial effectors directly into the plant cells to alter host signaling and suppress defenses, providing an appropriate environment for bacterial multiplication. Some rhizobial strains possess a symbiotic T3SS that seems to be involved in the suppression of host defenses to promote nodulation and determine the host range. In this work, we show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS negatively affects soybean nodulation in the early stages of the symbiotic process, which is associated with a reduction of the expression of early nodulation genes. This symbiotic phenotype could be the consequence of the bacterial triggering of soybean defense responses associated with the production of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these responses. Interestingly, the early induction of the transcription of GmMPK4, which negatively regulates SA accumulation and defense responses in soybean via WRKY33, could be associated with the differential defense responses induced by the parental and the T3SS mutant strain.

75 FR 25165 - Defense Federal Acquisition Regulation Supplement; Cost and Software Data Reporting System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-07

... 215, 234, 242, and 252 Defense Federal Acquisition Regulation Supplement; Cost and Software Data... Regulation Supplement (DFARS) to set forth DoD Cost and Software Data Reporting system requirements for major... set forth the DoD requirement for offerors to: Describe the standard Cost and Software Data Reporting...

Confinement of Radioactive Materials at Defense Nuclear Facilities

DTIC Science & Technology

2004-10-01

The design of defense nuclear facilities includes systems whose reliable operation is vital to the protection of the public, workers, and the...final safety-class barrier to the release of hazardous materials with potentially serious public consequences. The Defense Nuclear Facilities Safety...the public at certain defense nuclear facilities . This change has resulted in downgrading of the functional safety classification of confinement

Coevolutionary arms race versus host defense chase in a tropical herbivore-plant system.

PubMed

Endara, María-José; Coley, Phyllis D; Ghabash, Gabrielle; Nicholls, James A; Dexter, Kyle G; Donoso, David A; Stone, Graham N; Pennington, R Toby; Kursar, Thomas A

2017-09-05

Coevolutionary models suggest that herbivores drive diversification and community composition in plants. For herbivores, many questions remain regarding how plant defenses shape host choice and community structure. We addressed these questions using the tree genus Inga and its lepidopteran herbivores in the Amazon. We constructed phylogenies for both plants and insects and quantified host associations and plant defenses. We found that similarity in herbivore assemblages between Inga species was correlated with similarity in defenses. There was no correlation with phylogeny, a result consistent with our observations that the expression of defenses in Inga is independent of phylogeny. Furthermore, host defensive traits explained 40% of herbivore community similarity. Analyses at finer taxonomic scales showed that different lepidopteran clades select hosts based on different defenses, suggesting taxon-specific histories of herbivore-host plant interactions. Finally, we compared the phylogeny and defenses of Inga to phylogenies for the major lepidopteran clades. We found that closely related herbivores fed on Inga with similar defenses rather than on closely related plants. Together, these results suggest that plant defenses might be more evolutionarily labile than the herbivore traits related to host association. Hence, there is an apparent asymmetry in the evolutionary interactions between Inga and its herbivores. Although plants may evolve under selection by herbivores, we hypothesize that herbivores may not show coevolutionary adaptations, but instead "chase" hosts based on the herbivore's own traits at the time that they encounter a new host, a pattern more consistent with resource tracking than with the arms race model of coevolution.

Coevolutionary arms race versus host defense chase in a tropical herbivore–plant system

PubMed Central

Coley, Phyllis D.; Ghabash, Gabrielle; Nicholls, James A.; Donoso, David A.; Stone, Graham N.; Pennington, R. Toby; Kursar, Thomas A.

2017-01-01

Coevolutionary models suggest that herbivores drive diversification and community composition in plants. For herbivores, many questions remain regarding how plant defenses shape host choice and community structure. We addressed these questions using the tree genus Inga and its lepidopteran herbivores in the Amazon. We constructed phylogenies for both plants and insects and quantified host associations and plant defenses. We found that similarity in herbivore assemblages between Inga species was correlated with similarity in defenses. There was no correlation with phylogeny, a result consistent with our observations that the expression of defenses in Inga is independent of phylogeny. Furthermore, host defensive traits explained 40% of herbivore community similarity. Analyses at finer taxonomic scales showed that different lepidopteran clades select hosts based on different defenses, suggesting taxon-specific histories of herbivore–host plant interactions. Finally, we compared the phylogeny and defenses of Inga to phylogenies for the major lepidopteran clades. We found that closely related herbivores fed on Inga with similar defenses rather than on closely related plants. Together, these results suggest that plant defenses might be more evolutionarily labile than the herbivore traits related to host association. Hence, there is an apparent asymmetry in the evolutionary interactions between Inga and its herbivores. Although plants may evolve under selection by herbivores, we hypothesize that herbivores may not show coevolutionary adaptations, but instead “chase” hosts based on the herbivore’s own traits at the time that they encounter a new host, a pattern more consistent with resource tracking than with the arms race model of coevolution. PMID:28827317

A Systems Approach to Finding Cost-Effective Alternatives to European Ballistic Missile Defense

DTIC Science & Technology

2013-09-01

has holes in its ability to cover the entire region as required. What are the existing approaches to ballistic missile defense in Europe? 4. What Are...however, this report focuses on ballistic missiles which use stellar or inertial guidance systems which are not subject to electromagnetic...location as the Baseline system (35.6° N, 32.5° E) while the other was placed north of Turkey in the Black Sea (41.5° N, 38.1° E). Each Aegis ship was

Total Quality Management in the Department of Defense

DTIC Science & Technology

1989-09-01

DTI ELECT SDu TOTAL QUALITY MANAGEMENT IN THE DEPARTMENT OF DEFENSE THESIS BRUCE E. SPRINGS, B.S. CAPTAIN, USAF AFIT/GLN/LSR/ 89S -57 I1- DEPARTMENT...13 0 3 AFIT/GLM/LSR/89S-57 TOTAL QUALITY MANAGEMENT IN THE DEPARTMENT OF DEFENSE THESIS BRUCE E. SPRINGS, B.S. CAPTAIN, USAF AFIT/GLH/LSR/89S-57...Defense. # AFIT/GLM/LSR/89S-57 TOTAL QUALITY MANAGEMENT IN THE DEPARTMENT OF DEFENSE THESIS Presented to the Faculty of the School of Systems and Logistics

Effects of Gain/Loss Framing in Cyber Defense Decision-Making

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

Bos, Nathan; Paul, Celeste; Gersh, John

Cyber defense requires decision making under uncertainty. Yet this critical area has not been a strong focus of research in judgment and decision-making. Future defense systems, which will rely on software-defined networks and may employ ‘moving target’ defenses, will increasingly automate lower level detection and analysis, but will still require humans in the loop for higher level judgment. We studied the decision making process and outcomes of 17 experienced network defense professionals who worked through a set of realistic network defense scenarios. We manipulated gain versus loss framing in a cyber defense scenario, and found significant effects in one ofmore » two focal problems. Defenders that began with a network already in quarantine (gain framing) used a quarantine system more than those that did not (loss framing). We also found some difference in perceived workload and efficacy. Alternate explanations of these findings and implications for network defense are discussed.« less

Defense Science Board Task Force Report on Cyber Defense Management

DTIC Science & Technology

2016-09-01

manage cyber security is often a verymanual and labor intensive process. When a crisis hits, DoD responses range from highly automatedand instrumented...DSB Task Force Report on Cyber Defense Management September 2016 (U) This page intentionally blank REPORT OF THE DEFENSE SCIENCE BOARD STUDY ON Cyber ...DEFENSE FOR ACQUISITION, TECHNOLOGY & LOGISTICS SUBJECT: Final Report of the Defense Science Board (DSB) Task Force on Cyber Defense Management I am

Plant innate immunity: an updated insight into defense mechanism.

PubMed

Muthamilarasan, Mehanathan; Prasad, Manoj

2013-06-01

Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and effector-triggered immunity (ETI). MTI confers basal resistance, while ETI confers durable resistance, often resulting in hypersensitive response. Plants also possess systemic acquired resistance (SAR), which provides long-term defense against a broad-spectrum of pathogens. Salicylic-acid-mediated systemic acquired immunity provokes the defense response throughout the plant system during pathogen infection at a particular site. Trans-generational immune priming allows the plant to heritably shield their progeny towards pathogens previously encountered. Plants circumvent the viral infection through RNA interference phenomena by utilizing small RNAs. This review summarizes the molecular mechanisms of plant immune system, and the latest breakthroughs reported in plant defense. We discuss the plant–pathogen interactions and integrated defense responses in the context of presenting an integral understanding in plant molecular immunity.

Department of Defense high power laser program guidance

NASA Astrophysics Data System (ADS)

Muller, Clifford H.

1994-06-01

The DoD investment of nominally $200 million per year is focused on four high power laser (HPL) concepts: Space-Based Laser (SBL), a Ballistic Missile Defense Organization effort that addresses boost-phase intercept for Theater Missile Defense and National Missile Defense; Airborne Laser (ABL), an Air Force effort that addresses boost-phase intercept for Theater Missile Defense; Ground-Based Laser (GBL), an Air Force effort addressing space control; and Anti-Ship Missile Defense (ASMD), a Navy effort addressing ship-based defense. Each organization is also supporting technology development with the goal of achieving less expensive, brighter, and lighter high power laser systems. These activities represent the building blocks of the DoD program to exploit the compelling characteristics of the high power laser. Even though DoD's HPL program are focused and moderately strong, additional emphasis in a few technical areas could help reduce risk in these programs. In addition, a number of options are available for continuing to use the High-Energy Laser System Test Facility (HELSTF) at White Sands Missile Range. This report provides a brief overview and guidance for the five efforts which comprise the DoD HPL program (SBL, ABL, GBL, ASMD, HELSTF).

Multi-Objective Optimization of System Capability Satisficing in Defense Acquisition

DTIC Science & Technology

2012-04-30

sponsored by the USD(AT&L). Second, we issue an annual internal call for proposals to seek NPS faculty research supporting the interests of our...program sponsors. Finally, we serve as a “broker” to market specific research topics identified by our sponsors to NPS graduate students. This three...expanding the technology readiness level within defense acquisition. International Journal of Defense Acquisition Management, 1, 39–58. Tan, W

DELFIC: Department of Defense Fallout Prediction System. Volume I - Fundamentals

DTIC Science & Technology

1979-12-31

102 H2590D. DTIC•;. 17.) 1 i{1•ELECT ’ Prepared for " JAUG 2 ? 1980 Director DEFENSE NUCLEAR AGENCY B Wai’hington, D. C. 20305 808 1O8x Destroy this...2 1. INTRODUCTION AND OVERVIEW -- --- - -------------- - --- ---- 7 2. INITIALIZATION AND CLOUD RISE...61 6 1. INTRODUCTION AND OVERVIEW DELFIC (DEfense Land Fallout Interpretative Code) is intended for re- search in local nuclear fallout

76 FR 8303 - Defense Federal Acquisition Regulation Supplement; Award-Fee Contracts (DFARS Case 2006-D021)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-14

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 216 and 252 RIN 0750...) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY... Regulations System, OUSD (AT&L) DPAP/DARS, 3060 Defense Pentagon, Room 3B855, Washington, DC 20301-3060...

Ground-Based Missile Defense (National Missile Defense): Is It Feasible?

DTIC Science & Technology

2004-03-19

Westview Press), 191. 47 Ibid. 192. 48 Dr. Nicholas Berry, National Missile Defense: What Does It All Mean ? National Missile Defense: Views from Asia...153. 18 19 BIBLIOGRAPHY Berry, Nicholas. National Missile Defense: What Does It All Mean ? National Missile Defense: Views from Asia, Center for

Functioning of Microsomal Cytochrome P450s: Murburn Concept Explains the Metabolism of Xenobiotics in Hepatocytes.

PubMed

Manoj, Kelath Murali; Parashar, Abhinav; Gade, Sudeep K; Venkatachalam, Avanthika

2016-01-01

Using oxygen and NADPH, the redox enzymes cytochrome P450 (CYP) and its reductase (CPR) work in tandem to carry out the phase I metabolism of a vast majority of drugs and xenobiotics. As per the erstwhile understanding of the catalytic cycle, binding of the substrate to CYP's heme distal pocket allows CPR to pump electrons through a CPR-CYP complex. In turn, this trigger (a thermodynamic push of electrons) leads to the activation of oxygen at CYP's heme-center, to give Compound I, a two-electron deficient enzyme reactive intermediate. The formation of diffusible radicals and reactive oxygen species (DROS, hitherto considered an undesired facet of the system) was attributed to the heme-center. Recently, we had challenged these perceptions and proposed the murburn ("mured burning" or "mild unrestricted burning") concept to explain heme enzymes' catalytic mechanism, electron-transfer phenomena and the regulation of redox equivalents' consumption. Murburn concept incorporates a one-electron paradigm, advocating obligatory roles for DROS. The new understanding does not call for high-affinity substrate-binding at the heme distal pocket of the CYP (the first and the most crucial step of the erstwhile paradigm) or CYP-CPR protein-protein complexations (the operational backbone of the erstwhile cycle). Herein, the dynamics of reduced nicotinamide nucleotides' consumption, peroxide formation and depletion, product(s) formation, etc. was investigated with various controls, by altering reaction variables, environments and through the incorporation of diverse molecular probes. In several CYP systems, control reactions lacking the specific substrate showed comparable or higher peroxide in milieu, thereby discrediting the foundations of the erstwhile hypothesis. The profiles obtained by altering CYP:CPR ratios and the profound inhibitions observed upon the incorporation of catalytic amounts of horseradish peroxidase confirm the obligatory roles of DROS in milieu, ratifying

77 FR 2653 - Defense Federal Acquisition Regulation Supplement; Pilot Program for Acquisition of Military...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 212 and 252 RIN 0750-AH27 Defense Federal Acquisition Regulation Supplement; Pilot Program for Acquisition of Military-Purpose Nondevelopmental Items (DFARS Case 2011-D034) AGENCY: Defense Acquisition Regulations System...

Good neighbors make good defenses: associational refuges reduce defense investment in African savanna plants.

PubMed

Coverdale, Tyler C; Goheen, Jacob R; Palmer, Todd M; Pringle, Robert M

2018-06-25

Intraspecific variation in plant defense phenotype is common and has wide-ranging ecological consequences. Yet prevailing theories of plant defense allocation, which primarily account for interspecific differences in defense phenotype, often fail to predict intraspecific patterns. Furthermore, although individual variation in defense phenotype is often attributed to ecological interactions, few general mechanisms have been proposed to explain the ubiquity of variable defense phenotype within species. Here, we show experimentally that associational refuges and induced resistance interact to create predictable intraspecific variation in defense phenotype in African savanna plants. Physically defended species from four families (Acanthaceae, Asparagaceae, Cactaceae, and Solanaceae) growing in close association with spinescent Acacia trees had 39-78% fewer spines and thorns than did isolated conspecifics. For a subset of these species, we used a series of manipulative experiments to show that this variability is maintained primarily by a reduction in induced responses among individuals that seldom experience mammalian herbivory, whether due to association with Acacia trees or to experimental herbivore exclusion. Unassociated plants incurred 4- to 16-fold more browsing damage than did associated individuals and increased spine density by 16-38% within one month following simulated browsing. In contrast, experimental clipping induced no net change in spine density among plants growing beneath Acacia canopies or inside long-term herbivore exclosures. Associated and unassociated individuals produced similar numbers of flowers and seeds, but seedling recruitment and survival were vastly greater in refuge habitats, suggesting a net fitness benefit of association. We conclude that plant-plant associations consistently decrease defense investment in this system by reducing both the frequency of herbivory and the intensity of induced responses, and that inducible responses

Assistant Secretary of Defense for Homeland Defense and Global Security

Science.gov Websites

Defense for Policy ASD for Asian and Pacific Security Affairs ASD for Homeland Defense Global Security Special Operations/Low-Intensity Conflict Counternarcotics and Global Threats Stability and Humanitarian HomeOUSDP OfficesASD for Homeland Defense Global Security Assistant Secretary of Defense for Homeland

76 FR 13297 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... 215 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations System... Director, Defense Procurement and Acquisition Policy. DATES: Effective Date: March 11, 2011. Applicability... adding a section at 215.300 with a reference to Director, Defense Procurement and Acquisition Policy...

75 FR 75444 - Defense Federal Acquisition Regulation Supplement; Government Property (DFARS Case 2009-D008)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-03

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 201, 245, and 252 RIN...-D008) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Proposed... demilitarization shall be demilitarized by the Purchaser under the supervision of qualified Department of Defense...

78 FR 19467 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [Docket Number DARS-2013-0010... Mentor-Prot[eacute]g[eacute] Program AGENCY: Defense Acquisition Regulations System, Department of... Collection DFARS Appendix I-112.2(a)-(d) requires mentor firms to report on the progress made under active...

76 FR 6006 - Defense Federal Acquisition Regulation Supplement; Reporting of Government Property Lost, Stolen...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 245 and 252 [DFARS Case 2008-D049] RIN 0750-AG64 Defense Federal Acquisition Regulation Supplement; Reporting of Government Property Lost, Stolen, Damaged, or Destroyed AGENCY: Defense Acquisition Regulations System; Department of...

Type III secretion system effector proteins: double agents in bacterial disease and plant defense.

PubMed

Alfano, James R; Collmer, Alan

2004-01-01

Many phytopathogenic bacteria inject virulence effector proteins into plant cells via a Hrp type III secretion system (TTSS). Without the TTSS, these pathogens cannot defeat basal defenses, grow in plants, produce disease lesions in hosts, or elicit the hypersensitive response (HR) in nonhosts. Pathogen genome projects employing bioinformatic methods to identify TTSS Hrp regulon promoters and TTSS pathway targeting signals suggest that phytopathogenic Pseudomonas, Xanthomonas, and Ralstonia spp. harbor large arsenals of effectors. The Hrp TTSS employs customized cytoplasmic chaperones, conserved export components in the bacterial envelope (also used by the TTSS of animal pathogens), and a more specialized set of TTSS-secreted proteins to deliver effectors across the plant cell wall and plasma membrane. Many effectors can act as molecular double agents that betray the pathogen to plant defenses in some interactions and suppress host defenses in others. Investigations of the functions of effectors within plant cells have demonstrated the plasma membrane and nucleus as subcellular sites for several effectors, revealed some effectors to possess cysteine protease or protein tyrosine phosphatase activity, and provided new clues to the coevolution of bacterium-plant interactions.

The science, technology, and politics of ballistic missile defense

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

Coyle, Philip E.

America's missile defense systems are deployed at home and abroad. This includes the Groundbased Missile Defense (GMD) system in Alaska and California, the Phased Adaptive Approach in Europe (EPAA), and regional systems in the Middle East and Asia. Unfortunately these systems lack workable architectures, and many of the required elements either don't work or are missing. Major review and reconsideration is needed of all elements of these systems. GMD performance in tests has gotten worse with time, when it ought to be getting better. A lack of political support is not to blame as the DoD spends about $10 billionmore » per year, and proposes to add about $5 billion over the next five years. Russia objects to the EPAA as a threat to its ICBM forces, and to the extensive deployment of U.S. military forces in countries such as Poland, the Czech Republic and Romania, once part of the Soviet Union. Going forward the U.S. should keep working with Russia whose cooperation will be key to diplomatic gains in the Middle East and elsewhere. Meanwhile, America's missile defenses face an enduring set of issues, especially target discrimination in the face of attacks designed to overwhelm the defenses, stage separation debris, chaff, decoys, and stealth. Dealing with target discrimination while also replacing, upgrading, or adding to the many elements of U.S. missiles defenses presents daunting budget priorities. A new look at the threat is warranted, and whether the U.S. needs to consider every nation that possesses even short-range missiles a threat to America. The proliferation of missiles of all sizes around the world is a growing problem, but expecting U.S. missile defenses to deal with all those missiles everywhere is unrealistic, and U.S. missile defenses, effective or not, are justifying more and more offensive missiles.« less

The science, technology, and politics of ballistic missile defense

NASA Astrophysics Data System (ADS)

Coyle, Philip E.

2014-05-01

America's missile defense systems are deployed at home and abroad. This includes the Groundbased Missile Defense (GMD) system in Alaska and California, the Phased Adaptive Approach in Europe (EPAA), and regional systems in the Middle East and Asia. Unfortunately these systems lack workable architectures, and many of the required elements either don't work or are missing. Major review and reconsideration is needed of all elements of these systems. GMD performance in tests has gotten worse with time, when it ought to be getting better. A lack of political support is not to blame as the DoD spends about 10 billion per year, and proposes to add about 5 billion over the next five years. Russia objects to the EPAA as a threat to its ICBM forces, and to the extensive deployment of U.S. military forces in countries such as Poland, the Czech Republic and Romania, once part of the Soviet Union. Going forward the U.S. should keep working with Russia whose cooperation will be key to diplomatic gains in the Middle East and elsewhere. Meanwhile, America's missile defenses face an enduring set of issues, especially target discrimination in the face of attacks designed to overwhelm the defenses, stage separation debris, chaff, decoys, and stealth. Dealing with target discrimination while also replacing, upgrading, or adding to the many elements of U.S. missiles defenses presents daunting budget priorities. A new look at the threat is warranted, and whether the U.S. needs to consider every nation that possesses even short-range missiles a threat to America. The proliferation of missiles of all sizes around the world is a growing problem, but expecting U.S. missile defenses to deal with all those missiles everywhere is unrealistic, and U.S. missile defenses, effective or not, are justifying more and more offensive missiles.

Defense Strategies for Asymmetric Networked Systems with Discrete Components.

PubMed

Rao, Nageswara S V; Ma, Chris Y T; Hausken, Kjell; He, Fei; Yau, David K Y; Zhuang, Jun

2018-05-03

We consider infrastructures consisting of a network of systems, each composed of discrete components. The network provides the vital connectivity between the systems and hence plays a critical, asymmetric role in the infrastructure operations. The individual components of the systems can be attacked by cyber and physical means and can be appropriately reinforced to withstand these attacks. We formulate the problem of ensuring the infrastructure performance as a game between an attacker and a provider, who choose the numbers of the components of the systems and network to attack and reinforce, respectively. The costs and benefits of attacks and reinforcements are characterized using the sum-form, product-form and composite utility functions, each composed of a survival probability term and a component cost term. We present a two-level characterization of the correlations within the infrastructure: (i) the aggregate failure correlation function specifies the infrastructure failure probability given the failure of an individual system or network, and (ii) the survival probabilities of the systems and network satisfy first-order differential conditions that capture the component-level correlations using multiplier functions. We derive Nash equilibrium conditions that provide expressions for individual system survival probabilities and also the expected infrastructure capacity specified by the total number of operational components. We apply these results to derive and analyze defense strategies for distributed cloud computing infrastructures using cyber-physical models.

Defense Strategies for Asymmetric Networked Systems with Discrete Components

PubMed Central

Rao, Nageswara S. V.; Ma, Chris Y. T.; Hausken, Kjell; He, Fei; Yau, David K. Y.

2018-01-01

We consider infrastructures consisting of a network of systems, each composed of discrete components. The network provides the vital connectivity between the systems and hence plays a critical, asymmetric role in the infrastructure operations. The individual components of the systems can be attacked by cyber and physical means and can be appropriately reinforced to withstand these attacks. We formulate the problem of ensuring the infrastructure performance as a game between an attacker and a provider, who choose the numbers of the components of the systems and network to attack and reinforce, respectively. The costs and benefits of attacks and reinforcements are characterized using the sum-form, product-form and composite utility functions, each composed of a survival probability term and a component cost term. We present a two-level characterization of the correlations within the infrastructure: (i) the aggregate failure correlation function specifies the infrastructure failure probability given the failure of an individual system or network, and (ii) the survival probabilities of the systems and network satisfy first-order differential conditions that capture the component-level correlations using multiplier functions. We derive Nash equilibrium conditions that provide expressions for individual system survival probabilities and also the expected infrastructure capacity specified by the total number of operational components. We apply these results to derive and analyze defense strategies for distributed cloud computing infrastructures using cyber-physical models. PMID:29751588

Hepatic Xenobiotic Metabolizing Enzyme Gene Expression ...

EPA Pesticide Factsheets

BACKGROUND: Differences in responses to environmental chemicals and drugs between life stages are likely due in part to differences in the expression of xenobiotic metabolizing enzymes and transporters (XMETs). No comprehensive analysis of the mRNA expression of XMETs has been carried out through life stages in any species. RESULTS: Using full-genome arrays, the mRNA expression of all XMETs and their regulatory proteins was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND32), middle age (12 months), and old age (18 and 24 months) in the C57BL/6J (C57) mouse liver and compared to adults. Fetal and neonatal life stages exhibited dramatic differences in XMET mRNA expression compared to the relatively minor effects of old age. The total number of XMET probe sets that differed from adults was 636, 500, 84, 5, 43, and 102 for GD19, PND7, PND32, 12 months, 18 months and 24 months, respectively. At all life stages except PND32, under-expressed genes outnumbered over-expressed genes. The altered XMETs included those in all of the major metabolic and transport phases including introduction of reactive or polar groups (Phase I), conjugation (Phase II) and excretion (Phase III). In the fetus and neonate, parallel increases in expression were noted in the dioxin receptor, Nrf2 components and their regulated genes while nuclear receptors and regulated genes were generally down-regulated. Suppression of male-specific XMETs w

CRISPR-Cas Defense System and Potential Prophages in Cyanobacteria Associated with the Coral Black Band Disease

PubMed Central

Buerger, Patrick; Wood-Charlson, Elisha M.; Weynberg, Karen D.; Willis, Bette L.; van Oppen, Madeleine J. H.

2016-01-01

Understanding how pathogens maintain their virulence is critical to developing tools to mitigate disease in animal populations. We sequenced and assembled the first draft genome of Roseofilum reptotaenium AO1, the dominant cyanobacterium underlying pathogenicity of the virulent coral black band disease (BBD), and analyzed parts of the BBD-associated Geitlerinema sp. BBD_1991 genome in silico. Both cyanobacteria are equipped with an adaptive, heritable clustered regularly interspaced short palindromic repeats (CRISPR)-Cas defense system type I-D and have potential virulence genes located within several prophage regions. The defense system helps to prevent infection by viruses and mobile genetic elements via identification of short fingerprints of the intruding DNA, which are stored as templates in the bacterial genome, in so-called “CRISPRs.” Analysis of CRISPR target sequences (protospacers) revealed an unusually high number of self-targeting spacers in R. reptotaenium AO1 and extraordinary long CRIPSR arrays of up to 260 spacers in Geitlerinema sp. BBD_1991. The self-targeting spacers are unlikely to be a form of autoimmunity; instead these target an incomplete lysogenic bacteriophage. Lysogenic virus induction experiments with mitomycin C and UV light did not reveal an actively replicating virus population in R. reptotaenium AO1 cultures, suggesting that phage functionality is compromised or excision could be blocked by the CRISPR-Cas system. Potential prophages were identified in three regions of R. reptotaenium AO1 and five regions of Geitlerinema sp. BBD_1991, containing putative BBD relevant virulence genes, such as an NAD-dependent epimerase/dehydratase (a homolog in terms of functionality to the third and fourth most expressed gene in BBD), lysozyme/metalloendopeptidases and other lipopolysaccharide modification genes. To date, viruses have not been considered to be a component of the BBD consortium or a contributor to the virulence of R. reptotaenium

CRISPR-Cas Defense System and Potential Prophages in Cyanobacteria Associated with the Coral Black Band Disease.

PubMed

Buerger, Patrick; Wood-Charlson, Elisha M; Weynberg, Karen D; Willis, Bette L; van Oppen, Madeleine J H

2016-01-01

Understanding how pathogens maintain their virulence is critical to developing tools to mitigate disease in animal populations. We sequenced and assembled the first draft genome of Roseofilum reptotaenium AO1, the dominant cyanobacterium underlying pathogenicity of the virulent coral black band disease (BBD), and analyzed parts of the BBD-associated Geitlerinema sp. BBD_1991 genome in silico . Both cyanobacteria are equipped with an adaptive, heritable clustered regularly interspaced short palindromic repeats (CRISPR)-Cas defense system type I-D and have potential virulence genes located within several prophage regions. The defense system helps to prevent infection by viruses and mobile genetic elements via identification of short fingerprints of the intruding DNA, which are stored as templates in the bacterial genome, in so-called "CRISPRs." Analysis of CRISPR target sequences (protospacers) revealed an unusually high number of self-targeting spacers in R. reptotaenium AO1 and extraordinary long CRIPSR arrays of up to 260 spacers in Geitlerinema sp. BBD_1991. The self-targeting spacers are unlikely to be a form of autoimmunity; instead these target an incomplete lysogenic bacteriophage. Lysogenic virus induction experiments with mitomycin C and UV light did not reveal an actively replicating virus population in R. reptotaenium AO1 cultures, suggesting that phage functionality is compromised or excision could be blocked by the CRISPR-Cas system. Potential prophages were identified in three regions of R. reptotaenium AO1 and five regions of Geitlerinema sp. BBD_1991, containing putative BBD relevant virulence genes, such as an NAD-dependent epimerase/dehydratase (a homolog in terms of functionality to the third and fourth most expressed gene in BBD), lysozyme/metalloendopeptidases and other lipopolysaccharide modification genes. To date, viruses have not been considered to be a component of the BBD consortium or a contributor to the virulence of R. reptotaenium AO1

75 FR 20954 - Defense Federal Acquisition Regulation Supplement; Organizational Conflicts of Interest in Major...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 202, 203, 212, and 252 RIN 0750-AG63 Defense Federal Acquisition Regulation Supplement; Organizational Conflicts of Interest... System, Department of Defense (DoD). ACTION: Proposed rule with request for comments. SUMMARY: DoD is...

Hitting the sweet spot-glycans as targets of fungal defense effector proteins.

PubMed

Künzler, Markus

2015-05-06

Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparably low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between different antagonists of a specific taxon or, if possible, even of different taxa. In order to restrict the activity of the defense effector molecules to physiologically relevant taxa, these target epitopes should, on the other hand, be taxon-specific and easily accessible. Glycans fulfill all these requirements and are therefore a preferred target of defense effector molecules, in particular defense proteins. Here, we review this defense strategy using the example of the defense system of multicellular (filamentous) fungi against microbial competitors and animal predators.

Two Horizontally Transferred Xenobiotic Resistance Gene Clusters Associated with Detoxification of Benzoxazolinones by Fusarium Species

PubMed Central

Glenn, Anthony E.; Davis, C. Britton; Gao, Minglu; Gold, Scott E.; Mitchell, Trevor R.; Proctor, Robert H.; Stewart, Jane E.; Snook, Maurice E.

2016-01-01

Microbes encounter a broad spectrum of antimicrobial compounds in their environments and often possess metabolic strategies to detoxify such xenobiotics. We have previously shown that Fusarium verticillioides, a fungal pathogen of maize known for its production of fumonisin mycotoxins, possesses two unlinked loci, FDB1 and FDB2, necessary for detoxification of antimicrobial compounds produced by maize, including the γ-lactam 2-benzoxazolinone (BOA). In support of these earlier studies, microarray analysis of F. verticillioides exposed to BOA identified the induction of multiple genes at FDB1 and FDB2, indicating the loci consist of gene clusters. One of the FDB1 cluster genes encoded a protein having domain homology to the metallo-β-lactamase (MBL) superfamily. Deletion of this gene (MBL1) rendered F. verticillioides incapable of metabolizing BOA and thus unable to grow on BOA-amended media. Deletion of other FDB1 cluster genes, in particular AMD1 and DLH1, did not affect BOA degradation. Phylogenetic analyses and topology testing of the FDB1 and FDB2 cluster genes suggested two horizontal transfer events among fungi, one being transfer of FDB1 from Fusarium to Colletotrichum, and the second being transfer of the FDB2 cluster from Fusarium to Aspergillus. Together, the results suggest that plant-derived xenobiotics have exerted evolutionary pressure on these fungi, leading to horizontal transfer of genes that enhance fitness or virulence. PMID:26808652

Study of the measurement of defense style using Bond's Defense Style Questionnaire.

PubMed

Nishimura, R

1998-08-01

Two hundred and seventy healthy university students were surveyed in December 1995 using Bond's Defense Style Questionnaire (DSQ) to measure the subjects' defense mechanisms. At the same time, a survey using Byrne's R-S Scale (Repression-Sensitization Scale) of the MMPI (Minnesota multiphasic personality inventory) and five psychiatric symptom indexes (anxiety, sense of inadequacy, sensitivity, depression and impulsive anger) selected from the CMI (Cornell Medical Index-Health Questionnaire) was conducted. Three factors were extracted from the DSQ through factor analysis: immature defenses, neurotic defenses, and mature defenses. The results of analysis of variance revealed the following: (i) for anxiety and anxiety related symptoms, both immature defenses and neurotic defenses indicated principal effect; (ii) for impulsive anger and depression, immature defenses presented principal effect; and (iii) for sensitivity and impulsive anger, interaction between a mature defense style and neurotic defense style was noted. The relationship between defense styles and psychiatric symptoms in healthy people is studied in this paper.

Xenobiotic Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes Modulated by ToxCast Chemicals

EPA Science Inventory

ToxCast chemicals were assessed for induction or suppression of xenobiotic metabolizing enzyme and transporter gene expression using primary human hepatocytes. The mRNA levels of 14 target and 2 control genes were measured: ABCB1, ABCB11, ABCG2, SLCO1B1, CYP1A1, CYP1A2, CYP2B6, C...

The evolution of a teledentistry system within the Department of Defense.

PubMed Central

Rocca, M. A.; Kudryk, V. L.; Pajak, J. C.; Morris, T.

1999-01-01

Total Dental Access (TDA) is the teledentistry project within the Department of Defense. This project enables referring dentists from the US Armed Forces to consult with specialists on the status of a patient. TDA focuses on three areas of dentistry: patient care, continuing education and dentist-laboratory communications. One of the goals of this project is to increase patient access to quality dental care. The other goal is to establish a cost effective telemedicine system. This paper describes the evolution of a teledentistry system, the main features of POTS-based, ISDN-based and Web-based systems used, advantages, disadvantages and cost-effectiveness of these systems. Data has been collected on the frequency of use, technical problems occurred, avoided patient or specialist travel and the total number of consults. A cost-effectiveness analysis has been conducted on the data collected. The results of this analysis will be presented. PMID:10566495

The evolution of a teledentistry system within the Department of Defense.

PubMed

Rocca, M A; Kudryk, V L; Pajak, J C; Morris, T

1999-01-01

Total Dental Access (TDA) is the teledentistry project within the Department of Defense. This project enables referring dentists from the US Armed Forces to consult with specialists on the status of a patient. TDA focuses on three areas of dentistry: patient care, continuing education and dentist-laboratory communications. One of the goals of this project is to increase patient access to quality dental care. The other goal is to establish a cost effective telemedicine system. This paper describes the evolution of a teledentistry system, the main features of POTS-based, ISDN-based and Web-based systems used, advantages, disadvantages and cost-effectiveness of these systems. Data has been collected on the frequency of use, technical problems occurred, avoided patient or specialist travel and the total number of consults. A cost-effectiveness analysis has been conducted on the data collected. The results of this analysis will be presented.

Cyber Defense Management

DTIC Science & Technology

2016-09-01

manage cyber security is often a verymanual and labor intensive process. When a crisis hits, DoD responses range from highly automatedand instrumented...DSB Task Force Report on Cyber Defense Management September 2016 (U) This page intentionally blank REPORT OF THE DEFENSE SCIENCE BOARD STUDY ON Cyber ...DEFENSE FOR ACQUISITION, TECHNOLOGY & LOGISTICS SUBJECT: Final Report of the Defense Science Board (DSB) Task Force on Cyber Defense Management I am

A Model of an Integrated Air Defense System (IADS) for the TACOPS program

DTIC Science & Technology

1991-09-01

SUBJECT TERMS (Continue on reverse If necessary and Identify by block number) FIELD GROUP SUB-GROUP Integrated Air Defense System, iADS, TACOPS...needed. Selection criteria for picking a Measurement Of Effectiveness (MOE) are presented. Acceslon For I NTIS CRA&I DTIC TAB 0 Unannouticed 1 ...Justification B y ............................................... Di.,t ibiation Av.iabilily Codes Avai i:.djor Dist A- 1 THESIS DISCLAIMER The reader is cautioned

Effects of parasite pressure on parasite mortality and reproductive output in a rodent-flea system: inferring host defense trade-offs.

PubMed

Warburton, Elizabeth M; Kam, Michael; Bar-Shira, Enav; Friedman, Aharon; Khokhlova, Irina S; Koren, Lee; Asfur, Mustafa; Geffen, Eli; Kiefer, Daniel; Krasnov, Boris R; Degen, A Allan

2016-09-01

Evaluating host resistance via parasite fitness helps place host-parasite relationships within evolutionary and ecological contexts; however, few studies consider both these processes simultaneously. We investigated how different levels of parasite pressure affect parasite mortality and reproductive success in relationship to host defense efforts, using the rodent Gerbillus nanus and the flea Xenopsylla conformis as a host-parasite system. Fifteen immune-naïve male rodents were infested with 20, 50, or 100 fleas for four weeks. During this time number of new imagoes produced per adult flea (our flea reproductive output metric), flea mortality, and change in circulating anti-flea immunoglobulin G (our measure of adaptive immune defense) were monitored. Three hypotheses guided this work: (1) increasing parasite pressure would heighten host defenses; (2) parasite mortality would increase and parasite reproductive output would decrease with increasing investment in host defense; and (3) hosts under high parasite pressure could invest in behavioral and/or immune responses. We predicted that at high infestation levels (a) parasite mortality would increase; (b) flea reproductive output per individual would decrease; and (c) host circulating anti-flea antibody levels would increase. The hypotheses were partially supported. Flea mortality significantly increased and flea reproductive output significantly decreased as flea pressure increased. Host adaptive immune defense did not significantly change with increasing flea pressure. Therefore, we inferred that investment in host behavioral defense, either alone or in combination with density-dependent effects, may be more efficient at increasing flea mortality and decreasing flea reproductive output than antibody production during initial infestation in this system.

Pipecolic Acid Orchestrates Plant Systemic Acquired Resistance and Defense Priming via Salicylic Acid-Dependent and -Independent Pathways

PubMed Central

Bernsdorff, Friederike; Döring, Anne-Christin; Gruner, Katrin; Schuck, Stefan; Bräutigam, Andrea; Zeier, Jürgen

2016-01-01

We investigated the relationships of the two immune-regulatory plant metabolites, salicylic acid (SA) and pipecolic acid (Pip), in the establishment of plant systemic acquired resistance (SAR), SAR-associated defense priming, and basal immunity. Using SA-deficient sid2, Pip-deficient ald1, and sid2 ald1 plants deficient in both SA and Pip, we show that SA and Pip act both independently from each other and synergistically in Arabidopsis thaliana basal immunity to Pseudomonas syringae. Transcriptome analyses reveal that SAR establishment in Arabidopsis is characterized by a strong transcriptional response systemically induced in the foliage that prepares plants for future pathogen attack by preactivating multiple stages of defense signaling and that SA accumulation upon SAR activation leads to the downregulation of photosynthesis and attenuated jasmonate responses systemically within the plant. Whereas systemic Pip elevations are indispensable for SAR and necessary for virtually the whole transcriptional SAR response, a moderate but significant SA-independent component of SAR activation and SAR gene expression is revealed. During SAR, Pip orchestrates SA-dependent and SA-independent priming of pathogen responses in a FLAVIN-DEPENDENT-MONOOXYGENASE1 (FMO1)-dependent manner. We conclude that a Pip/FMO1 signaling module acts as an indispensable switch for the activation of SAR and associated defense priming events and that SA amplifies Pip-triggered responses to different degrees in the distal tissue of SAR-activated plants. PMID:26672068

Pipecolic Acid Orchestrates Plant Systemic Acquired Resistance and Defense Priming via Salicylic Acid-Dependent and -Independent Pathways.

PubMed

Bernsdorff, Friederike; Döring, Anne-Christin; Gruner, Katrin; Schuck, Stefan; Bräutigam, Andrea; Zeier, Jürgen

2016-01-01

We investigated the relationships of the two immune-regulatory plant metabolites, salicylic acid (SA) and pipecolic acid (Pip), in the establishment of plant systemic acquired resistance (SAR), SAR-associated defense priming, and basal immunity. Using SA-deficient sid2, Pip-deficient ald1, and sid2 ald1 plants deficient in both SA and Pip, we show that SA and Pip act both independently from each other and synergistically in Arabidopsis thaliana basal immunity to Pseudomonas syringae. Transcriptome analyses reveal that SAR establishment in Arabidopsis is characterized by a strong transcriptional response systemically induced in the foliage that prepares plants for future pathogen attack by preactivating multiple stages of defense signaling and that SA accumulation upon SAR activation leads to the downregulation of photosynthesis and attenuated jasmonate responses systemically within the plant. Whereas systemic Pip elevations are indispensable for SAR and necessary for virtually the whole transcriptional SAR response, a moderate but significant SA-independent component of SAR activation and SAR gene expression is revealed. During SAR, Pip orchestrates SA-dependent and SA-independent priming of pathogen responses in a FLAVIN-DEPENDENT-MONOOXYGENASE1 (FMO1)-dependent manner. We conclude that a Pip/FMO1 signaling module acts as an indispensable switch for the activation of SAR and associated defense priming events and that SA amplifies Pip-triggered responses to different degrees in the distal tissue of SAR-activated plants. © 2016 American Society of Plant Biologists. All rights reserved.

Monocrotophos Induces the Expression and Activity of Xenobiotic Metabolizing Enzymes in Pre-Sensitized Cultured Human Brain Cells

PubMed Central

Tripathi, Vinay K.; Kumar, Vivek; Singh, Abhishek K.; Kashyap, Mahendra P.; Jahan, Sadaf; Pandey, Ankita; Alam, Sarfaraz; Khan, Feroz; Khanna, Vinay K.; Yadav, Sanjay; Lohani, Mohtshim; Pant, Aditya B.

2014-01-01

The expression and metabolic profile of cytochrome P450s (CYPs) is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y) and glial (U373-MG) cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC), cyclophosphamide (CPA), ethanol and known neurotoxicant- monocrotophos (MCP), a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h) of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against xenobiotics

Defensive medicine and outcomes for medical malpractice liability.

PubMed

Genovese, Umberto; Amato, Simona; Del Sordo, Sara; Mobilia, Francesca; Casali, Michelangelo B

2014-01-01

Defensive medicine is a significant force driving the high costs of healthcare systems and has a substantial influence on physicians' behavior because they primarily concern about malpractice liability and not patient's health protection. This attitude disagrees with deontological duties and could impair physicians' ability of judgment and clinical reasoning. Reducing defensive medicine also could mean improving the quality in healthcare systems and eliminating unnecessary costs.

Transport behaviour of xenobiotic micropollutants in surface waters - an experimental assessment

NASA Astrophysics Data System (ADS)

Schwientek, Marc; Kuch, Bertram; Rügner, Hermann; Dobramysl, Lorenz; Grathwohl, Peter

2013-04-01

Xenobiotics are substances that do not exist in natural systems but are increasingly produced by industrial processes and introduced into the environment. While many of these compounds are eliminated in waste water treatment plants, some are only barely degraded and are discharged into receiving water bodies. Often little is known about their acute or chronic toxicity and even less about their persistence or transport behaviour in aquatic systems. In the present study, the stability and turnover of selected micropollutants along a 7.5 km long segment of the River Ammer in Southwest Germany was investigated (catchment area 134 km²). This stream carries a proportion of treated wastewater which is clearly above the average in German rivers, mainly supplied by a major waste water treatment plant at the upstream end of the studied stream segment. An experimental mass balance approach was chosen where in- and outflow of water and target compounds into and out of the balanced stream segment was measured during base flow conditions. To cover a complete diurnal cycle of wastewater input, pooled samples were collected every 2 h over a sampling period of 24 h. A comparison of bulk mass fluxes showed that carbamazepine, a pharmaceutical, and phosphorous flame retardants, such as TCPP, behave conservative under the given conditions. Some retention was observed for the disinfectant product Triclosan and some polycyclic musk fragrances (e.g., HHCB). TAED, a bleaching activator used in detergents, was completely eliminated along the stream segment. The outcome of the experiment demonstrates the very different persistence of some widely-used micropollutants in aquatic systems. However, the mechanisms involved in their attenuation as well as the fate of the most persistent compounds still remain subject to further research.

Defense Medical Human Resources System-internet (DMHRSi): A Case Study on Compliance and Accuracy

DTIC Science & Technology

2009-06-02

including suggestions for reducing the burden, to Department of Defense, Washington Headquarters Services, Directorate for Information Operations ...military, contractor operated facilities. The hospital also houses the second oldest Family Practice Residency in the Army (DeWitt, 2008). The...collection and analysis of financial, workload, and personnel data within the organization. The MHS utilizes information managemen * systems like the

Dynamic defense workshop :

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

Crosby, Sean Michael; Doak, Justin E.; Haas, Jason Juedes.

2013-02-01

On September 5th and 6th, 2012, the Dynamic Defense Workshop: From Research to Practice brought together researchers from academia, industry, and Sandia with the goals of increasing collaboration between Sandia National Laboratories and external organizations, de ning and un- derstanding dynamic, or moving target, defense concepts and directions, and gaining a greater understanding of the state of the art for dynamic defense. Through the workshop, we broadened and re ned our de nition and understanding, identi ed new approaches to inherent challenges, and de ned principles of dynamic defense. Half of the workshop was devoted to presentations of current state-of-the-artmore » work. Presentation topics included areas such as the failure of current defenses, threats, techniques, goals of dynamic defense, theory, foundations of dynamic defense, future directions and open research questions related to dynamic defense. The remainder of the workshop was discussion, which was broken down into sessions on de ning challenges, applications to host or mobile environments, applications to enterprise network environments, exploring research and operational taxonomies, and determining how to apply scienti c rigor to and investigating the eld of dynamic defense.« less

The glutathione defense system in the pathogenesis of rheumatoid arthritis.

PubMed

Hassan, M Q; Hadi, R A; Al-Rawi, Z S; Padron, V A; Stohs, S J

2001-01-01

In order to assess a possible role of the natural glutathione defense system in the pathogenesis of rheumatoid arthritis (RA), serum reduced glutathione levels (GSH), glutathione reductase (GSR), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and alkaline phosphatase (ALP) activities, lipid peroxidation (MDA content) and indexes of inflammation were evaluated in 58 rheumatic patients. Rheumatoid athritis was associated with significant depletion (ca. 50%) in GSH levels compared with normal control subjects. Serum levels of the detoxifying enzymes GSR and GSH-Px decreased by ca. 50% and 45%, respectively, whereas a threefold increase in the activity of GST was observed. A 1.2-fold increase in ALP was observed in patients with RA. These effects were accompanied by a 3.1-fold increase in serum MDA content. The MDA content was higher in RA patients who were seropositive for rheumatoid factor as well as positive for C-reactive proteins. The erythrocyte sedimentation rate for all patients with RA was approximately 13.8-fold higher than for the control group, and was higher among RA patients who were positive for C-reactive proteins and exhibited seropositivity for rheumatoid factor. Patients with RA receiving gold therapy exhibited significantly lower MDA levels whereas all other factors that were measured were not effected. The results support a hypothesis that defense mechanisms against reactive oxygen species are impaired in RA. Copyright 2001 John Wiley & Sons, Ltd.

76 FR 35424 - Information Collection Requirements; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System Information Collection Requirements; Defense Federal Acquisition Regulation Supplement; Construction and Architect-Engineer Contracts AGENCY..., Construction and Architect-Engineer Contracts, and Related Clauses at DFARS 252.236; OMB Control Number 0704...

Inducible defenses in food webs: Chapter 3.4

USGS Publications Warehouse

Vos, Matthijs; Kooi, Bob W.; DeAngelis, Donald L.; Mooij, Wolf M.; de Ruiter, Peter; Wolters, Volkmar; Moore, John C.; Melville-Smith, Kimberly

2005-01-01

This chapter reviews the predicted effects of induced defenses on trophic structure and two aspects of stability, “local” stability and persistence, as well as presenting novel results on a third, resilience. Food webs are structures of populations in a given location organized according to their predator–prey interactions. Interaction strengths and, therefore, prey defenses are generally recognized as important ecological factors affecting food webs. Despite this, surprisingly, little light has been shed on the food web-level consequences of inducible defenses. Inducible defenses occur in many taxa in both terrestrial and aquatic food webs. They include refuge use, reduced activity, adaptive life history changes, the production of toxins, synomones and extrafloral nectar, and the formation of colonies, helmets, thorns, or spines. In the chapter, theoretical results for the effects of inducible defenses on trophic structure and the three aspects of stability are reviewed. This is done, in part, using bifurcation analysis—a type of analysis that is applied to nonlinear dynamic systems described by a set of ordinary differential or difference equations. The work presented in the chapter suggests that heterogeneity, as caused by induced defenses in prey species, has major effects on the functioning of food webs. Inducible defenses occur in many species in both aquatic and terrestrial systems, and theoretical work indicates they have major effects on important food web properties such as trophic structure, local stability, persistence, and resilience.

Defense Science and Technology RELIANCE. Defense Technology Objectives Success Stories

DTIC Science & Technology

2001-03-01

27 MD.04 Medical Countermeasures for Botulinum Toxin ...flexibility of U.S. forces. Completed. 1998 SPONSORS DoD Chemical and Biological Defense Program MEDICAL COUNTERMEASURES FOR BOTULINUM TOXIN (MD.04) 29...system operates satisfactorily against a high-level jamming environment in the target area. On four AGTFT free flights, the AGTFT flight test vehicles

75 FR 45104 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0225] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Administrative Matters... Supplement (DFARS) Part 204, Administrative Matters, and related clauses at DFARS 252.204; DD Form 2051...

Vertebrate defense against parasites: Interactions between avoidance, resistance, and tolerance.

PubMed

Klemme, Ines; Karvonen, Anssi

2017-01-01

Hosts can utilize different types of defense against the effects of parasitism, including avoidance, resistance, and tolerance. Typically, there is tremendous heterogeneity among hosts in these defense mechanisms that may be rooted in the costs associated with defense and lead to trade-offs with other life-history traits. Trade-offs may also exist between the defense mechanisms, but the relationships between avoidance, resistance, and tolerance have rarely been studied. Here, we assessed these three defense traits under common garden conditions in a natural host-parasite system, the trematode eye-fluke Diplostomum pseudospathaceum and its second intermediate fish host. We looked at host individuals originating from four genetically distinct populations of two closely related salmonid species (Atlantic salmon, Salmo salar and sea trout, Salmo trutta trutta ) to estimate the magnitude of variation in these defense traits and the relationships among them. We show species-specific variation in resistance and tolerance and population-specific variation in resistance. Further, we demonstrate evidence for a trade-off between resistance and tolerance. Our results suggest that the variation in host defense can at least partly result from a compromise between different interacting defense traits, the relative importance of which is likely to be shaped by environmental components. Overall, this study emphasizes the importance of considering different components of the host defense system when making predictions on the outcome of host-parasite interactions.

22 CFR 120.2 - Designation of defense articles and defense services.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Designation of defense articles and defense services. 120.2 Section 120.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.2 Designation of defense articles and defense services. The Arms...

22 CFR 120.2 - Designation of defense articles and defense services.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Designation of defense articles and defense services. 120.2 Section 120.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.2 Designation of defense articles and defense services. The Arms...

22 CFR 120.2 - Designation of defense articles and defense services.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Designation of defense articles and defense services. 120.2 Section 120.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.2 Designation of defense articles and defense services. The Arms...

22 CFR 120.2 - Designation of defense articles and defense services.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Designation of defense articles and defense services. 120.2 Section 120.2 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.2 Designation of defense articles and defense services. The Arms...

22 CFR 120.44 - Foreign defense article or defense service.

Code of Federal Regulations, 2014 CFR

2014-04-01

... defense service means any article or service described on the U.S. Munitions List of non-U.S. origin... U.S. and foreign origin defense articles and defense services described on the U.S. Munitions List...

Design Skills and Prototyping for Defense Systems

DTIC Science & Technology

2015-04-30

however, the utility of prototyping has had a demonstrably mixed record in defense acquisition. Some programs, such as the Manhattan Project , were...almost completely undefined. The first production reactors for the Manhattan Project suffered a near- catastrophic engineering design flaw stemming...architecture, as was seen in the F-117 and Manhattan Project development efforts. Architectural Prototyping Simply maintaining design teams or developing

Silicon induced systemic defense responses in perennial ryegrass against Magnaporthe oryzae infection

USDA-ARS?s Scientific Manuscript database

Sustainable integrated disease management for gray leaf spot of perennial ryegrass may involve use of plant defense elicitors with compatible traditional fungicides to reduce disease incidence and severity. Silicon (Si) is a potential inducer or modulator of plant defenses against different pathogen...

77 FR 35921 - Defense Federal Acquisition Regulation Supplement: Item Unique Identifier Update (DFARS Case 2011...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 211, 212, 218, 246, 252 and Appendix F to Chapter 2 RIN 0750-AH64 Defense Federal Acquisition Regulation Supplement: Item Unique Identifier Update (DFARS Case 2011-D055) AGENCY: Defense Acquisition Regulations System...

The biocontrol endophytic bacterium Pseudomonas fluorescens PICF7 induces systemic defense responses in aerial tissues upon colonization of olive roots.

PubMed

Gómez-Lama Cabanás, Carmen; Schilirò, Elisabetta; Valverde-Corredor, Antonio; Mercado-Blanco, Jesús

2014-01-01

Pseudomonas fluorescens PICF7, a native olive root endophyte and effective biocontrol agent (BCA) against Verticillium wilt of olive, is able to trigger a broad range of defense responses in root tissues of this woody plant. In order to elucidate whether strain PICF7 also induces systemic defense responses in above-ground organs, aerial tissues of olive plants grown under non-gnotobiotic conditions were collected at different time points after root bacterization with this endophytic BCA. A suppression subtractive hybridization (SSH) cDNA library, enriched in up-regulated genes, was generated. This strategy enabled the identification of 376 ESTs (99 contigs and 277 singlets), many of them related to response to different stresses. Five ESTs, involved in defense responses, were selected to carry out time-course quantitative real-time PCR (qRT-PCR) experiments aiming to: (1) validate the induction of these genes, and (2) shed light on their expression pattern along time (from 1 to 15 days). Induction of olive genes potentially coding for lipoxygenase 2, catalase, 1-aminocyclopropane-1-carboxylate oxidase, and phenylananine ammonia-lyase was thus confirmed at some time points. Computational analysis also revealed that different transcription factors were up-regulated in olive aerial tissues (i.e., JERF, bHLH, WRKY), as previously reported for roots. Results confirmed that root colonization by this endophytic bacterium does not only trigger defense responses in this organ but also mounts a wide array of systemic defense responses in distant tissues (stems, leaves). This sheds light on how olive plants respond to the "non-hostile" colonization by a bacterial endophyte and how induced defense response can contribute to the biocontrol activity of strain PICF7.

The biocontrol endophytic bacterium Pseudomonas fluorescens PICF7 induces systemic defense responses in aerial tissues upon colonization of olive roots

PubMed Central

Gómez-Lama Cabanás, Carmen; Schilirò, Elisabetta; Valverde-Corredor, Antonio; Mercado-Blanco, Jesús

2014-01-01

Pseudomonas fluorescens PICF7, a native olive root endophyte and effective biocontrol agent (BCA) against Verticillium wilt of olive, is able to trigger a broad range of defense responses in root tissues of this woody plant. In order to elucidate whether strain PICF7 also induces systemic defense responses in above-ground organs, aerial tissues of olive plants grown under non-gnotobiotic conditions were collected at different time points after root bacterization with this endophytic BCA. A suppression subtractive hybridization (SSH) cDNA library, enriched in up-regulated genes, was generated. This strategy enabled the identification of 376 ESTs (99 contigs and 277 singlets), many of them related to response to different stresses. Five ESTs, involved in defense responses, were selected to carry out time-course quantitative real-time PCR (qRT-PCR) experiments aiming to: (1) validate the induction of these genes, and (2) shed light on their expression pattern along time (from 1 to 15 days). Induction of olive genes potentially coding for lipoxygenase 2, catalase, 1-aminocyclopropane-1-carboxylate oxidase, and phenylananine ammonia-lyase was thus confirmed at some time points. Computational analysis also revealed that different transcription factors were up-regulated in olive aerial tissues (i.e., JERF, bHLH, WRKY), as previously reported for roots. Results confirmed that root colonization by this endophytic bacterium does not only trigger defense responses in this organ but also mounts a wide array of systemic defense responses in distant tissues (stems, leaves). This sheds light on how olive plants respond to the “non-hostile” colonization by a bacterial endophyte and how induced defense response can contribute to the biocontrol activity of strain PICF7. PMID:25250017

A Strategic Approach to Network Defense: Framing the Cloud

DTIC Science & Technology

2011-03-10

accepted network defensive principles, to reduce risks associated with emerging virtualization capabilities and scalability of cloud computing . This expanded...defensive framework can assist enterprise networking and cloud computing architects to better design more secure systems.

Rethinking Defensive Information Warfare

DTIC Science & Technology

2004-06-01

Countless studies, however, have demonstrated the weakness in this system.15 The tension between easily remembered passwords and suffi...vulnerabilities Undiscovered flaws The patch model for Internet security has failed spectacularly. Caida , 2004 Signature-Based Defense Anti virus, intrusion

[Study of defense styles, defenses and coping strategies in alcohol-dependent population].

PubMed

Ribadier, A; Varescon, I

2017-05-01

Defense mechanisms have been seen to greatly change over time and across different definitions made by different theoretical currents. Recently with the definition provided by the DSM IV, defense mechanisms have integrated the concept of coping as a defensive factor. These mechanisms are no longer considered just through a psychodynamic approach but also through a cognitive and behavioral one. In recent years, new theories have therefore integrated these two components of the defensive operation. According to Chabrol and Callahan (2013), defense mechanisms precede coping strategies. In individuals with psychopathological disorders, these authors indicate a relative stability of these mechanisms. Also, we asked about the presence of unique characteristics among people with alcohol dependence. Indeed, studies conducted with people with alcohol dependence highlight the presence of a neurotic defense style and some highly immature defenses (projection, acting out, splitting and somatization). In terms of coping strategies, persons with alcohol dependence preferentially use avoidant strategies and strategies focused on emotion. However, although several studies have been conducted to assess coping strategies and defense styles within a population of individuals with an alcohol problem, at the present time none of them has taken into account all these aspects of defense mechanisms. The aim of this study is therefore to study the defenses and defense styles and coping strategies in an alcohol-dependent population. This multicenter study (3 CHU, 1 center of supportive care and prevention in addiction and 1 clinic) received a favorable opinion of an Institutional Review Board (IRB Registration #: 00001072). Eighty alcohol-dependent individuals responded to a questionnaire assessing sociodemographic characteristics and elements related to the course of consumption. Coping strategies were assessed by means of a questionnaire validated in French: the Brief Cope. The Defense

77 FR 34940 - Defense Audit Advisory Committee (DAAC); Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... DEPARTMENT OF DEFENSE Office of the Secretary Defense Audit Advisory Committee (DAAC); Notice of... following Federal advisory committee meeting of the Defense Audit Advisory Committee (DAAC) will be held... reporting processes, systems of internal controls, audit processes, and processes for monitoring compliance...

Optimal defense theory explains deviations from latitudinal herbivory defense hypothesis.

PubMed

Kooyers, Nicholas J; Blackman, Benjamin K; Holeski, Liza M

2017-04-01

The latitudinal herbivory defense hypothesis (LHDH) postulates that the prevalence of species interactions, including herbivory, is greater at lower latitudes, leading to selection for increased levels of plant defense. While latitudinal defense clines may be caused by spatial variation in herbivore pressure, optimal defense theory predicts that clines could also be caused by ecogeographic variation in the cost of defense. For instance, allocation of resources to defense may not increase plant fitness when growing seasons are short and plants must reproduce quickly. Here we use a common garden experiment to survey genetic variation for constitutive and induced phenylpropanoid glycoside (PPG) concentrations across 35 Mimulus guttatus populations over a ~13° latitudinal transect. Our sampling regime is unique among studies of the LHDH in that it allows us to disentangle the effects of growing season length from those of latitude, temperature, and elevation. For five of the seven PPGs surveyed, we find associations between latitude and plant defense that are robust to population structure. However, contrary to the LHDH, only two PPGs were found at higher levels in low latitude populations, and total PPG concentrations were higher at higher latitudes. PPG levels are strongly correlated with growing season length, with higher levels of PPGs in plants from areas with longer growing seasons. Further, flowering time is positively correlated with the concentration of nearly all PPGs, suggesting that there may be a strong trade-off between development time and defense production. Our results reveal that ecogeographic patterns in plant defense may reflect variation in the cost of producing defense compounds in addition to variation in herbivore pressure. Thus, the biogeographic pattern predicted by the LHDH may not be accurate because the underlying factors driving variation in defense, in this case, growing season length, are not always associated with latitude in the same

Ballistic missile defense effectiveness

NASA Astrophysics Data System (ADS)

Lewis, George N.

2017-11-01

The potential effectiveness of ballistic missile defenses today remains a subject of debate. After a brief discussion of terminal and boost phase defenses, this chapter will focus on long-range midcourse defenses. The problems posed by potential countermeasures to such midcourse defenses are discussed as are the sensor capabilities a defense might have available to attempt to discriminate the actual missile warhead in a countermeasures environment. The role of flight testing in assessing ballistic missile defense effectiveness is discussed. Arguments made about effectiveness by missile defense supporters and critics are summarized.

Modulation of Xenobiotic Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes by ToxCast Chemicals

EPA Science Inventory

ToxCast chemicals were assessed for induction or suppression of xenobiotic metabolizing enzyme and transporter gene expression using primary human hepatocytes. The mRNA levels of 14 target and 2 control genes were measured: ABCB1, ABCB11, ABCG2, SLCO1B1, CYP1A1, CYP1A2, CYP2B6, C...

48 CFR 18.202 - Defense or recovery from certain attacks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Defense or recovery from certain attacks. 18.202 Section 18.202 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS Emergency Acquisition Flexibilities 18.202 Defense or recovery from certain...

76 FR 72391 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID DOD-2011-OS-0055] Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Revised Defense Logistics Agency...

Missile Defense: Actions Needed to Improve Transparency and Accountability

DTIC Science & Technology

2011-04-13

suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway...Established resource, schedule, test, operational capacity, technical, and contract baselines for several missile defense systems. It reported...Europe as well as the Ground-based Midcourse Defense system. View GAO-11-555T or key components. For more information, contact Cristina T

78 FR 18325 - Defense Transportation Regulation, Part IV

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... received in connection with the Defense Personal Property Program (DP3) Phase III Direct Procurement Method... at http://www.transcom.mil/dtr/part-iv/phaseiii.cfm (DPM SECTION). All identified changes will be... Defense Personal Property System (DPS) Phase III programming projected for FY17. FOR FURTHER INFORMATION...

78 FR 38235 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

.... DATES: Effective Date: June 26, 2013. FOR FURTHER INFORMATION CONTACT: Mrs. Kortnee Stewart, Defense.... Kortnee Stewart, Editor, Defense Acquisition Regulations System. Therefore, 48 CFR parts 225 and 252 are...

Defense without aggression

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

Harvey, H.

1988-09-01

In introducing this group of articles on nonoffensive defense the author notes that the prospect of nuclear disarmament in Europe is boosting ideas, which have been around for a decade, from theory to politics. This special section of articles looks at an emerging theory that may reduce reliance on nuclear weapons by bringing stability to the conventional standoff in central Europe. The idea is to rearrange conventional forces so that they can defend but not attack. Under such monikers as nonoffensive defense (the main term used in these articles), nonprovocative defense, defensive defense, reasonable sufficiency, and mutual defensive superiority, thesemore » proposals suggest that nations can restructure weapons, personnel, and strategy to assure their own military security without posing a threat to other nations. 5 refs.« less

Goldwater-Nichols at 30: Defense Reform and Issues for Congress

DTIC Science & Technology

2016-06-02

observers maintain that a reform of the broader interagency system on national security matters is needed. Despite these disagreements, several...Taken together, however, the issues raised by these questions suggest the systemic nature of the challenges with which the Department of Defense...External Defense Expert Reform Proposals ............................................................................ 24 Formulating Requirements

Influence of IR sensor technology on the military and civil defense

NASA Astrophysics Data System (ADS)

Becker, Latika

2006-02-01

Advances in basic infrared science and developments in pertinent technology applications have led to mature designs being incorporated in civil as well as military area defense systems. Military systems include both tactical and strategic, and civil area defense includes homeland security. Technical challenges arise in applying infrared sensor technology to detect and track targets for space and missile defense. Infrared sensors are valuable due to their passive capability, lower mass and power consumption, and their usefulness in all phases of missile defense engagements. Nanotechnology holds significant promise in the near future by offering unique material and physical properties to infrared components. This technology is rapidly developing. This presentation will review the current IR sensor technology, its applications, and future developments that will have an influence in military and civil defense applications.

A Systems Engineering Approach to Aircraft Kinetic Kill Countermeasures Technology: Development of an Active Aircraft Defense System for the C/KC-135 Aircraft. Volume 1

DTIC Science & Technology

1995-12-01

comparison among all candidate systems , the reliability of each aircraft defense would evenly affect the evaluation of each system , and would have the...more reliable data. Obviously the more reliable and accurate the data evaluated though the hierarchy chart, the better the results. 29 IV. System ...1.3.5 System Evaluation ................................................................ 6 1.3.6 Decision M aking

76 FR 36095 - Defense Transportation Regulation, Part IV

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

... with the Defense Personal Property Program (DP3) Phase III Domestic Small Shipments (dS2) and... Regulation, Part IV Web site at http://www.transcom.mil/dtr/part-iv/phaseiii.cfm . All identified changes... based on completion of Defense Personal Property System (DPS) Phase III programming projected for FY15...

78 FR 33993 - Defense Federal Acquisition Regulation Supplement; Clarification of “F” Orders in the Procurement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 204 RIN 0750-AH80 Defense Federal Acquisition Regulation Supplement; Clarification of ``F'' Orders in the Procurement Instrument Identification Number Structure (DFARS Case 2012-D040); Correction AGENCY: Defense Acquisition Regulations System...

76 FR 21849 - Defense Federal Acquisition Regulation Supplement; Ships Bunkers Easy Acquisition (SEA) Card® and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-19

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 213 RIN 0750-AH07 Defense Federal Acquisition Regulation Supplement; Ships Bunkers Easy Acquisition (SEA) Card[supreg] and Aircraft Ground Services (DFARS Case 2009-D019) AGENCY: Defense Acquisition Regulations System, Department of...

76 FR 58149 - Defense Federal Acquisition Regulation Supplement; Ships Bunkers Easy Acquisition (SEA) Card® and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-20

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 213 RIN 0750-AH07 Defense Federal Acquisition Regulation Supplement; Ships Bunkers Easy Acquisition (SEA) Card[supreg] and Aircraft Ground Services (DFARS Case 2009-D019) AGENCY: Defense Acquisition Regulations System, Department of...

75 FR 54526 - Defense Federal Acquisition Regulation Supplement; Additional Requirements Applicable to...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

... Procurement of Major Systems of the Department of Defense.'' DATES: Effective Date: September 8, 2010. FOR... 217 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations System. 0... funding or reprogramming for procurement of a major system under a multiyear contract authorized under...

Use of biomarkers to evaluate the ecological risk of xenobiotics associated with agriculture.

PubMed

Lima, Liana Bezerra Dias de; Morais, Paula Benevides de; Andrade, Ricardo Lopes Tortorela de; Mattos, Luciana Vieira; Moron, Sandro Estevan

2018-06-01

This research aimed to evaluate the ecological risk of xenobiotics associated with agricultural activities by determining metal contents and biomarker responses using tucunaré (Cichla sp.) as a bioindicator. The work was conducted in the southwest region of the state of Tocantins, in the cities of Lagoa da Confusão and Pium. Water samples and specimens of Cichla sp. were collected in the Javaés and Formoso Rivers at three collection points (A, B and C). The concentrations of Cd, Pb, Cu, Cr, Mn, Ni and Zn in water and fish were analyzed. In fish, genotoxic, biochemical (glucose serum levels, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) and histological (gills and liver) biomarkers were assessed. In the water, the Cr and Mn concentrations at the three collection points exceeded the values for Class 1 rivers. In the muscle, Cr was above the maximum limit allowed for human consumption at the three collection points, although the values at Points B and C were not significantly different from that at Point A (p > 0.05). At the three collection points, the micronucleus test revealed a low frequency of micronuclei. Significant hyperglycemia and a decrease in the AST activity of the fish collected at Point C was observed. In the gills, the most frequent alterations were at Stages I and II, which indicated mild to moderate damage, and epithelial detachment was the most frequent variation. In the liver tissue, the most frequently observed histological changes were at Stages I and II and included cytoplasmic vacuolization, nuclear hypertrophy, dilated sinusoids and bile stagnation. The integrated evaluation of these biomarkers indicated that fish collected from areas with intense agricultural activities presented adaptive responses that were likely caused by the availability and bioaccumulation of certain xenobiotics in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Section 847 Requirements for Senior Defense Officials Seeking Employment with Defense Contractors

DTIC Science & Technology

2016-03-31

847 Requirements for Senior Defense Officials Seeking Employment with Defense Contractors M A R C H 3 1 , 2 0 1 6 Report No. DODIG-2016-070...Senior Defense Officials Seeking Employment with Defense Contractors Visit us at www.dodig.mil March 31, 2016 Objectives The objectives of our project...description of future duties from a Defense contractor . • Some ethics officials issued nonspecific post-Government employment guidance as a Section 847

Comparative Transcriptome Analysis Reveals a Preformed Defense System in Apple Root of a Resistant Genotype of G.935 in the Absence of Pathogen

PubMed Central

Shao, Jonathan; Zhou, Zhe; Davis, Robert E.

2017-01-01

Two apple rootstock genotypes G.935 and B.9 were recently demonstrated to exhibit distinct resistance responses following infection by Pythium ultimum. As part of an effort to elucidate the genetic regulation of apple root resistance to soilborne pathogens, preinoculation transcriptome variations in roots of these two apple rootstock genotypes are hypothesized to contribute to the observed disease resistance phenotypes. Results from current comparative transcriptome analysis demonstrated elevated transcript abundance for many genes which function in a system-wide defense response in the root tissue of the resistant genotype of G.935 in comparison with susceptible B.9. Based on the functional annotation, these differentially expressed genes encode proteins that function in several tiers of defense responses, such as pattern recognition receptors for pathogen detection and subsequent signal transduction, defense hormone biosynthesis and signaling, transcription factors with known roles in defense activation, enzymes of secondary metabolism, and various classes of resistance proteins. The data set suggested a more poised status, which is ready to defend pathogen infection, in the root tissues of resistant genotype of G.935, compared to the susceptible B.9. The significance of preformed defense in the absence of a pathogen toward overall resistance phenotypes in apple root and the potential fitness cost due to the overactivated defense system were discussed. PMID:28465679

Prevalence and Mechanisms of Dynamic Chemical Defenses in Tropical Sponges

PubMed Central

Rohde, Sven; Nietzer, Samuel; Schupp, Peter J.

2015-01-01

Sponges and other sessile invertebrates are lacking behavioural escape or defense mechanisms and rely therefore on morphological or chemical defenses. Studies from terrestrial systems and marine algae demonstrated facultative defenses like induction and activation to be common, suggesting that sessile marine organisms also evolved mechanisms to increase the efficiency of their chemical defense. However, inducible defenses in sponges have not been investigated so far and studies on activated defenses are rare. We investigated whether tropical sponge species induce defenses in response to artificial predation and whether wounding triggers defense activation. Additionally, we tested if these mechanisms are also used to boost antimicrobial activity to avoid bacterial infection. Laboratory experiments with eight pacific sponge species showed that 87% of the tested species were chemically defended. Two species, Stylissa massa and Melophlus sarasinorum, induced defenses in response to simulated predation, which is the first demonstration of induced antipredatory defenses in marine sponges. One species, M. sarasinorum, also showed activated defense in response to wounding. Interestingly, 50% of the tested sponge species demonstrated induced antimicrobial defense. Simulated predation increased the antimicrobial defenses in Aplysinella sp., Cacospongia sp., M. sarasinorum, and S. massa. Our results suggest that wounding selects for induced antimicrobial defenses to protect sponges from pathogens that could otherwise invade the sponge tissue via feeding scars. PMID:26154741