22 CFR 230.07 - Fiscal Agent obligations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Fiscal Agent obligations. 230.07 Section 230.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUB. L. 108-11-STANDARD TERMS AND CONDITIONS § 230.07...

22 CFR 230.07 - Fiscal Agent obligations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Fiscal Agent obligations. 230.07 Section 230.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUB. L. 108-11-STANDARD TERMS AND CONDITIONS § 230.07...

22 CFR 230.07 - Fiscal Agent obligations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Fiscal Agent obligations. 230.07 Section 230.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ISRAEL LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUB. L. 108-11-STANDARD TERMS AND CONDITIONS § 230.07...

Mitigating randomness of consumer preferences under certain conditional choices

NASA Astrophysics Data System (ADS)

Bothos, John M. A.; Thanos, Konstantinos-Georgios; Papadopoulou, Eirini; Daveas, Stelios; Thomopoulos, Stelios C. A.

2017-05-01

Agent-based crowd behaviour consists a significant field of research that has drawn a lot of attention in recent years. Agent-based crowd simulation techniques have been used excessively to forecast the behaviour of larger or smaller crowds in terms of certain given conditions influenced by specific cognition models and behavioural rules and norms, imposed from the beginning. Our research employs conditional event algebra, statistical methodology and agent-based crowd simulation techniques in developing a behavioural econometric model about the selection of certain economic behaviour by a consumer that faces a spectre of potential choices when moving and acting in a multiplex mall. More specifically we try to analyse the influence of demographic, economic, social and cultural factors on the economic behaviour of a certain individual and then we try to link its behaviour with the general behaviour of the crowds of consumers in multiplex malls using agent-based crowd simulation techniques. We then run our model using Generalized Least Squares and Maximum Likelihood methods to come up with the most probable forecast estimations, regarding the agent's behaviour. Our model is indicative about the formation of consumers' spectre of choices in multiplex malls under the condition of predefined preferences and can be used as a guide for further research in this area.

The comparison of socio-economic conditions and personal hygiene habits of neuro-Behçet's disease and multiple sclerosis patients.

PubMed

Pehlivan, Münevver; Kürtüncü, Murat; Tüzün, Erdem; Shugaiv, Erkingül; Mutlu, Melike; Eraksoy, Mefküre; Akman-Demir, Gülşen

2011-07-01

The "hygiene hypothesis" suggests that a reduction in the exposure to infectious agents due to improved health conditions has contributed to the increased incidence of autoimmune disorders in developed countries. In keeping with the hygiene hypothesis, many autoimmune disorders such as multiple sclerosis (MS) are more frequently observed in developed countries. To identify the relevance of hygiene hypothesis in neuro-Behçet's disease (NBD), another chronic inflammatory disease of the central nervous system, we developed and administered a multiple choice questionnaire to evaluate the hygiene conditions and practices of age and gender-matched NBD patients (n = 50) and control MS (n =5 0) and headache (n = 50) patients. Overall, MS patients had the highest socio-economic and hygiene features, whereas NBD patients displayed a lower socio-economic status group and showed poorer hygiene conditions than MS and headache controls. These poor hygiene conditions might be increasing the susceptibility of exposure to infectious agents that might, at least in part, trigger the inflammatory responses involved in NBD pathogenesis. Copyright © 2011 Elsevier GmbH. All rights reserved.

Unresolved issues in hematopoietic stem cell transplantation for severe combined immunodeficiency: Need for safer conditioning and reduced late effects

PubMed Central

Horn, Biljana; Cowan, Morton J.

2017-01-01

In this review we discuss recent outcomes of hematopoietic cell transplantation (HCT) for patients with severe combined immunodeficiency (SCID), including survival, T- and B-cell reconstitution, and late effects, particularly those related to genotype, use of conditioning regimen, and use of alternative donors. We identify the following issues that require additional data, which can be obtained through cooperative studies: outcomes of patients with SCID who did not receive conditioning before alternative donor HCT; outcomes of patients with SCID who did not receive graft-versus-host disease prophylaxis after T cell–replete HCT; late effects of HCT for patients with SCID, including neurocognitive outcomes, growth, and development; and their relationship to genotype and use of alkylating agents for conditioning. Careful follow-up of outcomes of all newborns receiving diagnoses based on newborn screening programs for SCID is essential because data are scarce on the effects of conditioning regimens in very young patients. A consensus on the definition of T- and B-cell recovery, criteria for additional “boosts,” pharmacokinetic data of chemotherapy agents used in young children, and uniformity of the use of various chemotherapy agents are needed to compare results among institutions. Finally, development of new nontoxic conditioning regimens for HCT that can be safely used in very young children is required. PMID:23622119

Effect of certain psychopharmacological preparations on adaptation under stress conditions

NASA Technical Reports Server (NTRS)

Stanishevskaya, A. V.; Mezentseva, L. N.

1980-01-01

Experiments staged on rats demonstrated that the formation of pathological states caused by stress and accompanied by the development of ulcerative lesion of the gastric mucosa are associated with the degree of the catecholamines level drop in the mesencephalon and hypothalamus. The application of seduxen and also of combinations consisting of L-DOPA with seduxen, or with an L-adrenoblocking agent pyroxan tends to reduce the frequency of developing alcerative lesions of the stomach. The protective effect produced by the combination of L-DOPA with an L-adrenoblocking agent pyroxan is barred by an additional administration of an B-adrenoblocking agent, inderal.

FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

PubMed Central

Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

2015-01-01

Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative regimens of a variety of other hematological and non-hematological malignancies. The addition of newer agents to conditioning like bortezomib or lenalidomide for myeloma, or clofarabine for myeloid malignancies, may improve antitumor effects for transplantation, while in combination with alemtuzumab may represent a backbone for future cellular therapy due to reliable engraftment and low toxicity profile. This review summarizes the development and the current use of this remarkable drug in hematopoietic stem-cell transplantation. PMID:22922522

18-Methoxycoronaridine, a potential anti-obesity agent, does not produce a conditioned taste aversion in rats

PubMed Central

Taraschenko, Olga D.; Maisonneuve, Isabelle M.; Glick, Stanley D.

2015-01-01

18-Methoxycoronaridine (18-MC), a selective antagonist of α3β4 nicotinic receptors, has been shown to reduce the self-administration of several drugs of abuse. Recently, this agent has also been shown to attenuate sucrose reward, decrease sucrose intake and prevent the development of sucrose-induced obesity in rats. The present experiments were designed to determine whether the latter effect was due to an 18-MC-induced conditioned taste aversion to sucrose. Both 18-MC (20 mg/ kg, i.p.) and control agent, lithium chloride (100 mg/kg, i.p.), reduced sucrose intake 24 h after association with sucrose; however, only lithium chloride reduced sucrose intake 72h later. Consistent with previous data, 18-MC appears to have proactive effect for 24h and it does not induce a conditioned taste aversion. PMID:20457177

Biobotic insect swarm based sensor networks for search and rescue

NASA Astrophysics Data System (ADS)

Bozkurt, Alper; Lobaton, Edgar; Sichitiu, Mihail; Hedrick, Tyson; Latif, Tahmid; Dirafzoon, Alireza; Whitmire, Eric; Verderber, Alexander; Marin, Juan; Xiong, Hong

2014-06-01

The potential benefits of distributed robotics systems in applications requiring situational awareness, such as search-and-rescue in emergency situations, are indisputable. The efficiency of such systems requires robotic agents capable of coping with uncertain and dynamic environmental conditions. For example, after an earthquake, a tremendous effort is spent for days to reach to surviving victims where robotic swarms or other distributed robotic systems might play a great role in achieving this faster. However, current technology falls short of offering centimeter scale mobile agents that can function effectively under such conditions. Insects, the inspiration of many robotic swarms, exhibit an unmatched ability to navigate through such environments while successfully maintaining control and stability. We have benefitted from recent developments in neural engineering and neuromuscular stimulation research to fuse the locomotory advantages of insects with the latest developments in wireless networking technologies to enable biobotic insect agents to function as search-and-rescue agents. Our research efforts towards this goal include development of biobot electronic backpack technologies, establishment of biobot tracking testbeds to evaluate locomotion control efficiency, investigation of biobotic control strategies with Gromphadorhina portentosa cockroaches and Manduca sexta moths, establishment of a localization and communication infrastructure, modeling and controlling collective motion by learning deterministic and stochastic motion models, topological motion modeling based on these models, and the development of a swarm robotic platform to be used as a testbed for our algorithms.

Social conditioning and extinction paradigm: a translational study in virtual reality.

PubMed

Shiban, Youssef; Reichenberger, Jonas; Neumann, Inga D; Mühlberger, Andreas

2015-01-01

In human beings, experiments investigating fear conditioning with social stimuli are rare. The current study aims at translating an animal model for social fear conditioning (SFC) to a human sample using an operant SFC paradigm in virtual reality. Forty participants actively (using a joystick) approached virtual male agents that served as conditioned stimuli (CS). During the acquisition phase, unconditioned stimuli (US), a combination of an air blast (5 bar, 10 ms) and a female scream (95 dB, 40 ms), were presented when participants reached a defined proximity to the agent with a contingency of 75% for CS+ agents and never for CS- agents. During the extinction and the test phases, no US was delivered. Outcome variables were pleasantness ratings and physiological reactions in heart rate (HR) and fear-potentiated startle. Additionally, the influence of social anxiety, which was measured with the Social Phobia Inventory scale, was evaluated. As expected after the acquisition phase the CS+ was rated clearly less pleasant than the CS-. This difference vanished during extinction. Furthermore, the HR remained high for the CS+, while the HR for the CS- was clearly lower after than before the acquisition. Furthermore, a clear difference between CS+ and CS- after the acquisition indicated successful conditioning on this translational measure. Contrariwise no CS+/CS- differences were observed in the physiological variables during extinction. Importantly, at the generalization test, higher socially fearful participants rated pleasantness of all agents as low whereas the lower socially fearful participants rated pleasantness as low only for the CS+. SFC was successfully induced and extinguished confirming operant conditioning in this SFC paradigm. These findings suggest that the paradigm is suitable to expand the knowledge about the learning and unlearning of social fears. Further studies should investigate the operant mechanisms of development and treatment of social anxiety disorder.

A capillary electrophoresis chip for the analysis of print and film photographic developing agents in commercial processing solutions using indirect fluorescence detection.

PubMed

Sirichai, S; de Mello, A J

2001-01-01

The separation and detection of both print and film developing agents (CD-3 and CD-4) in photographic processing solutions using chip-based capillary electrophoresis is presented. For simultaneous detection of both analytes under identical experimental conditions a buffer pH of 11.9 is used to partially ionise the analytes. Detection is made possible by indirect fluorescence, where the ions of the analytes displace the anionic fluorescing buffer ion to create negative peaks. Under optimal conditions, both analytes can be analyzed within 30 s. The limits of detection for CD-3 and CD-4 are 0.17 mM and 0.39 mM, respectively. The applicability of the method for the analysis of seasoned photographic processing developer solutions is also examined.

Biological control of Ixodes ricinus larvae and nymphs with Metarhizium anisopliae blastospores.

PubMed

Wassermann, Marion; Selzer, Philipp; Steidle, Johannes L M; Mackenstedt, Ute

2016-07-01

The entomopathogenic fungus Metarhizium anisopliae is used as a biological pest control agent against various arthropod species, including ticks. However, the efficacy depends on tick species, tick stage and fungus strain. We studied the effect of M. anisopliae on engorged larvae and nymphs of Ixodes ricinus, the most abundant tick species in Europe, under laboratory and semi-field conditions. A significant reduction of engorged larvae and nymphs could be shown under laboratory as well as under semi-field conditions. Only 3.5% of the larvae treated in the lab and only 18.5% kept under semi-field conditions were able to develop into nymphs compared to the recovered nymphs of the control groups, which were regarded as 100%. Only 7.1% of nymphs were recovered as adult ticks after fungal treatment under semi-field conditions compared to the control (100%). The efficacy of blastospores of M. anisopliae against engorged larvae and nymphs of I. ricinus under semi-field conditions was demonstrated in this study, showing their high potential as a biological control agent of ticks. Further studies will have to investigate the effect of this agent against other stages of I. ricinus as well as other tick species before its value as a biological control agent against ticks can be fully assessed. Copyright © 2016 Elsevier GmbH. All rights reserved.

Topical benzocaine-induced methemoglobinemia in the pediatric population.

PubMed

So, Tsz-Yin; Farrington, Elizabeth

2008-01-01

Topical benzocaine is an anesthetic agent that is often used before procedures and clinical tests, such as esophagoscopy, bronchoscopy, and endotracheal intubation. However, a potential deadly condition known as methemoglobinemia can occur with this agent. It causes the oxidation of hemoglobin to methemoglobinemia to occur more rapidly than the reduction of methemoglobin back to hemoglobin. Certain congenital and clinical conditions that affect oxygen delivery can increase the patient's risk of having methemoglobinemia develop with the use of benzocaine. Topical benzocaine-induced methemoglobinemia can occur in the pediatric population. Prompt management with intravenous methylene blue should be initiated for reversal.

Structural estimation of a principal-agent model: moral hazard in medical insurance.

PubMed

Vera-Hernández, Marcos

2003-01-01

Despite the importance of principal-agent models in the development of modern economic theory, there are few estimations of these models. I recover the estimates of a principal-agent model and obtain an approximation to the optimal contract. The results show that out-of-pocket payments follow a concave profile with respect to costs of treatment. I estimate the welfare loss due to moral hazard, taking into account income effects. I also propose a new measure of moral hazard based on the conditional correlation between contractible and noncontractible variables.

Application of agent-based system for bioprocess description and process improvement.

PubMed

Gao, Ying; Kipling, Katie; Glassey, Jarka; Willis, Mark; Montague, Gary; Zhou, Yuhong; Titchener-Hooker, Nigel J

2010-01-01

Modeling plays an important role in bioprocess development for design and scale-up. Predictive models can also be used in biopharmaceutical manufacturing to assist decision-making either to maintain process consistency or to identify optimal operating conditions. To predict the whole bioprocess performance, the strong interactions present in a processing sequence must be adequately modeled. Traditionally, bioprocess modeling considers process units separately, which makes it difficult to capture the interactions between units. In this work, a systematic framework is developed to analyze the bioprocesses based on a whole process understanding and considering the interactions between process operations. An agent-based approach is adopted to provide a flexible infrastructure for the necessary integration of process models. This enables the prediction of overall process behavior, which can then be applied during process development or once manufacturing has commenced, in both cases leading to the capacity for fast evaluation of process improvement options. The multi-agent system comprises a process knowledge base, process models, and a group of functional agents. In this system, agent components co-operate with each other in performing their tasks. These include the description of the whole process behavior, evaluating process operating conditions, monitoring of the operating processes, predicting critical process performance, and providing guidance to decision-making when coping with process deviations. During process development, the system can be used to evaluate the design space for process operation. During manufacture, the system can be applied to identify abnormal process operation events and then to provide suggestions as to how best to cope with the deviations. In all cases, the function of the system is to ensure an efficient manufacturing process. The implementation of the agent-based approach is illustrated via selected application scenarios, which demonstrate how such a framework may enable the better integration of process operations by providing a plant-wide process description to facilitate process improvement. Copyright 2009 American Institute of Chemical Engineers

The Potential of Streptomyces as Biocontrol Agents against the Rice Blast Fungus, Magnaporthe oryzae (Pyricularia oryzae).

PubMed

Law, Jodi Woan-Fei; Ser, Hooi-Leng; Khan, Tahir M; Chuah, Lay-Hong; Pusparajah, Priyia; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

2017-01-01

Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae ). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10-30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyce s bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae . The ability of various S treptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae . In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents.

The Potential of Streptomyces as Biocontrol Agents against the Rice Blast Fungus, Magnaporthe oryzae (Pyricularia oryzae)

PubMed Central

Law, Jodi Woan-Fei; Ser, Hooi-Leng; Khan, Tahir M.; Chuah, Lay-Hong; Pusparajah, Priyia; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

2017-01-01

Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10–30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyces bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae. The ability of various Streptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae. In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents. PMID:28144236

Generalized paired-agent kinetic model for in vivo quantification of cancer cell-surface receptors under receptor saturation conditions

NASA Astrophysics Data System (ADS)

Sadeghipour, N.; Davis, S. C.; Tichauer, K. M.

2017-01-01

New precision medicine drugs oftentimes act through binding to specific cell-surface cancer receptors, and thus their efficacy is highly dependent on the availability of those receptors and the receptor concentration per cell. Paired-agent molecular imaging can provide quantitative information on receptor status in vivo, especially in tumor tissue; however, to date, published approaches to paired-agent quantitative imaging require that only ‘trace’ levels of imaging agent exist compared to receptor concentration. This strict requirement may limit applicability, particularly in drug binding studies, which seek to report on a biological effect in response to saturating receptors with a drug moiety. To extend the regime over which paired-agent imaging may be used, this work presents a generalized simplified reference tissue model (GSRTM) for paired-agent imaging developed to approximate receptor concentration in both non-receptor-saturated and receptor-saturated conditions. Extensive simulation studies show that tumor receptor concentration estimates recovered using the GSRTM are more accurate in receptor-saturation conditions than the standard simple reference tissue model (SRTM) (% error (mean  ±  sd): GSRTM 0  ±  1 and SRTM 50  ±  1) and match the SRTM accuracy in non-saturated conditions (% error (mean  ±  sd): GSRTM 5  ±  5 and SRTM 0  ±  5). To further test the approach, GSRTM-estimated receptor concentration was compared to SRTM-estimated values extracted from tumor xenograft in vivo mouse model data. The GSRTM estimates were observed to deviate from the SRTM in tumors with low receptor saturation (which are likely in a saturated regime). Finally, a general ‘rule-of-thumb’ algorithm is presented to estimate the expected level of receptor saturation that would be achieved in a given tissue provided dose and pharmacokinetic information about the drug or imaging agent being used, and physiological information about the tissue. These studies suggest that the GSRTM is necessary when receptor saturation exceeds 20% and highlight the potential for GSRTM to accurately measure receptor concentrations under saturation conditions, such as might be required during high dose drug studies, or for imaging applications where high concentrations of imaging agent are required to optimize signal-to-noise conditions. This model can also be applied to PET and SPECT imaging studies that tend to suffer from noisier data, but require one less parameter to fit if images are converted to imaging agent concentration (quantitative PET/SPECT).

Safety Assessment of Pentaerythrityl Tetraesters as Used in Cosmetics.

PubMed

Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2015-09-01

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of 16 pentaerythrityl tetraester compounds as used in cosmetics. These ingredients mostly function as hair-conditioning agents, skin-conditioning agents-miscellaneous and binders, skin-conditioning agents-occlusive, viscosity-increasing agents-nonaqueous, and skin-conditioning agents-emollient. The Panel reviewed the available animal and human data related to these ingredients and previous safety assessments of the fatty acid moieties. The Panel concluded that pentaerythrityl tetraisostearate and the other pentaerythrityl tetraester compounds were safe in the practices of use and concentration as given in this safety assessment. © The Author(s) 2015.

Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents.

PubMed

Abed, Dhulfiqar Ali; Goldstein, Melanie; Albanyan, Haifa; Jin, Huijuan; Hu, Longqin

2015-07-01

The Keap1-Nrf2-ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1-Nrf2 protein-protein interaction (PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1-Nrf2 PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1׳s cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1-Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1-Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.

Thioesters for the in vitro evaluation of agents to image brain cholinesterases.

PubMed

Macdonald, Ian R; Jollymore, Courtney T; Reid, G Andrew; Pottie, Ian R; Martin, Earl; Darvesh, Sultan

2013-06-01

Cholinesterases are associated with pathology characteristic of conditions such as Alzheimer's disease and are therefore, considered targets for neuroimaging. Ester derivatives of N-methylpiperidinol are promising potential imaging agents; however, methodology is lacking for evaluating these compounds in vitro. Here, we report the synthesis and evaluation of a series of N-methylpiperidinyl thioesters, possessing comparable properties to their corresponding esters, which can be directly evaluated for cholinesterase kinetics and histochemical distribution in human brain tissue. N-methylpiperidinyl esters and thioesters were synthesized and they demonstrated comparable cholinesterase kinetics. Furthermore, thioesters were capable, using histochemical method, to visualize cholinesterase activity in human brain tissue. N-methylpiperidinyl thioesters can be rapidly evaluated for cholinesterase kinetics and visualization of enzyme distribution in brain tissue which may facilitate development of cholinesterase imaging agents for application to conditions such as Alzheimer's disease.

Effects of exogenous agents on brain development: stress, abuse and therapeutic compounds.

PubMed

Archer, Trevor

2011-10-01

The range of exogenous agents likely to affect, generally detrimentally, the normal development of the brain and central nervous system defies estimation although the amount of accumulated evidence is enormous. The present review is limited to certain types of chemotherapeutic and "use-and-abuse" compounds and environmental agents, exemplified by anesthetic, antiepileptic, sleep-inducing and anxiolytic compounds, nicotine and alcohol, and stress as well as agents of infection; each of these agents have been investigated quite extensively and have been shown to contribute to the etiopathogenesis of serious neuropsychiatric disorders. To greater or lesser extent, all of the exogenous agents discussed in the present treatise have been investigated for their influence upon neurodevelopmental processes during the period of the brain growth spurt and during other phases uptill adulthood, thereby maintaining the notion of critical phases for the outcome of treatment whether prenatal, postnatal, or adolescent. Several of these agents have contributed to the developmental disruptions underlying structural and functional brain abnormalities that are observed in the symptom and biomarker profiles of the schizophrenia spectrum disorders and the fetal alcohol spectrum disorders. In each case, the effects of the exogenous agents upon the status of the affected brain, within defined parameters and conditions, is generally permanent and irreversible. © 2010 Blackwell Publishing Ltd.

Young children with autism spectrum disorder use predictive eye movements in action observation.

PubMed

Falck-Ytter, Terje

2010-06-23

Does a dysfunction in the mirror neuron system (MNS) underlie the social symptoms defining autism spectrum disorder (ASD)? Research suggests that the MNS matches observed actions to motor plans for similar actions, and that these motor plans include directions for predictive eye movements when observing goal-directed actions. Thus, one important question is whether children with ASD use predictive eye movements in action observation. Young children with ASD as well as typically developing children and adults were shown videos in which an actor performed object-directed actions (human agent condition). Children with ASD were also shown control videos showing objects moving by themselves (self-propelled condition). Gaze was measured using a corneal reflection technique. Children with ASD and typically developing individuals used strikingly similar goal-directed eye movements when observing others' actions in the human agent condition. Gaze was reactive in the self-propelled condition, suggesting that prediction is linked to seeing a hand-object interaction. This study does not support the view that ASD is characterized by a global dysfunction in the MNS.

[Forensic medical expertise of the injurious exposure].

PubMed

Shadymov, A B

2014-01-01

The objective of the present study was to develop the standardized approach to the evaluation of the character of injurious exposure with a view to objective interpretation of the conditions of injury formation and the properties of the traumatic agent. The main attention was given to such parameters of the injurious exposure as loading conditions (mass, speed, direction) and the surface properties of the traumatic agent (area, shape, hardness). It is expected that the use of the proposed system for the evaluation of the injurious exposure in the practical work of forensic medical experts will enhance the reliability of their conclusions and help to avoid mistakes.

Bridging the Gap between Academic Research and Regional Development in the Basque Country

ERIC Educational Resources Information Center

Karlsen, James; Larrea, Miren; Wilson, James R.; Aranguren, Mari Jose

2012-01-01

The discussion in this article focuses on how the gap between academic knowledge and regional development can be bridged, creating conditions for change processes between researchers and regional agents. Institutional entrepreneurs can create regional development organisations and research organisations, but in order to fulfil regional needs it is…

Biogenic Growth of Alloys and Core-Shell Nanostructures Using Urease as a Nanoreactor at Ambient Conditions

PubMed Central

Sharma, Bhagwati; Mandani, Sonam; Sarma, Tridib K.

2013-01-01

Biomineralization is an extremely efficient biologically guided process towards the advancement of nano-bio integrated materials. As a prime module of the natural world, enzymes are expected to play a major role in biogenic growth of inorganic nanostructures. Although there have been developments in designing enzyme-responsive nanoparticle systems or generation of inorganic nanostructures in an enzyme-stimulated environment, reports regarding action of enzymes as reducing agents themselves for the growth of inorganic nanoparticles still remains elusive. Here we present a mechanistic investigation towards the synthesis of metal and metallic alloy nanoparticles using a commonly investigated enzyme, Jack bean urease (JBU), as a reducing as well as stabilizing agent under physiological conditions. The catalytic functionality of urease was taken advantage of towards the development of metal-ZnO core-shell nanocomposites, making urease an ideal bionanoreactor for synthesizing higher order nanostructures such as alloys and core- shell under ambient conditions. PMID:24018831

Social Dynamics in Web Page through Inter-Agent Interaction

NASA Astrophysics Data System (ADS)

Takeuchi, Yugo; Katagiri, Yasuhiro

Social persuasion abounds in human-human interactions. Attitudes and behaviors of people are invariably influenced by the attitudes and behaviors of other people as well as our social roles/relationships toward them. In the pedagogic scene, the relationship between teacher and learner produces one of the most typical interactions, in which the teacher makes the learner spontaneously study what he/she teaches. This study is an attempt to elucidate the nature and effectiveness of social persuasion in human-computer interaction environments. We focus on the social dynamics of multi-party interactions that involve both human-agent and inter-agent interactions. An experiment is conducted in a virtual web-instruction setting employing two types of agents: conductor agents who accompany and guide each learner throughout his/her learning sessions, and domain-expert agents who provide explanations and instructions for each stage of the instructional materials. In this experiment, subjects are assigned two experimental conditions: the authorized condition, in which an agent respectfully interacts with another agent, and the non-authorized condition, in which an agent carelessly interacts with another agent. The results indicate performance improvements in the authorized condition of inter-agent interactions. An analysis is given from the perspective of the transfer of authority from inter-agent to human-agent interactions based on social conformity. We argue for pedagogic advantages of social dynamics created by multiple animated character agents.

New Therapeutic Approaches for Familial Hypercholesterolemia.

PubMed

Ajufo, Ezim; Rader, Daniel J

2018-01-29

Familial hypercholesterolemia (FH) is a common genetic condition characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), premature atherosclerotic cardiovascular disease, and considerable unmet medical need with conventional LDL-C-lowering therapies. Between 2012 and 2015, the US Food and Drug Administration approved four novel LDL-C-lowering agents for use in patients with FH based on the pronounced LDL-C-lowering efficacy of these medicines. We review the four novel approved agents, as well as promising LDL-C-lowering agents in clinical development, with a focus on their mechanism of action, efficacy in FH cohorts, and safety.

Mitochondrial toxicity in human pregnancy: an update on clinical and experimental approaches in the last 10 years.

PubMed

Morén, Constanza; Hernández, Sandra; Guitart-Mampel, Mariona; Garrabou, Glòria

2014-09-22

Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.

Do two and three year old children use an incremental first-NP-as-agent bias to process active transitive and passive sentences?: A permutation analysis

PubMed Central

Chang, Franklin; Rowland, Caroline; Ferguson, Heather; Pine, Julian

2017-01-01

We used eye-tracking to investigate if and when children show an incremental bias to assume that the first noun phrase in a sentence is the agent (first-NP-as-agent bias) while processing the meaning of English active and passive transitive sentences. We also investigated whether children can override this bias to successfully distinguish active from passive sentences, after processing the remainder of the sentence frame. For this second question we used eye-tracking (Study 1) and forced-choice pointing (Study 2). For both studies, we used a paradigm in which participants simultaneously saw two novel actions with reversed agent-patient relations while listening to active and passive sentences. We compared English-speaking 25-month-olds and 41-month-olds in between-subjects sentence structure conditions (Active Transitive Condition vs. Passive Condition). A permutation analysis found that both age groups showed a bias to incrementally map the first noun in a sentence onto an agent role. Regarding the second question, 25-month-olds showed some evidence of distinguishing the two structures in the eye-tracking study. However, the 25-month-olds did not distinguish active from passive sentences in the forced choice pointing task. In contrast, the 41-month-old children did reanalyse their initial first-NP-as-agent bias to the extent that they clearly distinguished between active and passive sentences both in the eye-tracking data and in the pointing task. The results are discussed in relation to the development of syntactic (re)parsing. PMID:29049390

Considerations in detecting CDC select agents under field conditions

NASA Astrophysics Data System (ADS)

Spinelli, Charles; Soelberg, Scott; Swanson, Nathaneal; Furlong, Clement; Baker, Paul

2008-04-01

Surface Plasmon Resonance (SPR) has become a widely accepted technique for real-time detection of interactions between receptor molecules and ligands. Antibody may serve as receptor and can be attached to the gold surface of the SPR device, while candidate analyte fluids contact the detecting antibody. Minute, but detectable, changes in refractive indices (RI) indicate that analyte has bound to the antibody. A decade ago, an inexpensive, robust, miniature and fully integrated SPR chip, called SPREETA, was developed. University of Washington (UW) researchers subsequently developed a portable, temperature-regulated instrument, called SPIRIT, to simultaneously use eight of these three-channel SPREETA chips. A SPIRIT prototype instrument was tested in the field, coupled to a remote reporting system on a surrogate unmanned aerial vehicle (UAV). Two target protein analytes were released sequentially as aerosols with low analyte concentration during each of three flights and were successfully detected and verified. Laboratory experimentation with a more advanced SPIRIT instrument demonstrated detection of very low levels of several select biological agents that might be employed by bioterrorists. Agent detection under field-like conditions is more challenging, especially as analyte concentrations are reduced and complex matricies are introduced. Two different sample preconditioning protocols have been developed for select agents in complex matrices. Use of these preconditioning techniques has allowed laboratory detection in spiked heavy mud of Francisella tularensis at 10 3 CFU/ml, Bacillus anthracis spores at 10 3 CFU/ml, Staphylococcal enterotoxin B (SEB) at 1 ng/ml, and Vaccinia virus (a smallpox simulant) at 10 5 PFU/ml. Ongoing experiments are aimed at simultaneous detection of multiple agents in spiked heavy mud, using a multiplex preconditioning protocol.

HURON (HUman and Robotic Optimization Network) Multi-Agent Temporal Activity Planner/Scheduler

NASA Technical Reports Server (NTRS)

Hua, Hook; Mrozinski, Joseph J.; Elfes, Alberto; Adumitroaie, Virgil; Shelton, Kacie E.; Smith, Jeffrey H.; Lincoln, William P.; Weisbin, Charles R.

2012-01-01

HURON solves the problem of how to optimize a plan and schedule for assigning multiple agents to a temporal sequence of actions (e.g., science tasks). Developed as a generic planning and scheduling tool, HURON has been used to optimize space mission surface operations. The tool has also been used to analyze lunar architectures for a variety of surface operational scenarios in order to maximize return on investment and productivity. These scenarios include numerous science activities performed by a diverse set of agents: humans, teleoperated rovers, and autonomous rovers. Once given a set of agents, activities, resources, resource constraints, temporal constraints, and de pendencies, HURON computes an optimal schedule that meets a specified goal (e.g., maximum productivity or minimum time), subject to the constraints. HURON performs planning and scheduling optimization as a graph search in state-space with forward progression. Each node in the graph contains a state instance. Starting with the initial node, a graph is automatically constructed with new successive nodes of each new state to explore. The optimization uses a set of pre-conditions and post-conditions to create the children states. The Python language was adopted to not only enable more agile development, but to also allow the domain experts to easily define their optimization models. A graphical user interface was also developed to facilitate real-time search information feedback and interaction by the operator in the search optimization process. The HURON package has many potential uses in the fields of Operations Research and Management Science where this technology applies to many commercial domains requiring optimization to reduce costs. For example, optimizing a fleet of transportation truck routes, aircraft flight scheduling, and other route-planning scenarios involving multiple agent task optimization would all benefit by using HURON.

Social conditioning and extinction paradigm: a translational study in virtual reality

PubMed Central

Shiban, Youssef; Reichenberger, Jonas; Neumann, Inga D.; Mühlberger, Andreas

2015-01-01

In human beings, experiments investigating fear conditioning with social stimuli are rare. The current study aims at translating an animal model for social fear conditioning (SFC) to a human sample using an operant SFC paradigm in virtual reality. Forty participants actively (using a joystick) approached virtual male agents that served as conditioned stimuli (CS). During the acquisition phase, unconditioned stimuli (US), a combination of an air blast (5 bar, 10 ms) and a female scream (95 dB, 40 ms), were presented when participants reached a defined proximity to the agent with a contingency of 75% for CS+ agents and never for CS– agents. During the extinction and the test phases, no US was delivered. Outcome variables were pleasantness ratings and physiological reactions in heart rate (HR) and fear-potentiated startle. Additionally, the influence of social anxiety, which was measured with the Social Phobia Inventory scale, was evaluated. As expected after the acquisition phase the CS+ was rated clearly less pleasant than the CS–. This difference vanished during extinction. Furthermore, the HR remained high for the CS+, while the HR for the CS– was clearly lower after than before the acquisition. Furthermore, a clear difference between CS+ and CS– after the acquisition indicated successful conditioning on this translational measure. Contrariwise no CS+/CS– differences were observed in the physiological variables during extinction. Importantly, at the generalization test, higher socially fearful participants rated pleasantness of all agents as low whereas the lower socially fearful participants rated pleasantness as low only for the CS+. SFC was successfully induced and extinguished confirming operant conditioning in this SFC paradigm. These findings suggest that the paradigm is suitable to expand the knowledge about the learning and unlearning of social fears. Further studies should investigate the operant mechanisms of development and treatment of social anxiety disorder. PMID:25904889

Robust consensus algorithm for multi-agent systems with exogenous disturbances under convergence conditions

NASA Astrophysics Data System (ADS)

Jiang, Yulian; Liu, Jianchang; Tan, Shubin; Ming, Pingsong

2014-09-01

In this paper, a robust consensus algorithm is developed and sufficient conditions for convergence to consensus are proposed for a multi-agent system (MAS) with exogenous disturbances subject to partial information. By utilizing H∞ robust control, differential game theory and a design-based approach, the consensus problem of the MAS with exogenous bounded interference is resolved and the disturbances are restrained, simultaneously. Attention is focused on designing an H∞ robust controller (the robust consensus algorithm) based on minimisation of our proposed rational and individual cost functions according to goals of the MAS. Furthermore, sufficient conditions for convergence of the robust consensus algorithm are given. An example is employed to demonstrate that our results are effective and more capable to restrain exogenous disturbances than the existing literature.

Inherently safe in situ uranium recovery

DOEpatents

Krumhansl, James L; Brady, Patrick V

2014-04-29

An in situ recovery of uranium operation involves circulating reactive fluids through an underground uranium deposit. These fluids contain chemicals that dissolve the uranium ore. Uranium is recovered from the fluids after they are pumped back to the surface. Chemicals used to accomplish this include complexing agents that are organic, readily degradable, and/or have a predictable lifetime in an aquifer. Efficiency is increased through development of organic agents targeted to complexing tetravalent uranium rather than hexavalent uranium. The operation provides for in situ immobilization of some oxy-anion pollutants under oxidizing conditions as well as reducing conditions. The operation also artificially reestablishes reducing conditions on the aquifer after uranium recovery is completed. With the ability to have the impacted aquifer reliably remediated, the uranium recovery operation can be considered inherently safe.

Biosensor Based on Self-Assembling Acetylcholinesterase on Carbon Nanotubes for Flow injection/Amperometric Detection of Organophosphate Pesticides and Nerve Agents

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

Liu, Guodong; Lin, Yuehe

A highly sensitive flow-injection amperometric biosensor for organophosphate pesticides and nerve agents based on self-assembly of acetylcholinesterase (AChE) on carbon nanotube (CNT)-modified glassy carbon (GC) electrode is described. AChE is immobilized on the negatively-charged CNT surface by alternatively assembling a cationic polydiallyldimethylammonium chloride (PDDA) layer and an AChE layer. Transmission electron microscopy images confirm the formation of layer-by-layer nanostructures on carboxyl functionalized CNTs. The unique sandwich-like structure (PDDA/AChE/PDDA) on the CNT surface formed by self-assembly provides a favorable microenvironment to keep the bioactivity of AChE and to prevent enzyme molecule leakage. The electrocatalytic activity of CNT leads to a greatlymore » improved electrochemical detection of the enzymatically generated thiocholine product, including a low oxidation overvoltage (+150 mV), higher sensitivity, and stability. The developed PDDA/AChE/PDDA/CNT/GC biosensor integrated into a flow injection system was used to monitor organophosphate pesticides and nerve agents, such as paraoxon. The sensor performance, including inhibition time and regeneration conditions, was optimized with respect to operating conditions. Under the optimal conditions, the biosensor was used to measure as low as 0.4 pM paraoxon with a 6-min inhibition time. The biosensor had excellent operational lifetime stability with no decrease in the activity of enzymes for more than 20 repeated measurements over a 1-week period. The developed biosensor system is an ideal tool for online monitoring of organophosphate pesticides and nerve agents.« less

In Situ Observation of Plastic Foaming under Static Condition, Extensional Flow and Shear Flow

NASA Astrophysics Data System (ADS)

Wong, Anson Sze Tat

Traditional blowing agents (e.g., hydrochlorofluorocarbons) in plastic foaming processes has been phasing out due to environmental regulations. Plastic foaming industry is forced to employ greener alternatives (e.g., carbon dioxide, nitrogen), but their foaming processes are technologically challenging. Moreover, to improve the competitiveness of the foaming industry, it is imperative to develop a new generation of value-added plastic foams with cell structures that can be tailored to different applications. In this context, the objective of this thesis is to achieve a thorough understanding on cell nucleation and growth phenomena that determine cell structures in plastic foaming processes. The core research strategy is to develop innovative visualization systems to capture and study these phenomena. A system with accurate heating and cooling control has been developed to observe and study crystallization-induced foaming behaviors of polymers under static conditions. The cell nucleation and initial growth behavior of polymers blown with different blowing agents (nitrogen, argon and helium, and carbon dioxide-nitrogen mixtures) have also been investigated in great detail. Furthermore, two innovative systems have been developed to simulate the dynamic conditions in industrial foaming processes: one system captures a foaming process under an easily adjustable and uniform extensional strain in a high temperature and pressure environment, while the other achieves the same target, but with shear strain. Using these systems, the extensional and shear effects on bubble nucleation and initial growth processes has been investigated independently in an isolated manner, which has never been achieved previously. The effectiveness of cell nucleating agents has also been evaluated under dynamic conditions, which have led to the identification of new foaming mechanisms based on polymer-chain alignment and generation of microvoids under stress. Knowledge generated from these researches and the wide range of future studies made possible by the visualization systems will be valuable to the development of innovative plastic foaming technologies and foams.

DYNACLIPS (DYNAmic CLIPS): A dynamic knowledge exchange tool for intelligent agents

NASA Technical Reports Server (NTRS)

Cengeloglu, Yilmaz; Khajenoori, Soheil; Linton, Darrell

1994-01-01

In a dynamic environment, intelligent agents must be responsive to unanticipated conditions. When such conditions occur, an intelligent agent may have to stop a previously planned and scheduled course of actions and replan, reschedule, start new activities and initiate a new problem solving process to successfully respond to the new conditions. Problems occur when an intelligent agent does not have enough knowledge to properly respond to the new situation. DYNACLIPS is an implementation of a framework for dynamic knowledge exchange among intelligent agents. Each intelligent agent is a CLIPS shell and runs a separate process under SunOS operating system. Intelligent agents can exchange facts, rules, and CLIPS commands at run time. Knowledge exchange among intelligent agents at run times does not effect execution of either sender and receiver intelligent agent. Intelligent agents can keep the knowledge temporarily or permanently. In other words, knowledge exchange among intelligent agents would allow for a form of learning to be accomplished.

Antibiofilm agents: A new perspective for antimicrobial strategy.

PubMed

Li, Xi-Hui; Lee, Joon-Hee

2017-10-01

Biofilms are complex microbial architectures that attach to surfaces and encase microorganisms in a matrix composed of self-produced hydrated extracellular polymeric substances (EPSs). In biofilms, microorganisms become much more resistant to antimicrobial treatments, harsh environmental conditions, and host immunity. Biofilm formation by microbial pathogens greatly enhances survival in hosts and causes chronic infections that result in persistent inflammation and tissue damages. Currently, it is believed over 80% of chronic infectious diseases are mediated by biofilms, and it is known that conventional antibiotic medications are inadequate at eradicating these biofilm-mediated infections. This situation demands new strategies for biofilm-associated infections, and currently, researchers focus on the development of antibiofilm agents that are specific to biofilms, but are nontoxic, because it is believed that this prevents the development of drug resistance. Here, we review the most promising antibiofilm agents undergoing intensive research and development.

Agent-Based Chemical Plume Tracing Using Fluid Dynamics

NASA Technical Reports Server (NTRS)

Zarzhitsky, Dimitri; Spears, Diana; Thayer, David; Spears, William

2004-01-01

This paper presents a rigorous evaluation of a novel, distributed chemical plume tracing algorithm. The algorithm is a combination of the best aspects of the two most popular predecessors for this task. Furthermore, it is based on solid, formal principles from the field of fluid mechanics. The algorithm is applied by a network of mobile sensing agents (e.g., robots or micro-air vehicles) that sense the ambient fluid velocity and chemical concentration, and calculate derivatives. The algorithm drives the robotic network to the source of the toxic plume, where measures can be taken to disable the source emitter. This work is part of a much larger effort in research and development of a physics-based approach to developing networks of mobile sensing agents for monitoring, tracking, reporting and responding to hazardous conditions.

Theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma.

PubMed

Lee, Jangwook; Min, Hyun-Su; You, Dong Gil; Kim, Kwangmeyung; Kwon, Ick Chan; Rhim, Taiyoun; Lee, Kuen Yong

2016-02-10

The development of safe and efficient diagnostic/therapeutic agents for treating cancer in clinics remains challenging due to the potential toxicity of conventional agents. Although the annual incidence of neuroblastoma is not that high, the disease mainly occurs in children, a population vulnerable to toxic contrast agents and therapeutics. We demonstrate here that cancer-targeting, gas-generating polymeric nanoparticles are useful as a theranostic tool for ultrasound (US) imaging and treating neuroblastoma. We encapsulated calcium carbonate using poly(d,l-lactide-co-glycolide) and created gas-generating polymer nanoparticles (GNPs). These nanoparticles release carbon dioxide bubbles under acidic conditions and enhance US signals. When GNPs are modified using rabies virus glycoprotein (RVG) peptide, a targeting moiety to neuroblastoma, RVG-GNPs effectively accumulate at the tumor site and substantially enhance US signals in a tumor-bearing mouse model. Intravenous administration of RVG-GNPs also reduces tumor growth in the mouse model without the use of conventional therapeutic agents. This approach to developing theranostic agents with disease-targeting ability may provide useful strategy for the detection and treatment of cancers, allowing safe and efficient clinical applications with fewer side effects than may occur with conventional agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Terrestrial condition assessment for national forests of the USDA Forest Service in the continental US

Treesearch

David Cleland; Keith Reynolds; Robert Vaughan; Barbara Schrader; Harbin Li; Larry Laing

2017-01-01

The terrestrial condition assessment (TCA) evaluates effects of uncharacteristic stressors and disturbance agents on land-type associations (LTAs) to identify restoration opportunities on national forest system (NFS) lands in the United States. A team of agency scientists and managers, representing a broad array of natural resource disciplines, developed a logic...

Ultrathin graphene oxide-based hollow fiber membranes with brush-like CO2-philic agent for highly efficient CO2 capture.

PubMed

Zhou, Fanglei; Tien, Huynh Ngoc; Xu, Weiwei L; Chen, Jung-Tsai; Liu, Qiuli; Hicks, Ethan; Fathizadeh, Mahdi; Li, Shiguang; Yu, Miao

2017-12-13

Among the current CO 2 capture technologies, membrane gas separation has many inherent advantages over other conventional techniques. However, fabricating gas separation membranes with both high CO 2 permeance and high CO 2 /N 2 selectivity, especially under wet conditions, is a challenge. In this study, sub-20-nm thick, layered graphene oxide (GO)-based hollow fiber membranes with grafted, brush-like CO 2 -philic agent alternating between GO layers are prepared by a facile coating process for highly efficient CO 2 /N 2 separation under wet conditions. Piperazine, as an effective CO 2 -philic agent, is introduced as a carrier-brush into the GO nanochannels with chemical bonding. The membrane exhibits excellent separation performance under simulated flue gas conditions with CO 2 permeance of 1,020 GPU and CO 2 /N 2 selectivity as high as 680, demonstrating its potential for CO 2 capture from flue gas. We expect this GO-based membrane structure combined with the facile coating process to facilitate the development of ultrathin GO-based membranes for CO 2 capture.

Developing a consensus framework and risk profile for agents of opportunity in academic medical centers: implications for public health preparedness.

PubMed

Farmer, Brenna M; Nelson, Lewis S; Graham, Margaret E; Bendzans, Carly; McCrillis, Aileen M; Portelli, Ian; Zhang, Meng; Goldberg, Judith; Rosenberg, Sheldon D; Goldfrank, Lewis R; Tunik, Michael

2010-12-01

Agents of opportunity (AO) in academic medical centers (AMC) are defined as unregulated or lightly regulated substances used for medical research or patient care that can be used as "dual purpose" substances by terrorists to inflict damage upon populations. Most of these agents are used routinely throughout AMC either during research or for general clinical practice. To date, the lack of careful regulations for AOs creates uncertain security conditions and increased malicious potential. Using a consensus-based approach, we collected information and opinions from staff working in an AMC and 4 AMC-affiliated hospitals concerning identification of AO, AO attributes, and AMC risk and preparedness, focusing on AO security and dissemination mechanisms and likely hospital response. The goal was to develop a risk profile and framework for AO in the institution. Agents of opportunity in 4 classes were identified and an AO profile was developed, comprising 16 attributes denoting information critical to preparedness for AO misuse. Agents of opportunity found in AMC present a unique and vital gap in public health preparedness. Findings of this project may provide a foundation for a discussion and consensus efforts to determine a nationally accepted risk profile framework for AO. This foundation may further lead to the implementation of appropriate regulatory policies to improve public health preparedness. Agents of opportunity modeling of dissemination properties should be developed to better predict AO risk.

Failures in Phase III: Causes and Consequences.

PubMed

Seruga, Bostjan; Ocana, Alberto; Amir, Eitan; Tannock, Ian F

2015-10-15

Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. ©2015 American Association for Cancer Research.

In Vitro Conservation of Date Palm Shoot-Tip Explants and Callus Cultures Under Minimal Growth Conditions.

PubMed

El-Dawayati, Maiada M

2017-01-01

Date palm fruit production has great economic significance for many countries. There is a fundamental necessity to conserve valuable date palm germplasm, but there are various problems with in vivo and ex situ conservation. In vitro storage has several advantages over conventional germplasm conservation methods. The in vitro technique offers a developed method of slow-growth storage, which is considered as an alternate solution for short- and medium-term storage of date palm germplasm under controlled conditions. Minimal growth conditions for germplasm conservation are generally achieved by reducing growth rate through modification of environmental growing conditions and culture, by using low temperatures, and the addition of growth retardants and osmotic agents. This chapter describes a protocol for short-term in vitro conservation of date palm shoot-tip and callus cultures under slow-growth storage conditions, using sucrose as an osmotic agent and abscisic acid (ABA) as a growth retardant at 15 °C for 12 months.

Synchronization of multi-agent systems with metric-topological interactions.

PubMed

Wang, Lin; Chen, Guanrong

2016-09-01

A hybrid multi-agent systems model integrating the advantages of both metric interaction and topological interaction rules, called the metric-topological model, is developed. This model describes planar motions of mobile agents, where each agent can interact with all the agents within a circle of a constant radius, and can furthermore interact with some distant agents to reach a pre-assigned number of neighbors, if needed. Some sufficient conditions imposed only on system parameters and agent initial states are presented, which ensure achieving synchronization of the whole group of agents. It reveals the intrinsic relationships among the interaction range, the speed, the initial heading, and the density of the group. Moreover, robustness against variations of interaction range, density, and speed are investigated by comparing the motion patterns and performances of the hybrid metric-topological interaction model with the conventional metric-only and topological-only interaction models. Practically in all cases, the hybrid metric-topological interaction model has the best performance in the sense of achieving highest frequency of synchronization, fastest convergent rate, and smallest heading difference.

Physics-based agent to simulant correlations for vapor phase mass transport.

PubMed

Willis, Matthew P; Varady, Mark J; Pearl, Thomas P; Fouse, Janet C; Riley, Patrick C; Mantooth, Brent A; Lalain, Teri A

2013-12-15

Chemical warfare agent simulants are often used as an agent surrogate to perform environmental testing, mitigating exposure hazards. This work specifically addresses the assessment of downwind agent vapor concentration resulting from an evaporating simulant droplet. A previously developed methodology was used to estimate the mass diffusivities of the chemical warfare agent simulants methyl salicylate, 2-chloroethyl ethyl sulfide, di-ethyl malonate, and chloroethyl phenyl sulfide. Along with the diffusivity of the chemical warfare agent bis(2-chloroethyl) sulfide, the simulant diffusivities were used in an advection-diffusion model to predict the vapor concentrations downwind from an evaporating droplet of each chemical at various wind velocities and temperatures. The results demonstrate that the simulant-to-agent concentration ratio and the corresponding vapor pressure ratio are equivalent under certain conditions. Specifically, the relationship is valid within ranges of measurement locations relative to the evaporating droplet and observation times. The valid ranges depend on the relative transport properties of the agent and simulant, and whether vapor transport is diffusion or advection dominant. Published by Elsevier B.V.

Development of inhibition as a function of the presence of a supernatural agent.

PubMed

King, Ashley C

2011-01-01

In this study the author examined the developmental differences in inhibition and cognition of 4-8-year-old children as a function of the suggested presence of a supernatural agent. Previous evolutionarily-relevant research has suggested that humans are naturally primed to think in terms of supernatural agents and that, given the correct context, individuals readily accept novel supernatural entities and alter their behavior accordingly. All children in this study played 4 games designed to assess their present level of inhibitory and cognitive development. Children in the experimental condition were also introduced to an invisible Princess Alice and were told that she was watching during the games. Following these measures, all children engaged in a resistance-to-temptation task. Results revealed that cognitively advanced children were more likely to express belief in Princess Alice than were less cognitively advanced children. This research provides support that cognitive maturity, rather than immaturity, may be necessary for children to express belief in novel supernatural agents.

Novel targeted therapies for eosinophilic disorders

PubMed Central

Wechsler, Michael E.; Fulkerson, Patricia C.; Bochner, Bruce S.; Gauvreau, Gail M.; Gleich, Gerald J.; Henkel, Tim; Kolbeck, Roland; Mathur, Sameer K.; Ortega, Hector; Patel, Jatin; Prussin, Calman; Renzi, Paolo; Rothenberg, Marc E.; Roufosse, Florence; Simon, Dagmar; Simon, Hans-Uwe; Wardlaw, Andrew; Weller, Peter F.; Klion, Amy D.

2013-01-01

Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders. PMID:22935585

Study on Heat Transfer Agent Models of Transmission Line and Transformer

NASA Astrophysics Data System (ADS)

Wang, B.; Zhang, P. P.

2018-04-01

When using heat transfer simulation to study the dynamic overload of transmission line and transformer, it needs to establish the mathematical expression of heat transfer. However, the formula is a nonlinear differential equation or equation set and it is not easy to get general solutions. Aiming at this problem, some different temperature change processes caused by different initial conditions are calculated by differential equation and equation set. New agent models are developed according to the characteristics of different temperature change processes. The results show that the agent models have high precision and can solve the problem that the original equation cannot be directly applied in some practical engineers.

A Deceptively Simple Solution for Refractory Melasma: Glycolic Acid Peels and Hydroquinone at Home

PubMed Central

Oka, Aiko; Osawa, Ema; Koshima, Isao

2017-01-01

Summary: Although various treatment methods for melasma have developed, substantial improvement of the condition is sometimes difficult. We have experientially found that some of refractory melasma caused by daily friction can easily be treated by using a combination of a peeling agent (20% glycolic acid) and a depigmenting agent (5% hydroquinone) twice daily at home. And here, by performing skin biopsies, we revealed the pathological mechanism: hyperkeratosis caused by repeated physical stimulus, which prevents infiltration of topical therapeutic agents, was dramatically reduced by chemical peeling, resulting that the melanin pigments were effectively cleared by topical hydroquinone. PMID:28607861

Distributed decision-making in electric power system transmission maintenance scheduling using multi-agent systems (MAS)

NASA Astrophysics Data System (ADS)

Zhang, Zhong

In this work, motivated by the need to coordinate transmission maintenance scheduling among a multiplicity of self-interested entities in restructured power industry, a distributed decision support framework based on multiagent negotiation systems (MANS) is developed. An innovative risk-based transmission maintenance optimization procedure is introduced. Several models for linking condition monitoring information to the equipment's instantaneous failure probability are presented, which enable quantitative evaluation of the effectiveness of maintenance activities in terms of system cumulative risk reduction. Methodologies of statistical processing, equipment deterioration evaluation and time-dependent failure probability calculation are also described. A novel framework capable of facilitating distributed decision-making through multiagent negotiation is developed. A multiagent negotiation model is developed and illustrated that accounts for uncertainty and enables social rationality. Some issues of multiagent negotiation convergence and scalability are discussed. The relationships between agent-based negotiation and auction systems are also identified. A four-step MAS design methodology for constructing multiagent systems for power system applications is presented. A generic multiagent negotiation system, capable of inter-agent communication and distributed decision support through inter-agent negotiations, is implemented. A multiagent system framework for facilitating the automated integration of condition monitoring information and maintenance scheduling for power transformers is developed. Simulations of multiagent negotiation-based maintenance scheduling among several independent utilities are provided. It is shown to be a viable alternative solution paradigm to the traditional centralized optimization approach in today's deregulated environment. This multiagent system framework not only facilitates the decision-making among competing power system entities, but also provides a tool to use in studying competitive industry relative to monopolistic industry.

Presidential Green Chemistry Challenge: 1996 Greener Reaction Conditions Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 1996 award winner, Dow Chemical Company, developed a process to manufacture polystyrene foam sheet packaging that uses carbon dioxide (CO2) as a blowing agent, eliminating CFC-12 and HCFC-22.

Quantitative non-invasive intracellular imaging of Plasmodium falciparum infected human erythrocytes

NASA Astrophysics Data System (ADS)

Edward, Kert; Farahi, Faramarz

2014-05-01

Malaria is a virulent pathological condition which results in over a million annual deaths. The parasitic agent Plasmodium falciparum has been extensively studied in connection with this epidemic but much remains unknown about its development inside the red blood cell host. Optical and fluorescence imaging are among the two most common procedures for investigating infected erythrocytes but both require the introduction of exogenous contrast agents. In this letter, we present a procedure for the non-invasive in situ imaging of malaria infected red blood cells. The procedure is based on the utilization of simultaneously acquired quantitative phase and independent topography data to extract intracellular information. Our method allows for the identification of the developmental stages of the parasite and facilitates in situ analysis of the morphological changes associated with the progression of this disease. This information may assist in the development of efficacious treatment therapies for this condition.

Modeling the Population Dynamics of Antibiotic-Resistant Bacteria:. AN Agent-Based Approach

NASA Astrophysics Data System (ADS)

Murphy, James T.; Walshe, Ray; Devocelle, Marc

The response of bacterial populations to antibiotic treatment is often a function of a diverse range of interacting factors. In order to develop strategies to minimize the spread of antibiotic resistance in pathogenic bacteria, a sound theoretical understanding of the systems of interactions taking place within a colony must be developed. The agent-based approach to modeling bacterial populations is a useful tool for relating data obtained at the molecular and cellular level with the overall population dynamics. Here we demonstrate an agent-based model, called Micro-Gen, which has been developed to simulate the growth and development of bacterial colonies in culture. The model also incorporates biochemical rules and parameters describing the kinetic interactions of bacterial cells with antibiotic molecules. Simulations were carried out to replicate the development of methicillin-resistant S. aureus (MRSA) colonies growing in the presence of antibiotics. The model was explored to see how the properties of the system emerge from the interactions of the individual bacterial agents in order to achieve a better mechanistic understanding of the population dynamics taking place. Micro-Gen provides a good theoretical framework for investigating the effects of local environmental conditions and cellular properties on the response of bacterial populations to antibiotic exposure in the context of a simulated environment.

Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis.

PubMed

Seal, John B; Alverdy, John C; Zaborina, Olga; An, Gary

2011-09-19

There is a growing realization that alterations in host-pathogen interactions (HPI) can generate disease phenotypes without pathogen invasion. The gut represents a prime region where such HPI can arise and manifest. Under normal conditions intestinal microbial communities maintain a stable, mutually beneficial ecosystem. However, host stress can lead to changes in environmental conditions that shift the nature of the host-microbe dialogue, resulting in escalation of virulence expression, immune activation and ultimately systemic disease. Effective modulation of these dynamics requires the ability to characterize the complexity of the HPI, and dynamic computational modeling can aid in this task. Agent-based modeling is a computational method that is suited to representing spatially diverse, dynamical systems. We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis. An agent-based model (ABM) of virulence regulation in Pseudomonas aeruginosa was developed by translating bacterial and host cell sense-and-response mechanisms into behavioral rules for computational agents and integrated into a virtual environment representing the host-microbe interface in the gut. The resulting gut milieu ABM (GMABM) was used to: 1) investigate a potential clinically relevant laboratory experimental condition not yet developed--i.e. non-lethal transient segmental intestinal ischemia, 2) examine the sufficiency of existing hypotheses to explain experimental data--i.e. lethality in a model of major surgical insult and stress, and 3) produce behavior to potentially guide future experimental design--i.e. suggested sample points for a potential laboratory model of non-lethal transient intestinal ischemia. Furthermore, hypotheses were generated to explain certain discrepancies between the behaviors of the GMABM and biological experiments, and new investigatory avenues proposed to test those hypotheses. Agent-based modeling can account for the spatio-temporal dynamics of an HPI, and, even when carried out with a relatively high degree of abstraction, can be useful in the investigation of system-level consequences of putative mechanisms operating at the individual agent level. We suggest that an integrated and iterative heuristic relationship between computational modeling and more traditional laboratory and clinical investigations, with a focus on identifying useful and sufficient degrees of abstraction, will enhance the efficiency and translational productivity of biomedical research.

Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis

PubMed Central

2011-01-01

Background There is a growing realization that alterations in host-pathogen interactions (HPI) can generate disease phenotypes without pathogen invasion. The gut represents a prime region where such HPI can arise and manifest. Under normal conditions intestinal microbial communities maintain a stable, mutually beneficial ecosystem. However, host stress can lead to changes in environmental conditions that shift the nature of the host-microbe dialogue, resulting in escalation of virulence expression, immune activation and ultimately systemic disease. Effective modulation of these dynamics requires the ability to characterize the complexity of the HPI, and dynamic computational modeling can aid in this task. Agent-based modeling is a computational method that is suited to representing spatially diverse, dynamical systems. We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis. Methodology/Principal Findings An agent-based model (ABM) of virulence regulation in Pseudomonas aeruginosa was developed by translating bacterial and host cell sense-and-response mechanisms into behavioral rules for computational agents and integrated into a virtual environment representing the host-microbe interface in the gut. The resulting gut milieu ABM (GMABM) was used to: 1) investigate a potential clinically relevant laboratory experimental condition not yet developed - i.e. non-lethal transient segmental intestinal ischemia, 2) examine the sufficiency of existing hypotheses to explain experimental data - i.e. lethality in a model of major surgical insult and stress, and 3) produce behavior to potentially guide future experimental design - i.e. suggested sample points for a potential laboratory model of non-lethal transient intestinal ischemia. Furthermore, hypotheses were generated to explain certain discrepancies between the behaviors of the GMABM and biological experiments, and new investigatory avenues proposed to test those hypotheses. Conclusions/Significance Agent-based modeling can account for the spatio-temporal dynamics of an HPI, and, even when carried out with a relatively high degree of abstraction, can be useful in the investigation of system-level consequences of putative mechanisms operating at the individual agent level. We suggest that an integrated and iterative heuristic relationship between computational modeling and more traditional laboratory and clinical investigations, with a focus on identifying useful and sufficient degrees of abstraction, will enhance the efficiency and translational productivity of biomedical research. PMID:21929759

Melasma: A rare adverse effect of clomipramine.

PubMed

Kar, Sujita Kumar

2016-01-01

Melasma is a hyperpigmented dermatological condition common in females. Drugs such as steroids, cosmetics, and photosensitizing agents are known to cause melasma. We report here a case of an adult male with obsessive-compulsive disorder, receiving clomipramine, who developed melasma.

Coaxial electrospinning for encapsulation and controlled release of fragile water-soluble bioactive agents.

PubMed

Jiang, Hongliang; Wang, Liqun; Zhu, Kangjie

2014-11-10

Coaxial electrospinning is a robust technique for one-step encapsulation of fragile, water-soluble bioactive agents, including growth factors, DNA and even living organisms, into core-shell nanofibers. The coaxial electrospinning process eliminates the damaging effects due to direct contact of the agents with organic solvents or harsh conditions during emulsification. The shell layer serves as a barrier to prevent the premature release of the water-soluble core contents. By varying the structure and composition of the nanofibers, it is possible to precisely modulate the release of the encapsulated agents. Promising work has been done with coaxially electrospun non-woven mats integrated with bioactive agents for use in tissue engineering, in local delivery and in wound healing, etc. This paper reviews the origins of the coaxial electrospinning method, its updated status and potential future developments for controlled release of the class of fragile, water-soluble bioactive agents. Copyright © 2014 Elsevier B.V. All rights reserved.

Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent

PubMed Central

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

Evaluation of the onset of failure under mechanical and thermal stresses on luting agent for metal–ceramic and metal crowns by finite element analysis

PubMed Central

Agnihotri, Hema; Bhatnagar, Naresh; Rao, G. Venugopal; Jain, Veena; Parkash, Hari; Kar, Aswini Kumar

2010-01-01

Long-term clinical failures of cemented prosthesis depend, to a large extent, on the integrity of the luting agent. The causative factors that lead to microfracture and, hence, failure of the luting agents are the stresses acting inside the oral cavity. Therefore, the present study was designed to develop an understanding of the relationship between stresses in the tooth and the failure potential of the luting agent. Two-dimensional finite element stress analysis was performed on the mandibular second premolar. The behavior of zinc-phosphate and glass-ionomer were studied under different crowns (metal–ceramic and metal crown) and loading conditions (mechanical force of 450 N acting vertically over the occlusal surface, thermal loads of 60° and 0°C). It was observed from the study that failure threshold of the luting agent was influenced both by the elastic modulus of the luting agent and by the type of the crown. PMID:22114426

Agent Collaborative Target Localization and Classification in Wireless Sensor Networks

PubMed Central

Wang, Xue; Bi, Dao-wei; Ding, Liang; Wang, Sheng

2007-01-01

Wireless sensor networks (WSNs) are autonomous networks that have been frequently deployed to collaboratively perform target localization and classification tasks. Their autonomous and collaborative features resemble the characteristics of agents. Such similarities inspire the development of heterogeneous agent architecture for WSN in this paper. The proposed agent architecture views WSN as multi-agent systems and mobile agents are employed to reduce in-network communication. According to the architecture, an energy based acoustic localization algorithm is proposed. In localization, estimate of target location is obtained by steepest descent search. The search algorithm adapts to measurement environments by dynamically adjusting its termination condition. With the agent architecture, target classification is accomplished by distributed support vector machine (SVM). Mobile agents are employed for feature extraction and distributed SVM learning to reduce communication load. Desirable learning performance is guaranteed by combining support vectors and convex hull vectors. Fusion algorithms are designed to merge SVM classification decisions made from various modalities. Real world experiments with MICAz sensor nodes are conducted for vehicle localization and classification. Experimental results show the proposed agent architecture remarkably facilitates WSN designs and algorithm implementation. The localization and classification algorithms also prove to be accurate and energy efficient.

Foundations of “new” social science: Institutional legitimacy from philosophy, complexity science, postmodernism, and agent-based modeling

PubMed Central

Henrickson, Leslie; McKelvey, Bill

2002-01-01

Since the death of positivism in the 1970s, philosophers have turned their attention to scientific realism, evolutionary epistemology, and the Semantic Conception of Theories. Building on these trends, Campbellian Realism allows social scientists to accept real-world phenomena as criterion variables against which theories may be tested without denying the reality of individual interpretation and social construction. The Semantic Conception reduces the importance of axioms, but reaffirms the role of models and experiments. Philosophers now see models as “autonomous agents” that exert independent influence on the development of a science, in addition to theory and data. The inappropriate molding effects of math models on social behavior modeling are noted. Complexity science offers a “new” normal science epistemology focusing on order creation by self-organizing heterogeneous agents and agent-based models. The more responsible core of postmodernism builds on the idea that agents operate in a constantly changing web of interconnections among other agents. The connectionist agent-based models of complexity science draw on the same conception of social ontology as do postmodernists. These recent developments combine to provide foundations for a “new” social science centered on formal modeling not requiring the mathematical assumptions of agent homogeneity and equilibrium conditions. They give this “new” social science legitimacy in scientific circles that current social science approaches lack. PMID:12011408

Extraction of Aerosol-Deposited Yersinia pestis from Indoor Surfaces To Determine Bacterial Environmental Decay.

PubMed

Gut, Ian M; Bartlett, Ryan A; Yeager, John J; Leroux, Brian; Ratnesar-Shumate, Shanna; Dabisch, Paul; Karaolis, David K R

2016-05-01

Public health and decontamination decisions following an event that causes indoor contamination with a biological agent require knowledge of the environmental persistence of the agent. The goals of this study were to develop methods for experimentally depositing bacteria onto indoor surfaces via aerosol, evaluate methods for sampling and enumerating the agent on surfaces, and use these methods to determine bacterial surface decay. A specialized aerosol deposition chamber was constructed, and methods were established for reproducible and uniform aerosol deposition of bacteria onto four coupon types. The deposition chamber facilitated the control of relative humidity (RH; 10 to 70%) following particle deposition to mimic the conditions of indoor environments, as RH is not controlled by standard heating, ventilation, and air conditioning (HVAC) systems. Extraction and culture-based enumeration methods to quantify the viable bacteria on coupons were shown to be highly sensitive and reproducible. To demonstrate the usefulness of the system for decay studies,Yersinia pestis persistence as a function of surface type at 21 °C and 40% RH was determined to be >40%/min for all surfaces. Based upon these results, at typical indoor temperature and RH, a 6-log reduction in titer would expected to be achieved within 1 h as the result of environmental decay on surfaces without active decontamination. The developed approach will facilitate future persistence and decontamination studies with a broad range of biological agents and surfaces, providing agent decay data to inform both assessments of risk to personnel entering a contaminated site and decontamination decisions following biological contamination of an indoor environment. Public health and decontamination decisions following contamination of an indoor environment with a biological agent require knowledge of the environmental persistence of the agent. Previous studies on Y. pestis persistence have utilized large liquid droplet deposition to provide persistence data. As a result, methods were developed to deposit aerosols containing bacteria onto indoor surfaces, reproducibly enumerate bacteria harvested from coupons, and determine surface decay utilizing Y. pestis The results of this study provide foundational methods required to evaluate surface decay of bacteria and potentially other biological agents, such as viruses, in aerosol particles as a function of surface type and environment. Integrating the data from both aerosol and liquid deposition surface decay studies will provide medical and public health personnel with a more complete understanding of agent persistence on surfaces in contaminated areas for assessment of health risks and to inform decontamination decisions. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Extraction of Aerosol-Deposited Yersinia pestis from Indoor Surfaces To Determine Bacterial Environmental Decay

PubMed Central

Bartlett, Ryan A.; Yeager, John J.; Leroux, Brian; Ratnesar-Shumate, Shanna; Dabisch, Paul

2016-01-01

ABSTRACT Public health and decontamination decisions following an event that causes indoor contamination with a biological agent require knowledge of the environmental persistence of the agent. The goals of this study were to develop methods for experimentally depositing bacteria onto indoor surfaces via aerosol, evaluate methods for sampling and enumerating the agent on surfaces, and use these methods to determine bacterial surface decay. A specialized aerosol deposition chamber was constructed, and methods were established for reproducible and uniform aerosol deposition of bacteria onto four coupon types. The deposition chamber facilitated the control of relative humidity (RH; 10 to 70%) following particle deposition to mimic the conditions of indoor environments, as RH is not controlled by standard heating, ventilation, and air conditioning (HVAC) systems. Extraction and culture-based enumeration methods to quantify the viable bacteria on coupons were shown to be highly sensitive and reproducible. To demonstrate the usefulness of the system for decay studies, Yersinia pestis persistence as a function of surface type at 21°C and 40% RH was determined to be >40%/min for all surfaces. Based upon these results, at typical indoor temperature and RH, a 6-log reduction in titer would expected to be achieved within 1 h as the result of environmental decay on surfaces without active decontamination. The developed approach will facilitate future persistence and decontamination studies with a broad range of biological agents and surfaces, providing agent decay data to inform both assessments of risk to personnel entering a contaminated site and decontamination decisions following biological contamination of an indoor environment. IMPORTANCE Public health and decontamination decisions following contamination of an indoor environment with a biological agent require knowledge of the environmental persistence of the agent. Previous studies on Y. pestis persistence have utilized large liquid droplet deposition to provide persistence data. As a result, methods were developed to deposit aerosols containing bacteria onto indoor surfaces, reproducibly enumerate bacteria harvested from coupons, and determine surface decay utilizing Y. pestis. The results of this study provide foundational methods required to evaluate surface decay of bacteria and potentially other biological agents, such as viruses, in aerosol particles as a function of surface type and environment. Integrating the data from both aerosol and liquid deposition surface decay studies will provide medical and public health personnel with a more complete understanding of agent persistence on surfaces in contaminated areas for assessment of health risks and to inform decontamination decisions. PMID:26944839

Reduction of mercury from mackerel fillet using combined solution of cysteine, EDTA, and sodium chloride.

PubMed

Hajeb, P; Jinap, S

2012-06-13

An acidic solution containing mercury chelating agents to eliminate mercury in raw fish (mackerel) fillet was developed. The solution contained hydrochloric acid, sodium hydroxide, cysteine, EDTA, and NaCl. The optimum conditions for mercury reduction were achieved using response surface methodology (RSM) at cysteine concentration of 1.25%, EDTA of 275 mg/L, NaCl of 0.5%, pH of 3.75, and exposure time of 18 min. The optimized conditions produced a solution which can remove up to 91% mercury from raw fish fillet. Cysteine and EDTA were identified as potential chelating agents with the greatest potential for use. The solution can be employed in fish industries to reduce mercury in highly contaminated fish.

Development of an injectable PHBV microparticles-GG hydrogel hybrid system for regenerative medicine.

PubMed

Pacheco, Daniela P; Amaral, Maria H; Reis, Rui L; Marques, Alexandra P; Correlo, Vítor M

2015-01-15

Uncontrollable displacements that greatly affect the concentration of active agents at the target tissues are among a major limitation of the use of microparticulate drug delivery systems (DDS). Under this context a biphasic injectable DDS combining poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles (MPs) and a gellan gum (GG) injectable hydrogel is herein proposed for the localized delivery and long-term retention of MPs carrying hydrophilic and hydrophobic model active agents. A double emulsion-solvent evaporation method was adopted to develop the PHBV MPs, carrying bovine serum albumin (BSA) or dexamethasone (Dex) as hydrophilic and hydrophobic active agents' models, respectively. Moreover, this method was modified, together with the properties of the hydrogel to tailor the delivery profile of the active agents. Variations of the composition of the organic phase during the process allowed tuning surface topography, particle size distribution and core porosity of the PHBV MPs and, thus, the in vitro release profile of Dex but not of BSA. Besides, after embedding hydrogels of higher GG concentration led to a slower and more sustained release of both active agents, independently of the processing conditions of the microparticulate system. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Cancer Prevention: Current Status & Future Directions

PubMed Central

Maresso, Karen Colbert; Tsai, Kenneth Y.; Brown, Powel H.; Szabo, Eva; Lippman, Scott; Hawk, Ernest

2016-01-01

The heterogeneity and complexity of advanced cancers strongly supports the rationale for an enhanced focus on molecular prevention as a priority strategy to reduce the burden of cancer. Molecular prevention encompasses traditional chemopreventive agents as well as vaccinations and therapeutic approaches to cancer-predisposing conditions. Despite challenges to the field, we now have refined insights into cancer etiology and early pathogenesis; successful risk assessment and new risk models; agents with broad preventive efficacy (e.g., aspirin) in common chronic diseases, including cancer; and a successful track record of more than 10 agents approved by the FDA for the treatment of precancerous lesions or cancer risk reduction. The development of molecular preventive agents does not differ significantly from the development of therapies for advanced cancers, yet has unique challenges and special considerations given that it most often involves healthy or asymptomatic individuals. Agents, biomarkers, cohorts, overall design, and endpoints are key determinants of molecular preventive trials, as with therapeutic trials, although distinctions exist for each within the preventive setting. Progress in the development and evolution of molecular preventive agents has been steadier in some organ systems, such as breast and skin, than in others. In order for molecular prevention to be fully realized as an effective strategy, a number of challenges to the field must be addressed. Here we provide a brief overview of the context for and special considerations of molecular prevention along with a discussion of the results of major randomized controlled trials. PMID:26284997

Air Activated Self-Decontaminating Polydicyclopentadiene PolyHIPE Foams for Rapid Decontamination of Chemical Warfare Agents.

PubMed

McGann, Christopher L; Daniels, Grant C; Giles, Spencer L; Balow, Robert B; Miranda-Zayas, Jorge L; Lundin, Jeffrey G; Wynne, James H

2018-06-01

The threat of chemical warfare agents (CWA) compels research into novel self-decontaminating materials (SDM) for the continued safety of first-responders, civilians, and active service personnel. The capacity to actively detoxify, as opposed to merely sequester, offending agents under typical environmental conditions defines the added value of SDMs in comparison to traditional adsorptive materials. Porous polymers, synthesized via the high internal phase emulsion (HIPE) templating, provide a facile fabrication method for materials with permeable open cellular structures that may serve in air filtration applications. PolyHIPEs comprising polydicyclopentadiene (polyDCPD) networks form stable hydroperoxide species following activation in air under ambient conditions. The hydroperoxide-containing polyDCPD materials react quickly with CWA simulants, Demeton-S and 2-chloroethyl ethyl sulfide, forming oxidation products as confirmed via gas chromatography mass spectrometry. The simplicity of the detoxification chemistry paired with the porous foam form factor presents an exciting opportunity for the development of self-decontaminating filter media. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development and verification of an agent-based model of opinion leadership.

PubMed

Anderson, Christine A; Titler, Marita G

2014-09-27

The use of opinion leaders is a strategy used to speed the process of translating research into practice. Much is still unknown about opinion leader attributes and activities and the context in which they are most effective. Agent-based modeling is a methodological tool that enables demonstration of the interactive and dynamic effects of individuals and their behaviors on other individuals in the environment. The purpose of this study was to develop and test an agent-based model of opinion leadership. The details of the design and verification of the model are presented. The agent-based model was developed by using a software development platform to translate an underlying conceptual model of opinion leadership into a computer model. Individual agent attributes (for example, motives and credibility) and behaviors (seeking or providing an opinion) were specified as variables in the model in the context of a fictitious patient care unit. The verification process was designed to test whether or not the agent-based model was capable of reproducing the conditions of the preliminary conceptual model. The verification methods included iterative programmatic testing ('debugging') and exploratory analysis of simulated data obtained from execution of the model. The simulation tests included a parameter sweep, in which the model input variables were adjusted systematically followed by an individual time series experiment. Statistical analysis of model output for the 288 possible simulation scenarios in the parameter sweep revealed that the agent-based model was performing, consistent with the posited relationships in the underlying model. Nurse opinion leaders act on the strength of their beliefs and as a result, become an opinion resource for their uncertain colleagues, depending on their perceived credibility. Over time, some nurses consistently act as this type of resource and have the potential to emerge as opinion leaders in a context where uncertainty exists. The development and testing of agent-based models is an iterative process. The opinion leader model presented here provides a basic structure for continued model development, ongoing verification, and the establishment of validation procedures, including empirical data collection.

Emergence of Swarming Behavior: Foraging Agents Evolve Collective Motion Based on Signaling.

PubMed

Witkowski, Olaf; Ikegami, Takashi

2016-01-01

Swarming behavior is common in biology, from cell colonies to insect swarms and bird flocks. However, the conditions leading to the emergence of such behavior are still subject to research. Since Reynolds' boids, many artificial models have reproduced swarming behavior, focusing on details ranging from obstacle avoidance to the introduction of fixed leaders. This paper presents a model of evolved artificial agents, able to develop swarming using only their ability to listen to each other's signals. The model simulates a population of agents looking for a vital resource they cannot directly detect, in a 3D environment. Instead of a centralized algorithm, each agent is controlled by an artificial neural network, whose weights are encoded in a genotype and adapted by an original asynchronous genetic algorithm. The results demonstrate that agents progressively evolve the ability to use the information exchanged between each other via signaling to establish temporary leader-follower relations. These relations allow agents to form swarming patterns, emerging as a transient behavior that improves the agents' ability to forage for the resource. Once they have acquired the ability to swarm, the individuals are able to outperform the non-swarmers at finding the resource. The population hence reaches a neutral evolutionary space which leads to a genetic drift of the genotypes. This reductionist approach to signal-based swarming not only contributes to shed light on the minimal conditions for the evolution of a swarming behavior, but also more generally it exemplifies the effect communication can have on optimal search patterns in collective groups of individuals.

Agent-based model to rural urban migration analysis

NASA Astrophysics Data System (ADS)

Silveira, Jaylson J.; Espíndola, Aquino L.; Penna, T. J. P.

2006-05-01

In this paper, we analyze the rural-urban migration phenomenon as it is usually observed in economies which are in the early stages of industrialization. The analysis is conducted by means of a statistical mechanics approach which builds a computational agent-based model. Agents are placed on a lattice and the connections among them are described via an Ising-like model. Simulations on this computational model show some emergent properties that are common in developing economies, such as a transitional dynamics characterized by continuous growth of urban population, followed by the equalization of expected wages between rural and urban sectors (Harris-Todaro equilibrium condition), urban concentration and increasing of per capita income.

Animal models.

PubMed

Walker, Ellen A

2010-01-01

As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

Participatory development: an approach sensitive to class and gender.

PubMed

Connell, D

1997-08-01

This article begins by presenting development experience gained in the Indonesian province of Irian Jaya as a means of highlighting the centrality of popular participation to the development process. Important lessons from the ongoing development work in Irian Jaya were that it is not sufficient to consult beneficiaries and then act on their behalf or to engage in a development process unless the participants understand the project's conceptual orientation and language and have the tools to assess their needs and options for constructive change effectively. Also, developers must supply participants with information about the larger economic and political context in which they are operating. The article continues with an exploration of the ways in which a focus on class and gender raises participatory development to a new level. Constraints on transformative participation are then defined as 1) the political conditions and power structures existing in the country and community, 2) administrative opposition, 3) sociocultural impediments, and 4) limitations imposed by daily life. While it may be impossible to avoid the effects of such constraints, development agents can help villagers anticipate their impact and support efforts to cope with them. Participatory development challenges the status quo by enhancing economic equity and social equality and, if effective, will engender opposition, especially when a large amount of funding is at stake. Opposition can take many forms, including ridicule or resistance and can get personal. The demand to produce quick results also creates restraints on development agents. It is concluded that the development agent must engage key sectors of the local population in the development process and nurture this participation. Development agents should act as facilitators rather than independent initiators telling people what is best for them. Development agents must become very familiar with the community to earn the trust that is needed to guide people toward self-analysis and priority-setting.

Omission bias and perceived intention in children and adults.

PubMed

Hayashi, Hajimu

2015-06-01

Omission bias refers to the tendency to judge acts of commission as morally worse than equivalent acts of omission. Children aged 7-8 and 11-12 years, as well as adults, made moral judgements about acts of commission and omission in two conditions in which the protagonist obtained a self-directed benefit. In the antisocial condition, the other person was harmed; in the selfish condition, the other person was not harmed. The results showed that adults and both age groups of children judged that the agent who did something (act of commission) was morally worse than the agent who did nothing (omission) for both antisocial and selfish conditions, although this judgement tendency was clearer in the selfish condition than in the antisocial condition. Agent intention was held constant across commission and omission, but most participants rated the intention of the agent who did something as stronger than that of the agent who did nothing. These results suggest that omission bias occurs regardless of differences in age and situation. In addition, perceived intention appears to change in conjunction with omission bias. © 2015 The British Psychological Society.

Cell Penetrating Peptides in the Delivery of Biopharmaceuticals

PubMed Central

Munyendo, Were LL; Lv, Huixia; Benza-Ingoula, Habiba; Baraza, Lilechi D.; Zhou, Jianping

2012-01-01

The cell membrane is a highly selective barrier. This limits the cellular uptake of molecules including DNA, oligonucleotides, peptides and proteins used as therapeutic agents. Different approaches have been employed to increase the membrane permeability and intracellular delivery of these therapeutic molecules. One such approach is the use of Cell Penetrating Peptides (CPPs). CPPs represent a new and innovative concept, which bypasses the problem of bioavailability of drugs. The success of CPPs lies in their ability to unlock intracellular and even intranuclear targets for the delivery of agents ranging from peptides to antibodies and drug-loaded nanoparticles. This review highlights the development of cell penetrating peptides for cell-specific delivery strategies involving biomolecules that can be triggered spatially and temporally within a cell transport pathway by change in physiological conditions. The review also discusses conjugations of therapeutic agents to CPPs for enhanced intracellular delivery and bioavailability that are at the clinical stage of development. PMID:24970133

Thrombopoietic agents.

PubMed

Stasi, Roberto; Bosworth, Jenny; Rhodes, Elizabeth; Shannon, Muriel S; Willis, Fenella; Gordon-Smith, Edward C

2010-01-01

Thrombopoietin (TPO) is the key cytokine involved in thrombopoiesis, and is the endogenous ligand for the thrombopoietin receptor that is expressed on the surface of platelets, megakaryocytes, and megakaryocytic precursors. First-generation thrombopoietic agents were recombinant forms of human TPO, and their development was discontinued after prolonged thrombocytopenia due to neutralizing auto-antibodies cross-reacting with endogenous TPO was observed. Second-generation thrombopoiesis-stimulating molecules are now available, which have unique pharmacological properties and no sequence homology to endogenous TPO. Two of these new agents, romiplostim and eltrombopag, have already completed phase III trials in primary immune thrombocytopenia and have been granted marketing authorization for use in this disease. Phase II and III trials with these novel drugs are ongoing in other conditions characterized by thrombocytopenia, such as chemotherapy, chronic liver disease, and the myelodysplastic syndromes. Most of the other second-generation thrombopoietic growth factors are in early phase clinical development. Copyright 2010 Elsevier Ltd. All rights reserved.

Evolution of Implicit and Explicit Communication in Mobile Robots

NASA Astrophysics Data System (ADS)

de Greeff, Joachim; Nolfi, Stefano

This work investigates the conditions in which a population of embodied agents evolved for the ability to display coordinated/cooperative skills can develop an ability to communicate, whether and to what extent the evolved communication system can complexify during the course of the evolutionary process, and how the characteristics of such communication system varies evolutionarily. The analysis of the obtained results indicates that evolving robots develop a capacity to access/generate information which has a communicative value, an ability to produce different signals encoding useful regularities, and an ability to react appropriately to explicit and implicit signals. The analysis of the obtained results allows us to formulate detailed hypothesis on the evolution of communication for what concern aspects such us: (i) how communication can emerge from a population of initially non-communicating agents, (ii) how communication systems can complexify, (iii) how signals/meanings can originate and how they can be grounded in agents' sensory-motor states.

Cold pearl surfactant-based blends.

PubMed

Crombie, R L

1997-10-01

Pearlizing agents have been used for many years in cosmetic formulations to add a pearlescent effect. Cold pearl surfactant-based blends are mixtures of glycol stearates and surfactants which can be blended in the cold into a wide range of personal-care formulations to create a pearlescent lustre effect. Under controlled manufacturing conditions constant viscosities and crystalline characteristics can be obtained. The development of these blends has been driven by efforts to improve the economics of adding solid pearlizing agents directly into a hot mix formulation. This paper summarizes the history of pearlizers, describes their advantages and physical chemistry of the manufacturing process. Finally some suggestions for applications are given. Les agents nacrants sont utilises depuis de nombreuses annees dans les formulations cosmetiques pour ajouter un effet nacre. Les melanges a froid a base de tensioactif nacre sont des melanges de stearates de glycol et de tensioactifs qui peuvent etre melanges a froid dans une large gamme de formulations d'hygiene personnelle pour creer un effet de lustre nacre. On peut obtenir des viscosites et des proprietes cristallines constantes avec des conditions de fabrication maitrisees. Le developpement de ces melanges a ete porte par les efforts pour ameliorer les couts de l'ajout d'agents nacrants solides directement dans une formulation melangee de l'ajout d'agents nacrants solides directement dans une formulation melangee a chaud. Cet article resume l'histoire des agents nacrants, decrit leurs avantages et al physico-chimie du procede de fabrication. On emet a la fin cetaines suggestions d'applications.

Adapting Price Predictions in TAC SCM

NASA Astrophysics Data System (ADS)

Pardoe, David; Stone, Peter

In agent-based markets, adapting to the behavior of other agents is often necessary for success. When it is not possible to directly model individual competitors, an agent may instead model and adapt to the market conditions that result from competitor behavior. Such an agent could still benefit from reasoning about specific competitor strategies by considering how various combinations of these strategies would impact the conditions being modeled. We present an application of such an approach to a specific prediction problem faced by the agent TacTex-06 in the Trading Agent Competition's Supply Chain Management scenario (TAC SCM).

Development of a Minimum Performance Standard for Hand-Held Fire Extinguishers as a Replacement for Halon 1211 on Civilian Transport Category Aircraft

NASA Astrophysics Data System (ADS)

Webster, Harry

2002-08-01

One or more Halon 1211 hand-held fire extinguishers are specified in Federal Aviation Regulation (FAR) Part 25.851 as a requirement on transport category aircraft with 31 or more seats. Halon 1211 has been linked to the destruction of the ozone layer and production of new Halon 1211 has been halted per the Montreal Protocol in 1993. The phase out of Halon 1211, as the hand-held firefighting agent of choice, for civilian transport category aircraft has necessitated the development of a Minimum Performance Standard (MPS) to evaluate replacement agents. The purpose of the MPS is to insure that there is no reduction in safety, both in terms of effectiveness in fighting onboard fires and toxicity to the passengers and crew. The MPS specifies two new tests that replacement agents must pass in addition to requiring national certifications such as provided by Underwriters Laboratories. The first test evaluates the "flooding" characteristics of the agent against a hidden in-flight fire. This test determines the ability of a streaming agent to function as a flooding agent. The second test evaluates the performance of the agent in fighting a terrorist fire scenario and the associated toxicity hazard. This test measures the agent's ability to extinguish a triple-seat fire in an aircraft cabin under in-flight conditions and the toxicity characteristics of both the neat agent and the products of decomposition. This MPS will insure that the replacement agents will meet or exceed the performance of Halon 1211 both in fighting fires and maintaining a safe breathing environment in aircraft cabins.

You changed your mind! Infants interpret a change in word as signaling a change in an agent's goals.

PubMed

Jin, Kyong-Sun; Song, Hyun-Joo

2017-10-01

Language provides information about our psychological states. For instance, adults can use language to convey information about their goals or preferences. The current research examined whether 14- and 12-month-old infants could interpret a change in an agent's word as signaling a change in her goals. In two experiments, 14-month-olds (Experiment 1) and 12-month-olds (Experiment 2) were first familiarized to an event in which an agent uttered a novel word and then reached for one of two novel objects. During the test trials, the agent uttered a different novel word (different-word condition) or the same word (same-word condition) and then reached for the same object or the other object. Both 14- and 12-month-olds in the different-word condition expected the agent to change her goal and reach for the other object. In contrast, the infants in the same-word condition expected the agent to maintain her goal. In Experiment 3, 12-month-olds who heard two distinct sounds instead of the agent's novel words expected the agent to maintain her goal regardless of the change in the nonlinguistic sounds. Together, these results indicate that by 12months of age infants can use an agent's verbal information to detect a change in her goals. Copyright © 2017 Elsevier Inc. All rights reserved.

Profiling Bad Apples.

ERIC Educational Resources Information Center

LaFee, Scott

2000-01-01

Many school administrators want to develop profiling procedures to identify violence-prone students before bullets start flying. Warning signs (chronic depression, anger, abusive home conditions, violent history) are a staring point. Two FBI agents recommend visiting classrooms, identifying troubled kids, and ensuring that they get help. (MLH)

Mathematical model of the competition life cycle under limited resources conditions: Problem statement for business community

NASA Astrophysics Data System (ADS)

Shelomentsev, A. G.; Medvedev, M. A.; Berg, D. B.; Lapshina, S. N.; Taubayev, A. A.; Davletbaev, R. H.; Savina, D. V.

2017-12-01

Present study is devoted to the development of competition life cycle mathematical model in the closed business community with limited resources. Growth of each agent is determined by the balance of input and output resource flows: input (cash) flow W is covering the variable V and constant C costs and growth dA/dt of the agent's assets A. Value of V is proportional to assets A that allows us to write down a first order non-stationary differential equation of the agent growth. Model includes the number of such equations due to the number of agents. The amount of resources that is available for agents vary in time. The balances of their input and output flows are changing correspondingly to the different stages of the competition life cycle. According to the theory of systems, the most complete description of any object or process is the model of its life cycle. Such a model describes all stages of its development: from the appearance ("birth") through development ("growth") to extinction ("death"). The model of the evolution of an individual firm, not contradicting the economic meaning of events actually observed in the market, is the desired result from modern AVMs for applied use. With a correct description of the market, rules for participants' actions, restrictions, forecasts can be obtained, which modern mathematics and the economy can not give.

Can an agent’s false belief be corrected by an appropriate communication? Psychological reasoning in 18-month-old infants

PubMed Central

Song, Hyun-joo; Onishi, Kristine H.; Baillargeon, Renée; Fisher, Cynthia

2008-01-01

Do 18-month-olds understand that an agent’s false belief can be corrected by an appropriate, though not an inappropriate, communication? In Experiment 1, infants watched a series of events involving two agents, a ball, and two containers: a box and a cup. To start, agent1 played with the ball and then hid it in the box, while agent2 looked on. Next, in agent1’s absence, agent2 moved the ball from the box to the cup. When agent1 returned, agent2 told her “The ball is in the cup!” (informative-intervention condition) or “I like the cup!” (uninformative-intervention condition). During test, agent1 reached for either the box (box event) or the cup (cup event). In the informative-intervention condition, infants who saw the box event looked reliably longer than those who saw the cup event; in the uninformative-intervention condition, the reverse pattern was found. These results suggest that infants expected agent1’s false belief about the ball’s location to be corrected when she was told “The ball is in the cup!”, but not “I like the cup!”. In Experiment 2, agent2 simply pointed to the ball’s new location, and infants again expected agent1’s false belief to be corrected. These and control results provide additional evidence that infants in the second year of life can attribute false beliefs to agents. In addition, the results suggest that by 18 months of age infants expect agents’ false beliefs to be corrected by relevant communications involving words or gestures. PMID:18976745

Stepwise flow diagram for the development of formulations of non spore-forming bacteria against foliar pathogens: The case of Lysobacter capsici AZ78.

PubMed

Segarra, Guillem; Puopolo, Gerardo; Giovannini, Oscar; Pertot, Ilaria

2015-12-20

The formulation is a significant step in biopesticide development and is an efficient way to obtain consistency in terms of biological control under field conditions. Nonetheless, there is still a lack of information regarding the processes needed to achieve efficient formulation of non spore-forming bacterial biological control agents. In response to this, we propose a flow diagram made up of six steps including selection of growth parameters, checking of minimum shelf life, selection of protective additives, checking that the additives have no adverse effects, validation of the additive mix under field conditions and choosing whether to use additives as co-formulants or tank mix additives. This diagram is intended to provide guidance and decision-making criteria for the formulation of non spore-forming bacterial biological control agents against foliar pathogens. The diagram was then validated by designing an efficient formulation for a Gram-negative bacterium, Lysobacter capsici AZ78, to control grapevine downy mildew caused by Plasmopara viticola. A harvest of 10(10)L. capsici AZ78cellsml(-1) was obtained in a bench top fermenter. The viability of cells decreased by only one order of magnitude after one year of storage at 4°C. The use of a combination of corn steep liquor, lignosulfonate, and polyethyleneglycol in the formulation improved the survival of L. capsici AZ78 cells living on grapevine leaves under field conditions by one order of magnitude. Furthermore, the use of these additives also guaranteed a reduction of 71% in P. viticola attacks. In conclusion, this work presents a straightforward stepwise flow diagram to help researchers develop formulations for biological control agents that are easy to prepare, stable, not phytotoxic and able to protect the microorganims under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Modeling and Visualizing Flow of Chemical Agents Across Complex Terrain

NASA Technical Reports Server (NTRS)

Kao, David; Kramer, Marc; Chaderjian, Neal

2005-01-01

Release of chemical agents across complex terrain presents a real threat to homeland security. Modeling and visualization tools are being developed that capture flow fluid terrain interaction as well as point dispersal downstream flow paths. These analytic tools when coupled with UAV atmospheric observations provide predictive capabilities to allow for rapid emergency response as well as developing a comprehensive preemptive counter-threat evacuation plan. The visualization tools involve high-end computing and massive parallel processing combined with texture mapping. We demonstrate our approach across a mountainous portion of North California under two contrasting meteorological conditions. Animations depicting flow over this geographical location provide immediate assistance in decision support and crisis management.

Innovative MIOR Process Utilizing Indigenous Reservoir Constituents

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

D. O. Hitzman; A. K. Stepp; D. M. Dennis

This research program is directed at improving the knowledge of reservoir ecology and developing practical microbial solutions for improving oil production. The goal is to identify indigenous microbial populations which can produce beneficial metabolic products and develop a methodology to stimulate those select microbes with nutrient amendments to increase oil recovery. This microbial technology has the capability of producing multiple oil-releasing agents. Experimental laboratory work is underway. Microbial cultures have been isolated from produced water samples. Comparative laboratory studies demonstrating in situ production of microbial products as oil recovery agents were conducted in sand packs with natural field waters withmore » cultures and conditions representative of oil reservoirs. Field pilot studies are underway.« less

Exploration for Agents with Different Personalities in Unknown Environments

NASA Astrophysics Data System (ADS)

Doumit, Sarjoun; Minai, Ali

We present in this paper a personality-based architecture (PA) that combines elements from the subsumption architecture and reinforcement learning to find alternate solutions for problems facing artificial agents exploring unknown environments. The underlying PA algorithm is decomposed into layers according to the different (non-contiguous) stages that our agent passes in, which in turn are influenced by the sources of rewards present in the environment. The cumulative rewards collected by an agent, in addition to its internal composition serve as factors in shaping its personality. In missions where multiple agents are deployed, our solution-goal is to allow each of the agents develop its own distinct personality in order for the collective to reach a balanced society, which then can accumulate the largest possible amount of rewards for the agent and society as well. The architecture is tested in a simulated matrix world which embodies different types of positive rewards and negative rewards. Varying experiments are performed to compare the performance of our algorithm with other algorithms under the same environment conditions. The use of our architecture accelerates the overall adaptation of the agents to their environment and goals by allowing the emergence of an optimal society of agents with different personalities. We believe that our approach achieves much efficient results when compared to other more restrictive policy designs.

Agent-Based Modeling of Chronic Diseases: A Narrative Review and Future Research Directions

PubMed Central

Lawley, Mark A.; Siscovick, David S.; Zhang, Donglan; Pagán, José A.

2016-01-01

The United States is experiencing an epidemic of chronic disease. As the US population ages, health care providers and policy makers urgently need decision models that provide systematic, credible prediction regarding the prevention and treatment of chronic diseases to improve population health management and medical decision-making. Agent-based modeling is a promising systems science approach that can model complex interactions and processes related to chronic health conditions, such as adaptive behaviors, feedback loops, and contextual effects. This article introduces agent-based modeling by providing a narrative review of agent-based models of chronic disease and identifying the characteristics of various chronic health conditions that must be taken into account to build effective clinical- and policy-relevant models. We also identify barriers to adopting agent-based models to study chronic diseases. Finally, we discuss future research directions of agent-based modeling applied to problems related to specific chronic health conditions. PMID:27236380

Agent-Based Modeling of Chronic Diseases: A Narrative Review and Future Research Directions.

PubMed

Li, Yan; Lawley, Mark A; Siscovick, David S; Zhang, Donglan; Pagán, José A

2016-05-26

The United States is experiencing an epidemic of chronic disease. As the US population ages, health care providers and policy makers urgently need decision models that provide systematic, credible prediction regarding the prevention and treatment of chronic diseases to improve population health management and medical decision-making. Agent-based modeling is a promising systems science approach that can model complex interactions and processes related to chronic health conditions, such as adaptive behaviors, feedback loops, and contextual effects. This article introduces agent-based modeling by providing a narrative review of agent-based models of chronic disease and identifying the characteristics of various chronic health conditions that must be taken into account to build effective clinical- and policy-relevant models. We also identify barriers to adopting agent-based models to study chronic diseases. Finally, we discuss future research directions of agent-based modeling applied to problems related to specific chronic health conditions.

An agent-based modeling framework for evaluating hypotheses on risks for developing autism: effects of the gut microbial environment.

PubMed

Weston, Bronson; Fogal, Benjamin; Cook, Daniel; Dhurjati, Prasad

2015-04-01

The number of cases diagnosed with Autism Spectrum Disorders is rising at an alarming rate with the Centers for Disease Control estimating the 2014 incidence rate as 1 in 68. Recently, it has been hypothesized that gut bacteria may contribute to the development of autism. Specifically, the relative balances between the inflammatory microbes clostridia and desulfovibrio and the anti-inflammatory microbe bifidobacteria may become destabilized prior to autism development. The imbalance leads to a leaky gut, characterized by a more porous epithelial membrane resulting in microbial toxin release into the blood, which may contribute to brain inflammation and autism development. To test how changes in population dynamics of the gut microbiome may lead to the imbalanced microbial populations associated with autism patients, we constructed a novel agent-based model of clostridia, desulfovibrio, and bifidobacteria population interactions in the gut. The model demonstrates how changing physiological conditions in the gut can affect the population dynamics of the microbiome. Simulations using our agent-based model indicate that despite large perturbations to initial levels of bacteria, the populations robustly achieve a single steady-state given similar gut conditions. These simulation results suggests that disturbance such as a prebiotic or antibiotic treatment may only transiently affect the gut microbiome. However, sustained prebiotic treatments may correct low population counts of bifidobacteria. Furthermore, our simulations suggest that clostridia growth rate is a key determinant of risk of autism development. Treatment of high-risk infants with supra-physiological levels of lysozymes may suppress clostridia growth rate, resulting in a steep decrease in the clostridia population and therefore reduced risk of autism development. Copyright © 2015 Elsevier Ltd. All rights reserved.

An agent-oriented approach to automated mission operations

NASA Technical Reports Server (NTRS)

Truszkowski, Walt; Odubiyi, Jide

1994-01-01

As we plan for the next generation of Mission Operations Control Center (MOCC) systems, there are many opportunities for the increased utilization of innovative knowledge-based technologies. The innovative technology discussed is an advanced use of agent-oriented approaches to the automation of mission operations. The paper presents an overview of this technology and discusses applied operational scenarios currently being investigated and prototyped. A major focus of the current work is the development of a simple user mechanism that would empower operations staff members to create, in real time, software agents to assist them in common, labor intensive operations tasks. These operational tasks would include: handling routine data and information management functions; amplifying the capabilities of a spacecraft analyst/operator to rapidly identify, analyze, and correct spacecraft anomalies by correlating complex data/information sets and filtering error messages; improving routine monitoring and trend analysis by detecting common failure signatures; and serving as a sentinel for spacecraft changes during critical maneuvers enhancing the system's capabilities to support nonroutine operational conditions with minimum additional staff. An agent-based testbed is under development. This testbed will allow us to: (1) more clearly understand the intricacies of applying agent-based technology in support of the advanced automation of mission operations and (2) access the full set of benefits that can be realized by the proper application of agent-oriented technology in a mission operations environment. The testbed under development addresses some of the data management and report generation functions for the Explorer Platform (EP)/Extreme UltraViolet Explorer (EUVE) Flight Operations Team (FOT). We present an overview of agent-oriented technology and a detailed report on the operation's concept for the testbed.

[Experimental surgical model of hydrocele for the use of sclerotherapy].

PubMed

Castillo Jimeno, J M; Santiago, A M; Sebastián, J L; Ruiz, J L; Pérez Unzu, A; Puras, A; Marcotegui, F

1990-10-01

Sclerosant therapy for different pathological conditions (testicular hydrocele, pneumothorax) is a little known and scantily used procedure in the clinical setting. We have developed a surgical procedure in the dog that permits reproducing adult hydrocele. This experimental model is useful for morphometric assessment of the sclerosant effects of the commonly used agents (magnesium silicate hydrate, carbolic acid, ethanolamine oleate, hydroxytetracycline chlorhydrate and quinacrine chlorhydrate). Our results show that the degree of sclerosis achieved with quinacrine and hydrotetracycline is significantly superior to that obtained with other agents.

[Laboratory diagnosis of toxoplasmosis].

PubMed

Strhársky, J; Mad'arová, L; Klement, C

2009-04-01

Under Central European climatic conditions, toxoplasmosis is one of the most common human parasitic diseases. A wide range of methods for both direct and indirect detection of the causative agent are currently available for the laboratory diagnosis of toxoplasmosis. The purpose of the article is to review the history of the discovery of the causative agent of toxoplasmosis and how laboratory diagnostic methods were developed and improved. The main emphasis is placed on current options in the diagnosis of Toxoplasma gondii, more precisely on the serodiagnosis and new trends in molecular biology-based techniques.

Coping with Exercise-Induced Asthma in Sports.

ERIC Educational Resources Information Center

Katz, Roger M.

1987-01-01

This article reviews the history of research on exercise-induced asthma (EIA) and the pathophysiology of the condition, including its development and influencing factors. Four groups of drugs that are effective against EIA--theopyhlline, beta-adrenergic agents, cromolyn sodium, and anticholinergics--are discussed. (Author/CB)

Suppression of Phytophthora capsici on bell pepper with isolates of Trichoderma

USDA-ARS?s Scientific Manuscript database

Biologically based disease management strategies, including biological control, are being developed for Phytophthora capsici on bell pepper. Biological control agents that are effective in controlling this disease under a number of soil environmental conditions when applied alone or with cover crop...

Continuous microcellular foaming of polyvinyl chloride and compatibilization of polyvinyl chloride and polylactide composites

NASA Astrophysics Data System (ADS)

Shah, Bhavesh

This dissertation focuses on overcoming existing limitations of WPCs which prevent them from realizing their full market potential. These limitations include: (i) lack of a continuous extrusion process for microcellular foaming of polyvinyl chloride (PVC) and its composites using supercritical fluids to reduce the high density of the WPCs, (ii) need for an efficient coupling agent for WPCs to overcome the poor compatibility between wood and plastic, and (iii) unproven use of wood as a filler for the biopolymer polylactide (PLA) to make "green" composites. These limitations were addressed through experimentation to develop a continuous extrusion process for microcellular foaming, and through surface modification of wood flour using natural coupling agents. The effects of wood flour, acrylic modifier and plasticizer content on the rheological properties of PVC based WPCs were studied using an extrusion capillary rheometer and a two-level factorial design. Wood flour content and acrylic modifier content were the major factors affecting the die swell ratio. Addition of plasticizer decreased the true viscosity of unfilled and filled PVC, irrespective of the acrylic modifier content. However, the addition of acrylic modifier significantly increased the viscosity of unfilled PVC but decreased the composite viscosity. Results of the rheological study were used to set baseline conditions for the continuous extrusion foaming of PVC WPCs using supercritical CO 2. Effects of material composition and processing conditions on the morphology of foamed samples were investigated. Foamed samples were produced using various material compositions and processing conditions, but steady-state conditions could not be obtained for PVC. Thus the relationships could not be determined. Incompatibility between wood flour and PVC was the focus of another study. The natural polymers chitin and chitosan were used as novel coupling agents to improve interfacial adhesion between the polymer matrix and wood fiber. Results indicated that addition of chitin and chitosan significantly increased the flexural properties and storage modulus of PVC WPCs, compared to composites without coupling agent. Significant improvements were attained with 0.5 wt. % chitosan and with 6.67 wt. % chitin. Based on the efficiency of chitosan as a coupling agent for PVC based WPCs, a biodegradable composite using polylactide (PLA) and chitosan was developed. Wood flour (0--40 wt. %) was evaluated as a filler for PLA composites and its effect on mechanical, thermal and chemical properties was studied with and without chitosan (0--10 wt. %). Addition of wood flour significantly increased the flexural and storage moduli of PLA-wood flour composites, but had no effect on glass transition temperature (Tg). Chitosan had no significant effect on any of the properties of the composites studied. Development of an efficient and effective coupling agent for PVC wood composite is a significant development which will increase performance while reducing cost. Wood filled PLA composites can further expand WPCs into applications such as packaging and automotive. Results from these studies have broadened the current knowledge base for WPC products and will be useful in the continued expansion of wood composites technology into a variety of industries.

Adaptive Sniping for Volatile and Stable Continuous Double Auction Markets

NASA Astrophysics Data System (ADS)

Toft, I. E.; Bagnall, A. J.

This paper introduces a new adaptive sniping agent for the Continuous Double Auction. We begin by analysing the performance of the well known Kaplan sniper in two extremes of market conditions. We generate volatile and stable market conditions using the well known Zero Intelligence-Constrained agent and a new zero-intelligence agent Small Increment (SI). ZI-C agents submit random but profitable bids/offers and cause high volatility in prices and individual trader performance. Our new zero-intelligence agent, SI, makes small random adjustments to the outstanding bid/offer and hence is more cautious than ZI-C. We present results for SI in self-play and then analyse Kaplan in volatile and stable markets. We demonstrate that the non-adaptive Kaplan sniper can be configured to suit either market conditions, but no single configuration is performs well across both market types. We believe that in a dynamic auction environment where current or future market conditions cannot be predicted a viable sniping strategy should adapt its behaviour to suit prevailing market conditions. To this end, we propose the Adaptive Sniper (AS) agent for the CDA. AS traders classify sniping opportunities using a statistical model of market activity and adjust their classification thresholds using a Widrow-Hoff adapted search. Our AS agent requires little configuration, and outperforms the original Kaplan sniper in volatile and stable markets, and in a mixed trader type scenario that includes adaptive strategies from the literature.

Socioeconomic and Behavioral Factors Leading to Acquired Bacterial Resistance to Antibiotics in Developing Countries

PubMed Central

Okeke, Iruka N.; Lamikanra, Adebayo

1999-01-01

In developing countries, acquired bacterial resistance to antimicrobial agents is common in isolates from healthy persons and from persons with community-acquired infections. Complex socioeconomic and behavioral factors associated with antibiotic resistance, particularly regarding diarrheal and respiratory pathogens, in developing tropical countries, include misuse of antibiotics by health professionals, unskilled practitioners, and laypersons; poor drug quality; unhygienic conditions accounting for spread of resistant bacteria; and inadequate surveillance. PMID:10081668

Chemical-Sensing Cables Detect Potential Threats

NASA Technical Reports Server (NTRS)

2007-01-01

Intelligent Optical Systems Inc. (IOS) completed Phase I and II Small Business Innovation Research (SBIR) contracts with NASA's Langley Research Center to develop moisture- and pH-sensitive sensors to detect corrosion or pre-corrosive conditions, warning of potentially dangerous conditions before significant structural damage occurs. This new type of sensor uses a specially manufactured optical fiber whose entire length is chemically sensitive, changing color in response to contact with its target, and demonstrated to detect potentially corrosive moisture incursions to within 2 cm. After completing the work with NASA, the company received a Defense Advanced Research Projects Agency (DARPA) Phase III SBIR to develop the sensors further for detecting chemical warfare agents, for which they proved just as successful. The company then worked with the U.S. Department of Defense (DoD) to fine tune the sensors for detecting potential threats, such as toxic industrial compounds and nerve agents. In addition to the work with government agencies, Intelligent Optical Systems has sold the chemically sensitive fiber optic cables to major automotive and aerospace companies, who are finding a variety of uses for the devices. Marketed under the brand name Distributed Intrinsic Chemical Agent Sensing and Transmission (DICAST), these unique continuous-cable fiber optic chemical sensors can serve in a variety of applications: Corrosive-condition monitoring, aiding experimentation with nontraditional power sources, as an economical means of detecting chemical release in large facilities, as an inexpensive "alarm" systems to alert the user to a change in the chemical environment anywhere along the cable, or in distance-resolved optical time domain reflectometry systems to provide detailed profiles of chemical concentration versus length.

Adaptive architectures for resilient control of networked multiagent systems in the presence of misbehaving agents

NASA Astrophysics Data System (ADS)

Torre, Gerardo De La; Yucelen, Tansel

2018-03-01

Control algorithms of networked multiagent systems are generally computed distributively without having a centralised entity monitoring the activity of agents; and therefore, unforeseen adverse conditions such as uncertainties or attacks to the communication network and/or failure of agent-wise components can easily result in system instability and prohibit the accomplishment of system-level objectives. In this paper, we study resilient coordination of networked multiagent systems in the presence of misbehaving agents, i.e. agents that are subject to exogenous disturbances that represent a class of adverse conditions. In particular, a distributed adaptive control architecture is presented for directed and time-varying graph topologies to retrieve a desired networked multiagent system behaviour. Apart from the existing relevant literature that make specific assumptions on the graph topology and/or the fraction of misbehaving agents, we show that the considered class of adverse conditions can be mitigated by the proposed adaptive control approach that utilises a local state emulator - even if all agents are misbehaving. Illustrative numerical examples are provided to demonstrate the theoretical findings.

A Systematic Review of Pedagogical Agents' Persona, Motivation, and Cognitive Load Implications for Learners

ERIC Educational Resources Information Center

Schroeder, Noah L.; Adesope, Olusola O.

2014-01-01

After more than a decade of pedagogical agent research, this review synthesizes the affective implications of learning with pedagogical agents. The review investigates different affective measures within 99 pedagogical agent outcome measures. The results suggest that learners may prefer pedagogical agents compared to non-agent control conditions,…

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems.

PubMed

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.

In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies

PubMed Central

McDermott, Martina; Eustace, Alex J.; Busschots, Steven; Breen, Laura; Crown, John; Clynes, Martin; O’Donovan, Norma; Stordal, Britta

2014-01-01

The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug resistance. PMID:24639951

Cytocompatibility and response of osteoblastic-like cells to starch-based polymers: effect of several additives and processing conditions.

PubMed

Gomes, M E; Reis, R L; Cunha, A M; Blitterswijk, C A; de Bruijn, J D

2001-07-01

This work reports on the biocompatibility evaluation of new biodegradable starch-based polymers that are under consideration for use in orthopaedic temporary applications and as tissue engineering scaffolds. It has been shown in previous works that by using these polymers it is both possible to produce polymer/hydroxyapatite (HA) composites (with or without the use of coupling agents) with mechanical properties matching those of the human bone, and to obtain 3D structures generated by solid blowing agents, that are suitable for tissue engineering applications. This study was focused on establishing the influence of several additives (ceramic fillers, blowing agents and coupling agents) and processing methods/conditions on the biocompatibility of the materials described above. The cytotoxicity of the materials was evaluated using cell culture methods, according to ISO/EN 109935 guidelines. A cell suspension of human osteosarcoma cells (HOS) was also seeded on a blend of corn starch with ethylene vinyl alcohol (SEVA-C) and on SEVA-C/HA composites, in order to have a preliminary indication on cell adhesion and proliferation on the materials surface. In general, the obtained results show that all the different materials based on SEVA-C, (which are being investigated for use in several biomedical applications), as well as all the additives (including the novel coupling agents) and different processing methods required to obtain the different properties/products, can be used without inducing a cytotoxic behaviour to the developed biomaterials.

Exploring Agricultural Livelihood Transitions with an Agent-Based Virtual Laboratory: Global Forces to Local Decision-Making

PubMed Central

Magliocca, Nicholas R.; Brown, Daniel G.; Ellis, Erle C.

2013-01-01

Rural populations are undergoing rapid changes in both their livelihoods and land uses, with associated impacts on ecosystems, global biogeochemistry, and climate change. A primary challenge is, thus, to explain these shifts in terms of the actors and processes operating within a variety of land systems in order to understand how land users might respond locally to future changes in broader-scale environmental and economic conditions. Using ‘induced intensification’ theory as a benchmark, we develop a generalized agent-based model to investigate mechanistic explanations of relationships between agricultural intensity and population density, environmental suitability, and market influence. Land-use and livelihood decisions modeled from basic micro-economic theories generated spatial and temporal patterns of agricultural intensification consistent with predictions of induced intensification theory. Further, agent actions in response to conditions beyond those described by induced intensification theory were explored, revealing that interactions among environmental constraints, population pressure, and market influence may produce transitions to multiple livelihood regimes of varying market integration. The result is new hypotheses that could modify and enrich understanding of the classic relationship between agricultural intensity and population density. The strength of this agent-based model and the experimental results is the generalized form of the decision-making processes underlying land-use and livelihood transitions, creating the prospect of a virtual laboratory for systematically generating hypotheses of how agent decisions and interactions relate to observed land-use and livelihood patterns across diverse land systems. PMID:24039892

Invited review of a workshop: anabolic hormones in bone: basic research and therapeutic potential.

PubMed

Margolis, R N; Canalis, E; Partridge, N C

1996-03-01

Age-, postmenopause-, and disease-related conditions that result in low bone mass represent important public health issues. Maintenance of bone mass is a balance between bone resorption and formation and is influenced by diet, body composition, activity level, and the interactions between and among a large number of hormones, growth factors, and cytokines. Recent research has emphasized establishing a more complete understanding of the hormonal regulation of bone and developing anabolic agents with therapeutic potential for the treatment of low bone mass. The NIDDK at the NIH recently sponsored a Workshop, entitled Anabolic Hormones in Bone: Basic Research and Therapeutic Potential, that attempted to define the current state of the art knowledge of hormones, growth factors, and cytokines that affect bone mass, with particular emphasis on those that could potentially have a role as anabolic agents in bone. This review presents a condensed proceedings of that workshop along with a summary of the optimal requisites for the development of anabolic agents with therapeutic potential in bone.

Developments in the use of nanocapsules in oncology

PubMed Central

Yurgel, V.; Collares, T.; Seixas, F.

2013-01-01

The application of nanotechnology to medicine can provide important benefits, especially in oncology, a fact that has resulted in the emergence of a new field called Nanooncology. Nanoparticles can be engineered to incorporate a wide variety of chemotherapeutic or diagnostic agents. A nanocapsule is a vesicular system that exhibits a typical core-shell structure in which active molecules are confined to a reservoir or within a cavity that is surrounded by a polymer membrane or coating. Delivery systems based on nanocapsules are usually transported to a targeted tumor site and then release their contents upon change in environmental conditions. An effective delivery of the therapeutic agent to the tumor site and to the infiltrating tumor cells is difficult to achieve in many cancer treatments. Therefore, new devices are being developed to facilitate intratumoral distribution, to protect the active agent from premature degradation and to allow its sustained and controlled release. This review focuses on recent studies on the use of nanocapsules for cancer therapy and diagnosis. PMID:23802234

Analysis of chemical warfare agents in food products by atmospheric pressure ionization-high field asymmetric waveform ion mobility spectrometry-mass spectrometry.

PubMed

Kolakowski, Beata M; D'Agostino, Paul A; Chenier, Claude; Mester, Zoltán

2007-11-01

Flow injection high field asymmetric waveform ion mobility spectrometry (FAIMS)-mass spectrometry (MS) methodology was developed for the detection and identification of chemical warfare (CW) agents in spiked food products. The CW agents, soman (GD), sarin (GB), tabun (GA), cyclohexyl sarin (GF), and four hydrolysis products, ethylphosphonic acid (EPA), methylphosphonic acid (MPA), pinacolyl methylphosphonic acid (Pin MPA), and isopropyl methylphosphonic acid (IMPA) were separated and detected by positive ion and negative ion atmospheric pressure ionization-FAIMS-MS. Under optimized conditions, the compensation voltages were 7.2 V for GD, 8.0 V for GA, 7.2 V for GF, 7.6 V for GB, 18.2 V for EPA, 25.9 V for MPA, -1.9 V for PinMPA, and +6.8 V for IMPA. Sample preparation was kept to a minimum, resulting in analysis times of 3 min or less per sample. The developed methodology was evaluated by spiking bottled water, canola oil, cornmeal, and honey samples at low microgram per gram (or microg/mL) levels with the CW agents or CW agent hydrolysis products. The detection limits observed for the CW agents in the spiked food samples ranged from 3 to 15 ng/mL in bottled water, 1-33 ng/mL in canola oil, 1-34 ng/g in cornmeal, and 13-18 ng/g in honey. Detection limits were much higher for the CW agent hydrolysis products, with only MPA being detected in spiked honey samples.

Active oligonucleotides incorporating alkylating an agent as potential sequence- and base selective modifier of gene expression.

PubMed

Sasaki, S

2001-04-01

A number of cross-linking (alkylating) agents have been developed and incorporated into the oligonulceotides for sequence selective control of gene expression. Recently, potential application of such active oligonucleotides has been expanding from use for improvement of inhibition efficiency to new biotechnology that may enable chemical alteration of genetic information. These interests in active oligonucleotides have encouraged the generation of new cross-linking agents that exhibit high efficiency for application of either in vitro or in vivo. This mini review summarizes structures of alkylating agents, in particular, a new basic skeleton for cross-linking, a 2'-deoxyribose derivative of 2-amino-6-vinylpurine that has been recently developed by the author's group. The 2-amino-6-vinylpurine has been shown to form a complex with cytidine under acidic conditions, and brings the vinyl and the amino reactive groups into proximity to achieve efficient alkylation. A new strategy was designed so that the reactivity of 2-amino-6-vinylpurine can be induced from the corresponding phenylsulfoxide derivative within a duplex with the complementary strand. The validity of the new strategy has been proven by achievement of cytidine-selective cross-linking with remarkably efficiency.

Animal models of sepsis.

PubMed

Fink, Mitchell P

2014-01-01

Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.

Safety of diabetes drugs in patients with heart failure.

PubMed

Carrasco-Sánchez, F J; Ostos-Ruiz, A I; Soto-Martín, M

2018-03-01

Heart failure (HF) and diabetes mellitus are 2 clinical conditions that often coexist, particularly in patients older than 65 years. Diabetes mellitus promotes the development of HF and confers a poorer prognosis. Hypoglycaemic agents (either by their mechanism of action, hypoglycaemic action or adverse effects) can be potentially dangerous for patients with HF. In this study, we performed a review of the available evidence on the safety of diabetes drugs in HF, focused on the main observational and experimental studies. Recent studies on cardiovascular safety have evaluated, although as a secondary objective, the impact of new hypoglycaemic agents on HF, helping us understand the neutrality, risks and potential benefits of these agents. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Design of a multi-agent hydroeconomic model to simulate a complex human-water system: Early insights from the Jordan Water Project

NASA Astrophysics Data System (ADS)

Yoon, J.; Klassert, C. J. A.; Lachaut, T.; Selby, P. D.; Knox, S.; Gorelick, S.; Rajsekhar, D.; Tilmant, A.; Avisse, N.; Harou, J. J.; Gawel, E.; Klauer, B.; Mustafa, D.; Talozi, S.; Sigel, K.

2015-12-01

Our work focuses on development of a multi-agent, hydroeconomic model for purposes of water policy evaluation in Jordan. The model adopts a modular approach, integrating biophysical modules that simulate natural and engineered phenomena with human modules that represent behavior at multiple levels of decision making. The hydrologic modules are developed using spatially-distributed groundwater and surface water models, which are translated into compact simulators for efficient integration into the multi-agent model. For the groundwater model, we adopt a response matrix method approach in which a 3-dimensional MODFLOW model of a complex regional groundwater system is converted into a linear simulator of groundwater response by pre-processing drawdown results from several hundred numerical simulation runs. Surface water models for each major surface water basin in the country are developed in SWAT and similarly translated into simple rainfall-runoff functions for integration with the multi-agent model. The approach balances physically-based, spatially-explicit representation of hydrologic systems with the efficiency required for integration into a complex multi-agent model that is computationally amenable to robust scenario analysis. For the multi-agent model, we explicitly represent human agency at multiple levels of decision making, with agents representing riparian, management, supplier, and water user groups. The agents' decision making models incorporate both rule-based heuristics as well as economic optimization. The model is programmed in Python using Pynsim, a generalizable, open-source object-oriented code framework for modeling network-based water resource systems. The Jordan model is one of the first applications of Pynsim to a real-world water management case study. Preliminary results from a tanker market scenario run through year 2050 are presented in which several salient features of the water system are investigated: competition between urban and private farmer agents, the emergence of a private tanker market, disparities in economic wellbeing to different user groups caused by unique supply conditions, and response of the complex system to various policy interventions.

Simple fluorescence-based high throughput cell viability assay for filamentous fungi.

PubMed

Chadha, S; Kale, S P

2015-09-01

Filamentous fungi are important model organisms to understand the eukaryotic process and have been frequently exploited in research and industry. These fungi are also causative agents of serious diseases in plants and humans. Disease management strategies include in vitro susceptibility testing of the fungal pathogens to environmental conditions and antifungal agents. Conventional methods used for antifungal susceptibilities are cumbersome, time-consuming and are not suitable for a large-scale analysis. Here, we report a rapid, high throughput microplate-based fluorescence method for investigating the toxicity of antifungal and stress (osmotic, salt and oxidative) agents on Magnaporthe oryzae and compared it with agar dilution method. This bioassay is optimized for the resazurin reduction to fluorescent resorufin by the fungal hyphae. Resazurin bioassay showed inhibitory rates and IC50 values comparable to the agar dilution method and to previously reported IC50 or MICs for M. oryzae and other fungi. The present method can screen range of test agents from different chemical classes with different modes of action for antifungal activities in a simple, sensitive, time and cost effective manner. A simple fluorescence-based high throughput method is developed to test the effects of stress and antifungal agents on viability of filamentous fungus Magnaporthe oryzae. This resazurin fluorescence assay can detect inhibitory effects comparable to those obtained using the growth inhibition assay with added advantages of simplicity, time and cost effectiveness. This high throughput viability assay has a great potential in large-scale screening of the chemical libraries of antifungal agents, for evaluating the effects of environmental conditions and hyphal kinetic studies in mutant and natural populations of filamentous fungi. © 2015 The Society for Applied Microbiology.

Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

PubMed Central

Pasadhika, Sirichai; Rosenbaum, James T

2014-01-01

Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis. PMID:24600203

Multidrug Efflux Pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus Bacterial Food Pathogens

PubMed Central

Andersen, Jody L.; He, Gui-Xin; Kakarla, Prathusha; KC, Ranjana; Kumar, Sanath; Lakra, Wazir Singh; Mukherjee, Mun Mun; Ranaweera, Indrika; Shrestha, Ugina; Tran, Thuy; Varela, Manuel F.

2015-01-01

Foodborne illnesses caused by bacterial microorganisms are common worldwide and constitute a serious public health concern. In particular, microorganisms belonging to the Enterobacteriaceae and Vibrionaceae families of Gram-negative bacteria, and to the Staphylococcus genus of Gram-positive bacteria are important causative agents of food poisoning and infection in the gastrointestinal tract of humans. Recently, variants of these bacteria have developed resistance to medically important chemotherapeutic agents. Multidrug resistant Escherichia coli, Salmonella enterica, Vibrio cholerae, Enterobacter spp., and Staphylococcus aureus are becoming increasingly recalcitrant to clinical treatment in human patients. Of the various bacterial resistance mechanisms against antimicrobial agents, multidrug efflux pumps comprise a major cause of multiple drug resistance. These multidrug efflux pump systems reside in the biological membrane of the bacteria and actively extrude antimicrobial agents from bacterial cells. This review article summarizes the evolution of these bacterial drug efflux pump systems from a molecular biological standpoint and provides a framework for future work aimed at reducing the conditions that foster dissemination of these multidrug resistant causative agents through human populations. PMID:25635914

Emerging Drugs for Uveitis

PubMed Central

Larson, Theresa; Nussenblatt, Robert B.; Sen, H. Nida

2010-01-01

Importance of the Field Uveitis is a challenging disease covering both infectious and noninfectious conditions. The current treatment strategies are hampered by the paucity of randomized controlled trials (RCTs) and few trials comparing efficacy of different agents. Areas Covered in this Review This review describes the current and future treatments of uveitis. A literature search was performed in PUBMED from 1965 to 2010 on drugs treating ocular inflammation with emphasis placed on more recent, larger studies. What the Reader Will Gain Readers should gain a basic understanding of current treatment strategies beginning with corticosteroids and transitioning to steroid sparing agents. Steroid sparing agents include the antimetabolites which include methotrexate, azathioprine, and mycophenolate mofetil; the calcineurin inhibitors which include cyclosporine, tacrolimus; alkylating agents which include cyclophosphamide and chlorambucil; and biologics which include the TNF-α inhibitors infliximab, adalimumab, and etanercept; daclizumab, interferon α2a, and rituximab. Take Home Message Newer agents are typically formulated from existing drugs or developed based on new advances in immunology. Future treatment will require a better understanding of the mechanisms involved in autoimmune diseases and better delivery systems in order to provide targeted treatment with minimal side effects. PMID:21210752

Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

PubMed

Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

2017-12-02

Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

Multidrug efflux pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus bacterial food pathogens.

PubMed

Andersen, Jody L; He, Gui-Xin; Kakarla, Prathusha; K C, Ranjana; Kumar, Sanath; Lakra, Wazir Singh; Mukherjee, Mun Mun; Ranaweera, Indrika; Shrestha, Ugina; Tran, Thuy; Varela, Manuel F

2015-01-28

Foodborne illnesses caused by bacterial microorganisms are common worldwide and constitute a serious public health concern. In particular, microorganisms belonging to the Enterobacteriaceae and Vibrionaceae families of Gram-negative bacteria, and to the Staphylococcus genus of Gram-positive bacteria are important causative agents of food poisoning and infection in the gastrointestinal tract of humans. Recently, variants of these bacteria have developed resistance to medically important chemotherapeutic agents. Multidrug resistant Escherichia coli, Salmonella enterica, Vibrio cholerae, Enterobacter spp., and Staphylococcus aureus are becoming increasingly recalcitrant to clinical treatment in human patients. Of the various bacterial resistance mechanisms against antimicrobial agents, multidrug efflux pumps comprise a major cause of multiple drug resistance. These multidrug efflux pump systems reside in the biological membrane of the bacteria and actively extrude antimicrobial agents from bacterial cells. This review article summarizes the evolution of these bacterial drug efflux pump systems from a molecular biological standpoint and provides a framework for future work aimed at reducing the conditions that foster dissemination of these multidrug resistant causative agents through human populations.

Development of Anti-Virulence Approaches for Candidiasis via a Novel Series of Small-Molecule Inhibitors of Candida albicans Filamentation

PubMed Central

Romo, Jesus A.; Pierce, Christopher G.; Chaturvedi, Ashok K.; Lazzell, Anna L.; McHardy, Stanton F.

2017-01-01

ABSTRACT Candida albicans remains the main etiologic agent of candidiasis, the most common fungal infection and now the third most frequent infection in U.S. hospitals. The scarcity of antifungal agents and their limited efficacy contribute to the unacceptably high morbidity and mortality rates associated with these infections. The yeast-to-hypha transition represents the main virulence factor associated with the pathogenesis of C. albicans infections. In addition, filamentation is pivotal for robust biofilm development, which represents another major virulence factor for candidiasis and further complicates treatment. Targeting pathogenic mechanisms rather than growth represents an attractive yet clinically unexploited approach in the development of novel antifungal agents. Here, we performed large-scale phenotypic screening assays with 30,000 drug-like small-molecule compounds within ChemBridge’s DIVERSet chemical library in order to identify small-molecule inhibitors of C. albicans filamentation, and our efforts led to the identification of a novel series of bioactive compounds with a common biaryl amide core structure. The leading compound of this series, N-[3-(allyloxy)-phenyl]-4-methoxybenzamide, was able to prevent filamentation under all liquid and solid medium conditions tested, suggesting that it impacts a common core component of the cellular machinery that mediates hypha formation under different environmental conditions. In addition to filamentation, this compound also inhibited C. albicans biofilm formation. This leading compound also demonstrated in vivo activity in clinically relevant murine models of invasive and oral candidiasis. Overall, our results indicate that compounds within this series represent promising candidates for the development of novel anti-virulence approaches to combat C. albicans infections. PMID:29208749

Optimization of space system development resources

NASA Astrophysics Data System (ADS)

Kosmann, William J.; Sarkani, Shahram; Mazzuchi, Thomas

2013-06-01

NASA has had a decades-long problem with cost growth during the development of space science missions. Numerous agency-sponsored studies have produced average mission level cost growths ranging from 23% to 77%. A new study of 26 historical NASA Science instrument set developments using expert judgment to reallocate key development resources has an average cost growth of 73.77%. Twice in history, a barter-based mechanism has been used to reallocate key development resources during instrument development. The mean instrument set development cost growth was -1.55%. Performing a bivariate inference on the means of these two distributions, there is statistical evidence to support the claim that using a barter-based mechanism to reallocate key instrument development resources will result in a lower expected cost growth than using the expert judgment approach. Agent-based discrete event simulation is the natural way to model a trade environment. A NetLogo agent-based barter-based simulation of science instrument development was created. The agent-based model was validated against the Cassini historical example, as the starting and ending instrument development conditions are available. The resulting validated agent-based barter-based science instrument resource reallocation simulation was used to perform 300 instrument development simulations, using barter to reallocate development resources. The mean cost growth was -3.365%. A bivariate inference on the means was performed to determine that additional significant statistical evidence exists to support a claim that using barter-based resource reallocation will result in lower expected cost growth, with respect to the historical expert judgment approach. Barter-based key development resource reallocation should work on spacecraft development as well as it has worked on instrument development. A new study of 28 historical NASA science spacecraft developments has an average cost growth of 46.04%. As barter-based key development resource reallocation has never been tried in a spacecraft development, no historical results exist, and a simulation of using that approach must be developed. The instrument development simulation should be modified to account for spacecraft development market participant differences. The resulting agent-based barter-based spacecraft resource reallocation simulation would then be used to determine if significant statistical evidence exists to prove a claim that using barter-based resource reallocation will result in lower expected cost growth.

Controllability of multi-agent systems with time-delay in state and switching topology

NASA Astrophysics Data System (ADS)

Ji, Zhijian; Wang, Zidong; Lin, Hai; Wang, Zhen

2010-02-01

In this article, the controllability issue is addressed for an interconnected system of multiple agents. The network associated with the system is of the leader-follower structure with some agents taking leader role and others being followers interconnected via the neighbour-based rule. Sufficient conditions are derived for the controllability of multi-agent systems with time-delay in state, as well as a graph-based uncontrollability topology structure is revealed. Both single and double integrator dynamics are considered. For switching topology, two algebraic necessary and sufficient conditions are derived for the controllability of multi-agent systems. Several examples are also presented to illustrate how to control the system to shape into the desired configurations.

Green synthesis of noble nanometals (Au, Pt, Pd) using glycerol under microwave irradiation conditions

EPA Science Inventory

A newer application of glycerol in the field of nanomaterials synthesis has been developed from both the economic and environmental points of view. Glycerol can act as a reducing agent for the fabrication of noble nanometals, such as Au, Pt, and Pd, under microwave irradiation. T...

Progress in the development and optimization of polyoxometalate delignification systems

Treesearch

R.H. Atalla; I.A. Weinstock; J.S. Bond; R.S. Reiner; E.L. Springer; C.G. Hill; Yu. Geletii; V.A. Grigoriev; A.J. Bailey; L. Delannoy; C.L. Hill

2002-01-01

We have reported the use of polyoxometalates (POMs) as selective, regenerable delignification agents that are inherently thermodynamically stable, and self-buffering. The re-activation with oxygen is under conditions that mineralize the organic byproducts of the delignification process. Thus, the POMs provide the basis for a closed bleach plant wherein the consumable...

Progress in the development and optimization of polyoxometalate delignification systems

Treesearch

R.H. Atalla; I.A. Weinstock; R.S. Reiner; E.L. Springer; C.G. Hill

2003-01-01

We have reported the use of polyoxometalates (POMs) as selective, regenerable delignification agents that are inherently thermodynamically stable, and self-buffering. The re-activation with oxygen is under conditions that mineralize the organic byproducts of the delignification process. Thus, the POMs provide the basis for a closed bleach plant wherein the consumable...

Influence of temperature on the reproductive and developmental biology of Ontsira mellipes (Hymenoptera: Braconidae): Implications for biological control of the Asian Longhorned Beetle (Coleoptera: Cerambycidae)

USDA-ARS?s Scientific Manuscript database

Ontsira mellipes Ashmead (Hymenoptera: Braconidae) is a North American parasitoid that develops on the invasive pest, Anoplophora glabripennis (Moltschulsky) (Coleoptera: Cerambycidae) under laboratory conditions, and is currently being considered as a potential new-association biocontrol agent. In ...

A Hybrid Approach for Supporting Adaptivity in E-Learning Environments

ERIC Educational Resources Information Center

Al-Omari, Mohammad; Carter, Jenny; Chiclana, Francisco

2016-01-01

Purpose: The purpose of this paper is to identify a framework to support adaptivity in e-learning environments. The framework reflects a novel hybrid approach incorporating the concept of the event-condition-action (ECA) model and intelligent agents. Moreover, a system prototype is developed reflecting the hybrid approach to supporting adaptivity…

2010 Review on the Extension of the AMedP-8(C) Methodology to New Agents, Materials, and Conditions

DTIC Science & Technology

2010-12-01

tularemia ). Applied Research Associates (ARA), under contract to the Defense Threat Reduction Agency (DTRA), has begun the development of similar...x P Included in IDA 2010 Analyses 1 Biological Staphylococcal Enterotoxin B x P Included in IDA 2010 Analyses 1 Biological Tularemia x P

Recent advances in polyoxometalate based delignification

Treesearch

R. H. Atalla; L. A. Weinstock; R. S. Reiner; C. J. Houtman; S. Reichel; C. G. Hill; C. L. Hill

1999-01-01

A new delignification technology based on the use of polyoxometalates (POMs) as delignification agents is under development at the USDA Forest Service, Forest Products Labotatory (FPL), in Madison, Wisconsin. These reagents are chlorine free and can be used under conditions wherein they oxidize lignin and chromophores in wood pulp fibers while leaving the cellulose...

Candidatus Liberibacter solanacearum' development in Russet Norkotah under commercial storage conditions

USDA-ARS?s Scientific Manuscript database

‘Candidatus Liberibacter solanacearum’ (Lso) is the causal agent of zebra chip (ZC) disease in potato. Following the recent appearance of ZC in the Pacific Northwest region of the US, where waves of the vector arrive towards late-summer and early fall and tubers are stored for future marketing, emph...

Analysis of Long-Term Temperature Variations in the Human Body.

PubMed

Dakappa, Pradeepa Hoskeri; Mahabala, Chakrapani

2015-01-01

Body temperature is a continuous physiological variable. In normal healthy adults, oral temperature is estimated to vary between 36.1°C and 37.2°C. Fever is a complex host response to many external and internal agents and is a potential contributor to many clinical conditions. Despite being one of the foremost vital signs, temperature and its analysis and variations during many pathological conditions has yet to be examined in detail using mathematical techniques. Classical fever patterns based on recordings obtained every 8-12 h have been developed. However, such patterns do not provide meaningful information in diagnosing diseases. Because fever is a host response, it is likely that there could be a unique response to specific etiologies. Continuous long-term temperature monitoring and pattern analysis using specific analytical methods developed in engineering and physics could aid in revealing unique fever responses of hosts and in different clinical conditions. Furthermore, such analysis can potentially be used as a novel diagnostic tool and to study the effect of pharmaceutical agents and other therapeutic protocols. Thus, the goal of our article is to present a comprehensive review of the recent relevant literature and analyze the current state of research regarding temperature variations in the human body.

Process and data fragmentation-oriented enterprise network integration with collaboration modelling and collaboration agents

NASA Astrophysics Data System (ADS)

Li, Qing; Wang, Ze-yuan; Cao, Zhi-chao; Du, Rui-yang; Luo, Hao

2015-08-01

With the process of globalisation and the development of management models and information technology, enterprise cooperation and collaboration has developed from intra-enterprise integration, outsourcing and inter-enterprise integration, and supply chain management, to virtual enterprises and enterprise networks. Some midfielder enterprises begin to serve for different supply chains. Therefore, they combine related supply chains into a complex enterprise network. The main challenges for enterprise network's integration and collaboration are business process and data fragmentation beyond organisational boundaries. This paper reviews the requirements of enterprise network's integration and collaboration, as well as the development of new information technologies. Based on service-oriented architecture (SOA), collaboration modelling and collaboration agents are introduced to solve problems of collaborative management for service convergence under the condition of process and data fragmentation. A model-driven methodology is developed to design and deploy the integrating framework. An industrial experiment is designed and implemented to illustrate the usage of developed technologies in this paper.

Intelligent Software Agents: Sensor Integration and Response

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

Kulesz, James J; Lee, Ronald W

2013-01-01

Abstract In a post Macondo world the buzzwords are Integrity Management and Incident Response Management. The twin processes are not new but the opportunity to link the two is novel. Intelligent software agents can be used with sensor networks in distributed and centralized computing systems to enhance real-time monitoring of system integrity as well as manage the follow-on incident response to changing, and potentially hazardous, environmental conditions. The software components are embedded at the sensor network nodes in surveillance systems used for monitoring unusual events. When an event occurs, the software agents establish a new concept of operation at themore » sensing node, post the event status to a blackboard for software agents at other nodes to see , and then react quickly and efficiently to monitor the scale of the event. The technology addresses a current challenge in sensor networks that prevents a rapid and efficient response when a sensor measurement indicates that an event has occurred. By using intelligent software agents - which can be stationary or mobile, interact socially, and adapt to changing situations - the technology offers features that are particularly important when systems need to adapt to active circumstances. For example, when a release is detected, the local software agent collaborates with other agents at the node to exercise the appropriate operation, such as: targeted detection, increased detection frequency, decreased detection frequency for other non-alarming sensors, and determination of environmental conditions so that adjacent nodes can be informed that an event is occurring and when it will arrive. The software agents at the nodes can also post the data in a targeted manner, so that agents at other nodes and the command center can exercise appropriate operations to recalibrate the overall sensor network and associated intelligence systems. The paper describes the concepts and provides examples of real-world implementations including the Threat Detection and Analysis System (TDAS) at the International Port of Memphis and the Biological Warning and Incident Characterization System (BWIC) Environmental Monitoring (EM) Component. Technologies developed for these 24/7 operational systems have applications for improved real-time system integrity awareness as well as provide incident response (as needed) for production and field applications.« less

An agent based architecture for high-risk neonate management at neonatal intensive care unit.

PubMed

Malak, Jaleh Shoshtarian; Safdari, Reza; Zeraati, Hojjat; Nayeri, Fatemeh Sadat; Mohammadzadeh, Niloofar; Farajollah, Seide Sedighe Seied

2018-01-01

In recent years, the use of new tools and technologies has decreased the neonatal mortality rate. Despite the positive effect of using these technologies, the decisions are complex and uncertain in critical conditions when the neonate is preterm or has a low birth weight or malformations. There is a need to automate the high-risk neonate management process by creating real-time and more precise decision support tools. To create a collaborative and real-time environment to manage neonates with critical conditions at the NICU (Neonatal Intensive Care Unit) and to overcome high-risk neonate management weaknesses by applying a multi agent based analysis and design methodology as a new solution for NICU management. This study was a basic research for medical informatics method development that was carried out in 2017. The requirement analysis was done by reviewing articles on NICU Decision Support Systems. PubMed, Science Direct, and IEEE databases were searched. Only English articles published after 1990 were included; also, a needs assessment was done by reviewing the extracted features and current processes at the NICU environment where the research was conducted. We analyzed the requirements and identified the main system roles (agents) and interactions by a comparative study of existing NICU decision support systems. The Universal Multi Agent Platform (UMAP) was applied to implement a prototype of our multi agent based high-risk neonate management architecture. Local environment agents interacted inside a container and each container interacted with external resources, including other NICU systems and consultation centers. In the NICU container, the main identified agents were reception, monitoring, NICU registry, and outcome prediction, which interacted with human agents including nurses and physicians. Managing patients at the NICU units requires online data collection, real-time collaboration, and management of many components. Multi agent systems are applied as a well-known solution for management, coordination, modeling, and control of NICU processes. We are currently working on an outcome prediction module using artificial intelligence techniques for neonatal mortality risk prediction. The full implementation of the proposed architecture and evaluation is considered the future work.

Rational Design, Development, and Stability Assessment of a Macrocyclic Four-Hydroxamate-Bearing Bifunctional Chelating Agent for 89 Zr.

PubMed

Seibold, Uwe; Wängler, Björn; Wängler, Carmen

2017-09-21

Zirconium-89 is a positron-emitting radionuclide of high interest for medical imaging applications with positron emission tomography (PET). For the introduction of this radiometal into biologically active targeting vectors, the chelating agent desferrioxamine B (DFO) is commonly applied. However, DFO is known to form 89 Zr complexes of limited in vivo stability. Herein we describe the rational design and chemical development of a new macrocyclic four-hydroxamate-bearing chelating agent-1,10,19,28-tetrahydroxy-1,5,10,14,19,23,28,32-octaazacyclohexatriacontan-2,6,11,15,20,24,29,33-octaone (CTH36)-for the stable complexation of Zr 4+ . For this purpose, we first performed computational studies to determine the optimal chelator geometry before we developed different synthesis pathways toward the target structures. The best results were obtained using an efficient solution-phase-based synthesis strategy toward the target chelating agent. To enable efficient and chemoselective conjugation to biomolecules, a tetrazine-modified variant of CTH36 was also developed. The excellent conjugation characteristics of the so-functionalized chelator were demonstrated on the example of the model peptide TCO-c(RGDfK). We determined the optimal 89 Zr radiolabeling parameters for CTH36 as well as its bioconjugate, and found that 89 Zr radiolabeling proceeds efficiently under very mild reaction conditions. Finally, we performed comparative complex stability tests for 89 Zr-CHT36-c(RGDfK) and 89 Zr-DFO-c(RGDfK), showing improved complex stability for the newly developed chelator CTH36. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fragile X syndrome: a preclinical review on metabotropic glutamate receptor 5 (mGluR5) antagonists and drug development.

PubMed

Pop, Andreea S; Gomez-Mancilla, Baltazar; Neri, Giovanni; Willemsen, Rob; Gasparini, Fabrizio

2014-03-01

Fragile X syndrome (FXS) is considered the leading inherited cause of intellectual disability and autism. In FXS, the fragile X mental retardation 1 (FMR1) gene is silenced and the fragile X mental retardation protein (FMRP) is not expressed, resulting in the characteristic features of the syndrome. Despite recent advances in understanding the pathophysiology of FXS, there is still no cure for this condition; current treatment is symptomatic. Preclinical research is essential in the development of potential therapeutic agents. This review provides an overview of the preclinical evidence supporting metabotropic glutamate receptor 5 (mGluR5) antagonists as therapeutic agents for FXS. According to the mGluR theory of FXS, the absence of FMRP leads to enhanced glutamatergic signaling via mGluR5, which leads to increased protein synthesis and defects in synaptic plasticity including enhanced long-term depression. As such, efforts to develop agents that target the underlying pathophysiology of FXS have focused on mGluR5 modulation. Animal models, particularly the Fmr1 knockout mouse model, have become invaluable in exploring therapeutic approaches on an electrophysiological, behavioral, biochemical, and neuroanatomical level. Two direct approaches are currently being investigated for FXS treatment: reactivating the FMR1 gene and compensating for the lack of FMRP. The latter approach has yielded promising results, with mGluR5 antagonists showing efficacy in clinical trials. Targeting mGluR5 is a valid approach for the development of therapeutic agents that target the underlying pathophysiology of FXS. Several compounds are currently in development, with encouraging results.

Ultrasonically promoted nitrolysis of DAPT to HMX in ionic liquid.

PubMed

Hua, Qian; Zhiwen, Ye; Chunxu, Lv

2008-04-01

The present work aims at developing a new process to synthesize HMX from DAPT using ultrasound in ionic liquid. Reaction has been carried out in ultrasonic bath, effect of various parameters such as presence and absence of ultrasound, volume and type of solvent, temperature, concentration of nitrating agent has been investigated with an aim of obtaining the optimum conditions for the synthesis of HMX. It was observed that ultrasonically promoted nitroylsis of DAPT to HMX has exhibited significant enhancement in yield at ambient condition.

Ovulation induction in women with polycystic ovary syndrome: an update.

PubMed

Bhagavath, Balasubramanian; Carson, Sandra A

2012-03-01

Infertility is frequently caused by anovulation. The affected women present with irregular menstrual cycles and the most common diagnosis is polycystic ovary syndrome. Ovulation induction is commonly used to treat these women. Clomiphene citrate (a selective estrogen receptor modulator or SERM) remains the most used medication for treating this condition. Alternatives that have been used include other SERMs such as tamoxifen, aromatase inhibitors, insulin sensitizing agents, and ovarian drilling. Evidence for and against the effectiveness of these agents has fluctuated over the last decade. Controversies surrounding the use of ovulation induction such as development of functional cysts, high-order multiple births, and development of ovarian cancer have been further studied and some controversies have almost been laid to rest in the last decade. Copyright © 2012 Mosby, Inc. All rights reserved.

Candidate Species Selection and Controlled Environment Injuries

NASA Technical Reports Server (NTRS)

Tibbitts, T. W.

1982-01-01

Research was undertaken to attempt to identify the causal agents for intumescences that develop on many different species of plants in controlled environments. Concentration and filtration procedures were not successful in identifying any particular compounds. The injury was found to develop, even though the atmosphere for the plants is filtered through activated charcoal, potassium permanganate, or is subjected to catalytic combustion at 450 C. Thus, the causal agent is apparently either an oxidized compound or specific element, or the result of some unrecognized variation in physical conditions around the plants. The research has demonstrated that the injury is controlled to a significant extent by temperature. Growing temperatures of 20 degrees and 25 degrees C resulted in serious injury on plants, but temperatures of 30 C resulted in very little injury.

Zirconium Hydroxide-coated Nanofiber Mats for Nerve Agent Decontamination.

PubMed

Kim, Sohee; Ying, Wu Bin; Jung, Hyunsook; Ryu, Sam Gon; Lee, Bumjae; Lee, Kyung Jin

2017-03-16

Diverse innovative fabrics with specific functionalities have been developed for requirements such as self-decontamination of chemical/biological pollutants and toxic nerve agents. In this work, Zr(OH) 4 -coated nylon-6,6 nanofiber mats were fabricated for the decontamination of nerve agents. Nylon-6,6 fabric was prepared via the electrospinning process, followed by coating with Zr(OH) 4 , which was obtained by the hydrolysis of Zr(OBu) 4 by a sol-gel reaction on nanofiber surfaces. The reaction conditions were optimized by varying the amounts of Zr(OBu) 4 ,the reaction time, and the temperature of the sol-gel reaction. The composite nanofibers show high decontamination efficiency against diisopropylfluorophosphate, which is a nerve agent analogue, due to its high nucleophilicity that aids in the catalysis of the hydrolysis of the phosphonate ester bonds. Composite nanofiber mats have a large potential and can be applied in specific fields such as military and medical markets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Epidemiological aspects in occupational neurology. Investigational methodology

PubMed

Solé-García, M D

In the working population, unsatisfactory working conditions (in the broadest sense) may cause effects whose gravity depends mainly on the characteristics of exposure and the general condition of the individual. These effects may, in practice, be classified as occupational accidents and professional illness (both legal concepts), illnesses related to work, diminished quality of life and effects on offspring. Agents as varied as head injuries and metals are known to cause from loss of memory or behavior disorders to chronic toxic encephalopathy or Parkinsonism. There is little data on exposure to neurotoxic agents or disorders of the central nervous system caused by work and what there is not reliable. Therefore it is necessary to facilitate and encourage collaboration between neurologists and occupational medicine specialists so as to determine the importance/extent of the problem, undertake investigation as to aetiology and develop methods for early detection of these disorders.

Determination and validation of six sunscreen agents in suncare products by UPLC and HPLC.

PubMed

Lee, So-Mi; Jeong, Hye-Jin; Chang, Ih Seop

2008-01-01

Methylene bis-benzotriazolyl tetramethyl butylphenol and bis-ethylhexyloxy phenol methoxyphenyl triazine are sunscreen agents that have hydrophobic behaviors in common. They were not normally assayed with the following four sunscreen agents that have hydrophilic behaviors in a single chromatographic run: ethylhexyl methoxycinnamate, isoamyl p-methoxycinnamate, ethylhexyl salicylate, and ethylhexyl triazone. For that reason, methylene bis-benzotriazolyl tetramethyl butylphenol and bis-ethylhexyloxy phenol methoxyphenyl triazine require much time in order to assay products with those materials. A rapid, selective, and reproducible determination method needs to be developed for the simultaneous examination of methylene bis-benzotriazolyl tetramethyl butylphenol and bis-ethylhexyloxy phenol methoxyphenyl triazine with the sunscreen agents, ethylhexyl methoxycinnamate, isoamyl p-methoxycinnamate, ethylhexyl salicylate, and ethylhexyl triazone. This new technique could reduce time in examining the sunscreen agents and be effective for quality control of suncare products. In this paper, the HPLC and UPLC system is used for developing the determination of the sunscreen agents. Several evaluations of some mixtures of eluents and columns were obtained for the optimal condition of separation. In HPLC, the optimal peak resolution was obtained through ethanol-water gradient elution and a 75-mm C18 column with a 3.5-microm-sized particle on a flow rate of 1.0 ml/min. In UPLC, the most distinctive peak resolution was obtained through methanol-water gradient elution and a 50-mm C18 column with a 1.7-microm-sized particle on a flow rate 0.4 ml/min. Both of those chromatographic determination methods could be used in the examination of six types of sunscreen agents without any interference from other product excipients in the agents. The proposed determination methods were validated for specificity, linearity, repeatability, system stability, intermediate precision, and accuracy. Consequently, HPLC and UPLC determination methods could be rapid, selective, and proper applications for the assay of sunscreen agents in suncare products.

Defining anural malformations in the context of a developmental problem

USGS Publications Warehouse

Meteyer, C.U.; Cole, Rebecca A.; Converse, K.A.; Docherty, D.E.; Wolcott, M.; Helgen, J.C.; Levey, R.; Eaton-Poole, L.; Burkhart, J.G.

2000-01-01

This paper summarizes terminology and general concepts involved in animal development for the purpose of providing background for the study and understanding of frog malformations. The results of our radiographic investigation of rear limb malformations in Rana pipiens provide evidence that frog malformations are the product of early developmental errors. Although bacteria, parasites and viruses were identified in these metamorphosed frogs, the relevant window to look for the teratogenic effect of these agents is in the early tadpole stage during limb development. As a result, our microbiological findings must be regarded as inconclusive relative to determining their contribution to malformations because we conducted our examinations on metamorphosed frogs not tadpoles. Future studies need to look at teratogenic agents (chemical, microbial, physical or mechanical) that are present in the embryo, tadpole, and their environments at the stages of development that are relevant for the malformation type. The impact of these teratogenic agents then needs to be assessed in appropriate animal models using studies that are designed to mimic field conditions. The results of these laboratory tests should then be analyzed in such a way that will allow comparison with the findings in the wild-caught tadpoles and frogs.

Comparative evaluation of shear bond strength of metallic brackets bonded with two different bonding agents under dry conditions and with saliva contamination.

PubMed

Khanehmasjedi, Mashallah; Naseri, Mohammad Ali; Khanehmasjedi, Samaneh; Basir, Leila

2017-02-01

This study compared the shear bond strength of metallic brackets bonded with Single Bond and Assure bonding agents under dry and saliva-contamination conditions. Sixty sound premolar teeth were selected, and stainless-steel brackets were bonded on enamel surfaces with Single Bond and Assure bonding agents under dry condition or with saliva contamination. Shear bond strength values of brackets were measured in a universal testing machine. The adhesive remnant index scores were determined after debonding of the brackets under a stereomicroscope. One-way analysis of variance (ANOVA) was used to analyze bond strength. Two-by-two comparisons were made with post hoc Tukey tests (p<0.001). Frequencies of adhesive remnant index scores were analyzed by Kruskal-Wallis test. Bond strength values of brackets to tooth structure were 9.29±8.56 MPa and 21.25±8.93 MPa with the use of Assure resin bonding agent under saliva-contamination and dry conditions, respectively. These values were 10.13±6.69 MPa and 14.09±6.6 MPa, respectively, under the same conditions with the use of Single Bond adhesive. Contamination with saliva resulted in a significant decrease in the bond strength of brackets to tooth structure with the application of Assure adhesive resin (p<0.001). There were no significant differences in the adhesive remnant index scores between the study groups. Application of Single Bond and Assure bonding agents resulted in adequate bond strength of brackets to tooth structures. Contamination with saliva significantly decreased the bond strength of Assure bonding agent compared with dry conditions. Copyright © 2016. Published by Elsevier Taiwan LLC.

Synthesis of a new hardener agent for self-healing epoxy resins

NASA Astrophysics Data System (ADS)

Raimondo, Marialuigia; Guadagno, Liberata; Naddeo, Carlo; Longo, Pasquale; Mariconda, Annaluisa; Agovino, Anna

2014-05-01

Actually, the development of smart composites capable of self-repair in aeronautical structures is still at the planning stage owing to complex issues to overcome. One of the critical points in the development of self-healing epoxy resin is related to the impossibility to employ primary amines as hardeners. In this paper, the synthesis of a new hardener for self-healing resins is shown together with applicability conditions/ranges.

Using computer agents to explain medical documents to patients with low health literacy.

PubMed

Bickmore, Timothy W; Pfeifer, Laura M; Paasche-Orlow, Michael K

2009-06-01

Patients are commonly presented with complex documents that they have difficulty understanding. The objective of this study was to design and evaluate an animated computer agent to explain research consent forms to potential research participants. Subjects were invited to participate in a simulated consent process for a study involving a genetic repository. Explanation of the research consent form by the computer agent was compared to explanation by a human and a self-study condition in a randomized trial. Responses were compared according to level of health literacy. Participants were most satisfied with the consent process and most likely to sign the consent form when it was explained by the computer agent, regardless of health literacy level. Participants with adequate health literacy demonstrated the highest level of comprehension with the computer agent-based explanation compared to the other two conditions. However, participants with limited health literacy showed poor comprehension levels in all three conditions. Participants with limited health literacy reported several reasons, such as lack of time constraints, ability to re-ask questions, and lack of bias, for preferring the computer agent-based explanation over a human-based one. Animated computer agents can perform as well as or better than humans in the administration of informed consent. Animated computer agents represent a viable method for explaining health documents to patients.

Self-healing fiber-reinforced composite

NASA Astrophysics Data System (ADS)

Lee, Minwook; Yoon, Sam; Yarin, Alexander

In the present work two parts of the healing agent (commercially available epoxy resin and hardener) are encapsulated in separate polymeric nanofibers. The fibers are generated by a single-step dual coaxial solution blowing. The core-shell fibers with the diameters in the 200-2600 nm range are encased in the PDMS (polydimethyl siloxane) matrix to form a self-healing composite material. Under fatigue conditions, the core-shell fibers inside the composite material are ruptured and the healing agents released into the surrounding matrix. Various fatigue conditions including repeated bending and stretching are used to damage the composites and the degree of self-healing is quantified after that. Also, an incision resembling a crack is pre-notched and crack propagation is studied. It is found that the presence of the self-healing agents in the fibers significantly retards crack propagation due to curing by the epoxy at the ruptured site. The stiffness of the composites is also measured for the samples containing self-healing fibers inside them before and after the fatigue tests. A novel theory of crack propagation is proposed, which explains the observed jump-like growth of sub-critical cracks. This work was supported by the International Collaboration Program funded by the Agency for Defense Development.

An experimental-computational platform for investigating microbial interactions and dynamics in communities with two codependent species

NASA Astrophysics Data System (ADS)

Fuentes-Cabrera, Miguel; Anderson, John D.; Wilmoth, Jared; Ginovart, Marta; Prats, Clara; Portell-Canal, Xavier; Retterer, Scott

Microbial interactions are critical for governing community behavior and structure in natural environments. Examination of microbial interactions in the lab involves growth under ideal conditions in batch culture; conditions that occur in nature are, however, characterized by disequilibrium. Of particular interest is the role that system variables play in shaping cell-to-cell interactions and organization at ultrafine spatial scales. We seek to use experiments and agent-based modeling to help discover mechanisms relevant to microbial dynamics and interactions in the environment. Currently, we are using an agent-based model to simulate microbial growth, dynamics and interactions that occur on a microwell-array device developed in our lab. Bacterial cells growing in the microwells of this platform can be studied with high-throughput and high-content image analyses using brightfield and fluorescence microscopy. The agent-based model is written in the language Netlogo, which in turn is ''plugged into'' a computational framework that allows submitting many calculations in parallel for different initial parameters; visualizing the outcomes in an interactive phase-like diagram; and searching, with a genetic algorithm, for the parameters that lead to the most optimal simulation outcome.

Optimization of Fermentation Conditions for the Production of Bacteriocin Fermentate

DTIC Science & Technology

2015-03-30

pentosaceus 43200 were obtained from ATCC. Lactobacillus (L.) plantarum NCDO 955, which was used as an indicator organism, and a strain of pediocin-producing...Development of food grade media for the preparation of Lactobacillus plantarum starter culture. J. Gen. Appl. Microbiol. 52: 349-356. Shurtleff, W...MEDIA FERMENTATION BROTH SAFETY INHIBITION BACTERIOCINS LACTOBACILLUS ANTIMICROBIAL AGENTS

CHARACTERISTICS OF SPILLED OILS, FUELS, AND PETROLEUM PRODUCTS: 3A. SIMULATION OF OIL SPILLS AND DISPERSANTS UNDER CONDITIONS OF UNCERTAINTY

EPA Science Inventory

At the request of the US EPA Oil Program Center, ERD is developing an oil spill model that focuses on fate and transport of oil components under various response scenarios. This model includes various simulation options, including the use of chemical dispersing agents on oil sli...

Construction and Organization of a BSL-3 Cryo-Electron Microscopy Laboratory at UTMB

PubMed Central

Sherman, Michael B.; Trujillo, Juan; Leahy, Ian; Razmus, Dennis; DeHate, Robert; Lorcheim, Paul; Czarneski, Mark A.; Zimmerman, Domenica; Newton, Je T’Aime M.; Haddow, Andrew D.; Weaver, Scott C.

2013-01-01

A unique cryo-electron microscopy facility has been designed and constructed at the University of Texas Medical Branch (UTMB) to study the three-dimensional organization of viruses and bacteria classified as select agents at biological safety level (BSL)-3, and their interactions with host cells. A 200 keV high-end cryo-electron microscope was installed inside a BSL-3 containment laboratory and standard operating procedures were developed and implemented to ensure its safe and efficient operation. We also developed a new microscope decontamination protocol based on chlorine dioxide gas with a continuous flow system, which allowed us to expand the facility capabilities to study bacterial agents including spore-forming species. The new unified protocol does not require agent-specific treatment in contrast to the previously used heat decontamination. To optimize the use of the cryo-electron microscope and to improve safety conditions, it can be remotely controlled from a room outside of containment, or through a computer network world-wide. Automated data collection is provided by using JADAS (single particle imaging) and SerialEM (tomography). The facility has successfully operated for more than a year without an incident and was certified as a select agent facility by the Centers for Disease Control. PMID:23274136

Construction and organization of a BSL-3 cryo-electron microscopy laboratory at UTMB.

PubMed

Sherman, Michael B; Trujillo, Juan; Leahy, Ian; Razmus, Dennis; Dehate, Robert; Lorcheim, Paul; Czarneski, Mark A; Zimmerman, Domenica; Newton, Je T'aime M; Haddow, Andrew D; Weaver, Scott C

2013-03-01

A unique cryo-electron microscopy facility has been designed and constructed at the University of Texas Medical Branch (UTMB) to study the three-dimensional organization of viruses and bacteria classified as select agents at biological safety level (BSL)-3, and their interactions with host cells. A 200keV high-end cryo-electron microscope was installed inside a BSL-3 containment laboratory and standard operating procedures were developed and implemented to ensure its safe and efficient operation. We also developed a new microscope decontamination protocol based on chlorine dioxide gas with a continuous flow system, which allowed us to expand the facility capabilities to study bacterial agents including spore-forming species. The new unified protocol does not require agent-specific treatment in contrast to the previously used heat decontamination. To optimize the use of the cryo-electron microscope and to improve safety conditions, it can be remotely controlled from a room outside of containment, or through a computer network world-wide. Automated data collection is provided by using JADAS (single particle imaging) and SerialEM (tomography). The facility has successfully operated for more than a year without an incident and was certified as a select agent facility by the Centers for Disease Control. Copyright © 2012 Elsevier Inc. All rights reserved.

Evolution of tinea capitis in the Nanchang area, Southern China: a 50-year survey (1965-2014).

PubMed

Zhan, Ping; Geng, Chengfang; Li, Zhihua; Jin, Yun; Jiang, Qing; Tao, Li; Luo, Yunpeng; Xiong, Zhiwei; Wu, Shaoxi; Li, Dongmei; Liu, Weida; de Hoog, G Sybren

2015-05-01

Tinea capitis remains a common public health problem worldwide especially in developing areas. Aetiologic agents and clinical pattern vary with geography and history of socioeconomic conditions. Three community surveys and a prospective study were carried out over the past 50 years (1965-2014) in the Qingyunpu District of Nanchang, Southern China. Clinical presentation and spectrum of aetiological agents were monitored to understand the evolution of tinea capitis. In 1965 favus was highly epidemic and Trichophyton schoenleinii presented as the overwhelming aetiological agents of scalp infection in the study area, with a prevalence of 3.41% of the population. During a governmental campaign to eliminate tinea capitis initiated in mid of 1960s, favus was successfully controlled and the prevalence decreased to less than 0.01% in 1977. After that period, clinical presentation and spectrum of fungi changed with social development. Trichophyton schoenleinii was replaced by Trichophyton violaceum and Trichophyton mentagrophytes. Nowadays, the species corresponds with a dominant black dot type of tinea capitis in the Nanchang area. The prevalence of causative agents of tinea capitis is not only related to geography but also to socioeconomic factors. Multiple factors have to be considered for the management for control of this disease. © 2015 Blackwell Verlag GmbH.

Stimuli-disassembling gold nanoclusters for diagnosis of early stage oral cancer by optical coherence tomography

NASA Astrophysics Data System (ADS)

Kim, Chang Soo; Ingato, Dominique; Wilder-Smith, Petra; Chen, Zhongping; Kwon, Young Jik

2018-01-01

A key design consideration in developing contrast agents is obtaining distinct, multiple signal changes in diseased tissue. Plasmonic gold nanoparticles (Au NPs) have been developed as contrast agents due to their strong surface plasmon resonance (SPR). This study aims to demonstrate that stimuli-responsive plasmonic Au nanoclusters (Au NCs) can be used as a contrast agent for optical coherence tomography (OCT) in detecting early-stage cancer. Au NPs were clustered via acid-cleavable linkers to synthesize Au NCs that disassemble under mildly acidic conditions into individual Au NPs, simultaneously diminishing SPR effect (quantified by scattering intensity) and increasing Brownian motion (quantified by Doppler variance). The acid-triggered morphological and accompanying optico-physical property changes of the acid-disassembling Au NCs were confirmed by TEM, DLS, UV/Vis, and OCT. Stimuli-responsive Au NCs were applied in a hamster check pouch model carrying early-stage squamous carcinoma tissue. The tissue was visualized by OCT imaging, which showed reduced scattering intensity and increased Doppler variance in the dysplastic tissue. This study demonstrates the promise of diagnosing early-stage cancer using molecularly programmable, inorganic nanomaterial-based contrast agents that are capable of generating multiple, stimuli-triggered diagnostic signals in early-stage cancer.[Figure not available: see fulltext.

Drugs currently under investigation for the treatment of invasive candidiasis.

PubMed

McCarthy, Matthew W; Walsh, Thomas J

2017-07-01

The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

In vitro skin permeation and decontamination of the organophosphorus pesticide paraoxon under various physical conditions--evidence for a wash-in effect.

PubMed

Misik, Jan; Pavlikova, Ruzena; Josse, Denis; Cabal, Jiri; Kuca, Kamil

2012-09-01

Misuse of various chemicals, such as chemical warfare agents, industrial chemicals or pesticides during warfare or terrorists attacks requires adequate protection. Thus, development and evaluation of novel decontamination dispositives and techniques are needed. In this study, in vitro permeation and decontamination of a potentially hazardous compound paraoxon, an active metabolite of organophosphorus pesticide parathion, was investigated. Skin permeation and decontamination experiments were carried out in modified Franz diffusion cells. Pig skin was used as a human skin model. Commercially produced detergent-based washing solutions FloraFree(™) and ArgosTM were used as decontamination means. The experiments were done under "warm", "cold", "dry" and "wet" skin conditions in order to determine an effect of various physical conditions on skin permeation of paraoxon and on a subsequent decontamination process. There was no significant difference in skin permeation of paraoxon under warm, cold and dry conditions, whereas wet conditions provided significantly higher permeation rates. In the selected conditions, decontamination treatments performed 1 h after a skin exposure did not decrease the agent volume that permeated through the skin. An exception were wet skin conditions with non-significant decontamination efficacy 18 and 28% for the FloraFree(™) and Argos(™) treatment, respectively. In contrast, the skin permeation of paraoxon under warm, cold and dry conditions increased up to 60-290% following decontamination compared to non-decontaminated controls. This has previously been described as a skin wash-in effect.

Evaluation of tissue fixation methods to inactivate Mycobacterium bovis under routine laboratory conditions

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis (M. bovis) is the etiological agent of tuberculosis in mammals including humans. The seriousness of disease and low infective dose require that the agent be handled under biosafety level 3 conditions. Many experimental protocols include histological examination of infected tissue...

Method of predicting a change in an economy

DOEpatents

Pryor, Richard J [Albuquerque, NM; Basu, Nipa [Albany, NY

2006-01-10

An economy whose activity is to be predicted comprises a plurality of decision makers. Decision makers include, for example, households, government, industry, and banks. The decision makers are represented by agents, where an agent can represent one or more decision makers. Each agent has decision rules that determine the agent's actions. Each agent can affect the economy by affecting variable conditions characteristic of the economy or the internal state of other agents. Agents can communicate actions through messages. On a multiprocessor computer, the agents can be assigned to processing elements.

Evolutionary game dynamics of controlled and automatic decision-making

NASA Astrophysics Data System (ADS)

Toupo, Danielle F. P.; Strogatz, Steven H.; Cohen, Jonathan D.; Rand, David G.

2015-07-01

We integrate dual-process theories of human cognition with evolutionary game theory to study the evolution of automatic and controlled decision-making processes. We introduce a model in which agents who make decisions using either automatic or controlled processing compete with each other for survival. Agents using automatic processing act quickly and so are more likely to acquire resources, but agents using controlled processing are better planners and so make more effective use of the resources they have. Using the replicator equation, we characterize the conditions under which automatic or controlled agents dominate, when coexistence is possible and when bistability occurs. We then extend the replicator equation to consider feedback between the state of the population and the environment. Under conditions in which having a greater proportion of controlled agents either enriches the environment or enhances the competitive advantage of automatic agents, we find that limit cycles can occur, leading to persistent oscillations in the population dynamics. Critically, however, these limit cycles only emerge when feedback occurs on a sufficiently long time scale. Our results shed light on the connection between evolution and human cognition and suggest necessary conditions for the rise and fall of rationality.

Evolutionary game dynamics of controlled and automatic decision-making.

PubMed

Toupo, Danielle F P; Strogatz, Steven H; Cohen, Jonathan D; Rand, David G

2015-07-01

We integrate dual-process theories of human cognition with evolutionary game theory to study the evolution of automatic and controlled decision-making processes. We introduce a model in which agents who make decisions using either automatic or controlled processing compete with each other for survival. Agents using automatic processing act quickly and so are more likely to acquire resources, but agents using controlled processing are better planners and so make more effective use of the resources they have. Using the replicator equation, we characterize the conditions under which automatic or controlled agents dominate, when coexistence is possible and when bistability occurs. We then extend the replicator equation to consider feedback between the state of the population and the environment. Under conditions in which having a greater proportion of controlled agents either enriches the environment or enhances the competitive advantage of automatic agents, we find that limit cycles can occur, leading to persistent oscillations in the population dynamics. Critically, however, these limit cycles only emerge when feedback occurs on a sufficiently long time scale. Our results shed light on the connection between evolution and human cognition and suggest necessary conditions for the rise and fall of rationality.

The use of monoamine pharmacological agents in the treatment of sexual dysfunction: evidence in the literature.

PubMed

Moll, Jennifer L; Brown, Candace S

2011-04-01

The monoamine neurotransmitters serotonin, dopamine, and norepinephrine play an important role in many medical and psychological conditions, including sexual responsiveness and behavior. Pharmacological agents that modulate monoamines may help alleviate sexual dysfunction. To provide an overview of pharmacological agents that modulate monoamines and their use in the treatment of sexual dysfunction. EMBASE and PubMed search for articles published between 1950 and 2010 using key words "sexual dysfunction,"monoamines,"monoaminergic receptors," and "generic names for pharmacological agents." To assess the literature evaluating the efficacy of monoamine pharmacologic agents used in the treatment of sexual dysfunction. The literature primarily cites the use of monoaminergic agents to treat sexual side effects from serotonergic reuptake inhibitors (SSRIs), with bupropion, buspirone and ropinirole providing the most convincing evidence. Controlled trials have shown that bupropion improves overall sexual dysfunction, but not frequency of sexual activity in depressed and nondepressed patients. Nefazodone and apomorphine have been used to treat sexual dysfunction, but their use is limited by significant side effect and safety profiles. New research on pharmacologic agents with subtype selectivity at dopaminergic and serotonergic receptors and those that possess dual mechanisms of action are being investigated. There has been tremendous progress over the past 50 years in understanding the role of monoamines in sexual function and the effect of pharmacologic agents which stimulate or antagonize monoaminergic receptors on sexual dysfunction. Nevertheless, large, double-blind, placebo-controlled studies evaluating the efficacy of currently available agents in populations without comorbid disorders are limited, preventing adequate interpretation of data. Continued research on sexual function and specific receptor subtypes will result in the development of more selective pharmacologic agents with the goal of increasing efficacy without the dose-limiting side effects of nonselective agents. © 2011 International Society for Sexual Medicine.

Effervescence-assisted dispersive liquid-liquid microextraction using a solid effervescent agent as a novel dispersion technique for the analysis of fungicides in apple juice.

PubMed

Jiang, Wenqing; Chen, Xiaochu; Liu, Fengmao; You, Xiangwei; Xue, Jiaying

2014-11-01

A novel effervescence-assisted dispersive liquid-liquid microextraction method has been developed for the determination of four fungicides in apple juice samples. In this method, a solid effervescent agent is added into samples to assist the dispersion of extraction solvent. The effervescent agent is environmentally friendly and only produces an increase in the ionic strength and a negligible variation in the pH value of the aqueous sample, which does not interfere with the extraction of the analytes. The parameters affecting the extraction efficiency were investigated including the composition of effervescent agent, effervescent agent amount, formulation of effervescent agent, adding mode of effervescent agent, type and volume of extraction solvent, and pH. Under optimized conditions, the method showed a good linearity within the range of 0.05-2 mg/L for pyrimethanil, fludioxonil, and cyprodinil, and 0.1-4 mg/L for kresoxim-methyl, with the correlation coefficients >0.998. The limits of detection for the method ranged between 0.005 and 0.01 mg/L. The recoveries of the target fungicides in apple juice samples were in the range of 72.4-110.8% with the relative standard deviations ranging from 1.2 to 6.8%. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distributed Leader-Following Finite-Time Consensus Control for Linear Multiagent Systems under Switching Topology

PubMed Central

Xu, Xiaole; Chen, Shengyong

2014-01-01

This paper investigates the finite-time consensus problem of leader-following multiagent systems. The dynamical models for all following agents and the leader are assumed the same general form of linear system, and the interconnection topology among the agents is assumed to be switching and undirected. We mostly consider the continuous-time case. By assuming that the states of neighbouring agents are known to each agent, a sufficient condition is established for finite-time consensus via a neighbor-based state feedback protocol. While the states of neighbouring agents cannot be available and only the outputs of neighbouring agents can be accessed, the distributed observer-based consensus protocol is proposed for each following agent. A sufficient condition is provided in terms of linear matrix inequalities to design the observer-based consensus protocol, which makes the multiagent systems achieve finite-time consensus under switching topologies. Then, we discuss the counterparts for discrete-time case. Finally, we provide an illustrative example to show the effectiveness of the design approach. PMID:24883367

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…

Using Animated Agents in Learner-Controlled Training: The Effects of Design Control

ERIC Educational Resources Information Center

Behrend, Tara S.; Thompson, Lori Foster

2012-01-01

Animated agents have the potential to increase engagement and learning during online training by acting as personalized tutors. However, little is known about the conditions that make these agents most effective. In this study, 183 e-learners completed a Microsoft Excel training course. Approximately half were assigned an agent with predetermined…

Preschool Children's Understanding of Conflicting Desires

ERIC Educational Resources Information Center

Cassidy, Kimberly Wright; Cosetti, Maura; Jones, Ressa; Kelton, Emily; Rafal, Valerie Meier; Richman, Lisa; Stanhaus, Heather

2005-01-01

This study examines the conditions under which 3-year-olds can use the desires of others to predict others' behavior. In Study 1, children were highly successful in predicting the actions of an agent based on that agent's desires when they were explicitly told about the agent's desires, even when the agent's desires were strongly different from…

EFFECTS OF CHRONIC EXERCISE CONDITIONING ON THERMAL RESPONSES TO LIPOPOLYSACCHARIDE AND TURPENTINE ABSCESS IN FEMALE RATS.

EPA Science Inventory

Chronic exercise conditioning has been shown to alter basal thermoregulatory processes as well as the response to inflammatory agents. Two such agents, lipopolysaccharide (LPS) and turpentine (TPT) are inducers of fever in rats. LPS, given intraperitoneally (i.p.), involves a sys...

Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

PubMed

Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

2016-04-01

Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

Moving beyond subcutaneous insulin: the application of adjunctive therapies to the treatment of type 1 diabetes.

PubMed

Ang, Kathleen H; Sherr, Jennifer L

2017-09-01

With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D. Areas covered: This review focuses on agents that have been utilized, including inhaled insulin preparations, pramlintide, metformin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dual SGLT1/2 inhibitors. Furthermore, with approval of the first hybrid closed loop (CL) system, the development of dual hormone CL systems is being explored. While the most common agent applied to these dual systems has been glucagon, research has been conducted to assess how some of the adjunctive therapies described above could aide with achieving postprandial glucose control while on CL insulin delivery. Expert opinion: By becoming less insulin-centric and incorporating some of these other agents, it is possible we may be able to better combat T1D.

21 CFR 184.1978 - Carnauba wax.

Code of Federal Regulations, 2010 CFR

2010-04-01

... lubricant and release agent as defined in § 170.3(o)(18) of this chapter; and as a surface-finishing agent... manufacturing practice conditions of use: (1) The ingredient is used as an anticaking agent as defined § 170.3(o...

Heterogeneous information-based artificial stock market

NASA Astrophysics Data System (ADS)

Pastore, S.; Ponta, L.; Cincotti, S.

2010-05-01

In this paper, an information-based artificial stock market is considered. The market is populated by heterogeneous agents that are seen as nodes of a sparsely connected graph. Agents trade a risky asset in exchange for cash. Besides the amount of cash and assets owned, each agent is characterized by a sentiment. Moreover, agents share their sentiments by means of interactions that are identified by the graph. Interactions are unidirectional and are supplied with heterogeneous weights. The agent's trading decision is based on sentiment and, consequently, the stock price process depends on the propagation of information among the interacting agents, on budget constraints and on market feedback. A central market maker (clearing house mechanism) determines the price process at the intersection of the demand and supply curves. Both closed- and open-market conditions are considered. The results point out the validity of the proposed model of information exchange among agents and are helpful for understanding the role of information in real markets. Under closed market conditions, the interaction among agents' sentiments yields a price process that reproduces the main stylized facts of real markets, e.g. the fat tails of the returns distributions and the clustering of volatility. Within open-market conditions, i.e. with an external cash inflow that results in asset price inflation, also the unitary root stylized fact is reproduced by the artificial stock market. Finally, the effects of model parameters on the properties of the artificial stock market are also addressed.

Genetic abnormalities in leukemia secondary to treatment in patients with Hodgkin's disease.

PubMed

Salas, Consuelo; Pérez-Vera, Patricia; Frías, Sara

2011-01-01

Hodgkin's disease has been treated mainly with two chemotherapy schedules, MOPP (nitrogen mustard, Oncovin, procarbazine and prednisone), which includes alkylating agents, and ABVD (adriamycin, bleomycin, vinblastine and dacarbazine), which includes topoisomerase II inhibitors, either with or without radiation therapy. Due to the types of agents used, patients with Hodgkin's disease often develop secondary leukemias. The alkylating agents included in the MOPP scheme were the first drugs associated with the development of therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML); both entities are the result of the clonal selection of cells with accumulated genomic lesions induced by antineoplastic therapy. In patients who developed t-MDS and t-AML, eight alternative routes with specific cytogenetic and molecular changes have been identified, and the routes are related to the type of therapy, alkylating agents or DNA topoisomerase II inhibitors. At the cytogenetic level, patients treated with alkylating agents show deletion 5q/monosomy 5 and deletion 7q/monosomy 7; in contrast, those who were treated with topoisomerase II inhibitors show 11q23 translocations involving the MLL gene. At the molecular level, there are two types of mutations: Class I, which alter the RAS-BRAF signal transduction pathways and increase cell proliferation; Class II, which disrupt genes that encode transcription factors and NPM1 that are involved in cell differentiation, and the inactivation of p53 tumor suppressor gene. Knowledge of the genetic alterations in these conditions is important for the classification, treatment and prognosis of patients as well as essential for increasing the knowledge of the biology of these diseases, which leads to identifying potential therapeutic targets.

On System Engineering a Barter-Based Re-allocation of Space System Key Development Resources

NASA Astrophysics Data System (ADS)

Kosmann, William J.

NASA has had a decades-long problem with cost growth during the development of space science missions. Numerous agency-sponsored studies have produced average mission level development cost growths ranging from 23 to 77%. A new study of 26 historical NASA science instrument set developments using expert judgment to re-allocate key development resources has an average cost growth of 73.77%. Twice in history, during the Cassini and EOS-Terra science instrument developments, a barter-based mechanism has been used to re-allocate key development resources. The mean instrument set development cost growth was -1.55%. Performing a bivariate inference on the means of these two distributions, there is statistical evidence to support the claim that using a barter-based mechanism to re-allocate key instrument development resources will result in a lower expected cost growth than using the expert judgment approach. Agent-based discrete event simulation is the natural way to model a trade environment. A NetLogo agent-based barter-based simulation of science instrument development was created. The agent-based model was validated against the Cassini historical example, as the starting and ending instrument development conditions are available. The resulting validated agent-based barter-based science instrument resource re-allocation simulation was used to perform 300 instrument development simulations, using barter to re-allocate development resources. The mean cost growth was -3.365%. A bivariate inference on the means was performed to determine that additional significant statistical evidence exists to support a claim that using barter-based resource re-allocation will result in lower expected cost growth, with respect to the historical expert judgment approach. Barter-based key development resource re-allocation should work on science spacecraft development as well as it has worked on science instrument development. A new study of 28 historical NASA science spacecraft developments has an average cost growth of 46.04%. As barter-based key development resource re-allocation has never been tried in a spacecraft development, no historical results exist, and an inference on the means test is not possible. A simulation of using barter-based resource re-allocation should be developed. The NetLogo instrument development simulation should be modified to account for spacecraft development market participant differences. The resulting agent-based barter-based spacecraft resource re-allocation simulation would then be used to determine if significant statistical evidence exists to prove a claim that using barter-based resource re-allocation will result in lower expected cost growth.

Anti-IL-23 and Anti-IL-17 Biologic Agents for the Treatment of Immune-Mediated Inflammatory Conditions.

PubMed

Frieder, Jillian; Kivelevitch, Dario; Haugh, Isabel; Watson, Ian; Menter, Alan

2018-01-01

Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn's disease, rheumatoid arthritis, in addition to other immune-mediated conditions. Here we review the IL-23/IL-17 immune pathways and discuss the key clinical and safety data of the anti-IL-23 and anti-IL-17 biologic agents in psoriasis and other immune-mediated diseases. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Molecularly imprinted covalent organic polymers for the selective extraction of benzoxazole fluorescent whitening agents from food samples.

PubMed

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.

Twelve-Month-Olds' Understanding of Intention Transfer through Communication

PubMed Central

Cheung, Him; Xiao, Wen; Lai, Ching Man

2012-01-01

Do infants understand that intention can be transferred through communication? We answered this question by examining 12-month-olds' looking times in a violation-of-expectation paradigm with two human agents. In familiarization, the non-acting agent spoke, clapped her hands, read aloud a book, or remained silent before the acting agent grasped one (the target) of two objects. During test only the non-actor remained, grasping either the target or distractor. The infants looked longer in the distractor than target condition, suggesting violation of expectation, only if the non-actor had spoken or clapped in familiarization. Because the non-actor never had grasped any of the objects in familiarization, the infants' expectation on her behavior could have developed from the understanding that her intention was transferred to the actor, who executed it by grasping the target in familiarization, via speaking and clapping as acts of communication (but not reading aloud and remaining silent). PMID:23029427

Twelve-month-olds' understanding of intention transfer through communication.

PubMed

Cheung, Him; Xiao, Wen; Lai, Ching Man

2012-01-01

Do infants understand that intention can be transferred through communication? We answered this question by examining 12-month-olds' looking times in a violation-of-expectation paradigm with two human agents. In familiarization, the non-acting agent spoke, clapped her hands, read aloud a book, or remained silent before the acting agent grasped one (the target) of two objects. During test only the non-actor remained, grasping either the target or distractor. The infants looked longer in the distractor than target condition, suggesting violation of expectation, only if the non-actor had spoken or clapped in familiarization. Because the non-actor never had grasped any of the objects in familiarization, the infants' expectation on her behavior could have developed from the understanding that her intention was transferred to the actor, who executed it by grasping the target in familiarization, via speaking and clapping as acts of communication (but not reading aloud and remaining silent).

Design and assembly of new non-viral RNAi delivery agents by microwave-assisted quaternization (MAQ) of tertiary amines

PubMed Central

Ghosh, Animesh; Mukherjee, Koushik; Jiang, Xinpeng; Zhou, Ying; McCarroll, Joshua; Qu, James; Swain, Pamela M.; Baigude, Huricha; Rana, Tariq M.

2010-01-01

RNA interference (RNAi), a gene-silencing phenomenon whereby double-stranded RNA (dsRNA) triggers the sequence-specific degradation of homologous mRNA. RNAi has been quickly and widely applied to discover gene functions and holds great potential to provide a new class of therapeutic agents. However, new chemistry and delivery approaches are greatly needed to silence disease-causing genes without toxic effects. We reasoned that conjugation of the cholesterol moiety to cationic lipids would enhance RNAi efficiencies and lower the toxic effects of lipid-mediated RNAi delivery. Here, we report the first design and synthesis of new cholesterol-conjugated cationic lipids for RNAi delivery using microwave-assisted quaternization (MAQ) of tertiary amines. This strategy can be employed to develop new classes of non-viral gene delivery agents under safe and fast reaction conditions. PMID:20722369

The context of discrimination: workplace conditions, institutional environments, and sex and race discrimination charges.

PubMed

Hirsh, C Elizabeth; Kornrich, Sabino

2008-03-01

This article explores the organizational conditions under which discrimination charges occur. Drawing on structural and organizational theories of the workplace, the authors demonstrate how organizational conditions affect workers' and regulatory agents' understandings of unlawful discrimination. Using a national sample of work establishments, matched to discrimination-charge data obtained from the Equal Employment Opportunity Commission (EEOC), the authors examine how characteristics of the workplace and institutional environment affect variation in the incidence of workers' charges of sex and race discrimination and in the subset of discrimination claims that are verified by EEOC investigators. The findings indicate that workplace conditions, including size, composition, and minority management, affect workers' charges as well as verified claims; the latter are also affected by institutional factors, such as affirmative action requirements, subsidiary status, and industrial sector. These results suggest that internal workplace conditions affect both workers' and regulatory agents' interpretations of potentially discriminatory experiences, while institutional conditions matter only for regulatory agents' interpretations of those events.

Context Dependence of Protein Misfolding and Structural Strains in Neurodegenerative Diseases

PubMed Central

Mehta, Anil K.; Rosen, Rebecca F.; Childers, W. Seth; Gehman, John D.; Walker, Lary C.; Lynn, David G.

2014-01-01

Vast arrays of structural forms are accessible to simple amyloid peptides and environmental conditions can direct assembly into single phases. These insights are now being applied to the aggregation of the Aβ peptide of Alzheimer’s disease (AD) and the identification of causative phases. We extend use of the imaging agent Pittsburgh compound B (PiB) to discriminate among Aβ phases and begin to define conditions of relevance to the disease state. And we specifically highlight the development of methods for defining the structures of these more complex phases. PMID:23893572

Management of hyperpigmentation in darker racial ethnic groups.

PubMed

Grimes, Pearl E

2009-06-01

Dyschromias, in particular hyperpigmentation, are major issues of concern for people of color. Pigmentary disorders such as melasma and postinflammatory hyperpigmentation (PIH) can cause psychological and emotional distress and can pose a negative impact on a person's health-related quality of life. The precise etiology of these conditions is unknown. Therapies for melasma and PIH target various points during the cycle of melanin production and degradation. Therapies for these conditions include topical agents and resurfacing procedures. Hydroquinone remains the gold standard of topical agents. Other efficacious agents include kojic acid, azelaic acid, mequinol, and retinoids. Cosmeceutical agents include licorice, arbutin, soy, N-acetyl glucosamine, and niacinamide. Resurfacing procedures that have been used to treat melasma and PIH include chemical peels, microdermabrasion, lasers, and intense pulsed light. These procedures are best used in combination with topical bleaching agents. Given the propensity of darker skin to hyperpigment, resurfacing procedures should be used with care and caution. Maximal results are best achieved with repetitive, superficial, resurfacing modalities. In addition, ultraviolet protective measures such as broad-spectrum sunscreens are fundamental to the successful management of these conditions.

Home composting using different ratios of bulking agent to food waste.

PubMed

Guidoni, Lucas Lourenço Castiglioni; Marques, Roger Vasques; Moncks, Rodrigo Bilhalva; Botelho, Fabiana Torma; da Paz, Matheus Francisco; Corrêa, Luciara Bilhalva; Corrêa, Érico Kunde

2018-02-01

The negative environmental impacts associated with home composting may be due to the absence of a defined operation criteria for the degradation process. In addition to the potentially low environmental impact in terms of energy and water usage, which is minimal to the manufacture of the composting unit and avoiding the processing and transportation of waste or byproduct, composting at home can also promote a reduction in the emission of unpleasant gases. The proportion of the food waste and bulking agents in the composting mixture may be decisive to fulfill good practices of waste stabilization. The aim of this study was to investigate how different ratios of bulking agent and organic household waste can affect the progress and outcome of the composting process. Three treatments, varying in the ratio of rice husk: raw fruit and vegetable leftovers (70:30, 50:50, 30:70; v:v) were used in a home composting system on a pilot scale. Results show that the proportion of starting materials used in the composting mixture influenced the degradation of organic matter, nitrogen dynamics of the process and its toxicity on germinating plants. The proportions with greater amounts of food waste had higher concentrations of mineral matter, higher peak temperature, and a better initial carbon-to-nitrogen ratio, while the proportion containing 70% of bulking agent lacked odors and leachate generation and showed a low nitrogen loss. A higher proportion of food waste presented better conditions for microbiological development and less time to obtain characteristics of matured composts. A higher proportion of bulking agents resulted in favorable conditions for household handling and less potential for environmental impacts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of postfire management on forest regeneration in a managed hemiboreal forest, Estonia

Treesearch

Kristi Parro; Marek Metslaid; Getter Renel; Allan Sims; John Stanturf; Kalev Jogiste; Kajar Koster

2015-01-01

Fire is a significant agent for the development of boreal and hemiboreal forests, altering soil and light conditions, affecting seedbanks, and removing seed trees. Burned areas should be managed with care, as inappropriate techniques prolong the regeneration period and reduce the diversity and resilience of stands to disturbances. To study the effects of fire and...

Tenure and Asymmetric Information: An Analysis of an Incentive Institution for Faculty Development in Research Universities

ERIC Educational Resources Information Center

Song, Jing

2008-01-01

From the perspective of asymmetric information, a principal-agent model is used to put forward a new theoretical explanation for the validity and effectiveness of tenure. Furthermore, through an analysis of the conditions of implementing an effective tenure system, it is argued that such a system is more efficient in research universities. Based…

Development of a sampling system for Armillaria rhizomorphs in mixed oak stands: a progress report

Treesearch

Mark J. Twery; Philip M. Wargo

1991-01-01

The assessment of the problems caused by gypsy moth is dependent on a number of characteristics of a forest stand. One of the main impacts of defoliation is the mortality of standing trees. Mortality is seldom caused directly by defoliation, but is usually associated with a secondary agent which attacks the tree in its weakened condition.

Melatonergic drugs in development.

PubMed

Carocci, Alessia; Catalano, Alessia; Sinicropi, Maria Stefania

2014-01-01

Melatonin (N-acetyl-5-methoxytryptamine) is widely known as "the darkness hormone". It is a major chronobiological regulator involved in circadian phasing and sleep-wake cycle in humans. Numerous other functions, including cyto/neuroprotection, immune modulation, and energy metabolism have been ascribed to melatonin. A variety of studies have revealed a role for melatonin and its receptors in different pathophysiological conditions. However, the suitability of melatonin as a drug is limited because of its short half-life, poor oral bioavailability, and ubiquitous action. Due to the therapeutic potential of melatonin in a wide variety of clinical conditions, the development of new agents able to interact selectively with melatonin receptors has become an area of great interest during the last decade. Therefore, the field of melatonergic receptor agonists comprises a great number of structurally different chemical entities, which range from indolic to nonindolic compounds. Melatonergic agonists are suitable for sleep disturbances, neuropsychiatric disorders related to circadian dysphasing, and metabolic diseases associated with insulin resistance. The results of preclinical studies on animal models show that melatonin receptor agonists can be considered promising agents for the treatment of central nervous system-related pathologies. An overview of recent advances in the field of investigational melatonergic drugs will be presented in this review.

[Quasi-adaptive response to alkylating agents in Escherichia coli and Ada-protein functions].

PubMed

Vasil'eva, S V; Moshkovskaia, E Iu; Terekhov, A S; Mikoian, V D; Vanin, A F

2008-01-01

In 2005 we have described in exponentially growing E. coli cells a new fundamental genetic phenomenon,--quasi-adaptive response to alkylating compounds (quasi-Ada). Phenotypic expression of quasi-Ada is similar to the true Ada response. However, in contrast to the letter, it develops in the course of pretreatment of the cells by a sublethal dose of nonalkylating agent, an NO-containing dinitrosyl iron complex with glutathione (DNICglu). To reveal the mechanisms of quasi-adaptation and its association with the function of the Ada regulatory protein, here we used a unique property of dual gene expression regulation of aidB1 gene, a part of the Ada-regulon, namely its relative independence from Ada protein in anaerobic conditions. Based on the results of aidB1 gene expression analysis an EPR spectra of E. coli MV2176 cells (aidB1::lacZ) in aerobic and anaerobic conditions after the corresponding treatments, we conclude that the function and the spatial structure of meAda and [(Cys-)2Fe+(NO+)2]Ada are identical and thus the nitrosylated protein represents a regulator of the Ada regulon gene expression during quasi-adaptation development.

Impact of Environmental Conditions (pH, Ionic Strength, And Electrolyte Type) On The Surface Charge And Aggregation Of Silver Nanoparticles Suspensions

EPA Science Inventory

The impact of capping agents and environmental conditions (pH, ionic strength, and background electrolytes) on surface charge and aggregation potential of silver nanoparticles (AgNPs) suspensions were investigated. Capping agents are chemicals used in the synthesis of nanopartic...

Dogs Identify Agents in Third-Party Interactions on the Basis of the Observed Degree of Contingency.

PubMed

Tauzin, Tibor; Kovács, Krisztina; Topál, József

2016-08-01

To investigate whether dogs could recognize contingent reactivity as a marker of agents' interaction, we performed an experiment in which dogs were presented with third-party contingent events. In the perfect-contingency condition, dogs were shown an unfamiliar self-propelled agent (SPA) that performed actions corresponding to audio clips of verbal commands played by a computer. In the high-but-imperfect-contingency condition, the SPA responded to the verbal commands on only two thirds of the trials; in the low-contingency condition, the SPA responded to the commands on only one third of the trials. In the test phase, the SPA approached one of two tennis balls, and then the dog was allowed to choose one of the balls. The proportion of trials on which a dog chose the object indicated by the SPA increased with the degree of contingency: Dogs chose the target object significantly above chance level only in the perfect-contingency condition. This finding suggests that dogs may use the degree of temporal contingency observed in third-party interactions as a cue to identify agents. © The Author(s) 2016.

Staphylococcus aureus: methicillin-susceptible S. aureus to methicillin-resistant S. aureus and vancomycin-resistant S. aureus.

PubMed

Rehm, Susan J; Tice, Alan

2010-09-15

The evolution of methicillin-resistant and vancomycin-resistant Staphylococcus aureus has demanded serious review of antimicrobial use and development of new agents and revised approaches to prevent and overcome drug resistance. Depending on local conditions and patient risk factors, empirical therapy of suspected S. aureus infection may require coverage of drug-resistant organisms with newer agents and novel antibiotic combinations. The question of treatment with inappropriate antibiotics raises grave concerns with regard to methicillin-resistant S. aureus selection, overgrowth, and increased virulence. Several strategies to reduce the nosocomial burden of resistance are suggested, including shortened hospital stays and outpatient parenteral antimicrobial therapy of the most serious infections.

A solid phase enzyme-linked immunosorbent assay for the antigenic detection of Legionella pneumophila (serogroup 1): A compliment for the space station diagnostic capability

NASA Technical Reports Server (NTRS)

Hejtmancik, Kelly E.

1987-01-01

It is necessary that an adequate microbiology capability be provided as part of the Health Maintenance Facility (HMF) to support expected microbial disease events and environmental monitoring during long periods of space flight. The application of morphological and biochemical studies to confirm the presence of certain bacterial and fungal disease agents are currently available and under consideration. This confirmation would be facilitated through employment of serological methods to aid in the identification of bacterial, fungal, and viral agents. A number of serological approaches are currently being considered, including the use of Enzyme Linked Immunosorbent Assay (ELISA) technology, which could be utilized during microgravity conditions. A solid phase, membrane supported ELISA for the detection of Legionella pneumophila, an expected disease agent, was developed to show a potential model system that would meet the HMF requirements and specifications for the future space station. These studies demonstrate the capability of membrane supported ELISA systems for identification of expected microbial disease agents as part of the HMF.

Therapeutic Potential of Phytochemicals in Combination with Drugs for Cardiovascular Disorders.

PubMed

Shen, James Z; Ng, Ting L J; Ho, Wing S

2017-01-01

The incidence of cardiovascular disorders is increasing worldwide. Heart disease is the leading cause of death for both men and women. High blood pressure, high low-density lipoprotein cholesterol level, and smoking are key risk factors for heart disease. Other medical conditions such as diabetes, overweight, obesity and lifestyle can put people at a higher risk for coronary heart disease. The preventive measures based on the common drugs may help reduce the risk of cardiovascular diseases. The present review highlights the contributions of therapeutic potential of phytochemicals in management of cardiovascular diseases. However, the delivery efficiency of therapeutic agents can be enhanced in order to improve the efficacy of phytochemicals as a therapeutic agent. The oral administration of phytochemicals as therapeutic agents is a common approach. The review highlights the recent development of natural products for the complementary treatment of cardiovascular diseases. These findings indicate that the combination of therapeutic drugs and natural products may improve the treatment efficacy of therapeutic agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

HYPOXIA-ACTIVATED PRO-DRUG TH-302 EXHIBITS POTENT TUMOUR SUPPRESSIVE ACTIVITY AND COOPERATES WITH CHEMOTHERAPY AGAINST OSTEOSARCOMA

PubMed Central

Liapis, Vasilios; Labrinidis, Agatha; Zinonos, Irene; Hay, Shelley; Ponomarev, Vladimir; Panagopoulos, Vasilios; DeNichilo, Mark; Ingman, Wendy; Atkins, Gerald J.; Findlay, David M.; Zannettino, Andrew CW.; Evdokiou, Andreas

2015-01-01

Tumour hypoxia is a major cause of treatment failure for a variety of malignancies. However, tumour hypoxia also offers treatment opportunities, exemplified by the development compounds that target hypoxic regions within tumours. TH-302 is a pro-drug created by the conjugation of 2-nitroimidazole to bromo-isophosphoramide (Br-IPM). When TH-302 is delivered to regions of hypoxia, Br-IPM, the DNA cross linking toxin, is released. In this study we assessed the cytotoxic activity of TH-302 against osteosarcoma cells in vitro and evaluated its anticancer efficacy as a single agent, and in combination with doxorubicin, in an orthotopic mouse model of human osteosarcoma (OS). In vitro, TH-302 was potently cytotoxic to osteosarcoma cells selectively under hypoxic conditions, whereas primary normal human osteoblasts were protected. Animals transplanted with OS cells directly into their tibiae and left untreated developed mixed osteolytic/osteosclerotic bone lesions and subsequently developed lung metastases. TH-302 reduced tumor burden in bone and cooperated with doxorubicin to protect bone from osteosarcoma induced bone destruction, while it also reduced lung metastases. TH-302 may therefore be an attractive therapeutic agent with strong activity as a single agent and in combination with chemotherapy against OS. PMID:25444931

Hypoxia-activated pro-drug TH-302 exhibits potent tumor suppressive activity and cooperates with chemotherapy against osteosarcoma.

PubMed

Liapis, Vasilios; Labrinidis, Agatha; Zinonos, Irene; Hay, Shelley; Ponomarev, Vladimir; Panagopoulos, Vasilios; DeNichilo, Mark; Ingman, Wendy; Atkins, Gerald J; Findlay, David M; Zannettino, Andrew C W; Evdokiou, Andreas

2015-02-01

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, tumor hypoxia also offers treatment opportunities, exemplified by the development compounds that target hypoxic regions within tumors. TH-302 is a pro-drug created by the conjugation of 2-nitroimidazole to bromo-isophosphoramide (Br-IPM). When TH-302 is delivered to regions of hypoxia, Br-IPM, the DNA cross linking toxin, is released. In this study we assessed the cytotoxic activity of TH-302 against osteosarcoma cells in vitro and evaluated its anticancer efficacy as a single agent, and in combination with doxorubicin, in an orthotopic mouse model of human osteosarcoma (OS). In vitro, TH-302 was potently cytotoxic to osteosarcoma cells selectively under hypoxic conditions, whereas primary normal human osteoblasts were protected. Animals transplanted with OS cells directly into their tibiae and left untreated developed mixed osteolytic/osteosclerotic bone lesions and subsequently developed lung metastases. TH-302 reduced tumor burden in bone and cooperated with doxorubicin to protect bone from osteosarcoma induced bone destruction, while it also reduced lung metastases. TH-302 may therefore be an attractive therapeutic agent with strong activity as a single agent and in combination with chemotherapy against OS. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

[Evaluation of anti-inflammatory activity of extracts from Siberian plants].

PubMed

Nesterova, Iu V; Povet'eva, T N; Aksinenko, S G; Suslov, N I; Gaĭdamovich, N N; Nagorniak, Iu G; Popova, E V; Kravtsova, S S; Andreeva, T I

2009-01-01

Experimental investigations have shown that water-alcohol extracts from plants containing alkaloids (Aconitum baikalense, Aconitum septentrionale, Delphinium elatum L., Conium maculatum) and salicylic acid (Filipendula ulmaria, Salix viminalis, Fragaria vesca, Rubus idaeus) inhibited the development of main symptoms of inflammation, viz. exudation, pain, fever, to the same extent as non-steroidal anti-inflammatory agents. The substances studied in this work may be used to develop new efficient pharmacological preparations for the treatment of different inflammatory conditions associated with severe pain syndrome.

Improved Success of Sparse Matrix Protein Crystallization Screening with Heterogeneous Nucleating Agents

PubMed Central

Thakur, Anil S.; Robin, Gautier; Guncar, Gregor; Saunders, Neil F. W.; Newman, Janet; Martin, Jennifer L.; Kobe, Bostjan

2007-01-01

Background Crystallization is a major bottleneck in the process of macromolecular structure determination by X-ray crystallography. Successful crystallization requires the formation of nuclei and their subsequent growth to crystals of suitable size. Crystal growth generally occurs spontaneously in a supersaturated solution as a result of homogenous nucleation. However, in a typical sparse matrix screening experiment, precipitant and protein concentration are not sampled extensively, and supersaturation conditions suitable for nucleation are often missed. Methodology/Principal Findings We tested the effect of nine potential heterogenous nucleating agents on crystallization of ten test proteins in a sparse matrix screen. Several nucleating agents induced crystal formation under conditions where no crystallization occurred in the absence of the nucleating agent. Four nucleating agents: dried seaweed; horse hair; cellulose and hydroxyapatite, had a considerable overall positive effect on crystallization success. This effect was further enhanced when these nucleating agents were used in combination with each other. Conclusions/Significance Our results suggest that the addition of heterogeneous nucleating agents increases the chances of crystal formation when using sparse matrix screens. PMID:17971854

Topical preparations for pain relief: efficacy and patient adherence

PubMed Central

Jorge, Liliana L; Feres, Caroline C; Teles, Vitor EP

2011-01-01

There has been an increasing focus on development of new routes of drug administration to provide tailored treatments for patients, without decreasing efficacy of analgesia, in proportion to the progression of the knowledge of pain mechanisms. While acute pain acts as an alarm, chronic pain is a syndrome requiring meticulous selection of analgesic drugs of high bioavailability for long-term use. Such criteria are challenges that topical medications aim to overcome, allowing progressive delivery of active component, maintaining stable plasma levels, with a good safety profile. This review presents recent findings regarding topical formulations of the most widely used drugs for pain treatment, such as nonsteroidal anti-inflammatory agents, anesthetics, and capsaicin, and the role of physical agents as delivery enhancers (phonophoresis and iontophoresis). Although the number of topical agents is limited for use in peripheral conditions, increasing evidence supports the efficacy of these preparations in blocking nociceptive and neuropathic pain. Patient adherence to medical treatment is also a challenge, especially in chronic painful conditions. It is known that reduction of treatment complexity and pill burden are good strategies to increase patient compliance, as discussed here. However, the role of topical presentations, when compared to traditional routes, has not yet been fully explored and thus remains unclear. PMID:21386951

Agent-based station for on-line diagnostics by self-adaptive laser Doppler vibrometry

NASA Astrophysics Data System (ADS)

Serafini, S.; Paone, N.; Castellini, P.

2013-12-01

A self-adaptive diagnostic system based on laser vibrometry is proposed for quality control of mechanical defects by vibration testing; it is developed for appliances at the end of an assembly line, but its characteristics are generally suited for testing most types of electromechanical products. It consists of a laser Doppler vibrometer, equipped with scanning mirrors and a camera, which implements self-adaptive bahaviour for optimizing the measurement. The system is conceived as a Quality Control Agent (QCA) and it is part of a Multi Agent System that supervises all the production line. The QCA behaviour is defined so to minimize measurement uncertainty during the on-line tests and to compensate target mis-positioning under guidance of a vision system. Best measurement conditions are reached by maximizing the amplitude of the optical Doppler beat signal (signal quality) and consequently minimize uncertainty. In this paper, the optimization strategy for measurement enhancement achieved by the down-hill algorithm (Nelder-Mead algorithm) and its effect on signal quality improvement is discussed. Tests on a washing machine in controlled operating conditions allow to evaluate the efficacy of the method; significant reduction of noise on vibration velocity spectra is observed. Results from on-line tests are presented, which demonstrate the potential of the system for industrial quality control.

Extraction-spectrophotometric determination of tris(2-chloroethyl)amine using phthaleins.

PubMed

Rozsypal, Tomas; Halamek, Emil

2017-06-01

Procedures for the extraction-spectrophotometric determination of tris(2-chloroethyl)amine, an alkylating agent known as a drug as well as a chemical warfare agent (nitrogen mustard HN-3), with 7 acid-base indicators of a triphenylmethane lactone type, phthaleins, were developed. Representatives of phthaleins without an oxygen bridge (thymolphthalein, o-cresolphthalein, naphtholphthalein) and with an oxygen bridge (fluorescein, 2',7'-dichlorofluorescein, eosin B and eosin Y) were used. The methods were based on the formation of ion pair complexes. Chloroform was used as a non-polar solvent for an extraction. The conditions to determine were optimized for the optimal pH of the buffer and the concentration of a phthalein as a reagent. The dependence on the reaction time in a water phase and the stoichiometry of extraction products were studied. The detection limits and the limits of the determination of separate procedures and conditional extraction constants were determined. Comparison with the spectrophotometric method of the group determination of alkyl halides and acyl halides using alkaline ethanol-water solution of thymolphthalein, the so-called T-135 agent, was conducted. While studying the selectivity, the possible interference of bis(2-chloroethyl)sulphide and 3 nitrogen mustards in the proposed procedures were verified. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of Different Silage Storing Conditions on the Oxygen Concentration in the Silo and Fermentation Quality of Rice.

PubMed

Uegaki, Ryuichi; Kawano, Kazuo; Ohsawa, Ryo; Kimura, Toshiyuki; Yamamura, Kohji

2017-06-21

We investigated the effects of different silage storing conditions on the oxygen concentration in the silo and fermentation quality of rice (Oryza sativa L.). Forage rice was ensiled in bottles (with or without space at the bottlemouth, with solid or pinhole cap, and with oxygen scavenger, ethanol transpiration agent, oxygen scavenger and ethanol transpiration agent, or no adjuvant) and stored for 57 days. The oxygen concentration decreased with the addition of the oxygen scavenger and increased with that of the ethanol transpiration agent. The oxygen scavenger facilitated silage fermentation and fungus generation, whereas the ethanol transpiration agent suppressed silage fermentation and fungus generation. However, the combined use of the oxygen scavenger and ethanol transpiration agent facilitated silage fermentation and also suppressed fungus generation. Overall, this study revealed the negative effects of oxygen on the internal silo and the positive effects of the combined use of the oxygen scavenger and ethanol transpiration agent on silage fermentation quality.

Application of Pharmacokinetic and Pharmacodynamic Analysis to the Development of Liposomal Formulations for Oncology

PubMed Central

Ait-Oudhia, Sihem; Mager, Donald E.; Straubinger, Robert M.

2014-01-01

Liposomal formulations of anticancer agents have been developed to prolong drug circulating lifetime, enhance anti-tumor efficacy by increasing tumor drug deposition, and reduce drug toxicity by avoiding critical normal tissues. Despite the clinical approval of numerous liposome-based chemotherapeutics, challenges remain in the development and clinical deployment of micro- and nano-particulate formulations, as well as combining these novel agents with conventional drugs and standard-of-care therapies. Factors requiring optimization include control of drug biodistribution, release rates of the encapsulated drug, and uptake by target cells. Quantitative mathematical modeling of formulation performance can provide an important tool for understanding drug transport, uptake, and disposition processes, as well as their role in therapeutic outcomes. This review identifies several relevant pharmacokinetic/pharmacodynamic models that incorporate key physical, biochemical, and physiological processes involved in delivery of oncology drugs by liposomal formulations. They capture observed data, lend insight into factors determining overall antitumor response, and in some cases, predict conditions for optimizing chemotherapy combinations that include nanoparticulate drug carriers. PMID:24647104

VIP as a potential therapeutic agent in gram negative sepsis.

PubMed

Ibrahim, Hiba; Barrow, Paul; Foster, Neil

2012-12-01

Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

Amisulpride and symptomatic bradycardia: a case report.

PubMed

Huang, Li-Chung; Huang, Li-Yen; Tseng, Shih-Yen; Hou, Yuh-Ming; Hsiao, Cheng-Cheng

2015-01-01

Amisulpride is a second-generation antipsychotic agent indicated for the treatment of schizophrenia and other major psychotic illnesses. Amisulpride-induced bradycardia is a rare condition of unknown etiology and mechanism. Asymptomatic bradycardia has been associated with amisulpride in only two cases. In our case, the association was rated as "probable" on the Naranjo adverse drug reaction probability scale. Case report. A 45-year-old male patient developed symptomatic bradycardia during usage of amisulpride (400-800 mg/day), which dramatically improved after the complete termination of amisulpride usage. The psychiatric condition remained relatively stable without bradycardia after administration of another antipsychotic agent [risperidone (3 mg/day)]. This is the first case report of symptomatic bradycardia associated with the use of amisulpride. Although bradycardia is a rare adverse reaction to antipsychotics, this finding may alert psychiatrists and physicians to this antipsychotic drug side effect. Further study is needed to disclose the role of antipsychotics in bringing about symptomatic bradycardia. Copyright © 2015 Elsevier Inc. All rights reserved.

Computer modeling describes gravity-related adaptation in cell cultures.

PubMed

Alexandrov, Ludmil B; Alexandrova, Stoyana; Usheva, Anny

2009-12-16

Questions about the changes of biological systems in response to hostile environmental factors are important but not easy to answer. Often, the traditional description with differential equations is difficult due to the overwhelming complexity of the living systems. Another way to describe complex systems is by simulating them with phenomenological models such as the well-known evolutionary agent-based model (EABM). Here we developed an EABM to simulate cell colonies as a multi-agent system that adapts to hyper-gravity in starvation conditions. In the model, the cell's heritable characteristics are generated and transferred randomly to offspring cells. After a qualitative validation of the model at normal gravity, we simulate cellular growth in hyper-gravity conditions. The obtained data are consistent with previously confirmed theoretical and experimental findings for bacterial behavior in environmental changes, including the experimental data from the microgravity Atlantis and the Hypergravity 3000 experiments. Our results demonstrate that it is possible to utilize an EABM with realistic qualitative description to examine the effects of hypergravity and starvation on complex cellular entities.

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease.

PubMed

Godlewska, Urszula; Brzoza, Piotr; Sroka, Aneta; Majewski, Pawel; Jentsch, Holger; Eckert, Martin; Eick, Sigrun; Potempa, Jan; Zabel, Brian A; Cichy, Joanna

2017-01-01

Periodontal inflammation is one of the most common chronic inflammatory conditions in humans. Despite recent advances in identifying and characterizing oral microbiota dysbiosis in the pathogenesis of gum disease, just how host factors maintain a healthy homeostatic oral microbial community or prevent the development of a pathogenic oral microbiota remains poorly understood. An important determinant of microbiota fate is local antimicrobial proteins. Here, we report that chemoattractant protein chemerin, which we recently identified as a potent endogenous antimicrobial agent in body barriers such as the skin, is present in the oral cavity under homeostatic and inflammatory conditions. Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against select bacteria strategically positioned in dental biofilm. Gingival crevicular samples from patients with gingivitis but not periodontitis contain abundant bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration. Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin. Together, these data suggest that as an antimicrobial agent and leukocyte chemoattractant, chemerin likely contributes to antimicrobial immune defense in the oral cavity.

Coevolution in management fashion: an agent-based model of consultant-driven innovation.

PubMed

Strang, David; David, Robert J; Akhlaghpour, Saeed

2014-07-01

The rise of management consultancy has been accompanied by increasingly marked faddish cycles in management techniques, but the mechanisms that underlie this relationship are not well understood. The authors develop a simple agent-based framework that models innovation adoption and abandonment on both the supply and demand sides. In opposition to conceptions of consultants as rhetorical wizards who engineer waves of management fashion, firms and consultants are treated as boundedly rational actors who chase the secrets of success by mimicking their highest-performing peers. Computational experiments demonstrate that consultant-driven versions of this dynamic in which the outcomes of firms are strongly conditioned by their choice of consultant are robustly faddish. The invasion of boom markets by low-quality consultants undercuts popular innovations while simultaneously restarting the fashion cycle by prompting the flight of high-quality consultants into less densely occupied niches. Computational experiments also indicate conditions involving consultant mobility, aspiration levels, mimic probabilities, and client-provider matching that attenuate faddishness.

Epidemiology, Prevention, and Assessment of Tardive Dyskinesia and Advances in Treatment.

PubMed

Correll, Christoph U; Kane, John M; Citrome, Leslie L

​​ Tardive dyskinesia (TD) is a disorder characterized by involuntary movements, typically of the orofacial muscles and also of the extremities and other muscle groups. The condition is associated with exposure to dopamine receptor blocking agents, including antipsychotics. Because the indications and off-label uses for these agents have expanded over the last 2 decades, a larger number of patients are receiving antipsychotic medications than in the past. While evidence suggests that patients being treated with second-generation antipsychotics have less risk for developing TD than those treated with first-generation antipsychotics, the decreased risk is not as great as was originally expected. In addition, patients with chronic psychiatric conditions often require long-term use of antipsychotics, putting them at risk for TD. This article addresses the prevalence, risk factors, and prevention of TD; assessment strategies including diagnostic criteria and rating scales; and evidence for TD treatments, including 2 newly approved medications: deutetrabenazine and valbenazine. ​​​. © Copyright 2017 Physicians Postgraduate Press, Inc.

Reprint of: Clinical management of tardive dyskinesia: Five steps to success.

PubMed

Citrome, Leslie

2018-06-15

Tardive dyskinesia (TD) has long been thought to be a generally irreversible consequence of the use of dopamine receptor blocking agents. There is now an opportunity to successfully manage this condition with agents approved by the US Food and Drug Administration. This is important because TD has not been eliminated with the use of second-generation antipsychotics, and the expansion of antipsychotics to treat conditions other than schizophrenia has resulted in millions of additional individuals at risk for developing TD. Recognition of TD requires careful observation; a structured approach using the Abnormal Involuntary Movement Scale is encouraged. Harm reduction can be achieved by using antipsychotics judiciously when possible and by paying attention to other modifiable risk factors such as drug-induced parkinsonian symptoms and the use of anticholinergic medication. Once TD has emerged and is associated with dysfunction or distress, treatment with a VMAT2 inhibitor such as deutetrabenazine or valbenazine is well supported by several controlled clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical management of tardive dyskinesia: Five steps to success.

PubMed

Citrome, Leslie

2017-12-15

Tardive dyskinesia (TD) has long been thought to be a generally irreversible consequence of the use of dopamine receptor blocking agents. There is now an opportunity to successfully manage this condition with agents approved by the US Food and Drug Administration. This is important because TD has not been eliminated with the use of second-generation antipsychotics, and the expansion of antipsychotics to treat conditions other than schizophrenia has resulted in millions of additional individuals at risk for developing TD. Recognition of TD requires careful observation; a structured approach using the Abnormal Involuntary Movement Scale is encouraged. Harm reduction can be achieved by using antipsychotics judiciously when possible and by paying attention to other modifiable risk factors such as drug-induced parkinsonian symptoms and the use of anticholinergic medication. Once TD has emerged and is associated with dysfunction or distress, treatment with a VMAT2 inhibitor such as deutetrabenazine or valbenazine is well supported by several controlled clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

The current state of GPCR-based drug discovery to treat metabolic disease.

PubMed

Sloop, Kyle W; Emmerson, Paul J; Statnick, Michael A; Willard, Francis S

2018-02-02

One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. © 2018 The British Pharmacological Society.

Development of toughened epoxy polymers for high performance composite and ablative applications

NASA Technical Reports Server (NTRS)

Allen, V. R.

1982-01-01

A survey of current procedures for the assessment of state of cure in epoxy polymers and for the evaluation of polymer toughness as related to nature of the crosslinking agent was made to facilitate a cause-effect study of the chemical modification of epoxy polymers. Various conformations of sample morphology were examined to identify testing variables and to establish optimum conditions for the selected physical test methods. Dynamic viscoelasticity testing was examined in conjunction with chemical analyses to allow observation of the extent of the curing reaction with size of the crosslinking agent the primary variable. Specifically the aims of the project were twofold: (1) to consider the experimental variables associated with development of "extent of cure" analysis, and (2) to assess methodology of fracture energy determination and to prescribe a meaningful and reproducible procedure. The following is separated into two categories for ease of presentation.

Development of a magnetic solid-phase extraction coupled with high-performance liquid chromatography method for the analysis of polyaromatic hydrocarbons.

PubMed

Ma, Yan; Xie, Jiawen; Jin, Jing; Wang, Wei; Yao, Zhijian; Zhou, Qing; Li, Aimin; Liang, Ying

2015-07-01

A novel magnetic solid phase extraction coupled with high-performance liquid chromatography method was established to analyze polyaromatic hydrocarbons in environmental water samples. The extraction conditions, including the amount of extraction agent, extraction time, pH and the surface structure of the magnetic extraction agent, were optimized. The results showed that the amount of extraction agent and extraction time significantly influenced the extraction performance. The increase in the specific surface area, the enlargement of pore size, and the reduction of particle size could enhance the extraction performance of the magnetic microsphere. The optimized magnetic extraction agent possessed a high surface area of 1311 m(2) /g, a large pore size of 6-9 nm, and a small particle size of 6-9 μm. The limit of detection for phenanthrene and benzo[g,h,i]perylene in the developed analysis method was 3.2 and 10.5 ng/L, respectively. When applied to river water samples, the spiked recovery of phenanthrene and benzo[g,h,i]perylene ranged from 89.5-98.6% and 82.9-89.1%, respectively. Phenanthrene was detected over a concentration range of 89-117 ng/L in three water samples withdrawn from the midstream of the Huai River, and benzo[g,h,i]perylene was below the detection limit. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization of Surface-Enhanced Raman Spectroscopy Conditions for Implementation into a Microfluidic Device for Drug Detection.

PubMed

Kline, Neal D; Tripathi, Ashish; Mirsafavi, Rustin; Pardoe, Ian; Moskovits, Martin; Meinhart, Carl; Guicheteau, Jason A; Christesen, Steven D; Fountain, Augustus W

2016-11-01

A microfluidic device is being developed by University of California-Santa Barbara as part of a joint effort with the United States Army to develop a portable, rapid drug detection device. Surface-enhanced Raman spectroscopy (SERS) is used to provide a sensitive, selective detection technique within the microfluidic platform employing metallic nanoparticles as the SERS medium. Using several illicit drugs as analytes, the work presented here describes the efforts of the Edgewood Chemical Biological Center to optimize the microfluidic platform by investigating the role of nanoparticle material, nanoparticle size, excitation wavelength, and capping agents on the performance, and drug concentration detection limits achievable with Ag and Au nanoparticles that will ultimately be incorporated into the final design. This study is particularly important as it lays out a systematic comparison of limits of detection and potential interferences from working with several nanoparticle capping agents-such as tannate, citrate, and borate-which does not seem to have been done previously as the majority of studies only concentrate on citrate as the capping agent. Morphine, cocaine, and methamphetamine were chosen as test analytes for this study and were observed to have limits of detection (LOD) in the range of (1.5-4.7) × 10 -8 M (4.5-13 ng/mL), with the borate capping agent having the best performance.

Radiosynthesis and Biodistribution of 99mTc-Metronidazole as an Escherichia coli Infection Imaging Radiopharmaceutical.

PubMed

Iqbal, Anam; Naqvi, Syed Ali Raza; Rasheed, Rashid; Mansha, Asim; Ahmad, Matloob; Zahoor, Ameer Fawad

2018-05-01

Bacterial infection poses life-threatening challenge to humanity and stimulates to the researchers for developing better diagnostic and therapeutic agents complying with existing theranostic techniques. Nuclear medicine technique helps to visualize hard-to-diagnose deep-seated bacterial infections using radionuclide-labeled tracer agents. Metronidazole is an antiprotozoal antibiotic that serves as a preeminent anaerobic chemotherapeutic agent. The aim of this study was to develop technetium-99m-labeled metronidazole radiotracer for the detection of deep-seated bacterial infections. Radiosynthesis of 99m Tc-metronidazole was carried by reacting reduced technetium-99m and metronidazole at neutral pH for 30 min. The stannous chloride dihydrate was used as the reducing agent. At optimum radiolabeling conditions, ~ 94% radiochemical was obtained. Quality control analysis was carried out with a chromatographic paper and instant thin-layer chromatographic analysis. The biodistribution study of radiochemical was performed using Escherichia coli bacterial infection-induced rat model. The scintigraphic study was performed using E. coli bacterial infection-induced rabbit model. The results showed promising accumulation at the site of infection and its rapid clearance from the body. The tracer showed target-to-non-target ratio 5.57 ± 0.04 at 1 h post-injection. The results showed that 99m Tc-MNZ has promising potential to accumulate at E. coli bacterial infection that can be used for E. coli infection imaging.

The use of hormonal contraceptive agents and mood disorders in women.

PubMed

Svendal, Gjertrud; Berk, Michael; Pasco, Julie A; Jacka, Felice N; Lund, Anders; Williams, Lana J

2012-09-01

Mood disorders are a major cause of disability in developed countries, and contraceptive agents among the most widely used medications. The relationship between contraceptive agents and mood is unclear. The aim of this study was therefore to investigate the association between current contraception use and mood disorders in a random population-based sample of women. This study examined epidemiological data obtained from 498 women aged 20-50year participating in the Geelong Osteoporosis Study (GOS). Mood disorders were diagnosed using a clinical interview (SCID-I/NP) and information on medication use and other lifestyle factors were documented. After adjusting for age and socioeconomic status (SES), women taking progestin-only contraceptive agents had an increased likelihood of a current mood disorder (OR 3.0 95%CI: 1.1-7.8, p=0.03). In contrast, women taking combined contraceptive agents had a decreased likelihood of a current mood disorder, adjusting this for age and SES (OR 0.3 95%CI: 0.1, 0.9 p=0.03). These findings were not explained by weight, physical activity level, past depression, number of medical conditions or cigarette smoking. This study is cross-sectional, which precludes any determination regarding the direction of the relationships. These data suggest a protective effect of the combined contraceptive pill, and a deleterious effect of progestin only agents in regards to mood disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

PubMed Central

Ahn, Brian J.; Pollack, Ian F.; Okada, Hideho

2013-01-01

Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas. PMID:24202450

The effect of salivary pH on diametral tensile strength of resin modified glass ionomer cement coated with coating agent

NASA Astrophysics Data System (ADS)

Ismayanti, D.; Triaminingsih, S.; Eriwati, Y. K.

2017-08-01

The aim of this study was to evaluate the effect of artificial saliva with different acidities on the diametral tensile strength of Resin Modified Glass Ionomer Cement (RMGIC) coated with varnish and nanofilled coating agent. The specimens coated with coating agents were immersed in artificial saliva with pH of 4.5, 5.5, and 7 for 24 hours in an incubatorat 37°C. The diametral tensile strength of the specimens was tested with Universal Testing Machine. There were no significant differences on the diametral tensile strength of all specimens that were put into groups based on the acidity of the saliva and the type of coating agent (p>0.05). Both varnish and nanofilled coating agent stayed on the RMGIC in the acidic condition that simulated the true condition of oral cavity in people with high caries risk for the 24 hours of maturation.

Place preference and vocal learning rely on distinct reinforcers in songbirds.

PubMed

Murdoch, Don; Chen, Ruidong; Goldberg, Jesse H

2018-04-30

In reinforcement learning (RL) agents are typically tasked with maximizing a single objective function such as reward. But it remains poorly understood how agents might pursue distinct objectives at once. In machines, multiobjective RL can be achieved by dividing a single agent into multiple sub-agents, each of which is shaped by agent-specific reinforcement, but it remains unknown if animals adopt this strategy. Here we use songbirds to test if navigation and singing, two behaviors with distinct objectives, can be differentially reinforced. We demonstrate that strobe flashes aversively condition place preference but not song syllables. Brief noise bursts aversively condition song syllables but positively reinforce place preference. Thus distinct behavior-generating systems, or agencies, within a single animal can be shaped by correspondingly distinct reinforcement signals. Our findings suggest that spatially segregated vocal circuits can solve a credit assignment problem associated with multiobjective learning.

An Agent-Based Modeling Template for a Cohort of Veterans with Diabetic Retinopathy.

PubMed

Day, Theodore Eugene; Ravi, Nathan; Xian, Hong; Brugh, Ann

2013-01-01

Agent-based models are valuable for examining systems where large numbers of discrete individuals interact with each other, or with some environment. Diabetic Veterans seeking eye care at a Veterans Administration hospital represent one such cohort. The objective of this study was to develop an agent-based template to be used as a model for a patient with diabetic retinopathy (DR). This template may be replicated arbitrarily many times in order to generate a large cohort which is representative of a real-world population, upon which in-silico experimentation may be conducted. Agent-based template development was performed in java-based computer simulation suite AnyLogic Professional 6.6. The model was informed by medical data abstracted from 535 patient records representing a retrospective cohort of current patients of the VA St. Louis Healthcare System Eye clinic. Logistic regression was performed to determine the predictors associated with advancing stages of DR. Predicted probabilities obtained from logistic regression were used to generate the stage of DR in the simulated cohort. The simulated cohort of DR patients exhibited no significant deviation from the test population of real-world patients in proportion of stage of DR, duration of diabetes mellitus (DM), or the other abstracted predictors. Simulated patients after 10 years were significantly more likely to exhibit proliferative DR (P<0.001). Agent-based modeling is an emerging platform, capable of simulating large cohorts of individuals based on manageable data abstraction efforts. The modeling method described may be useful in simulating many different conditions where course of disease is described in categorical stages.

Thermal Process Development

DTIC Science & Technology

1983-04-08

constraints and legislation, the methods used for disposing of military lethal agents such as GB, VX, and HD, have changed from land and sea burial to...uction is the most generally accepted method of destroying toxic organic materials for all cases where the toxicity is associated with the totality of...8217., preferred method can be based on estimates or determinations of the required incineration conditions and an appraisal of the requirement for

Influence of the activating agent and the inert gas (type and flow) used in an activation process for the porosity development of carbon nanofibers.

PubMed

Jiménez, Vicente; Sánchez, Paula; Valverde, José Luis; Romero, Amaya

2009-08-15

Carbon nanofibers (CNFs) were activated with different activating agents (KOH, KHCO(3) and K(2)CO(3)). The effects of different activations conditions, including type of protector gas (He, Ar and N(2)) and helium flow rate on the properties of activated carbon nanofibers were studied. The structural changes in activated CNFs were investigated using the following characterization techniques: N(2) adsorption isotherms at 77K, XRD, temperature-programmed desorption of hydrogen, TEM, TPO and elemental composition. The results showed that the surface area increased by a factor of 3.3, 2.0 and 1.8 referred to the parent CNFs after the treatment with KOH, K(2)CO(3) and KHCO(3), respectively. In addition, KOH generated a greater pore volume than the other activating agents; micropores were mainly generated during the process. Finally, different carrier gases were added during the activation in order to study their influence on the pore opening behavior of CNFs. It was found that the activation degree increased in the following order: Ar

Global critical materials markets: An agent-based modeling approach

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

Riddle, Matthew; Macal, Charles M.; Conzelmann, Guenter

As part of efforts to position the United States as a leader in clean energy technology production, the U. S. Department of Energy (DOE) issued two Critical Materials Strategy reports, which assessed 16 materials on the basis of their importance to clean energy development and their supply risk ( U.S. Department of Energy (DOE), 2010 and DOE, 2011). To understand the implications for clean energy of disruptions in supplies of critical materials, it is important to understand supply chain dynamics from mining to final product production. As a case study of critical material supply chains, we focus on the supplymore » of two rare earth metals, neodymium (Nd) and dysprosium (Dy), for permanent magnets used in wind turbines, electric vehicles and other applications. We introduce GCMat, a dynamic agent-based model that includes interacting agents at five supply chain stages consisting of mining, metal refining, magnet production, final product production and demand. Agents throughout the supply chain make pricing, production and inventory management decisions. Deposit developers choose which deposits to develop based on market conditions and detailed data on 57 rare earth deposits. Wind turbine and electric vehicle producers choose from a set of possible production technologies that require different amounts of rare earths. We ran the model under a baseline scenario and four alternative scenarios with different demand and production technology inputs. Model results from 2010 to 2013 fit well with historical data. Projections through 2025 show a number of possible future price, demand, and supply trajectories. For each scenario, we highlight reasons for turning points under market conditions, for differences between Nd and Dy markets, and for differences between scenarios. Because GCMat can model causal dynamics and provide fine-grain representation of agents and their decisions, it provides explanations for turning points under market conditions that are not otherwise available from other modeling approaches. Our baseline projections show very different behaviors for Nd and Dy prices. Nd prices continue to drop and remain low even at the end of our simulation period as new capacity comes online and leads to a market in which production capacity outpaces demand. Dy price movements, on the other hand, change directions several times with several key turning points related to inventory behaviors of particular agents in the supply chain and asymmetric supply and demand trends. Scenario analyses show the impact of stronger demand growth for rare earths, and in particular finds that Nd price impacts are significantly delayed as compared to Dy. This is explained by the substantial excess production capacity for Nd in the early simulation years that keeps prices down. Scenarios that explore the impact of reducing the Dy content of magnets show the intricate interdependencies of these two markets as price trends for both rare earths reverse directions – reducing the Dy content of magnets reduces Dy demand, which drives down Dy prices and translates into lower magnet prices. This in turn raises the demand for magnets and therefore the demand for Nd and eventually drives up the Nd price.« less

PEGylated Bovine Carboxyhemoglobin (SANGUINATE™): Results of Clinical Safety Testing and Use in Patients.

PubMed

Abuchowski, A

2016-01-01

Oxygen transfer agents have long been sought as a means to treat hypoxia caused by congenital or acquired conditions. Hemoglobin-based oxygen carriers were in clinical development as blood substitutes, but development was halted due to the finding of significant vasoactivity. Rather than develop a blood substitute, a product for indications characterized by hypoxia is in development. PEGylated bovine carboxyhemoglobin (SANGUINATE™) is both a carbon monoxide releasing molecule and an oxygen transfer agent. It is comprised of three functional components that act to inhibit vasoconstriction, reduce inflammation and optimize the delivery of oxygen. SANGUINATE has the potential to reduce or prevent the effects of ischemia by inhibiting vasoconstriction and re-oxygenating tissue. Phase 1 safety trials in healthy volunteers were completed in 2013. SANGUINATE was shown to be safe and well tolerated with no serious adverse effects. Phase Ib studies have been completed in stable patients with Sickle Cell Disease. SANGUINATE has also been administered to two patients under emergency use protocols. Both patients exhibited improved status following treatment with SANGUINATE.

Pythium species and isolate diversity influence inhibition by the biological control agent Streptomyces lydicus

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...

77 FR 38865 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

...) (17 CFR 240.17Ad-4) is used to document when transfer agents are exempt, or no longer exempt, from the minimum performance standards and certain recordkeeping provisions of the Commission's transfer agent rules. Rule 17Ad-4(c) sets forth the conditions under which a registered transfer agent loses its exempt...

New Therapeutic Approaches in Diabetic Retinopathy

PubMed Central

Vaziri, Kamyar; Schwartz, Stephen G.; Relhan, Nidhi; Kishor, Krishna S.; Flynn Jr, Harry W.

2015-01-01

Diabetic retinopathy is a common microvascular complication of diabetes mellitus. It affects a substantial proportion of US adults over age 40. The condition is a leading cause of visual loss. Much attention has been given to expanding the role of current treatments along with investigating various novel therapies and drug delivery methods. In the treatment of diabetic macular edema (DME), intravitreal pharmacotherapies, especially anti-vascular endothelial growth factor (anti-VEGF) agents, have gained popularity. Currently, anti-VEGF agents are often used as first-line agents in center-involved DME, with recent data suggesting that among these agents, aflibercept leads to better visual outcomes in patients with worse baseline visual acuities. While photocoagulation remains the standard treatment for proliferative diabetic retinopathy (PDR), recent FDA approvals of ranibizumab and aflibercept in the management of diabetic retinopathy associated with DME may suggest a potential for pharmacologic treatments of PDR as well. Novel therapies, including small interfering RNAs, chemokines, kallikrein-kinin inhibitors, and various anti-angiogenic agents, are currently being evaluated for the management of diabetic retinopathy and DME. In addition to these strategies, novel drug delivery methods such as sustained-release implants and refillable reservoir implants are either under active evaluation or have recently gained FDA approval. This review provides an update on the novel developments in the treatment of diabetic retinopathy. PMID:26676668

VMAT2 inhibitors for the treatment of tardive dyskinesia.

PubMed

Scorr, Laura M; Factor, Stewart A

2018-06-15

Tardive dyskinesia (TD) is an often disabling hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Although initially thought to most commonly occur with typical antipsychotics, the incidence is likely similar with atypical antipsychotics and antiemetics such as metoclopramide. Increased prescribing of these agents as well as low rates of remission have contributed to a rising prevalence of TD. Although this condition was described nearly 60 years ago, it is only within the past year that two novel therapeutic agents were FDA approved. Characterization of the VMAT2 inhibitor tetrabenazine, which was identified as a therapeutic agent for TD in older clinical trials, has yielded two distinct pharmacologic strategies to optimize response. The first strategy, used to create deutetrabenazine, employed deuterization of tetrabenazine to stabilize the pharmacokinetics and eliminate high peak plasma levels. The second strategy was the creation of a prodrug, valbenazine, for the two most active isoforms of tetrabenazine that also resulted in more stable pharmacokinetics and eliminated peak plasma levels. Both agents have been demonstrated to be effective and safe for the treatment of TD in multicenter, controlled trials and their development has led to a resurgence of interest in the characterization and treatment of this movement disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

Protective effect of conditioning agents on Afro-ethnic hair chemically treated with thioglycolate-based straightening emulsion.

PubMed

Dias, Tania Cristina de Sá; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles

2008-06-01

Straightening is a chemical process by which excessively curly hair is straightened in an irreversible way. Generally, products are formulated as emulsions with high pH value (9.0-12.0), which, after applied on hair, cause considerable damage, making it dry and fragile. This research work evaluated the protective effect of lauryl PEG/PPG-18/18 methicone, cyclopentasiloxane (and) PEG-12 dimethicone cross-polymer, jojoba oil, and aqua (and) cystine bis-PG propyl silanetriol, as conditioning agents, on Afro-ethnic hair locks treated with thioglycolate-based straightening emulsions by protein loss, combability, and traction to rupture. Standard Afro-ethnic hair locks were prepared following a protocol for straightening emulsion application. Considering the assays performed, the addition of conditioning agents to the straightening emulsion with ammonium thioglycolate benefited the hair fiber, thus diminishing protein loss, protecting the hair thread, and improving resistance to breakage. Jojoba oil and lauryl PEG/PPG-18/18 methicone were the conditioning agents that presented the best results. Straightening emulsions with ammonium thioglycolate containing aqua (and) cystine bis-PG propyl silanetriol and cyclopentasiloxane (and) PEG-12 dimethicone cross-polymer were the ones that provided higher breakage resistance of the thread.

Measurements of scene spectral radiance variability

NASA Astrophysics Data System (ADS)

Seeley, Juliette A.; Wack, Edward C.; Mooney, Daniel L.; Muldoon, Michael; Shey, Shen; Upham, Carolyn A.; Harvey, John M.; Czerwinski, Richard N.; Jordan, Michael P.; Vallières, Alexandre; Chamberland, Martin

2006-05-01

Detection performance of LWIR passive standoff chemical agent sensors is strongly influenced by various scene parameters, such as atmospheric conditions, temperature contrast, concentration-path length product (CL), agent absorption coefficient, and scene spectral variability. Although temperature contrast, CL, and agent absorption coefficient affect the detected signal in a predictable manner, fluctuations in background scene spectral radiance have less intuitive consequences. The spectral nature of the scene is not problematic in and of itself; instead it is spatial and temporal fluctuations in the scene spectral radiance that cannot be entirely corrected for with data processing. In addition, the consequence of such variability is a function of the spectral signature of the agent that is being detected and is thus different for each agent. To bracket the performance of background-limited (low sensor NEDN), passive standoff chemical sensors in the range of relevant conditions, assessment of real scene data is necessary1. Currently, such data is not widely available2. To begin to span the range of relevant scene conditions, we have acquired high fidelity scene spectral radiance measurements with a Telops FTIR imaging spectrometer 3. We have acquired data in a variety of indoor and outdoor locations at different times of day and year. Some locations include indoor office environments, airports, urban and suburban scenes, waterways, and forest. We report agent-dependent clutter measurements for three of these backgrounds.

Influence of diluent and sample processing methods on the recovery of the biocontrol agent Pantoea agglomerans CPA-2 from different fruit surfaces.

PubMed

Torres, R; Viñas, I; Usall, J; Remón, D; Teixidó, N

2012-08-01

Determining the populations of biocontrol agents applied as a postharvest treatment on fruit surfaces is fundamental to the assessment of the microorganisms' ability to colonise and persist on fruit. To obtain maximum recovery, we must develop a methodology that involves both diluent and processing methods and that does not affect the viability of the microorganisms. The effect of diluent composition was evaluated using three diluents: phosphate buffer, peptone saline and buffered peptone saline. An additional study was performed to compare three processing methods (shaking plus sonication, stomaching and shaking plus centrifugation) on the recovery efficiency of Pantoea agglomerans strain CPA-2 from apples, oranges, nectarines and peaches treated with this biocontrol agent. Overall, slight differences occurred among diluents, although the phosphate buffer maintained the most ideal pH for CPA-2 growth (between 5.2 and 6.2). Stomaching, using the phosphate buffer as diluent, was the best procedure for recovering and enumerating the biocontrol agent; this fact suggested that no lethal effects from naturally occurring antimicrobial compounds present on the fruit skins and/or produced when the tissues were disrupted affected the recovery of the CPA-2 cells, regardless of fruit type. The growth pattern of CPA-2 on fruits maintained at 20°C and under cold conditions was similar to that obtained in previous studies, which confirms the excellent adaptation of this strain to conditions commonly used for fruit storage. Copyright © 2012 Elsevier B.V. All rights reserved.

Biomorphic Multi-Agent Architecture for Persistent Computing

NASA Technical Reports Server (NTRS)

Lodding, Kenneth N.; Brewster, Paul

2009-01-01

A multi-agent software/hardware architecture, inspired by the multicellular nature of living organisms, has been proposed as the basis of design of a robust, reliable, persistent computing system. Just as a multicellular organism can adapt to changing environmental conditions and can survive despite the failure of individual cells, a multi-agent computing system, as envisioned, could adapt to changing hardware, software, and environmental conditions. In particular, the computing system could continue to function (perhaps at a reduced but still reasonable level of performance) if one or more component( s) of the system were to fail. One of the defining characteristics of a multicellular organism is unity of purpose. In biology, the purpose is survival of the organism. The purpose of the proposed multi-agent architecture is to provide a persistent computing environment in harsh conditions in which repair is difficult or impossible. A multi-agent, organism-like computing system would be a single entity built from agents or cells. Each agent or cell would be a discrete hardware processing unit that would include a data processor with local memory, an internal clock, and a suite of communication equipment capable of both local line-of-sight communications and global broadcast communications. Some cells, denoted specialist cells, could contain such additional hardware as sensors and emitters. Each cell would be independent in the sense that there would be no global clock, no global (shared) memory, no pre-assigned cell identifiers, no pre-defined network topology, and no centralized brain or control structure. Like each cell in a living organism, each agent or cell of the computing system would contain a full description of the system encoded as genes, but in this case, the genes would be components of a software genome.

Safety Assessment of Panax spp Root-Derived Ingredients as Used in Cosmetics.

PubMed

Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2015-01-01

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 13 Panax spp root-derived ingredients as used in cosmetics. Panax "spp" indicates that multiple species within the genus are used in cosmetics, but not all species within that genus. Four species are being considered in this safety assessment. These ingredients function mostly as skin-conditioning agents-miscellaneous, fragrance ingredients, skin-conditioning agents-humectant, skin-conditioning agents-emollient, and cosmetic astringents. The Panel reviewed available data related to these ingredients and addressed the issue of pulegone, a constituent of these ingredients and other ingredients, such as peppermint oil. The Panel concluded that these Panax spp root-derived ingredients are safe in the practices of use and concentration as given in this safety assessment. © The Author(s) 2015.

Increasing nest predation will be insufficient to maintain polar bear body condition in the face of sea ice loss.

PubMed

Dey, Cody J; Richardson, Evan; McGeachy, David; Iverson, Samuel A; Gilchrist, Hugh G; Semeniuk, Christina A D

2017-05-01

Climate change can influence interspecific interactions by differentially affecting species-specific phenology. In seasonal ice environments, there is evidence that polar bear predation of Arctic bird eggs is increasing because of earlier sea ice breakup, which forces polar bears into nearshore terrestrial environments where Arctic birds are nesting. Because polar bears can consume a large number of nests before becoming satiated, and because they can swim between island colonies, they could have dramatic influences on seabird and sea duck reproductive success. However, it is unclear whether nest foraging can provide an energetic benefit to polar bear populations, especially given the capacity of bird populations to redistribute in response to increasing predation pressure. In this study, we develop a spatially explicit agent-based model of the predator-prey relationship between polar bears and common eiders, a common and culturally important bird species for northern peoples. Our model is composed of two types of agents (polar bear agents and common eider hen agents) whose movements and decision heuristics are based on species-specific bioenergetic and behavioral ecological principles, and are influenced by historical and extrapolated sea ice conditions. Our model reproduces empirical findings that polar bear predation of bird nests is increasing and predicts an accelerating relationship between advancing ice breakup dates and the number of nests depredated. Despite increases in nest predation, our model predicts that polar bear body condition during the ice-free period will continue to decline. Finally, our model predicts that common eider nests will become more dispersed and will move closer to the mainland in response to increasing predation, possibly increasing their exposure to land-based predators and influencing the livelihood of local people that collect eider eggs and down. These results show that predator-prey interactions can have nonlinear responses to changes in climate and provides important predictions of ecological change in Arctic ecosystems. © 2016 John Wiley & Sons Ltd.

Simultaneous virtual prediction of anti-Escherichia coli activities and ADMET profiles: A chemoinformatic complementary approach for high-throughput screening.

PubMed

Speck-Planche, Alejandro; Cordeiro, M N D S

2014-02-10

Escherichia coli remains one of the principal pathogens that cause nosocomial infections, medical conditions that are increasingly common in healthcare facilities. E. coli is intrinsically resistant to many antibiotics, and multidrug-resistant strains have emerged recently. Chemoinformatics has been a great ally of experimental methodologies such as high-throughput screening, playing an important role in the discovery of effective antibacterial agents. However, there is no approach that can design safer anti-E. coli agents, because of the multifactorial nature and complexity of bacterial diseases and the lack of desirable ADMET (absorption, distribution, metabolism, elimination, and toxicity) profiles as a major cause of disapproval of drugs. In this work, we introduce the first multitasking model based on quantitative-structure biological effect relationships (mtk-QSBER) for simultaneous virtual prediction of anti-E. coli activities and ADMET properties of drugs and/or chemicals under many experimental conditions. The mtk-QSBER model was developed from a large and heterogeneous data set of more than 37800 cases, exhibiting overall accuracies of >95% in both training and prediction (validation) sets. The utility of our mtk-QSBER model was demonstrated by performing virtual prediction of properties for the investigational drug avarofloxacin (AVX) under 260 different experimental conditions. Results converged with the experimental evidence, confirming the remarkable anti-E. coli activities and safety of AVX. Predictions also showed that our mtk-QSBER model can be a promising computational tool for virtual screening of desirable anti-E. coli agents, and this chemoinformatic approach could be extended to the search for safer drugs with defined pharmacological activities.

Green Synthesis of Silver Nanoparticles Using Sodium Alginate and Lignosulphonic Acid Blends

NASA Astrophysics Data System (ADS)

Thakur, Amrita; Reddy, Giridhar

2017-08-01

A simple method based on the principles of green chemistry has been developed to synthesize stable silver nanoparticles (AgNP) for possible biomedical applications. Blend of sodium alginate (SA) and lignosulphonic acid (LS) prepared in the ratio of 80/20 mass percent respectively was used as reducing and stabilizing agent. This blend is biocompatible and has shown drug release ability under physiological conditions. Use of blend has an added advantage as LS has the ability to reduce silver while the blend matrix acts as a stabilizing agent. Effect of precursor concentration (AgNO3) and temperature was investigated. Progress of synthesis was monitored using UV-Vis spectroscopy. Higher temperature and lower silver nitrate concentration showed better synthesis of AgNP.

Matrix metalloproteinase inhibitor therapy to prevent complications as well as therapy for Ehler-Danlos syndrome.

PubMed

Sastry, P S R K

2002-09-01

Matrixmetalloproteinase inhibitors have been developed as anti-cancer agents. Their usage in pancreatic cancer and other such malignancies is under trial at present. An interesting undesired-effect of one of these agents is contracture of the hand. Ehler-Danlos syndrome is an inherited group of diseases with varying types. At present there is no known treatment or prevention for the complications associated with this inherited condition. Sometimes it is the adverse events of a drug, which provides an insight into its efficacy for another indication. It is hereby being hypothesized that the matrixmetalloproteinase inhibitors especially marimastat may be an effective drug for treatment of Ehler-Danlos syndrome and/or prevention of its major complications.

Personalized Pain Medicine: The Clinical Value of Psychophysical Assessment of Pain Modulation Profile

PubMed Central

Granovsky, Yelena; Yarnitsky, David

2013-01-01

Experimental pain stimuli can be used to simulate patients’ pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests—conditioned pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine. PMID:24228167

Personalized pain medicine: the clinical value of psychophysical assessment of pain modulation profile.

PubMed

Granovsky, Yelena; Yarnitsky, David

2013-01-01

Experimental pain stimuli can be used to simulate patients' pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests-conditioned pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.

Fuzzy adaptive iterative learning coordination control of second-order multi-agent systems with imprecise communication topology structure

NASA Astrophysics Data System (ADS)

Chen, Jiaxi; Li, Junmin

2018-02-01

In this paper, we investigate the perfect consensus problem for second-order linearly parameterised multi-agent systems (MAS) with imprecise communication topology structure. Takagi-Sugeno (T-S) fuzzy models are presented to describe the imprecise communication topology structure of leader-following MAS, and a distributed adaptive iterative learning control protocol is proposed with the dynamic of leader unknown to any of the agent. The proposed protocol guarantees that the follower agents can track the leader perfectly on [0,T] for the consensus problem. Under alignment condition, a sufficient condition of the consensus for closed-loop MAS is given based on Lyapunov stability theory. Finally, a numerical example and a multiple pendulum system are given to illustrate the effectiveness of the proposed algorithm.

Understanding overpressure in the FAA aerosol can test by C3H2F3Br (2-BTP)✩

PubMed Central

Linteris, Gregory Thomas; Babushok, Valeri Ivan; Pagliaro, John Leonard; Burgess, Donald Raymond; Manion, Jeffrey Alan; Takahashi, Fumiaki; Katta, Viswanath Reddy; Baker, Patrick Thomas

2018-01-01

Thermodynamic equilibrium calculations, as well as perfectly-stirred reactor (PSR) simulations with detailed reaction kinetics, are performed for a potential halon replacement, C3H2F3Br (2-BTP, C3H2F3Br, 2-Bromo-3,3,3-trifluoropropene), to understand the reasons for the unexpected enhanced combustion rather than suppression in a mandated FAA test. The high pressure rise with added agent is shown to depend on the amount of agent, and is well-predicted by an equilibrium model corresponding to stoichiometric reaction of fuel, oxygen, and agent. A kinetic model for the reaction of C3H2F3Br in hydrocarbon-air flames has been applied to understand differences in the chemical suppression behavior of C3H2F3Br vs. CF3Br in the FAA test. Stirred-reactor simulations predict that in the conditions of the FAA test, the inhibition effectiveness of C3H2F3Br at high agent loadings is relatively insensitive to the overall stoichiometry (for fuel-lean conditions), and the marginal inhibitory effect of the agent is greatly reduced, so that the mixture remains flammable over a wide range of conditions. Most important, the flammability of the agent-air mixtures themselves (when compressively preheated), can support low-strain flames which are much more difficult to extinguish than the easy-to extinguish, high-strain primary fireball from the impulsively released fuel mixture. Hence, the exothermic reaction of halogenated hydrocarbons in air should be considered in other situations with strong ignition sources and low strain flows, especially at preheated conditions. PMID:29628525

Effects of Cueing by a Pedagogical Agent in an Instructional Animation: A Cognitive Load Approach

ERIC Educational Resources Information Center

Yung, Hsin I.; Paas, Fred

2015-01-01

This study investigated the effects of a pedagogical agent that cued relevant information in a story-based instructional animation on the cardiovascular system. Based on cognitive load theory, it was expected that the experimental condition with the pedagogical agent would facilitate students to distinguish between relevant and irrelevant…

Simulation of low temperature combustion mechanism of different combustion-supporting agents in close-coupled DOC and DPF system.

PubMed

Jiao, Penghao; Li, Zhijun; Li, Qiang; Zhang, Wen; He, Li; Wu, Yue

2018-07-01

In the coupled Diesel Oxidation Catalyst (DOC) and Diesel Particular Filter (DPF) system, soot cannot be completely removed by only using the passive regeneration. And DPF active regeneration is necessary. The research method in this paper is to spray different kinds of combustion-supporting agents to the DOC in the front of the DPF. Therefore, the low temperature combustion mechanism of different kinds of combustion-supporting agents in DOC was studied, in order to grasp the law of combustion in DOC, and the influence of follow-up emission on DPF removal of soot. During the study, CH 4 H 2 mixture and diesel (n-heptane + toluene) were used as combustion-supporting agents respectively. The simplified mechanisms of two kinds of gas mixtures used as the combustion-supporting agents in DPF have been constructed and testified in the paper. In this paper, the combustion and emission conditions of the two combustion-supporting agents were analyzed so as to meet the practical requirements of different working conditions. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

Cancer.gov

The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and

Enhanced Growth and Hepatic Differentiation of Fetal Liver Epithelial Cells through Combinational and Temporal Adjustment of Soluble Factors

PubMed Central

Qian, Lichuan; Krause, Diane S.; Saltzman, W. Mark

2012-01-01

Fetal liver epithelial cells (FLEC) are valuable for liver cell therapy and tissue engineering, but methods for culture and characterization of these cells are not well developed. This work explores the influence of multiple soluble factors on FLEC, with the long-term goal of developing an optimal culture system to generate functional liver tissue. Our comparative analysis suggests hepatocyte growth factor (HGF) is required throughout the culture period. In the presence of HGF, addition of oncostatin M (OSM) at culture initiation results in concurrent growth and maturation, while constant presence of protective agents like ascorbic acid enhances cell survival. Study observations led to the development of a culture medium that provided optimal growth and hepatic differentiation conditions. FLEC expansion was observed to be ~2 fold of that under standard conditions, albumin secretion rate was 2 – 3 times greater than maximal values obtained with other media, and the highest level of glycogen accumulation among all conditions was observed with the developed medium. Our findings serve to advance culture methods for liver progenitors in cell therapy and tissue engineering applications. PMID:21922669

Allergic reactions to indoor air pollutants.

PubMed Central

Karol, M H

1991-01-01

Inhalation of airborne chemicals can result in allergic sensitization with episodic pulmonary responses occurring on subsequent exposures. Responses may occur in the upper respiratory tract (rhinitis), the lower respiratory tract (wheeze, bronchospasm) or systemically, for example, a febrile response. The mechanisms underlying these responses are not always clear but include production of reaginic antibody, activation of T-lymphocyte subsets, and release of spasmogenic and inflammatory mediators from pulmonary cell populations. A variety of agents have been associated with elicitation of these reactions including chemical vapors, dusts and particulates, and microbial organisms. As a result of the widespread occurrence of allergy in indoor environments, conditions conducive to development of allergy have received close attention. Agent-related factors include the nature of the chemical, its concentration, and the frequency and length of exposure to the agent. Host-related factors include the sex, age, and race of the host, as well as the general physical well being. The interactive nature of the host's immune system with the environment is the ultimate determinant of allergic disease. PMID:1821377

Time-resolved nanoseconds dynamics of ultrasound contrast agent microbubbles manipulated and controlled by optical tweezers

NASA Astrophysics Data System (ADS)

Garbin, Valeria; Cojoc, Dan; Ferrari, Enrico; Di Fabrizio, Enzo; Overvelde, Marlies L. J.; Versluis, Michel; van der Meer, Sander M.; de Jong, Nico; Lohse, Detlef

2006-08-01

Optical tweezers enable non-destructive, contact-free manipulation of ultrasound contrast agent (UCA) microbubbles, which are used in medical imaging for enhancing the echogenicity of the blood pool and to quantify organ perfusion. The understanding of the fundamental dynamics of ultrasound-driven contrast agent microbubbles is a first step for exploiting their acoustical properties and to develop new diagnostic and therapeutic applications. In this respect, optical tweezers can be used to study UCA microbubbles under controlled and repeatable conditions, by positioning them away from interfaces and from neighboring bubbles. In addition, a high-speed imaging system is required to record the dynamics of UCA microbubbles in ultrasound, as their oscillations occur on the nanoseconds timescale. In this work, we demonstrate the use of an optical tweezers system combined with a high-speed camera capable of 128-frame recordings at up to 25 million frames per second (Mfps), for the study of individual UCA microbubble dynamics as a function of the distance from solid interfaces.

Expansion of space station diagnostic capability to include serological identification of viral and bacterial infections

NASA Technical Reports Server (NTRS)

Hejtmancik, Kelly E.

1987-01-01

It is necessary that an adequate microbiology capability be provided as part of the Health Maintenance Facility (HMF) to support expected microbial disease events during long periods of space flight. The applications of morphological and biochemical studies to confirm the presence of certain bacterial and fungal disease agents are currently available and under consideration. This confirmation would be greatly facilitated through employment of serological methods to aid in the identification for not only bacterial and fungal agents, but viruses as well. A number of serological approached were considered, particularly the use of Enzyme Linked Immunosorbent Assays (ELISAs), which could be utilized during space flight conditions. A solid phase, membrane supported ELISA for the detection of Bordetella pertussis was developed to show a potential model system that would meet the HMF requirements and specifications for the future space station. A second model system for the detection of Legionella pneumophilia, an expected bacterial disease agent, is currently under investigation.

Roles of Change Agents in Development. Occasional Paper #3.

ERIC Educational Resources Information Center

O'Gorman, Frances

The roles of change agents in community development are manifest (surface actions of agents interacting with clients) and latent (derived from undercurrents that give directions to the agents' actions). Manifest roles are as starter (facilitator, analyzer, leadership developer); go-between (informer, linker); and accomplisher (organizer,…

The curing agent sodium nitrite, used in the production of fermented sausages, is less inhibiting to the bacteriocin-producing meat starter culture Lactobacillus curvatus LTH 1174 under anaerobic conditions.

PubMed

Verluyten, Jurgen; Messens, Winy; De Vuyst, Luc

2003-07-01

Curvacin A is a listericidal bacteriocin produced by Lactobacillus curvatus LTH 1174, a strain isolated from fermented sausage. The response of this strain to an added curing agent (sodium nitrite) in terms of cell growth and bacteriocin production was investigated in vitro by laboratory fermentations with modified MRS broth. The strain was highly sensitive to nitrite; even a concentration of 10 ppm of curing agent inhibited its growth and both volumetric and specific bacteriocin production. A meat simulation medium containing 5 ppm of sodium nitrite was tested to investigate the influence of the gas phase on the growth and bacteriocin production of L. curvatus LTH 1174. Aerating the culture during growth had no effect on biomass formation, but the oxidative stress caused a higher level of specific bacteriocin production and led to a metabolic shift toward acetic acid production. Anaerobic conditions, on the other hand, led to an increased biomass concentration and less growth inhibition. Also, higher maximum volumetric bacteriocin activities and a higher level of specific bacteriocin production were obtained in the presence of sodium nitrite than in fermentations under aerobic conditions or standard conditions of air supply. These results indicate that the inhibitory effect of the curing agent is at least partially masked under anaerobic conditions.

The Curing Agent Sodium Nitrite, Used in the Production of Fermented Sausages, Is Less Inhibiting to the Bacteriocin-Producing Meat Starter Culture Lactobacillus curvatus LTH 1174 under Anaerobic Conditions

PubMed Central

Verluyten, Jurgen; Messens, Winy; De Vuyst, Luc

2003-01-01

Curvacin A is a listericidal bacteriocin produced by Lactobacillus curvatus LTH 1174, a strain isolated from fermented sausage. The response of this strain to an added curing agent (sodium nitrite) in terms of cell growth and bacteriocin production was investigated in vitro by laboratory fermentations with modified MRS broth. The strain was highly sensitive to nitrite; even a concentration of 10 ppm of curing agent inhibited its growth and both volumetric and specific bacteriocin production. A meat simulation medium containing 5 ppm of sodium nitrite was tested to investigate the influence of the gas phase on the growth and bacteriocin production of L. curvatus LTH 1174. Aerating the culture during growth had no effect on biomass formation, but the oxidative stress caused a higher level of specific bacteriocin production and led to a metabolic shift toward acetic acid production. Anaerobic conditions, on the other hand, led to an increased biomass concentration and less growth inhibition. Also, higher maximum volumetric bacteriocin activities and a higher level of specific bacteriocin production were obtained in the presence of sodium nitrite than in fermentations under aerobic conditions or standard conditions of air supply. These results indicate that the inhibitory effect of the curing agent is at least partially masked under anaerobic conditions. PMID:12839751

Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer

DTIC Science & Technology

2015-12-01

normal DNA synthesis. In contrast, pol eta shows a combination of high efficiency and low fidelity when replicating 8-oxo-G. These combined properties...are consistent with a pro- mutagenic role for pol eta when replicating this DNA lesion under cellular conditions. Studies with modified nucleotide...analogs indicate that pol eta relies heavily on hydrogen-bonding interactions during normal and translesion synthesis. However, some nucleobase

A Catastrophic Consequence of Cramp.

PubMed

Htet, Zay Myo; Karim, Mahzuz

2018-01-01

Quinine has long been used for the treatment of conditions such as malaria and leg cramps, and is also present at low levels in some beverages; however, it can cause serious side effects. We describe a patient who developed severe haemolysis, thrombocytopaenia, and acute kidney injury following the ingestion of a single dose of quinine. This case demonstrates the importance of awareness of such potentially life-threatening consequences of exposure to this agent.

Near-Infrared Squaraine Dye Encapsulated Micelles for in Vivo Fluorescence and Photoacoustic Bimodal Imaging.

PubMed

Sreejith, Sivaramapanicker; Joseph, James; Lin, Manjing; Menon, Nishanth Venugopal; Borah, Parijat; Ng, Hao Jun; Loong, Yun Xian; Kang, Yuejun; Yu, Sidney Wing-Kwong; Zhao, Yanli

2015-06-23

Combined near-infrared (NIR) fluorescence and photoacoustic imaging techniques present promising capabilities for noninvasive visualization of biological structures. Development of bimodal noninvasive optical imaging approaches by combining NIR fluorescence and photoacoustic tomography demands suitable NIR-active exogenous contrast agents. If the aggregation and photobleaching are prevented, squaraine dyes are ideal candidates for fluorescence and photoacoustic imaging. Herein, we report rational selection, preparation, and micelle encapsulation of an NIR-absorbing squaraine dye (D1) for in vivo fluorescence and photoacoustic bimodal imaging. D1 was encapsulated inside micelles constructed from a biocompatible nonionic surfactant (Pluoronic F-127) to obtain D1-encapsulated micelles (D1(micelle)) in aqueous conditions. The micelle encapsulation retains both the photophysical features and chemical stability of D1. D1(micelle) exhibits high photostability and low cytotoxicity in biological conditions. Unique properties of D1(micelle) in the NIR window of 800-900 nm enable the development of a squaraine-based exogenous contrast agent for fluorescence and photoacoustic bimodal imaging above 820 nm. In vivo imaging using D1(micelle), as demonstrated by fluorescence and photoacoustic tomography experiments in live mice, shows contrast-enhanced deep tissue imaging capability. The usage of D1(micelle) proven by preclinical experiments in rodents reveals its excellent applicability for NIR fluorescence and photoacoustic bimodal imaging.

The Other Bladder Syndrome: Underactive Bladder

PubMed Central

Miyazato, Minoru; Yoshimura, Naoki; Chancellor, Michael B

2013-01-01

Detrusor underactivity, or underactive bladder (UAB), is defined as a contraction of reduced strength and/or duration resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span. UAB can be observed in many neurologic conditions and myogenic failure. Diabetic cystopathy is the most important and inevitable disease developing from UAB, and can occur silently and early in the disease course. Careful neurologic and urodynamic examinations are necessary for the diagnosis of UAB. Proper management is focused on prevention of upper tract damage, avoidance of overdistension, and reduction of residual urine. Scheduled voiding, double voiding, al-blockers, and intermittent self-catheterization are the typical conservative treatment options. Sacral nerve stimulation may be an effective treatment option for UAB. New concepts such as stem cell therapy and neurotrophic gene therapy are being explored. Other new agents for UAB that act on prostaglandin E2 and EP2 receptors are currently under development. The pharmaceutical and biotechnology industries that have a pipeline in urology and women’s health may want to consider UAB as a potential target condition. Scientific counsel and review of the current pharmaceutical portfolio may uncover agents, including those in other therapeutic fields, that may benefit the management of UAB. PMID:23671401

14 CFR 25.1199 - Extinguishing agent containers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... discharge. (e) If a pyrotechnic capsule is used to discharge the extinguishing agent, each container must be installed so that temperature conditions will not cause hazardous deterioration of the pyrotechnic capsule...

14 CFR 25.1199 - Extinguishing agent containers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... discharge. (e) If a pyrotechnic capsule is used to discharge the extinguishing agent, each container must be installed so that temperature conditions will not cause hazardous deterioration of the pyrotechnic capsule...

Consensus pursuit of heterogeneous multi-agent systems under a directed acyclic graph

NASA Astrophysics Data System (ADS)

Yan, Jing; Guan, Xin-Ping; Luo, Xiao-Yuan

2011-04-01

This paper is concerned with the cooperative target pursuit problem by multiple agents based on directed acyclic graph. The target appears at a random location and moves only when sensed by the agents, and agents will pursue the target once they detect its existence. Since the ability of each agent may be different, we consider the heterogeneous multi-agent systems. According to the topology of the multi-agent systems, a novel consensus-based control law is proposed, where the target and agents are modeled as a leader and followers, respectively. Based on Mason's rule and signal flow graph analysis, the convergence conditions are provided to show that the agents can catch the target in a finite time. Finally, simulation studies are provided to verify the effectiveness of the proposed approach.

The prevention of oral mucositis in patients with blood cancers: current concepts and emerging landscapes.

PubMed

Niscola, Pasquale; Tendas, Andrea; Cupelli, Luca; Catalano, Gianfranco; Scaramucci, Laura; Giovannini, Marco; Trinchieri, Vito; Sharma, Atul; Efficace, Fabio; Cartoni, Claudio; Piccioni, Daniela; Perrotti, Alessio; Dentamaro, Teresa; de Fabritiis, Paolo; Keefe, Dorothy M K

2012-12-01

The prevention of oral mucositis (OM) in the management of hematological malignancies continues to represent an unmet clinical need. Addressing this issue has major clinical implications as OM can also greatly impair patient's quality of life. To review currently available measures and investigational agents to prevent OM in hematological patients. we searched for OM and related issues using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. Many agents targeting different mechanisms of mucosal damage have been applied in order to prevent OM; most of them have failed or its efficacy has not been fully demonstrated. Palifermin is the first pharmaceutical/biological agent approved for the prevention of OM; its use is currently restricted to patients who have received radiotherapy-containing conditioning regimens prior to autologous hematopoietic stem cell transplantation. No clear benefit by this agent has been demonstrated outside of this specific setting and its application should be limited to clinical trials. Other interventions, such as other growth factors and non mitogenic measures are under investigation or in development and their application in the hematological setting is expected in the short term.

The synergistic effect of maltose enhances the anti-melanogenic activity of acarbose.

PubMed

Bin, Bum-Ho; Kim, Sung Tae; Bhin, Jinhyuk; Byoun, Kyounghee; Lee, Tae Ryong; Cho, Eun-Gyung

2017-04-01

Melanocytes play an important role in maintaining epidermal homeostasis by producing melanin and protecting the skin from harmful environmental factors. However, excessive up- or down-regulation of melanin production often causes hyper- or hypo-pigmented disorders, respectively, which affect the patient's quality of life. Therefore, various strategies for modulating melanin levels have been developed by the pharmaceutical and cosmetic industries. We reported previously that voglibose, which is a well-known anti-hyperglycemic agent, could be used as an anti-melanogenic agent by inhibiting α-glucosidase activity and reducing tyrosinase protein levels. Of the other representative anti-hyperglycemic agents, acarbose showed less anti-melanogenic activity despite its potent anti-hyperglycemic efficacy. In this study, we report that acarbose exhibited considerable anti-melanogenic activity when melanocytes were co-treated with acarbose and a digestible sugar, such as maltose. Simultaneous treatment with maltose augmented the inhibitory effect of acarbose on α-glucosidase activity by enhancing its stability under physiological conditions, leading to the down-regulation of tyrosinase. These results suggest that the co-treatment of anti-hyperglycemic agents with hydrolysable sugars may be a useful tool for reducing glucosidase-associated melanogenesis as a potent sugar-based anti-melanogenic regimen.

Natural products and food components with anti-Helicobacter pylori activities.

PubMed

Takeuchi, Hiroaki; Trang, Vu Thu; Morimoto, Norihito; Nishida, Yoshie; Matsumura, Yoshihisa; Sugiura, Tetsuro

2014-07-21

The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world's population. H. pylori that establishes life-long infection in the stomach is definitely associated with gastro-duodenal diseases and a wide variety of non-gastrointestinal tract conditions such as immune thrombocytopenia. Triple therapy which consists of a proton pump inhibitor and combinations of two antibiotics (amoxicillin, clarithromycin or amoxicillin, metronidazol) is commonly used for H. pylori eradication. Recently, the occurrence of drug-resistant H. pylori and the adverse effect of antibiotics have severely weakened eradication therapy. Generally antibiotics induce the disturbance of human gastrointestinal microflora. Furthermore, there are inappropriate cases of triple therapy such as allergy to antibiotics, severe complications (liver and/or kidney dysfunction), the aged and people who reject the triple therapy. These prompt us to seek alterative agents instead of antibiotics and to develop more effective and safe therapy with these agents. The combination of these agents actually may result in lower a dose of antibiotics. There are many reports world-wide that non-antibiotic substances from natural products potentially have an anti-H. pylori agent. We briefly review the constituents derived from nature that fight against H. pylori in the literature with our studies.

Flexible, secure agent development framework

DOEpatents

Goldsmith,; Steven, Y [Rochester, MN

2009-04-07

While an agent generator is generating an intelligent agent, it can also evaluate the data processing platform on which it is executing, in order to assess a risk factor associated with operation of the agent generator on the data processing platform. The agent generator can retrieve from a location external to the data processing platform an open site that is configurable by the user, and load the open site into an agent substrate, thereby creating a development agent with code development capabilities. While an intelligent agent is executing a functional program on a data processing platform, it can also evaluate the data processing platform to assess a risk factor associated with performing the data processing function on the data processing platform.

[Development of a liquid fermentation system and encystment for a nitrogen-fixing bacterium strain having biofertilizer potential].

PubMed

Camelo-Rusinque, Mauricio; Moreno-Galván, Andrés; Romero-Perdomo, Felipe; Bonilla-Buitrago, Ruth

The indiscriminate use of chemical fertilizers has contributed to the deterioration of the biological, physical and chemical properties of the soil, resulting in the loss of its productive capacity. For this reason, the use of biofertilizers has emerged as a technological alternative. The objective of this research was to develop a suitable liquid fermentation system and encystment for the multiplication of Azotobacter chroococcum AC1 strain, a bacterium employed in a biofertilizer formulation produced at present by CARPOICA, Colombia. Sequential statistical designs were used to determine the conditions in the fermentation system. The interaction between agitation, aeration and pH was evaluated on the viable biomass (CFU/ml) of AC1. In addition, the encystment ability of the strain was evaluated using two encystment agents and the potential plant growth-promoting rhizobacteria (PGPR) activity was assessed by different techniques, such as nitrogen fixation by ARA, phosphate solubilization by the phospho-molybdenum-blue reaction and indolic compound production by colorimetric reaction using the Salkowski reagent. Results showed significant effects (p<0.05) on the viable biomass in the three conditions (pH, aeration and agitation) tested individually, in one dual interaction and one tripartite interaction, were demonstrated to have a positive effect on the response variable aeration and agitation. The addition of the two encystment agents evaluated, AE01 and AE02, demonstrated the ability of AC1 to form cysts under stress conditions. Likewise, fermentation and encystment conditions did not affect the biological activities tested. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Gadolinium-based magnetic resonance imaging contrast agents in interventional radiology.

PubMed

Atar, Eli

2004-07-01

Gadolinium-based agents are widely used in magnetic resonance imaging as contrast agents. These agents are radio-opaque enough for diagnostic imaging of the vascular tree by using digitally subtracted images as well as for imaging of the biliary system and the urinary tract. The recommended doses for gadolinium do not impair renal function or cause adverse reactions in patients with iodine sensitivity; thus patients with such conditions can safely undergo diagnostic angiography, either by MRI angiography or by catheterization using gadolinium as contrast agent, for diagnostic and therapeutic purposes.

The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross-linking agents and their chemotherapeutic potential.

PubMed

Su, Tsann-Long; Lee, Te-Chang; Kakadiya, Rajesh

2013-11-01

Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents in clinics. The advance in the development of these agents as potential antitumor agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order to develop highly effective anticancer agents, it is necessary to understand the chemophysical properties, structure-activity relationships, therapeutic potency, toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide more information for future drug design and strategies for combination chemotherapy. The rational drug design, chemical syntheses, antitumor activity, mechanism of action, and development of combined chemotherapy regimens, including a DNA repair inhibitor, are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

14 CFR 23.1199 - Extinguishing agent containers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... pyrotechnic capsule is used to discharge the extinguishing agent, each container must be installed so that temperature conditions will not cause hazardous deterioration of the pyrotechnic capsule. [Amdt. 23-34, 52 FR...

14 CFR 23.1199 - Extinguishing agent containers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... pyrotechnic capsule is used to discharge the extinguishing agent, each container must be installed so that temperature conditions will not cause hazardous deterioration of the pyrotechnic capsule. [Amdt. 23-34, 52 FR...

Safety Assessment of Polyether Lanolins as Used in Cosmetics.

PubMed

Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan; Heldreth, Bart

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 39 polyether lanolin ingredients as used in cosmetics. These ingredients function mostly as hair conditioning agents, skin conditioning agent-emollients, and surfactant-emulsifying agents. The Panel reviewed available animal and clinical data, from previous CIR safety assessments of related ingredients and components. The similar structure, properties, functions, and uses of these ingredients enabled grouping them and using the available toxicological data to assess the safety of the entire group. The Panel concluded that these polyether lanolin ingredients are safe in the practices of use and concentration as given in this safety assessment.

[Job stress in agents at the socio-educational service centers in the state of Rio Grande do Sul].

PubMed

Greco, Patrícia Bitencourt Toscani; Magnago, Tânia Solange Bosi de Souza; Beck, Carmem Lúcia Colomé; Urbanetto, Janete de Souza; Prochnow, Andrea

2013-03-01

The study was both to understand the association of work stress, socio-demographic and labor characteristics, habits and working conditions of the Socio-educational agents in the state of Rio Grande do Sul Brazil. It was a cross-sectional study with 881 agents of the Socio-educational Service Centers in the state of Rio Grande do Sul. The Brazilian version of the Job Stress Scale for assessment of work stress has been applied. Were classified in a situation of high strain 19.2% of the agents. The following factors were related to job stress, the need for counseling lack of leisure time, day shift work, dissatisfaction with the workplace, the need for absence from work due to health problems and insufficient scale work. There is a need to further research working conditions and execution of Occupational Health Service acting in order to minimize the effects of psychological demands at work of a socio-educational agent

Iron oxide functionalized graphene nano-composite for dispersive solid phase extraction of chemical warfare agents from aqueous samples.

PubMed

Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Goud, D Raghavender; Dubey, D K; Pardasani, Deepak

2015-05-15

Present study deals with the preparation and evaluation of graphene based magnetic nano-composite for dispersive solid phase extraction of Chemical Weapons Convention (CWC) relevant chemicals from aqueous samples. Nano-composite, Fe3O4@SiO2-G was synthesized by covalently bonding silica coated Fe3O4 onto the graphene sheets. Nerve agents (NA), Sulfur mustard (SM) and their non-toxic environmental markers were the target analytes. Extraction parameters like amount of sorbent, extraction time and desorption conditions were optimized. Dispersion of 20 milligram of sorbent in 200mL of water sample for 20min. followed by methanol/chloroform extraction produced average to good recoveries (27-94%) of targeted analytes. Recoveries of real agents exhibited great dependency upon sample pH and ionic strength. Sarin produced maximum recovery under mild acidic conditions (56% at pH 5) while VX demanded alkaline media (83% at pH 9). Salts presence in the aqueous samples was found to be advantageous, raising the recoveries to as high as 94% for SM. Excellent limits of detection (LOD) for sulphur mustard and VX (0.11ngmL(-1) and 0.19ngmL(-1) respectively) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals. Copyright © 2015 Elsevier B.V. All rights reserved.

[Ecology of vector systems: a tangle of complexity].

PubMed

Rodhain, F

2008-06-01

The long co-evolutionary process between arthropods and microorganisms has resulted in a wide variety of relationships. One such relationship involves a wide range of infectious agents (virus, bacteria, protozoa, helminthes) that use blood-feeding arthropods (insects and mites) as vectors for transmission from one vertebrate to another. Transmission involves three components, i.e., microorganism, vector(s), and vertebrate host(s). Study under natural conditions has shown that the underlying mechanisms are extremely complex with circulation of the infectious agents depending on numerous conditions linked not only to bioecology but also to genetic factors in all three component populations. The role of arthropods sometimes goes beyond that of a transmitter of disease. In some cases they also serve as reservoirs or disseminators. In addition changes in the environment whether due to natural causes or human activities (e.g. pollution, agropastoralism, urbanization, transportation network development, and climate change) can have profound and rapid effects on the mechanisms underlying these vector systems. In short the ecology of vector systems closely reflects the extreme complexity of epidemiological studies on diseases caused by infectious agents depending on this type of transmission. As a result prediction of infectious risks and planning of preventive action are difficult. It appears obvious that a good understanding of vector systems in their natural context will require a truly ecological approach to the diseases that must be the focus of extremely close epidemiologic surveillance. Achieving this goal will necessitate more than the skills of physicians and veterinarians. It will require the contribution of specialists from a variety of fields such as microbiology, entomology, systematics, climatology, ecology, urbanism, social sciences, economic development, and many others.

Multifactorial Optimization of Contrast-Enhanced Nanofocus Computed Tomography for Quantitative Analysis of Neo-Tissue Formation in Tissue Engineering Constructs.

PubMed

Sonnaert, Maarten; Kerckhofs, Greet; Papantoniou, Ioannis; Van Vlierberghe, Sandra; Boterberg, Veerle; Dubruel, Peter; Luyten, Frank P; Schrooten, Jan; Geris, Liesbet

2015-01-01

To progress the fields of tissue engineering (TE) and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells/tissue combined with scaffolds) becomes essential. In this study, we have defined the most optimal staining conditions for contrast-enhanced nanofocus computed tomography for three dimensional visualization and quantitative analysis of in vitro engineered neo-tissue (i.e. extracellular matrix containing cells) in perfusion bioreactor-developed Ti6Al4V constructs. A fractional factorial 'design of experiments' approach was used to elucidate the influence of the staining time and concentration of two contrast agents (Hexabrix and phosphotungstic acid) and the neo-tissue volume on the image contrast and dataset quality. Additionally, the neo-tissue shrinkage that was induced by phosphotungstic acid staining was quantified to determine the operating window within which this contrast agent can be accurately applied. For Hexabrix the staining concentration was the main parameter influencing image contrast and dataset quality. Using phosphotungstic acid the staining concentration had a significant influence on the image contrast while both staining concentration and neo-tissue volume had an influence on the dataset quality. The use of high concentrations of phosphotungstic acid did however introduce significant shrinkage of the neo-tissue indicating that, despite sub-optimal image contrast, low concentrations of this staining agent should be used to enable quantitative analysis. To conclude, design of experiments allowed us to define the most optimal staining conditions for contrast-enhanced nanofocus computed tomography to be used as a routine screening tool of neo-tissue formation in Ti6Al4V constructs, transforming it into a robust three dimensional quality control methodology.

Increase of chromium yield by slag reduction during production of chromium steels

NASA Astrophysics Data System (ADS)

Bažan, J.; Socha, L.; Kurka, V.; Jonšta, P.; Sušovský, M.

2017-02-01

The paper is focused on the evaluation of the course of Cr2O3 reduction from slag to alloyed steel under laboratory conditions. The experiments were aimed at the evaluation of increase in the chromium content in the melt together with the studying the behaviour of Cr2O3 and the mechanism of reduction by means of three reducing agents. Anthracite, ferrosilicon and mixtures of anthracite and ferrosilicon belong among the selected reducing agents. The experimental melts were focused on the proposal of a theoretical calculation of the consumption of selected reducing agents, study of reduction under laboratory conditions at application of alloyed steel with content of chromium of 12.16 wt. %, temperatures of 1600 °C and 1650 °C, together with the change of amount of reducing agents and reduction time. The results indicated in the paper constitute basic information on the possibilities of Cr2O3 reduction from slag; they will be used for verification of results in the pilot plant and operation experiments which will simulate operating conditions in the electric arc furnace.

The effects of crowding agents Dextran-70k and PEG-8k on actin structure and unfolding reaction

NASA Astrophysics Data System (ADS)

Gagarskaia, Iuliia A.; Povarova, Olga I.; Uversky, Vladimir N.; Kuznetsova, Irina M.; Turoverov, Konstantin K.

2017-07-01

Recently, an increasing number of studies on proteins' structure, stability and folding are trying to bring the experimental conditions closer to those existing in a living cell, namely to the conditions of macromolecular crowding. In vitro such conditions are typically imitated by the ;inert; highly water-soluble polymers with different hydrodynamic dimensions. In this work, the effects of crowded milieu on the structure and conformational stability of actin, which is a key component of the muscle contraction system, was examined. The crowded milieu was simulated by high concentrations of PEG-8k or Dextran-70k. It was revealed that both crowding agents decelerated but not inhibited actin unfolding and made a compact state of inactivated actin thermodynamically more favorable in comparison with the unfolded state. At the same time, the high viscosity of the solution of crowding agents slowed down all processes and especially inactivated actin formation, since it involves the interaction of 14-16 partially unfolded actin molecules. The effects of crowding agent were larger when its hydrodynamic dimensions were closer to the size of globular actin.

Commerce, Research and Education: Contributions and Challenges of Marine Extension Work in NOAA Sea Grant Program-Puerto Rico, Michigan and National office

NASA Astrophysics Data System (ADS)

Aleman Diaz, A.

2006-12-01

The National Sea Grant program represents NOAA's nationwide university-based program in support of coastal resource use and conservation. This program is composed of 30 university-based programs that work with local coastal communities. This study focuses on a historical and multi-sited ethnographic approach that analyzes two Sea Grant Programs and their connection to the overarching NOAA national goals from 1980- 2000.The project aims to offer insight on how the extension agent position facilitates the resolution of coastal and marine management and tourism issues. The extension agents are staff who have an extensive knowledge of available coastal resources and have the role of translating this information to coastal stakeholders. Additionally, these agents assess the needs of coastal communities and report back to the program making their role into a position that can effectively alter and/or contribute to institutional and environmental management programs at broader, cross-country and global levels. The extension programs in Michigan and Puerto Rico were examined to understand how local programs respond to cultural and regional processes shaping marine extension and the management of issues faced by coastal stakeholders. A total of 36 semi- structured in-depth interviews were completed at each site, to address the following questions: (1) How do extension agents view their role at the Puerto Rico and Michigan offices and in the Sea Grant program? How do they view the conditions of their work? (2) How do their views compare to the accomplishments by each Sea Grant administration and internal inquiries? How do their views reveal conditions documented in Puerto Rico and Michigan (e.g., social, cultural, political, economic, etc)? (3) What kind of strategies do agents develop for the management of specific coastal and tourism related projects? (4) How do the Puerto Rico and Michigan offices coordinate their work, and collaborate with other "college" programs and with the National office? Although differences based on organizational structure were evident, there were similarities regarding the marine extension work history, practices, and challenges among these local programs. Preliminary findings suggests that current challenges for Sea Grant marine extension include maintenance of non- advocacy and mediation roles among coastal stakeholders, their positioning relative to research especially conducting and delivering of science to public, and development of their multi-faceted skills sets essential to extension. Simultaneously, the Sea Grant program and marine extension agents provide comprehensive ways for integrated resource management like avenues for dialogue and information-technology transfer with bottom up approaches.

Homeopathy: clarifying its relationship to hormesis.

PubMed

Calabrese, Edward J; Jonas, Wayne B

2010-07-01

This paper presents the case that certain types of homeopathic medicine may represent a form of hormesis, that is, either pre- or post-conditioning hormesis. An example of a post-conditioning model by van Wijk and colleagues demonstrated successful enhancement of adaptive responses using below-toxic threshold doses (i.e. hormetic doses) of inducing agents when administered subsequent to a highly toxic chemical exposure, thus satisfying a basic experimental biomedical standard. Of note is that this model uses exposures within a measurable predicted hormetic range, unlike most forms of homeopathy. This experimental framework (along with a pre-conditioning model developed by Bellavite) provides a possible vehicle by which certain aspect(s) of homeopathy may be integrated into mainstream biomedical assessment and clinical practice.

Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Jang, Eunji; Han, Seungmin; Lee, Kwangyeol; Suh, Jin-Suck; Haam, Seungjoo; Huh, Yong-Min

2014-06-01

We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse.

PubMed

Peterson, Richard G; Jackson, Charles Van; Zimmerman, Karen M; Alsina-Fernandez, Jorge; Michael, M Dodson; Emmerson, Paul J; Coskun, Tamer

2017-01-01

The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances. The FATZO mouse develops obesity spontaneously when fed a normal chow diet. Glucose intolerance with increased insulin levels are apparent in FATZO mice as young as 6 weeks of age. These progress to hyperglycemia/pre-diabetes and frank diabetes with decreasing insulin levels as they age. The disease in these mice is multi-faceted, similar to the metabolic syndrome apparent in obese individuals, and thus provides a long pre-diabetic state for determining the preventive value of new interventions. We have assessed the utility of this new model for the pre-clinical screening of agents to stop or slow progression of the metabolic syndrome to severe diabetes. Our assessment included: 1) characterization of the spontaneous development of disease, 2) comparison of metabolic disturbances of FATZO mice to control mice and 3) validation of the model with regard to the effectiveness of current and emerging anti-diabetic agents; rosiglitazone, metformin and semaglutide. Male FATZO mice spontaneously develop significant metabolic disease when compared to normal controls while maintaining hyperglycemia in the presence of high leptin levels and hyperinsulinemia. The disease condition responds to commonly used antidiabetic agents.

Imagining others' handedness: visual and motor processes in the attribution of the dominant hand to an imagined agent.

PubMed

Marzoli, Daniele; Menditto, Silvia; Lucafò, Chiara; Tommasi, Luca

2013-08-01

In a previous study, we found that when required to imagine another person performing an action, participants reported a higher correspondence between their own dominant hand and the hand used by the imagined person when the agent was visualized from the back compared to when the agent was visualized from the front. This suggests a greater involvement of motor representations in the back-view perspective, possibly indicating a greater proneness to put oneself in the agent's shoes in such a condition. In order to assess whether bringing to the foreground the right or left hand of an imagined agent can foster the activation of the corresponding motor representations, we required 384 participants to imagine a person-as seen from the right or left side-performing a single manual action and to indicate the hand used by the imagined person during movement execution. The proportion of right- versus left-handed reported actions was higher in the right-view condition than in the left-view condition, suggesting that a lateral vantage point may activate the corresponding hand motor representations, which is in line with previous research indicating a link between the hemispheric specialization of one's own body and the visual representation of others' bodies. Moreover, in agreement with research on hand laterality judgments, the effect of vantage point was stronger for left-handers (who reported a higher proportion of right- than left-handed actions in the right-view condition and a slightly higher proportion of left- than right-handed actions in the left-view condition) than for right-handers (who reported a higher proportion of right- than left-handed actions in both view conditions), indicating that during the mental simulation of others' actions, right-handers rely on sensorimotor processes more than left-handers, while left-handers rely on visual processes more than right-handers.

Beyond Verb Meaning: Experimental Evidence for Incremental Processing of Semantic Roles and Event Structure.

PubMed

Philipp, Markus; Graf, Tim; Kretzschmar, Franziska; Primus, Beatrice

2017-01-01

We present an event-related potentials (ERP) study that addresses the question of how pieces of information pertaining to semantic roles and event structure interact with each other and with the verb's meaning. Specifically, our study investigates German verb-final clauses with verbs of motion such as fliegen 'fly' and schweben 'float, hover,' which are indeterminate with respect to agentivity and event structure. Agentivity was tested by manipulating the animacy of the subject noun phrase and event structure by selecting a goal adverbial, which makes the event telic, or a locative adverbial, which leads to an atelic reading. On the clause-initial subject, inanimates evoked an N400 effect vis-à-vis animates. On the adverbial phrase in the atelic (locative) condition, inanimates showed an N400 in comparison to animates. The telic (goal) condition exhibited a similar amplitude like the inanimate-atelic condition. Finally, at the verbal lexeme, the inanimate condition elicited an N400 effect against the animate condition in the telic (goal) contexts. In the atelic (locative) condition, items with animates evoked an N400 effect compared to inanimates. The combined set of findings suggest that clause-initial animacy is not sufficient for agent identification in German, which seems to be completed only at the verbal lexeme in our experiment. Here non-agents (inanimates) changing their location in a goal-directed way and agents (animates) lacking this property are dispreferred and this challenges the assumption that change of (locational) state is generally a defining characteristic of the patient role. Besides this main finding that sheds new light on role prototypicality, our data seem to indicate effects that, in our view, are related to complexity, i.e., minimality. Inanimate subjects or goal arguments increase processing costs since they have role or event structure restrictions that animate subjects or locative modifiers lack.

2014 Review on the Extension of the AMedP-8(C) Methodology to New Agents, Materials, and Conditions

DTIC Science & Technology

2015-08-01

chemical agents, five biological agents, seven radioisotopes , nuclear fallout, or prompt nuclear effects.1 Each year since 2009, OTSG has sponsored IDA...evaluated four agents: anthrax, botulinum toxin, sarin (GB), and distilled mustard (HD), first using the default parameters and methods in HPAC and...the IDA team then made incremental changes to the default casualty parameters and methods to control for all known data and methodological

Multi-agent coordination in directed moving neighbourhood random networks

NASA Astrophysics Data System (ADS)

Shang, Yi-Lun

2010-07-01

This paper considers the consensus problem of dynamical multiple agents that communicate via a directed moving neighbourhood random network. Each agent performs random walk on a weighted directed network. Agents interact with each other through random unidirectional information flow when they coincide in the underlying network at a given instant. For such a framework, we present sufficient conditions for almost sure asymptotic consensus. Numerical examples are taken to show the effectiveness of the obtained results.

Physical agents used in the management of chronic pain by physical therapists.

PubMed

Allen, Roger J

2006-05-01

Evidence supporting the use of specific physical agents in the management of chronic pain conditions is not definitive; it is largely incomplete and sometimes contradictory. However, the use of agents in chronic pain management programs is common. Within the broad use of physical agents, they are rarely the sole modality of treatment. A 1995 American Physical Therapy Association position statement asserts that "Without documentation which justifies the necessity of the exclusive use of physical agents/modalities, the use of physical agents/modalities, in the absence of other skilled therapeutic or educational intervention, should not be considered physical therapy". Physical agents may serve as useful adjunctive modalities of pain relief or to enhance the effectiveness of other elements in therapy geared toward resolution of movement impairments and restoration of physical function. Given that a conclusive aggregate of findings is unlikely to exist for all permutations of patient conditions, combined with interacting therapeutic modalities, an evidence-based approach to pain management is not always possible or beneficial to the patient. In the face of inconclusive evidence, a theory-based approach may help determine if the therapeutic effect ofa given physical agent has the possibility of being a useful clinical tool in the context of treating a particular patient's mechanism of pain generation. Until controlled efficacy findings are definitive, careful individual patient response monitoring of thoughtful theoretical application of adjunctive physical agents may be a prudent approach to the management of chronic pain.

Epigenetic Modifications in Essential Hypertension

PubMed Central

Wise, Ingrid A.; Charchar, Fadi J.

2016-01-01

Essential hypertension (EH) is a complex, polygenic condition with no single causative agent. Despite advances in our understanding of the pathophysiology of EH, hypertension remains one of the world’s leading public health problems. Furthermore, there is increasing evidence that epigenetic modifications are as important as genetic predisposition in the development of EH. Indeed, a complex and interactive genetic and environmental system exists to determine an individual’s risk of EH. Epigenetics refers to all heritable changes to the regulation of gene expression as well as chromatin remodelling, without involvement of nucleotide sequence changes. Epigenetic modification is recognized as an essential process in biology, but is now being investigated for its role in the development of specific pathologic conditions, including EH. Epigenetic research will provide insights into the pathogenesis of blood pressure regulation that cannot be explained by classic Mendelian inheritance. This review concentrates on epigenetic modifications to DNA structure, including the influence of non-coding RNAs on hypertension development. PMID:27023534

Acute and Long-Term Impact of Chemical Weapons: Lessons from the Iran-Iraq War.

PubMed

Haines, D D; Fox, S C

2014-07-01

Chemical weapons have given the human experience of warfare a uniquely terrifying quality that has inspired a general repugnance and led to periodic attempts to ban their use. Nevertheless, since ancient times, toxic agents have been consistently employed to kill and terrorize target populations. The evolution of these weapons is examined here in ways that may allow military, law enforcement, and scientific professionals to gain a perspective on conditions that, in the past, have motivated their use - both criminally and as a matter of national policy during military campaigns. Special emphasis is placed on the genocidal use of chemical weapons by the regime of Saddam Hussein, both against Iranians and on Kurdish citizens of his own country, during the Iran-Iraq War of 1980-88. The historical development of chemical weapons use is summarized to show how progressively better insight into biochemistry and physiology was adapted to this form of warfare. Major attributes of the most frequently used chemical agents and a description of how they affected military campaigns are explained. Portions of this review describing chemical-casualty care devote particular focus to Iranian management of neurotoxic (nerve) agent casualties due to the unique nature of this experience. Both nerve and blistering "mustard" agents were used extensively against Iranian forces. However, Iran is the only nation in history to have sustained large-scale attacks with neurotoxic weapons. For this reason, an understanding of the successes and failures of countermeasures to nerve-agent use developed by the Iranian military are particularly valuable for future civil defense and military planning. A detailed consideration of these strategies is therefore considered. Finally, the outcomes of clinical research into severe chronic disease triggered by mustard-agent exposure are examined in the context of the potential of these outcomes to determine the etiology of illness among US and Allied veterans of the 1991 Persian Gulf War. Copyright © 2014 Central Police University.

Recent Trends in Soft Tissue Infection Imaging

PubMed Central

Petruzzi, Nicholas; Shanthly, Nylla; Thakur, Mathew

2009-01-01

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, CNS, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of 18F-FDG PET and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to monitor the therapeutic response in a variety of conditions. Current studies suggest PET should be considered the most accurate quantitative method. Scintigraphy has much to offer in localizing abdominal infection as well as inflammation. We may begin to see a gradual increase in the usage of FDG PET in detecting occult abdominal infections. Commonly used modalities for imaging inflammatory bowel disease are scintigraphy with 111In-oxine/99mTc-HMPAO labeled autologous white blood cells. The literature on CNS infection imaging is relatively scarce. Few clinical studies have been performed and numerous new agents have been developed for this use with varying results. Further studies are needed to more clearly delineate the future direction of this field. In evaluating the post-operative spine, 99mTc-ciprofloxacin SPECT was reported to be >80% sensitive in patients more than 6 months post-surgery. FDG PET has also been suggested for this purpose and may play a larger role than originally thought. It appears PET/CT is gaining support, especially in imaging those with fever of unknown origin or nonfunctional immune systems. While an infection specific agent is lacking, the development of one would greatly advance our ability to detect, localize, and quantify infections. Overall, imaging such an agent via SPECT/CT or PET/CT will pave the way for greater clinical reliability in the localization of infection. PMID:19187804

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents.

PubMed

Choi, Chang-Ik

2016-08-27

Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.

Most recent developments in strategies to reduce the progression of structural changes in osteoarthritis: today and tomorrow

PubMed Central

Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Raynauld, Jean-Pierre

2006-01-01

Osteoarthritis (OA), the most common of all arthritic conditions, is a social and financial burden to all nations. The most recent research has significantly advanced our understanding of the cause of OA and risk factors associated with it. These findings have provided useful information that has helped in the daily management of patients with OA. Some preventative measures and a number of therapeutic agents and drugs are available, which may help to reduce the progression of OA in certain patients. Moreover, the most recent progress in research has significantly enhanced our knowledge of the factors involved in the development of the disease and of the mechanisms responsible for its progression. This has allowed identification of several new therapeutic targets in a number of pathophysiological pathways. Consequently, the field is opening up to a new era in which drugs and agents that can specifically block important mechanisms responsible for the structural changes that occur in OA can be brought into development and eventually into clinical trials. PMID:16569256

INNOVATIVE MIOR PROCESS UTILIZING INDIGENOUS RESERVOIR CONSTITUENTS

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

D.O. Hitzman; S.A. Bailey

This research program is directed at improving the knowledge of reservoir ecology and developing practical microbial solutions for improving oil production. The goal is to identify indigenous microbial populations which can produce beneficial metabolic products and develop a methodology to stimulate those select microbes with inorganic nutrient amendments to increase oil recovery.This microbial technology has the capability of producing multiple oil releasing agents. The potential of the system will be illustrated and demonstrated by the example of biopolymer production on oil recovery. Research has begun on the program and experimental laboratory work is underway. Polymer-producing cultures have been isolated frommore » produced water samples and initially characterized. Concurrently, a microcosm scale sand-packed column has been designed and developed for testing cultures of interest, including polymer-producing strains. In research that is planned to begin in future work, comparative laboratory studies demonstrating in situ production of microbial products as oil recovery agents will be conducted in sand pack and cores with synthetic and natural field waters at concentrations, flooding rates, and with cultures and conditions representative of oil reservoirs.« less

Instrument response measurements of ion mobility spectrometers in situ: maintaining optimal system performance of fielded systems

NASA Astrophysics Data System (ADS)

Wallis, Eric; Griffin, Todd M.; Popkie, Norm, Jr.; Eagan, Michael A.; McAtee, Robert F.; Vrazel, Danet; McKinly, Jim

2005-05-01

Ion Mobility Spectroscopy (IMS) is the most widespread detection technique in use by the military for the detection of chemical warfare agents, explosives, and other threat agents. Moreover, its role in homeland security and force protection has expanded due, in part, to its good sensitivity, low power, lightweight, and reasonable cost. With the increased use of IMS systems as continuous monitors, it becomes necessary to develop tools and methodologies to ensure optimal performance over a wide range of conditions and extended periods of time. Namely, instrument calibration is needed to ensure proper sensitivity and to correct for matrix or environmental effects. We have developed methodologies to deal with the semi-quantitative nature of IMS and allow us to generate response curves that allow a gauge of instrument performance and maintenance requirements. This instrumentation communicates to the IMS systems via a software interface that was developed in-house. The software measures system response, logs information to a database, and generates the response curves. This paper will discuss the instrumentation, software, data collected, and initial results from fielded systems.

Needs, Pains, and Motivations in Autonomous Agents.

PubMed

Starzyk, Janusz A; Graham, James; Puzio, Leszek

This paper presents the development of a motivated learning (ML) agent with symbolic I/O. Our earlier work on the ML agent was enhanced, giving it autonomy for interaction with other agents. Specifically, we equipped the agent with drives and pains that establish its motivations to learn how to respond to desired and undesired events and create related abstract goals. The purpose of this paper is to explore the autonomous development of motivations and memory in agents within a simulated environment. The ML agent has been implemented in a virtual environment created within the NeoAxis game engine. Additionally, to illustrate the benefits of an ML-based agent, we compared the performance of our algorithm against various reinforcement learning (RL) algorithms in a dynamic test scenario, and demonstrated that our ML agent learns better than any of the tested RL agents.This paper presents the development of a motivated learning (ML) agent with symbolic I/O. Our earlier work on the ML agent was enhanced, giving it autonomy for interaction with other agents. Specifically, we equipped the agent with drives and pains that establish its motivations to learn how to respond to desired and undesired events and create related abstract goals. The purpose of this paper is to explore the autonomous development of motivations and memory in agents within a simulated environment. The ML agent has been implemented in a virtual environment created within the NeoAxis game engine. Additionally, to illustrate the benefits of an ML-based agent, we compared the performance of our algorithm against various reinforcement learning (RL) algorithms in a dynamic test scenario, and demonstrated that our ML agent learns better than any of the tested RL agents.

The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

PubMed

Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

2014-08-21

Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response slows down as the tumor shrinks due to the heterogeneity and low concentration of agents in the tumor interior compared with the cases where other pathological effects may combine to flatten the IFP and thus reduce the heterogeneity. We conclude that dual normalizations of the micronevironment - both the vasculature and the interstitium - are needed to maximize the effects of chemotherapy, while normalization of only one of these may be insufficient to overcome the physical resistance and may thus lead to sub-optimal outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems

PubMed Central

Wu, Min; Frieboes, Hermann B.; Chaplain, Mark A.J.; McDougall, Steven R.; Cristini, Vittorio; Lowengrub, John

2014-01-01

Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but leads to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response slows down as the tumor shrinks due to the heterogeneity and low concentration of agents in the tumor interior compared with the cases where other pathological effects may combine to flatten the IFP and thus reduce the heterogeneity. We conclude that dual normalizations of the micronevironment - both the vasculature and the interstitium - are needed to maximize the effects of chemotherapy, while normalization of only one of these may be insufficient to overcome the physical resistance and thus leads to sub-optimal outcomes. PMID:24751927

ISS method for coordination control of nonlinear dynamical agents under directed topology.

PubMed

Wang, Xiangke; Qin, Jiahu; Yu, Changbin

2014-10-01

The problems of coordination of multiagent systems with second-order locally Lipschitz continuous nonlinear dynamics under directed interaction topology are investigated in this paper. A completely nonlinear input-to-state stability (ISS)-based framework, drawing on ISS methods, with the aid of results from graph theory, matrix theory, and the ISS cyclic-small-gain theorem, is proposed for the coordination problem under directed topology, which can effectively tackle the technical challenges caused by locally Lipschitz continuous dynamics. Two coordination problems, i.e., flocking with a virtual leader and containment control, are considered. For both problems, it is assumed that only a portion of the agents can obtain the information from the leader(s). For the first problem, the proposed strategy is shown effective in driving a group of nonlinear dynamical agents reach the prespecified geometric pattern under the condition that at least one agent in each strongly connected component of the information-interconnection digraph with zero in-degree has access to the state information of the virtual leader; and the strategy proposed for the second problem can guarantee the nonlinear dynamical agents moving to the convex hull spanned by the positions of multiple leaders under the condition that for each agent there exists at least one leader that has a directed path to this agent.

An Inverse Analysis Approach to the Characterization of Chemical Transport in Paints

PubMed Central

Willis, Matthew P.; Stevenson, Shawn M.; Pearl, Thomas P.; Mantooth, Brent A.

2014-01-01

The ability to directly characterize chemical transport and interactions that occur within a material (i.e., subsurface dynamics) is a vital component in understanding contaminant mass transport and the ability to decontaminate materials. If a material is contaminated, over time, the transport of highly toxic chemicals (such as chemical warfare agent species) out of the material can result in vapor exposure or transfer to the skin, which can result in percutaneous exposure to personnel who interact with the material. Due to the high toxicity of chemical warfare agents, the release of trace chemical quantities is of significant concern. Mapping subsurface concentration distribution and transport characteristics of absorbed agents enables exposure hazards to be assessed in untested conditions. Furthermore, these tools can be used to characterize subsurface reaction dynamics to ultimately design improved decontaminants or decontamination procedures. To achieve this goal, an inverse analysis mass transport modeling approach was developed that utilizes time-resolved mass spectroscopy measurements of vapor emission from contaminated paint coatings as the input parameter for calculation of subsurface concentration profiles. Details are provided on sample preparation, including contaminant and material handling, the application of mass spectrometry for the measurement of emitted contaminant vapor, and the implementation of inverse analysis using a physics-based diffusion model to determine transport properties of live chemical warfare agents including distilled mustard (HD) and the nerve agent VX. PMID:25226346

Global adaptation in networks of selfish components: emergent associative memory at the system scale.

PubMed

Watson, Richard A; Mills, Rob; Buckley, C L

2011-01-01

In some circumstances complex adaptive systems composed of numerous self-interested agents can self-organize into structures that enhance global adaptation, efficiency, or function. However, the general conditions for such an outcome are poorly understood and present a fundamental open question for domains as varied as ecology, sociology, economics, organismic biology, and technological infrastructure design. In contrast, sufficient conditions for artificial neural networks to form structures that perform collective computational processes such as associative memory/recall, classification, generalization, and optimization are well understood. Such global functions within a single agent or organism are not wholly surprising, since the mechanisms (e.g., Hebbian learning) that create these neural organizations may be selected for this purpose; but agents in a multi-agent system have no obvious reason to adhere to such a structuring protocol or produce such global behaviors when acting from individual self-interest. However, Hebbian learning is actually a very simple and fully distributed habituation or positive feedback principle. Here we show that when self-interested agents can modify how they are affected by other agents (e.g., when they can influence which other agents they interact with), then, in adapting these inter-agent relationships to maximize their own utility, they will necessarily alter them in a manner homologous with Hebbian learning. Multi-agent systems with adaptable relationships will thereby exhibit the same system-level behaviors as neural networks under Hebbian learning. For example, improved global efficiency in multi-agent systems can be explained by the inherent ability of associative memory to generalize by idealizing stored patterns and/or creating new combinations of subpatterns. Thus distributed multi-agent systems can spontaneously exhibit adaptive global behaviors in the same sense, and by the same mechanism, as with the organizational principles familiar in connectionist models of organismic learning.

Radiolabeling of a cyclic RGD (cyclo Arg-Gly-Asp-d-Tyr-Lys) peptide using sodium hypochlorite as an oxidizing agent.

PubMed

Doll, Stephanie; Woolum, Karen; Kumar, Krishan

2016-09-01

A simple and rapid nonradioactive iodide labeling/radiolabeling method for peptides, using an inexpensive oxidizing agent such as sodium hypochlorite and a cyclic peptide, cRGDyK (cyclo Arg-Gly-Asp-d-Tyr-Lys), was developed in this work. Labeling reaction was optimized by conducting experiments under variable ratios of the reagents, the reaction times, and the pH. The study demonstrated that radiolabeling of the cyclic peptide was fast and pH independent. Monoiodinated and di-iodinated cRGDyK were formed under all conditions and varied with the ratio of the reagents and the reaction time. Total percent of the iodinated cRGDyK (monoiodinated and di-iodinated cRGDyK) varied between 44 and 100 depending on the reaction conditions. Excess cyclic peptide over equal molar ratio of sodium iodide and sodium hypochlorite yielded in predominant amounts of monoiodinated cRGDyK, ie, >60% under 2:1:1 ratio and ~88% under 5:1:1 ratio of cRGDyK:sodium iodide:sodium hypochlorite. Copyright © 2016 John Wiley & Sons, Ltd.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

PubMed Central

Maselli, Diego J.; Keyt, Holly; Restrepo, Marcos I.

2017-01-01

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases. PMID:28509852

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.

PubMed

Maselli, Diego J; Keyt, Holly; Restrepo, Marcos I

2017-05-16

The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa , Methicillin-resistant Staphylococcus aureus , Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease

PubMed Central

Godlewska, Urszula; Brzoza, Piotr; Sroka, Aneta; Majewski, Pawel; Jentsch, Holger; Eckert, Martin; Eick, Sigrun; Potempa, Jan; Zabel, Brian A.; Cichy, Joanna

2017-01-01

Periodontal inflammation is one of the most common chronic inflammatory conditions in humans. Despite recent advances in identifying and characterizing oral microbiota dysbiosis in the pathogenesis of gum disease, just how host factors maintain a healthy homeostatic oral microbial community or prevent the development of a pathogenic oral microbiota remains poorly understood. An important determinant of microbiota fate is local antimicrobial proteins. Here, we report that chemoattractant protein chemerin, which we recently identified as a potent endogenous antimicrobial agent in body barriers such as the skin, is present in the oral cavity under homeostatic and inflammatory conditions. Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against select bacteria strategically positioned in dental biofilm. Gingival crevicular samples from patients with gingivitis but not periodontitis contain abundant bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration. Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin. Together, these data suggest that as an antimicrobial agent and leukocyte chemoattractant, chemerin likely contributes to antimicrobial immune defense in the oral cavity. PMID:28424689

Triggered pore-forming agents

DOEpatents

Bayley, Hagan; Walker, Barbara J.; Chang, Chung-yu; Niblack, Brett; Panchal, Rekha

1998-01-01

An inactive pore-forming agent which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell.

[New era in antiplatelet therapy based on results from recent clinical trials].

PubMed

Páramo, José Antonio

2011-10-22

Antiplatelet therapy has been successful in reducing mortality and morbidity in cardiovascular diseases (e.g. acute coronary syndromes). Recent advances in understanding the molecular basis of the role of platelets in atherothrombosis have enabled the development of new agents with the potential to further reduce mortality and morbidity. Some limitations associated with the use of aspirin and clopidogrel have led to potential alternatives, including more potent ADP antagonists such as prasugrel, ticagrelor, cangrelor, and thrombin receptor antagonists, which have shown additional benefit in large randomized controlled trials. These new agents open a realistic prospect of a personalized choice of the most appropriate antiplatelet therapy tailored for an individual patient and a clinical condition. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Information-driven trade and price-volume relationship in artificial stock markets

NASA Astrophysics Data System (ADS)

Liu, Xinghua; Liu, Xin; Liang, Xiaobei

2015-07-01

The positive relation between stock price changes and trading volume (price-volume relationship) as a stylized fact has attracted significant interest among finance researchers and investment practitioners. However, until now, consensus has not been reached regarding the causes of the relationship based on real market data because extracting valuable variables (such as information-driven trade volume) from real data is difficult. This lack of general consensus motivates us to develop a simple agent-based computational artificial stock market where extracting the necessary variables is easy. Based on this model and its artificial data, our tests have found that the aggressive trading style of informed agents can produce a price-volume relationship. Therefore, the information spreading process is not a necessary condition for producing price-volume relationship.

Cellular growth in plants requires regulation of cell wall biochemistry.

PubMed

Chebli, Youssef; Geitmann, Anja

2017-02-01

Cell and organ morphogenesis in plants are regulated by the chemical structure and mechanical properties of the extracellular matrix, the cell wall. The two primary load bearing components in the plant cell wall, the pectin matrix and the cellulose/xyloglucan network, are constantly remodelled to generate the morphological changes required during plant development. This remodelling is regulated by a plethora of loosening and stiffening agents such as pectin methyl-esterases, calcium ions, expansins, and glucanases. The tight spatio-temporal regulation of the activities of these agents is a sine qua non condition for proper morphogenesis at cell and tissue levels. The pectin matrix and the cellulose-xyloglucan network operate in concert and their behaviour is mutually dependent on their chemical, structural and mechanical modifications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Developing Dynamic Field Theory Architectures for Embodied Cognitive Systems with cedar.

PubMed

Lomp, Oliver; Richter, Mathis; Zibner, Stephan K U; Schöner, Gregor

2016-01-01

Embodied artificial cognitive systems, such as autonomous robots or intelligent observers, connect cognitive processes to sensory and effector systems in real time. Prime candidates for such embodied intelligence are neurally inspired architectures. While components such as forward neural networks are well established, designing pervasively autonomous neural architectures remains a challenge. This includes the problem of tuning the parameters of such architectures so that they deliver specified functionality under variable environmental conditions and retain these functions as the architectures are expanded. The scaling and autonomy problems are solved, in part, by dynamic field theory (DFT), a theoretical framework for the neural grounding of sensorimotor and cognitive processes. In this paper, we address how to efficiently build DFT architectures that control embodied agents and how to tune their parameters so that the desired cognitive functions emerge while such agents are situated in real environments. In DFT architectures, dynamic neural fields or nodes are assigned dynamic regimes, that is, attractor states and their instabilities, from which cognitive function emerges. Tuning thus amounts to determining values of the dynamic parameters for which the components of a DFT architecture are in the specified dynamic regime under the appropriate environmental conditions. The process of tuning is facilitated by the software framework cedar , which provides a graphical interface to build and execute DFT architectures. It enables to change dynamic parameters online and visualize the activation states of any component while the agent is receiving sensory inputs in real time. Using a simple example, we take the reader through the workflow of conceiving of DFT architectures, implementing them on embodied agents, tuning their parameters, and assessing performance while the system is coupled to real sensory inputs.

Developing Dynamic Field Theory Architectures for Embodied Cognitive Systems with cedar

PubMed Central

Lomp, Oliver; Richter, Mathis; Zibner, Stephan K. U.; Schöner, Gregor

2016-01-01

Embodied artificial cognitive systems, such as autonomous robots or intelligent observers, connect cognitive processes to sensory and effector systems in real time. Prime candidates for such embodied intelligence are neurally inspired architectures. While components such as forward neural networks are well established, designing pervasively autonomous neural architectures remains a challenge. This includes the problem of tuning the parameters of such architectures so that they deliver specified functionality under variable environmental conditions and retain these functions as the architectures are expanded. The scaling and autonomy problems are solved, in part, by dynamic field theory (DFT), a theoretical framework for the neural grounding of sensorimotor and cognitive processes. In this paper, we address how to efficiently build DFT architectures that control embodied agents and how to tune their parameters so that the desired cognitive functions emerge while such agents are situated in real environments. In DFT architectures, dynamic neural fields or nodes are assigned dynamic regimes, that is, attractor states and their instabilities, from which cognitive function emerges. Tuning thus amounts to determining values of the dynamic parameters for which the components of a DFT architecture are in the specified dynamic regime under the appropriate environmental conditions. The process of tuning is facilitated by the software framework cedar, which provides a graphical interface to build and execute DFT architectures. It enables to change dynamic parameters online and visualize the activation states of any component while the agent is receiving sensory inputs in real time. Using a simple example, we take the reader through the workflow of conceiving of DFT architectures, implementing them on embodied agents, tuning their parameters, and assessing performance while the system is coupled to real sensory inputs. PMID:27853431

Nanoparticle dispersion in environmentally relevant culture media: a TiO2 case study and considerations for a general approach

NASA Astrophysics Data System (ADS)

Horst, Allison M.; Ji, Zhaoxia; Holden, Patricia A.

2012-08-01

Nanoparticle exposure in toxicity studies requires that nanoparticles are bioavailable by remaining highly dispersed in culture media. However, reported dispersion approaches are variable, mostly study-specific, and not transferable owing to their empirical basis. Furthermore, many published approaches employ proteinaceous dispersants in rich laboratory media, both of which represent end members in environmental scenarios. Here, a systematic approach was developed to disperse initially agglomerated TiO2 nanoparticles (Aeroxide® TiO2 P25, Evonik, NJ; primary particle size range 6.4-73.8 nm) in oligotrophic culture medium for environmentally relevant bacterial toxicity studies. Based on understanding particle-particle interactions in aqueous media and maintaining environmental relevance, the approach involves (1) quantifying the relationship between pH and zeta potential to determine the point of zero charge of select nanoparticles in water; (2) nominating, then testing and selecting, environmentally relevant stabilizing agents; and (3) dispersing via "condition and capture" whereby stock dry powder nanoparticles are sonicated in pre-conditioned (with base, or acid, plus stabilizing agent) water, then diluted into culture media. The "condition and capture" principle is transferable to other nanoparticle and media chemistries: simultaneously, mechanically and electrostatically, nanoparticles can be dispersed with surrounding stabilizers that coat and sterically hinder reagglomeration in the culture medium.

Planning guidance for the Chemical Stockpile Emergency Preparedness Program

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

Shumpert, B.L.; Watson, A.P.; Sorensen, J.H.

1995-02-01

This planning guide was developed under the direction of the U.S. Army and the Federal Emergency Management Agency (FEMA) which jointly coordinate and direct the development of the Chemical Stockpile Emergency Preparedness Program (CSEPP). It was produced to assist state, local, and Army installation planners in formulating and coordinating plans for chemical events that may occur at the chemical agent stockpile storage locations in the continental United States. This document provides broad planning guidance for use by both on-post and off-post agencies and organizations in the development of a coordinated plan for responding to chemical events. It contains checklists tomore » assist in assuring that all important aspects are included in the plans and procedures developed at each Chemical Stockpile Disposal Program (CSDP) location. The checklists are supplemented by planning guidelines in the appendices which provide more detailed guidance regarding some issues. The planning guidance contained in this document will help ensure that adequate coordination between on-post and off-post planners occurs during the planning process. This planning guide broadly describes an adequate emergency planning base that assures that critical planning decisions will be made consistently at every chemical agent stockpile location. This planning guide includes material drawn from other documents developed by the FEMA, the Army, and other federal agencies with emergency preparedness program responsibilities. Some of this material has been developed specifically to meet the unique requirements of the CSEPP. In addition to this guidance, other location-specific documents, technical studies, and support studies should be used as needed to assist in the planning at each of the chemical agent stockpile locations to address the specific hazards and conditions at each location.« less

Nanomaterials for miRNA delivery and non-invasive imaging in cardiovascular regeneration

NASA Astrophysics Data System (ADS)

Gomes, Renata Sofia Mota

The development of noninvasive platforms to assess cell fate after transplantation is of utmost importance in the context of Regenerative Medicine. Magnetic Resonance Imaging (MRI) is a powerful non-invasive imaging platform, heavily relying on the use of contrast agents, mostly nanoparticles (NPs). Gadolinium (Gd) and Superparamagnetic Iron Oxide (SPIO) NPs are contrast agents in clinical use, however these agents may cause liver toxicity, give rise to image artifacts in MRI, and typically have not been used as a drug delivery system. In this work, we developed a novel NP formulation containing fluorine to overcome the previous limitations. The NPs are based on poly(lactic-co-glycolic acid) (PLGA) which is a biocompatible and versatile polymer approved for human use . PLGA NPs containing fluorine were developed to label and track cells overtime and as vectors for microRNA (miR) delivery, which improves cell survival in hypoxic conditions. Herein we show that the fluorine-based NPs are a reliable approach to track non-invasively cells with clinical relevance (endothelial cells and cord-blood derived mononuclear cells) and simultaneously control the intracellular delivery of pro-survival and pro-angiogenic miRs. Also systems for in vitro and in vivo imaging via MRI of fluorine are developed and here explained. Furthermore in vivo studies are performed which show the therapeutic uses of such system. Additionally we also address the optimization of protocols for stem cell culture which may enhance proliferation and promote pluripotency in cardiac stem cells (CSCs) so as we can fully explore the potential of these cells in vivo using out novel theranostic NPs platform. We are the first authors developing and relating these novel developments.

Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing

PubMed Central

O'Collins, Victoria E; Macleod, Malcolm R; Cox, Susan F; Van Raay, Leena; Aleksoska, Elena; Donnan, Geoffrey A; Howells, David W

2011-01-01

There is some evidence that in animal models of acute ischaemic stroke, combinations of neuroprotective agents might be more efficacious than the same agents administered alone. Hence, we developed pragmatic, empirical criteria based on therapeutic target, cost, availability, efficacy, administration, and safety to select drugs for testing in combination in animal models of acute stroke. Magnesium sulphate, melatonin, and minocycline were chosen from a library of neuroprotective agents, and were tested in a more ‘realistic' model favoured by the STAIR (Stroke Therapy Academic Industry Roundtable). Outcome was assessed with infarct volume, neurologic score, and two newly developed scales measuring general health and physiologic homeostasis. Owing to the failure to achieve neuroprotection in aged, hypertensive animals with drug delivery at 3 hours, the bar was lowered in successive experiments to determine whether neuroprotection could be achieved under conditions more conducive to recovery. Testing in younger animals showed more favourable homeostasis and general health scores than did testing in older animals, but infarct volume and neurologic scores did not differ with age, and treatment efficacy was again not shown. Testing with shorter occlusions resulted in smaller infarct volumes; nevertheless, treatment efficacy was still not observed. It was concluded that this combination, in these stroke models, was not effective. PMID:20978519

An Agent-Based Model for Analyzing Control Policies and the Dynamic Service-Time Performance of a Capacity-Constrained Air Traffic Management Facility

NASA Technical Reports Server (NTRS)

Conway, Sheila R.

2006-01-01

Simple agent-based models may be useful for investigating air traffic control strategies as a precursory screening for more costly, higher fidelity simulation. Of concern is the ability of the models to capture the essence of the system and provide insight into system behavior in a timely manner and without breaking the bank. The method is put to the test with the development of a model to address situations where capacity is overburdened and potential for propagation of the resultant delay though later flights is possible via flight dependencies. The resultant model includes primitive representations of principal air traffic system attributes, namely system capacity, demand, airline schedules and strategy, and aircraft capability. It affords a venue to explore their interdependence in a time-dependent, dynamic system simulation. The scope of the research question and the carefully-chosen modeling fidelity did allow for the development of an agent-based model in short order. The model predicted non-linear behavior given certain initial conditions and system control strategies. Additionally, a combination of the model and dimensionless techniques borrowed from fluid systems was demonstrated that can predict the system s dynamic behavior across a wide range of parametric settings.

Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

PubMed Central

Zhou, Jiehua; Rossi, John J.

2014-01-01

One hundred years ago, Dr. Paul Ehrlich popularized the “magic bullet” concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, “targeted therapy” that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges. PMID:24936916

Combinations of biocontrol agents for management of plant-parasitic nematodes and soilborne plant-pathogenic fungi.

PubMed

Meyer, Susan L F; Roberts, Daniel P

2002-03-01

Numerous microbes are antagonistic to plant-parasitic nematodes and soilborne plant-pathogenic fungi, but few of these organisms are commercially available for management of these pathogens. Inconsistent performance of applied biocontrol agents has proven to be a primary obstacle to the development of successful commercial products. One of the strategies for overcoming inconsistent performance is to combine the disease-suppressive activity of two (or more) beneficial microbes in a biocontrol preparation. Such combinations have potential for more extensive colonization of the rhizosphere, more consistent expression of beneficial traits under a broad range of soil conditions, and antagonism to a larger number of plant pests or pathogens than strains applied individually. Conversely, microbes applied in combination also may have antagonistic interactions with each other. Increased, decreased, and unaltered suppression of the target pathogen or pest has been observed when biocontrol microbes have been applied in combination. Unfortunately, the ecological basis for increased or decreased suppression has not been determined in many cases and needs further consideration. The complexity of interactions involved in the application of multiple organisms for biological control has slowed progress toward development of successful formulations. However, this approach has potential for overcoming some of the efficacy problems that occur with application of individual biocontrol agents.

Spacecraft sanitation agent development

NASA Technical Reports Server (NTRS)

1972-01-01

The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

TACtic- A Multi Behavioral Agent for Trading Agent Competition

NASA Astrophysics Data System (ADS)

Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

The potential of a fluorescent-based approach for bioassay of antifungal agents against chili anthracnose disease in Thailand.

PubMed

Chutrakul, Chanikul; Khaokhajorn, Pratoomporn; Auncharoen, Patchanee; Boonruengprapa, Tanapong; Mongkolporn, Orarat

2013-01-01

Severe chili anthracnose disease in Thailand is caused by Colletotrichum gloeosporioides and C. capsici. To discover anti-anthracnose substances we developed an efficient dual-fluorescent labeling bioassay based on a microdilution approach. Indicator strains used in the assay were constructed by integrating synthetic green fluorescent protein (sGFP) and Discosoma sp. red fluorescent protein (DsRedExp) genes into the genomes of C. gloeosporioides or C. capsici respectively. Survival of co-spore cultures in the presence of inhibitors was determined by the expression levels of these fluorescent proteins. This developed assay has high potential for utilization in the investigation of selective inhibition activity to either one of the pathogens as well as the broad-range inhibitory effect against both pathogens. The value of using the dual-fluorescent assay is rapid, reliable, and consistent identification of anti-anthracnose agents. Most of all, the assay enables the identification of specific inhibitors under the co-cultivation condition.

15th International Conference on Human Antibodies and Hybridomas. 14-16 April 2010, Tiara Park Atlantico Hotel, Porto, Portugal.

PubMed

Kotlan, Beatrix

2010-11-01

Antibodies and antibody conjugates are currently one of the largest classes of new drug entities under development. These versatile molecules are being investigated for the treatment of many pathological conditions, such as cancer and infectious, inflammatory and autoimmune diseases. Antibodies can exert biological effects as naked antibodies by themselves, or can be used as delivery agents conjugated with various drugs (e.g., immunoconjugates) and as tools of multistep targeting. Site-specific delivery of therapeutic agents has been the ultimate goal of the pharmaceutical industry, as it has the potential to maximize drug efficiency while minimizing side effects. Antibodies have much potential for this objective. Thus, it is useful to summarize some of the main strategies currently being employed for the development of these diverse therapeutic molecules and to highlight the recent novelties in the field. These goals were the focus of the 15th International Conference on Human Antibodies and Hybridomas, held during 14-16 April 2010 in Porto, Portugal.

Anthelmintic efficacy of cinnamaldehyde and cinnamic acid from cortex cinnamon essential oil against Dactylogyrus intermedius.

PubMed

Ling, Fei; Jiang, Chao; Liu, Guanglu; Li, Mingshuang; Wang, Gaoxue

2015-12-01

Utilization of chemical pesticide to control monogenean diseases is often restricted in many countries due to the development of pesticide resistance and concerns of chemical residues and environmental contamination. Thus, the use of antiparasitic agents from plants has been explored as a possible way for controlling monogenean infections. Extracts from Cinnamomum cassia were investigated under in vivo conditions against Dactylogyrus intermedius in goldfish. The two bioactive compounds, cinnamaldehyde and cinnamic acid, were identified using nuclear magnetic resonance and electrospray ionization mass spectrometry. The 48 h median effective concentrations (EC(50)) for these compounds against D. intermedius were 0·57 and 6·32 mg L(-1), respectively. The LD(50) of cinnamaldehyde and cinnamic acid were 13·34 and 59·66 mg L(-1) to goldfish in 48 h acute toxicity tests, respectively. These data confirm that cinnamaldehyde is effective against D. intermedius, and the cinnamaldehyde exhibits potential for the development of a candidate antiparasitic agent.

Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

PubMed

Uthaman, Saji; Bom, Joon-suk; Kim, Hyeon Sik; John, Johnson V; Bom, Hee-Seung; Kim, Seon-Jong; Min, Jung-Joon; Kim, Il; Park, In-Kyu

2016-05-01

Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI. © 2016 Wiley Periodicals, Inc.

Engaging Experts: Science-Policy Interactions and the Introduction of Congestion Charging in Stockholm.

PubMed

Broström, Anders; McKelvey, Maureen

2018-01-01

This article analyzes the conditions for mobilizing the science base for development of public policy. It does so by focusing upon the science-policy interface, specifically the processes of direct interaction between scientists and scientifically trained experts, on the one hand, and agents of policymaking organizations, on the other. The article defines two dimensions - cognitive distance and expert autonomy - which are argued to influence knowledge exchange, in such a way as to shape the outcome. A case study on the implementation of congestion charges in Stockholm, Sweden, illustrates how the proposed framework pinpoints three central issues for understanding these processes: (1) Differentiating the roles of, e.g., a science-based consultancy firm and an academic environment in policy formation; (2) Examining the fit between the organizational form of the science-policy interface and the intended goals; and (3) Increasing our understanding of when policymaker agents themselves need to develop scientific competence in order to interact effectively with scientific experts.

[GENOTYPING OF THE BURKHOLDERIA MALLEI STRAINS BASED ON DIFFERENT REGION ANALYSIS].

PubMed

Bondareva, O S; Savchenko, S S; Tkachenko, G A; Ledeneva, M L; Lemasova, L V; Antonov, V A

2016-01-01

Development of the genotyping methods of glanders agent is urgent due to its high pathogenicity, lack of effective preventive measures and threat of the use of Burkholderia mallei as a biological weapon. In this work we proposed a scheme for the typing of the B. mallei strains based on different region analysis (DFR). The choice of variable loci differentially presented in various strains of glanders agents was performed by analyzing annotated whole-genome sequences of the B. mallei strains. Primers and fluorescence probes were designed for 9 selected loci. The amplification conditions for different regions were optimized in two variants: with electrophoretic detection and hybridization-fluorescence detection in the strip format. The possibility of applying the DFR analysis to genetic characterization of strains was assessed in 14 B. mallei strains. The genetic profiles of the studied B. mallei strains revealed that the developed DFR-typing scheme was characterized by high discrimination power (Hunter-Gaston index value was 0.92), reproducibility, rapidity, easy interpretation, and applicability for epidemiological surveillance of glanders.

Construction of a microscopic agent-based model for firms' dynamics

NASA Astrophysics Data System (ADS)

Iyetomi, Hiroshi; Aoyama, Hideaki; Fujiwara, Yoshi; Ikeda, Yuichi; Kaizoji, Taisei; Soma, Wataru

2005-07-01

A workable microscopic model for firms' dynamics has been constructed. The model consists of firm agents and a bank agent dynamics of which are described by balance sheets. The size distribution of firms and the temporal evolution of the bank show critical dependence on whether or not firms use perfect information on their financial conditions to draw up next production plans.

21 CFR 184.1425 - Magnesium carbonate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... manufacturing practice conditions of use: (1) The ingredient is used as an anticaking and free-flow agent as defined in § 170.3(o)(1) of this chapter; a flour treating agent as defined in § 170.3(o)(13) of this chapter; a lubricant and release agent as defined in § 170.3(o)(18) of this chapter; a nutrient supplement...

Area and percent of forest affected by abiotic agents beyond reference conditions

Treesearch

2012-01-01

Criterion 3, Indicator 16, of the Montréal Process Criteria and Indicators for the Conservation and Sustainable Management of Temperate and Boreal Forests was designed to assess the impact of abiotic agents upon forests (Montréal Process Working Group 2007). Various abiotic agents, both natural and human-induced, can change forest structure and species composition....

Effect of dissolved oxygen concentration on iron efficiency: Removal of three chloroacetic acids.

PubMed

Tang, Shun; Wang, Xiao-mao; Mao, Yu-qin; Zhao, Yu; Yang, Hong-wei; Xie, Yuefeng F

2015-04-15

The monochloroacetic, dichloroacetic and trichloroacetic acid (MCAA, DCAA and TCAA) removed by metallic iron under controlled dissolved oxygen conditions (0, 0.75, 1.52, 2.59, 3.47 or 7.09 mg/L DO) was investigated in well-mixed batch systems. The removal of CAAs increased first and then decreased with increasing DO concentration. Compared with anoxic condition, the reduction of MCAA and DCAA was substantially enhanced in the presence of O2, while TCAA reduction was significantly inhibited above 2.59 mg/L. The 1.52 mg/L DO was optimum for the formation of final product, acetic acid. Chlorine mass balances were 69-102%, and carbon mass balances were 92-105%. With sufficient mass transfer from bulk to the particle surface, the degradation of CAAs was limited by their reduction or migration rate within iron particles, which were dependent on the change of reducing agents and corrosion coatings. Under anoxic conditions, the reduction of CAAs was mainly inhibited by the available reducing agents in the conductive layer. Under low oxic conditions, the increasing reducing agents and thin lepidocrocite layer were favorable for CAA dechlorination. Under high oxic conditions, the redundant oxygen competing for reducing agents and significant lepidocrocite growth became the major restricting factors. Various CAA removal mechanisms could be potentially applied to explaining the effect of DO concentration on iron efficiency for contaminant reduction in water and wastewater treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multifunctional agents for concurrent imaging and therapy in cardiovascular disease

PubMed Central

McCarthy, Jason R.

2010-01-01

The development of agents for the simultaneous detection and treatment of disease has recently gained significant attention. These multifunctional theranostic agents posses a number of advantages over their monofunctional counterparts, as they potentially allow for the concomitant determination of agent localization, release, and efficacy. Whereas the development of these agents for use in cancers has received the majority of the attention, their use in cardiovascular disease is steadily increasing. As such, this review summarized some of the most poignant recent advances in the development of theranostic agents for the treatment of this class of diseases. PMID:20654664

Seasonal variation in the biocontrol efficiency of bacterial wilt is driven by temperature-mediated changes in bacterial competitive interactions.

PubMed

Wei, Zhong; Huang, Jianfeng; Yang, Tianjie; Jousset, Alexandre; Xu, Yangchun; Shen, Qirong; Friman, Ville-Petri

2017-10-01

Microbe-based biocontrol applications hold the potential to become an efficient way to control plant pathogen disease outbreaks in the future. However, their efficiency is still very variable, which could be due to their sensitivity to the abiotic environmental conditions.Here, we assessed how environmental temperature variation correlates with ability of Ralstonia pickettii , an endophytic bacterial biocontrol agent, to suppress the Ralstonia solanacearum pathogen during different tomato crop seasons in China.We found that suppression of the pathogen was highest when the seasonal mean temperatures were around 20 °C and rapidly decreased with increasing mean crop season temperatures. Interestingly, low levels of disease incidence did not correlate with low pathogen or high biocontrol agent absolute densities. Instead, the biocontrol to pathogen density ratio was a more important predictor of disease incidence levels between different crop seasons. To understand this mechanistically, we measured the growth and strength of competition between the biocontrol agent and the pathogen over a naturally occurring temperature gradient in vitro . We found that the biocontrol strain grew relatively faster at low temperature ranges, and the pathogen at high temperature ranges, and that similar to field experiments, pathogen suppression peaked at 20 °C.Together, our results suggest that temperature-mediated changes in the strength of bacterial competition could potentially explain the variable R. solanacearum biocontrol outcomes between different crop seasons in China. Synthesis and applications . Our results suggest that abiotic environmental conditions, such as temperature, can affect the efficacy of biocontrol applications. Thus, in order to develop more consistent biocontrol applications in the future, we might need to find and isolate bacterial strains that can retain their functionality regardless of the changing environmental conditions.

Anabolic agent use in adults with cystic fibrosis.

PubMed

Green, Heather D; Barry, Peter J; Jones, Andrew M

2015-10-01

The use of non-prescribed anabolic agents amongst non-athletes is increasing with young, adult males with cystic fibrosis (CF) in the highest risk demographic. There is evidence that anabolic agents increase weight and muscle mass in adults with a variety of catabolic conditions but there is no evidence for their use in hormone sufficient adults with CF. We report a case of anabolic agent use in a male adult with CF and review the clinical features of anabolic agent use with a focus on adults with CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

INNOVATIVE MIOR PROCESS UTILIZING INDIGENOUS RESERVOIR CONSTITUENTS

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

D.O. Hitzman; A.K. Stepp; D.M. Dennis

This research program was directed at improving the knowledge of reservoir ecology and developing practical microbial solutions and technologies for improving oil production. The goal was to identify and utilize indigenous microbial populations which can produce beneficial metabolic products and develop a methodology to stimulate those select microbes with nutrient amendments to increase oil recovery. This microbial technology has the capability of producing multiple oil-releasing agents. Experimental laboratory work in model sandpack cores was conducted using microbial cultures isolated from produced water samples. Comparative laboratory studies demonstrating in situ production of microbial products as oil recovery agents were conducted inmore » sand packs with natural field waters using cultures and conditions representative of oil reservoirs. Increased oil recovery in multiple model sandpack systems was achieved and the technology and results were verified by successful field studies. Direct application of the research results has lead to the development of a feasible, practical, successful, and cost-effective technology which increases oil recovery. This technology is now being commercialized and applied in numerous field projects to increase oil recovery. Two field applications of the developed technology reported production increases of 21% and 24% in oil recovery.« less

Patterns of antimicrobial agent prescription in a sentinel population of canine and feline veterinary practices in the United Kingdom.

PubMed

Singleton, D A; Sánchez-Vizcaíno, F; Dawson, S; Jones, P H; Noble, P J M; Pinchbeck, G L; Williams, N J; Radford, A D

2017-06-01

Antimicrobial resistance is an increasingly important global health threat and the use of antimicrobial agents is a key risk factor in its development. This study describes antimicrobial agent prescription (AAP) patterns over a 2year period using electronic health records (EHRs) from booked consultations in a network of 457 sentinel veterinary premises in the United Kingdom. A semi-automated classification methodology was used to map practitioner defined product codes in 918,333 EHRs from 413,870 dogs and 352,730 EHRs from 200,541 cats, including 289,789 AAPs. AAP as a proportion of total booked consultations was more frequent in dogs (18.8%, 95% confidence interval, CI, 18.2-19.4) than cats (17.5%, 95% CI 16.9-18.1). Prescription of topical antimicrobial agents was more frequent in dogs (7.4%, 95% CI 7.2-7.7) than cats (3.2%, 95% CI 3.1-3.3), whilst prescription of systemic antimicrobial agents was more frequent in cats (14.8%, 95% CI 14.2-15.4) than dogs (12.2%, 95% CI 11.7-12.7). A decreasing temporal pattern was identified for prescription of systemic antimicrobial agents in dogs and cats. Premises which prescribed antimicrobial agents frequently for dogs also prescribed frequently for cats. AAP was most frequent during pruritus consultations in dogs and trauma consultations in cats. Clavulanic acid potentiated amoxicillin was the most frequently prescribed antimicrobial agent in dogs (28.6% of prescriptions, 95% CI 27.4-29.8), whereas cefovecin, a third generation cephalosporin, was the most frequently prescribed antimicrobial agent in cats (36.2%, 95% CI 33.9-38.5). This study demonstrated patterns in AAP over time and for different conditions in a population of companion animals in the United Kingdom. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Studies on the stripping of cerium from the loaded tbp-kerosene solution

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

Rizk, S.E.; Abdel Rahman, N.; Daoud, J.A.

2008-07-01

The reductive stripping of Ce(IV) from the loaded organic phase (30% TBP in kerosene) was investigated, using two stripping agents, EDTA and H{sub 2}O{sub 2}, in nitric acid. The results are compared to determine the optimum conditions for the reduction of Ce(IV) in the organic phase to Ce(III) in the aqueous phase. For each of the two stripping agents, the effect of different parameters affecting the reduction process was investigated: stripping-agent concentration, nitric acid concentration, phase ratio, shaking time, and temperature. The results are compared and discussed in terms of the conditions required for maximum reductive stripping of Ce(IV). (authors)

Drug dependence: its significance and characteristics

PubMed Central

Eddy, Nathan B.; Halbach, H.; Isbell, Harris; Seevers, Maurice H.

1965-01-01

It has become impossible in practice, and is scientifically unsound, to maintain a single definition for all forms of drug addiction and/or habituation. A feature common to these conditions as well as to drug abuse in general is dependence, psychic or physical or both, of the individual on a chemical agent. Therefore, better understanding should be attained by substitution of the term drug dependence of this or that type, according to the agent or class of agents involved, in discussions of these conditions, especially inter-disciplinary. Short descriptions, followed by concise listings of their characteristics, are formulated for the various types of dependence on at present widely abused major groups of substances. PMID:5294186

Chemopreventive Agent Development | Division of Cancer Prevention

Cancer.gov

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Effect of blood flow on near-the-wall mass transport of drugs and other bioactive agents: a simple formula to estimate boundary layer concentrations.

PubMed

Rugonyi, Sandra

2008-04-01

Transport of bioactive agents through the blood is essential for cardiovascular regulatory processes and drug delivery. Bioactive agents and other solutes infused into the blood through the wall of a blood vessel or released into the blood from an area in the vessel wall spread downstream of the infusion/release region and form a thin boundary layer in which solute concentration is higher than in the rest of the blood. Bioactive agents distributed along the vessel wall affect endothelial cells and regulate biological processes, such as thrombus formation, atherogenesis, and vascular remodeling. To calculate the concentration of solutes in the boundary layer, researchers have generally used numerical simulations. However, to investigate the effect of blood flow, infusion rate, and vessel geometry on the concentration of different solutes, many simulations are needed, leading to a time-consuming effort. In this paper, a relatively simple formula to quantify concentrations in a tube downstream of an infusion/release region is presented. Given known blood-flow rates, tube radius, solute diffusivity, and the length of the infusion region, this formula can be used to quickly estimate solute concentrations when infusion rates are known or to estimate infusion rates when solute concentrations at a point downstream of the infusion region are known. The developed formula is based on boundary layer theory and physical principles. The formula is an approximate solution of the advection-diffusion equations in the boundary layer region when solute concentration is small (dilute solution), infusion rate is modeled as a mass flux, and there is no transport of solute through the wall or chemical reactions downstream of the infusion region. Wall concentrations calculated using the formula developed in this paper were compared to the results from finite element models. Agreement between the results was within 10%. The developed formula could be used in experimental procedures to evaluate drug efficacy, in the design of drug-eluting stents, and to calculate rates of release of bioactive substances at active surfaces using downstream concentration measurements. In addition to being simple and fast to use, the formula gives accurate quantifications of concentrations and infusion rates under steady-state and oscillatory flow conditions, and therefore can be used to estimate boundary layer concentrations under physiological conditions.

The use of immunosuppression in autoimmune hepatitis: A current literature review.

PubMed

Cropley, Angela; Weltman, Martin

2017-03-01

Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre's approach to treatment of AIH in the context of a contemporary review of the literature.

Towards an agent-oriented programming language based on Scala

NASA Astrophysics Data System (ADS)

Mitrović, Dejan; Ivanović, Mirjana; Budimac, Zoran

2012-09-01

Scala and its multi-threaded model based on actors represent an excellent framework for developing purely reactive agents. This paper presents an early research on extending Scala with declarative programming constructs, which would result in a new agent-oriented programming language suitable for developing more advanced, BDI agent architectures. The main advantage the new language over many other existing solutions for programming BDI agents is a natural and straightforward integration of imperative and declarative programming constructs, fitted under a single development framework.

Evaluation of water security in Jordan using a multi-agent, hydroeconomic model: Initial model results from the Jordan Water Project

NASA Astrophysics Data System (ADS)

Yoon, J.; Klassert, C. J. A.; Lachaut, T.; Selby, P. D.; Knox, S.; Gorelick, S.; Rajsekhar, D.; Tilmant, A.; Avisse, N.; Harou, J. J.; Medellin-Azuara, J.; Gawel, E.; Klauer, B.; Mustafa, D.; Talozi, S.; Sigel, K.; Zhang, H.

2016-12-01

Our work focuses on development of a multi-agent, hydroeconomic model for water policy evaluation in Jordan. Jordan ranks among the most water-scarce countries in the world, a situation exacerbated due to a recent influx of refugees escaping the ongoing civil war in neighboring Syria. The modular, multi-agent model is used to evaluate interventions for enhancing Jordan's water security, integrating biophysical modules that simulate natural and engineered phenomena with human modules that represent behavior at multiple levels of decision making. The hydrologic modules are developed using spatially-distributed groundwater and surface water models, which are translated into compact simulators for efficient integration into the multi-agent model. For the multi-agent model, we explicitly account for human agency at multiple levels of decision making, with agents representing riparian, management, supplier, and water user groups. Human agents are implemented as autonomous entities in the model that make decisions in relation to one another and in response to hydrologic and socioeconomic conditions. The integrated model is programmed in Python using Pynsim, a generalizable, open-source object-oriented software framework for modeling network-based water resource systems. The modeling time periods include historical (2006-2014) and future (present-2050) time spans. For the historical runs, the model performance is validated against historical data for several observations that reflect the interacting dynamics of both the hydrologic and human components of the system. A historical counterfactual scenario is also constructed to isolate and identify the impacts of the recent Syrian civil war and refugee crisis on Jordan's water system. For the future period, model runs are conducted to evaluate potential supply, demand, and institutional interventions over a wide range of plausible climate and socioeconomic scenarios. In addition, model sensitivity analysis is conducted revealing the hydrologic and human aspects of the system that most strongly influence water security outcomes, providing insight into coupled human-water system dynamics as well as priority areas of focus for continued model improvement.

A Methodology For Developing an Agent Systems Reference Architecture

DTIC Science & Technology

2010-05-01

agent framworks , we create an abstraction noting similarities and differences. The differences are documented as points of variation. The result...situated in the physical en- vironment. Addressing how conceptual components of an agent system is beneficial to agent system architects, developers, and

Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles.

PubMed

Huang, Haitao; Yue, Tao; Xu, Ke; Golzarian, Jafar; Yu, Jiahui; Huang, Jin

2015-07-01

Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Chemical cleaning/disinfection and ageing of organic UF membranes: a review.

PubMed

Regula, C; Carretier, E; Wyart, Y; Gésan-Guiziou, G; Vincent, A; Boudot, D; Moulin, P

2014-06-01

Membrane separation processes have become a basic unit operation for process design and product development. These processes are used in a variety of separation and concentration steps, but in all cases, the membranes must be cleaned regularly to remove both organic and inorganic material deposited on the surface and/or into the membrane bulk. Cleaning/disinfection is a vital step in maintaining the permeability and selectivity of the membrane in order to get the plant to its original capacity, to minimize risks of bacteriological contamination, and to make acceptable products. For this purpose, a large number of chemical cleaning/disinfection agents are commercially available. In general, these cleaning/disinfection agents have to improve the membrane flux to a certain extent. However, they can also cause irreversible damages in membrane properties and performances over the long term. Until now, there is considerably less literature dedicated to membrane ageing than to cleaning/disinfection. The knowledge in cleaning/disinfection efficiency has recently been improved. But in order to develop optimized cleaning/disinfection protocols there still remains a challenge to better understand membrane ageing. In order to compensate for the lack of correlated cleaning/disinfection and ageing data from the literature, this paper investigates cleaning/disinfection efficiencies and ageing damages of organic ultrafiltration membranes. The final aim is to provide less detrimental cleaning/disinfection procedures and to propose some guidelines which should have been taken into consideration in term of membrane ageing studies. To carry out this study, this article will detail the background of cleaning/disinfection and aging membrane topics in a first introductive part. In a second part, key factors and endpoints of cleaning/disinfection and aging membranes will be discussed deeply: the membrane role and the cleaning parameters roles, such as water quality, storing conditions, cleaning/disinfection/aging agents/conditions/protocols. The third and last part will be developed the parameters, methods and ways of characterization at our disposal and commonly used to develop and implement membrane cleaning and/or ageing studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Beliefs about human agency influence the neural processing of gaze during joint attention.

PubMed

Caruana, Nathan; de Lissa, Peter; McArthur, Genevieve

2017-04-01

The current study measured adults' P350 and N170 ERPs while they interacted with a character in a virtual reality paradigm. Some participants believed the character was controlled by a human ("avatar" condition, n = 19); others believed it was controlled by a computer program ("agent" condition, n = 19). In each trial, participants initiated joint attention in order to direct the character's gaze toward a target. In 50% of trials, the character gazed toward the target (congruent responses), and in 50% of trials the character gazed to a different location (incongruent response). In the avatar condition, the character's incongruent gaze responses generated significantly larger P350 peaks at centro-parietal sites than congruent gaze responses. In the agent condition, the P350 effect was strikingly absent. Left occipitotemporal N170 responses were significantly smaller in the agent condition compared to the avatar condition for both congruent and incongruent gaze shifts. These data suggest that beliefs about human agency may recruit mechanisms that discriminate the social outcome of a gaze shift after approximately 350 ms, and that these mechanisms may modulate the early perceptual processing of gaze. These findings also suggest that the ecologically valid measurement of social cognition may depend upon paradigms that simulate genuine social interactions.

Tools to Assess Community-Based Cumulative Risk and Exposures

EPA Science Inventory

Multiple agents and stressors can interact in a given community to adversely affect human and ecological conditions. A cumulative risk assessment (CRA) analyzes, characterizes, and potentially quantifies the effects from multiple stressors, which include chemical agents (for exam...

Triggered pore-forming agents

DOEpatents

Bayley, H.; Walker, B.J.; Chang, C.Y.; Niblack, B.; Panchal, R.

1998-07-07

An inactive pore-forming agent is revealed which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell. 30 figs.

Casuist BDI-Agent: A New Extended BDI Architecture with the Capability of Ethical Reasoning

NASA Astrophysics Data System (ADS)

Honarvar, Ali Reza; Ghasem-Aghaee, Nasser

Since the intelligent agent is developed to be cleverer, more complex, and yet uncontrollable, a number of problems have been recognized. The capability of agents to make moral decisions has become an important question, when intelligent agents have developed more autonomous and human-like. We propose Casuist BDI-Agent architecture which extends the power of BDI architecture. Casuist BDI-Agent architecture combines CBR method in AI and bottom up casuist approach in ethics in order to add capability of ethical reasoning to BDI-Agent.

A development framework for distributed artificial intelligence

NASA Technical Reports Server (NTRS)

Adler, Richard M.; Cottman, Bruce H.

1989-01-01

The authors describe distributed artificial intelligence (DAI) applications in which multiple organizations of agents solve multiple domain problems. They then describe work in progress on a DAI system development environment, called SOCIAL, which consists of three primary language-based components. The Knowledge Object Language defines models of knowledge representation and reasoning. The metaCourier language supplies the underlying functionality for interprocess communication and control access across heterogeneous computing environments. The metaAgents language defines models for agent organization coordination, control, and resource management. Application agents and agent organizations will be constructed by combining metaAgents and metaCourier building blocks with task-specific functionality such as diagnostic or planning reasoning. This architecture hides implementation details of communications, control, and integration in distributed processing environments, enabling application developers to concentrate on the design and functionality of the intelligent agents and agent networks themselves.

Modeling Environmental Impacts on Cognitive Performance for Artificially Intelligent Entities

DTIC Science & Technology

2017-06-01

of the agent behavior model is presented in a military-relevant virtual game environment. We then outline a quantitative approach to test the agent...relevant virtual game environment. We then outline a quantitative approach to test the agent behavior model within the virtual environment. Results show...x Game View of Hot Environment Condition Displaying Total “f” Cost for Each Searched Waypoint Node

Evasion in the plane

NASA Technical Reports Server (NTRS)

Leitmann, G.; Liu, H. S.

1977-01-01

Dynamic systems were considered subject to control by two agents, one of whom desires that no trajectory of the system emanating from outside a given set, intersects that set no matter what the admissible actions of the other agent. Constructive conditions sufficient to yield a feedback control for the agent seeking avoidance were employed to deduce an evader control for the planar pursuit-evasion problem with bounded normal accelerations.

Development of a Model System to Evaluate Local Recurrence in Osteosarcoma and Assessment of the Effects of Bone Morphogenetic Protein-2.

PubMed

Geller, David S; Singh, Michael Y; Zhang, Wendong; Gill, Jonathan; Roth, Michael E; Kim, Mimi Y; Xie, Xianhong; Singh, Christopher K; Dorfman, Howard D; Villanueva-Siles, Esperanza; Park, Amy; Piperdi, Sajida; Gorlick, Richard

2015-07-01

It is increasingly relevant to better define what constitutes an adequate surgical margin in an effort to improve reconstructive longevity and functional outcomes following osteosarcoma surgery. In addition, nonunion remains a challenging problem in some patients following allograft reconstruction. Bone morphogenetic protein-2 (BMP-2) could enhance osseous union, but has been historically avoided due to concerns that it may promote tumor recurrence. An orthotopic xenograft murine model was utilized to describe the natural temporal course of osteosarcoma growth. Tumors were treated either with surgery alone, surgery and single-agent chemotherapy, or surgery and dual-agent chemotherapy to assess the relationship between surgical margin and local recurrence. The effect of BMP-2 on local recurrence was similarly assessed. Osteosarcoma tumor growth was categorized into reproducible phases. Margins greater than 997 μm resulted in local control following surgery alone. Margins greater than 36 μm resulted in local control following surgery and single-agent chemotherapy. Margins greater than 12 μm resulted in local control following surgery and dual-agent chemotherapy. The application of exogenous BMP-2 does not confer an increased risk of local recurrence. This model reliably reproduces the clinical, radiographic, and surgical conditions encountered in human osteosarcoma. It successfully incorporates relevant chemotherapy, further paralleling the human experience. Surgical margins required to achieve local control in osteosarcoma can be reduced using single-agent chemotherapy and further decreased using dual-agent chemotherapy. The application of BMP-2 does not increase local recurrence in this model. ©2014 American Association for Cancer Research.

Enantiomerically Pure Acetals in Organic Synthesis: Resolutions and Diastereoselective Alkylations of Alpha-Hydroxy Esters

DTIC Science & Technology

1990-01-01

sensitivity of the alkylating agent to the reaction conditions. In either case , a decision was made to use 5-iodo-2- methyl -l-pentene as the alkylating ...agent, and the reaction conditions. In most cases the diastereomeric products of the alkylation were also separated by column chromatography. This...equatorially substituted product. Oxidation of the alcohol to the ketone followed by treatment with an alkyl Grignard reagent gave only the product which

Multiwell cell culture plate format with integrated microfluidic perfusion system

NASA Astrophysics Data System (ADS)

Domansky, Karel; Inman, Walker; Serdy, Jim; Griffith, Linda G.

2006-01-01

A new cell culture analog has been developed. It is based on the standard multiwell cell culture plate format but it provides perfused three-dimensional cell culture capability. The new capability is achieved by integrating microfluidic valves and pumps into the plate. The system provides a means to conduct high throughput assays for target validation and predictive toxicology in the drug discovery and development process. It can be also used for evaluation of long-term exposure to drugs or environmental agents or as a model to study viral hepatitis, cancer metastasis, and other diseases and pathological conditions.

Online Deception Detection Using BDI Agents

ERIC Educational Resources Information Center

Merritts, Richard A.

2013-01-01

This research has two facets within separate research areas. The research area of Belief, Desire and Intention (BDI) agent capability development was extended. Deception detection research has been advanced with the development of automation using BDI agents. BDI agents performed tasks automatically and autonomously. This study used these…

Development of agent-based on-line adaptive signal control (ASC) framework using connected vehicle (CV) technology.

DOT National Transportation Integrated Search

2016-04-01

In this study, we developed an adaptive signal control (ASC) framework for connected vehicles (CVs) using agent-based modeling technique. : The proposed framework consists of two types of agents: 1) vehicle agents (VAs); and 2) signal controller agen...

Sun/shade conditions affect recruitment and local adaptation of a columnar cactus in dry forests.

PubMed

Miranda-Jácome, Antonio; Montaña, Carlos; Fornoni, Juan

2013-02-01

Facilitation among plants in water-limited environments (i.e. where evapotranspiration overcomes the availability of water during the growing season) has been considered a local adaptation to water and light conditions. Among cacti, early life-history stages can benefit from the facilitative effects of nurse plants that reduce solar radiation and water stress. However, whether light condition itself acts as an agent of selection through facilitation remains untested. The aim of this study was to determine (1) whether light conditions affect seedling recruitment, (2) whether the positive effect of shade on seedling recruitment is more intense under more stressful conditions and (3) whether shade condition (facilitation) reduces the magnitude of local adaptation on seedling recruitment relative to full sunlight conditions. A reciprocal transplant experiment, coupled with the artificial manipulation of sun/shade conditions, was performed to test for the effects of local adaptation on germination, seedling survival and growth, using two demes of the columnar cactus Pilosocereus leucocephalus, representing different intensities of stressful conditions. Full sunlight conditions reduced recruitment success and supported the expectation of lower recruitment in more stressful environments. Significant local adaptation was mainly detected under full sunlight conditions, indicating that this environmental factor acts as an agent of selection at both sites. The results supported the expectation that the magnitude of local adaptation, driven by the effects of facilitative nurse plants, is less intense under reduced stressful conditions. This study is the first to demonstrate that sun/shade conditions act as a selective agent accounting for local adaptation in water-limited environments, and that facilitation provided by nurse plants in these environments can attenuate the patterns of local adaptation among plants benefiting from the nurse effect.

Sun/shade conditions affect recruitment and local adaptation of a columnar cactus in dry forests

PubMed Central

Miranda-Jácome, Antonio; Montaña, Carlos; Fornoni, Juan

2013-01-01

Background and Aims Facilitation among plants in water-limited environments (i.e. where evapotranspiration overcomes the availability of water during the growing season) has been considered a local adaptation to water and light conditions. Among cacti, early life-history stages can benefit from the facilitative effects of nurse plants that reduce solar radiation and water stress. However, whether light condition itself acts as an agent of selection through facilitation remains untested. The aim of this study was to determine (1) whether light conditions affect seedling recruitment, (2) whether the positive effect of shade on seedling recruitment is more intense under more stressful conditions and (3) whether shade condition (facilitation) reduces the magnitude of local adaptation on seedling recruitment relative to full sunlight conditions. Methods A reciprocal transplant experiment, coupled with the artificial manipulation of sun/shade conditions, was performed to test for the effects of local adaptation on germination, seedling survival and growth, using two demes of the columnar cactus Pilosocereus leucocephalus, representing different intensities of stressful conditions. Key Results Full sunlight conditions reduced recruitment success and supported the expectation of lower recruitment in more stressful environments. Significant local adaptation was mainly detected under full sunlight conditions, indicating that this environmental factor acts as an agent of selection at both sites. Conclusions The results supported the expectation that the magnitude of local adaptation, driven by the effects of facilitative nurse plants, is less intense under reduced stressful conditions. This study is the first to demonstrate that sun/shade conditions act as a selective agent accounting for local adaptation in water-limited environments, and that facilitation provided by nurse plants in these environments can attenuate the patterns of local adaptation among plants benefiting from the nurse effect. PMID:23223204

Modified extrusion-spheronization as a technique of microencapsulation for stabilization of choline bitartrate using hydrogenated soya bean oil.

PubMed

Gangurde, Avinash Bhaskar; Sav, Ajay Kumar; Javeer, Sharadchandra Dagadu; Moravkar, Kailas K; Pawar, Jaywant N; Amin, Purnima D

2015-01-01

Choline bitartrate (CBT) is a vital nutrient for fetal brain development and memory function. It is hygroscopic in nature which is associated with stability related problem during storage such as development of fishy odor and discoloration. Microencapsulation method was adopted to resolve the stability problem and for this hydrogenated soya bean oil (HSO) was used as encapsulating agent. Industrially feasible modified extrusion-spheronization technique was selected for microencapsulation. HSO was used as encapsulating agent, hydroxypropyl methyl cellulose E5/E15 as binder and microcrystalline cellulose as spheronization aid. Formulated pellets were evaluated for parameters such as flow property, morphological characteristics, hardness-friability index (HFI), drug content, encapsulation efficiency, and in vitro drug release. The optimized formulations were also characterized for particle size (by laser diffractometry), differential scanning calorimetry, powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy, and scanning electron microscopy. The results from the study showed that coating of 90% and 60% CBT was successful with respect to all desired evaluation parameters. Optimized formulation was kept for 6 months stability study as per ICH guidelines, and there was no change in color, moisture content, drug content, and no fishy odor was observed. Microencapsulated pellets of CBT using HSO as encapsulating agent were developed using modified extrusion spheronization technique. Optimized formulations, CBT 90% (F5), and CBT 60% (F10), were found to be stable for 4M and 6M, respectively, at accelerated conditions.

Laser speckle-imaging of blood microcirculation in the brain cortex of laboratory rats in stress

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

Vilensky, M A; Semyachkina-Glushkovskaya, Oxana V; Timoshina, P A

2012-06-30

The results of experimental approbation of the method of laser full-field speckle-imaging for monitoring the changes in blood microcirculation state of the brain cortex of laboratory rats under the conditions of developing stroke and administration of vasodilating and vasoconstrictive agents are presented. The studies aimed at the choice of the optimal conditions of speckle-image formation and recording were performed and the software implementing an adaptive algorithm for processing the data of measurements was created. The transfer of laser radiation to the probed region of the biotissue was implemented by means of a silica-polymer optical fibre. The problems and prospects ofmore » speckle-imaging of cerebral microcirculation of blood in laboratory and clinical conditions are discussed.« less

Humidity induced phase transformation of poloxamer 188 and its effect on physical stability of amorphous solid dispersion of AMG 579, a PDE10A inhibitor.

PubMed

Wu, Qiong; Kennedy, Michael T; Nagapudi, Karthik; Kiang, Y-H

2017-04-15

Poloxamer 188, a commonly used emulsifying and solubilizing agent, was found to be the cause of crystallization of an investigational drug, AMG 579, from its amorphous solid dispersion at accelerated storage conditions. Investigation of this physical stability issue included thorough characterization of poloxamer 188 at non-ambient conditions. At 40°C, poloxamer 188 becomes deliquescent above relative humidity of 75%. Upon returning to ambient conditions, the deliquescent poloxamer 188 loses water and re-solidifies. The reversible phase transformation of poloxamer 188 may cause physical and chemical stability issues and this risk should be assessed when selecting it as an excipient for formulation development. Copyright © 2017 Elsevier B.V. All rights reserved.

Iron-montmorillonite clays as active sorbents for the decontamination of hazardous chemical warfare agents.

PubMed

Carniato, F; Bisio, C; Evangelisti, C; Psaro, R; Dal Santo, V; Costenaro, D; Marchese, L; Guidotti, M

2018-02-27

A class of heterogeneous catalysts based on commercial bentonite from natural origin, containing at least 80 wt% of montmorillonite clay, was designed to transform selectively and under mild conditions toxic organosulfur and organophosphorus chemical warfare agents into non-noxious products with a reduced impact on health and environment. The bentonite from the natural origin was modified by introducing iron species and acid sites in the interlayer space, aiming to obtain a sorbent with strong catalytic oxidising and hydrolytic properties. The catalytic performance of these materials was evaluated in the oxidative abatement of (2-chloroethyl)ethyl sulfide (CEES), a simulant of sulfur mustard, in the presence of aqueous hydrogen peroxide as an oxidant. A new decontamination formulation was, moreover, proposed and obtained by mixing sodium perborate, as a solid oxidant, to iron-bentonite catalysts. Solid-phase decontamination tests, performed on a cotton textile support contaminated with organosulfide and organophosphonate simulant agents revealed the good activity of the solid formulation, especially in the in situ detoxification of blistering agents. Tests carried out on the real blistering warfare agent, sulfur mustard (HD agent), showed that, thanks to the co-presence of the iron-based clay together with the solid oxidant component, a good decontamination of the test surface from the real warfare agent could be achieved (80% contaminant degradation, under ambient conditions, in 24 h).

Autonomic and Coevolutionary Sensor Networking

NASA Astrophysics Data System (ADS)

Boonma, Pruet; Suzuki, Junichi

(WSNs) applications are often required to balance the tradeoffs among conflicting operational objectives (e.g., latency and power consumption) and operate at an optimal tradeoff. This chapter proposes and evaluates a architecture, called BiSNET/e, which allows WSN applications to overcome this issue. BiSNET/e is designed to support three major types of WSN applications: , and hybrid applications. Each application is implemented as a decentralized group of, which is analogous to a bee colony (application) consisting of bees (agents). Agents collect sensor data or detect an event (a significant change in sensor reading) on individual nodes, and carry sensor data to base stations. They perform these data collection and event detection functionalities by sensing their surrounding network conditions and adaptively invoking behaviors such as pheromone emission, reproduction, migration, swarming and death. Each agent has its own behavior policy, as a set of genes, which defines how to invoke its behaviors. BiSNET/e allows agents to evolve their behavior policies (genes) across generations and autonomously adapt their performance to given objectives. Simulation results demonstrate that, in all three types of applications, agents evolve to find optimal tradeoffs among conflicting objectives and adapt to dynamic network conditions such as traffic fluctuations and node failures/additions. Simulation results also illustrate that, in hybrid applications, data collection agents and event detection agents coevolve to augment their adaptability and performance.

A historical look at chlorofluorocarbon refrigerants

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

Bhatti, M.S.

1999-07-01

A class of chemical compounds called chlorofluorocarbon refrigerants has been in widespread use since the 1930s in such diverse applications as refrigerants for refrigerating and air-conditioning systems, blowing agents for plastic foams, solvents for microelectronic circuitry and dry cleaning, sterilants for medical instruments, aerosol propellants for personal hygiene products and pesticides, and freezants for food. This paper describes the historical development of the chlorofluorocarbon refrigerants and gives brief biographical sketches of the inventors. 85 refs., 8 figs., 4 tabs.

Development of Bicarbonate-Activated Peroxide as a Chemical and Biological Warfare Agent Decontaminant

DTIC Science & Technology

2006-06-30

may operate for certain substrates. The reaction of equation 1 proceeds with the intermediacy of CO2 as shown in Figure 1. Although it is well...competition between paths 5 and 6 will depend on the conditions and the nature of the substrate S. Note that figures, equations , etc. in the...1 shows the complete reaction scheme used to model the equilibration reaction at low temperature. Table 1 Kinetic equations and their

Biological agents with potential for misuse: a historical perspective and defensive measures.

PubMed

Bhalla, Deepak K; Warheit, David B

2004-08-15

Biological and chemical agents capable of producing serious illness or mortality have been used in biowarfare from ancient times. Use of these agents has progressed from crude forms in early and middle ages, when snakes and infected cadavers were used as weapons in battles, to sophisticated preparations for use during and after the second World War. Cults and terrorist organizations have attempted the use of biological agents with an aim to immobilize populations or cause serious harm. The reasons for interest in these agents by individuals and organizations include relative ease of acquisition, potential for causing mass casualty or panic, modest financing requirement, availability of technology, and relative ease of delivery. The Centers for Disease Control and Prevention has classified Critical Biological Agents into three major categories. This classification was based on several criteria, which include severity of impact on human health, potential for delivery in a weapon, capacity to cause panic and special needs for development, and stockpiling of medication. Agents that could cause the greatest harm following deliberate use were placed in category A. Category B included agents capable of producing serious harm and significant mortality but of lower magnitude than category A agents. Category C included emerging pathogens that could be developed for mass dispersion in future and their potential as a major health threat. A brief description of the category A bioagents is included and the pathophysiology of two particularly prominent agents, namely anthrax and smallpox, is discussed in detail. The potential danger from biological agents and their ever increasing threat to human populations have created a need for developing technologies for their early detection, for developing treatment strategies, and for refinement of procedures to ensure survival of affected individuals so as to attain the ultimate goal of eliminating the threat from intentional use of these agents. International treaties limiting development and proliferation of weapons and continuing development of defense strategies and safe guards against agents of concern are important elements of plans for eliminating this threat.

The importance of expressing antimicrobial agents on water basis in growth/no growth interface models: a case study for Zygosaccharomyces bailii.

PubMed

Dang, T D T; Vermeulen, A; Mertens, L; Geeraerd, A H; Van Impe, J F; Devlieghere, F

2011-01-31

In a previous study on Zygosaccharomyces bailii, three growth/no growth models have been developed, predicting growth probability of the yeast at different conditions typical for acidified foods (Dang, T.D.T., Mertens, L., Vermeulen, A., Geeraerd, A.H., Van Impe, J.F., Debevere, J., Devlieghere, F., 2010. Modeling the growth/no growth boundary of Z. bailii in acidic conditions: A contribution to the alternative method to preserve foods without using chemical preservatives. International Journal of Food Microbiology 137, 1-12). In these broth-based models, the variables were pH, water activity and acetic acid, with acetic acid concentration expressed in volume % on the total culture medium (i.e., broth). To continue the previous study, validation experiments were performed for 15 selected combinations of intrinsic factors to assess the performance of the model at 22°C (60days) in a real food product (ketchup). Although the majority of experimental results were consistent, some remarkable deviations between prediction and validation were observed, e.g., Z. bailii growth occurred in conditions where almost no growth had been predicted. A thorough investigation revealed that the difference between two ways of expressing acetic acid concentration (i.e., on broth basis and on water basis) is rather significant, particularly for media containing high amounts of dry matter. Consequently, the use of broth-based concentrations in the models was not appropriate. Three models with acetic acid concentration expressed on water basis were established and it was observed that predictions by these models well matched the validation results; therefore a "systematic error" in broth-based models was recognized. In practice, quantities of antimicrobial agents are often calculated based on the water content of food products. Hence, to assure reliable predictions and facilitate the application of models (developed from lab media with high dry matter contents), it is important to express antimicrobial agents' concentrations on a common basis-the water content. Reviews over other published growth/no growth models in literature are carried out and expressions of the stress factors' concentrations (on broth basis) found in these models confirm this finding. Copyright © 2010 Elsevier B.V. All rights reserved.

Cognitive Model of Trust Dynamics Predicts Human Behavior within and between Two Games of Strategic Interaction with Computerized Confederate Agents

PubMed Central

Collins, Michael G.; Juvina, Ion; Gluck, Kevin A.

2016-01-01

When playing games of strategic interaction, such as iterated Prisoner's Dilemma and iterated Chicken Game, people exhibit specific within-game learning (e.g., learning a game's optimal outcome) as well as transfer of learning between games (e.g., a game's optimal outcome occurring at a higher proportion when played after another game). The reciprocal trust players develop during the first game is thought to mediate transfer of learning effects. Recently, a computational cognitive model using a novel trust mechanism has been shown to account for human behavior in both games, including the transfer between games. We present the results of a study in which we evaluate the model's a priori predictions of human learning and transfer in 16 different conditions. The model's predictive validity is compared against five model variants that lacked a trust mechanism. The results suggest that a trust mechanism is necessary to explain human behavior across multiple conditions, even when a human plays against a non-human agent. The addition of a trust mechanism to the other learning mechanisms within the cognitive architecture, such as sequence learning, instance-based learning, and utility learning, leads to better prediction of the empirical data. It is argued that computational cognitive modeling is a useful tool for studying trust development, calibration, and repair. PMID:26903892

The role of alternative and natural agents, cryotherapy, and/or laser for management of alimentary mucositis.

PubMed

Migliorati, Cesar A; Oberle-Edwards, Loree; Schubert, Mark

2006-06-01

To review the literature and update the current guidelines of alternative/natural agents, cryotherapy, and/or laser therapy in the management of alimentary mucositis (AM). The original guidelines developed by the Multinational Association for Supportive Care in Cancer (MASCC)/International Society for Oral Oncology (ISOO) mucositis study group were the basis for this study. A medical librarian conducted an initial Medline search to identify research articles published between 2002 and 2005 in English language. A search term combination that included stomatitis, mucositis, mucous membrane, neoplasm, lasers, complimentary therapies, amino acids, antioxidants, vitamins, minerals, plant extracts, and cryotherapy was conducted. This initial search identified articles with a strong scientific methodology that included both preclinical and clinical research. Using standardized scoring forms, authors reviewed and scored individual articles. A consensus result of the review was achieved in a meeting of reviewers in June of 2005. The initial search identified a total of 167 new articles. Of these, 14 were selected and reviewed: alternative/natural therapy (one preclinical study); cryotherapy (four clinical studies); lasers (two clinical studies); and alternative/natural agents (seven clinical studies). A new guideline could be established for the use of cryotherapy in the management of AM in hematopoietic stem cell transplant (HSCT) patients receiving melphalan in the conditioning phase. The rapid progress in the understanding of AM created a need for new prevention and management protocols. Frequent literature review is now necessary to identify agents and protocols being developed in this important area of supportive care in cancer.

Enzyme-linked immunosorbent assay for detection of organophosphorylated butyrylcholinesterase: A biomarker of exposure to organophosphate agents

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

Wang, Liming; Du, Dan; Lu, Donglai

2011-05-05

A sandwich enzyme-linked immunosorbent assay (sELISA) is developed for detection of organophosphorylated butyrylcholinesterase (OP-BChE), a potential biomarker for human exposure to organophosphate insecticides and nerve agents. A pair of antibodies specific to OP-BChE adduct were identified through systematic screening of several anti BChE antibodies (anti-BChE) and anti-phosphoserine antibodies (anti-Pser) from different sources. The selected anti-BChE (set as capture antibody) antibodies recognize both phosphorylated and nonphosphorylated BChE. These antibodies can therefore be used to capture both BChE and OP-BChE from the sample matrices. The anti- Pser (set as detecting antibody) was used to recognize the OP moiety of OP-BChE adducts. Withmore » the combination of the selected antibody pair, several key parameters (such as the concentration of anti-BChE and anti-Pser, and the blocking agent) were optimized to enhance the sensitivity and selectivity of the sELISA. Under the optimal conditions, the sELISA has shown a wide linear range from 0.03 nM to 30 nM, with a detection limit of 0.03 nM. Furthermore, the sELISA was successfully applied to detect OP-BChE using in-vitro biological samples such as rat plasma spiked with OP-BChE with excellent adduct recovery (z>99 %). These results demonstrate that this novel approach holds great promise to develop an ELISA kit and offers a simple and cost-effective tool for screening/evaluating exposure to organophosphate insecticides and nerve agents.« less

Learning Hierarchical Skills for Game Agents from Video of Human Behavior

DTIC Science & Technology

2009-01-01

intelligent agents for computer games is an im- portant aspect of game development . However, traditional methods are expensive, and the resulting agents...Constructing autonomous agents is an essential task in game development . In this paper, we outlined a system that an- alyzes preprocessed video footage of

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease.

PubMed

Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

2017-09-21

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.

Membrane stabilization activity as anti-inflammatory mechanisms of Vernonia amygdalina leaves extracts

NASA Astrophysics Data System (ADS)

Nuryanto, MK; Paramita, S.; Iskandar, A.

2018-04-01

Inflammation is a normal process in the human body as a response to injury from healing process. Meanwhile, chronic inflammation will cause new health problems to patients. Anti-inflammatory agents generally used for those conditions, have several side effects to patients. The aim of this research was to find alternative anti-inflammatory agents, especially from natural sources. Vernonia amygdalina knew locally as “daun afrika” belong to family Apiaceae is one of those potential natural sources for alternative anti-inflammatory agents. This plant is known astraditionalmedicine from East Kalimantanfor health problems caused by the muscle stiffness and used as material in this research. The experimental method of anti-inflammatory measurement using membrane stabilization activity for V. amygdalina leaves extracts. The results showed that significant differences of EC50(p<0.05)achieved between indomethacin as the positive control (26.39 ± 2.91 µg/mL) with V. amygdalina leaves extracts for concentration 1% (131.81 ± 2.95 µg/mL) and 10% (62.54 ± 2.05 µg/mL). EC50 of V.amygdalina leaves extracts showed the potential anti-inflammatory activities. It could be concluded that V. amygdalina leaves extracts to have anti-inflammatory activities, which could be further developed as a new natural source of the anti-inflammatory agents.

Evoecotoxicology: Environmental Changes and Life Features Development during the Evolutionary Process—the Record of the Past at Developmental Stages of Living Organisms

PubMed Central

Herkovits, Jorge

2006-01-01

For most of evolutionary history, scientific understanding of the environment and life forms is extremely limited. In this commentary I discuss the hypothesis that ontogenetic features of living organisms can be considered biomarkers of coevolution between organisms and physicochemical agents during Earth’s history. I provide a new vision of evolution based on correlations between metabolic features and stage-dependent susceptibility of organisms to physicochemical agents with well-known environmental signatures. Thus, developmental features potentially reflect environmental changes during evolution. From this perspective, early multicellular life forms would have flourished in the anoxic Earth more than 2 billion years ago, which is at least 1.2 billion years in advance of available fossil evidence. The remarkable transition to aerobic metabolism in gastrula-stage embryos potentially reflects evolution toward tridermic organisms by 2 billion years ago. Noteworthy changes in embryonic resistance to physicochemical agents at different developmental stages that can be observed in living organisms potentially reflect the influence of environmental stress conditions during different periods of evolutionary history. Evoecotoxicology, as a multidisciplinary and transdisciplinary approach, can enhance our understanding of evolution, including the phylogenetic significance of differences in susceptibility/resistance to physicochemical agents in different organisms. PMID:16882515

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease

PubMed Central

Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

2017-01-01

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date. PMID:28934123

Social Fear Conditioning Paradigm in Virtual Reality: Social vs. Electrical Aversive Conditioning

PubMed Central

Reichenberger, Jonas; Porsch, Sonja; Wittmann, Jasmin; Zimmermann, Verena; Shiban, Youssef

2017-01-01

In a previous study we could show that social fear can be induced and extinguished using virtual reality (VR). In the present study, we aimed to investigate the belongingness effect in an operant social fear conditioning (SFC) paradigm which consisted of an acquisition and an extinction phase. Forty-three participants used a joystick to approach different virtual male agents that served as conditioned stimuli. Participants were randomly allocated to one of two experimental conditions. In the electroshock condition, the unconditioned stimulus (US) used during acquisition was an electric stimulation. In the social threat condition, the US consisted of an offense: a spit in the face, mimicked by a sound and a weak air blast to the participant’s neck combined with an insult. In both groups the US was presented when participants were close to the agent (75% contingency for CS+). Outcome variables included subjective, psychophysiological and behavioral data. As expected, fear and contingency ratings increased significantly during acquisition and the differentiation between CS+ and CS- vanished during extinction. Furthermore, a clear difference in skin conductance between CS+ and CS- at the beginning of the acquisition indicated that SFC had been successful. However, a fast habituation to the US was found toward the end of the acquisition phase for the physiological response. Furthermore, participants showed avoidance behavior toward CS+ in both conditions. The results show that social fear can successfully be induced and extinguished in VR in a human sample. Thus, our paradigm can help to gain insight into learning and unlearning of social fear. Regarding the belongingness effect, the social threat condition benefits from a better differentiation between the aversive and the non-aversive stimuli. As next step we suggest comparing social-phobic patients to healthy controls in order to investigate possible differences in discrimination learning and to foster the development of more efficient treatments for social phobia. PMID:29250000

Social Fear Conditioning Paradigm in Virtual Reality: Social vs. Electrical Aversive Conditioning.

PubMed

Reichenberger, Jonas; Porsch, Sonja; Wittmann, Jasmin; Zimmermann, Verena; Shiban, Youssef

2017-01-01

In a previous study we could show that social fear can be induced and extinguished using virtual reality (VR). In the present study, we aimed to investigate the belongingness effect in an operant social fear conditioning (SFC) paradigm which consisted of an acquisition and an extinction phase. Forty-three participants used a joystick to approach different virtual male agents that served as conditioned stimuli. Participants were randomly allocated to one of two experimental conditions. In the electroshock condition, the unconditioned stimulus (US) used during acquisition was an electric stimulation. In the social threat condition, the US consisted of an offense: a spit in the face, mimicked by a sound and a weak air blast to the participant's neck combined with an insult. In both groups the US was presented when participants were close to the agent (75% contingency for CS+). Outcome variables included subjective, psychophysiological and behavioral data. As expected, fear and contingency ratings increased significantly during acquisition and the differentiation between CS+ and CS- vanished during extinction. Furthermore, a clear difference in skin conductance between CS+ and CS- at the beginning of the acquisition indicated that SFC had been successful. However, a fast habituation to the US was found toward the end of the acquisition phase for the physiological response. Furthermore, participants showed avoidance behavior toward CS+ in both conditions. The results show that social fear can successfully be induced and extinguished in VR in a human sample. Thus, our paradigm can help to gain insight into learning and unlearning of social fear. Regarding the belongingness effect, the social threat condition benefits from a better differentiation between the aversive and the non-aversive stimuli. As next step we suggest comparing social-phobic patients to healthy controls in order to investigate possible differences in discrimination learning and to foster the development of more efficient treatments for social phobia.

Method For Reactivating Solid Catalysts Used For Alklation Reactions

DOEpatents

Ginosar, Daniel M.; Thompson, David N.; Coates, Kyle; Zalewski, David J.; Fox, Robert V.

2005-05-03

A method for reactivating a solid alkylation catalyst is provided which can be performed within a reactor that contains the alkylation catalyst or outside the reactor. Effective catalyst reactivation is achieved whether the catalyst is completely deactivated or partially deactivated. A fluid reactivating agent is employed to dissolve catalyst fouling agents and also to react with such agents and carry away the reaction products. The deactivated catalyst is contacted with the fluid reactivating agent under pressure and temperature conditions such that the fluid reactivating agent is dense enough to effectively dissolve the fouling agents and any reaction products of the fouling agents and the reactivating agent. Useful pressures and temperatures for reactivation include near-critical, critical, and supercritical pressures and temperatures for the reactivating agent. The fluid reactivating agent can include, for example, a branched paraffin containing at least one tertiary carbon atom, or a compound that can be isomerized to a molecule containing at least one tertiary carbon atom.

Method for reactivating solid catalysts used in alkylation reactions

DOEpatents

Ginosar, Daniel M.; Thompson, David N.; Coates, Kyle; Zalewski, David J.; Fox, Robert V.

2003-06-17

A method for reactivating a solid alkylation catalyst is provided which can be performed within a reactor that contains the alkylation catalyst or outside the reactor. Effective catalyst reactivation is achieved whether the catalyst is completely deactivated or partially deactivated. A fluid reactivating agent is employed to dissolve catalyst fouling agents and also to react with such agents and carry away the reaction products. The deactivated catalyst is contacted with the fluid reactivating agent under pressure and temperature conditions such that the fluid reactivating agent is dense enough to effectively dissolve the fouling agents and any reaction products of the fouling agents and the reactivating agent. Useful pressures and temperatures for reactivation include near-critical, critical, and supercritical pressures and temperatures for the reactivating agent. The fluid reactivating agent can include, for example, a branched paraffin containing at least one tertiary carbon atom, or a compound that can be isomerized to a molecule containing at least one tertiary carbon atom.

Preparation and anticoagulant activity of N-succinyl chitosan sulfates.

PubMed

Wang, Tan; Zhou, Yue; Xie, Weiguo; Chen, Lingyun; Zheng, Hua; Fan, Lihong

2012-12-01

In order to develop a promising substitute for heparin, N-succinyl chitosan (NSC) was chemically modified by sulfating agent N(SO(3)Na)(3), which were synthesized with sodium bisulfite and sodium nitrite in aqueous solution. The N-succinyl chitosan sulfates (NSCS) products were characterized by infrared spectroscopy (FT-IR) and (13)C NMR. The degree of substitution (DS) of NSCS depended on the ratio of sulfating agent to N-succinyl chitosan, reaction temperature, reaction time and pH of sulfation agent. N-succinyl chitosan sulfates with DS of 1.97 were obtained under optimal conditions. The in vitro coagulation assay of NSCS was determined by activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) assays. The results showed that NSCS obviously prolonged APTT. The anticoagulant activity strongly depended on DS, molecular weight (M(w)) and concentration of NSCS. The anticoagulant activity of NSCS promoted with the increase of DS and concentration, and NSCS exhibited the best anticoagulant activity with the M(w) of 1.37×10(4). Copyright © 2012. Published by Elsevier B.V.

Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design.

PubMed

Tziona, Paraskevi; Theodosis-Nobelos, Panagiotis; Rekka, Eleni A

2017-01-01

Non-steroidal anti-inflammatory drugs are the oldest and most widely used medicines. However, their untoward effects, especially gastrointestinal toxicity, remain the main obstacle to their application. Because of their mechanism of action, cycloxygenase (COX) inhibition, in combination with the weekly acidic character of most of them, major protective mechanisms of the gastrointestinal system are suppressed and deregulated. In this review, several compounds designed to retain anti-inflammatory activity, but devoid of gastrointestinal side effects, are presented. Thus, gastro-protective drugs, selective COX-2 inhibitors, nitric monoxide- and hydrogen sulphide-releasing agents, prodrugs, lipoxygenase (LOX) inhibitors and dual COX/LOX inhibitors are presented. Their mechanism of action, as well as their advantages and disadvantages are discussed. Efforts, aiming to the development of safe non-steroidal anti-inflammatory agents, are evolving, however there are still several problems concerning gastro-protection to be efficiently solved, thus, design of effective and safe agents for the treatment of inflammatory conditions still remains a major challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Thermal Destruction Of CB Contaminants Bound On Building ...

EPA Pesticide Factsheets

Symposium Paper An experimental and theoretical program has been initiated by the U.S. EPA to investigate issues of chemical/biological agent destruction in incineration systems when the agent in question is bound on common porous building interior materials. This program includes 3-dimensional computational fluid dynamics modeling with matrix-bound agent destruction kinetics, bench-scale experiments to determine agent destruction kinetics while bound on various matrices, and pilot-scale experiments to scale-up the bench-scale experiments to a more practical scale. Finally, model predictions are made to predict agent destruction and combustion conditions in two full-scale incineration systems that are typical of modern combustor design.

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

[Problem of bioterrorism under modern conditions].

PubMed

Vorob'ev, A A; Boev, B V; Bondarenko, V M; Gintsburg, A L

2002-01-01

It is practically impossible to discuss the problem of bioterrorism (BT) and to develop effective programs of decreasing the losses and expenses suffered by the society from the BT acts without evaluation of the threat and prognosis of consequences based on research and empiric data. Stained international situation following the act of terrorism (attack on the USA) on September 11, 2001, makes the scenarios of the bacterial weapon use (the causative agents of plague, smallpox, anthrax, etc.) by international terrorists most probable. In this connection studies on the analysis and prognostication of the consequences of BT, including mathematical and computer modelling, are necessary. The authors present the results of initiative studies on the analysis and prognostication of the consequences of the hypothetical act of BT with the use of the smallpox causative agent in a city with the population of about 1,000,000 inhabitants. The analytical prognostic studies on the operative analysis and prognostication of the consequences of the BT act with the use of the smallpox causative agent has demonstrated that the mathematical (computer) model of the epidemic outbreak of smallpox is an effective instrument of calculation studies. Prognostic evaluations of the consequences of the act of BT under the conditions of different reaction of public health services (time of detection, interventions) have been obtained with the use of modelling. In addition, the computer model is necessary for training health specialists to react adequately to the acts of BT with the use of different kinds of bacteriological weapons.

Multi-agent integrated password management (MIPM) application secured with encryption

NASA Astrophysics Data System (ADS)

Awang, Norkhushaini; Zukri, Nurul Hidayah Ahmad; Rashid, Nor Aimuni Md; Zulkifli, Zuhri Arafah; Nazri, Nor Afifah Mohd

2017-10-01

Users use weak passwords and reuse them on different websites and applications. Password managers are a solution to store login information for websites and help users log in automatically. This project developed a system that acts as an agent managing passwords. Multi-Agent Integrated Password Management (MIPM) is an application using encryption that provides users with secure storage of their login account information such as their username, emails and passwords. This project was developed on an Android platform with an encryption agent using Java Agent Development Environment (JADE). The purpose of the embedded agents is to act as a third-party software to ease the encryption process, and in the future, the developed encryption agents can form part of the security system. This application can be used by the computer and mobile users. Currently, users log into many applications causing them to use unique passwords to prevent password leaking. The crypto agent handles the encryption process using an Advanced Encryption Standard (AES) 128-bit encryption algorithm. As a whole, MIPM is developed on the Android application to provide a secure platform to store passwords and has high potential to be commercialised for public use.

Large-Scale Water Resources Management within the Framework of GLOWA-Danube - Part B: The Water Supply Model

NASA Astrophysics Data System (ADS)

Nickel, D.; Barthel, R.; Schmid, C.; Braun, J.

2003-04-01

The research project GLOWA-Danube, financed by the German Federal Government, investigates long-term changes in the water cycle of the Upper Danube river basin in light of global climatic change. Its concrete aim is to build a fully integrated decision support tool that combines the competence of eleven different institutes in domains covering all major aspects governing the water cycle - from the formation of clouds to groundwater flow patterns to the behaviour of the water consumer. The research group "Water Supply" at the Institute of Hydraulic Engineering (IWS), Universitaet Stuttgart, has the central task of creating an agent-based model of the water supply sector. The Water Supply model will act as a link between the various physical models determining water quality and availability on the one hand and the actors models determining water demand on the other, which together form the tool DANUBIA. Ultimately, with the help of scenario testing, the water supply model will indicate the ability of the water supply system in the Upper Danube catchment to adapt to changing boundary conditions using different management approaches. The specific aim of the Water Supply model is the creation of a model which is not only able to simulate the present day system of water extraction, treatment and distribution but also its development and change with time. As most changes to the system are brought about by decisions made by relevant actors in the field of water management or their behaviour (in response to political and economic boundary conditions, changes in water demand or water quality, advances in technology etc.), the use of agent-based modelling was chosen, whereby an agent is seen as a computer system (in our case representing a human or group of humans) which is aware of its environment, has defined objectives and is able to act independently in order to meet these objectives. Whereas agent-based modelling has received much attention over the past decades, the use of this type of modelling for water supply systems is something very new. The initial step is the development of a conceptual water supply model (using JAVA), in which both the model boundaries and area of expertise as well as parameters to be exchanged between the Water Supply model and other models are defined. The data required to create model for such a large area is not available from the authorities, common interest organisations or in the public statistics. In order to gain access to more specific information regarding individual water supply companies, the Water Supply group is currently carrying out a wide-spread questionnaire addressed to all water supply companies in the GLOWA-Danube model area - well over 1000 in total in Bavaria, Baden-Wuerttemberg, Austria and Switzerland. The questionnaire contains questions pertaining to the two distinct fields, "economics and pricing" and "technical aspects", and aims at gathering information regarding the present day situation of the water supply system, the developments over the past 10 years as well as planned developments for the immediate future. Later, the focus will shift towards the stakeholders from the field of water resources management. A catalogue of decision-making rules will be prepared as a basis for discussion and will be debated with the relevant stakeholders. These rules will provide the basis for decision-making algorithms which will allow model agents to respond to their environment, communicate with one anther and behave in a goal-oriented manner to bring about change in the water supply system in response to changing conditions with regard to the climate, water quality, political and social boundary conditions, and changing demand.

A spatial web/agent-based model to support stakeholders' negotiation regarding land development.

PubMed

Pooyandeh, Majeed; Marceau, Danielle J

2013-11-15

Decision making in land management can be greatly enhanced if the perspectives of concerned stakeholders are taken into consideration. This often implies negotiation in order to reach an agreement based on the examination of multiple alternatives. This paper describes a spatial web/agent-based modeling system that was developed to support the negotiation process of stakeholders regarding land development in southern Alberta, Canada. This system integrates a fuzzy analytic hierarchy procedure within an agent-based model in an interactive visualization environment provided through a web interface to facilitate the learning and negotiation of the stakeholders. In the pre-negotiation phase, the stakeholders compare their evaluation criteria using linguistic expressions. Due to the uncertainty and fuzzy nature of such comparisons, a fuzzy Analytic Hierarchy Process is then used to prioritize the criteria. The negotiation starts by a development plan being submitted by a user (stakeholder) through the web interface. An agent called the proposer, which represents the proposer of the plan, receives this plan and starts negotiating with all other agents. The negotiation is conducted in a step-wise manner where the agents change their attitudes by assigning a new set of weights to their criteria. If an agreement is not achieved, a new location for development is proposed by the proposer agent. This process is repeated until a location is found that satisfies all agents to a certain predefined degree. To evaluate the performance of the model, the negotiation was simulated with four agents, one of which being the proposer agent, using two hypothetical development plans. The first plan was selected randomly; the other one was chosen in an area that is of high importance to one of the agents. While the agents managed to achieve an agreement about the location of the land development after three rounds of negotiation in the first scenario, seven rounds were required in the second scenario. The proposed web/agent-based model facilitates the interaction and learning among stakeholders when facing multiple alternatives. Copyright © 2013 Elsevier Ltd. All rights reserved.

Distributed consensus for discrete-time heterogeneous multi-agent systems

NASA Astrophysics Data System (ADS)

Zhao, Huanyu; Fei, Shumin

2018-06-01

This paper studies the consensus problem for a class of discrete-time heterogeneous multi-agent systems. Two kinds of consensus algorithms will be considered. The heterogeneous multi-agent systems considered are converted into equivalent error systems by a model transformation. Then we analyse the consensus problem of the original systems by analysing the stability problem of the error systems. Some sufficient conditions for consensus of heterogeneous multi-agent systems are obtained by applying algebraic graph theory and matrix theory. Simulation examples are presented to show the usefulness of the results.

Can partisan voting lead to truth?

NASA Astrophysics Data System (ADS)

Masuda, Naoki; Redner, S.

2011-02-01

We study an extension of the voter model in which each agent is endowed with an innate preference for one of two states that we term as 'truth' or 'falsehood'. Due to interactions with neighbors, an agent that innately prefers truth can be persuaded to adopt a false opinion (and thus be discordant with its innate preference) or the agent can possess an internally concordant 'true' opinion. Parallel states exist for agents that inherently prefer falsehood. We determine the conditions under which a population of such agents can ultimately reach a consensus for the truth, reach a consensus for falsehood, or reach an impasse where an agent tends to adopt the opinion that is in internal concordance with its innate preference with the outcome that consensus is never achieved.

Method for distributed agent-based non-expert simulation of manufacturing process behavior

DOEpatents

Ivezic, Nenad; Potok, Thomas E.

2004-11-30

A method for distributed agent based non-expert simulation of manufacturing process behavior on a single-processor computer comprises the steps of: object modeling a manufacturing technique having a plurality of processes; associating a distributed agent with each the process; and, programming each the agent to respond to discrete events corresponding to the manufacturing technique, wherein each discrete event triggers a programmed response. The method can further comprise the step of transmitting the discrete events to each agent in a message loop. In addition, the programming step comprises the step of conditioning each agent to respond to a discrete event selected from the group consisting of a clock tick message, a resources received message, and a request for output production message.

Agent planning in AgScala

NASA Astrophysics Data System (ADS)

Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

2013-10-01

Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

Cell mechanics in biomedical cavitation

PubMed Central

Wang, Qianxi; Manmi, Kawa; Liu, Kuo-Kang

2015-01-01

Studies on the deformation behaviours of cellular entities, such as coated microbubbles and liposomes subject to a cavitation flow, become increasingly important for the advancement of ultrasonic imaging and drug delivery. Numerical simulations for bubble dynamics of ultrasound contrast agents based on the boundary integral method are presented in this work. The effects of the encapsulating shell are estimated by adapting Hoff's model used for thin-shell contrast agents. The viscosity effects are estimated by including the normal viscous stress in the boundary condition. In parallel, mechanical models of cell membranes and liposomes as well as state-of-the-art techniques for quantitative measurement of viscoelasticity for a single cell or coated microbubbles are reviewed. The future developments regarding modelling and measurement of the material properties of the cellular entities for cutting-edge biomedical applications are also discussed. PMID:26442142

APOBEC3G: a Double Agent in Defense

PubMed Central

Smith, Harold C.

2011-01-01

APOBEC3G (A3G) is an effective cellular host defense factor under experimental conditions in which a functional form of the HIV-encoded protein Vif cannot be expressed. Wild type Vif targets A3G for proteasomal degradation and along with it, any host defense advantage A3G might provide is severely diminished or lost. Recent evidence cast doubt on the potency of A3G in host defense and suggested that it could, under some circumstances, promote the emergence of more virulent HIV strains. In this article, I argue that it is time to recognize that A3G has the potential to act as a double agent. The path forward relies on understanding how cellular and viral regulatory mechanisms enable A3G antiviral function and on developing novel research reagents to explore these pathways. PMID:21239176

RAFT polymerization and some of its applications.

PubMed

Moad, Graeme; Rizzardo, Ezio; Thang, San H

2013-08-01

Reversible addition-fragmentation chain transfer (RAFT) is one of the most robust and versatile methods for controlling radical polymerization. With appropriate selection of the RAFT agent for the monomers and reaction conditions, it is applicable to the majority of monomers subject to radical polymerization. The process can be used in the synthesis of well-defined homo-, gradient, diblock, triblock, and star polymers and more complex architectures, which include microgels and polymer brushes. In this Focus Review we describe how the development of RAFT and RAFT application has been facilitated by the adoption of continuous flow techniques using tubular reactors and through the use of high-throughput methodology. Applications described include the use of RAFT in the preparation of polymers for optoelectronics, block copolymer therapeutics, and star polymer rheology control agents. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative Evaluation of Firefighting Foam Agents

DTIC Science & Technology

1979-08-01

incorporating these basic concepts under a military specification, are being produced on a world-wide MIL - F - 24385 , Navy (reference 6). basis. The original...Program Office for 24385 (Navy), Fire Extinguishing Aircraft Ground Fire Suppression and Agent, Aqueous- F Ilm-Forming-Foam Rescue, SMF, AGFSkS 71-1...fluoroprotein foams (FPF), and three protein foam (?’ F ) agents. Large-scale fire tests were performed under fixed fire conditions employing air

Area and percent of forest affected by biotic agents beyond reference conditions

Treesearch

Jeffrey A. Mai

2012-01-01

Criterion 3, Indicator 15, of the Montréal Process identifies the impact that biotic processes and agents have on forests (Montréal Process Working Group 2007). Where change due to these agents and processes occurs beyond a critical threshold, forest ecosystem health and vitality may be significantly altered and a forest’s ability to recover could be reduced or lost....

Rituximab treatment in primary angiitis of the central nervous system.

PubMed

Patel, Shreeya; Ross, Laura; Oon, Shereen; Nikpour, Mandana

2018-06-01

Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis affecting the brain and spinal cord. Treatment with biological agents has revolutionised the treatment of many rheumatic conditions but there is scant literature regarding the use of biological agents in PACNS. We present three cases of PACNS treated with rituximab, including two cases of relapsed disease, and a literature review suggesting a role for rituximab in this condition. © 2018 Royal Australasian College of Physicians.

Potential of Neoactinolaimus as a biological control agent of root-knot and reniform nematodes

USDA-ARS?s Scientific Manuscript database

The predatory nematode Neoactinolaimus spp. (family Actinolaimidae) was examined as a potential biological control agent against root-knot (Meloidogyne spp.) and reniform (Rotylenchulus reniformis) nematodes in laboratory conditions. Neoactinolaimus possesses a large odontostylet to puncture the cu...

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR CHLOROETHANE (EXTERNAL REVIEW DRAFT)

EPA Science Inventory

Chloroethane (CE) is a gaseous halohydrocarbon under ambient conditions. Its uses include: a topical analgesic, an anesthetic when mixed with nitrous dioxide or trichloroethane, a degreasing agent, and an agent to blow styrene in foaming operations. Anecdotal human reports indica...

Laboratory security and emergency response guidance for laboratories working with select agents. Centers for Disease Control and Prevention.

PubMed

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.

Facile preparation of uniform FeSe2 nanoparticles for PA/MR dual-modal imaging and photothermal cancer therapy

NASA Astrophysics Data System (ADS)

Fu, Tingting; Chen, Yuyan; Hao, Jiali; Wang, Xiaoyong; Liu, Gang; Li, Yonggang; Liu, Zhuang; Cheng, Liang

2015-12-01

Recently, magnetic photothermal nanomaterials have emerged as a new class of bio-nanomaterials for application in cancer diagnosis and therapy. Hence, we developed a new kind of magnetic nanomaterials, iron diselenide (FeSe2) nanoparticles, for multimodal imaging-guided photothermal therapy (PTT) to improve the efficacy of cancer treatment. By controlling the reaction time and temperature, FeSe2 nanoparticles were synthesized by a simple solution-phase method. After modification with polyethylene glycol (PEG), the obtained FeSe2-PEG nanoparticles showed high stability under various physiological conditions. FeSe2-PEG could serve as a T2-weighted magnetic resonance (MR) imaging contrast agent because of its strong superparamagnetic properties, with its r2 relaxivity determined to be 133.38 mM-1 S-1, a value higher than that of the clinically used Feridex. On the other hand, with high absorbance in the near-infrared (NIR) region, FeSe2-PEG also appeared to be a useful contrast agent for photoacoustic imaging (PA) as well as an effective photothermal agent for PTT cancer treatment, as demonstrated in our animal tumor model experiments. Moreover, long-term toxicity tests have proven that FeSe2-PEG nanoparticles after systematic administration rendered no appreciable toxicity to the treated animals, and could be gradually excreted from the major organs of mice. Our work indicates that FeSe2-PEG nanoparticles would be a new class of theranostic agents promising for application in bioimaging and cancer therapy.Recently, magnetic photothermal nanomaterials have emerged as a new class of bio-nanomaterials for application in cancer diagnosis and therapy. Hence, we developed a new kind of magnetic nanomaterials, iron diselenide (FeSe2) nanoparticles, for multimodal imaging-guided photothermal therapy (PTT) to improve the efficacy of cancer treatment. By controlling the reaction time and temperature, FeSe2 nanoparticles were synthesized by a simple solution-phase method. After modification with polyethylene glycol (PEG), the obtained FeSe2-PEG nanoparticles showed high stability under various physiological conditions. FeSe2-PEG could serve as a T2-weighted magnetic resonance (MR) imaging contrast agent because of its strong superparamagnetic properties, with its r2 relaxivity determined to be 133.38 mM-1 S-1, a value higher than that of the clinically used Feridex. On the other hand, with high absorbance in the near-infrared (NIR) region, FeSe2-PEG also appeared to be a useful contrast agent for photoacoustic imaging (PA) as well as an effective photothermal agent for PTT cancer treatment, as demonstrated in our animal tumor model experiments. Moreover, long-term toxicity tests have proven that FeSe2-PEG nanoparticles after systematic administration rendered no appreciable toxicity to the treated animals, and could be gradually excreted from the major organs of mice. Our work indicates that FeSe2-PEG nanoparticles would be a new class of theranostic agents promising for application in bioimaging and cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06840a

Both glucocentric and cardiocentric approaches are necessary for a resilient disease such as diabetes.

PubMed

Caramelli, Bruno; Gualandro, Danielle Menosi

2018-03-01

Diabetes mellitus (DM) is a complex disease that compromises almost all systems in the human organism. Independently of the intrinsic mechanisms, the source of all consequences of DM is hyperglycemia, a condition associated to intense metabolic changes that will lead to increased morbidity and mortality in the long term. Several different therapeutic hypoglycemic oral agents were developed and significantly facilitated the treatment of hyperglycemia acting at different sites, since patients could take more than one agent. This glucocentric approach was somehow criticized as those hypoglycemic drugs have shown weaker than expected benefits in terms of cardiovascular outcomes and there was a sub use of statins and antihypertensive agents in this population. On the other hand, the catastrophic cardiovascular consequences of hypoglycemia in older adults submitted to tight glycemic control and the results of recent clinical trials that showed impressive reduction in cardiovascular outcomes with less potent antidiabetic agents seem to pave the way to a cardiocentric approach including a lax treatment of DM. Interestingly, the results obtained in recent studies with SGLT2 inhibitors are being mostly attributed to mechanisms other than its hypoglycemic effect in spite of including patients at high cardiovascular risk already taking hypoglycemic agents. Considering the worldwide growing number of patients with diabetes, caregivers must follow a dialectical thinking and choose a synthesis approach where glycemic control is the first and foremost target to be achieved, followed by control of cardiovascular risk factors.

The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

PubMed Central

Tucci, Sonia A; Boyland, Emma J; Halford, Jason CG

2010-01-01

Obesity is a global epidemic associated with significant morbidity and mortality in adults and ill health in children. A proven successful approach in weight management has been the disruption of nutrient digestion, with orlistat having been used to treat obesity for the last 10 years. Although orlistat-induced weight loss remains modest, it produces meaningful reductions in risk factors for obesity-related conditions such as diabetes and cardiovascular disease. Moreover, this lipase inhibitor is free of the serious side effects that have dogged appetite-suppressing drugs. This success had driven investigation into new generation nutraceuticals, supplements and pharmaceutical agents that inhibit the breakdown of complex carbohydrates and fats within the gut. This review focuses on agents purported to inhibit intestinal enzymes responsible for macronutrient digestion. Except for some synthetic products, the majority of agents reviewed are either botanical extracts or bacterial products. Currently, carbohydrate digestion inhibitors are under development to improve glycemic control and these may also induce some weight loss. However, colonic fermentation induced side effects, such as excess gas production, remain an issue for these compounds. The α-glucosidase inhibitor acarbose, and the α-amylase inhibitor phaseolamine, have been used in humans with some promising results relating to weight loss. Nonetheless, few of these agents have made it into clinical studies and without any clinical proof of concept or proven efficacy it is unlikely any will enter the market soon. PMID:21437083

Preclinical Pharmacology and Structure-Activity Studies of Epothilones

NASA Astrophysics Data System (ADS)

Altmann, Karl-Heinz

Microtubule inhibitors are an important class of anticancer agents (1), with clinical applications in the treatment of a variety of cancer types, either as single agents or as part of different combination regimens (2, 3). Microtubule-interacting agents can be grouped into two distinct functional classes, namely, compounds that inhibit the assembly of tubulin heterodimers into microtubule polymers (“tubulin polymerization inhibitors”) and those that stabilize microtubules under normally destabilizing conditions (“microtubule stabilizers”) (4). The latter will also promote the assembly of tubulin heterodimers into microtubule polymers and, as will be discussed later, the induction of tubulin polymerization is often used as a biochemical readout for a quantitative assessment of the interaction of microtubule-stabilizing agents with tubulin. Tubulin polymerization inhibitors such as vincristine and vinblastine have been employed in cancer therapy for more than 40 years (vincristine and vinblastine received FDA approval in 1963 and 1965, respectively). In contrast, the clinical history of microtubule-stabilizing agents is significantly shorter and its beginning dates back no more than 15 years. The first microtubule stabilizer to be introduced into clinical practice was the natural product taxol (paclitaxel; Taxol®) in 1993 (Fig. 1), with FDA approval for the semi-synthetic taxol analog docetaxel (Taxotere®) following three years later. Both compounds rapidly became an important part of today’s armamentarium in the battle against cancer,which marks the emergence of microtubule-stabilizing anti-cancer drugs as an important milestone in the development of modern cancer chemotherapy (5).

Making the Best Better: Assessing the Professional Development Needs of Kentucky 4-H Agents

ERIC Educational Resources Information Center

Stamper, Charles E.

2017-01-01

University of Kentucky Cooperative Extension Specialist for 4-H Youth Development conducted a comprehensive needs assessment of the professional development system of Kentucky 4-H Youth Development Agents. A qualitative research design was used to give nine 4-H Agents the opportunity to identify the strengths and challenges of the current…

User modeling for distributed virtual environment intelligent agents

NASA Astrophysics Data System (ADS)

Banks, Sheila B.; Stytz, Martin R.

1999-07-01

This paper emphasizes the requirement for user modeling by presenting the necessary information to motivate the need for and use of user modeling for intelligent agent development. The paper will present information on our current intelligent agent development program, the Symbiotic Information Reasoning and Decision Support (SIRDS) project. We then discuss the areas of intelligent agents and user modeling, which form the foundation of the SIRDS project. Included in the discussion of user modeling are its major components, which are cognitive modeling and behavioral modeling. We next motivate the need for and user of a methodology to develop user models to encompass work within cognitive task analysis. We close the paper by drawing conclusions from our current intelligent agent research project and discuss avenues of future research in the utilization of user modeling for the development of intelligent agents for virtual environments.

Conditioned pain modulation: a predictor for development and treatment of neuropathic pain.

PubMed

Granovsky, Yelena

2013-09-01

Psychophysical evaluation of endogenous pain inhibition via conditioned pain modulation (CPM) represents a new generation of laboratory tests for pain assessment. In this review we discuss recent findings on CPM in neuropathic pain and refer to psychophysical, neurophysiological, and methodological aspects of its clinical implications. Typically, chronic neuropathic pain patients express less efficient CPM, to the extent that incidence of acquiring neuropathic pain (e.g. post-surgery) and its intensity can be predicted by a pre-surgery CPM assessment. Moreover, pre-treatment CPM evaluation may assist in the correct choice of serotonin-noradrenalin reuptake inhibitor analgesic agents for individual patients. Evaluation of pain modulation capabilities can serve as a step forward in individualizing pain medicine.

Climate Change and Socio-Hydrological Dynamics: Adaptations and Feedbacks

NASA Astrophysics Data System (ADS)

Woyessa, Yali E.; Welderufael, Worku A.

2012-10-01

A functioning ecological system results in ecosystem goods and services which are of direct value to human beings. Ecosystem services are the conditions and processes which sustain and fulfil human life, and maintain biodiversity and the production of ecosystem goods. However, human actions affect ecological systems and the services they provide through various activities, such as land use, water use, pollution and climate change. Climate change is perhaps one of the most important sustainable development challenges that threatens to undo many of the development efforts being made to reach the targets set for the Millennium Development Goals. Understanding the provision of ecosystem services and how they change under different scenarios of climate and biophysical conditions could assist in bringing the issue of ecosystem services into decision making process. Similarly, the impacts of land use change on ecosystems and biodiversity have received considerable attention from ecologists and hydrologists alike. Land use change in a catchment can impact on water supply by altering hydrological processes, such as infiltration, groundwater recharge, base flow and direct runoff. In the past a variety of models were used for predicting landuse changes. Recently, the focus has shifted away from using mathematically oriented models to agent-based modeling (ABM) approach to simulate land use scenarios. The agent-based perspective, with regard to land-use cover change, is centered on the general nature and rules of land-use decision making by individuals. A conceptual framework is developed to investigate the possibility of incorporating the human dimension of land use decision and climate change model into a hydrological model in order to assess the impact of future land use scenario and climate change on the ecological system in general and water resources in particular.

Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions

NASA Astrophysics Data System (ADS)

Gibard, Clémentine; Bhowmik, Subhendu; Karki, Megha; Kim, Eun-Kyong; Krishnamurthy, Ramanarayanan

2018-02-01

Prebiotic phosphorylation of (pre)biological substrates under aqueous conditions is a critical step in the origins of life. Previous investigations have had limited success and/or require unique environments that are incompatible with subsequent generation of the corresponding oligomers or higher-order structures. Here, we demonstrate that diamidophosphate (DAP)—a plausible prebiotic agent produced from trimetaphosphate—efficiently (amido)phosphorylates a wide variety of (pre)biological building blocks (nucleosides/tides, amino acids and lipid precursors) under aqueous (solution/paste) conditions, without the need for a condensing agent. Significantly, higher-order structures (oligonucleotides, peptides and liposomes) are formed under the same phosphorylation reaction conditions. This plausible prebiotic phosphorylation process under similar reaction conditions could enable the systems chemistry of the three classes of (pre)biologically relevant molecules and their oligomers, in a single-pot aqueous environment.

Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions

NASA Astrophysics Data System (ADS)

Gibard, Clémentine; Bhowmik, Subhendu; Karki, Megha; Kim, Eun-Kyong; Krishnamurthy, Ramanarayanan

2017-11-01

Prebiotic phosphorylation of (pre)biological substrates under aqueous conditions is a critical step in the origins of life. Previous investigations have had limited success and/or require unique environments that are incompatible with subsequent generation of the corresponding oligomers or higher-order structures. Here, we demonstrate that diamidophosphate (DAP)-a plausible prebiotic agent produced from trimetaphosphate - efficiently (amido)phosphorylates a wide variety of (pre)biological building blocks (nucleosides/tides, amino acids and lipid precursors) under aqueous (solution/paste) conditions, without the need for a condensing agent. Significantly, higher-order structures (oligonucleotides, peptides and liposomes) are formed under the same phosphorylation reaction conditions. This plausible prebiotic phosphorylation process under similar reaction conditions could enable the systems chemistry of the three classes of (pre)biologically relevant molecules and their oligomers, in a single-pot aqueous environment.

Work of community health agents in the Family Health Strategy: meta-synthesis

PubMed Central

Alonso, Carolina Maria do Carmo; Béguin, Pascal Daniel; Duarte, Francisco José de Castro Moura

2018-01-01

ABSTRACT OBJECTIVE To systematize and analyze the evidence from qualitative studies that address the perception of Brazilian Community Health Agents about their work. METHODS This is a systematic review of the meta-synthesis type on the work of community health agents, carried out from the Virtual Health Library using the descriptors “Agente Comunitário de Saúde” and “Trabalho”, in Portuguese. The strategy was constructed by crossing descriptors, using the Boolean operator “AND”, and filtering Brazilian articles, published from 2004 to 2014, which resulted in 129 identified articles. We removed quantitative or quanti-qualitative research articles, essays, debates, literature reviews, reports of experiences, and research that did not include Brazilian Community Health Agents as subjects. Using these criteria, we selected and analyzed 33 studies that allowed us to identify common subjects and differences between them, to group the main conclusions, to classify subjects, and to interpret the content. RESULTS The analysis resulted in three thematic units: characteristics of the work of community health agents, problems related to the work of community health agents, and positive aspects of the work of community health agents. On the characteristics, we could see that the work of the community health agents is permeated by the political and social dimensions of the health work with predominant use of light technologies. The main input is the knowledge that this professional obtains with the contact with families, which is developed with home visits. On the problems in the work of community health agents, we could identify the lack of limits in their attributions, poor conditions, obstacles in the relationship with the community and teams, weak professional training, and bureaucracy. The positive aspects we identified were the recognition of the work by families, resolution, bonding, work with peers, and work close to home. CONCLUSIONS This review provided an overview of the difficulties and positive aspects that are present in the daily work of community health agents. Given this, we have raised two challenges. The first one refers to how public policy makers need to appropriation the research results and the second one refers to the need to invest in studies that are designed to generate solutions for the difficulties faced by community health agents in their work. PMID:29489997

Work of community health agents in the Family Health Strategy: meta-synthesis.

PubMed

Alonso, Carolina Maria do Carmo; Béguin, Pascal Daniel; Duarte, Francisco José de Castro Moura

2018-01-01

OBJECTIVE To systematize and analyze the evidence from qualitative studies that address the perception of Brazilian Community Health Agents about their work. METHODS This is a systematic review of the meta-synthesis type on the work of community health agents, carried out from the Virtual Health Library using the descriptors "Agente Comunitário de Saúde" and "Trabalho", in Portuguese. The strategy was constructed by crossing descriptors, using the Boolean operator "AND", and filtering Brazilian articles, published from 2004 to 2014, which resulted in 129 identified articles. We removed quantitative or quanti-qualitative research articles, essays, debates, literature reviews, reports of experiences, and research that did not include Brazilian Community Health Agents as subjects. Using these criteria, we selected and analyzed 33 studies that allowed us to identify common subjects and differences between them, to group the main conclusions, to classify subjects, and to interpret the content. RESULTS The analysis resulted in three thematic units: characteristics of the work of community health agents, problems related to the work of community health agents, and positive aspects of the work of community health agents. On the characteristics, we could see that the work of the community health agents is permeated by the political and social dimensions of the health work with predominant use of light technologies. The main input is the knowledge that this professional obtains with the contact with families, which is developed with home visits. On the problems in the work of community health agents, we could identify the lack of limits in their attributions, poor conditions, obstacles in the relationship with the community and teams, weak professional training, and bureaucracy. The positive aspects we identified were the recognition of the work by families, resolution, bonding, work with peers, and work close to home. CONCLUSIONS This review provided an overview of the difficulties and positive aspects that are present in the daily work of community health agents. Given this, we have raised two challenges. The first one refers to how public policy makers need to appropriation the research results and the second one refers to the need to invest in studies that are designed to generate solutions for the difficulties faced by community health agents in their work.

Acoustic characterization of ultrasound contrast microbubbles and echogenic liposomes: Applications to imaging and drug-delivery

NASA Astrophysics Data System (ADS)

Paul, Shirshendu

Micron- to nanometer - sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes (ELIPs), are being actively developed for possible clinical implementations in diagnostic imaging and ultrasound mediated drug/gene delivery. The primary objective of this thesis is to characterize the acoustic behavior of and the ultrasound-mediated contents release from these contrast agents for developing multi-functional ultrasound contrast agents. Subharmonic imaging using contrast microbubbles can improve image quality by providing a higher signal to noise ratio. However, the design and development of contrast microbubbles with favorable subharmonic behavior requires accurate mathematical models capable of predicting their nonlinear dynamics. To this goal, 'strain-softening' viscoelastic interfacial models of the encapsulation were developed and subsequently utilized to simulate the dynamics of encapsulated microbubbles. A hierarchical two-pronged approach of modeling --- a model is applied to one set of experimental data to obtain the model parameters (material characterization), and then the model is validated against a second independent experiment --- is demonstrated in this thesis for two lipid coated (SonazoidRTM and DefinityRTM) and a few polymer (polylactide) encapsulated microbubbles. The proposed models were successful in predicting several experimentally observed behaviors e.g., low subharmonic thresholds and "compression-only" radial oscillations. Results indicate that neglecting the polydisperse size distribution of contrast agent suspensions, a common practice in the literature, can lead to inaccurate results. In vitro experimental investigation of the dependence of subharmonic response from these microbubbles on the ambient pressure is also in conformity with the recent numerical investigations, showing both increase or decrease under appropriate excitation conditions. Experimental characterization of the ELIPs and polymersomes was performed with the goal of demonstrating their potential as ultrasound agents with simultaneous imaging and drug/gene delivery applications --- 'dual-purpose' contrast agents. Both in vitro acoustic studies and ultrasound imaging (performed in NDSU by our collaborators) showed the echogenicity of the various formulations studied. We believe that this echogenicity results from the larger diameter liposomes present in the polydisperse suspension obtained after reconstitution of the lyophilized powders. Although, ultrasound excitation (< 5 MHz) alone was incapable of causing optimal release of contents, a dual-triggering strategy (with enzymes or redox) proved successful, resulting in a total release of up to 80-90%. Considering these experimental results, it can be concluded that these novel formulations hold the potential of providing powerful treatment strategies for many diseases, including cardiovascular ones and various cancers.

Basic emotions and adaptation. A computational and evolutionary model.

PubMed

Pacella, Daniela; Ponticorvo, Michela; Gigliotta, Onofrio; Miglino, Orazio

2017-01-01

The core principles of the evolutionary theories of emotions declare that affective states represent crucial drives for action selection in the environment and regulated the behavior and adaptation of natural agents in ancestrally recurrent situations. While many different studies used autonomous artificial agents to simulate emotional responses and the way these patterns can affect decision-making, few are the approaches that tried to analyze the evolutionary emergence of affective behaviors directly from the specific adaptive problems posed by the ancestral environment. A model of the evolution of affective behaviors is presented using simulated artificial agents equipped with neural networks and physically inspired on the architecture of the iCub humanoid robot. We use genetic algorithms to train populations of virtual robots across generations, and investigate the spontaneous emergence of basic emotional behaviors in different experimental conditions. In particular, we focus on studying the emotion of fear, therefore the environment explored by the artificial agents can contain stimuli that are safe or dangerous to pick. The simulated task is based on classical conditioning and the agents are asked to learn a strategy to recognize whether the environment is safe or represents a threat to their lives and select the correct action to perform in absence of any visual cues. The simulated agents have special input units in their neural structure whose activation keep track of their actual "sensations" based on the outcome of past behavior. We train five different neural network architectures and then test the best ranked individuals comparing their performances and analyzing the unit activations in each individual's life cycle. We show that the agents, regardless of the presence of recurrent connections, spontaneously evolved the ability to cope with potentially dangerous environment by collecting information about the environment and then switching their behavior to a genetically selected pattern in order to maximize the possible reward. We also prove the determinant presence of an internal time perception unit for the robots to achieve the highest performance and survivability across all conditions.

Rituximab in the treatment of follicular lymphoma: the future of biosimilars in the evolving therapeutic landscape

PubMed Central

Subramanian, Janakiraman; Cavenagh, Jamie; Desai, Bhardwaj; Jacobs, Ira

2017-01-01

Follicular lymphoma (FL) is the second most common type of non-Hodgkin’s lymphoma. FL is an incurable disease with treatment options ranging from a “watch-and-wait” approach to localized therapy with radiation or systemic therapy with rituximab in combination with chemotherapy regimens. This review summarizes the role of rituximab across the spectrum of FL treatment and the evolving therapeutic landscape with the emergence of novel agents currently in clinical development. Despite the prospect of new agents on the horizon, it is widely accepted that rituximab will remain as the cornerstone of therapy because of its established long-term efficacy. Many biologics, including rituximab, have lost exclusivity of composition-of-matter patent or will do so in the next few years, which is a concern for patients and physicians alike. Moreover, access to rituximab is challenging, particularly in countries with restricted resources. Together, these concerns have fueled the development of safe and effective biosimilars. The term “biosimilar” refers to a biologic product that is highly similar to an approved reference (or originator) product, notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences in purity, potency, or safety. Biosimilars are developed to treat the same condition(s) using the same treatment regimens as an approved reference biologic, and have the potential to increase access to more affordable treatment of FL. Herein, we also discuss the potential benefits of eagerly awaited rituximab biosimilars, which may mitigate the impact of the lack of access to rituximab. PMID:28479860

Quadratic stabilisability of multi-agent systems under switching topologies

NASA Astrophysics Data System (ADS)

Guan, Yongqiang; Ji, Zhijian; Zhang, Lin; Wang, Long

2014-12-01

This paper addresses the stabilisability of multi-agent systems (MASs) under switching topologies. Necessary and/or sufficient conditions are presented in terms of graph topology. These conditions explicitly reveal how the intrinsic dynamics of the agents, the communication topology and the external control input affect stabilisability jointly. With the appropriate selection of some agents to which the external inputs are applied and the suitable design of neighbour-interaction rules via a switching topology, an MAS is proved to be stabilisable even if so is not for each of uncertain subsystem. In addition, a method is proposed to constructively design a switching rule for MASs with norm-bounded time-varying uncertainties. The switching rules designed via this method do not rely on uncertainties, and the switched MAS is quadratically stabilisable via decentralised external self-feedback for all uncertainties. With respect to applications of the stabilisability results, the formation control and the cooperative tracking control are addressed. Numerical simulations are presented to demonstrate the effectiveness of the proposed results.

Percolation and cooperation with mobile agents: geometric and strategy clusters.

PubMed

Vainstein, Mendeli H; Brito, Carolina; Arenzon, Jeferson J

2014-08-01

We study the conditions for persistent cooperation in an off-lattice model of mobile agents playing the Prisoner's Dilemma game with pure, unconditional strategies. Each agent has an exclusion radius r(P), which accounts for the population viscosity, and an interaction radius r(int), which defines the instantaneous contact network for the game dynamics. We show that, differently from the r(P)=0 case, the model with finite-sized agents presents a coexistence phase with both cooperators and defectors, besides the two absorbing phases, in which either cooperators or defectors dominate. We provide, in addition, a geometric interpretation of the transitions between phases. In analogy with lattice models, the geometric percolation of the contact network (i.e., irrespective of the strategy) enhances cooperation. More importantly, we show that the percolation of defectors is an essential condition for their survival. Differently from compact clusters of cooperators, isolated groups of defectors will eventually become extinct if not percolating, independently of their size.

The use of immunosuppression in autoimmune hepatitis: A current literature review

PubMed Central

Cropley, Angela; Weltman, Martin

2017-01-01

Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre’s approach to treatment of AIH in the context of a contemporary review of the literature. PMID:28288505

The causal structure of utility conditionals.

PubMed

Bonnefon, Jean-François; Sloman, Steven A

2013-01-01

The psychology of reasoning is increasingly considering agents' values and preferences, achieving greater integration with judgment and decision making, social cognition, and moral reasoning. Some of this research investigates utility conditionals, ''if p then q'' statements where the realization of p or q or both is valued by some agents. Various approaches to utility conditionals share the assumption that reasoners make inferences from utility conditionals based on the comparison between the utility of p and the expected utility of q. This article introduces a new parameter in this analysis, the underlying causal structure of the conditional. Four experiments showed that causal structure moderated utility-informed conditional reasoning. These inferences were strongly invited when the underlying structure of the conditional was causal, and significantly less so when the underlying structure of the conditional was diagnostic. This asymmetry was only observed for conditionals in which the utility of q was clear, and disappeared when the utility of q was unclear. Thus, an adequate account of utility-informed inferences conditional reasoning requires three components: utility, probability, and causal structure. Copyright © 2012 Cognitive Science Society, Inc.

Plants' Metabolites as Potential Antiobesity Agents

PubMed Central

Gooda Sahib, Najla; Saari, Nazamid; Ismail, Amin; Khatib, Alfi; Mahomoodally, Fawzi; Abdul Hamid, Azizah

2012-01-01

Obesity and obesity-related complications are on the increase both in the developed and developing world. Since existing pharmaceuticals fail to come up with long-term solutions to address this issue, there is an ever-pressing need to find and develop new drugs and alternatives. Natural products, particularly medicinal plants, are believed to harbor potential antiobesity agents that can act through various mechanisms either by preventing weight gain or promoting weight loss amongst others. The inhibition of key lipid and carbohydrate hydrolyzing and metabolizing enzymes, disruption of adipogenesis, and modulation of its factors or appetite suppression are some of the plethora of targeted approaches to probe the antiobesity potential of medicinal plants. A new technology such as metabolomics, which deals with the study of the whole metabolome, has been identified to be a promising technique to probe the progression of diseases, elucidate their pathologies, and assess the effects of natural health products on certain pathological conditions. This has been applied to drug research, bone health, and to a limited extent to obesity research. This paper thus endeavors to give an overview of those plants, which have been reported to have antiobesity effects and highlight the potential and relevance of metabolomics in obesity research. PMID:22666121

Enhancing the quality of aged latent fingerprints developed by superglue fuming: loss and replenishment of initiator.

PubMed

Wargacki, Stephen P; Lewis, Linda A; Dadmun, Mark D

2008-09-01

The recovery and identification of latent fingerprints from a crime scene are crucial to many investigations. The cyanoacrylate (superglue) fuming method (CFM), which develops fingerprints by growing a polymer coating over the print residue, is a powerful method but encounters severe limitations when prints are aged or exposed to harsh environmental conditions. We examine the aging process and how the changes that occur to a fingerprint residue over time influence the growth of polymer during development. We identify loss of initiator by erosion and degradation that, when coupled with a loss of water from the print residue, result in a decreased ability to polymerize ethylcyanoacrylate. Then, we present a methodology by which the ability of aged latent fingerprints to polymerize ethylcyanoacrylate is recovered. Two print enhancement agents, acetic acid and ammonia, are demonstrated to improve the growth of polymer from the print ridges by over an order of magnitude, while retaining the integrity of the print structure. Comparison between the two enhancement agents indicate that the enhancement occurs due to ridge coating by the ammonia or acetic acid and pH control of the latent print.

Development and application of an in-cell cleanup pressurized liquid extraction with ultra-high-performance liquid chromatography-tandem mass spectrometry to detect prohibited antiviral agents sensitively in livestock and poultry feces.

PubMed

Wu, Huizhen; Wang, Jianmei; Yang, Hua; Li, Guoqin; Zeng, Yinhuan; Xia, Wei; Li, Zuguang; Qian, Mingrong

2017-03-10

An in-cell cleanup pressurized liquid extraction was developed to analyze prohibited antiviral agents in livestock and poultry feces. Extraction and cleanup were integrated into one step. The extraction was performed using methanol-acetonitrile (1:1, v/v) with 0.5% glacial acetic acid at 90°C, and 0.75g of PSA was used as the adsorbent during the extraction procedure. Under optimal conditions, the average recoveries for 11 antiviral drugs were 71.5-112.5% at three spiked levels (20, 40, and 100μgkg -1 ). The detection limits and detection quantitations of the analysis method for the eleven antiviral drugs were 0.6-1.4 and 1.4-4.7μgkg -1 , respectively. Finally, the method was applied to analyze amantadine, oseltamivir and its metabolites oseltamivir acid in duck feces based on an experiment of an oral dose of two antiviral drugs in duck. The amantadine, oseltamivir and oseltamivir acid can be detected in feces within approximately four weeks after amantadine and oseltamivir were orally administered. The results indicate that the residue analysis in feces is a noninvasive method to monitor inhibited antiviral agents efficiently in livestock and poultry breeding. Copyright © 2017. Published by Elsevier B.V.

Mental health claims management and return to work: qualitative insights from Melbourne, Australia.

PubMed

Brijnath, Bianca; Mazza, Danielle; Singh, Nabita; Kosny, Agnieszka; Ruseckaite, Rasa; Collie, Alex

2014-12-01

Mental health conditions (MHC) are an increasing reason for claiming injury compensation in Australia; however little is known about how these claims are managed by different gatekeepers to injury entitlements. This study, drawing on the views of four stakeholders-general practitioners (GPs), injured persons, employers and compensation agents, aims to describe current management of MHC claims and to identify the current barriers to return to work (RTW) for injured persons with a MHC claim and/or mental illness. Ninety-three in-depth interviews were undertaken with GPs, compensation agents, employers and injured persons. Data were collected in Melbourne, Australia. Thematic techniques were used to analyse data. MHC claims were complex to manage because of initial assessment and diagnostic difficulties related to the invisibility of the injury, conflicting medical opinions and the stigma associated with making a MHC claim. Mental illness also developed as a secondary issue in the recovery process. These factors made MHC difficult to manage and impeded timely RTW. It is necessary to undertake further research (e.g. guideline development) to improve current practice in order to enable those with MHC claims to make a timely RTW. Further education and training interventions (e.g. on diagnosis and management of MHC) are also needed to enable GPs, employers and compensation agents to better assess and manage MHC claims.

Ground truth methods for optical cross-section modeling of biological aerosols

NASA Astrophysics Data System (ADS)

Kalter, J.; Thrush, E.; Santarpia, J.; Chaudhry, Z.; Gilberry, J.; Brown, D. M.; Brown, A.; Carter, C. C.

2011-05-01

Light detection and ranging (LIDAR) systems have demonstrated some capability to meet the needs of a fastresponse standoff biological detection method for simulants in open air conditions. These systems are designed to exploit various cloud signatures, such as differential elastic backscatter, fluorescence, and depolarization in order to detect biological warfare agents (BWAs). However, because the release of BWAs in open air is forbidden, methods must be developed to predict candidate system performance against real agents. In support of such efforts, the Johns Hopkins University Applied Physics Lab (JHU/APL) has developed a modeling approach to predict the optical properties of agent materials from relatively simple, Biosafety Level 3-compatible bench top measurements. JHU/APL has fielded new ground truth instruments (in addition to standard particle sizers, such as the Aerodynamic particle sizer (APS) or GRIMM aerosol monitor (GRIMM)) to more thoroughly characterize the simulant aerosols released in recent field tests at Dugway Proving Ground (DPG). These instruments include the Scanning Mobility Particle Sizer (SMPS), the Ultraviolet Aerodynamic Particle Sizer (UVAPS), and the Aspect Aerosol Size and Shape Analyser (Aspect). The SMPS was employed as a means of measuring smallparticle concentrations for more accurate Mie scattering simulations; the UVAPS, which measures size-resolved fluorescence intensity, was employed as a path toward fluorescence cross section modeling; and the Aspect, which measures particle shape, was employed as a path towards depolarization modeling.

Small-Scale Terrorist Attacks Using Chemical and Biological Agents: An Assessment Framework and Preliminary Comparisons

DTIC Science & Technology

2004-05-20

Unknown Cholera ( Vibrio cholerae ) + — — — + Unknown Salmonella Typhimurium + — + — — Unknown Typhoid fever (Salmonella Typhi) + O — — — Unknown... Cholera bb ( Vibrio cholerae ) Cholera occurs in many of the developing countries of Africa and Asia, especially where sanitary conditions are not optimal...Safety Data Sheet - Infectious Substances for Vibrio cholerae , found online at [http://www.hc-sc.gc.ca/pphb-dgspsp/msds-ftss/msds164e.html]; D. Hank

Ecological-geomorphological assessment of the suburban area of Astana

NASA Astrophysics Data System (ADS)

Akiyanova, F. Zh; Zinabdin, N. B.; Kenzhebayeva, A. Zh; Adilbekova, F. G.; Ilyassova, A. T.; Karakulov, E. M.

2018-01-01

The results of ecological-geomorphological assessment of the suburban zone of Astana is presented in the paper. Climatic and hydrological factors, which are the agents of pollutants’ transport and caused the development of exogenous processes in the suburban area of Astana were studied and mapped. On the base of the geoinformation technologies and field studies the geomorphologic structure and morphogenetic processes were studied. The analysis of the data complex led to assess ecological-geomorphological conditions of the suburban area of Astana.

Integrating homoeopathy in health systems.

PubMed Central

Poitevin, B.

1999-01-01

Homoeopathy is a therapy which involves many components and three main agents: the patient, with his or her condition and personal characteristics; the medication used, with its composition and manufacturing procedure; and the physician, with his or her approach to treatment and concepts of health. The development of research and evaluation structures, combined with a critical education in the discipline, would help to improve practices and define homoeopathy's potential role in relation to the other therapies, both conventional and unconventional, used in Western health systems. PMID:10083716

Effectiveness of expedient sheltering in place in a residence.

PubMed

Jetter, James J; Whitfield, Calvin

2005-03-17

The objective of this study was to evaluate the effectiveness of expedient sheltering in place in a residence for protection against airborne hazards, as outlined in the U.S. Department of Homeland Security (DHS) guidance to the public. An improved method was developed to determine the air flow rate for a shelter inside a house. Expedient sheltering measures (plastic sheeting and duct tape) were applied to a room inside a test house by participants who followed the DHS guidance. Measured air flow rates were used to determine protection factors for various scenarios. Protection factors were calculated for the house and shelter under various occupancy times, weather conditions, and outdoor exposure times for hazardous agents. Protection factors ranged from 1.3 to 539, depending on the conditions. Results indicate that proper sealing can make a substantial difference in the effectiveness of the shelter. Sheltering in place can be most beneficial if people enter shelters before the arrival of a cloud of hazardous agent, and people exit shelters as soon as the cloud passes over. However, sheltering in place can be detrimental if people enter or exit shelters too late. CO2 and O2 concentrations inside the shelter are not likely to reach dangerous levels under most scenarios, but concentrations could reach dangerous levels under certain conditions, and concentration levels could affect individuals with respiratory problems.

Stock markets as Minority Games: cognitive heterogeneity and equilibrium emergence

NASA Astrophysics Data System (ADS)

Brandouy, O.

2005-04-01

Standard finance theory generally assumes homogeneous agents relatively to their preferences, heuristics and investment strategies. We propose to study, in an agent-based simulation, the emergence of equilibrium under various heterogeneous conditions. Market interaction is stylized with the Minority Game representation. It is shown that inductive rational equilibrium emerges even though agents do not share the same representations of the value. This may lead to consider again the roots of EMH and REH.

Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. I: Investigation of mobile phase and MS conditions.

PubMed

Nováková, Lucie; Grand-Guillaume Perrenoud, Alexandre; Nicoli, Raul; Saugy, Martial; Veuthey, Jean-Luc; Guillarme, Davy

2015-01-01

The conditions for the analysis of selected doping substances by UHPSFC-MS/MS were optimized to ensure suitable peak shapes and maximized MS responses. A representative mixture of 31 acidic and basic doping agents was analyzed, in both ESI+ and ESI- modes. The best compromise for all compounds in terms of MS sensitivity and chromatographic performance was obtained when adding 2% water and 10mM ammonium formate in the CO2/MeOH mobile phase. Beside mobile phase, the nature of the make-up solvent added for interfacing UHPSFC with MS was also evaluated. Ethanol was found to be the best candidate as it was able to compensate for the negative effect of 2% water addition in ESI- mode and provided a suitable MS response for all doping agents. Sensitivity of the optimized UHPSFC-MS/MS method was finally assessed and compared to the results obtained in conventional UHPLC-MS/MS. Sensitivity was improved by 5-100-fold in UHPSFC-MS/MS vs. UHPLC-MS/MS for 56% of compounds, while only one compound (bumetanide) offered a significantly higher MS response (4-fold) under UHPLC-MS/MS conditions. In the second paper of this series, the optimal conditions for UHPSFC-MS/MS analysis will be employed to screen >100 doping agents in urine matrix and results will be compared to those obtained by conventional UHPLC-MS/MS. Copyright © 2014 Elsevier B.V. All rights reserved.

Brain heparan sulphate proteoglycans are altered in developing foetus when exposed to in-utero hyperglycaemia.

PubMed

Sandeep, M S; Nandini, C D

2017-08-01

In-utero exposure of foetus to hyperglycaemic condition affects the growth and development of the organism. The brain is one of the first organs that start to develop during embryonic period and glycosaminoglycans (GAGs) and proteoglycans (PGs) are one of the key molecules involved in its development. But studies on the effect of hyperglycaemic conditions on brain GAGs/PGs are few and far between. We, therefore, looked into the changes in brain GAGs and PGs at various developmental stages of pre- and post-natal rats from non-diabetic and diabetic mothers as well as in adult rats induced with diabetes using a diabetogenic agent, Streptozotocin. Increased expression of GAGs especially that of heparan sulphate class in various developmental stages were observed in the brain as a result of in-utero hyperglycaemic condition but not in that of adult rats. Changes in disaccharides of heparan sulphate (HS) were observed in various developmental stages. Furthermore, various HSPGs namely, syndecans-1 and -3 and glypican-1 were overexpressed in offspring from diabetic mother. However, in adult diabetic rats, only glypican-1 was overexpressed. The offsprings from diabetic mothers became hyperphagic at the end of 8 weeks after birth which can have implications in the long run. Our results highlight the likely impact of the in-utero exposure of foetus to hyperglycaemic condition on brain GAGs/PGs compared to diabetic adult rats.

Measured and perceived effects of computerized scientist mentors on student learning and motivation in science

NASA Astrophysics Data System (ADS)

Bowman, Catherine Dodds Dunham

Unease about declining U.S. science literacy and inquiry skills drives much innovation in science education, including the quest for authentic science experiences for students. One response is student-scientist partnerships (SSP), involving small numbers of students in scientific investigations with scientist mentors. Alternatively, science inquiry programs provide large numbers of students with opportunities to pursue their own investigations but without extensive access to experts, potentially limiting the possible cognitive and affective gains. This mixed methods study investigates whether it is possible to replicate some of SSPs' benefits on a larger scale through use of a computerized agent designed as a "virtual" scientist mentor. Middle school students (N=532) were randomly assigned to two versions of an agent (or to a control group) providing either content-only or content and interpersonal mentoring while they participated in a three-week curriculum. Results indicate that, on average, students gained in content knowledge but there was no statistically significant difference between the three conditions. In terms of motivation, students exhibited no change, on average, with no statistically significant difference between the three conditions. These data indicate that the treatment conditions neither facilitate nor inhibit student learning and motivation. Interviews with a subsample (n=70), however, suggest that students believe the agents facilitated their learning, eased the workload, provided a trusted source of information, and were enjoyable to use. Teachers reported that the agents provided alternative views of scientists and science, generated class discussion, and met the needs of high and low-achieving students. This difference between measured and perceived benefits may result from measures that were not sufficiently sensitive to capture differences. Alternatively, a more sophisticated agent might better replicate mentoring functions known to produce cognitive and affective gains. Even without established learning or motivational gains, practitioners may want to employ agents for their ability to provide reliable information, expanded perspectives on science and scientists, and a non-intimidating setting for students to ask questions. For computerized agent researchers, this study provides a first step in exploring the affordances and challenges of sustained use of agents in real school settings with the goal of improving science education.

Development of a Spatial and Temporal Agent-Based Model for Studying Water and Health Relationships: The Case Study of Two Villages in Limpopo, South Africa

PubMed Central

Demarest, Jeffrey; Pagsuyoin, Sheree; Learmonth, Gerard; Mellor, Jonathan; Dillingham, Rebecca

2014-01-01

Diarrhea, the second leading cause of child morbidity and mortality, can have detrimental effects in the physical and cognitive development of children in developing countries. Health interventions (e.g., increased access to health services and safe water) designed to address this problem are difficult to implement in resource-limited settings. In this paper, we present a tool for understanding the complex relationship between water and public health in rural areas of a developing country. A spatial and temporal agent-based model (ABM) was developed to simulate the current water, sanitation, and health status in two villages in Limpopo Province, South Africa. The model was calibrated using empirical data and published sources. It was used to simulate the effects of poor water quality on the frequency of diarrheal episodes in children, and consequently on child development. Preliminary simulation results show that at the current total coliform levels in the water sources of the studied villages, children are expected to experience stunting by as much as −1.0 standard deviations from the World Health Organization height norms. With minor modifications, the calibrated ABM can be used to design and evaluate intervention strategies for improving child health in these villages. The model can also be applied to other regions worldwide that face the same environmental challenges and conditions as the studied villages. PMID:25530709

Microgel-in-Microgel Biopolymer Delivery Systems: Controlled Digestion of Encapsulated Lipid Droplets under Simulated Gastrointestinal Conditions.

PubMed

Ma, Da; Tu, Zong-Cai; Wang, Hui; Zhang, Zipei; McClements, David Julian

2018-04-18

Structural design principles are increasingly being used to develop colloidal delivery systems for bioactive agents. In this study, oil droplets were encapsulated within microgel-in-microgel systems. Initially, a nanoemulsion was formed that contained small whey protein-coated oil droplets ( d 43 = 211 nm). These oil droplets were then loaded into either carrageenan-in-alginate (O/M C /M A ) or alginate-in-carrageenan (O/M A /M C ) microgels. A vibrating nozzle encapsulation unit was used to form the smaller inner microgels ( d 43 = 170-324 μm), while a hand-held syringe was used to form the larger outer microgels ( d 43 = 2200-3400 μm). Calcium alginate microgels (O/M A ) were more stable to simulated gastrointestinal tract (GIT) conditions than potassium carrageenan microgels (O/M C ), which was attributed to the stronger cross-links formed by divalent calcium ions than the monovalent potassium ions. As a result, the microgel-in-microgel systems had different gastrointestinal fates depending upon the nature of the external microgel phase; i.e., the O/M C /M A system was more resistant to rupture than the O/M A /M C system. The rate of lipid digestion under simulated small intestine conditions decreased in the following order: free oil droplets > O/M C > O/M A > O/M A /M C > O/M C /M A . This effect was attributed to differences in the integrity and dimensions of the microgels in the small intestine, because a hydrogel network surrounding the oil droplets inhibits lipid hydrolysis by lipase. The structured microgels developed in this study may have interesting applications for the protection or controlled release of bioactive agents.

Chronic low back pain: a mini-review on pharmacological management and pathophysiological insights from clinical and pre-clinical data.

PubMed

Park, Thomas S W; Kuo, Andy; Smith, Maree T

2018-05-12

Globally, low back pain (LBP) is one of the most common health problems affecting humans. The lifetime prevalence of non-specific LBP is approximately 84%, with the chronic prevalence at about 23%. Chronic LBP in humans is defined as LBP that persists for more than 12 weeks without a significant pain improvement. Although there are numerous evidence-based guidelines on the management of acute LBP, this is not the case for chronic LBP, which is regarded as particularly difficult to treat. Research aimed at discovering new drug treatments for alleviation of chronic mechanical LBP is lacking due to the paucity of knowledge on the pathobiology of this condition, despite its high morbidity in the affected adult population. For a debilitating condition such as chronic LBP, it is necessary to assess the sustained effects of pharmacotherapy of various agents spanning months to years. Although many rodent models of mechanical LBP have been developed to mimic the human condition, some of the major shortcomings of many of these models are (1) the presence of a concurrent neuropathic component that develops secondary to posterior intervertebral disc puncture, (2) severe model phenotype, and/or (3) use of behavioural endpoints that have yet to be validated for pain. Hence, there is a great, unmet need for research aimed at discovering new biological targets in rodent models of chronic mechanical LBP for use in drug discovery programs as a means to potentially produce new highly effective and well-tolerated analgesic agents to improve relief of chronic LBP. On a cautionary note, it must be borne in mind that because humans and rats display orthograde and pronograde postures, respectively, the different mechanical forces on their spines add to the difficulty in translation of promising rodent data to humans.

Adenovirus-Mediated Gene Therapy Against Viral Biothreat Agents

DTIC Science & Technology

2016-04-12

economy. Vaccine development is an important strategy to thwart the threat of these viral biothreat agents. There is an urgent need to improve...Alberta, Tl A 8K6. Canada E-mail: josh. wu@drdc-rddc.gc.ca .• 78 JoshQ.H. Wu existing vaccines against these agents and to develop new ones. Gene...of vaccines against viral biothreat agents. Genes encoding protective antigens of viral biothreat agents can be carried by these viral vectors and

[EPIDEMIOLOGIC FEATURES OFNOROVIRUS INFECTION OUTBREAK IN THE REPUBLIC OF NORTH OSSETIA-ALANIA].

PubMed

Maletskaya, O V; Tibilov, A G; Prislegina, D A; Gazieva, G K; Otaraeva, N I; Volynkina, A S; Saveliev, V N; Lyamkin, G I; Zaitsev, A A; Kulichenko, A N

2016-01-01

Analysis of epidemiologic features of a norovirus outbreak in Alagir city of the Republic of North Ossetia-Alania and effectiveness of measures of its liquidation. Data from maps-schemes of water supply system of Alagir city and statistical documentation of Centre of Hygiene and Epidemiology in the Republic of North Ossetia-Alania were used in the study. Indication of norovirus in clinical material and water samples was carried out bypolymerase chain reaction method. Etiological agent of outbreak disease was established--genotype II norovirus. Realization of fecal-oral mechanisms of water transmission pathway of the causative agent of norovirus infection was detected. Conditions facilitating emergence and development of the indicated outbreak were determined--non-satisfactory sanitary-technical condition of water. supply system of the city. The studied water outbreak of norovirus infection was caused by GII.17 genotype virus, that currently gradually displaces GII.IV genotype, and was characterized by an intensive start, involvement of all population age groups into the epidemic process (with primary infection of adults), low family focality, predominance of average severity disease forms in the clinical presentation. The counter-epidemic measures carried out ensured rapid localization and liquidation of the norovirus infection outbreak.

Ultrasonic Measurement of Erosion/corrosion Rates in Industrial Piping Systems

NASA Astrophysics Data System (ADS)

Sinclair, A. N.; Safavi, V.; Honarvar, F.

2011-06-01

Industrial piping systems that carry aggressive corrosion or erosion agents may suffer from a gradual wall thickness reduction that eventually threatens pipe integrity. Thinning rates could be estimated from the very small change in wall thickness values measured by conventional ultrasound over a time span of at least a few months. However, measurements performed over shorter time spans would yield no useful information—minor signal distortions originating from grain noise and ultrasonic equipment imperfections prevent a meaningful estimate of the minuscule reduction in echo travel time. Using a Model-Based Estimation (MBE) technique, a signal processing scheme has been developed that enables the echo signals from the pipe wall to be separated from the noise. This was implemented in a laboratory experimental program, featuring accelerated erosion/corrosion on the inner wall of a test pipe. The result was a reduction in the uncertainty in the wall thinning rate by a factor of four. This improvement enables a more rapid response by system operators to a change in plant conditions that could pose a pipe integrity problem. It also enables a rapid evaluation of the effectiveness of new corrosion inhibiting agents under plant operating conditions.

Evolving role of immunotherapy in the treatment of refractory warts

PubMed Central

Thappa, Devinder M; Chiramel, Minu J

2016-01-01

Cutaneous and genital warts are common dermatological conditions caused by the human papilloma virus (HPV). Although it is a benign condition, it causes disfigurement, has a tendency to koebnerize, and can be transmitted to others. This makes adequate and timely treatment important. There are several conventional treatments available with variable response. Topical and systemic immunotherapy has now found a significant place in the treatment of warts because of its nondestructive action, ease of use, and promising results. Through this review, we would like to present a brief overview of the various immunotherapeutic agents used. These include more established agents such as imiquimod, Mycobacterium w vaccine, bacillus Calmette-Guérin vaccine, measles, mumps, and rubella vaccine, Candida antigen, trichophyton antigen, tuberculin, zinc, cimetidine, levamisole, HPV vaccine, and autoimplantation therapy. Other agents such as contact immunotherapy which is sparsely used now than before and newer agents such as Corynebacterium parvum, sinecatechins, echinacea, propolis, glycyrrizinic acid, and Vitamin D have also been discussed. The mechanism of action of these agents, along with their dosage, mode of administration, duration of use, expected outcomes and comparative efficacy, evidence for their use, and expected side effects, if any, are reviewed. PMID:27730031

A theory of utility conditionals: Paralogical reasoning from decision-theoretic leakage.

PubMed

Bonnefon, Jean-François

2009-10-01

Many "if p, then q" conditionals have decision-theoretic features, such as antecedents or consequents that relate to the utility functions of various agents. These decision-theoretic features leak into reasoning processes, resulting in various paralogical conclusions. The theory of utility conditionals offers a unified account of the various forms that this phenomenon can take. The theory is built on 2 main components: (1) a representational tool (the utility grid), which summarizes in compact form the decision-theoretic features of a conditional, and (2) a set of folk axioms of decision, which reflect reasoners' beliefs about the way most agents make their decisions. Applying the folk axioms to the utility grid of a conditional allows for the systematic prediction of the paralogical conclusions invited by the utility grid's decision-theoretic features. The theory of utility conditionals significantly extends the scope of current theories of conditional inference and moves reasoning research toward a greater integration with decision-making research.

75 FR 55797 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-14

...] Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral... entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment... antiviral agents (DAAs), defined as agents that interfere with specific steps in the hepatitis C virus (HCV...

Current and Developing Technologies for Monitoring Agents of Bioterrorism and Biowarfare

PubMed Central

Lim, Daniel V.; Simpson, Joyce M.; Kearns, Elizabeth A.; Kramer, Marianne F.

2005-01-01

Recent events have made public health officials acutely aware of the importance of rapidly and accurately detecting acts of bioterrorism. Because bioterrorism is difficult to predict or prevent, reliable platforms to rapidly detect and identify biothreat agents are important to minimize the spread of these agents and to protect the public health. These platforms must not only be sensitive and specific, but must also be able to accurately detect a variety of pathogens, including modified or previously uncharacterized agents, directly from complex sample matrices. Various commercial tests utilizing biochemical, immunological, nucleic acid, and bioluminescence procedures are currently available to identify biological threat agents. Newer tests have also been developed to identify such agents using aptamers, biochips, evanescent wave biosensors, cantilevers, living cells, and other innovative technologies. This review describes these current and developing technologies and considers challenges to rapid, accurate detection of biothreat agents. Although there is no ideal platform, many of these technologies have proved invaluable for the detection and identification of biothreat agents. PMID:16223949

Silk Based Bioinks for Soft Tissue Reconstruction Using 3-Dimensional (3D) Printing with in vitro and in vivo Assessments

PubMed Central

Rodriguez, María J.; Brown, Joseph; Giordano, Jodie; Lin, Samuel J.; Omenetto, Fiorenzo G.; Kaplan, David L.

2016-01-01

In the field of soft tissue reconstruction, custom implants could address the need for materials that can fill complex geometries. Our aim was to develop a material system with optimal rheology for material extrusion, that can be processed in physiological and non-toxic conditions and provide structural support for soft tissue reconstruction. To meet this need we developed silk based bioinks using gelatin as a bulking agent and glycerol as a non-toxic additive to induce physical crosslinking. We developed these inks optimizing printing efficacy and resolution for patient-specific geometries that can be used for soft tissue reconstruction. We demonstrated in vitro that the material was stable under physiological conditions and could be tuned to match soft tissue mechanical properties. We demonstrated in vivo that the material was biocompatible and could be tuned to maintain shape and volume up to three months while promoting cellular infiltration and tissue integration. PMID:27940389

Photovoltaic module encapsulation design and materials section, volume 2

NASA Technical Reports Server (NTRS)

Cuddihy, E. F.

1984-01-01

Tests for chemical structure, material properties, water absorption, aging and curing agent of Ethylene Vinyl Acetate (EVA) and UV absorption studies are carried out. A computer model was developed for thermal optical modeling, to investigate dependence between module operating temperature and solar insolation, and heat dissapation behavior. Structural analyses were performed in order to determine the stress distribution under wind and heat conditions. Curves are shown for thermal loading conditions. An electrical isolation was carried out to investigate electrical stress aging of non-metallic encapsulation materials and limiting material flaws, and to develop a computer model of electrical fields and stresses in encapsulation materials. In addition, a mathematical model was developed and tests were conducted to predict hygroscopic and thermal expansion and contraction on a plastic coated wooden substrate. Thermal cycle and humidity freezing cycle tests, partial discharge tests, and hail impact tests were also carried out. Finally, the effects of soiling on the surface of photovoltaic modules were investigated. Two antisoiling coatings, a fluorinated silane and perflourodecanoic acid were considered.

Silk based bioinks for soft tissue reconstruction using 3-dimensional (3D) printing with in vitro and in vivo assessments.

PubMed

Rodriguez, María J; Brown, Joseph; Giordano, Jodie; Lin, Samuel J; Omenetto, Fiorenzo G; Kaplan, David L

2017-02-01

In the field of soft tissue reconstruction, custom implants could address the need for materials that can fill complex geometries. Our aim was to develop a material system with optimal rheology for material extrusion, that can be processed in physiological and non-toxic conditions and provide structural support for soft tissue reconstruction. To meet this need we developed silk based bioinks using gelatin as a bulking agent and glycerol as a non-toxic additive to induce physical crosslinking. We developed these inks optimizing printing efficacy and resolution for patient-specific geometries that can be used for soft tissue reconstruction. We demonstrated in vitro that the material was stable under physiological conditions and could be tuned to match soft tissue mechanical properties. We demonstrated in vivo that the material was biocompatible and could be tuned to maintain shape and volume up to three months while promoting cellular infiltration and tissue integration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiac Cachexia: Perspectives for Prevention and Treatment.

PubMed

Okoshi, Marina Politi; Capalbo, Rafael Verardino; Romeiro, Fernando G; Okoshi, Katashi

2017-01-01

Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment.

Analysis of DIRAC's behavior using model checking with process algebra

NASA Astrophysics Data System (ADS)

Remenska, Daniela; Templon, Jeff; Willemse, Tim; Bal, Henri; Verstoep, Kees; Fokkink, Wan; Charpentier, Philippe; Graciani Diaz, Ricardo; Lanciotti, Elisa; Roiser, Stefan; Ciba, Krzysztof

2012-12-01

DIRAC is the grid solution developed to support LHCb production activities as well as user data analysis. It consists of distributed services and agents delivering the workload to the grid resources. Services maintain database back-ends to store dynamic state information of entities such as jobs, queues, staging requests, etc. Agents use polling to check and possibly react to changes in the system state. Each agent's logic is relatively simple; the main complexity lies in their cooperation. Agents run concurrently, and collaborate using the databases as shared memory. The databases can be accessed directly by the agents if running locally or through a DIRAC service interface if necessary. This shared-memory model causes entities to occasionally get into inconsistent states. Tracing and fixing such problems becomes formidable due to the inherent parallelism present. We propose more rigorous methods to cope with this. Model checking is one such technique for analysis of an abstract model of a system. Unlike conventional testing, it allows full control over the parallel processes execution, and supports exhaustive state-space exploration. We used the mCRL2 language and toolset to model the behavior of two related DIRAC subsystems: the workload and storage management system. Based on process algebra, mCRL2 allows defining custom data types as well as functions over these. This makes it suitable for modeling the data manipulations made by DIRAC's agents. By visualizing the state space and replaying scenarios with the toolkit's simulator, we have detected race-conditions and deadlocks in these systems, which, in several cases, were confirmed to occur in the reality. Several properties of interest were formulated and verified with the tool. Our future direction is automating the translation from DIRAC to a formal model.

Conditional Toxin Splicing Using a Split Intein System.

PubMed

Alford, Spencer C; O'Sullivan, Connor; Howard, Perry L

2017-01-01

Protein toxin splicing mediated by split inteins can be used as a strategy for conditional cell ablation. The approach requires artificial fragmentation of a potent protein toxin and tethering each toxin fragment to a split intein fragment. The toxin-intein fragments are, in turn, fused to dimerization domains, such that addition of a dimerizing agent reconstitutes the split intein. These chimeric toxin-intein fusions remain nontoxic until the dimerizer is added, resulting in activation of intein splicing and ligation of toxin fragments to form an active toxin. Considerations for the engineering and implementation of conditional toxin splicing (CTS) systems include: choice of toxin split site, split site (extein) chemistry, and temperature sensitivity. The following method outlines design criteria and implementation notes for CTS using a previously engineered system for splicing a toxin called sarcin, as well as for developing alternative CTS systems.

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

PubMed

Dick, Andrew D; Rosenbaum, James T; Al-Dhibi, Hassan A; Belfort, Rubens; Brézin, Antoine P; Chee, Soon Phaik; Davis, Janet L; Ramanan, Athimalaipet V; Sonoda, Koh-Hei; Carreño, Ester; Nascimento, Heloisa; Salah, Sawsen; Salek, Sherveen; Siak, Jay; Steeples, Laura

2018-05-01

An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions'.

PubMed

Akhtar, Naseem; Khan, Riaz A

2016-10-01

Skin cancer is among one of the most common human malignancies wide-spread world-over with mortality statistics rising continuously at an alarming rate. The increasing frequency of these malignancies has marked the need for adopting effective treatment plan coupled with better and site-specific delivery options for the desired therapeutic agent's availability at the affected site. The concurrent delivery approaches to cancerous tissues are under constant challenge and, as a result, are evolving and gaining advancements in terms of delivery modes, therapeutic agents and site-specificity of the therapeutics delivery. The lipid-based liposomal drug delivery is an attractive and emerging option, and which is meticulously shaping up beyond a threshold level to a promising, and viable route for the effective delivery of therapeutic agents and other required injuctions to the skin cancer. An update on liposomal delivery of chemotherapeutic agents, natural-origin compounds, photosensitizer, and DNA repair enzymes as well as other desirable and typical delivery modes employed in drug delivery and in the treatment of skin cancers is discussed in details. Moreover, liposomal delivery of nucleic acid-based therapeutics, i.e., small interfering RNA (siRNA), mRNA therapy, and RGD-linked liposomes are among the other promising novel technology under constant development. The current clinical applicability, viable clinical plans, future prospects including transport feasibility of delivery vesicles and imaging techniques in conjunction with the therapeutic agents is also discussed. The ongoing innovations in liposomal drug delivery technology for skin cancers hold promise for further development of the methodology for better, more effective and site-specific delivery as part of the better treatment plan by ensuring faster drug transport, better and full payload delivery with enough and required concentration of the dose. Copyright © 2016 Elsevier B.V. All rights reserved.

A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

PubMed

Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

2018-03-20

Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p < 0.05, p < 0.01, and p < 0.001) in the zebrafish model. The larval zebrafish heart failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

Agent-Based Negotiation in Uncertain Environments

NASA Astrophysics Data System (ADS)

Debenham, John; Sierra, Carles

An agent aims to secure his projected needs by attempting to build a set of (business) relationships with other agents. A relationship is built by exchanging private information, and is characterised by its intimacy — degree of closeness — and balance — degree of fairness. Each argumentative interaction between two agents then has two goals: to satisfy some immediate need, and to do so in a way that develops the relationship in a desired direction. An agent's desire to develop each relationship in a particular way then places constraints on the argumentative utterances. The form of negotiation described is argumentative interaction constrained by a desire to develop such relationships.

[The development and implementation of polymerase chain reaction to detect in real-time operation mode yersinia pestis in field material].

PubMed

Afanas'ev, M V; Chipanin, E V; Shestakov, V E; Denisov, A V; Fomina, L A; Ostiak, A S; Balakhonov, S V

2013-03-01

The article presents the results of development and practical implementation of system of polymerase chain reaction testing in real-time operation mode to detect agent of plague infield material. In laboratory conditions the system demonstrated good results and hence it was applied in conditions of field laboratory of epidemiologic team during planned epizootologic examination of Gorno-Altaisk hot spot of plague. The sampling consisted of more than 1400 objects. It was demonstrated that high sensitivity and specificity is immanent to proposed system. The adaptation of the system to the real time amplifier "Smart Cycler" (Cephid, USA) having some specific technical characteristics makes it possible to consider the proposed test-system as an effective sensitive and precise instrument for screening studies in the process of regular epizootologic examinations of hot spots of plague.

21 CFR 184.1655 - Propane.

Code of Federal Regulations, 2013 CFR

2013-04-01

... also known as dimethylmethane or propyl hydrid. It is a colorless, odorless, flammable gas at normal... oil, adsorption to surface-active agents, or refrigeration. (b) The ingredient must be of a purity... manufacturing practice conditions of use: (1) The ingredient is used as a propellant, aerating agent, and gas as...

21 CFR 184.1655 - Propane.

Code of Federal Regulations, 2011 CFR

2011-04-01

... also known as dimethylmethane or propyl hydrid. It is a colorless, odorless, flammable gas at normal... oil, adsorption to surface-active agents, or refrigeration. (b) The ingredient must be of a purity... manufacturing practice conditions of use: (1) The ingredient is used as a propellant, aerating agent, and gas as...

21 CFR 184.1655 - Propane.

Code of Federal Regulations, 2012 CFR

2012-04-01

... also known as dimethylmethane or propyl hydrid. It is a colorless, odorless, flammable gas at normal... oil, adsorption to surface-active agents, or refrigeration. (b) The ingredient must be of a purity... manufacturing practice conditions of use: (1) The ingredient is used as a propellant, aerating agent, and gas as...

Midazolam: An Improved Anticonvulsant Treatment for Nerve Agent-Induced Seizures

DTIC Science & Technology

2002-01-01

variety of compounds that different authors had championed as being capable of stopping or moderating nerve agent seizures (e.g., memantine , clonidine...e.g., memantine , neuroactive steroids; EEG seizures were still evident) or required such a narrow dose range or specific treatment conditions that

Immunomodulatory therapy for ocular inflammatory disease: a basic manual and review of the literature.

PubMed

Okada, Annabelle A

2005-01-01

Corticosteroids are used as first-line treatment for many ocular inflammatory conditions. The risk of adverse effects, however, necessitates conversion to steroid-sparing immunomodulatory therapy (IMT) for disease that is recurrent, chronic, or poorly responsive to treatment. Combination drug treatments with multiple agent 'recipes' are also considered. Immunomodulatory agents include the broad categories of antimetabolites (azathioprine, methotrexate, mycophenolate mofetil), alkylating agents (cyclophosphamide, chlorambucil), T-cell inhibitors (cyclosporine, tacrolimus), and cytokines (interferon alfa). This article reviews and summarizes the evidence for IMT agent use in the treatment of various forms of ocular inflammation.

A new adhesive technique for internal fixation in midfacial surgery

PubMed Central

Endres, Kira; Marx, Rudolf; Tinschert, Joachim; Wirtz, Dieter Christian; Stoll, Christian; Riediger, Dieter; Smeets, Ralf

2008-01-01

Background The current surgical therapy of midfacial fractures involves internal fixation in which bone fragments are fixed in their anatomical positions with osteosynthesis plates and corresponding screws until bone healing is complete. This often causes new fractures to fragile bones while drilling pilot holes or trying to insert screws. The adhesive fixation of osteosynthesis plates using PMMA bone cement could offer a viable alternative for fixing the plates without screws. In order to achieve the adhesive bonding of bone cement to cortical bone in the viscerocranium, an amphiphilic bone bonding agent was created, analogous to the dentin bonding agents currently on the market. Methods The adhesive bonding strengths were measured using tension tests. For this, metal plates with 2.0 mm diameter screw holes were cemented with PMMA bone cement to cortical bovine bone samples from the femur diaphysis. The bone was conditioned with an amphiphilic bone bonding agent prior to cementing. The samples were stored for 1 to 42 days at 37 degrees C, either moist or completely submerged in an isotonic NaCl-solution, and then subjected to the tension tests. Results Without the bone bonding agent, the bonding strength was close to zero (0.2 MPa). Primary stability with bone bonding agent is considered to be at ca. 8 MPa. Moist storage over 42 days resulted in decreased adhesion forces of ca. 6 MPa. Wet storage resulted in relatively constant bonding strengths of ca. 8 MPa. Conclusion A new amphiphilic bone bonding agent was developed, which builds an optimizied interlayer between the hydrophilic bone surface and the hydrophobic PMMA bone cement and thus leads to adhesive bonding between them. Our in vitro investigations demonstrated the adhesive bonding of PMMA bone cement to cortical bone, which was also stable against hydrolysis. The newly developed adhesive fixing technique could be applied clinically when the fixation of osteosynthesis plates with screws is impossible. With the detected adhesion forces of ca. 6 to 8 MPa, it is assumed that the adhesive fixation system is able to secure bone fragments from the non-load bearing midfacial regions in their orthotopic positions until fracture consolidation is complete. PMID:18489785

Recent trends in soft-tissue infection imaging.

PubMed

Petruzzi, Nicholas; Shanthly, Nylla; Thakur, Mathew

2009-03-01

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, central nervous system, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection-specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory tract infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to monitor the therapeutic response in a variety of conditions. Current studies suggest PET should be considered the most accurate quantitative method. Scintigraphy has much to offer in localizing abdominal infection as well as inflammation. We may begin to see a gradual increase in the usage of (18)F-FDG-PET in detecting occult abdominal infections. Commonly used modalities for imaging inflammatory bowel disease are scintigraphy with (111)In-oxine/(99m)Tc-HMPAO labeled autologous white blood cells. The literature on central nervous system infection imaging is relatively scarce. Few clinical studies have been performed and numerous new agents have been developed for this use with varying results. Further studies are needed to more clearly delineate the future direction of this field. In evaluating the postoperative spine, (99m)Tc-ciprofloxacin single-photon emission computed tomography (SPECT) was reported to be >80% sensitive in patients more than 6 months after surgery. FDG-PET has also been suggested for this purpose and may play a larger role than originally thought. It appears PET/computed tomography (CT) is gaining support, especially in imaging those with fever of unknown origin or nonfunctional immune systems. Although an infection-specific agent is lacking, the development of one would greatly advance our ability to detect, localize, and quantify infections. Overall, imaging such an agent via SPECT/CT or PET/CT will pave the way for greater clinical reliability in the localization of infection.

A Comparative Study of the Retentive Strengths of Commercial and Indigenously Developed Luting Cements using Both Lathe-cut and Clinically Simulated Specimens.

PubMed

Mathew, Joe; Kurian, Byju P; Philip, Biju; Mohammed, Sunil; Menon, Preetha; Raj, Rajan S

2016-08-01

Superior adhesive strength in luting agents is of paramount significance in fixed partial denture success. In this in vitro study five cements were tested for retentive qualities, using both lathe-cut and hand-prepared specimens. A total of 104 freshly extracted tooth specimens were prepared. Seventy of them were lathe-cut and 30 specimens were hand-prepared to simulate clinical conditions. Five different cements were tested, which included a compomer, a composite, a zinc phosphate, and 2 glass-ionomer luting cements. Of the 5, 2 trial cements were indigenously developed by Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Trivandrum, India - a glass-ionomer cement (Chitra GIC) and a chemical-cure composite (Chitra CCC). All cements were compared within each group and between groups (lathe-prepared and hand-prepared). GC Fuji 1 (GC America) exhibited superior retentive strengths in both lathe-cut and hand-prepared specimens, whereas the compomer cement displayed the lowest values when tested. In lathe-cut specimens, statistical analysis showed no significant difference between GC Fuji 1 and indigenously developed Chitra CCC. Both Chitra CCC and GC Fuji 1 have comparable strengths in lathe-cut samples, making Chitra CCC a potential luting agent. Statistical analysis reveals that all cements, except GC Fuji 1, exhibited a significant decrease in strength due to the change in design uniformity. The chemical bonding of GC Fuji 1 proves to be quite strong irrespective of shape and precision of the tooth crown. The indigenously developed Chitra GIC and Chitra CCC showed promising results to be used as a potential luting agent.

New antiobesity agents: lorcaserin (Belviq) and phentermine/topiramate ER (Qsymia).

PubMed

Shyh, Grace; Cheng-Lai, Angela

2014-01-01

Obesity is a risk factor for a wide range of conditions, including cardiovascular disease. Although lifestyle modifications remain the cornerstone for the management of obesity, pharmacologic agents may be a helpful addition to patients who have comorbidities and do not respond adequately to diet and exercise. Lorcaserin and phentermine/topiramate ER are 2 long-awaited agents, approved in 2012 for obesity management, 13 years since orlistat received US Food and Drug Administration approval in 1999. Lorcaserin is a serotonin agonist, whereas phentermine/topiramate is a combination of a sympathomimetic agent and an antiepileptic drug; both these agents have been shown to reduce weight significantly and improve cardiovascular and metabolic parameters, such as blood pressure, lipids, and HbA1C. This article reviews the pharmacology and clinical efficacy and safety of each of these agents. The differences among the three available agents for long-term management of obesity will also be examined.

Current concepts in the pharmacological management of obesity.

PubMed

Carek, P J; Dickerson, L M

1999-06-01

The pharmacological management of obesity has gained increasing attention as new weight loss treatments are approved and a significant proportion of the public strives to lose weight. Obesity is associated with a high mortality rate, multiple chronic medical conditions, and carries an enormous financial burden. Obesity is a multifactorial condition, most often due to an imbalance in energy intake and expenditure. Despite the greater focus on management of obesity, weight loss remains a difficult goal to achieve. Obesity is a chronic medical condition that may require long term treatment, therefore the risks and benefits of all pharmacological agents must be carefully considered. Noradrenergic appetite suppressants (ie. phenyl-propanolamine, phentermine) result in weight loss but stimulatory effects limit their use. The serotonergic agents (fenfluramine, dexfenfluramine) were effective weight loss drugs, but were voluntarily withdrawn from the US market last year because of cardiovascular and pulmonary complications. The combination noradrenergic/serotonergic agent sibutramine is indicated for the management of obesity, particularly in the presence of other cardiovascular risk factors. Modest weight loss is achieved with sibutramine, although weight gain is significant after discontinuation. In addition, long term safety data are not yet available. The thermogenic combination of ephedrine plus caffeine is minimally effective, and adverse effects are usually transient. Other thermogenic agents, such as beta3-agonists, are still under investigation. Agents may alter digestion through lipase inhibition (orlistat) or fat substitution (olestra). Orlistat decreases systemic absorption of dietary fat, decreasing body weight and cholesterol. Olestra is a fat substitute that has been incorporated into snack foods. Olestra substitution for dietary fat has not been studied as a weight loss strategy, although olestra has no caloric value and may be beneficial. The use of orlistat and olestra may be limited by gastrointestinal adverse effects. Finally, the manipulation of leptin and neuropeptide Y are under investigation for the treatment of obesity. Pharmacological agents should be used as an aid to a structured diet and exercise regimen in the treatment of obesity. Weight loss agents may result in initial weight loss, but sustained weight loss is not always achieved even with continuation of treatment. The effect of weight loss obtained while using pharmacotherapeutic agents on morbidity and mortality has not been established. Therefore, diet and exercise should be the focus of any weight loss programme. There is a continued need for safe and effective pharmacotherapeutic agents for the treatment of obesity.

The Spanish toxic oil syndrome 20 years after its onset: a multidisciplinary review of scientific knowledge.

PubMed

Gelpí, Emilio; de la Paz, Manuel Posada; Terracini, Benedetto; Abaitua, Ignacio; de la Cámara, Agustín Gómez; Kilbourne, Edwin M; Lahoz, Carlos; Nemery, Bénoit; Philen, Rossanne M; Soldevilla, Luis; Tarkowski, Stanislaw

2002-05-01

In 1981, in Spain, the ingestion of an oil fraudulently sold as olive oil caused an outbreak of a previously unrecorded condition, later known as toxic oil syndrome (TOS), clinically characterized by intense incapacitating myalgias, marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons affected, approximately 300 died shortly after the onset of the disease and a larger number developed chronic disease. For more than 15 years, a scientific committee supported by the World Health Organization's Regional Office for Europe and by the Institute of Health Carlos III in Madrid has guided investigation intended to identify the causal agent(s), to assess toxicity and mode of action, to establish the pathogenesis of the disease, and to detect late consequences. This report summarizes advances in research on this front. No late mortality excess has been detected. Among survivors, the prevalence of some chronic conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to reproduce the condition in laboratory animals have been unsuccessful, and no condition similar to TOS has been reported in the scientific literature. Laboratory findings suggest an autoimmune mechanism for TOS, such as high levels of seric soluble interleukin-2 receptor. Epidemiologic studies integrated with chemical analyses of case-related oils have shown that the disease is strongly associated with the consumption of oils containing fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP). These chemicals have also been found in oils synthesized under conditions simulating those hypothesized to have occurred when the toxic oil was produced in 1981. Whether PAP esters are simply markers of toxicity of oils or have the capability to induce the disease remains to be elucidated.

The Spanish toxic oil syndrome 20 years after its onset: a multidisciplinary review of scientific knowledge.

PubMed Central

Gelpí, Emilio; de la Paz, Manuel Posada; Terracini, Benedetto; Abaitua, Ignacio; de la Cámara, Agustín Gómez; Kilbourne, Edwin M; Lahoz, Carlos; Nemery, Bénoit; Philen, Rossanne M; Soldevilla, Luis; Tarkowski, Stanislaw

2002-01-01

In 1981, in Spain, the ingestion of an oil fraudulently sold as olive oil caused an outbreak of a previously unrecorded condition, later known as toxic oil syndrome (TOS), clinically characterized by intense incapacitating myalgias, marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons affected, approximately 300 died shortly after the onset of the disease and a larger number developed chronic disease. For more than 15 years, a scientific committee supported by the World Health Organization's Regional Office for Europe and by the Institute of Health Carlos III in Madrid has guided investigation intended to identify the causal agent(s), to assess toxicity and mode of action, to establish the pathogenesis of the disease, and to detect late consequences. This report summarizes advances in research on this front. No late mortality excess has been detected. Among survivors, the prevalence of some chronic conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to reproduce the condition in laboratory animals have been unsuccessful, and no condition similar to TOS has been reported in the scientific literature. Laboratory findings suggest an autoimmune mechanism for TOS, such as high levels of seric soluble interleukin-2 receptor. Epidemiologic studies integrated with chemical analyses of case-related oils have shown that the disease is strongly associated with the consumption of oils containing fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP). These chemicals have also been found in oils synthesized under conditions simulating those hypothesized to have occurred when the toxic oil was produced in 1981. Whether PAP esters are simply markers of toxicity of oils or have the capability to induce the disease remains to be elucidated. PMID:12003748

Biological control of ticks

USGS Publications Warehouse

Samish, M.; Ginsberg, H.; Glazer, I.; Bowman, A.S.; Nuttall, P.

2004-01-01

Ticks have numerous natural enemies, but only a few species have been evaluated as tick biocontrol agents (BCAs). Some laboratory results suggest that several bacteria are pathogenic to ticks, but their mode of action and their potential value as biocontrol agents remain to be determined. The most promising entomopathogenic fungi appear to be Metarhizium anisopliae and Beauveria bassiana, strains of which are already commercially available for the control of some pests. Development of effective formulations is critical for tick management. Entomopathogenic nematodes that are pathogenic to ticks can potentially control ticks, but improved formulations and selection of novel nematode strains are needed. Parasitoid wasps of the genus Ixodiphagus do not typically control ticks under natural conditions, but inundative releases show potential value. Most predators of ticks are generalists, with a limited potential for tick management (one possible exception is oxpeckers in Africa). Biological control is likely to play a substantial role in future IPM programmes for ticks because of the diversity of taxa that show high potential as tick BCAs. Considerable research is required to select appropriate strains, develop them as BCAs, establish their effectiveness, and devise production strategies to bring them to practical use.

Sporicidal performance induced by photocatalytic production of organic peroxide under visible light irradiation

NASA Astrophysics Data System (ADS)

Yamaguchi, Yuichi; Shimodo, Takahito; Chikamori, Noriyasu; Usuki, Sho; Kanai, Yoshihiro; Endo, Takeshi; Katsumata, Ken-Ichi; Terashima, Chiaki; Ikekita, Masahiko; Fujishima, Akira; Suzuki, Tomonori; Sakai, Hideki; Nakata, Kazuya

2016-09-01

Bacteria that cause serious food poisoning are known to sporulate under conditions of nutrient and water shortage. The resulting spores have much greater resistance to common sterilization methods, such as heating at 100 °C and exposure to various chemical agents. Because such bacteria cannot be inactivated with typical alcohol disinfectants, peroxyacetic acid (PAA) often is used, but PAA is a harmful agent that can seriously damage human health. Furthermore, concentrated hydrogen peroxide, which is also dangerous, must be used to prepare PAA. Thus, the development of a facile and safe sporicidal disinfectant is strongly required. In this study, we have developed an innovative sporicidal disinfection method that employs the combination of an aqueous ethanol solution, visible light irradiation, and a photocatalyst. We successfully produced a sporicidal disinfectant one hundred times as effective as commercially available PAA, while also resolving the hazards and odor problems associated with PAA. The method presented here can potentially be used as a replacement for the general disinfectants employed in the food and health industries.

UV-vis spectrophotometric determination of trinitrotoluene (TNT) with trioctylmethylammonium chloride as ion pair assisted and disperser agent after dispersive liquid-liquid microextraction.

PubMed

Larki, Arash; Nasrabadi, Mehdi Rahimi; Pourreza, Nahid

2015-06-01

In the present study, a simple, fast and inexpensive method based on dispersive liquid-liquid microextraction (DLLME) prior to microvolume UV-vis spectrophotometry was developed for the preconcentration and determination of trinitrotoluene (TNT). The procedure is based on the color reaction of TNT in alkaline medium and extraction into CCl4 as an ion pair assisted by trioctylmethylammonium chloride, which also acts as a disperser agent. Experimental parameters affecting the DLLME method such as pH, concentration of sodium hydroxide, amount of trioctylmethylammonium chloride, type and volume of extraction solvent were investigated and optimized. Under the optimum conditions, the limit of detection (LOD) was 0.9ng/mL and the calibration curve was linear in the range of 3-200ng/mL. The relative standard deviation for 25 and 100ng/mL of TNT were 3.7% and 1.5% (n=6), respectively. The developed DLLME method was applied for the determination of TNT in different water and soil samples. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Foodborne illness: new developments concerning an old problem.

PubMed

Kasowski, Eric J; Gackstetter, Gary D; Sharp, Trueman W

2002-08-01

Foodborne illnesses continue to cause substantial morbidity and mortality in the United States, primarily as gastroenteritis but occasionally as other syndromes as well. Most of these illnesses are caused by a variety of widely known infectious agents, principally viruses, and are probably the result of common mistakes in food handling in the home or in restaurants. The epidemiology of foodborne illness is evolving. Major changes in food production, distribution, and consumption have created opportunities for new pathogens to emerge and for old ones to reemerge, and the potential for widespread outbreaks is increasing. Antibiotic resistance in bacterial pathogens resulting from the widespread use of antimicrobial agents in animal husbandry is also an important concern. Clinicians must be aware of the changing epidemiology of foodborne illness to recognize and manage these conditions in the clinical setting. In addition, clinicians are critical in the reporting of recognized or suspected foodborne illness, so that public health authorities are able to investigate, understand, and ultimately better control them. A number of new techniques have been employed, and others under development will improve our ability to recognize and cope with foodborne diseases.

Acute Kidney Failure

MedlinePlus

... through your urine Impaired blood flow to the kidneys Diseases and conditions that may slow blood flow ... anaphylaxis) Severe burns Severe dehydration Damage to the kidneys These diseases, conditions and agents may damage the ...

Physicochemical and microbiological stability of azathioprine in InOrpha suspending agent studied under various conditions.

PubMed

Amin, Alexandre; Bourget, Philippe; Vidal, Fabrice; Cartier, François; Beauvais, Raphaëlle; Afonso, Veronica Do Nascimento

2015-01-01

Azathioprine is an antineoplastic antimetabolite drug currently used as an immunosuppressive agent after organ transplantation and for several dysimmunitary diseases. The usual daily dose ranges from 1 to 5 mg/kg orally. Azathioprine is marketed in France under the trade name Imurel in tablet form for oral administration that contains either 25 mg or 50 mg of the active ingredient. This Galenic formulation is not suitable for pediatric use and often requires a grinding operation or a dose fractionation to facilitate administration. In addition to a potential risk of imprecision in the administered dose, tablet grinding might unnecessarily expose nurses and families to a toxic compound. To overcome this problem, the objective of this study was to develop and evaluate the physicochemical and microbiological stabilities of azathioprine in a sugar-free, alcohol-free, and paraben-free InOrpha suspending agent. The studied samples were formulated into a 10-mg/mL suspension and stored in 24 plastic bottles of 60 mL at two different temperature conditions (between 2 degrees C to 8 degrees C and room temperature). Two series of 12 samples were tested for physicochemical stability using high-performance liquid chromatography as well as for a microbiological status for 35 days (daily opening of the bottles from day 0 of compounding) and for 56 days, upon daily flask opening (first opening at day 28 from compounding and daily opening for 28 consecutive days). The high-performance liquid chromatography method developed is linear, accurate, precise, and robust. In addition, a forced degradation study validated the selectivity and the specificity requirements of the method validated as stability indicating. At room temperature storage, high-performance liquid chromatography analysis showed that tested samples had concentrations ranging from 90% to 110% of the initial concentration throughout the course of the study. Microbiological status remained stable during the 56 days of investigation. Based on the data collected, the study led to the development of a new Galenic formulation of azathioprine that is suitable for pediatric use and can be safely stored at room temperature for 28 days (before and after opening for a maximum of 56 consecutive days).

Comparing administered and market-based water allocation systems using an agent-based modeling approach

NASA Astrophysics Data System (ADS)

Zhao, J.; Cai, X.; Wang, Z.

2009-12-01

It also has been well recognized that market-based systems can have significant advantages over administered systems for water allocation. However there are not many successful water markets around the world yet and administered systems exist commonly in water allocation management practice. This paradox has been under discussion for decades and still calls for attention for both research and practice. This paper explores some insights for the paradox and tries to address why market systems have not been widely implemented for water allocation. Adopting the theory of agent-based system we develop a consistent analytical model to interpret both systems. First we derive some theorems based on the analytical model, with respect to the necessary conditions for economic efficiency of water allocation. Following that the agent-based model is used to illustrate the coherence and difference between administered and market-based systems. The two systems are compared from three aspects: 1) the driving forces acting on the system state, 2) system efficiency, and 3) equity. Regarding economic efficiency, penalty on the violation of water use permits (or rights) under an administered system can lead to system-wide economic efficiency, as well as being acceptable by some agents, which follows the theory of the so-call rational violation. Ideal equity will be realized if penalty equals incentive with an administered system and if transaction costs are zero with a market system. The performances of both agents and the over system are explained with an administered system and market system, respectively. The performances of agents are subject to different mechanisms of interactions between agents under the two systems. The system emergency (i.e., system benefit, equilibrium market price, etc), resulting from the performance at the agent level, reflects the different mechanism of the two systems, the “invisible hand” with the market system and administrative measures (penalty and subsidy) with the administered system. Furthermore, the impact of hydrological uncertainty on the performance of water users under the two systems is analyzed by extending the deterministic model to a stochastic one subject to the uncertainty of water availability. It is found that the system response to hydrologic uncertainty depends on risk management mechanics - sharing risk equally among the agents or by prescribed priorities on some agents. Figure1. Agent formulation and its implications in administered system and market-based system

Concepts and theoretical specifications of a Coastal Vulnerability Dynamic Simulator (COVUDS): A multi-agent system for simulating coastal vulnerability towards management of coastal ecosystem services

NASA Astrophysics Data System (ADS)

Orencio, P. M.; Endo, A.; Taniguchi, M.

2014-12-01

Disaster-causing natural hazards such as floods, erosions, earthquakes or slope failures were particularly observed to be concentrated in certain geographical regions. In the Asia-pacific region, coastal ecosystems were suffering because of perennial threats driven by chronic fluctuations in climate variability (e.g., typhoons, ENSO), or by dynamically occurring events (e.g., earthquakes, tsunamis). Among the many people that were found prone to such a risky condition were the ones inhabiting near the coastal areas. Characteristically, aside from being located at the forefront of these events, the coastal communities have impacted the resource by the kind of behavioral patterns they exhibited, such as overdependence and overexploitation to achieve their wellbeing. In this paper, we introduce the development of an approach to an assessment of the coupled human- environment using a multi- agent simulation (MAS) model known as Coastal Vulnerability Dynamic Simulator (COVUDS). The COVUDS comprised a human- environmental platform consisting multi- agents with corresponding spatial- based dynamic and static variables. These variables were used to present multiple hypothetical future situations that contribute to the purpose of supporting a more rational management of the coastal ecosystem and their environmental equities. Initially, we present the theoretical and conceptual components that would lead to the development of the COVUDS. These consisted of the human population engaged in behavioral patterns affecting the conditions of coastal ecosystem services; the system of the biophysical environment and changes in patches brought by global environment and local behavioral variations; the policy factors that were important for choosing area- specific interventions; and the decision- making mechanism that integrates the first three components. To guide a future scenario-based application that will be undertaken in a coastal area in the Philippines, the components of the model will be presented within a platform following a parameterized architecture.

Breast cancer: the role of angiogenesis and antiangiogenic therapy.

PubMed

Miller, Kathy D; Dul, Carrie L

2004-10-01

Angiogenesis plays a role in breast cancer development. Preclinical and clinical evidence is reviewed. Development of targeted antiangiogenic agents provides new challenges to clinical trial design. Current antiangiogenic therapy with traditional agents and novel agents are classified and reviewed.

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse

PubMed Central

Jackson, Charles Van; Zimmerman, Karen M.; Alsina-Fernandez, Jorge; Michael, M. Dodson; Emmerson, Paul J.; Coskun, Tamer

2017-01-01

The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances. The FATZO mouse develops obesity spontaneously when fed a normal chow diet. Glucose intolerance with increased insulin levels are apparent in FATZO mice as young as 6 weeks of age. These progress to hyperglycemia/pre-diabetes and frank diabetes with decreasing insulin levels as they age. The disease in these mice is multi-faceted, similar to the metabolic syndrome apparent in obese individuals, and thus provides a long pre-diabetic state for determining the preventive value of new interventions. We have assessed the utility of this new model for the pre-clinical screening of agents to stop or slow progression of the metabolic syndrome to severe diabetes. Our assessment included: 1) characterization of the spontaneous development of disease, 2) comparison of metabolic disturbances of FATZO mice to control mice and 3) validation of the model with regard to the effectiveness of current and emerging anti-diabetic agents; rosiglitazone, metformin and semaglutide. Conclusion: Male FATZO mice spontaneously develop significant metabolic disease when compared to normal controls while maintaining hyperglycemia in the presence of high leptin levels and hyperinsulinemia. The disease condition responds to commonly used antidiabetic agents. PMID:28640857

Pharmacologic pain treatment of musculoskeletal disorders: current perspectives and future prospects.

PubMed

Curatolo, M; Bogduk, N

2001-03-01

The authors aimed to provide an educational update on the current evidence of the effectiveness of drug therapy in the treatment of musculoskeletal pain and to offer a perspective of possible future developments. The authors used a pragmatic review of data provided by available systematic reviews and seminal controlled studies pertaining to the treatment of regional musculoskeletal pain problems. Epidural steroids may offer limited, short-term benefit for sciatica. Local injections of steroids are either ineffective or provide short-lasting benefits. Nonsteroidal anti-inflammatory drugs and opioids reduce pain, but the effect size is modest. The literature does not support convincingly the use of antidepressants. Certain muscle relaxants may be useful in the treatment of back pain. Hyaluronic acid, neutraceutical agents, avocado-soybean unsaponifiable agents, oxaceprol and diacerein may be effective in the treatment of osteoarthritis, but the information regarding these new agents does not allow wholesale endorsement of these substances. Selective epidural injection of steroids at a target nerve root approached through the intervertebral foramin has the potential to replace the traditional epidural approach. Long-acting, C--fiber-specific local anesthetics are under investigation and could provide long-lasting pain relief without motor or sensory impairment. In the future, central hypersensitivity in chronic musculoskeletal pain might be treated using antagonists of the N-methyl-D-aspartate receptor. Cannabinoid agents produce antinociception and prevent experimentally induced hyperalgesia in animals, and they may find a role in pain management. Methods to optimize drug combinations are available. The effectiveness of the currently available drugs in the treatment of musculoskeletal pain conditions is disappointing. Recent developments may open new perspectives in this area of pain medicine.

Control Architecture for Robotic Agent Command and Sensing

NASA Technical Reports Server (NTRS)

Huntsberger, Terrance; Aghazarian, Hrand; Estlin, Tara; Gaines, Daniel

2008-01-01

Control Architecture for Robotic Agent Command and Sensing (CARACaS) is a recent product of a continuing effort to develop architectures for controlling either a single autonomous robotic vehicle or multiple cooperating but otherwise autonomous robotic vehicles. CARACaS is potentially applicable to diverse robotic systems that could include aircraft, spacecraft, ground vehicles, surface water vessels, and/or underwater vessels. CARACaS incudes an integral combination of three coupled agents: a dynamic planning engine, a behavior engine, and a perception engine. The perception and dynamic planning en - gines are also coupled with a memory in the form of a world model. CARACaS is intended to satisfy the need for two major capabilities essential for proper functioning of an autonomous robotic system: a capability for deterministic reaction to unanticipated occurrences and a capability for re-planning in the face of changing goals, conditions, or resources. The behavior engine incorporates the multi-agent control architecture, called CAMPOUT, described in An Architecture for Controlling Multiple Robots (NPO-30345), NASA Tech Briefs, Vol. 28, No. 11 (November 2004), page 65. CAMPOUT is used to develop behavior-composition and -coordination mechanisms. Real-time process algebra operators are used to compose a behavior network for any given mission scenario. These operators afford a capability for producing a formally correct kernel of behaviors that guarantee predictable performance. By use of a method based on multi-objective decision theory (MODT), recommendations from multiple behaviors are combined to form a set of control actions that represents their consensus. In this approach, all behaviors contribute simultaneously to the control of the robotic system in a cooperative rather than a competitive manner. This approach guarantees a solution that is good enough with respect to resolution of complex, possibly conflicting goals within the constraints of the mission to be accomplished by the vehicle(s).

Squalene synthase inhibitors: An update on the search for new antihyperlipidemic and antiatherosclerotic agents.

PubMed

Kourounakis, A P; Katselou, M G; Matralis, A N; Ladopoulou, E M; Bavavea, E

2011-01-01

Atherosclerosis and related heart disease is strongly associated with elevated blood levels of total (and LDL) cholesterol. Due to the widespread incidence as well as severity of this pathological condition, major efforts have been made for the discovery and development of hypocholesteroleamic agents. In the past few decades, HMG-CoA reductase inhibitors (statins) are being extensively used as lipid lowering drugs. These agents act predominantly by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) that is the rate limiting step of cholesterol biosynthesis. Both the success as well as drawbacks of HMGRIs, have led to the investigation and design of inhibitors of other (downstream) enzymes involved in the multistep cholesterol biosynthetic pathway. One such class of agents consists of the squalene sythase inhibitors which act at the first and solely committed step towards the biosynthesis of the cholesterol nucleus. This target is considered not to interfere with the biosynthesis of other biologically important molecules and thus a better side-effect profile is expected for these inhibitors. Several classes of squalene synthase inhibitors (SQSIs), such as substrate or transition-state analogues, zaragozic acids or 2,8- dioxabicyclo[3.2.1]octane derivatives, dicarboxylic acid and quinuclidine derivatives, 4,1-benzoxazepine as well as substituted morpholine derivatives, have been studied as potent inhibitors of squalene synthase. So far only one benzoxazepine derivative (TAK-475) has been evaluated in advanced clinical trials. In this article we review the up to date research and literature on the therapeutic potential of this relatively new class of compounds, the drug discovery efforts towards the development of active squalene synthase inhibitors, their activity profile and effectiveness, as well as their structure-activity relationships.

High CO2 concentration as an inductor agent to drive production of recombinant phytotoxic antimicrobial peptides in plant biofactories.

PubMed

Ruiz, Cristina; Pla, Maria; Company, Nuri; Riudavets, Jordi; Nadal, Anna

2016-03-01

Cationic α-helical antimicrobial peptides such as BP100 are of increasing interest for developing novel phytosanitary or therapeutic agents and products with industrial applications. Biotechnological production of these peptides in plants can be severely impaired due to the toxicity exerted on the host by high-level expression. This can be overcome by using inducible promoters with extremely low activity throughout plant development, although the yields are limited. We examined the use of modified atmospheres using the increased levels of [CO2], commonly used in the food industry, as the inductor agent to biotechnologically produce phytotoxic compounds with higher yields. Here we show that 30% [CO2] triggered a profound transcriptional response in rice leaves, including a change in the energy provision from photosynthesis to glycolysis, and the activation of stress defense mechanisms. Five genes with central roles in up-regulated pathways were initially selected and their promoters successfully used to drive the expression of phytotoxic BP100 in genetically modified (GM) rice. GM plants had a normal phenotype on development and seed production in non-induction conditions. Treatment with 30 % [CO2] led to recombinant peptide accumulation of up to 1 % total soluble protein when the Os.hb2 promoter was used. This is within the range of biotechnological production of other peptides in plants. Using BP100 as a proof-of-concept we demonstrate that very high [CO2] can be considered an economically viable strategy to drive production of recombinant phytotoxic antimicrobial peptides in plant biofactories.

Modified extrusion-spheronization as a technique of microencapsulation for stabilization of choline bitartrate using hydrogenated soya bean oil

PubMed Central

Gangurde, Avinash Bhaskar; Sav, Ajay Kumar; Javeer, Sharadchandra Dagadu; Moravkar, Kailas K; Pawar, Jaywant N; Amin, Purnima D

2015-01-01

Introduction: Choline bitartrate (CBT) is a vital nutrient for fetal brain development and memory function. It is hygroscopic in nature which is associated with stability related problem during storage such as development of fishy odor and discoloration. Aim: Microencapsulation method was adopted to resolve the stability problem and for this hydrogenated soya bean oil (HSO) was used as encapsulating agent. Materials and Methods: Industrially feasible modified extrusion-spheronization technique was selected for microencapsulation. HSO was used as encapsulating agent, hydroxypropyl methyl cellulose E5/E15 as binder and microcrystalline cellulose as spheronization aid. Formulated pellets were evaluated for parameters such as flow property, morphological characteristics, hardness-friability index (HFI), drug content, encapsulation efficiency, and in vitro drug release. The optimized formulations were also characterized for particle size (by laser diffractometry), differential scanning calorimetry, powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy, and scanning electron microscopy. Results and Discussions: The results from the study showed that coating of 90% and 60% CBT was successful with respect to all desired evaluation parameters. Optimized formulation was kept for 6 months stability study as per ICH guidelines, and there was no change in color, moisture content, drug content, and no fishy odor was observed. Conclusion: Microencapsulated pellets of CBT using HSO as encapsulating agent were developed using modified extrusion spheronization technique. Optimized formulations, CBT 90% (F5), and CBT 60% (F10), were found to be stable for 4M and 6M, respectively, at accelerated conditions. PMID:26682198

Heterapoderopsis bicallosicollis (Coleoptera: Attelabidae): a potential biological control agent for Triadica sebifera.

PubMed

Wang, Yi; Ding, Jianqing; Wheeler, Gregory S; Purcell, Matthew F; Zhang, Guoan

2009-08-01

Native to China, Chinese tallow, Triadica sebifera L. Small (Euphorbiaceae), is an invasive plant in the southeastern United States. The leaf-rolling weevil, Heterapoderopsis bicallosicollis Voss, is a common herbivore attacking this plant in China. To evaluate its potential as a biological control agent of T. sebifera, biology and host specificity of this weevil were studied in China. H. bicallosicollis occurs over a wide, native, geographic range and its immatures successfully develop at 15-35 degrees C, indicating its physiological potential to establish and persist throughout the range of climatic conditions where the target plant grows in the United States. Adults make feeding holes on leaves. Before oviposition, the female makes a sealed leaf roll called a nidus and then lays one to two eggs inside. Eggs, larvae, and pupae develop within nidi, and larvae survive only when they develop inside the nidi. This requirement makes the weevil highly host specific to T. sebifera. In laboratory no-choice tests of 54 species from eight families, adults fed on only 3 plant species, T. sebifera, Sapium chihsinianum S. K. Lee, and Phyllanthus urinaria L. and only oviposited on T. sebifera. These results were confirmed where, in multiple-choice tests, adults only oviposited on T. sebifera. Given that T. sebifera is the only species in the genus Triadica in the United States, the results of this study suggest that H. bicallosicollis is a potential biological control agent of T. sebifera and should be considered to be imported into quarantine in the United States for further tests on native North American species.

Automating CapCom Using Mobile Agents and Robotic Assistants

NASA Technical Reports Server (NTRS)

Clancey, William J.; Sierhaus, Maarten; Alena, Richard L.; Berrios, Daniel; Dowding, John; Graham, Jeffrey S.; Tyree, Kim S.; Hirsh, Robert L.; Garry, W. Brent; Semple, Abigail

2005-01-01

We have developed and tested an advanced EVA communications and computing system to increase astronaut self-reliance and safety, reducing dependence on continuous monitoring and advising from mission control on Earth. This system, called Mobile Agents (MA), is voice controlled and provides information verbally to the astronauts through programs called personal agents. The system partly automates the role of CapCom in Apollo-including monitoring and managing EVA navigation, scheduling, equipment deployment, telemetry, health tracking, and scientific data collection. EVA data are stored automatically in a shared database in the habitat/vehicle and mirrored to a site accessible by a remote science team. The program has been developed iteratively in the context of use, including six years of ethnographic observation of field geology. Our approach is to develop automation that supports the human work practices, allowing people to do what they do well, and to work in ways they are most familiar. Field experiments in Utah have enabled empirically discovering requirements and testing alternative technologies and protocols. This paper reports on the 2004 system configuration, experiments, and results, in which an EVA robotic assistant (ERA) followed geologists approximately 150 m through a winding, narrow canyon. On voice command, the ERA took photographs and panoramas and was directed to move and wait in various locations to serve as a relay on the wireless network. The MA system is applicable to many space work situations that involve creating and navigating from maps (including configuring equipment for local topology), interacting with piloted and unpiloted rovers, adapting to environmental conditions, and remote team collaboration involving people and robots.