Ultraviolet Raman scattering from persistent chemical warfare agents

NASA Astrophysics Data System (ADS)

Kullander, Fredrik; Wästerby, Pär.; Landström, Lars

2016-05-01

Laser induced Raman scattering at excitation wavelengths in the middle ultraviolet was examined using a pulsed tunable laser based spectrometer system. Droplets of chemical warfare agents, with a volume of 2 μl, were placed on a silicon surface and irradiated with sequences of laser pulses. The Raman scattering from V-series nerve agents, Tabun (GA) and Mustard gas (HD) was studied with the aim of finding the optimum parameters and the requirements for a detection system. A particular emphasis was put on V-agents that have been previously shown to yield relatively weak Raman scattering in this excitation band.

Embodied Agents, E-SQ and Stickiness: Improving Existing Cognitive and Affective Models

NASA Astrophysics Data System (ADS)

de Diesbach, Pablo Brice

This paper synthesizes results from two previous studies of embodied virtual agents on commercial websites. We analyze and criticize the proposed models and discuss the limits of the experimental findings. Results from other important research in the literature are integrated. We also integrate concepts from profound, more business-related, analysis that deepens on the mechanisms of rhetoric in marketing and communication, and the possible role of E-SQ in man-agent interaction. We finally suggest a refined model for the impacts of these agents on web site users, and limits of the improved model are commented.

Review of CO₂ as a Euthanasia Agent for Laboratory Rats and Mice.

PubMed

Boivin, Gregory P; Hickman, Debra L; Creamer-Hente, Michelle A; Pritchett-Corning, Kathleen R; Bratcher, Natalie A

2017-09-01

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current body of knowledge on the subject. Potential areas for further investigation and recommendations are provided.

Persistent lymphadenopathy in homosexual men: a clinical and ultrastructural study.

PubMed

Anderson, M G; Dixey, J; Key, P; Ellis, D S; Tovey, G; McCaul, T F; Murray-Lyon, I M; Gazzard, B; Lawrence, A; Evans, B

1984-04-21

Ultrastructural changes (tubuloreticular structures and tube and ring shaped forms) previously described in patients with acquired immunodeficiency syndrome (AIDS) are described for the first time in the lymph nodes and circulating lymphocytes of patients with persistent lymphadenopathy. These observations support the view that the persistent lymphadenopathy syndrome and AIDS are caused by the same transmissible agent(s).

Review of CO2 as a Euthanasia Agent for Laboratory Rats and Mice

PubMed Central

Boivin, Gregory P; Hickman, Debra L; Creamer-Hente, Michelle A; Pritchett-Corning, Kathleen R; Bratcher, Natalie A

2017-01-01

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current body of knowledge on the subject. Potential areas for further investigation and recommendations are provided. PMID:28903819

A Chronic Longitudinal Characterization of Neurobehavioral and Neuropathological Cognitive Impairment in a Mouse Model of Gulf War Agent Exposure

PubMed Central

Zakirova, Zuchra; Crynen, Gogce; Hassan, Samira; Abdullah, Laila; Horne, Lauren; Mathura, Venkatarajan; Crawford, Fiona; Ait-Ghezala, Ghania

2016-01-01

Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component that includes memory impairment as well as neurological and musculoskeletal deficits. Previous studies have shown that in the First Persian Gulf War conflict (1990–1991) exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and permethrin (PER), were key contributors to the etiology of GWI. For this study, we used our previously established mouse model of GW agent exposure (10 days PB+PER) and undertook an extensive lifelong neurobehavioral characterization of the mice from 11 days to 22.5 months post exposure in order to address the persistence and chronicity of effects suffered by the current GWI patient population, 24 years post-exposure. Mice were evaluated using a battery of neurobehavioral testing paradigms, including Open Field Test (OFT), Elevated Plus Maze (EPM), Three Chamber Testing, Radial Arm Water Maze (RAWM), and Barnes Maze (BM) Test. We also carried out neuropathological analyses at 22.5 months post exposure to GW agents after the final behavioral testing. Our results demonstrate that PB+PER exposed mice exhibit neurobehavioral deficits beginning at the 13 months post exposure time point and continuing trends through the 22.5 month post exposure time point. Furthermore, neuropathological changes, including an increase in GFAP staining in the cerebral cortices of exposed mice, were noted 22.5 months post exposure. Thus, the persistent neuroinflammation evident in our model presents a platform with which to identify novel biological pathways, correlating with emergent outcomes that may be amenable to therapeutic targeting. Furthermore, in this work we confirmed our previous findings that GW agent exposure causes neuropathological changes, and have presented novel data which demonstrate increased disinhibition, and lack of social preference in PB+PER exposed mice at 13 months after exposure. We also extended upon our previous work to cover the lifespan of the laboratory mouse using a battery of neurobehavioral techniques. PMID:26793076

Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis

PubMed Central

Dulai, Parambir S; Marquez, Evelyn; Khera, Rohan; Prokop, Larry J; Limburg, Paul J; Gupta, Samir; Murad, Mohammad Hassan

2016-01-01

Objective To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis. Data sources Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries. Study selection Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events. Data extraction Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria. Results 15 randomized controlled trials (12 234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous colorectal cancer could not be estimated. Conclusions Among individuals with previous colorectal neoplasia, non-aspirin NSAIDs are the most effective agents for the prevention of advanced metachronous neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile. Registration PROSPERO (CRD42015029598). PMID:27919915

Ultrasensitive detection of explosives and chemical warfare agents by low-pressure photoionization mass spectrometry.

PubMed

Sun, Wanqi; Liang, Miao; Li, Zhen; Shu, Jinian; Yang, Bo; Xu, Ce; Zou, Yao

2016-08-15

On-spot monitoring of threat agents needs high sensitive instrument. In this study, a low-pressure photoionization mass spectrometer (LPPI-MS) was employed to detect trace amounts of vapor-phase explosives and chemical warfare agent mimetics under ambient conditions. Under 10-s detection time, the limits of detection of 2,4-dinitrotoluene, nitrotoluene, nitrobenzene, and dimethyl methyl phosphonate were 30, 0.5, 4, and 1 parts per trillion by volume, respectively. As compared to those obtained previously with PI mass spectrometric techniques, an improvement of 3-4 orders of magnitude was achieved. This study indicates that LPPI-MS will open new opportunities for the sensitive detection of explosives and chemical warfare agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of genetic diversity of Fusarium tupiense, the main causal agent of mango malformation disease in southern Spain

USDA-ARS?s Scientific Manuscript database

Mango malformation disease (MMD) has become an important global disease affecting this crop. The aim of this study was to identify the main causal agents of MMD in the Axarquía region of southern Spain and determine their genetic diversity. Fusarium mangiferae was previously described in the Axarquí...

Systemic use of tumor necrosis factor alpha as an anticancer agent

PubMed Central

Roberts, Nicholas J.; Zhou, Shibin; Diaz, Luis A.; Holdhoff, Matthias

2011-01-01

Tumor necrosis factor-α (TNF-α) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-α with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-α in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-α as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-α. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-α in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID:22036896

Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label

PubMed Central

2011-01-01

Introduction The purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated off-label with biological agents in daily practice. Methods The BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD. Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the period in which they were treated with biological agents. Results A total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010. The first biological therapies included rituximab in 264 (77%) patients, infliximab in 37 (11%), etanercept in 21 (6%), adalimumab in 19 (5%), and 'other' agents in 3 (1%). Forty-five severe infections occurred in 37 patients after a mean follow-up of 26.76 months. These infections resulted in four deaths. The crude rate of severe infections was 90.9 events/1000 person-years (112.5 for rituximab, 76.9 for infliximab, 66.9 for adalimumab and 30.5 for etanercept respectively). In patients treated with more than two courses of rituximab, the crude rate of severe infection was 226.4 events/1000 person-years. A pathogen was identified in 24 (53%) severe infections. The most common sites of severe infection were the lower respiratory tract (39%), bacteremia/sepsis (20%) and the urinary tract (16%). There were no significant differences relating to gender, SAD, agent, other previous therapies, number of previous immunosuppressive agents received or other therapies administered concomitantly. Cox regression analysis showed that age (P = 0.015) was independently associated with an increased risk of severe infection. Survival curves showed a lower survival rate in patients with severe infections (log-rank and Breslow tests < 0.001). Conclusions The rates of severe infections in SAD patients with severe, refractory disease treated depended on the biological agent used, with the highest rates being observed for rituximab and the lowest for etanercept. The rate of infection was especially high in patients receiving three or more courses of rituximab. In patients with severe infections, survival was significantly reduced. Older age was the only significant predictive factor of severe infection. PMID:21745378

X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents

PubMed Central

Rand, Danielle; Uchida, Masaki; Douglas, Trevor; Rose-Petruck, Christoph

2014-01-01

Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based “nanobubble” contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size. PMID:25321797

Evaluation of mitoguazone in patients with refractory chronic lymphocytic leukemia: a phase II study (P-H482) of the Eastern Cooperative Oncology Group.

PubMed

Wiernik, P H; Gordon, L I; Oken, M M; Harris, J E; O'Connell, M J

1999-10-01

Mitoguazone is a unique antitumor agent that interferes with polyamine synthesis that has been reported to have activity against AIDS-related malignant lymphoma. We, therefore, tested this agent for activity against chronic lymphocytic leukemia (CLL) in this phase II study. Mitoguazone, 500 mg/M2 was given intravenously weekly to 13 patients with relapsed or refractory, previously treated Rai stages 2-4 CLL. There were no complete or partial responses as judged by standard criteria. Toxicity was acceptable. Mitoguazone in the dose and schedule employed in this study has no significant activity as a single agent in patients with relapsed or refractory CLL.

TOPICAL REVIEW: Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

NASA Astrophysics Data System (ADS)

Qin, Shengping; Caskey, Charles F.; Ferrara, Katherine W.

2009-03-01

Microbubble contrast agents and the associated imaging systems have developed over the past 25 years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium.

Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

PubMed Central

Qin, Shengping; Caskey, Charles F; Ferrara, Katherine W

2010-01-01

Microbubble contrast agents and the associated imaging systems have developed over the past twenty-five years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium. PMID:19229096

Lossed in translation: an off-the-shelf method to recover probabilistic beliefs from loss-averse agents.

PubMed

Offerman, Theo; Palley, Asa B

2016-01-01

Strictly proper scoring rules are designed to truthfully elicit subjective probabilistic beliefs from risk neutral agents. Previous experimental studies have identified two problems with this method: (i) risk aversion causes agents to bias their reports toward the probability of [Formula: see text], and (ii) for moderate beliefs agents simply report [Formula: see text]. Applying a prospect theory model of risk preferences, we show that loss aversion can explain both of these behavioral phenomena. Using the insights of this model, we develop a simple off-the-shelf probability assessment mechanism that encourages loss-averse agents to report true beliefs. In an experiment, we demonstrate the effectiveness of this modification in both eliminating uninformative reports and eliciting true probabilistic beliefs.

Uncertainty in a spatial evacuation model

NASA Astrophysics Data System (ADS)

Mohd Ibrahim, Azhar; Venkat, Ibrahim; Wilde, Philippe De

2017-08-01

Pedestrian movements in crowd motion can be perceived in terms of agents who basically exhibit patient or impatient behavior. We model crowd motion subject to exit congestion under uncertainty conditions in a continuous space and compare the proposed model via simulations with the classical social force model. During a typical emergency evacuation scenario, agents might not be able to perceive with certainty the strategies of opponents (other agents) owing to the dynamic changes entailed by the neighborhood of opponents. In such uncertain scenarios, agents will try to update their strategy based on their own rules or their intrinsic behavior. We study risk seeking, risk averse and risk neutral behaviors of such agents via certain game theory notions. We found that risk averse agents tend to achieve faster evacuation time whenever the time delay in conflicts appears to be longer. The results of our simulations also comply with previous work and conform to the fact that evacuation time of agents becomes shorter once mutual cooperation among agents is achieved. Although the impatient strategy appears to be the rational strategy that might lead to faster evacuation times, our study scientifically shows that the more the agents are impatient, the slower is the egress time.

Influence of anionic surface-active agents on the uptake of heavy metals by water hyacinth (Eichhornia crassipes)

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

Muramoto, S.; Oki, Y.

1984-10-01

In a previous paper, the ability of water hyacinth to remove toxic heavy metals, cadmium, lead, and mercury, from a metal-containing solution was reported. However, information on the effects of surface-active agents on the metal uptake from waste water by water hyacinth is insufficient. Surface-active agents including anionic detergents have been found in lake, ponds, and rivers polluted by waste from industry and municipal sewage treatment plants. The present study examines the uptake of cadmium or nickel in the presence of the anionic detergent sodium dedecyl sulfate.

Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis.

PubMed

Wu, Xiao-Jun; Zhi, Yi; He, Peng; Zhou, Xiao-Zhou; Zheng, Ji; Chen, Zhi-Wen; Zhou, Zhan-Song

2016-01-01

Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients. Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0). Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups. In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective trials due to its potential survival benefit in advanced UC patients.

TRAFFIC-RELATED AIR POLLUTANTS AND CHILDREN'S RESPIRATORY HEALTH IN EL PASO AND DETROIT

EPA Science Inventory

Hypotheses -Specific Agent • Diesel exhaust particles • Ultrafine particles • Coarse-mode particles (road dust) • Noise and stress • Nonspecific irritants Previous Epidemiology • Kanawha Valley Health Study • Munich Traffic Study • Dutch Traffic Studies • S....

PERCHLORATE ACCUMULATION FROM FERTILIZER IN LEAFY VEGETATION

EPA Science Inventory

Perchlorate contaminated water and soil has been identified in many areas of the United States. Previous studies indicated that the primary source of contamination was from industry and military operations that use perchlorate as an oxidzing agent. However, recent studies have fo...

The role of bevacizumab on tumour angiogenesis and in the management of gynaecological cancers: A review.

PubMed

Chellappan, Dinesh Kumar; Leng, Kun Hooi; Jia, Lee Jia; Aziz, Nur Amirah Binti Abdul; Hoong, Wong Chun; Qian, Yap Cheng; Ling, Fam Yi; Wei, Gwee Sing; Ying, Tiong; Chellian, Jestin; Gupta, Gaurav; Dua, Kamal

2018-06-01

The study aims to analyze the effectiveness of bevacizumab in addressing the complications associated with gynecological cancers and evaluates effective treatments for various gynecological cancers. The study follows a systematic review approach that has been implemented to analyze the qualitative published data from previous studies. Studies related with the trials of angiogenesis and bevacizumab were selected in the review. In general, the management of gynecological cancers include chemotherapy, surgery and radiation therapy. Results suggest bevacizumab as an effective treatment modality for cervical and several other cancers. Overall, bevacizumab showed promising results in improving the overall survival rate of gynecological cancer patients through the combination of bevacizumab with other chemotherapeutic agents. Bevacizumab possess less documented adverse effects when compared to other chemotherapeutic agents. The manifestation and severity of adverse effects reported varied according to the chemotherapeutic agent(s) that were used with bevacizumab in combination therapy. Overall, bevacizumab effectively improved the survival rate in patients with several gynaecological cancers. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Managing security risks for inter-organisational information systems: a multiagent collaborative model

NASA Astrophysics Data System (ADS)

Feng, Nan; Wu, Harris; Li, Minqiang; Wu, Desheng; Chen, Fuzan; Tian, Jin

2016-09-01

Information sharing across organisations is critical to effectively managing the security risks of inter-organisational information systems. Nevertheless, few previous studies on information systems security have focused on inter-organisational information sharing, and none have studied the sharing of inferred beliefs versus factual observations. In this article, a multiagent collaborative model (MACM) is proposed as a practical solution to assess the risk level of each allied organisation's information system and support proactive security treatment by sharing beliefs on event probabilities as well as factual observations. In MACM, for each allied organisation's information system, we design four types of agents: inspection agent, analysis agent, control agent, and communication agent. By sharing soft findings (beliefs) in addition to hard findings (factual observations) among the organisations, each organisation's analysis agent is capable of dynamically predicting its security risk level using a Bayesian network. A real-world implementation illustrates how our model can be used to manage security risks in distributed information systems and that sharing soft findings leads to lower expected loss from security risks.

Spatiotemporal trends in the discovery of new swine infectious agents.

PubMed

Fournié, Guillaume; Kearsley-Fleet, Lianne; Otte, Joachim; Pfeiffer, Dirk Udo

2015-09-28

A literature review was conducted to assess the spatiotemporal trend and diversity of infectious agents that were newly found in pigs between 1985 and 2010. We identified 173 new variants from 91 species, of which 73 species had not been previously described in pigs. These new species, of which one third was zoonotic, were taxonomically diverse. They were identified throughout the study period, predominantly in the main pork producing countries, with the rate of discovery of new virus variants doubling within the last 10 years of the study period. Whilst infectious agent species newly detected in high-income countries were more likely to be associated with higher virulence, zoonotic agents prevailed in low- and middle-income countries. Although this trend is influenced by factors conditioning infectious agent detection - diagnostic methods, surveillance efforts, research interests -, it may suggest that different scales and types of production systems promote emergence of certain types of infectious agents. Considering the rapid transformation of the swine industry, concerted efforts are needed for improving our understanding of the factors influencing the emergence of infectious agents. This information then needs to inform the design of risk-based surveillance systems and strategies directly mitigating the risk associated with these factors.

Dendritic growth model of multilevel marketing

NASA Astrophysics Data System (ADS)

Pang, James Christopher S.; Monterola, Christopher P.

2017-02-01

Biologically inspired dendritic network growth is utilized to model the evolving connections of a multilevel marketing (MLM) enterprise. Starting from agents at random spatial locations, a network is formed by minimizing a distance cost function controlled by a parameter, termed the balancing factor bf, that weighs the wiring and the path length costs of connection. The paradigm is compared to an actual MLM membership data and is shown to be successful in statistically capturing the membership distribution, better than the previously reported agent based preferential attachment or analytic branching process models. Moreover, it recovers the known empirical statistics of previously studied MLM, specifically: (i) a membership distribution characterized by the existence of peak levels indicating limited growth, and (ii) an income distribution obeying the 80 - 20 Pareto principle. Extensive types of income distributions from uniform to Pareto to a "winner-take-all" kind are also modeled by varying bf. Finally, the robustness of our dendritic growth paradigm to random agent removals is explored and its implications to MLM income distributions are discussed.

Pressure-dependent attenuation with microbubbles at low mechanical index.

PubMed

Tang, Meng-Xing; Eckersley, Robert J; Noble, J Alison

2005-03-01

It has previously been shown that the attenuation of ultrasound (US) by microbubble contrast agents is dependent on acoustic pressure (Chen et al. 2002). Although previous studies have modelled the pressure-dependence of attenuation in single bubbles, this paper investigates this subject by considering a bulk volume of bubbles together with other linear attenuators. Specifically, a new pressure-dependent attenuation model for an inhomogeneous volume of attenuators is proposed. In this model, the effect of the attenuation on US propagation is considered. The model was validated using experimental measurements on the US contrast agent Sonovue. The results indicate, at low acoustic pressures, a linear relationship between the attenuation of Sonovue, measured in dB, and the insonating acoustic pressure.

From Agents to Continuous Change via Aesthetics: Learning Mechanics with Visual Agent-Based Computational Modeling

ERIC Educational Resources Information Center

Sengupta, Pratim; Farris, Amy Voss; Wright, Mason

2012-01-01

Novice learners find motion as a continuous process of change challenging to understand. In this paper, we present a pedagogical approach based on agent-based, visual programming to address this issue. Integrating agent-based programming, in particular, Logo programming, with curricular science has been shown to be challenging in previous research…

An agent-based computational model for tuberculosis spreading on age-structured populations

NASA Astrophysics Data System (ADS)

Graciani Rodrigues, C. C.; Espíndola, Aquino L.; Penna, T. J. P.

2015-06-01

In this work we present an agent-based computational model to study the spreading of the tuberculosis (TB) disease on age-structured populations. The model proposed is a merge of two previous models: an agent-based computational model for the spreading of tuberculosis and a bit-string model for biological aging. The combination of TB with the population aging, reproduces the coexistence of health states, as seen in real populations. In addition, the universal exponential behavior of mortalities curves is still preserved. Finally, the population distribution as function of age shows the prevalence of TB mostly in elders, for high efficacy treatments.

Male bladder cancer risk and occupational exposure according to a job-exposure matrix-a case-control study in British Columbia, Canada.

PubMed

Richardson, Kathryn; Band, Pierre R; Astrakianakis, George; Le, Nhu D

2007-12-01

The authors investigated the risk of bladder cancer in association with exposure to over 12 000 occupational chemical agents, complex mixtures, and other substances (hereafter referred to as chemical agents). Adult males diagnosed with cancer between 1983 and 1990 in British Columbia, Canada, were surveyed. Detailed occupational histories and confounding information was provided by a self-administered questionnaire. Cancer controls were matched to bladder cancer cases, resulting in 1062 cases and 8057 controls for the analysis. An extensive United-States-based job-exposure matrix was applied to estimate cumulative exposure to occupational chemical agents. Odds ratios for bladder cancer due to exposure to chemical agents were estimated via conditional logistic regression analyses, adjusted for important confounders. A significantly (P<0.05) increased risk was detected for ever exposure to 635 chemical agents, and 341 chemical agents exhibited a significantly increasing dose-response relationship. Adjustment for multiple comparisons resulted in a subset of 29 chemical agents that continued to show significant results. A principal components analysis classified these 29 chemical agents into five independent groups, distinguished mainly by job. Exposures to these chemical agents were largely due to employment in the logging and construction industries and occupations involving motor vehicles. Consistent results were observed for bladder carcinogens reported in the literature. This study suggests that several specific chemical agents were significantly associated with the risk of bladder cancer. The chemical agents were mainly derivatives or combustion products of fossil fuels. The results corroborate important findings from the literature and document a risk for specific chemical agents not previously reported.

Optimal Reward Functions in Distributed Reinforcement Learning

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Tumer, Kagan

2000-01-01

We consider the design of multi-agent systems so as to optimize an overall world utility function when (1) those systems lack centralized communication and control, and (2) each agents runs a distinct Reinforcement Learning (RL) algorithm. A crucial issue in such design problems is to initialize/update each agent's private utility function, so as to induce best possible world utility. Traditional 'team game' solutions to this problem sidestep this issue and simply assign to each agent the world utility as its private utility function. In previous work we used the 'Collective Intelligence' framework to derive a better choice of private utility functions, one that results in world utility performance up to orders of magnitude superior to that ensuing from use of the team game utility. In this paper we extend these results. We derive the general class of private utility functions that both are easy for the individual agents to learn and that, if learned well, result in high world utility. We demonstrate experimentally that using these new utility functions can result in significantly improved performance over that of our previously proposed utility, over and above that previous utility's superiority to the conventional team game utility.

Development of haemostatic decontaminants for treatment of wounds contaminated with chemical warfare agents. 3: Evaluation of in vitro topical decontamination efficacy using damaged skin.

PubMed

Lydon, Helen L; Hall, Charlotte A; Dalton, Christopher H; Chipman, J Kevin; Graham, John S; Chilcott, Robert P

2017-08-01

Previous studies have demonstrated that haemostatic products with an absorptive mechanism of action retain their clotting efficiency in the presence of toxic materials and are effective in decontaminating chemical warfare (CW) agents when applied to normal, intact skin. The purpose of this in vitro study was to assess three candidate haemostatic products for effectiveness in the decontamination of superficially damaged porcine skin exposed to the radiolabelled CW agents, soman (GD), VX and sulphur mustard (HD). Controlled physical damage (removal of the upper 100 μm skin layer) resulted in a significant enhancement of the dermal absorption of all three CW agents. Of the haemostatic products assessed, WoundStat™ was consistently the most effective, being equivalent in performance to a standard military decontaminant (fuller's earth). These data suggest that judicious application of haemostatic products to wounds contaminated with CW agents may be a viable option for the clinical management of casualties presenting with contaminated, haemorrhaging injuries. Further studies using a relevant animal model are required to confirm the potential clinical efficacy of WoundStat™ for treating wounds contaminated with CW agents. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

How the indirect reciprocity with co-evolving norm and strategy for 2 × 2 prisoner's dilemma game works for emerging cooperation

NASA Astrophysics Data System (ADS)

Tanimoto, Jun; Sagara, Hirokji

2015-11-01

We built a new indirect reciprocity model based on binary image scores, where an agent's strategy and norm co-evolve. The norm, meaning what behavior is evaluated as "good" or "bad," stipulates how image scores of two agents playing a game is altered, which has been presumed to be a fixed value in most previous studies. Also, unlike former studies, our model allows an agent to play with an agent who has a different norm. This point of relaxing the freedom of the model pulls down cooperation level vis-à-vis the case where an agent always plays with another one having same norm. However, it is observed that a rather larger dilemma shows robust cooperation establishing compared with a smaller dilemma, since a norm that punishes a so-called second-order free-rider is prompted. To encourage the evolution of norms to be able to punish second-order free-riders, a society needs a small number of defectors. This is elucidated by the fact that cases with action error are more cooperative than those without action error.

Cosmetic Preservatives as Therapeutic Corneal and Scleral Tissue Cross-Linking Agents

PubMed Central

Babar, Natasha; Kim, MiJung; Cao, Kerry; Shimizu, Yukari; Kim, Su-Young; Takaoka, Anna; Trokel, Stephen L.; Paik, David C.

2015-01-01

Purpose. Previously, aliphatic β-nitroalcohols (BNAs) have been studied as a means to chemically induce tissue cross-linking (TXL) of cornea and sclera. There are a number of related and possibly more potent agents, known as formaldehyde releasers (FARs), that are in commercial use as preservatives in cosmetics and other personal care products. The present study was undertaken in order to screen such compounds for potential clinical utility as therapeutic TXL agents. Methods. A chemical registry of 62 FARs was created from a literature review and included characteristics relevant to TXL such as molecular weight, carcinogenicity/mutagenicity, toxicity, hydrophobicity, and commercial availability. From this registry, five compounds [diazolidinyl urea (DAU), imidazolidinyl urea (IMU), sodium hydroxymethylglycinate (SMG), DMDM hydantoin (DMDM), 5-Ethyl-3,7-dioxa-1-azabicyclo [3.3.0] octane (OCT)] were selected for efficacy screening using two independent systems, an ex vivo rabbit corneal cross-linking simulation setup and incubation of cut scleral tissue pieces. Treatments were conducted at pH 7.4 or 8.5 for 30 minutes. Efficacy was evaluated using thermal denaturation temperature (Tm), and cell toxicity was studied using the trypan blue exclusion method. Results. Cross-linking effects in the five selected FARs were pH and concentration dependent. Overall, the Tm shifts were in agreement with both cornea and sclera. By comparison with BNAs previously reported upon, the FARs identified in this study were significantly more potent but with similar or better cytotoxicity. Conclusions. The FARs, a class of compounds well known to the cosmetic industry, may have utility as therapeutic TXL agents. The compounds studied thus far show promise and will be further tested. PMID:25634979

Gryphon: A Hybrid Agent-Based Modeling and Simulation Platform for Infectious Diseases

NASA Astrophysics Data System (ADS)

Yu, Bin; Wang, Jijun; McGowan, Michael; Vaidyanathan, Ganesh; Younger, Kristofer

In this paper we present Gryphon, a hybrid agent-based stochastic modeling and simulation platform developed for characterizing the geographic spread of infectious diseases and the effects of interventions. We study both local and non-local transmission dynamics of stochastic simulations based on the published parameters and data for SARS. The results suggest that the expected numbers of infections and the timeline of control strategies predicted by our stochastic model are in reasonably good agreement with previous studies. These preliminary results indicate that Gryphon is able to characterize other future infectious diseases and identify endangered regions in advance.

Safety Assessment of Diethanolamine and Its Salts as Used in Cosmetics.

PubMed

Fiume, Monice M; Heldreth, Bart; 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

The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of diethanolamine and its salts as used in cosmetics. Diethanolamine functions as a pH adjuster; the 16 salts included in this rereview reportedly function as surfactants, emulsifying agents, viscosity increasing agents, hair or skin conditioning agents, foam boosters, or antistatic agents. The Panel reviewed available animal and clinical data, as well as information from previous CIR reports. Since data were not available for each individual ingredient, and since the salts dissociate freely in water, the Panel extrapolated from previous reports to support safety. The Panel concluded that diethanolamine and its salts are safe for use when formulated to be nonirritating. These ingredients should not be used in cosmetic products in which N-nitroso compounds can be formed.

Effect of a Dispersant Agent in Fine Coal Recovery from Washery Tailings by Oil Agglomeration (Preliminary Study)

NASA Astrophysics Data System (ADS)

Yasar, Özüm; Uslu, Tuncay

2017-12-01

Among the fine coal cleaning methods, the oil agglomeration process has important advantages such as high process recovery, more clean product, simple dewatering stage. Several coal agglomeration studies have been undertaken recently and effects of different variables on the process performance have been investigated. However, unlike flotation studies, most of the previous agglomeration studies have not used dispersing agents to minimize slime coating effects of clays. In this study, agglomeration process was applied for recovery of fine coals from coal washery tailings containing remarkable amount of fine coal. Negative effect of fine clays during recovery was tried to be eliminated by using dispersing agent instead of de-sliming. Although ash reductions over 90 % were achieved, performance remained below expectations in terms of combustible matter recovery. However, this study is a preliminary one. It is considered that more satisfied results will be obtained in the next studies by changing the variables such as solid ratio, oil dosage, dispersant type and dosage.

Lung cancer risk among workers in the construction industry: results from two case-control studies in Montreal.

PubMed

Lacourt, Aude; Pintos, Javier; Lavoué, Jérôme; Richardson, Lesley; Siemiatycki, Jack

2015-09-22

Given the large number of workers in the construction industry, it is important to derive accurate and valid estimates of cancer risk, and in particular lung cancer risk. In most previous studies, risks among construction workers were compared with general populations including blue and white collar workers. The main objectives of this study were to assess whether construction workers experience excess lung cancer risk, and whether exposure to selected construction industry exposures carries excess risks. We wished to address these objectives within the sub-population of blue collar workers. Two case-control studies were conducted in Montreal. Combined, they included 1593 lung cancer cases and 1427 controls, of whom 1304 cases and 1081 controls had been blue collar workers. Detailed lifetime job histories were obtained and translated by experts into histories of exposure to chemical agents. The two key analyses were to estimate odds ratio (OR) estimates of lung cancer risk: a) for all blue-collar construction workers compared with other blue-collar workers, and b) for construction workers exposed to each of 20 exposure agents found in the construction industry compared with construction workers unexposed to those agents. All analyses were conducted using unconditional logistic regression adjusted for socio-demographic factors and smoking history. The OR for all construction workers combined was 1.11 (95 % CI: 0.90-1.38), based on 381 blue collar construction workers. Analyses of specific exposures were hampered by small numbers and imprecise estimates. While none of 20 occupational agents examined was significantly associated with lung cancer, the following agents manifested non-significantly elevated ORs: asbestos, silica, Portland cement, soil dust, calcium oxide and calcium sulfate. Compared with other blue collar workers, there was only a slight increased risk of lung cancer for subjects who ever held an occupation in the construction industry. The analyses of agents within the construction industry produced imprecise estimates of risk, but nevertheless pointed to some plausible associations. Excess risks for asbestos and silica were in line with previous knowledge. The possible excess risks with the other inorganic dusts require further corroboration.

An update on adverse drug reactions related to β-lactam antibiotics.

PubMed

Vardakas, Konstantinos Z; Kalimeris, Georgios D; Triarides, Nikolaos A; Falagas, Matthew E

2018-05-01

β-lactams have been consistently associated with the majority of drug-related adverse events. Generally, these are mild under proper dosing and judicious selection. Areas covered: Immediate hypersensitivity reactions are the most feared adverse events encountered after β-lactam administration. Emerging evidence shows that immediate reactions are not as common as previously thought. Specialist consultation and testing seems prudent before a patient is officially declared allergic to β-lactams. The risk of cross-reactions between not only members of the β-lactam super-family but also between specific classes is also lower than previously thought. Newer studies have shown that cross-reactions are not universal and pertain to specific agents with similar side chains or metabolites of the β-lactam core. The frequency of severe kidney or liver toxicity, neurotoxicity, cytopenias and Clostiridium difficile infection following β-lactam administration seem to be agent-specific. Expert opinion: The currently available data denote that in addition to age, gender, co-morbidity, renal or liver function, and co-administered agents, the antibiotic levels rather than the dose itself seem to be associated with the emergence of adverse events. Most of them subside with time after withdrawal of the offending agent, but the number of cases resulting in chronic disabilities or even deaths in not negligible.

Resolving the Framework Position of Organic Structure-Directing Agents in Hierarchical Zeolites via Polarized Stimulated Raman Scattering.

PubMed

Fleury, Guillaume; Steele, Julian A; Gerber, Iann C; Jolibois, F; Puech, P; Muraoka, Koki; Keoh, Sye Hoe; Chaikittisilp, Watcharop; Okubo, Tatsuya; Roeffaers, Maarten B J

2018-04-05

The direct synthesis of hierarchically intergrown silicalite-1 can be achieved using a specific diquaternary ammonium agent. However, the location of these molecules in the zeolite framework, which is critical to understand the formation of the material, remains unclear. Where traditional characterization tools have previously failed, herein we use polarized stimulated Raman scattering (SRS) microscopy to resolve molecular organization inside few-micron-sized crystals. Through a combination of experiment and first-principles calculations, our investigation reveals the preferential location of the templating agent inside the linear pores of the MFI framework. Besides illustrating the attractiveness of SRS microscopy in the field of material science to study and spatially resolve local molecular distribution as well as orientation, these results can be exploited in the design of new templating agents for the preparation of hierarchical zeolites.

Chemical and Biological Studies of Nakiterpiosin and Nakiterpiosinone

PubMed Central

Gao, Shuanhu; Wang, Qiaoling; Huang, Lily Jun-Shen; Lum, Lawrence; Chen, Chuo

2009-01-01

Nakiterpiosin and nakiterpiosinone are two related C-nor-D-homosteroids isolated from the sponge Terpios hoshinota that show promise as anti-cancer agents. We have previously described the asymmetric synthesis and the revision of the relative configuration of nakiterpiosin. We now provide detailed information on the stereochemical analysis that supports our structure revision and the synthesis of the originally proposed and revised nakiterpiosin. In addition, we herein describe a refined approach for the synthesis of nakiterpiosin, the first synthesis of nakiterpiosinone, and preliminary mechanistic studies of nakiterpiosin's action in mammalian cells. Cells treated with nakiterpiosin exhibit compromised formation of the primary cilium, an organelle that functions as an assembly point for components of the Hedgehog signal transduction pathway. We provide evidence that the biological effects exhibited by nakiterpiosin are mechanistically distinct from those of well-established anti-mitotic agents such as taxol. Nakiterpiosin may be useful as an anti-cancer agent in those tumors resistant to existing anti-mitotic agents and those dependent on Hedgehog pathway responses for growth. PMID:20000429

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.

Using Synchronous Boolean Networks to Model Several Phenomena of Collective Behavior

PubMed Central

Kochemazov, Stepan; Semenov, Alexander

2014-01-01

In this paper, we propose an approach for modeling and analysis of a number of phenomena of collective behavior. By collectives we mean multi-agent systems that transition from one state to another at discrete moments of time. The behavior of a member of a collective (agent) is called conforming if the opinion of this agent at current time moment conforms to the opinion of some other agents at the previous time moment. We presume that at each moment of time every agent makes a decision by choosing from the set (where 1-decision corresponds to action and 0-decision corresponds to inaction). In our approach we model collective behavior with synchronous Boolean networks. We presume that in a network there can be agents that act at every moment of time. Such agents are called instigators. Also there can be agents that never act. Such agents are called loyalists. Agents that are neither instigators nor loyalists are called simple agents. We study two combinatorial problems. The first problem is to find a disposition of instigators that in several time moments transforms a network from a state where the majority of simple agents are inactive to a state with the majority of active agents. The second problem is to find a disposition of loyalists that returns the network to a state with the majority of inactive agents. Similar problems are studied for networks in which simple agents demonstrate the contrary to conforming behavior that we call anticonforming. We obtained several theoretical results regarding the behavior of collectives of agents with conforming or anticonforming behavior. In computational experiments we solved the described problems for randomly generated networks with several hundred vertices. We reduced corresponding combinatorial problems to the Boolean satisfiability problem (SAT) and used modern SAT solvers to solve the instances obtained. PMID:25526612

Investigational Antimicrobial Agents of 2013

PubMed Central

Pucci, Michael J.

2013-01-01

SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

Chlamydia gallinacea: a widespread emerging Chlamydia agent with zoonotic potential in backyard poultry.

PubMed

Li, L; Luther, M; Macklin, K; Pugh, D; Li, J; Zhang, J; Roberts, J; Kaltenboeck, B; Wang, C

2017-10-01

Chlamydia gallinacea, a new chlamydial agent, has been reported in four European countries as well as Argentina and China. Experimentally infected chickens with C. gallinacea in previous study showed no clinical signs but had significantly reduced gains in body weight (6·5-11·4%). Slaughterhouse workers exposed to infected chickens have developed atypical pneumonia, indicating C. gallinacea is likely a zoonotic agent. In this study, FRET-PCR confirmed that C. gallinacea was present in 12·4% (66/531) of oral-pharyngeal samples from Alabama backyard poultry. Phylogenetic comparisons based on ompA variable domain showed that 16 sequenced samples represented 14 biotypes. We report for the first time the presence of C. gallinacea in North America, and this warrants further research on the organism's pathogenicity, hosts, transmission, and zoonotic potential.

Clinicopathological features of mycosis fungoides in patients exposed to Agent Orange during the Vietnam War.

PubMed

Jang, Min Soo; Jang, Jun Gyu; Han, Sang Hwa; Park, Jong Bin; Kang, Dong Young; Kim, Sang Tae; Suh, Kee Suck

2013-08-01

There are no reports on the clinicopathological features of mycosis fungoides (MF) among veterans exposed to Agent Orange, one of the herbicides used during the Vietnam War. To evaluate the clinical, histopathological and genotypic findings of Vietnam War veterans with MF and a positive history of exposure to Agent Orange, we performed a comparative clinicopathological study between MF patients with a history of Agent Orange exposure and those without a history of Agent Orange exposure. Twelve Vietnam War veterans with MF were identified. The mean interval from Agent Orange exposure to diagnosis was 24.5 years (range, 9-35). Skin lesions were significantly present on exposed and unexposed areas. Most patients (75%) experienced pruritus (mean visual analog scale score of 6.7). MF was manifested by plaques in 10 patients and by lichenification in five. Histopathological features of most cases were consistent with MF. Biopsy specimens also demonstrated irregular acanthosis (66.7%). In the comparative study, MF patients with a history of Agent Orange exposure differed significantly from those without exposure to Agent Orange in demographic and clinical characteristics. In addition, patients with exposure had an increased tendency for lesions in the exposed area. Notably, our patients showed a higher frequency (33.3%) of mycosis fungoides palmaris et plantaris than in previous studies. Histologically, irregular acanthosis was more frequently observed than ordinary MF. Our results indicate that dermatologists should pay close attention to these clinicopathological differences. Careful assessment of history of exposure to defoliants is warranted in some cases suspicious for MF. © 2013 Japanese Dermatological Association.

Agent Orange exposure and cancer incidence in Korean Vietnam veterans: a prospective cohort study.

PubMed

Yi, Sang-Wook; Ohrr, Heechoul

2014-12-01

During the Vietnam War, US and allied military sprayed approximately 77 million liters of tactical herbicides including Agent Orange, contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. To the authors' knowledge, few studies to date have examined the association between Agent Orange exposure and cancer incidence among Korean veterans who were exposed to Agent Orange during the Vietnam War. An Agent Orange exposure index, based on the proximity of the veteran's military unit to the area that was sprayed with Agent Orange, was developed using a geographic information system-based model. Cancer incidence was followed for 180,251 Vietnam veterans from 1992 through 2003. After adjustment for age and military rank, high exposure to Agent Orange was found to significantly increase the risk of all cancers combined (adjusted hazards ratio [aHR], 1.08). Risks for cancers of the mouth (aHR, 2.54), salivary glands (aHR, 6.96), stomach (aHR, 1.14), and small intestine (aHR, 2.30) were found to be significantly higher in the high-exposure group compared with the low-exposure group. Risks for cancers of all sites combined (aHR, 1.02) and for cancers of the salivary glands (aHR, 1.47), stomach (aHR, 1.03), small intestine (aHR, 1.24), and liver (aHR, 1.02) were elevated with a 1-unit increase in the exposure index. Exposure to Agent Orange several decades earlier may increase the risk of cancers in all sites combined, as well as several specific cancers, among Korean veterans of the Vietnam War, including some cancers that were not found to be clearly associated with exposure to Agent Orange in previous cohort studies primarily based on Western populations. © 2014 American Cancer Society.

Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

PubMed

Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

2014-03-01

There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P < 0.001). No toxicity-related death was reported. The use of anti-cancer systemic therapy is safe and efficient in gastric MALT lymphoma. In this retrospective study, the combination of rituximab plus chlorambucil seems more efficient than rituximab or alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

A pilot comparative study of topical latanoprost and tacrolimus in combination with narrow-band ultraviolet B phototherapy and microneedling for the treatment of nonsegmental vitiligo.

PubMed

Korobko, Igor V; Lomonosov, Konstantin M

2016-11-01

Prostaglandins and their analogues are beneficial as topical agents in vitiligo treatment, yet neither of the previous study addressed their comparative efficiency with conventional topical agents used in vitiligo treatment. In this pilot (24 patients) left-right comparative study we addressed efficiency of prostaglandin F2α analogue latanoprost versus tacrolimus when combined with narrow-band ultraviolet B and microneedling in repigmentation of nonsegmental vitiligo lesions. Our results confirm potency of prostaglandins, in particular, that of latanoprost, in inducing repigmentation, with the efficiency being at least comparable to that of tacrolimus, while contribution of microneedling remains unclear. In summary, results of our study provide further evidences for justified use of prostaglandins, in particular, latanoprost, in vitiligo treatment. In turn, this warrants future studies on the topic aiming to conclusively introduce prostaglandin-based formulations as conventional agents for vitiligo management. © 2016 Wiley Periodicals, Inc.

Role of Glutamate Release and Metabotropic Autoreceptors in Seizureogenic Actions of Cholinomimetic Agents

DTIC Science & Technology

2001-10-01

produced by centrally-active cholinomimetic agents and to evaluate possible palliative treatments for central cholinomimetic toxicity. The scope of...REPORT: 10/01/00-09/30/01 AWARD NUMBER: DAMD17-98-1-8617 evaluation of the effects by intracerebral infusion of the organophosphate agent paraoxon on EEG...agents. Previously, we had reported successful induction of seizure-like changes in EEG activity of anesthetized rats following intracerebral infusion

Antihyperglycemic Agents Are Inversely Associated With Intracranial Aneurysm Rupture.

PubMed

Can, Anil; Castro, Victor M; Yu, Sheng; Dligach, Dmitriy; Finan, Sean; Gainer, Vivian S; Shadick, Nancy A; Savova, Guergana; Murphy, Shawn; Cai, Tianxi; Weiss, Scott T; Du, Rose

2018-01-01

Previous studies have suggested a protective effect of diabetes mellitus on aneurysmal subarachnoid hemorrhage risk. However, reports are inconsistent, and objective measures of hyperglycemia in these studies are lacking. Our aim was to investigate the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agent use and glycated hemoglobin levels. The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariate and multivariate logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agents and glycated hemoglobin levels. Propensity score weighting was used to account for selection bias. In both unweighted and weighted multivariate analysis, antihyperglycemic agent use was inversely and significantly associated with ruptured aneurysms (unweighted odds ratio, 0.58; 95% confidence interval, 0.39-0.87; weighted odds ratio, 0.57; 95% confidence interval, 0.34-0.96). In contrast, glycated hemoglobin levels were not significantly associated with rupture status. Antihyperglycemic agent use rather than hyperglycemia is associated with decreased risk of aneurysmal subarachnoid hemorrhage, suggesting a possible protective effect of glucose-lowering agents in the pathogenesis of aneurysm rupture. © 2017 American Heart Association, Inc.

Erotic Stimulus Processing under Amisulpride and Reboxetine: A Placebo-Controlled fMRI Study in Healthy Subjects

PubMed Central

Wiegers, Maike; Metzger, Coraline D.; Walter, Martin; Grön, Georg; Abler, Birgit

2015-01-01

Background: Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Methods: Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Results: Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. Conclusions: In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents. PMID:25612894

Artificial intelligence for optimal anemia management in end-stage renal disease.

PubMed

Brier, Michael E; Gaweda, Adam E

2016-08-01

Computational intelligence for the prediction of hemoglobin to guide the selection of erythropoiesis-stimulating agent dose results in improved anemia management. The models used for the prediction result from the use of individual patient data and help to increase the number of hemoglobin observations within the target range. The benefits of using these modeling techniques appear to be a decrease in erythropoiesis-stimulating agent use and a decrease in the number of transfusions. This study confirms the results of previous smaller studies and suggests that additional beneficial results may be achieved. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

In Vitro Activities of Iboga Alkaloid Congeners Coronaridine and 18-Methoxycoronaridine against Leishmania amazonensis

PubMed Central

Delorenzi, Jan Carlo; Freire-de-Lima, Leonardo; Gattass, Cerli R.; de Andrade Costa, Deise; He, Liwen; Kuehne, Martin E.; Saraiva, Elvira M. B.

2002-01-01

In previous studies, we demonstrated the leishmanicide effect of coronaridine, a natural indole alkaloid isolated from stem bark of Peschiera australis (Delorenzi et al., Antimicrob. Agents Chemother. 45:1349-1354, 2001). In this study we show the leishmanicidal effect of the synthetic coronaridine and its racemic 18-methoxylated analog, 18-methoxycoronaridine. Both alkaloids revealed a potent leishmanicide effect against Leishmania amazonensis, a causative agent of cutaneous and diffuse cutaneous leishmaniasis in the New World. Despite their potent leishmanicide effect, both alkaloids were neither toxic to murine macrophages nor did they modulate their oxidative or cytokine production responses. PMID:12069962

Geographical influences of an emerging network of gang rivalries

NASA Astrophysics Data System (ADS)

Hegemann, Rachel A.; Smith, Laura M.; Barbaro, Alethea B. T.; Bertozzi, Andrea L.; Reid, Shannon E.; Tita, George E.

2011-10-01

We propose an agent-based model to simulate the creation of street gang rivalries. The movement dynamics of agents are coupled to an evolving network of gang rivalries, which is determined by previous interactions among agents in the system. Basic gang data, geographic information, and behavioral dynamics suggested by the criminology literature are integrated into the model. The major highways, rivers, and the locations of gangs’ centers of activity influence the agents’ motion. We use a policing division of the Los Angeles Police Department as a case study to test our model. We apply common metrics from graph theory to analyze our model, comparing networks produced by our simulations and an instance of a Geographical Threshold Graph to the existing network from the criminology literature.

Promotion of cooperation by payoff-driven migration

NASA Astrophysics Data System (ADS)

Chen, Ya-Shan; Yang, Han-Xin; Guo, Wen-Zhong

2016-05-01

Migration plays an important role in the evolution of cooperation. Previous studies concerning mobile population often assumed that all agents move with the identical velocity. In this paper, we propose a payoff-driven migration in which the velocity of an agent depends on his/her payoff. A parameter α is introduced to adjust the influence of payoff, when α = 0 means that agents all move with the identical velocity while α > 0 means that the lower the payoff is, the faster the moving speed is, and vice versa. For the prisoner's dilemma game, we find that in comparison with the case that agents all move with the same speed, cooperation could be promoted strongly when payoff-dependent velocity is considered. Remarkably, the cooperation level is not a monotonic function of α, and there exists an optimal value of α which can lead to the maximum cooperation level. For the snowdrift game, the cooperation level increases with α.

Aviation Engine Test Facilities (AETF) fire protection study

NASA Astrophysics Data System (ADS)

Beller, R. C.; Burns, R. E.; Leonard, J. T.

1989-07-01

An analysis is presented to the effectiveness of various types of fire fighting agents in extinguishing the kinds of fires anticipated in Aviation Engine Test Facilities (AETF), otherwise known as Hush Houses. The agents considered include Aqueous Film-Forming Foam, Halon 1301, Halon 1211 and water. Previous test work has shown the rapidity with which aircraft, especially high performance aircraft, can be damaged by fire. Based on this, tentative criteria for this evaluation included a maximum time of 20 s from fire detection to extinguishment and a period of 30 min in which the agent would prevent reignition. Other issues examined included: toxicity, corrosivity, ease of personnel egress, system reliability, and cost effectiveness. The agents were evaluated for their performance in several fire scenarios, including: under frame fire, major engine fire, engine disintegration fire, high-volume pool fire with simultaneous spill fire, internal electrical fire, and runaway engine fire.

From iconic handshapes to grammatical contrasts: longitudinal evidence from a child homesigner

PubMed Central

Coppola, Marie; Brentari, Diane

2014-01-01

Many sign languages display crosslinguistic consistencies in the use of two iconic aspects of handshape, handshape type and finger group complexity. Handshape type is used systematically in form-meaning pairings (morphology): Handling handshapes (Handling-HSs), representing how objects are handled, tend to be used to express events with an agent (“hand-as-hand” iconicity), and Object handshapes (Object-HSs), representing an object's size/shape, are used more often to express events without an agent (“hand-as-object” iconicity). Second, in the distribution of meaningless properties of form (morphophonology), Object-HSs display higher finger group complexity than Handling-HSs. Some adult homesigners, who have not acquired a signed or spoken language and instead use a self-generated gesture system, exhibit these two properties as well. This study illuminates the development over time of both phenomena for one child homesigner, “Julio,” age 7;4 (years; months) to 12;8. We elicited descriptions of events with and without agents to determine whether morphophonology and morphosyntax can develop without linguistic input during childhood, and whether these structures develop together or independently. Within the time period studied: (1) Julio used handshape type differently in his responses to vignettes with and without an agent; however, he did not exhibit the same pattern that was found previously in signers, adult homesigners, or gesturers: while he was highly likely to use a Handling-HS for events with an agent (82%), he was less likely to use an Object-HS for non-agentive events (49%); i.e., his productions were heavily biased toward Handling-HSs; (2) Julio exhibited higher finger group complexity in Object- than in Handling-HSs, as in the sign language and adult homesigner groups previously studied; and (3) these two dimensions of language developed independently, with phonological structure showing a sign language-like pattern at an earlier age than morphosyntactic structure. We conclude that iconicity alone is not sufficient to explain the development of linguistic structure in homesign systems. Linguistic input is not required for some aspects of phonological structure to emerge in childhood, and while linguistic input is not required for morphology either, it takes time to emerge in homesign. PMID:25191283

Illusory versus genuine control in agent-based games

NASA Astrophysics Data System (ADS)

Satinover, J. B.; Sornette, D.

2009-02-01

In the Minority, Majority and Dollar Games (MG, MAJG, G) agents compete for rewards, acting in accord with the previously best-performing of their strategies. Different aspects/kinds of real-world markets are modelled by these games. In the MG, agents compete for scarce resources; in the MAJG agents imitate the group to exploit a trend; in the G agents attempt to predict and benefit both from trends and changes in the direction of a market. It has been previously shown that in the MG for a reasonable number of preliminary time steps preceding equilibrium (Time Horizon MG, THMG), agents’ attempt to optimize their gains by active strategy selection is “illusory”: the hypothetical gains of their strategies is greater on average than agents’ actual average gains. Furthermore, if a small proportion of agents deliberately choose and act in accord with their seemingly worst performing strategy, these outperform all other agents on average, and even attain mean positive gain, otherwise rare for agents in the MG. This latter phenomenon raises the question as to how well the optimization procedure works in the THMAJG and THG. We demonstrate that the illusion of control is absent in THMAJG and THG. This provides further clarification of the kinds of situations subject to genuine control, and those not, in set-ups a priori defined to emphasize the importance of optimization.

Optimal Wonderful Life Utility Functions in Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Tumer, Kagan; Swanson, Keith (Technical Monitor)

2000-01-01

The mathematics of Collective Intelligence (COINs) is concerned with the design of multi-agent systems so as to optimize an overall global utility function when those systems lack centralized communication and control. Typically in COINs each agent runs a distinct Reinforcement Learning (RL) algorithm, so that much of the design problem reduces to how best to initialize/update each agent's private utility function, as far as the ensuing value of the global utility is concerned. Traditional team game solutions to this problem assign to each agent the global utility as its private utility function. In previous work we used the COIN framework to derive the alternative Wonderful Life Utility (WLU), and experimentally established that having the agents use it induces global utility performance up to orders of magnitude superior to that induced by use of the team game utility. The WLU has a free parameter (the clamping parameter) which we simply set to zero in that previous work. Here we derive the optimal value of the clamping parameter, and demonstrate experimentally that using that optimal value can result in significantly improved performance over that of clamping to zero, over and above the improvement beyond traditional approaches.

Mutation Spectrum Induced by Conazole Fungicides in LacI Transgenic C57BL/6 Mouse Liver.

EPA Science Inventory

Conazoles are antifungal agents used in both agricultural and pharmaceutical settings. Some conazoles, including propiconazole and triadimefon, induce hepatocellular tumors in mice, while other conazoles do not. We reported in a previous study that both propiconazole and triadime...

Teachers as Agents of Change in Curricular Reform: The Position of Dance Revisited

ERIC Educational Resources Information Center

MacLean, Justine

2018-01-01

This paper reports findings from a recent large-scale survey of Physical Education (PE) teachers' perceptions of teaching dance and compares them to results of a study completed 10 years previously [MacLean, J. (2007). A longitudinal study to ascertain the factors that impact on the confidence of undergraduate physical education student teachers…

Comparative Study of Antimalarial and Other Drugs on G6PD Deficient Red Cells.

DTIC Science & Technology

the WR compounds previously studied. The suggested use of xylitol as a protective agent against hemolytic drugs (Wang et al) had raised considerable...expectation. Unfortunately, xylitol at the dosages of 20 and 30 g./day was unable, in our experimental set up (transfusion of 51 Cr tagged G6PD

Chemoprevention of Cigarette Smoke–Induced Alterations of MicroRNA Expression in Rat Lungs

PubMed Central

Izzotti, Alberto; Calin, George A.; Steele, Vernon E.; Cartiglia, Cristina; Longobardi, Mariagrazia; Croce, Carlo M.; De Flora, Silvio

2015-01-01

We previously showed that exposure to environmental cigarette smoke (ECS) for 28 days causes extensive downregulation of microRNA expression in the lungs of rats, resulting in the overexpression of multiple genes and proteins. In the present study, we evaluated by microarray the expression of 484 microRNAs in the lungs of either ECS-free or ECS-exposed rats treated with the orally administered chemopreventive agents N-acetylcysteine, oltipraz, indole-3-carbinol, 5,6-benzoflavone, and phenethyl isothiocyanate (as single agents or in combinations). This is the first study of microRNA modulation by chemopreventive agents in nonmalignant tissues. Scatterplot, hierarchical cluster, and principal component analyses of microarray and quantitative PCR data showed that none of the above chemopreventive regimens appreciably affected the baseline microRNA expression, indicating potential safety. On the other hand, all of them attenuated ECS-induced alterations but to a variable extent and with different patterns, indicating potential preventive efficacy. The main ECS-altered functions that were modulated by chemopreventive agents included cell proliferation, apoptosis, differentiation, Ras activation, P53 functions, NF-κB pathway, transforming growth factor–related stress response, and angiogenesis. Some micro-RNAs known to be polymorphic in humans were downregulated by ECS and were protected by chemopreventive agents. This study provides proof-of-concept and validation of technology that we are further refining to screen and prioritize potential agents for continued development and to help elucidate their biological effects and mechanisms. Therefore, microRNA analysis may provide a new tool for predicting at early carcinogenesis stages both the potential safety and efficacy of cancer chemopreventive agents. PMID:20051373

Model of mobile agents for sexual interactions networks

NASA Astrophysics Data System (ADS)

González, M. C.; Lind, P. G.; Herrmann, H. J.

2006-02-01

We present a novel model to simulate real social networks of complex interactions, based in a system of colliding particles (agents). The network is build by keeping track of the collisions and evolves in time with correlations which emerge due to the mobility of the agents. Therefore, statistical features are a consequence only of local collisions among its individual agents. Agent dynamics is realized by an event-driven algorithm of collisions where energy is gained as opposed to physical systems which have dissipation. The model reproduces empirical data from networks of sexual interactions, not previously obtained with other approaches.

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.

Use of an optical clearing agent to enhance the visibility of subsurface structures and lesions from tooth occlusal surfaces

NASA Astrophysics Data System (ADS)

Kang, Hobin; Darling, Cynthia L.; Fried, Daniel

2016-08-01

The purpose of this study is to show that optical clearing agents can be used to increase the visibility of deeply penetrating occlusal lesions that have reached the underlying dentin and spread laterally under the enamel. Previous studies have shown that high refractive index fluids can increase the contrast of caries lesions. Extracted teeth with natural occlusal lesions were imaged with optical coherence tomography (OCT) with and without the addition of a transparent vinyl polysiloxane impression material (VPS) currently used in vivo. The relative intensity of the reflectivity from the underlying lesion area for each sample was measured before and after application of the VPS. Lesion presence was confirmed with polarized light microscopy and microradiography. Application of VPS significantly increased (P<0.0001) the integrated reflectivity of subsurface dentinal lesions. This study shows that optical clearing agents can be used to increase the optical penetration and the visibility of subsurface lesions and the dentinal-enamel junction under sound and demineralized enamel in OCT images.

Influence of bleaching agents on surface roughness of sound or eroded dental enamel specimens.

PubMed

Azrak, Birgül; Callaway, Angelika; Kurth, Petra; Willershausen, Brita

2010-12-01

The aim of the present in vitro study was to assess the effect of bleaching agents on eroded and sound enamel specimens. Enamel specimens prepared from human permanent anterior teeth were incubated with different bleaching agents containing active ingredients as 7.5 or 13.5% hydrogen peroxide or 35% carbamide peroxide, ranging in pH from 4.9 to 10.8. The effect of the tooth whitening agents on surface roughness was tested for sound enamel surfaces as well as for eroded enamel specimens. To provoke erosive damage, the enamel specimens were incubated for 10 hours with apple juice (pH = 3.4). Afterwards, pretreated and untreated dental slices were incubated with one of the bleaching agents for 10 hours. The surface roughness (R(a)) of all enamel specimens (N = 80) was measured using an optical profilometric device. A descriptive statistical analysis of the R(a) values was performed. The study demonstrated that exposure to an acidic bleaching agent (pH = 4.9) resulted in a higher surface roughness (p = 0.043) than treatment with a high peroxide concentration (pH = 6.15). If the enamel surface was previously exposed to erosive beverages, subsequent bleaching may enhance damage to the dental hard tissue. Bleaching agents with a high concentration of peroxide or an acidic pH can influence the surface roughness of sound or eroded enamel. © 2010, COPYRIGHT THE AUTHORS. JOURNAL COMPILATION © 2010, WILEY PERIODICALS, INC.

When nightclub security agents assault clients more insight through a qualitative approach.

PubMed

Romain-Glassey, Nathalie; Gut, Melody; De Puy, Jacqueline; Mangin, Patrice

2014-08-01

Between 2007 and 2009, aggressions by security agents of nightclubs on clients increased from 6% to 10% among community violence situations encountered at the Violence Medical Unit (VMU) at the Lausanne University Hospital in Switzerland. Most victims were young men who had been drinking alcohol before the assault. About one quarter (25.7%) presented with one or several fractures, all of them in the head area. (For more details, refer to the previous article "When nightclub security agents assault clients" published in 2012(1).) Following this first study, we performed a second qualitative study in order to bring more information about the context and highlight victims' behaviors and experiences. Four themes emerged: how the assault began; the assault itself; third-party involvement; and the psychological state of victims when they consulted the VMU. The findings of this second study complemented the statistical results of the first study by showing under what circumstances security agents of nightclubs respond with physical violence to situations they consider a threat to security. Furthermore, the study described consequences for the victims that could be quite serious. Our findings support the need for nightclubs to improve selection and training of security staff. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2013-10-30

under the following clinical trial protocol: o S1203: A Randomized Phase III Study of Standard Cytarabine plus Daunorubicin (7+3) Therapy or Idarubicin...with High Dose Cytarabine (IA) versus IA with Vorinostat (IA+V) in Younger Patients with Previously Untreated Acute Myeloid Leukemia (AML) o

Reciprocity in computer-human interaction: source-based, norm-based, and affect-based explanations.

PubMed

Lee, Seungcheol Austin; Liang, Yuhua Jake

2015-04-01

Individuals often apply social rules when they interact with computers, and this is known as the Computers Are Social Actors (CASA) effect. Following previous work, one approach to understand the mechanism responsible for CASA is to utilize computer agents and have the agents attempt to gain human compliance (e.g., completing a pattern recognition task). The current study focuses on three key factors frequently cited to influence traditional notions of compliance: evaluations toward the source (competence and warmth), normative influence (reciprocity), and affective influence (mood). Structural equation modeling assessed the effects of these factors on human compliance with computer request. The final model shows that norm-based influence (reciprocity) increased the likelihood of compliance, while evaluations toward the computer agent did not significantly influence compliance.

Agent-based model for rural-urban migration: A dynamic consideration

NASA Astrophysics Data System (ADS)

Cai, Ning; Ma, Hai-Ying; Khan, M. Junaid

2015-10-01

This paper develops a dynamic agent-based model for rural-urban migration, based on the previous relevant works. The model conforms to the typical dynamic linear multi-agent systems model concerned extensively in systems science, in which the communication network is formulated as a digraph. Simulations reveal that consensus of certain variable could be harmful to the overall stability and should be avoided.

Stabilizing the boundary between US politics and science: the role of the Office of Technology Transfer as a boundary organization.

PubMed

Guston, D H

1999-02-01

The sociological study of boundary-work and the political-ecomomic approach of principal-agent theory can be complementary ways of examining the relationship between society and science: boundary-work provides the empirical nuance to the principal-agent scheme, and principal-agent theory provides structure to the thick boundary description. This paper motivates this complementarity to examine domestic technology transfer in the USA from the intramural laboratories of the US National Institutes of Health (NIH). It casts US policy for technology transfer in the principal-agent framework, in which politicians attempt to manage the moral hazard of the productivity of research by providing specific incentives to the agents for engaging in measurable research-based innovation. Such incentives alter the previously negotiated boundary between politics and science. The paper identifies the crucial role of the NIH Office of Technology Transfer (OTT) as a boundary organization, which medicates the new boundary negotiations in its routine work, and stabilizes the boundary by performing successfully as an agent for both politicians and scientists. The paper hypothesizes that boundary organizations like OTT are general phenomena at the boundary between politics and science.

Agent Model Development for Assessing Climate-Induced Geopolitical Instability.

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

Boslough, Mark B.; Backus, George A.

2005-12-01

We present the initial stages of development of new agent-based computational methods to generate and test hypotheses about linkages between environmental change and international instability. This report summarizes the first year's effort of an originally proposed three-year Laboratory Directed Research and Development (LDRD) project. The preliminary work focused on a set of simple agent-based models and benefited from lessons learned in previous related projects and case studies of human response to climate change and environmental scarcity. Our approach was to define a qualitative model using extremely simple cellular agent models akin to Lovelock's Daisyworld and Schelling's segregation model. Such modelsmore » do not require significant computing resources, and users can modify behavior rules to gain insights. One of the difficulties in agent-based modeling is finding the right balance between model simplicity and real-world representation. Our approach was to keep agent behaviors as simple as possible during the development stage (described herein) and to ground them with a realistic geospatial Earth system model in subsequent years. This work is directed toward incorporating projected climate data--including various C02 scenarios from the Intergovernmental Panel on Climate Change (IPCC) Third Assessment Report--and ultimately toward coupling a useful agent-based model to a general circulation model.3« less

Mu Opioids and Their Receptors: Evolution of a Concept

PubMed Central

Pan, Ying-Xian

2013-01-01

Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated. PMID:24076545

The application of embodied conversational agents for mentoring African American STEM doctoral students

NASA Astrophysics Data System (ADS)

Gosha, Kinnis

This dissertation presents the design, development and short-term evaluation of an embodied conversational agent designed to mentor human users. An embodied conversational agent (ECA) was created and programmed to mentor African American computer science majors on their decision to pursue graduate study in computing. Before constructing the ECA, previous research in the fields of embodied conversational agents, relational agents, mentorship, telementorship and successful mentoring programs and practices for African American graduate students were reviewed. A survey used to find areas of interest of the sample population. Experts were then interviewed to collect information on those areas of interest and a dialogue for the ECA was constructed based on the interview's transcripts. A between-group, mixed method experiment was conducted with 37 African American male undergraduate computer science majors where one group used the ECA mentor while the other group pursued mentoring advice from a human mentor. Results showed no significant difference between the ECA and human mentor when dealing with career mentoring functions. However, the human mentor was significantly better than the ECA mentor when addressing psychosocial mentoring functions.

Progress in the development of gelling agents for improved culturability of microorganisms

PubMed Central

Das, Nabajit; Tripathi, Naveen; Basu, Srijoni; Bose, Chandra; Maitra, Susmit; Khurana, Sukant

2015-01-01

Gelling agents are required for formulating both solid and semisolid media, vital for the isolation of microorganisms. Gelatin was the first gelling agent to be discovered but it soon paved the way for agar, which has far superior material qualities. Source depletion, issues with polymerase-chain-reaction and inability to sustain extermophiles etc., necessitate the need of other gelling agents. Many new gelling agents, such as xantham gum, gellan gum, carrageenan, isubgol, and guar gum have been formulated, raising the hopes for the growth of previously unculturable microorganisms. We evaluate the progress in the development of gelling agents, with the hope that our synthesis would help accelerate research in the field. PMID:26257708

The $-game

NASA Astrophysics Data System (ADS)

Vitting Andersen, J.; Sornette, D.

2003-01-01

We propose a payoff function extending Minority Games (MG) that captures the competition between agents to make money. In contrast with previous MG, the best strategies are not always targeting the minority but are shifting opportunistically between the minority and the majority. The emergent properties of the price dynamics and of the wealth of agents are strikingly different from those found in MG. As the memory of agents is increased, we find a phase transition between a self-sustained speculative phase in which a ``stubborn majority'' of agents effectively collaborate to arbitrage a market-maker for their mutual benefit and a phase where the market-maker always arbitrages the agents. A subset of agents exhibit a sustained non-equilibrium risk-return profile.

Calcineurin inhibition enhances motor neuron survival following injury

PubMed Central

Hui, Kelvin KW; Liadis, Nicole; Robertson, Jennifer; Kanungo, Anish; Henderson, Jeffrey T

2010-01-01

Abstract The immunosuppressive agents cyclosporin A (CsA) and FK-506 have previously been shown to exhibit neurotrophic and neuroprotective properties in vivo. Given that significant clinical expertise exists for both drugs, they represent an attractive starting point for treatment of acute neural injuries. One putative mechanism for neuroprotection by these drugs relates to inhibition of calcineurin activity. However each drug–immunophilin complex can potentially influence additional signal transduction pathways. Furthermore, several non-immunosuppressive immunophilin ligands have been described as possessing neuroprotective properties, suggesting that neuroprotection may be separable from calcineurin inhibition. In the present study, we examined the mechanism of this neuroprotection in facial motor neurons following axotomy-induced injury. Similar to previous studies in rats, CsA and FK-506 enhanced motor neuron survival in mice following acute injury. To examine the mechanism responsible for neuroprotection by these agents, pharmacologic inhibitors of several potential alternate signalling pathways (17-(allylamino)-17-demethoxygeldanamycin, rapamycin, cypermethrin) were evaluated with respect to neuroprotection. Of these, only cypermethrin, a direct calcineurin inhibitor not previously associated with neuronal survival properties, was observed to significantly enhance motor neuron survival following injury. The results demonstrate for the first time that direct inhibition of calcineurin is neuroprotective in vivo. These data support a model in which calcineurin inhibition promotes neuronal survival, distinct from effects upon neurite outgrowth. PMID:19243469

Erotic stimulus processing under amisulpride and reboxetine: a placebo-controlled fMRI study in healthy subjects.

PubMed

Graf, Heiko; Wiegers, Maike; Metzger, Coraline D; Walter, Martin; Grön, Georg; Abler, Birgit

2014-10-31

Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4 mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents. © The Author 2015. Published by Oxford University Press on behalf of CINP.

New tools for characterizing swarming systems: A comparison of minimal models

NASA Astrophysics Data System (ADS)

Huepe, Cristián; Aldana, Maximino

2008-05-01

We compare three simple models that reproduce qualitatively the emergent swarming behavior of bird flocks, fish schools, and other groups of self-propelled agents by using a new set of diagnosis tools related to the agents’ spatial distribution. Two of these correspond in fact to different implementations of the same model, which had been previously confused in the literature. All models appear to undergo a very similar order-to-disorder phase transition as the noise level is increased if we only compare the standard order parameter, which measures the degree of agent alignment. When considering our novel quantities, however, their properties are clearly distinguished, unveiling previously unreported qualitative characteristics that help determine which model best captures the main features of realistic swarms. Additionally, we analyze the agent clustering in space, finding that the distribution of cluster sizes is typically exponential at high noise, and approaches a power-law as the noise level is reduced. This trend is sometimes reversed at noise levels close to the phase transition, suggesting a non-trivial critical behavior that could be verified experimentally. Finally, we study a bi-stable regime that develops under certain conditions in large systems. By computing the probability distributions of our new quantities, we distinguish the properties of each of the coexisting metastable states. Our study suggests new experimental analyses that could be carried out to characterize real biological swarms.

Characteristics of liver cirrhosis in Italy: Evidence for a decreasing role of HCV aetiology.

PubMed

Stroffolini, Tommaso; Sagnelli, Evangelista; Gaeta, Giovanni Battista; Sagnelli, Caterina; Andriulli, Angelo; Brancaccio, Giuseppina; Pirisi, Mario; Colloredo, Guido; Morisco, Filomena; Furlan, Caterina; Almasio, Piero Luigi

2017-03-01

Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014. Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study. The mean age of subjects was 60.3years, with a male/female ratio of 1.7; 74.9% of cases had Child A cirrhosis and 17.9% superimposed hepatocellular carcinoma. HCV infection, alone or in combination with other aetiologic agents, was responsible of 58.6% of cases, HBV aetiology accounted for the 17.6% and alcohol abuse for the 16.0%. Compared with virus-related cirrhotic patients, those alcohol-related more frequently showed decompensation (p=0.02). Compared to previous surveys performed in 1992 and in 2001, we observe a statistically significant (p<0.05) decreasing role of both HCV infection and alcohol abuse as aetiologic agents of liver cirrhosis in Italy, explaining, at least in part, the slow, progressive decline of the mortality rate for liver cirrhosis in the last decades in this country (from 34.5 deaths/100,000 inhabitants in1980 to 10.8 in 2012). Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Lurking in the Shadows: Emerging Rodent Infectious Diseases

PubMed Central

Besselsen, David G.; Franklin, Craig L.; Livingston, Robert S.; Riley, Lela K.

2013-01-01

Rodent parvoviruses, Helicobacter spp., murine norovirus, and several other previously unknown infectious agents have “emerged” in laboratory rodents relatively recently. These agents have been discovered serendipitously or through active investigation of atypical serology results, cell culture contamination, unexpected histopathology, or previously unrecognized clinical disease syndromes. The potential research impact of these agents is not fully known. Infected rodents have demonstrated immunomodulation, tumor suppression, clinical disease (particularly in immunodeficient rodents), and histopathology. Perturbations of organismal and cellular physiology also likely occur. These agents posed unique challenges to laboratory animal resource programs once discovered; it was necessary to develop specific diagnostic assays and an understanding of their epidemiology and transmission routes before attempting eradication, and then evaluate eradication methods for efficacy. Even then management approaches varied significantly, from apathy to total exclusion, and such inconsistency has hindered the sharing and transfer of rodents among institutions, particularly for genetically modified rodent models that may not be readily available. As additional infectious agents are discovered in laboratory rodents in coming years, much of what researchers have learned from experiences with the recently identified pathogens will be applicable. This article provides an overview of the discovery, detection, and research impact of infectious agents recently identified in laboratory rodents. We also discuss emerging syndromes for which there is a suspected infectious etiology, and the unique challenges of managing newly emerging infectious agents. PMID:18506061

Asthma caused by occupational exposures is common – A systematic analysis of estimates of the population-attributable fraction

PubMed Central

Torén, Kjell; Blanc, Paul D

2009-01-01

Background The aim of this paper is to highlight emerging data on occupational attributable risk in asthma. Despite well documented outbreaks of disease and the recognition of numerous specific causal agents, occupational exposures previously had been relegated a fairly minor role relative to other causes of adult onset asthma. In recent years there has been a growing recognition of the potential importance of asthma induced by work-related exposures Methods We searched Pub Med from June 1999 through December 2007. We identified six longitudinal general population-based studies; three case-control studies and eight cross-sectional analyses from seven general population-based samples. For an integrated analysis we added ten estimates prior to 1999 included in a previous review. Results The longitudinal studies indicate that 16.3% of all adult-onset asthma is caused by occupational exposures. In an overall synthesis of all included studies the overall median PAR value was 17.6%. Conclusion Clinicians should consider the occupational history when evaluating patients in working age who have asthma. At a societal level, these findings underscore the need for further preventive action to reduce the occupational exposures to asthma-causing agents. PMID:19178702

3% Amuchina is as effective as the 50% concentration in the prevention of exit-site infection in children on chronic peritoneal dialysis.

PubMed

Grosman, Mònica D; Mosquera, Vanesa M; Hernandez, Maria G; Agostini, Silvana; Adragna, Marta; Sojo, Ernesto T

2005-01-01

In a previous communication, we demonstrated that, in the prevention of exit-site infection (ESI) in children, the cleansing agent 50% Amuchina (electrolytic chloroxidizer. Amuchina SpA, Genoa, Italy) is more effective than 10% povidone iodine and as effective as 4% chlorhexidine, but with fewer adverse secondary effects. In the present study, we assessed, in an Argentine pediatric population, whether Amuchina 3% is as effective as Amuchina 50% in preventing ESI in children on chronic peritoneal dialysis. In an open-label, single-center prospective study, 27 children (mean age: 7.2 years; range: 1.7-17 years) used 3% Amuchina as a cleansing agent for the daily care of a healthy exit site. Of the 27 children, 14 were switched from 50% Amuchina to 3% Amuchina, and 13 were using the 3% Amuchina for the first time. The control group consisted of 18 patients who had previously used 50% Amuchina as a cleansing agent. We followed the recommendations of the International Society for Peritoneal Dialysis with regard to exit-site care, which include keeping the cleansing agent out of the sinus and rinsing the exit site with sterile water. Amuchina was used from the first post-implantation care of the exit site. No adverse secondary effects were seen with the use of Amuchina at either concentration. Patients using 3% Amuchina presented an ESI rate similar to that of patients using Amuchina 50%. The cost of 3% Amuchina was significantly lower than that of the 50% concentration, and it was even lower than the cost for 10% povidone iodine or 4% chlorhexidine. Although more research trials are needed to assess the efficacy of 3% Amuchina, we conclude that 3% Amuchina is the best and most cost-effective cleansing agent for the daily care of a healthy exit site in children on chronic peritoneal dialysis.

Identifying Requirements for Effective Human-Automation Teamwork

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

Jeffrey C. Joe; John O'Hara; Heather D. Medema

Previous studies have shown that poorly designed human-automation collaboration, such as poorly designed communication protocols, often leads to problems for the human operators, such as: lack of vigilance, complacency, and loss of skills. These problems often lead to suboptimal system performance. To address this situation, a considerable amount of research has been conducted to improve human-automation collaboration and to make automation function better as a “team player.” Much of this research is based on an understanding of what it means to be a good team player from the perspective of a human team. However, the research is often based onmore » a simplified view of human teams and teamwork. In this study, we sought to better understand the capabilities and limitations of automation from the standpoint of human teams. We first examined human teams to identify the principles for effective teamwork. We next reviewed the research on integrating automation agents and human agents into mixed agent teams to identify the limitations of automation agents to conform to teamwork principles. This research resulted in insights that can lead to more effective human-automation collaboration by enabling a more realistic set of requirements to be developed based on the strengths and limitations of all agents.« less

Mathematical modeling of malaria infection with innate and adaptive immunity in individuals and agent-based communities.

PubMed

Gurarie, David; Karl, Stephan; Zimmerman, Peter A; King, Charles H; St Pierre, Timothy G; Davis, Timothy M E

2012-01-01

Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns). We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT) studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB) communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities. Our approach represents a novel, convenient and versatile method to model Plasmodium falciparum infection.

Attenuation of a select agent-excluded Burkholderia pseudomallei capsule mutant in hamsters.

PubMed

Gutierrez, Maria G; Warawa, Jonathan M

2016-05-01

Burkholderia pseudomallei is a Tier 1 select agent and potential bioweapon. Given it is potential to cause a lethal respiratory disease, research with fully virulent B. pseudomallei is conducted in Biosafety Level 3 (BSL-3) laboratory spaces. The logistical, financial, and administrative burden of Tier 1 select agent BSL-3 research has created an interest in mitigating such burdens through the use of either attenuated B. pseudomallei strains at BSL-2, or research with surrogate species, such as Burkholderia thailandensis. Previously, attenuated B. pseudomallei auxotroph mutants (asd and purM) have been approved for exclusion from select agent requirements, allowing for in vitro studies to be conducted at BSL-2. Acapsular B. pseudomallei mutants are known to be strongly attenuated in a variety of animal models, and yet acapsular B. pseudomallei mutants do not require nutritional supplementation, and can be studied within cultured macrophages, performing phenotypically similarly to parent strains. We demonstrate that the loss of a 30.8 kb region of the wcb capsule operon allows for a dramatic >4.46 log attenuation in a hamster intraperitoneal infection model, and report that this strain, JW270, has met criteria for exclusion from select agent requirements. Copyright © 2016 Elsevier B.V. All rights reserved.

Statistical physics of the spatial Prisoner's Dilemma with memory-aware agents

NASA Astrophysics Data System (ADS)

Javarone, Marco Alberto

2016-02-01

We introduce an analytical model to study the evolution towards equilibrium in spatial games, with `memory-aware' agents, i.e., agents that accumulate their payoff over time. In particular, we focus our attention on the spatial Prisoner's Dilemma, as it constitutes an emblematic example of a game whose Nash equilibrium is defection. Previous investigations showed that, under opportune conditions, it is possible to reach, in the evolutionary Prisoner's Dilemma, an equilibrium of cooperation. Notably, it seems that mechanisms like motion may lead a population to become cooperative. In the proposed model, we map agents to particles of a gas so that, on varying the system temperature, they randomly move. In doing so, we are able to identify a relation between the temperature and the final equilibrium of the population, explaining how it is possible to break the classical Nash equilibrium in the spatial Prisoner's Dilemma when considering agents able to increase their payoff over time. Moreover, we introduce a formalism to study order-disorder phase transitions in these dynamics. As result, we highlight that the proposed model allows to explain analytically how a population, whose interactions are based on the Prisoner's Dilemma, can reach an equilibrium far from the expected one; opening also the way to define a direct link between evolutionary game theory and statistical physics.

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population.

PubMed

Ferrari, R; Ford, I; Fox, K; Steg, P G; Tendera, M

2008-01-01

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. (c) 2007 S. Karger AG, Basel

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.

Field experiments to evaluate host plant specificity of prospective agents of Onopordum acanthium in Bulgaria

USDA-ARS?s Scientific Manuscript database

Scotch thistle, Onopordum acanthium, is an invasive alien weed in North America that originates from Europe. Previous field observations in Bulgaria have confirmed the presence of prospective biological control agents including Cassida rubiginosa, Chaetostomella cylindrica, Eublemma amoena, Larinus ...

Associated degeneration of ventral tegmental area dopaminergic neurons in the rat nigrostriatal lactacystin model of parkinsonism and their neuroprotection by valproate

PubMed Central

Harrison, Ian F.; Anis, Hiba K.; Dexter, David T.

2016-01-01

Parkinson’s disease (PD) manifests clinically as bradykinesia, rigidity, and development of a resting tremor, primarily due to degeneration of dopaminergic nigrostriatal pathways in the brain. Intranigral administration of the irreversible ubiquitin proteasome system inhibitor, lactacystin, has been used extensively to model nigrostriatal degeneration in rats, and study the effects of candidate neuroprotective agents on the integrity of the dopaminergic nigrostriatal system. Recently however, adjacent extra-nigral brain regions such as the ventral tegmental area (VTA) have been noted to also become affected in this model, yet their integrity in studies of candidate neuroprotective agents in the model have largely been overlooked. Here we quantify the extent and distribution of dopaminergic degeneration in the VTA of rats intranigrally lesioned with lactacystin, and quantify the extent of VTA dopaminergic neuroprotection after systemic treatment with an epigenetic therapeutic agent, valproate, shown previously to protect dopaminergic SNpc neurons in this model. We found that unilateral intranigral administration of lactacystin resulted in a 53.81% and 31.72% interhemispheric loss of dopaminergic SNpc and VTA neurons, respectively. Daily systemic treatment of lactacystin lesioned rats with valproate however resulted in dose-dependant neuroprotection of VTA neurons. Our findings demonstrate that not only is the VTA also affected in the intranigral lactacystin rat model of PD, but that this extra-nigral brain region is substrate for neuroprotection by valproate, an agent shown previously to induce neuroprotection and neurorestoration of SNpc dopaminergic neurons in this model. Our results therefore suggest that valproate is a candidate for extra-nigral as well as intra-nigral neuroprotection. PMID:26742637

Associated degeneration of ventral tegmental area dopaminergic neurons in the rat nigrostriatal lactacystin model of parkinsonism and their neuroprotection by valproate.

PubMed

Harrison, Ian F; Anis, Hiba K; Dexter, David T

2016-02-12

Parkinson's disease (PD) manifests clinically as bradykinesia, rigidity, and development of a resting tremor, primarily due to degeneration of dopaminergic nigrostriatal pathways in the brain. Intranigral administration of the irreversible ubiquitin proteasome system inhibitor, lactacystin, has been used extensively to model nigrostriatal degeneration in rats, and study the effects of candidate neuroprotective agents on the integrity of the dopaminergic nigrostriatal system. Recently however, adjacent extra-nigral brain regions such as the ventral tegmental area (VTA) have been noted to also become affected in this model, yet their integrity in studies of candidate neuroprotective agents in the model have largely been overlooked. Here we quantify the extent and distribution of dopaminergic degeneration in the VTA of rats intranigrally lesioned with lactacystin, and quantify the extent of VTA dopaminergic neuroprotection after systemic treatment with an epigenetic therapeutic agent, valproate, shown previously to protect dopaminergic SNpc neurons in this model. We found that unilateral intranigral administration of lactacystin resulted in a 53.81% and 31.72% interhemispheric loss of dopaminergic SNpc and VTA neurons, respectively. Daily systemic treatment of lactacystin lesioned rats with valproate however resulted in dose-dependant neuroprotection of VTA neurons. Our findings demonstrate that not only is the VTA also affected in the intranigral lactacystin rat model of PD, but that this extra-nigral brain region is substrate for neuroprotection by valproate, an agent shown previously to induce neuroprotection and neurorestoration of SNpc dopaminergic neurons in this model. Our results therefore suggest that valproate is a candidate for extra-nigral as well as intra-nigral neuroprotection. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Calcium modulation of the effects of serotonin, carbachol, and histamine on rabbit ileal ion transport.

PubMed Central

Chough, S. P.; Goldenring, J. R.; Hurst, R. D.; Ballantyne, G. H.; Modlin, I. M.

1993-01-01

In mammalian intestine, a number of secretagogues have been shown to work through either cyclic nucleotide or calcium mediated pathways to elicit ion secretion. Because excessive intestinal electrolyte and fluid secretion is central to the pathogenesis of a variety of diarrheal disorders, understanding of these processes is essential to the development of future clinical treatments. In the current study, the effects of serotonin (5HT), histamine, and carbachol on intestinal ion transport were examined in in vitro preparations of rabbit ileum. All three agonists induced a rapid and transient increase short-circuit current (delta Isc) across ileal mucosa. Inhibition of the delta Isc response of all three agents in chloride-free solution or in the presence of bumetanide confirmed that chloride is the main electrolyte involved in electrogenic ion secretion. Pretreatment of tissue with tetrodotoxin or atropine did not effect secretagogue-mediated electrolyte secretion. While tachyphylaxis of delta Isc response was shown to develop after repeated exposure of a secretagogue to tissue, delta Isc responses after sequential addition of different agonists indicate that cross-tachyphylaxis between agents did not occur. Serotonin, histamine, and carbachol have previously been reported to mediate electrolyte secretion through calcium-dependent pathways. To access the role of extracellular calcium in regulating ion secretion, the effect of verapamil on each agent was tested; verapamil decreased 5HT-induced delta Isc by 65.2% and histamine response by 33.5%, but had no effect on carbachol-elicited chloride secretion. An additive secretory effect was found upon simultaneous exposure of 5HT and carbachol to the system; no other combination of agents produced a significant additive effect. Findings from this study support previous work which has suggested that multiple calcium pathways may be involved in mediating chloride secretion in mammalian intestine. PMID:7716972

Opportunistic Behavior in Motivated Learning Agents.

PubMed

Graham, James; Starzyk, Janusz A; Jachyra, Daniel

2015-08-01

This paper focuses on the novel motivated learning (ML) scheme and opportunistic behavior of an intelligent agent. It extends previously developed ML to opportunistic behavior in a multitask situation. Our paper describes the virtual world implementation of autonomous opportunistic agents learning in a dynamically changing environment, creating abstract goals, and taking advantage of arising opportunities to improve their performance. An opportunistic agent achieves better results than an agent based on ML only. It does so by minimizing the average value of all need signals rather than a dominating need. This paper applies to the design of autonomous embodied systems (robots) learning in real-time how to operate in a complex environment.

Dogs (Canis familiaris) adjust their social behaviour to the differential role of inanimate interactive agents.

PubMed

Petró, Eszter; Abdai, Judit; Gergely, Anna; Topál, József; Miklósi, Ádám

2016-03-01

Dogs are able to flexibly adjust their social behaviour to situation-specific characteristics of their human partner's behaviour in problem situations. However, dogs do not necessarily detect the specific role played by the human in a particular situation: they may form expectations about their partners' behaviour based on previous experiences with them. Utilising inanimate objects (UMO-unidentified moving object) as interacting agents offers new possibilities for investigating social behaviour, because in this way we can remove or control the influence of previous experience with the partner. The aim of the present study was to investigate whether dogs are able to recognise the different roles of two UMOs and are able to adjust their communicative behaviour towards them. In the learning phase of the experiment, dogs were presented with a two-way food-retrieval problem in which two UMOs, which differed in their physical appearance and abilities, helped the dog obtain a piece of food in their own particular manner. After a short experience with both UMOs, dogs in the test phase faced one of the problems in the presence of both inanimate agents. Overall, dogs displayed similar levels of gazing behaviour towards the UMOs, but in the first test they looked, approached and touched the relevant partner first. This rapid adjustment of social behaviour towards UMOs suggests that dogs may generalise their experiences with humans to unfamiliar agents and are able to select the appropriate partner when facing a problem situation.

Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium

USDA-ARS?s Scientific Manuscript database

Pteridium aquilinum, one of the most important poisonous plants in the world, is known to be carcinogenic to animals and humans. Moreover, our previous studies showed that the immunosuppressive effects of ptaquiloside, its main toxic agent, were prevented by selenium in mouse natural killer (NK) cel...

Inuloxins A-D and derivatives as antileishmanial agents: structure-activity relationship study

USDA-ARS?s Scientific Manuscript database

Inuloxins A-D (1-4) and a-costic acid (5), the phytotoxic compounds previously isolated from Inula viscosa, as well as synthetic derivatives of inuloxin A (compounds 6-10), inuloxin C (compound 11) and inuloxin D (compound 12) were tested in vitro for their activity against Leishmania donovani, the ...

Combination Lithium and Divalproex Sodium in Pediatric Bipolar Symptom Restabilization

ERIC Educational Resources Information Center

Findling, Robert L.; McNamara, Nora K.; Stansbrey, Robert; Gracious, Barbara L.; Whipkey, Resaca E.; Demeter, Christine A.; Reed, Michael D.; Youngstrom, Eric A.; Calabrese, Joseph R.

2006-01-01

Objective: It has been reported that bipolar disorder may become less responsive to previously effective treatment with each symptomatic relapse. The primary goal of this study was to assess the rate of restabilization after the resumption of lithium ([Li[superscript +]) plus divalproex (DVPX) following relapse on either agent as monotherapy.…

Antimicrobial activity of topical agents against Propionibacterium acnes: an in vitro study of clinical isolates from a hospital in Shanghai, China.

PubMed

Ma, Ying; Zhang, Nanxue; Wu, Shi; Huang, Haihui; Cao, Yanpei

2016-12-01

This study aimed to compare the antimicrobial activities of topical agents against Propionibacterium acnes isolated from patients admitted to a hospital in Shanghai, China. The minimal inhibitory concentrations of the cultured P. acnes were determined in accordance with the Clinical and Laboratory Standards Institute. Susceptibilities to clindamycin and erythromycin were compared in terms of gender, age, disease duration, previous treatment, and disease severity. A total of 69 P. acnes strains were isolated from 98 patients (70.41%). The susceptibility to triple antibiotic ointment (neomycin/bacitracin/polymyxin B) and bacitracin was 100%. The susceptibility to fusidic acid was 92.7%. The resistance rates to neomycin sulfate, erythromycin, and clindamycin were 11.7%, 49.3%, and 33.4%, respectively. The high resistance rate to clindamycin and erythromycin was significantly affected by gender, previous treatment, and disease severity rather than by age and disease duration. Topical antibiotics should not be used separately for long-term therapy to avoid multiresistance. The use of topical antibiotics should be determined by clinicians on the basis of clinical conditions.

Recombinant EphB4-HSA Fusion Protein and Azacitidine or Decitabine for Relapsed or Refractory Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Patients Previously Treated With a Hypomethylating Agent

ClinicalTrials.gov

2017-08-18

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Myeloid Leukemia

Brain activation related to the perception of minimal agency cues: the role of the mirror system.

PubMed

Stosic, Marina; Brass, Marcel; Van Hoeck, Nicole; Ma, Ning; Van Overwalle, Frank

2014-02-01

Recent fMRI studies indicate that the posterior superior temporal sulcus (pSTS) and the mirror system are involved in analyzing goal-directed actions performed by non-human objects. However, these studies have some limitations: the animations showed moving shapes that resemble humans and human movement, or showed the interaction of two moving shapes rather than one alone. This may have prompted participants to assume a human agent instead of an object. To avoid this potential confound, in this study, animations showed a small circular shape (agent) jumping toward a bigger circular shape (goal) with an obstacle separating them. We manipulated agency of the small circular shape by showing its movements as self-propelled (Agent condition) or as launched by a lever mechanism (Non-agent condition). The small shape succeeded in avoiding an obstacle and reaching the goal object or failed to do so. Our results showed that goal-directed actions performed by an agentic shape recruited the mirror system (the inferior parietal lobe and the premotor cortex) in comparison with shapes that were launched. Success or failure to avoid the obstacle had no effect on these areas. These results complement and further extend previous findings indicating that the mirror system does not appear to be selective for biological actions and their goals, nor does it require the presence of a human, human body parts or human-made objects. Instead, it seems to play a general role in representing goal-directed actions of agents regardless of their form. © 2013.

APC10.1 cells as a model for assessing the efficacy of potential chemopreventive agents in the Apc(Min) mouse model in vivo.

PubMed

Sale, Stewart; Fong, Isabel L; de Giovanni, Carla; Landuzzi, Lorena; Brown, Karen; Steward, William P; Gescher, Andreas J

2009-11-01

Apc(Min) mice are widely used for mechanism and efficacy studies associated with the development of chemopreventive agents. APC10.1 cells have been derived from Apc(Min) mouse adenomas and retain the heterozygous Apc genotype. We tested the hypothesis that this cell type may provide an in vitro model to predict chemopreventive activity of agents in the Apc(Min) mouse in vivo. The growth inhibitory properties of 14 putative colorectal cancer chemopreventive agents, tricin, apigenin, 3',4',5',5,7-pentamethoxyflavone, resveratrol, curcumin, 3,4-methylenedioxy-3',4',5'-trimethoxychalcone (DMU135), 3,4,5,4'-tetramethoxystilbene (DMU212), celecoxib, aspirin, piroxicam, all-trans-retinoic acid, difluoromethylornithine (DFMO), quercetin and cyanidin-3-glucoside, were studied in this cell line, and the IC(50) values were calculated. The IC(50) values were plotted against previously published data of reduction of adenoma numbers caused by these agents in Apc(Min) mice. The correlation co-efficient was 0.678 (p<0.01), suggesting that there was a tentative correlation between the ability to inhibit the growth of APC10.1 cells and the ability to delay adenoma development in vivo. If this relationship is supported by using further agents, APC10.1 cells may serve in the future as an initial screen to prioritise compounds for assessing chemopreventive efficacy in Apc(Min) mice in vivo. Such a screen could reduce the number of animals required to find active agents, help reduce costs and increase throughput.

Toxicity potential of disinfection agent in tannery wastewater.

PubMed

Tisler, Tatjana; Zagorc-Koncan, Jana; Cotman, Magda; Drolc, Andreja

2004-09-01

Wastewater from a tannery was investigated using chemical-specific analyses and assessment of the acute toxicity of the whole effluent over a 2-year period. The wastewater samples were overloaded with organic and inorganic compounds, and measured concentrations of the chemical parameters as well as dilution factors estimating acute toxicity, frequently exceeded the permissible limits for the discharge of wastewater from a tannery into the receiving stream. In the later part of the monitoring programme, the toxicity of the samples was significantly increased in comparison to the previous samples. The agent for hide disinfection was assumed to be the reason for the increased toxicity of the wastewater samples, and the extremely high acute and chronic toxicity of the agent to bacteria, algae, daphnids, and fish confirmed this suspicion. The most sensitive species was Daphnia magna; the 48 h EC50 was 0.70 x 10(-5)v/v% and the 21d IC25 was 0.40 x 10(-6)v/v% of the agent. After withdrawal of this highly toxic agent for hide disinfection from the technological process in the tannery, the toxicity of the wastewater declined to the previous level.

Copper Vapor Generator

DTIC Science & Technology

1974-09-01

flow. A volumetric quench.ng agent should quench the lower laser level m a t.me ᝺^ sec without mterfenng w.th the excitation process. A high-speed...quenchtng agent should not ^" »ff. AlLu^ A« Ire Imon gases do not appear promrsmg. there are some other more complex posstb.hues st.ll to be pursued...dimension along the How). Unless a volumetric quenching agent is discovered and employed, those copper atoms which contributed to the previous laser

Molecular detection of various rickettsiae in mites (acari: trombiculidae) in southern Jeolla Province, Korea.

PubMed

Choi, Yeon-Joo; Lee, Eun-Mi; Park, Jin-Mi; Lee, Kyung-Min; Han, Seung-Hoon; Kim, Jae-Kwon; Lee, Seung-Hyun; Song, Hyeon-Je; Choi, Myung-Sik; Kim, Ik-Sang; Park, Kyung-Hee; Jang, Won-Jong

2007-01-01

This study revealed the presence of various rickettsial agents in mites from wild rodents collected in Southern Jeolla Province, Korea, by nested polymerase chain reaction (PCR) and sequence analysis of a partial citrate synthase and rickettsia outer membrane protein B genes. Rickettsial agents closely related to the Rickettsia species TwKM02, R. australis, and the Rickettsia species Cf15 were successfully identified in this study, for the first time in Korea, and R. japonica, R. akari, R. conorii, R. felis, and R. typhi were also detected, as previously described. The data presented in this paper extend knowledge on the geographic distribution of SFG rickettsiae in eastern Asia and it may necessary to consider the role of mites in rickettsial transmission.

Resistance profiles to antimicrobial agents in bacteria isolated from acute endodontic infections: systematic review and meta-analysis.

PubMed

Lang, Pauline M; Jacinto, Rogério C; Dal Pizzol, Tatiane S; Ferreira, Maria Beatriz C; Montagner, Francisco

2016-11-01

Infected root canal or acute apical abscess exudates can harbour several species, including Fusobacterium, Porphyromonas, Prevotella, Parvimonas, Streptococcus, Treponema, Olsenella and not-yet cultivable species. A systematic review and meta-analysis was performed to assess resistance rates to antimicrobial agents in clinical studies that isolated bacteria from acute endodontic infections. Electronic databases and the grey literature were searched up to May 2015. Clinical studies in humans evaluating the antimicrobial resistance of primary acute endodontic infection isolates were included. PRISMA guidelines were followed. A random-effect meta-analysis was employed. The outcome was described as the pooled resistance rates for each antimicrobial agent. Heterogeneity and sensitivity analyses were performed. Subgroup analyses were conducted based upon report or not of the use of antibiotics prior to sampling as an exclusion factor (subgroups A and B, respectively). Data from seven studies were extracted. Resistance rates for 15 different antimicrobial agents were evaluated (range, 3.5-40.0%). Lower resistance rates were observed for amoxicillin/clavulanic acid and amoxicillin; higher resistance rates were detected for tetracycline. Resistance rates varied according to previous use of an antimicrobial agent as demonstrated by the subgroup analyses. Heterogeneity was observed for the resistance profiles of penicillin G in subgroup A and for amoxicillin, clindamycin, metronidazole and tetracycline in subgroup B. Sensitivity analyses demonstrated that resistance rates changed for metronidazole, clindamycin, tetracycline and amoxicillin. These findings suggest that clinical isolates had low resistance to β-lactams. Further well-designed studies are needed to clarify whether the differences in susceptibility among the antimicrobial agents may influence clinical responses to treatment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Dynamic phase transition in the prisoner's dilemma on a lattice with stochastic modifications

NASA Astrophysics Data System (ADS)

Saif, M. Ali; Gade, Prashant M.

2010-03-01

We present a detailed study of the prisoner's dilemma game with stochastic modifications on a two-dimensional lattice, in the presence of evolutionary dynamics. By very nature of the rules, the cooperators have incentives to cheat and fear being cheated. They may cheat even when this is not dictated by the evolutionary dynamics. We consider two variants here. In each case, the agents mimic the action (cooperation or defection) in the previous time step of the most successful agent in the neighborhood. But over and above this, the fraction p of cooperators spontaneously change their strategy to pure defector at every time step in the first variant. In the second variant, there are no pure cooperators. All cooperators keep defecting with probability p at every time step. In both cases, the system switches from a coexistence state to an all-defector state for higher values of p. We show that the transition between these states unambiguously belongs to the directed percolation universality class in 2 + 1 dimensions. We also study the local persistence. The persistence exponents obtained are higher than the ones obtained in previous studies, underlining their dependence on details of the dynamics.

Evaluation of experimental epoxy monomers

NASA Technical Reports Server (NTRS)

Hodges, W. T.; St.clair, T. L.; Pratt, J. R.; Ficklin, R.

1985-01-01

Future generation aircraft need higher performance polymer matrices to fully achieve the weight savings possible with composite materials. New resins are being formulated in an effort to understand basic polymer behavior and to develop improved resins. Some polymer/curing agent combinations that could be useful are difficult to process. In the area of epoxies, a major problem is that some components have physical properties which make them difficult to utilize as matrix resins. A previous study showed that the use of ultrasonic energy can be advantageous in the mixing of curing agents into a standard epoxy resin, such as MY 720 (Ciba-Geigy designation). This work is expanded to include three novel epoxides.

New leads in speculative behavior

NASA Astrophysics Data System (ADS)

Kindler, A.; Bourgeois-Gironde, S.; Lefebvre, G.; Solomon, S.

2017-02-01

The Kiyotaki and Wright (1989) (henceforth KW) model of money emergence as a medium of exchange has been studied from various perspectives in recent papers. In the present work we propose a minimalistic model for the behavior of agents in the KW framework, which may either reproduce the theoretical predictions of Kiyotaki and Wright (1989) on the emerging Nash equilibria, or (less closely) the empirical results of Brown (1996), Duffy and Ochs (1999) and our own, introduced in a first part of the present paper. The main import is the systematic computer scanning of speculative monetary equilibria under drastic bounded rationality of agents, based on behavior previously observed in the lab.

Evolution of tag-based cooperation on Erdős-Rényi random graphs

NASA Astrophysics Data System (ADS)

Lima, F. W. S.; Hadzibeganovic, Tarik; Stauffer, Dietrich

2014-12-01

Here, we study an agent-based model of the evolution of tag-mediated cooperation on Erdős-Rényi random graphs. In our model, agents with heritable phenotypic traits play pairwise Prisoner's Dilemma-like games and follow one of the four possible strategies: Ethnocentric, altruistic, egoistic and cosmopolitan. Ethnocentric and cosmopolitan strategies are conditional, i.e. their selection depends upon the shared phenotypic similarity among interacting agents. The remaining two strategies are always unconditional, meaning that egoists always defect while altruists always cooperate. Our simulations revealed that ethnocentrism can win in both early and later evolutionary stages on directed random graphs when reproduction of artificial agents was asexual; however, under the sexual mode of reproduction on a directed random graph, we found that altruists dominate initially for a rather short period of time, whereas ethnocentrics and egoists suppress other strategists and compete for dominance in the intermediate and later evolutionary stages. Among our results, we also find surprisingly regular oscillations which are not damped in the course of time even after half a million Monte Carlo steps. Unlike most previous studies, our findings highlight conditions under which ethnocentrism is less stable or suppressed by other competing strategies.

Importance of positive feedbacks and overconfidence in a self-fulfilling Ising model of financial markets

NASA Astrophysics Data System (ADS)

Sornette, Didier; Zhou, Wei-Xing

2006-10-01

Following a long tradition of physicists who have noticed that the Ising model provides a general background to build realistic models of social interactions, we study a model of financial price dynamics resulting from the collective aggregate decisions of agents. This model incorporates imitation, the impact of external news and private information. It has the structure of a dynamical Ising model in which agents have two opinions (buy or sell) with coupling coefficients, which evolve in time with a memory of how past news have explained realized market returns. We study two versions of the model, which differ on how the agents interpret the predictive power of news. We show that the stylized facts of financial markets are reproduced only when agents are overconfident and mis-attribute the success of news to predict return to herding effects, thereby providing positive feedbacks leading to the model functioning close to the critical point. Our model exhibits a rich multifractal structure characterized by a continuous spectrum of exponents of the power law relaxation of endogenous bursts of volatility, in good agreement with previous analytical predictions obtained with the multifractal random walk model and with empirical facts.

Acting to gain information

NASA Technical Reports Server (NTRS)

Rosenchein, Stanley J.; Burns, J. Brian; Chapman, David; Kaelbling, Leslie P.; Kahn, Philip; Nishihara, H. Keith; Turk, Matthew

1993-01-01

This report is concerned with agents that act to gain information. In previous work, we developed agent models combining qualitative modeling with real-time control. That work, however, focused primarily on actions that affect physical states of the environment. The current study extends that work by explicitly considering problems of active information-gathering and by exploring specialized aspects of information-gathering in computational perception, learning, and language. In our theoretical investigations, we analyzed agents into their perceptual and action components and identified these with elements of a state-machine model of control. The mathematical properties of each was developed in isolation and interactions were then studied. We considered the complexity dimension and the uncertainty dimension and related these to intelligent-agent design issues. We also explored active information gathering in visual processing. Working within the active vision paradigm, we developed a concept of 'minimal meaningful measurements' suitable for demand-driven vision. We then developed and tested an architecture for ongoing recognition and interpretation of visual information. In the area of information gathering through learning, we explored techniques for coping with combinatorial complexity. We also explored information gathering through explicit linguistic action by considering the nature of conversational rules, coordination, and situated communication behavior.

Chromoblastomycosis: study of 27 cases and review of medical literature.

PubMed

Correia, Rafaela Teixeira Marinho; Valente, Neusa Y S; Criado, Paulo Ricardo; Martins, José Eduardo da Costa

2010-01-01

Chromoblastomycosis is a subcutaneous mycosis that occurs mainly in rural workers although is being more commonly found among people working in other sectors. The fungus penetrates the skin after its inoculation and the most frequently isolated agent is the Fonsecaea pedrosoi. This study aims at evaluating patients suffering from chromoblastomycosis admitted into the Department of Dermatology of the University Hospital of the Faculty of Medicine of São Paulo State during the ten-year period from 1997 to 2007. It is a retrospective study and the medical report cards of 27 Brazilian patients diagnosed as suffering from Chromoblastomycosis from 1997 to 2007 at the Dermatology Department of the Medical School, University of Sao Paulo were reviewed. The following items were analyzed: previous therapeutic approaches; treatment implemented by the group; length of time between the appearing of the lesion and diagnosis; age; gender; profession; origin; site of lesions; isolated agents found in culture and histopathology. Twenty two patients were from the state of Sao Paulo whereas the others came from the states of Bahia and Rondonia. 37% of them were rural workers. Men were more frequently infected (85%). Lesions were more commonly found on the lower limbs (59.2%). In 52% of the cases the isolated agent was the dematiaceous fungus Fonsecaea. pedrosoi. Biopsies showed sclerotic bodies in 92.5% of the cases. Data found are in accordance with medical literature on the subject. The disease had been previously studied in our institution in 1983 by Cucé et al. This present study is the second retrospective one about the characteristics of patients suffering from chromoblastmycosis which has been published in indexed medical literature in the state of Sao Paulo.

White rot of garlic and onion (Causal agent, Sclerotium cepivorum): A status report from the Pacific Northwest

USDA-ARS?s Scientific Manuscript database

There is evidence from literature, state department of agriculture documents, and recent diagnoses that Sclerotium cepivorum, causal agent of white rot of garlic and onion, is spreading and/or becoming more established in the Pacific Northwest. Previously documented distributions are summarized, an...

Amyotrophic Lateral Sclerosis Associated with Statin Use: A Disproportionality Analysis of the FDA's Adverse Event Reporting System.

PubMed

Golomb, Beatrice A; Verden, Abril; Messner, Alexis K; Koslik, Hayley J; Hoffman, Keith B

2018-04-01

Apparent elevations in reporting of amyotrophic lateral sclerosis (ALS)-like conditions associated with statin use have been previously described from data obtained via US and European databases. The aim of this study was to examine US FDA Adverse Event Reporting System (FAERS) data to compare reporting odds ratios (RORs) of ALS and ALS-like conditions between statins and other drugs, for each statin agent. We assessed for disproportional rates of reported ALS and ALS-related conditions for each statin agent separately by using the ROR formula. FAERS data were analyzed through September 2015. RORs for ALS were elevated for all statins, with elevations possibly stronger for lipophilic statins. RORs ranged from 9.09 (6.57-12.6) and 16.2 (9.56-27.5) for rosuvastatin and pravastatin (hydrophilic) to 17.0 (14.1-20.4), 23.0 (18.3-29.1), and 107 (68.5-167) for atorvastatin, simvastatin, and lovastatin (lipophilic), respectively. For simvastatin, an ROR of 57.1 (39.5-82.7) was separately present for motor neuron disease. These findings extend previous evidence showing that significantly elevated ALS reporting extends to individual statin agents, and add to concerns about potential elevated occurrence of ALS-like conditions in association with statin usage.

Combat and herbicide exposures in Vietnam among a sample of American Legionnaires

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

Stellman, S.D.; Stellman, J.M.; Sommer, J.F. Jr.

A cross-sectional survey of 6,810 randomly selected members of The American Legion in six states who served in the US Armed Forces during the Vietnam Era was conducted by a mailed questionnaire. Combat stress was evaluated by a previously validated eight-item scale. Exposure to Agent Orange and other herbicides was estimated via exposure probability index previously developed by the authors which uses an algorithm based on the combined Air Force and Joint Services HERBS files of spray data. Two-fifths of the men had served in Southeast Asia, generally at the same time during which the major proportion of herbicides weremore » used; the remaining subjects served elsewhere. Both combat and Agent Orange exposure exhibited distinct, meaningful distributions among Vietnam veterans with service in Southeast Asia and were also correlated with each other. Our analysis demonstrates conclusively that mere presence in Vietnam cannot be used as a proxy for exposure to Agent Orange. Categorization of Vietnam veterans according to herbicide exposure can be successfully accomplished, based on an existing detailed herbicide application data base. This analysis, together with the consistent dose-related results obtained in this series of papers on health and behavioral effects, demonstrates the utility of questionnaire-derived herbicide and combat exposure measures for epidemiologic study of Vietnam veterans.« less

Exogenous contrast agents for thermoacoustic imaging: An investigation into the underlying sources of contrast

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

Ogunlade, Olumide, E-mail: o.ogunlade@ucl.ac.uk; Beard, Paul

2015-01-15

Purpose: Thermoacoustic imaging at microwave excitation frequencies is limited by the low differential contrast exhibited by high water content tissues. To overcome this, exogenous thermoacoustic contrast agents based on gadolinium compounds, iron oxide, and single wall carbon nanotubes have previously been suggested and investigated. However, these previous studies did not fully characterize the electric, magnetic, and thermodynamic properties of these agents thus precluding identification of the underlying sources of contrast. To address this, measurements of the complex permittivity, complex permeability, DC conductivity, and Grüneisen parameter have been made. These measurements allowed the origins of the contrast provided by each substancemore » to be identified. Methods: The electric and magnetic properties of the contrast agents were characterized at 3 GHz using two rectangular waveguide cavities. The DC conductivity was measured separately using a conductivity meter. Thermoacoustic signals were then acquired and compared to those generated in water. Finally, 3D electromagnetic simulations were used to decouple the different contributions to the absorbed power density. Results: It was found that the gadolinium compounds provided appreciable electric contrast but not originating from the gadolinium itself. The contrast was either due to dissociation of the gadolinium salt which increased ionic conductivity or its nondissociated polar fraction which increased dielectric polarization loss or a combination of both. In addition, very high concentrations were required to achieve appreciable contrast, to the extent that the Grüneisen parameter increased significantly and became a source of contrast. Iron oxide particles were found to produce low but measurable dielectric contrast due to dielectric polarization loss, but this is attributed to the coating of the particles not the iron oxide. Single wall carbon nanotubes did not provide measurable contrast of any type. Conclusions: It is concluded that gadolinium based contrast agents, iron oxide particles, and single walled carbon nanotubes have little intrinsic merit as thermoacoustic contrast agents. Simple electrolytes such as saline which yield high contrast based on ionic conductivity provide much higher dielectric contrast per unit solute concentration and are likely to be significantly more effective as contrast agents.« less

Rickettsia sp. Strain Atlantic Rainforest Infection in a Patient from a Spotted Fever-Endemic Area in Southern Brazil

PubMed Central

Krawczak, Felipe S.; Muñoz-Leal, Sebastián; Guztzazky, Ana Carolina; Oliveira, Stefan V.; Santos, Fabiana C. P.; Angerami, Rodrigo N.; Moraes-Filho, Jonas; de Souza, Julio C.; Labruna, Marcelo B.

2016-01-01

Santa Catarina State in southern Brazil is the state with the second highest number of laboratory-confirmed cases of spotted fever illness in Brazil. However, all these cases were confirmed solely by serological analysis (seroconversion to spotted fever group rickettsiae), which has not allowed identification of the rickettsial agent. Here, a clinical case of spotted fever illness from Santa Catarina is shown by seroconversion and molecular analysis to be caused by Rickettsia sp. strain Atlantic rainforest. This is the third confirmed clinical case due to this emerging rickettsial agent in Brazil. Like the previous two cases, the patient presented an inoculation eschar at the tick bite site. Our molecular diagnosis was performed on DNA extracted from the crust removed from the eschar. These results are supported by previous epidemiological studies in Santa Catarina, which showed that nearly 10% of the most common human-biting ticks were infected by Rickettsia sp. strain Atlantic rainforest. PMID:27325804

Rickettsia sp. Strain Atlantic Rainforest Infection in a Patient from a Spotted Fever-Endemic Area in Southern Brazil.

PubMed

Krawczak, Felipe S; Muñoz-Leal, Sebastián; Guztzazky, Ana Carolina; Oliveira, Stefan V; Santos, Fabiana C P; Angerami, Rodrigo N; Moraes-Filho, Jonas; de Souza, Julio C; Labruna, Marcelo B

2016-09-07

Santa Catarina State in southern Brazil is the state with the second highest number of laboratory-confirmed cases of spotted fever illness in Brazil. However, all these cases were confirmed solely by serological analysis (seroconversion to spotted fever group rickettsiae), which has not allowed identification of the rickettsial agent. Here, a clinical case of spotted fever illness from Santa Catarina is shown by seroconversion and molecular analysis to be caused by Rickettsia sp. strain Atlantic rainforest. This is the third confirmed clinical case due to this emerging rickettsial agent in Brazil. Like the previous two cases, the patient presented an inoculation eschar at the tick bite site. Our molecular diagnosis was performed on DNA extracted from the crust removed from the eschar. These results are supported by previous epidemiological studies in Santa Catarina, which showed that nearly 10% of the most common human-biting ticks were infected by Rickettsia sp. strain Atlantic rainforest. © The American Society of Tropical Medicine and Hygiene.

Updates in nutrition and polypharmacy.

PubMed

Little, Milta O

2018-01-01

Medications have the potential to affect nutritional status in negative ways, especially as the number of medications increase. The inter-relation between polypharmacy and malnutrition is complex and not fully delineated in previous studies. More research has been done and compiled in the last year, which helps to clarify this relationship. This review brings together the most recent literature with the previous research to help healthcare providers to better assess and manage medication therapy in older adults. Recent evidence confirms a synergistic negative effect of polypharmacy and malnutrition on outcomes of older adults. In addition, several drug classes, including common antihypertensive agents, acetylcholinesterase inhibitors, multivitamins, proton pump inhibitors, HMG-CoA reductase inhibitors (statins), antiplatelet agents and metformin, have been implicated in important drug-nutrient interactions. These are reviewed in detail here. Ongoing research endeavors are described. Healthcare practitioners can use this review to identify potentially inappropriate medications and patients at highest risk of experiencing a medication-related adverse reaction in order to systematically deprescribe these high-risk medications.

A functional form for injected MRI Gd-chelate contrast agent concentration incorporating recirculation, extravasation and excretion

NASA Astrophysics Data System (ADS)

Horsfield, Mark A.; Thornton, John S.; Gill, Andrew; Jager, H. Rolf; Priest, Andrew N.; Morgan, Bruno

2009-05-01

A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T1-weighted data from the descending aorta and hepatic portal vein, and on T*2-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

Motion Planning in a Society of Intelligent Mobile Agents

NASA Technical Reports Server (NTRS)

Esterline, Albert C.; Shafto, Michael (Technical Monitor)

2002-01-01

The majority of the work on this grant involved formal modeling of human-computer integration. We conceptualize computer resources as a multiagent system so that these resources and human collaborators may be modeled uniformly. In previous work we had used modal for this uniform modeling, and we had developed a process-algebraic agent abstraction. In this work, we applied this abstraction (using CSP) in uniformly modeling agents and users, which allowed us to use tools for investigating CSP models. This work revealed the power of, process-algebraic handshakes in modeling face-to-face conversation. We also investigated specifications of human-computer systems in the style of algebraic specification. This involved specifying the common knowledge required for coordination and process-algebraic patterns of communication actions intended to establish the common knowledge. We investigated the conditions for agents endowed with perception to gain common knowledge and implemented a prototype neural-network system that allows agents to detect when such conditions hold. The literature on multiagent systems conceptualizes communication actions as speech acts. We implemented a prototype system that infers the deontic effects (obligations, permissions, prohibitions) of speech acts and detects violations of these effects. A prototype distributed system was developed that allows users to collaborate in moving proxy agents; it was designed to exploit handshakes and common knowledge Finally. in work carried over from a previous NASA ARC grant, about fifteen undergraduates developed and presented projects on multiagent motion planning.

Use of an optical clearing agent to enhance the visibility of subsurface structures and lesions from tooth occlusal surfaces

PubMed Central

Kang, Hobin; Darling, Cynthia L.; Fried, Daniel

2016-01-01

Abstract. The purpose of this study is to show that optical clearing agents can be used to increase the visibility of deeply penetrating occlusal lesions that have reached the underlying dentin and spread laterally under the enamel. Previous studies have shown that high refractive index fluids can increase the contrast of caries lesions. Extracted teeth with natural occlusal lesions were imaged with optical coherence tomography (OCT) with and without the addition of a transparent vinyl polysiloxane impression material (VPS) currently used in vivo. The relative intensity of the reflectivity from the underlying lesion area for each sample was measured before and after application of the VPS. Lesion presence was confirmed with polarized light microscopy and microradiography. Application of VPS significantly increased (P<0.0001) the integrated reflectivity of subsurface dentinal lesions. This study shows that optical clearing agents can be used to increase the optical penetration and the visibility of subsurface lesions and the dentinal–enamel junction under sound and demineralized enamel in OCT images. PMID:27071709

Continuum mechanics analysis of fracture progression in the vitrified cryoprotective agent DP6

PubMed Central

Steif, Paul S.; Palastro, Matthew C.; Rabin, Yoed

2008-01-01

As part of an ongoing effort to study the continuum mechanics effects associated with cryopreservation, the current report focuses on the prediction of fracture formation in cryoprotective agents. Fractures had been previously observed in 1 mℓ samples of the cryoprotective agent cocktail DP6, contained in a standard 15 mℓ glass vial, and subjected to various cooling rates. These experimental observations were obtained by means of a cryomacroscope, which has been recently presented by the current research team. High and low cooling rates were found to produce very distinct patterns of cracking. The current study seeks to explain the observed patterns on the basis of stresses predicted from finite element analysis, which relies on a simple viscoelastic constitutive model and on estimates of the critical stress for cracking. The current study demonstrates that the stress which results in instantaneous fracture at low cooling rates is consistent with the stress to initiate fracture at high cooling rate. This consistency supports the credibility of the proposed constitutive model and analysis, and the unified criterion for fracturing, that is, a critical stress threshold. PMID:18412493

Influence of DNA Repair on Nonlinear Dose-Responses for Mutation

PubMed Central

Johnson, George E.

2013-01-01

Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is one of the most mutagenic simple alkylators. Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents. Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0.0075 µg/ml (72.8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476). Mechanistic studies reveal that the NOGEL is dependent upon repair of O6-methylguanine (O6MeG) by the suicide enzyme O6MeG-DNA methyltransferase (MGMT). Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis. PMID:23288051

Influence of DNA repair on nonlinear dose-responses for mutation.

PubMed

Thomas, Adam D; Jenkins, Gareth J S; Kaina, Bernd; Bodger, Owen G; Tomaszowski, Karl-Heinz; Lewis, Paul D; Doak, Shareen H; Johnson, George E

2013-03-01

Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is one of the most mutagenic simple alkylators. Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents. Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0.0075 µg/ml (72.8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476). Mechanistic studies reveal that the NOGEL is dependent upon repair of O(6)-methylguanine (O(6)MeG) by the suicide enzyme O(6)MeG-DNA methyltransferase (MGMT). Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis.

Fronto-parietal coding of goal-directed actions performed by artificial agents.

PubMed

Kupferberg, Aleksandra; Iacoboni, Marco; Flanagin, Virginia; Huber, Markus; Kasparbauer, Anna; Baumgartner, Thomas; Hasler, Gregor; Schmidt, Florian; Borst, Christoph; Glasauer, Stefan

2018-03-01

With advances in technology, artificial agents such as humanoid robots will soon become a part of our daily lives. For safe and intuitive collaboration, it is important to understand the goals behind their motor actions. In humans, this process is mediated by changes in activity in fronto-parietal brain areas. The extent to which these areas are activated when observing artificial agents indicates the naturalness and easiness of interaction. Previous studies indicated that fronto-parietal activity does not depend on whether the agent is human or artificial. However, it is unknown whether this activity is modulated by observing grasping (self-related action) and pointing actions (other-related action) performed by an artificial agent depending on the action goal. Therefore, we designed an experiment in which subjects observed human and artificial agents perform pointing and grasping actions aimed at two different object categories suggesting different goals. We found a signal increase in the bilateral inferior parietal lobule and the premotor cortex when tool versus food items were pointed to or grasped by both agents, probably reflecting the association of hand actions with the functional use of tools. Our results show that goal attribution engages the fronto-parietal network not only for observing a human but also a robotic agent for both self-related and social actions. The debriefing after the experiment has shown that actions of human-like artificial agents can be perceived as being goal-directed. Therefore, humans will be able to interact with service robots intuitively in various domains such as education, healthcare, public service, and entertainment. © 2017 Wiley Periodicals, Inc.

Using Improved Equation of State to Model Simultaneous Nucleation and Bubble Growth in Thermoplastic Foams

NASA Astrophysics Data System (ADS)

Khan, Irfan; Costeux, Stephane; Adrian, David; Cristancho, Diego

2013-11-01

Due to environmental regulations carbon-dioxide (CO2) is increasingly being used to replace traditional blowing agents in thermoplastic foams. CO2 is dissolved in the polymer matrix under supercritical conditions. In order to predict the effect of process parameters on foam properties using numerical modeling, the P-V-T relationship of the blowing agents should accurately be represented at the supercritical state. Previous studies in the area of foam modeling have all used ideal gas equation of state to predict the behavior of the blowing agent. In this work the Peng-Robinson equation of state is being used to model the blowing agent during its diffusion into the growing bubble. The model is based on the popular ``Influence Volume Approach,'' which assumes a growing boundary layer with depleted blowing agent surrounds each bubble. Classical nucleation theory is used to predict the rate of nucleation of bubbles. By solving the mass balance, momentum balance and species conservation equations for each bubble, the model is capable of predicting average bubble size, bubble size distribution and bulk porosity. The effect of the improved model on the bubble growth and foam properties are discussed.

Changing perspectives of stress gastritis prophylaxis.

PubMed

Smythe, M A; Zarowitz, B J

1994-09-01

To present recent advances in stress gastritis prophylaxis in the critically ill and review considerations in selection of a prophylactic agent. Information was obtained from MEDLINE search, reference lists from articles identified in search, and from review articles. Emphasis was placed on controlled trials conducted within the last 5 years. All literature was assessed for methodology, results, and conclusions. Results of prospective, randomized trials, and meta-analyses are summarized. Histamine2-receptor antagonists, antacids, and sucralfate appear equally effective in preventing stress gastritis in the critically ill. A definitive cause-effect relationship between histamine2-receptor antagonists and increased incidence of nosocomial pneumonia has not yet been established. The indications for using a prophylactic agent and consideration in selecting an agent should include an evaluation of the following: risk factors for gastritis including the type of intensive care patient, comparative efficacy, adverse effects, drug interactions, cost, and ease of administration. The least expensive, safest agent requiring minimal monitoring is sucralfate. Prevention of stress gastritis has never been shown to reduce morbidity or mortality significantly. Controversies still exist regarding the need to provide prophylaxis, the choice of an agent, and the relative importance of previously identified risk factors. Further well-designed studies are needed before consensus can be reached.

Mesoscopic Effects in an Agent-Based Bargaining Model in Regular Lattices

PubMed Central

Poza, David J.; Santos, José I.; Galán, José M.; López-Paredes, Adolfo

2011-01-01

The effect of spatial structure has been proved very relevant in repeated games. In this work we propose an agent based model where a fixed finite population of tagged agents play iteratively the Nash demand game in a regular lattice. The model extends the multiagent bargaining model by Axtell, Epstein and Young [1] modifying the assumption of global interaction. Each agent is endowed with a memory and plays the best reply against the opponent's most frequent demand. We focus our analysis on the transient dynamics of the system, studying by computer simulation the set of states in which the system spends a considerable fraction of the time. The results show that all the possible persistent regimes in the global interaction model can also be observed in this spatial version. We also find that the mesoscopic properties of the interaction networks that the spatial distribution induces in the model have a significant impact on the diffusion of strategies, and can lead to new persistent regimes different from those found in previous research. In particular, community structure in the intratype interaction networks may cause that communities reach different persistent regimes as a consequence of the hindering diffusion effect of fluctuating agents at their borders. PMID:21408019

Mesoscopic effects in an agent-based bargaining model in regular lattices.

PubMed

Poza, David J; Santos, José I; Galán, José M; López-Paredes, Adolfo

2011-03-09

The effect of spatial structure has been proved very relevant in repeated games. In this work we propose an agent based model where a fixed finite population of tagged agents play iteratively the Nash demand game in a regular lattice. The model extends the multiagent bargaining model by Axtell, Epstein and Young modifying the assumption of global interaction. Each agent is endowed with a memory and plays the best reply against the opponent's most frequent demand. We focus our analysis on the transient dynamics of the system, studying by computer simulation the set of states in which the system spends a considerable fraction of the time. The results show that all the possible persistent regimes in the global interaction model can also be observed in this spatial version. We also find that the mesoscopic properties of the interaction networks that the spatial distribution induces in the model have a significant impact on the diffusion of strategies, and can lead to new persistent regimes different from those found in previous research. In particular, community structure in the intratype interaction networks may cause that communities reach different persistent regimes as a consequence of the hindering diffusion effect of fluctuating agents at their borders.

Characterization of chemical warfare G-agent hydrolysis products by surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Inscore, Frank E.; Gift, Alan D.; Maksymiuk, Paul; Farquharson, Stuart

2004-12-01

The United States and its allies have been increasingly challenged by terrorism, and since the September 11, 2001 attacks and the war in Afghanistan and Iraq, homeland security has become a national priority. The simplicity in manufacturing chemical warfare agents, the relatively low cost, and previous deployment raises public concern that they may also be used by terrorists or rogue nations. We have been investigating the ability of surface-enhanced Raman spectroscopy (SERS) to detect extremely low concentrations (e.g. part-per-billion) of chemical agents, as might be found in poisoned water. Since trace quantities of nerve agents can be hydrolyzed in the presence of water, we have expanded our studies to include such degradation products. Our SERS-active medium consists of silver or gold nanoparticles incorporated into a sol-gel matrix, which is immobilized in a glass capillary. The choice of sol-gel precursor allows controlling hydrophobicity, while the porous silica network offers a unique environment for stabilizing the SERS-active metals. Here we present the use of these metal-doped sol-gels to selectively enhance the Raman signal of the hydrolyzed products of the G-series nerve agents.

Effects of Manipulation on Attributions of Causation, Free Will, and Moral Responsibility.

PubMed

Murray, Dylan; Lombrozo, Tania

2017-03-01

If someone brings about an outcome without intending to, is she causally and morally responsible for it? What if she acts intentionally, but as the result of manipulation by another agent? Previous research has shown that an agent's mental states can affect attributions of causal and moral responsibility to that agent, but little is known about what effect one agent's mental states can have on attributions to another agent. In Experiment 1, we replicate findings that manipulation lowers attributions of responsibility to manipulated agents. Experiments 2-7 isolate which features of manipulation drive this effect, a crucial issue for both philosophical debates about free will and attributions of responsibility in situations involving social influence more generally. Our results suggest that "bypassing" a manipulated agent's mental states generates the greatest reduction in responsibility, and we explain our results in terms of the effects that one agent's mental states can have on the counterfactual relations between another agent and an outcome. Copyright © 2016 Cognitive Science Society, Inc.

[Affinity between CrIII and purified DNA, studied by competition with an intercalating agent: ethidium bromide].

PubMed

Vecchio, D; Balbi, C; Russo, P; Parodi, S; Santi, L

1981-05-30

The affinity between CrIII and purified calf- thymus DNA was studied at neutral pH by competition with ethidium bromide. Competition results indicated an affinity between CrIII and DNA of the order of 10(5) 1/mole. These results are in good agreement with previous results CrIII - DNA affinity was studied by the independent method of equilibrium dialysis and chromium dosage by atomic spectrometry.

Influence of Bleaching on Flavor of 34% Whey Protein Concentrate and Residual Benzoic Acid Concentration in Dried Whey Proteins

USDA-ARS?s Scientific Manuscript database

Previous studies have shown that bleaching negatively affects the flavor of 70% whey protein concentrate (WPC70), but bleaching effects on lower-protein products have not been established. Benzoyl peroxide (BP), a whey bleaching agent, degrades to benzoic acid (BA) and may elevate BA concentrations...

Influence of bleaching on flavor of 34% whey protein concentrate and residual benzoic acid concentration in dried whey products

USDA-ARS?s Scientific Manuscript database

Previous studies have shown that bleaching negatively affects the flavor of 70% whey protein concentrate (WPC70), but bleaching effects on lower-protein products have not been established. Benzoyl peroxide (BP), a whey bleaching agent, degrades to benzoic acid (BA) and may elevate BA concentrations...

Rural School Children Picturing Family Life

ERIC Educational Resources Information Center

de Lange, Naydene; Olivier, Tilla; Geldenhuys, Johanna; Mitchell, Claudia

2012-01-01

Rurality is an active agent and central to the lived experiences of children growing up on a farm and attending a farm school. It is a key to their everyday experiences, and influences family life, schooling and their future. Previous studies elsewhere in the world have explored the notion of childhood in rural contexts, but there is a dearth of…

Investigation of depilatory mechanism by use of multiphoton fluorescent microscopy

NASA Astrophysics Data System (ADS)

Lin, Chiao-Ying; Lee, Gie-ne; Jee, Shiou-Hwa; Dong, Chen-Yuan; Lin, Sung-Jan

2007-07-01

Transdermal drug delivery provides a non-invasive route of drug administration, and can be a alternative method to oral delivery and injection. The stratum corneum (SC) of skin acts as the main barrier to transdermal drug delivery. Studies suggest that depilatory enhances permeability of drug through the epidermis. However, transdermal delivery pathway and mechanism are not completely understood. Previous studies have found that depilatory changes the keratinocytes of epidermis, and cause the protein in combination with lipid extraction of SC to become disordered. Nevertheless, those studies did not provide images of those processes. The aim of this study is to characterize the penetration enhancing effect of depilatory agent and the associated structural alterations of stratum corneum. Fresh human foreskin is treated by a depilatory agent for 10 minutes and then subjected to the treatment of fluorescent model drugs of hydrophilic rhodamine and hydrophobic rhodamine-RE. The penetration of model drugs is imaged and quantified by multiphoton microscopy. Our results showed that the penetration of both hydrophilic and hydrophobic agents can be enhanced and multifocal detachment of surface corneocytes is revealed. Nile red staining revealed, instead of a regular motar distribution of lipid around the brick of corneocytes, a disorganized and homogenized pattern of lipid distribution. We concluded that depilatory agents enhance drug penetration by disrupting both the cellular integrity of corneocytes and the regular packing of intercellular lipid of stratum corneum.

Spatial prisoner's dilemma game with volunteering in Newman-Watts small-world networks

NASA Astrophysics Data System (ADS)

Wu, Zhi-Xi; Xu, Xin-Jian; Chen, Yong; Wang, Ying-Hai

2005-03-01

A modified spatial prisoner’s dilemma game with voluntary participation in Newman-Watts small-world networks is studied. Some reasonable ingredients are introduced to the game evolutionary dynamics: each agent in the network is a pure strategist and can only take one of three strategies (cooperator, defector, and loner); its strategical transformation is associated with both the number of strategical states and the magnitude of average profits, which are adopted and acquired by its coplayers in the previous round of play; a stochastic strategy mutation is applied when it gets into the trouble of local commons that the agent and its neighbors are in the same state and get the same average payoffs. In the case of very low temptation to defect, it is found that agents are willing to participate in the game in typical small-world region and intensive collective oscillations arise in more random region.

Etiologic agent of an epidemic of cutaneous leishmaniasis in Tolima, Colombia.

PubMed

Rodríguez-Barraquer, Isabel; Góngora, Rafael; Prager, Martín; Pacheco, Robinson; Montero, Luz Mery; Navas, Adriana; Ferro, Cristina; Miranda, Maria Consuelo; Saravia, Nancy G

2008-02-01

American cutaneous leishmaniasis (ACL) has been characterized as a zoonotic disease. However, peridomestic and domestic transmission have been recorded in at least nine countries in Central and South America. The present study was undertaken to identify the etiologic agent of a peridomestic epidemic of ACL in the Department of Tolima, Colombia. Leishmania isolates were obtained during the diagnosis of 56 patients with ACL who consulted the local leishmaniasis control program in three municipalities in Tolima. Species were identified using monoclonal antibodies and isoenzyme electrophoresis. A total of 53 (94.6%) of 56 isolates were identified as Leishmania (Viannia) guyanensis. Three isolates (5.4%) were identified as L. (V.) panamensis. Leishmania (V.) guyanensis is the probable etiologic agent of the largest epidemic of cutaneous leishmaniasis recorded in Colombia. This species has not previously been reported outside the Amazon and southeastern regions of Colombia, and has not been described in the peridomestic setting or linked with an epidemic.

Efficacy of postexposure therapy against glanders in mice.

PubMed

Waag, David M

2015-04-01

Burkholderia mallei, the causative agent of glanders, is a CDC Tier 1 Select Agent for which there is no preventive vaccine and antibiotic therapy is difficult. In this study, we show that a combination of vaccination using killed cellular vaccine and therapy using moxifloxacin, azithromycin, or sulfamethoxazole-trimethoprim can protect BALB/c mice from lethal infection even when given 5 days after infectious challenge. Vaccination only, or antibiotic therapy only, was not efficacious. Although antibiotics evaluated experimentally can protect when given before or 1 day after challenge, this time course is not realistic in the cases of natural infection or biological attack, when the patient seeks treatment after symptoms develop or after a biological attack has been confirmed and the agent has been identified. Antibiotics can be efficacious after a prolonged interval between exposure and treatment, but only if the animals were previously vaccinated. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Efficacy of Postexposure Therapy against Glanders in Mice

PubMed Central

2015-01-01

Burkholderia mallei, the causative agent of glanders, is a CDC Tier 1 Select Agent for which there is no preventive vaccine and antibiotic therapy is difficult. In this study, we show that a combination of vaccination using killed cellular vaccine and therapy using moxifloxacin, azithromycin, or sulfamethoxazole-trimethoprim can protect BALB/c mice from lethal infection even when given 5 days after infectious challenge. Vaccination only, or antibiotic therapy only, was not efficacious. Although antibiotics evaluated experimentally can protect when given before or 1 day after challenge, this time course is not realistic in the cases of natural infection or biological attack, when the patient seeks treatment after symptoms develop or after a biological attack has been confirmed and the agent has been identified. Antibiotics can be efficacious after a prolonged interval between exposure and treatment, but only if the animals were previously vaccinated. PMID:25645854

Identification of a consistent polyene component of purple pigment in diseased sclerites of Caribbean corals across region, species, and insult agent

NASA Astrophysics Data System (ADS)

Fetterolf, Monty L.; Leverette, Chad L.; Perez, Christopher; Smith, Garriet W.

2017-10-01

Gorgonians respond to insult (damage and disease) by producing sclerites containing a purple pigment as opposed to the normal white sclerites. Raman microscopy is used to study the purple areas of three species of diseased coral, Gorgonia ventalina, Pseudoplexaura porosa, and Eunicea laciniata obtained from Puerto Rico. These spectra were compared to Gorgonia ventalina samples previously reported that were obtained from San Salvador, Bahamas. Spectra from two samples of G. ventalina that had been infected by different agents, Aspergillus sydowii and a slime mold, were also obtained. The results indicate that the purple compounds (polyenes) generated by the coral in response to infection are similar regardless of region from which the coral were harvested, of species of coral, and of the infective agent. A discussion of the Raman spectra of G. ventalina and the other coral species is presented.

Effect of smear layer deproteinization on bonding of self-etch adhesives to dentin: a systematic review and meta-analysis

PubMed Central

Alshaikh, Khaldoan H.; Mahmoud, Salah H.

2018-01-01

Objectives The aim of this systematic review was to critically analyze previously published studies of the effects of dentin surface pretreatment with deproteinizing agents on the bonding of self-etch (SE) adhesives to dentin. Additionally, a meta-analysis was conducted to quantify the effects of the above-mentioned surface pretreatment methods on the bonding of SE adhesives to dentin. Materials and Methods An electronic search was performed using the following databases: Scopus, PubMed and ScienceDirect. The online search was performed using the following keywords: ‘dentin’ or ‘hypochlorous acid’ or ‘sodium hypochlorite’ and ‘self-etch adhesive.’ The following categories were excluded during the assessment process: non-English articles, randomized clinical trials, case reports, animal studies, and review articles. The reviewed studies were subjected to meta-analysis to quantify the effect of the application time and concentration of sodium hypochlorite (NaOCl) and hypochlorous acid (HOCl) deproteinizing agents on bonding to dentin. Results Only 9 laboratory studies fit the inclusion criteria of this systematic review. The results of the meta-analysis revealed that the pooled average microtensile bond strength values to dentin pre-treated with deproteinizing agents (15.71 MPa) was significantly lower than those of the non-treated control group (20.94 MPa). Conclusions In light of the currently available scientific evidence, dentin surface pretreatment with deproteinizing agents does not enhance the bonding of SE adhesives to dentin. The HOCl deproteinizing agent exhibited minimal adverse effects on bonding to dentin in comparison with NaOCl solutions. PMID:29765895

Over-the-Counter Agents for the Treatment of Occasional Disturbed Sleep or Transient Insomnia: A Systematic Review of Efficacy and Safety

PubMed Central

Culpepper, Larry; Wingertzahn, Mark A.

2015-01-01

Objective: To investigate the level of evidence supporting the use of common over-the-counter (OTC) agents (diphenhydramine, doxylamine, melatonin, and valerian) for occasional disturbed sleep or insomnia. Data sources: A systematic review of the literature was conducted on July 31, 2014, using MEDLINE (PubMed) and the search terms (insomnia OR sleep) AND (over*the*counter OR OTC OR non*prescription OR antihistamine OR doxylamine OR diphenhydramine OR melatonin OR valerian) with the filters English, human, and clinical trials. Study selection: Identified publications (from 2003 to July 31, 2014, following previous published literature reviews) that met the inclusion criteria were selected. The criteria included randomized placebo-controlled clinical studies that utilized overnight objective (polysomnography) or next-day participant-reported sleep-related endpoints and that were conducted in healthy participants with or without occasional disturbed sleep or diagnosed insomnia. Results: Measures of efficacy and tolerability were summarized for each study individually and grouped according to OTC agent: H1 antagonists or antihistamines (3 studies, diphenhydramine), melatonin (8), and valerian or valerian/hops (7). Of the 3 sleep agents, studies conducted with melatonin, especially prolonged-release formulations in older individuals with diagnosed insomnia, demonstrated the most consistent beneficial effects (vs placebo) on sleep measures, specifically sleep onset and sleep quality, with favorable tolerability. In contrast, the clinical trial data for diphenhydramine, immediate-release melatonin, and valerian suggested limited beneficial effects. Conclusions: A review of randomized controlled studies over the past 12 years suggests commonly used OTC sleep-aid agents, especially diphenhydamine and valerian, lack robust clinical evidence supporting efficacy and safety. PMID:27057416

Learning and exploration in action-perception loops.

PubMed

Little, Daniel Y; Sommer, Friedrich T

2013-01-01

Discovering the structure underlying observed data is a recurring problem in machine learning with important applications in neuroscience. It is also a primary function of the brain. When data can be actively collected in the context of a closed action-perception loop, behavior becomes a critical determinant of learning efficiency. Psychologists studying exploration and curiosity in humans and animals have long argued that learning itself is a primary motivator of behavior. However, the theoretical basis of learning-driven behavior is not well understood. Previous computational studies of behavior have largely focused on the control problem of maximizing acquisition of rewards and have treated learning the structure of data as a secondary objective. Here, we study exploration in the absence of external reward feedback. Instead, we take the quality of an agent's learned internal model to be the primary objective. In a simple probabilistic framework, we derive a Bayesian estimate for the amount of information about the environment an agent can expect to receive by taking an action, a measure we term the predicted information gain (PIG). We develop exploration strategies that approximately maximize PIG. One strategy based on value-iteration consistently learns faster than previously developed reward-free exploration strategies across a diverse range of environments. Psychologists believe the evolutionary advantage of learning-driven exploration lies in the generalized utility of an accurate internal model. Consistent with this hypothesis, we demonstrate that agents which learn more efficiently during exploration are later better able to accomplish a range of goal-directed tasks. We will conclude by discussing how our work elucidates the explorative behaviors of animals and humans, its relationship to other computational models of behavior, and its potential application to experimental design, such as in closed-loop neurophysiology studies.

Studies of the transmissibility of the agent of bovine spongiform encephalopathy to the domestic chicken

PubMed Central

2011-01-01

Background Transmission of the prion disease bovine spongiform encephalopathy (BSE) occurred accidentally to cattle and several other mammalian species via feed supplemented with meat and bone meal contaminated with infected bovine tissue. Prior to United Kingdom controls in 1996 on the feeding of mammalian meat and bone meal to farmed animals, the domestic chicken was potentially exposed to feed contaminated with the causal agent of BSE. Although confirmed prion diseases are unrecorded in avian species a study was undertaken to transmit BSE to the domestic chicken by parenteral and oral inoculations. Transmissibility was assessed by clinical monitoring, histopathological examinations, detection of a putative disease form of an avian prion protein (PrP) in recipient tissues and by mouse bioassay of tissues. Occurrence of a progressive neurological syndrome in the primary transmission study was investigated by sub-passage experiments. Results No clinical, pathological or bioassay evidence of transmission of BSE to the chicken was obtained in the primary or sub-passage experiments. Survival data showed no significant differences between control and treatment groups. Neurological signs observed, not previously described in the domestic chicken, were not associated with significant pathology. The diagnostic techniques applied failed to detect a disease associated form of PrP. Conclusion Important from a risk assessment perspective, the present study has established that the domestic chicken does not develop a prion disease after large parenteral exposures to the BSE agent or after oral exposures equivalent to previous exposures via commercial diets. Future investigations into the potential susceptibility of avian species to mammalian prion diseases require species-specific immunochemical techniques and more refined experimental models. PMID:22093239

Effect of Antithrombotic Agents on the Patency of PTFE-Covered Stents in the Inferior Vena Cava: An Experimental Study

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

Makutani, Shiro; Kichikawa, Kimihiko; Uchida, Hideo

Purpose: To evaluate the efficacy of antithrombotic agents in the prevention of stenosis of polytetrafluoroethylene (PTFE)-covered stents in the venous system. Methods: Spiral Z stents covered with PTFE (PTFE-covered stents) were placed in the inferior vena cava (IVC) of 34 dogs. Nineteen dogs, used as a control group, were sacrificed at 2, 4, and 12 weeks. Fifteen dogs, previously given antithrombotic agents [cilostazol (n= 5), warfarin potassium (n= 5), cilostazol plus warfarin potassium (n= 5)] were sacrificed at 4 weeks, and then examined angiographically and histopathologically. The effect of the antithrombotic agents was compared between groups. Results: The patency ratemore » of the antithrombotic agent group was 93% (14/15), which was higher than the control group rate of 63% (12/19). The mean stenosis rate of the patent stent at both ends and at the midportion was lower at 4 weeks in the antithrombotic agent group than in the control group. In particular, the mean stenosis rate in the cilostazol plus warfarin potassium group was significantly lower than the control group (Tukey's test, p < 0.05). The mean neointimal thickness of the patent stent at both ends and at the midportion was thinner at 4 weeks in the antithrombotic agent group than in the control group. In particular, the thickness of the neointima in the cilostazol plus warfarin potassium group was significantly decreased when compared with the control group (Tukey's test p < 0.05). At 4 weeks, endothelialization in the antithrombotic agent group tended to be almost identical to that in the control group. Conclusion: The present study suggests that administration of an antithrombotic agent is an effective way of preventing the stenosis induced by a neointimal thickening of PTFE-covered stents in the venous system.« less

Dermatomyositis-like syndrome induced by nonsteroidal anti-inflammatory agents.

PubMed

Grob, J J; Collet, A M; Bonerandi, J J

1989-01-01

A dermatomyositis-like syndrome developed in a patient treated with a nonsteroidal anti-inflammatory agent (NSAI), niflumic acid, and regressed after the cessation of treatment. Previously an eruption had occurred under treatment with another NSAI, diclofenac. Our report shows that NSAI can induce not only lupus-like syndromes but also other connective tissue disorders.

Current Status and Clinical Studies of Oriental Herbs in Sexual Medicine in Korea

PubMed Central

Shin, Yu Seob; Zhao, Chen; Zhang, Li Tao

2015-01-01

Erectile dysfunction (ED) is one of the most common diseases among aging men. Although previous studies have shown that type 5 phosphodiesterase inhibitors (PDE5-Is) are very effective for the treatment of ED, many researchers are currently attempting to identify therapeutic agents from natural sources with comparable or better effects than PDE5-Is. Herbal medicine is thought to be advantageous because it is natural; moreover, it not only treats isolated symptoms, but also maintains general well-being. Furthermore, since newly created chemical compound libraries have limited structural diversity with regard to pharmaceutical agents, more attention has recently been paid to the ability of oriental herbs to enhance physical health, including sexual function. Herein, we review the current status of Korean preclinical or clinical studies of the application of oriental herbs to sexual medicine. PMID:26331122

An epidemiologic study to screen for chronic myelocytic leukemia in war victims exposed to mustard gas.

PubMed Central

Ghanei, Mostafa; Vosoghi, Ali Akbar

2002-01-01

Chemical agents such as mustard gas (or sulfur mustard), which has alkylating characteristics, were used against Iranian combatants in the Iraq-Iran war. Previous studies have not shown a strong link between these chemical agents and the development of chronic myelocytic leukemia (CML). The purpose of this study was to evaluate the increased risk of CML development in Iranian soldiers exposed to mustard gas during the war. Based on a descriptive study of 2,500 cases with documented exposure to various chemical warfare agents, 665 patients had documented exposure to mustard gas. We screened the latter using the leukocyte alkaline phosphatase (LAP) test and performed further cytochemical studies on cases with positive results. From among the 665 cases with documented exposure to mustard gas, 9 cases had LAP scores < 20; 2 of these 9 cases had CML and a score of zero (0.3%). We detected cytogenetic abnormalities in 7 patients with low LAP scores and atypical lymphocytes of 5-11% in 40 patients. The risk ratio of CML developing in victims exposed to mustard gas (cutaneous or respiratory) may be higher in comparison with the normal population, although confounding factors (e.g., the possibility of exposure to combined chemical agents, excluding patients who did not manifest blisters) limited our results. Because the increased development of CML in young patients with a documented history of exposure to mustard gas cannot be disregarded, further studies are needed. PMID:12003756

Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis.

PubMed

Kastberger, Gerald; Weihmann, Frank; Hoetzl, Thomas

2010-03-01

The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes.

Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis

PubMed Central

Weihmann, Frank; Hoetzl, Thomas

2010-01-01

The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes. PMID:20585516

Sirtuin 3 enhanced drug sensitivity of human hepatoma cells through glutathione S-transferase pi 1/JNK signaling pathway

PubMed Central

Cai, Xue-Fei; Zhang, Wen-Lu; Ren, Ji-Hua; Zhou, Li; Chen, Xiang; Chen, Ke; Li, Wan-Yu; Liu, Bo; Yang, Qiu-Xia; Cheng, Sheng-Tao; Huang, Li-Xia; Huang, Ai-Long; Chen, Juan

2016-01-01

SIRT3, a class III histone deacetylase, has been implicated in various cancers as a novel therapeutic target. In hepatocellular carcinoma (HCC), we previously reported that SIRT3 induced cell apoptosis by regulating GSK-3β/Bax signaling pathway. Downregulation of SIRT3 in HCC cells facilitates tumor cell survival. In this study, we found that chemotherapeutic agents (doxorubicin, cisplatin and epirubicin) and sorafenib treatment downregulated SIRT3 mRNA and protein levels in three HCC cell lines. MTS assay found that SIRT3 overexpression sensitized liver cancer cells to chemotherapeutic agents and sorafenib in SMMC-7721, Huh-7 and PLC/PRF/5 cell lines. Moreover, SIRT3 overexpression promoted chemotherapeutic agents-induced or sorafenib-induced apoptosis as evidenced by flow cytometry, enhanced PARP cleavage and enhanced Caspase-9 cleavage in three HCC cells. In contrast, SIRT3 silencing increased drug resistance of HCC cells to chemotherapeutic agents. Mechanistic study found that SIRT3 downregulated the mRNA and protein levels of glutathione S-transferase pi 1 (GSTP1), which is a member of phase II detoxification enzymes families involved in metabolizing for chemotherapeutic agents. Moreover, SIRT3 decreased the amount of GSTP1 that was associated with JNK, which finally contributed the activation of JNK activity and activation of downstream target c-Jun and Bim. Importantly, GSTP1 overexpression or JNK inhibitor abolished SIRT3-induced apoptosis in HCC cells exposed to chemotherapeutic agents. Finally, there was a negative correlation between SIRT3 expression and GSTP1 expression in human HCC tissues. Together, our findings revealed SIRT3 could enhance the drug sensitivity of HCC cells to an array of chemotherapeutic agents. SIRT3 may serve as a potential target for improving the chemosensitivity of HCC patients. PMID:27367026

Sirtuin 3 enhanced drug sensitivity of human hepatoma cells through glutathione S-transferase pi 1/JNK signaling pathway.

PubMed

Tao, Na-Na; Zhou, Hong-Zhong; Tang, Hua; Cai, Xue-Fei; Zhang, Wen-Lu; Ren, Ji-Hua; Zhou, Li; Chen, Xiang; Chen, Ke; Li, Wan-Yu; Liu, Bo; Yang, Qiu-Xia; Cheng, Sheng-Tao; Huang, Li-Xia; Huang, Ai-Long; Chen, Juan

2016-08-02

SIRT3, a class III histone deacetylase, has been implicated in various cancers as a novel therapeutic target. In hepatocellular carcinoma (HCC), we previously reported that SIRT3 induced cell apoptosis by regulating GSK-3β/Bax signaling pathway. Downregulation of SIRT3 in HCC cells facilitates tumor cell survival. In this study, we found that chemotherapeutic agents (doxorubicin, cisplatin and epirubicin) and sorafenib treatment downregulated SIRT3 mRNA and protein levels in three HCC cell lines. MTS assay found that SIRT3 overexpression sensitized liver cancer cells to chemotherapeutic agents and sorafenib in SMMC-7721, Huh-7 and PLC/PRF/5 cell lines. Moreover, SIRT3 overexpression promoted chemotherapeutic agents-induced or sorafenib-induced apoptosis as evidenced by flow cytometry, enhanced PARP cleavage and enhanced Caspase-9 cleavage in three HCC cells. In contrast, SIRT3 silencing increased drug resistance of HCC cells to chemotherapeutic agents. Mechanistic study found that SIRT3 downregulated the mRNA and protein levels of glutathione S-transferase pi 1 (GSTP1), which is a member of phase II detoxification enzymes families involved in metabolizing for chemotherapeutic agents. Moreover, SIRT3 decreased the amount of GSTP1 that was associated with JNK, which finally contributed the activation of JNK activity and activation of downstream target c-Jun and Bim. Importantly, GSTP1 overexpression or JNK inhibitor abolished SIRT3-induced apoptosis in HCC cells exposed to chemotherapeutic agents. Finally, there was a negative correlation between SIRT3 expression and GSTP1 expression in human HCC tissues. Together, our findings revealed SIRT3 could enhance the drug sensitivity of HCC cells to an array of chemotherapeutic agents. SIRT3 may serve as a potential target for improving the chemosensitivity of HCC patients.

Major bleeding events and risk stratification of antithrombotic agents in hemodialysis: Results from the DOPPS

PubMed Central

Sood, Manish M.; Larkina, Maria; Thumma, Jyothi R.; Tentori, Francesca; Gillespie, Brenda W.; Fukuhara, Shunichi; Mendelssohn, David C.; Chan, Kevin; de Sequera, Patricia; Komenda, Paul; Rigatto, Claudio; Robinson, Bruce M.

2013-01-01

Benefits and risks of antithrombotic agents remain unclear in the hemodialysis population. We aimed to determine variation in antithrombotic agent use, rates of major bleeding events, and to determine factors predictive of stroke and bleeding to allow for risk stratification, enabling more rational decisions about using antithrombotic agents. The sample included 48,144 patients in 12 countries in the Dialysis Outcomes and Practice Patterns Study Phase I–IV. Antithrombotic agents included oral anticoagulants (OAC), ASA and anti-platelet agents (APA). OAC prescription, comorbidities and vascular access were assessed at study entry; data on clinical events including hospitalization due to bleeding were collected every four months during follow-up. There was wide variation in OAC (0.3–18%), APA (3–25%) and ASA use (8–36%), and major bleeding rates (0.05–0.22 events/year) among countries. Rates of all-cause mortality, cardiovascular mortality, and bleeding events requiring hospitalization were elevated in patients prescribed OAC across adjusted models. The CHADS2 score predicted the risk of stroke in atrial fibrillation patients. Gastrointestinal bleeding in the past 12 months was highly predictive of major bleeding events; for patients with previous gastrointestinal bleeding, the rate of bleeding exceeded the rate of stroke by at least 2-fold across categories of CHADS2 score. Prescription of antithrombotic agents varied greatly. The CHADS2 score and a history of gastrointestinal bleeding were predictive of stroke and bleeding events, respectively, with bleeding rates substantially exceeding stroke rates in all groups including patients at high stroke risk. Appropriate risk stratification and a cautious approach should be considered before OAC use in the dialysis population. PMID:23677245

Theoretical analysis of the effects of light intensity on the photocorrosion of semiconductor electrodes

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

Benito, R.M.; Nozik, A.J.

1985-07-18

A kinetic model was developed to describe the effects of light intensity on the photocorrosion of n-type semiconductor electrodes. The model is an extension of previous work by Gomes and co-workers that includes the possibility of multiple steps for the oxidation reaction of the reducing agent in the electrolyte. Six cases are considered where the semiconductor decomposition reaction is multistep (each step involves a hole); the oxidation reaction of the reducing agent is multistep (each step after the first involves a hole or a chemical intermediate), and the first steps of the competing oxidation reactions are reversible or irreversible. Itmore » was found, contrary to previous results, that the photostability of semiconductor electrodes could increase with increased light intensity if the desired oxidation reaction of the reducing agent in the electrolyte was multistep with the first step being reversible. 14 references, 5 figures, 1 table.« less

A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin

PubMed Central

Zorofchian Moghadamtousi, Soheil; Abdul Kadir, Habsah; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan

2014-01-01

Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent. PMID:24877064

Use of antithrombotic agents in patients with intracerebral cavernous malformations.

PubMed

Flemming, Kelly D; Link, Michael J; Christianson, Teresa J H; Brown, Robert D

2013-01-01

The goal of this study was to determine the risk of using antithrombotic agents in patients with established intracerebral cavernous malformations (ICMs). From a previously described cohort of 292 patients with radiographically defined ICMs, 40 required an antithrombotic after the ICM was diagnosed. Patients underwent follow-up to determine the incidence of hemorrhage. The mean age of these 40 patients was 62.4 years; there were 21 male and 19 female patients. Five (12.5%) of the 40 patients initially presented with hemorrhage and 4 (10%) had multiple ICMs. Of these patients, 32 were placed on an antiplatelet agent alone, 6 on an anticoagulant alone, and 2 were placed on both. In patients necessitating any antithrombotic agent, 1 patient developed a prospective hemorrhage over the 258 person-years of follow-up (prospective hemorrhage rate 0.41% per person-year). Antithrombotics likely do not precipitate hemorrhage in patients with known ICMs. However, caution should be exercised in the use of antithrombotics in patients with ICMs at high risk for hemorrhage. The risks and benefits of antithrombotics in each situation should be carefully weighed against the natural history of ICM.

Control of Synchronization Regimes in Networks of Mobile Interacting Agents

NASA Astrophysics Data System (ADS)

Perez-Diaz, Fernando; Zillmer, Ruediger; Groß, Roderich

2017-05-01

We investigate synchronization in a population of mobile pulse-coupled agents with a view towards implementations in swarm-robotics systems and mobile sensor networks. Previous theoretical approaches dealt with range and nearest-neighbor interactions. In the latter case, a synchronization-hindering regime for intermediate agent mobility is found. We investigate the robustness of this intermediate regime under practical scenarios. We show that synchronization in the intermediate regime can be predicted by means of a suitable metric of the phase response curve. Furthermore, we study more-realistic K -nearest-neighbor and cone-of-vision interactions, showing that it is possible to control the extent of the synchronization-hindering region by appropriately tuning the size of the neighborhood. To assess the effect of noise, we analyze the propagation of perturbations over the network and draw an analogy between the response in the hindering regime and stable chaos. Our findings reveal the conditions for the control of clock or activity synchronization of agents with intermediate mobility. In addition, the emergence of the intermediate regime is validated experimentally using a swarm of physical robots interacting with cone-of-vision interactions.

Causal Responsibility and Counterfactuals

PubMed Central

Lagnado, David A; Gerstenberg, Tobias; Zultan, Ro'i

2013-01-01

How do people attribute responsibility in situations where the contributions of multiple agents combine to produce a joint outcome? The prevalence of over-determination in such cases makes this a difficult problem for counterfactual theories of causal responsibility. In this article, we explore a general framework for assigning responsibility in multiple agent contexts. We draw on the structural model account of actual causation (e.g., Halpern & Pearl, 2005) and its extension to responsibility judgments (Chockler & Halpern, 2004). We review the main theoretical and empirical issues that arise from this literature and propose a novel model of intuitive judgments of responsibility. This model is a function of both pivotality (whether an agent made a difference to the outcome) and criticality (how important the agent is perceived to be for the outcome, before any actions are taken). The model explains empirical results from previous studies and is supported by a new experiment that manipulates both pivotality and criticality. We also discuss possible extensions of this model to deal with a broader range of causal situations. Overall, our approach emphasizes the close interrelations between causality, counterfactuals, and responsibility attributions. PMID:23855451

The coevolution of partner switching and strategy updating in non-excludable public goods game

NASA Astrophysics Data System (ADS)

Li, Yixiao; Shen, Bin

2013-10-01

Spatial public goods game is a popular metaphor to model the dilemma of collective cooperation on graphs, yet the non-excludable property of public goods has seldom been considered in previous models. Based upon a coevolutionary model where agents play public goods games and adjust their partnerships, the present model incorporates the non-excludable property of public goods: agents are able to adjust their participation in the games hosted by others, whereas they cannot exclude others from their own games. In the coevolution, a directed and dynamical network which represents partnerships among autonomous agents is evolved. We find that non-excludable property counteracts the positive effect of partner switching, i.e., the equilibrium level of cooperation is lower than that in the situation of excludable public goods game. Therefore, we study the effect of individual punishment that cooperative agents pay a personal cost to decrease benefits of those defective neighbors who participate in their hosted games. It is found that the cooperation level in the whole population is heightened in the presence of such a costly behavior.

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

Brief introductory guide to agent-based modeling and an illustration from urban health research.

PubMed

Auchincloss, Amy H; Garcia, Leandro Martin Totaro

2015-11-01

There is growing interest among urban health researchers in addressing complex problems using conceptual and computation models from the field of complex systems. Agent-based modeling (ABM) is one computational modeling tool that has received a lot of interest. However, many researchers remain unfamiliar with developing and carrying out an ABM, hindering the understanding and application of it. This paper first presents a brief introductory guide to carrying out a simple agent-based model. Then, the method is illustrated by discussing a previously developed agent-based model, which explored inequalities in diet in the context of urban residential segregation.

Brief introductory guide to agent-based modeling and an illustration from urban health research

PubMed Central

Auchincloss, Amy H.; Garcia, Leandro Martin Totaro

2017-01-01

There is growing interest among urban health researchers in addressing complex problems using conceptual and computation models from the field of complex systems. Agent-based modeling (ABM) is one computational modeling tool that has received a lot of interest. However, many researchers remain unfamiliar with developing and carrying out an ABM, hindering the understanding and application of it. This paper first presents a brief introductory guide to carrying out a simple agent-based model. Then, the method is illustrated by discussing a previously developed agent-based model, which explored inequalities in diet in the context of urban residential segregation. PMID:26648364

Synthesis and evaluation of novel caged DNA alkylating agents bearing 3,4-epoxypiperidine structure.

PubMed

Kawada, Yuji; Kodama, Tetsuya; Miyashita, Kazuyuki; Imanishi, Takeshi; Obika, Satoshi

2012-07-14

Previously, we reported that the 3,4-epoxypiperidine structure, whose design was based on the active site of DNA alkylating antitumor antibiotics, azinomycins A and B, possesses prominent DNA cleavage activity. In this report, novel caged DNA alkylating agents, which were designed to be activated by UV irradiation, were synthesized by the introduction of four photo-labile protecting groups to a 3,4-epoxypiperidine derivative. The DNA cleavage activity and cytotoxicity of the caged DNA alkylating agents were examined under UV irradiation. Four caged DNA alkylating agents showed various degrees of bioactivity depending on the photosensitivity of the protecting groups.

Evaluation of New Cleanup Agents for Analysis of Pesticide Residues in Tea.

PubMed

Ueda, Yuko; Honda, Katsuhisa

2017-01-01

We evaluated the effectiveness of new cleanup agents (S-NH 2 and S-Si) compared with other previously reported cleanup agents (octadecylsilane, graphitized carbon, aminopropyl and silica gel) for removal of interfering substances such as catechin and caffeine prior to analysis of pesticide residues in tea. S-NH 2 and S-Si were highly efficient in removal of catechin and caffeine, respectively. Recoveries of 80 pesticides using S-NH 2 and S-Si were tested, and more than 70% of pesticides showed recovery greater than 70%. These results indicate that S-NH 2 and S-Si agents will be useful for analysis of pesticide residues in tea.

Synthesis route and three different core-shell impacts on magnetic characterization of gadolinium oxide-based nanoparticles as new contrast agents for molecular magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Moghimi, Hamid Reza; Zohdiaghdam, Reza; Rafiei, Behrooz; Gorji, Ensieh

2012-10-01

Despite its good resolution, magnetic resonance imaging intrinsically has low sensitivity. Recently, contrast agent nanoparticles have been used as sensitivity and contrast enhancer. The aim of this study was to investigate a new controlled synthesis method for gadolinium oxide-based nanoparticle preparation. For this purpose, diethyleneglycol coating of gadolinium oxide (Gd2O3-DEG) was performed using new supervised polyol route, and small particulate gadolinium oxide (SPGO) PEGylation was obtained with methoxy-polyethylene-glycol-silane (550 and 2,000 Da) coatings as SPGO-mPEG-silane550 and 2,000, respectively. Physicochemical characterization and magnetic properties of these three contrast agents in comparison with conventional Gd-DTPA were verified by dynamic light scattering transmission electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray diffraction, vibrating sample magnetometer, and the signal intensity and relaxivity measurements were performed using 1.5-T MRI scanner. As a result, the nanoparticle sizes of Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000 could be reached to 5.9, 51.3, 194.2 nm, respectively. The image signal intensity and longitudinal ( r 1) and transverse relaxivity ( r 2) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r 2/ r 1 ratios of 1.13, 0.89, 33.34, and 33.72 for Gd-DTPA, Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000, respectively. The achievement of new synthesis route of Gd2O3-DEG resulted in lower r 2/ r 1 ratio for Gd2O3-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r 2/ r 1 ratios of two PEGylated-SPGO contrast agents in our study in comparison with r 2/ r 1 ratio of previous PEGylation ( r 2/ r 1 = 81.9 for mPEG-silane 6,000 MW) showed that these new three introduced contrast agents could potentially be proper contrast enhancers for cellular and molecular MR imaging.

WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

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

Grassberger, C; Paganetti, H

Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumedmore » to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo-radiation could minimize the probability of resistance, increasing tumor control significantly.« less

Contributions of gopher mound and casting disturbances to plant community structure in a Cascade Range meadow complex

Treesearch

M. Case; C.B. Halpern; S.A. Levin

2013-01-01

Pocket gophers (Geomyidae) are major agents of disturbance in North American grasslands. Gopher mounds bury existing plants and influence community structure through various mechanisms. However, in mountain meadows that experience winter snowpack, gophers also create winter castings, smaller tube-shaped deposits, previously ignored in studies of plant–gopher...

Durability of one-part polyurethane bonds to wood improved by HMR coupling agent

Treesearch

Charles B. Vick; E. Arnold Okkonen

2000-01-01

In a previous study on the strength and durability of a new class of wood adhesives called one-part polyurethanes, four commercial one-part polyurethanes, along with a resorcinol-formaldehyde adhesive representing a standard of performance, were compared in bonds to yellow birch and Douglas-fir in a series of industry-accepted tests (7). The polyurethanes all performed...

Potential role of small noncoding RNAs in regulating hypovirulence in Rhizoctonia solani anastomosis group 3

USDA-ARS?s Scientific Manuscript database

Double-stranded RNA (dsRNA) elements are frequently associated with fungi. In Rhizoctonia solani anastomosis group-3 (AG3), the 3.6 kb dsRNA element M2 has been associated with the hypovirulence of Rhs1A1 strain, enabling its use as a biological control agent. Previous studies that examined the rol...

VdCYC8, encoding CYC8 glucose repression mediator protein, is required for microsclerotia formation and full virulence in Verticillium dahliae

USDA-ARS?s Scientific Manuscript database

Verticillium dahliae is the primary causal agent for Verticillium wilt disease on a diverse array of economically important crops, including cotton. In previous research, we screened a T-DNA insertional mutant library of the highly virulent isolate Vd080 derived from cotton. In this study, the targ...

Stream water quality concerns linger long after the smoke clears: Learning from Front Range wildfires

Treesearch

Chuck Rhoades; Susan Miller; Tim Covino; Alex Chow; Frank McCormick

2017-01-01

Large, high-severity wildfires alter the ecological processes that determine how watersheds retain and release nutrients and affect stream water quality. These changes usually abate a few years after a fire but recent studies indicate they may persist longer than previously expected. Wildfires are a natural disturbance agent, but due to the increased frequency and...

The herb community of a tropical forest in central Panama: dynamics and impact of mammalian herbivores

Treesearch

Alejandro A. Royo; Walter P. Carson

2005-01-01

Mammals are hypothesized to either promote plant diversity by preventing competitive exclusion or limit diversity by reducing the abundance of sensitive plant species through their activities as browsers or disturbance agents. Previous studies of herbivore impacts in plant communities have focused on tree species and ignored the herbaceous community. In an experiment...

The role of technetium-99m stannous pyrophosphate in myocardial imaging to recognize, localize and identify extension of acute myocardial infarction in patients

NASA Technical Reports Server (NTRS)

Willerson, J. T.; Parkey, R. W.; Bonte, F. J.; Stokely, E. M.; Buja, E. M.

1975-01-01

The ability of technetium-99m stannous pyrophosphate myocardial scintigrams to aid diagnostically in recognizing, localizing, and identifying extension of acute myocardial infarction in patients was evaluated. The present study is an extension of previous animal and patient evaluations that were recently performed utilizing this myocardial imaging agent.

Towards harmonised procedures in wildlife epidemiological investigations: a serosurvey of infection with Mycobacterium bovis and closely related agents in wild boar (Sus scrofa) in Switzerland.

PubMed

Beerli, Olivia; Blatter, Sohvi; Boadella, Mariana; Schöning, Janne; Schmitt, Sarah; Ryser-Degiorgis, Marie-Pierre

2015-01-01

Bovine tuberculosis (bTB) is a (re-)emerging disease in European countries, including Switzerland. This study assesses the seroprevalence of infection with Mycobacterium bovis and closely related agents in wild boar (Sus scrofa) in Switzerland, because wild boar are potential maintenance hosts of these pathogens. The study employs harmonised laboratory methods to facilitate comparison with the situation in other countries. Eighteen out of 743 blood samples tested seropositive (2.4%, CI: 1.5-3.9%) by ELISA, and the results for 61 animals previously assessed using culture and PCR indicated that this serological test was not 100% specific for M. bovis, cross-reacting with M. microti. Nevertheless, serology appears to be an appropriate test methodology in the harmonisation of wild boar testing throughout Europe. In accordance with previous findings, the low seroprevalence found in wild boar suggests wildlife is an unlikely source of the M. bovis infections recently detected in cattle in Switzerland. This finding contrasts with the epidemiological situation pertaining in southern Spain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of biological control agents and exotic plant invasion on deer mouse populations

Treesearch

Yvette K. Ortega; Dean E. Pearson; Kevin S. McKelvey

2004-01-01

Exotic insects are commonly introduced as biological control agents to reduce densities of invasive exotic plants. Although current biocontrol programs for weeds take precautions to minimize ecological risks, little attention is paid to the potential nontarget effects of introduced food subsidies on native consumers. Previous research demonstrated that two gall flies (...

Mobile, Virtual Enhancements for Rehabilitation (MOVER)

DTIC Science & Technology

2013-11-28

Modeling Autobiographical Memory for Believable Agents, AIIDE, Boston, MA. 2013. From the abstract: “We present a multi-layer hierarchical...connectionist network model for simulating human autobiographical memory in believable agents. Grounded in psychological theory, this model improves on...previous attempts to model agents’ event knowledge by providing a more dynamic and nondeterministic representation of autobiographical memories .” This

Transfer of conflict and cooperation from experienced games to new games: a connectionist model of learning

PubMed Central

Spiliopoulos, Leonidas

2015-01-01

The question of whether, and if so how, learning can be transfered from previously experienced games to novel games has recently attracted the attention of the experimental game theory literature. Existing research presumes that learning operates over actions, beliefs or decision rules. This study instead uses a connectionist approach that learns a direct mapping from game payoffs to a probability distribution over own actions. Learning is operationalized as a backpropagation rule that adjusts the weights of feedforward neural networks in the direction of increasing the probability of an agent playing a myopic best response to the last game played. One advantage of this approach is that it expands the scope of the model to any possible n × n normal-form game allowing for a comprehensive model of transfer of learning. Agents are exposed to games drawn from one of seven classes of games with significantly different strategic characteristics and then forced to play games from previously unseen classes. I find significant transfer of learning, i.e., behavior that is path-dependent, or conditional on the previously seen games. Cooperation is more pronounced in new games when agents are previously exposed to games where the incentive to cooperate is stronger than the incentive to compete, i.e., when individual incentives are aligned. Prior exposure to Prisoner's dilemma, zero-sum and discoordination games led to a significant decrease in realized payoffs for all the game classes under investigation. A distinction is made between superficial and deep transfer of learning both—the former is driven by superficial payoff similarities between games, the latter by differences in the incentive structures or strategic implications of the games. I examine whether agents learn to play the Nash equilibria of games, how they select amongst multiple equilibria, and whether they transfer Nash equilibrium behavior to unseen games. Sufficient exposure to a strategically heterogeneous set of games is found to be a necessary condition for deep learning (and transfer) across game classes. Paradoxically, superficial transfer of learning is shown to lead to better outcomes than deep transfer for a wide range of game classes. The simulation results corroborate important experimental findings with human subjects, and make several novel predictions that can be tested experimentally. PMID:25873855

Safety assessment of Vitis vinifera (grape)-derived ingredients as used in cosmetics.

PubMed

Fiume, Monice M; 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

2014-01-01

The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 24 Vitis vinifera (grape)-derived ingredients and found them safe in the present practices of use and concentration in cosmetics. These ingredients function in cosmetics mostly as skin-conditioning agents, but some function as antioxidants, flavoring agents, and/or colorants. The Panel reviewed the available animal and clinical data to determine the safety of these ingredients. Additionally, some constituents of grapes have been assessed previously for safety as cosmetic ingredients by the Panel, and others are compounds that have been discussed in previous Panel safety assessments. © The Author(s) 2014.

Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis: Retrospective Analysis of an 18-Year Longitudinal Study.

PubMed

Forslin, Y; Shams, S; Hashim, F; Aspelin, P; Bergendal, G; Martola, J; Fredrikson, S; Kristoffersen-Wiberg, M; Granberg, T

2017-07-01

Gadolinium-based contrast agents have been associated with lasting high T1-weighted signal intensity in the dentate nucleus and globus pallidus, with histopathologically confirmed gadolinium retention. We aimed to longitudinally investigate the relationship of multiple gadolinium-based contrast agent administrations to the Signal Intensity Index in the dentate nucleus and globus pallidus and any associations with cognitive function in multiple sclerosis. The Signal Intensity Index in the dentate nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving multiple gadolinium-based contrast agent administrations and 23 healthy age- and sex-matched controls. Participants also underwent comprehensive neuropsychological testing. Patients with MS had a higher Signal Intensity Index in the dentate nucleus ( P < .001), but not in the globus pallidus ( P = .19), compared with non-gadolinium-based contrast agent-exposed healthy controls by an unpaired t test. Increasing numbers of gadolinium-based contrast agent administrations were associated with an increased Signal Intensity Index in the dentate nucleus (β = 0.45, P < .001) and globus pallidus (β = 0.60, P < .001). This association remained stable with corrections for the age, disease duration, and physical disability for both the dentate nucleus (β = 0.43, P = .001) and globus pallidus (β = 0.58, P < .001). An increased Signal Intensity Index in the dentate nucleus among patients with MS was associated with lower verbal fluency scores, which remained significant after correction for several aspects of disease severity (β = -0.40 P = .013). Our data corroborate previous reports of lasting gadolinium retention in brain tissues. An increased Signal Intensity Index in the dentate nucleus and globus pallidus was associated with lower verbal fluency, which does not prove causality but encourages further studies on cognition and gadolinium-based contrast agent administration. © 2017 by American Journal of Neuroradiology.

Open trial of cimetidine in the prevention of upper gastro-intestinal haemorrhage in patients with severe intracranial injury.

PubMed

Mouawad, E; Deloof, T; Genette, F; Vandesteene, A

1983-01-01

The present study evaluates the efficacy of Cimetidine in the prevention of clinically important gastro-intestinal haemorrhage in patients suffering from severe head injury. Fifty patients (39 males and 11 females) were included in the study. We excluded from the trial patients on anticoagulant therapy or concomitant non-steroid anti-inflammatory agents, pregnant and lactating women, and patients with previous histories of peptic ulcer disease.

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.

Probing voltage sensing domain of KCNQ2 channel as a potential target to combat epilepsy: a comparative study.

PubMed

Mehta, Pakhuri; Srivastava, Shubham; Choudhary, Bhanwar Singh; Sharma, Manish; Malik, Ruchi

2017-12-01

Multidrug resistance along with side-effects of available anti-epileptic drugs and unavailability of potent and effective agents in submicromolar quantities presents the biggest therapeutic challenges in anti-epileptic drug discovery. The molecular modeling techniques allow us to identify agents with novel structures to match the continuous urge for its discovery. KCNQ2 channel represents one of the validated targets for its therapy. The present study involves identification of newer anti-epileptic agents by means of a computer-aided drug design adaptive protocol involving both structure-based virtual screening of Asinex library using homology model of KCNQ2 and 3D-QSAR based virtual screening with docking analysis, followed by dG bind and ligand efficiency calculations with ADMET studies, of which 20 hits qualified all the criterions. The best ligands of both screenings with least potential for toxicity predicted computationally were then taken for molecular dynamic simulations. All the crucial amino acid interactions were observed in hits of both screenings such as Glu130, Arg207, Arg210 and Phe137. Robustness of docking protocol was analyzed through Receiver operating characteristic (ROC) curve values 0.88 (Area under curve AUC = 0.87) in Standard Precision and 0.84 (AUC = 0.82) in Extra Precision modes. Novelty analysis indicates that these compounds have not been reported previously as anti-epileptic agents.

Bacterial endotoxin adhesion to different types of orthodontic adhesives

PubMed Central

ROMUALDO, Priscilla Coutinho; GUERRA, Thaís Rodrigues; ROMANO, Fábio Lourenço; da SILVA, Raquel Assed Bezerra; BRANDÃO, Izaíra Tincani; SILVA, Célio Lopes; da SILVA, Lea Assed Bezerra; NELSON-FILHO, Paulo

2017-01-01

Abstract Bacterial endotoxin (LPS) adhesion to orthodontic brackets is a known contributing factor to inflammation of the adjacent gingival tissues. Objective The aim of this study was to assess whether LPS adheres to orthodontic adhesive systems, comparing two commercial brands. Material and Methods Forty specimens were fabricated from Transbond XT and Light Bond composite and bonding agent components (n=10/component), then contaminated by immersion in a bacterial endotoxin solution. Contaminated and non-contaminated acrylic resin samples were used as positive and negative control groups, respectively. LPS quantification was performed by the Limulus Amebocyte Lysate QCL-1000™ test. Data obtained were scored and subjected to the Chi-square test using a significance level of 5%. Results There was endotoxin adhesion to all materials (p<0.05). No statistically significant difference was found between composites/bonding agents and acrylic resin (p>0.05). There was no significant difference (p>0.05) among commercial brands. Affinity of endotoxin was significantly greater for the bonding agents (p=0.0025). Conclusions LPS adhered to both orthodontic adhesive systems. Regardless of the brand, the endotoxin had higher affinity for the bonding agents than for the composites. There is no previous study assessing the affinity of LPS for orthodontic adhesive systems. This study revealed that LPS adheres to orthodontic adhesive systems. Therefore, additional care is recommended to orthodontic applications of these materials. PMID:28877283

HIV prevention trial design in an era of effective pre-exposure prophylaxis.

PubMed

Cutrell, Amy; Donnell, Deborah; Dunn, David T; Glidden, David V; Grobler, Anneke; Hanscom, Brett; Stancil, Britt S; Meyer, R Daniel; Wang, Ronnie; Cuffe, Robert L

2017-01-01

Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness protecting at-risk individuals from HIV-1 infection. Despite this record of effectiveness, concerns persist about the diminished protective effect observed in women compared with men and the influence of adherence and risk behaviors on effectiveness in targeted subpopulations. Furthermore, the high prophylactic efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates. Trials of new agents would typically require use of non-inferiority (NI) designs in which acceptable efficacy for an experimental agent is determined using pre-defined margins based on the efficacy of the proven active comparator (i.e. TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in designing registrational studies. Under- or over-estimation of the margin can call into question the utility of the study in the registration package. The dependence on previous placebo-controlled trials introduces the same issues as external/historical controls. These issues will need to be addressed using trial design features such as re-estimated NI margins, enrichment strategies, run-in periods, crossover between study arms, and adaptive re-estimation of sample sizes. These measures and other innovations can help to ensure that new PrEP agents are made available to the public using stringent standards of evidence.

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

Microarrays--new possibilities for detecting biological factors hazardous for humans and animals, and for use in environmental protection.

PubMed

Mirski, Tomasz; Bartoszcze, Michał; Bielawska-Drózd, Agata; Gryko, Romuald; Kocik, Janusz; Niemcewicz, Marcin; Chomiczewski, Krzysztof

2016-01-01

Both the known biological agents that cause infectious diseases, as well as modified (ABF-Advanced Biological Factors) or new, emerging agents pose a significant diagnostic problem using previously applied methods, both classical, as well as based on molecular biology methods. The latter, such as PCR and real-time PCR, have significant limitations, both quantitative (low capacity), and qualitative (limited number of targets). The article discusses the results of studies on using the microarray method for the identification of viruses (e.g. Orthopoxvirus group, noroviruses, influenza A and B viruses, rhino- and enteroviruses responsible for the FRI (Febrile Respiratory Illness), European bunyaviruses, and SARS-causing viruses), and bacteria (Mycobacterium spp., Yersinia spp., Campylobacter spp., Streptococcus pneumoniae, Salmonella typhi, Salmonella enterica, Staphylococcus aureus, Neisseria meningitidis, Clostridium difficile , Helicobacter pylori), including multiple antibiotic-resistant strains. The method allows for the serotyping and genotyping of bacteria, and is useful in the diagnosis of genetically modified agents. It allows the testing of thousands of genes in one experiment. In addition to diagnosis, it is applicable for gene expression studies, analysis of the function of genes, microorganisms virulence, and allows the detection of even single mutations. The possibility of its operational application in epidemiological surveillance, and in the detection of disease outbreak agents is demonstrated.

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.

The time course of indirect moral judgment in gossip processing modulated by different agents.

PubMed

Peng, Xiaozhe; Jiao, Can; Cui, Fang; Chen, Qingfei; Li, Peng; Li, Hong

2017-10-01

Previous studies have investigated personal moral violations with different references (i.e., the protagonists in moral scenarios are the participants themselves or unknown other individuals). However, the roles of various agents in moral judgments have remained unclear. In the present study, ERPs were used to investigate moral judgments when the participants viewed gossip that described (im)moral behaviors committed by different agents (self, friend, celebrity). The results demonstrate that the P2 and late positive component (LPC) correspond to two successive processes of indirect moral judgment when individuals process gossip. Specifically, the P2 amplitude in the celebrity condition was more sensitive in distinguishing immoral behaviors from moral behaviors than that in the other two conditions, whereas the moral valence effect on the LPC was predominately driven by the self-reference. These findings expand our current understanding of moral judgments in a gossip evaluation task and demonstrate that the early processing of gossip depends on both the entertainment value of the agent and the salience of moral behaviors. Processing in the later stage reflects reactions to intensified affective stimuli, or reflects cognitive effort that was required to resolve the conflict between negative gossip about self and the self-positivity bias. © 2017 Society for Psychophysiological Research.

Contrast-enhanced dual-energy subtraction imaging using electronic spectrum-splitting and multi-prism x-ray lenses

NASA Astrophysics Data System (ADS)

Fredenberg, Erik; Cederström, Björn; Lundqvist, Mats; Ribbing, Carolina; Åslund, Magnus; Diekmann, Felix; Nishikawa, Robert; Danielsson, Mats

2008-03-01

Dual-energy subtraction imaging (DES) is a method to improve the detectability of contrast agents over a lumpy background. Two images, acquired at x-ray energies above and below an absorption edge of the agent material, are logarithmically subtracted, resulting in suppression of the signal from the tissue background and a relative enhancement of the signal from the agent. Although promising, DES is still not widely used in clinical practice. One reason may be the need for two distinctly separated x-ray spectra that are still close to the absorption edge, realized through dual exposures which may introduce motion unsharpness. In this study, electronic spectrum-splitting with a silicon-strip detector is theoretically and experimentally investigated for a mammography model with iodinated contrast agent. Comparisons are made to absorption imaging and a near-ideal detector using a signal-to-noise ratio that includes both statistical and structural noise. Similar to previous studies, heavy absorption filtration was needed to narrow the spectra at the expense of a large reduction in x-ray flux. Therefore, potential improvements using a chromatic multi-prism x-ray lens (MPL) for filtering were evaluated theoretically. The MPL offers a narrow tunable spectrum, and we show that the image quality can be improved compared to conventional filtering methods.

31 CFR 202.5 - Previously designated depositaries.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Previously designated depositaries. 202.5 Section 202.5 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE DEPOSITARIES AND FINANCIAL AGENTS...

31 CFR 202.5 - Previously designated depositaries.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Previously designated depositaries. 202.5 Section 202.5 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE DEPOSITARIES AND FINANCIAL AGENTS...

Control of Root Rot and Wilt Diseases of Roselle under Field Conditions

PubMed Central

Hassan, Naglaa; Elsharkawy, Mohsen Mohamed; Shimizu, Masafumi

2014-01-01

Roselle (Hibiscus sabdariffa L.) is one of the most important medicinal crops in many parts of the world. In this study, the effects of microelements, antioxidants, and bioagents on Fusarium oxysporum, F. solani, and Macrophomina phaseolina, the causal pathogens of root rot and wilt diseases in roselle, were examined under field conditions. Preliminary studies were carried out in vitro in order to select the most effective members to be used in field control trials. Our results showed that microelements (copper and manganese), antioxidants (salicylic acid, ascorbic acid, and EDTA), a fungicide (Dithane M45) and biological control agents (Trichoderma harzianum and Bacillus subtilis) were significantly reduced the linear growth of the causal pathogens. Additionally, application of the previous microelements, antioxidants, a fungicide and biological control agents significantly reduced disease incidence of root rot and wilt diseases under field conditions. Copper, salicylic acid, and T. harzianum showed the best results in this respect. In conclusion, microelements, antioxidants, and biocontrol agents could be used as alternative strategies to fungicides for controlling root rot and wilt diseases in roselle. PMID:25606010

Synthesis of structurally diverse major groove DNA interstrand crosslinks using three different aldehyde precursors

PubMed Central

Mukherjee, Shivam; Guainazzi, Angelo; Schärer, Orlando D.

2014-01-01

DNA interstrand crosslinks (ICLs) are extremely cytotoxic lesions that block essential cellular processes, such as replication and transcription. Crosslinking agents are widely used in cancer chemotherapy and form an array of structurally diverse ICLs. Despite the clinical success of these agents, resistance of tumors to crosslinking agents, for example, through repair of these lesions by the cellular machinery remains a problem. We have previously reported the synthesis of site-specific ICLs mimicking those formed by nitrogen mustards to facilitate the studies of cellular responses to ICL formation. Here we extend these efforts and report the synthesis of structurally diverse major groove ICLs that induce severe, little or no distortion in the DNA. Our approach employs the incorporation of aldehyde precursors of different lengths into complementary strands and ICL formation using a double reductive amination with a variety of amines. Our studies provide insight into the structure and reactivity parameters of ICL formation by double reductive amination and yield a set of diverse ICLs that will be invaluable for exploring structure–activity relationships in ICL repair. PMID:24782532

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.

Increasing nerve agent treatment efficacy by P-glycoprotein inhibition.

PubMed

Joosen, Marloes J A; Vester, Stefanie M; Hamelink, Jouk; Klaassen, Steven D; van den Berg, Roland M

2016-11-25

One of the shortcomings of current treatment of nerve agent poisoning is that not all drugs effectively penetrate the blood-brain barrier (BBB), whereas most nerve agents easily do. P-glycoprotein (Pgp) efflux transporters at the BBB may contribute to this aspect. It was previously shown that Pgp inhibition by tariquidar enhanced the efficacy of nerve agent treatment when administered as a pretreatment. In the present study soman-induced seizures were also substantially prevented when the animals were intravenously treated with tariquidar post-poisoning, in addition to HI-6 and atropine. In these animals, approximately twice as much AChE activity was present in their brain as compared to control rats. The finding that tariquidar did not affect distribution of soman to the brain indicates that the potentiating effects were a result of interactions of Pgp inhibition with drug distribution. In line with this, atropine appeared to be a substrate for Pgp in in vitro studies in a MDR1/MDCK cell model. This indicates that tariquidar might induce brain region specific effects on atropine distribution, which could contribute to the therapeutic efficacy increase found. Furthermore, the therapeutic enhancement by tariquidar was compared to that of the less specific and less potent Pgp inhibitor cyclosporine A. This compound appeared to induce a protective effect similar to tariquidar. In conclusion, treatment with a Pgp inhibitor resulted in enhanced therapeutic efficacy of HI-6 and atropine in a soman-induced seizure model in the rat. The mechanism underlying these effects should be further investigated. To that end, the potentiating effect of nerve agent treatment should be addressed against a broader range of nerve agents, for oximes and atropine separately, and for those at lower doses. In particular when efficacy against more nerve agents is shown, a Pgp inhibitor such as tariquidar might be a valid addition to nerve agent antidotes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Non-steroidal anti-inflammatory and cytoprotective drug co-prescription in general practice. A general practitioner-based survey in France.

PubMed

Clinard, F; Bardou, M; Sgro, C; Lefevre, N; Raphael, F; Paille, F; Dumas, M; Hillon, P; Bonithon-Kopp, C

2001-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most frequently prescribed drugs. Gastrointestinal damage, the most common side effect of NSAIDs. can be limited by the prescription of cytoprotective agents. In order to assess determinants of NSAID-associated cytoprotective agent prescriptions in primary care practice, we performed a general practitioner (GP)-based study. After a 2-month intensive information campaign, the participation of all GPs of the Côte d'Or (France) administrative area was requested. During a 2-month period, GPs had to return a mailed questionnaire on NSAID prescription for up to ten consecutive patients aged over 18 years who required NSAIDs. This 30-item questionnaire included questions about the patient, the type of NSAID and the GP. GP participation rate was 24%, and 791 prescriptions were provided. GPs who participated in the study were representative of GPs of the area in terms of sex, time elapsed since graduation and GP practice area. Around 80% of the patients included in the study were under the age of 65 years. The proportion of prescriptions combining NSAIDs and gastroprotective agents was 29.5%. Omeprazole accounted for 58% of the coprescriptions and misoprostol for 29%. Independent determinants associated with the co-prescription of a cytoprotective agent were age [odds ratio (OR) 4.1; confidence interval (CI) 95% 2.3 7.4], previous history of poor NSAID tolerance (OR 10.4; CI 95% 5.8-18.6), previous history of moderate to severe digestive disorders (OR 13.4; CI 95% 5.1 35.4) and indication for chronic illness (OR 1.8, CI 95% 1.1-3.1). Prescriptions of cytoprotective drugs were in conformity with official guidelines for 78.3% of the patients. Although around 60% of the patients with risk factors for poor tolerance received a gastroprotective drug, 50% of the patients over 65 years did not receive it. Conversely, nearly 12% of the patients with no risk factors were prescribed cytoprotective agents. Patient history was the main reason put forward by GPs for prescribing cytoprotective drugs. Although a large majority of GP prescriptions were in accordance with official recommendations, inadequate NSAID prescription practices remain relatively frequent especially with regard to the elderly.

Agent-based simulation of a financial market

NASA Astrophysics Data System (ADS)

Raberto, Marco; Cincotti, Silvano; Focardi, Sergio M.; Marchesi, Michele

2001-10-01

This paper introduces an agent-based artificial financial market in which heterogeneous agents trade one single asset through a realistic trading mechanism for price formation. Agents are initially endowed with a finite amount of cash and a given finite portfolio of assets. There is no money-creation process; the total available cash is conserved in time. In each period, agents make random buy and sell decisions that are constrained by available resources, subject to clustering, and dependent on the volatility of previous periods. The model proposed herein is able to reproduce the leptokurtic shape of the probability density of log price returns and the clustering of volatility. Implemented using extreme programming and object-oriented technology, the simulator is a flexible computational experimental facility that can find applications in both academic and industrial research projects.

Fluorescent and scattering contrast agents in a mouse model of colorectal cancer

NASA Astrophysics Data System (ADS)

Winkler, Amy M.; Rice, Photini F. S.; Troutman, Timothy S.; Backer, Marina V.; Backer, Joseph M.; Drezek, Rebekah A.; Romanowski, Marek; Barton, Jennifer K.

2008-02-01

In previous work we have demonstrated the utility of laser-induced fluorescence (LIF) and optical coherence tomography (OCT) to identify adenoma in mouse models of colorectal cancer with high sensitivity and specificity. However, improved sensitivity to early disease, as well as the ability to distinguish confounders (e.g. fecal contamination, natural variations in mucosal thickness), is desired. In this study, we investigated the signal enhancement of fluorescent and scattering contrast agents in the colons of AOM-treated mice. The fluorescent tracer scVEGF/Cy, targeted to receptors for vascular endothelial growth factor, was visualized on a dual modality OCT/LIF endoscopic system with 1300-nm center wavelength OCT source and 635-nm LIF excitation. Scattering agents were tested with an 890-nm center wavelength endoscopic OCT system. Agents included nanoshells, 120-nm in diameter, and nanorods, 20-nm in diameter by 80-nm in length. Following imaging, colons were excised. Tissue treated with fluorophore was imaged on an epifluorescence microscope. Histological sections were obtained and stained with H&E and silver enhancer to verify disease and identify regions of gold uptake, respectively. Non-specific signal enhancement was observed with the scattering contrast agents. Specificity for adenoma was seen with the scVEGF/Cy dye.

Occupation and male lung cancer: a case-control study in northern Sweden.

PubMed Central

Damber, L A; Larsson, L G

1987-01-01

Using a case-control study comprising about 600 men with lung cancer in northern Sweden the potential risk of different occupations and groups of occupations was studied. Longitudinal data concerning occupation, employment, and smoking habits were obtained by questionnaires. Some occupational groups (underground miners, copper smelter workers, electricians, and plumbers) exposed to previously known lung carcinogenic agents such as radon daughters, arsenic, and asbestos, had considerably increased odds ratios, which persisted after adjustment for smoking. A slightly raised odds ratio was observed in a group of blue collar workers potentially exposed to lung carcinogenic agents; this rise in the group as a whole mainly disappeared after adjustment for smoking. Farmers and foresters had strikingly low odds ratios, which could only partly be explained by their more moderate smoking habits. The population aetiological fraction attributable to occupation was estimated as 9%. PMID:3620367

Integrating informative priors from experimental research with Bayesian methods: an example from radiation epidemiology.

PubMed

Hamra, Ghassan; Richardson, David; Maclehose, Richard; Wing, Steve

2013-01-01

Informative priors can be a useful tool for epidemiologists to handle problems of sparse data in regression modeling. It is sometimes the case that an investigator is studying a population exposed to two agents, X and Y, where Y is the agent of primary interest. Previous research may suggest that the exposures have different effects on the health outcome of interest, one being more harmful than the other. Such information may be derived from epidemiologic analyses; however, in the case where such evidence is unavailable, knowledge can be drawn from toxicologic studies or other experimental research. Unfortunately, using toxicologic findings to develop informative priors in epidemiologic analyses requires strong assumptions, with no established method for its utilization. We present a method to help bridge the gap between animal and cellular studies and epidemiologic research by specification of an order-constrained prior. We illustrate this approach using an example from radiation epidemiology.

Integrating Informative Priors from Experimental Research with Bayesian Methods

PubMed Central

Hamra, Ghassan; Richardson, David; MacLehose, Richard; Wing, Steve

2013-01-01

Informative priors can be a useful tool for epidemiologists to handle problems of sparse data in regression modeling. It is sometimes the case that an investigator is studying a population exposed to two agents, X and Y, where Y is the agent of primary interest. Previous research may suggest that the exposures have different effects on the health outcome of interest, one being more harmful than the other. Such information may be derived from epidemiologic analyses; however, in the case where such evidence is unavailable, knowledge can be drawn from toxicologic studies or other experimental research. Unfortunately, using toxicologic findings to develop informative priors in epidemiologic analyses requires strong assumptions, with no established method for its utilization. We present a method to help bridge the gap between animal and cellular studies and epidemiologic research by specification of an order-constrained prior. We illustrate this approach using an example from radiation epidemiology. PMID:23222512

Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression

PubMed Central

Lener, Marc S.; Kadriu, Bashkim; Zarate, Carlos A.

2017-01-01

Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder (MDD) and bipolar depression. In clinical studies of individuals with MDD and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants. This review will highlight the evidence supporting the antidepressant effects of subanesthetic-dose ketamine as well as other glutamatergic modulators, such as D-cycloserine (DCS), riluzole, CP-101,606, CERC-301 (previously known as MK-0657), basimglurant, JNJ-40411813, dextromethorphan, nitrous oxide (N2O), GLYX-13, and esketamine. PMID:28194724

Deliberate or unintended: Intentions modulate empathic responses to others' economic payoffs in social interactions.

PubMed

Ma, Qingguo; Meng, Liang; Shen, Qiang

2017-12-01

Previous studies examining empathy have revealed the neural substrates of how the physical pain of others is represented in the human brain. However, little is known about the empathic modulation of behavioral and neural responses to others' economic payoffs, especially in the social context. In the present study, we engaged participants in a revised Dictator Game as observers who observe the powerless players receiving varied offers proposed by the dominant players, establishing the link between empathy and fairness perception. Results showed that unfair division schemes elicited a more pronounced FRN than fair ones only if a human agent proposed the initial offer. In addition, observers sacrificed their own payments to adjust unfair proposals, especially when a human agent proposed the offer. Thus, results of the current study demonstrated that perceived intention modulates behavioral and neural responses to others' economic payoffs in social interactions.

Social inertia and diversity in collaboration networks

NASA Astrophysics Data System (ADS)

Ramasco, J. J.

2007-04-01

Random graphs are useful tools to study social interactions. In particular, the use of weighted random graphs allows to handle a high level of information concerning which agents interact and in which degree the interactions take place. Taking advantage of this representation, we recently defined a magnitude, the Social Inertia, that measures the eagerness of agents to keep ties with previous partners. To study this magnitude, we used collaboration networks that are specially appropriate to obtain valid statitical results due to the large size of publically available databases. In this work, I study the Social Inertia in two of these empirical networks, IMDB movie database and condmat. More specifically, I focus on how the Inertia relates to other properties of the graphs, and show that the Inertia provides information on how the weight of neighboring edges correlates. A social interpretation of this effect is also offered.

Blood transcriptomics: applications in toxicology

PubMed Central

Joseph, Pius; Umbright, Christina; Sellamuthu, Rajendran

2015-01-01

The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article. PMID:23456664

Peri-Prosthetic Knee Infection Management: Spacers Loaded with Two or Three Antibiotic Agents.

PubMed

Ortola, David Joaquin; Fenga, Domenico; Marcellino, Sandra; Rosi, Massimiliano; Centofanti, Francesco; Rosa, Michele Attilio

2017-07-01

The purpose of this work was to compare pre-made antibiotic-loaded spacers with two commercially available antibiotic agents and custom-made cements with three antibiotic agents added. We evaluated: (a) the validity of our procedures, (b) the control of the rate of infection in the long term, (c) complications, and (d) quality of life and patient satisfaction. A retrospective cohort study was performed on 112 consecutively treated patients between January 2010 and December 2013; 56 patients were treated with a pre-formed cement spacer (clindamycin + gentamicin), and 56 patients were treated with a spacer loaded with three antibiotic agents (clindamycin + gentamicin + vancomycin). Demographic data were collected: Classification of infection according to criteria of Cierny-Mader; microbiologic results; number of previous operations; and years of disease. Infection control or relapse after at least 18 months of follow-up was evaluated. Complications were recorded. Every patient completed the SF-36 test and Oxford Knee Score. With a follow-up of 32.87 months (standard deviation 12.04), at the end of treatment, amputation occurred in three of 112 patients because of recurrence of infection, and one patient died from other causes not related to the infection. The study population presented a rate of recurrence of infection of 2.70%. Our results suggest that a two stage re-implant with three antibiotic agents added to the spacer should be considered to avoid rescue procedures, especially in patients with multi-resistant micro-organism infections.

The Redox Cycler Plasmodione Is a Fast-Acting Antimalarial Lead Compound with Pronounced Activity against Sexual and Early Asexual Blood-Stage Parasites.

PubMed

Ehrhardt, Katharina; Deregnaucourt, Christiane; Goetz, Alice-Anne; Tzanova, Tzvetomira; Gallo, Valentina; Arese, Paolo; Pradines, Bruno; Adjalley, Sophie H; Bagrel, Denyse; Blandin, Stephanie; Lanzer, Michael; Davioud-Charvet, Elisabeth

2016-09-01

Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox cyclers-a strategy that is broadly recognized for the development of new antimalarial agents. Here we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intraerythrocytic stages of the human malaria parasite Plasmodium falciparum We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intraerythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common mechanisms of resistance to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a high killing speed, as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that plasmodione is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Redox Cycler Plasmodione Is a Fast-Acting Antimalarial Lead Compound with Pronounced Activity against Sexual and Early Asexual Blood-Stage Parasites

PubMed Central

Ehrhardt, Katharina; Deregnaucourt, Christiane; Goetz, Alice-Anne; Tzanova, Tzvetomira; Gallo, Valentina; Arese, Paolo; Pradines, Bruno; Adjalley, Sophie H.; Bagrel, Denyse; Blandin, Stephanie; Lanzer, Michael

2016-01-01

Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox cyclers—a strategy that is broadly recognized for the development of new antimalarial agents. Here we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intraerythrocytic stages of the human malaria parasite Plasmodium falciparum. We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intraerythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common mechanisms of resistance to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a high killing speed, as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that plasmodione is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents. PMID:27297478

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

A Generalized Quantum-Inspired Decision Making Model for Intelligent Agent

PubMed Central

Loo, Chu Kiong

2014-01-01

A novel decision making for intelligent agent using quantum-inspired approach is proposed. A formal, generalized solution to the problem is given. Mathematically, the proposed model is capable of modeling higher dimensional decision problems than previous researches. Four experiments are conducted, and both empirical experiments results and proposed model's experiment results are given for each experiment. Experiments showed that the results of proposed model agree with empirical results perfectly. The proposed model provides a new direction for researcher to resolve cognitive basis in designing intelligent agent. PMID:24778580

[Management of Patients on Antithrombotic Agents Undergoing Endoscopy].

PubMed

Kim, Joon Sung; Kim, Byung Wook

2018-05-25

Antithrombotic agents are used increasingly in Asia. The management of patients on antithrombotics undergoing elective or emergency endoscopy has become an increasing clinical challenge for gastroenterologists. Current practice guidelines have been developed by societies from western countries. On the other hand, these guidelines cannot meet the specific needs of the Asian Pacific region, raising the need for separate guidelines in Asia. This review compares the recommendations of previous guidelines with the most recently published Asian guidelines regarding the management of patients on antithrombotic agents undergoing elective and emergency endoscopy.

[Short-term relevance of lower respiratory viral coinfection in inpatients under 2 years of age].

PubMed

Gil, Joana; Almeida, Sofia; Constant, Carolina; Pinto, Sara; Barreto, Rosário; Cristino, José Melo; Machado, Maria do Céu; Bandeira, Teresa

2018-03-01

Advances in molecular diagnosis have made it possible to detect previously unknown viral agents as causative agents of lower respiratory tract infections (LRTI). The frequency and relevance of viral coinfections is still debatable. compare clinical presentation and severity between single virus infection and viral coinfection in children admitted for LRTI. A 3-year period observational study (2012-2015) included children younger than two years admitted for LRTI. Viral identification was performed using PCR technique for 16 viruses. Clinical data and use of health resources was gathered during hospital stay using a standard collection form and we compared single virus infection and viral coinfections. The study included 524 samples (451 patients); 448 (85,5%) had at least one virus identified. Viral coinfections were found in 159 (35,5%). RSV and HRV were the most commonly identified virus; bronchiolitis and pneumonia the most frequent diagnosis. Patients with viral coinfections were older, attended day-care centers, had previous recurrent wheezing more frequently and were more symptomatic at admission. These patients did not have more complementary exams performed but were prescribed medications more often. Viral coinfection group did not show longer length of hospital stay and oxygen need, more need for ICU nor ventilatory support. Our study showed a significant proportion of viral coinfections in young infants admitted with LRTI and confirmed previous data showing that prescription was more frequent in inpatients with viral coinfections, without an association with worst clinical outcome. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Human-level control through deep reinforcement learning.

PubMed

Mnih, Volodymyr; Kavukcuoglu, Koray; Silver, David; Rusu, Andrei A; Veness, Joel; Bellemare, Marc G; Graves, Alex; Riedmiller, Martin; Fidjeland, Andreas K; Ostrovski, Georg; Petersen, Stig; Beattie, Charles; Sadik, Amir; Antonoglou, Ioannis; King, Helen; Kumaran, Dharshan; Wierstra, Daan; Legg, Shane; Hassabis, Demis

2015-02-26

The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.

Human-level control through deep reinforcement learning

NASA Astrophysics Data System (ADS)

Mnih, Volodymyr; Kavukcuoglu, Koray; Silver, David; Rusu, Andrei A.; Veness, Joel; Bellemare, Marc G.; Graves, Alex; Riedmiller, Martin; Fidjeland, Andreas K.; Ostrovski, Georg; Petersen, Stig; Beattie, Charles; Sadik, Amir; Antonoglou, Ioannis; King, Helen; Kumaran, Dharshan; Wierstra, Daan; Legg, Shane; Hassabis, Demis

2015-02-01

The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.

Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents.

PubMed

Yang, Jir-Jei; Yin, Jiu-Haw; Yang, Ding-I

2007-05-11

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) kills tumor cells via multiple actions including alkylation and carbamoylation. Previously, we have reported that formation of S-nitrosoglutathione (GSNO) in glioma cells overexpressing inducible nitric oxide synthase (iNOS) contributed to nitric oxide (NO)-dependent carbamoylating chemoresistance against BCNU. To further characterize the effects of NO on alkylating cytotoxicity, colony formation assay was applied to evaluate the effects of various NO donors on rat C6 glioma cells challenged with alkylating agents. We demonstrate that NO donors including GSNO, diethylamine NONOate (DEA/NO), and sodium nitroprusside (SNP) substantially reduced the extent of colony formation in glioma cells treated with alkylating agents, namely methyl methanesulfonate (MMS), N-methyl-N-nitrosourea (MNU), and N-ethyl-N-nitrosourea (ENU). Without alkylating agents these NO-releasing agents alone had no effects on clongenic potential of rat C6 glioma cells. Among these three NO donors used, the effectiveness in potentiating alkylating cytotoxicity is in the order of "GSNO>DEA/NO>SNP" when applied at the same dosages. GSNO also exerted similar synergistic actions reducing the extents of colony formation when co-administrated with 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-hydrazine (compound #1), another alkylating agent that mimics the chloroethylating action of BCNU. Together with our previous findings, we propose that NO donors may be used as adjunct chemotherapy with alkylating agents for such malignant brain tumors as glioblastoma multiforme (GBM). In contrast, production of NO as a result of iNOS induction, such as that occurring after surgical resection of brain tumors, may compromise the efficacy of carbamoylating chemotherapy.

Collective navigation of cargo-carrying swarms

PubMed Central

Shklarsh, Adi; Finkelshtein, Alin; Ariel, Gil; Kalisman, Oren; Ingham, Colin; Ben-Jacob, Eshel

2012-01-01

Much effort has been devoted to the study of swarming and collective navigation of micro-organisms, insects, fish, birds and other organisms, as well as multi-agent simulations and to the study of real robots. It is well known that insect swarms can carry cargo. The studies here are motivated by a less well-known phenomenon: cargo transport by bacteria swarms. We begin with a concise review of how bacteria swarms carry natural, micrometre-scale objects larger than the bacteria (e.g. fungal spores) as well as man-made beads and capsules (for drug delivery). A comparison of the trajectories of virtual beads in simulations (using different putative coupling between the virtual beads and the bacteria) with the observed trajectories of transported fungal spores implies the existence of adaptable coupling. Motivated by these observations, we devised new, multi-agent-based studies of cargo transport by agent swarms. As a first step, we extended previous modelling of collective navigation of simple bacteria-inspired agents in complex terrain, using three putative models of agent–cargo coupling. We found that cargo-carrying swarms can navigate efficiently in a complex landscape. We further investigated how the stability, elasticity and other features of agent–cargo bonds influence the collective motion and the transport of the cargo, and found sharp phase shifts and dual successful strategies for cargo delivery. Further understanding of such mechanisms may provide valuable clues to understand cargo-transport by smart swarms of other organisms as well as by man-made swarming robots. PMID:24312731

Infants use relative numerical group size to infer social dominance

PubMed Central

Pun, Anthea; Birch, Susan A. J.; Baron, Andrew Scott

2016-01-01

Detecting dominance relationships, within and across species, provides a clear fitness advantage because this ability helps individuals assess their potential risk of injury before engaging in a competition. Previous research has demonstrated that 10- to 13-mo-old infants can represent the dominance relationship between two agents in terms of their physical size (larger agent = more dominant), whereas younger infants fail to do so. It is unclear whether infants younger than 10 mo fail to represent dominance relationships in general, or whether they lack sensitivity to physical size as a cue to dominance. Two studies explored whether infants, like many species across the animal kingdom, use numerical group size to assess dominance relationships and whether this capacity emerges before their sensitivity to physical size. A third study ruled out an alternative explanation for our findings. Across these studies, we report that infants 6–12 mo of age use numerical group size to infer dominance relationships. Specifically, preverbal infants expect an agent from a numerically larger group to win in a right-of-way competition against an agent from a numerically smaller group. In addition, this is, to our knowledge, the first study to demonstrate that infants 6–9 mo of age are capable of understanding social dominance relations. These results demonstrate that infants’ understanding of social dominance relations may be based on evolutionarily relevant cues and reveal infants’ early sensitivity to an important adaptive function of social groups. PMID:26884199

Adaptive behaviors in multi-agent source localization using passive sensing.

PubMed

Shaukat, Mansoor; Chitre, Mandar

2016-12-01

In this paper, the role of adaptive group cohesion in a cooperative multi-agent source localization problem is investigated. A distributed source localization algorithm is presented for a homogeneous team of simple agents. An agent uses a single sensor to sense the gradient and two sensors to sense its neighbors. The algorithm is a set of individualistic and social behaviors where the individualistic behavior is as simple as an agent keeping its previous heading and is not self-sufficient in localizing the source. Source localization is achieved as an emergent property through agent's adaptive interactions with the neighbors and the environment. Given a single agent is incapable of localizing the source, maintaining team connectivity at all times is crucial. Two simple temporal sampling behaviors, intensity-based-adaptation and connectivity-based-adaptation, ensure an efficient localization strategy with minimal agent breakaways. The agent behaviors are simultaneously optimized using a two phase evolutionary optimization process. The optimized behaviors are estimated with analytical models and the resulting collective behavior is validated against the agent's sensor and actuator noise, strong multi-path interference due to environment variability, initialization distance sensitivity and loss of source signal.

4-Alkylated homoibotenic acid (HIBO) analogues: versatile pharmacological agents with diverse selectivity profiles towards metabotropic and ionotropic glutamate receptor subtypes.

PubMed

Madsen, Ulf; Pickering, Darryl S; Nielsen, Birgitte; Bräuner-Osborne, Hans

2005-01-01

4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies, and the series of 4-alkyl-HIBO analogues have been extended in this paper in the search for versatile agents. Pharmacological characterization of five new analogues, branched and unbranched 4-alkyl-HIBO analogues, have been carried out. The present compounds are all weak antagonists at Group I mGluRs (mGluR1 and 5) presenting only small differences in potencies (Ki values ranging from 89 to 670 microM). Affinities were studied at native and cloned iGluRs, and the compounds described show preference for the AMPA receptor subtypes GluR1 and 2 over GluR3 and 4. However, compared to previous 4-alkyl-HIBO analogues, these compounds show a remarkably high affinity for the Kain preferring subtype GluR5. The observed GluR5 affinities were either similar or higher compared to their GluR1 and 2 affinity. Isopropyl-HIBO showed the highest affinity for GluR5 (Ki=0.16 microM), and represents a unique compound with high affinity towards the three subtypes GluR1, 2 and 5. In general, these compounds represent new selectivity profiles compared to previously reported Glu receptor analogues.

Safety of anti-TNF therapy in inflammatory bowel disease during pregnancy.

PubMed

Khan, Nabeel; Asim, Hamna; Lichtenstein, Gary R

2014-12-01

The highest incidence of inflammatory bowel disease (IBD) is seen between the second and fourth decades of life, which is the most fertile age for women. Increased disease activity has been shown to effect female fertility and pregnancy outcomes, stressing the need for drugs that can safely induce and maintain clinical remission without harming either the mother or fetus. Anti-TNF-α agents have been shown to be effective in both inducing and maintaining remission among IBD patients. This review highlights the results of previous studies conducted on pregnant women who were exposed to anti-TNF-α agents during the course of their pregnancy. The drugs reviewed include infliximab (IFX), adalimumab (ADA), certolizumab pegol (CZP) and golimumab (GMB). Of > 200 articles reviewed, 105 were included in the manuscript based on relevance. The keywords used were anti-TNF, infliximab, adalimumab, certolizumab, golimumab, biologics, pregnancy and inflammatory bowel disease. Anti-TNF agents have been studied extensively during pregnancy from the early case reports to the more recent prospective Pregnancy in IBD and Neonatal Outcomes study. A comprehensive review of the literature has shown that biologics can be safely used during pregnancy. In view of this safety data, it is recommended to maintain therapy during pregnancy.

Erwinia mallotivora sp., a New Pathogen of Papaya (Carica papaya) in Peninsular Malaysia

PubMed Central

Amin, Noriha Mat; Bunawan, Hamidun; Redzuan, Rohaiza Ahmad; Jaganath, Indu Bala S.

2011-01-01

Erwinia mallotivora was isolated from papaya infected with dieback disease showing the typical symptoms of greasy, water-soaked lesions and spots on leaves. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain belonged to the genus Erwinia and was united in a monophyletic group with E. mallotivora DSM 4565 (AJ233414). Earlier studies had indicated that the causal agent for this disease was E. papayae. However, our current studies, through Koch’s postulate, have confirmed that papaya dieback disease is caused by E. mallotivora. To our knowledge, this is the first new discovery of E. mallotivora as a causal agent of papaya dieback disease in Peninsular Malaysia. Previous reports have suggested that E. mallotivora causes leaf spot in Mallotus japonicus. However, this research confirms it also to be pathogenic to Carica papaya. PMID:21339975

Erwinia mallotivora sp., a new pathogen of papaya (Carica papaya) in Peninsular Malaysia.

PubMed

Amin, Noriha Mat; Bunawan, Hamidun; Redzuan, Rohaiza Ahmad; Jaganath, Indu Bala S

2010-12-24

Erwinia mallotivora was isolated from papaya infected with dieback disease showing the typical symptoms of greasy, water-soaked lesions and spots on leaves. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain belonged to the genus Erwinia and was united in a monophyletic group with E. mallotivora DSM 4565 (AJ233414). Earlier studies had indicated that the causal agent for this disease was E. papayae. However, our current studies, through Koch's postulate, have confirmed that papaya dieback disease is caused by E. mallotivora. To our knowledge, this is the first new discovery of E. mallotivora as a causal agent of papaya dieback disease in Peninsular Malaysia. Previous reports have suggested that E. mallotivora causes leaf spot in Mallotus japonicus. However, this research confirms it also to be pathogenic to Carica papaya.

Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents

PubMed Central

Suryadevara, Praveen Kumar; Racherla, Kishore Kumar; Olepu, Srinivas; Norcross, Neil R.; Tatipaka, Hari Babu; Arif, Jennifer A.; Planer, Joseph D.; Lepesheva, Galina; Verlinde, Christophe L. M. J.; Buckner, Frederick S.; Gelb, Michael H.

2014-01-01

New dialkylimidazole based sterol 14α-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50<1 nM) against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T.cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate. PMID:24120539

The Role of Parents and Peers in Understanding Female Adolescent Sexuality--Testing Perceived Peer Norms as Mediators between Some Parental Variables and Sexuality

ERIC Educational Resources Information Center

Rajhvajn Bulat, Linda; Ajdukovic, Marina; Ajdukovic, Dea

2016-01-01

Previous research has confirmed peers and parents as significant agents of socialisation with respect to young people's sexuality. The aim of this cross-sectional cohort study was to examine how parental and peer variables predict young women's sexual behaviour and sexuality-related thoughts and emotions, and whether perceived peer influences…

Application of a receptor-binding-capture qRTPCR assay to concentrate human norovirus from sewage and to study the distribution and stability of the virus

USDA-ARS?s Scientific Manuscript database

Human noroviruses (HuNoVs) are major agents of gastroenteritis and water is an important route of transmission. Using magnetic beads conjugated with blood group-like antigens previously reported as receptors for HuNoV, we developed a simple and rapid receptor-binding capture and magnetic sequestra...

Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial.

PubMed

Malorni, L; Curigliano, G; Minisini, A M; Cinieri, S; Tondini, C A; D'Hollander, K; Arpino, G; Bernardo, A; Martignetti, A; Criscitiello, C; Puglisi, F; Pestrin, M; Sanna, G; Moretti, E; Risi, E; Biagioni, C; McCartney, A; Boni, L; Buyse, M; Migliaccio, I; Biganzoli, L; Di Leo, A

2018-06-11

The activity of palbociclib as a single agent in advanced breast cancer has not been extensively studied, with the only available clinical data limited to heavily pre-treated patients. Pre-clinical data suggests palbociclib may partially reverse endocrine resistance, though this hypothesis has not been evaluated in previous clinical studies. This phase II, open-label, multi-center study examined the activity of palbociclib monotherapy, as well as palbociclib given in combination with the same endocrine therapy (ET) that was received prior to disease progression, in post-menopausal women with moderately pre-treated, estrogen receptor-positive, HER2 negative advanced breast cancer. Eligible women with advanced disease which had progressed on one or two prior ETs were randomized 1:1 to receive either palbociclib alone, or palbociclib in combination with the ET as previously received. Primary endpoint was clinical benefit rate (CBR); secondary endpoints included progression-free survival (PFS). Between October 2012 and July 2016, a total of 115 patients were randomized. The CBR was 54% (95% CI 41.5 - 63.7) for combination therapy, and 60% (95% CI 47.8 - 72.9) for monotherapy. Median PFS was 10.8 months (95% CI 5.6 - 12.7) for combination therapy, and 6.5 months (95% CI, 5.4 to 8.5) for monotherapy (hazard ratio [HR] 0.69; 95% CI 0.4 - 1.1, exploratory P-value = 0.12). Exploratory analyses revealed the PFS advantage for combination therapy was seen in the subgroup of patients who received prior ET for >6 months (HR 0.53; 95% CI 0.3 - 0.9, exploratory P-value = 0.02), but not in those who received prior ET for ≤6 months. Palbociclib has clinical activity as a single agent in women with moderately pre-treated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET. NCT02549430.

[Susceptibility to antimicrobial agents of 2,060 strains of different bacteria isolated in infectious processes in children].

PubMed

Filloy, L; Borjas, E; Sierra, A

1981-01-01

Susceptibility to antibiotics of 2060 strains of the following bacteria was studied: Escherichia coli, Klebsiella pneumoniae, Salmonella, Shigella, Proteus, Staphylococcus aureus that were isolated in 1978-79 from different infections in children hospitalized at the Hospital Infantil de Mexico. The antimicrobials submitted to the test of susceptibility were: ampicillin, amikacin, carbenicillin, cephalothin, cefoxitin, chloramphenicol, gentamicin, kanamycin, neomycin and sulfamethoxazole-trimethoprim. Present results are compared with previous studies.

Microbiology and Epidemiology of Infectious Spinal Disease

PubMed Central

Jeong, Se-Jin; Youm, Jin-Young; Kim, Hyun-Woo; Ha, Ho-Gyun; Yi, Jin-Seok

2014-01-01

Objective Infectious spinal disease is regarded as an infection by a specific organism that affects the vertebral body, intervertebral disc and adjacent perivertebral soft tissue. Its incidence seems to be increasing as a result of larger proportion of the older patients with chronic debilitating disease, the rise of intravenous drug abuser, and the increase in spinal procedure and surgery. In Korea, studies assessing infectious spinal disease are rare and have not been addressed in recent times. The objectives of this study are to describe the epidemiology of all kind of spinal infectious disease and their clinical and microbiological characteristics as well as to assess the diagnostic methodology and the parameters related to the outcomes. Methods A retrospective study was performed in all infectious spinal disease cases presenting from January 2005 to April 2010 to three tertiary teaching hospitals within a city of 1.5 million in Korea. Patient demographics, risk factors, clinical features, and outcomes were assessed. Risk factors entailed the presence of diabetes, chronic renal failure, liver cirrhosis, immunosuppressants, remote infection, underlying malignancy and previous spinal surgery or procedure. We comparatively analyzed the results between the groups of pyogenic and tuberculous spinal infection. SPSS version 14 statistical software was used to perform the analyses of the data. The threshold for statistical significance was established at p<0.05. Results Ninety-two cases fulfilled the inclusion criteria and were reviewed. Overall, patients of tuberculous spinal infection (TSI) and pyogenic spinal infection (PSI) entailed 20 (21.7%) and 72 (78.3%) cases, respectively. A previous spinal surgery or procedure was the most commonly noted risk factor (39.1%), followed by diabetes (15.2%). The occurrence of both pyogenic and tuberculous spondylitis was predominant in the lumbar spine. Discs are more easily invaded in PSI. At initial presentation, white cell blood count and C-reactive protein levels were higher in PSI compared to TSI (p<0.05). Etiological agents were identified in 53.3%, and the most effective method for identification of etiological agents was tissue culture (50.0%). Staphyococcus aureus was the most commonly isolated infective agent associated with pyogenic spondylitis, followed by E. coli. Surgical treatment was performed in 31.5% of pyogenic spondylitis and in 35.0% of tuberculous spondylitis cases. Conclusion Many previous studies in Korea usually reported that tuberculous spondylitis is the predominant infection. However, in our study, the number of pyogenic infection was 3 times greater than that of tuberculous spinal disease. Etiological agents were identified in a half of all infectious spinal disease. For better outcomes, we should try to identify the causative microorganism before antibiotic therapy and make every effort to improve the result of culture and biopsy. PMID:25289121

Metareasoning and Social Evaluations in Cognitive Agents

NASA Astrophysics Data System (ADS)

Pinyol, Isaac; Sabater-Mir, Jordi

Reputation mechanisms have been recognized one of the key technologies when designing multi-agent systems. They are specially relevant in complex open environments, becoming a non-centralized mechanism to control interactions among agents. Cognitive agents tackling such complex societies must use reputation information not only for selecting partners to interact with, but also in metareasoning processes to change reasoning rules. This is the focus of this paper. We argue about the necessity to allow, as a cognitive systems designers, certain degree of freedom in the reasoning rules of the agents. We also describes cognitive approaches of agency that support this idea. Furthermore, taking as a base the computational reputation model Repage, and its integration in a BDI architecture, we use the previous ideas to specify metarules and processes to modify at run-time the reasoning paths of the agent. In concrete we propose a metarule to update the link between Repage and the belief base, and a metarule and a process to update an axiom incorporated in the belief logic of the agent. Regarding this last issue we also provide empirical results that show the evolution of agents that use it.

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.

Anti-inflammatory drugs and analgesics for managing symptoms in people with cystic fibrosis-related arthritis.

PubMed

Thornton, Judith; Rangaraj, Satyapal

2016-01-21

Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy (CFA) and hypertrophic pulmonary osteoarthropathy (HPO). Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its intense treatment. This is an update of a previously published review. To review the effectiveness and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis in adults and children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 19 January 2016. Randomised controlled studies which compared the efficacy and safety of anti-inflammatory and analgesic agents (e.g. non-steroidal anti-inflammatory agents, systemic corticosteroids, intra-articular corticosteroids) with each other, with no treatment or with placebo for CFA and HPO. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that CFA may be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. While this approach may be sufficient to manage symptoms, it is disappointing that no randomised controlled trials to rigorously evaluate these agents were found, nor could the authors identify any quasi-randomised. This systematic review has identified the need for a well-designed adequately-powered randomised controlled trial to assess the efficacy and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis (CFA and HPO) in adults and children with cystic fibrosis. Studies should also better define the two conditions. A study has recently been conducted in CFA and may help fill this gap when analysed and published.There are no trials included in the review up to January 2016. We will continue to run searches to identify any potentially relevant studies; however, we do not plan to update other sections of the review until new studies are published.

A Model for Assessing the Clinical and Economic Benefits of Bone-forming Agents for Reducing Fractures in Postmenopausal Women at High, Near-term Risk of Osteoporotic Fracture.

PubMed

O'Hanlon, Claire E; Parthan, Anju; Kruse, Morgan; Cartier, Shannon; Stollenwerk, Bjorn; Jiang, Yawen; Caloyeras, John P; Crittenden, Daria B; Barron, Richard

2017-07-01

The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime horizon with sequenced antiresorptive agents for maintenance treatment. Analyses were performed by using a Markov cohort model accounting for time-specific fracture protection effects of bone-forming agents followed by antiresorptive treatment with denosumab. The alternative bone-forming agent profiles were defined by using assumptions regarding the onset and total magnitude of protection against fractures with teriparatide. The model cohort comprised 70-year-old female patients with T scores below -2.5 and a previous vertebral fracture. Outcomes included clinical fractures, direct costs, and quality-adjusted life years. The simulated treatment strategies were compared by calculating their incremental "value" (net monetary benefit). Improvements in the onset and magnitude of fracture protection (vs the teriparatide reference case) produced a net monetary benefit of $17,000,000 per 10,000 treated patients during the (1.5-year) bone-forming agent treatment period and $80,000,000 over a lifetime horizon that included 3.5 years of maintenance treatment with denosumab. Incorporating time-specific fracture effects in the Markov cohort model allowed for estimation of a range of cost savings, quality-adjusted life years gained, and clinical fractures avoided at different levels of fracture protection onset and magnitude. Results provide a first estimate of the potential "value" new bone-forming agents (romosozumab and abaloparatide) may confer relative to teriparatide. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Genotypic and phenotypic characterization of Cryptococcus flavescens, beneficial biocontrol agents for controlling Fusarium head blight of wheat

USDA-ARS?s Scientific Manuscript database

Cryptococcus flavescens strain OH182.9_3C (3C) previously displayed significant biological control activity against Fusarium head blight, a globally important disease of wheat; however, the diversity within C. flavescens has not been previously characterized. Multilocus sequence typing was performed...

A clinical trial of pefloxacin and ofloxacin in lepromatous leprosy.

PubMed

Fajardo, Tranquilino T; Villahermosa, Laarni G; Cruz, Eduardo C Dela; Cellona, Roland V; Balagon, Ma Victoria F; Abalos, Rodolfo M; Gelber, Robert H

2004-12-01

A 2-month clinical trial of pefloxacin and ofloxacin in previously untreated multibacillary patients was conducted at the Leonard Wood Memorial Leprosy Research Center, Cebu, the Philippines. Treatment with either pefloxacin or ofloxacin resulted in rapid clinical improvement, in this regard pefloxacin appearing somewhat superior. Reactions and side effects were minimal. Single doses of either agent did not result in significant killing of Mycobacterium leprae, but significant bactericidal activity was observed for all fluoroquinolone-treated patients by one week of daily therapy (n = 21), and either agent independently by 3 weeks of daily therapy. At the completion of therapy only two of 10 pefloxacin-treated patients and 0 of 11 ofloxacin-treated patients harboured any detectable viable M. leprae from active lesions, confirming previous work that these fluoroquinolones exhibit bactericidal activity in leprosy patients and more than that found previously for dapsone and clofazimine.

Agent Orange exposure and disease prevalence in Korean Vietnam veterans: the Korean veterans health study.

PubMed

Yi, Sang-Wook; Hong, Jae-Seok; Ohrr, Heechoul; Yi, Jee-Jeon

2014-08-01

Between 1961 and 1971, military herbicides were used by the United States and allied forces for military purposes. Agent Orange, the most-used herbicide, was a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid, and contained an impurity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Many Korean Vietnam veterans were exposed to Agent Orange during the Vietnam War. The aim of this study was to evaluate the association between Agent Orange exposure and the prevalence of diseases of the endocrine, nervous, circulatory, respiratory, and digestive systems. The Agent Orange exposure was assessed by a geographic information system-based model. A total of 111,726 Korean Vietnam veterans were analyzed for prevalence using the Korea National Health Insurance claims data from January 2000 to September 2005. After adjusting for covariates, the high exposure group had modestly elevated odds ratios (ORs) for endocrine diseases combined and neurologic diseases combined. The adjusted ORs were significantly higher in the high exposure group than in the low exposure group for hypothyroidism (OR=1.13), autoimmune thyroiditis (OR=1.93), diabetes mellitus (OR=1.04), other endocrine gland disorders including pituitary gland disorders (OR=1.43), amyloidosis (OR=3.02), systemic atrophies affecting the nervous system including spinal muscular atrophy (OR=1.27), Alzheimer disease (OR=1.64), peripheral polyneuropathies (OR=1.09), angina pectoris (OR=1.04), stroke (OR=1.09), chronic obstructive pulmonary diseases (COPD) including chronic bronchitis (OR=1.05) and bronchiectasis (OR=1.16), asthma (OR=1.04), peptic ulcer (OR=1.03), and liver cirrhosis (OR=1.08). In conclusion, Agent Orange exposure increased the prevalence of endocrine disorders, especially in the thyroid and pituitary gland; various neurologic diseases; COPD; and liver cirrhosis. Overall, this study suggests that Agent Orange/2,4-D/TCDD exposure several decades earlier may increase morbidity from various diseases, some of which have rarely been explored in previous epidemiologic studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

Updating the carbon footprint of the Galician fishing activity (NW Spain).

PubMed

Iribarren, Diego; Vázquez-Rowe, Ian; Hospido, Almudena; Moreira, María Teresa; Feijoo, Gumersindo

2011-03-15

Recent life cycle assessment studies have revealed the relevance of cooling agent leakage when assessing the greenhouse gas (GHG) emissions generated by fishing vessel operations. The goal of this communication is to update the carbon footprinting of the Galician fishing activity (NW Spain) by including the GHG emissions from cooling agent leakage. Results proved the relevant role played by refrigerants regarding their contribution to the carbon footprint of fishing activities. Thus, an overall increase of 13% was found when comparing the final global carbon footprint for the Galician fishing activity with previous calculations that did not include these emissions. Nevertheless, further efforts should be made in order to provide robust data in this respect. Copyright © 2011 Elsevier B.V. All rights reserved.

You Look Human, But Act Like a Machine: Agent Appearance and Behavior Modulate Different Aspects of Human-Robot Interaction.

PubMed

Abubshait, Abdulaziz; Wiese, Eva

2017-01-01

Gaze following occurs automatically in social interactions, but the degree to which gaze is followed depends on whether an agent is perceived to have a mind, making its behavior socially more relevant for the interaction. Mind perception also modulates the attitudes we have toward others, and determines the degree of empathy, prosociality, and morality invested in social interactions. Seeing mind in others is not exclusive to human agents, but mind can also be ascribed to non-human agents like robots, as long as their appearance and/or behavior allows them to be perceived as intentional beings. Previous studies have shown that human appearance and reliable behavior induce mind perception to robot agents, and positively affect attitudes and performance in human-robot interaction. What has not been investigated so far is whether different triggers of mind perception have an independent or interactive effect on attitudes and performance in human-robot interaction. We examine this question by manipulating agent appearance (human vs. robot) and behavior (reliable vs. random) within the same paradigm and examine how congruent (human/reliable vs. robot/random) versus incongruent (human/random vs. robot/reliable) combinations of these triggers affect performance (i.e., gaze following) and attitudes (i.e., agent ratings) in human-robot interaction. The results show that both appearance and behavior affect human-robot interaction but that the two triggers seem to operate in isolation, with appearance more strongly impacting attitudes, and behavior more strongly affecting performance. The implications of these findings for human-robot interaction are discussed.

Pairing of heterochromatin in response to cellular stress.

PubMed

Abdel-Halim, H I; Mullenders, L H F; Boei, J J W A

2006-07-01

We previously reported that exposure of human cells to DNA-damaging agents (X-rays and mitomycin C (MMC)) induces pairing of the homologous paracentromeric heterochromatin of chromosome 9 (9q12-13). Here, we show that UV irradiation and also heat shock treatment of human cells lead to similar effects. Since the various agents induce very different types and frequencies of damage to cellular constituents, the data suggest a general stress response as the underlying mechanism. Moreover, local UV irradiation experiments revealed that pairing of heterochromatin is an event that can be triggered without induction of DNA damage in the heterochromatic sequences. The repair deficient xeroderma pigmentosum cells (group F) previously shown to fail pairing after MMC displayed elevated pairing after heat shock treatment but not after UV exposure. Taken together, the present results indicate that pairing of heterochromatin following exposure to DNA-damaging agents is initiated by a general stress response and that the sensing of stress or the maintenance of the paired status of the heterochromatin might be dependent on DNA repair.

Maintaining Fluoroquinolone Class Efficacy: Review of Influencing Factors

PubMed Central

2003-01-01

Previous experience with antimicrobial resistance has emphasized the importance of appropriate stewardship of these pharmacotherapeutic agents. The introduction of fluoroquinolones provided potent new drugs directed primarily against gram-negative pathogens, while the newer members of this class demonstrate more activity against gram-positive species, including Streptococcus pneumoniae. Although these agents are clinically effective against a broad range of infectious agents, emergence of resistance and associated clinical failures have prompted reexamination of their use. Appropriate use revolves around two key objectives: 1) only prescribing antimicrobial therapy when it is beneficial and 2) using the agents(s) with optimal activity against the expected pathogens(s). Pharmacodynamic principles and properties can be applied to achieve the latter objective when prescribing agents belonging to the fluoroquinolone class. A focused approach emphasizing “correct-spectrum” coverage may reduce development of antimicrobial resistance and maintain class efficacy. PMID:12533274

Towards the Verification of Human-Robot Teams

NASA Technical Reports Server (NTRS)

Fisher, Michael; Pearce, Edward; Wooldridge, Mike; Sierhuis, Maarten; Visser, Willem; Bordini, Rafael H.

2005-01-01

Human-Agent collaboration is increasingly important. Not only do high-profile activities such as NASA missions to Mars intend to employ such teams, but our everyday activities involving interaction with computational devices falls into this category. In many of these scenarios, we are expected to trust that the agents will do what we expect and that the agents and humans will work together as expected. But how can we be sure? In this paper, we bring together previous work on the verification of multi-agent systems with work on the modelling of human-agent teamwork. Specifically, we target human-robot teamwork. This paper provides an outline of the way we are using formal verification techniques in order to analyse such collaborative activities. A particular application is the analysis of human-robot teams intended for use in future space exploration.

Design and Control of Large Collections of Learning Agents

NASA Technical Reports Server (NTRS)

Agogino, Adrian

2001-01-01

The intelligent control of multiple autonomous agents is an important yet difficult task. Previous methods used to address this problem have proved to be either too brittle, too hard to use, or not scalable to large systems. The 'Collective Intelligence' project at NASA/Ames provides an elegant, machine-learning approach to address these problems. This approach mathematically defines some essential properties that a reward system should have to promote coordinated behavior among reinforcement learners. This work has focused on creating additional key properties and algorithms within the mathematics of the Collective Intelligence framework. One of the additions will allow agents to learn more quickly, in a more coordinated manner. The other will let agents learn with less knowledge of their environment. These additions will allow the framework to be applied more easily, to a much larger domain of multi-agent problems.

Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds

PubMed Central

Boudhar, Aicha; Ng, Xiao Wei; Loh, Chiew Yee; Chia, Wan Ni; Tan, Zhi Ming; Nosten, Francois

2016-01-01

Resistance to antimalarial therapies, including artemisinin, has emerged as a significant challenge. Reversal of acquired resistance can be achieved using agents that resensitize resistant parasites to a previously efficacious therapy. Building on our initial work describing novel chemoreversal agents (CRAs) that resensitize resistant parasites to chloroquine (CQ), we herein report new hybrid single agents as an innovative strategy in the battle against resistant malaria. Synthetically linking a CRA scaffold to chloroquine produces hybrid compounds with restored potency toward a range of resistant malaria parasites. A preferred compound, compound 35, showed broad activity and good potency against seven strains resistant to chloroquine and artemisinin. Assessment of aqueous solubility, membrane permeability, and in vitro toxicity in a hepatocyte line and a cardiomyocyte line indicates that compound 35 has a good therapeutic window and favorable drug-like properties. This study provides initial support for CQ-CRA hybrid compounds as a potential treatment for resistant malaria. PMID:26953199

Topical Microbicides and HIV Prevention in the Female Genital Tract

PubMed Central

Cottrell, Mackenzie L; Kashuba, Angela D. M.

2014-01-01

Worldwide, HIV disproportionately affects women who are often unable to negotiate traditional HIV preventive strategies such as condoms. In the absence of an effective vaccine or cure, chemoprophylaxis may be a valuable self-initiated alternative. Topical microbicides have been investigated as one such option. The first generation topical microbicides were non-specific, broad-spectrum antimicrobial agents, including surfactants, polyanions, and acid buffering gels, that generally exhibited contraceptive properties. After extensive clinical study, none prevented HIV infection, and their development was abandoned. Second generation topical microbicides include agents with selective mechanisms of antiviral activity. Most are currently being used for, or have previously been explored as, drugs for treatment of HIV. The most advanced of these is tenofovir 1% gel: the first topical agent shown to significantly reduce HIV infection by 39% compared to placebo. This review summarizes the evolution of topical microbicides for HIV chemoprophylaxis, highlights important concepts learned, and offers current and future considerations for this area of research. PMID:24664786

Identification of a consistent polyene component of purple pigment in diseased sclerites of Caribbean corals across region, species, and insult agent.

PubMed

Fetterolf, Monty L; Leverette, Chad L; Perez, Christopher; Smith, Garriet W

2017-10-05

Gorgonians respond to insult (damage and disease) by producing sclerites containing a purple pigment as opposed to the normal white sclerites. Raman microscopy is used to study the purple areas of three species of diseased coral, Gorgonia ventalina, Pseudoplexaura porosa, and Eunicea laciniata obtained from Puerto Rico. These spectra were compared to Gorgonia ventalina samples previously reported that were obtained from San Salvador, Bahamas. Spectra from two samples of G. ventalina that had been infected by different agents, Aspergillus sydowii and a slime mold, were also obtained. The results indicate that the purple compounds (polyenes) generated by the coral in response to infection are similar regardless of region from which the coral were harvested, of species of coral, and of the infective agent. A discussion of the Raman spectra of G. ventalina and the other coral species is presented. Copyright © 2017 Elsevier B.V. All rights reserved.

The safety of antiangiogenic agents and PARP inhibitors in platinum-sensitive recurrent ovarian cancer.

PubMed

Lorusso, Domenica; Fontanella, Caterina; Maltese, Giuseppa; Lepori, Stefano; Tripodi, Elisa; Bogani, Giorgio; Raspagliesi, Francesco

2017-06-01

Recurrence is a common event in endothelial ovarian cancer (EOC) patients, and the choice of the most appropriate treatment is driven by the platinum-free interval, molecular characteristics of the disease such as BRCA mutational status, previous treatments and toxicity. Areas covered: This review focuses on the main hematologic and non-hematologic toxicities correlated with the use of licensed antiangiogenic agents and PARP inhibitors in recurrent platinum-sensitive EOC, providing recommendations for their management. Expert opinion: The clinical research over the next years will be focused on a more precise characterization of molecular pathways underlying tumorigenesis of the five ovarian tumors, to improve the decision-making process in these rare diseases. For this purpose, new study designs and international collaborations will become mandatory. Immunotherapy, antiangiogenic agents and PARP inhibitors will be combined to build a treatment strategy algorithm which will allow patients to receive all the available treatment option, in the more appropriate sequence.

Regulation of the yeast RAD2 gene: DNA damage-dependent induction correlates with protein binding to regulatory sequences and their deletion influences survival.

PubMed

Siede, W; Friedberg, E C

1992-03-01

In the yeast Saccharomyces cerevisiae the RAD2 gene is absolutely required for damage-specific incision of DNA during nucleotide excision repair and is inducible by DNA-damaging agents. In the present study we correlated sensitivity to killing by DNA-damaging agents with the deletion of previously defined specific promoter elements. Deletion of the element DRE2 increased the UV sensitivity of cells in both the G1/early S and S/G2 phases of the cell cycle as well as in stationary phase. On the other hand, increased UV sensitivity associated with deletion of the sequence-related element DRE1 was restricted to cells irradiated in G1/S. Specific binding of protein(s) to the promoter elements DRE1 and DRE2 was observed under non-inducing conditions using gel retardation assays. Exposure of cells to DNA-damaging agents resulted in increased protein binding that was dependent on de novo protein synthesis.

Effect of wavelength and dye selection on biosensor response

NASA Astrophysics Data System (ADS)

Ligler, Frances S.; Breslin, Kristen A.; Cao, Lynn K.; Anderson, George P.

1995-05-01

The availability of low cost laser diodes and new fluorescent dyes has made portable biosensors a reality. Previously, we have examined the variation in the fluorescent signal generated in an antigen-antibody reaction when the antigen is labeled with dyes exciting at different wavelengths. In this study, we looked at the effect of changing dyes and wavelengths on a sandwich immunoassay for the F1 antigen from Yersinia pestis, the etiologic agent of plaque. The F1 immunoassay has previously been demonstrated to work in serum, plasma, and even whole blood, when performed using a fiber optic biosensor. In this study, we demonstrated that changing to cyanine dyes enhanced the sensitivity of the detection without altering the immunochemistry of the assay.

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.

The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM.

PubMed

Follin-Arbelet, Virginie; Misund, Kristine; Naderi, Elin Hallan; Ugland, Hege; Sundan, Anders; Blomhoff, Heidi Kiil

2015-08-26

We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM.

The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM

PubMed Central

Follin-Arbelet, Virginie; Misund, Kristine; Hallan Naderi, Elin; Ugland, Hege; Sundan, Anders; Kiil Blomhoff, Heidi

2015-01-01

We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM. PMID:26306624

Cost-effectiveness of oral antiplatelet agents--current and future perspectives.

PubMed

Arnold, Suzanne V; Cohen, David J; Magnuson, Elizabeth A

2011-08-09

Cardiovascular disease is both highly prevalent and exceedingly costly to treat. Several novel antiplatelet agents have been found to be effective in reducing the morbidity and mortality associated with cardiovascular disease. Understanding both the economic and the clinical implications of these novel therapies is particularly important. In this article, the results of published evaluations of the cost-effectiveness of oral antiplatelet strategies for use across a range of clinical conditions and treatment settings are reviewed. The results of these studies support the use of aspirin for primary prevention in high-risk patients and for secondary prevention in all patients with previous cardiovascular events. Although the optimal duration of dual antiplatelet therapy after an event remains uncertain, favorable cost-effectiveness estimates have been demonstrated for aspirin plus clopidogrel versus aspirin alone after a myocardial infarction or percutaneous coronary intervention. Moreover, prasugrel has been shown to be more cost-effective than clopidogrel for patients with an acute coronary syndrome and planned percutaneous coronary intervention. As novel antiplatelet agents emerge and existing agents are tested in different patient populations, the evaluation of the relative economic efficiency of these oral antiplatelet treatment strategies will continue to be instrumental to optimally inform clinical and health-policy decision-making.

Identification of a Divided Genome for VSH-1, the Prophage-Like Gene Transfer Agent of Brachyspira hyodysenteriae

USDA-ARS?s Scientific Manuscript database

The Brachyspira hyodysenteriae B204 genome sequence revealed three VSH-1 tail genes hvp31, hvp60, and hvp37, in a 3.6 kb cluster. The location and transcription direction of these genes relative to the previously described VSH-1 16.3 kb gene operon indicate that the gene transfer agent VSH-1 has a ...

The Prevalence and Characteristics of Performance-Enhancing Drug Use Among Bodybuilding Athletes in the South of Iran, Bushehr.

PubMed

Haerinejad, Mohammad Javad; Ostovar, Afshin; Farzaneh, Mohamad Reza; Keshavarz, Mojtaba

2016-09-01

Several reports have implied progressive increase of performance-enhancing drug (PED) use among Iranian athletes. More importantly, most of the previous research in the Iranian population had mainly focused on the anabolic steroid abuse, and ignored other agents. The aim of this study was to investigate the prevalence and characteristics of PED use among bodybuilding athletes in Bushehr, south of Iran. Four hundred and fifty three male bodybuilding athletes were recruited from Bushehr gyms between February and May of 2015. Men were eligible to participate in the survey if they had regularly participated in the strength-training exercise (minimum of 1 year and 4 hour/week). Data were collected via a face-to-face interview. The survey consisted of three separate parts including demographic data, exercise pattern and PED use. According to this study, 234 (51.7%) of bodybuilding athletes had used PEDs. The PED users reported an average of 3.80 ± 4.52 agents' use in their programs and they had used PEDs for the average of 3.24 ± 3.99 years. The most prevalent agents which had been abused by the athletes were anabolic steroids (used by 185 athletes (79.4% of athletes). Furthermore, 110 (47%) of athletes reported stimulant agents' use during their routines. The most prevalent motivation for using PEDs was increasing muscle mass that was reported by 164 (70.1%) of PED users. In addition, sexual and dermatologic effects were the most prevalent adverse effects reported by the PED user athletes (114 (49.4%) and 103 (44.2%), respectively). This study showed the high rate of PED use among recreational and professional Iranian bodybuilding athletes that can expose them to the serious side effects of these agents.

Exposure to carcinogens for defined job categories in Norway's offshore petroleum industry, 1970 to 2005

PubMed Central

Steinsvåg, Kjersti; Bråtveit, Magne; Moen, Bente E

2007-01-01

Objectives To identify and describe the exposure to selected known and suspected carcinogenic agents, mixtures and exposure circumstances for defined job categories in Norway's offshore petroleum industry from 1970 to 2005, in order to provide exposure information for a planned cohort study on cancer. Methods Background information on possible exposure was obtained through company visits, including interviewing key personnel (n = 83) and collecting monitoring reports (n = 118) and other relevant documents (n = 329). On the basis of a previous questionnaire administered to present and former offshore employees in 1998, 27 job categories were defined. Results This study indicated possible exposure to 18 known and suspected carcinogenic agents, mixtures or exposure circumstances. Monitoring reports were obtained on seven agents (benzene, mineral oil mist and vapour, respirable and total dust, asbestos fibres, refractory ceramic fibres, formaldehyde and tetrachloroethylene). The mean exposure level of 367 personal samples of benzene was 0.037 ppm (range: less than the limit of detection to 2.6 ppm). Asbestos fibres were detected (0.03 fibres/cm3) when asbestos‐containing brake bands were used in drilling draw work in 1988. Personal samples of formaldehyde in the process area ranged from 0.06 to 0.29 mg/m3. Descriptions of products containing known and suspected carcinogens, exposure sources and processes were extracted from the collected documentation and the interviews of key personnel. Conclusions This study described exposure to 18 known and suspected carcinogenic agents, mixtures and exposure circumstances for 27 job categories in Norway's offshore petroleum industry. For a planned cohort study on cancer, quantitative estimates of exposure to benzene, and mineral oil mist and vapour might be developed. For the other agents, information in the present study can be used for further assessment of exposure, for instance, by expert judgement. More systematic exposure surveillance is needed in this industry. For future studies, new monitoring programmes need to be implemented. PMID:17043075

Exposure to carcinogens for defined job categories in Norway's offshore petroleum industry, 1970 to 2005.

PubMed

Steinsvåg, Kjersti; Bråtveit, Magne; Moen, Bente E

2007-04-01

To identify and describe the exposure to selected known and suspected carcinogenic agents, mixtures and exposure circumstances for defined job categories in Norway's offshore petroleum industry from 1970 to 2005, in order to provide exposure information for a planned cohort study on cancer. Background information on possible exposure was obtained through company visits, including interviewing key personnel (n = 83) and collecting monitoring reports (n = 118) and other relevant documents (n = 329). On the basis of a previous questionnaire administered to present and former offshore employees in 1998, 27 job categories were defined. This study indicated possible exposure to 18 known and suspected carcinogenic agents, mixtures or exposure circumstances. Monitoring reports were obtained on seven agents (benzene, mineral oil mist and vapour, respirable and total dust, asbestos fibres, refractory ceramic fibres, formaldehyde and tetrachloroethylene). The mean exposure level of 367 personal samples of benzene was 0.037 ppm (range: less than the limit of detection to 2.6 ppm). Asbestos fibres were detected (0.03 fibres/cm3) when asbestos-containing brake bands were used in drilling draw work in 1988. Personal samples of formaldehyde in the process area ranged from 0.06 to 0.29 mg/m3. Descriptions of products containing known and suspected carcinogens, exposure sources and processes were extracted from the collected documentation and the interviews of key personnel. This study described exposure to 18 known and suspected carcinogenic agents, mixtures and exposure circumstances for 27 job categories in Norway's offshore petroleum industry. For a planned cohort study on cancer, quantitative estimates of exposure to benzene, and mineral oil mist and vapour might be developed. For the other agents, information in the present study can be used for further assessment of exposure, for instance, by expert judgement. More systematic exposure surveillance is needed in this industry. For future studies, new monitoring programmes need to be implemented.

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

A Diversified Investment Strategy Using Autonomous Agents

NASA Astrophysics Data System (ADS)

Barbosa, Rui Pedro; Belo, Orlando

In a previously published article, we presented an architecture for implementing agents with the ability to trade autonomously in the Forex market. At the core of this architecture is an ensemble of classification and regression models that is used to predict the direction of the price of a currency pair. In this paper, we will describe a diversified investment strategy consisting of five agents which were implemented using that architecture. By simulating trades with 18 months of out-of-sample data, we will demonstrate that data mining models can produce profitable predictions, and that the trading risk can be diminished through investment diversification.

Deducing the multi-trader population driving a financial market

NASA Astrophysics Data System (ADS)

Gupta, Nachi; Hauser, Raphael; Johnson, Neil

2005-12-01

We have previously laid out a basic framework for predicting financial movements and pockets of predictability by tracking the distribution of a multi-trader population playing on an artificial financial market model. This work explores extensions to this basic framework. We allow for more intelligent agents with a richer strategy set, and we no longer constrain the distribution over these agents to a probability space. We then introduce a fusion scheme which accounts for multiple runs of randomly chosen sets of possible agent types. We also discuss a mechanism for bias removal on the estimates.

Reactivation of Brain Acetylcholinesterase by Monoisonitrosoacetone Increases the Therapeutic Efficacy Against Nerve Agents in Guinea Pigs

DTIC Science & Technology

2010-01-01

hese findings support previous reports that protection of ChE nzyme activity in the brain as well as in peripheral tissues with entrally acting... activity . Animals were injected s.c. with either saline (0.5ml/kg) or a 1.0× LD50 dose of GB (42.0g/kg), GF (57.0g/kg), or VX (8.0g/kg). The severity...of toxic signs of each animal was scored at 13min after nerve agent. Fifteen minutes after nerve agent injection, when the inhibition of ChE activity

Analyzing phase diagrams and phase transitions in networked competing populations

NASA Astrophysics Data System (ADS)

Ni, Y.-C.; Yin, H. P.; Xu, C.; Hui, P. M.

2011-03-01

Phase diagrams exhibiting the extent of cooperation in an evolutionary snowdrift game implemented in different networks are studied in detail. We invoke two independent payoff parameters, unlike a single payoff often used in most previous works that restricts the two payoffs to vary in a correlated way. In addition to the phase transition points when a single payoff parameter is used, phase boundaries separating homogeneous phases consisting of agents using the same strategy and a mixed phase consisting of agents using different strategies are found. Analytic expressions of the phase boundaries are obtained by invoking the ideas of the last surviving patterns and the relative alignments of the spectra of payoff values to agents using different strategies. In a Watts-Strogatz regular network, there exists a re-entrant phenomenon in which the system goes from a homogeneous phase into a mixed phase and re-enters the homogeneous phase as one of the two payoff parameters is varied. The non-trivial phase diagram accompanying this re-entrant phenomenon is quantitatively analyzed. The effects of noise and cooperation in randomly rewired Watts-Strogatz networks are also studied. The transition between a mixed phase and a homogeneous phase is identify to belong to the directed percolation universality class. The methods used in the present work are applicable to a wide range of problems in competing populations of networked agents.

Favipiravir can evoke lethal mutagenesis and extinction of foot-and-mouth disease virus.

PubMed

de Avila, Ana Isabel; Moreno, Elena; Perales, Celia; Domingo, Esteban

2017-04-02

Antiviral agents are increasingly considered an option for veterinary medicine. An understanding of their mechanism of activity is important to plan their administration either as monotherapy or in combination with other agents. Previous studies have shown that the broad spectrum antiviral agent favipiravir (T-705) and its derivatives T-1105 and T-1106 are efficient inhibitors of foot-and-mouth disease virus (FMDV) replication in cell culture and in vivo. However, no mechanism for their activity against FMDV has been proposed. In the present study we show that favipiravir (T-705) can act as a lethal mutagen for FMDV in cell culture. Evidence includes virus extinction associated with increase in mutation frequency in the mutant spectrum of 860 residues of the 3D (polymerase)-coding region, and a decrease of specific infectivity while the consensus nucleotide sequence of the region analyzed remained invariant. The mutational spectrum evoked by favipiravir differs from that observed with other viruses in that no predominant transition type is observed, indicating that a movement towards A,U- or G,C-rich regions of sequence space is not a prerequisite for virus extinction. We discuss prospects for the use of favipiravir to assist in the control of FMDV, and its possible broader use in veterinary medicine as an extension of its current status as antiviral agent for human influenza virus. Copyright © 2017 Elsevier B.V. All rights reserved.

Absorption of the nerve agent VX (O-ethyl-S-[2(di-isopropylamino)ethyl] methyl phosphonothioate) through pig, human and guinea pig skin in vitro.

PubMed

Dalton, Christopher H; Hattersley, Ian J; Rutter, Stephen J; Chilcott, Robert P

2006-12-01

The physico-chemical properties of VX make the skin the most likely route of absorption into the human body. The development of effective medical countermeasures against such percutaneous threat agents relies on the use of appropriate animal models, as the inherent toxicity of nerve agents precludes the use of human volunteers. Previous studies have characterised the mechanism of nerve agent toxicity in rodent models, however, it is generally accepted that one of the most appropriate animal models for human skin absorption is the domestic pig. The purpose of the present study was to measure and compare the skin absorption kinetics of VX in vitro using pig, human and guinea pig skin to highlight any potential species differences in skin permeability. When undiluted VX was applied directly to the skin, the permeability of guinea pig skin was approximately 7-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. When VX diluted with isopropyl alcohol was applied to the skin, the permeability of guinea pig skin was approximately 4-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. From this data it may be inferred that dermatomed, abdominal pig skin is an appropriate model for the human skin absorption of VX.

Prevalence of GORD (gastro-oesophageal reflux disease) in Type 2 diabetes and a comparison of clinical profiles between diabetic patients with and without GORD.

PubMed

Horikawa, A; Ishii-Nozawa, R; Ohguro, M; Takagi, S; Ohtuji, M; Yamada, M; Kuzuya, N; Ujihara, N; Ujihara, M; Takeuchi, K

2009-03-01

To examine the incidence of gastro-oesophageal reflux disease (GORD) and its associated factors in patients with Type 2 diabetes mellitus (Type 2 DM). In 859 Type 2 DM outpatients, we conducted a QUEST inquiry and considered those showing a QUEST score of 4 or higher as having GORD. We surveyed clinical variables (physical findings, gender, age, duration of disease, glycated haemoglobin (HbA(1c)), type of oral glucose-lowering agent, presence or absence of insulin therapy, complications, and presence or absence of agents that may be associated with GORD [Ca channel blocker (CCB) anti-platelet agents]) to investigate their association with the onset of GORD. We analysed 813 subjects, of whom 56.6% were male. The mean age was 63.7 +/- 11.3 years and HbA(1c) 7.2 +/- 1.2%. The incidence of GORD was 29.0% (n = 221). GORD was positively correlated with body weight, body mass index (BMI) and HbA(1c). It was negatively correlated with age, serum creatinine and proportion of patients treated with pioglitazone or CCB. In addition, GORD was more common in females. The incidence of GORD was significantly higher in younger patients. Previous studies have suggested a relationship of GORD with pioglitazone/CCB. However, the results of this study do not support this; these agents may not induce GORD.

Punishment does not promote cooperation under exploration dynamics when anti-social punishment is possible.

PubMed

P Hauser, Oliver; A Nowak, Martin; G Rand, David

2014-11-07

It has been argued that punishment promotes the evolution of cooperation when mutation rates are high (i.e. when agents engage in 'exploration dynamics'). Mutations maintain a steady supply of agents that punish free-riders, and thus free-riders are at a disadvantage. Recent experiments, however, have demonstrated that free-riders sometimes also pay to punish cooperators. Inspired by these empirical results, theoretical work has explored evolutionary dynamics where mutants are rare, and found that punishment does not promote the evolution of cooperation when this 'anti-social punishment' is allowed. Here we extend previous theory by studying the effect of anti-social punishment on the evolution of cooperation across higher mutation rates, and by studying voluntary as well as compulsory Public Goods Games. We find that for intermediate and high mutation rates, adding punishment does not promote cooperation in either compulsory or voluntary public goods games if anti-social punishment is possible. This is because mutations generate agents that punish cooperators just as frequently as agents that punish defectors, and these two effects cancel each other out. These results raise questions about the effectiveness of punishment for promoting cooperation when mutations are common, and highlight how decisions about which strategies to include in the strategy set can have profound effects on the resulting dynamics. Copyright © 2014 Elsevier Ltd. All rights reserved.

PCBs Alter Dopamine Mediated Function in Aging Workers

DTIC Science & Technology

2011-01-01

inhibitors, COX-2 inhibi- tors, other non - steroidal anti - inflammatory agents, opiate agonists, miscellaneous analgesics and antipyretics, thyroid...DA) similar to changes previously seen in PCB exposed adult non -human primates. To test that hypothesis we used [123I]β-CIT SPECT imaging to...adult non -human primates (Seegal et al., 1994a), also occur in occupationally exposed humans. In this study, we used in vivo molecular imaging of the

"Nothing I Ever Do Seems to Please My Parents": Female and Male Self-Esteem as a Function of Mother's and Father's Nurturance.

ERIC Educational Resources Information Center

Buri, John R.; And Others

Parents are the primary agents in the development and definition of the self. Previous research has reported nurturance as the most notable parental factor in global self-esteem. This study examined the relationship of parental nurturance to self-esteem for the first time with subjects older than high school students. College students (N=333)…

Misoprostol for tinnitus.

PubMed

Crinnion, C L; McCart, G M

1995-01-01

Practitioners should realize that further study of misoprostol in larger patient populations must be undertaken to determine its efficacy and safety in the treatment of tinnitus. Previous approaches to treating tinnitus have included carbamazepine, phenytoin, lidocaine, tocainide, flecainide acetate, alprazolam, and nortriptyline. Studies using lidocaine, nortriptyline, or alprazolam have shown encouraging results. The relative contribution of misoprostol remains to be seen; however, it may offer a new treatment option to patients who have experienced adverse effects or have contraindications to the pharmacologic agents currently available.

The spermicidal potency of Coca-Cola and Pepsi-Cola.

PubMed

Hong, C Y; Shieh, C C; Wu, P; Chiang, B N

1987-09-01

The inhibitory effect of Old Coke, caffeine-free New Coke, New Coke, Diet Coke and Pepsi-Cola on human sperm motility was studied with a trans-membrane migration method. None of them could decrease sperm motility to less than 70% of control within one hour. A previous study which claimed a marked variation of spermicidal potencies among different formulations of Coca-Cola could not be confirmed. Even if cola has a spermicidal effect, its potency is relatively weak as compared with other well-known spermicidal agents.

Further characterization of Bacillus subtilis antibiotic biosensors and their use for antibacterial mode-of-action studies.

PubMed

Mariner, Katherine R; Ooi, Nicola; Roebuck, Deborah; O'Neill, Alex J; Chopra, Ian

2011-04-01

We further examined the usefulness of previously reported Bacillus subtilis biosensors for antibacterial mode-of-action studies. The biosensors could not detect the tRNA synthetase inhibitors mupirocin, indolmycin, and borrelidin, some inhibitors of peptidoglycan synthesis, and most membrane-damaging agents. However, the biosensors confirmed the modes of action of several RNA polymerase inhibitors and DNA intercalators and provided new insights into the possible modes of action of ciprofloxacin, anhydrotetracycline, corralopyronin, 8-hydroxyquinoline, and juglone.

Asthma risk and occupation as a respiratory therapist.

PubMed

Christiani, D C; Kern, D G

1993-09-01

In the modern hospital environment, many health care workers are exposed to hazardous substances. Among these hazards are respiratory sensitizers, irritants, and infectious agents. A previous cross-sectional study of Rhode Island respiratory therapists reported an excess risk of asthma after entry into that profession. Before the results of that study were published, we conducted a confirmatory mailed questionnaire survey of 2,086 Massachusetts respiratory therapists and 2,030 physical therapists and physical therapy assistants. Neither the survey questionnaire nor the accompanying cover letter revealed the focus of our investigation. A history of physician-diagnosed asthma was reported by 16% of respiratory therapists and 8% of control subjects. When analysis was restricted to those who developed asthma after entry into their profession, respiratory therapists still had a significant excess, 7.4 versus 2.8%. The odds ratio for respiratory therapy was 2.5 (95% Cl, 1.6 to 3.3) after adjustment for age, family history, atopic history, smoking, and gender. These results confirm the previous report of excess risk of asthma among respiratory therapists. This excess risk develops after entry into the profession and does not appear to be explained by bias or confounding. Efforts should be directed to identifying potential agents responsible for this form of occupational asthma.

Native range assessment of classical biological control agents: impact of inundative releases as pre-introduction evaluation.

PubMed

Jenner, W H; Mason, P G; Cappuccino, N; Kuhlmann, U

2010-08-01

Diadromus pulchellus Wesmael (Hymenoptera: Ichneumonidae) is a pupal parasitoid under consideration for introduction into Canada for the control of the invasive leek moth, Acrolepiopsis assectella (Zeller) (Lepidoptera: Acrolepiidae). Since study of the parasitoid outside of quarantine was not permitted in Canada at the time of this project, we assessed its efficacy via field trials in its native range in central Europe. This was done by simulating introductory releases that would eventually take place in Canada when a permit for release is obtained. In 2007 and 2008, experimental leek plots were artificially infested with pest larvae to mimic the higher pest densities common in Canada. Based on a preliminary experiment showing that leek moth pupae were suitable for parasitism up to 5-6 days after pupation, D. pulchellus adults were mass-released into the field plots when the first host cocoons were observed. The laboratory-reared agents reproduced successfully in all trials and radically reduced leek moth survival. Taking into account background parasitism caused by naturally occurring D. pulchellus, the released agents parasitized at least 15.8%, 43.9%, 48.1% and 58.8% of the available hosts in the four release trials. When this significant contribution to leek moth mortality is added to previously published life tables, in which pupal parasitism was absent, the total pupal mortality increases from 60.1% to 76.7%. This study demonstrates how field trials involving environmental manipulation in an agent's native range can yield predictions of the agent's field efficacy once introduced into a novel area.

A review of the possible mechanisms of action of tocotrienol - a potential antiosteoporotic agent.

PubMed

Chin, Kok-Yong; Mo, Huanbiao; Soelaiman, Ima-Nirwana

2013-12-01

Osteoporosis is posing a tremendous healthcare problem globally. Much effort has been invested in finding novel antiosteoporotic agents to stop the progression of this disease. Tocotrienol, one of the isoforms of vitamin E, is poised as a potential antiosteoporotic agent. Previous studies showed that tocotrienol as a single isomer or as a mixture demonstrated both anabolic and antiresorptive effects in various rodent models of osteoporosis. In vitro experiments further demonstrated that tocotrienol could up-regulate genes related to osteoblastogenesis and modify receptor activator of nuclear factor kappa B signaling against osteoclastogenesis. Additionally, tocotrienol was also shown to be a strong 3- hydroxy-3-methyl-glutaryl-CoA reductase down-regulator with a mechanism different from that of statins. Inhibition of the mevalonate pathway affects both osteoblast and osteoclast formation in favor of the former. Tocopherol, a more commonly used isoform of vitamin E does not possess similar effects. Tocotrienol is also a potent antioxidant. It can scavenge free radicals and prevent oxidative damage on osteoblast thus promoting its survival. It may also up-regulate the antioxidant defense network in osteoclast and indirectly act against free radical signaling essential in osteoclastogenesis. The effects of tocotrienol on Wnt/β-catenin signaling essential in osteoblastogenesis have not been determined. More mechanistic studies need to be conducted to illustrate the antiosteoporotic effects of tocotrienol. Clinical trials are also required to confirm its effects in humans. In conclusion, tocotrienol demonstrates great potential as an antiosteoporotic agent and much research effort should be invested to develop it as an agent to curb osteoporosis.

Occupation, exposure to chemicals, sensitizing agents, and risk of multiple myeloma in Sweden.

PubMed

Lope, Virginia; Pérez-Gómez, Beatriz; Aragonés, Nuria; López-Abente, Gonzalo; Gustavsson, Per; Plato, Nils; Zock, Jan-Paul; Pollán, Marina

2008-11-01

This study sought to identify occupations with high incidence of multiple myeloma and to investigate possible excess risk associated with occupational exposure to chemicals and sensitizing agents in Sweden. A historical cohort of 2,992,166 workers was followed up (1971--1989) through record linkage with the National Cancer and Death Registries. For each job category, age and period standardized incidence ratios and age and period adjusted relative risks of multiple myeloma were calculated using Poisson models. Exposure to chemicals and to sensitizing agents was also assessed using two job-exposure matrices. Men and women were analyzed separately. During follow-up, 3,127 and 1,282 myelomas were diagnosed in men and women, respectively. In men, excess risk was detected among working proprietors, agricultural, horticultural and forestry enterprisers, bakers and pastry cooks, dental technicians, stone cutters/carvers, and prison/reformatory officials. In women, this excess was observed among attendants in psychiatric care, metal workers, bakers and pastry cooks, and paper/paperboard product workers. Workers, particularly bakers and pastry cooks, exposed to high molecular weight sensitizing agents registered an excess risk of over 40% across the sexes. Occasional, although intense, exposure to pesticides was also associated with risk of myeloma in our cohort. Our study supports a possible etiologic role for farming and use of pesticides in myeloma risk. The high incidence found in both female and male bakers and pastry cooks has not been described previously. Further research is required to assess the influence of high molecular weight sensitizing agents on risk of multiple myeloma.

Activities of several benzimidazoles and tubulin inhibitors against Giardia spp. in vitro.

PubMed Central

Morgan, U M; Reynoldson, J A; Thompson, R C

1993-01-01

Previous studies in our laboratory have shown that albendazole is effective against Giardia spp. in vitro and in vivo, prompting an investigation of the effects of several related benzimidazoles (BZs) on the viability of this protozoan parasite. A range of BZs was tested, and their effects were compared with those of a number of microtubule inhibitors. The effects produced by the two types of drugs were markedly similar, namely, trophozoite detachment and distortion of morphology and general structure, indicating a potential antimicrotubule mode of action for BZs. Mebendazole, albendazole, and fenbendazole proved to be among the most effective BZs tested, exhibiting apparent irreversibility. Nocodazole, oxfendazole, and albendazole sulfoxide, among others, produced transient inhibitions only. Further studies are required to evaluate all available BZs and other antigiardial agents to ensure the development of the most effective and safest antigiardial agent possible. PMID:8452365

Cyclosporine and ketoconazole for the treatment of perianal fistulas in dogs.

PubMed

Patricelli, Alison J; Hardie, Robert J; McAnulty, Jonathan E

2002-04-01

To evaluate efficacy and cost of using cyclosporine and ketoconazole for the treatment of perianal fistulas in dogs. Clinical trial. 12 dogs with perianal fistulas. Dogs received cyclosporine and ketoconazole orally (target whole blood trough cyclosporine concentrations of 400 to 600 ng/ml). Study endpoints were resolution of clinical signs, remission, and recurrence of disease. Adverse effects and cost of medications were reported. Results were compared with those from previous studies in humans and in dogs in which single agent cyclosporine treatment for perianal fistulas was used. All dogs had resolution of clinical signs. Eight dogs went into remission; however, 5 of those 8 had recurrence of fistulas. Adverse effects of treatment were minimal and well tolerated. Cost of treatment was comparable to traditional surgical options and less than single agent cyclosporine treatment. Administration of cyclosporine with ketoconazole is an effective and cost-comparable treatment for perianal fistulas in dogs.

Long-term health experience of jet engine manufacturing workers: VI: incidence of malignant central nervous system neoplasms in relation to estimated workplace exposures.

PubMed

Marsh, Gary M; Youk, Ada O; Buchanich, Jeanine M; Xu, Hui; Downing, Sarah; Kennedy, Kathleen J; Esmen, Nurtan A; Hancock, Roger P; Lacey, Steven E; Fleissner, Mary Lou

2013-06-01

To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with specific chemical or physical exposures. Subjects were 210,784 workers employed from 1952 to 2001. We conducted a cohort incidence study and two nested case-control studies with focus on the North Haven facility where we previously observed a not statistically significant overall elevation in GB rates. We estimated individual-level exposure metrics for 11 agents. In the total cohort, none of the agent metrics considered was associated with increased GB risk. The GB incidence rates in North Haven were also not related to workplace exposures, including the "blue haze" exposure unique to North Haven. If not due to chance alone, GB rates in North Haven may reflect external occupational factors, nonoccupational factors, or workplace factors unique to North Haven unmeasured in the current evaluation.

Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents.

PubMed

Suryadevara, Praveen Kumar; Racherla, Kishore Kumar; Olepu, Srinivas; Norcross, Neil R; Tatipaka, Hari Babu; Arif, Jennifer A; Planer, Joseph D; Lepesheva, Galina I; Verlinde, Christophe L M J; Buckner, Frederick S; Gelb, Michael H

2013-12-01

New dialkylimidazole based sterol 14α-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50 <1 nM) against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T. cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate. Copyright © 2013 Elsevier Ltd. All rights reserved.

Harnessing and Modulating Inflammation in Strategies for Bone Regeneration

PubMed Central

Mountziaris, Paschalia M.; Spicer, Patrick P.; Kasper, F. Kurtis

2011-01-01

Inflammation is an immediate response that plays a critical role in healing after fracture or injury to bone. However, in certain clinical contexts, such as in inflammatory diseases or in response to the implantation of a biomedical device, the inflammatory response may become chronic and result in destructive catabolic effects on the bone tissue. Since our previous review 3 years ago, which identified inflammatory signals critical for bone regeneration and described the inhibitory effects of anti-inflammatory agents on bone healing, a multitude of studies have been published exploring various aspects of this emerging field. In this review, we distinguish between regenerative and damaging inflammatory processes in bone, update our discussion of the effects of anti-inflammatory agents on bone healing, summarize recent in vitro and in vivo studies demonstrating how inflammation can be modulated to stimulate bone regeneration, and identify key future directions in the field. PMID:21615330

Exploratory study on the effects of novel diamine curing agents and isocyanate precursors on the properties on new epoxy and urethane adhesives

NASA Technical Reports Server (NTRS)

Glasgow, D. G.; Garthwait, C.

1977-01-01

Aromatic diamines based on diphenyl sulfone and benzophenone were studied as epoxy adhesive curing agents. Previously found differences in adhesive strengths for meta vs para orientation were not found in these series. The use of aluminum and alumina as fillers in a m,m prime-methylene dianiline-cured epoxy adhesive was not found to be beneficial to adhesive strength. Alumina filled adhesives had much lower strength than unfilled adhesives. The unfilled m,m prime-methylene dianiline-based epoxy adhesive had excellent resistance to moisture relative to a p,p prime-methylene dianiline-based adhesive and maintained good strengths up to 250 F. A glass fiber composite based on a m,m prime-methylene dianiline-cured epoxy appeared to be equivalent to the p,p prime-methylene dianiline-cured epoxy as judged by short beam shear tests.

Culture and Next-generation sequencing-based drug susceptibility testing unveil high levels of drug-resistant-TB in Djibouti: results from the first national survey.

PubMed

Tagliani, Elisa; Hassan, Mohamed Osman; Waberi, Yacine; De Filippo, Maria Rosaria; Falzon, Dennis; Dean, Anna; Zignol, Matteo; Supply, Philip; Abdoulkader, Mohamed Ali; Hassangue, Hawa; Cirillo, Daniela Maria

2017-12-15

Djibouti is a small country in the Horn of Africa with a high TB incidence (378/100,000 in 2015). Multidrug-resistant TB (MDR-TB) and resistance to second-line agents have been previously identified in the country but the extent of the problem has yet to be quantified. A national survey was conducted to estimate the proportion of MDR-TB among a representative sample of TB patients. Sputum was tested using XpertMTB/RIF and samples positive for MTB and resistant to rifampicin underwent first line phenotypic susceptibility testing. The TB supranational reference laboratory in Milan, Italy, undertook external quality assurance, genotypic testing based on whole genome and targeted-deep sequencing and phylogenetic studies. 301 new and 66 previously treated TB cases were enrolled. MDR-TB was detected in 34 patients: 4.7% of new and 31% of previously treated cases. Resistance to pyrazinamide, aminoglycosides and capreomycin was detected in 68%, 18% and 29% of MDR-TB strains respectively, while resistance to fluoroquinolones was not detected. Cluster analysis identified transmission of MDR-TB as a critical factor fostering drug resistance in the country. Levels of MDR-TB in Djibouti are among the highest on the African continent. High prevalence of resistance to pyrazinamide and second-line injectable agents have important implications for treatment regimens.

Stability, reliability and cross-mode correlations of tests in a recommended 8-minute performance assessment battery

NASA Technical Reports Server (NTRS)

Wilkes, R. L.; Kennedy, R. S.; Dunlap, W. P.; Lane, N. E.

1986-01-01

A need exists for an automated performance test system to study drugs, agents, treatments, and stresses of interest to the aviation, space, and environmental medical community. The purpose of this present study is to evaluate tests for inclusion in the NASA-sponsored Automated Performance Test System (APTS). Twenty-one subjects were tested over 10 replications with tests previously identified as good candidates for repeated-measure research. The tests were concurrently administered in paper-and-pencil and microcomputer modes. Performance scores for the two modes were compared. Data from trials 1 to 10 were examined for indications of test stability and reliability. Nine of the ten APT system tests achieved stability. Reliabilities were generally high. Cross-correlation of microbased tests with traditional paper-and-pencil versions revealed similarity of content within tests in the different modes, and implied at least three cognition and two motor factors. This protable, inexpensive, rugged, computerized battery of tests is recommended for use in repeated-measures studies of environmental and drug effects on performance. Identification of other tests compatible with microcomputer testing and potentially capable of tapping previously unidentified factors is recommended. Documentation of APTS sensitivity to environmental agents is available for more than a dozen facilities and is reported briefly. Continuation of such validation remains critical in establishing the efficacy of APTS tests.

Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

PubMed

Thigpen, T; Brady, M F; Homesley, H D; Soper, J T; Bell, J

2001-01-15

In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

PubMed Central

Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

2015-01-01

Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

Community-aware task allocation for social networked multiagent systems.

PubMed

Wang, Wanyuan; Jiang, Yichuan

2014-09-01

In this paper, we propose a novel community-aware task allocation model for social networked multiagent systems (SN-MASs), where the agent' cooperation domain is constrained in community and each agent can negotiate only with its intracommunity member agents. Under such community-aware scenarios, we prove that it remains NP-hard to maximize system overall profit. To solve this problem effectively, we present a heuristic algorithm that is composed of three phases: 1) task selection: select the desirable task to be allocated preferentially; 2) allocation to community: allocate the selected task to communities based on a significant task-first heuristics; and 3) allocation to agent: negotiate resources for the selected task based on a nonoverlap agent-first and breadth-first resource negotiation mechanism. Through the theoretical analyses and experiments, the advantages of our presented heuristic algorithm and community-aware task allocation model are validated. 1) Our presented heuristic algorithm performs very closely to the benchmark exponential brute-force optimal algorithm and the network flow-based greedy algorithm in terms of system overall profit in small-scale applications. Moreover, in the large-scale applications, the presented heuristic algorithm achieves approximately the same overall system profit, but significantly reduces the computational load compared with the greedy algorithm. 2) Our presented community-aware task allocation model reduces the system communication cost compared with the previous global-aware task allocation model and improves the system overall profit greatly compared with the previous local neighbor-aware task allocation model.

Bidding Agents That Perpetrate Auction Fraud

NASA Astrophysics Data System (ADS)

Trevathan, Jarrod; McCabe, Alan; Read, Wayne

This paper presents a software bidding agent that inserts fake bids on the seller's behalf to inflate an auction's price. This behaviour is referred to as shill bidding. Shill bidding is strictly prohibited by online auctioneers, as it defrauds unsuspecting buyers by forcing them to pay more for the item. The malicious bidding agent was constructed to aid in developing shill detection techniques. We have previously documented a simple shill bidding agent that incrementally increases the auction price until it reaches the desired profit target, or it becomes too risky to continue bidding. This paper presents an adaptive shill bidding agent which when used over a series of auctions with substitutable items, can revise its strategy based on bidding behaviour in past auctions. The adaptive agent applies a novel prediction technique referred to as the Extremum Consistency (EC) algorithm, to determine the optimal price to aspire for. The EC algorithm has successfully been used in handwritten signature verification for determining the maximum and minimum values in an input stream. The agent's ability to inflate the price has been tested in a simulated marketplace and experimental results are presented.

When Does Diversity Trump Ability (and Vice Versa) in Group Decision Making? A Simulation Study

PubMed Central

Luan, Shenghua; Katsikopoulos, Konstantinos V.; Reimer, Torsten

2012-01-01

It is often unclear which factor plays a more critical role in determining a group's performance: the diversity among members of the group or their individual abilities. In this study, we addressed this “diversity vs. ability” issue in a decision-making task. We conducted three simulation studies in which we manipulated agents' individual ability (or accuracy, in the context of our investigation) and group diversity by varying (1) the heuristics agents used to search task-relevant information (i.e., cues); (2) the size of their groups; (3) how much they had learned about a good cue search order; and (4) the magnitude of errors in the information they searched. In each study, we found that a manipulation reducing agents' individual accuracy simultaneously increased their group's diversity, leading to a conflict between the two. These conflicts enabled us to identify certain conditions under which diversity trumps individual accuracy, and vice versa. Specifically, we found that individual accuracy is more important in task environments in which cues differ greatly in the quality of their information, and diversity matters more when such differences are relatively small. Changing the size of a group and the amount of learning by an agent had a limited impact on this general effect of task environment. Furthermore, we found that a group achieves its highest accuracy when there is an intermediate amount of errors in the cue information, regardless of the environment and the heuristic used, an effect that we believe has not been previously reported and warrants further investigation. PMID:22359562

Detection of human pathogenic Ehrlichia muris-like agent in Peromyscus leucopus.

PubMed

Castillo, Caroline G; Eremeeva, Marina E; Paskewitz, Susan M; Sloan, Lynne M; Lee, Xia; Irwin, William E; Tonsberg, Stefan; Pritt, Bobbi S

2015-03-01

An Ehrlichia muris-like (EML) bacterium was recently detected in humans and Ixodes scapularis ticks in Minnesota and Wisconsin. The reservoir for this agent is unknown. To investigate the occurrence of the EML agent, groEL PCR testing and sequencing was performed on blood from small mammals and white-tailed deer that were collected in areas where human and tick infections were previously demonstrated. DNA of the EML agent was detected in two Peromyscus leucopus of 146 small mammals (1.4%); while 181 O. virginianus tested negative. This report provides the first evidence that DNA from the EML agent is found in P. leucopus, the same animal that is a reservoir for Anaplasma phagocytophilum in this region. The role of white-tailed deer remains inconclusive. Further sampling is warranted to understand the spatial and temporal distribution, transmission and maintenance of this pathogen. Copyright © 2014 Elsevier GmbH. All rights reserved.

Fairness emergence from zero-intelligence agents

NASA Astrophysics Data System (ADS)

Duan, Wen-Qi; Stanley, H. Eugene

2010-02-01

Fairness plays a key role in explaining the emergence and maintenance of cooperation. Opponent-oriented social utility models were often proposed to explain the origins of fairness preferences in which agents take into account not only their own outcomes but are also concerned with the outcomes of their opponents. Here, we propose a payoff-oriented mechanism in which agents update their beliefs only based on the payoff signals of the previous ultimatum game, regardless of the behaviors and outcomes of the opponents themselves. Employing adaptive ultimatum game, we show that (1) fairness behaviors can emerge out even under such minimalist assumptions, provided that agents are capable of responding to their payoff signals, (2) the average game payoff per agent per round decreases with the increasing discrepancy rate between the average giving rate and the average asking rate, and (3) the belief update process will lead to 50%-50% fair split provided that there is no mutation in the evolutionary dynamics.

Enhancing the Prevention and Treatment of Orthopaedic Infections Associated with Traumatic Injury

DTIC Science & Technology

2017-10-01

minipeg-2 derivative have antimicrobial activity in and of themselves (see previous progress report). This absence of antibacterial activity is not...necessarily desirable, as antibacterial activity of the targeting agent itself could prove useful. However, it does suggest that these agents are less...of the minipeg linker (BS-4-134 and BS-4-142). However, unlike our daptomycin conjugates, antibacterial activity was essentially abolished with all of

Effective Treatment of Folliculitis Decalvans Using Selected Antimicrobial Agents

PubMed Central

Sillani, Caulloo; Bin, Zhang; Ying, Zhao; Zeming, Cai; Jian, Yang; Xingqi, Zhang

2010-01-01

Folliculitis Decalvans (FD) is a rare neutrophilic infammation of the scalp characterized by painful, recurrent purulent follicular exudation resulting in primary cicatricial alopecia. However, unclear etiology makes FD treatment a difficult task. A wide variety of topical and systemic agents have been tried previously, with varied results. We present here a case series report of a set of 13 patients with FD on antimicrobial therapy. PMID:21188019

Effects of a novel anti-aggressive agent upon two types of brain stimulated emotional behavior.

PubMed

Katz, R J; Thomas, E

1976-07-09

The effects of anti-aggressive agent Sch 12679 were evaluated upon stable baselines of rage and predation elicited by electrical stimulation of the hypothalamus in cats. Sch 12679 depressed approach and terminal aspects of both forms of attack. This is consistent with previous reports, and suggests the drug is effective in reducing many forms of aggression including brain stimulated emotional behavior.

Reflections of Oneself: Neurocognitive Evidence for Dissociable Forms of Self-Referential Recollection.

PubMed

Bergström, Zara M; Vogelsang, David A; Benoit, Roland G; Simons, Jon S

2015-09-01

Research links the medial prefrontal cortex (mPFC) with a number of social cognitive processes that involve reflecting on oneself and other people. Here, we investigated how mPFC might support the ability to recollect information about oneself and others relating to previous experiences. Participants judged whether they had previously related stimuli conceptually to themselves or someone else, or whether they or another agent had performed actions. We uncovered a functional distinction between dorsal and ventral mPFC subregions based on information retrieved from episodic long-term memory. The dorsal mPFC was generally activated when participants attempted to retrieve social information about themselves and others, regardless of whether this information concerned the conceptual or agentic self or other. In contrast, a role was discerned for ventral mPFC during conceptual but not agentic self-referential recollection, indicating specific involvement in retrieving memories related to self-concept rather than bodily self. A subsequent recognition test for new items that had been presented during the recollection task found that conceptual and agentic recollection attempts resulted in differential incidental encoding of new information. Thus, we reveal converging fMRI and behavioral evidence for distinct neurocognitive forms of self-referential recollection, highlighting that conceptual and bodily aspects of self-reflection can be dissociated. © The Author 2014. Published by Oxford University Press.

Reflections of Oneself: Neurocognitive Evidence for Dissociable Forms of Self-Referential Recollection

PubMed Central

Bergström, Zara M.; Vogelsang, David A.; Benoit, Roland G.; Simons, Jon S.

2015-01-01

Research links the medial prefrontal cortex (mPFC) with a number of social cognitive processes that involve reflecting on oneself and other people. Here, we investigated how mPFC might support the ability to recollect information about oneself and others relating to previous experiences. Participants judged whether they had previously related stimuli conceptually to themselves or someone else, or whether they or another agent had performed actions. We uncovered a functional distinction between dorsal and ventral mPFC subregions based on information retrieved from episodic long-term memory. The dorsal mPFC was generally activated when participants attempted to retrieve social information about themselves and others, regardless of whether this information concerned the conceptual or agentic self or other. In contrast, a role was discerned for ventral mPFC during conceptual but not agentic self-referential recollection, indicating specific involvement in retrieving memories related to self-concept rather than bodily self. A subsequent recognition test for new items that had been presented during the recollection task found that conceptual and agentic recollection attempts resulted in differential incidental encoding of new information. Thus, we reveal converging fMRI and behavioral evidence for distinct neurocognitive forms of self-referential recollection, highlighting that conceptual and bodily aspects of self-reflection can be dissociated. PMID:24700584

Evaluation of CO2, N2 and He as Fire Suppression Agents in Microgravity

NASA Technical Reports Server (NTRS)

Ruff, Gary A.; Hicks, Michael; Pettegrew, Richard

2004-01-01

The U.S. modules of the International Space Station use gaseous CO2 as the fire extinguishing agent. This was selected as a result of extensive experience with CO2 as a fire suppressant in terrestrial applications, trade studies on various suppressants, and experiments. The selection of fire suppressants and suppression strategies for NASA s Lunar and Martian exploration missions will be based on the same studies and normal-gravity data unless reduced gravity fire suppression data is obtained. In this study, the suppressant agent concentrations required to extinguish a flame in low velocity convective flows within the 20-sec of low gravity on the KC-135 aircraft were investigated. Suppressant gas mixtures of CO2, N2, and He with the balance being oxygen/nitrogen mixtures with either 21% or 25% O2 were used to suppress flames on a 19-mm diameter PMMA cylinder in reduced gravity. For each of the suppressant mixtures, limiting concentrations were established that would extinguish the flame at any velocity. Similarly, concentrations were established that would not extinguish the flame. The limiting concentrations were generally consistent with previous studies but did suggest that geometry had an effect on the limiting conditions. Between the extinction and non-extinction limits, the suppression characteristics depended on the extinguishing agent, flow velocity, and O2 concentration. The limiting velocity data from the CO2, He, and N2 suppressants were well correlated using an effective mixture enthalpy per mole of O2, indicating that all act via O2 displacement and cooling mechanisms. In reduced gravity, the agent concentration required to suppress the flames increased as the velocity increased, up to approximately 10 cm/s (the maximum velocity evaluated in this experiment). The effective enthalpy required to extinguish flames at velocities of 10 cm/s is approximately the same as the concentrations in normal gravity. A computational study is underway to further evaluate these findings.

An artificial bioindicator system for network intrusion detection.

PubMed

Blum, Christian; Lozano, José A; Davidson, Pedro Pinacho

An artificial bioindicator system is developed in order to solve a network intrusion detection problem. The system, inspired by an ecological approach to biological immune systems, evolves a population of agents that learn to survive in their environment. An adaptation process allows the transformation of the agent population into a bioindicator that is capable of reacting to system anomalies. Two characteristics stand out in our proposal. On the one hand, it is able to discover new, previously unseen attacks, and on the other hand, contrary to most of the existing systems for network intrusion detection, it does not need any previous training. We experimentally compare our proposal with three state-of-the-art algorithms and show that it outperforms the competing approaches on widely used benchmark data.

Short communication: The influence of solids concentration and bleaching agent on bleaching efficacy and flavor of sweet whey powder.

PubMed

Jervis, M G; Smith, T J; Drake, M A

2015-04-01

Recent studies have demonstrated the effect of bleaching conditions and bleaching agent on flavor and functional properties of whey protein ingredients. Solids concentration at bleaching significantly affected bleaching efficacy and flavor effects of different bleaching agents. It is not known if these parameters influence quality of sweet whey powder (SWP). The purpose of this study was to determine the effects of solids concentration and bleaching agent on the flavor and bleaching efficacy of SWP. Colored cheddar whey was manufactured, fat separated, and pasteurized. Subsequently, the whey (6.7% solids) was bleached, concentrated using reverse osmosis (RO) to 14% solids, and then spray dried, or whey was concentrated before bleaching and then spray dried. Bleaching treatments included a control (no bleaching, 50 °C, 60 min), hydrogen peroxide (HP; 250 mg/kg, 50 °C, 60 min), benzoyl peroxide (50 mg/kg, 50 °C, 60 min), lactoperoxidase (20 mg/kg of HP, 50 °C, 30 min), and external peroxidase (MaxiBright, DSM Food Specialties, Delft, the Netherlands; 2 dairy bleaching units/mL, 50 °C, 30 min). The experiment was repeated in triplicate. Sensory properties and volatile compounds of SWP were evaluated by a trained panel and gas chromatography-mass spectrometry, respectively. Bleaching efficacy (norbixin destruction) and benzoic acid were measured by HPLC. Differences in bleaching efficacy, sensory and volatile compound profiles, and benzoic acid were observed with different bleaching agents, consistent with previous studies. Solids concentration affected bleaching efficacy of HP, but not other bleaching agents. The SWP from whey bleached with HP or lactoperoxidase following RO had increased cardboard and fatty flavors and higher concentrations of lipid oxidation compounds compared with SWP from whey bleached before RO. The SWP bleached with benzoyl peroxide after RO contained less benzoic acid than SWP from whey bleached before RO. These results indicate that solids concentration at bleaching and bleaching agent affect quality of SWP. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Emergence of cooperation as a non-equilibrium transition in noisy spatial games

NASA Astrophysics Data System (ADS)

Menon, Shakti N.; Sasidevan, V.; Sinha, Sitabhra

2018-04-01

The emergence of cooperation among selfish agents that have no incentive to cooperate is a non-trivial phenomenon that has long intrigued biologists, social scientists and physicists. The iterated Prisoner's Dilemma (IPD) game provides a natural framework for investigating this phenomenon. Here, agents repeatedly interact with their opponents, and their choice to either cooperate or defect is determined at each round by knowledge of the previous outcomes. The spatial version of IPD, where each agent interacts only with their nearest neighbors on a specified connection topology, has been used to study the evolution of cooperation under conditions of bounded rationality. In this paper we study how the collective behavior that arises from the simultaneous actions of the agents (implemented by synchronous update) is affected by (i) uncertainty, measured as noise intensity K, (ii) the payoff b, quantifying the temptation to defect and (iii) the nature of the underlying connection topology. In particular, we study the phase transitions between states characterized by distinct collective dynamics as the connection topology is gradually altered from a two-dimensional lattice to a random network. This is achieved by rewiring links between agents with a probability p following the small-world network construction paradigm. On crossing a specified threshold value of b, the game switches from being Prisoner's Dilemma, characterized by a unique equilibrium, to Stag Hunt, a well-known coordination game having multiple equilibria. We observe that the system can exhibit three collective states corresponding to a pair of absorbing states (viz., all agents cooperating or defecting) and a fluctuating state characterized by agents switching intermittently between cooperation and defection. As noise and temptation can be interpreted as temperature and an external field respectively, a strong analogy can be drawn between the phase diagrams of such games with that of interacting spin systems. Considering the 3-dimensional p-K-b parameter space allows us to investigate the different phase transitions that occur between these collective states and characterize them using finite-size scaling. We find that the values of the critical exponents depend on the connection topology and are different from the Directed Percolation (DP) universality class.

Potential Mechanism of Action of 3'-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus.

PubMed

Favela-Hernández, Juan Manuel J; Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Garza-González, Elvira; Camacho-Corona, María del Rayo

2015-07-08

Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

Potential mechanism of action of 3'-demethoxy-6-O-demethyl-isoguaiacin on methicillin resistant Staphylococcus aureus.

PubMed

Favela-Hernández, Juan Manuel J; Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Garza-González, Elvira; Camacho-Corona, María Del Rayo

2015-07-08

Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.

Effect of essential oil of Satureja hortensis against Bacillus pumilus, which cause of soft rot on some plants

NASA Astrophysics Data System (ADS)

Dadaşoǧlu, Fatih

2017-04-01

In this study, it is aimmed to be determined the antimicrobial effects of the essential oil in vitro conditions, extracted from wild forms of plant which is known as Satureja hortensis around the world and grows naturally at Erzurum province of Turkey against Bacillus pumilus isolates, which are the agent of Soft Rot for some fruits and vegetables. For this purpose, 18 isolates of B. pumilus which have been determined as the agent of Soft Rot in previous studies performed in plants such as potatos, onions, strawberries, melons and watermelons. As the positive control, Streptomycin antibiotics sold as ready produce were used. According to the obtained results, the essential oil have the antibactericidal effect of 19-29 mm against 18 isolates of B. pumilus. It has been observed that the antibiotics used as the positive control has the antibacterial effect of 16-22 mm. In conclusion, the essential oil has the lethal effect against 18 B. pumilus isolates which are agents of Soft Rot. It is assesed that these essential oil extracted from Satureja hortensis can be used against these Soft Rot pathogens.

Inhibitory Activities of Phenolic Compounds Isolated from Adina rubella Leaves Against 5α-Reductase Associated with Benign Prostatic Hypertrophy.

PubMed

Yin, Jun; Heo, Jun Hyeok; Hwang, Yoon Jeong; Le, Thi Tam; Lee, Min Won

2016-07-07

Adina rubella Hance (AR), a plant native to Korea, has been used as traditional medicine for dysentery, eczema, intoxication, and external hemorrhages. Previous phytochemical studies of AR have reported several components, including terpenoids, phenolics, and alkaloids. The current study evaluated the anti-oxidative and anti-inflammatory activities and 5α-reductase inhibition of isolated compounds of AR leaves to find a potential therapeutic agent for benign prostatic hypertrophy (BPH). Repeated chromatographic isolation of an 80% acetone extract of AR leaves yielded seven phenolic compounds: caffeic acid (1), chlorogenic acid (2), methyl chlorogenate (3), quercetin-3-rutinoside (4), kaempferol-3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (5), hyperoside (6), and grandifloroside (7). Compound 7 is a novel compound in AR. Caffeoyl derivatives 1-3 and 7 showed good anti-oxidative activities. In particular, caffeic acid (1) and grandifloroside (7) showed potent anti-inflammatory activities, and 7 also exhibited potent inhibitory activity against TNF-α and 5α-reductase. Our results show that the extract and grandifloroside (7) from leaves of AR might be developed as a source of potent anti-oxidative and anti-inflammatory agents and therapeutic agent for BPH.

Rational expectations, psychology and inductive learning via moving thresholds

NASA Astrophysics Data System (ADS)

Lamba, H.; Seaman, T.

2008-06-01

This paper modifies a previously introduced class of heterogeneous agent models in a way that allows for the inclusion of different types of agent motivations and behaviours in a consistent manner. The agents operate within a highly simplified environment where they are only able to be long or short one unit of the asset. The price of the asset is influenced by both an external information stream and the demand of the agents. The current strategy of each agent is defined by a pair of moving thresholds straddling the current price. When the price crosses either of the thresholds for a particular agent, that agent switches position and a new pair of thresholds is generated. The threshold dynamics can mimic different sources of investor motivation, running the gamut from purely rational information-processing, through rational (but often undesirable) behaviour induced by perverse incentives and moral hazards, to purely psychological effects. The simplest model of this kind precisely conforms to the Efficient Market Hypothesis (EMH) and this allows causal relationships to be established between actions at the agent level and violations of EMH price statistics at the global level. In particular, the effects of herding behaviour and perverse incentives are examined.

Team Formation and Communication Restrictions in Collectives

NASA Technical Reports Server (NTRS)

Agogino, Adrian K.; Turner, Kagan

2003-01-01

A collective of agents often needs to maximize a "world utility" function which rates the performance of an entire system, while subject to communication restrictions among the agents. Such communication restrictions make it difficult for agents which try to pursue their own "private" utilities to take actions that also help optimize the world utility. Team formation presents a solution to this problem, where by joining other agents, an agent can significantly increase its knowledge about the environment and improve its chances of both optimizing its own utility and that its doing so will contribute to the world utility. In this article we show how utilities that have been previously shown to be effective in collectives can be modified to be more effective in domains with moderate communication restrictions resulting in performance improvements of up to 75%. Additionally we show that even severe communication constraints can be overcome by forming teams where each agent of a team shares the same utility, increasing performance an additional 25%. We show that utilities and team sizes can be manipulated to form the best compromise between how "aligned" an agent s utility is with the world utility and how easily an agent can learn that utility.

Aspirin and the prevention of venous thromboembolism following total joint arthroplasty: commonly asked questions.

PubMed

Azboy, I; Barrack, R; Thomas, A M; Haddad, F S; Parvizi, J

2017-11-01

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences. Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a 'milder' agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents. The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use. There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE. Cite this article: Bone Joint J 2017;99-B:1420-30. ©2017 Azboy et al.

Effects of pH buffering agents on the anaerobic hydrolysis acidification stage of kitchen waste.

PubMed

Wang, Yaya; Zang, Bing; Gong, Xiaoyan; Liu, Yu; Li, Guoxue

2017-10-01

This study investigated effects of initial pH buffering agents on the lab-scale anaerobic hydrolysis acidification stage of kitchen waste (KW). Different cheap, available and suitable buffering agents (NaOH(s), NaOH(l), CaO(s)-NaOH, KOH(l)-NaOH, K 2 HPO 4 (s)-KOH, Na 2 CO 3 (s)-NaOH) were added under optimal adjusting mode (first two days: per 16h, after: one time per day) which was obtained in previous work. The effects of buffering agents were evaluated according to indexes of pH, VFAs, NH 4 + -N, TS, VS, VS/TS, TS and VS removal rate. The results showed treatment 5 with adding K 2 HPO 4 -KOH buffering agents had the most stable pH (6.7-7.0). Also treatment 5, 2, 4 and 6 provided stable pH ranging in 5-8. Among the treatments, treatment 6 with adding Na 2 CO 3 as initial buffering agents and 10mol/L NaOH as regulator was chosen as the optimal mode for highest VFAs content (44.05g/L) with high acetic acid and butyrate acid proportion (42.64%), TS and VS removal rate (44.84% and 58.67%, respectively), low VS/TS ratio (58.55), fewer adding dosage and low adjusting frequency. The VFAs content of treatment 6 at the end of hydrolysis acidification stage could be used for methanogenic phase of anaerobic two-phase digestion. Thus, treatment 6 (adding Na 2 CO 3 as initial buffering agents and 10mol/L NaOH as regulator) with highest VFAs content and TS and VS removal rate could be considered using in anaerobic hydrolysis acidification stage pH adjustment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aspirin and the prevention of venous thromboembolism following total joint arthroplasty

PubMed Central

Azboy, I.; Barrack, R.; Thomas, A. M.; Haddad, F. S.; Parvizi, J.

2017-01-01

The number of arthroplasties being performed increases each year. Patients undergoing an arthroplasty are at risk of venous thromboembolism (VTE) and appropriate prophylaxis has been recommended. However, the optimal protocol and the best agent to minimise VTE under these circumstances are not known. Although many agents may be used, there is a difference in their efficacy and the risk of bleeding. Thus, the selection of a particular agent relies on the balance between the desire to minimise VTE and the attempt to reduce the risk of bleeding, with its undesirable, and occasionally fatal, consequences. Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis following arthroplasty. Many studies have shown its efficacy in minimising VTE under these circumstances. It is inexpensive and well-tolerated, and its use does not require routine blood tests. It is also a ‘milder’ agent and unlikely to result in haematoma formation, which may increase both the risk of infection and the need for further surgery. Aspirin is also unlikely to result in persistent wound drainage, which has been shown to be associated with the use of agents such as low-molecular-weight heparin (LMWH) and other more aggressive agents. The main objective of this review was to summarise the current evidence relating to the efficacy of aspirin as a VTE prophylaxis following arthroplasty, and to address some of the common questions about its use. There is convincing evidence that, taking all factors into account, aspirin is an effective, inexpensive, and safe form of VTE following arthroplasty in patients without a major risk factor for VTE, such as previous VTE. Cite this article: Bone Joint J 2017;99-B:1420–30. PMID:29092979

Dentine tubule infection and endodontic therapy implications.

PubMed

Oguntebi, B R

1994-07-01

A critical review of the literature suggests that the microenvironment of dentinal tubules appears to favour the selection of relatively few bacterial types irrespective of the aetiology of the infection process; coronal dental caries or pulpar necrosis. These bacteria may constitute an important reservoir from which root canal infection and reinfection may occur following pulp necrosis or during and after endodontic treatment. Previous studies of this microflora have utilized microbiological culture techniques which need to be supplemented by those that allow in situ demonstration as well as identification of the bacteria. Newer treatment strategies that are designed to eliminate this microflora must include agents that can penetrate the dentinal tubules and destroy these microorganisms, since they are located in an area beyond the host defence mechanisms where they cannot be reached by systemically administered antimicrobial agents.

From automata to animate beings: the scope and limits of attributing socialness to artificial agents.

PubMed

Hortensius, Ruud; Cross, Emily S

2018-05-11

Understanding the mechanisms and consequences of attributing socialness to artificial agents has important implications for how we can use technology to lead more productive and fulfilling lives. Here, we integrate recent findings on the factors that shape behavioral and brain mechanisms that support social interactions between humans and artificial agents. We review how visual features of an agent, as well as knowledge factors within the human observer, shape attributions across dimensions of socialness. We explore how anthropomorphism and dehumanization further influence how we perceive and interact with artificial agents. Based on these findings, we argue that the cognitive reconstruction within the human observer is likely to be far more crucial in shaping our interactions with artificial agents than previously thought, while the artificial agent's visual features are possibly of lesser importance. We combine these findings to provide an integrative theoretical account based on the "like me" hypothesis, and discuss the key role played by the Theory-of-Mind network, especially the temporal parietal junction, in the shift from mechanistic to social attributions. We conclude by highlighting outstanding questions on the impact of long-term interactions with artificial agents on the behavioral and brain mechanisms of attributing socialness to these agents. © 2018 New York Academy of Sciences.

Nicotinic α4β2 receptor imaging agents. Part IV. Synthesis and biological evaluation of 3-(2-(S)-3,4-dehydropyrrolinyl methoxy)-5-(3'-¹⁸F-fluoropropyl)pyridine (¹⁸F-Nifrolene) using PET.

PubMed

Pichika, Rama; Kuruvilla, Sharon A; Patel, Narmisha; Vu, Kenny; Sinha, Sangamitra; Easwaramoorthy, Balu; Narayanan, Tanjore K; Shi, Bingzhi; Christian, Bradley; Mukherjee, Jogeshwar

2013-01-01

Imaging agents for nicotinic α4β2 receptors in the brain have been under way for studying various CNS disorders. Previous studies from our laboratories have reported the successful development of agonist, ¹⁸F-nifene. In attempts to develop potential antagonists, ¹⁸F-nifrolidine and ¹⁸F-nifzetidine were previously reported. Further optimization of these fluoropropyl derivatives has now been carried out resulting in 3-(2-(S)-3,4-dehydropyrrolinylmethoxy)-5-(3'-Fluoropropyl)pyridine (nifrolene) as a new high affinity agent for nicotinic α4β2 receptors. Nifrolene in rat brain homogenate assays--labeled with ³H-cytisine--exhibited a binding affinity of 0.36 nM. The fluorine-18 analog, ¹⁸F-nifrolene, was synthesized in approximately 10%-20% yield and specific activity was estimated to be >2000 Ci/mmol. Rat brain slices indicated selective binding to anterior thalamic nuclei, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. This selective binding was displaced >90% by 300 μM nicotine. Thalamus to cerebellum ratio (>10) was the highest for ¹⁸F-nifrolene with several other regions showing selective binding. In vivo rat PET studies exhibited rapid uptake of ¹⁸F-nifrolene in the brain with specific retention in the thalamus and other brain regions while clearing out from the cerebellum. Thalamus to cerebellum ratio value in the rat was >4. Administration of nicotine caused a rapid decline in the thalamic ¹⁸F-nifrolene suggesting reversible binding to nicotinic receptors. PET imaging studies of ¹⁸F-nifrolene in anesthetized rhesus monkey revealed highest binding in the thalamus followed by regions of the lateral cingulated and temporal cortex. Cerebellum showed the least binding. Thalamus to cerebellum ratio in the monkey brain was >3 at 120 min. These ratios of ¹⁸F-nifrolene are higher than measured for ¹⁸F-nifrolidine and ¹⁸F-nifzetidine. ¹⁸F-Nifrolene thus shows promise as a new PET imaging agent for α4β2 nAChR. Copyright © 2013 Elsevier Inc. All rights reserved.

Two Simple Rules for Improving the Accuracy of Empiric Treatment of Multidrug-Resistant Urinary Tract Infections.

PubMed

Linsenmeyer, Katherine; Strymish, Judith; Gupta, Kalpana

2015-12-01

The emergence of multidrug-resistant (MDR) uropathogens is making the treatment of urinary tract infections (UTIs) more challenging. We sought to evaluate the accuracy of empiric therapy for MDR UTIs and the utility of prior culture data in improving the accuracy of the therapy chosen. The electronic health records from three U.S. Department of Veterans Affairs facilities were retrospectively reviewed for the treatments used for MDR UTIs over 4 years. An MDR UTI was defined as an infection caused by a uropathogen resistant to three or more classes of drugs and identified by a clinician to require therapy. Previous data on culture results, antimicrobial use, and outcomes were captured from records from inpatient and outpatient settings. Among 126 patient episodes of MDR UTIs, the choices of empiric therapy against the index pathogen were accurate in 66 (52%) episodes. For the 95 patient episodes for which prior microbiologic data were available, when empiric therapy was concordant with the prior microbiologic data, the rate of accuracy of the treatment against the uropathogen improved from 32% to 76% (odds ratio, 6.9; 95% confidence interval, 2.7 to 17.1; P < 0.001). Genitourinary tract (GU)-directed agents (nitrofurantoin or sulfa agents) were equally as likely as broad-spectrum agents to be accurate (P = 0.3). Choosing an agent concordant with previous microbiologic data significantly increased the chance of accuracy of therapy for MDR UTIs, even if the previous uropathogen was a different species. Also, GU-directed or broad-spectrum therapy choices were equally likely to be accurate. The accuracy of empiric therapy could be improved by the use of these simple rules. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Laryngospasm With Apparent Aspiration During Sedation With Nitrous Oxide.

PubMed

Babl, Franz E; Grindlay, Joanne; Barrett, Michael Joseph

2015-11-01

Nitrous oxide and oxygen mixture has become increasingly popular for the procedural sedation and analgesia of children in the emergency department. In general, nitrous oxide is regarded as a very safe agent according to large case series. We report a case of single-agent nitrous oxide sedation of a child, complicated by laryngospasm and radiographically confirmed bilateral upper lobe pulmonary opacities. Although rarely reported with parenteral sedative agents, laryngospasm and apparent aspiration has not been previously reported in isolated nitrous oxide sedation. This case highlights that, similar to other sedative agents, nitrous oxide administration also needs to be conducted by staff and in settings in which airway emergencies can be appropriately managed. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Companion diagnostics for the targeted therapy of gastric cancer.

PubMed

Yoo, Changhoon; Park, Young Soo

2015-10-21

Gastric cancer is the fourth most common type of cancer and represents a major cause of cancer-related deaths worldwide. With recent biomedical advances in our understanding of the molecular characteristics of gastric cancer, many genetic alterations have been identified as potential targets for its treatment. Multiple novel agents are currently under development as the demand for active agents that improve the survival of gastric cancer patients constantly increases. Based on lessons from previous trials of targeted agents, it is now widely accepted that the establishment of an optimal diagnostic test to select molecularly defined patients is of equal importance to the development of active agents against targetable genetic alterations. Herein, we highlight the current status and future perspectives of companion diagnostics in the treatment of gastric cancer.

Facile synthesis and biological evaluation of novel symmetrical biphenyls as antitumor agents.

PubMed

Zhang, Jie; Zhang, Yanmin; Pan, Xiaoyan; Wang, Chen; Hu, Zhigang; Wang, Sicen; He, Langchong

2012-03-01

As a continuation to our previous work in developing anticancer agents, eighteen symmetrical biphenyl derivatives structurally related to taspine were synthesized and evaluated in vitro and in vivo. All the compounds were prepared with varied substitutions in the phenyl ring of aniline moiety. The cytotoxicity and anticancer activity of biphenyls was evaluated against various human tumor and normal cell line. Antiproliferative assays indicated that some of them exhibited potent anticancer activity. The potent antiproliferative activity of these compounds against ECV304 suggested that these biphenyls could be served as antiangiogenic agents. The highly active compound (2) also exhibited potent growth inhibition against cancer cell lines in vivo. Our findings demonstrated that these symmetrical biphenyl derivatives would be a promising candidate as novel anticancer agents.

Pattern Analysis in Social Networks with Dynamic Connections

NASA Astrophysics Data System (ADS)

Wu, Yu; Zhang, Yu

In this paper, we explore how decentralized local interactions of autonomous agents in a network relate to collective behaviors. Most existing work in this area models social network in which agent relations are fixed; instead, we focus on dynamic social networks where agents can rationally adjust their neighborhoods based on their individual interests. We propose a new connection evaluation rule called the Highest Weighted Reward (HWR) rule, with which agents dynamically choose their neighbors in order to maximize their own utilities based on the rewards from previous interactions. Our experiments show that in the 2-action pure coordination game, our system will stabilize to a clustering state where all relationships in the network are rewarded with the optimal payoff. Our experiments also reveal additional interesting patterns in the network.

Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

PubMed

Hosoya, Tatsuo; Kuriyama, Satoru; Ohno, Iwao; Kawamura, Tetsuya; Ogura, Makoto; Ikeda, Masato; Ishikawa, Masahiro; Hayashi, Fumihiro; Kanai, Tatsuya; Tomonari, Haruo; Soejima, Michimasa; Akaba, Kiyoaki; Tokudome, Goro; Endo, S; Fukui, A; Gomi, H; Hamaguchi, A; Hanaoka, K; Hara, Y; Hara, Y; Hasegawa, T; Hayakawa, H; Hikida, M; Hirano, K; Horiguchi, M; Hosoya, M; Ichida, K; Imai, T; Ishii, T; Ishikawa, H; Kameda, C; Kasai, T; Kobayashi, A; Kobayashi, H; Kurashige, M; Kusama, Y; Maezawa, H; Maezawa, Y; Maruyama, Y; Matsuda, H; Matsuo, N; Matsuo, T; Miura, Y; Miyajima, M; Miyakawa, M; Miyazaki, Y; Mizuguchi, M; Nakao, M; Nokano, H; Ohkido, I; Ohtsuka, Y; Okada, K; Okamoto, H; Okonogi, H; Saikawa, H; Saito, H; Sekiguchi, C; Suetsugu, Y; Sugano, N; Suzuki, T; Suzuki, T; Takahashi, H; Takahashi, Y; Takamizawa, S; Takane, K; Morita, T; Takazoe, K; Tanaka, H; Tanaka, S; Terawaki, H; Toyoshima, R; Tsuboi, N; Udagawa, T; Ueda, H; Ueda, Y; Uetake, M; Unemura, S; Utsunomiya, M; Utsunomiya, Y; Yamada, T; Yamada, Y; Yamaguchi, Y; Yamamoto, H; Yokoo, T; Yokoyama, K; Yonezawa, H; Yoshida, H; Yoshida, M; Yoshizawa, T

2012-04-01

Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

An Experimental Study of Hafting Adhesives and the Implications for Compound Tool Technology

PubMed Central

Zipkin, Andrew M.; Wagner, Mark; McGrath, Kate; Brooks, Alison S.; Lucas, Peter W.

2014-01-01

Experimental studies of hafting adhesives and modifications to compound tool components can demonstrate the extent to which human ancestors understood and exploited material properties only formally defined by science within the last century. Discoveries of Stone Age hafting adhesives at archaeological sites in Europe, the Middle East, and Africa have spurred experiments that sought to replicate or create models of such adhesives. Most of these studies, however, have been actualistic in design, focusing on replicating ancient applications of adhesive technology. In contrast, this study tested several glues based on Acacia resin within a materials science framework to better understand the effect of each adhesive ingredient on compound tool durability. Using an overlap joint as a model for a compound tool, adhesives formulated with loading agents from a range of particle sizes and mineral compositions were tested for toughness on smooth and rough substrates. Our results indicated that overlap joint toughness is significantly increased by using a roughened joint surface. Contrary to some previous studies, there was no evidence that particle size diversity in a loading agent improved adhesive effectiveness. Generally, glues containing quartz or ochre loading agents in the silt and clay-sized particle class yielded the toughest overlap joints, with the effect of particle size found to be more significant for rough rather than smooth substrate joints. Additionally, no particular ochre mineral or mineral mixture was found to be a clearly superior loading agent. These two points taken together suggest that Paleolithic use of ochre-loaded adhesives and the criteria used to select ochres for this purpose may have been mediated by visual and symbolic considerations rather than purely functional concerns. PMID:25383871

An experimental study of hafting adhesives and the implications for compound tool technology.

PubMed

Zipkin, Andrew M; Wagner, Mark; McGrath, Kate; Brooks, Alison S; Lucas, Peter W

2014-01-01

Experimental studies of hafting adhesives and modifications to compound tool components can demonstrate the extent to which human ancestors understood and exploited material properties only formally defined by science within the last century. Discoveries of Stone Age hafting adhesives at archaeological sites in Europe, the Middle East, and Africa have spurred experiments that sought to replicate or create models of such adhesives. Most of these studies, however, have been actualistic in design, focusing on replicating ancient applications of adhesive technology. In contrast, this study tested several glues based on Acacia resin within a materials science framework to better understand the effect of each adhesive ingredient on compound tool durability. Using an overlap joint as a model for a compound tool, adhesives formulated with loading agents from a range of particle sizes and mineral compositions were tested for toughness on smooth and rough substrates. Our results indicated that overlap joint toughness is significantly increased by using a roughened joint surface. Contrary to some previous studies, there was no evidence that particle size diversity in a loading agent improved adhesive effectiveness. Generally, glues containing quartz or ochre loading agents in the silt and clay-sized particle class yielded the toughest overlap joints, with the effect of particle size found to be more significant for rough rather than smooth substrate joints. Additionally, no particular ochre mineral or mineral mixture was found to be a clearly superior loading agent. These two points taken together suggest that Paleolithic use of ochre-loaded adhesives and the criteria used to select ochres for this purpose may have been mediated by visual and symbolic considerations rather than purely functional concerns.

Electrochemical alkaline Fe(VI) water purification and remediation.

PubMed

Licht, Stuart; Yu, Xingwen

2005-10-15

Fe(VI) is an unusual and strongly oxidizing form of iron, which provides a potentially less hazardous water-purifying agent than chlorine. A novel on-line electrochemical Fe(VI) water purification methodology is introduced. Fe(VI) addition had been a barrier to its effective use in water remediation, because solid Fe(VI) salts require complex (costly) syntheses steps and solutions of Fe(VI) decompose. Online electrochemical Fe(VI) water purification avoids these limitations, in which Fe(VI) is directly prepared in solution from an iron anode as the FeO42- ion, and is added to the contaminant stream. Added FeO42- decomposes, by oxidizing a wide range of water contaminants including sulfides (demonstrated in this study) and other sulfur-containing compounds, cyanides (demonstrated in this study), arsenic (demonstrated in this study), ammonia and other nitrogen-containing compounds (previously demonstrated), a wide range of organics (phenol demonstrated in this study), algae, and viruses (each previously demonstrated).

Xenobiotic Kinetics and Toxicity among Fish and Mammals

DTIC Science & Technology

1992-02-29

infusion studies similar to those described in the previous progress report for rat have been initiated. Due to its limited water solubility and lesser...potency in fish than rat, a solubilizing agent is needed and we have determined that 5% polysorbate 80 in water can be administered to fish without...affecting acetylcholinesterase (ACHE) activity. We have infused three fish and measured AChE activity in brain, heart, and jaw muscle after the fish

Decentralization and the Composition of Public Expenditures

DTIC Science & Technology

2012-01-01

decentralized governance and expenditure composition by means of a distance-sensitive representative agent model. Then we estimate the impact of fiscal...countries with regards to population age structure. We are not certain of what effects that may have in our estimates , but previous studies have found find...variables to estimate a scalar value for g(xβ), which then is multiplied to each variables coefficient. For this, we choose the mean values of the

Dual-energy contrast-enhanced spectral mammography (CESM).

PubMed

Daniaux, Martin; De Zordo, Tobias; Santner, Wolfram; Amort, Birgit; Koppelstätter, Florian; Jaschke, Werner; Dromain, Clarisse; Oberaigner, Willi; Hubalek, Michael; Marth, Christian

2015-10-01

Dual-energy contrast-enhanced mammography is one of the latest developments in breast care. Imaging with contrast agents in breast cancer was already known from previous magnetic resonance imaging and computed tomography studies. However, high costs, limited availability-or high radiation dose-led to the development of contrast-enhanced spectral mammography (CESM). We reviewed the current literature, present our experience, discuss the advantages and drawbacks of CESM and look at the future of this innovative technique.

Exploratory Development of Corrosion Inhibiting Primers

DTIC Science & Technology

1977-07-01

Phenolic Hardener From previous studies, phenol formaldehyde resins of the novolac (two-step) type have given superior properties when used to cure epoxy...novolacs and three resole (one-step) type phenol- formaldehyde resins which also perform as epoxide curing agents. First, Model #1, as de;crihed in Section...results. Varcum 4326 resin was chosen at this stage for further use with the model systems. It is a low molecular weight phenol- formaldehyde resin used

Decontamination of Subway Infrastructure Materials ...

EPA Pesticide Factsheets

Report This report provides the results of an assessment to determine the decontamination efficacy of methyl bromide (MB) fumigant in inactivating Bacillus anthracis (B.a.; causative agent for anthrax) spores on materials typically found in subway system infrastructure. To facilitate future decontaminations employing MB in a subway environment, this investigation focused on finding efficacious conditions when using MB at temperatures that may be encountered in an underground subway system (i.e., temperatures lower than used in previous studies).

Bacterial diversity indicates dietary overlap among bats of different feeding habits.

PubMed

Banskar, Sunil; Mourya, Devendra T; Shouche, Yogesh S

2016-01-01

Bats are among the most conspicuous mammals with extraordinary adaptations. They play a key role in the ecosystem. Frugivorous bats are important seed dispersing agents that help in maintaining forest tree diversity, while insectivorous bats are natural insect pest control agents. Several previous reports suggest that bats are reservoir of viruses; nonetheless their bacterial counterparts are relatively less explored. The present study describes the microbial diversity associated with the intestine of bats from different regions of India. Our observations stipulate that there is substantial sharing of bacterial communities between the insectivorous and frugivorous bats, which signifies fairly large dietary overlap. We also observed the presence of higher abundance of Mycoplasma in Cynopterus species of bats, indicating possible Mycoplasma infection. Considering the scarcity of literature related to microbial communities of bat intestinal tract, this study can direct future microbial diversity studies in bats with reference to their dietary habits, host-bacteria interaction and zoonosis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Positive stereotypes, negative outcomes: Reminders of the positive components of complementary gender stereotypes impair performance in counter-stereotypical tasks.

PubMed

Kahalon, Rotem; Shnabel, Nurit; Becker, Julia C

2018-04-01

Gender stereotypes are complementary: Women are perceived to be communal but not agentic, whereas men are perceived to be agentic but not communal. The present research tested whether exposure to reminders of the positive components of these gender stereotypes can lead to stereotype threat and subsequent performance deficits on the complementary dimension. Study 1 (N = 116 female participants) revealed that compared to a control/no-stereotype condition, exposure to reminders of the stereotype about women's communality (but not to reminders of the stereotype about women's beauty) impaired women's math performance. In Study 2 (N = 86 male participants), reminders of the stereotype about men's agency (vs. a control/no-stereotype condition) impaired men's performance in a test of socio-emotional abilities. Consistent with previous research on stereotype threat, in both studies the effect was evident among participants with high domain identification. These findings extend our understanding of the potentially adverse implications of seemingly positive gender stereotypes. © 2018 The British Psychological Society.

Inhibition of heterologously expressed cystic fibrosis transmembrane conductance regulator Cl− channels by non-sulphonylurea hypoglycaemic agents

PubMed Central

Cai, Z; Lansdell, K A; Sheppard, D N

1999-01-01

Hypoglycaemia-inducing sulphonylureas, such as glibenclamide, inhibit cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels. In search of modulators of CFTR, we investigated the effects of the non-sulphonylurea hypoglycaemic agents meglitinide, repaglinide, and mitiglinide (KAD-1229) on CFTR Cl− channels in excised inside-out membrane patches from C127 cells expressing wild-type human CFTR. When added to the intracellular solution, meglitinide and mitiglinide inhibited CFTR Cl− currents with half-maximal concentrations of 164±19 μM and 148±36 μM, respectively. However, repaglinide only weakly inhibited CFTR Cl− currents. To understand better how non-sulphonylurea hypoglycaemic agents inhibit CFTR, we studied single channels. Channel blockade by both meglitinide and mitiglinide was characterized by flickery closures and a significant decrease in open probability (Po). In contrast, repaglinide was without effect on either channel gating or Po, but caused a small decrease in single-channel current amplitude. Analysis of the dwell time distributions of single channels indicated that both meglitinide and mitiglinide greatly decreased the open time of CFTR. Mitiglinide-induced channel closures were about 3-fold longer than those of meglitinide. Inhibition of CFTR by meglitinide and mitiglinide was voltage-dependent: at positive voltages channel blockade was relieved. The data demonstrate that non-sulphonylurea hypoglycaemic agents inhibit CFTR. This indicates that these agents have a wider specificity of action than previously recognized. Like glibenclamide, non-sulphonylurea hypoglycaemic agents may inhibit CFTR by occluding the channel pore and preventing Cl− permeation. PMID:10498841

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.

Seldon v.3.0

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

Berry, Nina; Ko, Teresa; Shneider, Max

Seldon is an agent-based social simulation framework that uniquely integrates concepts from a variety of different research areas including psychology, social science, and agent-based modeling. Development has been taking place for a number of years, previously focusing on gang and terrorist recruitment. The toolkit consists of simple agents (individuals) and abstract agents (groups of individuals representing social/institutional concepts) that interact according to exchangeable rule sets (i.e. linear attraction, linear reinforcement). Each agent has a set of customizable attributes that get modified during the interactions. Interactions create relationships between agents, and each agent has a maximum amount of relationship energy thatmore » it can expend. As relationships evolve, they form multiple levels of social networks (i.e. acquaintances, friends, cliques) that in turn drive future interactions. Agents can also interact randomly if they are not connected through a network, mimicking the chance interactions that real people have in everyday life. We are currently integrating Seldon with the cognitive framework (also developed at Sandia). Each individual agent has a lightweight cognitive model that is created automatically from textual sources. Cognitive information is exchanged during interactions, and can also be injected into a running simulation. The entire framework has been parallelized to allow for larger simulations in an HPC environment. We have also added more detail to the agents themselves (a"Big Five" personality model) and their interactions (an enhanced relationship model) for a more realistic representation.« less

Tracking dynamic team activity

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

Tambe, M.

1996-12-31

AI researchers are striving to build complex multi-agent worlds with intended applications ranging from the RoboCup robotic soccer tournaments, to interactive virtual theatre, to large-scale real-world battlefield simulations. Agent tracking - monitoring other agent`s actions and inferring their higher-level goals and intentions - is a central requirement in such worlds. While previous work has mostly focused on tracking individual agents, this paper goes beyond by focusing on agent teams. Team tracking poses the challenge of tracking a team`s joint goals and plans. Dynamic, real-time environments add to the challenge, as ambiguities have to be resolved in real-time. The central hypothesismore » underlying the present work is that an explicit team-oriented perspective enables effective team tracking. This hypothesis is instantiated using the model tracing technology employed in tracking individual agents. Thus, to track team activities, team models are put to service. Team models are a concrete application of the joint intentions framework and enable an agent to track team activities, regardless of the agent`s being a collaborative participant or a non-participant in the team. To facilitate real-time ambiguity resolution with team models: (i) aspects of tracking are cast as constraint satisfaction problems to exploit constraint propagation techniques; and (ii) a cost minimality criterion is applied to constrain tracking search. Empirical results from two separate tasks in real-world, dynamic environments one collaborative and one competitive - are provided.« less

Fusarium proliferatum as an agent of disseminated infection in an immunosuppressed patient.

PubMed Central

Summerbell, R C; Richardson, S E; Kane, J

1988-01-01

Fusarium proliferatum was reported as the agent of a fatal disseminated infection in a child with lymphoblastic leukemia. The fungus has not been reported previously to cause disease in humans, but it is closely related to the known opportunistic pathogen F. verticillioides. It was distinguished by the production of clavate microconidia in chains from proliferating phialides. Resistance to amphotericin B and flucytosine in vitro was shown. Images PMID:3422646

What matters when judging intentionality-moral content or normative status? Testing the rational scientist model of the side-effect.

PubMed

Papadopoulos, C; Hayes, B K

2018-06-01

Previous work has demonstrated a "side-effect effect," such that intentionality is more likely to be attributed to agents who bring about negatively valenced as opposed to positively valenced side effects. The rational-scientist model explains this by suggesting that norm-violating side effects are more informative for inferring intentionality than norm-conforming side effects. In the present study we reexamined this account, addressing limitations of previous empirical tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence and norm status were manipulated factorially, enabling an examination of the impact of norm status on intentionality judgments in both positively and negatively valenced side effects. Additionally, the impact of side-effect norm status on the perceived valences of side effects and agents was examined. Effects of norm status were found for both positive and negative side effects. Violation of an ostensibly neutral norm led to negative perceptions of the side effect. However, a norm status effect on intentionality judgments persisted when these effects were controlled. These results support the view that the side-effect effect is the result of the rational use of social-cognitive evidence.

Contextual Factors Among Indiscriminate or Large Attacks on Food or Water Supplies, 1946-2015

PubMed Central

Hunter, Paul R.

2016-01-01

This research updates previous inventories of malicious attacks on food and water and includes data from 1946 through mid-2015. A systematic search of news reports, databases, and previous inventories of poisoning events was undertaken. Incidents that threatened or were intended to achieve direct harm to humans and that were either relatively large (more than 4 victims) or indiscriminate in intent or realization were included. Agents could be chemical, biological, or radionuclear. Reports of candidate incidents were subjected to systematic inclusion and exclusion criteria as well as validity analysis (not always clearly undertaken in previous inventories of such attacks). We summarize contextual aspects of the attacks that may be important for scenario prioritization, modelling, and defensive preparedness. Opportunity, and particularly access to dangerous agents, is key to most realized attacks. The most common motives and relative success rate in causing harm were very different between food and water attacks. The likelihood that people were made ill or died also varied by food or water mode and according to motive and opportunity for delivery of the hazardous agent. Deaths and illness associated with attacks during food manufacture and prior to sale have been fewer than those in some other contexts. Valuable opportunities for food defense improvements are identified in other contexts, especially food prepared in private or community settings. PMID:26889577

Anesthetic Agent-Specific Effects on Synaptic Inhibition

PubMed Central

MacIver, M. Bruce

2014-01-01

Background Anesthetics enhance gamma-aminobutyric acid (GABA)-mediated inhibition in the central nervous system. Different agents have been shown to act on tonic versus synaptic GABA receptors to different degrees, but it remains unknown whether different forms of synaptic inhibition are also differentially engaged. With this in mind, we tested the hypothesis that different types of GABA-mediated synapses exhibit different anesthetic sensitivities. The present study compared effects produced by isoflurane, halothane, pentobarbital, thiopental and propofol on paired pulse GABAA receptor-mediated synaptic inhibition. Effects on glutamate-mediated facilitation were also studied. Methods Synaptic responses were measured in rat hippocampal brain slices. Orthodromic paired pulse stimulation was used to assess anesthetic effects on either glutamate-mediated excitatory inputs or GABA-mediated inhibitory inputs to CA1 neurons. Antidromic stimulation was used to assess anesthetic effects on CA1 background excitability. Agents were studied at equi-effective concentrations for population spike depression to compare their relative degree of effect on synaptic inhibition. Results Differing degrees of anesthetic effect on paired pulse facilitation at excitatory glutamate synapses were evident, and blocking GABA inhibition revealed a previously unseen presynaptic action for pentobarbital. Although all five anesthetics depressed synaptically evoked excitation of CA1 neurons, the involvement of enhanced GABA-mediated inhibition differed considerably among agents. Single pulse inhibition was enhanced by propofol, thiopental and pentobarbital, but only marginally by halothane and isoflurane. In contrast, isoflurane enhanced paired pulse inhibition strongly, as did thiopental, but propofol, pentobarbital and halothane were less effective. Conclusions These observations support the idea that different GABA synapses use receptors with differing subunit compositions, and that anesthetics exhibit differing degrees of selectivity for these receptors. The differing anesthetic sensitivities seen in the present study, at glutamate and GABA synapses, help explain the unique behavioral/clinical profiles produced by different classes of anesthetics, and indicate that there are selective targets for new agent development. PMID:24977633

Anesthetic agent-specific effects on synaptic inhibition.

PubMed

MacIver, M Bruce

2014-09-01

Anesthetics enhance γ-aminobutyric acid (GABA)-mediated inhibition in the central nervous system. Different agents have been shown to act on tonic versus synaptic GABA receptors to different degrees, but it remains unknown whether different forms of synaptic inhibition are also differentially engaged. With this in mind, we tested the hypothesis that different types of GABA-mediated synapses exhibit different anesthetic sensitivities. The present study compared effects produced by isoflurane, halothane, pentobarbital, thiopental, and propofol on paired-pulse GABAA receptor-mediated synaptic inhibition. Effects on glutamate-mediated facilitation were also studied. Synaptic responses were measured in rat hippocampal brain slices. Orthodromic paired-pulse stimulation was used to assess anesthetic effects on either glutamate-mediated excitatory inputs or GABA-mediated inhibitory inputs to CA1 neurons. Antidromic stimulation was used to assess anesthetic effects on CA1 background excitability. Agents were studied at equieffective concentrations for population spike depression to compare their relative degree of effect on synaptic inhibition. Differing degrees of anesthetic effect on paired-pulse facilitation at excitatory glutamate synapses were evident, and blocking GABA inhibition revealed a previously unseen presynaptic action for pentobarbital. Although all 5 anesthetics depressed synaptically evoked excitation of CA1 neurons, the involvement of enhanced GABA-mediated inhibition differed considerably among agents. Single-pulse inhibition was enhanced by propofol, thiopental, and pentobarbital, but only marginally by halothane and isoflurane. In contrast, isoflurane enhanced paired-pulse inhibition strongly, as did thiopental, but propofol, pentobarbital, and halothane were less effective. These observations support the idea that different GABA synapses use receptors with differing subunit compositions and that anesthetics exhibit differing degrees of selectivity for these receptors. The differing anesthetic sensitivities seen in the present study, at glutamate and GABA synapses, help explain the unique behavioral/clinical profiles produced by different classes of anesthetics and indicate that there are selective targets for new agent development.

Mechanisms of modafinil: A review of current research

PubMed Central

Gerrard, Paul; Malcolm, Robert

2007-01-01

The novel wake-promoting agent modafinil has been in use for the treatment of several sleep disorders for a few years and is now undergoing clinical trials for its use in the treatment of stimulant addiction, but its primary mechanism of action remains elusive. Previous laboratory studies have shown that modafinil has antioxidative and neuroprotective effects, which have not previously been suggested to be related to its wake-promoting effects. However, recent research indicates that free radicals may be related to sleep induction as well as cellular damage, suggesting that a common target of action may mediate modafinil’s ability to oppose both of these effects. In this review we summarize and discuss previously published research on modafinil’s neural, cytoprotective, and cognitive effects, and we propose possible primary biochemical targets that could underlie the effects of modafinil observed in these studies. We also suggest neurocognitive mechanisms responsible for modafinil’s cognitive enhancing effects and its therapeutic potential in the treatment of stimulant addiction. PMID:19300566

Eye tracking uncovered great apes' ability to anticipate that other individuals will act according to false beliefs.

PubMed

Kano, Fumihiro; Krupenye, Christopher; Hirata, Satoshi; Call, Josep

2017-01-01

Using a novel eye-tracking test, we recently showed that great apes anticipate that other individuals will act according to false beliefs. This finding suggests that, like humans, great apes understand others' false beliefs, at least in an implicit way. One key question raised by our study is why apes have passed our tests but not previous ones. In this article, we consider this question by detailing the development of our task. We considered 3 major differences in our task compared with the previous ones. First, we monitored apes' eye movements, and specifically their anticipatory looks, to measure their predictions about how agents will behave. Second, we adapted our design from an anticipatory-looking false belief test originally developed for human infants. Third, we developed novel test scenarios that were specifically designed to capture the attention of our ape participants. We then discuss how each difference may help explain differences in performance on our task and previous ones, and finally propose some directions for future studies.

Leishmania species identification using FTA card sampling directly from patients' cutaneous lesions in the state of Lara, Venezuela.

PubMed

Kato, Hirotomo; Watanabe, Junko; Mendoza Nieto, Iraida; Korenaga, Masataka; Hashiguchi, Yoshihisa

2011-10-01

A molecular epidemiological study was performed using FTA card materials directly sampled from lesions of patients with cutaneous leishmaniasis (CL) in the state of Lara, Venezuela, where causative agents have been identified as Leishmania (Viannia) braziliensis and L. (Leishmania) venezuelensis in previous studies. Of the 17 patients diagnosed with CL, Leishmania spp. were successfully identified in 16 patients based on analysis of the cytochrome b gene and rRNA internal transcribed spacer sequences. Consistent with previous findings, seven of the patients were infected with L. (V.) braziliensis. However, parasites from the other nine patients were genetically identified as L. (L.) mexicana, which differed from results of previous enzymatic and antigenic analyses. These results strongly suggest that L. (L.) venezuelensis is a variant of L. (L.) mexicana and that the classification of L. (L.) venezuelensis should be reconsidered. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Engaging adolescents in a computer-based weight management program: avatars and virtual coaches could help.

PubMed

LeRouge, Cynthia; Dickhut, Kathryn; Lisetti, Christine; Sangameswaran, Savitha; Malasanos, Toree

2016-01-01

This research focuses on the potential ability of animated avatars (a digital representation of the user) and virtual agents (a digital representation of a coach, buddy, or teacher) to deliver computer-based interventions for adolescents' chronic weight management. An exploration of the acceptance and desire of teens to interact with avatars and virtual agents for self-management and behavioral modification was undertaken. The utilized approach was inspired by community-based participatory research. Data was collected from 2 phases: Phase 1) focus groups with teens, provider interviews, parent interviews; and Phase 2) mid-range prototype assessment by teens and providers. Data from all stakeholder groups expressed great interest in avatars and virtual agents assisting self-management efforts. Adolescents felt the avatars and virtual agents could: 1) reinforce guidance and support, 2) fit within their lifestyle, and 3) help set future goals, particularly after witnessing the effect of their current behavior(s) on the projected physical appearance (external and internal organs) of avatars. Teens wanted 2 virtual characters: a virtual agent to act as a coach or teacher and an avatar (extension of themselves) to serve as a "buddy" for empathic support and guidance and as a surrogate for rewards. Preferred modalities for use include both mobile devices to accommodate access and desktop to accommodate preferences for maximum screen real estate to support virtualization of functions that are more contemplative and complex (e.g., goal setting). Adolescents expressed a desire for limited co-user access, which they could regulate. Data revealed certain barriers and facilitators that could affect adoption and use. The current study extends the support of teens, parents, and providers for adding avatars or virtual agents to traditional computer-based interactions. Data supports the desire for a personal relationship with a virtual character in support of previous studies. The study provides a foundation for further work in the area of avatar-driven motivational interviewing. This study provides evidence supporting the use of avatars and virtual agents, designed using participatory approaches, to be included in the continuum of care. Increased probability of engagement and long-term retention of overweight, obese adolescent users and suggests expanding current chronic care models toward more comprehensive, socio-technical representations. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Chronic kidney disease of unknown etiology in Sri Lanka

PubMed Central

2016-01-01

Introduction In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1–22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. Methods A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Results Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Discussion Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization. PMID:27399161

Chronic kidney disease of unknown etiology in Sri Lanka.

PubMed

Rajapakse, Senaka; Shivanthan, Mitrakrishnan Chrishan; Selvarajah, Mathu

2016-07-01

In the last two decades, chronic kidney disease of unknown etiology (CKDu) has emerged as a significant contributor to the burden of chronic kidney disease (CKD) in rural Sri Lanka. It is characterized by the absence of identified causes for CKD. The prevalence of CKDu is 15.1-22.9% in some Sri Lankan districts, and previous research has found an association with farming occupations. A systematic literature review in Pubmed, Embase, Scopus, and Lilacs databases identified 46 eligible peer-reviewed articles and one conference abstract. Geographical mapping indicates a relationship between CKDu and agricultural irrigation water sources. Health mapping studies, human biological studies, and environment-based studies have explored possible causative agents. Most studies focused on likely causative agents related to agricultural practices, geographical distribution based on the prevalence and incidence of CKDu, and contaminants identified in drinking water. Nonetheless, the link between agrochemicals or heavy metals and CKDu remains to be established. No definitive cause for CKDu has been identified. Evidence to date suggests that the disease is related to one or more environmental agents, however pinpointing a definite cause for CKDu is challenging. It is plausible that CKDu is multifactorial. No specific guidelines or recommendations exist for treatment of CKDu, and standard management protocols for CKD apply. Changes in agricultural practices, provision of safe drinking water, and occupational safety precautions are recommended by the World Health Organization.

Serological studies on the infection of dogs in Ontario with Borrelia burgdorferi, the etiological agent of Lyme disease

PubMed Central

Artsob, Harvey; Barker, Ian K.; Fister, Richard; Sephton, Gregory; Dick, Daryl; Lynch, John A.; Key, Doug

1993-01-01

A serological study was undertaken to determine whether dogs in Ontario are being exposed to Borrelia burgdorferi, the etiological agent of Lyme disease. This study consisted of a survey of randomly selected dogs and testing of diagnostic submissions from candidate Lyme disease cases. The survey of 1,095 dogs, bled between January 1988 and August 1989, revealed a total of 65 (5.9%) enzyme-linked immunosorbent assay (ELISA) reactors, of which 22 had immuno-fluorescent antibody assay (IFA) titers ≥1:32. All but one of the IFA-positive and 10 of the ELISA-positive, IFA-negative sera were further tested by western blot. Eight western blot positive and three equivocal reactors were obtained. Three of the eight confirmed reactors had visited areas known to be endemic for Lyme disease, leaving five reactors that might have been infected in previously undocumented areas for B. burgdorferi activity in Ontario. Diagnostic submissions of sera from 223 dogs were received between August 1987 and February 1992. Test results revealed 21 (9.4%) IFA reactors, of which only six had significant titers (≥1:256) and were reactive by an immunodot Borrelia test. All six dogs had travelled to known Lyme endemic areas. Based on results obtained from this study, it seems likely that the agent of Lyme disease is not widespread in Ontario. PMID:17424284

Comparative Safety of Antidepressant Agents for Children and Adolescents Regarding Suicidal Acts

PubMed Central

Schneeweiss, Sebastian; Patrick, Amanda R.; Solomon, Daniel H.; Dormuth, Colin R.; Miller, Matt; Mehta, Jyotsna; Lee, Jennifer C.; Wang, Philip S.

2010-01-01

OBJECTIVE The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents. METHODS We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antidepressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death. RESULTS Of 20 906 children who initiated antidepressant therapy, 16 774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9–30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54–1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46–2.43]), paroxetine (RR: 0.80 [95% CI: 0.47–1.37]), and sertraline (RR: 1.02 [95% CI: 0.56–1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43–2.00]). CONCLUSION Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants. PMID:20385637

Tunable Semiconducting Polymer Nanoparticles with INDT-Based Conjugated Polymers for Photoacoustic Molecular Imaging.

PubMed

Stahl, Thomas; Bofinger, Robin; Lam, Ivan; Fallon, Kealan J; Johnson, Peter; Ogunlade, Olumide; Vassileva, Vessela; Pedley, R Barbara; Beard, Paul C; Hailes, Helen C; Bronstein, Hugo; Tabor, Alethea B

2017-06-21

Photoacoustic imaging combines both excellent spatial resolution with high contrast and specificity, without the need for patients to be exposed to ionizing radiation. This makes it ideal for the study of physiological changes occurring during tumorigenesis and cardiovascular disease. In order to fully exploit the potential of this technique, new exogenous contrast agents with strong absorbance in the near-infrared range, good stability and biocompatibility, are required. In this paper, we report the formulation and characterization of a novel series of endogenous contrast agents for photoacoustic imaging in vivo. These contrast agents are based on a recently reported series of indigoid π-conjugated organic semiconductors, coformulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, to give semiconducting polymer nanoparticles of about 150 nm diameter. These nanoparticles exhibited excellent absorption in the near-infrared region, with good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients of up to three times higher than those previously reported. The absorption maximum is conveniently located in the spectral region of low absorption of chromophores within human tissue. Using the most promising semiconducting polymer nanoparticle, we have demonstrated wavelength-dependent differential contrast between vasculature and the nanoparticles, which can be used to unambiguously discriminate the presence of the contrast agent in vivo.

Does Environmental Knowledge Inhibit Hominin Dispersal?

PubMed

Wren, Colin D; Costopoulos, Andre

2015-07-01

We investigated the relationship between the dispersal potential of a hominin population, its local-scale foraging strategies, and the characteristics of the resource environment using an agent-based modeling approach. In previous work we demonstrated that natural selection can favor a relatively low capacity for assessing and predicting the quality of the resource environment, especially when the distribution of resources is highly clustered. That work also suggested that the more knowledge foraging populations had about their environment, the less likely they were to abandon the landscape they know and disperse into novel territory. The present study gives agents new individual and social strategies for learning about their environment. For both individual and social learning, natural selection favors decreased levels of environmental knowledge, particularly in low-heterogeneity environments. Social acquisition of detailed environmental knowledge results in crowding of agents, which reduces available reproductive space and relative fitness. Agents with less environmental knowledge move away from resource clusters and into areas with more space available for reproduction. These results suggest that, rather than being a requirement for successful dispersal, environmental knowledge strengthens the ties to particular locations and significantly reduces the dispersal potential as a result. The evolved level of environmental knowledge in a population depends on the characteristics of the resource environment and affects the dispersal capacity of the population.

Assessing the effects of hydrogen peroxide bleaching agent on the shear bond strength of orthodontic brackets.

PubMed

Andrighetto, Augusto Ricardo; de Leão Withers, Eduardo Henrique; Grando, Karlos Giovani; Ambrosio, Aldrieli Regina; Shimizu, Roberto Hideo; Melo, Ana Cláudia

2016-01-01

Tooth bleaching is, today, one of the most widespread cosmetic treatments in dental practice,  so it is important to determine whether it can interfere with orthodontic bonding or not. The aim of this study was to assess the in vitro effects of 35% hydrogen peroxide bleaching agent on the shear bond strength of orthodontic brackets. Forty-five upper bicuspids were divided into three groups (n = 15). In the control Group (C), the brackets were bonded without previous bleaching treatment. Group 1 (G1) was treated with 35% hydrogen peroxide bleaching agent 24 h before bracket bonding. Group 2 was also bleached, and the brackets were bonded after 30 days. The shear bond strength of the brackets was measured using an EMIC machine, and the results were analyzed by ANOVA. There were no statistically significant differences between the three groups (P > 0.05), with Group C showing a mean bond strength of 9.72 ± 2.63 MPa, G1 of 8.09 ± 2.63 MPa, and G2 of 11.15 ± 4.42 MPa. It was possible to conclude that 35% hydrogen peroxide bleaching agent does not affect the shear strength of orthodontic brackets bonded 24 h and 30 days after bleaching.

Age-Related Inducibility of Carboxylesterases by the Antiepileptic Agent Phenobarbital and Implications in Drug Metabolism and Lipid Accumulation 1, 2

PubMed Central

Xiao, Da; Chen, Yi-Tzai; Yang, Dongfang; Yan, Bingfang

2014-01-01

Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids. PMID:22513142

Modulation of K(ATP) currents in rat ventricular myocytes by hypoxia and a redox reaction.

PubMed

Yan, Xi-Sheng; Ma, Ji-Hua; Zhang, Pei-Hua

2009-10-01

The present study investigated the possible regulatory mechanisms of redox agents and hypoxia on the K(ATP) current (I(KATP)) in acutely isolated rat ventricular myocytes. Single-channel and whole-cell patch-clamp techniques were used to record the K(ATP) current (I(KATP)) in acutely isolated rat ventricular myocytes. Oxidized glutathione (GSSG, 1 mmol/L) increased the I(KATP), while reduced glutathione (GSH, 1 mmol/L) could reverse the increased I(KATP) during normoxia. To further corroborate the effect of the redox agent on the K(ATP) channel, we employed the redox couple DTT (1 mmol/L)/H2O2 (0.3, 0.6, and 1 mmol/L) and repeated the previous processes, which produced results similar to the previous redox couple GSH/GSSG during normoxia. H2O2 increased the I(KATP) in a concentration dependent manner, which was reversed by DTT (1 mmol/L). In addition, our results have shown that 15 min of hypoxia increased the I(KATP), while GSH (1 mmol/L) could reverse the increased I(KATP). Furthermore, in order to study the signaling pathways of the I(KATP) augmented by hypoxia and the redox agent, we applied a protein kinase C(PKC) inhibitor bisindolylmaleimide VI (BIM), a protein kinase G(PKG) inhibitor KT5823, a protein kinase A (PKA) inhibitor H-89, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitors KN-62 and KN-93. The results indicated that BIM, KT5823, KN-62, and KN-93, but not H-89, inhibited the I(KATP) augmented by hypoxia and GSSG; in addition, these results suggest that the effects of both GSSG and hypoxia on K(ATP) channels involve the activation of the PKC, PKG, and CaMK II pathways, but not the PKA pathway. The present study provides electrophysiological evidence that hypoxia and the oxidizing reaction are closely related to the modulation of I(KATP).

Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine, and atropine effect in cysteamine lesions in totally gastrectromized rats: a model for cytoprotective studies.

PubMed

Sikirić, P; Mikus, D; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Perić, J; Konjevoda, P; Perović, D; Jurina, L; Hanzevacki, M; Separović, J; Gjurasin, M; Jadrijević, S; Jelovac, N; Miklić, P; Buljat, G; Marović, A

1997-05-01

A superior effectiveness in various lesion assays was noted for the novel pentadecapeptide BPC 157, originated from human gastric juice protein (BPC) and claimed to be a cytoprotective agent. From this viewpoint, as a previously untreated experimental improvement to create an acid-free environmental for cytoprotection studies, total gastrectomy was done 24 hr before the ulcerogenic procedure. In the absence of stomach and gastric acid, the damaging effects of cysteamine (400 mg/kg subcutaneously, death 24 hr thereafter), to date thought to be an acid-related duodenal ulcerogen, and the BPC 157 cytoprotective effect (10 microg or 10 ng/kg intraperitoneally) were further challenged. BPC 157 was compared with reference agents [cimetidine (50), ranitidine (10), omeprazole (10), bromocriptine (10) and atropine (10) (mg/kg intraperitoneally, 1 hr before cysteamine] known to be also cytoprotective. In naive rats, with intact stomach, all of them showed a strong beneficial effect. Interestingly, in gastrectomized animals, the application of BPC 157 or the reference agents before cysteamine significantly prevented the otherwise severe duodenal lesion development noted in the control gastrectomized cysteamine rats. In groups without cysteamine, no lesions were noted (laparotomy, gastrectomy only, 24 or 48 hr postsurgical period), nor was lesion potentiation seen in cysteamine-treated laparotomized animals. In summary, these findings--equal damaging effect of cysteamine and equal protection of pentadecapeptide BPC 157 and reference agents in gastrectomized and rats with intact stomach--seem to be particularly relevant for a cytoprotective viewpoint. Without a stomach, the cysteamine damaging effect was convincingly defined as an essential gastric acid-independent injury (analogous to ethanol gastric lesions). Likewise, a high "cytoprotective capacity," apparently acid independent, common for all tested agents (novel pentadecapeptide BPC 157, cimetidine, ranitidine, omeprazole and atropine) could be clearly stressed.

Social Validation Influences Individuals' Judgments about Ownership.

PubMed

Casiraghi, Leandro; Faigenbaum, Gustavo; Chehtman, Alejandro; Sigman, Mariano

2018-01-01

In all domains, from informal to formal, there are conflicts about property and ownership which resolution demands consideration of alleged claims from more than one party. In this work we asked adults ( N = 359) to judge cases in which a character held a property claim over an item, but is challenged by a second character who holds a different, subsequent claim over it. The specific goal of this work is to investigate how the resolution of such conflicts depends on the social endorsement of ownership claims. To achieve this aim, we designed variations of conflictive situations over property in which we manipulated details regarding the knowledge of the second agent of other third-parties about the first agent's actions. In essence, our questions were: if an agent claims ownership of something which has a previous property claim on (1) does it matter whether said agent knew of the first's agent actions or not? And (2) does it matter whether third parties were aware or notified of the first one's claim? The results confirm that adults resolve the settling of property rights based not only on the nature of ownership claims but also on the social acknowledgment of such claims, in accordance with what is stipulated in legal systems worldwide. Participants considered the second character in the stories to hold a lesser right over the object under dispute when she knew of the first character's claim. Participants also considered that the first character's claim was reinforced when there were witnesses for her actions, but not when third parties were merely communicated of such actions. This is the first study to our knowledge that studies how social validation of ownership claims drives adults' judgments on property claims.

The efficacy of the direct clinical intervention for infectious diseases by a pediatric infectious disease specialist in the pediatric ward of a tertiary medical facility without a pediatric antimicrobial stewardship program.

PubMed

Hoshina, T; Yamamoto, N; Ogawa, M; Nakamoto, T; Kusuhara, K

2017-08-01

Antimicrobial stewardship programs (ASPs) have been introduced in most hospital complexes; however, they are not always useful for pediatric patients. The aim of this study is to investigate the efficacy of direct clinical intervention for infectious diseases by a pediatric infectious disease specialist in a tertiary medical facility without pediatric ASP. This retrospective study included 1,821 patients who were hospitalized in the pediatric ward of a large metropolitan hospital from 2010 to 2015. The clinical course, the use of intravenous antimicrobial agents and the results of a microbiological analysis were compared between the period after the beginning of direct intervention by the specialist (post-intervention period) and the previous period (pre-intervention period). In the post-intervention period, the proportion of the patients who received intravenous antimicrobial agents, the number of antimicrobial agents used for each episode, and the proportion of episodes in which an antimicrobial agent was re-administrated were significantly lower (P = 0.006, P = 0.004, P = 0.036, respectively), and the duration of antimicrobial treatment was significantly shorter (P < 0.001). In addition, narrower spectrum antimicrobial agents were used, and the incidence of meropenem-sensitive Pseudomonas aeruginosa significantly increased (P = 0.037) in the post-intervention period. There was no change of mortality between the two periods. Direct clinical intervention by a pediatric infectious diseases specialist is useful for the treatment of infectious diseases in the pediatric ward of a tertiary medical facility without a pediatric ASP. The creation of a pediatric ASP is recommended in hospital complexes.

A novel compound DT-010 protects against doxorubicin-induced cardiotoxicity in zebrafish and H9c2 cells by inhibiting reactive oxygen species-mediated apoptotic and autophagic pathways.

PubMed

Tang, Fan; Zhou, Xinhua; Wang, Liang; Shan, Luchen; Li, Chuwen; Zhou, Hefeng; Lee, Simon Ming-Yuen; Hoi, Maggie Pui-Man

2018-02-05

Doxorubicin (Dox) is an effective anti-cancer agent but limited by its cardiotoxicity, thus the search for pharmacological agents for enhancing anti-cancer activities and protecting against cardiotoxicity has been a subject of great interest. We have previously reported the synergistic anti-cancer effects of a novel compound DT-010. In the present study, we further investigated the cardioprotective effects of DT-010 in zebrafish embryos in vivo and the molecular underlying mechanisms in H9c2 cardiomyocytes in vitro. We showed that DT-010 prevented the Dox-induced morphological distortions in the zebrafish heart and the associated cardiac impairments, and especially improved ventricular functions. By using H9c2 cells model, we showed that DT-010 directly inhibited the generation of reactive oxygen species by Dox and protected cell death and cellular damage. We further observed that DT-010 protected against Dox-induced myocardiopathy via inhibiting downstream molecular pathways in response to oxidative stress, including reactive oxygen species-mediated MAPK signaling pathways ERK and JNK, and apoptotic pathways involving the activation of caspase 3, caspase 7, and PARP signaling. Recent studies also suggest the importance of alterations in cardiac autophagy in Dox cardiotoxicity. We further showed that DT-010 could inhibit the induction of autophagosomes formation by Dox via regulating the upstream Akt/AMPK/mTOR signaling. Since Dox-induced cardiotoxicity is multifactorial, our results suggest that multi-functional agent such as DT-010 might be an effective therapeutic agent for combating cardiotoxicity associated with chemotherapeutic agents such as Dox. Copyright © 2017 Elsevier B.V. All rights reserved.

Generation of Rayleigh waves into mortar and concrete samples.

PubMed

Piwakowski, B; Fnine, Abdelilah; Goueygou, M; Buyle-Bodin, F

2004-04-01

The paper deals with a non-destructive method for characterizing the degraded cover of concrete structures using high-frequency ultrasound. In a preliminary study, the authors emphasized on the interest of using higher frequency Rayleigh waves (within the 0.2-1 MHz frequency band) for on-site inspection of concrete structures with subsurface damage. The present study represents a continuation of the previous work and aims at optimizing the generation and reception of Rayleigh waves into mortar and concrete be means of wedge transducers. This is performed experimentally by checking the influence of the wedge material and coupling agent on the surface wave parameters. The selection of the best combination wedge/coupling is performed by searching separately for the best wedge material and the best coupling material. Three wedge materials and five coupling agents were tested. For each setup the five parameters obtained from the surface wave measurement i.e. the frequency band, the maximal available central frequency, the group velocity error and its standard deviation and finally the error in velocity dispersion characteristic were investigated and classed as a function of the wedge material and the coupling agent. The selection criteria were chosen so as to minimize the absorption of both materials, the randomness of measurements and the systematic error of the group velocity and of dispersion characteristic. Among the three tested wedge materials, Teflon was found to be the best. The investigation on the coupling agent shows that the gel type materials are the best solutions. The "thick" materials displaying higher viscosity were found as the worst. The results show also that the use of a thin plastic film combined with the coupling agent even increases the bandwidth and decreases the uncertainty of measurements.

Design and Analysis of Cost-Efficient Sensor Deployment for Tracking Small UAS with Agent-Based Modeling.

PubMed

Shin, Sangmi; Park, Seongha; Kim, Yongho; Matson, Eric T

2016-04-22

Recently, commercial unmanned aerial systems (UAS) have gained popularity. However, these UAS are potential threats to people in terms of safety in public places, such as public parks or stadiums. To reduce such threats, we consider a design, modeling, and evaluation of a cost-efficient sensor system that detects and tracks small UAS. In this research, we focus on discovering the best sensor deployments by simulating different types and numbers of sensors in a designated area, which provide reasonable detection rates at low costs. Also, the system should cover the crowded areas more thoroughly than vacant areas to reduce direct threats to people underneath. This research study utilized the Agent-Based Modeling (ABM) technique to model a system consisting of independent and heterogeneous agents that interact with each other. Our previous work presented the ability to apply ABM to analyze the sensor configurations with two types of radars in terms of cost-efficiency. The results from the ABM simulation provide a list of candidate configurations and deployments that can be referred to for applications in the real world environment.

Curiosity driven reinforcement learning for motion planning on humanoids

PubMed Central

Frank, Mikhail; Leitner, Jürgen; Stollenga, Marijn; Förster, Alexander; Schmidhuber, Jürgen

2014-01-01

Most previous work on artificial curiosity (AC) and intrinsic motivation focuses on basic concepts and theory. Experimental results are generally limited to toy scenarios, such as navigation in a simulated maze, or control of a simple mechanical system with one or two degrees of freedom. To study AC in a more realistic setting, we embody a curious agent in the complex iCub humanoid robot. Our novel reinforcement learning (RL) framework consists of a state-of-the-art, low-level, reactive control layer, which controls the iCub while respecting constraints, and a high-level curious agent, which explores the iCub's state-action space through information gain maximization, learning a world model from experience, controlling the actual iCub hardware in real-time. To the best of our knowledge, this is the first ever embodied, curious agent for real-time motion planning on a humanoid. We demonstrate that it can learn compact Markov models to represent large regions of the iCub's configuration space, and that the iCub explores intelligently, showing interest in its physical constraints as well as in objects it finds in its environment. PMID:24432001

Design and Analysis of Cost-Efficient Sensor Deployment for Tracking Small UAS with Agent-Based Modeling

PubMed Central

Shin, Sangmi; Park, Seongha; Kim, Yongho; Matson, Eric T.

2016-01-01

Recently, commercial unmanned aerial systems (UAS) have gained popularity. However, these UAS are potential threats to people in terms of safety in public places, such as public parks or stadiums. To reduce such threats, we consider a design, modeling, and evaluation of a cost-efficient sensor system that detects and tracks small UAS. In this research, we focus on discovering the best sensor deployments by simulating different types and numbers of sensors in a designated area, which provide reasonable detection rates at low costs. Also, the system should cover the crowded areas more thoroughly than vacant areas to reduce direct threats to people underneath. This research study utilized the Agent-Based Modeling (ABM) technique to model a system consisting of independent and heterogeneous agents that interact with each other. Our previous work presented the ability to apply ABM to analyze the sensor configurations with two types of radars in terms of cost-efficiency. The results from the ABM simulation provide a list of candidate configurations and deployments that can be referred to for applications in the real world environment. PMID:27110790

Discovery of 1-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzyl)-5-(trifluoromethyl)pyridin-2(1H)-one, an orally active multi-target agent for the treatment of diabetic nephropathy.

PubMed

Chen, Jun; Peng, Zhangzhe; Lu, Miaomiao; Xiong, Xuan; Chen, Zhuo; Li, Qianbin; Cheng, Zeneng; Jiang, Dejian; Tao, Lijian; Hu, Gaoyun

2018-01-15

Oxidative stress, inflammation and fibrosis can cause irreversible damage on cell structure and function of kidney and are key pathological factors in Diabetic Nephropathy (DN). Therefore, multi-target agents are urgently need for the clinical treatment of DN. Using Pirfenidone as a lead compound and based on the previous research, two novel series (5-trifluoromethyl)-2(1H)-pyridone analogs were designed and synthesized. SAR of (5-trifluoromethyl)-2(1H)-pyridone derivatives containing nitrogen heterocyclic ring have been established for in vitro potency. In addition, compound 8, a novel agent that act on multiple targets of anti-DN with IC 50 of 90μM in NIH3T3 cell lines, t 1/2 of 4.89±1.33h in male rats and LD 50 >2000mg/kg in mice, has been advanced to preclinical studies as an oral treatment for DN. Copyright © 2017 Elsevier Ltd. All rights reserved.

Agency Problems and Airport Security: Quantitative and Qualitative Evidence on the Impact of Security Training.

PubMed

de Gramatica, Martina; Massacci, Fabio; Shim, Woohyun; Turhan, Uğur; Williams, Julian

2017-02-01

We analyze the issue of agency costs in aviation security by combining results from a quantitative economic model with a qualitative study based on semi-structured interviews. Our model extends previous principal-agent models by combining the traditional fixed and varying monetary responses to physical and cognitive effort with nonmonetary welfare and potentially transferable value of employees' own human capital. To provide empirical evidence for the tradeoffs identified in the quantitative model, we have undertaken an extensive interview process with regulators, airport managers, security personnel, and those tasked with training security personnel from an airport operating in a relatively high-risk state, Turkey. Our results indicate that the effectiveness of additional training depends on the mix of "transferable skills" and "emotional" buy-in of the security agents. Principals need to identify on which side of a critical tipping point their agents are to ensure that additional training, with attached expectations of the burden of work, aligns the incentives of employees with the principals' own objectives. © 2016 Society for Risk Analysis.

Endogenous ethanol affects biopolyester molecular weight in recombinant Escherichia coli.

PubMed

Hiroe, Ayaka; Hyakutake, Manami; Thomson, Nicholas M; Sivaniah, Easan; Tsuge, Takeharu

2013-11-15

In biopolyester synthesis, polyhydroxyalkanoate (PHA) synthase (PhaC) catalyzes the polymerization of PHA in bacterial cells, followed by a chain transfer (CT) reaction in which the PHA polymer chain is transferred from PhaC to a CT agent. Accordingly, the frequency of CT reaction determines PHA molecular weight. Previous studies have shown that exogenous alcohols are effective CT agents. This study aimed to clarify the effect of endogenous ethanol as a CT agent for poly[(R)-3-hydroxybutyrate] [P(3HB)] synthesis in recombinant Escherichia coli, by comparing with that of exogenous ethanol. Ethanol supplementation to the culture medium reduced P(3HB) molecular weights by up to 56% due to ethanol-induced CT reaction. NMR analysis of P(3HB) polymers purified from the culture supplemented with (13)C-labeled ethanol showed the formation of a covalent bond between ethanol and P(3HB) chain at the carboxyl end. Cultivation without ethanol supplementation resulted in the reduction of P(3HB) molecular weight with increasing host-produced ethanol depending on culture aeration. On the other hand, production in recombinant BW25113(ΔadhE), an alcohol dehydrogenase deletion strain, resulted in a 77% increase in molecular weight. Analysis of five E. coli strains revealed that the estimated number of CT reactions was correlated with ethanol production. These results demonstrate that host-produced ethanol acts as an equally effective CT agent as exogenous ethanol, and the control of ethanol production is important to regulate the PHA molecular weight.

Anticlotting agents and the surgical management of glaucoma.

PubMed

Sozeri, Yasemin; Salim, Sarwat

2018-03-01

A large subset of patients with glaucoma uses anticlotting agents. No standardized guidelines currently exist for managing these agents in the specific perioperative setting of glaucoma surgery. The present review focuses on currently available anticlotting agents, their influence on hemorrhagic complications following glaucoma surgery, and management strategies for their use in the perioperative period RECENT FINDINGS: Anticlotting agents increase the risk of perioperative hemorrhagic complications following glaucoma surgery. Other factors that increase that risk have been identified as well, including the type of glaucoma surgery, preoperative intraocular pressure, postoperative hypotony, previous ocular surgeries, and race. Although general guidelines in the perioperative management of blood thinning agents exist, the best way to apply these guidelines specifically to glaucoma surgery remains unclear. Blood thinners are widely used and can increase the risk of hemorrhagic complications in patients undergoing glaucoma surgery. Managing these agents in the perioperative setting is challenging and should be done in collaboration with the patient's primary care provider, hematologist, or cardiologist. Management strategies should be tailored to each individual's risk of hemorrhage versus thromboembolism. Additionally, surgical plans can be modified to help minimize hemorrhagic outcomes, especially in patients who are deemed to be at high risk for perioperative bleeding.

Managing a Common Pool Resource: Real Time Decision-Making in a Groundwater Aquifer

NASA Astrophysics Data System (ADS)

Sahu, R.; McLaughlin, D.

2017-12-01

In a Common Pool Resource (CPR) such as a groundwater aquifer, multiple landowners (agents) are competing for a limited resource of water. Landowners pump out the water to grow their own crops. Such problems can be posed as differential games, with agents all trying to control the behavior of the shared dynamic system. Each agent aims to maximize his/her own personal objective like agriculture yield, being aware that the action of every other agent collectively influences the behavior of the shared aquifer. The agents therefore choose a subgame perfect Nash equilibrium strategy that derives an optimal action for each agent based on the current state of the aquifer and assumes perfect information of every other agents' objective function. Furthermore, using an Iterated Best Response approach and interpolating techniques, an optimal pumping strategy can be computed for a more-realistic description of the groundwater model under certain assumptions. The numerical implementation of dynamic optimization techniques for a relevant description of the physical system yields results qualitatively different from the previous solutions obtained from simple abstractions.This work aims to bridge the gap between extensive modeling approaches in hydrology and competitive solution strategies in differential game theory.

[Not Available].

PubMed

Oddo, Antonio

2016-07-28

This new paper on chemical risk from anaesthetic agents in operating theatres is the natural progression of that published in this journal in supplement 1-2013, as it constitutes a development and complement of the previous work and an applicative confirmation from the highest organ of administrative justice, the Consiglio di Stato, regarding, in particular, the obligation of adopting the technically most advanced "measures" to eliminate or, at least, minimise risk in the use of new generation and the most commonly-used anaesthetic agents (sevoflurane and desflurane). Therefore, in this paper, the authors commence by referring to the starting point, consisting in the conclusions of the previous study, which highlighted the extraordinary convergence of technical and scientific, legislative and case law data on the same result, constituted by the possibility, and consequent obligation, of implementing, also in operating theatres, the greatest technologically possible safety, starting with the choice of the most suitable equipment, methods and quality systems for avoiding the diffusion, dispersion and /or leakage of volatile hazardous agents that may contribute - together with those chemical reactions that are foreseeable and avoidable, given the characteristics of the materials, substances and relative "packaging" - to workplace pollution, which can, in any case, reach levels that are hazardous due to the concentration of anaesthetic gases. Subsequently, once the "scientific" fruit of the previous contributions has been discussed, the authors evaluate the impact of the result already achieved in practice with concrete cases and the judgement expressed with a series of judgements issued in rapid succession by the Consiglio di Stato, showing the application, not merely of the legislative "data" but also of the references and citations that these "data" contain regarding the "knowledge acquired regarding the relationship with technical progress". Lastly, the Authors provide, as a further, definitive conclusion, the singular unit of the guidelines provided by case law, the result of a univocal and continuous multitude of judgements issued at the highest degree of administrative justice, albeit for very diverse situations and circumstances, which provide, therefore, a direction and an operative guide for which they are called on to adopt roles and responsibilities for the choices of "products", "systems" and "methods" destined to affect - for the use of anaesthetic agents - the health and safety of healthcare staff and of patients themselves.

IMAGE: A Design Integration Framework Applied to the High Speed Civil Transport

NASA Technical Reports Server (NTRS)

Hale, Mark A.; Craig, James I.

1993-01-01

Effective design of the High Speed Civil Transport requires the systematic application of design resources throughout a product's life-cycle. Information obtained from the use of these resources is used for the decision-making processes of Concurrent Engineering. Integrated computing environments facilitate the acquisition, organization, and use of required information. State-of-the-art computing technologies provide the basis for the Intelligent Multi-disciplinary Aircraft Generation Environment (IMAGE) described in this paper. IMAGE builds upon existing agent technologies by adding a new component called a model. With the addition of a model, the agent can provide accountable resource utilization in the presence of increasing design fidelity. The development of a zeroth-order agent is used to illustrate agent fundamentals. Using a CATIA(TM)-based agent from previous work, a High Speed Civil Transport visualization system linking CATIA, FLOPS, and ASTROS will be shown. These examples illustrate the important role of the agent technologies used to implement IMAGE, and together they demonstrate that IMAGE can provide an integrated computing environment for the design of the High Speed Civil Transport.

Occupational voice demands and their impact on the call-centre industry.

PubMed

Hazlett, D E; Duffy, O M; Moorhead, S A

2009-04-20

Within the last decade there has been a growth in the call-centre industry in the UK, with a growing awareness of the voice as an important tool for successful communication. Occupational voice problems such as occupational dysphonia, in a business which relies on healthy, effective voice as the primary professional communication tool, may threaten working ability and occupational health and safety of workers. While previous studies of telephone call-agents have reported a range of voice symptoms and functional vocal health problems, there have been no studies investigating the use and impact of vocal performance in the communication industry within the UK. This study aims to address a significant gap in the evidence-base of occupational health and safety research. The objectives of the study are: 1. to investigate the work context and vocal communication demands for call-agents; 2. to evaluate call-agents' vocal health, awareness and performance; and 3. to identify key risks and training needs for employees and employers within call-centres. This is an occupational epidemiological study, which plans to recruit call-centres throughout the UK and Ireland. Data collection will consist of three components: 1. interviews with managers from each participating call-centre to assess their communication and training needs; 2. an online biopsychosocial questionnaire will be administered to investigate the work environment and vocal demands of call-agents; and 3. voice acoustic measurements of a random sample of participants using the Multi-dimensional Voice Program (MDVP). Qualitative content analysis from the interviews will identify underlying themes and issues. A multivariate analysis approach will be adopted using Structural Equation Modelling (SEM), to develop voice measurement models in determining the construct validity of potential factors contributing to occupational dysphonia. Quantitative data will be analysed using SPSS version 15. Ethical approval is granted for this study from the School of Communication, University of Ulster. The results from this study will provide the missing element of voice-based evidence, by appraising the interactional dimensions of vocal health and communicative performance. This information will be used to inform training for call-agents and to contribute to health policies within the workplace, in order to enhance vocal health.

Time-Extended Policies in Mult-Agent Reinforcement Learning

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian K.

2004-01-01

Reinforcement learning methods perform well in many domains where a single agent needs to take a sequence of actions to perform a task. These methods use sequences of single-time-step rewards to create a policy that tries to maximize a time-extended utility, which is a (possibly discounted) sum of these rewards. In this paper we build on our previous work showing how these methods can be extended to a multi-agent environment where each agent creates its own policy that works towards maximizing a time-extended global utility over all agents actions. We show improved methods for creating time-extended utilities for the agents that are both "aligned" with the global utility and "learnable." We then show how to crate single-time-step rewards while avoiding the pi fall of having rewards aligned with the global reward leading to utilities not aligned with the global utility. Finally, we apply these reward functions to the multi-agent Gridworld problem. We explicitly quantify a utility's learnability and alignment, and show that reinforcement learning agents using the prescribed reward functions successfully tradeoff learnability and alignment. As a result they outperform both global (e.g., team games ) and local (e.g., "perfectly learnable" ) reinforcement learning solutions by as much as an order of magnitude.

SINGLE AGENT CARBOPLATIN VERSUS CARBOPLATIN PLUS PEGYLATED LIPOSOMAL DOXORUBICIN IN RECURRENT OVARIAN CANCER: FINAL SURVIVAL RESULTS OF A SWOG (S0200) PHASE 3 RANDOMIZED TRIAL

PubMed Central

Markman, Maurie; Moon, James; Wilczynski, Sharon; Lopez, Ana Maria; Rowland, Kendrith M.; Michelin, David P.; Lanzotti, Victor J.; Anderson, Garnet L.; Alberts, David S.

2009-01-01

Objectives Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent. Methods To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m2) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. Results In the limited number of patients (n=61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p=0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p=0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p=0.0008), with 5 being ≥ grade 3 in severity. Conclusion Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions. PMID:20044128

Treatment of Peripheral T-Cell Lymphoma: Many Shades of Gray.

PubMed

Lunning, Matthew A

2015-08-01

Previously obscured within other designations of aggressive lymphomas, peripheral T-cell lymphoma (PTCL) now represents 23 different subtypes of non-Hodgkin lymphoma (NHL). Despite the many subtypes now recognized, PTCL represents only approximately 10% of all NHL cases diagnosed. Positron emission tomography/computed tomography has become essential to accurate staging and response-evaluation for PTCL. In comparison to aggressive B-cell NHL, patients with PTCL will more often be refractory to initial therapy, and chemosensitive patients will have shorter disease-free periods. Anthracycline-based regimens, often with the inclusion of etoposide, are commonly used during induction therapy. Consolidation with high-dose therapy and autologous stem cell transplantation (ASCT) in first chemosensitive remission appears to provide the best outcome in common nodal PTCL subtypes. The commonly defined nodal subtypes are PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic lymphoma kinase (ALK)-positive or ALK-negative anaplastic large-cell lymphoma (ALCL). Four agents have been approved by the US Food and Drug Administration for use in the relapsed/refractory (rel/ref) setting, including belinostat (2014), romidepsin (2011), brentuximab vedotin (2011), and pralatrexate (2009). Brentuximab vedotin was approved only for the ALCL subtype. These agents continue to be studied as combinations in the rel/ref setting and as additions or substitutions for other agents in upfront multiagent chemotherapy regimens. Patients who have responded to treatment in the rel/ref setting and are considered transplant-eligible should be considered for allogeneic stem cell transplantation, especially those with previous ASCT. Upfront allogeneic stem cell transplantation remains a research question in the majority of PTCL subtypes, but data are emerging.

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.

Mental Rotation in False Belief Understanding.

PubMed

Xie, Jiushu; Cheung, Him; Shen, Manqiong; Wang, Ruiming

2018-05-01

This study examines the spontaneous use of embodied egocentric transformation (EET) in understanding false beliefs in the minds of others. EET involves the participants mentally transforming or rotating themselves into the orientation of an agent when trying to adopt his or her visuospatial perspective. We argue that psychological perspective taking such as false belief reasoning may also involve EET because of what has been widely reported in the embodied cognition literature, showing that our processing of abstract, propositional information is often grounded in concrete bodily sensations which are not apparently linked to higher cognition. In Experiment 1, an agent placed a ball into one of two boxes and left. The ball then rolled out and moved either into the other box (new box) or back into the original one (old box). The participants were to decide from which box they themselves or the agent would try to recover the ball. Results showed that false belief performance was affected by increased orientation disparity between the participants and the agent, suggesting involvement of embodied transformation. In Experiment 2, false belief was similarly induced and the participants were to decide if the agent would try to recover the ball in one specific box. Orientation disparity was again found to affect false belief performance. The present results extend previous findings on EET in visuospatial perspective taking and suggest that false belief reasoning, which is a kind of psychological perspective taking, can also involve embodied rotation, consistent with the embodied cognition view. Copyright © 2018 Cognitive Science Society, Inc.

Moving Just Like You: Motor Interference Depends on Similar Motility of Agent and Observer

PubMed Central

Kupferberg, Aleksandra; Huber, Markus; Helfer, Bartosz; Lenz, Claus; Knoll, Alois; Glasauer, Stefan

2012-01-01

Recent findings in neuroscience suggest an overlap between brain regions involved in the execution of movement and perception of another’s movement. This so-called “action-perception coupling” is supposed to serve our ability to automatically infer the goals and intentions of others by internal simulation of their actions. A consequence of this coupling is motor interference (MI), the effect of movement observation on the trajectory of one’s own movement. Previous studies emphasized that various features of the observed agent determine the degree of MI, but could not clarify how human-like an agent has to be for its movements to elicit MI and, more importantly, what ‘human-like’ means in the context of MI. Thus, we investigated in several experiments how different aspects of appearance and motility of the observed agent influence motor interference (MI). Participants performed arm movements in horizontal and vertical directions while observing videos of a human, a humanoid robot, or an industrial robot arm with either artificial (industrial) or human-like joint configurations. Our results show that, given a human-like joint configuration, MI was elicited by observing arm movements of both humanoid and industrial robots. However, if the joint configuration of the robot did not resemble that of the human arm, MI could longer be demonstrated. Our findings present evidence for the importance of human-like joint configuration rather than other human-like features for perception-action coupling when observing inanimate agents. PMID:22761853

Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure.

PubMed

Svensson, J Peter; Quirós Pesudo, Laia; McRee, Siobhan K; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D

2013-01-01

Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N'-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.

Genomic Phenotyping by Barcode Sequencing Broadly Distinguishes between Alkylating Agents, Oxidizing Agents, and Non-Genotoxic Agents, and Reveals a Role for Aromatic Amino Acids in Cellular Recovery after Quinone Exposure

PubMed Central

Svensson, J. Peter; Quirós Pesudo, Laia; McRee, Siobhan K.; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D.

2013-01-01

Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N′-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic ‘barcode’, were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput ‘barcode’ sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised. PMID:24040048

Development of silica-encapsulated silver nanoparticles as contrast agents intended for dual-energy mammography.

PubMed

Karunamuni, Roshan; Naha, Pratap C; Lau, Kristen C; Al-Zaki, Ajlan; Popov, Anatoliy V; Delikatny, Edward J; Tsourkas, Andrew; Cormode, David P; Maidment, Andrew D A

2016-09-01

Dual-energy (DE) mammography has recently entered the clinic. Previous theoretical and phantom studies demonstrated that silver provides greater contrast than iodine for this technique. Our objective was to characterize and evaluate in vivo a prototype silver contrast agent ultimately intended for DE mammography. The prototype silver contrast agent was synthesized using a three-step process: synthesis of a silver core, silica encapsulation and PEG coating. The nanoparticles were then injected into mice to determine their accumulation in various organs, blood half-life and dual-energy contrast. All animal procedures were approved by the institutional animal care and use committee. The final diameter of the nanoparticles was measured to be 102 (±9) nm. The particles were removed from the vascular circulation with a half-life of 15 min, and accumulated in macrophage-rich organs such as the liver, spleen and lymph nodes. Dual-energy subtraction techniques increased the signal difference-to-noise ratio of the particles by as much as a factor of 15.2 compared to the single-energy images. These nanoparticles produced no adverse effects in mice. Silver nanoparticles are an effective contrast agent for dual-energy x-ray imaging. With further design improvements, silver nanoparticles may prove valuable in breast cancer screening and diagnosis. • Silver has potential as a contrast agent for DE mammography. • Silica-coated silver nanoparticles are biocompatible and suited for in vivo use. • Silver nanoparticles produce strong contrast in vivo using DE mammography imaging systems.

Global and Regional Brain Assessment with Quantitative MR Imaging in Patients with Prior Exposure to Linear Gadolinium-based Contrast Agents.

PubMed

Kuno, Hirofumi; Jara, Hernán; Buch, Karen; Qureshi, Muhammad Mustafa; Chapman, Margaret N; Sakai, Osamu

2017-04-01

Purpose To assess the association of global and regional brain relaxation times in patients with prior exposure to linear gadolinium-based contrast agents (GBCAs). Materials and Methods The institutional review board approved this cross-sectional study. Thirty-five patients (nine who had received GBCA gadopentetate dimeglumine injections previously [one to eight times] and 26 patients who did not) who underwent brain magnetic resonance (MR) imaging with a mixed fast spin-echo pulse sequence were assessed. The whole brain was segmented according to white and gray matter by using a dual-clustering algorithm. In addition, regions of interest were measured in the globus pallidus, dentate nucleus, thalamus, and pons. The Mann-Whitney U test was used to assess the difference between groups. Multiple regression analysis was performed to assess the association of T1 and T2 with prior GBCA exposure. Results T1 values of gray matter were significantly shorter for patients with than for patients without prior GBCA exposure (P = .022). T1 of the gray matter of the whole brain (P < .001), globus pallidus (P = .002), dentate nucleus (P = .046), and thalamus (P = .026) and T2 of the whole brain (P = .004), dentate nucleus (P = .023), and thalamus (P = .002) showed a significant correlation with the accumulated dose of previous GBCA administration. There was no significant correlation between T1 and the accumulated dose of previous GBCA injections in the white matter (P = .187). Conclusion Global and regional quantitative assessments of T1 and T2 demonstrated an association with prior GBCA exposure, especially for gray matter structures. The results of this study confirm previous research findings that there is gadolinium deposition in wider distribution throughout the brain. © RSNA, 2016 Online supplemental material is available for this article.

Efficient priority queueing routing strategy on networks of mobile agents

NASA Astrophysics Data System (ADS)

Wu, Gan-Hua; Yang, Hui-Jie; Pan, Jia-Hui

2018-03-01

As a consequence of their practical implications for communications networks, traffic dynamics on complex networks have recently captivated researchers. Previous routing strategies for improving transport efficiency have paid little attention to the orders in which the packets should be forwarded, just simply used first-in-first-out queue discipline. Here, we apply a priority queuing discipline and propose a shortest-distance-first routing strategy on networks of mobile agents. Numerical experiments reveal that the proposed scheme remarkably improves both the network throughput and the packet arrival rate and reduces both the average traveling time and the rate of waiting time to traveling time. Moreover, we find that the network capacity increases with an increase in both the communication radius and the number of agents. Our work may be helpful for the design of routing strategies on networks of mobile agents.

Design of Monoamine Reuptake Inhibitors: SSRIs, SNRIs and NRIs

NASA Astrophysics Data System (ADS)

Whitlock, Gavin A.; Andrews, Mark D.; Brown, Alan D.; Fish, Paul V.; Stobie, Alan; Wakenhut, Florian

This review will detail the medicinal chemistry involved in the design, synthesis and discovery of selective serotonin, noradrenaline reuptake inhibitors and dual serotonin/noradrenaline reuptake inhibitors. In particular, this review will focus exclusively on series and compounds which have been disclosed within the medicinal chemistry literature between January 2000 and June 2008. Background information on previously disclosed clinical agents, such as atomoxetine, milnacipran and reboxetine, is included for comparison purposes with more recently disclosed agents.

Academic and Nonacademic Validating Agents on Latinas Mathematics and Science Self Concept A Quantitative Study Utilizing the High School Longitudinal Study of 2009

NASA Astrophysics Data System (ADS)

Garza, Jennifer M.

The purpose of this study is to inform and further the discussion of academic (i.e. teachers and school counselors) and non-academic (i.e. parents, family, friends, etc.) validating agents on Latina students' mathematics and science self-concepts. This study found a relationship between Latina students' interactions with academic and non-academic validating agents and their math and science self-concept at the K-12 level. Through the review of the literature the researcher addresses identifiable factors and strategies that inform the field of education in the areas of validation theory, family characteristics, and access to STEM fields for Latina students. The researcher used an established instrument designed, administered, and validated through the National Center for Education Statistics (NCES). For purposes of this study, a categorical subset of participants who self-identified as being a Latina student was used. As a result, the total subset number in this study was N=1,882. To determine if academic and non-academic validating agents had an observable statistically significant relationship with Latina students' math and science self-concept, a series of one-way ANOVAs were calculated to compare differences in students' math and science self-concept based on academic and non-academic validating agents for the weighted sample of Latinas for the HLS:09 survey. A path analysis was also employed to assess the factors involved in Latina students' math and science self-concepts. The findings are consistent with previous research involving the influence that academic and non-academic validating agents have on the math and science self-concept of Latina students. The results indicated that students who had teachers that believed in the students, regardless of family background, social economic status or home environment influences had higher math and science self concepts than those who did not. Similarly, it was found that students who had counselors that set high standards of learning and believed that all students could do well had higher math and science self concept than those who did not. Students who had parents that encouraged and discussed taking more math and science courses had higher math and science self concepts than those who did not.

Multi-Agent Technology for Air Space Deconfliction

DTIC Science & Technology

2008-01-01

previously accepted limit of the runway count is also omitted although in the case study used in the reported research the JFK airport is considered...La Guardia, Republic. Fig. 2.3 depicts the approach zone of JFK airport . In general words, the airport airspace topology is divided into two zones: (i...be omitted when necessary or if the customer believes they are too hard. Fig.2.3. Approach zone of JFK airport 11 4. Development of a realistic

m- And p-halobenzoyl derivatives of p-halo-DL-phenylalanine as inhibitors in a microbial antitumor prescreen.

PubMed

Otani, T T; Briley, M R

1983-05-01

Meta- and p-halobenzoyl-p-halo-phenylalanine compounds were prepared and tested for growth-inhibitory activity in a Lactobacillus casei system. The activity of 13 of the most active of these compounds, reported here, was greater than that of any other acyl derivatives of amino acid analogs previously studied in this system and was from 2 to 8 times greater than that of 6-mercaptopurine, a known antitumor agent.

Multifunctional role of osteopontin in directing intrafibrillar mineralization of collagen and activation of osteoclasts

PubMed Central

Rodriguez, Douglas E.; Thula-Mata, Taili; Toro, Edgardo J.; Yeh, Ya-Wen; Holt, Carl; Holliday, L. Shannon; Gower, Laurie B.

2013-01-01

Mineralized collagen composites are of interest because they have the potential to provide a bone-like scaffold that stimulates the natural processes of resorption and remodeling. Working toward this goal, our group has previously shown that the nanostructure of bone can be reproduced using a polymer-induced liquid-precursor (PILP) process, which enables intrafibrillar mineralization of collagen with hydroxyapatite (HA) to be achieved. This prior work used polyaspartic acid (pASP), a simple mimic for acidic non-collagenous proteins (NCPs), to generate nanodroplets/nanoparticles of an amorphous mineral precursor which can infiltrate the interstices of type-I collagen fibrils. In this study we show that osteopontin (OPN) can similarly serve as a process-directing agent for the intrafibrillar mineralization of collagen, even though OPN is generally considered a mineralization inhibitor. We also found that inclusion of OPN in the mineralization process promotes the interaction of mouse marrow-derived osteoclasts with PILP-remineralized bone that was previously demineralized, as measured by actin ring formation. While osteoclast activation occurred when pASP was used as the process-directing agent, using OPN resulted in a dramatic effect on osteoclast activation, presumably because of the inherent arginine-glycine-aspartate acid (RGD) ligands of OPN. By capitalizing on the multifunctionality of OPN, these studies may lead the way to producing biomimetic bone substitutes with the capability of tailorable bioresorption rates. PMID:24140612

[Use of antihypertensive drug therapy and risk of development of congestive heart failure].

PubMed

Sobrino, Javier; Plana, Jaume; Felip, Angela; Doménech, Mónica; Reth, Peter; Adrián, María Jesús; de la Sierra, Alejandro

2004-09-18

It has been suggested that the use of some antihypertensive agents may favour the development of congestive heart failure. The aim of the present study was to evaluate such a possible association in patients who had a new diagnosis of congestive heart failure. This was a retrospective case-control study of 81 patients who had a first hospital admission with a new diagnosis of congestive heart failure (cases) and 162 patients admitted for other hypertensive complications (controls). Previous antihypertensive drug use was registered and the possible association with congestive heart failure was evaluated. The presence of congestive heart failure was not associated with the use of any antihypertensive drug class. When treatments were grouped in classic (diuretics and betablockers) or modern (calcium channel blockers, angiotensin-converting-enzyme inhibitors, alphablockers or angiotensin receptor blockers), a negative association was observed with the latter group, which was observed in 48.1% of cases and 63.6% of controls (odds ratio: 0.532; 95% confidence interval, 0.310-0.913). This association was lost after adjustment for other cardiovascular risk factors or previous hypertensive complications. The development of congestive heart failure was not associated with the use of any specific antihypertensive drug class. From the present evidence, it is not possible to recommend a specific antihypertensive agent in patients at risk of developing congestive heart failure but without evidence of such disease.

MRS of brain metabolite levels demonstrates the ability of scavenging of excess brain glutamate to protect against nerve agent induced seizures.

PubMed

Ruban, Angela; Biton, Inbal E; Markovich, Arik; Mirelman, David

2015-02-02

This study describes the use of in vivo magnetic resonance spectrocopy (MRS) to monitor brain glutamate and lactate levels in a paraoxon (PO) intoxication model. Our results show that the administration of recombinant glutamate-oxaloacetate transaminase (rGOT) in combination with oxaloacetate (OxAc) significantly reduces the brain-accumulated levels of glutamate. Previously we have shown that the treatment causes a rapid decrease of blood glutamate levels and creates a gradient between the brain and blood glutamate levels which leads to the efflux of excess brain glutamate into the blood stream thereby reducing its potential to cause neurological damage. The fact that this treatment significantly decreased the brain glutamate and lactate levels following PO intoxication suggests that it could become a new effective neuroprotective agent.

A Framework to Describe, Analyze and Generate Interactive Motor Behaviors

PubMed Central

Jarrassé, Nathanaël; Charalambous, Themistoklis; Burdet, Etienne

2012-01-01

While motor interaction between a robot and a human, or between humans, has important implications for society as well as promising applications, little research has been devoted to its investigation. In particular, it is important to understand the different ways two agents can interact and generate suitable interactive behaviors. Towards this end, this paper introduces a framework for the description and implementation of interactive behaviors of two agents performing a joint motor task. A taxonomy of interactive behaviors is introduced, which can classify tasks and cost functions that represent the way each agent interacts. The role of an agent interacting during a motor task can be directly explained from the cost function this agent is minimizing and the task constraints. The novel framework is used to interpret and classify previous works on human-robot motor interaction. Its implementation power is demonstrated by simulating representative interactions of two humans. It also enables us to interpret and explain the role distribution and switching between roles when performing joint motor tasks. PMID:23226231

A framework to describe, analyze and generate interactive motor behaviors.

PubMed

Jarrassé, Nathanaël; Charalambous, Themistoklis; Burdet, Etienne

2012-01-01

While motor interaction between a robot and a human, or between humans, has important implications for society as well as promising applications, little research has been devoted to its investigation. In particular, it is important to understand the different ways two agents can interact and generate suitable interactive behaviors. Towards this end, this paper introduces a framework for the description and implementation of interactive behaviors of two agents performing a joint motor task. A taxonomy of interactive behaviors is introduced, which can classify tasks and cost functions that represent the way each agent interacts. The role of an agent interacting during a motor task can be directly explained from the cost function this agent is minimizing and the task constraints. The novel framework is used to interpret and classify previous works on human-robot motor interaction. Its implementation power is demonstrated by simulating representative interactions of two humans. It also enables us to interpret and explain the role distribution and switching between roles when performing joint motor tasks.

The study of life change unit as stressor agents among Tehran University of Medical Sciences Hospitals' employees.

PubMed

Dargahi, Hossein; Sharifiy Yazdi, Mohammad Kazem

2010-01-01

Life crises as stressor agents can disrupt the best stress management regime. Different life crises have different impacts. A standard scale to rate change and its related stress impact has been developed commonly referred to as LCU (life change unit) rating. This allocates a number of life crisis units or life change units (LCUs) to different event and then evaluates them and takes action accordingly. This idea behind this approach of is to rundown the LCU table, totaling the LCUs for life crisis that have occurred in the previous one year. A cross-sectional, descriptive and analytical study was conducted among 900 Tehran University of Medical Sciences (TUMS) employees by a Holms and Rahe LCU questionnaire at 15 hospitals. The respondents were asked to determine their demographic information, list of stress symptoms which suffered from these diseases in the previous one year and finally, responded to 45 Life Change Unit as stressful life events and the value of each in "stress units" which occurred in the previous one year. The results showed that there is significant correlation between the employees LCU rating by sex, educational degree and size of hospital. Also we found that there are significant correlations between the employees stress symptoms with their LCU rating. Totally, 40% of the employees have less than 150 LCU rating (normal range) and 60% of them have 150-300 or more than 300 LCU rating (abnormal range). In conclusion most of TUMS hospitals' employees who had stress symptoms have more LCU rating. One third of these employees are not in danger of suffering the illness effect, while two third of them are in danger.

Reevaluation of 1999 Health-Based Environmental Screening Levels (HBESLs) for Chemical Warfare Agents

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

Watson, Annetta Paule; Dolislager, Fredrick G

2007-05-01

This report evaluates whether new information and updated scientific models require that changes be made to previously published health-based environmental soil screening levels (HBESLs) and associated environmental fate/breakdown information for chemical warfare agents (USACHPPM 1999). Specifically, the present evaluation describes and compares changes that have been made since 1999 to U.S. Environmental Protection Agency (EPA) risk assessment models, EPA exposure assumptions, as well as to specific chemical warfare agent parameters (e.g., toxicity values). Comparison was made between screening value estimates recalculated with current assumptions and earlier health-based environmental screening levels presented in 1999. The chemical warfare agents evaluated include themore » G-series and VX nerve agents and the vesicants sulfur mustard (agent HD) and Lewisite (agent L). In addition, key degradation products of these agents were also evaluated. Study findings indicate that the combined effect of updates and/or changes to EPA risk models, EPA default exposure parameters, and certain chemical warfare agent toxicity criteria does not result in significant alteration to the USACHPPM (1999) health-based environmental screening level estimates for the G-series and VX nerve agents or the vesicant agents HD and L. Given that EPA's final position on separate Tier 1 screening levels for indoor and outdoor worker screening assessments has not yet been released as of May 2007, the study authors find that the 1999 screening level estimates (see Table ES.1) are still appropriate and protective for screening residential as well as nonresidential sites. As such, risk management decisions made on the basis of USACHPPM (1999) recommendations do not require reconsideration. While the 1999 HBESL values are appropriate for continued use as general screening criteria, the updated '2007' estimates (presented below) that follow the new EPA protocols currently under development are also protective. When EPA finalizes and documents a position on the matter of indoor and outdoor worker screening assessments, site-specific risk assessments should make use of modified models and criteria. Screening values such as those presented in this report may be used to assess soil or other porous media to determine whether chemical warfare agent contamination is present as part of initial site investigations (whether due to intentional or accidental releases) and to determine whether weather/decontamination has adequately mitigated the presence of agent residual to below levels of concern. However, despite the availability of scientifically supported health-based criteria, there are significant resources needs that should be considered during sample planning. In particular, few analytical laboratories are likely to be able to meet these screening levels. Analyses will take time and usually have limited confidence at these concentrations. Therefore, and particularly for the more volatile agents, soil/destructive samples of porous media should be limited and instead enhanced with headspace monitoring and presence-absence wipe sampling.« less

Cognitive, cultural, and linguistic sources of a handshape distinction expressing agentivity.

PubMed

Brentari, Diane; Di Renzo, Alessio; Keane, Jonathan; Volterra, Virginia

2015-01-01

In this paper the cognitive, cultural, and linguistic bases for a pattern of conventionalization of two types of iconic handshapes are described. Work on sign languages has shown that handling handshapes (H-HSs: those that represent how objects are handled or manipulated) and object handshapes (O-HSs: those that represent the class, size, or shape of objects) express an agentive/non-agentive semantic distinction in many sign languages. H-HSs are used in agentive event descriptions and O-HSs are used in non-agentive event descriptions. In this work, American Sign Language (ASL) and Italian Sign Language (LIS) productions are compared (adults and children) as well as the corresponding groups of gesturers in each country using "silent gesture." While the gesture groups, in general, did not employ an H-HS/O-HS distinction, all participants (signers and gesturers) used iconic handshapes (H-HSs and O-HSs together) more often in agentive than in no-agent event descriptions; moreover, none of the subjects produced an opposite pattern than the expected one (i.e., H-HSs associated with no-agent descriptions and O-HSs associated with agentive ones). These effects are argued to be grounded in cognition. In addition, some individual gesturers were observed to produce the H-HS/O-HS opposition for agentive and non-agentive event descriptions-that is, more Italian than American adult gesturers. This effect is argued to be grounded in culture. Finally, the agentive/non-agentive handshape opposition is confirmed for signers of ASL and LIS, but previously unreported cross-linguistic differences were also found across both adult and child sign groups. It is, therefore, concluded that cognitive, cultural, and linguistic factors contribute to the conventionalization of this distinction of handshape type. Copyright © 2014 Cognitive Science Society, Inc.

Evolutionary dynamics and the phase structure of the minority game

NASA Astrophysics Data System (ADS)

Yuan, Baosheng; Chen, Kan

2004-06-01

We show that a simple evolutionary scheme, when applied to the minority game (MG), changes the phase structure of the game. In this scheme each agent evolves individually whenever his wealth reaches the specified bankruptcy level, in contrast to the evolutionary schemes used in the previous works. We show that evolution greatly suppresses herding behavior, and it leads to better overall performance of the agents. Similar to the standard nonevolutionary MG, the dependence of the standard deviation σ on the number of agents N and the memory length m can be characterized by a universal curve. We suggest a crowd-anticrowd theory for understanding the effect of evolution in the MG.

Source Update Capture in Information Agents

NASA Technical Reports Server (NTRS)

Ashish, Naveen; Kulkarni, Deepak; Wang, Yao

2003-01-01

In this paper we present strategies for successfully capturing updates at Web sources. Web-based information agents provide integrated access to autonomous Web sources that can get updated. For many information agent applications we are interested in knowing when a Web source to which the application provides access, has been updated. We may also be interested in capturing all the updates at a Web source over a period of time i.e., detecting the updates and, for each update retrieving and storing the new version of data. Previous work on update and change detection by polling does not adequately address this problem. We present strategies for intelligently polling a Web source for efficiently capturing changes at the source.

Detection and quantification of unbound phytochelatin 2 in plant extracts of Brassica napus grown with different levels of mercury.

PubMed

Iglesia-Turiño, Santiago; Febrero, Anna; Jauregui, Olga; Caldelas, Cristina; Araus, Jose Luis; Bort, Jordi

2006-10-01

The mercury (Hg) accumulation mechanism was studied in rape (Brassica napus) plants grown under a Hg concentration gradient (0 microm-1,000 microm). Hg mainly accumulated in roots. Therefore, the presence of phytochelatins (PCs) was studied in the roots of the plants. The high stability of the PC-Hg multicomplexes (mPC-nHg) seems to be the main reason for the lack of previous Hg-PC characterization studies. We propose a modification of the method to detect and quantify unbound PC of Hg in plant extracts via high-performance liquid chromatography coupled to electrospray tandem mass spectrometry and inductively coupled plasma mass spectrometry in parallel. We separated the PC from the Hg by adding the chelating agent sodium 2,3-dimercaptopropanesulfonate monohydrate. We only detected the presence of PC after the addition of the chelating agent. Some multicomplexes mPC-nHg could be formed but, due to their large sizes, could not be detected. In this study, only PC(2) was observed in plant samples. Hg accumulation was correlated with PC(2) concentration (r(2) = 0.98).

Diagnostic methods to determine microbiology of postpartum endometritis in South Asia: laboratory methods protocol used in the Postpartum Sepsis Study: a prospective cohort study.

PubMed

Shakoor, Sadia; Reller, Megan E; LeFevre, Amnesty; Hotwani, Aneeta; Qureshi, Shahida M; Yousuf, Farheen; Islam, Mohammad Shahidul; Connor, Nicholas; Rafiqullah, Iftekhar; Mir, Fatima; Arif, Shabina; Soofi, Sajid; Bartlett, Linda A; Saha, Samir

2016-02-25

The South Asian region has the second highest risk of maternal death in the world. To prevent maternal deaths due to sepsis and to decrease the maternal mortality ratio as per the World Health Organization Millenium Development Goals, a better understanding of the etiology of endometritis and related sepsis is required. We describe microbiological laboratory methods used in the maternal Postpartum Sepsis Study, which was conducted in Bangladesh and Pakistan, two populous countries in South Asia. Postpartum maternal fever in the community was evaluated by a physician and blood and urine were collected for routine analysis and culture. If endometritis was suspected, an endometrial brush sample was collected in the hospital for aerobic and anaerobic culture and molecular detection of bacterial etiologic agents (previously identified and/or plausible). The results emanating from this study will provide microbiologic evidence of the etiology and susceptibility pattern of agents recovered from patients with postpartum fever in South Asia, data critical for the development of evidence-based algorithms for management of postpartum fever in the region.

SAR Studies on Trisubstituted Benzimidazoles as Inhibitors of Mtb FtsZ for the Development of Novel Antitubercular Agents

PubMed Central

Awasthi, Divya; Kumar, Kunal; Knudson, Susan E.; Slayden, Richard A.; Ojima, Iwao

2014-01-01

FtsZ, an essential protein for bacterial cell division, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of two lead 2,5,6-trisubstituted benzimidazoles, 1 and 2, targeting Mtb-FtsZ in our previous study, an extensive SAR study for optimization of these lead compounds was performed through systematic modification of the 5 and 6 positions. This study has successfully led to the discovery of a highly potent advanced lead 5f (MIC 0.06 µg/mL) and several other compounds with comparable potencies. These advanced lead compounds possess a dimethylamino group at the 6 position. The functional groups at the 5 position exhibit substantial effects on the antibacterial activity as well. In vitro experiments such as the FtsZ polymerization inhibitory assay and TEM analysis of Mtb-FtsZ treated with 5f and others indicate that Mtb-FtsZ is the molecular target for their antibacterial activity. PMID:24266862

SAR studies on trisubstituted benzimidazoles as inhibitors of Mtb FtsZ for the development of novel antitubercular agents.

PubMed

Awasthi, Divya; Kumar, Kunal; Knudson, Susan E; Slayden, Richard A; Ojima, Iwao

2013-12-12

FtsZ, an essential protein for bacterial cell division, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of two lead 2,5,6-trisubstituted benzimidazoles, 1 and 2, targeting Mtb-FtsZ in our previous study, an extensive SAR study for optimization of these lead compounds was performed through systematic modification of the 5 and 6 positions. This study has successfully led to the discovery of a highly potent advanced lead 5f (MIC = 0.06 μg/mL) and several other compounds with comparable potencies. These advanced lead compounds possess a dimethylamino group at the 6 position. The functional groups at the 5 position exhibit substantial effects on the antibacterial activity as well. In vitro experiments such as the FtsZ polymerization inhibitory assay and TEM analysis of Mtb-FtsZ treated with 5f and others indicate that Mtb-FtsZ is the molecular target for their antibacterial activity.

Effect of Rebamipide, a Novel Antiulcer Agent, on Helicobacter pylori Adhesion to Gastric Epithelial Cells

PubMed Central

Hayashi, Shunji; Sugiyama, Toshiro; Amano, Ken-Ichi; Isogai, Hiroshi; Isogai, Emiko; Aihara, Miki; Kikuchi, Mikio; Asaka, Masahiro; Yokota, Kenji; Oguma, Keiji; Fujii, Nobuhiro; Hirai, Yoshikazu

1998-01-01

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to human gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in the prevention of H. pylori infection. Experiments were performed to evaluate the effect of rebamipide, a novel antiulcer agent, on H. pylori adhesion to gastric epithelial cells. MKN-28 and MKN-45 cells, derived from human gastric carcinomas, were used as target cells. Ten H. pylori strains isolated from patients with chronic gastritis and gastric ulcer were used in the study. We evaluated the effect of rebamipide on H. pylori adhesion to MKN-28 and MKN-45 cells quantitatively using our previously established enzyme-linked immunosorbent assay. The adhesion of H. pylori to MKN-28 and MKN-45 cells was significantly inhibited by pretreatment of these cells with 100 μg of rebamipide per ml. However, the adhesion was not affected by the pretreatment of H. pylori with rebamipide. On the other hand, the viabilities of H. pylori, MKN-28 cells, and MKN-45 cells were not affected by rebamipide. Our studies suggest that rebamipide inhibits the adhesion of H. pylori to gastric epithelial cells. PMID:9687380

Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review

PubMed Central

Wyke, Stacey; Marczylo, Tim; Collins, Samuel; Gaulton, Tom; Foxall, Kerry; Amlôt, Richard; Duarte‐Davidson, Raquel

2017-01-01

Abstract Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non‐toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty‐two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems. PMID:28990191

Do occupation and work conditions really matter? A longitudinal analysis of psychological distress experiences among Canadian workers.

PubMed

Marchand, Alain; Demers, Andrée; Durand, Pierre

2005-07-01

This study analyses the relationship between occupation, work conditions and the experience of psychological distress within a model encompassing the stress promoted by constraints-resources embedded in macrosocial structures (occupational structure), structures of daily life (workplace, family, social networks outside the workplace) and agent personality (demography, physical health, psychological traits, life habits, stressful childhood events). Longitudinal data were derived from Statistics Canada's National Population Health Survey and comprised 6,359 workers nested in 471 occupations, followed four times between 1994-1995 and 2000-2001. Discrete time survival multilevel regressions were conducted on first and repeated episodes of psychological distress. Results showed that 42.9 per cent of workers had reported one episode of psychological distress and 18.7 per cent had done so more than once. Data supported the model and challenged the results of previous studies. The individual's position in the occupational structure plays a limited role when the structures of daily life and agent personality are accounted for. In the workplace, job insecurity and social support are important determinants, but greater decision authority increases the risk of psychological distress. Workplace constraints-resources are not moderated either by the other structures of daily life or by agent personality.

Adsorption of various antimicrobial agents to endotoxin removal polymyxin-B immobilized fiber (Toraymyxin®). Part 2: Adsorption of two drugs to Toraymyxin PMX-20R cartridges.

PubMed

Shimokawa, Ken-ichi; Takakuwa, Ryotaro; Wada, Yuko; Yamazaki, Noriko; Ishii, Fumiyoshi

2013-01-01

In our previous study, the degree of adsorption of 9 representative antimicrobial agents to Toraymyxin(®) PMX-F sheets was quantitatively evaluated. As a result, the adsorption rate was 22.1% for Linezolid in the presence of serum. Therefore, we investigated whether two types of antimicrobial agents (Ciprofroxacin and Linezolid) can be better adsorbed on PMX-F sheets. When the number of PMX-F sheets was increased in a step wise manner, specifically 2, 4, 6, 8 and 12, the adsorption rate increased linearly. In addition, the adsorption to polymyxin-B immobilized fiber (Toraymyxin(®) PMX-20R) cartridges, widely used to remove endotoxins from circulating blood in the treatment of sepsis, was quantitatively evaluated. As a result, in the presence of serum, Linezolid showed adsorption to PMX-20R, and the adsorption rate after 2h was 54.5%, and that after 4h was 65.8%. The results of this study suggest the necessity of monitoring blood antimicrobial concentration during treatment for sepsis with Linezolid, which showed adsorption to PMX-20R in an environment close to a clinical environment. Copyright © 2012 Elsevier B.V. All rights reserved.

Development of an Agent-Based Model to Investigate the Impact of HIV Self-Testing Programs on Men Who Have Sex With Men in Atlanta and Seattle.

PubMed

Luo, Wei; Katz, David A; Hamilton, Deven T; McKenney, Jennie; Jenness, Samuel M; Goodreau, Steven M; Stekler, Joanne D; Rosenberg, Eli S; Sullivan, Patrick S; Cassels, Susan

2018-06-29

In the United States HIV epidemic, men who have sex with men (MSM) remain the most profoundly affected group. Prevention science is increasingly being organized around HIV testing as a launch point into an HIV prevention continuum for MSM who are not living with HIV and into an HIV care continuum for MSM who are living with HIV. An increasing HIV testing frequency among MSM might decrease future HIV infections by linking men who are living with HIV to antiretroviral care, resulting in viral suppression. Distributing HIV self-test (HIVST) kits is a strategy aimed at increasing HIV testing. Our previous modeling work suggests that the impact of HIV self-tests on transmission dynamics will depend not only on the frequency of tests and testers' behaviors but also on the epidemiological and testing characteristics of the population. The objective of our study was to develop an agent-based model to inform public health strategies for promoting safe and effective HIV self-tests to decrease the HIV incidence among MSM in Atlanta, GA, and Seattle, WA, cities representing profoundly different epidemiological settings. We adapted and extended a network- and agent-based stochastic simulation model of HIV transmission dynamics that was developed and parameterized to investigate racial disparities in HIV prevalence among MSM in Atlanta. The extension comprised several activities: adding a new set of model parameters for Seattle MSM; adding new parameters for tester types (ie, regular, risk-based, opportunistic-only, or never testers); adding parameters for simplified pre-exposure prophylaxis uptake following negative results for HIV tests; and developing a conceptual framework for the ways in which the provision of HIV self-tests might change testing behaviors. We derived city-specific parameters from previous cohort and cross-sectional studies on MSM in Atlanta and Seattle. Each simulated population comprised 10,000 MSM and targeted HIV prevalences are equivalent to 28% and 11% in Atlanta and Seattle, respectively. Previous studies provided sufficient data to estimate the model parameters representing nuanced HIV testing patterns and HIV self-test distribution. We calibrated the models to simulate the epidemics representing Atlanta and Seattle, including matching the expected stable HIV prevalence. The revised model facilitated the estimation of changes in 10-year HIV incidence based on counterfactual scenarios of HIV self-test distribution strategies and their impact on testing behaviors. We demonstrated that the extension of an existing agent-based HIV transmission model was sufficient to simulate the HIV epidemics among MSM in Atlanta and Seattle, to accommodate a more nuanced depiction of HIV testing behaviors than previous models, and to serve as a platform to investigate how HIV self-tests might impact testing and HIV transmission patterns among MSM in Atlanta and Seattle. In our future studies, we will use the model to test how different HIV self-test distribution strategies might affect HIV incidence among MSM. ©Wei Luo, David A Katz, Deven T Hamilton, Jennie McKenney, Samuel M Jenness, Steven M Goodreau, Joanne D Stekler, Eli S Rosenberg, Patrick S Sullivan, Susan Cassels. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 29.06.2018.

Appropriateness of gram-negative agent use at a tertiary care hospital in the setting of significant antimicrobial resistance.

PubMed

Vora, Neil M; Kubin, Christine J; Furuya, E Yoko

2015-01-01

Background.  Practicing antimicrobial stewardship in the setting of widespread antimicrobial resistance among gram-negative bacilli, particularly in urban areas, is challenging. Methods.  We conducted a retrospective cross-sectional study at a tertiary care hospital with an established antimicrobial stewardship program in New York, New York to determine appropriateness of use of gram-negative antimicrobials and to identify factors associated with suboptimal antimicrobial use. Adult inpatients who received gram-negative agents on 2 dates, 1 June 2010 or 1 December 2010, were identified through pharmacy records. Clinical data were collected for each patient. Use of gram-negative agents was deemed optimal or suboptimal through chart review and according to hospital guidelines. Data were compared using χ(2) or Fischer's exact test for categorical variables and Student t test or Mann-Whitney U test for continuous variables. Results.  A total of 356 patients were included who received 422 gram-negative agents. Administration was deemed suboptimal in 26% of instances, with the most common reason being spectrum of activity too broad. In multivariable analysis, being in an intensive care unit (adjusted odds ratio [aOR], .49; 95% confidence interval [CI], .29-.84), having an infectious diseases consultation within the previous 7 days (aOR, .52; 95% CI, .28-.98), and having a history of multidrug-resistant gram-negative bacilli within the past year (aOR, .24; 95% CI, .09-.65) were associated with optimal gram-negative agent use. Beta-lactam/beta-lactamase inhibitor combination drug use (aOR, 2.6; 95% CI, 1.35-5.16) was associated with suboptimal use. Conclusions.  Gram-negative agents were used too broadly despite numerous antimicrobial stewardship program activities.

Prevention of shockwave induced functional and morphological alterations: an overview.

PubMed

Sarica, Kemal; Yencilek, Faruk

2008-03-01

Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia/reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

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.

Dynamic social networks facilitate cooperation in the N-player Prisoner’s Dilemma

NASA Astrophysics Data System (ADS)

Rezaei, Golriz; Kirley, Michael

2012-12-01

Understanding how cooperative behaviour evolves in network communities, where the individual members interact via social dilemma games, is an on-going challenge. In this paper, we introduce a social network based model to investigate the evolution of cooperation in the N-player Prisoner’s Dilemma game. As such, this work complements previous studies focused on multi-player social dilemma games and endogenous networks. Agents in our model, employ different game-playing strategies reflecting varying cognitive capacities. When an agent plays cooperatively, a social link is formed with each of the other N-1 group members. Subsequent cooperative actions reinforce this link. However, when an agent defects, the links in the social network are broken. Computational simulations across a range of parameter settings are used to examine different scenarios: varying population and group sizes; the group formation process (or partner selection); and agent decision-making strategies under varying dilemma constraints (cost-to-benefit ratios), including a “discriminator” strategy where the action is based on a function of the weighted links within an agent’s social network. The simulation results show that the proposed social network model is able to evolve and maintain cooperation. As expected, as the value of N increases the equilibrium proportion of cooperators in the population decreases. In addition, this outcome is dependent on the dilemma constraint (cost-to-benefit ratio). However, in some circumstances the dynamic social network plays an increasingly important role in promoting and sustaining cooperation, especially when the agents adopt the discriminator strategy. The adjustment of social links results in the formation of communities of “like-minded” agents. Subsequently, this local optimal behaviour promotes the evolution of cooperative behaviour at the system level.

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

PubMed Central

Lefranc, Florence; Carbone, Marianna; Mollo, Ernesto; Gavagnin, Margherita; Betancourt, Tania; Dasari, Ramesh

2016-01-01

Abstract The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity. PMID:27925266

Why we interact: on the functional role of the striatum in the subjective experience of social interaction.

PubMed

Pfeiffer, Ulrich J; Schilbach, Leonhard; Timmermans, Bert; Kuzmanovic, Bojana; Georgescu, Alexandra L; Bente, Gary; Vogeley, Kai

2014-11-01

There is ample evidence that human primates strive for social contact and experience interactions with conspecifics as intrinsically rewarding. Focusing on gaze behavior as a crucial means of human interaction, this study employed a unique combination of neuroimaging, eye-tracking, and computer-animated virtual agents to assess the neural mechanisms underlying this component of behavior. In the interaction task, participants believed that during each interaction the agent's gaze behavior could either be controlled by another participant or by a computer program. Their task was to indicate whether they experienced a given interaction as an interaction with another human participant or the computer program based on the agent's reaction. Unbeknownst to them, the agent was always controlled by a computer to enable a systematic manipulation of gaze reactions by varying the degree to which the agent engaged in joint attention. This allowed creating a tool to distinguish neural activity underlying the subjective experience of being engaged in social and non-social interaction. In contrast to previous research, this allows measuring neural activity while participants experience active engagement in real-time social interactions. Results demonstrate that gaze-based interactions with a perceived human partner are associated with activity in the ventral striatum, a core component of reward-related neurocircuitry. In contrast, interactions with a computer-driven agent activate attention networks. Comparisons of neural activity during interaction with behaviorally naïve and explicitly cooperative partners demonstrate different temporal dynamics of the reward system and indicate that the mere experience of engagement in social interaction is sufficient to recruit this system. Copyright © 2014 Elsevier Inc. All rights reserved.

Cyanobacteria as a Source for Novel Anti-Leukemic Compounds.

PubMed

Humisto, Anu; Herfindal, Lars; Jokela, Jouni; Karkman, Antti; Bjørnstad, Ronja; Choudhury, Romi R; Sivonen, Kaarina

2016-01-01

Cyanobacteria are an inspiring source of bioactive secondary metabolites. These bioactive agents are a diverse group of compounds which are varying in their bioactive targets, the mechanisms of action, and chemical structures. Cyanobacteria from various environments, especially marine benthic cyanobacteria, are found to be rich sources for the search for novel bioactive compounds. Several compounds with anticancer activities have been discovered from cyanobacteria and some of these have succeeded to enter the clinical trials. Varying anticancer agents are needed to overcome increasing challenges in cancer treatments. Different search methods are used to reveal anticancer compounds from natural products, but cell based methods are the most common. Cyanobacterial bioactive compounds as agents against acute myeloid leukemia are not well studied. Here we examined our new results combined with previous studies of anti-leukemic compounds from cyanobacteria with emphasis to reveal common features in strains producing such activity. We report that cyanobacteria harbor specific anti-leukemic compounds since several studied strains induced apoptosis against AML cells but were inactive against non-malignant cells like hepatocytes. We noted that particularly benthic strains from the Baltic Sea, such as Anabaena sp., were especially potential AML apoptosis inducers. Taken together, this review and re-analysis of data demonstrates the power of maintaining large culture collections for the search for novel bioactivities, and also how anti-AML activity in cyanobacteria can be revealed by relatively simple and low-cost assays.

Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse. (I) Development of a model for screening studies in skin decontamination and protection.

PubMed

Dorandeu, F; Taysse, L; Boudry, I; Foquin, A; Hérodin, F; Mathieu, J; Daulon, S; Cruz, C; Lallement, G

2011-06-01

Exposure to lethal chemical warfare agents (CWAs) is no longer only a military issue due to the terrorist threat. Among the CWAs of concern are the organophosphorus nerve agent O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX) and the vesicant sulfur mustard (SM). Although efficient means of decontamination are available, most of them lose their efficacy when decontamination is delayed after exposure of the bare skin. Alternatively, CWA skin penetration can be prevented by topical skin protectants. Active research in skin protection and decontamination is thus paramount. In vivo screening of decontaminants or skin protectants is usually time consuming and may be expensive depending on the animal species used. We were thus looking for a suitable, scientifically sound and cost-effective model, which is easy to handle. The euthymic hairless mouse Crl: SKH-1 (hr/hr) BR is widely used in some skin studies and has previously been described to be suitable for some experiments involving SM or SM analogs. To evaluate the response of this species, we studied the consequences of exposing male anaesthetized SKH-1 mice to either liquid VX or to SM, the latter being used in liquid form or as saturated vapours. Long-term effects of SM burn were also evaluated. The model was then used in the companion paper (Taysse et al.(1)).

Repeated dose 28-day oral toxicity study of DEAE-Dextran in mice: An advancement in safety chemotherapeutics.

PubMed

Bakrania, Anita K; Variya, Bhavesh C; Madan, Prem; Patel, Snehal S

2017-08-01

Cancer has emerged as a global threat with challenges for safe chemotherapeutics. Most of the currently available anti-cancer drugs exhibit significant toxicity. Amongst novel agents, interferons have exhibited anti-proliferative and cytoprotective roles. However, due to stability drawbacks of interferons, we have identified an interferon inducer DEAE-Dextran, which resolves the stability issues. Based on the previous history of toxicity pertaining to the current chemotherapeutic agents, it is equally essential to determine the safety of DEAE-Dextran. In the present study, repeated dose 28 day oral toxicity of DEAE-Dextran has been evaluated in accordance to OECD-407. We found absence of any CNS behavioral changes related to self-mutilation, walking backwards, aggressiveness on handling or tonic-clonic seizures during the 28 day study. Neither the motor activity nor grip strength was altered during the treatment duration with DEAE-Dextran implying absence of any effect on the skeletal muscles. Interestingly, we also found that treatment with DEAE-Dextran did not present any significant cardiac, hepatic, renal, gastrointestinal, lymphatic or reproductive system toxicity or alteration in the body's normal physiology based upon the various organ function tests. Henceforth, it may be concluded that DEAE-Dextran is a safe anti-cancer agent devoid of any sub-acute toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

PubMed

Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

2016-12-01

While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively). In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination. © 2016 by American Journal of Neuroradiology.

Towards a Cognitively Realistic Computational Model of Team Problem Solving Using ACT-R Agents and the ELICIT Experimentation Framework

DTIC Science & Technology

2014-06-01

intelligence analysis processes. However, as has been noted in previous work (e.g., [42]), there are a number of important differences between the nature of the...problem encountered in the context of the ELICIT task and the problems dealt with by intelligence analysts. Perhaps most importantly, the fact that a...see Section 7). 6 departure from the reality of most intelligence analysis situations: in most real-world intelligence analysis problems agents have

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

DTIC Science & Technology

2013-08-01

GFAP,IL6,CCL2, TNF, L118, Lif, IL10 Hip, Ctx Ctx Ctx CORT=corticosterone;(200mg/L) for days 7-14 P8= pyridostigmine bromide ;P8(2.5 mg/kg/day, s.c...reversible acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB), the insect repellent DEET and, potentially, the nerve agent, sarin. These...acetylcholinesterase (AChE) inhibitor, pyridostigmine bromide (PB), the insect repellent, DEET, and, potentially, acutely to the nerve agent sarin. Previously, we

Cognitive Modeling for Agent-Based Simulation of Child Maltreatment

NASA Astrophysics Data System (ADS)

Hu, Xiaolin; Puddy, Richard

This paper extends previous work to develop cognitive modeling for agent-based simulation of child maltreatment (CM). The developed model is inspired from parental efficacy, parenting stress, and the theory of planned behavior. It provides an explanatory, process-oriented model of CM and incorporates causality relationship and feedback loops from different factors in the social ecology in order for simulating the dynamics of CM. We describe the model and present simulation results to demonstrate the features of this model.

Community-acquired Legionella micdadei (Pittsburgh pneumonia agent) infection in Sweden.

PubMed

Bäck, E; Schvarcz, R; Kallings, I

1983-01-01

The first case of Legionella micdadei (Pittsburgh Pneumonia Agent) infection in Sweden is presented. A previously healthy 68-yr-old man fell ill with diarrhoea, fever, and mental confusion. Subsequently chest roentgenography revealed pneumonic infiltrates and a seroconversion to L. micdadei was shown. No source or transmission of infection was established. The only notable event was that the patient had been drinking rain-water from a barrel 1 day prior to his illness. An alimentary route of infection was considered.

Material Compatibility for Historic Items Decontaminated with ...

EPA Pesticide Factsheets

Report This project continued research of the effects of decontamination methods for biological agents on materials identified as representative of types of irreplaceable objects or works of art found in museums and/or archive settings. In the previous research, surrogate materials were checked for compatibility with four decontamination methods: chlorine dioxide, hydrogen peroxide vapor, methyl bromide, and ethylene oxide gas. This project investigated the effects of gamma irradiation, which has also been shown to be an effective decontamination method for biological agents, on the surrogate test materials.

Regulation of Ca(2+)-dependent protein turnover in skeletal muscle by thyroxine

NASA Technical Reports Server (NTRS)

Zeman, Richard J.; Bernstein, Paul L.; Ludemann, Robert; Etlinger, Joseph D.

1986-01-01

Dantrolene, an agent that inhibits Ca(2+) mobilization, improved protein balance in skeletal muscle, as thyroid status was increased, by altering rates of protein synthesis and degradation. Thyroxine (T4) caused increases in protein degradation that were blocked by leupeptin, a proteinase inhibitor previously shown to inhibit Ca(2+)-dependent nonlysosomal proteolysis in these muscles. In addition, T4 abolished sensitivity to the lysosomotropic agent methylamine and the autophagy inhibitor 3-methyladenine, suggesting that T4 inhibits autophagic/lysosomal proteolysis.

Safety Assessment of Synthetic Fluorphlogopite 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 (the Panel) reviewed the safety of synthetic fluorphlogopite as used in cosmetics. Synthetic fluorphlogopite functions as a bulking agent and a viscosity-increasing agent. The Panel reviewed available animal and human data related to this ingredient along with a previous safety assessment of other magnesium silicates. The Panel concluded that synthetic fluorphlogopite was safe as cosmetic ingredients in the practices of use and concentration as given in this safety assessment. © The Author(s) 2015.

Security patterns and a weighting scheme for mobile agents

NASA Astrophysics Data System (ADS)

Walker, Jessie J.

The notion of mobility has always been a prime factor in human endeavor and achievement. This need to migrate by humans has been distilled into software entities, which are their representatives on distant environments. Software agents are developed to act on behalf of a user. Mobile agents were born from the understanding that many times it was much more useful to move the code (program) to where the resources are located, instead of connecting remotely. Within the mobile agent research community, security has traditionally been the most defining issue facing the community and preventing the paradigm from gaining wide acceptance. There are still numerous difficult problems being addressed with very few practical solutions, such as the malicious host and agent problems. These problems are some of the most active areas of research within the mobile agent community. The major principles, facets, fundamental concepts, techniques and architectures of the field are well understood within the community. This is evident by the many mobile agent systems developed in the last decade that share common core components such as agent management, communication facilities, and mobility services. In other words new mobile agent systems and frameworks do not provide any new insights into agent system architecture or mobility services, agent coordination, communication that could be useful to the agent research community, although these new mobile agent systems do in many instances validate, refine, demonstrate the reuse of many previously proposed and discussed mobile agent research elements. Since mobile agent research for the last decade has been defined by security and related issues, our research into security patterns are within this narrow arena of mobile agent research. The research presented in this thesis examines the issue of mobile agent security from the standpoint of security pattern documented from the universe of mobile agent systems. In addition, we explore how these documented security patterns can be quantitatively compared based on a unique weighting scheme. The scheme is formalized into a theory that can be used improve the development of secure mobile agents and agent-based systems.

Fermentation product of soybean, black bean, and green bean mixture induces apoptosis in a wide variety of cancer cells.

PubMed

Chia, Jean-San; Du, Jia-Ling; Wu, Ming-Shiou; Hsu, Wei-Bin; Chiang, Chun-Pin; Sun, Andy; Lu, John Jenn-Yenn; Wang, Won-Bo

2013-05-01

Previous studies have shown that soybean fermentation products can act as cancer chemoprevention or therapeutic agents. In this study, the anticancer activities of a fermentation product of soybean, black bean, and green bean mixture (BN999) were investigated. We found that BN999 inhibited the growth of human breast cancer AU565 cells and prostate adenocarcinoma PC-3 cells but not that of normal human cells. BN999 induced apoptosis in various human cancer cells but not in normal human cells. BN999 treatment of AU565 cancer cells resulted in activation of calpain and caspase-8, -9, and -3, suggesting that BN999 induces apoptosis via receptor-, mitochondria-, and endoplasmic reticulum-mediated pathways. Finally, we showed that BN999 inhibited the growth of mouse CT-26 colon cancer xenografts in syngenic BALB/c mice without causing obvious side effects. Together, these data suggest that BN999 has potential to be used as a cancer chemoprevention or therapeutic agent.

A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents

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

Quintela, Barbara de M.; Conway, Jessica M.; Hyman, James M.

Here, the dynamics of hepatitis C virus (HCV) RNA during translation and replication within infected cells were added to a previous age-structured multiscale mathematical model of HCV infection and treatment. The model allows the study of the dynamics of HCV RNA inside infected cells as well as the release of virus from infected cells and the dynamics of subsequent new cell infections. The model was used to fit in vitro data and estimate parameters characterizing HCV replication. This is the first model to our knowledge to consider both positive and negative strands of HCV RNA with an age-structured multiscale modelingmore » approach. Using this model we also studied the effects of direct-acting antiviral agents (DAAs) in blocking HCV RNA intracellular replication and the release of new virions and fit the model to in vivo data obtained from HCV-infected subjects under therapy.« less

[Decontamination of chemical warfare agents by photocatalysis].

PubMed

Hirakawa, Tsutomu; Mera, Nobuaki; Sano, Taizo; Negishi, Nobuaki; Takeuchi, Koji

2009-01-01

Photocatalysis has been widely applied to solar-energy conversion and environmental purification. Photocatalyst, typically titanium dioxide (TiO(2)), produces active oxygen species under irradiation of ultraviolet light, and can decompose not only conventional pollutants but also different types of hazardous substances at mild conditions. We have recently started the study of photocatalytic decontamination of chemical warfare agents (CWAs) under collaboration with the National Research Institute of Police Science. This article reviews environmental applications of semiconductor photocatalysis, decontamination methods for CWAs, and previous photocatalytic studies applied to CWA degradation, together with some of our results obtained with CWAs and their simulant compounds. The data indicate that photocatalysis, which may not always give a striking power, certainly helps detoxification of such hazardous compounds. Unfortunately, there are not enough data obtained with real CWAs due to the difficulty in handling. We will add more scientific data using CWAs in the near future to develop useful decontamination systems that can reduce the damage caused by possible terrorism.

Reproducible insulin secretion from isolated rat pancreas preparations using an organ bath.

PubMed

Morita, Asuka; Ouchi, Motoshi; Terada, Misao; Kon, Hiroe; Kishimoto, Satoko; Satoh, Keitaro; Otani, Naoyuki; Hayashi, Keitaro; Fujita, Tomoe; Inoue, Ken-Ichi; Anzai, Naohiko

2018-02-09

Diabetes mellitus is a lifestyle-related disease that is characterized by inappropriate or diminished insulin secretion. Ex vivo pharmacological studies of hypoglycemic agents are often conducted using perfused pancreatic preparations. Pancreas preparations for organ bath experiments do not require cannulation and are therefore less complex than isolated perfused pancreas preparations. However, previous research has generated almost no data on insulin secretion from pancreas preparations using organ bath preparations. The purpose of this study was to investigate the applicability of isolated rat pancreas preparations using the organ bath technique in the quantitative analysis of insulin secretion from β-cells. We found that insulin secretion significantly declined during incubation in the organ bath, whereas it was maintained in the presence of 1 µM GLP-1. Conversely, amylase secretion exhibited a modest increase during incubation and was not altered in the presence of GLP-1. These results demonstrate that the pancreatic organ bath preparation is a sensitive and reproducible method for the ex vivo assessment of the pharmacological properties of hypoglycemic agents.

Mind perception of God in Japanese children.

PubMed

Moriguchi, Yusuke; Takahashi, Hideyuki; Nakamata, Tomoko; Todo, Naoya

2018-03-05

There is a theoretical debate regarding whether children represent God with reference to a human. Most previous studies have assessed this issue focusing on knowledge/omniscience in western children. This study used a theoretical framework characterising mental capacities in terms of motivational/emotional (experience) and cognitive (agency) mental capacities and tested whether Japanese children discriminated between God, a human, a baby and an invisible agent according to these capacities. Three- to 6-year-old children were asked about the experience and agency of the agents. The results revealed that children discriminated God from a human in terms of mental capacities including experience and agency in 3-year-old children. On the other hand, 4- to 6-year-old children, but not 3-year-old children, discriminated a human from a baby and an invisible person. The results suggest that the Japanese children's representations of God differed from their representation of a human during preschool years. © 2018 International Union of Psychological Science.

Towards High-Energy-Density Pseudocapacitive Flowable Electrodes by the Incorporation of Hydroquinone

DOE PAGES

Boota, M.; Hatzell, K. B.; Kumbur, E. C.; ...

2015-01-29

Our study reports an investigation of hydroquinone (HQ) as a multielectron organic redox molecule to enhance the performance of flowable electrodes. Moreover, two different methods to produce high-performance pseudocapacitive flowable electrodes were investigated for electrochemical flow capacitors. First, HQ molecules were deposited on carbon spheres (CSs) by a self-assembly approach using various HQ loadings. In the second approach, HQ was used as a redox-mediating agent in the electrolyte. Flowable electrodes composed of HQ showed a capacitance of 342 Fg 1, which is >200% higher than that of flowable electrodes based on nontreated CSs (160 Fg 1), and outperformed (in gravimetricmore » performance) many reported film electrodes. A similar trend in capacitance was observed if HQ was used as a redox agent in the electrolyte; however, its poor cycle life restricted further consideration. Additionally, a twofold increase in capacitance was observed under flow conditions compared to that of previous studies.« less

A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents

DOE PAGES

Quintela, Barbara de M.; Conway, Jessica M.; Hyman, James M.; ...

2018-04-04

Here, the dynamics of hepatitis C virus (HCV) RNA during translation and replication within infected cells were added to a previous age-structured multiscale mathematical model of HCV infection and treatment. The model allows the study of the dynamics of HCV RNA inside infected cells as well as the release of virus from infected cells and the dynamics of subsequent new cell infections. The model was used to fit in vitro data and estimate parameters characterizing HCV replication. This is the first model to our knowledge to consider both positive and negative strands of HCV RNA with an age-structured multiscale modelingmore » approach. Using this model we also studied the effects of direct-acting antiviral agents (DAAs) in blocking HCV RNA intracellular replication and the release of new virions and fit the model to in vivo data obtained from HCV-infected subjects under therapy.« less

Common Warming Pattern Emerges Irrespective of Forcing Location

NASA Astrophysics Data System (ADS)

Kang, Sarah M.; Park, Kiwoong; Jin, Fei-Fei; Stuecker, Malte F.

2017-10-01

The Earth's climate is changing due to the existence of multiple radiative forcing agents. It is under question whether different forcing agents perturb the global climate in a distinct way. Previous studies have demonstrated the existence of similar climate response patterns in response to aerosol and greenhouse gas (GHG) forcings. In this study, the sensitivity of tropospheric temperature response patterns to surface heating distributions is assessed by forcing an atmospheric general circulation model coupled to an aquaplanet slab ocean with a wide range of possible forcing patterns. We show that a common climate pattern emerges in response to localized forcing at different locations. This pattern, characterized by enhanced warming in the tropical upper troposphere and the polar lower troposphere, resembles the historical trends from observations and models as well as the future projections. Atmospheric dynamics in combination with thermodynamic air-sea coupling are primarily responsible for shaping this pattern. Identifying this common pattern strengthens our confidence in the projected response to GHG and aerosols in complex climate models.

Antibiosis and bmyB Gene Presence As Prevalent Traits for the Selection of Efficient Bacillus Biocontrol Agents against Crown Gall Disease.

PubMed

Frikha-Gargouri, Olfa; Ben Abdallah, Dorra; Bhar, Ilhem; Tounsi, Slim

2017-01-01

This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates. Moreover, potential in vitro biocontrol traits were investigated including biofilm formation, motility, hemolytic activity, detection of lipopeptide biosynthetic genes ( sfp, ituC and bmyB ) and production of antibacterial compounds. The obtained results indicated high correlations of the efficiency of the biocontrol with the reduction of gall weight ( p = 0.000) and the antibacterial activity in vitro ( p = 0.000). Moreover, there was strong correlations of the efficiency of the biocontrol ( p = 0.004) and the reduction in gall weight ( p = 0.000) with the presence of the bmyB gene. This gene directs the synthesis of the lipopeptide bacillomycin belonging to the iturinic family of lipopeptides. These results were also confirmed by the two-way hierarchical cluster analysis and the correspondence analysis showing the relatedness of these four variables. According to the obtained results a new screening procedure of Bacillus biocontrol agents against crown gall disease could be advanced consisting on two step selection procedure. The first consists on selecting strains with high antibacterial activity in vitro or those harbouring the bmyB gene. Further selection has to be performed on tomato plants in vivo . Moreover, based on the results of the biocontrol assay, five potent strains exhibiting high biocontrol abilities were selected. They were identified as Bacillus subtilis or Bacillus amyloliquefaciens . These strains were found to produce either surfactin or surfactin and iturin lipopeptides. In conclusion, our study presented a new and effective method to evaluate the biocontrol ability of antagonistic Bacillus strains against crown gall disease that could increase the efficiency of screening method of biocontrol agents. Besides, the selected strains could be used as novel biocontrol agents against pathogenic Agrobacterium tumefaciens strains.

Antibiosis and bmyB Gene Presence As Prevalent Traits for the Selection of Efficient Bacillus Biocontrol Agents against Crown Gall Disease

PubMed Central

Frikha-Gargouri, Olfa; Ben Abdallah, Dorra; Bhar, Ilhem; Tounsi, Slim

2017-01-01

This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates. Moreover, potential in vitro biocontrol traits were investigated including biofilm formation, motility, hemolytic activity, detection of lipopeptide biosynthetic genes (sfp, ituC and bmyB) and production of antibacterial compounds. The obtained results indicated high correlations of the efficiency of the biocontrol with the reduction of gall weight (p = 0.000) and the antibacterial activity in vitro (p = 0.000). Moreover, there was strong correlations of the efficiency of the biocontrol (p = 0.004) and the reduction in gall weight (p = 0.000) with the presence of the bmyB gene. This gene directs the synthesis of the lipopeptide bacillomycin belonging to the iturinic family of lipopeptides. These results were also confirmed by the two-way hierarchical cluster analysis and the correspondence analysis showing the relatedness of these four variables. According to the obtained results a new screening procedure of Bacillus biocontrol agents against crown gall disease could be advanced consisting on two step selection procedure. The first consists on selecting strains with high antibacterial activity in vitro or those harbouring the bmyB gene. Further selection has to be performed on tomato plants in vivo. Moreover, based on the results of the biocontrol assay, five potent strains exhibiting high biocontrol abilities were selected. They were identified as Bacillus subtilis or Bacillus amyloliquefaciens. These strains were found to produce either surfactin or surfactin and iturin lipopeptides. In conclusion, our study presented a new and effective method to evaluate the biocontrol ability of antagonistic Bacillus strains against crown gall disease that could increase the efficiency of screening method of biocontrol agents. Besides, the selected strains could be used as novel biocontrol agents against pathogenic Agrobacterium tumefaciens strains. PMID:28855909

114.1 What is New in the Treatment of Schizophrenia?

PubMed Central

Correll, Christoph

2017-01-01

Abstract Background: Despite psychopharmacological advances, the evidence-based pharmacologic treatment of schizophrenia is still restricted to antidopaminergic compounds that predominantly address positive symptoms and agitation as well as aggression. Rational augmentation strategies to enhance effects in treatment resistant cases and to address relevant negative and cognitive symptoms are needed. Methods: Systematic review and critical appraisal of (1) meta-analytic evidence of augmentation and combination treatments, as well as (2) agents that are in phase III development for different domains on schizophrenia. Results: Out of 3397 publications, 29 meta-analyses testing 42 combination strategies in 381 individual trials and 19 833 participants were included. For total symptom reduction, 32 strategies augmenting any antipsychotic and 5 strategies augmenting clozapine were examined. Fourteen combination treatments outperformed control (SMD/Hedges’ g= −1.27 to −0.23). No combination strategies with clozapine outperformed control. Methodological quality of the meta-analyses was generally high (mean score = 9.4/11). However, content quality of the meta-analyzed studies was low (mean score = 2.8/8). Poorer content quality was significantly related to higher effect sizes in total psychopathology. We also identified 253 recent phase III clinical trials in schizophrenia that included 16 investigational compounds. Encenicline and valbenazine are first-in-class candidates for treatment of cognitive deficits and tardive dyskinesia, respectively, but recent encenicline data were negative. Eleven add-on compounds were previously approved for other therapeutic indications; they are for the most part being studied at academic medical centers and smaller pharmaceutical companies for new therapeutic targets (negative symptoms and cognitive deficits) or for specific populations with comorbidities and adverse effects (e.g., tardive dyskinesia and weight gain/obesity). Details of these agents will be discussed. Conclusion: Several augmentation and combination treatments have been studies, but despite selected agents being recommended in meta-analyses, no high-quality evidence exists for effective agents. Furthermore, although a number of different agents with dopaminergic and extradopaminergic mechanisms are in later stage development, some showing promising earlier results, none of the agents that do not modulate dopaminergic transmission have yet accumulated sufficient evidence to be recommendable for clinical use. An exception are agents that are being developed for the improvement of tardive dyskinesia.

Canine infection with Dirofilaria immitis, Borrelia burgdorferi, Anaplasma spp., and Ehrlichia spp. in the United States, 2010–2012

PubMed Central

2014-01-01

Background The geographic distribution of canine infection with vector-borne disease agents in the United States appears to be expanding. Methods To provide an updated assessment of geographic trends in canine infection with Dirofilaria immitis, Borrelia burgdorferi, Ehrlichia spp., and Anaplasma spp., we evaluated results from an average of 3,588,477 dogs tested annually by veterinarians throughout the United States from 2010 – 2012. Results As in an earlier summary report, the percent positive test results varied by agent and region, with antigen of D. immitis and antibody to Ehrlichia spp. most commonly identified in the Southeast (2.9% and 3.2%, respectively) and antibody to both B. burgdorferi and Anaplasma spp. most commonly identified in the Northeast (13.3% and 7.1%, respectively) and upper Midwest (4.4% and 3.9%, respectively). Percent positive test results for D. immitis antigen were lower in every region considered, including in the Southeast, than previously reported. Percent positive test results for antibodies to B. burgdorferi and Ehrlichia spp. were higher nationally than previously reported, and, for antibodies to Anaplasma spp., were higher in the Northeast but lower in the Midwest and West, than in the initial report. Annual reports of human cases of Lyme disease, ehrlichiosis, and anaplasmosis were associated with percent positive canine test results by state for each respective tick-borne disease agent (R2 = 0.701, 0.457, and 0.314, respectively). Within endemic areas, percent positive test results for all three tick-borne agents demonstrated evidence of geographic expansion. Conclusions Continued national monitoring of canine test results for vector-borne zoonotic agents is an important tool for accurately mapping the geographic distribution of these agents, and greatly aids our understanding of the veterinary and public health threats they pose. PMID:24886589

Tests on ticks from wild birds collected in the eastern United States for rickettsiae and viruses

USGS Publications Warehouse

Clifford, C.M.; Sonenshine, D.E.; Atwood, E.L.; Robbins, C.S.; Hughes, L.E.

1969-01-01

Results of tests for rickettsiae and viruses on 4,266 ticks taken from more than 10,000 birds, comprising 150 species, in the eastern United States indicated the presence of two agents: Rickettsia rickettsii and an agent of the typhus group. Infection with R. rickettsii was indicated in 24 pools of Haemaphysalis leporispalustris, five pools of Ixodes dentatus, one pool of Ixodes brunneus, and two pools that contained both I. dentatus and H. leporispalustris. The pools positive for R. rickettsii were from a variety of locations in the eastern U. S. The typhus-group agent was demonstrated only once, in a single pool of H. leporispalustris taken at Kent Point, Maryland. A strain of R. rickettsii was isolated from a pool of 21 larval H. leporispalustris collected at Ocean City, Maryland. This agent possessed several characteristics of other strains of low virulence isolated previously in this region by various authors.

Limit cycles and the benefits of a short memory in rock-paper-scissors games.

PubMed

Burridge, James

2015-10-01

When playing games in groups, it is an advantage for individuals to have accurate statistical information on the strategies of their opponents. Such information may be obtained by remembering previous interactions. We consider a rock-paper-scissors game in which agents are able to recall their last m interactions, used to estimate the behavior of their opponents. At critical memory length, a Hopf bifurcation leads to the formation of stable limit cycles. In a mixed population, agents with longer memories have an advantage, provided the system has a stable fixed point, and there is some asymmetry in the payoffs of the pure strategies. However, at a critical concentration of long memory agents, the appearance of limit cycles destroys their advantage. By introducing population dynamics that favors successful agents, we show that the system evolves toward the bifurcation point.

Limit cycles and the benefits of a short memory in rock-paper-scissors games

NASA Astrophysics Data System (ADS)

Burridge, James

2015-10-01

When playing games in groups, it is an advantage for individuals to have accurate statistical information on the strategies of their opponents. Such information may be obtained by remembering previous interactions. We consider a rock-paper-scissors game in which agents are able to recall their last m interactions, used to estimate the behavior of their opponents. At critical memory length, a Hopf bifurcation leads to the formation of stable limit cycles. In a mixed population, agents with longer memories have an advantage, provided the system has a stable fixed point, and there is some asymmetry in the payoffs of the pure strategies. However, at a critical concentration of long memory agents, the appearance of limit cycles destroys their advantage. By introducing population dynamics that favors successful agents, we show that the system evolves toward the bifurcation point.

Autonomous Visual Navigation of an Indoor Environment Using a Parsimonious, Insect Inspired Familiarity Algorithm

PubMed Central

Brayfield, Brad P.

2016-01-01

The navigation of bees and ants from hive to food and back has captivated people for more than a century. Recently, the Navigation by Scene Familiarity Hypothesis (NSFH) has been proposed as a parsimonious approach that is congruent with the limited neural elements of these insects’ brains. In the NSFH approach, an agent completes an initial training excursion, storing images along the way. To retrace the path, the agent scans the area and compares the current scenes to those previously experienced. By turning and moving to minimize the pixel-by-pixel differences between encountered and stored scenes, the agent is guided along the path without having memorized the sequence. An important premise of the NSFH is that the visual information of the environment is adequate to guide navigation without aliasing. Here we demonstrate that an image landscape of an indoor setting possesses ample navigational information. We produced a visual landscape of our laboratory and part of the adjoining corridor consisting of 2816 panoramic snapshots arranged in a grid at 12.7-cm centers. We show that pixel-by-pixel comparisons of these images yield robust translational and rotational visual information. We also produced a simple algorithm that tracks previously experienced routes within our lab based on an insect-inspired scene familiarity approach and demonstrate that adequate visual information exists for an agent to retrace complex training routes, including those where the path’s end is not visible from its origin. We used this landscape to systematically test the interplay of sensor morphology, angles of inspection, and similarity threshold with the recapitulation performance of the agent. Finally, we compared the relative information content and chance of aliasing within our visually rich laboratory landscape to scenes acquired from indoor corridors with more repetitive scenery. PMID:27119720

On the relevance of Gibson's affordance concept for geographical information science (GISc).

PubMed

Jonietz, David; Timpf, Sabine

2015-09-01

J. J. Gibson's concept of affordances has provided a theoretical basis for various studies in geographical information science (GISc). This paper sets out to explain its popularity from a GISc perspective. Based on a short review of previous work, it will be argued that its main contributions to GISc are twofold, including an action-centered view of spatial entities and the notion of agent-environment mutuality. Using the practical example of pedestrian behavior simulation, new potentials for using and extending affordances are discussed.

Adenovirus-Mediated p202 Gene Transfer in Breast Cancer Gene Therapy

DTIC Science & Technology

2005-05-01

transcriptional regulation of genes important for cell cycle control, differentiation, and apoptosis (1, 3, 4). Our previous studies have shown that p202...leads to induction of p53 and activation of p53 target gene (e.g., p21 CIP 1). 10. The positive regulation of p53 by IFIXcd can be observed only in...cancers. Together, our data suggest that both Ad-p202 and IFIX may be further developed into efficient therapeutic agents for human cancer gene

Boldness by habituation and social interactions: a model.

PubMed

Oosten, Johanneke E; Magnhagen, Carin; Hemelrijk, Charlotte K

2010-04-01

Most studies of animal personality attribute personality to genetic traits. But a recent study by Magnhagen and Staffan (Behav Ecol Sociobiol 57:295-303, 2005) on young perch in small groups showed that boldness, a central personality trait, is also shaped by social interactions and by previous experience. The authors measured boldness by recording the duration that an individual spent near a predator and the speed with which it fed there. They found that duration near the predator increased over time and was higher the higher the average boldness of other group members. In addition, the feeding rate of shy individuals was reduced if other members of the same group were bold. The authors supposed that these behavioral dynamics were caused by genetic differences, social interactions, and habituation to the predator. However, they did not quantify exactly how this could happen. In the present study, we therefore use an agent-based model to investigate whether these three factors may explain the empirical findings. We choose an agent-based model because this type of model is especially suited to study the relation between behavior at an individual level and behavioral dynamics at a group level. In our model, individuals were either hiding in vegetation or feeding near a predator, whereby their behavior was affected by habituation and by two social mechanisms: social facilitation to approach the predator and competition over food. We show that even if we start the model with identical individuals, these three mechanisms were sufficient to reproduce the behavioral dynamics of the empirical study, including the consistent differences among individuals. Moreover, if we start the model with individuals that already differ in boldness, the behavioral dynamics produced remained the same. Our results indicate the importance of previous experience and social interactions when studying animal personality empirically.

Modeling of a production system using the multi-agent approach

NASA Astrophysics Data System (ADS)

Gwiazda, A.; Sękala, A.; Banaś, W.

2017-08-01

The method that allows for the analysis of complex systems is a multi-agent simulation. The multi-agent simulation (Agent-based modeling and simulation - ABMS) is modeling of complex systems consisting of independent agents. In the case of the model of the production system agents may be manufactured pieces set apart from other types of agents like machine tools, conveyors or replacements stands. Agents are magazines and buffers. More generally speaking, the agents in the model can be single individuals, but you can also be defined as agents of collective entities. They are allowed hierarchical structures. It means that a single agent could belong to a certain class. Depending on the needs of the agent may also be a natural or physical resource. From a technical point of view, the agent is a bundle of data and rules describing its behavior in different situations. Agents can be autonomous or non-autonomous in making the decision about the types of classes of agents, class sizes and types of connections between elements of the system. Multi-agent modeling is a very flexible technique for modeling and model creating in the convention that could be adapted to any research problem analyzed from different points of views. One of the major problems associated with the organization of production is the spatial organization of the production process. Secondly, it is important to include the optimal scheduling. For this purpose use can approach multi-purposeful. In this regard, the model of the production process will refer to the design and scheduling of production space for four different elements. The program system was developed in the environment NetLogo. It was also used elements of artificial intelligence. The main agent represents the manufactured pieces that, according to previously assumed rules, generate the technological route and allow preprint the schedule of that line. Machine lines, reorientation stands, conveyors and transport devices also represent the other type of agent that are utilized in the described simulation. The article presents the idea of an integrated program approach and shows the resulting production layout as a virtual model. This model was developed in the NetLogo multi-agent program environment.

Conditioned place avoidance of zebrafish (Danio rerio) to three chemicals used for euthanasia and anaesthesia.

PubMed

Wong, Devina; von Keyserlingk, Marina A G; Richards, Jeffrey G; Weary, Daniel M

2014-01-01

Zebrafish are becoming one of the most used vertebrates in developmental and biomedical research. Fish are commonly killed at the end of an experiment with an overdose of tricaine methanesulfonate (TMS, also known as MS-222), but to date little research has assessed if exposure to this or other agents qualifies as euthanasia (i.e. a "good death"). Alternative agents include metomidate hydrochloride and clove oil. We use a conditioned place avoidance paradigm to compare aversion to TMS, clove oil, and metomidate hydrochloride. Zebrafish (n = 51) were exposed to the different anaesthetics in the initially preferred side of a light/dark box. After exposure to TMS zebrafish spent less time in their previously preferred side; aversion was less pronounced following exposure to metomidate hydrochloride and clove oil. Nine of 17 fish exposed to TMS chose not to re-enter the previously preferred side, versus 2 of 18 and 3 of 16 refusals for metomidate hydrochloride and clove oil, respectively. We conclude that metomidate hydrochloride and clove oil are less aversive than TMS and that these agents be used as humane alternatives to TMS for killing zebrafish.

An agent-based simulation combined with group decision-making technique for improving the performance of an emergency department.

PubMed

Yousefi, M; Ferreira, R P M

2017-03-30

This study presents an agent-based simulation modeling in an emergency department. In a traditional approach, a supervisor (or a manager) allocates the resources (receptionist, nurses, doctors, etc.) to different sections based on personal experience or by using decision-support tools. In this study, each staff agent took part in the process of allocating resources based on their observation in their respective sections, which gave the system the advantage of utilizing all the available human resources during the workday by being allocated to a different section. In this simulation, unlike previous studies, all staff agents took part in the decision-making process to re-allocate the resources in the emergency department. The simulation modeled the behavior of patients, receptionists, triage nurses, emergency room nurses and doctors. Patients were able to decide whether to stay in the system or leave the department at any stage of treatment. In order to evaluate the performance of this approach, 6 different scenarios were introduced. In each scenario, various key performance indicators were investigated before and after applying the group decision-making. The outputs of each simulation were number of deaths, number of patients who leave the emergency department without being attended, length of stay, waiting time and total number of discharged patients from the emergency department. Applying the self-organizing approach in the simulation showed an average of 12.7 and 14.4% decrease in total waiting time and number of patients who left without being seen, respectively. The results showed an average increase of 11.5% in total number of discharged patients from emergency department.

An agent-based simulation combined with group decision-making technique for improving the performance of an emergency department

PubMed Central

Yousefi, M.; Ferreira, R.P.M.

2017-01-01

This study presents an agent-based simulation modeling in an emergency department. In a traditional approach, a supervisor (or a manager) allocates the resources (receptionist, nurses, doctors, etc.) to different sections based on personal experience or by using decision-support tools. In this study, each staff agent took part in the process of allocating resources based on their observation in their respective sections, which gave the system the advantage of utilizing all the available human resources during the workday by being allocated to a different section. In this simulation, unlike previous studies, all staff agents took part in the decision-making process to re-allocate the resources in the emergency department. The simulation modeled the behavior of patients, receptionists, triage nurses, emergency room nurses and doctors. Patients were able to decide whether to stay in the system or leave the department at any stage of treatment. In order to evaluate the performance of this approach, 6 different scenarios were introduced. In each scenario, various key performance indicators were investigated before and after applying the group decision-making. The outputs of each simulation were number of deaths, number of patients who leave the emergency department without being attended, length of stay, waiting time and total number of discharged patients from the emergency department. Applying the self-organizing approach in the simulation showed an average of 12.7 and 14.4% decrease in total waiting time and number of patients who left without being seen, respectively. The results showed an average increase of 11.5% in total number of discharged patients from emergency department. PMID:28380196

Acute dyskinetic reaction in a healthy toddler following methylphenidate ingestion.

PubMed

Waugh, Jeff L

2013-07-01

Acute dyskinetic or dystonic reactions are a long-recognized complication of medications that alter dopamine signaling. Most reactions occur following exposure to agents that block dopamine receptors (e.g., neuroleptics). However, agents that increase dopaminergic transmission (such as methylphenidate) can also trigger acute dyskinesias. This has been previously reported only in patients also taking dopamine antagonists or, less commonly, in children with developmental abnormalities. The present report describes a previously healthy toddler who developed transient torticollis and orolingual dyskinesias following accidental exposure to methylphenidate. He had no preexisting movement disorder, central nervous system injury, or developmental abnormalities--in short, none of the previously reported risk factors for this side effect. The unique features of this case led to the hypothesis that developmental shifts in dopamine signaling were the basis for his particular sensitivity to methylphenidate. If confirmed, this hypothesis has implications for the treatment of common childhood attentional and behavioral disorders. The article includes a literature review of dyskinetic/dystonic reactions in children and the developmental regulation of dopamine metabolism. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of media composition, including gelling agents, on isolation of previously uncultured rumen bacteria.

PubMed

Nyonyo, T; Shinkai, T; Tajima, A; Mitsumori, M

2013-01-01

The aim of this study was to develop novel anaerobic media using gellan gum for the isolation of previously uncultured rumen bacteria. Four anaerobic media, a basal liquid medium (BM) with agar (A-BM), a modified BM (MBM) with agar (A-MBM), an MBM with phytagel (P-MBM) and an MBM with gelrite (G-MBM) were used for the isolation of rumen bacteria and evaluated for the growth of previously uncultured rumen bacteria. Of the 214 isolates composed of 144 OTUs, 103 isolates (83 OTUs) were previously uncultured rumen bacteria. Most of the previously uncultured strains were obtained from A-MBM, G-MBM and P-MBM, but the predominant cultural members, isolated from each medium, differed. A-MBM and G-MBM showed significantly higher numbers of different OTUs derived from isolates than A-BM (P < 0·05). The Shannon index indicated that the isolates of A-MBM showed the highest diversity (H' = 3·89) compared with those of G-MBM, P-MBM and A-BM (H' = 3·59, 3·23 and 3·39, respectively). Although previously uncultured rumen bacteria were isolated from all media used, the ratio of previously uncultured bacteria to total isolates was increased in A-MBM, P-MBM and G-MBM. © 2012 The Society for Applied Microbiology.

Contributions to Pursuit-Evasion Game Theory

NASA Astrophysics Data System (ADS)

Oyler, Dave Wilson

This dissertation studies adversarial conflicts among a group of agents moving in the plane, possibly among obstacles, where some agents are pursuers and others are evaders. The goal of the pursuers is to capture the evaders, where capture requires a pursuer to be either co-located with an evader, or in close proximity. The goal of the evaders is to avoid capture. These scenarios, where different groups compete to accomplish conflicting goals, are referred to as pursuit-evasion games, and the agents are called players. Games featuring one pursuer and one evader are analyzed using dominance, where a point in the plane is said to be dominated by a player if that player is able to reach the point before the opposing players, regardless of the opposing players' actions. Two generalizations of the Apollonius circle are provided. One solves games with environments containing obstacles, and the other provides an alternative solution method for the Homicidal Chauffeur game. Optimal pursuit and evasion strategies based on dominance are provided. One benefit of dominance analysis is that it extends to games with many players. Two foundational games are studied; one features multiple pursuers against a single evader, and the other features a single pursuer against multiple evaders. Both are solved using dominance through a reduction to single pursuer, single evader games. Another game featuring competing teams of pursuers is introduced, where an evader cooperates with friendly pursuers to rendezvous before being captured by adversaries. Next, the assumption of complete and perfect information is relaxed, and uncertainties in player speeds, player positions, obstacle locations, and cost functions are studied. The sensitivity of the dominance boundary to perturbations in parameters is provided, and probabilistic dominance is introduced. The effect of information is studied by comparing solutions of games with perfect information to games with uncertainty. Finally, a pursuit law is developed that requires minimal information and highlights a limitation of dominance regions. These contributions extend pursuit-evasion game theory to a number of games that have not previously been solved, and in some cases, the solutions presented are more amenable to implementation than previous methods.

Using Mobile TLA as a Logic for Dynamic I/O Automata

NASA Astrophysics Data System (ADS)

Kapus, Tatjana

Input/Output (I/O) automata and the Temporal Logic of Actions (TLA) are two well-known techniques for the specification and verification of concurrent systems. Over the past few years, they have been extended to the so-called dynamic I/O automata and, respectively, Mobile TLA (MTLA) in order to be more appropriate for mobile agent systems. Dynamic I/O automata is just a mathematical model, whereas MTLA is a logic with a formally defined language. In this paper, therefore, we investigate how MTLA could be used as a formal language for the specification of dynamic I/O automata. We do this by writing an MTLA specification of a travel agent system which has been specified semi-formally in the literature on that model. In this specification, we deal with always existing agents as well as with an initially unknown number of dynamically created agents, with mobile and non-mobile agents, with I/O-automata-style communication, and with the changing communication capabilities of mobile agents. We have previously written a TLA specification of this system. This paper shows that an MTLA specification of such a system can be more elegant and faithful to the dynamic I/O automata definition because the agent existence and location can be expressed directly by using agent and location names instead of special variables as in TLA. It also shows how the reuse of names for dynamically created and destroyed agents within the dynamic I/O automata framework can be specified in MTLA.

Evaluating food additives as antifungal agents against Monilinia fructicola in vitro and in hydroxypropyl methylcellulose-lipid composite edible coatings for plums.

PubMed

Karaca, Hakan; Pérez-Gago, María B; Taberner, Verònica; Palou, Lluís

2014-06-02

Common food preservative agents were evaluated in in vitro tests for their antifungal activity against Monilinia fructicola, the most economically important pathogen causing postharvest disease of stone fruits. Radial mycelial growth was measured in Petri dishes of PDA amended with three different concentrations of the agents (0.01-0.2%, v/v) after 7 days of incubation at 25 °C. Thirteen out of fifteen agents tested completely inhibited the radial growth of the fungus at various concentrations. Among them, ammonium carbonate, ammonium bicarbonate and sodium bicarbonate were the most effective while sodium acetate and sodium formate were the least effective. The effective agents and concentrations were tested as ingredients of hydroxypropyl methylcellulose (HPMC)-lipid edible coatings against brown rot disease on plums previously inoculated with M. fructicola (curative activity). 'Friar' and 'Larry Ann' plums were inoculated with the pathogen, coated with stable edible coatings about 24h later, and incubated at 20 °C and 90% RH. Disease incidence (%) and severity (lesion diameter) were determined after 4, 6, and 8 days of incubation and the 'area under the disease progress stairs' (AUDPS) was calculated. Coatings containing bicarbonates and parabens significantly reduced brown rot incidence in plums, but potassium sorbate, used at 1.0% in the coating formulation, was the most effective agent with a reduction rate of 28.6%. All the tested coatings reduced disease severity to some extent, but coatings containing 0.1% sodium methylparaben or sodium ethylparaben or 0.2% ammonium carbonate or ammonium bicarbonate were superior to the rest, with reduction rates of 45-50%. Overall, the results showed that most of the agents tested in this study had significant antimicrobial activity against M. fructicola and the application of selected antifungal edible coatings is a promising alternative for the control of postharvest brown rot in plums. Copyright © 2014 Elsevier B.V. All rights reserved.

Indoor sorption of surrogates for sarin and related nerve agents.

PubMed

Singer, Brett C; Hodgson, Alfred T; Destaillats, Hugo; Hotchi, Toshifumi; Revzan, Kenneth L; Sextro, Richard G

2005-05-01

Sorption rate parameters were determined for three organophosphorus (OP) compounds [dimethyl methylphosphonate (DMMP), diethyl ethylphosphonate (DEEP), and triethyl phosphate (TEP)] as surrogates for the G-type nerve agents sarin (GB), soman (GD), and tabun (GA). OP surrogates were injected and vaporized with additional volatile organic compounds into a 50 m3 chamber finished with painted wallboard. Experiments were conducted at two furnishing levels: (i) chamber containing only hard surfaces including a desk, a bookcase, tables, and chairs and (ii) with the addition of plush materials including carpet with cushion, draperies, and upholstered furniture. Each furnishing level was studied with aged and new painted wallboard. Gas-phase concentrations were measured during sealed chamber adsorb and desorb phases and then fit to three mathematical variations of a previously proposed sorption model having a surface sink and allowing for an embedded sink. A four-parameter model allowing unequal transport rates between surface and embedded sinks provided excellent fits for all conditions. To evaluate the potential effect of sorption, this model was incorporated into an indoor air quality simulation model to predict indoor concentrations of a G-type agent and a nonsorbing agent for hypothetical outdoor releases with shelter-in-place (SIP) response. Sorption was simulated using a range of parameters obtained experimentally. Simulations considered outdoor Gaussian plumes of 1- and 5-h duration and infiltration rates of 0.1, 0.3, and 0.9 h(-1). Indoor toxic loads (TL) for a 10-h SIP were calculated as integral C2 dt for a G-type agent. For the 5-h plume, sheltering reduced TLs for the nonsorbing agent to approximately 10-65% of outdoor levels. Analogous TLs for a G-type agent were 2-31% or 0.3-12% of outdoor levels assuming slow or moderate sorption. The relative effect of sorption was more pronounced for the longer plume and higher infiltration rates.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

PubMed

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

PubMed Central

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. PMID:28744140

Mitochondrial uncoupling agents antagonize rotenone actions in rat substantia nigra dopamine neurons.

PubMed

Wu, Yan-Na; Munhall, Adam C; Johnson, Steven W

2011-06-13

Mild uncoupling of oxidative phosphorylation has been reported to reduce generation of reactive oxygen species (ROS) and therefore may be neuroprotective. We reported previously that the mitochondrial poison rotenone enhanced currents evoked by N-methyl-D-aspartate (NMDA) by a ROS-dependent mechanism in rat midbrain dopamine neurons. Thus, rotenone, which produces a model of Parkinson's disease in rodents, may increase the risk of dopamine neuron excitotoxicity. The purpose of this study was to test the hypothesis that oxidative phosphorylation uncoupling agents would antagonize the effect of rotenone on NMDA current. We used patch pipettes to record whole-cell currents under voltage-clamp (-60 mV) in substantia nigra dopamine neurons in slices of rat brain. Rotenone, NMDA and uncoupling agents were added to the brain slice superfusate. Inward currents evoked by NMDA (30 μM) more than doubled in amplitude after slices were superfused for 30 min with 100 nM rotenone. Continuous superfusion with the uncoupling agent carbonyl cyanide-p-trifluoromethoxy-phenylhydrazone (1-3 nM) or 2,4-dinitrophenol (100 nM) significantly antagonized and delayed the ability of rotenone to potentiate NMDA currents. Coenzyme Q₁₀ (1-10 nM), which has been reported to facilitate uncoupling protein activity, also antagonized this action of rotenone. These results suggest that mild uncoupling of oxidative phosphorylation may protect dopamine neurons against injury from mitochondrial poisons such as rotenone. Published by Elsevier B.V.

Climate change effects on international stability : a white paper.

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

Murphy, Kathryn; Taylor, Mark A.; Fujii, Joy

2004-12-01

This white paper represents a summary of work intended to lay the foundation for development of a climatological/agent model of climate-induced conflict. The paper combines several loosely-coupled efforts and is the final report for a four-month late-start Laboratory Directed Research and Development (LDRD) project funded by the Advanced Concepts Group (ACG). The project involved contributions by many participants having diverse areas of expertise, with the common goal of learning how to tie together the physical and human causes and consequences of climate change. We performed a review of relevant literature on conflict arising from environmental scarcity. Rather than simply reviewingmore » the previous work, we actively collected data from the referenced sources, reproduced some of the work, and explored alternative models. We used the unfolding crisis in Darfur (western Sudan) as a case study of conflict related to or triggered by climate change, and as an exercise for developing a preliminary concept map. We also outlined a plan for implementing agents in a climate model and defined a logical progression toward the ultimate goal of running both types of models simultaneously in a two-way feedback mode, where the behavior of agents influences the climate and climate change affects the agents. Finally, we offer some ''lessons learned'' in attempting to keep a diverse and geographically dispersed group working together by using Web-based collaborative tools.« less

Product Distribution Theory for Control of Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Lee, Chia Fan; Wolpert, David H.

2004-01-01

Product Distribution (PD) theory is a new framework for controlling Multi-Agent Systems (MAS's). First we review one motivation of PD theory, as the information-theoretic extension of conventional full-rationality game theory to the case of bounded rational agents. In this extension the equilibrium of the game is the optimizer of a Lagrangian of the (probability distribution of) the joint stare of the agents. Accordingly we can consider a team game in which the shared utility is a performance measure of the behavior of the MAS. For such a scenario the game is at equilibrium - the Lagrangian is optimized - when the joint distribution of the agents optimizes the system's expected performance. One common way to find that equilibrium is to have each agent run a reinforcement learning algorithm. Here we investigate the alternative of exploiting PD theory to run gradient descent on the Lagrangian. We present computer experiments validating some of the predictions of PD theory for how best to do that gradient descent. We also demonstrate how PD theory can improve performance even when we are not allowed to rerun the MAS from different initial conditions, a requirement implicit in some previous work.

The agencies method for coalition formation in experimental games

PubMed Central

Nash, John F.; Nagel, Rosemarie; Ockenfels, Axel; Selten, Reinhard

2012-01-01

In society, power is often transferred to another person or group. A previous work studied the evolution of cooperation among robot players through a coalition formation game with a non-cooperative procedure of acceptance of an agency of another player. Motivated by this previous work, we conduct a laboratory experiment on finitely repeated three-person coalition formation games. Human players with different strength according to the coalition payoffs can accept a transfer of power to another player, the agent, who then distributes the coalition payoffs. We find that the agencies method for coalition formation is quite successful in promoting efficiency. However, the agent faces a tension between short-term incentives of not equally distributing the coalition payoff and the long-term concern to keep cooperation going. In a given round, the strong player in our experiment often resolves this tension approximately in line with the Shapley value and the nucleolus. Yet aggregated over all rounds, the payoff differences between players are rather small, and the equal division of payoffs predicts about 80% of all groups best. One reason is that the voting procedure appears to induce a balance of power, independent of the individual player's strength: Selfish subjects tend to be voted out of their agency and are further disciplined by reciprocal behaviors. PMID:23175792

The agencies method for coalition formation in experimental games.

PubMed

Nash, John F; Nagel, Rosemarie; Ockenfels, Axel; Selten, Reinhard

2012-12-11

In society, power is often transferred to another person or group. A previous work studied the evolution of cooperation among robot players through a coalition formation game with a non-cooperative procedure of acceptance of an agency of another player. Motivated by this previous work, we conduct a laboratory experiment on finitely repeated three-person coalition formation games. Human players with different strength according to the coalition payoffs can accept a transfer of power to another player, the agent, who then distributes the coalition payoffs. We find that the agencies method for coalition formation is quite successful in promoting efficiency. However, the agent faces a tension between short-term incentives of not equally distributing the coalition payoff and the long-term concern to keep cooperation going. In a given round, the strong player in our experiment often resolves this tension approximately in line with the Shapley value and the nucleolus. Yet aggregated over all rounds, the payoff differences between players are rather small, and the equal division of payoffs predicts about 80% of all groups best. One reason is that the voting procedure appears to induce a balance of power, independent of the individual player's strength: Selfish subjects tend to be voted out of their agency and are further disciplined by reciprocal behaviors.

Overcoming platinum drug resistance with copper-lowering agents.

PubMed

Chen, Helen H W; Kuo, Macus Tien

2013-10-01

Platinum (Pt)-based antitumor agents have been the mainstay of cancer chemotherapy for the last three decades. While multiple mechanisms are responsible for treatment failure, deficiency in drug transport is an important contributor. The human high-affinity copper (Cu) transporter-1 (hCtr1) can also transport Pt-based drugs including cisplatin (cDDP) and carboplatin. Reduced hCtr1 expression frequently occurs in cDDP-resistant cell lines and in cancer in patients who failed chemotherapy with these drugs. We previously demonstrated that Cu chelation induces the expression of transcription factor Sp1 which binds the promoters of Sp1 and hCtr1, thereby, up-regulating their expression, whereas Cu overload shuts down hCtr1 and Sp1 expression by dissociating Sp1 from their promoter promoters. Thus, mammalian Cu homeostasis is transcriptionally regulated within a loop consisting of Sp1, hCtr1, and Cu in a three-way mutually regulated manner. These findings suggest that it is feasible to module cDDP transport capacity through intervention of mammalian Cu homeostasis. Indeed, we found that cDDP resistance can be overcome by Cu-lowering agents through enhanced hCtr1 expression by up-regulation of Sp1 in cultured cells. This discovery provided a mechanistic basis for the ongoing clinical study using Cu chelator to overcome cDDP resistance in ovarian cancer chemotherapy. Preliminary study using copper chelator (trientine) for enhancing the treatment efficacy of carboplatin in 5 ovarian cancer patients showed encouraging results. This short review describes the perspectives of using Cu-lowering agents in overcoming Pt resistance in cancer chemotherapy.

Temozolomide alone or in combination with doxorubicin as a rescue agent in 37 cases of canine multicentric lymphoma.

PubMed

Treggiari, E; Elliott, J W; Baines, S J; Blackwood, L

2018-06-01

Temozolomide (TMZ) is an alkylating agent previously used in conjunction with doxorubicin (DOX) to treat dogs with relapsed lymphoma. However, there are very limited data for this drug when used as single agent. The aim of this retrospective study was to evaluate the efficacy and toxicity of TMZ in dogs with relapsed multicentric lymphoma that failed multi-agent chemotherapy protocols, and compare the outcome to a group of dogs receiving the same drug in combination with DOX. Twenty-six patients were included in the TMZ group and 11 in the TMZ/DOX group. Responses were evaluated via retrospective review of the medical records. The overall median survival time (MST) for both groups was 40 days (range 1-527 days). For the TMZ group, median time to progression (TTP) was 15 days (range 1-202 days) and MST 40 days (range 1-527 days), with an overall response rate (ORR) of 32% and 46% recorded toxicities. For the TMZ/DOX group, median TTP was 19 days (range 2-87 days) and MST 24 days (range 3-91 days), with an ORR of 60% and 63% recorded toxicities. However, a proportion of haematological toxicoses may have gone undetected due to the absence of associated clinical signs. The difference in MST and TTP between the 2 groups was not statistically significant. Similarly, no negative prognostic factors were identified. Although responses were generally short lived, this study suggests that TMZ may achieve similar efficacy to TMZ/DOX whilst being associated with a lower frequency of recorded toxicities. © 2017 John Wiley & Sons Ltd.

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.

Doped Halloysite Nanotubes for Use in the 3D Printing of Medical Devices.

PubMed

Weisman, Jeffery A; Jammalamadaka, Udayabhanu; Tappa, Karthik; Mills, David K

2017-12-15

Previous studies have established halloysite nanotubes (HNTs) as viable nanocontainers capable of sustained release of a variety of antibiotics, corrosion agents, chemotherapeutics and growth factors either from their lumen or in outer surface coatings. Accordingly, halloysite nanotubes (HNTs) hold great promise as drug delivery carriers in the fields of pharmaceutical science and regenerative medicine. This study explored the potential of 3D printing drug doped HNT constructs. We used a model drug, gentamicin (GS) and polylactic acid (PLA) to fabricate GS releasing disks, beads, and pellets. Gentamicin was released from 3D printed constructs in a sustained manner and had a superior anti-bacterial growth inhibition effect that was dependent on GS doping concentration. While this study focused on a model drug, gentamicin, combination therapy is possible through the fabrication of medical devices containing HNTs doped with a suite of antibiotics or antifungals. Furthermore, tailored dosage levels, suites of antimicrobials, delivered locally would reduce the toxicity of individual agents, prevent the emergence of resistant strains, and enable the treatment of mixed infections.

Phase II Trial of β-All-trans-Retinoic Acid for Cervical Intraepithelial Neoplasia Delivered via a Collagen Sponge and Cervical Cap

PubMed Central

Graham, Vivian; Surwit, Earl S.; Weiner, Sheldon; Meyskens, Frank L.

1986-01-01

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer. ImagesFigure. 1. PMID:3765597

Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM.

PubMed

Miyake, Yuka; Ishikawa, Syungo; Kimura, Yu; Son, Aoi; Imai, Hirohiko; Matsuda, Tetsuya; Yamada, Hisatsugu; Toshimitsu, Akio; Kondo, Teruyuki

2015-12-18

Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r₁) values about four times higher than that of clinically used Gd-DTPA (Magnevist(®), Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (K(a)) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The K(a) values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

Exploratory Study on the Effects of Novel Diamine Curing Agents and Isocyanate Precursors on the Properties of New Epoxy and Urethane Adhesives

NASA Technical Reports Server (NTRS)

Glasgow, D. Gerald; Garthwait, Clayborn

1977-01-01

This report covers the results of investigations directed toward studying the effects of novel aromatic diamine structures on epoxy adhesive properties and includes work done under a modification to the original contract. Three aromatic diamines based on diphenylsulfone and benzophenone were studied as epoxy adhesive curing agents. Previously found differences in adhesive strengths for meta vs para orientation were not found in these series. The use of aluminum and alumina as fillers in a m,m'-methylene dianiline-cured epoxy adhesive was not found to be beneficial to adhesive strength. Alumina filled adhesives had much lower strength than unfilled adhesives. The unfilled m,m'-methylene dianiline-based epoxy adhesive had excellent resistance to moisture relative to a p,p'-methylene dianiline-based adhesive and maintained good strengths up to 250 F. A glass fiber composite based on a m,m'-methylene dianiline-cured epoxy appeared to be equivalent to the p,p'-methylene dianiline-cured epoxy as judged by short beam shear tests.

Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM

PubMed Central

Miyake, Yuka; Ishikawa, Syungo; Kimura, Yu; Son, Aoi; Imai, Hirohiko; Matsuda, Tetsuya; Yamada, Hisatsugu; Toshimitsu, Akio; Kondo, Teruyuki

2015-01-01

Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r1) values about four times higher than that of clinically used Gd-DTPA (Magnevist®, Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (Ka) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The Ka values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo. PMID:26694418

Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex.

PubMed

Hagberg, Gisela E; Mamedov, Ilgar; Power, Anthony; Beyerlein, Michael; Merkle, Hellmut; Kiselev, Valerij G; Dhingra, Kirti; Kubìček, Vojtĕch; Angelovski, Goran; Logothetis, Nikos K

2014-01-01

Calcium-sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI-based method capable of determining diffusion properties of conventional and calcium-sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium-sensitive contrast agents. The full pharmacokinetic time-course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel-wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look-Locker-based quantitative T(1) mapping, and T(1) -weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2-4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium-sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration. Copyright © 2014 John Wiley & Sons, Ltd.

Therapeutic management of orally treated type 2 diabetic patients, by French general practitioners in 2010: the DIAttitude Study.

PubMed

Halimi, S; Balkau, B; Attali, C; Detournay, B; Amelineau, E; Blickle, J-F

2012-03-01

To describe the behaviour of French general practitioners (GP) regarding intensification of hypoglycaemic agents in orally treated type 2 diabetic (T2D) patients, according to their HbA(1c) level. General practitioners were recruited from a panel of office-based general practitioners. T2D patients who had been orally treated for at least 6 months were included in the study; their characteristics were recorded, and their HbA(1c) values and hypoglycaemic treatments over the previous 24 months extracted from electronic records The major reasons for intensification (or no intensification) of hypoglycaemic agents were recorded at the inclusion visit. A total of 236 general practitioners recruited 2109 T2D patients: 1732 had at least one HbA(1c) value recorded in the previous 6 months, and 52%, 33% and 14% had been treated, with oral hypoglycaemic agents in monotherapy, bitherapy or tri-or quadritherapy, respectively. Of these patients, 702 (41%) remained uncontrolled (47%, 39% and 20% respectively) and according to the current French guidelines needed treatment intensification. Only 46 (7%) had their treatment intensified at inclusion. Of those without intensified treatment, 60% were treated with monotherapy; the main reason given by the general practitioners for not intensifying treatment was a satisfactory HbA(1c) level (53%), although 32% had an HbA(1c)>7%. Other reasons were: lifestyle advice had greater priority (20%); decision was postponed until the next visit (11%); HbA(1c) had decreased since last visit (7%; not confirmed by available data in 58% of cases); a medical priority other than diabetes (6%) and other reasons related to the patient (3%). For T2D patients managed by French general practitioners, guidelines are not consistently followed: HbA(1c) should be monitored more frequently and treatment adjusted according to HbA(1c) levels. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Identification of 24h Ixodes scapularis immunogenic tick saliva proteins.

PubMed

Lewis, Lauren A; Radulović, Željko M; Kim, Tae K; Porter, Lindsay M; Mulenga, Albert

2015-04-01

Ixodes scapularis is arguably the most medically important tick species in the United States. This tick transmits 5 of the 14 human tick-borne disease (TBD) agents in the USA: Borrelia burgdorferi, Anaplasma phagocytophilum, B. miyamotoi, Babesia microti, and Powassan virus disease. Except for the Powassan virus disease, I. scapularis-vectored TBD agents require more than 24h post attachment to be transmitted. This study describes identification of 24h immunogenic I. scapularis tick saliva proteins, which could provide opportunities to develop strategies to stop tick feeding before transmission of the majority of pathogens. A 24h fed female I. scapularis phage display cDNA expression library was biopanned using rabbit antibodies to 24h fed I. scapularis female tick saliva proteins, subjected to next generation sequencing, de novo assembly, and bioinformatic analyses. A total of 182 contigs were assembled, of which ∼19% (35/182) are novel and did not show identity to any known proteins in GenBank. The remaining ∼81% (147/182) of contigs were provisionally identified based on matches in GenBank including ∼18% (27/147) that matched protein sequences previously annotated as hypothetical and putative tick saliva proteins. Others include proteases and protease inhibitors (∼3%, 5/147), transporters and/or ligand binding proteins (∼6%, 9/147), immunogenic tick saliva housekeeping enzyme-like (17%, 25/147), ribosomal protein-like (∼31%, 46/147), and those classified as miscellaneous (∼24%, 35/147). Notable among the miscellaneous class include antimicrobial peptides (microplusin and ricinusin), myosin-like proteins that have been previously found in tick saliva, and heat shock tick saliva protein. Data in this study provides the foundation for in-depth analysis of I. scapularis feeding during the first 24h, before the majority of TBD agents can be transmitted. Copyright © 2015 Elsevier GmbH. All rights reserved.

Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study.

PubMed

Merchan, Jaime R; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J; Flynn, Patrick J; Fruth, Briant F; Erlichman, Charles

2015-03-01

Bevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. In the phase I portion, eligible patients were treated with temsirolimus (25 mg IV weekly) and escalating doses of IV bevacizumab (level 1 = 5 mg/kg; level 2 = 10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression-free rate. Secondary endpoints were response rate, toxicity evaluation, and PFS and OS. Maximum tolerated dose was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (temsirolimus 25 mg IV weekly and bevacizumab 10 mg/kg IV every 2 weeks). The 6-month progression-free rate was 40 % (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response, stable disease, and progressive disease were seen in 23, 63, and 14 % of patients, respectively. Most common grade 3-4 AEs included fatigue (17.8 %), hypertriglyceridemia (11.1 %), stomatitis (8.9 %), proteinuria (8.9 %), abdominal pain (6.7 %), and anemia (6.7 %). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Temsirolimus and bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population.

Evaluation of the Effects of Lime-bassanite-charcoal Amendment on the Immobilization of Cadmium in Contaminated Soil.

PubMed

Huang, Shunhong; Yang, Yi; Li, Qian; Su, Zhen; Yuan, Cuiyu; Ouyang, Kun

2017-03-01

The effects of amendments, such as lime, bassanite, sodium phosphate, steel slag and charcoal, and their compounds on the immobilization of cadmium (Cd) are investigated. The lime-bassanite-charcoal compound shows the best remediation performance compared to other agents in conducted experiments. The optimum condition for lime-bassanite-charcoal application in contaminated soil is lime-bassanite-charcoal with a mass ratio of 1:1/3:2/3, a dose of 2% of the soil weight, and a liquid-to-solid ratio of 35%-40%; additionally, the agents should be added before water addition. The highest Cd removal rate was 58.94% (±1.19%) with a ∆pH of 0.23, which is much higher than the rates reported in previous studies. The compound amendment was used in a field experiment, demonstrating a Cd removal efficiency of 48.78% (±4.23), further confirming its effectiveness.

Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation.

PubMed

Teive, H A; Brandi, I V; Camargo, C H; Bittencourt, M A; Bonfim, C M; Friedrich, M L; de Medeiros, C R; Werneck, L C; Pasquini, R

2001-09-01

Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.

A putative role for Toxocara species in the aetiology of multiple sclerosis.

PubMed

Söndergaard, Hans Peter; Theorell, Töres

2004-01-01

Multiple sclerosis (MS) is a disease of unknown aetiology. The finding of monoclonal antibodies in MS has been attributed to various infectious agents. Nematodes, such as Toxocara species have not been explored as possible aetiologic agents of MS. Some epidemiological studies have found an association between exposure to stress and household pets prior to the diagnosis of MS. In a case known to the authors, slight malaise and eosinophilia in peripheral blood preceded the diagnosis of MS by one year in a middle-aged man who lived in rural surroundings with cats in the household. The ubiquitary parasite Toxocara catis or canis is prevalent and serum antibodies are found regularly in populations examined. It is able to develop into the larval stage in human beings. The hypothesis presented here is that MS could be initiated by such infections in previously unexposed subjects under conditions of long-term stress.

The origin of Behçet's disease geoepidemiology: possible role of a dual microbial-driven genetic selection.

PubMed

Piga, Matteo; Mathieu, Alessandro

2014-01-01

It is recognised that the genetic profiles that give rise to chronic inflammatory diseases, under the influence of environmental agents, might have been implicated in the host defence mechanism against lethal infections in the past. Behçet's disease (BD) is an immune-mediated inflammatory disease, expressed as vasculitis, triggered by environmental factors in genetically susceptible individuals. We carried out a review of published data to draw up an evolutionary adaptation model, as Author's perspective, for genetic susceptibility factors and inflammatory immune response involved in BD pathogenesis. Two lethal infectious agents, Plasmodium Falciparum and Yersinia Pestis, are proposed as the putative driving forces that favoured the fixing of the major genetic susceptibility factors to BD, thus determining its geoepidemiology. Further studies are needed to confirm the validity of this evolutionary model which includes and integrates the key insights of previous hypotheses.

Solving Assembly Sequence Planning using Angle Modulated Simulated Kalman Filter

NASA Astrophysics Data System (ADS)

Mustapa, Ainizar; Yusof, Zulkifli Md.; Adam, Asrul; Muhammad, Badaruddin; Ibrahim, Zuwairie

2018-03-01

This paper presents an implementation of Simulated Kalman Filter (SKF) algorithm for optimizing an Assembly Sequence Planning (ASP) problem. The SKF search strategy contains three simple steps; predict-measure-estimate. The main objective of the ASP is to determine the sequence of component installation to shorten assembly time or save assembly costs. Initially, permutation sequence is generated to represent each agent. Each agent is then subjected to a precedence matrix constraint to produce feasible assembly sequence. Next, the Angle Modulated SKF (AMSKF) is proposed for solving ASP problem. The main idea of the angle modulated approach in solving combinatorial optimization problem is to use a function, g(x), to create a continuous signal. The performance of the proposed AMSKF is compared against previous works in solving ASP by applying BGSA, BPSO, and MSPSO. Using a case study of ASP, the results show that AMSKF outperformed all the algorithms in obtaining the best solution.

NK cells are biologic and biochemical targets of 6-mercaptopurine in Crohn's disease patients.

PubMed

Yusung, Susy; McGovern, Dermot; Lin, Lin; Hommes, Daniel; Lagishetty, Venu; Braun, Jonathan

2017-02-01

NK cells, which contribute to immune defense against certain viral infections and neoplasia, are emerging as modifiers of chronic immunologic diseases including transplant rejection and autoimmune diseases. Immunobiology and genetic studies have implicated NK cells as a modifier of Crohn's disease, a condition often treated with thiopurine agents such as 6-mercaptopurine (6-MP). Here, we demonstrate that thiopurines mediate NK cell apoptosis via a caspase 3 and 9 inclusive pathway, and that this process is triggered by thiopurine-mediated inhibition of Rac1. We also show that CD patients in clinical remission maintained on 6-MP have decreased NK cell Rac1 activity, and decreased NK cell numbers in their intestinal biopsies. These observations suggest that thiopurine targeting of NK cells may be a previously unappreciated therapeutic action of these agents in IBD. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of vascularization on cancer nanochemotherapy outcomes

NASA Astrophysics Data System (ADS)

Paiva, L. R.; Ferreira, S. C.; Martins, M. L.

2016-08-01

Cancer therapy requires anticancer agents capable of efficient and uniform systemic delivery. One promising route to their development is nanotechnology. Here, a previous model for cancer chemotherapy based on a nanosized drug carrier (Paiva et al., 2011) is extended by including tissue vasculature and a three-dimensional growth. We study through computer simulations the therapy against tumors demanding either large or small nutrient supplies growing under different levels of tissue vascularization. Our results indicate that highly vascularized tumors demand more aggressive therapies (larger injected doses administrated at short intervals) than poorly vascularized ones. Furthermore, nanoparticle endocytic rate by tumor cells, not its selectivity, is the major factor that determines the therapeutic success. Finally, our finds indicate that therapies combining cytotoxic agents with antiangiogenic drugs that reduce the abnormal tumor vasculature, instead of angiogenic drugs that normalize it, can lead to successful treatments using feasible endocytic rates and administration intervals.

Enhancement of cooperation in the spatial prisoner's dilemma with a coherence-resonance effect through annealed randomness at a cooperator-defector boundary; comparison of two variant models

NASA Astrophysics Data System (ADS)

Tanimoto, Jun

2016-11-01

Inspired by the commonly observed real-world fact that people tend to behave in a somewhat random manner after facing interim equilibrium to break a stalemate situation whilst seeking a higher output, we established two models of the spatial prisoner's dilemma. One presumes that an agent commits action errors, while the other assumes that an agent refers to a payoff matrix with an added random noise instead of an original payoff matrix. A numerical simulation revealed that mechanisms based on the annealing of randomness due to either the action error or the payoff noise could significantly enhance the cooperation fraction. In this study, we explain the detailed enhancement mechanism behind the two models by referring to the concepts that we previously presented with respect to evolutionary dynamic processes under the names of enduring and expanding periods.

Current Status of New Anticoagulants in the Management of Venous Thromboembolism

PubMed Central

Montoya, Roberto C.; Gajra, Ajeet

2012-01-01

Venous Thromboembolism, manifested as deep venous thrombosis and pulmonary embolism, is a common problem associated with significant morbidity, mortality, and resource expenditure. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists are the most common treatment and prophylaxis, and have demonstrated their efficacy in a vast number of previous studies. Despite their broad use, these agents have important limitations that have led to the development of new drugs in a bid to overcome the disadvantages of the old ones without decreasing their therapeutic effect. These novel medications, some approved and others in different stages of development, include direct thrombin inhibitors like dabigatran etexilate, and direct activated factor X inhibitors like rivaroxaban. The current paper will review the characteristics, clinical trial results, and current and potential therapeutic uses of these new agents with a focus on the categories of direct thrombin inhibitors and activated factor X inhibitors. PMID:22496694

Evaluation of Secure Computation in a Distributed Healthcare Setting.

PubMed

Kimura, Eizen; Hamada, Koki; Kikuchi, Ryo; Chida, Koji; Okamoto, Kazuya; Manabe, Shirou; Kuroda, Tomohiko; Matsumura, Yasushi; Takeda, Toshihiro; Mihara, Naoki

2016-01-01

Issues related to ensuring patient privacy and data ownership in clinical repositories prevent the growth of translational research. Previous studies have used an aggregator agent to obscure clinical repositories from the data user, and to ensure the privacy of output using statistical disclosure control. However, there remain several issues that must be considered. One such issue is that a data breach may occur when multiple nodes conspire. Another is that the agent may eavesdrop on or leak a user's queries and their results. We have implemented a secure computing method so that the data used by each party can be kept confidential even if all of the other parties conspire to crack the data. We deployed our implementation at three geographically distributed nodes connected to a high-speed layer two network. The performance of our method, with respect to processing times, suggests suitability for practical use.