9 CFR 121.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-01-01
... select agent or toxin to APHIS or CDC. (i) The seizure of any of the following overlap select agents and.... This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after seizure of the overlap select agent or toxin. (ii) For all other overlap select agents or toxins, APHIS/CDC Form...
9 CFR 121.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... select agent or toxin that is contained in a specimen presented for proficiency testing will be exempt...
9 CFR 121.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... select agent or toxin that is contained in a specimen presented for proficiency testing will be exempt...
42 CFR 73.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-10-01
... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1...
9 CFR 121.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... presented for proficiency testing will be exempt from the requirements of this part for such agent or toxin...
9 CFR 121.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... presented for proficiency testing will be exempt from the requirements of this part for such agent or toxin...
9 CFR 121.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... presented for proficiency testing will be exempt from the requirements of this part for such agent or toxin...
9 CFR 121.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-01-01
... in paragraph (b) of this section that have been genetically modified. (d) Overlap select agents or... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE... elements, recombinant nucleic acids, and recombinant organisms: (1) Nucleic acids that can produce...
9 CFR 121.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2014 CFR
2014-01-01
... this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE...) Genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic organisms...
9 CFR 121.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2013 CFR
2013-01-01
... this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE...) Genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic organisms...
42 CFR 73.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2011 CFR
2011-10-01
... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...
42 CFR 73.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-10-01
... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...
42 CFR 73.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-10-01
... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...
42 CFR 73.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2013 CFR
2013-10-01
... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... pseudomallei. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within...
42 CFR 73.6 - Exemptions for overlap select agents and toxins.
Code of Federal Regulations, 2014 CFR
2014-10-01
... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... pseudomallei. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within...
42 CFR 73.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2014 CFR
2014-10-01
... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION... its naturally occurring environment provided that the select agent or toxin has not been intentionally... such agent or toxin or destroys the agent or toxin by a recognized sterilization or inactivation...
42 CFR 73.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2013 CFR
2013-10-01
... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION... its naturally occurring environment provided that the select agent or toxin has not been intentionally... an entity eligible to receive such agent or toxin or destroys the agent or toxin by a recognized...
9 CFR 121.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2011 CFR
2011-01-01
...; Hendra virus; Nipah virus; Rift Valley fever virus; Venezuelan equine encephalitis virus. (c) Genetic... melitensis, Hendra virus, Nipah virus, Rift Valley fever virus, and Venezuelan equine encephalitis virus...
42 CFR 73.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2011 CFR
2011-10-01
... pseudomallei (formerly Pseudomonas pseudomallei) Hendra virus Nipah virus Rift Valley fever virus Venezuelan... CDC or APHIS. (i) The seizure of Bacillus anthracis, Brucella melitensis, Hendra virus, Nipah virus...
42 CFR 73.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-10-01
... the Federal Register and will be listed on the CDC Web site at http://www.cdc.gov/. (2) If an excluded... CDC or APHIS. (i) The seizure of Bacillus anthracis, Brucella melitensis, Hendra virus, Nipah virus... telephone, facsimile, or e-mail. This report must be followed by submission of APHIS/CDC Form 4 within seven...
Smith, Jacinta; Gangadharan, Denise; Weyant, Robbin
2015-01-01
The Centers for Disease Control and Prevention (CDC) Division of Select Agents and Toxins (DSAT) regulates laboratories that possess, use, or transfer select agents and toxins in the United States. DSAT also mitigates biosafety risks through the review of "restricted experiments," which under the select agent regulations are experiments that pose heightened biosafety risks. From January 2006 through December 2013, DSAT received 618 requests from 109 entities to perform potentially restricted experiments. Of these requests, 85% were determined not to meet the regulatory definition of a restricted experiment, while 15% of the requests met the definition of a restricted experiment. Of the 91 restricted experiments proposed, DSAT approved 31 (34%) requests because the biosafety conditions proposed were commensurate with the experiments' biosafety risk. All 31 approved restricted experiments were for work with select toxins. DSAT did not approve 60 restricted experiment requests due to potentially serious biosafety risks to public health and safety. All 60 denied restricted experiments proposed inserting drug resistance traits into select agents that could compromise the control of disease. The select agents and toxins associated most frequently with requests that met the regulatory definition of a restricted experiment are Shiga toxin (n = 16), Burkholderia mallei (n = 15), Botulinum neurotoxin (n = 14), and Brucella abortus (n = 14). In general, all restricted experiment decisions are determined on a case-by-case basis. This article describes the trends and characteristics of the data associated with restricted experiment requests among select agents that have an impact on public health and safety (HHS only agents) or both public health and safety and animal health or products (overlap agents). The information presented here, coupled with the information published in the restricted experiment guidance document ( www.selectagents.gov ), is intended to promote awareness among the research community of the type of experiments that meet the regulatory definition of a restricted experiment as well as to provide a greater understanding of the restricted experiment review process.
Castañar, Laura; Pérez-Trujillo, Míriam; Nolis, Pau; Monteagudo, Eva; Virgili, Albert; Parella, Teodor
2014-04-04
A frequency-selective 1D (1) H nuclear magnetic resonance (NMR) experiment for the fast and sensitive determination of chemical-shift differences between overlapped resonances is proposed. The resulting fully homodecoupled (1) H NMR resonances appear as resolved 1D singlets without their typical J(HH) coupling constant multiplet structures. The high signal dispersion that is achieved is then exploited in enantiodiscrimination studies by using chiral solvating agents. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Smith, Jacinta; Weyant, Robbin
2015-01-01
The Centers for Disease Control and Prevention (CDC) Division of Select Agents and Toxins (DSAT) regulates laboratories that possess, use, or transfer select agents and toxins in the United States. DSAT also mitigates biosafety risks through the review of “restricted experiments,” which under the select agent regulations are experiments that pose heightened biosafety risks. From January 2006 through December 2013, DSAT received 618 requests from 109 entities to perform potentially restricted experiments. Of these requests, 85% were determined not to meet the regulatory definition of a restricted experiment, while 15% of the requests met the definition of a restricted experiment. Of the 91 restricted experiments proposed, DSAT approved 31 (34%) requests because the biosafety conditions proposed were commensurate with the experiments' biosafety risk. All 31 approved restricted experiments were for work with select toxins. DSAT did not approve 60 restricted experiment requests due to potentially serious biosafety risks to public health and safety. All 60 denied restricted experiments proposed inserting drug resistance traits into select agents that could compromise the control of disease. The select agents and toxins associated most frequently with requests that met the regulatory definition of a restricted experiment are Shiga toxin (n = 16), Burkholderia mallei (n = 15), Botulinum neurotoxin (n = 14), and Brucella abortus (n = 14). In general, all restricted experiment decisions are determined on a case-by-case basis. This article describes the trends and characteristics of the data associated with restricted experiment requests among select agents that have an impact on public health and safety (HHS only agents) or both public health and safety and animal health or products (overlap agents). The information presented here, coupled with the information published in the restricted experiment guidance document (www.selectagents.gov), is intended to promote awareness among the research community of the type of experiments that meet the regulatory definition of a restricted experiment as well as to provide a greater understanding of the restricted experiment review process. PMID:26347984
An Experimental Study of Hafting Adhesives and the Implications for Compound Tool Technology
Zipkin, Andrew M.; Wagner, Mark; McGrath, Kate; Brooks, Alison S.; Lucas, Peter W.
2014-01-01
Experimental studies of hafting adhesives and modifications to compound tool components can demonstrate the extent to which human ancestors understood and exploited material properties only formally defined by science within the last century. Discoveries of Stone Age hafting adhesives at archaeological sites in Europe, the Middle East, and Africa have spurred experiments that sought to replicate or create models of such adhesives. Most of these studies, however, have been actualistic in design, focusing on replicating ancient applications of adhesive technology. In contrast, this study tested several glues based on Acacia resin within a materials science framework to better understand the effect of each adhesive ingredient on compound tool durability. Using an overlap joint as a model for a compound tool, adhesives formulated with loading agents from a range of particle sizes and mineral compositions were tested for toughness on smooth and rough substrates. Our results indicated that overlap joint toughness is significantly increased by using a roughened joint surface. Contrary to some previous studies, there was no evidence that particle size diversity in a loading agent improved adhesive effectiveness. Generally, glues containing quartz or ochre loading agents in the silt and clay-sized particle class yielded the toughest overlap joints, with the effect of particle size found to be more significant for rough rather than smooth substrate joints. Additionally, no particular ochre mineral or mineral mixture was found to be a clearly superior loading agent. These two points taken together suggest that Paleolithic use of ochre-loaded adhesives and the criteria used to select ochres for this purpose may have been mediated by visual and symbolic considerations rather than purely functional concerns. PMID:25383871
An experimental study of hafting adhesives and the implications for compound tool technology.
Zipkin, Andrew M; Wagner, Mark; McGrath, Kate; Brooks, Alison S; Lucas, Peter W
2014-01-01
Experimental studies of hafting adhesives and modifications to compound tool components can demonstrate the extent to which human ancestors understood and exploited material properties only formally defined by science within the last century. Discoveries of Stone Age hafting adhesives at archaeological sites in Europe, the Middle East, and Africa have spurred experiments that sought to replicate or create models of such adhesives. Most of these studies, however, have been actualistic in design, focusing on replicating ancient applications of adhesive technology. In contrast, this study tested several glues based on Acacia resin within a materials science framework to better understand the effect of each adhesive ingredient on compound tool durability. Using an overlap joint as a model for a compound tool, adhesives formulated with loading agents from a range of particle sizes and mineral compositions were tested for toughness on smooth and rough substrates. Our results indicated that overlap joint toughness is significantly increased by using a roughened joint surface. Contrary to some previous studies, there was no evidence that particle size diversity in a loading agent improved adhesive effectiveness. Generally, glues containing quartz or ochre loading agents in the silt and clay-sized particle class yielded the toughest overlap joints, with the effect of particle size found to be more significant for rough rather than smooth substrate joints. Additionally, no particular ochre mineral or mineral mixture was found to be a clearly superior loading agent. These two points taken together suggest that Paleolithic use of ochre-loaded adhesives and the criteria used to select ochres for this purpose may have been mediated by visual and symbolic considerations rather than purely functional concerns.
A game theoretic algorithm to detect overlapping community structure in networks
NASA Astrophysics Data System (ADS)
Zhou, Xu; Zhao, Xiaohui; Liu, Yanheng; Sun, Geng
2018-04-01
Community detection can be used as an important technique for product and personalized service recommendation. A game theory based approach to detect overlapping community structure is introduced in this paper. The process of the community formation is converted into a game, when all agents (nodes) cannot improve their own utility, the game process will be terminated. The utility function is composed of a gain and a loss function and we present a new gain function in this paper. In addition, different from choosing action randomly among join, quit and switch for each agent to get new label, two new strategies for each agent to update its label are designed during the game, and the strategies are also evaluated and compared for each agent in order to find its best result. The overlapping community structure is naturally presented when the stop criterion is satisfied. The experimental results demonstrate that the proposed algorithm outperforms other similar algorithms for detecting overlapping communities in networks.
NASA Astrophysics Data System (ADS)
Nikolić, G. S.; Žerajić, S.; Cakić, M.
2011-10-01
Multivariate calibration method is a powerful mathematical tool that can be applied in analytical chemistry when the analytical signals are highly overlapped. The method with regression by partial least squares is proposed for the simultaneous spectrophotometric determination of adrenergic vasoconstrictors in decongestive solution containing two active components: phenyleprine hydrochloride and trimazoline hydrochloride. These sympathomimetic agents are that frequently associated in pharmaceutical formulations against the common cold. The proposed method, which is, simple and rapid, offers the advantages of sensitivity and wide range of determinations without the need for extraction of the vasoconstrictors. In order to minimize the optimal factors necessary to obtain the calibration matrix by multivariate calibration, different parameters were evaluated. The adequate selection of the spectral regions proved to be important on the number of factors. In order to simultaneously quantify both hydrochlorides among excipients, the spectral region between 250 and 290 nm was selected. A recovery for the vasoconstrictor was 98-101%. The developed method was applied to assay of two decongestive pharmaceutical preparations.
1992-01-30
Agent Resistant Coating, retractable nylon handles, ethylene propylenediene monomer ( EPDM ) rubber securing straps, and a woven monofilament polypropylene...without Z-folds: overlapping layers of fabric sewn as reinforcement in the cover opposite the spreader bars. These covers were made from fabrics that...problem is not isolated to the decon litter and mattress. Comparable slippage should be expected when the vinyl mattress is used with the new nylon
Group Cooperation without Group Selection: Modest Punishment Can Recruit Much Cooperation.
Krasnow, Max M; Delton, Andrew W; Cosmides, Leda; Tooby, John
2015-01-01
Humans everywhere cooperate in groups to achieve benefits not attainable by individuals. Individual effort is often not automatically tied to a proportionate share of group benefits. This decoupling allows for free-riding, a strategy that (absent countermeasures) outcompetes cooperation. Empirically and formally, punishment potentially solves the evolutionary puzzle of group cooperation. Nevertheless, standard analyses appear to show that punishment alone is insufficient, because second-order free riders (those who cooperate but do not punish) can be shown to outcompete punishers. Consequently, many have concluded that other processes, such as cultural or genetic group selection, are required. Here, we present a series of agent-based simulations that show that group cooperation sustained by punishment easily evolves by individual selection when you introduce into standard models more biologically plausible assumptions about the social ecology and psychology of ancestral humans. We relax three unrealistic assumptions of past models. First, past models assume all punishers must punish every act of free riding in their group. We instead allow punishment to be probabilistic, meaning punishers can evolve to only punish some free riders some of the time. This drastically lowers the cost of punishment as group size increases. Second, most models unrealistically do not allow punishment to recruit labor; punishment merely reduces the punished agent's fitness. We instead realistically allow punished free riders to cooperate in the future to avoid punishment. Third, past models usually restrict agents to interact in a single group their entire lives. We instead introduce realistic social ecologies in which agents participate in multiple, partially overlapping groups. Because of this, punitive tendencies are more expressed and therefore more exposed to natural selection. These three moves toward greater model realism reveal that punishment and cooperation easily evolve by direct selection--even in sizeable groups.
Nonrenal toxicities of acetaminophen, aspirin, and nonsteroidal anti-inflammatory agents.
Matzke, G R
1996-07-01
Approximately 2% of the United States population consumes an analgesic, antipyretic, or nonsteroidal antiinflammatory drug (NSAID) each day. Aspirin and acetaminophen have been available to the public without a prescription (over-the-counter) for decades, while most NSAIDs are still only available with a prescription from a physician. The recent trend of switching NSAIDs from prescription to over-the-counter status may be perceived by some as an indication of their inherent safety. However, all these agents have been associated with a unique but overlapping safety profile. In fact, significant adverse events (AEs) on multiple organ systems, including the kidney and gastrointestinal tract, have been reported with most of these agents. In this review, the incidence of the nonrenal AEs of aspirin, acetaminophen, and selected NSAIDs are tabulated. The strengths of the causative associations are highlighted, the relative risks for the gastrointestinal and cardiovascular AEs are discussed, and the relationship to patient risk factors and drug characteristics, such as dose and half-life, are reviewed. The selection of the optimal agent for an individual patient depends on the balance between the desired pharmacodynamic response, the patient's pharmacotherapy history, and the degree of AE risk one is willing to accept. Therapy should be initiated in all settings with the lowest possible dosage since the incidence of the major AEs is dose related.
A Symmetric Two-Locus Fertility Model
Feldman, Marcus W.; Liberman, Uri
1985-01-01
A model in which selection is mediated by differential fertilities among the genotypes at two diallelic loci is proposed. Fertility depends only on the number of heterozygous loci participating in the mating. Classes analogous to symmetric equilibria in symmetric viability models are determined explicitly and shown to exhibit stability behavior very different from the viability results. Linkage equilibrium is shown to occur in a relatively asymmetric fashion and to overlap in stability with linkage disequilibrium. In many cases single-locus or two-locus polymorphism is shown to be stable simultaneously with chromosome fixation even under very tight linkage. It is suggested that historical effects may be of great significance in the evolution of systems in which fertility is the primary agent of natural selection. PMID:3967817
Fenbendazole as a Potential Anticancer Drug
DUAN, QIWEN; LIU, YANFENG; ROCKWELL, SARA
2013-01-01
Background/Aims To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes. Materials and Methods We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens. Results Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia. Fenbendazole did not alter the dose-response curves for radiation or docetaxel; instead, the agents produced additive cytotoxicities. Febendazole in maximally-intensive regimens did not alter the growth of EMT6 tumors, or increase the antineoplastic effects of radiation. Conclusion These studies provided no evidence that fenbendazole would have value in cancer therapy, but suggested that this general class of compounds merits further investigation. PMID:23393324
Fenbendazole as a potential anticancer drug.
Duan, Qiwen; Liu, Yanfeng; Rockwell, Sara
2013-02-01
To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes. We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens. Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia. Fenbendazole did not alter the dose-response curves for radiation or docetaxel; instead, the agents produced additive cytotoxicities. Febendazole in maximally-intensive regimens did not alter the growth of EMT6 tumors, or increase the antineoplastic effects of radiation. These studies provided no evidence that fenbendazole would have value in cancer therapy, but suggested that this general class of compounds merits further investigation.
Micro-Level Adaptation, Macro-Level Selection, and the Dynamics of Market Partitioning
García-Díaz, César; van Witteloostuijn, Arjen; Péli, Gábor
2015-01-01
This paper provides a micro-foundation for dual market structure formation through partitioning processes in marketplaces by developing a computational model of interacting economic agents. We propose an agent-based modeling approach, where firms are adaptive and profit-seeking agents entering into and exiting from the market according to their (lack of) profitability. Our firms are characterized by large and small sunk costs, respectively. They locate their offerings along a unimodal demand distribution over a one-dimensional product variety, with the distribution peak constituting the center and the tails standing for the peripheries. We found that large firms may first advance toward the most abundant demand spot, the market center, and release peripheral positions as predicted by extant dual market explanations. However, we also observed that large firms may then move back toward the market fringes to reduce competitive niche overlap in the center, triggering nonlinear resource occupation behavior. Novel results indicate that resource release dynamics depend on firm-level adaptive capabilities, and that a minimum scale of production for low sunk cost firms is key to the formation of the dual structure. PMID:26656107
Micro-Level Adaptation, Macro-Level Selection, and the Dynamics of Market Partitioning.
García-Díaz, César; van Witteloostuijn, Arjen; Péli, Gábor
2015-01-01
This paper provides a micro-foundation for dual market structure formation through partitioning processes in marketplaces by developing a computational model of interacting economic agents. We propose an agent-based modeling approach, where firms are adaptive and profit-seeking agents entering into and exiting from the market according to their (lack of) profitability. Our firms are characterized by large and small sunk costs, respectively. They locate their offerings along a unimodal demand distribution over a one-dimensional product variety, with the distribution peak constituting the center and the tails standing for the peripheries. We found that large firms may first advance toward the most abundant demand spot, the market center, and release peripheral positions as predicted by extant dual market explanations. However, we also observed that large firms may then move back toward the market fringes to reduce competitive niche overlap in the center, triggering nonlinear resource occupation behavior. Novel results indicate that resource release dynamics depend on firm-level adaptive capabilities, and that a minimum scale of production for low sunk cost firms is key to the formation of the dual structure.
Group Cooperation without Group Selection: Modest Punishment Can Recruit Much Cooperation
Cosmides, Leda; Tooby, John
2015-01-01
Humans everywhere cooperate in groups to achieve benefits not attainable by individuals. Individual effort is often not automatically tied to a proportionate share of group benefits. This decoupling allows for free-riding, a strategy that (absent countermeasures) outcompetes cooperation. Empirically and formally, punishment potentially solves the evolutionary puzzle of group cooperation. Nevertheless, standard analyses appear to show that punishment alone is insufficient, because second-order free riders (those who cooperate but do not punish) can be shown to outcompete punishers. Consequently, many have concluded that other processes, such as cultural or genetic group selection, are required. Here, we present a series of agent-based simulations that show that group cooperation sustained by punishment easily evolves by individual selection when you introduce into standard models more biologically plausible assumptions about the social ecology and psychology of ancestral humans. We relax three unrealistic assumptions of past models. First, past models assume all punishers must punish every act of free riding in their group. We instead allow punishment to be probabilistic, meaning punishers can evolve to only punish some free riders some of the time. This drastically lowers the cost of punishment as group size increases. Second, most models unrealistically do not allow punishment to recruit labor; punishment merely reduces the punished agent’s fitness. We instead realistically allow punished free riders to cooperate in the future to avoid punishment. Third, past models usually restrict agents to interact in a single group their entire lives. We instead introduce realistic social ecologies in which agents participate in multiple, partially overlapping groups. Because of this, punitive tendencies are more expressed and therefore more exposed to natural selection. These three moves toward greater model realism reveal that punishment and cooperation easily evolve by direct selection—even in sizeable groups. PMID:25893241
Chen, Changchun; Wang, Shuhui; Wang, Huajing; Mao, Xiaoyan; Zhang, Tiancheng; Ji, Guanghui; Shi, Xin; Xia, Tian; Lu, Weijia; Zhang, Dapeng; Dai, Jianxin; Guo, Yajun
2012-01-01
Botulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT therapeutics, but the potencies of mAbs against BoNTs are usually less than that of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key epitopes with development of effective mAb is urgently needed. We selected 3 neutralizing mAbs which recognize different non-overlapping epitopes of BoNT/B from a panel of neutralizing antibodies against BoNT/B. By comparing the neutralizing effects among different combination groups, we found that 8E10, response to ganglioside receptor binding site, could synergy with 5G10 and 2F4, recognizing non-overlapping epitopes within Syt II binding sites. However, the combination of 5G10 with 2F4 blocking protein receptor binding sites did not achieve synergistical effects. Moreover, we found that the binding epitope of 8E10 was conserved among BoNT A, B, E, and F, which might cross-protect the challenge of different serotypes of BoNTs in vivo. The combination of two mAbs recognizing different receptors' binding domain in BoNTs has a synergistic effect. 8E10 is a potential universal partner for the synergistical combination with other mAb against protein receptor binding domain in BoNTs of other serotypes.
Weiner, Kevin S.; Grill-Spector, Kalanit
2011-01-01
The prevailing view of human lateral occipitotemporal cortex (LOTC) organization suggests a single area selective for images of the human body (extrastriate body area, EBA) that highly overlaps with the human motion-selective complex (hMT+). Using functional magnetic resonance imaging with higher resolution (1.5mm voxels) than past studies (3–4mm voxels), we examined the fine-scale spatial organization of these activations relative to each other, as well as to visual field maps in LOTC. Rather than one contiguous EBA highly overlapping hMT+, results indicate three limb-selective activations organized in a crescent surrounding hMT+: (1) an activation posterior to hMT+ on the lateral occipital sulcus/middle occipital gyrus (LOS/MOG) overlapping the lower vertical meridian shared between visual field maps LO-2 and TO-1, (2) an activation anterior to hMT+ on the middle temporal gyrus (MTG) consistently overlapping the lower vertical meridian of TO-2 and extending outside presently defined visual field maps, and (3) an activation inferior to hMT+ on the inferotemporal gyrus (ITG) overlapping the parafoveal representation of the TO cluster. This crescent organization of limb-selective activations surrounding hMT+ is reproducible over a span of three years and is consistent across different image types used for localization. Further, these regions exhibit differential position properties: preference for contralateral image presentation decreases and preference for foveal presentation increases from the limb-selective LOS to the MTG. Finally, the relationship between limb-selective activations and visual field maps extends to the dorsal stream where a posterior IPS activation overlaps V7. Overall, our measurements demonstrate a series of LOTC limb-selective activations that 1) have separate anatomical and functional boundaries, 2) overlap distinct visual field maps, and 3) illustrate differential position properties. These findings indicate that category selectivity alone is an insufficient organization principle for defining brain areas. Instead, multiple properties are necessary in order to parcellate and understand the functional organization of high-level visual cortex. PMID:21439386
DOE Office of Scientific and Technical Information (OSTI.GOV)
Du, Dan; Wang, Jun; Wang, Limin
An integrated lateral flow test strip with electrochemical sensor (LFTSES) device with rapid, selective and sensitive response for quantification of exposure to organophosphorus (OP) pesticides and nerve agents has been developed. The principle of this approach is based on parallel measurements of post-exposure and baseline acetylcholinesterase (AChE) enzyme activity, where reactivation of the phosphorylated AChE is exploited to enable measurement of total amount of AChE (including inhibited and active) which is used as a baseline for calculation of AChE inhibition. Quantitative measurement of phosphorylated adduct (OP-AChE) was realized by subtracting the active AChE from the total amount of AChE. Themore » proposed LFTSES device integrates immunochromatographic test strip technology with electrochemical measurement using a disposable screen printed electrode which is located under the test zone. It shows linear response between AChE enzyme activity and enzyme concentration from 0.05 to 10 nM, with detection limit of 0.02 nM. Based on this reactivation approach, the LFTSES device has been successfully applied for in vitro red blood cells inhibition studies using chlorpyrifos oxon as a model OP agent. This approach not only eliminates the difficulty in screening of low-dose OP exposure because of individual variation of normal AChE values, but also avoids the problem in overlapping substrate specificity with cholinesterases and avoids potential interference from other electroactive species in biological samples. It is baseline free and thus provides a rapid, sensitive, selective and inexpensive tool for in-field and point-of-care assessment of exposures to OP pesticides and nerve agents.« less
Anal Sphincter Augmentation Using Biological Material.
Alam, Nasra N; Narang, Sunil K; Köckerling, Ferdinand; Daniels, Ian R; Smart, Neil J
2015-01-01
The aim of this review is to provide an overview of the use of biological materials in the augmentation of the anal sphincter either as part of an overlapping sphincter repair (OSR) or anal bulking procedure. A systematic search of PubMed was conducted using the search terms "anal bulking agents," "anal sphincter repair," or "overlapping sphincter repair." Five studies using biological material as part of an overlapping sphincter repair (OSR) or as an anal bulking agent were identified. 122 patients underwent anal bulking with a biological material. Anorectal physiology was conducted in 27 patients and demonstrated deterioration in maximum resting pressure, and no significant change in maximum squeeze increment. Quality of life scores (QoLs) demonstrated improvements at 6 weeks and 6 months, but this had deteriorated at 12 months of follow up. Biological material was used in 23 patients to carry out an anal encirclement procedure. Improvements in QoLs were observed in patients undergoing OSR as well as anal encirclement using biological material. Incontinence episodes decreased to an average of one per week from 8 to 10 preoperatively. Sphincter encirclement with biological material has demonstrated improvements in continence and QoLs in the short term compared to traditional repair alone. Long-term studies are necessary to determine if this effect is sustained. As an anal bulking agent the benefits are short-term.
Tortora, Giampaolo; Bianco, Roberto; Daniele, Gennaro; Ciardiello, Fortunato; McCubrey, James A; Ricciardi, Maria Rosaria; Ciuffreda, Ludovica; Cognetti, Francesco; Tafuri, Agostino; Milella, Michele
2007-06-01
Accumulating evidence suggests that cancer can be envisioned as a "signaling disease", in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to "targeted" agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here, we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in haematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects.
Tortora, Giampaolo; Bianco, Roberto; Daniele, Gennaro; Ciardiello, Fortunato; McCubrey, James A; Ricciardi, Maria Rosaria; Ciuffreda, Ludovica; Cognetti, Francesco; Tafuri, Agostino; Milella, Michele
2007-01-01
Accumulating evidence suggests that cancer can be envisioned as a “signaling disease”, in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to “targeted” agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in hematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects. PMID:17482503
Oyarzún, Javiera P; Morís, Joaquín; Luque, David; de Diego-Balaguer, Ruth; Fuentemilla, Lluís
2017-08-09
System memory consolidation is conceptualized as an active process whereby newly encoded memory representations are strengthened through selective memory reactivation during sleep. However, our learning experience is highly overlapping in content (i.e., shares common elements), and memories of these events are organized in an intricate network of overlapping associated events. It remains to be explored whether and how selective memory reactivation during sleep has an impact on these overlapping memories acquired during awake time. Here, we test in a group of adult women and men the prediction that selective memory reactivation during sleep entails the reactivation of associated events and that this may lead the brain to adaptively regulate whether these associated memories are strengthened or pruned from memory networks on the basis of their relative associative strength with the shared element. Our findings demonstrate the existence of efficient regulatory neural mechanisms governing how complex memory networks are shaped during sleep as a function of their associative memory strength. SIGNIFICANCE STATEMENT Numerous studies have demonstrated that system memory consolidation is an active, selective, and sleep-dependent process in which only subsets of new memories become stabilized through their reactivation. However, the learning experience is highly overlapping in content and thus events are encoded in an intricate network of related memories. It remains to be explored whether and how memory reactivation has an impact on overlapping memories acquired during awake time. Here, we show that sleep memory reactivation promotes strengthening and weakening of overlapping memories based on their associative memory strength. These results suggest the existence of an efficient regulatory neural mechanism that avoids the formation of cluttered memory representation of multiple events and promotes stabilization of complex memory networks. Copyright © 2017 the authors 0270-6474/17/377748-11$15.00/0.
Ripple artifact reduction using slice overlap in slice encoding for metal artifact correction.
den Harder, J Chiel; van Yperen, Gert H; Blume, Ulrike A; Bos, Clemens
2015-01-01
Multispectral imaging (MSI) significantly reduces metal artifacts. Yet, especially in techniques that use gradient selection, such as slice encoding for metal artifact correction (SEMAC), a residual ripple artifact may be prominent. Here, an analysis is presented of the ripple artifact and of slice overlap as an approach to reduce the artifact. The ripple artifact was analyzed theoretically to clarify its cause. Slice overlap, conceptually similar to spectral bin overlap in multi-acquisition with variable resonances image combination (MAVRIC), was achieved by reducing the selection gradient and, thus, increasing the slice profile width. Time domain simulations and phantom experiments were performed to validate the analyses and proposed solution. Discontinuities between slices are aggravated by signal displacement in the frequency encoding direction in areas with deviating B0. Specifically, it was demonstrated that ripple artifacts appear only where B0 varies both in-plane and through-plane. Simulations and phantom studies of metal implants confirmed the efficacy of slice overlap to reduce the artifact. The ripple artifact is an important limitation of gradient selection based MSI techniques, and can be understood using the presented simulations. At a scan-time penalty, slice overlap effectively addressed the artifact, thereby improving image quality near metal implants. © 2014 Wiley Periodicals, Inc.
Jiang, Guan; Liu, Yan-Qun; Wei, Zhi-Ping; Pei, Dong-Sheng; Mao, Li-Jun; Zheng, Jun-Nian
2010-08-28
Malignant melanoma is one of the most lethal and aggressive human malignancies. It is notoriously resistant to all of the current therapeutic modalities, including chemotherapy. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to the malignancy of melanoma. Dacarbazine (DTIC) has been considered as the gold standard for melanoma treatment with a response rate of 15-20%. Unfortunately, the resistance to this chemotherapeutic agent occurs frequently. ZD55-IL-24 is a selective conditionally replicating adenovirus that can mediate the expression of interleukin-24 (IL-24) gene, which has a strong anti-tumor effect. In this study, we hypothesized that a combination of ZD55-IL-24-mediated gene virotherapy and chemotherapy using DTIC would produce an increased cytotoxicity against human melanoma cells in comparison with these agents alone. Our results showed that the combination of ZD55-IL-24 and DTIC significantly enhanced the anti-tumor activity by more effectively inducing apoptosis in melanoma cells than either agent used alone without any overlapping toxicity against normal cells. This additive or synergistic effect of ZD55-IL-24 in combination with DTIC in killing human malignant melanoma cells implies a promising novel approach for melanoma therapy. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ghobadi, Kimia; Ghaffari, Hamid R.; Aleman, Dionne M.
2013-09-15
Purpose: The purpose of this work is to advance the two-step approach for Gamma Knife{sup ®} Perfexion™ (PFX) optimization to account for dose homogeneity and overlap between the planning target volume (PTV) and organs-at-risk (OARs).Methods: In the first step, a geometry-based algorithm is used to quickly select isocentre locations while explicitly accounting for PTV-OARs overlaps. In this approach, the PTV is divided into subvolumes based on the PTV-OARs overlaps and the distance of voxels to the overlaps. Only a few isocentres are selected in the overlap volume, and a higher number of isocentres are carefully selected among voxels that aremore » immediately close to the overlap volume. In the second step, a convex optimization is solved to find the optimal combination of collimator sizes and their radiation duration for each isocentre location.Results: This two-step approach is tested on seven clinical cases (comprising 11 targets) for which the authors assess coverage, OARs dose, and homogeneity index and relate these parameters to the overlap fraction for each case. In terms of coverage, the mean V{sub 99} for the gross target volume (GTV) was 99.8% while the V{sub 95} for the PTV averaged at 94.6%, thus satisfying the clinical objectives of 99% for GTV and 95% for PTV, respectively. The mean relative dose to the brainstem was 87.7% of the prescription dose (with maximum 108%), while on average, 11.3% of the PTV overlapped with the brainstem. The mean beam-on time per fraction per dose was 8.6 min with calibration dose rate of 3.5 Gy/min, and the computational time averaged at 205 min. Compared with previous work involving single-fraction radiosurgery, the resulting plans were more homogeneous with average homogeneity index of 1.18 compared to 1.47.Conclusions: PFX treatment plans with homogeneous dose distribution can be achieved by inverse planning using geometric isocentre selection and mathematical modeling and optimization techniques. The quality of the obtained treatment plans are clinically satisfactory while the homogeneity index is improved compared to conventional PFX plans.« less
Biosafety Oversight and Compliance: What do you Mean, I have to Fill Out Another Form?!
Petrella, Brenda L
2015-11-03
This unit is an overview of biosafety compliance and oversight in the United States. Specific attention is given to the oversight of the Institutional Biosafety Committee (IBC) and how the purview of the IBC may overlap with other local committees, such as the Institutional Animal Care and Use Committee (IACUC) for animal research and the Institutional Review Board (IRB) for research on human subjects. Requirements for the Federal Select Agent Program and Dual Use Research of Concern (DURC) are also briefly reviewed for those working with materials and experiments covered under these regulations. This unit serves as a guide for new and established investigators who are navigating the regulatory world and how regulatory oversight applies to their research. Copyright © 2015 John Wiley & Sons, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Aiqiong; Du, Dan; Lin, Yuehe
Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detectionmore » of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.« less
Overlapping meta-analyses on the same topic: survey of published studies.
Siontis, Konstantinos C; Hernandez-Boussard, Tina; Ioannidis, John P A
2013-07-19
To assess how common it is to have multiple overlapping meta-analyses of randomized trials published on the same topic. Survey of published meta-analyses. PubMed. Meta-analyses published in 2010 were identified, and 5% of them were randomly selected. We further selected those that included randomized trials and examined effectiveness of any medical intervention. For eligible meta-analyses, we searched for other meta-analyses on the same topic (covering the same comparisons, indications/settings, and outcomes or overlapping subsets of them) published until February 2013. Of 73 eligible meta-analyses published in 2010, 49 (67%) had at least one other overlapping meta-analysis (median two meta-analyses per topic, interquartile range 1-4, maximum 13). In 17 topics at least one author was involved in at least two of the overlapping meta-analyses. No characteristics of the index meta-analyses were associated with the potential for overlapping meta-analyses. Among pairs of overlapping meta-analyses in 20 randomly selected topics, 13 of the more recent meta-analyses did not include any additional outcomes. In three of the four topics with eight or more published meta-analyses, many meta-analyses examined only a subset of the eligible interventions or indications/settings covered by the index meta-analysis. Conversely, for statins in the prevention of atrial fibrillation after cardiac surgery, 11 meta-analyses were published with similar eligibility criteria for interventions and setting: there was still variability on which studies were included, but the results were always similar or even identical across meta-analyses. While some independent replication of meta-analyses by different teams is possibly useful, the overall picture suggests that there is a waste of efforts with many topics covered by multiple overlapping meta-analyses.
Lin, Xiaohui; Li, Chao; Zhang, Yanhui; Su, Benzhe; Fan, Meng; Wei, Hai
2017-12-26
Feature selection is an important topic in bioinformatics. Defining informative features from complex high dimensional biological data is critical in disease study, drug development, etc. Support vector machine-recursive feature elimination (SVM-RFE) is an efficient feature selection technique that has shown its power in many applications. It ranks the features according to the recursive feature deletion sequence based on SVM. In this study, we propose a method, SVM-RFE-OA, which combines the classification accuracy rate and the average overlapping ratio of the samples to determine the number of features to be selected from the feature rank of SVM-RFE. Meanwhile, to measure the feature weights more accurately, we propose a modified SVM-RFE-OA (M-SVM-RFE-OA) algorithm that temporally screens out the samples lying in a heavy overlapping area in each iteration. The experiments on the eight public biological datasets show that the discriminative ability of the feature subset could be measured more accurately by combining the classification accuracy rate with the average overlapping degree of the samples compared with using the classification accuracy rate alone, and shielding the samples in the overlapping area made the calculation of the feature weights more stable and accurate. The methods proposed in this study can also be used with other RFE techniques to define potential biomarkers from big biological data.
Richards, Stephanie L; Pompei, Victoria C; Anderson, Alice
2014-01-01
New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non-select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non-select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non-select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non-select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non-select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non-select agent laboratories to improve occupational health and safety.
Pompei, Victoria C.; Anderson, Alice
2014-01-01
New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non–select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non–select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non–select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non–select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non–select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non–select agent laboratories to improve occupational health and safety. PMID:24552359
Task representation in individual and joint settings
Prinz, Wolfgang
2015-01-01
This paper outlines a framework for task representation and discusses applications to interference tasks in individual and joint settings. The framework is derived from the Theory of Event Coding (TEC). This theory regards task sets as transient assemblies of event codes in which stimulus and response codes interact and shape each other in particular ways. On the one hand, stimulus and response codes compete with each other within their respective subsets (horizontal interactions). On the other hand, stimulus and response code cooperate with each other (vertical interactions). Code interactions instantiating competition and cooperation apply to two time scales: on-line performance (i.e., doing the task) and off-line implementation (i.e., setting the task). Interference arises when stimulus and response codes overlap in features that are irrelevant for stimulus identification, but relevant for response selection. To resolve this dilemma, the feature profiles of event codes may become restructured in various ways. The framework is applied to three kinds of interference paradigms. Special emphasis is given to joint settings where tasks are shared between two participants. Major conclusions derived from these applications include: (1) Response competition is the chief driver of interference. Likewise, different modes of response competition give rise to different patterns of interference; (2) The type of features in which stimulus and response codes overlap is also a crucial factor. Different types of such features give likewise rise to different patterns of interference; and (3) Task sets for joint settings conflate intraindividual conflicts between responses (what), with interindividual conflicts between responding agents (whom). Features of response codes may, therefore, not only address responses, but also responding agents (both physically and socially). PMID:26029085
ERIC Educational Resources Information Center
van der Ven, Sanne H. G.; Boom, Jan; Kroesbergen, Evelyn H.; Leseman, Paul P. M.
2012-01-01
Variability in strategy selection is an important characteristic of learning new skills such as mathematical skills. Strategies gradually come and go during this development. In 1996, Siegler described this phenomenon as ''overlapping waves.'' In the current microgenetic study, we attempted to model these overlapping waves statistically. In…
A common mode of origin of power laws in models of market and earthquake
NASA Astrophysics Data System (ADS)
Bhattacharyya, Pratip; Chatterjee, Arnab; Chakrabarti, Bikas K.
2007-07-01
We show that there is a common mode of origin for the power laws observed in two different models: (i) the Pareto law for the distribution of money among the agents with random-saving propensities in an ideal gas-like market model and (ii) the Gutenberg-Richter law for the distribution of overlaps in a fractal-overlap model for earthquakes. We find that the power laws appear as the asymptotic forms of ever-widening log-normal distributions for the agents’ money and the overlap magnitude, respectively. The identification of the generic origin of the power laws helps in better understanding and in developing generalized views of phenomena in such diverse areas as economics and geophysics.
Design considerations for near-infrared filter photometry: effects of noise sources and selectivity.
Tarumi, Toshiyasu; Amerov, Airat K; Arnold, Mark A; Small, Gary W
2009-06-01
Optimal filter design of two-channel near-infrared filter photometers is investigated for simulated two-component systems consisting of an analyte and a spectrally overlapping interferent. The degree of overlap between the analyte and interferent bands is varied over three levels. The optimal design is obtained for three cases: a source or background flicker noise limited case, a shot noise limited case, and a detector noise limited case. Conventional photometers consist of narrow-band optical filters with their bands located at discrete wavelengths. However, the use of broadband optical filters with overlapping responses has been proposed to obtain as much signal as possible from a weak and broad analyte band typical of near-infrared absorptions. One question regarding the use of broadband optical filters with overlapping responses is the selectivity achieved by such filters. The selectivity of two-channel photometers is evaluated on the basis of the angle between the analyte and interferent vectors in the space spanned by the relative change recorded for each of the two detector channels. This study shows that for the shot noise limited or detector noise limited cases, the slight decrease in selectivity with the use of broadband optical filters can be compensated by the higher signal-to-noise ratio afforded by the use of such filters. For the source noise limited case, the best quantitative results are obtained with the use of narrow-band non-overlapping optical filters.
Method Of Signal Amplification In Multi-Chromophore Luminescence Sensors
Levitsky, Igor A.; Krivoshlykov, Sergei G.
2004-02-03
A fluorescence-based method for highly sensitive and selective detection of analyte molecules is proposed. The method employs the energy transfer between two or more fluorescent chromophores in a carefully selected polymer matrix. In one preferred embodiment, signal amplification has been achieved in the fluorescent sensing of dimethyl methylphosphonate (DMMP) using two dyes, 3-aminofluoranthene (AM) and Nile Red (NR), in a hydrogen bond acidic polymer matrix. The selected polymer matrix quenches the fluorescence of both dyes and shifts dye emission and absorption spectra relative to more inert matrices. Upon DMMP sorption, the AM fluorescence shifts to the red at the same time the NR absorption shifts to the blue, resulting in better band overlap and increased energy transfer between chromophores. In another preferred embodiment, the sensitive material is incorporated into an optical fiber system enabling efficient excitation of the dye and collecting the fluorescent signal form the sensitive material on the remote end of the system. The proposed method can be applied to multichromophore luminescence sensor systems incorporating N-chromophores leading to N-fold signal amplification and improved selectivity. The method can be used in all applications where highly sensitive detection of basic gases, such as dimethyl methylphosphonate (DMMP), Sarin, Soman and other chemical warfare agents having basic properties, is required, including environmental monitoring, chemical industry and medicine.
Code of Federal Regulations, 2010 CFR
2010-10-01
... select agent or toxin against unauthorized access, theft, loss, or release. (b) The security plan must be... activities, loss or theft of select agents or toxins, release of select agents or toxins, or alteration of... of select agents or toxins, (iv) Any release of a select agent or toxin, and (v) Any sign that...
Code of Federal Regulations, 2010 CFR
2010-01-01
... the select agent or toxin against unauthorized access, theft, loss, or release. (b) The security plan... activities, loss or theft of select agents or toxins, release of select agents or toxins, or alteration of... of select agents or toxins; (iv) Any release of a select agent or toxin; and (v) Any sign that...
Feasibility of Serial Saliva Collection for Surveillance of Swimming-Associated Illness
BACKGROUND. The symptoms of many swimming-associated illnesses overlap, and clinical diagnoses often require serum or stool samples. Therefore, it has been difficult to determine the contributions of different etiologic agents to swimming-associated illness. OBJECTIVES. We collec...
Integration of color, orientation, and size functional domains in the ventral pathway
Ghose, Geoffrey M.; Ts’o, Daniel Y.
2017-01-01
Abstract. Functional specialization within the extrastriate areas of the ventral pathway associated with visual form analysis is poorly understood. Studies comparing the functional selectivities of neurons within the early visual areas have found that there are more similar than different between the areas. We simultaneously imaged visually evoked activation over regions of V2 and V4 and parametrically varied three visual attributes for which selectivity exists in both areas: color, orientation, and size. We found that color selective regions were observed in both areas and were of similar size and spatial distribution. However, two major areal distinctions were observed: V4 contained a greater number and diversity of color-specific regions than V2 and exhibited a higher degree of overlap between domains for different functional attributes. In V2, size and color regions were largely segregated from orientation domains, whereas in V4 both color and size regions overlapped considerably with orientation regions. Our results suggest that higher-order composite selectivities in the extrastriate cortex may arise organically from the interactions afforded by an overlap of functional domains for lower order selectivities. PMID:28573155
76 FR 62412 - Agency Forms Undergoing Paperwork Reduction Act Review
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-07
... for Registration, (2) Request to Transfer Select Agent or Toxin, (3) Report of Theft, Loss, or Release..., or Release of Select Agent and Toxin, (4) Report of Identification of Select Agent or Toxin. There... Release of Select Agent or Toxin; (4) Report of Identification of Select Agent or Toxin; and (5) Request...
Paller, Channing J.; Bradbury, Penelope A.; Ivy, S. Percy; Seymour, Lesley; LoRusso, Patricia M.; Baker, Laurence; Rubinstein, Larry; Huang, Erich; Collyar, Deborah; Groshen, Susan; Reeves, Steven; Ellis, Lee M.; Sargent, Daniel J.; Rosner, Gary L.; LeBlanc, Michael L.; Ratain, Mark J.
2014-01-01
Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistical and regulatory challenges. The phase 1 trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute (NCI) Investigational Drug Steering Committee developed a set of recommendations for the phase 1 development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biological or pharmacological rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase 1 clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamic (i.e., biomarker). PMID:25125258
ADHD and autism: differential diagnosis or overlapping traits? A selective review.
Taurines, Regina; Schwenck, Christina; Westerwald, Eva; Sachse, Michael; Siniatchkin, Michael; Freitag, Christine
2012-09-01
According to DSM-IV TR and ICD-10, a diagnosis of autism or Asperger Syndrome precludes a diagnosis of attention-deficit/hyperactivity disorder (ADHD). However, despite the different conceptualization, population-based twin studies reported symptom overlap, and a recent epidemiologically based study reported a high rate of ADHD in autism and autism spectrum disorders (ASD). In the planned revision of the DSM-IV TR, dsm5 (www.dsm5.org), the diagnoses of autistic disorder and ADHD will not be mutually exclusive any longer. This provides the basis of more differentiated studies on overlap and distinction between both disorders. This review presents data on comorbidity rates and symptom overlap and discusses common and disorder-specific risk factors, including recent proteomic studies. Neuropsychological findings in the areas of attention, reward processing, and social cognition are then compared between both disorders, as these cognitive abilities show overlapping as well as specific impairment for one of both disorders. In addition, selective brain imaging findings are reported. Therapeutic options are summarized, and new approaches are discussed. The review concludes with a prospectus on open questions for research and clinical practice.
Management of Docetaxel Failures in Metastatic Castrate-Resistant Prostate Cancer
Pal, Sumanta K.; Lewis, Brian; Sartor, Oliver
2013-01-01
SYNOPSIS The treatment of metastatic castration resistant prostate cancer (mCRPC) has evolved markedly since the approval of docetaxel-based therapy in 2004. Since that time, 3 distinct agents have gained approval for use in the mCRPC setting, namely sipuleucel-T, cabazitaxel and abiraterone. Even more recently, phase III trials have demonstrated a survival benefit in association with the agents MDV-3100 and radium-223, and FDA approval is anticipated for both of these agents. Although these changes undoubtedly represent progress for the patient with mCRPC, for the practicing physician there is the additional challenge of determining the optimal sequencing for each of these agents. This dilemma is particularly relevant to the post-docetaxel setting, where the indication for several of these agents overlap. Herein, we provide the physician with detailed background on the efficacy and safety of these agents so as to provide a framework for their use in the clinic. PMID:23084533
77 FR 71702 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review
Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-04
... of Select Agents and Toxins; Biennial Review AGENCY: Centers for Disease Control and Prevention (CDC... designated certain select agents and toxins as Tier 1 agents. DATES: Effective Date: Effective December 4, 2012. FOR FURTHER INFORMATION CONTACT: Robbin Weyant, Director, Division of Select Agents and Toxins...
Sánchez, Regina; Ochoa, Abigahil; Mendoza, Angélica
2013-06-01
D Menidia humboldtiana, a native species of Mexico, is a common inhabitant of local reservoirs. It represents a highly appreciated fish of economic importance in the central part of the country because of its delicate flavor. Trophic behavior of this species is important to understand the relationships with other fish species in reservoirs. With the aim to study this specific topic, the trophic spectrum, selectivity coefficient and overlap, were determined among different sizes of the Silverside M humboldtiana. For this, both zooplankton and fish samples were taken during four different seasons of 1995. Zooplankton samples were taken through a mesh (125 micron), and all organisms were identified to generic level. Fish were captured and grouped into standard length intervals per season, and the stomach contents were obtained and analyzed. Trophic interactions included the stomach contents analysis (Laevastu method), the coefficient of selection (Chesson) and the trophic overlap (Morisita index modified by Horn) between sizes. A total of 14 zooplankton genera were identified, of which Bosmina was the most abundant (29 625 ind./10 L) followed by Cyclops (9496 ind./10 L), during the spring. Small size fishes (1-4.9cm) consumed high percentages of Cyclops in the spring (61.24%) and winter (69.82%). Ceriodaphnia was consumed by fish sizes of 3-10.9cm (72.41%) and 13-14.9cm (95.5%) during the summer; while in autumn, small sizes (1-4.9cm) ingested Mastigodiaptomus and Ceriodaphnia; Daphnia and Bosmina were consumed by fishes of 5-8.9cm and the biggest sizes (9-14.9 cm) feed on Ceriodaphnia. M. humboldtiana makes a selective predation by the genera Ceriodaphnia, Daphnia, Mastigodiaptomus, Bosmina and Cyclops, depending on the size length interval. The trophic overlap was very marked among all sizes on spring, autumn and winter, unlike in summer fish of 1-2.9 and 11-12.9 cm did not show overlap with other length intervals. M humboldtiana is a zooplanktivore species, which performs a selective predation and a marked trophic overlap between the different fish sizes.
Bacterial diversity indicates dietary overlap among bats of different feeding habits.
Banskar, Sunil; Mourya, Devendra T; Shouche, Yogesh S
2016-01-01
Bats are among the most conspicuous mammals with extraordinary adaptations. They play a key role in the ecosystem. Frugivorous bats are important seed dispersing agents that help in maintaining forest tree diversity, while insectivorous bats are natural insect pest control agents. Several previous reports suggest that bats are reservoir of viruses; nonetheless their bacterial counterparts are relatively less explored. The present study describes the microbial diversity associated with the intestine of bats from different regions of India. Our observations stipulate that there is substantial sharing of bacterial communities between the insectivorous and frugivorous bats, which signifies fairly large dietary overlap. We also observed the presence of higher abundance of Mycoplasma in Cynopterus species of bats, indicating possible Mycoplasma infection. Considering the scarcity of literature related to microbial communities of bat intestinal tract, this study can direct future microbial diversity studies in bats with reference to their dietary habits, host-bacteria interaction and zoonosis. Copyright © 2015 Elsevier GmbH. All rights reserved.
Management of Gastroesophageal Reflux Disease.
Gyawali, C Prakash; Fass, Ronnie
2018-01-01
Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Novel approaches to develop Rift Valley fever vaccines
Indran, Sabarish V.; Ikegami, Tetsuro
2012-01-01
Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. RVFV is classified as a Category A Priority pathogen and overlap select agent by CDC/USDA due to its potential impact on public health and agriculture. There is a gap in the safety and immunogenicity in traditional RVF vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses for protection, and the live-attenuated Smithburn vaccine has a risk to cause abortion and fetal malformation in pregnant ruminants. In this review, problems of traditional vaccines and the safety and efficacy of recently reported novel RVF candidate vaccines including subunit vaccines, virus vector, and replicons are discussed. PMID:23112960
Population structuring of multi-copy, antigen-encoding genes in Plasmodium falciparum
Artzy-Randrup, Yael; Rorick, Mary M; Day, Karen; Chen, Donald; Dobson, Andrew P; Pascual, Mercedes
2012-01-01
The coexistence of multiple independently circulating strains in pathogen populations that undergo sexual recombination is a central question of epidemiology with profound implications for control. An agent-based model is developed that extends earlier ‘strain theory’ by addressing the var gene family of Plasmodium falciparum. The model explicitly considers the extensive diversity of multi-copy genes that undergo antigenic variation via sequential, mutually exclusive expression. It tracks the dynamics of all unique var repertoires in a population of hosts, and shows that even under high levels of sexual recombination, strain competition mediated through cross-immunity structures the parasite population into a subset of coexisting dominant repertoires of var genes whose degree of antigenic overlap depends on transmission intensity. Empirical comparison of patterns of genetic variation at antigenic and neutral sites supports this role for immune selection in structuring parasite diversity. DOI: http://dx.doi.org/10.7554/eLife.00093.001 PMID:23251784
Novel approaches to develop Rift Valley fever vaccines.
Indran, Sabarish V; Ikegami, Tetsuro
2012-01-01
Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. RVFV is classified as a Category A Priority pathogen and overlap select agent by CDC/USDA due to its potential impact on public health and agriculture. There is a gap in the safety and immunogenicity in traditional RVF vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses for protection, and the live-attenuated Smithburn vaccine has a risk to cause abortion and fetal malformation in pregnant ruminants. In this review, problems of traditional vaccines and the safety and efficacy of recently reported novel RVF candidate vaccines including subunit vaccines, virus vector, and replicons are discussed.
MacLean, Alair
2010-01-01
This article examines the effects of peacetime cold war military service on the life course according to four potentially overlapping theories that state that military service (1) was a disruption, (2) was a positive turning point, (3) allowed veterans to accumulate advantage, and (4) was an agent of social reproduction. The article argues that the extent to which the effect of military service on veterans' lives corresponds with one or another of the preceding theories depends on historical shifts in three dimensions: conscription, conflict, and benefits. Military service during the peacetime draft era of the late 1950s had a neutral effect on the socioeconomic attainment of enlisted veterans. However, it had a positive effect on veterans who served as officers, which partly stemmed from status reproduction and selection. Yet net of pre-service and educational differences by rank, officers in this peacetime draft era were still able to accumulate advantage. PMID:20842210
R.E. Linzer; M. Garbelotto
2008-01-01
Two recently described pathogenic oomycetes, Phytophthora nemorosa and P. pseudosyringae, have overlapping host and geographic ranges in California and Oregon forests with P. ramorum, causal agent of ?sudden oak death? disease. Preliminary genetic evidence indicates P. nemorosa and P....
Rachel E. Linzer; David M. Rizzo; Santa Olga Cacciola; Matteo Garbelotto
2009-01-01
In California and Oregon, two recently described oomycete forest pathogens, Phytophthora nemorosa and P. pseudosyringae, overlap in their host and geographic ranges with the virulent P. ramorum, causal agent of "sudden oak death." Epidemiological observations, namely broader geographic...
Detection of communities with Naming Game-based methods
Ribeiro, Carlos Henrique Costa
2017-01-01
Complex networks are often organized in groups or communities of agents that share the same features and/or functions, and this structural organization is built naturally with the formation of the system. In social networks, we argue that the dynamic of linguistic interactions of agreement among people can be a crucial factor in generating this community structure, given that sharing opinions with another person bounds them together, and disagreeing constantly would probably weaken the relationship. We present here a computational model of opinion exchange that uncovers the community structure of a network. Our aim is not to present a new community detection method proper, but to show how a model of social communication dynamics can reveal the (simple and overlapping) community structure in an emergent way. Our model is based on a standard Naming Game, but takes into consideration three social features: trust, uncertainty and opinion preference, that are built over time as agents communicate among themselves. We show that the separate addition of each social feature in the Naming Game results in gradual improvements with respect to community detection. In addition, the resulting uncertainty and trust values classify nodes and edges according to role and position in the network. Also, our model has shown a degree of accuracy both for non-overlapping and overlapping communities that are comparable with most algorithms specifically designed for topological community detection. PMID:28797097
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Lin, Xiaoyun; Chen, Shao; Xue, Xiangyang; Lu, Lijun; Zhu, Shanli; Li, Wenshu; Chen, Xiangmin; Zhong, Xiaozhi; Jiang, Pengfei; Sename, Torsoo Sophia; Zheng, Yi; Zhang, Lifang
2016-01-01
Epstein–Barr virus (EBV) is prevalent throughout the world and is associated with several malignant diseases in humans. Latent membrane protein 2 (LMP2) of EBV plays a crucial role in the pathogenesis of EBV-associated tumors; therefore, LMP2 has been considered to be a potential immunodiagnostic and immunotherapeutic target. A multi-epitope-based antigen is a promising option for therapeutic vaccines and diagnoses of such malignancies. In this study, we systematically screened cytotoxic T lymphocyte (CTL), helper T cell (Th) and B-cell epitopes within EBV-LMP2 using bioinformatics. Based on the screen, two peptides rich in overlapping epitopes of both T cells and B cells were selected to construct a plasmid containing the sequence for a chimeric multi-epitope protein referred to as EBV-LMP2m, which is composed of LMP2aa195∼232 and LMP2aa419∼436. The EBV-LMP2m protein was expressed in E. coli BL21 (DE3) after prokaryotic codon optimization. Inoculation of the purified chimeric antigen in BALB/c mice induced not only high levels of specific IgG in the serum and secretory IgA in the vaginal mucus but also a specific CTL response. By using purified EBV-LMP2m as an antigen, the presence of specific IgG in the serum specimens of 202 nasopharyngeal carcinoma (NPC) patients was effectively detected with 52.84% sensitivity and 95.40% specificity, which represents an improvement over the traditional detection method based on VCA-IgA (60.53% sensitivity and 76.86% specificity). The above results indicate that EBV-LMP2m may be used not only as a potential target antigen for EBV-associated tumors but also a diagnostic agent for NPC patients. PMID:25864917
Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site
Strauss, Mike; Schotte, Lise; Thys, Bert; Filman, David J.
2016-01-01
ABSTRACT Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion. IMPORTANCE We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed. PMID:26764003
Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site.
Strauss, Mike; Schotte, Lise; Thys, Bert; Filman, David J; Hogle, James M
2016-01-13
Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion. We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Percentage of All Non-Overlapping Data (PAND): An Alternative to PND
ERIC Educational Resources Information Center
Parker, Richard I.; Hagan-Burke, Shanna; Vannest, Kimberly
2007-01-01
Although single-case researchers are not accustomed to analyzing data statistically, standards for research and accountability from government and other funding agents are creating pressure for more objective, reliable data. In addition, "evidence-based interventions" movements in special education, clinical psychology, and school psychology imply…
Consumption Taxes and Economic Efficiency with Idiosyncratic Wage Shocks
ERIC Educational Resources Information Center
Nishiyama, Shinichi; Smetters, Kent
2005-01-01
Fundamental tax reform is examined in an overlapping-generations model in which heterogeneous agents face idiosyncratic wage shocks and longevity uncertainty. A progressive income tax is replaced with a flat consumption tax. If idiosyncratic wage shocks are insurable (i.e., no risk), this reform improves (interim) efficiency, a result consistent…
Education Policy and Intergenerational Transfers in Equilibrium. NBER Working Paper No. 18782
ERIC Educational Resources Information Center
Abbott, Brant; Gallipoli, Giovanni; Meghir, Costas; Violante, Giovanni L.
2013-01-01
This paper compares partial and general equilibrium effects of alternative financial aid policies intended to promote college participation. We build an overlapping generations life-cycle, heterogeneous-agent, incomplete-markets model with education, labor supply, and consumption/saving decisions. Altruistic parents make inter vivos transfers to…
O'Hanlon, Rory; Pennell, Dudley J
2009-07-01
There is often considerable phenotypic overlap in hypertrophic and infiltrative cardiomyopathies. This overlap creates difficulties, when using routine imaging modalities, in arriving at a conclusive diagnosis. Cardiovascular magnetic resonance (CMR) can make diagnosis easier and more certain. Used with gadolinium contrast agent for tissue characterization, CMR offers a superior field of view and temporal resolution, enabling clinicians to make more confident assessments of etiology. CMR may also be a useful modality for stratifying risk and monitoring treatment responses over time in patients with hypertrophic or infiltrative cardiomyopathies. This article highlights the role of CMR in the assessment and, if relevant, the risk stratification of hypertrophic and infiltrative cardiomyopathies.
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Detection and isolation of nucleic acid sequences using competitive hybridization probes
Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.
1997-01-01
A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support. The immobilized target nucleic acids are then separated and detected by detecting the detectable marker attached to the second hybridization probe. A kit for performing the method is also provided.
Detection and isolation of nucleic acid sequences using competitive hybridization probes
Lucas, J.N.; Straume, T.; Bogen, K.T.
1997-04-01
A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support. The immobilized target nucleic acids are then separated and detected by detecting the detectable marker attached to the second hybridization probe. A kit for performing the method is also provided. 7 figs.
Tu, Jing; Lu, Na; Duan, Mengqin; Huang, Mengting; Chen, Liang; Li, Junji; Guo, Jing; Lu, Zuhong
2017-02-24
Multiple displacement amplification (MDA) is considered to be a conventional approach to comprehensive amplification from low input DNA. The chimeric reads generated in MDA lead to severe disruption in some studies, including those focusing on heterogeneity, structural variation, and genetic recombination. Meanwhile, the generation of by-products gives a new approach to gain insights into the reaction process of φ29 polymerase. Here, we analyzed 36.7 million chimeras and screened 196 billion chimeric hotspots in the human genome, as well as evaluating the hotspot selective preference of chimeras. No significant preference was captured in the distributions of chimeras and hotspots among chromosomes. Hotspots with overlaps for 12-13 nucleotides (nt) were most likely to be selected as templates in chimera generation. Meanwhile, a regularly selective preference was noticed in overlap GC content. The preferences in overlap length and GC content was shown to be pertinent to the sequence denaturation temperature, which pointed out the optimization direction for reducing chimeras. Distance preference between two segments of chimeras was 80-280 nt. The analysis is beneficial for reducing the chimeras in MDA, and the characterization of MDA chimeras is helpful in distinguishing MDA chimeras from chimeric sequences caused by disease.
Hotspot Selective Preference of the Chimeric Sequences Formed in Multiple Displacement Amplification
Tu, Jing; Lu, Na; Duan, Mengqin; Huang, Mengting; Chen, Liang; Li, Junji; Guo, Jing; Lu, Zuhong
2017-01-01
Multiple displacement amplification (MDA) is considered to be a conventional approach to comprehensive amplification from low input DNA. The chimeric reads generated in MDA lead to severe disruption in some studies, including those focusing on heterogeneity, structural variation, and genetic recombination. Meanwhile, the generation of by-products gives a new approach to gain insights into the reaction process of φ29 polymerase. Here, we analyzed 36.7 million chimeras and screened 196 billion chimeric hotspots in the human genome, as well as evaluating the hotspot selective preference of chimeras. No significant preference was captured in the distributions of chimeras and hotspots among chromosomes. Hotspots with overlaps for 12–13 nucleotides (nt) were most likely to be selected as templates in chimera generation. Meanwhile, a regularly selective preference was noticed in overlap GC content. The preferences in overlap length and GC content was shown to be pertinent to the sequence denaturation temperature, which pointed out the optimization direction for reducing chimeras. Distance preference between two segments of chimeras was 80–280 nt. The analysis is beneficial for reducing the chimeras in MDA, and the characterization of MDA chimeras is helpful in distinguishing MDA chimeras from chimeric sequences caused by disease. PMID:28245591
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...-91434-01] RIN 0694-AE67 Amendments to the Select Agents Controls in Export Control Classification Number... controls on certain select agents identified in Export Control Classification Number (ECCN) 1C360 on the...) list of select agents and toxins. The changes made by APHIS were part of a biennial review and...
Molecular imaging of Alzheimer disease pathology.
Kantarci, K
2014-06-01
Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents. © 2014 by American Journal of Neuroradiology.
Application of gold nanoparticles as contrast agents in confocal laser scanning microscopy
NASA Astrophysics Data System (ADS)
Lemelle, A.; Veksler, B.; Kozhevnikov, I. S.; Akchurin, G. G.; Piletsky, S. A.; Meglinski, I.
2009-01-01
Confocal laser scanning microscopy (CLSM) is a modern high-resolution optical technique providing detailed image of tissue structure with high (down to microns) spatial resolution. Aiming at a concurrent improvement of imaging depth and image quality the CLSM requires the use of contrast agents. Commonly employed fluorescent contrast agents, such as fluorescent dyes and proteins, suffer from toxicity, photo-bleaching and overlapping with the tissues autofluorescence. Gold nanoparticles are potentially highly attractive to be applied as a contrast agent since they are not subject to photo-bleaching and can target biochemical cells markers associated with the specific diseases. In current report we consider the applicability of gold nano-spheres as a contrast agent to enhance quality of CLSM images of skin tissues in vitro versus the application of optical clearing agent, such as glycerol. The enhancement of CLSM image contrast was observed with an application of gold nano-spheres diffused within the skin tissues. We show that optical clearing agents such as a glycerol provide better CLSM image contrast than gold nano-spheres.
Brandt, Laura A.; Benscoter, Allison; Harvey, Rebecca G.; Speroterra, Carolina; Bucklin, David N.; Romañach, Stephanie; Watling, James I.; Mazzotti, Frank J.
2017-01-01
Climate envelope models are widely used to describe potential future distribution of species under different climate change scenarios. It is broadly recognized that there are both strengths and limitations to using climate envelope models and that outcomes are sensitive to initial assumptions, inputs, and modeling methods Selection of predictor variables, a central step in modeling, is one of the areas where different techniques can yield varying results. Selection of climate variables to use as predictors is often done using statistical approaches that develop correlations between occurrences and climate data. These approaches have received criticism in that they rely on the statistical properties of the data rather than directly incorporating biological information about species responses to temperature and precipitation. We evaluated and compared models and prediction maps for 15 threatened or endangered species in Florida based on two variable selection techniques: expert opinion and a statistical method. We compared model performance between these two approaches for contemporary predictions, and the spatial correlation, spatial overlap and area predicted for contemporary and future climate predictions. In general, experts identified more variables as being important than the statistical method and there was low overlap in the variable sets (<40%) between the two methods Despite these differences in variable sets (expert versus statistical), models had high performance metrics (>0.9 for area under the curve (AUC) and >0.7 for true skill statistic (TSS). Spatial overlap, which compares the spatial configuration between maps constructed using the different variable selection techniques, was only moderate overall (about 60%), with a great deal of variability across species. Difference in spatial overlap was even greater under future climate projections, indicating additional divergence of model outputs from different variable selection techniques. Our work is in agreement with other studies which have found that for broad-scale species distribution modeling, using statistical methods of variable selection is a useful first step, especially when there is a need to model a large number of species or expert knowledge of the species is limited. Expert input can then be used to refine models that seem unrealistic or for species that experts believe are particularly sensitive to change. It also emphasizes the importance of using multiple models to reduce uncertainty and improve map outputs for conservation planning. Where outputs overlap or show the same direction of change there is greater certainty in the predictions. Areas of disagreement can be used for learning by asking why the models do not agree, and may highlight areas where additional on-the-ground data collection could improve the models.
Tung, Wan-Ping; Chen, Yi-Huey; Cheng, Wei-Chun; Chuang, Ming-Feng; Hsu, Wan-Tso; Kam, Yeong-Choy; Lehtinen, Richard M
2015-01-01
Overlapping offspring occurs when eggs are laid in a nest containing offspring from earlier reproduction. Earlier studies showed that the parentage is not always obvious due to difficulties in field observation and/or alternative breeding tactics. To unveil the parentage between overlapping offspring and parents is critical in understanding oviposition site selection and the reproductive strategies of parents. Amplectant pairs of an arboreal-breeding frog, Kurixalus eiffingeri, lay eggs in tadpole-occupied nests where offspring of different life stages (embryos and tadpoles) coexist. We used five microsatellite DNA markers to assess the parentage between parents and overlapping offspring. We also tested the hypothesis that the male or female frog would breed in the same breeding site because of the scarcity of nest sites. Results showed varied parentage patterns, which may differ from the phenomenon of overlapping egg clutches reported earlier. Parentage analyses showed that only 58 and 25% of the tadpole-occupied stumps were reused by the same male and female respectively, partially confirming our prediction. Re-nesting by the same individual was more common in males than females, which is most likely related to the cost of tadpole feeding and/or feeding schemes of females. On the other hand, results of parentage analyses showed that about 42 and 75% of male and female respectively bred in tadpole-occupied stumps where tadpoles were genetically unrelated. Results of a nest-choice experiment revealed that 40% of frogs chose tadpole-occupied bamboo cups when we presented identical stumps, without or with tadpoles, suggesting that the habitat saturation hypothesis does not fully explain why frogs used the tadpole-occupied stumps. Several possible benefits of overlapping offspring with different life stages were proposed. Our study highlights the importance of integrating molecular data with field observations to better understand the reproductive biology and nest site selection of anuran amphibians.
Zakirova, Zuchra; Reed, Jon; Crynen, Gogce; Horne, Lauren; Hassan, Samira; Mathura, Venkatarajan; Mullan, Michael; Crawford, Fiona; Ait-Ghezala, Ghania
2017-09-01
Long-term consequences of combined pyridostigmine bromide (PB) and permethrin (PER) exposure in C57BL6/J mice using a well-characterized mouse model of exposure to these Gulf War (GW) agents were explored at the protein level. We used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane-bound protein fractions from brain samples using two orthogonal isotopic labeling LC-MS/MS proteomic approaches-stable isotope dimethyl labeling and iTRAQ. The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation. Collectively, our work identified key pathways which were chronically impacted in the mouse CNS following acute GW agent exposure, this may lead to the identification of potential targets for therapeutic intervention in the future. Long-term consequences of combined PB and PER exposure in C57BL6/J mice using a well-characterized mouse model of exposure to these GW agents were explored at the protein level. Expanding on earlier work, we used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane-bound protein fractions from brain samples using two orthogonal isotopic labeling LC-MS/MS proteomic approaches-stable isotope dimethyl labeling and iTRAQ. The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation at 5 months postexposure to PB + PER. © 2017 The Authors. PROTEOMICS - Clinical Applications published by WILEY-VCH Verlag GmbH & Co. KGaA.
Zakirova, Zuchra; Reed, Jon; Crynen, Gogce; Horne, Lauren; Hassan, Samira; Mathura, Venkatarajan; Mullan, Michael; Crawford, Fiona
2017-01-01
Purpose Long‐term consequences of combined pyridostigmine bromide (PB) and permethrin (PER) exposure in C57BL6/J mice using a well‐characterized mouse model of exposure to these Gulf War (GW) agents were explored at the protein level. Experimental design We used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane‐bound protein fractions from brain samples using two orthogonal isotopic labeling LC‐MS/MS proteomic approaches—stable isotope dimethyl labeling and iTRAQ. Results The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. Conclusions and clinical relevance The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation. Collectively, our work identified key pathways which were chronically impacted in the mouse CNS following acute GW agent exposure, this may lead to the identification of potential targets for therapeutic intervention in the future. Long‐term consequences of combined PB and PER exposure in C57BL6/J mice using a well‐characterized mouse model of exposure to these GW agents were explored at the protein level. Expanding on earlier work, we used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semiacute GW agent exposure early in life. These analyses were performed on soluble and membrane‐bound protein fractions from brain samples using two orthogonal isotopic labeling LC‐MS/MS proteomic approaches—stable isotope dimethyl labeling and iTRAQ. The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation at 5 months postexposure to PB + PER. PMID:28371386
Peelen, Marius V; Wiggett, Alison J; Downing, Paul E
2006-03-16
Accurate perception of the actions and intentions of other people is essential for successful interactions in a social environment. Several cortical areas that support this process respond selectively in fMRI to static and dynamic displays of human bodies and faces. Here we apply pattern-analysis techniques to arrive at a new understanding of the neural response to biological motion. Functionally defined body-, face-, and motion-selective visual areas all responded significantly to "point-light" human motion. Strikingly, however, only body selectivity was correlated, on a voxel-by-voxel basis, with biological motion selectivity. We conclude that (1) biological motion, through the process of structure-from-motion, engages areas involved in the analysis of the static human form; (2) body-selective regions in posterior fusiform gyrus and posterior inferior temporal sulcus overlap with, but are distinct from, face- and motion-selective regions; (3) the interpretation of region-of-interest findings may be substantially altered when multiple patterns of selectivity are considered.
A Scalable O(N) Algorithm for Large-Scale Parallel First-Principles Molecular Dynamics Simulations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Osei-Kuffuor, Daniel; Fattebert, Jean-Luc
2014-01-01
Traditional algorithms for first-principles molecular dynamics (FPMD) simulations only gain a modest capability increase from current petascale computers, due to their O(N 3) complexity and their heavy use of global communications. To address this issue, we are developing a truly scalable O(N) complexity FPMD algorithm, based on density functional theory (DFT), which avoids global communications. The computational model uses a general nonorthogonal orbital formulation for the DFT energy functional, which requires knowledge of selected elements of the inverse of the associated overlap matrix. We present a scalable algorithm for approximately computing selected entries of the inverse of the overlap matrix,more » based on an approximate inverse technique, by inverting local blocks corresponding to principal submatrices of the global overlap matrix. The new FPMD algorithm exploits sparsity and uses nearest neighbor communication to provide a computational scheme capable of extreme scalability. Accuracy is controlled by the mesh spacing of the finite difference discretization, the size of the localization regions in which the electronic orbitals are confined, and a cutoff beyond which the entries of the overlap matrix can be omitted when computing selected entries of its inverse. We demonstrate the algorithm's excellent parallel scaling for up to O(100K) atoms on O(100K) processors, with a wall-clock time of O(1) minute per molecular dynamics time step.« less
76 FR 29754 - Proposed Data Collections Submitted for Public Comment and Recommendations
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-23
... Agent or Toxin, (3) Report of Theft, Loss, or Release of Select Agent and Toxin, (4) Report of..., Use, and Transfer of Select Agents and Toxins (OMB Control No. 0920-0576)--Revision--Office of Public Health Preparedness and Response (OPHPR), Division of Select Agents and Toxins, Centers for Disease...
Emergence of social structures via preferential selection
NASA Astrophysics Data System (ADS)
Lipowski, Adam; Lipowska, Dorota; Ferreira, Antonio Luis
2014-09-01
We examine a weighted-network multiagent model with preferential selection such that agents choose partners with probability p (w), where w is the number of their past selections. When p (w) increases sublinearly with the number of past selections [p(w)˜wα,α<1], agents develop a uniform preference for all other agents. At α =1, this state loses stability and more complex structures form. For a superlinear increase (α>1), strong heterogeneities emerge and agents make selections mainly within small and sometimes asymmetric clusters. Even in a few-agent case, the formation of such clusters resembles phase transitions with spontaneous symmetry breaking.
42 CFR 73.3 - HHS select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-10-01
... been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria are... Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses...
A Bayesian Approach to the Overlap Analysis of Epidemiologically Linked Traits.
Asimit, Jennifer L; Panoutsopoulou, Kalliope; Wheeler, Eleanor; Berndt, Sonja I; Cordell, Heather J; Morris, Andrew P; Zeggini, Eleftheria; Barroso, Inês
2015-12-01
Diseases often cooccur in individuals more often than expected by chance, and may be explained by shared underlying genetic etiology. A common approach to genetic overlap analyses is to use summary genome-wide association study data to identify single-nucleotide polymorphisms (SNPs) that are associated with multiple traits at a selected P-value threshold. However, P-values do not account for differences in power, whereas Bayes' factors (BFs) do, and may be approximated using summary statistics. We use simulation studies to compare the power of frequentist and Bayesian approaches with overlap analyses, and to decide on appropriate thresholds for comparison between the two methods. It is empirically illustrated that BFs have the advantage over P-values of a decreasing type I error rate as study size increases for single-disease associations. Consequently, the overlap analysis of traits from different-sized studies encounters issues in fair P-value threshold selection, whereas BFs are adjusted automatically. Extensive simulations show that Bayesian overlap analyses tend to have higher power than those that assess association strength with P-values, particularly in low-power scenarios. Calibration tables between BFs and P-values are provided for a range of sample sizes, as well as an approximation approach for sample sizes that are not in the calibration table. Although P-values are sometimes thought more intuitive, these tables assist in removing the opaqueness of Bayesian thresholds and may also be used in the selection of a BF threshold to meet a certain type I error rate. An application of our methods is used to identify variants associated with both obesity and osteoarthritis. © 2015 The Authors. *Genetic Epidemiology published by Wiley Periodicals, Inc.
ERIC Educational Resources Information Center
Gottlieb, Lauren J.; Rugg, Michael D.
2011-01-01
Prior research has demonstrated that the neural correlates of successful encoding ("subsequent memory effects") partially overlap with neural regions selectively engaged by the on-line demands of the study task. The primary goal of the present experiment was to determine whether this overlap is associated solely with encoding processes supporting…
Deconvolution method for accurate determination of overlapping peak areas in chromatograms.
Nelson, T J
1991-12-20
A method is described for deconvoluting chromatograms which contain overlapping peaks. Parameters can be selected to ensure that attenuation of peak areas is uniform over any desired range of peak widths. A simple extension of the method greatly reduces the negative overshoot frequently encountered with deconvolutions. The deconvoluted chromatograms are suitable for integration by conventional methods.
Klimka, A; Barth, S; Matthey, B; Roovers, R C; Lemke, H; Hansen, H; Arends, J-W; Diehl, V; Hoogenboom, H R; Engert, A
1999-01-01
The human CD30 receptor is highly overexpressed on the surface of Hodgkin Reed-Sternberg cells and has been shown to be an excellent target for selective immunotherapy using monoclonal antibody-based agents such as immunotoxins. To construct a new recombinant immunotoxin for possible clinical use in patients with Hodgkin's lymphoma, we have chosen the murine anti-CD30 hybridoma Ki-4 to generate a high-affinity Ki-4 single-chain variable fragment (scFv). Hybridoma V-genes were polymerase chain reaction-amplified, assembled, cloned and expressed as a mini-library for display on filamentous phage. Functional Ki-4 scFv were obtained by selection of binding phage on the Hodgkin lymphoma-derived, CD30-expressing cell line L540Cy. The selected recombinant Ki-4 scFv was shown to specifically bind to an overlapping epitope on the CD30 antigen with binding kinetics similar to those of the original antibody. The Ki-4 scFv was subsequently fused to a deletion mutant of Pseudomonas exotoxin A (ETÁ). The resulting immunotoxin Ki-4(scFv)-ETÁ specifically binds to CD30+ L540Cy cells and inhibits the protein synthesis by 50% at a concentration (IC50) of 43 pM. This recombinant immunotoxin is a promising candidate for further clinical evaluation in patients with Hodgkin's lymphoma or other CD30+ malignancies. © 1999 Cancer Research Campaign PMID:10376974
Modeling the dynamical interaction between epidemics on overlay networks
NASA Astrophysics Data System (ADS)
Marceau, Vincent; Noël, Pierre-André; Hébert-Dufresne, Laurent; Allard, Antoine; Dubé, Louis J.
2011-08-01
Epidemics seldom occur as isolated phenomena. Typically, two or more viral agents spread within the same host population and may interact dynamically with each other. We present a general model where two viral agents interact via an immunity mechanism as they propagate simultaneously on two networks connecting the same set of nodes. By exploiting a correspondence between the propagation dynamics and a dynamical process performing progressive network generation, we develop an analytical approach that accurately captures the dynamical interaction between epidemics on overlay networks. The formalism allows for overlay networks with arbitrary joint degree distribution and overlap. To illustrate the versatility of our approach, we consider a hypothetical delayed intervention scenario in which an immunizing agent is disseminated in a host population to hinder the propagation of an undesirable agent (e.g., the spread of preventive information in the context of an emerging infectious disease).
Hansen, Adam G.; Beauchamp, David A.
2014-01-01
Most predators eat only a subset of possible prey. However, studies evaluating diet selection rarely measure prey availability in a manner that accounts for temporal–spatial overlap with predators, the sensory mechanisms employed to detect prey, and constraints on prey capture.We evaluated the diet selection of cutthroat trout (Oncorhynchus clarkii) feeding on a diverse planktivore assemblage in Lake Washington to test the hypothesis that the diet selection of piscivores would reflect random (opportunistic) as opposed to non-random (targeted) feeding, after accounting for predator–prey overlap, visual detection and capture constraints.Diets of cutthroat trout were sampled in autumn 2005, when the abundance of transparent, age-0 longfin smelt (Spirinchus thaleichthys) was low, and 2006, when the abundance of smelt was nearly seven times higher. Diet selection was evaluated separately using depth-integrated and depth-specific (accounted for predator–prey overlap) prey abundance. The abundance of different prey was then adjusted for differences in detectability and vulnerability to predation to see whether these factors could explain diet selection.In 2005, cutthroat trout fed non-randomly by selecting against the smaller, transparent age-0 longfin smelt, but for the larger age-1 longfin smelt. After adjusting prey abundance for visual detection and capture, cutthroat trout fed randomly. In 2006, depth-integrated and depth-specific abundance explained the diets of cutthroat trout well, indicating random feeding. Feeding became non-random after adjusting for visual detection and capture. Cutthroat trout selected strongly for age-0 longfin smelt, but against similar sized threespine stickleback (Gasterosteus aculeatus) and larger age-1 longfin smelt in 2006. Overlap with juvenile sockeye salmon (O. nerka) was minimal in both years, and sockeye salmon were rare in the diets of cutthroat trout.The direction of the shift between random and non-random selection depended on the presence of a weak versus a strong year class of age-0 longfin smelt. These fish were easy to catch, but hard to see. When their density was low, poor detection could explain their rarity in the diet. When their density was high, poor detection was compensated by higher encounter rates with cutthroat trout, sufficient to elicit a targeted feeding response. The nature of the feeding selectivity of a predator can be highly dependent on fluctuations in the abundance and suitability of key prey.
Specific responses of human hippocampal neurons are associated with better memory.
Suthana, Nanthia A; Parikshak, Neelroop N; Ekstrom, Arne D; Ison, Matias J; Knowlton, Barbara J; Bookheimer, Susan Y; Fried, Itzhak
2015-08-18
A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.
ERIC Educational Resources Information Center
Ward, Robert; Ward, Ronnie
2008-01-01
This study examined the selective attention abilities of a simple, artificial, evolved agent and considered implications of the agent's performance for theories of selective attention and action. The agent processed two targets in continuous time, catching one and then the other. This task required many cognitive operations, including prioritizing…
Entropic forces drive contraction of cytoskeletal networks.
Braun, Marcus; Lansky, Zdenek; Hilitski, Feodor; Dogic, Zvonimir; Diez, Stefan
2016-05-01
The cytoskeleton is a network of interconnected protein filaments, which provide a three-dimensional scaffold for cells. Remodeling of the cytoskeleton is important for key cellular processes, such as cell motility, division, or morphogenesis. This remodeling is traditionally considered to be driven exclusively by processes consuming chemical energy, such as the dynamics of the filaments or the action of molecular motors. Here, we review two mechanisms of cytoskeletal network remodeling that are independent of the consumption of chemical energy. In both cases directed motion of overlapping filaments is driven by entropic forces, which arise from harnessing thermal energy present in solution. Entropic forces are induced either by macromolecular crowding agents or by diffusible crosslinkers confined to the regions where filaments overlap. Both mechanisms increase filament overlap length and lead to the contraction of filament networks. These force-generating mechanisms, together with the chemical energy-dependent mechanisms, need to be considered for the comprehensive quantitative picture of the remodeling of cytoskeletal networks in cells. © 2016 WILEY Periodicals, Inc.
Safety of treatment options for spondyloarthritis: a narrative review.
D'Angelo, Salvatore; Carriero, Antonio; Gilio, Michele; Ursini, Francesco; Leccese, Pietro; Palazzi, Carlo
2018-05-01
Spondyloarthritis (SpA) are chronic inflammatory diseases with overlapping pathogenic mechanisms and clinical features. Treatment armamentarium against SpA includes non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs, including sulfasalazine, methotrexate, leflunomide, cyclosporine), targeted synthetic DMARDs (apremilast) and biological DMARDs (TNF inhibitors, anti-IL 12/23 and anti-IL-17 agents). Areas covered: A narrative review of published literature on safety profile of available SpA treatment options was performed. Readers will be provided with a comprehensive overview on frequent and rare adverse events associated with each drug listed in current SpA treatment recommendations. Expert opinion: The overall safety profile of such molecules is good and serious adverse events are rare but need to be promptly recognized and treated. However, the monitoring of adverse events is a major challenge for clinicians because it is not adequately addressed by current treatment recommendations. A tailored treatment is crucial and rheumatologists must accurately select patients in order to identify those more susceptible to develop adverse events.
Ward, Robert; Ward, Ronnie
2008-10-01
This study examined the selective attention abilities of a simple, artificial, evolved agent and considered implications of the agent's performance for theories of selective attention and action. The agent processed two targets in continuous time, catching one and then the other. This task required many cognitive operations, including prioritizing the first target (T1) over the second (T2); selectively focusing responses on T1, while preventing T2 from interfering with responses; creating a memory for the unselected T2 item, so that it could be efficiently processed later; and reallocating processing towards T2 after catching T1. The evolved agent demonstrated all these abilities. Analysis shows that the agent used reactive inhibition to selectively focus behavior. That is, the more salient T2, the more strongly responses towards T2 were inhibited and the slower the agent was to subsequently reallocate processing towards T2. Reactive inhibition was also suggested in two experiments with people, performing a virtually identical catch task. The presence of reactive inhibition in the simple agent and in people suggests that it is an important mechanism for selective processing.
Multi-agent Reinforcement Learning Model for Effective Action Selection
NASA Astrophysics Data System (ADS)
Youk, Sang Jo; Lee, Bong Keun
Reinforcement learning is a sub area of machine learning concerned with how an agent ought to take actions in an environment so as to maximize some notion of long-term reward. In the case of multi-agent, especially, which state space and action space gets very enormous in compared to single agent, so it needs to take most effective measure available select the action strategy for effective reinforcement learning. This paper proposes a multi-agent reinforcement learning model based on fuzzy inference system in order to improve learning collect speed and select an effective action in multi-agent. This paper verifies an effective action select strategy through evaluation tests based on Robocop Keep away which is one of useful test-beds for multi-agent. Our proposed model can apply to evaluate efficiency of the various intelligent multi-agents and also can apply to strategy and tactics of robot soccer system.
A fully automated non-external marker 4D-CT sorting algorithm using a serial cine scanning protocol.
Carnes, Greg; Gaede, Stewart; Yu, Edward; Van Dyk, Jake; Battista, Jerry; Lee, Ting-Yim
2009-04-07
Current 4D-CT methods require external marker data to retrospectively sort image data and generate CT volumes. In this work we develop an automated 4D-CT sorting algorithm that performs without the aid of data collected from an external respiratory surrogate. The sorting algorithm requires an overlapping cine scan protocol. The overlapping protocol provides a spatial link between couch positions. Beginning with a starting scan position, images from the adjacent scan position (which spatial match the starting scan position) are selected by maximizing the normalized cross correlation (NCC) of the images at the overlapping slice position. The process was continued by 'daisy chaining' all couch positions using the selected images until an entire 3D volume was produced. The algorithm produced 16 phase volumes to complete a 4D-CT dataset. Additional 4D-CT datasets were also produced using external marker amplitude and phase angle sorting methods. The image quality of the volumes produced by the different methods was quantified by calculating the mean difference of the sorted overlapping slices from adjacent couch positions. The NCC sorted images showed a significant decrease in the mean difference (p < 0.01) for the five patients.
Improving Discoverability of Geophysical Data using Location Based Services
NASA Astrophysics Data System (ADS)
Morrison, D.; Barnes, R. J.; Potter, M.; Nylund, S. R.; Patrone, D.; Weiss, M.; Talaat, E. R.; Sarris, T. E.; Smith, D.
2014-12-01
The great promise of Virtual Observatories is the ability to perform complex search operations across the metadata of a large variety of different data sets. This allows the researcher to isolate and select the relevant measurements for their topic of study. The Virtual ITM Observatory (VITMO) has many diverse geophysical datasets that cover a large temporal and spatial range that present a unique search problem. VITMO provides many methods by which the user can search for and select data of interest including restricting selections based on geophysical conditions (solar wind speed, Kp, etc) as well as finding those datasets that overlap in time. One of the key challenges in improving discoverability is the ability to identify portions of datasets that overlap in time and in location. The difficulty is that location data is not contained in the metadata for datasets produced by satellites and would be extremely large in volume if it were available, making searching for overlapping data very time consuming. To solve this problem we have developed a series of light-weight web services that can provide a new data search capability for VITMO and others. The services consist of a database of spacecraft ephemerides and instrument fields of view; an overlap calculator to find times when the fields of view of different instruments intersect; and a magnetic field line tracing service that maps in situ and ground based measurements to the equatorial plane in magnetic coordinates for a number of field models and geophysical conditions. These services run in real-time when the user queries for data. They will allow the non-specialist user to select data that they were previously unable to locate, opening up analysis opportunities beyond the instrument teams and specialists, making it easier for future students who come into the field.
Efficient methods for overlapping group lasso.
Yuan, Lei; Liu, Jun; Ye, Jieping
2013-09-01
The group Lasso is an extension of the Lasso for feature selection on (predefined) nonoverlapping groups of features. The nonoverlapping group structure limits its applicability in practice. There have been several recent attempts to study a more general formulation where groups of features are given, potentially with overlaps between the groups. The resulting optimization is, however, much more challenging to solve due to the group overlaps. In this paper, we consider the efficient optimization of the overlapping group Lasso penalized problem. We reveal several key properties of the proximal operator associated with the overlapping group Lasso, and compute the proximal operator by solving the smooth and convex dual problem, which allows the use of the gradient descent type of algorithms for the optimization. Our methods and theoretical results are then generalized to tackle the general overlapping group Lasso formulation based on the l(q) norm. We further extend our algorithm to solve a nonconvex overlapping group Lasso formulation based on the capped norm regularization, which reduces the estimation bias introduced by the convex penalty. We have performed empirical evaluations using both a synthetic and the breast cancer gene expression dataset, which consists of 8,141 genes organized into (overlapping) gene sets. Experimental results show that the proposed algorithm is more efficient than existing state-of-the-art algorithms. Results also demonstrate the effectiveness of the nonconvex formulation for overlapping group Lasso.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-12-15
... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Amendments to the Select Agent and Toxin Regulations AGENCY: Animal and Plant Health Inspection Service, USDA... proposed rule that would amend and republish the list of select agents and toxins that have the potential...
Niche segregation between wild and domestic herbivores in Chilean Patagonia.
Iranzo, Esperanza C; Traba, Juan; Acebes, Pablo; González, Benito A; Mata, Cristina; Estades, Cristián F; Malo, Juan E
2013-01-01
Competition arises when two co-occuring species share a limiting resource. Potential for competition is higher when species have coexisted for a short time, as it is the case for herbivores and livestock introduced in natural systems. Sheep, introduced in the late 19(th) century in Patagonia, bear a great resemblance in size and diet to the guanaco, the main native herbivore in Patagonia. In such circumstances, it could be expected that the two species compete and one of them could be displaced. We investigated spatial overlap and habitat selection by coexisting sheep and guanaco in winter and in summer. Additionally, we studied habitat selection of the guanaco in a control situation free from sheep, both in summer and winter. We also determined overlap between species in areas with different intensity of use (named preferred and marginal areas) in order to further detect the potential level of competition in the case of overlapping. Guanaco and sheep showed significantly different habitat preferences through all seasons, in spite of their spatial overlap at landscape scale. Additionally, the habitat used by guanaco was similar regardless of the presence or absence of livestock, which further indicates that sheep is not displacing guanaco where they coexist. These results suggest that habitat segregation between guanaco and sheep is due to a differential habitat selection and not to a competitive displacement process. Therefore, the potential for competition is considered low, contrary to what has been previously observed, although this could be a density-dependent result.
The effect of relatedness and pack size on territory overlap in African wild dogs.
Jackson, Craig R; Groom, Rosemary J; Jordan, Neil R; McNutt, J Weldon
2017-01-01
Spacing patterns mediate competitive interactions between conspecifics, ultimately increasing fitness. The degree of territorial overlap between neighbouring African wild dog ( Lycaon pictus ) packs varies greatly, yet the role of factors potentially affecting the degree of overlap, such as relatedness and pack size, remain unclear. We used movement data from 21 wild dog packs to calculate the extent of territory overlap (20 dyads). On average, unrelated neighbouring packs had low levels of overlap restricted to the peripheral regions of their 95% utilisation kernels. Related neighbours had significantly greater levels of peripheral overlap. Only one unrelated dyad included overlap between 75%-75% kernels, but no 50%-50% kernels overlapped. However, eight of 12 related dyads overlapped between their respective 75% kernels and six between the frequented 50% kernels. Overlap between these more frequented kernels confers a heightened likelihood of encounter, as the mean utilisation intensity per unit area within the 50% kernels was 4.93 times greater than in the 95% kernels, and 2.34 times greater than in the 75% kernels. Related packs spent significantly more time in their 95% kernel overlap zones than did unrelated packs. Pack size appeared to have little effect on overlap between related dyads, yet among unrelated neighbours larger packs tended to overlap more onto smaller packs' territories. However, the true effect is unclear given that the model's confidence intervals overlapped zero. Evidence suggests that costly intraspecific aggression is greatly reduced between related packs. Consequently, the tendency for dispersing individuals to establish territories alongside relatives, where intensively utilised portions of ranges regularly overlap, may extend kin selection and inclusive fitness benefits from the intra-pack to inter-pack level. This natural spacing system can affect survival parameters and the carrying capacity of protected areas, having important management implications for intensively managed populations of this endangered species.
A distributed automatic target recognition system using multiple low resolution sensors
NASA Astrophysics Data System (ADS)
Yue, Zhanfeng; Lakshmi Narasimha, Pramod; Topiwala, Pankaj
2008-04-01
In this paper, we propose a multi-agent system which uses swarming techniques to perform high accuracy Automatic Target Recognition (ATR) in a distributed manner. The proposed system can co-operatively share the information from low-resolution images of different looks and use this information to perform high accuracy ATR. An advanced, multiple-agent Unmanned Aerial Vehicle (UAV) systems-based approach is proposed which integrates the processing capabilities, combines detection reporting with live video exchange, and swarm behavior modalities that dramatically surpass individual sensor system performance levels. We employ real-time block-based motion analysis and compensation scheme for efficient estimation and correction of camera jitter, global motion of the camera/scene and the effects of atmospheric turbulence. Our optimized Partition Weighted Sum (PWS) approach requires only bitshifts and additions, yet achieves a stunning 16X pixel resolution enhancement, which is moreover parallizable. We develop advanced, adaptive particle-filtering based algorithms to robustly track multiple mobile targets by adaptively changing the appearance model of the selected targets. The collaborative ATR system utilizes the homographies between the sensors induced by the ground plane to overlap the local observation with the received images from other UAVs. The motion of the UAVs distorts estimated homography frame to frame. A robust dynamic homography estimation algorithm is proposed to address this, by using the homography decomposition and the ground plane surface estimation.
NASA Technical Reports Server (NTRS)
Betts, Bruce H.
1994-01-01
Thermal infrared observations of Mars from spacecraft provide physical information about the upper thermal skin depth of the surface, which is on the order of a few centimeters in depth and thus very significant for lander site selection. The Termoskan instrument onboard the Soviet Phobos '88 spacecraft acquired the highest spatial-resolution thermal infrared data obtained for Mars, ranging in resolution from 300 m to 3 km per pixel. It simultaneously obtained broadband reflected solar flux data. Although the 6 deg N - 30 deg S Termoskan coverage only slightly overlaps the nominal Mars Pathfinder target range, the implications of Termoskan data for that overlap region and the extrapolations that can be made to other regions give important clues for optimal landing site selection.
Iwata, Momi; Lee, Yang; Yamashita, Tetsuo; Yagi, Takao; Iwata, So; Cameron, Alexander D; Maher, Megan J
2012-09-18
Bioenergy is efficiently produced in the mitochondria by the respiratory system consisting of complexes I-V. In various organisms, complex I can be replaced by the alternative NADH-quinone oxidoreductase (NDH-2), which catalyzes the transfer of an electron from NADH via FAD to quinone, without proton pumping. The Ndi1 protein from Saccharomyces cerevisiae is a monotopic membrane protein, directed to the matrix. A number of studies have investigated the potential use of Ndi1 as a therapeutic agent against complex I disorders, and the NDH-2 enzymes have emerged as potential therapeutic targets for treatments against the causative agents of malaria and tuberculosis. Here we present the crystal structures of Ndi1 in its substrate-free, NAD(+)- and ubiquinone- (UQ2) complexed states. The structures reveal that Ndi1 is a peripheral membrane protein forming an intimate dimer, in which packing of the monomeric units within the dimer creates an amphiphilic membrane-anchor domain structure. Crucially, the structures of the Ndi1-NAD(+) and Ndi1-UQ2 complexes show overlapping binding sites for the NAD(+) and quinone substrates.
Kelling, Craig J.; Isermann, Daniel A.; Sloss, Brian L.; Turnquist, Keith N.
2016-01-01
Over the last decade, the abundance of Largemouth Bass Micropterus salmoides has increased in many northern Wisconsin lakes, causing concern among anglers and biologists regarding the potential for Largemouth Bass to negatively affect populations of Walleye Sander vitreus through predation or competition for prey. Our objectives were to determine whether (1) diet overlap and predation occurred between adult Walleyes and Largemouth Bass in four northern Wisconsin lakes and (2) the use of DNA barcoding to reduce unidentifiable fish in diet samples affected conclusions regarding diet overlap. A single occurrence of Walleye predation was observed in the diets of 945 Largemouth Bass. Moderate to high diet overlap was observed between Largemouth Bass and Walleyes throughout much of the study period. The use of DNA barcoding reduced the amount of unidentified fish in diets to <1% and showed that failure to identify fish or fish parts can affect conclusions regarding diet overlap. Largemouth Bass predation is probably not a primary factor affecting Walleye abundance in the lakes we selected, but observed diet overlap suggests the potential for competition between the two species.
Generation of virtual monochromatic CBCT from dual kV/MV beam projections
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Hao; Liu, Bo; Yin, Fang-Fang, E-mail: fangfang.yin@duke.edu
Purpose: To develop a novel on-board imaging technique which allows generation of virtual monochromatic (VM) cone-beam CT (CBCT) with a selected energy from combined kilovoltage (kV)/megavoltage (MV) beam projections. Methods: With the current orthogonal kV/MV imaging hardware equipped in modern linear accelerators, both MV projections (from gantry angle of 0°–100°) and kV projections (90°–200°) were acquired as gantry rotated a total of 110°. A selected range of overlap projections between 90° to 100° were then decomposed into two material projections using experimentally determined parameters from orthogonally stacked aluminum and acrylic step-wedges. Given attenuation coefficients of aluminum and acrylic at amore » predetermined energy, one set of VM projections could be synthesized from two corresponding sets of decomposed projections. Two linear functions were generated using projection information at overlap angles to convert kV and MV projections at nonoverlap angles to approximate VM projections for CBCT reconstruction. The contrast-to-noise ratios (CNRs) were calculated for different inserts in VM CBCTs of a CatPhan phantom with various selected energies and compared with those in kV and MV CBCTs. The effect of overlap projection number on CNR was evaluated. Additionally, the effect of beam orientation was studied by scanning the CatPhan sandwiched with two 5 cm solid-water phantoms on both lateral sides and an electronic density phantom with two metal bolt inserts. Results: Proper selection of VM energy [30 and 40 keV for low-density polyethylene (LDPE), polymethylpentene, 2 MeV for Delrin] provided comparable or even better CNR results as compared with kV or MV CBCT. An increased number of overlap kV and MV projection demonstrated only marginal improvements of CNR for different inserts (with the exception of LDPE) and therefore one projection overlap was found to be sufficient for the CatPhan study. It was also evident that the optimal CBCT image quality was achieved when MV beams penetrated through the heavy attenuation direction of the object. Conclusions: A novel technique was developed to generate VM CBCTs from kV/MV projections. This technique has the potential to improve CNR at selected VM energies and to suppress artifacts at appropriate beam orientations.« less
Generation of virtual monochromatic CBCT from dual kV/MV beam projections
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Hao; Liu, Bo; Yin, Fang-Fang, E-mail: fangfang.yin@duke.edu
2013-12-15
Purpose: To develop a novel on-board imaging technique which allows generation of virtual monochromatic (VM) cone-beam CT (CBCT) with a selected energy from combined kilovoltage (kV)/megavoltage (MV) beam projections. Methods: With the current orthogonal kV/MV imaging hardware equipped in modern linear accelerators, both MV projections (from gantry angle of 0°–100°) and kV projections (90°–200°) were acquired as gantry rotated a total of 110°. A selected range of overlap projections between 90° to 100° were then decomposed into two material projections using experimentally determined parameters from orthogonally stacked aluminum and acrylic step-wedges. Given attenuation coefficients of aluminum and acrylic at amore » predetermined energy, one set of VM projections could be synthesized from two corresponding sets of decomposed projections. Two linear functions were generated using projection information at overlap angles to convert kV and MV projections at nonoverlap angles to approximate VM projections for CBCT reconstruction. The contrast-to-noise ratios (CNRs) were calculated for different inserts in VM CBCTs of a CatPhan phantom with various selected energies and compared with those in kV and MV CBCTs. The effect of overlap projection number on CNR was evaluated. Additionally, the effect of beam orientation was studied by scanning the CatPhan sandwiched with two 5 cm solid-water phantoms on both lateral sides and an electronic density phantom with two metal bolt inserts. Results: Proper selection of VM energy [30 and 40 keV for low-density polyethylene (LDPE), polymethylpentene, 2 MeV for Delrin] provided comparable or even better CNR results as compared with kV or MV CBCT. An increased number of overlap kV and MV projection demonstrated only marginal improvements of CNR for different inserts (with the exception of LDPE) and therefore one projection overlap was found to be sufficient for the CatPhan study. It was also evident that the optimal CBCT image quality was achieved when MV beams penetrated through the heavy attenuation direction of the object. Conclusions: A novel technique was developed to generate VM CBCTs from kV/MV projections. This technique has the potential to improve CNR at selected VM energies and to suppress artifacts at appropriate beam orientations.« less
Early top-down control of visual processing predicts working memory performance
Rutman, Aaron M.; Clapp, Wesley C.; Chadick, James Z.; Gazzaley, Adam
2009-01-01
Selective attention confers a behavioral benefit for both perceptual and working memory (WM) performance, often attributed to top-down modulation of sensory neural processing. However, the direct relationship between early activity modulation in sensory cortices during selective encoding and subsequent WM performance has not been established. To explore the influence of selective attention on WM recognition, we used electroencephalography (EEG) to study the temporal dynamics of top-down modulation in a selective, delayed-recognition paradigm. Participants were presented with overlapped, “double-exposed” images of faces and natural scenes, and were instructed to either remember the face or the scene while simultaneously ignoring the other stimulus. Here, we present evidence that the degree to which participants modulate the early P100 (97–129 ms) event-related potential (ERP) during selective stimulus encoding significantly correlates with their subsequent WM recognition. These results contribute to our evolving understanding of the mechanistic overlap between attention and memory. PMID:19413473
The Real-Time ObjectAgent Software Architecture for Distributed Satellite Systems
2001-01-01
real - time operating system selection are also discussed. The fourth section describes a simple demonstration of real-time ObjectAgent. Finally, the...experience with C++. After selecting the programming language, it was necessary to select a target real - time operating system (RTOS) and embedded...ObjectAgent software to run on the OSE Real Time Operating System . In addition, she is responsible for the integration of ObjectAgent
Kopp, Bruno; Tabeling, Sandra; Moschner, Carsten; Wessel, Karl
2007-08-17
Decision-making is a fundamental capacity which is crucial to many higher-order psychological functions. We recorded event-related potentials (ERPs) during a visual target-identification task that required go-nogo choices. Targets were identified on the basis of cross-dimensional conjunctions of particular colors and forms. Color discriminability was manipulated in three conditions to determine the effects of color distinctiveness on component processes of decision-making. Target identification was accompanied by the emergence of prefrontal P2a and P3b. Selection negativity (SN) revealed that target-compatible features captured attention more than target-incompatible features, suggesting that intra-dimensional attentional capture was goal-contingent. No changes of cross-dimensional selection priorities were measurable when color discriminability was altered. Peak latencies of the color-related SN provided a chronometric measure of the duration of attention-related neural processing. ERPs recorded over the frontocentral scalp (N2c, P3a) revealed that color-overlap distractors, more than form-overlap distractors, required additional late selection. The need for additional response selection induced by color-overlap distractors was severely reduced when color discriminability decreased. We propose a simple model of cross-dimensional perceptual decision-making. The temporal synchrony of separate color-related and form-related choices determines whether or not distractor processing includes post-perceptual stages. ERP measures contribute to a comprehensive explanation of the temporal dynamics of component processes of perceptual decision-making.
Kastenmayer, Robin J; Moore, Rashida M; Bright, Allison L; Torres-Cruz, Rafael; Elkins, William R
2012-01-01
In the interval between the publication of the seventh and eighth editions of the Guide for the Care and Use of Laboratory Animals (Guide), much has changed with regard to the regulation and funding of highly pathogenic biologic agents and toxins (Select Agents). Funding of research involving highly pathogenic agents has increased dramatically during this time, thus increasing the demand for facilities capable of supporting this work. The eighth edition of the Guide briefly mentions Select Agents and provides a limited set of references. Here we provide some background information regarding the relevant laws and regulations, as well as an overview of the programmatic requirements pertaining to the use of Select Agents, with a focus on use in animals. PMID:22776191
Kizilirmak, Jasmin M; Rösler, Frank; Bien, Siegfried; Khader, Patrick H
2015-07-21
The attention to memory theory (AtoM) proposes that the same brain regions might be involved in selective processing of perceived stimuli (selective attention) and memory representations (selective retrieval). Although this idea is compelling, given consistently found neural overlap between perceiving and remembering stimuli, recent comparisons brought evidence for overlap as well as considerable differences. Here, we present a paradigm that enables the investigation of the AtoM hypothesis from a novel perspective to gain further insight into the neural resources involved in AtoM. Selective attention in perception is often investigated as a control process that shows lingering effects on immediately following trials. Here, we employed a paradigm capable of modulating selective retrieval in a similarly dynamic manner as in such selective-attention paradigms by inducing trial-to-trial shifts between relevant and irrelevant memory representations as well as changes of the width of the internal focus on memory. We found evidence for an involvement of bilateral inferior parietal lobe and right inferior frontal gyrus in reorienting the attentional focus on previously accessed memory representations. Moreover, we could dissociate the right inferior from the parietal activation in separate contrasts, suggesting that the right inferior frontal gyrus plays a role in facilitating attentional reorienting to memory representations when competing representations have been activated in the preceding trial, potentially by resolving this competition. Our results support the AtoM theory, i.e. that ventral frontal and parietal regions are involved in automatic attentional reorienting in memory, and highlight the importance of further investigations of the overlap and differences between regions involved in internal (memory) and external (perceptual) attentional selection. Copyright © 2015 Elsevier B.V. All rights reserved.
9 CFR 121.3 - VS select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-01-01
... genetically modified. (d) VS select agents or toxins that meet any of the following criteria are excluded from... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND... recombinant organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses...
Long-term evolution of the Luteoviridae: time scale and mode of virus speciation.
Pagán, Israel; Holmes, Edward C
2010-06-01
Despite their importance as agents of emerging disease, the time scale and evolutionary processes that shape the appearance of new viral species are largely unknown. To address these issues, we analyzed intra- and interspecific evolutionary processes in the Luteoviridae family of plant RNA viruses. Using the coat protein gene of 12 members of the family, we determined their phylogenetic relationships, rates of nucleotide substitution, times to common ancestry, and patterns of speciation. An associated multigene analysis enabled us to infer the nature of selection pressures and the genomic distribution of recombination events. Although rates of evolutionary change and selection pressures varied among genes and species and were lower in some overlapping gene regions, all fell within the range of those seen in animal RNA viruses. Recombination breakpoints were commonly observed at gene boundaries but less so within genes. Our molecular clock analysis suggested that the origin of the currently circulating Luteoviridae species occurred within the last 4 millennia, with intraspecific genetic diversity arising within the last few hundred years. Speciation within the Luteoviridae may therefore be associated with the expansion of agricultural systems. Finally, our phylogenetic analysis suggested that viral speciation events tended to occur within the same plant host species and country of origin, as expected if speciation is largely sympatric, rather than allopatric, in nature.
Masking reduces orientation selectivity in rat visual cortex
Alwis, Dasuni S.; Richards, Katrina L.
2016-01-01
In visual masking the perception of a target stimulus is impaired by a preceding (forward) or succeeding (backward) mask stimulus. The illusion is of interest because it allows uncoupling of the physical stimulus, its neuronal representation, and its perception. To understand the neuronal correlates of masking, we examined how masks affected the neuronal responses to oriented target stimuli in the primary visual cortex (V1) of anesthetized rats (n = 37). Target stimuli were circular gratings with 12 orientations; mask stimuli were plaids created as a binarized sum of all possible target orientations. Spatially, masks were presented either overlapping or surrounding the target. Temporally, targets and masks were presented for 33 ms, but the stimulus onset asynchrony (SOA) of their relative appearance was varied. For the first time, we examine how spatially overlapping and center-surround masking affect orientation discriminability (rather than visibility) in V1. Regardless of the spatial or temporal arrangement of stimuli, the greatest reductions in firing rate and orientation selectivity occurred for the shortest SOAs. Interestingly, analyses conducted separately for transient and sustained target response components showed that changes in orientation selectivity do not always coincide with changes in firing rate. Given the near-instantaneous reductions observed in orientation selectivity even when target and mask do not spatially overlap, we suggest that monotonic visual masking is explained by a combination of neural integration and lateral inhibition. PMID:27535373
Ptak, Radek; Lazeyras, François; Di Pietro, Marie; Schnider, Armin; Simon, Stéphane R
2014-07-01
Patients with visual object agnosia fail to recognize the identity of visually presented objects despite preserved semantic knowledge. Object agnosia may result from damage to visual cortex lying close to or overlapping with the lateral occipital complex (LOC), a brain region that exhibits selectivity to the shape of visually presented objects. Despite this anatomical overlap the relationship between shape processing in the LOC and shape representations in object agnosia is unknown. We studied a patient with object agnosia following isolated damage to the left occipito-temporal cortex overlapping with the LOC. The patient showed intact processing of object structure, yet often made identification errors that were mainly based on the global visual similarity between objects. Using functional Magnetic Resonance Imaging (fMRI) we found that the damaged as well as the contralateral, structurally intact right LOC failed to show any object-selective fMRI activity, though the latter retained selectivity for faces. Thus, unilateral damage to the left LOC led to a bilateral breakdown of neural responses to a specific stimulus class (objects and artefacts) while preserving the response to a different stimulus class (faces). These findings indicate that representations of structure necessary for the identification of objects crucially rely on bilateral, distributed coding of shape features. Copyright © 2014 Elsevier Ltd. All rights reserved.
Distinct but Overlapping Patterns of Response to Words and Faces in the Fusiform Gyrus.
Harris, Richard J; Rice, Grace E; Young, Andrew W; Andrews, Timothy J
2016-07-01
Converging evidence suggests that the fusiform gyrus is involved in the processing of both faces and words. We used fMRI to investigate the extent to which the representation of words and faces in this region of the brain is based on a common neural representation. In Experiment 1, a univariate analysis revealed regions in the fusiform gyrus that were only selective for faces and other regions that were only selective for words. However, we also found regions that showed both word-selective and face-selective responses, particularly in the left hemisphere. We then used a multivariate analysis to measure the pattern of response to faces and words. Despite the overlap in regional responses, we found distinct patterns of response to both faces and words in the left and right fusiform gyrus. In Experiment 2, fMR adaptation was used to determine whether information about familiar faces and names is integrated in the fusiform gyrus. Distinct regions of the fusiform gyrus showed adaptation to either familiar faces or familiar names. However, there was no adaptation to sequences of faces and names with the same identity. Taken together, these results provide evidence for distinct, but overlapping, neural representations for words and faces in the fusiform gyrus. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Alpha-beta coordination method for collective search
Goldsmith, Steven Y.
2002-01-01
The present invention comprises a decentralized coordination strategy called alpha-beta coordination. The alpha-beta coordination strategy is a family of collective search methods that allow teams of communicating agents to implicitly coordinate their search activities through a division of labor based on self-selected roles and self-determined status. An agent can play one of two complementary roles. An agent in the alpha role is motivated to improve its status by exploring new regions of the search space. An agent in the beta role is also motivated to improve its status, but is conservative and tends to remain aggregated with other agents until alpha agents have clearly identified and communicated better regions of the search space. An agent can select its role dynamically based on its current status value relative to the status values of neighboring team members. Status can be determined by a function of the agent's sensor readings, and can generally be a measurement of source intensity at the agent's current location. An agent's decision cycle can comprise three sequential decision rules: (1) selection of a current role based on the evaluation of the current status data, (2) selection of a specific subset of the current data, and (3) determination of the next heading using the selected data. Variations of the decision rules produce different versions of alpha and beta behaviors that lead to different collective behavior properties.
7 CFR 331.10 - Restricting access to select agents and toxins; security risk assessments.
Code of Federal Regulations, 2010 CFR
2010-01-01
...; security risk assessments. 331.10 Section 331.10 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE POSSESSION, USE, AND TRANSFER OF SELECT AGENTS AND TOXINS § 331.10 Restricting access to select agents and toxins; security risk...
42 CFR 73.5 - Exemptions for HHS select agents and toxins.
Code of Federal Regulations, 2014 CFR
2014-10-01
... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other HHS select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...
42 CFR 73.5 - Exemptions for HHS select agents and toxins.
Code of Federal Regulations, 2013 CFR
2013-10-01
... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other HHS select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...
Automated seamline detection along skeleton for remote sensing image mosaicking
NASA Astrophysics Data System (ADS)
Zhang, Hansong; Chen, Jianyu; Liu, Xin
2015-08-01
The automatic generation of seamline along the overlap region skeleton is a concerning problem for the mosaicking of Remote Sensing(RS) images. Along with the improvement of RS image resolution, it is necessary to ensure rapid and accurate processing under complex conditions. So an automated seamline detection method for RS image mosaicking based on image object and overlap region contour contraction is introduced. By this means we can ensure universality and efficiency of mosaicking. The experiments also show that this method can select seamline of RS images with great speed and high accuracy over arbitrary overlap regions, and realize RS image rapid mosaicking in surveying and mapping production.
T. Ryan McCarley; Crystal A. Kolden; Nicole M. Vaillant; Andrew T. Hudak; Alistair M. S. Smith; Jason Kreitler
2017-01-01
Across the western United States, the three primary drivers of tree mortality and carbon balance are bark beetles, timber harvest, and wildfire. While these agents of forest change frequently overlap, uncertainty remains regarding their interactions and influence on specific subsequent fire effects such as change in canopy cover. Acquisition of pre- and post-fire Light...
ERIC Educational Resources Information Center
McGinnis, Theresa Ann; Garcia, Andrea
2012-01-01
In this article, we use narrative theory to analyze and discuss how one Salvadoran youth, Thomas, constructed three different yet overlapping narratives, including a digital story, on his family's movement across borders. We describe how each telling of his narratives is situated in time and space, where Thomas reveals his understandings of…
Key Planning Factors for Recovery from a Chemical Warfare Agent Incident
2012-07-01
confusion and degradation of public trust. Such consequences were brought to light for the U.S. during the Fukushima Daiichi nuclear power plant...appendices follow : the first describing the relationships among the National Disaster Recovery Framework Recovery Support Functions, the National...phases of action following a disaster incident— short-, intermediate-, and long-term—that can overlap, sometimes considerably. As shown in Figure 2
Radial sets: interactive visual analysis of large overlapping sets.
Alsallakh, Bilal; Aigner, Wolfgang; Miksch, Silvia; Hauser, Helwig
2013-12-01
In many applications, data tables contain multi-valued attributes that often store the memberships of the table entities to multiple sets such as which languages a person masters, which skills an applicant documents, or which features a product comes with. With a growing number of entities, the resulting element-set membership matrix becomes very rich of information about how these sets overlap. Many analysis tasks targeted at set-typed data are concerned with these overlaps as salient features of such data. This paper presents Radial Sets, a novel visual technique to analyze set memberships for a large number of elements. Our technique uses frequency-based representations to enable quickly finding and analyzing different kinds of overlaps between the sets, and relating these overlaps to other attributes of the table entities. Furthermore, it enables various interactions to select elements of interest, find out if they are over-represented in specific sets or overlaps, and if they exhibit a different distribution for a specific attribute compared to the rest of the elements. These interactions allow formulating highly-expressive visual queries on the elements in terms of their set memberships and attribute values. As we demonstrate via two usage scenarios, Radial Sets enable revealing and analyzing a multitude of overlapping patterns between large sets, beyond the limits of state-of-the-art techniques.
Agent Reward Shaping for Alleviating Traffic Congestion
NASA Technical Reports Server (NTRS)
Tumer, Kagan; Agogino, Adrian
2006-01-01
Traffic congestion problems provide a unique environment to study how multi-agent systems promote desired system level behavior. What is particularly interesting in this class of problems is that no individual action is intrinsically "bad" for the system but that combinations of actions among agents lead to undesirable outcomes, As a consequence, agents need to learn how to coordinate their actions with those of other agents, rather than learn a particular set of "good" actions. This problem is ubiquitous in various traffic problems, including selecting departure times for commuters, routes for airlines, and paths for data routers. In this paper we present a multi-agent approach to two traffic problems, where far each driver, an agent selects the most suitable action using reinforcement learning. The agent rewards are based on concepts from collectives and aim to provide the agents with rewards that are both easy to learn and that if learned, lead to good system level behavior. In the first problem, we study how agents learn the best departure times of drivers in a daily commuting environment and how following those departure times alleviates congestion. In the second problem, we study how agents learn to select desirable routes to improve traffic flow and minimize delays for. all drivers.. In both sets of experiments,. agents using collective-based rewards produced near optimal performance (93-96% of optimal) whereas agents using system rewards (63-68%) barely outperformed random action selection (62-64%) and agents using local rewards (48-72%) performed worse than random in some instances.
ERIC Educational Resources Information Center
Northcutt, Sherwin Dean; And Others
The study deals with various predictors of time spent on dairy subjects by Extension agents and predictors of contacts made by agents with dairy clientele. Purposes were to determine the relationships, if any, between various independent variables and groups of independent variables (agents' background and training, county dairy situation, agents'…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Firth, Andrew E., E-mail: a.firth@ucc.i; Blitvich, Bradley J., E-mail: blitvich@iastate.ed; Wills, Norma M., E-mail: nwills@genetics.utah.ed
2010-03-30
Flaviviruses have a positive-sense, single-stranded RNA genome of approx11 kb, encoding a large polyprotein that is cleaved to produce approx10 mature proteins. Cell fusing agent virus, Kamiti River virus, Culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. We present compelling bioinformatic evidence for a 253-295 codon overlapping gene (designated fifo) conserved throughout these insect-specific flaviviruses and immunofluorescent detection of its product. Fifo overlaps the NS2A/NS2B coding sequence in the - 1/+ 2 reading frame and is most likely expressed as a trans-frame fusion protein via ribosomal frameshifting at a conserved GGAUUUYmore » slippery heptanucleotide with 3'-adjacent RNA secondary structure (which stimulates efficient frameshifting in vitro). The discovery bears striking parallels to the recently discovered ribosomal frameshifting site in the NS2A coding sequence of the Japanese encephalitis serogroup of flaviviruses and suggests that programmed ribosomal frameshifting may be more widespread in flaviviruses than currently realized.« less
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-21
... Bioterrorism Preparedness and Response Act of 2002; Biennial Review and Republication of the Select Agent and... Act) requires the biennial review and republication of the HHS list of select agents and toxins. Accordingly, we are soliciting public comment on the current HHS list of select agents and toxins, including...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-17
... Bioterrorism Preparedness and Response Act of 2002: Biennial Review and Republication of the Select Agent and... public comment on the current HHS list of select agents and toxins. This document is extending the... changes to the list of select agents and toxins'' and mailed to: Centers for Disease Control and...
Keys, Ashley L.; Hitchins, Anthony D.; Smiley, R. Derike
2017-01-01
Microbial competition during selective enrichment negatively affects Listeria monocytogenes populations and may hinder the subsequent detection or recovery of this organism. Competition assays among 10 selected strains of Listeria and Citrobacter braakii were performed in buffered Listeria enrichment broth, 3-(N-morpholino)propanesulfonic acid–buffered Listeria enrichment broth, University of Vermont medium–modified Listeria enrichment broth, and Fraser broth. The individual contributions of each selective agent in these media were also assessed, as well as the contribution of incubation temperature. Acriflavine hydrochloride and sodium nalidixate were ineffective at preventing the overgrowth of C. braakii; this resulted in substantially lower populations of Listeria than when the competitor was absent. At the higher levels, both of these selective agents were detrimental to Listeria populations. The highest enrichment populations of Listeria were observed when either NaCl or LiCl was present. In the absence of selective agents, the final populations of Listeria following competitive growth with C. braakii were not substantially affected by temperature; however, in the presence of selective agents, the Listeria populations were statistically higher at the higher incubation temperature. There are a limited number of selective agents available for use in Listeria-specific enrichment media, resulting in formulations that are only somewhat selective for this species. The optimization of current formulations may help researchers to improve Listeria recovery, particularly from products with a high microbial load. The understanding of the behavior and interactions between target and nontarget microorganisms in the presence of these available selective agents is a necessary step in the optimization of Listeria selective enrichment formulations. PMID:28221922
Keys, Ashley L; Hitchins, Anthony D; Smiley, R Derike
2016-11-01
Microbial competition during selective enrichment negatively affects Listeria monocytogenes populations and may hinder the subsequent detection or recovery of this organism. Competition assays among 10 selected strains of Listeria and Citrobacter braakii were performed in buffered Listeria enrichment broth, 3-(N-morpholino)propanesulfonic acid-buffered Listeria enrichment broth, University of Vermont medium-modified Listeria enrichment broth, and Fraser broth. The individual contributions of each selective agent in these media were also assessed, as well as the contribution of incubation temperature. Acriflavine hydrochloride and sodium nalidixate were ineffective at preventing the overgrowth of C. braakii ; this resulted in substantially lower populations of Listeria than when the competitor was absent. At the higher levels, both of these selective agents were detrimental to Listeria populations. The highest enrichment populations of Listeria were observed when either NaCl or LiCl was present. In the absence of selective agents, the final populations of Listeria following competitive growth with C. braakii were not substantially affected by temperature; however, in the presence of selective agents, the Listeria populations were statistically higher at the higher incubation temperature. There are a limited number of selective agents available for use in Listeria -specific enrichment media, resulting in formulations that are only somewhat selective for this species. The optimization of current formulations may help researchers to improve Listeria recovery, particularly from products with a high microbial load. The understanding of the behavior and interactions between target and nontarget microorganisms in the presence of these available selective agents is a necessary step in the optimization of Listeria selective enrichment formulations.
Wood, Daniel K; Chouinard, Philippe A; Major, Alex J; Goodale, Melvyn A
2017-12-01
Most object-directed limb movements can be carried out with a comfortable grasp posture. However, the orientation of an object relative to our bodies can sometimes lead us to select an uncomfortable or awkward grasp posture due to limitations imposed by the biomechanics of the arm. In a series of experiments, we identified a network of cortical areas that are engaged during the selection of movement strategies. Neurologically intact participants and two brain-damaged patients with overlapping lesions in the right posterior superior parietal lobule (pSPL) performed a grasp posture selection task in which biomechanical constraints were the primary consideration for selecting an action. The task induced states of bistable actions whereby the same stimulus gave rise to categorically different grasp postures. In a behavioral experiment, the two patients displayed a large range of manual bistability with the contralesional hand, resulting in a higher incidence of awkward grasping postures. In neurologically intact participants, a separate functional magnetic resonance imaging (fMRI) experiment revealed activation of a parieto-frontal network, which included the posterior intraparietal sulcus (pIPS) along the banks of the pSPL that was parametrically modulated by the degree of bistability in grasp posture selection. Superimposing this activation over the patients' structural MRIs revealed that the pIPS/pSPL activation in the neurologically intact participants overlapped with lesioned cortical tissue in both patients; all other areas of activation overlapped with intact cortical tissue in the patients. These results provide converging evidence that the posterior parietal cortex plays a critical role in selecting biomechanically appropriate postures during reach-to-grasp behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.
Assessing risk to birds from industrial wind energy development via paired resource selection nodels
Tricia A. Miller; Robert P. Brooks; Michael Lanzone; David Brandes; Jeff Cooper; Kieran O' malley; Charles Maisonneuve; Junior Tremblay; Adam Duerr; Todd Katzner
2014-01-01
When wildlife habitat overlaps with industrial development animals may be harmed. Because wildlife and people select resources to maximize biological fitness and economic return, respectively, we estimated risk, the probability of eagles encountering and being affected by turbines, by overlaying models of resource selection for each entity. This conceptual framework...
USDA-ARS?s Scientific Manuscript database
The safety of weed biological control depends upon the selection and utilization of the target weed by the agent while causing minimal harm to non-target species. Selection of weed species by biological control agents is determined by the presence of behavioral cues, generally host secondary plant c...
USDA-ARS?s Scientific Manuscript database
The phytopathogen Ralstonia solanacearum is a species complex that contains a subset of strains that are quarantined or select agent pathogens. An unidentified R. solanacearum strain is considered a select agent in the US until proven otherwise, which can be done by phylogenetic analysis of a partia...
Wales, Andrew D.; Davies, Robert H.
2015-01-01
Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There is indeed experimental and observational evidence that exposure to these non-antibiotic antimicrobial agents can induce or select for bacterial adaptations that result in decreased susceptibility to one or more antibiotics. This may occur via cellular mechanisms that are protective across multiple classes of antimicrobial agents or by selection of genetic determinants for resistance to non-antibiotic agents that are linked to genes for antibiotic resistance. There may also be relevant effects of these antimicrobial agents on bacterial community structure and via non-specific mechanisms such as mobilization of genetic elements or mutagenesis. Notably, some co-selective adaptations have adverse effects on fitness in the absence of a continued selective pressure. The present review examines the evidence for the significance of these phenomena, particularly in respect of bacterial zoonotic agents that commonly occur in livestock and that may be transmitted, directly or via the food chain, to human populations. PMID:27025641
Requirements for facilities transferring or receiving select agents. Final rule.
2001-08-31
CDC administers regulations that govern the transfer of certain biological agents and toxins ("select agents"). These regulations require entities that transfer or receive select agents to register with CDC and comply with biosafety standards contained in the Third Edition of the CDC/NIH publication "Biosafety in Microbiological and Biomedical Laboratories ("BMBL")." On October 28,1999, CDC published a Notice of Proposed Rulemaking ("NPRM") seeking both to revise the biosafety standards facilities must follow when handling select agents and to provide new biosecurity standards for such facilities. These new standards are contained in the Fourth Edition of BMBL, which the NPRM proposed to incorporate by reference, thereby replacing the Third Edition. No comments were received in response to this proposal. CDC is therefore amending its regulations to incorporate the Fourth Edition.
NASA Astrophysics Data System (ADS)
Schaefer, R. K.; Morrison, D.; Potter, M.; Barnes, R. J.; Nylund, S. R.; Patrone, D.; Aiello, J.; Talaat, E. R.; Sarris, T.
2015-12-01
The great promise of Virtual Observatories is the ability to perform complex search operations across the metadata of a large variety of different data sets. This allows the researcher to isolate and select the relevant measurements for their topic of study. The Virtual ITM Observatory (VITMO) has many diverse geophysical datasets that cover a large temporal and spatial range that present a unique search problem. VITMO provides many methods by which the user can search for and select data of interest including restricting selections based on geophysical conditions (solar wind speed, Kp, etc) as well as finding those datasets that overlap in time. One of the key challenges in improving discoverability is the ability to identify portions of datasets that overlap in time and in location. The difficulty is that location data is not contained in the metadata for datasets produced by satellites and would be extremely large in volume if it were available, making searching for overlapping data very time consuming. To solve this problem we have developed a series of light-weight web services that can provide a new data search capability for VITMO and others. The services consist of a database of spacecraft ephemerides and instrument fields of view; an overlap calculator to find times when the fields of view of different instruments intersect; and a magnetic field line tracing service that maps in situ and ground based measurements to the equatorial plane in magnetic coordinates for a number of field models and geophysical conditions. These services run in real-time when the user queries for data. These services will allow the non-specialist user to select data that they were previously unable to locate, opening up analysis opportunities beyond the instrument teams and specialists, making it easier for future students who come into the field.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shivaram, Niranjan; Champenois, Elio G.; Cryan, James P.
We demonstrate a technique in velocity map imaging (VMI) that allows spatial gating of the laser focal overlap region in time resolved pump-probe experiments. This significantly enhances signal-to-noise ratio by eliminating background signal arising outside the region of spatial overlap of pump and probe beams. This enhancement is achieved by tilting the laser beams with respect to the surface of the VMI electrodes which creates a gradient in flight time for particles born at different points along the beam. By suitably pulsing our microchannel plate detector, we can select particles born only where the laser beams overlap. Furthermore, this spatialmore » gating in velocity map imaging can benefit nearly all photo-ion pump-probe VMI experiments especially when extreme-ultraviolet light or X-rays are involved which produce large background signals on their own.« less
Automated lung sound analysis for detecting pulmonary abnormalities.
Datta, Shreyasi; Dutta Choudhury, Anirban; Deshpande, Parijat; Bhattacharya, Sakyajit; Pal, Arpan
2017-07-01
Identification of pulmonary diseases comprises of accurate auscultation as well as elaborate and expensive pulmonary function tests. Prior arts have shown that pulmonary diseases lead to abnormal lung sounds such as wheezes and crackles. This paper introduces novel spectral and spectrogram features, which are further refined by Maximal Information Coefficient, leading to the classification of healthy and abnormal lung sounds. A balanced lung sound dataset, consisting of publicly available data and data collected with a low-cost in-house digital stethoscope are used. The performance of the classifier is validated over several randomly selected non-overlapping training and validation samples and tested on separate subjects for two separate test cases: (a) overlapping and (b) non-overlapping data sources in training and testing. The results reveal that the proposed method sustains an accuracy of 80% even for non-overlapping data sources in training and testing.
Shivaram, Niranjan; Champenois, Elio G.; Cryan, James P.; ...
2016-12-19
We demonstrate a technique in velocity map imaging (VMI) that allows spatial gating of the laser focal overlap region in time resolved pump-probe experiments. This significantly enhances signal-to-noise ratio by eliminating background signal arising outside the region of spatial overlap of pump and probe beams. This enhancement is achieved by tilting the laser beams with respect to the surface of the VMI electrodes which creates a gradient in flight time for particles born at different points along the beam. By suitably pulsing our microchannel plate detector, we can select particles born only where the laser beams overlap. Furthermore, this spatialmore » gating in velocity map imaging can benefit nearly all photo-ion pump-probe VMI experiments especially when extreme-ultraviolet light or X-rays are involved which produce large background signals on their own.« less
Identification of Matra Region and Overlapping Characters for OCR of Printed Bengali Scripts
NASA Astrophysics Data System (ADS)
Goswami, Subhra Sundar
One of the important reasons for poor recognition rate in optical character recognition (OCR) system is the error in character segmentation. In case of Bangla scripts, the errors occur due to several reasons, which include incorrect detection of matra (headline), over-segmentation and under-segmentation. We have proposed a robust method for detecting the headline region. Existence of overlapping characters (in under-segmented parts) in scanned printed documents is a major problem in designing an effective character segmentation procedure for OCR systems. In this paper, a predictive algorithm is developed for effectively identifying overlapping characters and then selecting the cut-borders for segmentation. Our method can be successfully used in achieving high recognition result.
VAS: A Vision Advisor System combining agents and object-oriented databases
NASA Technical Reports Server (NTRS)
Eilbert, James L.; Lim, William; Mendelsohn, Jay; Braun, Ron; Yearwood, Michael
1994-01-01
A model-based approach to identifying and finding the orientation of non-overlapping parts on a tray has been developed. The part models contain both exact and fuzzy descriptions of part features, and are stored in an object-oriented database. Full identification of the parts involves several interacting tasks each of which is handled by a distinct agent. Using fuzzy information stored in the model allowed part features that were essentially at the noise level to be extracted and used for identification. This was done by focusing attention on the portion of the part where the feature must be found if the current hypothesis of the part ID is correct. In going from one set of parts to another the only thing that needs to be changed is the database of part models. This work is part of an effort in developing a Vision Advisor System (VAS) that combines agents and objected-oriented databases.
Li, Juntao; Wang, Yanyan; Jiang, Tao; Xiao, Huimin; Song, Xuekun
2018-05-09
Diagnosing acute leukemia is the necessary prerequisite to treating it. Multi-classification on the gene expression data of acute leukemia is help for diagnosing it which contains B-cell acute lymphoblastic leukemia (BALL), T-cell acute lymphoblastic leukemia (TALL) and acute myeloid leukemia (AML). However, selecting cancer-causing genes is a challenging problem in performing multi-classification. In this paper, weighted gene co-expression networks are employed to divide the genes into groups. Based on the dividing groups, a new regularized multinomial regression with overlapping group lasso penalty (MROGL) has been presented to simultaneously perform multi-classification and select gene groups. By implementing this method on three-class acute leukemia data, the grouped genes which work synergistically are identified, and the overlapped genes shared by different groups are also highlighted. Moreover, MROGL outperforms other five methods on multi-classification accuracy. Copyright © 2017. Published by Elsevier B.V.
Kim, Hongkeun
2016-01-08
It remains unclear whether and to what extent the default network subregions involved in episodic memory (EM) and semantic memory (SM) processes overlap or are separated from one another. This study addresses this issue through a controlled meta-analysis of functional neuroimaging studies involving healthy participants. Various EM and SM task paradigms differ widely in the extent of default network involvement. Therefore, the issue at hand cannot be properly addressed without some control for this factor. In this regard, this study employs a two-stage analysis: a preliminary meta-analysis to select EM and SM task paradigms that recruit relatively extensive default network regions and a main analysis to compare the selected task paradigms. Based on a within-EM comparison, the default network contributed more to recollection/familiarity effects than to old/new effects, and based on a within-SM comparison, it contributed more to word/pseudoword effects than to semantic/phonological effects. According to a direct comparison of recollection/familiarity and word/pseudoword effects, each involving a range of default network regions, there were more overlaps than separations in default network subregions involved in these two effects. More specifically, overlaps included the bilateral posterior cingulate/retrosplenial cortex, left inferior parietal lobule, and left anteromedial prefrontal regions, whereas separations included only the hippocampal formation and the parahippocampal cortex region, which was unique to recollection/familiarity effects. These results indicate that EM and SM retrieval processes involving strong memory signals recruit extensive and largely overlapping default network regions and differ mainly in distinct contributions of hippocampus and parahippocampal regions to EM retrieval. Copyright © 2015 Elsevier Ltd. All rights reserved.
Migratory life histories explain the extreme egg-size dimorphism of Eudyptes penguins
Williams, Tony D.
2016-01-01
When successive stages in the life history of an animal directly overlap, physiological conflicts can arise resulting in carryover effects from one stage to another. The extreme egg-size dimorphism (ESD) of Eudyptes penguins, where the first-laid A-egg is approximately 18–57% smaller than the second-laid B-egg, has interested researchers for decades. Recent studies have linked variation in this trait to a carryover effect of migration that limits the physiology of yolk production and egg sizes. We assembled data on ESD and estimates of migration–reproduction overlap in penguin species and use phylogenetic methods to test the idea that migration–reproduction overlap explains variation in ESD. We show that migration overlap is generally restricted to Eudyptes relative to non-Eudyptes penguins, and that this overlap (defined as the amount of time that egg production occurs on land versus at sea during homeward migration) is significantly and positively correlated with the degree of ESD in Eudyptes. In the non-Eudyptes species, however, ESD was unrelated to migration overlap as these species mostly produce their clutches on land. Our results support the recent hypothesis that extreme ESD of Eudyptes penguins evolved, in part, as a response to selection for a pelagic overwinter migration behaviour. This resulted in a temporal overlap with, and thus a constraint on, the physiology of follicle development, leading to smaller A-egg size and greater ESD. PMID:27708146
Segmenting overlapping nano-objects in atomic force microscopy image
NASA Astrophysics Data System (ADS)
Wang, Qian; Han, Yuexing; Li, Qing; Wang, Bing; Konagaya, Akihiko
2018-01-01
Recently, techniques for nanoparticles have rapidly been developed for various fields, such as material science, medical, and biology. In particular, methods of image processing have widely been used to automatically analyze nanoparticles. A technique to automatically segment overlapping nanoparticles with image processing and machine learning is proposed. Here, two tasks are necessary: elimination of image noises and action of the overlapping shapes. For the first task, mean square error and the seed fill algorithm are adopted to remove noises and improve the quality of the original image. For the second task, four steps are needed to segment the overlapping nanoparticles. First, possibility split lines are obtained by connecting the high curvature pixels on the contours. Second, the candidate split lines are classified with a machine learning algorithm. Third, the overlapping regions are detected with the method of density-based spatial clustering of applications with noise (DBSCAN). Finally, the best split lines are selected with a constrained minimum value. We give some experimental examples and compare our technique with two other methods. The results can show the effectiveness of the proposed technique.
Investigation of FANCA gene in Fanconi anaemia patients in Iran
Saffar Moghadam, Ali Akbar; Mahjoubi, Frouzandeh; Reisi, Nahid; Vosough, Parvaneh
2016-01-01
Background & objectives: Fanconi anaemia (FA) is a syndrome with a predisposition to bone marrow failure, congenital anomalies and malignancies. It is characterized by cellular hypersensitivity to cross-linking agents such as mitomycin C (MMC). In the present study, a new approach was selected to investigate FANCA (Fanconi anaemia complementation group A) gene in patients clinically diagnosed with cellular hypersensitivity to DNA cross-linking agent MMC. Methods: Chromosomal breakage analysis was performed to prove the diagnosis of Fanconi anaemia in 318 families. Of these, 70 families had a positive result. Forty families agreed to molecular genetic testing. In total, there were 27 patients with unknown complementary types. Genomic DNA was extracted and total RNA was isolated from fresh whole blood of the patients. The first-strand cDNA was synthesized and the cDNA of each patient was then tested with 21 pairs of overlapping primers. High resolution melting curve analysis was used to screen FANCA, and LinReg software version 1.7 was utilized for analysis of expression. Results: In total, six sequence alterations were identified, which included two stop codons, two frames-shift mutations, one large deletion and one amino acid exchange. FANCA expression was downregulated in patients who had sequence alterations. Interpretation & conclusions: The results of the present study show that high resolution melting (HRM) curve analysis may be useful in the detection of sequence alteration. It is simpler and more costeffective than the multiplex ligation-dependent probe amplification (MLPA) procedure. PMID:27121516
Investigation of FANCA gene in Fanconi anaemia patients in Iran.
Moghadam, Ali Akbar Saffar; Mahjoubi, Frouzandeh; Reisi, Nahid; Vosough, Parvaneh
2016-02-01
Fanconi anaemia (FA) is a syndrome with a predisposition to bone marrow failure, congenital anomalies and malignancies. It is characterized by cellular hypersensitivity to cross-linking agents such as mitomycin C (MMC). In the present study, a new approach was selected to investigate FANCA (Fanconi anaemia complementation group A) gene in patients clinically diagnosed with cellular hypersensitivity to DNA cross-linking agent MMC. Chromosomal breakage analysis was performed to prove the diagnosis of Fanconi anaemia in 318 families. Of these, 70 families had a positive result. Forty families agreed to molecular genetic testing. In total, there were 27 patients with unknown complementary types. Genomic DNA was extracted and total RNA was isolated from fresh whole blood of the patients. The first-strand cDNA was synthesized and the cDNA of each patient was then tested with 21 pairs of overlapping primers. High resolution melting curve analysis was used to screen FANCA, and LinReg software version 1.7 was utilized for analysis of expression. In total, six sequence alterations were identified, which included two stop codons, two frames-shift mutations, one large deletion and one amino acid exchange. FANCA expression was downregulated in patients who had sequence alterations. The results of the present study show that high resolution melting (HRM) curve analysis may be useful in the detection of sequence alteration. It is simpler and more cost-effective than the multiplex ligation-dependent probe amplification (MLPA) procedure.
NASA Astrophysics Data System (ADS)
Hashimoto, Ryoji; Matsumura, Tomoya; Nozato, Yoshihiro; Watanabe, Kenji; Onoye, Takao
A multi-agent object attention system is proposed, which is based on biologically inspired attractor selection model. Object attention is facilitated by using a video sequence and a depth map obtained through a compound-eye image sensor TOMBO. Robustness of the multi-agent system over environmental changes is enhanced by utilizing the biological model of adaptive response by attractor selection. To implement the proposed system, an efficient VLSI architecture is employed with reducing enormous computational costs and memory accesses required for depth map processing and multi-agent attractor selection process. According to the FPGA implementation result of the proposed object attention system, which is accomplished by using 7,063 slices, 640×512 pixel input images can be processed in real-time with three agents at a rate of 9fps in 48MHz operation.
Analysis of the stress-strain state in single overlap joints using piezo-ceramic actuators
NASA Astrophysics Data System (ADS)
Pǎltânea, Veronica; Pǎltânea, Gheorghe; Popovici, Dorina; Jiga, Gabriel; Papanicolaou, George
2014-05-01
In this paper is presented a 2D approach to finite element modeling and an analytical calculus of a single lap bonded joint. As adherent material were selected a sheet of wood, aluminum and titanium. For adhesive part were selected Bison Super Wood D3 in case of the wood single lap joint and an epoxy resin type DGEBA-TETA for gluing together aluminum and titanium parts. In the article is described a combined method, which consists in the placement of the piezoelectric actuator inside of the adhesive part, in order to determine the tensile stress in the overlap joint. A comparison between the analytical and numerical results has been achieved through a multiphysics modeling - electrical and mechanical coupled problem. The technique used to calculate the mechanical parameters (First Principal Stress, displacements) was the three-point bending test, where different forces were applied in the mid-span of the structure, in order to maintain a constant displacement rate. The length of the overlap joint was modified from 20 to 50 mm.
Interference due to shared features between action plans is influenced by working memory span.
Fournier, Lisa R; Behmer, Lawrence P; Stubblefield, Alexandra M
2014-12-01
In this study, we examined the interactions between the action plans that we hold in memory and the actions that we carry out, asking whether the interference due to shared features between action plans is due to selection demands imposed on working memory. Individuals with low and high working memory spans learned arbitrary motor actions in response to two different visual events (A and B), presented in a serial order. They planned a response to the first event (A) and while maintaining this action plan in memory they then executed a speeded response to the second event (B). Afterward, they executed the action plan for the first event (A) maintained in memory. Speeded responses to the second event (B) were delayed when it shared an action feature (feature overlap) with the first event (A), relative to when it did not (no feature overlap). The size of the feature-overlap delay was greater for low-span than for high-span participants. This indicates that interference due to overlapping action plans is greater when fewer working memory resources are available, suggesting that this interference is due to selection demands imposed on working memory. Thus, working memory plays an important role in managing current and upcoming action plans, at least for newly learned tasks. Also, managing multiple action plans is compromised in individuals who have low versus high working memory spans.
Detecting independent and recurrent copy number aberrations using interval graphs.
Wu, Hsin-Ta; Hajirasouliha, Iman; Raphael, Benjamin J
2014-06-15
Somatic copy number aberrations SCNAS: are frequent in cancer genomes, but many of these are random, passenger events. A common strategy to distinguish functional aberrations from passengers is to identify those aberrations that are recurrent across multiple samples. However, the extensive variability in the length and position of SCNA: s makes the problem of identifying recurrent aberrations notoriously difficult. We introduce a combinatorial approach to the problem of identifying independent and recurrent SCNA: s, focusing on the key challenging of separating the overlaps in aberrations across individuals into independent events. We derive independent and recurrent SCNA: s as maximal cliques in an interval graph constructed from overlaps between aberrations. We efficiently enumerate all such cliques, and derive a dynamic programming algorithm to find an optimal selection of non-overlapping cliques, resulting in a very fast algorithm, which we call RAIG (Recurrent Aberrations from Interval Graphs). We show that RAIG outperforms other methods on simulated data and also performs well on data from three cancer types from The Cancer Genome Atlas (TCGA). In contrast to existing approaches that employ various heuristics to select independent aberrations, RAIG optimizes a well-defined objective function. We show that this allows RAIG to identify rare aberrations that are likely functional, but are obscured by overlaps with larger passenger aberrations. http://compbio.cs.brown.edu/software. © The Author 2014. Published by Oxford University Press.
TANDEM: A Trust-Based Agent Framework for Networked Decision Making
2015-09-10
selective (20–80 %), while the rest are good citizens, trust acts as a method to isolate misbehaving agents. If the majority of the agents have high...competence and low selectivity, then they can use trust to isolate route information around the misbehaving agents, improving Comm and Steps. The impact is...more dramatic when only 20–40 % of the agents are misbehaving . However, using trust results in reduced SA as the information available at the
DOE Office of Scientific and Technical Information (OSTI.GOV)
Villegier, J.C.; Goniche, M.; Renard, P.
1985-03-01
All-niobium nitride Josephson junctions have been prepared successfully using a new processing called SNOP: Selective Niobium (Nitride) Overlap Process. Such a process involves the ''trilayer'' deposition on the whole wafer before selective patterning of the electrodes by optically controlled Dry Reactive Ion Etching. Only two photomask levels are need to define an ''overlap'' or a ''cross-type'' junction with a good accuracy. The properties of the niobium nitride films deposited by DC-Magnetron sputtering and the surface oxide growth are analysed. The most critical point to obtain high quality and high gap value junctions resides in the early stage of the NbNmore » counterelectrode growth. Some possibilities to overcome such a handicap exist even if the fabrication needs substrate temperatures below 250/sup 0/C.« less
NASA Astrophysics Data System (ADS)
Coppock, Matthew B.; Farrow, Blake; Warner, Candice; Finch, Amethist S.; Lai, Bert; Sarkes, Deborah A.; Heath, James R.; Stratis-Cullum, Dimitra
2014-05-01
Current biodetection assays that employ monoclonal antibodies as primary capture agents exhibit limited fieldability, shelf life, and performance due to batch-to-batch production variability and restricted thermal stability. In order to improve upon the detection of biological threats in fieldable assays and systems for the Army, we are investigating protein catalyzed capture (PCC) agents as drop-in replacements for the existing antibody technology through iterative in situ click chemistry. The PCC agent oligopeptides are developed against known protein epitopes and can be mass produced using robotic methods. In this work, a PCC agent under development will be discussed. The performance, including affinity, selectivity, and stability of the capture agent technology, is analyzed by immunoprecipitation, western blotting, and ELISA experiments. The oligopeptide demonstrates superb selectivity coupled with high affinity through multi-ligand design, and improved thermal, chemical, and biochemical stability due to non-natural amino acid PCC agent design.
Combined node and link partitions method for finding overlapping communities in complex networks
Jin, Di; Gabrys, Bogdan; Dang, Jianwu
2015-01-01
Community detection in complex networks is a fundamental data analysis task in various domains, and how to effectively find overlapping communities in real applications is still a challenge. In this work, we propose a new unified model and method for finding the best overlapping communities on the basis of the associated node and link partitions derived from the same framework. Specifically, we first describe a unified model that accommodates node and link communities (partitions) together, and then present a nonnegative matrix factorization method to learn the parameters of the model. Thereafter, we infer the overlapping communities based on the derived node and link communities, i.e., determine each overlapped community between the corresponding node and link community with a greedy optimization of a local community function conductance. Finally, we introduce a model selection method based on consensus clustering to determine the number of communities. We have evaluated our method on both synthetic and real-world networks with ground-truths, and compared it with seven state-of-the-art methods. The experimental results demonstrate the superior performance of our method over the competing ones in detecting overlapping communities for all analysed data sets. Improved performance is particularly pronounced in cases of more complicated networked community structures. PMID:25715829
Brown, Thackery I.; Stern, Chantal E.
2014-01-01
Many life experiences share information with other memories. In order to make decisions based on overlapping memories, we need to distinguish between experiences to determine the appropriate behavior for the current situation. Previous work suggests that the medial temporal lobe (MTL) and medial caudate interact to support the retrieval of overlapping navigational memories in different contexts. The present study used functional magnetic resonance imaging (fMRI) in humans to test the prediction that the MTL and medial caudate play complementary roles in learning novel mazes that cross paths with, and must be distinguished from, previously learned routes. During fMRI scanning, participants navigated virtual routes that were well learned from prior training while also learning new mazes. Critically, some routes learned during scanning shared hallways with those learned during pre-scan training. Overlap between mazes required participants to use contextual cues to select between alternative behaviors. Results demonstrated parahippocampal cortex activity specific for novel spatial cues that distinguish between overlapping routes. The hippocampus and medial caudate were active for learning overlapping spatial memories, and increased their activity for previously learned routes when they became context dependent. Our findings provide novel evidence that the MTL and medial caudate play complementary roles in the learning, updating, and execution of context-dependent navigational behaviors. PMID:23448868
Jin, Ya; Yuan, Qi; Zhang, Jun; Manabe, Takashi; Tan, Wen
2015-09-01
Human bronchial smooth muscle cell soluble proteins were analyzed by a combined method of nondenaturing micro 2DE, grid gel-cutting, and quantitative LC-MS/MS and a native protein map was prepared for each of the identified 4323 proteins [1]. A method to evaluate the degree of similarity between the protein maps was developed since we expected the proteins comprising a protein complex would be separated together under nondenaturing conditions. The following procedure was employed using Excel macros; (i) maps that have three or more squares with protein quantity data were selected (2328 maps), (ii) within each map, the quantity values of the squares were normalized setting the highest value to be 1.0, (iii) in comparing a map with another map, the smaller normalized quantity in two corresponding squares was taken and summed throughout the map to give an "overlap score," (iv) each map was compared against all the 2328 maps and the largest overlap score, obtained when a map was compared with itself, was set to be 1.0 thus providing 2328 "overlap factors," (v) step (iv) was repeated for all maps providing 2328 × 2328 matrix of overlap factors. From the matrix, protein pairs that showed overlap factors above 0.65 from both protein sides were selected (431 protein pairs). Each protein pair was searched in a database (UniProtKB) on complex formation and 301 protein pairs, which comprise 35 protein complexes, were found to be documented. These results demonstrated that native protein maps and their similarity search would enable simultaneous analysis of multiple protein complexes in cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Generation of Affibody ligands binding interleukin-2 receptor alpha/CD25.
Grönwall, Caroline; Snelders, Eveline; Palm, Anna Jarelöv; Eriksson, Fredrik; Herne, Nina; Ståhl, Stefan
2008-06-01
Affibody molecules specific for human IL-2Ralpha, the IL-2 (interleukin-2) receptor alpha subunit, also known as CD25, were selected by phage-display technology from a combinatorial protein library based on the 58-residue Protein A-derived Z domain. The IL-2R system plays a major role in T-cell activation and the regulation of cellular immune responses. Moreover, CD25 has been found to be overexpressed in organ rejections, a number of autoimmune diseases and T-cell malignancies. The phage-display selection using Fc-fused target protein generated 16 unique Affibody molecules targeting CD25. The two most promising binders were characterized in more detail using biosensor analysis and demonstrated strong and selective binding to CD25. Kinetic biosensor analysis revealed that the two monomeric Affibody molecules bound to CD25 with apparent affinities of 130 and 240 nM respectively. The Affibody molecules were, on biosensor analysis, found to compete for the same binding site as the natural ligand IL-2 and the IL-2 blocking monoclonal antibody 2A3. Hence the Affibody molecules were assumed to have an overlapping binding site with IL-2 and antibodies targeting the IL-2 blocking Tac epitope (for example, the monoclonal antibodies Daclizumab and Basiliximab, both of which have been approved for therapeutic use). Furthermore, immunofluorescence microscopy and flow-cytometric analysis of CD25-expressing cells demonstrated that the selected Affibody molecules bound to CD4+ CD25+ PMBCs (peripheral-blood mononuclear cells), the IL-2-dependent cell line NK92 and phytohaemagglutinin-activated PMBCs. The potential use of the CD25-binding Affibody molecules as targeting agents for medical imaging and for therapeutic applications is discussed.
An efficient strategy for cell-based antibody library selection using an integrated vector system.
Yoon, Hyerim; Song, Jin Myung; Ryu, Chun Jeih; Kim, Yeon-Gu; Lee, Eun Kyo; Kang, Sunghyun; Kim, Sang Jick
2012-09-18
Cell panning of phage-displayed antibody library is a powerful tool for the development of therapeutic and imaging agents since disease-related cell surface proteins in native complex conformation can be directly targeted. Here, we employed a strategy taking advantage of an integrated vector system which allows rapid conversion of scFv-displaying phage into scFv-Fc format for efficient cell-based scFv library selection on a tetraspanin protein, CD9. A mouse scFv library constructed by using a phagemid vector, pDR-D1 was subjected to cell panning against stable CD9 transfectant, and the scFv repertoire from the enriched phage pool was directly transferred to a mammalian cassette vector, pDR-OriP-Fc1. The resulting constructs enabled transient expression of enough amounts of scFv-Fcs in HEK293E cells, and flow cytometric screening of binders for CD9 transfectant could be performed simply by using the culture supernatants. All three clones selected from the screening showed correct CD9-specificity. They could immunoprecipitate CD9 molecules out of the transfectant cell lysate and correctly stain endogenous CD9 expression on cancer cell membrane. Furthermore, competition assay with a known anti-CD9 monoclonal antibody (mAb) suggested that the binding epitopes of some of them overlap with that of the mAb which resides within the large extracellular loop of CD9. This study demonstrates that scFv-Fc from mammalian transient expression can be chosen as a reliable format for rapid screening and validation in cell-based scFv library selection, and the strategy described here will be applicable to efficient discovery of antibodies to diverse cell-surface targets.
Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging
NASA Astrophysics Data System (ADS)
Shan, Liang; Gu, Xinbin; Wang, Paul
2013-09-01
Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD,
Adaptive consensus of scale-free multi-agent system by randomly selecting links
NASA Astrophysics Data System (ADS)
Mou, Jinping; Ge, Huafeng
2016-06-01
This paper investigates an adaptive consensus problem for distributed scale-free multi-agent systems (SFMASs) by randomly selecting links, where the degree of each node follows a power-law distribution. The randomly selecting links are based on the assumption that every agent decides to select links among its neighbours according to the received data with a certain probability. Accordingly, a novel consensus protocol with the range of the received data is developed, and each node updates its state according to the protocol. By the iterative method and Cauchy inequality, the theoretical analysis shows that all errors among agents converge to zero, and in the meanwhile, several criteria of consensus are obtained. One numerical example shows the reliability of the proposed methods.
Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities
Soll, Jennifer M.; Sobol, Robert W.; Mosammaparast, Nima
2016-01-01
Alkylation chemotherapy is one of the most widely used systemic therapies for cancer. While somewhat effective, clinical responses and toxicities of these agents are highly variable. A major contributing factor for this variability is the numerous distinct lesions that are created upon alkylation damage. These adducts activate multiple repair pathways. There is mounting evidence that the individual pathways function cooperatively, suggesting that coordinated regulation of alkylation repair is critical to prevent toxicity. Furthermore, some alkylating agents produce adducts that overlap with newly discovered methylation marks, making it difficult to distinguish between bona fide damaged bases and so called ‘epigenetic’ adducts. We discuss new efforts aimed at deciphering the mechanisms that regulate these repair pathways, emphasizing their implications for cancer chemotherapy. PMID:27816326
Long-Term Evolution of the Luteoviridae: Time Scale and Mode of Virus Speciation▿ †
Pagán, Israel; Holmes, Edward C.
2010-01-01
Despite their importance as agents of emerging disease, the time scale and evolutionary processes that shape the appearance of new viral species are largely unknown. To address these issues, we analyzed intra- and interspecific evolutionary processes in the Luteoviridae family of plant RNA viruses. Using the coat protein gene of 12 members of the family, we determined their phylogenetic relationships, rates of nucleotide substitution, times to common ancestry, and patterns of speciation. An associated multigene analysis enabled us to infer the nature of selection pressures and the genomic distribution of recombination events. Although rates of evolutionary change and selection pressures varied among genes and species and were lower in some overlapping gene regions, all fell within the range of those seen in animal RNA viruses. Recombination breakpoints were commonly observed at gene boundaries but less so within genes. Our molecular clock analysis suggested that the origin of the currently circulating Luteoviridae species occurred within the last 4 millennia, with intraspecific genetic diversity arising within the last few hundred years. Speciation within the Luteoviridae may therefore be associated with the expansion of agricultural systems. Finally, our phylogenetic analysis suggested that viral speciation events tended to occur within the same plant host species and country of origin, as expected if speciation is largely sympatric, rather than allopatric, in nature. PMID:20375155
Microbial Resistance to Triclosan: A Case Study in Natural Selection
ERIC Educational Resources Information Center
Serafini, Amanda; Matthews, Dorothy M.
2009-01-01
Natural selection is the mechanism of evolution caused by the environmental selection of organisms most fit to reproduce, sometimes explained as "survival of the fittest." An example of evolution by natural selection is the development of bacteria that are resistant to antimicrobial agents as a result of exposure to these agents. Triclosan, which…
Jelaska, Sven D; Nikolić, Toni; Serić Jelaska, Lucija; Kusan, Vladimir; Peternel, Hrvoje; Guzvica, Goran; Major, Zoran
2010-03-01
Here we present the methodology used for terrestrial biodiversity analysis and site selection in Phase B of the UNDP/GEF COAST project. The analysis was focused on the problem of biodiversity evaluation in four Croatian counties stretching from sea level to the highest mountain in Croatia. Data on habitats, vascular flora, and fauna (mammals, birds, reptiles, amphibians, butterflies, ground beetles, and underground invertebrates) were collected and analyzed for each of the four counties. Emphasis was given to the richness of endangered species and the rarity of endemic species. Based on the spatial analyses of habitat, fauna, and flora data, four to six areas were selected from each county and ranked according to their biodiversity importance. Overlap between areas important for richness and those important for rarity was highest for data on flora (65.5%) and lowest for data on fauna (16.7%). When different data sets were compared, the lowest overlap was between flora and fauna (17.1%) and largest between fauna and habitats (23.9%). Simultaneous overlap among all three data sets was found in just 6.5% of the overall selected areas. These results suggest that less specific data, with respect to taxa threat status, could better serve as surrogate data in estimating overall biodiversity. In summary, this analysis has demonstrated that Dalmatia is a region with a high overall biodiversity that is important in a broader European context.
NASA Astrophysics Data System (ADS)
Jelaska, Sven D.; Nikolić, Toni; Šerić Jelaska, Lucija; Kušan, Vladimir; Peternel, Hrvoje; Gužvica, Goran; Major, Zoran
2010-03-01
Here we present the methodology used for terrestrial biodiversity analysis and site selection in Phase B of the UNDP/GEF COAST project. The analysis was focused on the problem of biodiversity evaluation in four Croatian counties stretching from sea level to the highest mountain in Croatia. Data on habitats, vascular flora, and fauna (mammals, birds, reptiles, amphibians, butterflies, ground beetles, and underground invertebrates) were collected and analyzed for each of the four counties. Emphasis was given to the richness of endangered species and the rarity of endemic species. Based on the spatial analyses of habitat, fauna, and flora data, four to six areas were selected from each county and ranked according to their biodiversity importance. Overlap between areas important for richness and those important for rarity was highest for data on flora (65.5%) and lowest for data on fauna (16.7%). When different data sets were compared, the lowest overlap was between flora and fauna (17.1%) and largest between fauna and habitats (23.9%). Simultaneous overlap among all three data sets was found in just 6.5% of the overall selected areas. These results suggest that less specific data, with respect to taxa threat status, could better serve as surrogate data in estimating overall biodiversity. In summary, this analysis has demonstrated that Dalmatia is a region with a high overall biodiversity that is important in a broader European context.
An extension to artifact-free projection overlaps
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Jianyu, E-mail: jianyulin@hotmail.com
2015-05-15
Purpose: In multipinhole single photon emission computed tomography, the overlapping of projections has been used to increase sensitivity. Avoiding artifacts in the reconstructed image associated with projection overlaps (multiplexing) is a critical issue. In our previous report, two types of artifact-free projection overlaps, i.e., projection overlaps that do not lead to artifacts in the reconstructed image, were formally defined and proved, and were validated via simulations. In this work, a new proposition is introduced to extend the previously defined type-II artifact-free projection overlaps so that a broader range of artifact-free overlaps is accommodated. One practical purpose of the new extensionmore » is to design a baffle window multipinhole system with artifact-free projection overlaps. Methods: First, the extended type-II artifact-free overlap was theoretically defined and proved. The new proposition accommodates the situation where the extended type-II artifact-free projection overlaps can be produced with incorrectly reconstructed portions in the reconstructed image. Next, to validate the theory, the extended-type-II artifact-free overlaps were employed in designing the multiplexing multipinhole spiral orbit imaging systems with a baffle window. Numerical validations were performed via simulations, where the corresponding 1-pinhole nonmultiplexing reconstruction results were used as the benchmark for artifact-free reconstructions. The mean square error (MSE) was the metric used for comparisons of noise-free reconstructed images. Noisy reconstructions were also performed as part of the validations. Results: Simulation results show that for noise-free reconstructions, the MSEs of the reconstructed images of the artifact-free multiplexing systems are very similar to those of the corresponding 1-pinhole systems. No artifacts were observed in the reconstructed images. Therefore, the testing results for artifact-free multiplexing systems designed using the extended type-II artifact-free overlaps numerically validated the developed theory. Conclusions: First, the extension itself is of theoretical importance because it broadens the selection range for optimizing multiplexing multipinhole designs. Second, the extension has an immediate application: using a baffle window to design a special spiral orbit multipinhole imaging system with projection overlaps in the orbit axial direction. Such an artifact-free baffle window design makes it possible for us to image any axial portion of interest of a long object with projection overlaps to increase sensitivity.« less
Impact-induced compositional variations on Mercury
NASA Astrophysics Data System (ADS)
Rivera-Valentin, E. G.; Barr, A. C.
2013-12-01
The surface of Mercury shows unexpected spectral variations spatially associated with crater and basin ejecta (the so-called 'low-reflectance material' or LRM; [1]). The low reflectance is suggested to be caused by a native darkening agent at depth that has been excavated and redeposited onto the surface [1]. Although LRM is generally associated with crater ejecta, it is not found within the ejecta blankets of many large impact craters, perhaps suggesting that the subsurface source is heterogeneous [2]. We have developed a 3-D Monte Carlo model of impact cratering, excavation, and ejecta blanket deposition. Our simulations of the effect of early impacts onto Mercury show that if the LRM originates from depth to cover ~15% of Mercury's surface [2], its source is ~30 km deep. Considering the estimated mercurian crustal thickness of 50 km [3] this implies the darkening agent is most probably located within a chemically distinct lower crust. Simulations show that repeated and overlapping impacts redistribute the darkening agent away from the basin source and create a weak association between crater size and LRM abundance. Thus subsurface heterogeneity is not required to produce the weak association between crater size and LRM abundance within crater ejecta; this is a natural consequence of overlapping impacts. Our results can elucidate the new high-resolution compositional mapping of Mercury's heavily cratered terrain and provide insight into subsurface composition. Acknowledgements: This work is supported by the Center for Lunar Origin and Evolution through the NASA Lunar Science Institute NNA09DB32A. References: [1] Denevi and Robinson, 2008, Icarus 197, 239-246. [2] Denevi et al., 2009, Science 324, 613-618. [3] Smith et al., 2012, Science 336, 214-217.
Men and Sexuality: Bibliography of Selected Resources.
ERIC Educational Resources Information Center
Planned Parenthood Federation of America, Inc., New York, NY. Education Dept.
This selective, annotated bibliography covers a range of topics associated with male sexuality, reproductive health, and sexism. The books listed in this document are organized in five categories which are not strictly exclusive, as most of the entries overlap topic areas. Part I, Men in Society, contains 10 entries dealing with masculinity,…
Migratory life histories explain the extreme egg-size dimorphism of Eudyptes penguins.
Crossin, Glenn T; Williams, Tony D
2016-10-12
When successive stages in the life history of an animal directly overlap, physiological conflicts can arise resulting in carryover effects from one stage to another. The extreme egg-size dimorphism (ESD) of Eudyptes penguins, where the first-laid A-egg is approximately 18-57% smaller than the second-laid B-egg, has interested researchers for decades. Recent studies have linked variation in this trait to a carryover effect of migration that limits the physiology of yolk production and egg sizes. We assembled data on ESD and estimates of migration-reproduction overlap in penguin species and use phylogenetic methods to test the idea that migration-reproduction overlap explains variation in ESD. We show that migration overlap is generally restricted to Eudyptes relative to non-Eudyptes penguins, and that this overlap (defined as the amount of time that egg production occurs on land versus at sea during homeward migration) is significantly and positively correlated with the degree of ESD in Eudyptes In the non-Eudyptes species, however, ESD was unrelated to migration overlap as these species mostly produce their clutches on land. Our results support the recent hypothesis that extreme ESD of Eudyptes penguins evolved, in part, as a response to selection for a pelagic overwinter migration behaviour. This resulted in a temporal overlap with, and thus a constraint on, the physiology of follicle development, leading to smaller A-egg size and greater ESD. © 2016 The Author(s).
Fluorination utilizing thermodynamically unstable fluorides and fluoride salts thereof
Bartlett, Neil; Whalen, J. Marc; Chacon, Lisa
2000-12-12
A method for fluorinating a carbon compound or cationic carbon compound utilizes a fluorination agent selected from thermodynamically unstable nickel fluorides and salts thereof in liquid anhydrous hydrogen fluoride. The desired carbon compound or cationic organic compound to undergo fluorination is selected and reacted with the fluorination agent by contacting the selected organic or cationic organic compound and the chosen fluorination agent in a reaction vessel for a desired reaction time period at room temperature or less.
Evolutionary consequences of antibiotic use for the resistome, mobilome and microbial pangenome
Gillings, Michael R.
2013-01-01
The widespread use and abuse of antibiotic therapy has evolutionary and ecological consequences, some of which are only just beginning to be examined. One well known consequence is the fixation of mutations and lateral gene transfer (LGT) events that confer antibiotic resistance. Sequential selection events, driven by different classes of antibiotics, have resulted in the assembly of diverse resistance determinants and mobile DNAs into novel genetic elements of ever-growing complexity and flexibility. These novel plasmids, integrons, and genomic islands have now become fixed at high frequency in diverse cell lineages by human antibiotic use. Consequently they can be regarded as xenogenetic pollutants, analogous to xenobiotic compounds, but with the critical distinction that they replicate rather than degrade when released to pollute natural environments. Antibiotics themselves must also be regarded as pollutants, since human production overwhelms natural synthesis, and a major proportion of ingested antibiotic is excreted unchanged into waste streams. Such antibiotic pollutants have non-target effects, raising the general rates of mutation, recombination, and LGT in all the microbiome, and simultaneously providing the selective force to fix such changes. This has the consequence of recruiting more genes into the resistome and mobilome, and of increasing the overlap between these two components of microbial genomes. Thus the human use and environmental release of antibiotics is having second order effects on the microbial world, because these small molecules act as drivers of bacterial evolution. Continued pollution with both xenogenetic elements and the selective agents that fix such elements in populations has potentially adverse consequences for human welfare. PMID:23386843
Evolutionary consequences of antibiotic use for the resistome, mobilome and microbial pangenome.
Gillings, Michael R
2013-01-01
The widespread use and abuse of antibiotic therapy has evolutionary and ecological consequences, some of which are only just beginning to be examined. One well known consequence is the fixation of mutations and lateral gene transfer (LGT) events that confer antibiotic resistance. Sequential selection events, driven by different classes of antibiotics, have resulted in the assembly of diverse resistance determinants and mobile DNAs into novel genetic elements of ever-growing complexity and flexibility. These novel plasmids, integrons, and genomic islands have now become fixed at high frequency in diverse cell lineages by human antibiotic use. Consequently they can be regarded as xenogenetic pollutants, analogous to xenobiotic compounds, but with the critical distinction that they replicate rather than degrade when released to pollute natural environments. Antibiotics themselves must also be regarded as pollutants, since human production overwhelms natural synthesis, and a major proportion of ingested antibiotic is excreted unchanged into waste streams. Such antibiotic pollutants have non-target effects, raising the general rates of mutation, recombination, and LGT in all the microbiome, and simultaneously providing the selective force to fix such changes. This has the consequence of recruiting more genes into the resistome and mobilome, and of increasing the overlap between these two components of microbial genomes. Thus the human use and environmental release of antibiotics is having second order effects on the microbial world, because these small molecules act as drivers of bacterial evolution. Continued pollution with both xenogenetic elements and the selective agents that fix such elements in populations has potentially adverse consequences for human welfare.
Finite Element Analysis of Composite Joint Configurations with Gaps and Overlaps
NASA Technical Reports Server (NTRS)
Krueger, Ronald
2014-01-01
The goal of the current study is to identify scenarios for which thermal and moisture effects become significant in the loading of a composite structure. In the current work, a simple configuration was defined, and material properties were selected. A Fortran routine was created to automate the mesh generation process. The routine was used to create the models for the initial mesh refinement study. A combination of element length and width suitable for further studies was identified. Also, the effect of the overlap length and gap length on computed shear and through-thickness stresses along the bondline of the joints was studied for the mechanical load case. Further, the influence of neighboring gaps and overlaps on these joint stresses was studied and was found to be negligible. The results suggest that for an initial study it is sufficient to focus on one configuration with fixed overlap and gap lengths to study the effects of mechanical, thermal and moisture loading and combinations thereof on computed joint stresses
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-29
... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Reorganization of the Select Agent and Toxin List AGENCY: Animal and Plant Health Inspection Service, USDA... Agricultural Bioterrorism Protection Act of 2002, we are soliciting public comment regarding the list of select...
Biological Select Agents and Toxins: Risk-Based Assessment Management and Oversight.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Burnett, LouAnn Crawford; Brodsky, Benjamin H.
Sandia National Laboratories' International Biological and Chemical Threat Reduction (SNL/IBCTR) conducted, on behalf of the Federal Select Agent Program (FSAP), a review of risk assessment in modern select agent laboratories. This review and analysis consisted of literature review, interviews of FSAP staff, entities regulated by FSAP, and deliberations of an expert panel. Additionally, SNL/IBCTR reviewed oversight mechanisms used by industries, US agencies, and other countries for high-consequence risks (e.g, nuclear, chemical, or biological materials, aviation, off-shore drilling, etc.) to determine if alternate oversight mechanisms existed that might be applicable to FSAP oversight of biological select agents and toxins. This reportmore » contains five findings, based on these reviews and analyses, with recommendations and suggested actions for FSAP to consider.« less
Pollinator-mediated natural selection in Penstemon digitalis.
Parachnowitsch, Amy; Kessler, André
2010-12-01
Measuring the agents of natural selection is important because it allows us to understand not only which traits are expected to evolve but also why they will evolve. Natural selection by pollinators on floral traits is often assumed because in outcrossing animal-pollinated plants flowers are generally thought to function as advertisements of rewards directed at pollinators. We tested the role of bee pollinators in selection on Penstemon digitalis and found that pollinators were driving selection for larger and more flowers. However, what makes our publication unique is the additional information we gained from reviewing the few other studies that also directly tested whether pollinators were agents of selection on floral traits. As we would expect if pollinators are important agents of selection, selection on floral traits was significantly stronger when pollinators were present than when they were experimentally removed. Taken together, these results suggest that pollinators can be important drivers of selection in contemporary populations.
Swept source optical coherence tomography of objects with arbitrary reflectivity profiles
NASA Astrophysics Data System (ADS)
Mezgebo, Biniyam; Nagib, Karim; Fernando, Namal; Kordi, Behzad; Sherif, Sherif
2018-03-01
Swept Source optical coherence tomography (SS-OCT) has become a well established imaging modality for both medical and industrial diagnostic applications. A cross-sectional SS-OCT image is obtained by applying an inverse discrete Fourier transform (DFT) to axial interferogram measured in the frequency domain (k-space). Fourier inversion of the obtained interferogram typically produces a potentially overlapping conjugate mirror image, whose overlap could be avoided by restricting the object to have its highest reflectivity at its surface. However, this restriction may not be fulfilled when imaging a very thin object that is placed on a highly reflective surface, or imaging an object containing a contrast agent with high reflectivity. In this paper, we show that oversampling of the SS-OCT signal in k-space would overcome the need for such restriction on the object. Our result is demonstrated using SS-OCT images of Axolotl salamander eggs.
[MCTD--mixed connective tissue disease].
Haustein, Uwe-Frithjof
2005-02-01
Mixed connective tissue disease is a disease entity characterized by overlapping symptoms of lupus erythematosus (LE), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA). Diagnostic criteria include high titers of antibodies against U1RNP as well as the presence of at least 3 of 5 of the following clinical features: edema of hands, synovitis, myositis, Raynaud phenomenon and acroscierosis. In terms of the pathogenesis, genetic as well as infectious (viral) factors appear to play a role. The acceptance of MCTD as a distinct disease entity is controversial. Terms such as "undifferentiated connective tissue disease" or "overlapping syndromes" are not helpful. One-quarter of MCTD patients transform into LE, while one-third progress to SSc. Therapeutic recommendations are glucocorticoids in combination with immunosuppressive agents and endothelin receptor antagonists. Double blind studies are not available. The prognosis is relatively good. Causes of death include pulmonary hypertension, infections and both pulmonary and cardiac failure.
Major, Kevin J; Poutous, Menelaos K; Ewing, Kenneth J; Dunnill, Kevin F; Sanghera, Jasbinder S; Aggarwal, Ishwar D
2015-09-01
Optical filter-based chemical sensing techniques provide a new avenue to develop low-cost infrared sensors. These methods utilize multiple infrared optical filters to selectively measure different response functions for various chemicals, dependent on each chemical's infrared absorption. Rather than identifying distinct spectral features, which can then be used to determine the identity of a target chemical, optical filter-based approaches rely on measuring differences in the ensemble response between a given filter set and specific chemicals of interest. Therefore, the results of such methods are highly dependent on the original optical filter choice, which will dictate the selectivity, sensitivity, and stability of any filter-based sensing method. Recently, a method has been developed that utilizes unique detection vector operations defined by optical multifilter responses, to discriminate between volatile chemical vapors. This method, comparative-discrimination spectral detection (CDSD), is a technique which employs broadband optical filters to selectively discriminate between chemicals with highly overlapping infrared absorption spectra. CDSD has been shown to correctly distinguish between similar chemicals in the carbon-hydrogen stretch region of the infrared absorption spectra from 2800-3100 cm(-1). A key challenge to this approach is how to determine which optical filter sets should be utilized to achieve the greatest discrimination between target chemicals. Previous studies used empirical approaches to select the optical filter set; however this is insufficient to determine the optimum selectivity between strongly overlapping chemical spectra. Here we present a numerical approach to systematically study the effects of filter positioning and bandwidth on a number of three-chemical systems. We describe how both the filter properties, as well as the chemicals in each set, affect the CDSD results and subsequent discrimination. These results demonstrate the importance of choosing the proper filter set and chemicals for comparative discrimination, in order to identify the target chemical of interest in the presence of closely matched chemical interferents. These findings are an integral step in the development of experimental prototype sensors, which will utilize CDSD.
Atlas ranking and selection for automatic segmentation of the esophagus from CT scans
NASA Astrophysics Data System (ADS)
Yang, Jinzhong; Haas, Benjamin; Fang, Raymond; Beadle, Beth M.; Garden, Adam S.; Liao, Zhongxing; Zhang, Lifei; Balter, Peter; Court, Laurence
2017-12-01
In radiation treatment planning, the esophagus is an important organ-at-risk that should be spared in patients with head and neck cancer or thoracic cancer who undergo intensity-modulated radiation therapy. However, automatic segmentation of the esophagus from CT scans is extremely challenging because of the structure’s inconsistent intensity, low contrast against the surrounding tissues, complex and variable shape and location, and random air bubbles. The goal of this study is to develop an online atlas selection approach to choose a subset of optimal atlases for multi-atlas segmentation to the delineate esophagus automatically. We performed atlas selection in two phases. In the first phase, we used the correlation coefficient of the image content in a cubic region between each atlas and the new image to evaluate their similarity and to rank the atlases in an atlas pool. A subset of atlases based on this ranking was selected, and deformable image registration was performed to generate deformed contours and deformed images in the new image space. In the second phase of atlas selection, we used Kullback-Leibler divergence to measure the similarity of local-intensity histograms between the new image and each of the deformed images, and the measurements were used to rank the previously selected atlases. Deformed contours were overlapped sequentially, from the most to the least similar, and the overlap ratio was examined. We further identified a subset of optimal atlases by analyzing the variation of the overlap ratio versus the number of atlases. The deformed contours from these optimal atlases were fused together using a modified simultaneous truth and performance level estimation algorithm to produce the final segmentation. The approach was validated with promising results using both internal data sets (21 head and neck cancer patients and 15 thoracic cancer patients) and external data sets (30 thoracic patients).
Shen, Wei; Qu, Qingqing; Tong, Xiuhong
2018-05-01
The aim of this study was to investigate the extent to which phonological information mediates the visual attention shift to printed Chinese words in spoken word recognition by using an eye-movement technique with a printed-word paradigm. In this paradigm, participants are visually presented with four printed words on a computer screen, which include a target word, a phonological competitor, and two distractors. Participants are then required to select the target word using a computer mouse, and the eye movements are recorded. In Experiment 1, phonological information was manipulated at the full-phonological overlap; in Experiment 2, phonological information at the partial-phonological overlap was manipulated; and in Experiment 3, the phonological competitors were manipulated to share either fulloverlap or partial-overlap with targets directly. Results of the three experiments showed that the phonological competitor effects were observed at both the full-phonological overlap and partial-phonological overlap conditions. That is, phonological competitors attracted more fixations than distractors, which suggested that phonological information mediates the visual attention shift during spoken word recognition. More importantly, we found that the mediating role of phonological information varies as a function of the phonological similarity between target words and phonological competitors.
Non-specific filtering of beta-distributed data.
Wang, Xinhui; Laird, Peter W; Hinoue, Toshinori; Groshen, Susan; Siegmund, Kimberly D
2014-06-19
Non-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methylation is measured as a proportion, bounded between 0 and 1, with variance a function of the mean. Filtering on standard deviation biases the selection of probes to those with mean values near 0.5. We explore the effect this has on clustering, and develop alternate filter methods that utilize a variance stabilizing transformation for Beta distributed data and do not share this bias. We compared results for 11 different non-specific filters on eight Infinium HumanMethylation data sets, selected to span a variety of biological conditions. We found that for data sets having a small fraction of samples showing abnormal methylation of a subset of normally unmethylated CpGs, a characteristic of the CpG island methylator phenotype in cancer, a novel filter statistic that utilized a variance-stabilizing transformation for Beta distributed data outperformed the common filter of using standard deviation of the DNA methylation proportion, or its log-transformed M-value, in its ability to detect the cancer subtype in a cluster analysis. However, the standard deviation filter always performed among the best for distinguishing subgroups of normal tissue. The novel filter and standard deviation filter tended to favour features in different genome contexts; for the same data set, the novel filter always selected more features from CpG island promoters and the standard deviation filter always selected more features from non-CpG island intergenic regions. Interestingly, despite selecting largely non-overlapping sets of features, the two filters did find sample subsets that overlapped for some real data sets. We found two different filter statistics that tended to prioritize features with different characteristics, each performed well for identifying clusters of cancer and non-cancer tissue, and identifying a cancer CpG island hypermethylation phenotype. Since cluster analysis is for discovery, we would suggest trying both filters on any new data sets, evaluating the overlap of features selected and clusters discovered.
Information security for compliance with select agent regulations.
Lewis, Nick; Campbell, Mark J; Baskin, Carole R
2015-01-01
The past decade has seen a significant rise in research on high-consequence human and animal pathogens, many now known as "select agents." While physical security around these agents is tightly regulated, information security standards are still lagging. The understanding of the threats unique to the academic and research environment is still evolving, in part due to poor communication between the various stakeholders. Perhaps as a result, information security guidelines published by select agent regulators lack the critical details and directives needed to achieve even the lowest security level of the Federal Information Security Management Act (FISMA). While only government agencies are currently required to abide by the provisions of FISMA (unless specified as preconditions for obtaining government grants or contracts--still a relatively rare or narrowly scoped occurrence), the same strategies were recently recommended by executive order for others. We propose that information security guidelines for select agent research be updated to promulgate and detail FISMA standards and processes and that the latter be ultimately incorporated into select agent regulations. We also suggest that information security in academic and research institutions would greatly benefit from active efforts to improve communication among the biosecurity, security, and information technology communities, and from a secure venue for exchange of timely information on emerging threats and solutions in the research environment.
Information Security for Compliance with Select Agent Regulations
Lewis, Nick; Campbell, Mark J.
2015-01-01
The past decade has seen a significant rise in research on high-consequence human and animal pathogens, many now known as “select agents.” While physical security around these agents is tightly regulated, information security standards are still lagging. The understanding of the threats unique to the academic and research environment is still evolving, in part due to poor communication between the various stakeholders. Perhaps as a result, information security guidelines published by select agent regulators lack the critical details and directives needed to achieve even the lowest security level of the Federal Information Security Management Act (FISMA). While only government agencies are currently required to abide by the provisions of FISMA (unless specified as preconditions for obtaining government grants or contracts—still a relatively rare or narrowly scoped occurrence), the same strategies were recently recommended by executive order for others. We propose that information security guidelines for select agent research be updated to promulgate and detail FISMA standards and processes and that the latter be ultimately incorporated into select agent regulations. We also suggest that information security in academic and research institutions would greatly benefit from active efforts to improve communication among the biosecurity, security, and information technology communities, and from a secure venue for exchange of timely information on emerging threats and solutions in the research environment. PMID:26042864
Method for photo-altering a biological system to improve biological effect
Hill, Richard A.; Doiron, Daniel R.; Crean, David H.
2000-08-01
Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.
1987-10-01
observed with free MTP-PE. In addition to our observations on peritoneal and alveolar macrophages, we also examined the effect of MTP-PE treatment on liver...Ir OIC FILE COPY C2 ILn 00 NM AD _____ N SELECTIVE TARGETING OF ANTIVIRAL AND IMMUNOMODULATING AGENTS IN THE TREATMENT OF ARENAVIRUS INFECTIONS "Kc...Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Injections 12. PERSONAL AUTHOR(S) J. David Gangemi 13a. TYPE OF
Image Discrimination Models With Stochastic Channel Selection
NASA Technical Reports Server (NTRS)
Ahumada, Albert J., Jr.; Beard, Bettina L.; Null, Cynthia H. (Technical Monitor)
1995-01-01
Many models of human image processing feature a large fixed number of channels representing cortical units varying in spatial position (visual field direction and eccentricity) and spatial frequency (radial frequency and orientation). The values of these parameters are usually sampled at fixed values selected to ensure adequate overlap considering the bandwidth and/or spread parameters, which are usually fixed. Even high levels of overlap does not always ensure that the performance of the model will vary smoothly with image translation or scale changes. Physiological measurements of bandwidth and/or spread parameters result in a broad distribution of estimated parameter values and the prediction of some psychophysical results are facilitated by the assumption that these parameters also take on a range of values. Selecting a sample of channels from a continuum of channels rather than using a fixed set can make model performance vary smoothly with changes in image position, scale, and orientation. It also facilitates the addition of spatial inhomogeneity, nonlinear feature channels, and focus of attention to channel models.
LaViolette, Peter S; Daun, Mitchell K; Paulson, Eric S; Schmainda, Kathleen M
2014-02-01
Abnormal brain tumor vasculature has recently been highlighted by a dynamic susceptibility contrast (DSC) MRI processing technique. The technique uses independent component analysis (ICA) to separate arterial and venous perfusion. The overlap of the two, i.e. arterio-venous overlap or AVOL, preferentially occurs in brain tumors and predicts response to anti-angiogenic therapy. The effects of contrast agent leakage on the AVOL biomarker have yet to be established. DSC was acquired during two separate contrast boluses in ten patients undergoing clinical imaging for brain tumor diagnosis. Three components were modeled with ICA, which included the arterial and venous components. The percentage of each component as well as a third component were determined within contrast enhancing tumor and compared. AVOL within enhancing tumor was also compared between doses. The percentage of enhancing tumor classified as not arterial or venous and instead into a third component with contrast agent leakage apparent in the time-series was significantly greater for the first contrast dose compared to the second. The amount of AVOL detected within enhancing tumor was also significantly greater with the second dose compared to the first. Contrast leakage results in large signal variance classified as a separate component by the ICA algorithm. The use of a second dose mitigates the effect and allows measurement of AVOL within enhancement.
Bardi, Lara; Desmet, Charlotte; Nijhof, Annabel; Wiersema, Jan R; Brass, Marcel
2017-03-01
There is extensive discussion on whether spontaneous and explicit forms of ToM are based on the same cognitive/neural mechanisms or rather reflect qualitatively different processes. For the first time, we analyzed the BOLD signal for false belief processing by directly comparing spontaneous and explicit ToM task versions. In both versions, participants watched videos of a scene including an agent who acquires a true or false belief about the location of an object (belief formation phase). At the end of the movies (outcome phase), participants had to react to the presence of the object. During the belief formation phase, greater activity was found for false vs true belief trials in the right posterior parietal cortex. The ROI analysis of the right temporo-parietal junction (TPJ), confirmed this observation. Moreover, the anterior medial prefrontal cortex (aMPFC) was active during the outcome phase, being sensitive to violation of both the participant's and agent's expectations about the location of the object. Activity in the TPJ and aMPFC was not modulated by the spontaneous/explicit task. Overall, these data show that neural mechanisms for spontaneous and explicit ToM overlap. Interestingly, a dissociation between TPJ and aMPFC for belief tracking and outcome evaluation, respectively, was also found. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
Enhanced optical transmission through double-overlapped annular aperture array
NASA Astrophysics Data System (ADS)
Wang, Chaonan; Bai, Ming; Jin, Ming
2012-07-01
In this paper, transmission properties through an array of concentric or eccentric double-overlapped annular apertures (CDOAAs or EDOAAs) are investigated. It is demonstrated that local surface plasmon-assisted TE11-like modes in CDOAAs exhibit a blue shift with the increasing overlapped factor. For EDOAAs with asymmetric annular apertures in both directions, a new resonant peak can be excited at a larger wavelength using linearly polarised light, which corresponds to extreme field localisation around the narrowest gap attributed to the gap plasmons' excitation and is quite sensitive to the offset of the eccentric centre island. These properties provide a possible method to achieve multiplexed and tunable wavelength selection using different local surface plasmon resonances and are of significant potential applicable value to the designing of tunable optical devices.
9 CFR 121.5 - Exemptions for VS select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... agent or toxin that is contained in a specimen presented for proficiency testing will be exempt from the...
9 CFR 121.5 - Exemptions for VS select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... agent or toxin that is contained in a specimen presented for proficiency testing will be exempt from the...
9 CFR 121.5 - Exemptions for VS select agents and toxins.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... agent or toxin that is contained in a specimen presented for proficiency testing will be exempt from the...
Three-dimensional spiral CT during arterial portography: comparison of three rendering techniques.
Heath, D G; Soyer, P A; Kuszyk, B S; Bliss, D F; Calhoun, P S; Bluemke, D A; Choti, M A; Fishman, E K
1995-07-01
The three most common techniques for three-dimensional reconstruction are surface rendering, maximum-intensity projection (MIP), and volume rendering. Surface-rendering algorithms model objects as collections of geometric primitives that are displayed with surface shading. The MIP algorithm renders an image by selecting the voxel with the maximum intensity signal along a line extended from the viewer's eye through the data volume. Volume-rendering algorithms sum the weighted contributions of all voxels along the line. Each technique has advantages and shortcomings that must be considered during selection of one for a specific clinical problem and during interpretation of the resulting images. With surface rendering, sharp-edged, clear three-dimensional reconstruction can be completed on modest computer systems; however, overlapping structures cannot be visualized and artifacts are a problem. MIP is computationally a fast technique, but it does not allow depiction of overlapping structures, and its images are three-dimensionally ambiguous unless depth cues are provided. Both surface rendering and MIP use less than 10% of the image data. In contrast, volume rendering uses nearly all of the data, allows demonstration of overlapping structures, and engenders few artifacts, but it requires substantially more computer power than the other techniques.
NASA Astrophysics Data System (ADS)
Gulistan, Aamir; Rahman, M. M.; Ghosh, Souvik; Rahman, B. M. A.
2018-03-01
A full-vectorial numerically efficient Finite Element Method (FEM) based computer code is developed to study complex light-sound interactions in a single mode fiber (SMF). The SBS gain or SBS threshold in a fiber is highly related to the overlap between the optical and acoustic modes. For a typical SMF the acoustic-optic overlap strongly depends on the optical and acoustic mode profiles and it is observed that the acoustic mode is more confined in the core than the optical mode and reported overlap is around 94 % between these fundamental optical and acoustic modes. However, it is shown here that selective co-doping of Aluminum and Germanium in core reduces the acoustic index while keeping the optical index of the same value and thus results in increased acoustic- optic overlap of 99.7%. On the other hand, a design of acoustic anti-guide fiber for high-power transmission systems is also proposed, where the overlap between acoustic and optical modes is reduced. Here, we show that by keeping the optical properties same as a standard SMF and introducing a Boron doped 2nd layer in the cladding, a very low value of 2.7% overlap is achieved. Boron doping in cladding 2nd layer results in a high acoustic index and acoustic modes shifts in the cladding from the core, allowing much high power delivery through this SMF.
7 CFR 331.3 - PPQ select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-01-01
...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...
7 CFR 331.3 - PPQ select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-01-01
...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...
NASA Astrophysics Data System (ADS)
Wohlmuth, Johannes; Andersen, Jørgen Vitting
2006-05-01
We use agent-based models to study the competition among investors who use trading strategies with different amount of information and with different time scales. We find that mixing agents that trade on the same time scale but with different amount of information has a stabilizing impact on the large and extreme fluctuations of the market. Traders with the most information are found to be more likely to arbitrage traders who use less information in the decision making. On the other hand, introducing investors who act on two different time scales has a destabilizing effect on the large and extreme price movements, increasing the volatility of the market. Closeness in time scale used in the decision making is found to facilitate the creation of local trends. The larger the overlap in commonly shared information the more the traders in a mixed system with different time scales are found to profit from the presence of traders acting at another time scale than themselves.
The use of an image registration technique in the urban growth monitoring
NASA Technical Reports Server (NTRS)
Parada, N. D. J. (Principal Investigator); Foresti, C.; Deoliveira, M. D. L. N.; Niero, M.; Parreira, E. M. D. M. F.
1984-01-01
The use of an image registration program in the studies of urban growth is described. This program permits a quick identification of growing areas with the overlap of the same scene in different periods, and with the use of adequate filters. The city of Brasilia, Brazil, is selected for the test area. The dynamics of Brasilia urban growth are analyzed with the overlap of scenes dated June 1973, 1978 and 1983. The results showed the utilization of the image registration technique for the monitoring of dynamic urban growth.
Herrera, Leidi
2014-01-01
Trypanosoma cruzi the etiological agent of American Trypanosomiasis or Chagas disease (ChD) is transmitted by triatomines vectors between mammals including man. T. cruzi has existed for circa 150 Ma in the Americas and nearly 10 million people are currently infected. The overlap between wild and domestic ecotopes where T. cruzi circulates is increasing. Host-parasite interactions have been determined by infection patterns in these cycles, all under natural or laboratorial conditions. This mini-review describes specific parasite niches, such as plant communities or biological corridors between domestic and wild landscapes, in order to help identify risk factors for ChD and define the boundaries between wild and domestic transmission cycles, with an emphasis on research undertaken in Venezuela.
Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope
Helmann, John D.
2016-01-01
Summary Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, σW is most closely associated with membrane-active agents, σX with cationic antimicrobial peptide resistance, and σV with resistance to lysozyme. Here, I highlight the role of the σM regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics. PMID:26901131
Siefert, Janet L
2009-01-01
This chapter defines the agents that provide for the movement of genetic material which fuels the adaptive potential of life on our planet. The chapter has been structured to be broadly comprehensive, arbitrarily categorizing the mobilome into four classes: (1) transposons, (2) plasmids, (3) bacteriophage, and (4) self-splicing molecular parasites.Our increasing understanding of the mobilome is as dynamic as the mobilome itself. With continuing discovery, it is clear that nature has not confined these genomic agents of change to neat categories, but rather the classification categories overlap and intertwine. Massive sequencing efforts and their published analyses are continuing to refine our understanding of the extent of the mobilome. This chapter provides a framework to describe our current understanding of the mobilome and a foundation on which appreciation of its impact on genome evolution can be understood.
Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H
2018-01-15
Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.
7 CFR 331.3 - PPQ select agents and toxins.
Code of Federal Regulations, 2014 CFR
2014-01-01
... (b) of this section that have been genetically modified. (d) Select agents or toxins that meet any of..., and recombinant and/or synthetic organisms: (1) Nucleic acids that can produce infectious forms of any...
7 CFR 331.3 - PPQ select agents and toxins.
Code of Federal Regulations, 2013 CFR
2013-01-01
... (b) of this section that have been genetically modified. (d) Select agents or toxins that meet any of..., and recombinant and/or synthetic organisms: (1) Nucleic acids that can produce infectious forms of any...
RAMTaB: Robust Alignment of Multi-Tag Bioimages
Raza, Shan-e-Ahmed; Humayun, Ahmad; Abouna, Sylvie; Nattkemper, Tim W.; Epstein, David B. A.; Khan, Michael; Rajpoot, Nasir M.
2012-01-01
Background In recent years, new microscopic imaging techniques have evolved to allow us to visualize several different proteins (or other biomolecules) in a visual field. Analysis of protein co-localization becomes viable because molecules can interact only when they are located close to each other. We present a novel approach to align images in a multi-tag fluorescence image stack. The proposed approach is applicable to multi-tag bioimaging systems which (a) acquire fluorescence images by sequential staining and (b) simultaneously capture a phase contrast image corresponding to each of the fluorescence images. To the best of our knowledge, there is no existing method in the literature, which addresses simultaneous registration of multi-tag bioimages and selection of the reference image in order to maximize the overall overlap between the images. Methodology/Principal Findings We employ a block-based method for registration, which yields a confidence measure to indicate the accuracy of our registration results. We derive a shift metric in order to select the Reference Image with Maximal Overlap (RIMO), in turn minimizing the total amount of non-overlapping signal for a given number of tags. Experimental results show that the Robust Alignment of Multi-Tag Bioimages (RAMTaB) framework is robust to variations in contrast and illumination, yields sub-pixel accuracy, and successfully selects the reference image resulting in maximum overlap. The registration results are also shown to significantly improve any follow-up protein co-localization studies. Conclusions For the discovery of protein complexes and of functional protein networks within a cell, alignment of the tag images in a multi-tag fluorescence image stack is a key pre-processing step. The proposed framework is shown to produce accurate alignment results on both real and synthetic data. Our future work will use the aligned multi-channel fluorescence image data for normal and diseased tissue specimens to analyze molecular co-expression patterns and functional protein networks. PMID:22363510
The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development
ERIC Educational Resources Information Center
Baker, Lauri M.; Hadley, Gregg
2014-01-01
The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…
Burnout among Extension Agents in the Ohio Cooperative Extension Service.
ERIC Educational Resources Information Center
Igodan, O. Chris; Newcomb, L. H.
A study examined the extent and causes of burnout among extension agents in Ohio. From the 241 extension agents working in the 88 counties of Ohio, researchers selected a random sample of 101 agents. Included in the sample were 34 agriculture agents, 33 home economics agents. Included in the sample agents were asked to complete a survey…
Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk
2008-12-01
Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.
Distributed Control of a Swarm of Autonomous Unmanned Aerial Vehicles
2003-03-01
wisdom, and love have provided a firm anchor in rough times, and a light in the darkness . “Come to me, all you who are weary and burdened, and I will...time. The light-gray trails represent the area that has been covered in the past 50 timesteps. The dark -gray areas are overlapping areas calculated...during the current timestep. The dark line encloses the total contigu- ous sensor area for this example. Note that while agent 1’s footprint does not
76 FR 12118 - Proposed Data Collections Submitted for Public Comment and Recommendations
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-04
... that come to CDC for Select Agents. The term select agents is used to describe a limited group of... bioterrorism, inflicting significant morbidity and mortality on susceptible populations. In light of current...
Guidelines for Contracting Microfilming Services.
ERIC Educational Resources Information Center
Byrne, Sherry
1986-01-01
Outlines the process involved in selecting an outside filming agent for the purpose of preserving a library's or archive's holdings. Guidelines include project planning, selecting a filming agent, and contract preparation and maintenance. A sample contract is included. (Author/EM)
Bagny Beilhe, Leïla; Piou, Cyril; Tadu, Zéphirin; Babin, Régis
2018-06-06
The use of ants for biological control of insect pests was the first reported case of conservation biological control. Direct and indirect community interactions between ants and pests lead to differential spatial pattern. We investigated spatial interactions between mirids, the major cocoa pest in West Africa and numerically dominant ant species, using bivariate point pattern analysis to identify potential biological control agents. We assume that potential biological control agents should display negative spatial interactions with mirids considering their niche overlap. The mirid/ant data were collected in complex cacao-based agroforestry systems sampled in three agroecological areas over a forest-savannah gradient in Cameroon. Three species, Crematogaster striatula Emery (Hymenoptera: Formicidae), Crematogaster clariventris Mayr (Hymenoptera: Formicidae), and Oecophylla longinoda Latreille (Hymenoptera: Formicidae) with high predator and aggressive behaviors were identified as dominant and showed negative spatial relationships with mirids. The weaver ant, O. longinoda was identified as the only potential biological control agent, considering its ubiquity in the plots, the similarity in niche requirements, and the spatial segregation with mirids resulting probably from exclusion mechanisms. Combining bivariate point pattern analysis to good knowledge of insect ecology was an effective method to identify a potentially good biological control agent.
NASA Astrophysics Data System (ADS)
Mutoh, Atsuko; Tokuhara, Shinya; Kanoh, Masayoshi; Oboshi, Tamon; Kato, Shohei; Itoh, Hidenori
It is generally thought that living things have trends in their preferences. The mechanism of occurrence of another trends in successive periods is concerned in their conformity. According to social impact theory, the minority is always exists in the group. There is a possibility that the minority make the transition to the majority by conforming agents. Because of agent's promotion of their conform actions, the majority can make the transition. We proposed an evolutionary model with both genes and memes, and elucidated the interaction between genes and memes on sexual selection. In this paper, we propose an agent model for sexual selection imported the concept of conformity. Using this model we try an environment where male agents and female agents are existed, we find that periodic phenomena of fashion are expressed. And we report the influence of conformity and differentiation on the transition of their preferences.
Differential Development of Selectivity for Faces and Bodies in the Fusiform Gyrus
ERIC Educational Resources Information Center
Peelen, Marius V.; Glaser, Bronwyn; Vuilleumier, Patrik; Eliez, Stephan
2009-01-01
Viewing faces or bodies activates category-selective areas of visual cortex, including the fusiform face area (FFA), fusiform body area (FBA), and extrastriate body area (EBA). Here, using fMRI, we investigate the development of these areas, focusing on the right FFA and FBA. Despite the overlap of functionally defined FFA and FBA (54%-75%…
The neural organization of perception in chess experts.
Krawczyk, Daniel C; Boggan, Amy L; McClelland, M Michelle; Bartlett, James C
2011-07-20
The human visual system responds to expertise, and it has been suggested that regions that process faces also process other objects of expertise including chess boards by experts. We tested whether chess and face processing overlap in brain activity using fMRI. Chess experts and novices exhibited face selective areas, but these regions showed no selectivity to chess configurations relative to other stimuli. We next compared neural responses to chess and to scrambled chess displays to isolate areas relevant to expertise. Areas within the posterior cingulate, orbitofrontal cortex, and right temporal cortex were active in this comparison in experts over novices. We also compared chess and face responses within the posterior cingulate and found this area responsive to chess only in experts. These findings indicate that the configurations in chess are not strongly processed by face-selective regions that are selective for faces in individuals who have expertise in both domains. Further, the area most consistently involved in chess did not show overlap with faces. Overall, these results suggest that expert visual processing may be similar at the level of recognition, but need not show the same neural correlates. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Hydrocarbon extraction agents and microbiological processes for their production
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zajic, J.E.; Gerson, D.F.
1987-02-03
A process is described for producing extraction agents useful in the separation of hydrocarbon values from mineral deposits. It comprises cultivating by an aerobic fermentation, in a growth promoting medium and under growth promoting conditions, and on a liquid hydrocarbon substrate, a selected microbial strain of a species of microorganism selected from the group consisting of Arthrobacter terregens, Arthrobacter xerosis, Bacillus megaterium, Corynebacterium lepus, Corynebacterium xerosis, Nocardia petroleophila, and Vibrio ficheri. This is done to produce an extraction agent of microbiological origin in the fermentation medium, subsequently recovering the extraction agent from the fermentation medium and drying the agent tomore » powdered form.« less
Lancaster, Matthew E; Shelhamer, Ryan; Homa, Donald
2013-04-01
Two experiments investigated category inference when categories were composed of correlated or uncorrelated dimensions and the categories overlapped minimally or moderately. When the categories minimally overlapped, the dimensions were strongly correlated with the category label. Following a classification learning phase, subsequent transfer required the selection of either a category label or a feature when one, two, or three features were missing. Experiments 1 and 2 differed primarily in the number of learning blocks prior to transfer. In each experiment, the inference of the category label or category feature was influenced by both dimensional and category correlations, as well as their interaction. The number of cues available at test impacted performance more when the dimensional correlations were zero and category overlap was high. However, a minimal number of cues were sufficient to produce high levels of inference when the dimensions were highly correlated; additional cues had a positive but reduced impact, even when overlap was high. Subjects were generally more accurate in inferring the category label than a category feature regardless of dimensional correlation, category overlap, or number of cues available at test. Whether the category label functioned as a special feature or not was critically dependent upon these embedded correlations, with feature inference driven more strongly by dimensional correlations.
Collagenase Santyl ointment: a selective agent for wound debridement.
Shi, Lei; Carson, Dennis
2009-01-01
Enzymatic debridement is a frequently used technique for removal of necrotic tissue from wounds. Proteases with specificity to break down the collagenous materials in necrotic tissues can achieve selective debridement, digesting denatured collagen in eschar while sparing nonnecrotic tissues. This article provides information about the selectivity of a collagenase-based debriding agent, including evidence of its safe and efficacious uses. Recent research has been conducted, investigating the chemical and biological properties of collagenase ointment, including healing in animal models, digestion power on different collagen types, cell migration activity from collagen degradation products, and compatibility with various wound dressings and metal ions. Evidence presented demonstrates that collagenase ointment is an effective, selective, and safe wound debriding agent.
Rudolph, Michael J; Vance, David J; Cheung, Jonah; Franklin, Matthew C; Burshteyn, Fiana; Cassidy, Michael S; Gary, Ebony N; Herrera, Cristina; Shoemaker, Charles B; Mantis, Nicholas J
2014-08-26
Ricin is a select agent toxin and a member of the RNA N-glycosidase family of medically important plant and bacterial ribosome-inactivating proteins. In this study, we determined X-ray crystal structures of the enzymatic subunit of ricin (RTA) in complex with the antigen binding domains (VHH) of five unique single-chain monoclonal antibodies that differ in their respective toxin-neutralizing activities. None of the VHHs made direct contact with residues involved in RTA's RNA N-glycosidase activity or induced notable allosteric changes in the toxin's subunit. Rather, the five VHHs had overlapping structural epitopes on the surface of the toxin and differed in the degree to which they made contact with prominent structural elements in two folding domains of the RTA. In general, RTA interactions were influenced most by the VHH CDR3 (CDR, complementarity-determining region) elements, with the most potent neutralizing antibody having the shortest and most conformationally constrained CDR3. These structures provide unique insights into the mechanisms underlying toxin neutralization and provide critically important information required for the rational design of ricin toxin subunit vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.
Predicting rates of inbreeding in populations undergoing selection.
Woolliams, J A; Bijma, P
2000-01-01
Tractable forms of predicting rates of inbreeding (DeltaF) in selected populations with general indices, nonrandom mating, and overlapping generations were developed, with the principal results assuming a period of equilibrium in the selection process. An existing theorem concerning the relationship between squared long-term genetic contributions and rates of inbreeding was extended to nonrandom mating and to overlapping generations. DeltaF was shown to be approximately (1)/(4)(1 - omega) times the expected sum of squared lifetime contributions, where omega is the deviation from Hardy-Weinberg proportions. This relationship cannot be used for prediction since it is based upon observed quantities. Therefore, the relationship was further developed to express DeltaF in terms of expected long-term contributions that are conditional on a set of selective advantages that relate the selection processes in two consecutive generations and are predictable quantities. With random mating, if selected family sizes are assumed to be independent Poisson variables then the expected long-term contribution could be substituted for the observed, providing (1)/(4) (since omega = 0) was increased to (1)/(2). Established theory was used to provide a correction term to account for deviations from the Poisson assumptions. The equations were successfully applied, using simple linear models, to the problem of predicting DeltaF with sib indices in discrete generations since previously published solutions had proved complex. PMID:10747074
42 CFR 73.10 - Restricting access to select agents and toxins; security risk assessments.
Code of Federal Regulations, 2011 CFR
2011-10-01
... AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING SELECT AGENTS AND TOXINS § 73.10 Restricting... or intelligence agency of committing a crime specified in 18 U.S.C. 2332b(g)(5), knowing involvement...
Leek, E Charles; d'Avossa, Giovanni; Tainturier, Marie-Josèphe; Roberts, Daniel J; Yuen, Sung Lai; Hu, Mo; Rafal, Robert
2012-01-01
This study examines how brain damage can affect the cognitive processes that support the integration of sensory input and prior knowledge during shape perception. It is based on the first detailed study of acquired ventral simultanagnosia, which was found in a patient (M.T.) with posterior occipitotemporal lesions encompassing V4 bilaterally. Despite showing normal object recognition for single items in both accuracy and response times (RTs), and intact low-level vision assessed across an extensive battery of tests, M.T. was impaired in object identification with overlapping figures displays. Task performance was modulated by familiarity: Unlike controls, M.T. was faster with overlapping displays of abstract shapes than with overlapping displays of common objects. His performance with overlapping common object displays was also influenced by both the semantic relatedness and visual similarity of the display items. These findings challenge claims that visual perception is driven solely by feedforward mechanisms and show how brain damage can selectively impair high-level perceptual processes supporting the integration of stored knowledge and visual sensory input.
Oligo-branched peptides for tumor targeting: from magic bullets to magic forks.
Falciani, Chiara; Pini, Alessandro; Bracci, Luisa
2009-02-01
Selective targeting of tumor cells is the final goal of research and drug discovery for cancer diagnosis, imaging and therapy. After the invention of hybridoma technology, the concept of magic bullet was introduced into the field of oncology, referring to selective killing of tumor cells, by specific antibodies. More recently, small molecules and peptides have also been proposed as selective targeting agents. We analyze the state of the art of tumor-selective agents that are presently available and tested in clinical settings. A novel approach based on 'armed' oligo-branched peptides as tumor targeting agents, is discussed and compared with existing tumor-selective therapies mediated by antibodies, small molecules or monomeric peptides. Oligo-branched peptides could be novel drugs that combine the advantages of antibodies and small molecules.
Aguilera-Mendoza, Longendri; Marrero-Ponce, Yovani; Tellez-Ibarra, Roberto; Llorente-Quesada, Monica T; Salgado, Jesús; Barigye, Stephen J; Liu, Jun
2015-08-01
The large variety of antimicrobial peptide (AMP) databases developed to date are characterized by a substantial overlap of data and similarity of sequences. Our goals are to analyze the levels of redundancy for all available AMP databases and use this information to build a new non-redundant sequence database. For this purpose, a new software tool is introduced. A comparative study of 25 AMP databases reveals the overlap and diversity among them and the internal diversity within each database. The overlap analysis shows that only one database (Peptaibol) contains exclusive data, not present in any other, whereas all sequences in the LAMP_Patent database are included in CAMP_Patent. However, the majority of databases have their own set of unique sequences, as well as some overlap with other databases. The complete set of non-duplicate sequences comprises 16 990 cases, which is almost half of the total number of reported peptides. On the other hand, the diversity analysis identifies the most and least diverse databases and proves that all databases exhibit some level of redundancy. Finally, we present a new parallel-free software, named Dover Analyzer, developed to compute the overlap and diversity between any number of databases and compile a set of non-redundant sequences. These results are useful for selecting or building a suitable representative set of AMPs, according to specific needs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Elhanan, Gai; Ochs, Christopher; Mejino, Jose L V; Liu, Hao; Mungall, Christopher J; Perl, Yehoshua
2017-06-01
To examine whether disjoint partial-area taxonomy, a semantically-based evaluation methodology that has been successfully tested in SNOMED CT, will perform with similar effectiveness on Uberon, an anatomical ontology that belongs to a structurally similar family of ontologies as SNOMED CT. A disjoint partial-area taxonomy was generated for Uberon. One hundred randomly selected test concepts that overlap between partial-areas were matched to a same size control sample of non-overlapping concepts. The samples were blindly inspected for non-critical issues and presumptive errors first by a general domain expert whose results were then confirmed or rejected by a highly experienced anatomical ontology domain expert. Reported issues were subsequently reviewed by Uberon's curators. Overlapping concepts in Uberon's disjoint partial-area taxonomy exhibited a significantly higher rate of all issues. Clear-cut presumptive errors trended similarly but did not reach statistical significance. A sub-analysis of overlapping concepts with three or more relationship types indicated a much higher rate of issues. Overlapping concepts from Uberon's disjoint abstraction network are quite likely (up to 28.9%) to exhibit issues. The results suggest that the methodology can transfer well between same family ontologies. Although Uberon exhibited relatively few overlapping concepts, the methodology can be combined with other semantic indicators to expand the process to other concepts within the ontology that will generate high yields of discovered issues. Copyright © 2017 Elsevier B.V. All rights reserved.
Older partner selection promotes the prevalence of cooperation in evolutionary games.
Yang, Guoli; Huang, Jincai; Zhang, Weiming
2014-10-21
Evolutionary games typically come with the interplays between evolution of individual strategy and adaptation to network structure. How these dynamics in the co-evolution promote (or obstruct) the cooperation is regarded as an important topic in social, economic, and biological fields. Combining spatial selection with partner choice, the focus of this paper is to identify which neighbour should be selected as a role to imitate during the process of co-evolution. Age, an internal attribute and kind of local piece of information regarding the survivability of the agent, is a significant consideration for the selection strategy. The analysis and simulations presented, demonstrate that older partner selection for strategy imitation could foster the evolution of cooperation. The younger partner selection, however, may decrease the level of cooperation. Our model highlights the importance of agent׳s age on the promotion of cooperation in evolutionary games, both efficiently and effectively. Copyright © 2014 Elsevier Ltd. All rights reserved.
Attenuation of a select agent-excluded Burkholderia pseudomallei capsule mutant in hamsters.
Gutierrez, Maria G; Warawa, Jonathan M
2016-05-01
Burkholderia pseudomallei is a Tier 1 select agent and potential bioweapon. Given it is potential to cause a lethal respiratory disease, research with fully virulent B. pseudomallei is conducted in Biosafety Level 3 (BSL-3) laboratory spaces. The logistical, financial, and administrative burden of Tier 1 select agent BSL-3 research has created an interest in mitigating such burdens through the use of either attenuated B. pseudomallei strains at BSL-2, or research with surrogate species, such as Burkholderia thailandensis. Previously, attenuated B. pseudomallei auxotroph mutants (asd and purM) have been approved for exclusion from select agent requirements, allowing for in vitro studies to be conducted at BSL-2. Acapsular B. pseudomallei mutants are known to be strongly attenuated in a variety of animal models, and yet acapsular B. pseudomallei mutants do not require nutritional supplementation, and can be studied within cultured macrophages, performing phenotypically similarly to parent strains. We demonstrate that the loss of a 30.8 kb region of the wcb capsule operon allows for a dramatic >4.46 log attenuation in a hamster intraperitoneal infection model, and report that this strain, JW270, has met criteria for exclusion from select agent requirements. Copyright © 2016 Elsevier B.V. All rights reserved.
Yokoyama, Jennifer S.; Karch, Celeste M.; Fan, Chun C.; Bonham, Luke W.; Kouri, Naomi; Ross, Owen A.; Rademakers, Rosa; Kim, Jungsu; Wang, Yunpeng; Höglinger, Günter U.; Muller, Ulrich; Ferrari, Raffaele; Hardy, John; Momeni, Parastoo; Sugrue, Leo P.; Hess, Christopher P.; Barkovich, A. James; Boxer, Adam L.; Seeley, William W.; Rabinovici, Gil D.; Rosen, Howard J.; Miller, Bruce L.; Schmansky, Nicholas J.; Fischl, Bruce; Hyman, Bradley T.; Dickson, Dennis W.; Schellenberg, Gerard D.; Andreassen, Ole A.; Dale, Anders M.; Desikan, Rahul S.
2017-01-01
Corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and a subset of frontotemporal dementia (FTD) are neurodegenerative disorders characterized by tau inclusions in neurons and glia (tauopathies). Although clinical, pathological and genetic evidence suggests overlapping pathobiology between CBD, PSP, and FTD, the relationship between these disorders is still not well understood. Using summary statistics (odds ratios and p-values) from large genome-wide association studies (total n = 14,286 cases and controls) and recently established genetic methods, we investigated the genetic overlap between CBD and PSP and CBD and FTD. We found up to 800-fold enrichment of genetic risk in CBD across different levels of significance for PSP or FTD. In addition to NSF (tagging the MAPT H1 haplotype), we observed that SNPs in or near MOBP, CXCR4, EGFR, and GLDC showed significant genetic overlap between CBD and PSP, whereas only SNPs tagging the MAPT haplotype overlapped between CBD and FTD. The risk alleles of the shared SNPs were associated with expression changes in cis-genes. Evaluating transcriptome levels across adult human brains, we found a unique neuroanatomic gene expression signature for each of the five overlapping gene loci (omnibus ANOVA p < 2.0 × 10−16). Functionally, we found that these shared risk genes were associated with protein interaction and gene co-expression networks and showed enrichment for several neurodevelopmental pathways. Our findings suggest: i) novel genetic overlap between CBD and PSP beyond the MAPT locus; ii) strong ties between CBD and FTD through the MAPT clade, and; iii) unique combinations of overlapping genes that may, in part, influence selective regional or neuronal vulnerability observed in specific tauopathies. PMID:28271184
Azimuthal Anisotropy in U +U and Au +Au Collisions at RHIC
NASA Astrophysics Data System (ADS)
Adamczyk, L.; Adkins, J. K.; Agakishiev, G.; Aggarwal, M. M.; Ahammed, Z.; Alekseev, I.; Alford, J.; Aparin, A.; Arkhipkin, D.; Aschenauer, E. C.; Averichev, G. S.; Banerjee, A.; Bellwied, R.; Bhasin, A.; Bhati, A. K.; Bhattarai, P.; Bielcik, J.; Bielcikova, J.; Bland, L. C.; Bordyuzhin, I. G.; Bouchet, J.; Brandin, A. V.; Bunzarov, I.; Burton, T. P.; Butterworth, J.; Caines, H.; Calderón de la Barca Sánchez, M.; Campbell, J. M.; Cebra, D.; Cervantes, M. C.; Chakaberia, I.; Chaloupka, P.; Chang, Z.; Chattopadhyay, S.; Chen, J. H.; Chen, X.; Cheng, J.; Cherney, M.; Christie, W.; Contin, G.; Crawford, H. J.; Das, S.; De Silva, L. C.; Debbe, R. R.; Dedovich, T. G.; Deng, J.; Derevschikov, A. A.; di Ruzza, B.; Didenko, L.; Dilks, C.; Dong, X.; Drachenberg, J. L.; Draper, J. E.; Du, C. M.; Dunkelberger, L. E.; Dunlop, J. C.; Efimov, L. G.; Engelage, J.; Eppley, G.; Esha, R.; Evdokimov, O.; Eyser, O.; Fatemi, R.; Fazio, S.; Federic, P.; Fedorisin, J.; Feng, Z.; Filip, P.; Fisyak, Y.; Flores, C. E.; Fulek, L.; Gagliardi, C. A.; Garand, D.; Geurts, F.; Gibson, A.; Girard, M.; Greiner, L.; Grosnick, D.; Gunarathne, D. S.; Guo, Y.; Gupta, S.; Gupta, A.; Guryn, W.; Hamad, A.; Hamed, A.; Haque, R.; Harris, J. W.; He, L.; Heppelmann, S.; Heppelmann, S.; Hirsch, A.; Hoffmann, G. W.; Hofman, D. J.; Horvat, S.; Huang, H. Z.; Huang, B.; Huang, X.; Huck, P.; Humanic, T. J.; Igo, G.; Jacobs, W. W.; Jang, H.; Jiang, K.; Judd, E. G.; Kabana, S.; Kalinkin, D.; Kang, K.; Kauder, K.; Ke, H. W.; Keane, D.; Kechechyan, A.; Khan, Z. H.; Kikola, D. P.; Kisel, I.; Kisiel, A.; Koetke, D. D.; Kollegger, T.; Kosarzewski, L. K.; Kotchenda, L.; Kraishan, A. F.; Kravtsov, P.; Krueger, K.; Kulakov, I.; Kumar, L.; Kycia, R. A.; Lamont, M. A. C.; Landgraf, J. M.; Landry, K. D.; Lauret, J.; Lebedev, A.; Lednicky, R.; Lee, J. H.; Li, W.; Li, Y.; Li, C.; Li, Z. M.; Li, X.; Li, X.; Lisa, M. A.; Liu, F.; Ljubicic, T.; Llope, W. J.; Lomnitz, M.; Longacre, R. S.; Luo, X.; Ma, L.; Ma, R.; Ma, Y. G.; Ma, G. L.; Magdy, N.; Majka, R.; Manion, A.; Margetis, S.; Markert, C.; Masui, H.; Matis, H. S.; McDonald, D.; Meehan, K.; Minaev, N. G.; Mioduszewski, S.; Mohanty, B.; Mondal, M. M.; Morozov, D. A.; Mustafa, M. K.; Nandi, B. K.; Nasim, Md.; Nayak, T. K.; Nigmatkulov, G.; Nogach, L. V.; Noh, S. Y.; Novak, J.; Nurushev, S. B.; Odyniec, G.; Ogawa, A.; Oh, K.; Okorokov, V.; Olvitt, D. L.; Page, B. S.; Pak, R.; Pan, Y. X.; Pandit, Y.; Panebratsev, Y.; Pawlik, B.; Pei, H.; Perkins, C.; Peterson, A.; Pile, P.; Planinic, M.; Pluta, J.; Poljak, N.; Poniatowska, K.; Porter, J.; Posik, M.; Poskanzer, A. M.; Pruthi, N. K.; Putschke, J.; Qiu, H.; Quintero, A.; Ramachandran, S.; Raniwala, S.; Raniwala, R.; Ray, R. L.; Ritter, H. G.; Roberts, J. B.; Rogachevskiy, O. V.; Romero, J. L.; Roy, A.; Ruan, L.; Rusnak, J.; Rusnakova, O.; Sahoo, N. R.; Sahu, P. K.; Sakrejda, I.; Salur, S.; Sandweiss, J.; Sarkar, A.; Schambach, J.; Scharenberg, R. P.; Schmah, A. M.; Schmidke, W. B.; Schmitz, N.; Seger, J.; Seyboth, P.; Shah, N.; Shahaliev, E.; Shanmuganathan, P. V.; Shao, M.; Sharma, B.; Sharma, M. K.; Shen, W. Q.; Shi, S. S.; Shou, Q. Y.; Sichtermann, E. P.; Sikora, R.; Simko, M.; Skoby, M. J.; Smirnov, D.; Smirnov, N.; Song, L.; Sorensen, P.; Spinka, H. M.; Srivastava, B.; Stanislaus, T. D. S.; Stepanov, M.; Stock, R.; Strikhanov, M.; Stringfellow, B.; Sumbera, M.; Summa, B. J.; Sun, X.; Sun, X. M.; Sun, Z.; Sun, Y.; Surrow, B.; Svirida, D. N.; Szelezniak, M. A.; Tang, Z.; Tang, A. H.; Tarnowsky, T.; Tawfik, A. N.; Thomas, J. H.; Timmins, A. R.; Tlusty, D.; Tokarev, M.; Trentalange, S.; Tribble, R. E.; Tribedy, P.; Tripathy, S. K.; Trzeciak, B. A.; Tsai, O. D.; Ullrich, T.; Underwood, D. G.; Upsal, I.; Van Buren, G.; van Nieuwenhuizen, G.; Vandenbroucke, M.; Varma, R.; Vasiliev, A. N.; Vertesi, R.; Videbaek, F.; Viyogi, Y. P.; Vokal, S.; Voloshin, S. A.; Vossen, A.; Wang, F.; Wang, Y.; Wang, H.; Wang, J. S.; Wang, Y.; Wang, G.; Webb, G.; Webb, J. C.; Wen, L.; Westfall, G. D.; Wieman, H.; Wissink, S. W.; Witt, R.; Wu, Y. F.; Xiao, Z.; Xie, W.; Xin, K.; Xu, Y. F.; Xu, N.; Xu, Z.; Xu, Q. H.; Xu, H.; Yang, Y.; Yang, Y.; Yang, C.; Yang, S.; Yang, Q.; Ye, Z.; Yepes, P.; Yi, L.; Yip, K.; Yoo, I.-K.; Yu, N.; Zbroszczyk, H.; Zha, W.; Zhang, X. P.; Zhang, J. B.; Zhang, J.; Zhang, Z.; Zhang, S.; Zhang, Y.; Zhang, J. L.; Zhao, F.; Zhao, J.; Zhong, C.; Zhou, L.; Zhu, X.; Zoulkarneeva, Y.; Zyzak, M.; STAR Collaboration
2015-11-01
Collisions between prolate uranium nuclei are used to study how particle production and azimuthal anisotropies depend on initial geometry in heavy-ion collisions. We report the two- and four-particle cumulants, v2{2 } and v2{4 }, for charged hadrons from U +U collisions at √{sNN }=193 GeV and Au +Au collisions at √{sNN}=200 GeV . Nearly fully overlapping collisions are selected based on the energy deposited by spectators in zero degree calorimeters (ZDCs). Within this sample, the observed dependence of v2{2 } on multiplicity demonstrates that ZDC information combined with multiplicity can preferentially select different overlap configurations in U +U collisions. We also show that v2 vs multiplicity can be better described by models, such as gluon saturation or quark participant models, that eliminate the dependence of the multiplicity on the number of binary nucleon-nucleon collisions.
Azimuthal anisotophy in U + U and Au + Au collisions at RHIC
Adamczyk, L.
2015-11-24
Collisions between prolate uranium nuclei are used to study how particle production and azimuthal anisotropies depend on initial geometry in heavy-ion collisions. We report the two- and four-particle cumulants, v 2{2} and v 2{4}, for charged hadrons from U+U collisions at √ SNN = 193 GeV and Au+Au collisions at √ SNN = 200 GeV. Nearly fully overlapping collisions are selected based on the energy deposited by spectators in zero degree calorimeters (ZDCs). Within this sample, the observed dependence of v 2{2} on multiplicity demonstrates that ZDC information combined with multiplicity can preferentially select different overlap configurations in U+U collisions.more » As a result, we also show that v 2 vs multiplicity can be better described by models, such as gluon saturation or quark participant models, that eliminate the dependence of the multiplicity on the number of binary nucleon-nucleon collisions.« less
Borenstein, Elhanan; Feldman, Marcus W; Aoki, Kenichi
2008-03-01
Cumulative cultural change requires organisms that are capable of both exploratory individual learning and faithful social learning. In our model, an organism's phenotype is initially determined innately (by its genotypic value) or by social learning (copying a phenotype from the parental generation), and then may or may not be modified by individual learning (exploration around the initial phenotype). The environment alternates periodically between two states, each defined as a certain range of phenotypes that can survive. These states may overlap, in which case the same phenotype can survive in both states, or they may not. We find that a joint social and exploratory individual learning strategy-the strategy that supports cumulative culture-is likely to spread when the environmental states do not overlap. In particular, when the environmental states are contiguous and mutation is allowed among the genotypic values, this strategy will spread in either moderately or highly stable environments, depending on the exact nature of the individual learning applied. On the other hand, natural selection often favors a social learning strategy without exploration when the environmental states overlap. We find only partial support for the "consensus" view, which holds that individual learning, social learning, and innate determination of behavior will evolve at short, intermediate, and long environmental periodicities, respectively.
Biasing spatial attention with semantic information: an event coding approach.
Amer, Tarek; Gozli, Davood G; Pratt, Jay
2017-04-21
We investigated the influence of conceptual processing on visual attention from the standpoint of Theory of Event Coding (TEC). The theory makes two predictions: first, an important factor in determining the influence of event 1 on processing event 2 is whether features of event 1 are bound into a unified representation (i.e., selection or retrieval of event 1). Second, whether processing the two events facilitates or interferes with each other should depend on the extent to which their constituent features overlap. In two experiments, participants performed a visual-attention cueing task, in which the visual target (event 2) was preceded by a relevant or irrelevant explicit (e.g., "UP") or implicit (e.g., "HAPPY") spatial-conceptual cue (event 1). Consistent with TEC, we found relevant explicit cues (which featurally overlap to a greater extent with the target) and implicit cues (which featurally overlap to a lesser extent), respectively, facilitated and interfered with target processing at compatible locations. Irrelevant explicit and implicit cues, on the other hand, both facilitated target processing, presumably because they were less likely selected or retrieved as an integrated and unified event file. We argue that such effects, often described as "attentional cueing", are better accounted for within the event coding framework.
Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Shimada, Yuji; Sasaki, Hitoshi; Matsumoto, Kohei; Takeda, Tsutomu; Ueyama, Hiroya; Matsumoto, Kenshi; Watanabe, Sumio
2017-12-01
Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective.
Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Shimada, Yuji; Sasaki, Hitoshi; Matsumoto, Kohei; Takeda, Tsutomu; Ueyama, Hiroya; Matsumoto, Kenshi; Watanabe, Sumio
2017-01-01
Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective. PMID:29021437
Isotope separation by photoselective dissociative electron capture
Stevens, C.G.
1978-08-29
Disclosed is a method of separating isotopes based on photoselective electron capture dissociation of molecules having an electron capture cross section dependence on the vibrational state of the molecule. A molecular isotope source material is irradiated to selectively excite those molecules containing a desired isotope to a predetermined vibrational state having associated therewith an electron capture energy region substantially non-overlapping with the electron capture energy ranges associated with the lowest vibration states of the molecules. The isotope source is also subjected to electrons having an energy corresponding to the non-overlapping electron capture region whereby the selectively excited molecules preferentially capture electrons and dissociate into negative ions and neutrals. The desired isotope may be in the negative ion product or in the neutral product depending upon the mechanism of dissociation of the particular isotope source used. The dissociation product enriched in the desired isotope is then separated from the reaction system by conventional means. Specifically, [sup 235]UF[sub 6] is separated from a UF[sub 6] mixture by selective excitation followed by dissociative electron capture into [sup 235]UF[sub 5]- and F. 2 figs.
Isotope separation by photoselective dissociative electron capture
Stevens, Charles G. [Pleasanton, CA
1978-08-29
A method of separating isotopes based on photoselective electron capture dissociation of molecules having an electron capture cross section dependence on the vibrational state of the molecule. A molecular isotope source material is irradiated to selectively excite those molecules containing a desired isotope to a predetermined vibrational state having associated therewith an electron capture energy region substantially non-overlapping with the electron capture energy ranges associated with the lowest vibration states of the molecules. The isotope source is also subjected to electrons having an energy corresponding to the non-overlapping electron capture region whereby the selectively excited molecules preferentially capture electrons and dissociate into negative ions and neutrals. The desired isotope may be in the negative ion product or in the neutral product depending upon the mechanism of dissociation of the particular isotope source used. The dissociation product enriched in the desired isotope is then separated from the reaction system by conventional means. Specifically, .sup.235 UF.sub.6 is separated from a UF.sub.6 mixture by selective excitation followed by dissociative electron capture into .sup.235 UF.sub.5 - and F.
Galinsky, Adam D; Hall, Erika V; Cuddy, Amy J C
2013-04-01
Six studies explored the overlap between racial and gender stereotypes, and the consequences of this overlap for interracial dating, leadership selection, and athletic participation. Two initial studies captured the explicit and implicit gender content of racial stereotypes: Compared with the White stereotype, the Asian stereotype was more feminine, whereas the Black stereotype was more masculine. Study 3 found that heterosexual White men had a romantic preference for Asians over Blacks and that heterosexual White women had a romantic preference for Blacks over Asians; preferences for masculinity versus femininity mediated participants' attraction to Blacks relative to Asians. The pattern of romantic preferences observed in Study 3 was replicated in Study 4, an analysis of the data on interracial marriages from the 2000 U.S. Census. Study 5 showed that Blacks were more likely and Asians less likely than Whites to be selected for a masculine leadership position. In Study 6, an analysis of college athletics showed that Blacks were more heavily represented in more masculine sports, relative to Asians. These studies demonstrate that the gender content of racial stereotypes has important real-world consequences.
Natural selection of memory-one strategies for the iterated prisoner's dilemma.
Kraines, D P; Kraines, V Y
2000-04-21
In the iterated Prisoner's Dilemma, mutually cooperative behavior can become established through Darwinian natural selection. In simulated interactions of stochastic memory-one strategies for the Iterated Prisoner's Dilemma, Nowak and Sigmund discovered that cooperative agents using a Pavlov (Win-Stay Lose-Switch) type strategy eventually dominate a random population. This emergence follows more directly from a deterministic dynamical system based on differential reproductive success or natural selection. When restricted to an environment of memory-one agents interacting in iterated Prisoner's Dilemma games with a 1% noise level, the Pavlov agent is the only cooperative strategy and one of very few others that cannot be invaded by a similar strategy. Pavlov agents are trusting but no suckers. They will exploit weakness but repent if punished for cheating. Copyright 2000 Academic Press.
Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope.
Helmann, John D
2016-04-01
Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, σ(W) is most closely associated with membrane-active agents, σ(X) with cationic antimicrobial peptide resistance, and σ(V) with resistance to lysozyme. Here, I highlight the role of the σ(M) regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics. Copyright © 2016 Elsevier Ltd. All rights reserved.
Tučník, Petr; Bureš, Vladimír
2016-01-01
Multi-criteria decision-making (MCDM) can be formally implemented by various methods. This study compares suitability of four selected MCDM methods, namely WPM, TOPSIS, VIKOR, and PROMETHEE, for future applications in agent-based computational economic (ACE) models of larger scale (i.e., over 10 000 agents in one geographical region). These four MCDM methods were selected according to their appropriateness for computational processing in ACE applications. Tests of the selected methods were conducted on four hardware configurations. For each method, 100 tests were performed, which represented one testing iteration. With four testing iterations conducted on each hardware setting and separated testing of all configurations with the-server parameter de/activated, altogether, 12800 data points were collected and consequently analyzed. An illustrational decision-making scenario was used which allows the mutual comparison of all of the selected decision making methods. Our test results suggest that although all methods are convenient and can be used in practice, the VIKOR method accomplished the tests with the best results and thus can be recommended as the most suitable for simulations of large-scale agent-based models.
Koskela, Harri; Hakala, Ullastiina; Vanninen, Paula
2010-06-15
Decontamination solutions, which are usually composed of strong alkaline chemicals, are used for efficient detoxification of chemical warfare agents (CWAs). The analysis of CWA degradation products directly in decontamination solutions is challenging due to the nature of the matrix. Furthermore, occasionally an unforeseen degradation pathway can result in degradation products which could be eluded to in standard analyses. Here, we present the results of the application of proton band-selective (1)H-(31)P NMR spectroscopy, i.e., band-selective 1D (1)H-(31)P heteronuclear single quantum coherence (HSQC) and band-selective 2D (1)H-(31)P HSQC-total correlation spectroscopy (TOCSY), for ester side chain characterization of organophosphorus nerve agent degradation products in decontamination solutions. The viability of the approach is demonstrated with a test mixture of typical degradation products of nerve agents sarin, soman, and VX. The proton band-selective (1)H-(31)P NMR spectroscopy is also applied in characterization of unusual degradation products of VX in GDS 2000 solution.
Frikha-Gargouri, Olfa; Ben Abdallah, Dorra; Bhar, Ilhem; Tounsi, Slim
2017-01-01
This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates. Moreover, potential in vitro biocontrol traits were investigated including biofilm formation, motility, hemolytic activity, detection of lipopeptide biosynthetic genes ( sfp, ituC and bmyB ) and production of antibacterial compounds. The obtained results indicated high correlations of the efficiency of the biocontrol with the reduction of gall weight ( p = 0.000) and the antibacterial activity in vitro ( p = 0.000). Moreover, there was strong correlations of the efficiency of the biocontrol ( p = 0.004) and the reduction in gall weight ( p = 0.000) with the presence of the bmyB gene. This gene directs the synthesis of the lipopeptide bacillomycin belonging to the iturinic family of lipopeptides. These results were also confirmed by the two-way hierarchical cluster analysis and the correspondence analysis showing the relatedness of these four variables. According to the obtained results a new screening procedure of Bacillus biocontrol agents against crown gall disease could be advanced consisting on two step selection procedure. The first consists on selecting strains with high antibacterial activity in vitro or those harbouring the bmyB gene. Further selection has to be performed on tomato plants in vivo . Moreover, based on the results of the biocontrol assay, five potent strains exhibiting high biocontrol abilities were selected. They were identified as Bacillus subtilis or Bacillus amyloliquefaciens . These strains were found to produce either surfactin or surfactin and iturin lipopeptides. In conclusion, our study presented a new and effective method to evaluate the biocontrol ability of antagonistic Bacillus strains against crown gall disease that could increase the efficiency of screening method of biocontrol agents. Besides, the selected strains could be used as novel biocontrol agents against pathogenic Agrobacterium tumefaciens strains.
Frikha-Gargouri, Olfa; Ben Abdallah, Dorra; Bhar, Ilhem; Tounsi, Slim
2017-01-01
This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates. Moreover, potential in vitro biocontrol traits were investigated including biofilm formation, motility, hemolytic activity, detection of lipopeptide biosynthetic genes (sfp, ituC and bmyB) and production of antibacterial compounds. The obtained results indicated high correlations of the efficiency of the biocontrol with the reduction of gall weight (p = 0.000) and the antibacterial activity in vitro (p = 0.000). Moreover, there was strong correlations of the efficiency of the biocontrol (p = 0.004) and the reduction in gall weight (p = 0.000) with the presence of the bmyB gene. This gene directs the synthesis of the lipopeptide bacillomycin belonging to the iturinic family of lipopeptides. These results were also confirmed by the two-way hierarchical cluster analysis and the correspondence analysis showing the relatedness of these four variables. According to the obtained results a new screening procedure of Bacillus biocontrol agents against crown gall disease could be advanced consisting on two step selection procedure. The first consists on selecting strains with high antibacterial activity in vitro or those harbouring the bmyB gene. Further selection has to be performed on tomato plants in vivo. Moreover, based on the results of the biocontrol assay, five potent strains exhibiting high biocontrol abilities were selected. They were identified as Bacillus subtilis or Bacillus amyloliquefaciens. These strains were found to produce either surfactin or surfactin and iturin lipopeptides. In conclusion, our study presented a new and effective method to evaluate the biocontrol ability of antagonistic Bacillus strains against crown gall disease that could increase the efficiency of screening method of biocontrol agents. Besides, the selected strains could be used as novel biocontrol agents against pathogenic Agrobacterium tumefaciens strains. PMID:28855909
Code of Federal Regulations, 2011 CFR
2011-01-01
... discourage research or other legitimate activities. (c) Understanding that research and laboratory work on... consultation, as needed, on topics of relevance to the SAP. Sec. 8. Sharing of Select Agent Program Information...
NASA Astrophysics Data System (ADS)
Wu, Di; Kofke, David A.
2005-08-01
We consider ways to quantify the overlap of the parts of phase space important to two systems, labeled A and B. Of interest is how much of the A-important phase space lies in that important to B, and how much of B lies in A. Two measures are proposed. The first considers four total-energy distributions, formed from all combinations made by tabulating either the A-system or the B-system energy when sampling either the A or B system. Measures for A in B and B in A are given by two overlap integrals defined on pairs of these distributions. The second measure is based on information theory, and defines two relative entropies which are conveniently expressed in terms of the dissipated work for free-energy perturbation (FEP) calculations in the A →B and B →A directions, respectively. Phase-space overlap is an important consideration in the performance of free-energy calculations. To demonstrate this connection, we examine bias in FEP calculations applied to a system of independent particles in a harmonic potential. Systems are selected to represent a range of overlap situations, including extreme subset, subset, partial overlap, and nonoverlap. The magnitude and symmetry of the bias (A →B vs B →A) are shown to correlate well with the overlap, and consequently with the overlap measures. The relative entropies are used to scale the amount of sampling to obtain a universal bias curve. This result leads to develop a simple heuristic that can be applied to determine whether a work-based free-energy measurement is free of bias. The heuristic is based in part on the measured free energy, but we argue that it is fail-safe inasmuch as any bias in the measurement will not promote a false indication of accuracy.
Pearse, Aaron T.; Brandt, David; Krapu, Gary
2016-01-01
Numerous wind energy projects have been constructed in the central and southern Great Plains, USA, the main wintering area for midcontinental Sandhill Cranes (Grus canadensis). In an initial assessment of the potential risks of wind towers to cranes, we estimated spatial overlap, investigated potential avoidance behavior, and determined the habitat associations of cranes. We used data from cranes marked with platform transmitting terminals (PTTs) with and without global positioning system (GPS) capabilities. We estimated the wintering distributions of PTT-marked cranes prior to the construction of wind towers, which we compared with current tower locations. Based on this analysis, we found 7% spatial overlap between the distributions of cranes and towers. When we looked at individually marked cranes, we found that 52% would have occurred within 10 km of a tower at some point during winter. Using data from cranes marked after tower construction, we found a potential indication of avoidance behavior, whereby GPS-marked cranes generally used areas slightly more distant from existing wind towers than would be expected by chance. Results from a habitat selection model suggested that distances between crane locations and towers may have been driven more by habitat selection than by avoidance, as most wind towers were constructed in locations not often selected by wintering cranes. Our findings of modest regional overlap and that few towers have been placed in preferred crane habitat suggest that the current distribution of wind towers may be of low risk to the continued persistence of wintering midcontinental Sandhill Cranes in the central and southern Great Plains.
NASA Astrophysics Data System (ADS)
Lee, Daeho; Lee, Seohyung
2017-11-01
We propose an image stitching method that can remove ghost effects and realign the structure misalignments that occur in common image stitching methods. To reduce the artifacts caused by different parallaxes, an optimal seam pair is selected by comparing the cross correlations from multiple seams detected by variable cost weights. Along the optimal seam pair, a histogram of oriented gradients is calculated, and feature points for matching are detected. The homography is refined using the matching points, and the remaining misalignment is eliminated using the propagation of deformation vectors calculated from matching points. In multiband blending, the overlapping regions are determined from a distance between the matching points to remove overlapping artifacts. The experimental results show that the proposed method more robustly eliminates misalignments and overlapping artifacts than the existing method that uses single seam detection and gradient features.
Shared neural processes support semantic control and action understanding
Davey, James; Rueschemeyer, Shirley-Ann; Costigan, Alison; Murphy, Nik; Krieger-Redwood, Katya; Hallam, Glyn; Jefferies, Elizabeth
2015-01-01
Executive–semantic control and action understanding appear to recruit overlapping brain regions but existing evidence from neuroimaging meta-analyses and neuropsychology lacks spatial precision; we therefore manipulated difficulty and feature type (visual vs. action) in a single fMRI study. Harder judgements recruited an executive–semantic network encompassing medial and inferior frontal regions (including LIFG) and posterior temporal cortex (including pMTG). These regions partially overlapped with brain areas involved in action but not visual judgements. In LIFG, the peak responses to action and difficulty were spatially identical across participants, while these responses were overlapping yet spatially distinct in posterior temporal cortex. We propose that the co-activation of LIFG and pMTG allows the flexible retrieval of semantic information, appropriate to the current context; this might be necessary both for semantic control and understanding actions. Feature selection in difficult trials also recruited ventral occipital–temporal areas, not implicated in action understanding. PMID:25658631
2009-01-01
Background In soybean somatic embryo transformation, the standard selection agent currently used is hygromycin. It may be preferable to avoid use of antibiotic resistance genes in foods. The objective of these experiments was to develop a selection system for producing transgenic soybean somatic embryos without the use of antibiotics such as hygromycin. Results When tested against different alternate selection agents our studies show that 0.16 μg/mL glufosinate, 40 mg/L isopropylamine-glyphosate, 0.5 mg/mL (S-(2 aminoethyl)-L-cysteine) (AEC) and the acetolactate synthase (ALS) inhibitors Exceed® and Synchrony® both at 150 μg/mL inhibited soybean somatic embryo growth. Even at the concentration of 2 mg/mL, lysine+threonine (LT) were poor selection agents. The use of AEC may be preferable since it is a natural compound. Unlike the plant enzyme, dihydrodipicolinate synthase (DHPS) from E. coli is not feed-back inhibited by physiological concentrations of lysine. The dapA gene which codes for E. coli DHPS was expressed in soybean somatic embryos under the control of the CaMV 35S promoter. Following introduction of the construct into embryogenic tissue of soybean, transgenic events were recovered by incubating the tissue in liquid medium containing AEC at a concentration of 5 mM. Only transgenic soybeans were able to grow at this concentration of AEC; no escapes were observed. Conclusion Genetically engineered soybeans expressing a lysine insensitive DHPS gene can be selected with the non-antibiotic selection agent AEC. We also report here the inhibitory effects of glufosinate, (isopropylamine-glyphosate) (Roundup®), AEC and the ALS inhibitors Exceed® and Synchrony® against different tissues of soybean PMID:19922622
NASA Astrophysics Data System (ADS)
Li, David S.; Yoon, Soon Joon; Matula, Thomas J.; O'Donnell, Matthew; Pozzo, Lilo D.
2017-03-01
A new light and sound sensitive nanoemulsion contrast agent is presented. The agents feature a low boiling point liquid perfluorocarbon core and a broad light spectrum absorbing polypyrrole (PPy) polymer shell. The PPy coated nanoemulsions can reversibly convert from liquid to gas phase upon cavitation of the liquid perfluorocarbon core. Cavitation can be initiated using a sufficiently high intensity acoustic pulse or from heat generation due to light absorption from a laser pulse. The emulsions can be made between 150 and 350 nm in diameter and PPy has a broad optical absorption covering both the visible spectrum and extending into the near-infrared spectrum (peak absorption 1053 nm). The size, structure, and optical absorption properties of the PPy coated nanoemulsions were characterized and compared to PPy nanoparticles (no liquid core) using dynamic light scattering, ultraviolet-visible spectrophotometry, transmission electron microscopy, and small angle X-ray scattering. The cavitation threshold and signal intensity were measured as a function of both acoustic pressure and laser fluence. Overlapping simultaneous transmission of an acoustic and laser pulse can significantly reduce the activation energy of the contrast agents to levels lower than optical or acoustic activation alone. We also demonstrate that simultaneous light and sound cavitation of the agents can be used in a new sono-photoacoustic imaging method, which enables greater sensitivity than traditional photoacoustic imaging.
42 CFR 73.9 - Responsible Official.
Code of Federal Regulations, 2012 CFR
2012-10-01
... toxins must be immediately reported by telephone, facsimile, or e-mail: Bacillus anthracis, Botulinum... SELECT AGENTS AND TOXINS § 73.9 Responsible Official. (a) An individual or entity required to register...) Ensure that annual inspections are conducted for each laboratory where select agents or toxins are stored...
The Scarlet Letter of Alkylation: A Mini Review of Selective Alkylating Agents
Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J
2012-01-01
If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to “tame” the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it is referred to herein, constitutes an extremely nascent and dynamic field in oncology. The pharmacodynamic response to this selective strategy depends on a delicate kinetic balance between specificity and the rate and extent of binding. Three representative compounds are presented: RRx-001, 3-bromopyruvate, and TH-302. The main impetus for the development of these compounds has been the avoidance of the serious complications of traditional alkylating agents; therefore, it is the thesis of this review that they should not experience stigma by association. PMID:22937173
Identification of selection footprints on the X chromosome in pig.
Ma, Yunlong; Zhang, Haihan; Zhang, Qin; Ding, Xiangdong
2014-01-01
Identifying footprints of selection can provide a straightforward insight into the mechanism of artificial selection and further dig out the causal genes related to important traits. In this study, three between-population and two within-population approaches, the Cross Population Extend Haplotype Homozygosity Test (XPEHH), the Cross Population Composite Likelihood Ratio (XPCLR), the F-statistics (Fst), the Integrated Haplotype Score (iHS) and the Tajima's D, were implemented to detect the selection footprints on the X chromosome in three pig breeds using Illumina Porcine60K SNP chip. In the detection of selection footprints using between-population methods, 11, 11 and 7 potential selection regions with length of 15.62 Mb, 12.32 Mb and 9.38 Mb were identified in Landrace, Chinese Songliao and Yorkshire by XPEHH, respectively, and 16, 13 and 17 potential selection regions with length of 15.20 Mb, 13.00 Mb and 19.21 Mb by XPCLR, 4, 2 and 4 potential selection regions with length of 3.20 Mb, 1.60 Mb and 3.20 Mb by Fst. For within-population methods, 7, 10 and 9 potential selection regions with length of 8.12 Mb, 8.40 Mb and 9.99 Mb were identified in Landrace, Chinese Songliao and Yorkshire by iHS, and 4, 3 and 2 potential selection regions with length of 3.20 Mb, 2.40 Mb and 1.60 Mb by Tajima's D. Moreover, the selection regions from different methods were partly overlapped, especially the regions around 22∼25 Mb were detected under selection in Landrace and Yorkshire while no selection in Chinese Songliao by all three between-population methods. Only quite few overlap of selection regions identified by between-population and within-population methods were found. Bioinformatics analysis showed that the genes relevant with meat quality, reproduction and immune were found in potential selection regions. In addition, three out of five significant SNPs associated with hematological traits reported in our genome-wide association study were harbored in potential selection regions.
Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems.
Whitacre, James M; Bender, Axel
2010-06-15
A generic mechanism--networked buffering--is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems.
A further analysis of the role of heterogeneity in coevolutionary spatial games
NASA Astrophysics Data System (ADS)
Cardinot, Marcos; Griffith, Josephine; O'Riordan, Colm
2018-03-01
Heterogeneity has been studied as one of the most common explanations of the puzzle of cooperation in social dilemmas. A large number of papers have been published discussing the effects of increasing heterogeneity in structured populations of agents, where it has been established that heterogeneity may favour cooperative behaviour if it supports agents to locally coordinate their strategies. In this paper, assuming an existing model of a heterogeneous weighted network, we aim to further this analysis by exploring the relationship (if any) between heterogeneity and cooperation. We adopt a weighted network which is fully populated by agents playing both the Prisoner's Dilemma or the Optional Prisoner's Dilemma games with coevolutionary rules, i.e., not only the strategies but also the link weights evolve over time. Surprisingly, results show that the heterogeneity of link weights (states) on their own does not always promote cooperation; rather cooperation is actually favoured by the increase in the number of overlapping states and not by the heterogeneity itself. We believe that these results can guide further research towards a more accurate analysis of the role of heterogeneity in social dilemmas.
Overlapping communities from dense disjoint and high total degree clusters
NASA Astrophysics Data System (ADS)
Zhang, Hongli; Gao, Yang; Zhang, Yue
2018-04-01
Community plays an important role in the field of sociology, biology and especially in domains of computer science, where systems are often represented as networks. And community detection is of great importance in the domains. A community is a dense subgraph of the whole graph with more links between its members than between its members to the outside nodes, and nodes in the same community probably share common properties or play similar roles in the graph. Communities overlap when nodes in a graph belong to multiple communities. A vast variety of overlapping community detection methods have been proposed in the literature, and the local expansion method is one of the most successful techniques dealing with large networks. The paper presents a density-based seeding method, in which dense disjoint local clusters are searched and selected as seeds. The proposed method selects a seed by the total degree and density of local clusters utilizing merely local structures of the network. Furthermore, this paper proposes a novel community refining phase via minimizing the conductance of each community, through which the quality of identified communities is largely improved in linear time. Experimental results in synthetic networks show that the proposed seeding method outperforms other seeding methods in the state of the art and the proposed refining method largely enhances the quality of the identified communities. Experimental results in real graphs with ground-truth communities show that the proposed approach outperforms other state of the art overlapping community detection algorithms, in particular, it is more than two orders of magnitude faster than the existing global algorithms with higher quality, and it obtains much more accurate community structure than the current local algorithms without any priori information.
Recombining overlapping BACs into a single larger BAC.
Kotzamanis, George; Huxley, Clare
2004-01-06
BAC clones containing entire mammalian genes including all the transcribed region and long range controlling elements are very useful for functional analysis. Sequenced BACs are available for most of the human and mouse genomes and in many cases these contain intact genes. However, large genes often span more than one BAC, and single BACs covering the entire region of interest are not available. Here we describe a system for linking two or more overlapping BACs into a single clone by homologous recombination. The method was used to link a 61-kb insert carrying the final 5 exons of the human CFTR gene onto a 160-kb BAC carrying the first 22 exons. Two rounds of homologous recombination were carried out in the EL350 strain of bacteria which can be induced for the Red genes. In the first round, the inserts of the two overlapping BACs were subcloned into modified BAC vectors using homologous recombination. In the second round, the BAC to be added was linearised with the very rare-cutting enzyme I-PpoI and electroporated into recombination efficient EL350 bacteria carrying the other BAC. Recombined BACs were identified by antibiotic selection and PCR screening and 10% of clones contained the correctly recombined 220-kb BAC. The system can be used to link the inserts from any overlapping BAC or PAC clones. The original orientation of the inserts is not important and desired regions of the inserts can be selected. The size limit for the fragments recombined may be larger than the 61 kb used here and multiple BACs in a contig could be combined by alternating use of the two pBACLink vectors. This system should be of use to many investigators wishing to carry out functional analysis on large mammalian genes which are not available in single BAC clones.
Thompson, Scott M; Vella, Adrian; Service, F John; Grant, Clive S; Thompson, Geoffrey B; Andrews, James C
2015-07-01
To determine the impact of variant pancreatic arterial anatomy and overlap in regional perfusion on the interpretation of selective arterial calcium stimulation (SACST) with hepatic venous sampling for preoperative localization of occult insulinoma. An institutional review board-approved retrospective review was undertaken of 42 patients with surgically confirmed, occult insulinoma who underwent SACST from January 1996 to March 2014. Location of the insulinoma was predicted initially based on the biochemical results of SACST alone according to Doppman's criteria. Pancreatic arteriograms were reviewed blinded to the biochemical results and the regional perfusion of each artery assessed. The anatomic and perfusion data were combined with the biochemical results to make a second prediction and compared with the surgical findings. The biochemical results were positive in 1, 2, and 3 arterial distributions in 73.8%, 21.4%, and 4.8% of patients, respectively. The celiac trunk and superior mesenteric artery (SMA) anatomy were aberrant in 38.1% and 35.7% of patients, respectively. Clinically significant variations included dorsal pancreatic artery replaced to SMA (21.4%) and celiac stenosis (4.8%). Significant variation and overlap in regional pancreatic perfusion was observed, particularly for the SMA. Sensitivity for insulinoma localization was 54.8% (diagnostic arteriography), 73.8% (biochemical data), 88.1% (biochemical, anatomic, perfusion data), and 92.8% (arteriographic, biochemical, anatomic, perfusion data). Careful review of the pancreatic arterial anatomy and regional perfusion is critical for correct interpretation of the biochemical results of SACST and improves the sensitivity of localization for occult insulinoma, particularly in the presence of pancreatic arterial variants or overlap in regional perfusion. Copyright © 2015 Elsevier Inc. All rights reserved.
42 CFR 73.9 - Responsible Official.
Code of Federal Regulations, 2013 CFR
2013-10-01
... SELECT AGENTS AND TOXINS § 73.9 Responsible Official. (a) An individual or entity required to register... onsite incidents involving select agents and toxins in accordance with the entity's incident response... toxins are stored or used in order to determine compliance with the requirements of this part. The...
42 CFR 73.9 - Responsible Official.
Code of Federal Regulations, 2014 CFR
2014-10-01
... SELECT AGENTS AND TOXINS § 73.9 Responsible Official. (a) An individual or entity required to register... onsite incidents involving select agents and toxins in accordance with the entity's incident response... toxins are stored or used in order to determine compliance with the requirements of this part. The...
Irvine, Andrew J; Pinto-Sanchez, Maria Ines; Bercik, Premysl; Moayyedi, Paul; Ford, Alexander C
2017-04-01
Gastro-oesophageal reflux and dyspepsia are felt to be separate upper gastrointestinal (GI) conditions. We aimed to measure the degree of overlap between them, and assess whether endoscopic findings differed. Demographic, symptom, upper GI endoscopy and histology data were collected from consecutive adults in secondary care. Patients were categorised according to whether they reported gastro-oesophageal reflux alone, dyspepsia alone or both, and patient demographics and endoscopic findings were compared. Of 1167 patients, 97 (8.3%) had gastro-oesophageal reflux alone, 571 (48.9%) dyspepsia alone, and 499 (42.8%) overlap. Patients with overlap symptoms were more likely to smoke, compared with those with gastro-oesophageal reflux alone, or dyspepsia alone (p = .009), but there were no other differences. Patients with gastro-oesophageal reflux alone or overlap had a higher prevalence of erosive oesophagitis (18.6% and 15.4% respectively, p < .001), but this was still the commonest diagnosis among those with dyspepsia alone (7.2%). No significant differences were seen in prevalence of other endoscopic findings. Gastro-oesophageal reflux and dyspepsia symptoms commonly overlap. There were minimal differences in demographics or spectrum of underlying organic disease between various symptom groups, suggesting that restrictive classifications according to predominant symptom may not be clinically useful.
Workload-Based Automated Interface Mode Selection
2012-03-22
Process . . . . . . . . . . . . . . . . . . . . . 31 3.5.10 Agent Reward Function . . . . . . . . . . . . . . . . 31 3.5.11 Accelerated Learning... Strategies . . . . . . . . . . . . 31 4. Experimental Methodology . . . . . . . . . . . . . . . . . . . . . . . . 33 4.1 System Engineering Methodology...26 5. Agent state function. . . . . . . . . . . . . . . . . . . . . . . . . . . 28 6. Agent reward function
Pyropheophorbide 2-deoxyglucosamide: a new photosensitizer targeting glucose transporters.
Zhang, Min; Zhang, Zhihong; Blessington, Dana; Li, Hui; Busch, Theresa M; Madrak, Vanessa; Miles, Jeremy; Chance, Britton; Glickson, Jerry D; Zheng, Gang
2003-01-01
To prepare near-infrared fluorescence imaging and photodynamic therapy agents targeted at glucose transporters, pyropheophorbide 2-deoxyglucosamide (Pyro-2DG) was synthesized and evaluated in a 9L glioma rat model. Fluorescence imaging studies demonstrate that Pyro-2DG is selectively accumulated in the tumor. Upon its photoactivation, we demonstrate that this agent efficiently causes selective mitochondrial damage to the region of a tumor that was photoirradiated after administration of this agent, but does not affect tissues photoirradiated in the absence of the agent or tissues treated with the agent that are not photoirradiated. Preliminary confocal microscopy studies suggest that Pyro-2DG is delivered and trapped in tumor cells via the GLUT/hexokinase pathway and therefore is useful both as a tumor-targeted NIR fluorescence imaging probe and as a PDT agent for the destruction of cancer.
Agent-specific learning signals for self–other distinction during mentalising
Dolan, Raymond J.; Kurth-Nelson, Zeb
2018-01-01
Humans have a remarkable ability to simulate the minds of others. How the brain distinguishes between mental states attributed to self and mental states attributed to someone else is unknown. Here, we investigated how fundamental neural learning signals are selectively attributed to different agents. Specifically, we asked whether learning signals are encoded in agent-specific neural patterns or whether a self–other distinction depends on encoding agent identity separately from this learning signal. To examine this, we tasked subjects to learn continuously 2 models of the same environment, such that one was selectively attributed to self and the other was selectively attributed to another agent. Combining computational modelling with magnetoencephalography (MEG) enabled us to track neural representations of prediction errors (PEs) and beliefs attributed to self, and of simulated PEs and beliefs attributed to another agent. We found that the representational pattern of a PE reliably predicts the identity of the agent to whom the signal is attributed, consistent with a neural self–other distinction implemented via agent-specific learning signals. Strikingly, subjects exhibiting a weaker neural self–other distinction also had a reduced behavioural capacity for self–other distinction and displayed more marked subclinical psychopathological traits. The neural self–other distinction was also modulated by social context, evidenced in a significantly reduced decoding of agent identity in a nonsocial control task. Thus, we show that self–other distinction is realised through an encoding of agent identity intrinsic to fundamental learning signals. The observation that the fidelity of this encoding predicts psychopathological traits is of interest as a potential neurocomputational psychiatric biomarker. PMID:29689053
Agent-specific learning signals for self-other distinction during mentalising.
Ereira, Sam; Dolan, Raymond J; Kurth-Nelson, Zeb
2018-04-01
Humans have a remarkable ability to simulate the minds of others. How the brain distinguishes between mental states attributed to self and mental states attributed to someone else is unknown. Here, we investigated how fundamental neural learning signals are selectively attributed to different agents. Specifically, we asked whether learning signals are encoded in agent-specific neural patterns or whether a self-other distinction depends on encoding agent identity separately from this learning signal. To examine this, we tasked subjects to learn continuously 2 models of the same environment, such that one was selectively attributed to self and the other was selectively attributed to another agent. Combining computational modelling with magnetoencephalography (MEG) enabled us to track neural representations of prediction errors (PEs) and beliefs attributed to self, and of simulated PEs and beliefs attributed to another agent. We found that the representational pattern of a PE reliably predicts the identity of the agent to whom the signal is attributed, consistent with a neural self-other distinction implemented via agent-specific learning signals. Strikingly, subjects exhibiting a weaker neural self-other distinction also had a reduced behavioural capacity for self-other distinction and displayed more marked subclinical psychopathological traits. The neural self-other distinction was also modulated by social context, evidenced in a significantly reduced decoding of agent identity in a nonsocial control task. Thus, we show that self-other distinction is realised through an encoding of agent identity intrinsic to fundamental learning signals. The observation that the fidelity of this encoding predicts psychopathological traits is of interest as a potential neurocomputational psychiatric biomarker.
Common neural substrates for visual working memory and attention.
Mayer, Jutta S; Bittner, Robert A; Nikolić, Danko; Bledowski, Christoph; Goebel, Rainer; Linden, David E J
2007-06-01
Humans are severely limited in their ability to memorize visual information over short periods of time. Selective attention has been implicated as a limiting factor. Here we used functional magnetic resonance imaging to test the hypothesis that this limitation is due to common neural resources shared by visual working memory (WM) and selective attention. We combined visual search and delayed discrimination of complex objects and independently modulated the demands on selective attention and WM encoding. Participants were presented with a search array and performed easy or difficult visual search in order to encode one or three complex objects into visual WM. Overlapping activation for attention-demanding visual search and WM encoding was observed in distributed posterior and frontal regions. In the right prefrontal cortex and bilateral insula blood oxygen-level-dependent activation additively increased with increased WM load and attentional demand. Conversely, several visual, parietal and premotor areas showed overlapping activation for the two task components and were severely reduced in their WM load response under the condition with high attentional demand. Regions in the left prefrontal cortex were selectively responsive to WM load. Areas selectively responsive to high attentional demand were found within the right prefrontal and bilateral occipital cortex. These results indicate that encoding into visual WM and visual selective attention require to a high degree access to common neural resources. We propose that competition for resources shared by visual attention and WM encoding can limit processing capabilities in distributed posterior brain regions.
Nature versus design: synthetic biology or how to build a biological non-machine.
Porcar, M; Peretó, J
2016-04-18
The engineering ideal of synthetic biology presupposes that organisms are composed of standard, interchangeable parts with a predictive behaviour. In one word, organisms are literally recognized as machines. Yet living objects are the result of evolutionary processes without any purposiveness, not of a design by external agents. Biological components show massive overlapping and functional degeneracy, standard-free complexity, intrinsic variation and context dependent performances. However, although organisms are not full-fledged machines, synthetic biologists may still be eager for machine-like behaviours from artificially modified biosystems.
Shah, Manish A; Power, Derek G; Kindler, Hedy L; Holen, Kyle D; Kemeny, Margaret M; Ilson, David H; Tang, Laura; Capanu, Marinela; Wright, John J; Kelsen, David P
2011-12-01
The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in gastric adenocarcinoma. We performed a phase II trial of bortezomib in patients with advanced gastric adenocarcinoma. Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 every 21 days. The primary endpoint was objective response rate(RR); the null hypothesis was RR <1% versus the alternative ≥15%. One response in the first stage(15 patients) was required before proceeding with an additional 18 patients. If at least 2 or more responses out of 33 were observed, further study with bortezomib was warranted. Correlative studies evaluated pre-treatment tumor expression of NFkB, IkB, p53, p21, and cyclin D1. We enrolled 16 patients (15 evaluable for response) from four institutions. No patients demonstrated an objective response(95% CI, 0-22%); one patient achieved stable disease. Fourteen out of 16 patients experienced ≥ grade 2 toxicity. The most common toxicity was fatigue in six patients (n = 4 grade 2, n = 2 grade 3). Seven patients experienced neuropathy (n = 5 grade 1, and 1 each grade 2 and 3). Seven (60%) had high cytoplasmic staining for NFkB. Single agent bortezomib is inactive in metastatic gastric adenocarcinoma and should not be pursued. Future study of proteasome inhibition in gastric adenocarcinoma should be considered in combination with targeted inhibition of other non-overlapping oncogenic pathways as a potential rational approach.
Napolitano, Stefania; Martini, Giulia; Martinelli, Erika; Della Corte, Carminia Maria; Morgillo, Floriana; Belli, Valentina; Cardone, Claudia; Matrone, Nunzia; Ciardiello, Fortunato; Troiani, Teresa
2017-01-01
Purpose We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM151 with irinotecan (induction therapy) followed by MM151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy). Furthermore, the ability of MM151 to overcome acquired resistance to cetuximab has been also evaluated in cetuximab-refractory CRC models. Results MM151 shown stronger antitumor activity as compared to cetuximab. The maintenance treatment with MM151 plus MEKi resulted the most effective therapeutic modality. In fact, this combination caused an almost complete suppression of tumor growth in SW48, LIM 1215 and CACO2 xenografts model at 30 week. Moreover, in this treatment group, mice with no evidence of tumor were more than double as compared to single agent treated mice. Its superior activity has also been demonstrated, in cetuximab-refractory CRC models. Conclusions These results provide experimental evidence that more efficient and complete EGFR blockade may determine better antitumor activity and could contribute to prevent and/or overcome acquired resistance to EGFR inhibitors. PMID:29137301
A Cohort Study of Thiazolidinediones and Fractures in Older Adults with Diabetes
Solomon, Daniel H.; Cadarette, Suzanne M.; Choudhry, Niteesh K.; Canning, Claire; Levin, Raisa; Stürmer, Til
2009-01-01
Context: Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-γ and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents. Objective: The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes. Design: We conducted a cohort study. Participants: Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study. Main Outcome: We measured the incidence of fracture within the cohort. Results: Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98–1.77; P = 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94–1.55; P = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin. Conclusions: As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin. PMID:19470635
Workplace exposures and oesophageal cancer
Parent, M.; Siemiatycki, J.; Fritschi, L.
2000-01-01
OBJECTIVES—To describe the relation between oesophageal cancer and many occupational circumstances with data from a population based case-control study. METHODS—Cases were 99 histologically confirmed incident cases of cancer of the oesophagus, 63 of which were squamous cell carcinomas. Various control groups were available; for the present analysis a group was used that comprised 533 population controls and 533 patients with other types of cancer. Detailed job histories were elicited from all subjects and were translated by a team of chemists and hygienists for evidence of exposure to 294 occupational agents. Based on preliminary results and a review of literature, a set of 35 occupational agents and 19 occupations and industry titles were selected for this analysis. Logistic regression analyses were adjusted for age, birthplace, education, respondent (self or proxy), smoking, alcohol, and β-carotene intake. RESULTS—Sulphuric acid and carbon black showed the strongest evidence of an association with oesophageal cancer, particularly squamous cell carcinoma. Other substances showed excess risks, but the evidence was more equivocal—namely chrysotile asbestos, alumina, mineral spirits, toluene, synthetic adhesives, other paints and varnishes, iron compounds, and mild steel dust. There was considerable overlap in occupational exposure patterns and results for some of these substances may be mutually confounded. None of the occupations or industry titles showed a clear excess risk; the strongest hints were for warehouse workers, food services workers, and workers from the miscellaneous food industry. CONCLUSIONS—The data provide some support for an association between oesophageal cancer and a handful of occupational exposures, particularly sulphuric acid and carbon black. Many of the associations found have never been examined before and warrant further investigation. Keywords: oesophageal cancer; occupational exposures; occupations PMID:10769298
Liu, Lei; Ang, Keng Pee; Elliott, J A K; Kent, Matthew Peter; Lien, Sigbjørn; MacDonald, Danielle; Boulding, Elizabeth Grace
2017-03-01
Comparative genome scans can be used to identify chromosome regions, but not traits, that are putatively under selection. Identification of targeted traits may be more likely in recently domesticated populations under strong artificial selection for increased production. We used a North American Atlantic salmon 6K SNP dataset to locate genome regions of an aquaculture strain (Saint John River) that were highly diverged from that of its putative wild founder population (Tobique River). First, admixed individuals with partial European ancestry were detected using STRUCTURE and removed from the dataset. Outlier loci were then identified as those showing extreme differentiation between the aquaculture population and the founder population. All Arlequin methods identified an overlapping subset of 17 outlier loci, three of which were also identified by BayeScan. Many outlier loci were near candidate genes and some were near published quantitative trait loci (QTLs) for growth, appetite, maturity, or disease resistance. Parallel comparisons using a wild, nonfounder population (Stewiacke River) yielded only one overlapping outlier locus as well as a known maturity QTL. We conclude that genome scans comparing a recently domesticated strain with its wild founder population can facilitate identification of candidate genes for traits known to have been under strong artificial selection.
Genetic Architecture Promotes the Evolution and Maintenance of Cooperation
Frénoy, Antoine; Taddei, François; Misevic, Dusan
2013-01-01
When cooperation has a direct cost and an indirect benefit, a selfish behavior is more likely to be selected for than an altruistic one. Kin and group selection do provide evolutionary explanations for the stability of cooperation in nature, but we still lack the full understanding of the genomic mechanisms that can prevent cheater invasion. In our study we used Aevol, an agent-based, in silico genomic platform to evolve populations of digital organisms that compete, reproduce, and cooperate by secreting a public good for tens of thousands of generations. We found that cooperating individuals may share a phenotype, defined as the amount of public good produced, but have very different abilities to resist cheater invasion. To understand the underlying genetic differences between cooperator types, we performed bio-inspired genomics analyses of our digital organisms by recording and comparing the locations of metabolic and secretion genes, as well as the relevant promoters and terminators. Association between metabolic and secretion genes (promoter sharing, overlap via frame shift or sense-antisense encoding) was characteristic for populations with robust cooperation and was more likely to evolve when secretion was costly. In mutational analysis experiments, we demonstrated the potential evolutionary consequences of the genetic association by performing a large number of mutations and measuring their phenotypic and fitness effects. The non-cooperating mutants arising from the individuals with genetic association were more likely to have metabolic deleterious mutations that eventually lead to selection eliminating such mutants from the population due to the accompanying fitness decrease. Effectively, cooperation evolved to be protected and robust to mutations through entangled genetic architecture. Our results confirm the importance of second-order selection on evolutionary outcomes, uncover an important genetic mechanism for the evolution and maintenance of cooperation, and suggest promising methods for preventing gene loss in synthetically engineered organisms. PMID:24278000
Monochloramine inactivation of bacterial select agents.
Rose, Laura J; Rice, Eugene W; Hodges, Lisa; Peterson, Alicia; Arduino, Matthew J
2007-05-01
Seven species of bacterial select agents were tested for susceptibility to monochloramine. Under test conditions, the monochloramine routinely maintained in potable water would reduce six of the species by 2 orders of magnitude within 4.2 h. Bacillus anthracis spores would require up to 3.5 days for the same inactivation with monochloramine.
Application of Grazing-Inspired Guidance Laws to Autonomous Information Gathering
2014-09-01
paths by expressing it as the Selective Traveling Salesman Problem subject to dynamic constraints. Tisdale et al. [11] utilized a receding horizon ap...vehicle failures by halving the initial fuel level on selected agents. Note that simulations start with agents 50s travel time away from where they
Maeng, Daniel D; Scanlon, Dennis P; Chernew, Michael E; Gronniger, Tim; Wodchis, Walter P; McLaughlin, Catherine G
2010-01-01
Objective To examine the extent to which health plan quality measures capture physician practice patterns rather than plan characteristics. Data Source We gathered and merged secondary data from the following four sources: a private firm that collected information on individual physicians and their health plan affiliations, The National Committee for Quality Assurance, InterStudy, and the Dartmouth Atlas. Study Design We constructed two measures of physician network overlap for all health plans in our sample and linked them to selected measures of plan performance. Two linear regression models were estimated to assess the relationship between the measures of physician network overlap and the plan performance measures. Principal Findings The results indicate that in the presence of a higher degree of provider network overlap, plan performance measures tend to converge to a lower level of quality. Conclusions Standard health plan performance measures reflect physician practice patterns rather than plans' effort to improve quality. This implies that more provider-oriented measurement, such as would be possible with accountable care organizations or medical homes, may facilitate patient decision making and provide further incentives to improve performance. PMID:20403064
2016-01-01
Multi-criteria decision-making (MCDM) can be formally implemented by various methods. This study compares suitability of four selected MCDM methods, namely WPM, TOPSIS, VIKOR, and PROMETHEE, for future applications in agent-based computational economic (ACE) models of larger scale (i.e., over 10 000 agents in one geographical region). These four MCDM methods were selected according to their appropriateness for computational processing in ACE applications. Tests of the selected methods were conducted on four hardware configurations. For each method, 100 tests were performed, which represented one testing iteration. With four testing iterations conducted on each hardware setting and separated testing of all configurations with the–server parameter de/activated, altogether, 12800 data points were collected and consequently analyzed. An illustrational decision-making scenario was used which allows the mutual comparison of all of the selected decision making methods. Our test results suggest that although all methods are convenient and can be used in practice, the VIKOR method accomplished the tests with the best results and thus can be recommended as the most suitable for simulations of large-scale agent-based models. PMID:27806061
Evolving effective behaviours to interact with tag-based populations
NASA Astrophysics Data System (ADS)
Yucel, Osman; Crawford, Chad; Sen, Sandip
2015-07-01
Tags and other characteristics, externally perceptible features that are consistent among groups of animals or humans, can be used by others to determine appropriate response strategies in societies. This usage of tags can be extended to artificial environments, where agents can significantly reduce cognitive effort spent on appropriate strategy choice and behaviour selection by reusing strategies for interacting with new partners based on their tags. Strategy selection mechanisms developed based on this idea have successfully evolved stable cooperation in games such as the Prisoner's Dilemma game but relies upon payoff sharing and matching methods that limit the applicability of the tag framework. Our goal is to develop a general classification and behaviour selection approach based on the tag framework. We propose and evaluate alternative tag matching and adaptation schemes for a new, incoming individual to select appropriate behaviour against any population member of an existing, stable society. Our proposed approach allows agents to evolve both the optimal tag for the environment as well as appropriate strategies for existing agent groups. We show that these mechanisms will allow for robust selection of optimal strategies by agents entering a stable society and analyse the various environments where this approach is effective.
What Influences Agents to Pursue a Career in Extension?
ERIC Educational Resources Information Center
Arnold, Shannon; Place, Nick
2010-01-01
The qualitative study reported here explored why agricultural agents pursue an Extension career. A purposive sample was used to select twelve Florida agricultural agents. Interviews investigated positive and negative influences that affected agents' employment decisions. Grounded theory was used as the primary data analysis method (Strauss &…
An affine projection algorithm using grouping selection of input vectors
NASA Astrophysics Data System (ADS)
Shin, JaeWook; Kong, NamWoong; Park, PooGyeon
2011-10-01
This paper present an affine projection algorithm (APA) using grouping selection of input vectors. To improve the performance of conventional APA, the proposed algorithm adjusts the number of the input vectors using two procedures: grouping procedure and selection procedure. In grouping procedure, the some input vectors that have overlapping information for update is grouped using normalized inner product. Then, few input vectors that have enough information for for coefficient update is selected using steady-state mean square error (MSE) in selection procedure. Finally, the filter coefficients update using selected input vectors. The experimental results show that the proposed algorithm has small steady-state estimation errors comparing with the existing algorithms.
Daryaei, Iman; Pagel, Mark D
2015-01-01
Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.
Comstedt, Pär; Asokliene, Loreta; Eliasson, Ingvar; Olsen, Björn; Wallensten, Anders; Bunikis, Jonas; Bergström, Sven
2009-01-01
Borrelia garinii, a causative agent of Lyme borreliosis in Europe and Asia, is naturally maintained in marine and terrestrial enzootic cycles, which primarily involve birds, including seabirds and migratory passerines. These bird groups associate with, correspondingly, Ixodes uriae and Ixodes ricinus ticks, of which the latter species may bite and transmit the infection to humans. Studies of the overlap between these two natural cycles of B. garinii have been limited, in part due to the absence of representative collections of this spirochete's samples, as well as of the lack of reliable measure of the genetic heterogeneity of its strains. As a prerequisite for understanding the epidemiological correlates of the complex maintenance of B. garinii, the present study sought to assess the diversity and phylogenetic relationships of this species' strains from its natural hosts and patients with Lyme borreliosis from subarctic Eurasia. We used sequence typing of the partial rrs-rrl intergenic spacer (IGS) of archived and prospective samples of B. garinii from I. uriae ticks collected predominantly on Commander Islands in North Pacific, as well as on the islands in northern Sweden and arctic Norway. We also typed B. garinii samples from patients with Lyme borreliosis and I. ricinus ticks infesting migratory birds in southern Sweden, or found questing in selected sites on the islands in the Baltic Sea and Lithuania. Fifty-two (68%) of 77 B. garinii samples representing wide geographical range and associated with I. ricinus and infection of humans contributed 12 (60%) of total 20 identified IGS variants. In contrast, the remaining 25 (32%) samples recovered from I. uriae ticks from a few islands accounted for as many as 10 (50%) IGS types, suggesting greater local diversity of B. garinii maintained by seabirds and their ticks. Two IGS variants of the spirochete in common for both tick species were found in I. ricinus larvae from migratory birds, an indication that B. garinii strains are exchanged between different ecological niches. Notably, B. garinii variants associated with I. uriae ticks were found in each of the six clusters, representing two phylogenetic lineages of this species identified among the studied samples. Our findings suggest that B. garinii in subarctic Eurasia comprises two partially overlapping populations with different levels of genetic heterogeneity, presumably, due to distinctive selective pressures on the spirochete in its marine and terrestrial enzootic cycles. PMID:19513109
Rapid Selection of Mesenchymal Stem and Progenitor Cells in Primary Prostate Stromal Cultures
Brennen, W. Nathaniel; Kisteman, L. Nelleke; Isaacs, John T.
2016-01-01
BACKGROUND Carcinoma-associated fibroblasts (CAFs) are a dominant component of the tumor microenvironment with pro-tumorigenic properties. Despite this knowledge, their physiologic origins remain poorly understood. Mesenchymal stem cells (MSCs) can be recruited from the bone marrow to areas of tissue damage and inflammation, including prostate cancer. MSCs can generate and have many overlapping properties with CAFs in preclinical models. METHODS Multiparameter flow cytometry and multipotent differentiation assays used to define MSCs in primary prostate stromal cultures derived from young (>25 yrs) organ donors and prostate cancer patients compared with bone marrow-derived stromal cultures. Population doubling times, population doublings, cell size, and differentiation potential determined under multiple culture conditions, including normoxia, hypoxia, and a variety of media. TGF-β measured by ELISA. RESULTS MSCs and stromal progenitors are not only present in normal and malignant prostate tissue, but are quickly selected for in primary stromal cultures derived from these tissues; becoming the dominant population within just a few passages. Growth potential inversely associated with TGF-β concentrations. All conditions generated populations with an average cell diameter >15 μm. All cultures tested had the ability to undergo osteogenic and chondrogenic differentiation, but unlike bone marrow-derived MSCs, primary stromal cultures derived from normal prostate tissue lack adipogenic differentiation potential. In contrast, a subset of stromal cultures derived from prostate cancer patients retain the ability to differentiate into adipocytes; a property that is significantly suppressed under hypoxic conditions in both bone marrow- and prostate-derived MSCs. CONCLUSIONS Primary prostate stromal cultures are highly enriched in cells with an MSC or stromal progenitor phenotype. The use of primary cultures such as these to study CAFs raises interesting implications when considering their overlapping properties. The lack of adipogenesis in stromal cultures derived from normal prostates suggests they have a lineage-restricted progenitor phenotype. The retention of adipogenic differentiation in cultures from a subset of prostate cancer patients suggests the active recruitment of less committed progenitors or MSCs from the bone marrow as a function of disease progression. This recruitment can potentially be exploited for prognostic purposes or a cell-based platform for the systemic delivery of cytotoxic agents to sites of prostate cancer. PMID:26732992
Rapid selection of mesenchymal stem and progenitor cells in primary prostate stromal cultures.
Brennen, W Nathaniel; Kisteman, L Nelleke; Isaacs, John T
2016-05-01
Carcinoma-associated fibroblasts (CAFs) are a dominant component of the tumor microenvironment with pro-tumorigenic properties. Despite this knowledge, their physiologic origins remain poorly understood. Mesenchymal stem cells (MSCs) can be recruited from the bone marrow to areas of tissue damage and inflammation, including prostate cancer. MSCs can generate and have many overlapping properties with CAFs in preclinical models. Multiparameter flow cytometry and multipotent differentiation assays used to define MSCs in primary prostate stromal cultures derived from young (<25 yrs) organ donors and prostate cancer patients compared with bone marrow-derived stromal cultures. Population doubling times, population doublings, cell size, and differentiation potential determined under multiple culture conditions, including normoxia, hypoxia, and a variety of media. TGF-β measured by ELISA. MSCs and stromal progenitors are not only present in normal and malignant prostate tissue, but are quickly selected for in primary stromal cultures derived from these tissues; becoming the dominant population within just a few passages. Growth potential inversely associated with TGF-β concentrations. All conditions generated populations with an average cell diameter >15 µm. All cultures tested had the ability to undergo osteogenic and chondrogenic differentiation, but unlike bone marrow-derived MSCs, primary stromal cultures derived from normal prostate tissue lack adipogenic differentiation potential. In contrast, a subset of stromal cultures derived from prostate cancer patients retain the ability to differentiate into adipocytes; a property that is significantly suppressed under hypoxic conditions in both bone marrow- and prostate-derived MSCs. Primary prostate stromal cultures are highly enriched in cells with an MSC or stromal progenitor phenotype. The use of primary cultures such as these to study CAFs raises interesting implications when considering their overlapping properties. The lack of adipogenesis in stromal cultures derived from normal prostates suggests they have a lineage-restricted progenitor phenotype. The retention of adipogenic differentiation in cultures from a subset of prostate cancer patients suggests the active recruitment of less committed progenitors or MSCs from the bone marrow as a function of disease progression. This recruitment can potentially be exploited for prognostic purposes or a cell-based platform for the systemic delivery of cytotoxic agents to sites of prostate cancer. © 2016 Wiley Periodicals, Inc.
Communities and classes in symmetric fractals
NASA Astrophysics Data System (ADS)
Krawczyk, Małgorzata J.
2015-07-01
Two aspects of fractal networks are considered: the community structure and the class structure, where classes of nodes appear as a consequence of a local symmetry of nodes. The analyzed systems are the networks constructed for two selected symmetric fractals: the Sierpinski triangle and the Koch curve. Communities are searched for by means of a set of differential equations. Overlapping nodes which belong to two different communities are identified by adding some noise to the initial connectivity matrix. Then, a node can be characterized by a spectrum of probabilities of belonging to different communities. Our main goal is that the overlapping nodes with the same spectra belong to the same class.
Mothia, Begum; Appleyard, Antony N; Wadman, Sjoerd; Tabor, Alethea B
2011-08-19
A methodology for the solid-phase synthesis of the overlapping lanthionine bridges found in many lantibiotics has been developed. A novel Teoc/TMSE-protected lanthionine derivative has been synthesized, and this lanthionine, and an Aloc/allyl-protected lanthionine derivative, have been incorporated into a linear peptide using solid-phase peptide synthesis. Selective deprotection of the silyl protecting groups, followed by sequential cyclization, deprotection of the allyl protecting groups, and further cyclization, enabled the regioselective formation of an analogue of rings D and E of nisin. © 2011 American Chemical Society
2011-01-01
3,5-Dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester is a promising antitubulin lead agent that targets the colchicine site of tubulin. C-2 analogues were synthesized and tested for microtubule depolymerizing and antiproliferative activity. Molecular modeling studies using both GOLD docking and HINT (Hydropathic INTeraction) scoring revealed two distinct binding modes that explain the structure–activity relationships and are in accord with the structural basis of colchicine binding to tubulin. The binding mode of higher activity compounds is buried deeper in the site and overlaps well with rings A and C of colchicine, while the lower activity binding mode shows fewer critical contacts with tubulin. The model distinguishes highly active compounds from those with weaker activities and provides novel insights into the colchicine site and compound design. PMID:22611477
Da, Chenxiao; Telang, Nakul; Barelli, Peter; Jia, Xin; Gupton, John T; Mooberry, Susan L; Kellogg, Glen E
2012-01-12
3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester is a promising antitubulin lead agent that targets the colchicine site of tubulin. C-2 analogs were synthesized and tested for microtubule depolymerizing and antiproliferative activity. Molecular modeling studies using both GOLD docking and HINT (Hydropathic INTeraction) scoring revealed two distinct binding modes that explain the structural-activity relationships and are in accord with the structural basis of colchicine binding to tubulin. The binding mode of higher activity compounds is buried deeper in the site and overlaps well with rings A and C of colchicine, while the lower activity binding mode shows fewer critical contacts with tubulin. The model distinguishes highly active compounds from those with weaker activities and provides novel insights into the colchicine site and compound design.
Abatacept as a successful therapy for myositis—a case-based review.
Kerola, Anne M; Kauppi, Markku J
2015-03-01
Only limited evidence exists on the therapeutic potential of biologic agents in the treatment of myositis. We present a brief review of the literature on off-label experiences of biologic agents in myositis, with a special interest in abatacept. Rituximab has been indicated to be beneficial and well tolerated in one large randomized controlled trial and many smaller studies. Initial data on tumour necrosis factor (TNF) inhibitors are conflicting. There are only a few case reports and mechanistic studies on the treatment of myositis with other biologics, including alemtuzumab, anakinra, tocilizumab and abatacept. We report a patient with severe myositis overlap syndrome, manifesting also as rheumatoid arthritis, peripheral vasculitis and interstitial lung disease. Her myositis was refractory to many conventional and biologic therapies but was well controlled with abatacept. This suggests that abatacept might be a beneficial option for the treatment of refractory myositis and that clinical trials are needed to further investigate its efficacy.
NASA Astrophysics Data System (ADS)
Sjahril, R.; Jamaluddin, I.; Nadir, M.; Asman; Dungga, N. E.
2018-05-01
Genetic transformation mediated by Agrobacterium tumefaciens requires an efficient selection method for successful progress of transformation. This study aims to determine the concentration and kind of antibiotics and selection agents used during transformation to formulate standard protocol of chrysanthemum in the process of propagating disease resistant Chrysanthemum mediated by Agrobacterium tumefaciens EHA105 (pEKB-WD). The experiments were performed by planting chrysanthemum explants leaf cutting (5 mm diameter on NAA medium 2 mg L-1 BAP 2 mg L-1) with addition of Kanamycin: 25, 50, 100, 150 and 200 (mg L-1); Hygromycin: 5, 10, 25, 50 and 75 (mg L-1); Paromomycin: 10, 25, 50, 75 and 100 (mg L-1). Experiment was arranged in a Completely Randomized Design (CRD). Each treatment was repeated five times thus 75 bottles of culture were used; each bottle consists of 5 pieces of leaf cuttings, resulted in total of 375 pieces. The results showed that selection agent had a critical value for Hygromycin 25 mg L-1 and Kanamycin 100 mg L-1 which can make explant experienced necrosis better than Paromomycin. Paromomycin at 100 mg L-1 was only able to kill explant’s periphery. Remained callus stayed fresh more than 50% so that when used as the selection agent could produce more escape cell. The optimum transformation with concentration of 10% Agrobacterium (vol/vol) with 30 minutes co-cultivation can produce more efficient transformed callus. Considering the high price of Hygromycin, it was best to use Kanamycin as selective agents.
Prickly coexistence or blunt competition? Opuntia refugia in an invaded rodent community.
Gregory, Stephen David; Macdonald, David W
2009-02-01
Endemic Nesoryzomys swarthi and invasive Rattus rattus exist in unlikely sympatry in Galápagos as female N. swarthi suffer from competition with R. rattus. This study evaluates the role of feeding habits in facilitating their co-occurrence. Spool-and-line tracking of 85 N. swarthi and 33 R. rattus was used to quantify their selected diets, foods of which were used in captive trials of 46 N. swarthi and 34 R. rattus to quantify their preferred diets. Selected diets were compared between species and seasons using niche measures, and contrasted to preferred diets to qualify inferences about competition. Diet overlap was highest in the wet season when food-particularly fruit-abundance was highest and R. rattus diet breadth was broadest. Preferred and selected diets were marginally correlated for R. rattus but uncorrelated for N. swarthi, suggesting that R. rattus interfere with N. swarthi foraging. Diet overlap was highest between female N. swarthi and R. rattus, perhaps due to female breeding requirements. Male N. swarthi avoided R. rattus-preferred foods, possibly to avoid aggressive encounters with R. rattus. During the dry season, when foods declined and the R. rattus population crashed, diet overlap was lowest as R. rattus diet narrowed in the absence of fruits. Female, and particularly male, N. swarthi diet broadened, with emphasis on acquiring Opuntia foods but N. swarthi-preferred and selected diets were uncorrelated, suggesting that their foraging was inhibited by R. rattus. In conclusion, the narrower diet breadth of R. rattus in contrast to N. swarthi suggests that this species may be less adapted to food acquisition at this site, particularly when fruits are absent. The year-round presence of R. rattus, however, appears to inhibit N. swarthi foraging for its preferred diet, and they instead specialise on Opuntia foods, which were uneaten by R. rattus and may provide N. swarthi with a localised competition refuge from encounters with R. rattus.
Detecting overlapping instances in microscopy images using extremal region trees.
Arteta, Carlos; Lempitsky, Victor; Noble, J Alison; Zisserman, Andrew
2016-01-01
In many microscopy applications the images may contain both regions of low and high cell densities corresponding to different tissues or colonies at different stages of growth. This poses a challenge to most previously developed automated cell detection and counting methods, which are designed to handle either the low-density scenario (through cell detection) or the high-density scenario (through density estimation or texture analysis). The objective of this work is to detect all the instances of an object of interest in microscopy images. The instances may be partially overlapping and clustered. To this end we introduce a tree-structured discrete graphical model that is used to select and label a set of non-overlapping regions in the image by a global optimization of a classification score. Each region is labeled with the number of instances it contains - for example regions can be selected that contain two or three object instances, by defining separate classes for tuples of objects in the detection process. We show that this formulation can be learned within the structured output SVM framework and that the inference in such a model can be accomplished using dynamic programming on a tree structured region graph. Furthermore, the learning only requires weak annotations - a dot on each instance. The candidate regions for the selection are obtained as extremal region of a surface computed from the microscopy image, and we show that the performance of the model can be improved by considering a proxy problem for learning the surface that allows better selection of the extremal regions. Furthermore, we consider a number of variations for the loss function used in the structured output learning. The model is applied and evaluated over six quite disparate data sets of images covering: fluorescence microscopy, weak-fluorescence molecular images, phase contrast microscopy and histopathology images, and is shown to exceed the state of the art in performance. Copyright © 2015 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wunschel, David S.; Valenzuela, Blandina R.; Kaiser, Brooke L. Deatherage
Toxins from biological sources are recognized as potential chemical weapon threats, with saxitoxin and ricin listed by the chemical weapons convention (CWC) as schedule one agents (CWC reference). These two toxins represent a metabolite (saxitoxin) and protein (ricin) from algal and plant sources, respectively. An array of toxins have been listed as "select agents" by the Health and Human Services (HHS) select agent program, including ricin, abrin, saxitoxin, tetrodotoxin, specific paralytic alpha conotoxin peptides, T-2 toxin, diacetoxyscirpenols, botulinum toxins, and staphylococcal enterotoxins [1]. The quantities of these toxins dictate whether they are considered select agents with federal oversight of theirmore » storage and use. While this list captures some of the naturally occurring toxins that may pose a threat to the public, there are a number of other naturally occurring toxins that may also be a concern.« less
Social dilemma structure hidden behind traffic flow with route selection
NASA Astrophysics Data System (ADS)
Tanimoto, Jun; Nakamura, Kousuke
2016-10-01
Several traffic flows contain social dilemma structures. Herein, we explored a route-selection problem using a cellular automaton simulation dovetailed with evolutionary game theory. In our model, two classes of driver-agents coexist: D agents (defective strategy), which refer to traffic information for route selection to move fast, and C agents (cooperative strategy), which are insensitive to information and less inclined to move fast. Although no evidence suggests that the social dilemma structure in low density causes vehicles to move freely and that in high density causes traffic jams, we found a structure that corresponds to an n-person (multiplayer) Chicken (n-Chicken) game if the provided traffic information is inappropriate. If appropriate traffic information is given to the agents, the n-Chicken game can be solved. The information delivered to vehicles is crucial for easing the social dilemma due to urban traffic congestion when developing technologies to support the intelligent transportation system (ITS).
Online Database Coverage of Pharmaceutical Journals.
ERIC Educational Resources Information Center
Snow, Bonnie
1984-01-01
Describes compilation of data concerning pharmaceutical journal coverage in online databases which aid information providers in collection development and database selection. Methodology, results (a core collection, overlap, timeliness, geographic scope), and implications are discussed. Eight references and a list of 337 journals indexed online in…
Production of sintered porous metal fluoride pellets
Anderson, L.W.; Stephenson, M.J.
1973-12-25
Porous pellets characterized by a moderately reactive crust and a softer core of higher reactivity are produced by forming agglomerates containing a metal fluoride powder and a selected amount ofwater. The metal fluoride is selected to be sinterable and essentially non-reactive with gaseous fluorinating agents. The agglomerates are contacted with a gaseous fluorinating agent under controlled conditions whereby the heat generated by localized reaction of the agent and water is limited to values effccting bonding by localized sintering. Porous pellets composed of cryolite (Na/sub 3/AlF/sub 6/) can be used to selectively remove trace quantities of niobium pentafluoride from a feed gas consisting predominantly of uranium hexafluoride. (Official Gazette)
Further development of high temperature-resistant graphite fiber coupling agents
NASA Technical Reports Server (NTRS)
Griffin, R. N.
1976-01-01
Potential coupling agents for graphite fibers were screened by their effect on the weight losses of Thornel 300, HMS, and HTS fibers at 588K for 200 and 400 hours. Unidirectional laminates were made from HMS and HTS fibers, untreated, and treated with each of the seven coupling agents. The matrix of all laminates was PMR polyimide (PMR-PR). On the basis of the best overall retention of elevated temperature interlaminar shear strength after 200 hours at 588K, composite weight after 200 hours at 588K, and fiber weight after 400 hours at 588K, ventromer T-1 applied from aqueous solution and pyrolyzed PPQ were selected for further evaluation as coupling agents for HTS fiber while ventromer T-2 and pyrolyzed PPQ were selected as coupling agents for HMS fiber. It was shown that pyrolyzed PPQ as a coupling agent improves the oxidative stability of HTS/PMR-PI composites.
Phenotypic and genetic overlap between autistic traits at the extremes of the general population.
Ronald, Angelica; Happé, Francesca; Price, Thomas S; Baron-Cohen, Simon; Plomin, Robert
2006-10-01
To investigate children selected from a community sample for showing extreme autistic-like traits and to assess the degree to which these individual traits--social impairments (SIs), communication impairments (CIs), and restricted repetitive behaviors and interests (RRBIs)--are caused by genes and environments, whether all of them are caused by the same genes and environments, and how often they occur together (as required by an autism diagnosis). The most extreme-scoring 5% were selected from 3,419 8-year-old pairs in the Twins Early Development Study assessed on the Childhood Asperger Syndrome Test. Phenotypic associations between extreme traits were compared with associations among the full-scale scores. Genetic associations between extreme traits were quantified using bivariate DeFries-Fulker extremes analysis. Phenotypic relationships between extreme SIs, CIs, and RRBIs were modest. There was a degree of genetic overlap between them, but also substantial genetic specificity. This first twin study assessing the links between extreme individual autistic-like traits (SIs, CIs, and RRBIs) found that all are highly heritable but show modest phenotypic and genetic overlap. This finding concurs with that of an earlier study from the same cohort that showed that a total autistic symptoms score at the extreme showed high heritability and that SIs, CIs, and RRBIs show weak links in the general population. This new finding has relevance for both clinical models and future molecular genetic studies.
Engell, Andrew D; McCarthy, Gregory
2013-07-01
Neuroimaging research has identified several category-selective regions in visual cortex that respond most strongly when viewing an exemplar image from a preferred category, such as faces. Recent studies, however, have suggested a more complex pattern of activation that has been heretofore unrecognized, e.g., the presence of additional patches of activation to faces beyond the well-studied fusiform face area, and the activation of ostensible face selective regions by animate motion of non-biological forms. Here, we characterize the spatial pattern of brain activity evoked by viewing faces or biological motion in large fMRI samples (N>120). We create probabilistic atlases for both face and biological motion activation, and directly compare their spatial patterns of activation. Our findings support the suggestion that the fusiform face area is composed of at least two separable foci of activation. The face-evoked response in the fusiform and nearby ventral temporal cortex has good reliability across runs; however, we found surprisingly high variability in lateral brain regions by faces, and for all brain regions by biological motion, which had an overall much lower effect size. We found that faces and biological motion evoke substantially overlapping activation distributions in both ventral and lateral occipitotemporal cortices. The peaks of activation for these different categories within these overlapping regions were close but distinct. Copyright © 2013 Elsevier Inc. All rights reserved.
[Obesity: a review of currently used antiobesity drugs and new compounds in clinical development].
Zieba, Remigiusz
2007-10-19
This review summarizes data on currently used antiobesity drugs and new compounds under clinical development. Three antiobesity drugs are currently accepted for long-term use. Sibutramine is a noradrenaline and serotonin reuptake inhibitor which reduces body weight by about 4-5 kg but increases heart rate and arterial blood pressure. Orlistat is a gastrointestinal lipase inhibitor which results in mean weight loss by about 3 kg and reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance; however, adverse gastrointestinal effects have been observed. Rimonabant is an endocannabinoid CB1 receptor antagonist which induces a 4-5 kg mean weight loss and improves glycemic and lipid profiles, but it induces anxiety and depressive disorders. Unfortunately, there are no data on the chronic administration of these drugs. Other drugs can induce weight loss, e.g. some antidepressants, antiseizure agents, and antidiabetic drugs. The moderate efficacy of currently used antiobesity drugs has led to an intense effort to identify new, safe antiobesity drugs with better therapeutic profiles. The new antiobesity drugs under clinical development include: 1) agents that affect neurotransmitters in the central nervous system, including noradrenaline and dopamine reuptake inhibitors (bupropion, radafaxine), selective 5HT2C receptor agonists (lorcaserin), and selective 5HT6 receptor antagonists, 2) agents that modulate the activity of neuropeptides influencing food intake, including leptin analogues, human ciliary neurotrophic factor (Axokine), neuropeptide Y antagonists, and melanine-concentrating hormone antagonists, 3) agents that affect the peripheral satiety signals and brain-gut axis, e.g. selective cholecystokinin receptor A agonists, PYY3-36, agents decreasing ghrelin activity, 4) thermogenic agents, e.g. selective beta3 receptor agonists and selective thyroid hormone receptor beta agonists, and 5) others, e.g. human growth hormone fragment (AOD9604) and gastrointestinal lipase inhibitor (cetilistat).
Detection of abrin holotoxin using novel monoclonal antibodies
USDA-ARS?s Scientific Manuscript database
Abrin, a member of ribosome-inactivating protein family, is produced by the Abrus precatorius plant. It has been determined to have the potential to pose a severe threat to both human and animal health and is listed as a select agent by the U.S. Federal Select Agent Program. However, an immunoassay ...
42 CFR 73.5 - Exemptions for HHS select agents and toxins.
Code of Federal Regulations, 2010 CFR
2010-10-01
... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... minor (Alastrim), or Yersinia pestis. This report must be followed by submission of APHIS/CDC Form 4.../CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent...
42 CFR 73.5 - Exemptions for HHS select agents and toxins.
Code of Federal Regulations, 2011 CFR
2011-10-01
... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... minor (Alastrim), or Yersinia pestis. This report must be followed by submission of APHIS/CDC Form 4.../CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent...
42 CFR 73.5 - Exemptions for HHS select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-10-01
... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... minor (Alastrim), or Yersinia pestis. This report must be followed by submission of APHIS/CDC Form 4.../CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent...
9 CFR 121.5 - Exemptions for VS select agents and toxins.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... toxin that is contained in a specimen presented for proficiency testing will be exempt from the...
9 CFR 121.5 - Exemptions for VS select agents and toxins.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... toxin that is contained in a specimen presented for proficiency testing will be exempt from the...
Lee, Jin Hwa; Rhee, Chin Kook; Kim, Kyungjoo; Kim, Jee-Ae; Kim, Sang Hyun; Yoo, Kwang Ha; Kim, Woo Jin; Park, Yong Bum; Park, Hye Yun; Jung, Ki-Suck
2017-01-01
The purpose of this study was to identify subtypes in patients with mild-to-moderate airflow limitation and to appreciate their clinical and socioeconomic implications. Subjects who were aged ≥20 years and had forced expiratory volume in 1 second (FEV 1 ) ≥60% predicted and FEV 1 /forced vital capacity <0.7 were selected from the fourth Korea National Health and Nutrition Examination Survey (KNHANES) in 2007-2012. The data were merged to the National Health Insurance reimbursement database during the same period. k-Means clustering was performed to explore subtypes. For clustering analysis, six key input variables - age, body mass index (BMI), FEV 1 % predicted, the presence or absence of self-reported wheezing, smoking status, and pack-years of smoking - were selected. Among a total of 2,140 subjects, five groups were identified through k-means clustering, namely putative "near-normal (n=232)," "asthmatic (n=392)," "chronic obstructive pulmonary disease (COPD) (n=37)," "asthmatic-overlap (n=893)," and "COPD-overlap (n=586)" subtypes. Near-normal group showed the oldest mean age (72±7 years) and highest FEV 1 (102%±8% predicted), and asthmatic group was the youngest (46±9 years). COPD and COPD-overlap groups were male predominant and all current or ex-smokers. While asthmatic group had the lowest prescription rate despite the highest proportion of self-reported wheezing, COPD, asthmatic-overlap, and COPD-overlap groups showed high prescription rate of respiratory medicine. Although COPD group formed only 1.7% of total subjects, they showed the highest mean medical cost and health care utilization, comprising 5.3% of the total medical cost. When calculating a ratio of total medical expense to household income, the mean ratio was highest in the COPD group. Clinical and epidemiological heterogeneities of subjects with mild-to-moderate airflow limitation and a different level of health care utilization by each subtype are shown. Identification of a subtype with high health care demand could be a priority for effective utilization of limited resources.
Southan, Christopher; Várkonyi, Péter; Muresan, Sorel
2009-07-06
Since 2004 public cheminformatic databases and their collective functionality for exploring relationships between compounds, protein sequences, literature and assay data have advanced dramatically. In parallel, commercial sources that extract and curate such relationships from journals and patents have also been expanding. This work updates a previous comparative study of databases chosen because of their bioactive content, availability of downloads and facility to select informative subsets. Where they could be calculated, extracted compounds-per-journal article were in the range of 12 to 19 but compound-per-protein counts increased with document numbers. Chemical structure filtration to facilitate standardised comparisons typically reduced source counts by between 5% and 30%. The pair-wise overlaps between 23 databases and subsets were determined, as well as changes between 2006 and 2008. While all compound sets have increased, PubChem has doubled to 14.2 million. The 2008 comparison matrix shows not only overlap but also unique content across all sources. Many of the detailed differences could be attributed to individual strategies for data selection and extraction. While there was a big increase in patent-derived structures entering PubChem since 2006, GVKBIO contains over 0.8 million unique structures from this source. Venn diagrams showed extensive overlap between compounds extracted by independent expert curation from journals by GVKBIO, WOMBAT (both commercial) and BindingDB (public) but each included unique content. In contrast, the approved drug collections from GVKBIO, MDDR (commercial) and DrugBank (public) showed surprisingly low overlap. Aggregating all commercial sources established that while 1 million compounds overlapped with PubChem 1.2 million did not. On the basis of chemical structure content per se public sources have covered an increasing proportion of commercial databases over the last two years. However, commercial products included in this study provide links between compounds and information from patents and journals at a larger scale than current public efforts. They also continue to capture a significant proportion of unique content. Our results thus demonstrate not only an encouraging overall expansion of data-supported bioactive chemical space but also that both commercial and public sources are complementary for its exploration.
Raboanatahiry, Nadia; Chao, Hongbo; Guo, Liangxing; Gan, Jianping; Xiang, Jun; Yan, Mingli; Zhang, Libin; Yu, Longjiang; Li, Maoteng
2017-10-12
Deciphering the genetic architecture of a species is a good way to understand its evolutionary history, but also to tailor its profile for breeding elite cultivars with desirable traits. Aligning QTLs from diverse population in one map and utilizing it for comparison, but also as a basis for multiple analyses assure a stronger evidence to understand the genetic system related to a given phenotype. In this study, 439 genes involved in fatty acid (FA) and triacylglycerol (TAG) biosyntheses were identified in Brassica napus. B. napus genome showed mixed gene loss and insertion compared to B. rapa and B. oleracea, and C genome had more inserted genes. Identified QTLs for oil (OC-QTLs) and fatty acids (FA-QTLs) from nine reported populations were projected on the physical map of the reference genome "Darmor-bzh" to generate a map. Thus, 335 FA-QTLs and OC-QTLs could be highlighted and 82 QTLs were overlapping. Chromosome C3 contained 22 overlapping QTLs with all trait studied except for C18:3. In total, 218 candidate genes which were potentially involved in FA and TAG were identified in 162 QTLs confidence intervals and some of them might affect many traits. Also, 76 among these candidate genes were found inside 57 overlapping QTLs, and candidate genes for oil content were in majority (61/76 genes). Then, sixteen genes were found in overlapping QTLs involving three populations, and the remaining 60 genes were found in overlapping QTLs of two populations. Interaction network and pathway analysis of these candidate genes indicated ten genes that might have strong influence over the other genes that control fatty acids and oil formation. The present results provided new information for genetic basis of FA and TAG formation in B. napus. A map including QTLs from numerous populations was built, which could serve as reference to study the genome profile of B. napus, and new potential genes emerged which might affect seed oil. New useful tracks were showed for the selection of population or/and selection of interesting genes for breeding improvement purpose.
Daryaei, Iman; Pagel, Mark D
2016-01-01
Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a “double-agent” approach to molecular imaging. Exogenous T2-exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T1 and T2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as “secret agents” in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging. PMID:27747191
Schizophrenia: multi-attribute utility theory approach to selection of atypical antipsychotics.
Bettinger, Tawny L; Shuler, Garyn; Jones, Donnamaria R; Wilson, James P
2007-02-01
Current guidelines/algorithms recommend atypical antipsychotics as first-line agents for the treatment of schizophrenia. Because there are extensive healthcare costs associated with the treatment of schizophrenia, many institutions and health systems are faced with making restrictive formulary decisions regarding the use of atypical antipsychotics. Often, medication acquisition costs are the driving force behind formulary decisions, while other treatment factors are not considered. To apply a multi-attribute utility theory (MAUT) analysis to aid in the selection of a preferred agent among the atypical antipsychotics for the treatment of schizophrenia. Five atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) were selected as the alternative agents to be included in the MAUT analysis. The attributes identified for inclusion in the analysis were efficacy, adverse effects, cost, and adherence, with relative weights of 35%, 35%, 20%, and 10%, respectively. For each agent, attribute scores were calculated, weighted, and then summed to generate a total utility score. The agent with the highest total utility score was considered the preferred agent. Aripiprazole, with a total utility score of 75.8, was the alternative agent with the highest total utility score in this model. This was followed by ziprasidone, risperidone, and quetiapine, with total utility scores of 71.8, 69.0, and 65.9, respectively. Olanzapine received the lowest total utility score. A sensitivity analysis was performed and failed to displace aripiprazole as the agent with the highest total utility score. This model suggests that aripiprazole should be considered a preferred agent for the treatment of schizophrenia unless found to be otherwise inappropriate.
Molecular Genetics of Successful Smoking Cessation: Convergent Genome-Wide Association Study Results
Uhl, George R.; Liu, Qing-Rong; Drgon, Tomas; Johnson, Catherine; Walther, Donna; Rose, Jed E.; David, Sean P.; Niaura, Ray; Lerman, Caryn
2008-01-01
Context Smoking remains a major public health problem. Twin studies indicate that the ability to quit smoking is substantially heritable, with genetics that overlap modestly with the genetics of vulnerability to dependence on addictive substances. Objectives To identify replicated genes that facilitate smokers’ abilities to achieve and sustain abstinence from smoking (hereinafter referred to as quit-success genes) found in more than 2 genome-wide association (GWA) studies of successful vs unsuccessful abstainers, and, secondarily, to nominate genes for selective involvement in smoking cessation success with bupropion hydrochloride vs nicotine replacement therapy (NRT). Design The GWA results in subjects from 3 centers, with secondary analyses of NRT vs bupropion responders. Setting Outpatient smoking cessation trial participants from 3 centers. Participants European American smokers who successfully vs unsuccessfully abstain from smoking with biochemical confirmation in a smoking cessation trial using NRT, bupropion, or placebo (N=550). Main Outcome Measures Quit-success genes, reproducibly identified by clustered nominally positive single-nucleotide polymorphisms (SNPs) in more than 2 independent samples with significant P values based on Monte Carlo simulation trials. The NRT-selective genes were nominated by clustered SNPs that display much larger t values for NRT vs placebo comparisons. The bupropion-selective genes were nominated by bupropion-selective results. Results Variants in quit-success genes are likely to alter cell adhesion, enzymatic, transcriptional, structural, and DNA, RNA, and/or protein-handling functions. Quit-success genes are identified by clustered nominally positive SNPs from more than 2 samples and are unlikely to represent chance observations (Monte Carlo P < .0003). These genes display modest overlap with genes identified in GWA studies of dependence on addictive substances and memory. Conclusions These results support polygenic genetics for success in abstaining from smoking, overlap with genetics of substance dependence and memory, and nominate gene variants for selective influences on therapeutic responses to bupropion vs NRT. Molecular genetics should help match the types and/or intensity of anti-smoking treatments with the smokers most likely to benefit from them. PMID:18519826
Contrast enhanced spectroscopic optical coherence tomography
NASA Technical Reports Server (NTRS)
Xu, Chenyang (Inventor); Boppart, Stephen A. (Inventor)
2010-01-01
A method of forming an image of a sample includes performing SOCT on a sample. The sample may include a contrast agent, which may include an absorbing agent and/or a scattering agent. A method of forming an image of tissue may include selecting a contrast agent, delivering the contrast agent to the tissue, acquiring SOCT data from the tissue, and converting the SOCT data into an image. The contributions to the SOCT data of an absorbing agent and a scattering agent in a sample may be quantified separately.
Darmann, Andreas; Nicosia, Gaia; Pferschy, Ulrich; Schauer, Joachim
2014-03-16
In this work we address a game theoretic variant of the Subset Sum problem, in which two decision makers (agents/players) compete for the usage of a common resource represented by a knapsack capacity. Each agent owns a set of integer weighted items and wants to maximize the total weight of its own items included in the knapsack. The solution is built as follows: Each agent, in turn, selects one of its items (not previously selected) and includes it in the knapsack if there is enough capacity. The process ends when the remaining capacity is too small for including any item left. We look at the problem from a single agent point of view and show that finding an optimal sequence of items to select is an [Formula: see text]-hard problem. Therefore we propose two natural heuristic strategies and analyze their worst-case performance when (1) the opponent is able to play optimally and (2) the opponent adopts a greedy strategy. From a centralized perspective we observe that some known results on the approximation of the classical Subset Sum can be effectively adapted to the multi-agent version of the problem.
Darmann, Andreas; Nicosia, Gaia; Pferschy, Ulrich; Schauer, Joachim
2014-01-01
In this work we address a game theoretic variant of the Subset Sum problem, in which two decision makers (agents/players) compete for the usage of a common resource represented by a knapsack capacity. Each agent owns a set of integer weighted items and wants to maximize the total weight of its own items included in the knapsack. The solution is built as follows: Each agent, in turn, selects one of its items (not previously selected) and includes it in the knapsack if there is enough capacity. The process ends when the remaining capacity is too small for including any item left. We look at the problem from a single agent point of view and show that finding an optimal sequence of items to select is an NP-hard problem. Therefore we propose two natural heuristic strategies and analyze their worst-case performance when (1) the opponent is able to play optimally and (2) the opponent adopts a greedy strategy. From a centralized perspective we observe that some known results on the approximation of the classical Subset Sum can be effectively adapted to the multi-agent version of the problem. PMID:25844012
Evolutionary game theory using agent-based methods.
Adami, Christoph; Schossau, Jory; Hintze, Arend
2016-12-01
Evolutionary game theory is a successful mathematical framework geared towards understanding the selective pressures that affect the evolution of the strategies of agents engaged in interactions with potential conflicts. While a mathematical treatment of the costs and benefits of decisions can predict the optimal strategy in simple settings, more realistic settings such as finite populations, non-vanishing mutations rates, stochastic decisions, communication between agents, and spatial interactions, require agent-based methods where each agent is modeled as an individual, carries its own genes that determine its decisions, and where the evolutionary outcome can only be ascertained by evolving the population of agents forward in time. While highlighting standard mathematical results, we compare those to agent-based methods that can go beyond the limitations of equations and simulate the complexity of heterogeneous populations and an ever-changing set of interactors. We conclude that agent-based methods can predict evolutionary outcomes where purely mathematical treatments cannot tread (for example in the weak selection-strong mutation limit), but that mathematics is crucial to validate the computational simulations. Copyright © 2016 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harilal, Sivanandan S.; LaHaye, Nicole L.; Phillips, Mark C.
We used a CW laser as a narrow-band (~50kHz) tunable LIF excitation source to probe absorption from selected atomic transitions (Al, U etc. ) in a ns laser ablation plume. A comparison of fluorescence signal with respect to emission spectroscopy show significant increase in the magnitude and persistence from selected Al and U transitions in a LIBS plume. The high spectral resolution provided by the LIF measurement allows peaks to be easily separated even if they overlap in the emission spectra.
Sealing effect of a polysaccharide nanosheet for murine cecal puncture.
Fujie, Toshinori; Kinoshita, Manabu; Shono, Satoshi; Saito, Akihiro; Okamura, Yosuke; Saitoh, Daizoh; Takeoka, Shinji
2010-07-01
Recent developments in nanobiotechnology have led us to develop a method of producing a free-standing polymer nanosheet composed of polysaccharides (ie, polysaccharide nanosheet) with a thickness of tens of nanometers. Owing to its enormous aspect ratio, the polysaccharide nanosheet is semi-absorbent and has a physical adhesive strength 7.5-fold greater than that of conventional films of >1 microm thickness. Herein, we have investigated the therapeutic sealing effect of this polysaccharide nanosheet on murine cecal puncture as a wound dressing material. Murine cecum was punctured and then overlapped with the polysaccharide nanosheet. Thereafter, we evaluated its sealing effect on bacterial peritonitis as well as the protection offered by the polysaccharide nanosheet against bacterial permeability using an in vitro transmembrane assay. The 39-nm-thick polysaccharide nanosheet overlapped tightly the perforated cecum. No adhering agents were required because of the ability of the polysaccharide nanosheet to adhere to the tissue surface by physical adsorption (eg, van der Waals interaction). Sealing the perforated cecum with the polysaccharide nanosheet increased survival rate without postoperative adhesion by comparison with untreated mice (90 vs 30%; P < .01). These data were supported by the improvement in peritonitis related to bacterial counts, white blood cell counts, and the serum tumor necrosis factor level. Moreover, using an in vitro transmembrane assay, we showed that the polysaccharide nanosheet inhibited effectively bacterial penetration. We have demonstrated the potential clinical benefits of the nanosheet-type biomaterial that can be used for repairing a cecal colotomy without chemical bonding agents. Copyright 2010 Mosby, Inc. All rights reserved.
Xu, Song; Liu, Renwang; Da, Yurong
2018-06-05
This study compared tumor-related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment. Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses were performed based on LUAD differentially expressed genes from The Cancer Genome Atlas (TCGA) project and genotype-tissue expression controls. These results were compared to various known compounds using the Connectivity Mapping dataset. The clinical significance of the hub genes identified by overlapping pathway enrichment analysis was further investigated using data mining from multiple sources. A drug-pathway network for LUAD was constructed, and molecular docking was carried out. After the integration of 57 LUAD-related pathways and 35 pathways affected by small molecules, five overlapping pathways were revealed. Among these five pathways, the p53 signaling pathway was the most significant, with CCNB1, CCNB2, CDK1, CDKN2A, and CHEK1 being identified as hub genes. The p53 signaling pathway is implicated as a risk factor for LUAD tumorigenesis and survival. A total of 88 molecules significantly inhibiting the five LUAD-related oncogenic pathways were involved in the LUAD drug-pathway network. Daunorubicin, mycophenolic acid, and pyrvinium could potentially target the hub gene CHEK1 directly. Our study highlights the critical pathways that should be targeted in the search for potential LUAD treatments, most importantly, the p53 signaling pathway. Some compounds, such as ciclopirox and AG-028671, may have potential roles for LUAD treatment but require further experimental verification. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Recent advances in Hepatitis E virus.
Meng, X J
2010-03-01
Hepatitis E virus (HEV), the causative agent of hepatitis E, belongs to the family Hepeviridae. At least four major genotypes of HEV have been recognized: genotypes 1 and 2 are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 are zoonotic and infect humans and several other animals in both developing and industrialized countries. Besides humans, strains of HEV have been genetically identified from swine, chickens, sika deer, mongeese, and rabbits. The genome of HEV consists of three open reading frames (ORFs): ORF1 codes for nonstructural proteins, ORF2 codes for capsid protein, and ORF3 codes for a small multifunctional protein. The ORF2 and ORF3 proteins are translated from a single bicistronic mRNA and overlap each other but neither overlaps ORF1. The recent determination of the 3D crystal structure of the HEV capsid protein should facilitate the development of vaccines and antivirals. The identification and characterization of animal strains of HEV from pigs and chickens and the demonstrated ability of cross-species infection by swine HEV raise public health concerns for zoonosis. Accumulating evidence indicated that hepatitis E is a zoonotic disease and pigs and more likely other animal species are reservoirs for HEV. This article provides an overview of the recent advances in hepatitis E and its causative agent, including nomenclature and genomic organization, gene expression and functions, 3D structure of the virions, changing perspectives on higher mortality during pregnancy and chronic hepatitis E, animal reservoirs, zoonotic risk, food safety, and novel animal models.
Habitat selection and overlap of Atlantic salmon and smallmouth bass juveniles in nursery streams
Wathen, G.; Coghlan, S.M.; Zydlewski, Joseph D.; Trial, J.G.
2011-01-01
Introduced smallmouth bass Micropterus dolomieu have invaded much of the historic freshwater habitat of Atlantic salmon Salmo salar in North America, yet little is known about the ecological interactions between the two species. We investigated the possibility of competition for habitat between age-0 Atlantic salmon and age-0 and age-1 smallmouth bass by means of in situ observations and a mesocosm experiment. We used snorkel observation to identify the degree and timing of overlap in habitat use in our in situ observations and to describe habitat shifts by Atlantic salmon in the presence of smallmouth bass in our mesocosm experiments. In late July 2008, we observed substantial overlap in the depths and mean water column velocities used by both species in sympatric in situ conditions and an apparent shift by age-0 Atlantic salmon to shallower water that coincided with the period of high overlap. In the mesocosm experiments, we detected no overlap or habitat shifts by age-0 Atlantic salmon in the presence age-1 smallmouth bass and low overlap and no habitat shifts of Atlantic salmon and age-0 smallmouth bass in fall 2009. In 2009, summer floods with sustained high flows and low temperatures resulted in the nearly complete reproductive failure of the smallmouth bass in our study streams, and we did not observe a midsummer habitat shift by Atlantic salmon similar to that seen in 2008. Although this prevented us from replicating our 2008 experiments under similar conditions, the virtual year-class failure of smallmouth bass itself is enlightening. We suggest that future studies incorporate the effects of varying temperature and discharge to determine how abiotic factors affect the interactions between these species and thus mediate the outcomes of potential competition.
The Multiple Component Alternative for Gifted Education.
ERIC Educational Resources Information Center
Swassing, Ray
1984-01-01
The Multiple Component Model (MCM) of gifted education includes instruction which may overlap in literature, history, art, enrichment, languages, science, physics, math, music, and dance. The model rests on multifactored identification and requires systematic development and selection of components with ongoing feedback and evaluation. (CL)
Experiences with serial and parallel algorithms for channel routing using simulated annealing
NASA Technical Reports Server (NTRS)
Brouwer, Randall Jay
1988-01-01
Two algorithms for channel routing using simulated annealing are presented. Simulated annealing is an optimization methodology which allows the solution process to back up out of local minima that may be encountered by inappropriate selections. By properly controlling the annealing process, it is very likely that the optimal solution to an NP-complete problem such as channel routing may be found. The algorithm presented proposes very relaxed restrictions on the types of allowable transformations, including overlapping nets. By freeing that restriction and controlling overlap situations with an appropriate cost function, the algorithm becomes very flexible and can be applied to many extensions of channel routing. The selection of the transformation utilizes a number of heuristics, still retaining the pseudorandom nature of simulated annealing. The algorithm was implemented as a serial program for a workstation, and a parallel program designed for a hypercube computer. The details of the serial implementation are presented, including many of the heuristics used and some of the resulting solutions.
Ulbrich, Philipp; Gail, Alexander
2017-01-01
When deciding between alternative options, a rational agent chooses on the basis of the desirability of each outcome, including associated costs. As different options typically result in different actions, the effort associated with each action is an essential cost parameter. How do humans discount physical effort when deciding between movements? We used an action-selection task to characterize how subjective effort depends on the parameters of arm transport movements and controlled for potential confounding factors such as delay discounting and performance. First, by repeatedly asking subjects to choose between 2 arm movements of different amplitudes or durations, performed against different levels of force, we identified parameter combinations that subjects experienced as identical in effort (isoeffort curves). Movements with a long duration were judged more effortful than short-duration movements against the same force, while movement amplitudes did not influence effort. Biomechanics of the movements also affected effort, as movements towards the body midline were preferred to movements away from it. Second, by introducing movement repetitions, we further determined that the cost function for choosing between effortful movements had a quadratic relationship with force, while choices were made on the basis of the logarithm of these costs. Our results show that effort-based action selection during reaching cannot easily be explained by metabolic costs. Instead, force-loaded reaches, a widely occurring natural behavior, imposed an effort cost for decision making similar to cost functions in motor control. Our results thereby support the idea that motor control and economic choice are governed by partly overlapping optimization principles. PMID:28586347
Paul, Steven M; Doherty, James J; Robichaud, Albert J; Belfort, Gabriel M; Chow, Brian Y; Hammond, Rebecca S; Crawford, Devon C; Linsenbardt, Andrew J; Shu, Hong-Jin; Izumi, Yukitoshi; Mennerick, Steven J; Zorumski, Charles F
2013-10-30
N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. NMDARs govern experience-dependent synaptic plasticity and have been implicated in the pathophysiology of various neuropsychiatric disorders including the cognitive deficits of schizophrenia and certain forms of autism. Certain neurosteroids modulate NMDARs experimentally but their low potency, poor selectivity, and very low brain concentrations make them poor candidates as endogenous ligands or therapeutic agents. Here we show that the major brain-derived cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC) is a very potent, direct, and selective positive allosteric modulator of NMDARs with a mechanism that does not overlap that of other allosteric modulators. At submicromolar concentrations 24(S)-HC potentiates NMDAR-mediated EPSCs in rat hippocampal neurons but fails to affect AMPAR or GABAA receptors (GABA(A)Rs)-mediated responses. Cholesterol itself and other naturally occurring oxysterols present in brain do not modulate NMDARs at concentrations ≤10 μM. In hippocampal slices, 24(S)-HC enhances the ability of subthreshold stimuli to induce long-term potentiation (LTP). 24(S)-HC also reverses hippocampal LTP deficits induced by the NMDAR channel blocker ketamine. Finally, we show that synthetic drug-like derivatives of 24(S)-HC, which potently enhance NMDAR-mediated EPSCs and LTP, restore behavioral and cognitive deficits in rodents treated with NMDAR channel blockers. Thus, 24(S)-HC may function as an endogenous modulator of NMDARs acting at a novel oxysterol modulatory site that also represents a target for therapeutic drug development.
Moving Just Like You: Motor Interference Depends on Similar Motility of Agent and Observer
Kupferberg, Aleksandra; Huber, Markus; Helfer, Bartosz; Lenz, Claus; Knoll, Alois; Glasauer, Stefan
2012-01-01
Recent findings in neuroscience suggest an overlap between brain regions involved in the execution of movement and perception of another’s movement. This so-called “action-perception coupling” is supposed to serve our ability to automatically infer the goals and intentions of others by internal simulation of their actions. A consequence of this coupling is motor interference (MI), the effect of movement observation on the trajectory of one’s own movement. Previous studies emphasized that various features of the observed agent determine the degree of MI, but could not clarify how human-like an agent has to be for its movements to elicit MI and, more importantly, what ‘human-like’ means in the context of MI. Thus, we investigated in several experiments how different aspects of appearance and motility of the observed agent influence motor interference (MI). Participants performed arm movements in horizontal and vertical directions while observing videos of a human, a humanoid robot, or an industrial robot arm with either artificial (industrial) or human-like joint configurations. Our results show that, given a human-like joint configuration, MI was elicited by observing arm movements of both humanoid and industrial robots. However, if the joint configuration of the robot did not resemble that of the human arm, MI could longer be demonstrated. Our findings present evidence for the importance of human-like joint configuration rather than other human-like features for perception-action coupling when observing inanimate agents. PMID:22761853
Mahan, Charles E
2015-04-01
Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.
2013-01-01
Background The aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide). Methods The INTEROCC study included cases diagnosed with glioma during 2000–2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure. Results The study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose–response relationships with cumulative exposure or with duration of exposure. Conclusion Thus, there was no evidence that these exposures influence risk of glioma. PMID:23587105
Lacourt, Aude; Cardis, Elisabeth; Pintos, Javier; Richardson, Lesley; Kincl, Laurel; Benke, Geza; Fleming, Sarah; Hours, Martine; Krewski, Daniel; McLean, Dave; Parent, Marie-Elise; Sadetzki, Siegal; Schlaefer, Klaus; Schlehofer, Brigitte; Lavoue, Jerome; van Tongeren, Martie; Siemiatycki, Jack
2013-04-12
The aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide). The INTEROCC study included cases diagnosed with glioma during 2000-2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure. The study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose-response relationships with cumulative exposure or with duration of exposure. Thus, there was no evidence that these exposures influence risk of glioma.
Brown, Thackery I.; Hasselmo, Michael E.; Stern, Chantal E.
2015-01-01
When navigating our world we often first plan or retrieve an ideal route to our goal, avoiding alternative paths that lead to other destinations. The medial temporal lobe (MTL) has been implicated in processing contextual information, sequence memory, and uniquely retrieving routes that overlap or “cross paths.” However, the identity of subregions of the hippocampus and neighboring cortex that support these functions in humans remains unclear. The present study used high-resolution functional magnetic resonance imaging (hr-fMRI) in humans to test whether the CA3/DG hippocampal subfield and para-hippocampal cortex are important for processing spatial context and route retrieval, and whether the CA1 subfield facilitates prospective planning of mazes that must be distinguished from alternative overlapping routes. During hr-fMRI scanning, participants navigated virtual mazes that were well-learned from prior training while also learning new mazes. Some routes learned during scanning shared hallways with those learned during pre-scan training, requiring participants to select between alternative paths. Critically, each maze began with a distinct spatial contextual Cue period. Our analysis targeted activity from the Cue period, during which participants identified the current navigational episode, facilitating retrieval of upcoming route components and distinguishing mazes that overlap. Results demonstrated that multiple MTL regions were predominantly active for the contextual Cue period of the task, with specific regions of CA3/DG, parahippocampal cortex, and perirhinal cortex being consistently recruited across trials for Cue periods of both novel and familiar mazes. During early trials of the task, both CA3/DG and CA1 were more active for overlapping than non-overlapping Cue periods. Trial-by-trial Cue period responses in CA1 tracked subsequent overlapping maze performance across runs. Together, our findings provide novel insight into the contributions of MTL subfields to processing spatial context and route retrieval, and support a prominent role for CA1 in distinguishing overlapping episodes during navigational “look-ahead” periods. PMID:24659134
9 CFR 121.10 - Restricting access to select agents and toxins; security risk assessments.
Code of Federal Regulations, 2010 CFR
2010-01-01
... education, training, and/or experience to handle or use such agents or toxins. (d) To apply for access... other organization that engages in intentional crimes of violence; or being an agent of a foreign power...
NASA Astrophysics Data System (ADS)
Smith, D.; Barnes, R. J.; Morrison, D.; Talaat, E. R.; Potter, M.; Patrone, D.; Weiss, M.; Sarris, T.
2013-12-01
Virtual Observatories are more than data portals that span multiple missions and data sets. They need to provide a system that is useable by a broad swath of people with different backgrounds. The great promise of Virtual Observatories is the ability to perform complex search operations on a large variety of different data sets. This allows the researcher to isolate and select the relevant measurements for their topic of study. The Virtual ITM Observatory (VITMO) is unique in having many diverse datasets that cover a large temporal and spatial range that present a unique search problem. VITMO provides many methods by which the user can search for and select data of interest including restricting selections based on geophysical conditions (solar wind speed, Kp, etc) as well as finding those datasets that overlap in time and/or space. We are developing a series of light-weight web services that will provide a new data search capability for VITMO and other VxOs. The services will consist of a database of spacecraft ephemerides and instrument fields of view; an overlap calculator to find times when the fields of view of different instruments intersect; and a magnetic field line tracing service that will map in situ and ground based measurements to the equatorial plane in magnetic coordinates for a number of field models and geophysical conditions. Each service on their own provides a useful new capability for virtual observatories; operating together they will provide a powerful new search tool. The ephemerides service is being built using the Navigation and Ancillary Information Facility (NAIF) SPICE toolkit (http://naif.jpl.nasa.gov/naif/index.html) allowing them to be extended to support any Earth orbiting satellite with the addition of the appropriate SPICE kernels or two-line element sets (TLE). An instrument kernel (IK) file will be used to describe the observational geometry of the instrument (e.g., Field-of-view size, shape, and orientation). The overlap calculator uses techniques borrowed from computer graphics to identify overlapping measurements in space and time. The calculator will allow a user defined uncertainty to be selected to allow 'near misses' to be found. The magnetic field tracing service will feature a database of pre-calculated field line tracings of ground stations but will also allow dynamic tracing of arbitrary coordinates. These services will allow the non-specialist user of VITMO to select data that they were previously unable to locate, opening up analysis opportunities beyond the instrument teams and making it much easier for future students who come into the field.
Communication Policies in Knowledge Networks
NASA Astrophysics Data System (ADS)
Ioannidis, Evangelos; Varsakelis, Nikos; Antoniou, Ioannis
2018-02-01
Faster knowledge attainment within organizations leads to improved innovation, and therefore competitive advantage. Interventions on the organizational network may be risky or costly or time-demanding. We investigate several communication policies in knowledge networks, which reduce the knowledge attainment time without interventions. We examine the resulting knowledge dynamics for real organizational networks, as well as for artificial networks. More specifically, we investigate the dependence of knowledge dynamics on: (1) the Selection Rule of agents for knowledge acquisition, and (2) the Order of implementation of "Selection" and "Filtering". Significant decrease of the knowledge attainment time (up to -74%) can be achieved by: (1) selecting agents of both high knowledge level and high knowledge transfer efficiency, and (2) implementing "Selection" after "Filtering" in contrast to the converse, implicitly assumed, conventional prioritization. The Non-Commutativity of "Selection" and "Filtering", reveals a Non-Boolean Logic of the Network Operations. The results demonstrate that significant improvement of knowledge dynamics can be achieved by implementing "fruitful" communication policies, by raising the awareness of agents, without any intervention on the network structure.
Roberts, Rebecca M.; Albert, Alison P.; Johnson, Darcia D.; Hicks, Lauri A.
2014-01-01
Appropriate selection of antibiotic drugs is critical to optimize treatment of infections and limit the spread of antibiotic resistance. To better inform public health efforts to improve prescribing of antibiotic drugs, we conducted in-depth interviews with 36 primary care providers in the United States (physicians, nurse practitioners, and physician assistants) to explore knowledge, attitudes, and self-reported practices regarding antibiotic drug resistance and antibiotic drug selection for common infections. Participants were generally familiar with guideline recommendations for antibiotic drug selection for common infections, but did not always comply with them. Reasons for nonadherence included the belief that nonrecommended agents are more likely to cure an infection, concern for patient or parent satisfaction, and fear of infectious complications. Providers inconsistently defined broad- and narrow-spectrum antibiotic agents. There was widespread concern for antibiotic resistance; however, it was not commonly considered when selecting therapy. Strategies to encourage use of first-line agents are needed in addition to limiting unnecessary prescribing of antibiotic drugs. PMID:25418868
Tsay, Ming-Yueh; Wu, Tai-Luan; Tseng, Ling-Li
2017-01-01
This study examines the completeness and overlap of coverage in physics of six open access scholarly communication systems, including two search engines (Google Scholar and Microsoft Academic), two aggregate institutional repositories (OAIster and OpenDOAR), and two physics-related open sources (arXiv.org and Astrophysics Data System). The 2001-2013 Nobel Laureates in Physics served as the sample. Bibliographic records of their publications were retrieved and downloaded from each system, and a computer program was developed to perform the analytical tasks of sorting, comparison, elimination, aggregation and statistical calculations. Quantitative analyses and cross-referencing were performed to determine the completeness and overlap of the system coverage of the six open access systems. The results may enable scholars to select an appropriate open access system as an efficient scholarly communication channel, and academic institutions may build institutional repositories or independently create citation index systems in the future. Suggestions on indicators and tools for academic assessment are presented based on the comprehensiveness assessment of each system.
Sim, Jaehyun; Sim, Jun; Park, Eunsung; Lee, Julian
2015-06-01
Many proteins undergo large-scale motions where relatively rigid domains move against each other. The identification of rigid domains, as well as the hinge residues important for their relative movements, is important for various applications including flexible docking simulations. In this work, we develop a method for protein rigid domain identification based on an exhaustive enumeration of maximal rigid domains, the rigid domains not fully contained within other domains. The computation is performed by mapping the problem to that of finding maximal cliques in a graph. A minimal set of rigid domains are then selected, which cover most of the protein with minimal overlap. In contrast to the results of existing methods that partition a protein into non-overlapping domains using approximate algorithms, the rigid domains obtained from exact enumeration naturally contain overlapping regions, which correspond to the hinges of the inter-domain bending motion. The performance of the algorithm is demonstrated on several proteins. © 2015 Wiley Periodicals, Inc.
Griffin, Philippa C.; Hangartner, Sandra B.; Fournier-Level, Alexandre; Hoffmann, Ary A.
2017-01-01
Adaptation to environmental stress is critical for long-term species persistence. With climate change and other anthropogenic stressors compounding natural selective pressures, understanding the nature of adaptation is as important as ever in evolutionary biology. In particular, the number of alternative molecular trajectories available for an organism to reach the same adaptive phenotype remains poorly understood. Here, we investigate this issue in a set of replicated Drosophila melanogaster lines selected for increased desiccation resistance—a classical physiological trait that has been closely linked to Drosophila species distributions. We used pooled whole-genome sequencing (Pool-Seq) to compare the genetic basis of their selection responses, using a matching set of replicated control lines for characterizing laboratory (lab-)adaptation, as well as the original base population. The ratio of effective population size to census size was high over the 21 generations of the experiment at 0.52–0.88 for all selected and control lines. While selected SNPs in replicates of the same treatment (desiccation-selection or lab-adaptation) tended to change frequency in the same direction, suggesting some commonality in the selection response, candidate SNP and gene lists often differed among replicates. Three of the five desiccation-selection replicates showed significant overlap at the gene and network level. All five replicates showed enrichment for ovary-expressed genes, suggesting maternal effects on the selected trait. Divergence between pairs of replicate lines for desiccation-candidate SNPs was greater than between pairs of control lines. This difference also far exceeded the divergence between pairs of replicate lines for neutral SNPs. Overall, while there was overlap in the direction of allele frequency changes and the network and functional categories affected by desiccation selection, replicates showed unique responses at all levels, likely reflecting hitchhiking effects, and highlighting the challenges in identifying candidate genes from these types of experiments when traits are likely to be polygenic. PMID:28007884
2014-01-01
Background In 2012 mobile phone numbers were included into the ongoing New South Wales Population Health Survey (NSWPHS) using an overlapping dual-frame design. Previously in the NSWPHS the sample was selected using random digit dialing (RDD) of landline phone numbers. The survey was undertaken using computer assisted telephone interviewing (CATI). The weighting strategy needed to be significantly expanded to manage the differing probabilities of selection by frame, including that of children of mobile-only phone users, and to adjust for the increased chance of selection of dual-phone users. This paper describes the development of the final weighting strategy to properly combine the data from two overlapping sample frames accounting for the fact that population benchmarks for the different sampling frames were not available at the state or regional level. Methods Estimates of the number of phone numbers for the landline and mobile phone frames used to calculate the differing probabilities of selection by frame, for New South Wales (NSW) and by stratum, were obtained by apportioning Australian estimates as none were available for NSW. The weighting strategy was then developed by calculating person selection probabilities, selection weights, applying a constant composite factor to the dual-phone users sample weights, and benchmarking to the latest NSW population by age group, sex and stratum. Results Data from the NSWPHS for the first quarter of 2012 was used to test the weighting strategy. This consisted of data on 3395 respondents with 2171 (64%) from the landline frame and 1224 (36%) from the mobile frame. However, in order to calculate the weights, data needed to be available for all core weighting variables and so 3378 respondents, 2933 adults and 445 children, had sufficient data to be included. Average person weights were 3.3 times higher for the mobile-only respondents, 1.3 times higher for the landline-only respondents and 1.7 times higher for dual-phone users in the mobile frame compared to the dual-phone users in the landline frame. The overall weight effect for the first quarter of 2012 was 1.93 and the coefficient of variation of the weights was 0.96. The weight effects for 2012 were similar to, and in many cases less than, the effects found in the corresponding quarter of the 2011 NSWPHS when only a landline based sample was used. Conclusions The inclusion of mobile phone numbers, through an overlapping dual-frame design, improved the coverage of the survey and an appropriate weighing procedure is feasible, although it added substantially to the complexity of the weighting strategy. Access to accurate Australian, State and Territory estimates of the number of landline and mobile phone numbers and type of phone use by at least age group and sex would greatly assist in the weighting of dual-frame surveys in Australia. PMID:25189826
Barr, Margo L; Ferguson, Raymond A; Hughes, Phil J; Steel, David G
2014-09-04
In 2012 mobile phone numbers were included into the ongoing New South Wales Population Health Survey (NSWPHS) using an overlapping dual-frame design. Previously in the NSWPHS the sample was selected using random digit dialing (RDD) of landline phone numbers. The survey was undertaken using computer assisted telephone interviewing (CATI). The weighting strategy needed to be significantly expanded to manage the differing probabilities of selection by frame, including that of children of mobile-only phone users, and to adjust for the increased chance of selection of dual-phone users. This paper describes the development of the final weighting strategy to properly combine the data from two overlapping sample frames accounting for the fact that population benchmarks for the different sampling frames were not available at the state or regional level. Estimates of the number of phone numbers for the landline and mobile phone frames used to calculate the differing probabilities of selection by frame, for New South Wales (NSW) and by stratum, were obtained by apportioning Australian estimates as none were available for NSW. The weighting strategy was then developed by calculating person selection probabilities, selection weights, applying a constant composite factor to the dual-phone users sample weights, and benchmarking to the latest NSW population by age group, sex and stratum. Data from the NSWPHS for the first quarter of 2012 was used to test the weighting strategy. This consisted of data on 3395 respondents with 2171 (64%) from the landline frame and 1224 (36%) from the mobile frame. However, in order to calculate the weights, data needed to be available for all core weighting variables and so 3378 respondents, 2933 adults and 445 children, had sufficient data to be included. Average person weights were 3.3 times higher for the mobile-only respondents, 1.3 times higher for the landline-only respondents and 1.7 times higher for dual-phone users in the mobile frame compared to the dual-phone users in the landline frame. The overall weight effect for the first quarter of 2012 was 1.93 and the coefficient of variation of the weights was 0.96. The weight effects for 2012 were similar to, and in many cases less than, the effects found in the corresponding quarter of the 2011 NSWPHS when only a landline based sample was used. The inclusion of mobile phone numbers, through an overlapping dual-frame design, improved the coverage of the survey and an appropriate weighing procedure is feasible, although it added substantially to the complexity of the weighting strategy. Access to accurate Australian, State and Territory estimates of the number of landline and mobile phone numbers and type of phone use by at least age group and sex would greatly assist in the weighting of dual-frame surveys in Australia.
Comparative vertical transmission of Rickettsia by Dermacentor variabilis and Amblyomma maculatum
Harris, Emma K.; Verhoeve, Victoria I.; Banajee, Kaikhushroo H.; Macaluso, Jacqueline A.; Azad, Abdu F.
2017-01-01
The geographical overlap of multiple Rickettsia and tick species coincides with the molecular detection of a variety of rickettsial agents in what may be novel tick hosts. However, little is known concerning transmissibility of rickettsial species by various tick hosts. To examine the vertical transmission potential between select tick and rickettsial species, two sympatric species of ticks, Dermacentor variabilis and Amblyomma maculatum, were exposed to five different rickettsial species, including Rickettsia rickettsii, Rickettsia parkeri, Rickettsia montanensis, Rickettsia amblyommatis, or flea-borne Rickettsia felis. Fitness-related metrics including engorgement weight, egg production index, nutrient index, and egg hatch percentage were then assessed. Subsamples of egg clutches and unfed larvae, nymphs, and adults for each cohort were assessed for transovarial and transstadial transmission of rickettsiae by qPCR. Rickettsial exposure had a minimal fitness effect in D. variabilis and transovarial transmission was observed for all groups except R. rickettsii. In contrast, rickettsial exposure negatively influenced A. maculatum fitness and transovarial transmission of rickettsiae was demonstrated only for R. amblyommatis- and R. parkeri-exposed ticks. Sustained maintenance of rickettsiae via transstadial transmission was diminished from F1 larvae to F1 adults in both tick species. The findings of this study suggest transovarial transmission specificity may not be tick species dependent, and sustained vertical transmission is not common. PMID:28433729
Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions
Czaja, Albert J.
2016-01-01
Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms. PMID:26934884
Tissue Engineering and Regenerative Medicine 2017: A Year in Review.
Park, Kyung Min; Shin, Young Min; Kim, Kyobum; Shin, Heungsoo
2018-04-26
In 2017, a new paradigm change caused by artificial intelligence and big data analysis resulted in innovation in each field of science and technology, and also significantly influenced progress in tissue engineering and regenerative medicine (TERM). TERM has continued to make technological advances based on interdisciplinary approaches and has contributed to the overall field of biomedical technology, including cancer biology, personalized medicine, development biology, and cell-based therapeutics. While researchers are aware that there is still a long way to go until TERM reaches the ultimate goal of patient treatment through clinical translation, the rapid progress in convergence studies led by technological improvements in TERM has been encouraging. In this review, we highlighted the significant advances made in TERM in 2017 (with an overlap of 5 months in 2016). We identified major progress in TERM in a manner similar to previous reviews published in the last few years. In addition, we carefully considered all four previous reviews during the selection process and chose main themes that minimize the duplication of the topics. Therefore, we have identified three areas that have been the focus of most journal publications in the TERM community in 2017: (i) advanced biomaterials and three-dimensional (3D) cell printing, (ii) exosomes as bioactive agents for regenerative medicine, and (iii) 3D culture in regenerative medicine.
Salloum, Shadi; Kluge, Silvia F; Kim, Arthur Y; Roggendorf, Michael; Timm, Joerg
2010-08-01
The NS3/4A serine protease of the hepatitis C virus (HCV) is one of the most attractive targets for specific antiviral agents. However, mutations conferring resistance may decrease the efficacy of these drugs. Although the level of resistance associated with specific mutations differs between different compounds, substitutions R155K and A156T reduce susceptibility to all protease inhibitors published so far. Interestingly, variants harboring the resistant mutation R155K were also detected as the predominant quasispecies in some treatment-naïve patients. Of note, key positions for resistance overlap with the HLA-A*68-restricted epitope HAVGIFRAAV(1175-1184). The aim of our study was to analyze the impact of protease inhibitor resistance mutations on the replication level and the antiviral CD8 T cell response against this HCV epitope. Our findings suggest that the R155K variant is associated with a relatively high replication level and with a substantial loss of cross-recognition by specific CD8 T cells targeting the epitope HAVGIFRAAV(1175-1184), providing a possible explanation for its existence in the absence of drug selection pressure. Copyright 2010 Elsevier B.V. All rights reserved.
7 CFR 331.3 - PPQ select agents and toxins.
Code of Federal Regulations, 2011 CFR
2011-01-01
... listed in paragraph (b) of this section if the nucleic acids: (i) Can be expressed in vivo or in vitro; or (ii) Are in a vector or recombinant host genome and can be expressed in vivo or in vitro. (3... select agents and toxins. (a) Except as provided in paragraphs (d) and (e) of this section, the...
A multiplex PCR assay to detect and differentiate select agent strains of Ralstonia solanacearum
USDA-ARS?s Scientific Manuscript database
Ralstonia solanacearum causes bacterial wilt in a variety of cash crops. R. solanacearum race 3 biovar 2 strains are considered select agents by the U.S. Government because they are not endemic to the U.S. and have the potential to cause brown rot disease in our potato production fields. Simple and...
The good, the bad, and the timely: how temporal order and moral judgment influence causal selection
Reuter, Kevin; Kirfel, Lara; van Riel, Raphael; Barlassina, Luca
2014-01-01
Causal selection is the cognitive process through which one or more elements in a complex causal structure are singled out as actual causes of a certain effect. In this paper, we report on an experiment in which we investigated the role of moral and temporal factors in causal selection. Our results are as follows. First, when presented with a temporal chain in which two human agents perform the same action one after the other, subjects tend to judge the later agent to be the actual cause. Second, the impact of temporal location on causal selection is almost canceled out if the later agent did not violate a norm while the former did. We argue that this is due to the impact that judgments of norm violation have on causal selection—even if the violated norm has nothing to do with the obtaining effect. Third, moral judgments about the effect influence causal selection even in the case in which agents could not have foreseen the effect and did not intend to bring it about. We discuss our findings in connection to recent theories of the role of moral judgment in causal reasoning, on the one hand, and to probabilistic models of temporal location, on the other. PMID:25477851
Jonsson, Colleen B; Cole, Kelly Stefano; Roy, Chad J; Perlin, David S; Byrne, Gerald
2013-04-29
Select agent research in the United States must meet federally-mandated biological surety guidelines and rules which are comprised of two main components: biosecurity and biosafety. Biosecurity is the process employed for ensuring biological agents are properly safeguarded against theft, loss, diversion, unauthorized access or use/release. Biosafety is those processes that ensure that operations with such agents are conducted in a safe, secure and reliable manner. As such, a biological surety program is generally concerned with biological agents that present high risk for adverse medical and/or agricultural consequences upon release outside of proper containment. The U.S. Regional and National Biocontainment Laboratories (RBL, NBL) represent expertise in this type of research, and are actively engaged in the development of programs to address these critical needs and federal requirements. While this comprises an ongoing activity for the RBLs, NBLs and other facilities that handle select agents as new guidelines and regulations are implemented, the present article is written with the goal of presenting a simplified yet comprehensive review of these requirements. Herein, we discuss the requirements and the various activities that the RBL/NBL programs have implemented to achieve these metrics set forth by various agencies within the U.S. Federal government.
Jonsson, Colleen B.; Cole, Kelly Stefano; Roy, Chad J.; Perlin, David S.; Byrne, Gerald
2014-01-01
Select agent research in the United States must meet federally-mandated biological surety guidelines and rules which are comprised of two main components: biosecurity and biosafety. Biosecurity is the process employed for ensuring biological agents are properly safeguarded against theft, loss, diversion, unauthorized access or use/release. Biosafety is those processes that ensure that operations with such agents are conducted in a safe, secure and reliable manner. As such, a biological surety program is generally concerned with biological agents that present high risk for adverse medical and/or agricultural consequences upon release outside of proper containment. The U.S. Regional and National Biocontainment Laboratories (RBL, NBL) represent expertise in this type of research, and are actively engaged in the development of programs to address these critical needs and federal requirements. While this comprises an ongoing activity for the RBLs, NBLs and other facilities that handle select agents as new guidelines and regulations are implemented, the present article is written with the goal of presenting a simplified yet comprehensive review of these requirements. Herein, we discuss the requirements and the various activities that the RBL/NBL programs have implemented to achieve these metrics set forth by various agencies within the U.S. Federal government. PMID:24900945
A Method to Administer Agents to the Larynx in an Awake Large Animal
ERIC Educational Resources Information Center
Durkes, Abigail; Sivasankar, M. Preeti
2017-01-01
Purpose: This research note describes an adapted experimental methodology to administer an exogenous agent to the larynx and upper airway of awake animals. The exogenous agent could be a perturbation. In the current study, the agent was isotonic saline. Isotonic saline was selected because it is safe, of similar composition to extracellular fluid,…
Hydroxypyridonate chelating agents and synthesis thereof
Raymond, K.N.; Scarrow, R.C.; White, D.L.
1985-11-12
Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.
Effects of Spousal Satisfaction and Selected Career Factors on Job Satisfaction of Extension Agents.
ERIC Educational Resources Information Center
Hebert, Michael; Kotrlik, Joe W.
1990-01-01
A survey of extension agents and their spouses (n=127, 83 percent) found that the strongest predictor of job satisfaction was spousal satisfaction. Four-H agents had lower job satisfaction, related to long, irregular working hours. Agents had low extrinsic satisfaction related to recognition, salary, policies, and decision-making power. Spouses…
Synthesis and characterization of a smart contrast agent sensitive to calcium.
Dhingra, Kirti; Maier, Martin E; Beyerlein, Michael; Angelovski, Goran; Logothetis, Nikos K
2008-08-07
A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows approximately 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.
Ding, Hui; Wang, Rongyu; Wang, Xiao; Ji, Wenhua
2018-06-21
Molecularly imprinted covalent organic polymers were constructed by an imine-linking reaction between 1,3,5-triformylphloroglucinol and 2,6-diaminopyridine and used for the selective solid-phase extraction of benzoxazole fluorescent whitening agents from food samples. Binding experiments showed that imprinting sites on molecularly imprinted polymers had higher selectivity for targets compared with those of the corresponding non-imprinted polymers. Parameters affecting the solid-phase extraction procedure were examined. Under optimal conditions, actual samples were treated and the eluent was analyzed with high-performance liquid chromatography with diode-array detection. The results showed that the established method owned the wide linearity, satisfactory detection limits and quantification limits, and acceptable recoveries. Thus, this developed method possesses the practical potential to the selectively determine benzoxazole fluorescent whitening agents in complex food samples. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Richmond, Jonathan Y; Nesby-O'Dell, Shanna L
2002-12-06
In recent years, concern has increased regarding use of biologic materials as agents of terrorism, but these same agents are often necessary tools in clinical and research microbiology laboratories. Traditional biosafety guidelines for laboratories have emphasized use of optimal work practices, appropriate containment equipment, well-designed facilities, and administrative controls to minimize risk of worker injury and to ensure safeguards against laboratory contamination. The guidelines discussed in this report were first published in 1999 (U.S. Department of Health and Human Services/CDC and National Institutes of Health. Biosafety in microbiological and biomedical laboratories [BMBL]. Richmond JY, McKinney RW, eds. 4th ed. Washington, DC: US Department of Health and Human Services, 1999 [Appendix F]). In that report, physical security concerns were addressed, and efforts were focused on preventing unauthorized entry to laboratory areas and preventing unauthorized removal of dangerous biologic agents from the laboratory. Appendix F of BMBL is now being revised to include additional information regarding personnel risk assessments, and inventory controls. The guidelines contained in this report are intended for laboratories working with select agents under biosafety-level 2, 3, or 4 conditions as described in Sections II and III of BMBL. These recommendations include conducting facility risk assessments and developing comprehensive security plans to minimize the probability of misuse of select agents. Risk assessments should include systematic, site-specific reviews of 1) physical security; 2) security of data and electronic technology systems; 3) employee security; 4) access controls to laboratory and animal areas; 5) procedures for agent inventory and accountability; 6) shipping/transfer and receiving of select agents; 7) unintentional incident and injury policies; 8) emergency response plans; and 9) policies that address breaches in security. The security plan should be an integral part of daily operations. All employees should be well-trained and equipped, and the plan should be reviewed annually, at least.
Decolonization in Prevention of Health Care-Associated Infections
Schweizer, Marin L.
2016-01-01
SUMMARY Colonization with health care-associated pathogens such as Staphylococcus aureus, enterococci, Gram-negative organisms, and Clostridium difficile is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on S. aureus decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for S. aureus nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin-containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as Candida. Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram-negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections. PMID:26817630
Science Teaching in Science Education
ERIC Educational Resources Information Center
Callahan, Brendan E.; Dopico, Eduardo
2016-01-01
Reading the interesting article "Discerning selective traditions in science education" by Per Sund, which is published in this issue of "CSSE," allows us to open the discussion on procedures for teaching science today. Clearly there is overlap between the teaching of science and other areas of knowledge. However, we must…
Identification of Selection Footprints on the X Chromosome in Pig
Zhang, Qin; Ding, Xiangdong
2014-01-01
Identifying footprints of selection can provide a straightforward insight into the mechanism of artificial selection and further dig out the causal genes related to important traits. In this study, three between-population and two within-population approaches, the Cross Population Extend Haplotype Homozygosity Test (XPEHH), the Cross Population Composite Likelihood Ratio (XPCLR), the F-statistics (Fst), the Integrated Haplotype Score (iHS) and the Tajima's D, were implemented to detect the selection footprints on the X chromosome in three pig breeds using Illumina Porcine60K SNP chip. In the detection of selection footprints using between-population methods, 11, 11 and 7 potential selection regions with length of 15.62 Mb, 12.32 Mb and 9.38 Mb were identified in Landrace, Chinese Songliao and Yorkshire by XPEHH, respectively, and 16, 13 and 17 potential selection regions with length of 15.20 Mb, 13.00 Mb and 19.21 Mb by XPCLR, 4, 2 and 4 potential selection regions with length of 3.20 Mb, 1.60 Mb and 3.20 Mb by Fst. For within-population methods, 7, 10 and 9 potential selection regions with length of 8.12 Mb, 8.40 Mb and 9.99 Mb were identified in Landrace, Chinese Songliao and Yorkshire by iHS, and 4, 3 and 2 potential selection regions with length of 3.20 Mb, 2.40 Mb and 1.60 Mb by Tajima's D. Moreover, the selection regions from different methods were partly overlapped, especially the regions around 22 ∼25 Mb were detected under selection in Landrace and Yorkshire while no selection in Chinese Songliao by all three between-population methods. Only quite few overlap of selection regions identified by between-population and within-population methods were found. Bioinformatics analysis showed that the genes relevant with meat quality, reproduction and immune were found in potential selection regions. In addition, three out of five significant SNPs associated with hematological traits reported in our genome-wide association study were harbored in potential selection regions. PMID:24740293
Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs
Freedman, Adam H.; Schweizer, Rena M.; Ortega-Del Vecchyo, Diego; Han, Eunjung; Davis, Brian W.; Gronau, Ilan; Silva, Pedro M.; Galaverni, Marco; Fan, Zhenxin; Marx, Peter; Lorente-Galdos, Belen; Ramirez, Oscar; Hormozdiari, Farhad; Alkan, Can; Vilà, Carles; Squire, Kevin; Geffen, Eli; Kusak, Josip; Boyko, Adam R.; Parker, Heidi G.; Lee, Clarence; Tadigotla, Vasisht; Siepel, Adam; Bustamante, Carlos D.; Harkins, Timothy T.; Nelson, Stanley F.; Marques-Bonet, Tomas; Ostrander, Elaine A.; Wayne, Robert K.; Novembre, John
2016-01-01
Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. PMID:26943675
NASA Astrophysics Data System (ADS)
Behling, Robert G.; Eifert, Joseph; Erickson, Marilyn C.; Gurtler, Joshua B.; Kornacki, Jeffrey L.; Line, Erick; Radcliff, Roy; Ryser, Elliot T.; Stawick, Bradley; Yan, Zhinong
This chapter, written by several contributing authors, is devoted to discussing selected microbes of contemporary importance. Microbes from three categories are described by the following: (1) infectious invasive agents like Salmonella, Listeria monocytogenes, and Campylobacter; (2) toxigenic pathogens such as Staphylococcus aureus, Bacillus cereus, and Clostridium botulinum; and (3) toxico-infectious agents like enterohemorrhagic Escherichia coli and Clostridium perfringens. In addition, emerging pathogens, like Cronobacter (Enterobacter) sakazakii, Arcobacter spp., and Mycobacterium avium subspecies paratuberculosis are also described.
2008-02-01
tu- mor cells. In this regard, herpesvirus samiri (HVS) was de- monstrated to be naturally selectively oncolytic for the pancreatic cancer line PANC-1...the hexon virus. Therefore, Ad can provide a versatile platform for selective binding of AuNPs, resulting in a multifunctional agent capable of...utility remained unaffected. Therefore, Ad can provide a versatile platform for selective binding of nanoparticles, resulting in a multifunctional agent
Riès, Stephanie K; Dhillon, Rummit K; Clarke, Alex; King-Stephens, David; Laxer, Kenneth D; Weber, Peter B; Kuperman, Rachel A; Auguste, Kurtis I; Brunner, Peter; Schalk, Gerwin; Lin, Jack J; Parvizi, Josef; Crone, Nathan E; Dronkers, Nina F; Knight, Robert T
2017-06-06
Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.
Fernández, Alberto; Carmona, Cristobal José; José Del Jesus, María; Herrera, Francisco
2017-09-01
Imbalanced classification is related to those problems that have an uneven distribution among classes. In addition to the former, when instances are located into the overlapped areas, the correct modeling of the problem becomes harder. Current solutions for both issues are often focused on the binary case study, as multi-class datasets require an additional effort to be addressed. In this research, we overcome these problems by carrying out a combination between feature and instance selections. Feature selection will allow simplifying the overlapping areas easing the generation of rules to distinguish among the classes. Selection of instances from all classes will address the imbalance itself by finding the most appropriate class distribution for the learning task, as well as possibly removing noise and difficult borderline examples. For the sake of obtaining an optimal joint set of features and instances, we embedded the searching for both parameters in a Multi-Objective Evolutionary Algorithm, using the C4.5 decision tree as baseline classifier in this wrapper approach. The multi-objective scheme allows taking a double advantage: the search space becomes broader, and we may provide a set of different solutions in order to build an ensemble of classifiers. This proposal has been contrasted versus several state-of-the-art solutions on imbalanced classification showing excellent results in both binary and multi-class problems.
Single-sensor multispeaker listening with acoustic metamaterials
Xie, Yangbo; Tsai, Tsung-Han; Konneker, Adam; Popa, Bogdan-Ioan; Brady, David J.; Cummer, Steven A.
2015-01-01
Designing a “cocktail party listener” that functionally mimics the selective perception of a human auditory system has been pursued over the past decades. By exploiting acoustic metamaterials and compressive sensing, we present here a single-sensor listening device that separates simultaneous overlapping sounds from different sources. The device with a compact array of resonant metamaterials is demonstrated to distinguish three overlapping and independent sources with 96.67% correct audio recognition. Segregation of the audio signals is achieved using physical layer encoding without relying on source characteristics. This hardware approach to multichannel source separation can be applied to robust speech recognition and hearing aids and may be extended to other acoustic imaging and sensing applications. PMID:26261314
Lyme disease: a selective medium for isolation of the suspected etiological agent, a spirochete.
Johnson, S E; Klein, G C; Schmid, G P; Bowen, G S; Feeley, J C; Schulze, T
1984-01-01
A simple procedure with a new selective culture medium for the isolation of the suspected etiological agent of Lyme disease from ticks is described. Live ticks (Ixodes dammini) were ground with a mortar and pestle, and the suspensions were inoculated into a selective and nonselective medium. The selective medium, which contained kanamycin and 5-fluorouracil, yielded positive spirochete cultures from 100% of the pooled ticks and from 79% of the single tick specimens. The isolation rate for the nonselective medium was 0% from the tick pools and 58% from the single tick specimens. PMID:6361065
Non-target effects of an introduced biological control agent on deer mouse ecology.
Pearson, D E; McKelvey, K S; Ruggiero, L F
2000-01-01
Release of exotic insects as biological control agents is a common approach to controlling exotic plants. Though controversy has ensued regarding the deleterious direct effects of biological control agents to non-target species, few have examined the indirect effects of a "well-behaved" biological control agent on native fauna. We studied a grassland in west-central Montana infested with spotted knapweed (Centaurea maculosa) to examine the effects of knapweed invasion and two gall flybiological control agents (Urophora affinis and U. quadrifasciata) on the native deer mouse (Peromyscus maniculatus). Stomach-content analysis revealed that Urophora were the primary food item in Peromyscus diets for most of the year and made up 84-86% of the winter diet. Stomach contents indicated that wild-caught mice consumed on average up to 247 Urophora larvae mouse -1 day -1 , while feeding trials revealed that deer mice could depredate nearly 5 times as many larvae under laboratory conditions. In feeding trials, deer mice selected knapweed seedheads with greater numbers of galls while avoiding uninfested seedheads. When Urophora larvae were present in knapweed seedheads, deer mice selected microhabitats with moderately high (31-45% cover) and high knapweed infestation (≥46% cover). After Urophora emerged and larvae were unavailable to Peromyscus, mice reversed habitat selection to favor sites dominated by native-prairie with low knapweed infestation (0-15%). Establishment of the biological control agent, Urophora spp., has altered deer mouse diets and habitat selection by effecting changes in foraging strategies. Deer mice and other predators may reduce Urophora populations below a threshold necessary to effectively control spotted knapweed.
[Application of niche theory in evaluation of main tourism scenic areas in Zhangjiajie City].
Xiang, Yan-ping; Xiang, Chang-guo; Chen, You-lian
2010-05-01
Five tourism scenic areas in Zhangjiajie City were selected as research objects, and fifty kinds of resource conditions affecting the development of tourism scenic area were taken as evaluation indices. Through disposing and consolidating the indices level by level, an analysis was made on the niche breadth and niche overlap of the five tourism scenic areas at three levels (I, II, and III). In the five scenic areas, index level had significant effects on the niche breadth (F = 10.278, P = 0.006), but less effects on the relative niche breadth, suggesting that in the evaluation of the development potential of tourism scenic area, relative niche breadth was more reasonable than absolute niche breadth. From level III to level I, the niche overlap of the five scenic areas was increasing, indicating that level choice would affect the evaluation of the actual niche overlap of the scenic areas. With the progressive refinement of the indices to certain level, and when the difference between observed and Monte Carlo-simulated Pianka indices achieved to significant level, this index level could be used as the minimum standard of the refinement, and the simulated niche overlap could be taken as an important reference in the competition evaluation of tourism scenic area.
AMD-stability in the presence of first-order mean motion resonances
NASA Astrophysics Data System (ADS)
Petit, A. C.; Laskar, J.; Boué, G.
2017-11-01
The angular momentum deficit (AMD)-stability criterion allows to discriminate between a priori stable planetary systems and systems for which the stability is not granted and needs further investigations. AMD-stability is based on the conservation of the AMD in the averaged system at all orders of averaging. While the AMD criterion is rigorous, the conservation of the AMD is only granted in absence of mean-motion resonances (MMR). Here we extend the AMD-stability criterion to take into account mean-motion resonances, and more specifically the overlap of first-order MMR. If the MMR islands overlap, the system will experience generalized chaos leading to instability. The Hamiltonian of two massive planets on coplanar quasi-circular orbits can be reduced to an integrable one degree of freedom problem for period ratios close to a first-order MMR. We use the reduced Hamiltonian to derive a new overlap criterion for first-order MMR. This stability criterion unifies the previous criteria proposed in the literature and admits the criteria obtained for initially circular and eccentric orbits as limit cases. We then improve the definition of AMD-stability to take into account the short term chaos generated by MMR overlap. We analyze the outcome of this improved definition of AMD-stability on selected multi-planet systems from the Extrasolar Planets Encyclopædia.
Solvent signal suppression for high-resolution MAS-DNP
NASA Astrophysics Data System (ADS)
Lee, Daniel; Chaudhari, Sachin R.; De Paëpe, Gaël
2017-05-01
Dynamic nuclear polarization (DNP) has become a powerful tool to substantially increase the sensitivity of high-field magic angle spinning (MAS) solid-state NMR experiments. The addition of dissolved hyperpolarizing agents usually results in the presence of solvent signals that can overlap and obscure those of interest from the analyte. Here, two methods are proposed to suppress DNP solvent signals: a Forced Echo Dephasing experiment (FEDex) and TRAnsfer of Populations in DOuble Resonance Echo Dephasing (TRAPDORED) NMR. These methods reintroduce a heteronuclear dipolar interaction that is specific to the solvent, thereby forcing a dephasing of recoupled solvent spins and leaving acquired NMR spectra free of associated resonance overlap with the analyte. The potency of these methods is demonstrated on sample types common to MAS-DNP experiments, namely a frozen solution (of L-proline) and a powdered solid (progesterone), both containing deuterated glycerol as a DNP solvent. The proposed methods are efficient, simple to implement, compatible with other NMR experiments, and extendable past spectral editing for just DNP solvents. The sensitivity gains from MAS-DNP in conjunction with FEDex or TRAPDORED then permits rapid and uninterrupted sample analysis.
[Optimal use of MRI mammography from the economic viewpoint].
Oellinger, H; Blohmer, J U; Siewert, C; Hadijuana, J; Gutberlet, M; Ehrenstein, T; Lichtenegger, W; Felix, R
1998-01-01
With the introduction of the contrast agent gadolinum DTPA there were hopes that "MRM" would prove to be the investigatory technique that would largely solve the problems of breast diagnostics. However, after the early years of acceptance, the new method of investigation became a subject of controversy. Nonetheless, MRM today occupies a recognized place in diagnostics for certain indications. It is still true, however, that reliable use of this procedure requires a great deal of experience, since there is a relatively large area of overlap between benign and malignant tumors. Further, the costs are significantly higher than those for conventional methods of investigation. New studies that have been conducted at the Charité, Campus Virchow Medical Center in Berlin, suggest that, if one takes the relevant indications into account, MRM can be economic and contribute significantly to cost reduction. Application of a newly developed software package has shown that the good discrimination in a suspect area resulting from contrast agent enhancement makes possible a reliable differentiation between malignant and benign tissue changes. A further result was that, when certain boundary conditions are satisfied, a contrast agent bolus of 0.1 mmol/kg BW is sufficient, making a double dose (0.2 mmol/kg BW) unnecessary.
Preferential partner selection in an evolutionary study of Prisoner's Dilemma.
Ashlock, D; Smucker, M D; Stanley, E A; Tesfatsion, L
1996-01-01
Partner selection is an important process in many social interactions, permitting individuals to decrease the risks associated with cooperation. In large populations, defectors may escape punishment by roving from partner to partner, but defectors in smaller populations risk social isolation. We investigate these possibilities for an evolutionary Prisoner's Dilemma in which agents use expected payoffs to choose and refuse partners. In comparison to random or round-robin partner matching, we find that the average payoffs attained with preferential partner selection tend to be more narrowly confined to a few isolated payoff regions. Most ecologies evolve to essentially full cooperative behavior, but when agents are intolerant of defections, or when the costs of refusal and social isolation are small, we also see the emergence of wallflower ecologies in which all agents are socially isolated. Between these two extremes, we see the emergence of ecologies whose agents tend to engage in a small number of defections followed by cooperation thereafter. The latter ecologies exhibit a plethora of interesting social interaction patterns.
Welliver, Mark; McDonough, John; Kalynych, Nicholas; Redfern, Robert
2008-01-01
Neuromuscular blockade, induced by neuromuscular blocking agents, has allowed prescribed immobility, improved surgical exposure, optimal airway management conditions, and facilitated mechanical ventilation. However, termination of the effects of neuromuscular blocking agents has, until now, remained limited. A novel cyclodextrin encapsulation process offers improved termination of the paralytic effects of aminosteroidal non-depolarizing neuromuscular blocking agents. Sugammadex sodium is the first in a new class of drug called selective relaxant binding agents. Currently, in clinical trials, sugammadex, a modified gamma cyclodextrin, has shown consistent and rapid termination of neuromuscular blockade with few side effects. The pharmacology of cyclodextrins in general and sugammadex in particular, together with the results of current clinical research are reviewed. The ability of sugammadex to terminate the action of neuromuscular blocking agents by direct encapsulation is compared to the indirect competitive antagonism of their effects by cholinesterase inhibitors. Also discussed are the clinical implications that extend beyond fast, effective reversal, including numerous potential perioperative benefits. PMID:19920893
An enhanced performance through agent-based secure approach for mobile ad hoc networks
NASA Astrophysics Data System (ADS)
Bisen, Dhananjay; Sharma, Sanjeev
2018-01-01
This paper proposes an agent-based secure enhanced performance approach (AB-SEP) for mobile ad hoc network. In this approach, agent nodes are selected through optimal node reliability as a factor. This factor is calculated on the basis of node performance features such as degree difference, normalised distance value, energy level, mobility and optimal hello interval of node. After selection of agent nodes, a procedure of malicious behaviour detection is performed using fuzzy-based secure architecture (FBSA). To evaluate the performance of the proposed approach, comparative analysis is done with conventional schemes using performance parameters such as packet delivery ratio, throughput, total packet forwarding, network overhead, end-to-end delay and percentage of malicious detection.
ERIC Educational Resources Information Center
Krauss, George E.
2009-01-01
The purpose of this study is to understand how selected insurance practitioners learn and developed in their practices setting. The selected insurance practitioners (collectively customer service representatives, insurance agents, and risk managers) are responsible for the counseling and placement of insurance products and the implementation of…
Identification of Drugs Inducing Phospholipidosis by Novel in vitro Data
Muehlbacher, Markus; Tripal, Philipp; Roas, Florian; Kornhuber, Johannes
2012-01-01
Drug-induced phospholipidosis (PLD) is a lysosomal storage disorder characterized by the accumulation of phospholipids within the lysosome. This adverse drug effect can occur in various tissues and is suspected to impact cellular viability. Therefore, it is important to test chemical compounds for their potential to induce PLD during the drug design process. PLD has been reported to be a side effect of many commonly used drugs, especially those with cationic amphiphilic properties. To predict drug-induced PLD in silico, we established a high-throughput cell-culture-based method to quantitatively determine the induction of PLD by chemical compounds. Using this assay, we tested 297 drug-like compounds at two different concentrations (2.5 μm and 5.0 μm). We were able to identify 28 previously unknown PLD-inducing agents. Furthermore, our experimental results enabled the development of a binary classification model to predict PLD-inducing agents based on their molecular properties. This random forest prediction system yields a bootstrapped validated accuracy of 86 %. PLD-inducing agents overlap with those that target similar biological processes; a high degree of concordance with PLD-inducing agents was identified for cationic amphiphilic compounds, small molecules that inhibit acid sphingomyelinase, compounds that cross the blood–brain barrier, and compounds that violate Lipinski’s rule of five. Furthermore, we were able to show that PLD-inducing compounds applied in combination additively induce PLD. PMID:22945602
The Identity and Identity Identification of Teachers
ERIC Educational Resources Information Center
Qu, Zhengwei
2008-01-01
When we tend to analyze the living conditions of teachers, system arrangement and identity identification can be considered a significant method for analysis. In reality, there appears a phenomenon of overlapping identification in the identity identification of teachers in China, which leads to plural selections in the identification manners of…
E. J. Fichtner; D. M. Rizzo; S. A. Kirk; J. F. Webber
2011-01-01
Phytophthora kernoviae exhibits comparable epidemiology to Phytophthora ramorum in invaded UK woodlands. Because both pathogens have an overlapping geographic range in the UK and often concurrently invade the same site, it is speculated that P. kernoviae may also invade North American (NA) forests...
A Comparison of Selected Bibliographic Database Subject Overlap for Agricultural Information
ERIC Educational Resources Information Center
Ritchie, Stephanie M.; Young, Lauren M.; Sigman, Jessica
2018-01-01
Agricultural researchers and science librarians must understand which research literature databases provide the most comprehensive coverage of agricultural subjects to support their inquiries. Once the domain of a few specialized databases, agricultural research literature is now covered by broad, multidisciplinary databases. The purpose of this…
[Guidelines for the treatment of constipation].
Park, Moo In; Shin, Jeong Eun; Myung, Seung Jae; Huh, Kyu Chan; Choi, Chang Hwan; Jung, Sung Ae; Choi, Suck Chei; Sohn, Chong Il; Choi, Myung Gyu
2011-02-01
While constipation is a common symptom in Korea, there are no existing treatment guidelines. Although constipation may occur as a result of organic cause, there is no obstructive mucosal or structural cause in the vast majority of patients with constipation. The present paper deals with only the management of functional constipation: lifestyle changes; bulking agents and stool softeners; osmotic agents; stimulant laxatives; prokinetics; biofeedback and surgical treatments. Exercise and dietary fiber are helpful in some patients with constipation. Laxatives including bulking agents, stool softeners, osmotic agents, and stimulant laxatives have been found to be more effective than placebo at relieving symptoms of constipation. New enterokinetic agents that affect peristalsis through selective interaction with 5-hydroxytryptamine-4 receptors can be effective in patients with constipation who cannot get adequate relief from current laxatives. Biofeedback can relieve symptoms in selected patients with pelvic floor dyssynergia. Surgical treatments can be helpful in some patients with refractory constipation.
Díaz-Orueta, Unai; Blanco-Campal, Alberto; Burke, Teresa
2018-05-01
ABSTRACTBackground:A detailed neuropsychological assessment plays an important role in the diagnostic process of Mild Cognitive Impairment (MCI). However, available brief cognitive screening tests for this clinical population are administered and interpreted based mainly, or exclusively, on total achievement scores. This score-based approach can lead to erroneous clinical interpretations unless we also pay attention to the test taking behavior or to the type of errors committed during test performance. The goal of the current study is to perform a rapid review of the literature regarding cognitive screening tools for dementia in primary and secondary care; this will include revisiting previously published systematic reviews on screening tools for dementia, extensive database search, and analysis of individual references cited in selected studies. A subset of representative screening tools for dementia was identified that covers as many cognitive functions as possible. How these screening tools overlap with each other (in terms of the cognitive domains being measured and the method used to assess them) was examined and a series of process-based approach (PBA) modifications for these overlapping features was proposed, so that the changes recommended in relation to one particular cognitive task could be extrapolated to other screening tools. It is expected that future versions of cognitive screening tests, modified using a PBA, will highlight the benefits of attending to qualitative features of test performance when trying to identify subtle features suggestive of MCI and/or dementia.
Home range overlap as a driver of intelligence in primates.
Grueter, Cyril C
2015-04-01
Various socioecological factors have been suggested to influence cognitive capacity in primates, including challenges associated with foraging and dealing with the complexities of social life. Alexander [Alexander, 1989]. Evolution of the human psyche. In: Mellars P, Stringer C, editors. The human revolution: Behavioural and biological perspectives on the origins of modern humans. Princeton: Princeton University Press. p 455-513] proposed an integrative model for the evolution of human cognitive abilities and complex sociality that incorporates competition among coalitions of conspecifics (inter-group conflict) as a major selective pressure. However, one of the premises of this model, i.e., that when confronted with inter-group conflict selection should favor enhanced cognition, has remained empirically untested. Using a comparative approach on species data, I aimed to test the prediction that primate species (n = 104) that face greater inter-group conflict have higher cognitive abilities (indexed by endocranial volume). The degree of inter-group conflict/complexity was approximated via the variable home range overlap among groups. I found a significant relationship between home range overlap and endocranial volume, even after controlling for other predictor variables and covariates such as group size and body mass. I conclude that brain size evolution cannot be attributed exclusively to social factors such as group size, but likely reflects a variety of social and ecological determinants including inter-group conflict which poses cognitive demands on monitoring both the wider social milieu as well as spatial attributes of the habitat. © 2014 Wiley Periodicals, Inc.
Method for distinguishing normal and transformed cells using G1 kinase inhibitors
Crissman, Harry A.; Gadbois, Donna M.; Tobey, Robert A.; Bradbury, E. Morton
1993-01-01
A G.sub.1 phase kinase inhibitor is applied in a low concentration to a population of normal and transformed mammalian cells. The concentration of G.sub.1 phase kinase inhibitor is selected to reversibly arrest normal mammalian cells in the G.sub.1 cell cycle without arresting growth of transformed cells. The transformed cells may then be selectively identified and/or cloned for research or diagnostic purposes. The transformed cells may also be selectively killed by therapeutic agents that do not affect normal cells in the G.sub.1 phase, suggesting that such G.sub.1 phase kinase inhibitors may form an effective adjuvant for use with chemotherapeutic agents in cancer therapy for optimizing the killing dose of chemotherapeutic agents while minimizing undesirable side effects on normal cells.
Method for distinguishing normal and transformed cells using G1 kinase inhibitors
Crissman, H.A.; Gadbois, D.M.; Tobey, R.A.; Bradbury, E.M.
1993-02-09
A G[sub 1] phase kinase inhibitor is applied in a low concentration to a population of normal and transformed mammalian cells. The concentration of G[sub 1] phase kinase inhibitor is selected to reversibly arrest normal mammalian cells in the G[sub 1] cell cycle without arresting growth of transformed cells. The transformed cells may then be selectively identified and/or cloned for research or diagnostic purposes. The transformed cells may also be selectively killed by therapeutic agents that do not affect normal cells in the G[sub 1] phase, suggesting that such G[sub 1] phase kinase inhibitors may form an effective adjuvant for use with chemotherapeutic agents in cancer therapy for optimizing the killing dose of chemotherapeutic agents while minimizing undesirable side effects on normal cells.
Integrating fluoroquinolones into the hospital formulary.
Bertino, J S
2001-10-01
With the increasing availability of new agents, selection of fluoroquinolones for formulary inclusion can be difficult. Appropriate evaluation of the important characteristics (pharmacokinetic and pharmacodynamic properties, antimicrobial activity, efficacy, tolerability, cost) of these agents should allow selection of the most cost-effective ones. Evidence from in vitro studies and clinical trials indicates differences exist among fluoroquinolones, especially in terms of activity against gram-positive, aerobic organisms. For selected clinical situations, it may be important to choose an agent that is available in both intravenous and oral formulations. Comparative drug costs, as well as costs associated with potential clinical failure and adverse events, should be evaluated carefully. Dosage regimens should be considered, as shorter durations of therapy and less frequent dose administration may lead to reduced labor costs and increased patient compliance, thereby improving effectiveness and economic efficiency.
DNA capture elements for rapid detection and identification of biological agents
NASA Astrophysics Data System (ADS)
Kiel, Johnathan L.; Parker, Jill E.; Holwitt, Eric A.; Vivekananda, Jeeva
2004-08-01
DNA capture elements (DCEs; aptamers) are artificial DNA sequences, from a random pool of sequences, selected for their specific binding to potential biological warfare agents. These sequences were selected by an affinity method using filters to which the target agent was attached and the DNA isolated and amplified by polymerase chain reaction (PCR) in an iterative, increasingly stringent, process. Reporter molecules were attached to the finished sequences. To date, we have made DCEs to Bacillus anthracis spores, Shiga toxin, Venezuelan Equine Encephalitis (VEE) virus, and Francisella tularensis. These DCEs have demonstrated specificity and sensitivity equal to or better than antibody.
Effects of β-blocker selectivity on blood pressure variability and stroke: a systematic review.
Webb, Alastair John Stewart; Fischer, Urs; Rothwell, Peter Malcolm
2011-08-23
β-Blockers increase variability in systolic blood pressure (SBP), which probably explains their lesser effectiveness in preventing stroke vs myocardial infarction compared with other agents. This increase in variability in blood pressure (BP) may be particularly marked on non-cardioselective agents, potentially calling into question the widespread first-line use of propranolol in migraine with aura, elderly patients with essential tremor or anxiety, and other groups at risk of stroke. We determined β-blocker subclass effects on variability in BP and stroke risk in a systematic review of randomized controlled trials (RCTs) comparing different types of β-blocker with placebo or other agents. We determined pooled estimates of the effect of treatment on group variability in BP (ratio of the variances [VR]) and on the risk of stroke vs myocardial infarction during follow-up. Compared with other antihypertensives, variability in SBP was increased more by nonselective β-blockers (VR=1.34, 1.13-1.59, p =0.002, 25 comparisons, 9,992 patients) than by β1-selective agents (VR=1.09, 95% confidence interval 1.00-1.19, p =0.053, 68 comparisons, 40,746 patients; difference-p =0.038). In direct comparisons, variability in SBP was also significantly lower with β1-selective vs nonselective β-blockers (VR=0.81, 0.68-0.97, p =0.03, 18 comparisons, 954 patients). In comparisons with other antihypertensives, the increase in stroke risk with nonselective β-blockers ([OR]=2.29, 1.32-3.96, p =0.002) was more marked than with β1-selective agents (OR=1.24, 1.08-1.42, p =0.003, difference-p =0.03), as was the risk of stroke relative to the risk of myocardial infarction: OR=1.50 (0.93-2.42) vs 0.99 (0.82-1.19). Use of β1-selective rather than nonselective agents may be advisable when β-blockers are indicated for patients at risk of stroke.
Miranda, Magdalena; Kent, Brianne A.; Weisstaub, Noelia V.
2017-01-01
Abstract Successful memory involves not only remembering over time but also keeping memories distinct. The ability to separate similar experiences into distinct memories is a main feature of episodic memory. Discrimination of overlapping representations has been investigated in the dentate gyrus of the hippocampus (DG), but little is known about this process in other regions such as the perirhinal cortex (Prh). We found in male rats that perirhinal brain-derived neurotrophic factor (BDNF) is required for separable storage of overlapping, but not distinct, object representations, which is identical to its role in the DG for spatial representations. Also, activity-regulated cytoskeletal-associated protein (Arc) is required for disambiguation of object memories, as measured by infusion of antisense oligonucleotides. This is the first time Arc has been implicated in the discrimination of objects with overlapping features. Although molecular mechanisms for object memory have been shown previously in Prh, these have been dependent on delay, suggesting a role specifically in memory duration. BDNF and Arc involvement were independent of delay—the same demand for memory persistence was present in all conditions—but only when discrimination of similar objects was required were these mechanisms recruited and necessary. Finally, we show that BDNF and Arc participate in the same pathway during consolidation of overlapping object memories. We provide novel evidence regarding the proteins involved in disambiguation of object memories outside the DG and suggest that, despite the anatomical differences, similar mechanisms underlie this process in the DG and Prh that are engaged depending on the similarity of the stimuli. PMID:29085903
Brain activity during auditory and visual phonological, spatial and simple discrimination tasks.
Salo, Emma; Rinne, Teemu; Salonen, Oili; Alho, Kimmo
2013-02-16
We used functional magnetic resonance imaging to measure human brain activity during tasks demanding selective attention to auditory or visual stimuli delivered in concurrent streams. Auditory stimuli were syllables spoken by different voices and occurring in central or peripheral space. Visual stimuli were centrally or more peripherally presented letters in darker or lighter fonts. The participants performed a phonological, spatial or "simple" (speaker-gender or font-shade) discrimination task in either modality. Within each modality, we expected a clear distinction between brain activations related to nonspatial and spatial processing, as reported in previous studies. However, within each modality, different tasks activated largely overlapping areas in modality-specific (auditory and visual) cortices, as well as in the parietal and frontal brain regions. These overlaps may be due to effects of attention common for all three tasks within each modality or interaction of processing task-relevant features and varying task-irrelevant features in the attended-modality stimuli. Nevertheless, brain activations caused by auditory and visual phonological tasks overlapped in the left mid-lateral prefrontal cortex, while those caused by the auditory and visual spatial tasks overlapped in the inferior parietal cortex. These overlapping activations reveal areas of multimodal phonological and spatial processing. There was also some evidence for intermodal attention-related interaction. Most importantly, activity in the superior temporal sulcus elicited by unattended speech sounds was attenuated during the visual phonological task in comparison with the other visual tasks. This effect might be related to suppression of processing irrelevant speech presumably distracting the phonological task involving the letters. Copyright © 2012 Elsevier B.V. All rights reserved.
USDA-ARS?s Scientific Manuscript database
Disease control of soilborne pathogens by biological control agents has often been inconsistent under field conditions. One factor that may contribute to this inconsistency is the variability in response among pathogen populations and/or communities to the selected biological control agent. One hund...
Issues of Dynamic Coalition Formation Among Rational Agents
2002-04-01
approaches of forming stable coalitions among rational agents. Issues and problems of dynamic coalition environments are discussed in section 3 while...2.2. 2.1.2 Coalition Algorithm, Coalition Formation Environment and Model Rational agents which are involved in a co-operative game (A,v) are...publicly available simulation environment for coalition formation among rational information agents based on selected classic coalition theories is, for
Meystre, Stéphane M; Ferrández, Óscar; Friedlin, F Jeffrey; South, Brett R; Shen, Shuying; Samore, Matthew H
2014-08-01
As more and more electronic clinical information is becoming easier to access for secondary uses such as clinical research, approaches that enable faster and more collaborative research while protecting patient privacy and confidentiality are becoming more important. Clinical text de-identification offers such advantages but is typically a tedious manual process. Automated Natural Language Processing (NLP) methods can alleviate this process, but their impact on subsequent uses of the automatically de-identified clinical narratives has only barely been investigated. In the context of a larger project to develop and investigate automated text de-identification for Veterans Health Administration (VHA) clinical notes, we studied the impact of automated text de-identification on clinical information in a stepwise manner. Our approach started with a high-level assessment of clinical notes informativeness and formatting, and ended with a detailed study of the overlap of select clinical information types and Protected Health Information (PHI). To investigate the informativeness (i.e., document type information, select clinical data types, and interpretation or conclusion) of VHA clinical notes, we used five different existing text de-identification systems. The informativeness was only minimally altered by these systems while formatting was only modified by one system. To examine the impact of de-identification on clinical information extraction, we compared counts of SNOMED-CT concepts found by an open source information extraction application in the original (i.e., not de-identified) version of a corpus of VHA clinical notes, and in the same corpus after de-identification. Only about 1.2-3% less SNOMED-CT concepts were found in de-identified versions of our corpus, and many of these concepts were PHI that was erroneously identified as clinical information. To study this impact in more details and assess how generalizable our findings were, we examined the overlap between select clinical information annotated in the 2010 i2b2 NLP challenge corpus and automatic PHI annotations from our best-of-breed VHA clinical text de-identification system (nicknamed 'BoB'). Overall, only 0.81% of the clinical information exactly overlapped with PHI, and 1.78% partly overlapped. We conclude that automated text de-identification's impact on clinical information is small, but not negligible, and that improved clinical acronyms and eponyms disambiguation could significantly reduce this impact. Copyright © 2014 Elsevier Inc. All rights reserved.
Prenatal Polyunsaturated Fatty Acid Levels and Risk of Autism Spectrum
2017-10-01
for the purpose of enhancing public understanding and increasing interest in learning and careers in science, technology, and the humanities ...in use or care of human subjects, vertebrate animals, biohazards, and/or select agents No significant changes in approach have been made. We did... human subjects, vertebrate animals, biohazards, and/or select agents during the reporting period. If required, were these changes approved by the
ERIC Educational Resources Information Center
Linares-Palomino, Pablo J.; Salido, Sofia; Altarejos, Joaquin; Nogueras, Manuel; Sanchez, Adolfo
2006-01-01
The selective syntheses of the cyclic monoterpenoids alpha-terpineol or alpha-cyclogeraniol from the acyclic monoterpenoid nerol using p-toluenesulfonic acid or chlorosulfonic acid as cyclizing agents, respectively, are described. The different behavior of nerol under diverse experimental conditions such as nature of the acid agents, solvents, and…
Pleticha, Josef; Maus, Timothy P; Jeng-Singh, Christian; Marsh, Michael P; Al-Saiegh, Fadi; Christner, Jodie A; Lee, Kendall H; Beutler, Andreas S
2013-05-30
Intrathecal (IT) administration is an important route of drug delivery, and its modelling in a large animal species is of critical value. Although domestic swine is the preferred species for preclinical pharmacology, no minimally invasive method has been established to deliver agents into the IT space. While a "blind" lumbar puncture (LP) can sample cerebrospinal fluid (CSF), it is unreliable for drug delivery in pigs. Using computed tomography (CT), we determined the underlying anatomical reasons for this irregularity. The pig spinal cord was visualised terminating at the S2-S3 level. The lumbar region contained only small amounts of CSF found in the lateral recess. Additional anatomical constraints included ossification of the midline ligaments, overlapping lamina with small interlaminar spaces, and a large bulk of epidural adipose tissue. Accommodating the the pig CT anatomy, we developed a lateral LP (LLP) injection technique that employs advanced planning of the needle path and monitoring of the IT injection progress. The key features of the LLP procedure involved choosing a vertebral level without overlapping lamina or spinal ligament ossification, a needle trajectory crossing the midline, and entering the IT space in its lateral recess. Effective IT delivery was validated by the injection of contrast media to obtain a CT myelogram. LLP represents a safe and reliable method to deliver agents to the lumbar pig IT space, which can be implemented in a straightforward way by any laboratory with access to CT equipment. Therefore, LLP is an attractive large animal model for preclinical studies of IT therapies. Copyright © 2013 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Frye-Mason, Greg; Leuschen, Martin; Wald, Lara; Paul, Kateri; Hancock, Lawrence F.
2005-05-01
A reactive chromophore developed at MIT exhibits sensitive and selective detection of surrogates for G-class nerve agents. This reporter acts by reacting with the agent to form an intermediate that goes through an internal cyclization reaction. The reaction locks the molecule into a form that provides a strong fluorescent signal. Using a fluorescent sensor platform, Nomadics has demonstrated rapid and sensitive detection of reactive simulants such as diethyl chloro-phosphate (simulant for sarin, soman, and related agents) and diethyl cyanophosphate (simulant for tabun). Since the unreacted chromophore does not fluoresce at the excitation wavelength used for the cyclized reporter, the onset of fluo-rescence can be easily detected. This fluorescence-based detection method provides very high sensitivity and could enable rapid detection at permissible exposure levels. Tests with potential interferents show that the reporter is very selective, with responses from only a few highly toxic, electrophilic chemicals such as phosgene, thionyl chloride, and strong acids such as HF, HCl, and nitric acid. Dimethyl methyl phosphonate (DMMP), a common and inactive simu-lant for other CW detectors, is not reactive enough to generate a signal. The unique selectivity to chemical reactivity means that a highly toxic and hazardous chemical is present when the reporter responds and illustrates that this sensor can provide very low false alarm rates. Current efforts focus on demonstrating the sensitivity and range of agents and toxic industrial chemicals detected with this reporter as well as developing additional fluorescent reporters for a range of chemical reactivity classes. The goal is to produce a hand-held sensor that can sensitively detect a broad range of chemical warfare agent and toxic industrial chemical threats.
Mutyam, Venkateshwar; Du, Ming; Xue, Xiaojiao; Keeling, Kim M; White, E Lucile; Bostwick, J Robert; Rasmussen, Lynn; Liu, Bo; Mazur, Marina; Hong, Jeong S; Falk Libby, Emily; Liang, Feng; Shang, Haibo; Mense, Martin; Suto, Mark J; Bedwell, David M; Rowe, Steven M
2016-11-01
Premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Several agents are known to suppress PTCs but are poorly efficacious or toxic. To determine whether there are clinically available agents that elicit translational readthrough and improve CFTR function sufficient to confer therapeutic benefit to patients with CF with PTCs. Two independent screens, firefly luciferase and CFTR-mediated transepithelial chloride conductance assay, were performed on a library of 1,600 clinically approved compounds using fisher rat thyroid cells stably transfected with stop codons. Select agents were further evaluated using secondary screening assays including short circuit current analysis on primary cells from patients with CF. In addition, the effect of CFTR modulators (ivacaftor) was tested in combination with the most efficacious agents. From the primary screen, 48 agents were selected as potentially active. Following confirmatory tests in the transepithelial chloride conductance assay and prioritizing agents based on favorable pharmacologic properties, eight agents were advanced for secondary screening. Ivacaftor significantly increased short circuit current following forskolin stimulation in cells treated with pyranoradine tetraphosphate, potassium p-aminobenzoate, and escin as compared with vehicle control. Escin, an herbal agent, consistently induced readthrough activity as demonstrated by enhanced CFTR expression and function in vitro. Clinically approved drugs identified as potential readthrough agents, in combination with ivacaftor, may induce nonsense suppression to restore therapeutic levels of CFTR function. One or more agents may be suitable to advance to human testing.
Noradrenergic modulation of neural erotic stimulus perception.
Graf, Heiko; Wiegers, Maike; Metzger, Coraline Danielle; Walter, Martin; Grön, Georg; Abler, Birgit
2017-09-01
We recently investigated neuromodulatory effects of the noradrenergic agent reboxetine and the dopamine receptor affine amisulpride in healthy subjects on dynamic erotic stimulus processing. Whereas amisulpride left sexual functions and neural activations unimpaired, we observed detrimental activations under reboxetine within the caudate nucleus corresponding to motivational components of sexual behavior. However, broadly impaired subjective sexual functioning under reboxetine suggested effects on further neural components. We now investigated the same sample under these two agents with static erotic picture stimulation as alternative stimulus presentation mode to potentially observe further neural treatment effects of reboxetine. 19 healthy males were investigated under reboxetine, amisulpride and placebo for 7 days each within a double-blind cross-over design. During fMRI static erotic picture were presented with preceding anticipation periods. Subjective sexual functions were assessed by a self-reported questionnaire. Neural activations were attenuated within the caudate nucleus, putamen, ventral striatum, the pregenual and anterior midcingulate cortex and in the orbitofrontal cortex under reboxetine. Subjective diminished sexual arousal under reboxetine was correlated with attenuated neural reactivity within the posterior insula. Again, amisulpride left neural activations along with subjective sexual functioning unimpaired. Neither reboxetine nor amisulpride altered differential neural activations during anticipation of erotic stimuli. Our results verified detrimental effects of noradrenergic agents on neural motivational but also emotional and autonomic components of sexual behavior. Considering the overlap of neural network alterations with those evoked by serotonergic agents, our results suggest similar neuromodulatory effects of serotonergic and noradrenergic agents on common neural pathways relevant for sexual behavior. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.
Bupathi, Manojkumar; Hajjar, Joud; Bean, Stacie; Fu, Siqing; Hong, David; Karp, Daniel; Stephen, Bettzy; Hess, Kenneth; Meric-Bernstam, Funda; Naing, Aung
2017-02-01
Infusion reactions (IRs) to anti-neoplastic agents require prompt recognition and immediate treatment to avert significant complications. We conducted a retrospective review of the medical records of consecutive patients who received anti-neoplastic therapy in the outpatient treatment center of the Department of Investigational Cancer Therapeutics from January 1, 2013 to November 30, 2013. Of the 597 patients who received treatment, 9 (1.5 %) had IRs (all ≤ grade 2). The most common IRs observed on first occurrence were chills (n = 5), itching, rash, and facial flushing (n = 3 each). There were no IR-related deaths. All the IRs were reversible with appropriate symptomatic treatment and the therapy was completed after temporary cessation of infusion in 7 of the 9 patients. The infusion was stopped in 2 patients due to symptoms suggestive of IgE-mediated allergic reaction and cytokine storm. Five of the 8 patients who were re-challenged with the same therapy developed a similar reaction. However, the infusion was completed in 4 of the 5 patients after administration of intravenous diphenhydramine and/or hydrocortisone, or slowing the rate of infusion. And, subsequent cycles with the same agents were uneventful. IRs to anti-neoplastic agents are rare. Though the clinical presentations are overlapping, most IRs are not IgE-mediated allergic reactions. Appropriate premedication and slow rate of infusion facilitates uneventful administration of the anti-neoplastic agents in subsequent cycles. Further study in a larger cohort of patients to identify biomarkers of hypersensitivity is warranted.
Locus-specific ancestry to detect recent response to selection in admixed Swiss Fleckvieh cattle.
Khayatzadeh, N; Mészáros, G; Utsunomiya, Y T; Garcia, J F; Schnyder, U; Gredler, B; Curik, I; Sölkner, J
2016-12-01
Identification of selection signatures is one of the current endeavors of evolutionary genetics. Admixed populations may be used to infer post-admixture selection. We calculated local ancestry for Swiss Fleckvieh, a composite of Simmental (SI) and Red Holstein Friesian (RHF), to infer such signals. Illumina Bovine SNP50 BeadChip data for 300 admixed, 88 SI and 97 RHF bulls were used. The average RHF ancestry across the whole genome was 0.70. To identify regions with high deviation from average, we considered two significance thresholds, based on a permutation test and extreme deviation from normal distribution. Regions on chromosomes 13 (46.3-47.3 Mb) and 18 (18.7-25.9 Mb) passed both thresholds in the direction of increased SI. Extended haplotype homozygosity within (iHS) and between (Rsb) populations was calculated to explore additional patterns of pre- and post-admixture selection signals. The Rsb score of admixed and SI was significant in a wide region of chromosome 18 (6.6-24.6 Mb) overlapped with one area of strong local ancestry deviation. FTO, with pleiotropic effect on milk and fertility, NOD2 on dairy and NKD1 and SALL1 on fertility traits are located there. Genetic differentiation of RHF and SI (F st ), an alternative indicator of pre-admixture selection in pure populations, was calculated. No considerable overlap of peaks of local ancestry deviations and F st was observed. We found two regions with significant signatures of post-admixture selection in this very young composite, applying comparatively stringent significance thresholds. The signals cover relatively large genomic areas and did not allow pinpointing of the gene(s) responsible for the apparent shift in ancestry proportions. © 2016 Stichting International Foundation for Animal Genetics.
Community-aware task allocation for social networked multiagent systems.
Wang, Wanyuan; Jiang, Yichuan
2014-09-01
In this paper, we propose a novel community-aware task allocation model for social networked multiagent systems (SN-MASs), where the agent' cooperation domain is constrained in community and each agent can negotiate only with its intracommunity member agents. Under such community-aware scenarios, we prove that it remains NP-hard to maximize system overall profit. To solve this problem effectively, we present a heuristic algorithm that is composed of three phases: 1) task selection: select the desirable task to be allocated preferentially; 2) allocation to community: allocate the selected task to communities based on a significant task-first heuristics; and 3) allocation to agent: negotiate resources for the selected task based on a nonoverlap agent-first and breadth-first resource negotiation mechanism. Through the theoretical analyses and experiments, the advantages of our presented heuristic algorithm and community-aware task allocation model are validated. 1) Our presented heuristic algorithm performs very closely to the benchmark exponential brute-force optimal algorithm and the network flow-based greedy algorithm in terms of system overall profit in small-scale applications. Moreover, in the large-scale applications, the presented heuristic algorithm achieves approximately the same overall system profit, but significantly reduces the computational load compared with the greedy algorithm. 2) Our presented community-aware task allocation model reduces the system communication cost compared with the previous global-aware task allocation model and improves the system overall profit greatly compared with the previous local neighbor-aware task allocation model.
Assembly of ordered contigs of cosmids selected with YACs of human chromosome 13
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fischer, S.G.; Cayanis, E.; Boukhgalter, B.
1994-06-01
The authors have developed an efficient method for assembling ordered cosmid contigs aligned to mega-YACs and midi-YACs (average insert sizes of 1.0 and 0.35 Mb, respectively) and used this general method to initiate high-resolution physical mapping of human chromosome 13 (Chr 13). Chr 13-enriched midi-YAC (mYAC) and mega-YAC (MYAC) sublibraries were obtained from corresponding CEPH total human YAC libraries by selecting colonies with inter-Alu PCR probes derived from Chr 13 monochromosomal cell hybrid DNA. These sublibraries were arrayed on filters at high density. In this approach, the MYAC 13 sublibrary is screened by hybridization with cytogenetically assigned Chr 13 DNAmore » probes to select one or a small subset of MYACs. Inter-Alu PCR products from each mYAC are then hybridized to the MYAC and mYAC sublibraries to identify overlapping YACs and to an arrayed Chr 13-specific cosmid library to select corresponding cosmids. The set of selected cosmids, gridded on filters at high density, is hybridized with inter-Alu PCR products from each of the overlapping YACs to identify subsets of cosmids and also with riboprobes from each cosmid of the arrayed set ({open_quotes}cosmid matrix cross-hybridization{close_quotes}). From these data, cosmid contigs are assembled by a specifically designed computer program. Application of this method generates cosmid contigs spanning the length of a MYAC with few gaps. To provide a high-resolution map, ends of cosmids are sequenced at preselected sites to position densely spaced sequence-tagged sites. 33 refs., 7 figs., 1 tab.« less
Reserve networks based on richness hotspots and representation vary with scale.
Shriner, Susan A; Wilson, Kenneth R; Flather, Curtis H
2006-10-01
While the importance of spatial scale in ecology is well established, few studies have investigated the impact of data grain on conservation planning outcomes. In this study, we compared species richness hotspot and representation networks developed at five grain sizes. We used species distribution maps for mammals and birds developed by the Arizona and New Mexico Gap Analysis Programs (GAP) to produce 1-km2, 100-kmn2, 625-km2, 2500-km2, and 10,000-km2 grid cell resolution distribution maps. We used these distribution maps to generate species richness and hotspot (95th quantile) maps for each taxon in each state. Species composition information at each grain size was used to develop two types of representation networks using the reserve selection software MARXAN. Reserve selection analyses were restricted to Arizona birds due to considerable computation requirements. We used MARXAN to create best reserve networks based on the minimum area required to represent each species at least once and equal area networks based on irreplaceability values. We also measured the median area of each species' distribution included in hotspot (mammals and birds of Arizona and New Mexico) and irreplaceability (Arizona birds) networks across all species. Mean area overlap between richness hotspot reserves identified at the five grain sizes was 29% (grand mean for four within-taxon/state comparisons), mean overlap for irreplaceability reserve networks was 32%, and mean overlap for best reserve networks was 53%. Hotspots for mammals and birds showed low overlap with a mean of 30%. Comparison of hotspots and irreplaceability networks showed very low overlap with a mean of 13%. For hotspots, median species distribution area protected within reserves declined monotonically from a high of 11% for 1-km2 networks down to 6% for 10,000-km2 networks. Irreplaceability networks showed a similar, but more variable, pattern of decline. This work clearly shows that map resolution has a profound effect on conservation planning outcomes and that hotspot and representation outcomes may be strikingly dissimilar. Thus, conservation planning is scale dependent, such that reserves developed using coarse-grained data do not subsume fine-grained reserves. Moreover, preserving both full species representation and species rich areas may require combined reserve design strategies.
Competition between SFG and two SHGs in broadband type-I QPM
NASA Astrophysics Data System (ADS)
Dang, Weirui; Chen, Yuping; Gong, Mingjun; Chen, Xianfeng
2013-03-01
In this paper, we have studied the characteristics of second-order nonlinear interactions with band-overlapped type-I quasi-phase-matching (QPM) second harmonic generation (SHG) and sum-frequency generation (SFG), and predicted a blue-shift with a band-narrowing of their bands and a sunken response in the SFG curve, which are due to the phase-matching-dependent competition between band-overlapped SHG and SFG processes. This prediction is then verified by the experiment in an 18-mm-long bulk MgO-doped periodically poled lithium niobate crystal (MgO:PPLN) and may provide the candidate solution to output controlling for flexible broadcast wavelength conversion, channel-selective wavelength conversion and all-optical logic gates by cascaded QPM second-order nonlinear processes.
The algorithm stitching for medical imaging
NASA Astrophysics Data System (ADS)
Semenishchev, E.; Marchuk, V.; Voronin, V.; Pismenskova, M.; Tolstova, I.; Svirin, I.
2016-05-01
In this paper we propose a stitching algorithm of medical images into one. The algorithm is designed to stitching the medical x-ray imaging, biological particles in microscopic images, medical microscopic images and other. Such image can improve the diagnosis accuracy and quality for minimally invasive studies (e.g., laparoscopy, ophthalmology and other). The proposed algorithm is based on the following steps: the searching and selection areas with overlap boundaries; the keypoint and feature detection; the preliminary stitching images and transformation to reduce the visible distortion; the search a single unified borders in overlap area; brightness, contrast and white balance converting; the superimposition into a one image. Experimental results demonstrate the effectiveness of the proposed method in the task of image stitching.
Sub-Audible Speech Recognition Based upon Electromyographic Signals
NASA Technical Reports Server (NTRS)
Jorgensen, Charles C. (Inventor); Agabon, Shane T. (Inventor); Lee, Diana D. (Inventor)
2012-01-01
Method and system for processing and identifying a sub-audible signal formed by a source of sub-audible sounds. Sequences of samples of sub-audible sound patterns ("SASPs") for known words/phrases in a selected database are received for overlapping time intervals, and Signal Processing Transforms ("SPTs") are formed for each sample, as part of a matrix of entry values. The matrix is decomposed into contiguous, non-overlapping two-dimensional cells of entries, and neural net analysis is applied to estimate reference sets of weight coefficients that provide sums with optimal matches to reference sets of values. The reference sets of weight coefficients are used to determine a correspondence between a new (unknown) word/phrase and a word/phrase in the database.
Attention and attribute overlap in preferential choice.
Bhatia, Sudeep
2017-07-01
Attributes that are common, or overlapping, across alternatives in two-alternative forced preferential choice tasks are often non-diagnostic. In many settings, attending to and evaluating these attributes does not help the decision maker determine which of the available alternatives is the most desirable. For this reason, many existing behavioural theories propose that decision makers ignore common attributes while deliberating. Across six experiments, we find that decision makers do direct their attention selectively and ignore attributes that are not present in or associated with either of the available alternatives. However, they are as likely to attend to common attributes as they are to attend to attributes that are unique to a single alternative. These results suggest the need for novel theories of attention in preferential choice.
Zhan, Tingting; Chevoneva, Inna; Iglewicz, Boris
2010-01-01
The family of weighted likelihood estimators largely overlaps with minimum divergence estimators. They are robust to data contaminations compared to MLE. We define the class of generalized weighted likelihood estimators (GWLE), provide its influence function and discuss the efficiency requirements. We introduce a new truncated cubic-inverse weight, which is both first and second order efficient and more robust than previously reported weights. We also discuss new ways of selecting the smoothing bandwidth and weighted starting values for the iterative algorithm. The advantage of the truncated cubic-inverse weight is illustrated in a simulation study of three-components normal mixtures model with large overlaps and heavy contaminations. A real data example is also provided. PMID:20835375
Seymour, Karen E.; Reinblatt, Shauna P.; Benson, Leora; Carnell, Susan
2015-01-01
Attention-deficit/hyperactivity disorder (ADHD) and conditions involving excessive eating (e.g. obesity, binge / loss of control eating) are increasingly prevalent within pediatric populations, and correlational and some longitudinal studies have suggested inter-relationships between these disorders. In addition, a number of common neural correlates are emerging across conditions, e.g. functional abnormalities within circuits subserving reward processing and executive functioning. To explore this potential cross-condition overlap in neurobehavioral underpinnings, we selectively review relevant functional neuroimaging literature, specifically focusing on studies probing i) reward processing, ii) response inhibition, and iii) emotional processing and regulation, and outline three specific shared neurobehavioral circuits. Based on our review, we also identify gaps within the literature that would benefit from further research. PMID:26098969
Study of a Flexible Low Profile Tunable Dipole Antenna Using Barium Strontium Titanate Varactors
NASA Technical Reports Server (NTRS)
Cure, David; Weller, Thomas; Miranda, Felix A.
2014-01-01
In this paper a flexible low profile dipole antenna using a frequency selective surface (FSS) with interdigital barium strontium titanate (BST) varactor-tuned unit cells is presented. The varactor chips were placed only along one dimension of the FSS to avoid the use of vias and simplify the DC bias network. The antenna uses overlapping metallic plates that resemble fish scales as a ground plane to improve the flexibility of the multi-material stack structure. The measured data of the antenna demonstrate tunability from 2.42 GHz to 2.66 GHz and 1.3 dB gain drop when using overlapping metallic plates instead of continuous ground plane. The total antenna thickness is approximately lambda/24.
Satake, Akiharu; Kobuke, Yoshiaki
2007-06-07
This paper reviews selected types of structurally well defined assemblies of porphyrins and phthalocyanines with strong electronic coupling. Face-to-face, head-to-tail, slipped cofacial, and non-parallel dimeric motifs constructed by covalent and non-covalent bonds are compared in the earlier sections. Their molecular orientation, electronic overlap, and absorption and fluorescence properties are discussed with a view towards the development of artificial photosynthetic systems and molecular electronics. Complementary coordination dimers are fully satisfactory in terms of structural stability, orientation factor, pi-electronic overlap, and zero fluorescence quenching. In later sections, several polymeric and macrocyclic porphyrin assemblies constructed by a combination of covalent bonds and complementary coordination bonds are discussed from the viewpoint of light-harvesting antenna functions.
Spectroscopy using the Hadamard Transform V2
NASA Technical Reports Server (NTRS)
Fixsen, D. J.; Greenhouse, M. A.; MacKenty, J. W.; Mather, J. C.
2009-01-01
The IRMOS (infrared multiobject spectrometer) is an imaging dispersive spectrometer, with a micromirror array to select desired objects. In standard operation, the mirrors are "opened" in patterns such that the resulting spectra do not overlap on the detector. The IRMOS can also be operated in a Hadamard mode, in which the spectra are allowed to overlap, but are modulated by opening the mirrors in many combinations. This mode enables the entire field of view to be observed with the same sensitivity as in the standard mode if the uncertainty is dominated by the detector read noise. We explain the concept and discuss the benefits with an example observation of the Orion Trapezium using the 2.1 m telescope at Kitt Peak National Observatory.
Edwards, Trent; Friesen, Craig; Schurman, Jennifer V
2018-03-17
The primary purpose of this study was to compare Rome III and IV evaluation criteria for irritable bowel syndrome (IBS), functional dyspepsia (FD), and an overlap syndrome consisting of both IBS and FD by assessing the frequency of each diagnosis in a population of children with chronic abdominal pain. Frequencies of Rome IV FD subtypes of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) were determined and FD/IBS overlap symptom associations were also assessed. We conducted a cross-sectional retrospective chart review of 106 pediatric patients who had completed standardized medical histories as part of their evaluation for chronic abdominal pain. The patients ranged from eight to 17 years of age and reported having abdominal pain at least weekly for 8 weeks. Patients whose evaluation revealed gastrointestinal disease were excluded. The patients' diagnoses were determined by a single pediatric gastroenterologist utilizing the specific criteria for Rome III and IV, respectively. Patients were significantly more likely to be diagnosed with FD (84.9% vs. 52.8%), IBS (69.8% vs. 34%), and FD/IBS overlap (58.5% vs. 17.9%) by Rome IV criteria, as compared to Rome III criteria. With regard to Rome IV FD subtypes, 81.1% fulfilled criteria for PDS, 11.1% fulfilled criteria for EPS, 6.7% fulfilled criteria for both, and 1.1% did not fulfill criteria for either. Finally, we found an increased frequency of diarrhea and pain with eating in the overlap group compared to the non-overlap group of Rome III, while only an increased frequency of diarrhea was found in the overlap group compared to the non-overlap group of Rome IV. Our data demonstrate that utilizing Rome IV criteria, as compared to Rome III, results in an increase in the diagnosis of FD, a two-fold increase in the diagnosis of IBS, and a three-fold increase in the diagnosis of FD/IBS overlap. Rome IV criteria appears to result in greater heterogeneity within diagnostic categories. It is important to determine whether Rome IV diagnoses are predictive of treatment response, and if so, whether assessing symptom variability within a diagnosis will enhance the ability to select patients for a particular treatment.
New pharmacologic approaches to the prevention of space/motion sickness
NASA Technical Reports Server (NTRS)
Kohl, Randall L.; Macdonald, Scott
1991-01-01
Three fundamental approaches used in the selection of new agents for the evaluation in the prevention of space-motion sickness (SMS) are reviewed, with emphasis on drugs under investigation at the Johnson Space Center. These approaches are: (1) the selection of agents from drug classes that possess pharmacologic properties of established antimotion sickness agents, (2) the selection of drugs that are used to prevent emesis caused by means other than the exposure to motion, and (3) basic research that characterizes individual differences in susceptibility to SMS. In the latter type of studies, it was found that subjects who were more resistant to SMS had higher plasma AVP after severe nausea than subjects with lower resistance. The review details the experimental data collected on AVP and adrenocorticotropin. It is noted that data support interrelated roles for AVP and opioid peptides in SMS.
Dysregulation of Ion Homeostasis by Antifungal Agents
Zhang, Yongqiang; Muend, Sabina; Rao, Rajini
2012-01-01
Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca2+ burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides. PMID:22493595
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tebbs, R S; Hinz, J M; Yamada, N A
The Fanconi anemia (FA) proteins overlap with those of homologous recombination through FANCD1/BRCA2, but the biochemical functions of other FA proteins are unknown. By constructing and characterizing a null fancg mutant of hamster CHO cells, we present several new insights for FA. The fancg cells show a broad sensitivity to genotoxic agents, not supporting the conventional concept of sensitivity to only DNA crosslinking agents. The aprt mutation rate is normal, but hprt mutations are reduced, which we ascribe to the lethality of large deletions. CAD and dhfr gene amplification rates are increased, implying excess chromosomal breakage during DNA replication, andmore » suggesting amplification as a contributing factor to cancer-proneness in FA patients. In S-phase cells, both spontaneous and mutagen-induced Rad51 nuclear foci are elevated. These results support a model in which FancG protein helps to prevent collapse of replication forks by allowing translesion synthesis or lesion bypass through homologous recombination.« less
The first report on mushroom green mould disease in Croatia.
Hatvani, Lóránt; Sabolić, Petra; Kocsubé, Sándor; Kredics, László; Czifra, Dorina; Vágvölgyi, Csaba; Kaliterna, Joško; Ivić, Dario; Đermić, Edyta; Kosalec, Ivan
2012-12-01
Green mould disease, caused by Trichoderma species, is a severe problem for mushroom growers worldwide, including Croatia. Trichoderma strains were isolated from green mould-affected Agaricus bisporus (button or common mushroom) compost and Pleurotus ostreatus (oyster mushroom) substrate samples collected from Croatian mushroom farms. The causal agents of green mould disease in the oyster mushroom were T. pleurotum and T. pleuroticola, similar to other countries. At the same time, the pathogen of A. bisporus was exclusively the species T. harzianum, which is different from earlier findings and indicates that the range of mushroom pathogens is widening. The temperature profiles of the isolates and their hosts overlapped, thus no range was found that would allow optimal growth of the mushrooms without mould contamination. Ferulic acid and certain phenolic compounds, such as thymol showed remarkable fungistatic effect on the Trichoderma isolates, but inhibited the host mushrooms as well. However, commercial fungicides prochloraz and carbendazim were effective agents for pest management. This is the first report on green mould disease of cultivated mushrooms in Croatia.
On the suitability of broadband attenuation measurement for characterizing contrast microbubbles.
Chatterjee, Dhiman; Sarkar, Kausik; Jain, Pankaj; Schreppler, Nathan E
2005-06-01
Broadband attenuation measurement has been widely used for characterizing ultrasound contrast agents. Chen et al. (2002) recently suggested that broadband attenuation data depend on the center frequency of the broadband excitation pulse and, therefore, that they are not a reliable measure of the bubble behavior. We investigated the suitability of measurement of broadband attenuation as a characterizing tool using the contrast agent Definity as a test case. Analyzing the attenuation data obtained with three broadband unfocused transducers with different center frequencies (2.25, 3.5 and 5 MHz), we found that attenuation is independent of the transducer used and matches in the overlap regions of any two transducers. Attenuation does not depend on excitation pressure amplitude as long as the excitation amplitude remains below a critical value ( approximately 0.26 MPa), indicating that the measurement of broadband attenuation below critical excitation can, indeed, be used for characterization. Furthermore, the linear relationship of attenuation with concentrations of Definity is also investigated.
Effects of mass media action on the Axelrod model with social influence
NASA Astrophysics Data System (ADS)
Rodríguez, Arezky H.; Moreno, Y.
2010-07-01
The use of dyadic interaction between agents, in combination with homophily (the principle that “likes attract”) in the Axelrod model for the study of cultural dissemination, has two important problems: the prediction of monoculture in large societies and an extremely narrow window of noise levels in which diversity with local convergence is obtained. Recently, the inclusion of social influence has proven to overcome them [A. Flache and M. W. Macy, e-print arXiv:0808.2710]. Here, we extend the Axelrod model with social influence interaction for the study of mass media effects through the inclusion of a superagent which acts over the whole system and has non-null overlap with each agent of the society. The dependence with different parameters as the initial social diversity, size effects, mass media strength, and noise is outlined. Our results might be relevant in several socioeconomic contexts and for the study of the emergence of collective behavior in complex social systems.
Effects of mass media action on the Axelrod model with social influence.
Rodríguez, Arezky H; Moreno, Y
2010-07-01
The use of dyadic interaction between agents, in combination with homophily (the principle that "likes attract") in the Axelrod model for the study of cultural dissemination, has two important problems: the prediction of monoculture in large societies and an extremely narrow window of noise levels in which diversity with local convergence is obtained. Recently, the inclusion of social influence has proven to overcome them [A. Flache and M. W. Macy, e-print arXiv:0808.2710]. Here, we extend the Axelrod model with social influence interaction for the study of mass media effects through the inclusion of a superagent which acts over the whole system and has non-null overlap with each agent of the society. The dependence with different parameters as the initial social diversity, size effects, mass media strength, and noise is outlined. Our results might be relevant in several socioeconomic contexts and for the study of the emergence of collective behavior in complex social systems.
The emergence of understanding in a computer model of concepts and analogy-making
NASA Astrophysics Data System (ADS)
Mitchell, Melanie; Hofstadter, Douglas R.
1990-06-01
This paper describes Copycat, a computer model of the mental mechanisms underlying the fluidity and adaptability of the human conceptual system in the context of analogy-making. Copycat creates analogies between idealized situations in a microworld that has been designed to capture and isolate many of the central issues of analogy-making. In Copycat, an understanding of the essence of a situation and the recognition of deep similarity between two superficially different situations emerge from the interaction of a large number of perceptual agents with an associative, overlapping, and context-sensitive network of concepts. Central features of the model are: a high degree of parallelism; competition and cooperation among a large number of small, locally acting agents that together create a global understanding of the situation at hand; and a computational temperature that measures the amount of perceptual organization as processing proceeds and that in turn controls the degree of randomness with which decisions are made in the system.
Dysregulation of ion homeostasis by antifungal agents.
Zhang, Yongqiang; Muend, Sabina; Rao, Rajini
2012-01-01
Ion-signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association, and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose-dependent Ca(2+) burst and long lasting pH changes in the model yeast Saccharomyces cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca(2+) stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane, as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion-signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.
Phenotypic and Genetic Overlap between Autistic Traits at the Extremes of the General Population
ERIC Educational Resources Information Center
Ronald, Angelica; Happe, Francesca; Price, Thomas S.; Baron-Cohen, Simon; Plomin, Robert
2006-01-01
Objective: To investigate children selected from a community sample for showing extreme autistic-like traits and to assess the degree to which these individual traits--social impairments (SIs), communication impairments (CIs), and restricted repetitive behaviors and interests (RRBIs)--are caused by genes and environments, whether all of them are…
Selective Guide to Literature on Agricultural Engineering. Engineering Literature Guides, Number 4.
ERIC Educational Resources Information Center
Cloud, Gayla Staples, Comp.
Agricultural engineering overlaps many other disciplines. This document is a survey of information sources in agricultural engineering and is intended to identify those core resources which can help engineers and librarians to find information about the discipline. Sections include: (1) "Guides to the Literature"; (2) "Bibliographies"; (3)…
ERIC Educational Resources Information Center
Li, Chuchu; Gollan, Tamar H.
2018-01-01
The current study investigated the hypothesis that cognates (i.e., translation equivalents that overlap in form, e.g., "lemon" is "limón" in Spanish) facilitate language switches. Spanish-English bilinguals were cued to switch languages while repeatedly naming pictures with cognate versus noncognate names in separate…
Karle, James W; Watter, Scott; Shedden, Judith M
2010-05-01
Research into the perceptual and cognitive effects of playing video games is an area of increasing interest for many investigators. Over the past decade, expert video game players (VGPs) have been shown to display superior performance compared to non-video game players (nVGPs) on a range of visuospatial and attentional tasks. A benefit of video game expertise has recently been shown for task switching, suggesting that VGPs also have superior cognitive control abilities compared to nVGPs. In two experiments, we examined which aspects of task switching performance this VGP benefit may be localized to. With minimal trial-to-trial interference from minimally overlapping task set rules, VGPs demonstrated a task switching benefit compared to nVGPs. However, this benefit disappeared when proactive interference between tasks was increased, with substantial stimulus and response overlap in task set rules. We suggest that VGPs have no generalized benefit in task switching-related cognitive control processes compared to nVGPs, with switch cost reductions due instead to a specific benefit in controlling selective attention. Copyright 2009 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Shen, Jun; Yang, Jehoon; Choi, In-Young; Li, Shizhe Steve; Chen, Zhengguang
2004-10-01
A novel single-shot in vivo spectral editing method is proposed in which the signal to be detected, is regenerated anew from the thermal equilibrium magnetization of a source to which it is J-coupled. The thermal equilibrium magnetization of the signal to be detected together with those of overlapping signals are suppressed by single-shot gradient dephasing prior to the signal regeneration process. Application of this new strategy to in vivo GABA editing using selective homonuclear polarization transfer allows complete suppression of overlapping creatine and glutathione while detecting the GABA-4 methylene resonance at 3.02 ppm with an editing yield similar to that of conventional editing methods. The NAA methyl group at 2.02 ppm was simultaneously detected and can be used as an internal navigator echo for correcting the zero order phase and frequency shifts and as an internal reference for concentration. This new method has been demonstrated for robust in vivo GABA editing in the rat brain and for study of GABA synthesis after acute vigabatrin administration.
NASA Astrophysics Data System (ADS)
Choi, In-Young; Lee, Sang-Pil; Shen, Jun
2005-01-01
A single-shot multiple quantum filtering method is developed that uses two double-band frequency selective pulses for enhanced spectral selectivity in combination with a slice-selective 90°, a slice-selective universal rotator 90°, and a spectral-spatial pulse composed of two slice-selective universal rotator 45° pulses for single-shot three-dimensional localization. The use of this selective multiple quantum filtering method for C3 and C4 methylene protons of GABA resulted in improved spectral selectivity for GABA and effective suppression of overlapping signals such as creatine and glutathione in each single scan, providing reliable measurements of the GABA doublet in all subjects. The concentration of GABA was measured to be 0.7 ± 0.2 μmol/g (means ± SD, n = 15) in the fronto-parietal region of the human brain in vivo.
Decolonization in Prevention of Health Care-Associated Infections.
Septimus, Edward J; Schweizer, Marin L
2016-04-01
Colonization with health care-associated pathogens such as Staphylococcus aureus, enterococci, Gram-negative organisms, and Clostridium difficile is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on S. aureus decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for S. aureus nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin-containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as Candida. Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram-negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
42 CFR 73.9 - Responsible Official.
Code of Federal Regulations, 2011 CFR
2011-10-01
... reported by submission of APHIS/CDC Form 4 within seven calendar days after identification. A copy of the... any other select agent or toxin, APHIS/CDC Form 4 must be submitted within seven calendar days after... agent or toxin, APHIS/CDC Form 4 must be submitted within 90 calendar days of receipt of the agent or...
Learning Natural Selection in 4th Grade with Multi-Agent-Based Computational Models
ERIC Educational Resources Information Center
Dickes, Amanda Catherine; Sengupta, Pratim
2013-01-01
In this paper, we investigate how elementary school students develop multi-level explanations of population dynamics in a simple predator-prey ecosystem, through scaffolded interactions with a multi-agent-based computational model (MABM). The term "agent" in an MABM indicates individual computational objects or actors (e.g., cars), and these…
76 FR 4480 - Privacy Act of 1974; Report of Modified or Altered System of Records
Federal Register 2010, 2011, 2012, 2013, 2014
2011-01-25
... of Subjects in Agent Orange, Vietnam Experience, and Selected Cancers Studies, HHS/CDC/CCEHIP/ NCEH.../NCEH proposes to alter System of Records, No. 09-20-0162, ``Records of Subjects in Agent Orange... Agent Orange) to possible adverse health consequences. Such possible effects to be evaluated include...
USDA-ARS?s Scientific Manuscript database
Current methods for detecting the presence of botulinum neurotoxins in food and other biological samples Botulinum neurotoxins (BoNTs), the causative agents of botulism, are among the most lethal human bacterial toxins and the causative agent of botulism. BoNTs are also classified as Select Agents ...
A New HIV Prevention Network Approach: Sociometric Peer Change Agent Selection
Schneider, John A.; Zhou, A. Ning; Laumann, Edward O.
2014-01-01
Internationally, the Peer Change Agent (PCA) model is the most frequently used conceptual framework for HIV prevention. Change agents themselves can be more important than the messages they convey. PCA selection is operationalized via heterogeneous methods based upon individual-level attributes. A sociometric position selection strategy, however, could increase peer influence potency and halt transmission at key network locations. In this study, we selected candidate PCAs based upon relative sociometric bridging and centrality scores and assessed their attributes in comparison to one another and to existing peer educators. We focused upon an emerging HIV epidemic among men who have sex with men in Southern India in 2011. PCAs selected based on their bridging score were more likely to be innovators when compared to other centrally-located PCAs, to PCAs located on the periphery, and to existing peer educators. We also found that sociodemographic attributes and risk behaviors were similar across all candidate PCAs, but risk behaviors of existing peer educators differed. Existing peer educators were more likely to engage in higher risk behavior such as receiving money for sex when compared to sociometrically selected peer changes agents. These existing peer educators were also more likely to exhibit leadership qualities within the overall network; they were, however, just as likely as other non-trained candidate peer change agents to report important HIV intravention behavior (encouraging condoms within their network). The importance of identifying bridges who may be able to diffuse innovation more effectively within high risk HIV networks is especially critical given recent efficacy data from novel HIV prevention interventions such as pre-exposure prophylaxis. Moreover, while existing peer educators were more likely to be leaders in our analysis, using peer educators with high risk behavior may have limited utility in enacting behavior change among sex worker peers or male clients in the network. PMID:24518188
USDA-ARS?s Scientific Manuscript database
Ralstonia solanacearum race 3 biovar 2 strains have the ability to cause brown rot of potato in temperate climates. Since these strains are not established in the U.S. and because of the potential risk they pose to the potato industry, the U.S. government has listed them as select agents. Cultivated...
Hobbs, Brian D; de Jong, Kim; Lamontagne, Maxime; Bossé, Yohan; Shrine, Nick; Artigas, María Soler; Wain, Louise V; Hall, Ian P; Jackson, Victoria E; Wyss, Annah B; London, Stephanie J; North, Kari E; Franceschini, Nora; Strachan, David P; Beaty, Terri H; Hokanson, John E; Crapo, James D; Castaldi, Peter J; Chase, Robert P; Bartz, Traci M; Heckbert, Susan R; Psaty, Bruce M; Gharib, Sina A; Zanen, Pieter; Lammers, Jan W; Oudkerk, Matthijs; Groen, H J; Locantore, Nicholas; Tal-Singer, Ruth; Rennard, Stephen I; Vestbo, Jørgen; Timens, Wim; Paré, Peter D; Latourelle, Jeanne C; Dupuis, Josée; O'Connor, George T; Wilk, Jemma B; Kim, Woo Jin; Lee, Mi Kyeong; Oh, Yeon-Mok; Vonk, Judith M; de Koning, Harry J; Leng, Shuguang; Belinsky, Steven A; Tesfaigzi, Yohannes; Manichaikul, Ani; Wang, Xin-Qun; Rich, Stephen S; Barr, R Graham; Sparrow, David; Litonjua, Augusto A; Bakke, Per; Gulsvik, Amund; Lahousse, Lies; Brusselle, Guy G; Stricker, Bruno H; Uitterlinden, André G; Ampleford, Elizabeth J; Bleecker, Eugene R; Woodruff, Prescott G; Meyers, Deborah A; Qiao, Dandi; Lomas, David A; Yim, Jae-Joon; Kim, Deog Kyeom; Hawrylkiewicz, Iwona; Sliwinski, Pawel; Hardin, Megan; Fingerlin, Tasha E; Schwartz, David A; Postma, Dirkje S; MacNee, William; Tobin, Martin D; Silverman, Edwin K; Boezen, H Marike; Cho, Michael H
2017-03-01
Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10 -6 ) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.
Wu, Tai-luan; Tseng, Ling-li
2017-01-01
This study examines the completeness and overlap of coverage in physics of six open access scholarly communication systems, including two search engines (Google Scholar and Microsoft Academic), two aggregate institutional repositories (OAIster and OpenDOAR), and two physics-related open sources (arXiv.org and Astrophysics Data System). The 2001–2013 Nobel Laureates in Physics served as the sample. Bibliographic records of their publications were retrieved and downloaded from each system, and a computer program was developed to perform the analytical tasks of sorting, comparison, elimination, aggregation and statistical calculations. Quantitative analyses and cross-referencing were performed to determine the completeness and overlap of the system coverage of the six open access systems. The results may enable scholars to select an appropriate open access system as an efficient scholarly communication channel, and academic institutions may build institutional repositories or independently create citation index systems in the future. Suggestions on indicators and tools for academic assessment are presented based on the comprehensiveness assessment of each system. PMID:29267327
Communication Studies of DMP and SMP Machines
NASA Technical Reports Server (NTRS)
Sohn, Andrew; Biswas, Rupak; Chancellor, Marisa K. (Technical Monitor)
1997-01-01
Understanding the interplay between machines and problems is key to obtaining high performance on parallel machines. This paper investigates the interplay between programming paradigms and communication capabilities of parallel machines. In particular, we explicate the communication capabilities of the IBM SP-2 distributed-memory multiprocessor and the SGI PowerCHALLENGEarray symmetric multiprocessor. Two benchmark problems of bitonic sorting and Fast Fourier Transform are selected for experiments. Communication-efficient algorithms are developed to exploit the overlapping capabilities of the machines. Programs are written in Message-Passing Interface for portability and identical codes are used for both machines. Various data sizes and message sizes are used to test the machines' communication capabilities. Experimental results indicate that the communication performance of the multiprocessors are consistent with the size of messages. The SP-2 is sensitive to message size but yields a much higher communication overlapping because of the communication co-processor. The PowerCHALLENGEarray is not highly sensitive to message size and yields a low communication overlapping. Bitonic sorting yields lower performance compared to FFT due to a smaller computation-to-communication ratio.
Bimodal Bilinguals Co-activate Both Languages during Spoken Comprehension
Shook, Anthony; Marian, Viorica
2012-01-01
Bilinguals have been shown to activate their two languages in parallel, and this process can often be attributed to overlap in input between the two languages. The present study examines whether two languages that do not overlap in input structure, and that have distinct phonological systems, such as American Sign Language (ASL) and English, are also activated in parallel. Hearing ASL-English bimodal bilinguals’ and English monolinguals’ eye-movements were recorded during a visual world paradigm, in which participants were instructed, in English, to select objects from a display. In critical trials, the target item appeared with a competing item that overlapped with the target in ASL phonology. Bimodal bilinguals looked more at competing items than at phonologically unrelated items, and looked more at competing items relative to monolinguals, indicating activation of the sign-language during spoken English comprehension. The findings suggest that language co-activation is not modality specific, and provide insight into the mechanisms that may underlie cross-modal language co-activation in bimodal bilinguals, including the role that top-down and lateral connections between levels of processing may play in language comprehension. PMID:22770677
Pollinators exert natural selection on flower size and floral display in Penstemon digitalis.
Parachnowitsch, Amy L; Kessler, André
2010-10-01
• A major gap in our understanding of floral evolution, especially micro-evolutionary processes, is the role of pollinators in generating patterns of natural selection on floral traits. Here we explicitly tested the role of pollinators in selecting floral traits in a herbaceous perennial, Penstemon digitalis. • We manipulated the effect of pollinators on fitness through hand pollinations and compared phenotypic selection in open- and hand-pollinated plants. • Despite the lack of pollen limitation in our population, pollinators mediated selection on floral size and floral display. Hand pollinations removed directional selection for larger flowers and stabilizing selection on flower number, suggesting that pollinators were the agents of selection on both of these traits. • We reviewed studies that measured natural selection on floral traits by biotic agents and generally found stronger signatures of selection imposed by pollinators than by herbivores and co-flowering plant species. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).
Learning to select useful landmarks.
Greiner, R; Isukapalli, R
1996-01-01
To navigate effectively, an autonomous agent must be able to quickly and accurately determine its current location. Given an initial estimate of its position (perhaps based on dead-reckoning) and an image taken of a known environment, our agent first attempts to locate a set of landmarks (real-world objects at known locations), then uses their angular separation to obtain an improved estimate of its current position. Unfortunately, some landmarks may not be visible, or worse, may be confused with other landmarks, resulting in both time wasted in searching for the undetected landmarks, and in further errors in the agent's estimate of its position. To address these problems, we propose a method that uses previous experiences to learn a selection function that, given the set of landmarks that might be visible, returns the subset that can be used to reliably provide an accurate registration of the agent's position. We use statistical techniques to prove that the learned selection function is, with high probability, effectively at a local optimum in the space of such functions. This paper also presents empirical evidence, using real-world data, that demonstrate the effectiveness of our approach.
Software for Partly Automated Recognition of Targets
NASA Technical Reports Server (NTRS)
Opitz, David; Blundell, Stuart; Bain, William; Morris, Matthew; Carlson, Ian; Mangrich, Mark; Selinsky, T.
2002-01-01
The Feature Analyst is a computer program for assisted (partially automated) recognition of targets in images. This program was developed to accelerate the processing of high-resolution satellite image data for incorporation into geographic information systems (GIS). This program creates an advanced user interface that embeds proprietary machine-learning algorithms in commercial image-processing and GIS software. A human analyst provides samples of target features from multiple sets of data, then the software develops a data-fusion model that automatically extracts the remaining features from selected sets of data. The program thus leverages the natural ability of humans to recognize objects in complex scenes, without requiring the user to explain the human visual recognition process by means of lengthy software. Two major subprograms are the reactive agent and the thinking agent. The reactive agent strives to quickly learn the user's tendencies while the user is selecting targets and to increase the user's productivity by immediately suggesting the next set of pixels that the user may wish to select. The thinking agent utilizes all available resources, taking as much time as needed, to produce the most accurate autonomous feature-extraction model possible.
Trust and cooperation among economic agents
Dasgupta, Partha
2009-01-01
The units that are subject to selection pressure in evolutionary biology are ‘strategies’, which are conditional actions (‘Do P if X occurs, otherwise do Q’). In contrast, the units in economics select strategies from available menus so as to further their projects and purposes. As economic agents do not live in isolation, each agent's optimum choice, in general, depends on the choices made by others. Because their projects and purposes involve the future, not just the present, each agent reasons about the likely present and future consequences of their respective choices. That is why beliefs, about what others may do and what the consequences of those choices could be, are at the basis of strategy selection. A catalogue of social environments is constructed in which agents not only promise each other's cooperation, but also rationally believe that the promises will be kept. Unfortunately, non-cooperation arising from mistrust can be the outcome in those same environments: societies harbour multiple ‘equilibria’ and can skid from cooperation to non-cooperation. Moreover, a pre-occupation among analysts with the Prisoners' Dilemma game has obscured the fact that cooperative arrangements can harbour not only inequality, but also exploitation. The analysis is used to discuss why international cooperation over the use of global public goods has proved to be so elusive. PMID:19805436
Dhillon, Rummit K.; Clarke, Alex; King-Stephens, David; Laxer, Kenneth D.; Weber, Peter B.; Kuperman, Rachel A.; Auguste, Kurtis I.; Brunner, Peter; Lin, Jack J.; Parvizi, Josef; Crone, Nathan E.; Dronkers, Nina F.; Knight, Robert T.
2017-01-01
Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70–150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain. PMID:28533406
Konuma, Tsuyoshi; Harada, Erisa; Sugase, Kenji
2015-12-01
Protein dynamics plays important roles in many biological events, such as ligand binding and enzyme reactions. NMR is mostly used for investigating such protein dynamics in a site-specific manner. Recently, NMR has been actively applied to large proteins and intrinsically disordered proteins, which are attractive research targets. However, signal overlap, which is often observed for such proteins, hampers accurate analysis of NMR data. In this study, we have developed a new methodology called relaxation dispersion difference that can extract conformational exchange parameters from overlapped NMR signals measured using relaxation dispersion spectroscopy. In relaxation dispersion measurements, the signal intensities of fluctuating residues vary according to the Carr-Purcell-Meiboon-Gill pulsing interval, whereas those of non-fluctuating residues are constant. Therefore, subtraction of each relaxation dispersion spectrum from that with the highest signal intensities, measured at the shortest pulsing interval, leaves only the signals of the fluctuating residues. This is the principle of the relaxation dispersion difference method. This new method enabled us to extract exchange parameters from overlapped signals of heme oxygenase-1, which is a relatively large protein. The results indicate that the structural flexibility of a kink in the heme-binding site is important for efficient heme binding. Relaxation dispersion difference requires neither selectively labeled samples nor modification of pulse programs; thus it will have wide applications in protein dynamics analysis.
Sharma, Samin K
2008-05-01
Over 20 years have passed since the introduction of the tri-iodinated low-osmolar nonionic contrast agents such as iopamidol, iohexol, ioversol and iopromide. During this time, most cardiology practices have switched to these nonionic agents to avoid the nuisance side effects and cardiac adverse events associated with the older ionic contrast agents. Although the improved tolerability of the nonionic agents is generally attributed to their decreased osmolality (approximately half that of the older ionic contrast agents), in fact, these contrast agents also differ from the older agents in their ionicity, viscosity and direct chemotoxicity. The impact of these properties on safety, together with cost differences, should be considered when selecting a contrast agent.
Study to determine cloud motion from meteorological satellite data
NASA Technical Reports Server (NTRS)
Clark, B. B.
1972-01-01
Processing techniques were tested for deducing cloud motion vectors from overlapped portions of pairs of pictures made from meteorological satellites. This was accomplished by programming and testing techniques for estimating pattern motion by means of cross correlation analysis with emphasis placed upon identifying and reducing errors resulting from various factors. Techniques were then selected and incorporated into a cloud motion determination program which included a routine which would select and prepare sample array pairs from the preprocessed test data. The program was then subjected to limited testing with data samples selected from the Nimbus 4 THIR data provided by the 11.5 micron channel.
Novel treatments for inflammatory bowel disease
Lee, Hyo Sun; Park, Soo-Kyung; Park, Dong Il
2018-01-01
Increased understanding of the immunopathology of inflammatory bowel disease (IBD) has led to the development of targeted therapies and has unlocked a new era in IBD treatment. The development of treatment options aimed at a variety of pathological mechanisms offers new hope for customized therapies. Beyond anti-tumor necrosis factor agents, selective lymphocyte trafficking inhibitors have been proposed as potent drugs for IBD. Among these, vedolizumab has recently been approved for both Crohn’s disease and ulcerative colitis. Numerous other agents for IBD treatment are currently under investigation, including Janus kinase inhibitors, anti-mucosal vascular addressin cell adhesion molecule-1 agents, an anti-SMAD7 antisense oligonucleotide, an anti-interleukin-12/23 monoclonal antibody, and a sphingosine-1-phosphate receptor-1 selective agonist. These agents will likely expand the treatment options available for the management of IBD patients in the future. In this review, we discuss the efficacy and safety of novel agents currently under investigation in IBD clinical trials. PMID:29223139
A smart magnetic resonance contrast agent for selective copper sensing.
Que, Emily L; Chang, Christopher J
2006-12-20
We describe the synthesis and properties of Copper-Gad-1 (CG1), a new type of smart magnetic resonance (MR) sensor for selective detection of copper. CG1 is composed of a gadolinium contrast agent core tethered to copper-selective recognition motif. Cu2+-induced modulation of inner-sphere water access to the Gd3+ center provides a sensing mechanism for reporting Cu2+ levels by reading out changes in longitudinal proton relaxivity values. CG1 features good selectivity for Cu2+ over abundant biological cations and a 41% increase in relaxivity upon Cu2+ binding and is capable of detecting micromolar changes in Cu2+ concentrations in aqueous media.
Atrial Fibrillation - A Common Ground for Neurology and Cardiology.
Abukhalil, Fawzi; Bodhit, Aakash; Cai, Peter Y; Ansari, Saeed; Thenkabail, Spandana; Ganji, Sarah; Saravanapavan, Pradeepan; Chandra Shekhar, Chandana; Waters, Michael F; Beaver, Thomas M; Shushrutha Hedna, Vishnumurthy
2013-01-01
Atrial fibrillation (AF) has a huge impact on clinical stroke because it is the primary cause of cardio-embolism, which constitutes ~20% of all strokes. As a result, there is a great need to explore safer and more effective primary and secondary prophylactic agents. In this article, we discuss the overlapping issues pertaining to AF from both a neurology and cardiology standpoint. We focus on the dynamic interplay of neurovascular and cardiovascular diseases in relation to AF, traditional and novel risk factors for AF leading to stroke, impact of AF on cognitive decline, and current upstream medical and surgical options for embolism prophylaxis.
Li, Yafei; Zhang, Yanan; Ding, Huanzhong; Mei, Xian; Liu, Wei; Zeng, Jiaxiong; Zeng, Zhenling
2016-11-09
Mutant prevention concentration (MPC) is an alternative pharmacodynamic parameter that has been used to measure antimicrobial activity and represents the propensities of antimicrobial agents to select resistant mutants. The concentration range between minimum inhibitory concentration (MIC) and MPC is defined as mutant selection window (MSW). The MPC and MSW parameters represent the ability of antimicrobial agents to inhibit the bacterial mutants selected. This study was conducted to determine the MIC and MPC values of four antimicrobials including ceftiofur, cefquinome, florfenicol and tilmicosin against 105 Riemerella anatipestifer isolates. The MIC 50 /MIC 90 values of clinical isolates tested in our study for ceftiofur, cefquinome, florfenicol and tilmicosin were 0.063/0.5、0.031/0.5、1/4、1/4 μg/mL, respectively; MPC 50 / MPC 90 values were 4/64、8/64、4/32、16/256 μg/mL, respectively. These results provided information on the use of these compounds in treating the R. anatipestifer infection; however, additional studies are needed to demonstrate their therapeutic efficacy. Based on the MSW theory, the hierarchy of these tested antimicrobial agents with respect to selecting resistant subpopulations was as follows: cefquinome > ceftiofur > tilmicosin > florfenicol. Cefquinome was the drug that presented the highest risk of selecting resistant mutant among the four antimicrobial agents.
Zhang, Zhen-Lei; Zhao, Chun-Lai; Chen, Qian; Xu, Kai; Qiao, Xin; Xu, Jing-Yuan
2018-06-01
Aberrant ribosome biogenesis and enlarged nucleoli have long been used by pathologists as a marker of aggressive tumors. Suppression of RNA polymerase I (Pol I) transcription machinery within the nucleolus could be a direct way to trigger the nucleolar stress and to inhibit the rapid proliferation of cancer cells. Here we modified cisplatin with an analogue of the selective inhibitor of RNA polymerase I-mediated transcription BMH-21 to develop a novel platinum-based Pol I selective inhibitor. We show that this novel monofunctional platinum-based agent, P1-B1, had enhanced antitumor activity of up to 17-fold greater than the clinical drug cisplatin in cisplatin-resistant non-small cell lung cancer cells. P1-B1 also had significantly lower cytotoxicity compared to cisplatin as well as the Pol I selective inhibitor BMH-21 in MRC-5 normal lung fibroblast cells, and the selectivity index (SI) greatly increases. Mechanistic investigations revealed that P1-B1 displayed significant nucleolar accumulation, selectively inhibited Pol I transcription, and induced nucleolar stress, leading to S-phase arrest and apoptosis. Our results suggest that the effects of P1-B1 are mechanistically distinct from those of conventional platinum agents and the recently described non-classical platinum compounds and that functionalizing platinum-based agents with directly Pol I transcription inhibition properties may represent an improved modality for cancer treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Estimated Chemical Warfare Agent Surface Clearance Goals for Remediation Pre-Planning
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dolislager, Frederick; Bansleben, Dr. Donald; Watson, Annetta Paule
2010-01-01
Health-based surface clearance goals, in units of mg/cm2, have been developed for the persistent chemical warfare agents sulfur mustard (HD) and nerve agent VX as well as their principal degradation products. Selection of model parameters and critical receptor (toddler child) allow calculation of surface residue estimates protective for the toddler child, the general population and adult employees of a facilty that has undergone chemical warfare agent attack.
Kamble, Suresh S; Kandasamy, Baburajan; Thillaigovindan, Ranjani; Goyal, Nitin Kumar; Talukdar, Pratim; Seal, Mukut
2015-05-01
Newer dentin bonding agents were developed to improve the quality of composite restoration and to reduce time consumption in its application. The aim of the present study was to evaluate tensile bond strength of 6(th), 7(th) and 8(th) generation bonding agents by in vitro method. Selected 60 permanent teeth were assigned into 20 in each group (Group I: 6(th) generation bonding agent-Adper SE plus 3M ESPE, Group II: 7(th) generation bonding agent-G-Bond GC Corp Japan and Group III: 8(th) generation dentin adhesives-FuturaBond, DC, Voco, Germany). With high-speed diamond disc, coronal dentin was exposed, and selected dentin bonding agents were applied, followed by composite restoration. All samples were saved in saline for 24 h and tensile bond strength testing was done using a universal testing machine. The obtained data were tabulated and statistically analyzed using ANOVA test. The tensile bond strength readings for 6(th) generation bonding agent was 32.2465, for 7(th) generation was 31.6734, and for 8(th)-generation dentine bonding agent was 34.74431. The highest tensile bond strength was seen in 8(th) generation bonding agent compared to 6(th) and 7(th) generation bonding agents. From the present study it can be conclude that 8(th) generation dentine adhesive (Futura DC, Voco, Germany) resulted in highest tensile bond strength compared to 6(th) (Adper SE plus, 3M ESPE) and 7(th) generation (G-Bond) dentin bonding agents.
Baron, Robert V; Conley, Yvette P; Gorin, Michael B; Weeks, Daniel E
2015-03-18
When studying the genetics of a human trait, we typically have to manage both genome-wide and targeted genotype data. There can be overlap of both people and markers from different genotyping experiments; the overlap can introduce several kinds of problems. Most times the overlapping genotypes are the same, but sometimes they are different. Occasionally, the lab will return genotypes using a different allele labeling scheme (for example 1/2 vs A/C). Sometimes, the genotype for a person/marker index is unreliable or missing. Further, over time some markers are merged and bad samples are re-run under a different sample name. We need a consistent picture of the subset of data we have chosen to work with even though there might possibly be conflicting measurements from multiple data sources. We have developed the dbVOR database, which is designed to hold data efficiently for both genome-wide and targeted experiments. The data are indexed for fast retrieval by person and marker. In addition, we store pedigree and phenotype data for our subjects. The dbVOR database allows us to select subsets of the data by several different criteria and to merge their results into a coherent and consistent whole. Data may be filtered by: family, person, trait value, markers, chromosomes, and chromosome ranges. The results can be presented in columnar, Mega2, or PLINK format. dbVOR serves our needs well. It is freely available from https://watson.hgen.pitt.edu/register . Documentation for dbVOR can be found at https://watson.hgen.pitt.edu/register/docs/dbvor.html .
Evaluating apparent competition in limiting the recovery of an endangered ungulate.
Johnson, Heather E; Hebblewhite, Mark; Stephenson, Thomas R; German, David W; Pierce, Becky M; Bleich, Vernon C
2013-01-01
Predation can disproportionately affect endangered prey populations when generalist predators are numerically linked to more abundant primary prey. Apparent competition, the term for this phenomenon, has been increasingly implicated in the declines of endangered prey populations. We examined the potential for apparent competition to limit the recovery of Sierra Nevada bighorn sheep (Ovis canadensis sierrae), an endangered subspecies under the US Endangered Species Act. Using a combination of location, demographic, and habitat data, we assessed whether cougar (Puma concolor) predation on endangered bighorn sheep was a consequence of their winter range overlap with abundant mule deer (Odocoileus hemionus). Consistent with the apparent competition hypothesis, bighorn sheep populations with higher spatial overlap with deer exhibited higher rates of cougar predation which had additive effects on adult survival. Bighorn sheep killed by cougars were primarily located within deer winter ranges, even though those areas constituted only a portion of the bighorn sheep winter ranges. We suspect that variation in sympatry between bighorn sheep and deer populations was largely driven by differences in habitat selection among bighorn sheep herds. Indeed, bighorn sheep herds that experienced the highest rates of predation and the greatest spatial overlap with deer also exhibited the strongest selection for low elevation habitat. Although predator-mediated apparent competition may limit some populations of bighorn sheep, it is not the primary factor limiting all populations, suggesting that the dynamics of different herds are highly idiosyncratic. Management plans for endangered species should consider the spatial distributions of key competitors and predators to reduce the potential for apparent competition to hijack conservation success.
Telonis-Scott, Marina; Sgrò, Carla M.; Hoffmann, Ary A.; Griffin, Philippa C.
2016-01-01
Repeated attempts to map the genomic basis of complex traits often yield different outcomes because of the influence of genetic background, gene-by-environment interactions, and/or statistical limitations. However, where repeatability is low at the level of individual genes, overlap often occurs in gene ontology categories, genetic pathways, and interaction networks. Here we report on the genomic overlap for natural desiccation resistance from a Pool-genome-wide association study experiment and a selection experiment in flies collected from the same region in southeastern Australia in different years. We identified over 600 single nucleotide polymorphisms associated with desiccation resistance in flies derived from almost 1,000 wild-caught genotypes, a similar number of loci to that observed in our previous genomic study of selected lines, demonstrating the genetic complexity of this ecologically important trait. By harnessing the power of cross-study comparison, we narrowed the candidates from almost 400 genes in each study to a core set of 45 genes, enriched for stimulus, stress, and defense responses. In addition to gene-level overlap, there was higher order congruence at the network and functional levels, suggesting genetic redundancy in key stress sensing, stress response, immunity, signaling, and gene expression pathways. We also identified variants linked to different molecular aspects of desiccation physiology previously verified from functional experiments. Our approach provides insight into the genomic basis of a complex and ecologically important trait and predicts candidate genetic pathways to explore in multiple genetic backgrounds and related species within a functional framework. PMID:26733490
Dufour, Claire M. S.; Meynard, Christine; Watson, Johan; Rioux, Camille; Benhamou, Simon; Perez, Julie; du Plessis, Jurie J.; Avenant, Nico; Pillay, Neville; Ganem, Guila
2015-01-01
Coexistence often involves niche differentiation either as the result of environmental divergence, or in response to competition. Disentangling the causes of such divergence requires that environmental variation across space is taken into account, which is rarely done in empirical studies. We address the role of environmental variation versus competition in coexistence between two rodent species: Rhabdomys bechuanae (bechuanae) and Rhabdomys dilectus dilectus (dilectus) comparing their habitat preference and home range (HR) size in areas with similar climates, where their distributions abut (allopatry) or overlap (sympatry). Using Outlying Mean Index analyses, we test whether habitat characteristics of the species deviate significantly from a random sample of available habitats. In allopatry, results suggest habitat selection: dilectus preferring grasslands with little bare soil while bechuanae occurring in open shrublands. In sympatry, shrubland type habitats dominate and differences are less marked, yet dilectus selects habitats with more cover than bechuanae. Interestingly, bechuanae shows larger HRs than dilectus, and both species display larger HRs in sympatry. Further, HR overlaps between species are lower than expected. We discuss our results in light of data on the phylogeography of the genus and propose that evolution in allopatry resulted in adaptation leading to different habitat preferences, even at their distribution margins, a divergence expected to facilitate coexistence. However, since sympatry occurs in sites where environmental characteristics do not allow complete species separation, competition may explain reduced inter-species overlap and character displacement in HR size. This study reveals that both environmental variation and competition may shape species coexistence. PMID:25693176
Peck-Richardson, Adam G.; Lyons, Donald E.; Roby, Daniel D.; Cushing, Daniel A.; Lerczak, James A.
2018-01-01
Ecological theory predicts that co-existing, morphologically similar species will partition prey resources when faced with resource limitations. We investigated local movements, foraging dive behavior, and foraging habitat selection by breeding adults of 2 closely related cormorant species, double-crested cormorants Phalacrocorax auritus and Brandt’s cormorants P. penicillatus. These species nest sympatrically at East Sand Island in the Columbia River estuary at the border of Oregon and Washington states, USA. Breeding individuals of each species were tracked using GPS tags with integrated temperature and depth data-loggers. The overall foraging areas and core foraging areas (defined as the 95% and 50% kernel density estimates of dive locations, respectively) of double-crested cormorants were much larger and covered a broader range of riverine, mixed-estuarine, and nearshore marine habitats. Brandt’s cormorant foraging areas were less expansive, were exclusively marine, and mostly overlapped with double-crested cormorant foraging areas. Within these areas of overlap, Brandt’s cormorants tended to dive deeper (median depth = 6.48 m) than double-crested cormorants (median depth = 2.67 m), and selected dive locations where the water was deeper. Brandt’s cormorants also utilized a deeper, more benthic portion of the water column than did double-crested cormorants. Nevertheless, the substantial overlap in foraging habitat between the 2 cormorant species in the Columbia River estuary, particularly for Brandt’s cormorants, suggests that superabundant prey resources allow these 2 large and productive cormorant colonies to coexist on a single island near the mouth of the Columbia River.
Magnetic cellulose-derivative structures
Walsh, M.A.; Morris, R.S.
1986-09-16
Structures to serve as selective magnetic sorbents are formed by dissolving a cellulose derivative such as cellulose triacetate in a solvent containing magnetic particles. The resulting solution is sprayed as a fine mist into a chamber containing a liquid coagulant such as n-hexane in which the cellulose derivative is insoluble but in which the coagulant is soluble or miscible. On contact with the coagulant, the mist forms free-flowing porous magnetic microspheric structures. These structures act as containers for the ion-selective or organic-selective sorption agent of choice. Some sorption agents can be incorporated during the manufacture of the structure. 3 figs.
Magnetic cellulose-derivative structures
Walsh, Myles A.; Morris, Robert S.
1986-09-16
Structures to serve as selective magnetic sorbents are formed by dissolving a cellulose derivative such as cellulose triacetate in a solvent containing magnetic particles. The resulting solution is sprayed as a fine mist into a chamber containing a liquid coagulant such as n-hexane in which the cellulose derivative is insoluble but in which the coagulant is soluble or miscible. On contact with the coagulant, the mist forms free-flowing porous magnetic microspheric structures. These structures act as containers for the ion-selective or organic-selective sorption agent of choice. Some sorbtion agents can be incorporated during the manufacture of the structure.
[THE NATIONAL NUTRIENT MEDIUM FOR DIAGNOSTIC OF PURULENT BACTERIAL MENINGITIS].
Podkopaev, Ya V; Domotenko, L V; Morozova, T P; Khramov, M K; Shepelin, A P
2015-05-01
The national growth mediums were developed for isolating and cultivating of main agents of purulent bacterial meningitis--haemophilus agar, chocolate agar, PBM-agar. The growing and selective characteristics of developed growth mediums are examined. The haemophilus agar ensures growth of Haemophilus influenzae. The chocolate agar, PBM-agar ensure growth of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. By growing characteristics, the national growth mediums match foreign analogues. Under application of growth mediums with selective additions it is possible to achieve selective isolation of main agents of purulent bacterial meningitis with inhibition of growth of microbes-associates.
Highly selective luminescent nanostructures for mitochondrial imaging and targeting
NASA Astrophysics Data System (ADS)
Fanizza, E.; Iacobazzi, R. M.; Laquintana, V.; Valente, G.; Caliandro, G.; Striccoli, M.; Agostiano, A.; Cutrignelli, A.; Lopedota, A.; Curri, M. L.; Franco, M.; Depalo, N.; Denora, N.
2016-02-01
Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino functionalized luminescent silica coated QD nanoparticles (QD@SiO2 NPs) provides a versatile nanoplatform to anchor a potent and selective TSPO ligand, characterized by a 2-phenyl-imidazo[1,2-a]pyridine acetamide structure along with a derivatizable carboxylic end group, useful to conjugate the TSPO ligand and achieve TSPO-QD@SiO2 NPs by means of a covalent amide bond. The colloidal stability and optical properties of the proposed nanomaterials are comprehensively investigated and their potential as mitochondrial imaging agents is fully assessed. Sub-cellular fractionation, together with confocal laser scanning fluorescence microscopy and co-localization analysis of targeted TSPO-QD@SiO2 NPs in C6 glioma cells overexpressing the TSPO, proves the great potential of these multifunctional nanosystems as in vitro selective mitochondrial imaging agents.Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino functionalized luminescent silica coated QD nanoparticles (QD@SiO2 NPs) provides a versatile nanoplatform to anchor a potent and selective TSPO ligand, characterized by a 2-phenyl-imidazo[1,2-a]pyridine acetamide structure along with a derivatizable carboxylic end group, useful to conjugate the TSPO ligand and achieve TSPO-QD@SiO2 NPs by means of a covalent amide bond. The colloidal stability and optical properties of the proposed nanomaterials are comprehensively investigated and their potential as mitochondrial imaging agents is fully assessed. Sub-cellular fractionation, together with confocal laser scanning fluorescence microscopy and co-localization analysis of targeted TSPO-QD@SiO2 NPs in C6 glioma cells overexpressing the TSPO, proves the great potential of these multifunctional nanosystems as in vitro selective mitochondrial imaging agents. Electronic supplementary information (ESI) available: Additional TEM micrographs, fluorescence and UV-Vis absorbance spectra of silica coated QD nanoparticles and TSPO ligand. See DOI: 10.1039/c5nr08139d
Development of Medical Technology for Contingency Response to Marrow Toxic Agents
2014-05-06
Development of Medical Technology for Contingency Response to Marrow Toxic Agents - Final Performance/Technical Report for January 01, 2011 to...Enhancing HLA Data for Selected Donors 44 IIB.1.6 Maintain a Quality Control Program 44 IIB.2.1 Collection of Primary Data 45 IIB.2.2 Validation of...Receptor Donor Selection KORI Korean LD Linkage Disequilibrium LTA Lymphotoxin Alpha MALDI-TOF Matrix-Assisted Laser Desorption/Ionization – Time Of
Ghosh, Chandradhish; Sarkar, Paramita; Samaddar, Sandip; Uppu, Divakara S S M; Haldar, Jayanta
2017-07-25
l-Lysines were conjugated to lipidated biphenyls using simple synthetic chemistry to obtain selective membrane-active antibacterial agents that inhibit cell-wall biosynthesis. The most selective compound bore promising activity against biofilm-related infections and intracellular bacteria, and also suppressed the stimulation of TNF-α induced by lipoteichoic acid. Belligerent to resistance development, it was active in a murine model of MRSA infection.
Ginley, David S; Curtis, Calvin J; Miedaner, Alex; van Hest, Marinus Franciscus Antonius Maria; Kaydanova, Tatiana
2014-02-04
Self-reducing metal inks and systems and methods for producing and using the same are disclosed. In an exemplary embodiment, a method may comprise selecting metal-organic (MO) precursor, selecting a reducing agent, and dissolving the MO precursor and the reducing agent in an organic solvent to produce a metal ink that remains in a liquid phase at room temperature. Metal inks, including self-reducing and fire-through metal inks, are also disclosed, as are various applications of the metal inks.
An opinion formation based binary optimization approach for feature selection
NASA Astrophysics Data System (ADS)
Hamedmoghadam, Homayoun; Jalili, Mahdi; Yu, Xinghuo
2018-02-01
This paper proposed a novel optimization method based on opinion formation in complex network systems. The proposed optimization technique mimics human-human interaction mechanism based on a mathematical model derived from social sciences. Our method encodes a subset of selected features to the opinion of an artificial agent and simulates the opinion formation process among a population of agents to solve the feature selection problem. The agents interact using an underlying interaction network structure and get into consensus in their opinions, while finding better solutions to the problem. A number of mechanisms are employed to avoid getting trapped in local minima. We compare the performance of the proposed method with a number of classical population-based optimization methods and a state-of-the-art opinion formation based method. Our experiments on a number of high dimensional datasets reveal outperformance of the proposed algorithm over others.
Jamier, Vincent; Ba, Lalla A; Jacob, Claus
2010-09-24
Various human diseases, including different types of cancer, are associated with a disturbed intracellular redox balance and oxidative stress (OS). The past decade has witnessed the emergence of redox-modulating compounds able to utilize such pre-existing disturbances in the redox state of sick cells for therapeutic advantage. Selenium- and tellurium-based agents turn the oxidizing redox environment present in certain cancer cells into a lethal cocktail of reactive species that push these cells over a critical redox threshold and ultimately kill them through apoptosis. This kind of toxicity is highly selective: normal, healthy cells remain largely unaffected, since changes to their naturally low levels of oxidizing species produce little effect. To further improve selectivity, multifunctional sensor/effector agents are now required that recognize the biochemical signature of OS in target cells. The synthesis of such compounds provides interesting challenges for chemistry in the future.
Selective advantage of tolerant cultural traits in the Axelrod-Schelling model
NASA Astrophysics Data System (ADS)
Gracia-Lázaro, C.; Floría, L. M.; Moreno, Y.
2011-05-01
The Axelrod-Schelling model incorporates into the original Axelrod’s model of cultural dissemination the possibility that cultural agents placed in culturally dissimilar environments move to other places, the strength of this mobility being controlled by an intolerance parameter. By allowing heterogeneity in the intolerance of cultural agents, and considering it as a cultural feature, i.e., susceptible of cultural transmission (thus breaking the original symmetry of Axelrod-Schelling dynamics), we address here the question of whether tolerant or intolerant traits are more likely to become dominant in the long-term cultural dynamics. Our results show that tolerant traits possess a clear selective advantage in the framework of the Axelrod-Schelling model. We show that the reason for this selective advantage is the development, as time evolves, of a positive correlation between the number of neighbors that an agent has in its environment and its tolerant character.
Selective advantage of tolerant cultural traits in the Axelrod-Schelling model.
Gracia-Lázaro, C; Floría, L M; Moreno, Y
2011-05-01
The Axelrod-Schelling model incorporates into the original Axelrod's model of cultural dissemination the possibility that cultural agents placed in culturally dissimilar environments move to other places, the strength of this mobility being controlled by an intolerance parameter. By allowing heterogeneity in the intolerance of cultural agents, and considering it as a cultural feature, i.e., susceptible of cultural transmission (thus breaking the original symmetry of Axelrod-Schelling dynamics), we address here the question of whether tolerant or intolerant traits are more likely to become dominant in the long-term cultural dynamics. Our results show that tolerant traits possess a clear selective advantage in the framework of the Axelrod-Schelling model. We show that the reason for this selective advantage is the development, as time evolves, of a positive correlation between the number of neighbors that an agent has in its environment and its tolerant character. © 2011 American Physical Society
Wide coverage biomedical event extraction using multiple partially overlapping corpora
2013-01-01
Background Biomedical events are key to understanding physiological processes and disease, and wide coverage extraction is required for comprehensive automatic analysis of statements describing biomedical systems in the literature. In turn, the training and evaluation of extraction methods requires manually annotated corpora. However, as manual annotation is time-consuming and expensive, any single event-annotated corpus can only cover a limited number of semantic types. Although combined use of several such corpora could potentially allow an extraction system to achieve broad semantic coverage, there has been little research into learning from multiple corpora with partially overlapping semantic annotation scopes. Results We propose a method for learning from multiple corpora with partial semantic annotation overlap, and implement this method to improve our existing event extraction system, EventMine. An evaluation using seven event annotated corpora, including 65 event types in total, shows that learning from overlapping corpora can produce a single, corpus-independent, wide coverage extraction system that outperforms systems trained on single corpora and exceeds previously reported results on two established event extraction tasks from the BioNLP Shared Task 2011. Conclusions The proposed method allows the training of a wide-coverage, state-of-the-art event extraction system from multiple corpora with partial semantic annotation overlap. The resulting single model makes broad-coverage extraction straightforward in practice by removing the need to either select a subset of compatible corpora or semantic types, or to merge results from several models trained on different individual corpora. Multi-corpus learning also allows annotation efforts to focus on covering additional semantic types, rather than aiming for exhaustive coverage in any single annotation effort, or extending the coverage of semantic types annotated in existing corpora. PMID:23731785
NASA Astrophysics Data System (ADS)
Lotfy, Hayam Mahmoud; Omran, Yasmin Rostom
2018-07-01
A novel, simple, rapid, accurate, and economical spectrophotometric method, namely absorptivity centering (a-Centering) has been developed and validated for the simultaneous determination of mixtures with partially and completely overlapping spectra in different matrices using either normalized or factorized spectrum using built-in spectrophotometer software without a need of special purchased program. Mixture I (Mix I) composed of Simvastatin (SM) and Ezetimibe (EZ) is the one with partial overlapping spectra formulated as tablets, while mixture II (Mix II) formed by Chloramphenicol (CPL) and Prednisolone acetate (PA) is that with complete overlapping spectra formulated as eye drops. These procedures do not require any separation steps. Resolution of spectrally overlapping binary mixtures has been achieved getting recovered zero-order (D0) spectrum of each drug, then absorbance was recorded at their maxima 238, 233.5, 273 and 242.5 nm for SM, EZ, CPL and PA, respectively. Calibration graphs were established with good correlation coefficients. The method shows significant advantages as simplicity, minimal data manipulation besides maximum reproducibility and robustness. Moreover, it was validated according to ICH guidelines. Selectivity was tested using laboratory-prepared mixtures. Accuracy, precision and repeatability were found to be within the acceptable limits. The proposed method is good enough to be applied to an assay of drugs in their combined formulations without any interference from excipients. The obtained results were statistically compared with those of the reported and official methods by applying t-test and F-test at 95% confidence level concluding that there is no significant difference with regard to accuracy and precision. Generally, this method could be used successfully for the routine quality control testing.
Lotfy, Hayam Mahmoud; Omran, Yasmin Rostom
2018-07-05
A novel, simple, rapid, accurate, and economical spectrophotometric method, namely absorptivity centering (a-Centering) has been developed and validated for the simultaneous determination of mixtures with partially and completely overlapping spectra in different matrices using either normalized or factorized spectrum using built-in spectrophotometer software without a need of special purchased program. Mixture I (Mix I) composed of Simvastatin (SM) and Ezetimibe (EZ) is the one with partial overlapping spectra formulated as tablets, while mixture II (Mix II) formed by Chloramphenicol (CPL) and Prednisolone acetate (PA) is that with complete overlapping spectra formulated as eye drops. These procedures do not require any separation steps. Resolution of spectrally overlapping binary mixtures has been achieved getting recovered zero-order (D 0 ) spectrum of each drug, then absorbance was recorded at their maxima 238, 233.5, 273 and 242.5 nm for SM, EZ, CPL and PA, respectively. Calibration graphs were established with good correlation coefficients. The method shows significant advantages as simplicity, minimal data manipulation besides maximum reproducibility and robustness. Moreover, it was validated according to ICH guidelines. Selectivity was tested using laboratory-prepared mixtures. Accuracy, precision and repeatability were found to be within the acceptable limits. The proposed method is good enough to be applied to an assay of drugs in their combined formulations without any interference from excipients. The obtained results were statistically compared with those of the reported and official methods by applying t-test and F-test at 95% confidence level concluding that there is no significant difference with regard to accuracy and precision. Generally, this method could be used successfully for the routine quality control testing. Copyright © 2018 Elsevier B.V. All rights reserved.