Advances in drug delivery system for platinum agents based combination therapy.

PubMed

Kang, Xiang; Xiao, Hai-Hua; Song, Hai-Qin; Jing, Xia-Bin; Yan, Le-San; Qi, Ruo-Gu

2015-12-01

Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.

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.

Optimisation of dynamic nuclear polarisation of [1-13C] pyruvate by addition of gadolinium-based contrast agents

NASA Astrophysics Data System (ADS)

Friesen-Waldner, Lanette; Chen, Albert; Mander, Will; Scholl, Timothy J.; McKenzie, Charles A.

2012-10-01

Dynamic nuclear polarisation (DNP) of carbon-13 (13C) enriched endogenous compounds provides a novel means for magnetic resonance imaging and spectroscopy of biological processes. Adding small amounts of gadolinium-based contrast agents (GBCAs) to the 13C-enriched substrate matrix increases the amount of hyperpolarisation that can be achieved, but also may decrease the longitudinal relaxation time (T1) of the 13C nucleus in solution. This study examined the effects of five different GBCA at concentrations of 0.5, 1, 2, and 3 mM on [1-13C]-enriched pyruvic acid. It was found that contrast agents with an open chain structure (Gadobenate dimeglumine, Gadopentetate dimeglumine, Gadodiamide) caused the largest enhancement (up to 82%) in solid state polarisation relative to solutions without GBCA. In the liquid state, T1 of pyruvate decreased by as much as 62% and polarisation was much lower (70%) relative to solutions without GBCA added. Conversely, for GBCA with macrocyclic structures (Gadoterate meglumine, Gadoteridol), the solid state polarisation enhancement was only slightly less than the open chain GBCA, but enhanced polarisation was retained much better in the liquid state with minimal decrease in T1 (25% at the highest GBCA concentrations). Near maximum polarisation in the solid state was obtained at a GBCA concentration of 2 mM, with a higher concentration of 3 mM producing minimal improvement. These results indicate that the macrocyclic contrast agents provide the best combination of high solid state and liquid state polarisations with minimal loss of T1 in experiments with hyperpolarised 13C-enriched pyruvate. This suggests that macrocyclic contrast agents should be the GBCA of choice for maximising signal in experiments with hyperpolarised 13C-enriched pyruvate, particularly for in vivo measurements where shortened substrate T1 is especially problematic.

The Use of Wetting Agents/Fume Supressants for Minimizing the Atmospheric Emissions from Hard Chromium Electroplating Baths

DTIC Science & Technology

2003-08-01

ESTCP FINAL REPORT For THE USE OF WETTING AGENTS/ FUME SUPPRESSANTS FOR MINIMIZING THE ATMOSPHERIC EMISSIONS FROM HARD CHROMIUM ...Introduction This project demonstrates that a “third” generation wetting agent / fume suppressant (WA/FS) chemical additive to hard chromium ...DOD operations fall in the same category.) Several papers, including Use of Fume Suppressants in Hard Chromium Baths - Quality Testing and Use

Local Risk-Minimization for Defaultable Claims with Recovery Process

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

Biagini, Francesca, E-mail: biagini@mathematik.uni-muenchen.de; Cretarola, Alessandra, E-mail: alessandra.cretarola@dmi.unipg.it

We study the local risk-minimization approach for defaultable claims with random recovery at default time, seen as payment streams on the random interval [0,{tau} Logical-And T], where T denotes the fixed time-horizon. We find the pseudo-locally risk-minimizing strategy in the case when the agent information takes into account the possibility of a default event (local risk-minimization with G-strategies) and we provide an application in the case of a corporate bond. We also discuss the problem of finding a pseudo-locally risk-minimizing strategy if we suppose the agent obtains her information only by observing the non-defaultable assets.

Multi-Agent Simulation of Allocating and Routing Ambulances Under Condition of Street Blockage after Natural Disaster

NASA Astrophysics Data System (ADS)

Azimi, S.; Delavar, M. R.; Rajabifard, A.

2017-09-01

In response to natural disasters, efficient planning for optimum allocation of the medical assistance to wounded as fast as possible and wayfinding of first responders immediately to minimize the risk of natural disasters are of prime importance. This paper aims to propose a multi-agent based modeling for optimum allocation of space to emergency centers according to the population, street network and number of ambulances in emergency centers by constraint network Voronoi diagrams, wayfinding of ambulances from emergency centers to the wounded locations and return based on the minimum ambulances travel time and path length implemented by NSGA and the use of smart city facilities to accelerate the rescue operation. Simulated annealing algorithm has been used for minimizing the difference between demands and supplies of the constrained network Voronoi diagrams. In the proposed multi-agent system, after delivering the location of the wounded and their symptoms, the constraint network Voronoi diagram for each emergency center is determined. This process was performed simultaneously for the multi-injuries in different Voronoi diagrams. In the proposed multi-agent system, the priority of the injuries for receiving medical assistance and facilities of the smart city for reporting the blocked streets was considered. Tehran Municipality District 5 was considered as the study area and during 3 minutes intervals, the volunteers reported the blocked street. The difference between the supply and the demand divided to the supply in each Voronoi diagram decreased to 0.1601. In the proposed multi-agent system, the response time of the ambulances is decreased about 36.7%.

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Agent Reward Shaping for Alleviating Traffic Congestion

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian

2006-01-01

Traffic congestion problems provide a unique environment to study how multi-agent systems promote desired system level behavior. What is particularly interesting in this class of problems is that no individual action is intrinsically "bad" for the system but that combinations of actions among agents lead to undesirable outcomes, As a consequence, agents need to learn how to coordinate their actions with those of other agents, rather than learn a particular set of "good" actions. This problem is ubiquitous in various traffic problems, including selecting departure times for commuters, routes for airlines, and paths for data routers. In this paper we present a multi-agent approach to two traffic problems, where far each driver, an agent selects the most suitable action using reinforcement learning. The agent rewards are based on concepts from collectives and aim to provide the agents with rewards that are both easy to learn and that if learned, lead to good system level behavior. In the first problem, we study how agents learn the best departure times of drivers in a daily commuting environment and how following those departure times alleviates congestion. In the second problem, we study how agents learn to select desirable routes to improve traffic flow and minimize delays for. all drivers.. In both sets of experiments,. agents using collective-based rewards produced near optimal performance (93-96% of optimal) whereas agents using system rewards (63-68%) barely outperformed random action selection (62-64%) and agents using local rewards (48-72%) performed worse than random in some instances.

Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients.

PubMed

Aziz, Kamran Ma

2015-01-01

Diabetes management during Ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia. As compared to oral hypoglycemic agents (OHAs) and sulfonylureas (SUs), which carry a higher and significant risk of hypoglycemia, newer antidiabetic agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated lower risk of hypoglycemia during Ramadan fasting, with better patient compliance. In addition to diabetes education and pre-Ramadan assessments, the physician should also consider use of DPP-4 inhibitors (such as vildagliptin) during Ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects. Severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with OHAs/SUs. Conversely, these research observations have also demonstrated comparative safety and efficacy with lower risk of hypoglycemia associated with vildagliptin. Current research review has collected evidence-based clinical trials and observations for the drug vildagliptin to minimize the risk of hypoglycemia during Ramadan fasting, while at the same time focusing the role of diabetes self-management education (DSME), pre-Ramadan assessments, and patient care.

Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients

PubMed Central

Aziz, Kamran MA

2015-01-01

Diabetes management during Ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia. As compared to oral hypoglycemic agents (OHAs) and sulfonylureas (SUs), which carry a higher and significant risk of hypoglycemia, newer antidiabetic agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated lower risk of hypoglycemia during Ramadan fasting, with better patient compliance. In addition to diabetes education and pre-Ramadan assessments, the physician should also consider use of DPP-4 inhibitors (such as vildagliptin) during Ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects. Severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with OHAs/SUs. Conversely, these research observations have also demonstrated comparative safety and efficacy with lower risk of hypoglycemia associated with vildagliptin. Current research review has collected evidence-based clinical trials and observations for the drug vildagliptin to minimize the risk of hypoglycemia during Ramadan fasting, while at the same time focusing the role of diabetes self-management education (DSME), pre-Ramadan assessments, and patient care. PMID:25931826

Synchronisation effects on the behavioural performance and information dynamics of a simulated minimally cognitive robotic agent.

PubMed

Moioli, Renan C; Vargas, Patricia A; Husbands, Phil

2012-09-01

Oscillatory activity is ubiquitous in nervous systems, with solid evidence that synchronisation mechanisms underpin cognitive processes. Nevertheless, its informational content and relationship with behaviour are still to be fully understood. In addition, cognitive systems cannot be properly appreciated without taking into account brain-body- environment interactions. In this paper, we developed a model based on the Kuramoto Model of coupled phase oscillators to explore the role of neural synchronisation in the performance of a simulated robotic agent in two different minimally cognitive tasks. We show that there is a statistically significant difference in performance and evolvability depending on the synchronisation regime of the network. In both tasks, a combination of information flow and dynamical analyses show that networks with a definite, but not too strong, propensity for synchronisation are more able to reconfigure, to organise themselves functionally and to adapt to different behavioural conditions. The results highlight the asymmetry of information flow and its behavioural correspondence. Importantly, it also shows that neural synchronisation dynamics, when suitably flexible and reconfigurable, can generate minimally cognitive embodied behaviour.

13 CFR 120.952 - Fiscal agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production of... performance of the Trustee and the underwriters. ...

13 CFR 120.952 - Fiscal agent.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production of... performance of the Trustee and the underwriters. ...

An Agent-Based Model for the Role of Short-Term Memory Enhancement in the Emergence of Grammatical Agreement.

PubMed

Vera, Javier

2018-01-01

What is the influence of short-term memory enhancement on the emergence of grammatical agreement systems in multi-agent language games? Agreement systems suppose that at least two words share some features with each other, such as gender, number, or case. Previous work, within the multi-agent language-game framework, has recently proposed models stressing the hypothesis that the emergence of a grammatical agreement system arises from the minimization of semantic ambiguity. On the other hand, neurobiological evidence argues for the hypothesis that language evolution has mainly related to an increasing of short-term memory capacity, which has allowed the online manipulation of words and meanings participating particularly in grammatical agreement systems. Here, the main aim is to propose a multi-agent language game for the emergence of a grammatical agreement system, under measurable long-range relations depending on the short-term memory capacity. Computer simulations, based on a parameter that measures the amount of short-term memory capacity, suggest that agreement marker systems arise in a population of agents equipped at least with a critical short-term memory capacity.

A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents.

PubMed

O'Neill, Hugh S; Herron, Caroline C; Hastings, Conn L; Deckers, Roel; Lopez Noriega, Adolfo; Kelly, Helena M; Hennink, Wim E; McDonnell, Ciarán O; O'Brien, Fergal J; Ruiz-Hernández, Eduardo; Duffy, Garry P

2017-01-15

Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome retention, thus providing a prolonged release in target tissues. Moreover, release can be controlled through the use of a minimally invasive external hyperthermic stimulus. Temporal control of release is particularly important for complex multi-step physiological processes, such as angiogenesis, in which different signals are required at different times in order to produce a robust vasculature. In the present work, we demonstrate the ability of Lipogel to provide a flexible, easily modifiable release platform. It is possible to tune the release kinetics of different drugs providing a passive release of one therapeutic agent loaded within the gel and activating the release of a second LTSL encapsulated agent via a hyperthermic stimulus. In addition, it was possible to modify the drug dosage within Lipogel by varying the duration of hyperthermia. This can allow for adaption of drug dosing in real time. As an in vitro proof of concept with this system, we investigated Lipogels ability to recruit stem cells and then elevate their production of vascular endothelial growth factor (VEGF) by controlling the release of a pro-angiogenic drug, desferroxamine (DFO) with an external hyperthermic stimulus. Initial cell recruitment was accomplished by the passive release of hepatocyte growth factor (HGF) from the hydrogel, inducing a migratory response in cells, followed by the delayed release of DFO from thermosensitive liposomes, resulting in a significant increase in VEGF expression. This delayed release could be controlled up to 14days. Moreover, by changing the duration of the hyperthermic pulse, a fine control over the amount of DFO released was achieved. The ability to trigger the release of therapeutic agents at a specific timepoint and control dosing level through changes in duration of hyperthermia enables sequential multi-dose profiles. This paper details the development of a heat responsive liposome loaded hydrogel for the controlled release of pro-angiogenic therapeutics. Lysolipid-based thermosensitive liposomes (LTSLs) embedded in a chitosan-based thermoresponsive hydrogel matrix represents a novel approach for the spatiotemporal release of therapeutic agents. This hydrogel platform demonstrates remarkable flexibility in terms of drug scheduling and sequencing, enabling the release of multiple agents and the ability to control drug dosing in a minimally invasive fashion. The possibility to tune the release kinetics of different drugs independently represents an innovative platform to utilise for a variety of treatments. This approach allows a significant degree of flexibility in achieving a desired release profile via a minimally invasive stimulus, enabling treatments to be tuned in response to changing symptoms and complications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Efficient Allocation of Resources for Defense of Spatially Distributed Networks Using Agent-Based Simulation.

PubMed

Kroshl, William M; Sarkani, Shahram; Mazzuchi, Thomas A

2015-09-01

This article presents ongoing research that focuses on efficient allocation of defense resources to minimize the damage inflicted on a spatially distributed physical network such as a pipeline, water system, or power distribution system from an attack by an active adversary, recognizing the fundamental difference between preparing for natural disasters such as hurricanes, earthquakes, or even accidental systems failures and the problem of allocating resources to defend against an opponent who is aware of, and anticipating, the defender's efforts to mitigate the threat. Our approach is to utilize a combination of integer programming and agent-based modeling to allocate the defensive resources. We conceptualize the problem as a Stackelberg "leader follower" game where the defender first places his assets to defend key areas of the network, and the attacker then seeks to inflict the maximum damage possible within the constraints of resources and network structure. The criticality of arcs in the network is estimated by a deterministic network interdiction formulation, which then informs an evolutionary agent-based simulation. The evolutionary agent-based simulation is used to determine the allocation of resources for attackers and defenders that results in evolutionary stable strategies, where actions by either side alone cannot increase its share of victories. We demonstrate these techniques on an example network, comparing the evolutionary agent-based results to a more traditional, probabilistic risk analysis (PRA) approach. Our results show that the agent-based approach results in a greater percentage of defender victories than does the PRA-based approach. © 2015 Society for Risk Analysis.

Evaluation of Inventory Reduction Strategies: Balad Air Base Case Study

DTIC Science & Technology

2012-03-01

produced by conducting individual simulations using a unique random seed generated by the default Anylogic © random number generator. The...develops an agent-based simulation model of the sustainment supply chain supporting Balad AB during its closure using the software AnyLogic ®. The...research. The goal of USAF Stockage Policy is to maximize customer support while minimizing inventory costs (DAF, 2011:1). USAF stocking decisions

ATM regulates 3-Methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents

PubMed Central

Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A.; Clarke, Ian D.; Barszczyk, Mark S.; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W.; Taylor, Michael D; Rutka, James T.; Jones, Chris; Dirks, Peter B.; Zadeh, Gelareh; Hawkins, Cynthia

2014-01-01

Alkylating agents are a frontline therapy for the treatment of several aggressive cancers including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed; increasing therapeutic response while minimizing toxicity. Using a siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM) were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. PMID:25100205

A Scalable and Robust Multi-Agent Approach to Distributed Optimization

NASA Technical Reports Server (NTRS)

Tumer, Kagan

2005-01-01

Modularizing a large optimization problem so that the solutions to the subproblems provide a good overall solution is a challenging problem. In this paper we present a multi-agent approach to this problem based on aligning the agent objectives with the system objectives, obviating the need to impose external mechanisms to achieve collaboration among the agents. This approach naturally addresses scaling and robustness issues by ensuring that the agents do not rely on the reliable operation of other agents We test this approach in the difficult distributed optimization problem of imperfect device subset selection [Challet and Johnson, 2002]. In this problem, there are n devices, each of which has a "distortion", and the task is to find the subset of those n devices that minimizes the average distortion. Our results show that in large systems (1000 agents) the proposed approach provides improvements of over an order of magnitude over both traditional optimization methods and traditional multi-agent methods. Furthermore, the results show that even in extreme cases of agent failures (i.e., half the agents fail midway through the simulation) the system remains coordinated and still outperforms a failure-free and centralized optimization algorithm.

Providing Effective Access to Shared Resources: A COIN Approach

NASA Technical Reports Server (NTRS)

Airiau, Stephane; Wolpert, David H.

2004-01-01

Managers of systems of shared resources typically have many separate goals. Examples are efficient utilization of the resources among its users and ensuring no user s satisfaction in the system falls below a preset minimal level. Since such goals will usually conflict with one another, either implicitly or explicitly the manager must determine the relative importance of the goals, encapsulating that into an overall utility function rating the possible behaviors of the entire system. Here we demonstrate a distributed, robust, and adaptive way to optimize that overall function. Our approach is to interpose adaptive agents between each user and the system, where each such agent is working to maximize its own private utility function. In turn, each such agent's function should be both relatively easy for the agent to learn to optimize, and "aligned" with the overall utility function of the system manager - an overall function that is based on but in general different from the satisfaction functions of the individual users. To ensure this we enhance the Collective INtelligence (COIN) framework to incorporate user satisfaction functions in the overall utility function of the system manager and accordingly in the associated private utility functions assigned to the users agents. We present experimental evaluations of different COIN-based private utility functions and demonstrate that those COIN-based functions outperform some natural alternatives.

Providing Effective Access to Shared Resources: A COIN Approach

NASA Technical Reports Server (NTRS)

Airiau, Stephane; Wolpert, David H.; Sen, Sandip; Tumer, Kagan

2003-01-01

Managers of systems of shared resources typically have many separate goals. Examples are efficient utilization of the resources among its users and ensuring no user's satisfaction in the system falls below a preset minimal level. Since such goals will usually conflict with one another, either implicitly or explicitly the manager must determine the relative importance of the goals, encapsulating that into an overall utility function rating the possible behaviors of the entire system. Here we demonstrate a distributed, robust, and adaptive way to optimize that overall function. Our approach is to interpose adaptive agents between each user and the system, where each such agent is working to maximize its own private utility function. In turn, each such agent's function should be both relatively easy for the agent to learn to optimize, and 'aligned' with the overall utility function of the system manager - an overall function that is based on but in general different from the satisfaction functions of the individual users. To ensure this we enhance the COllective INtelligence (COIN) framework to incorporate user satisfaction functions in the overall utility function of the system manager and accordingly in the associated private utility functions assigned to the users agents. We present experimental evaluations of different COIN-based private utility functions and demonstrate that those COIN-based functions outperform some natural alternatives.

Synthesis and antibacterial activity of Schiff bases and amines derived from alkyl 2-(2-formyl-4-nitrophenoxy)alkanoates.

PubMed

Goszczyńska, Agata; Kwiecień, Halina; Fijałkowski, Karol

A series of novel Schiff bases and secondary amines were obtained in good yields, as a result of the reductive amination of alkyl 2-(2-formyl-4-nitrophenoxy)alkanoates with both aniline and 4-methoxyaniline under established mild reaction conditions. Sodium triacetoxyborohydride as well as hydrogen in the presence of palladium on carbon were used as efficient reducing agents of the Schiff bases, in both direct and stepwise reductive amination processes. The Schiff bases, amines, and amine hydrochlorides were designed as potential antibacterial agents, and structure-activity relationship could be established following in vitro assays against Gram-positive and Gram-negative bacteria. The minimal inhibitory concentration and zone of inhibition were also determined. In these tests, some of Schiff bases and secondary amine hydrochlorides showed moderate-to-good activity against Gram-positive bacteria, including S. aureus , M. luteus , and S. mutans .

Evidence for surprise minimization over value maximization in choice behavior

PubMed Central

Schwartenbeck, Philipp; FitzGerald, Thomas H. B.; Mathys, Christoph; Dolan, Ray; Kronbichler, Martin; Friston, Karl

2015-01-01

Classical economic models are predicated on the idea that the ultimate aim of choice is to maximize utility or reward. In contrast, an alternative perspective highlights the fact that adaptive behavior requires agents’ to model their environment and minimize surprise about the states they frequent. We propose that choice behavior can be more accurately accounted for by surprise minimization compared to reward or utility maximization alone. Minimizing surprise makes a prediction at variance with expected utility models; namely, that in addition to attaining valuable states, agents attempt to maximize the entropy over outcomes and thus ‘keep their options open’. We tested this prediction using a simple binary choice paradigm and show that human decision-making is better explained by surprise minimization compared to utility maximization. Furthermore, we replicated this entropy-seeking behavior in a control task with no explicit utilities. These findings highlight a limitation of purely economic motivations in explaining choice behavior and instead emphasize the importance of belief-based motivations. PMID:26564686

7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Debentures and/or TCs. (iv) Arranging for the production of Offering Circulars, certificates, and such other... to determine those factors that will minimize or reduce the cost of funding Debentures. (iii) Monitor... the Secretary; (vii) Remain custodian of such other documentation as the Secretary shall direct by...

13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... periodic sales of Debentures and/or TCs. (iv) Arranging for the production of Offering Circulars... financial markets to determine those factors that will minimize or reduce the cost of funding Debentures... SBA; (vii) Remain custodian of such other documentation as SBA shall direct by written instructions...

13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Participating Securities and/or TCs. (iv) Arranging for the production of the Offering Circular, certificates... markets to determine those factors that will minimize or reduce the cost of funding Debentures or... instructions from SBA; (vii) Remain custodian of such other documentation as SBA shall direct by written...

Towards a mathematical theory of meaningful communication

NASA Astrophysics Data System (ADS)

Corominas-Murtra, Bernat; Fortuny, Jordi; Solé, Ricard V.

2014-04-01

Meaning has been left outside most theoretical approaches to information in biology. Functional responses based on an appropriate interpretation of signals have been replaced by a probabilistic description of correlations between emitted and received symbols. This assumption leads to potential paradoxes, such as the presence of a maximum information associated to a channel that creates completely wrong interpretations of the signals. Game-theoretic models of language evolution and other studies considering embodied communicating agents show that the correct (meaningful) match resulting from agent-agent exchanges is always achieved and natural systems obviously solve the problem correctly. Inspired by the concept of duality of the communicative sign stated by the swiss linguist Ferdinand de Saussure, here we present a complete description of the minimal system necessary to measure the amount of information that is consistently decoded. Several consequences of our developments are investigated, such as the uselessness of a certain amount of information properly transmitted for communication among autonomous agents.

Neurotoxicity Associated with Platinum-Based Anti-Cancer Agents: What are the Implications of Copper Transporters?

PubMed

Stojanovska, Vanesa; McQuade, Rachel; Rybalka, Emma; Nurgali, Kulmira

2017-01-01

Platinum-based anti-cancer agents, which include cisplatin, carboplatin and oxaliplatin, are an important class of drugs used in clinical setting to treat a variety of cancers. The cytotoxic efficacy of these drugs is mediated by the formation of inter-strand and intrastrand crosslinks, or platinum adducts on nuclear DNA. There is also evidence demonstrating that mitochondrial DNA is susceptible to platinum-adduct damage in dorsal root ganglia neurons. Although all platinum-based agents form similar DNA adducts, they are quite different in terms of activation, systemic toxicity and tolerance. Platinum-based agents are well known for their neurotoxicity and gastrointestinal side-effects which are major causes for dose limitation and treatment discontinuation compromising the efficacy of anti-cancer treatment. Accumulating evidence in non-neuronal cells shows that the copper transport system is associated with platinum drug sensitivity and resistance. There is minimal research concerning the role of copper transporters within the central and peripheral nervous systems. It is unclear whether neurons are more sensitive to platinum-based drugs, are insufficient in drug clearance, or whether platinum accumulation affects intracellular copper status and coppermediated functions. Understanding these mechanisms is important as neurotoxicity is the predominant side-effect of platinum-based chemotherapy. This review highlights the role of copper transpor ters in drug influx, differences in drug activation and side-effects caused by platinum-based agents, as well as their association with central and peripheral neuropathies and gastrointestinal toxicities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Suppression Characteristics of Cup-Burner Flames in Low Gravity

NASA Technical Reports Server (NTRS)

Takahashi, Fumiaki; Linteris, Gregory T.; Katta, Viswanath R.

2004-01-01

The structure and suppression of laminar methane-air co-flow diffusion flames formed on a cup burner have been studied experimentally and numerically using physically acting fire-extinguishing agents (CO2, N2, He, and Ar) in normal earth (lg) and zero gravity (0g). The computation uses a direct numerical simulation with detailed chemistry and radiative heat-loss models. An initial observation of the flame without agent was also made at the NASA Glenn 2.2-Second Drop Tower. An agent was introduced into a low-speed coflowing oxidizing stream by gradually replacing the air until extinguishment occurred under a fixed minimal fuel velocity. The suppression of cup-burner flames, which resemble real fires, occurred via a blowoff process (in which the flame base drifted downstream) rather than the global extinction phenomenon typical of counterflow diffusion flames. The computation revealed that the peak reactivity spot (the reaction kernel) formed in the flame base was responsible for attachment and blowoff phenomena of the trailing diffusion flame. The thermal and transport properties of the agents affected the flame extinguishment limits.

Clipping in neurocontrol by adaptive dynamic programming.

PubMed

Fairbank, Michael; Prokhorov, Danil; Alonso, Eduardo

2014-10-01

In adaptive dynamic programming, neurocontrol, and reinforcement learning, the objective is for an agent to learn to choose actions so as to minimize a total cost function. In this paper, we show that when discretized time is used to model the motion of the agent, it can be very important to do clipping on the motion of the agent in the final time step of the trajectory. By clipping, we mean that the final time step of the trajectory is to be truncated such that the agent stops exactly at the first terminal state reached, and no distance further. We demonstrate that when clipping is omitted, learning performance can fail to reach the optimum, and when clipping is done properly, learning performance can improve significantly. The clipping problem we describe affects algorithms that use explicit derivatives of the model functions of the environment to calculate a learning gradient. These include backpropagation through time for control and methods based on dual heuristic programming. However, the clipping problem does not significantly affect methods based on heuristic dynamic programming, temporal differences learning, or policy-gradient learning algorithms.

Clearance Properties of Nano-sized Particles and Molecules as Imaging Agents: Considerations and Caveats

PubMed Central

Longmire, Michelle; Choyke, Peter L.; Kobayashi, Hisataka

2009-01-01

Summary Nanoparticles possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities. Yet, some of the most promising nanoparticles demonstrate prolonged tissue retention and contain heavy metals. This presents serious concerns for toxicity. The creation of nanoparticles with optimal clearance characteristics will minimize toxicity risks by reducing the duration of exposure to these agents. Given that many nanoparticles possess easily modifiable surface and interior chemistry, if nanoparticle characteristics associated with optimal clearance from the body were well established, it would be feasible to design and create agents with more favorable clearance properties. This paper presents a thorough discussion of the physiologic aspects of nanoparticle clearance, focusing on renal mechanisms, as well as provides an overview of current research investigating clearance of specific types of nanoparticles and nano-sized macromolecules, including dendrimers, quantum dots, liposomes and carbon, gold, and silica-based nanoparticles. PMID:18817471

Vesicant extravasation part I: Mechanisms, pathogenesis, and nursing care to reduce risk.

PubMed

Sauerland, Carmel; Engelking, Constance; Wickham, Rita; Corbi, Dominick

2006-11-27

To review the literature regarding the incidence, current practice, guideline recommendations, nursing management, and knowledge gaps relevant to vesicant extravasation. Published research articles, books, case reports, and national guidelines. Vesicant extravasation is a relatively rare but significant complication of chemotherapy administration. Extravasation may have a range of consequences that can cause serious physical and quality-of-life effects. Knowledge of risk factors and preventive measures can reduce patient risk. Data-based and empirical management strategies such as immediate local measures (agent withdrawal, comfort measures, and medical interventions) may minimize risk for extravasation, as well as lead to timely recognition and management and decreased morbidity should extravasation occur. Vesicant extravasation and sequelae constitute a complex patient problem that clinicians should strive to prevent or to minimize injury should it occur. To this end, clinicians must demonstrate awareness of risks and use specialized knowledge while administering vesicant agents. Only nurses knowledgeable about extravasation and skilled in associated techniques should assume responsibility for vesicant administration.

Using Fast Healthcare Interoperability Resources (FHIR) for the Integration of Risk Minimization Systems in Hospitals.

PubMed

Saleh, Kutaiba; Stucke, Stephan; Uciteli, Alexandr; Faulbrück-Röhr, Sebastian; Neumann, Juliane; Tahar, Kais; Ammon, Danny; Schmidt, Tobias; Neumuth, Thomas; Besting, Andreas; Portheine, Frank; Herre, Heinrich; Kaeding, André; Specht, Martin

2017-01-01

With the growing strain of medical staff and complexity of patient care, the risk of medical errors increases. In this work we present the use of Fast Healthcare Interoperability Resources (FHIR) as communication standard for the integration of an ontology- and agent-based system to identify risks across medical processes in a clinical environment.

Evaluation of percutaneous permeation of repellent DEET and sunscreen oxybenzone from emulsion-based formulations in artificial membrane and human skin.

PubMed

Wang, Tao; Miller, Donald; Burczynski, Frank; Gu, Xiaochen

2014-02-01

Insect repellent DEET and sunscreen ingredient oxybenzone play an essential role in minimizing vector-borne diseases and skin cancers. The purpose of this study was to investigate the effects of emulsion type, addition of thickening agent and droplet size in three emulsion-based lotions on percutaneous permeation of DEET and oxybenzone using in vitro diffusion experiments, in order to minimize overall systemic permeation of the substances. Formulation C (water-in-oil emulsion) significantly increased overall permeation of DEET through human skin (56%) compared to Formulation A (oil-in-water emulsion). Formulation B (oil-in-water emulsion with thickening agent xanthan gum) significantly decreased the size of oil droplet containing DEET (16%), but no effect on oil droplets containing oxybenzone. Adding xanthan gum also increased overall permeation of DEET and oxybenzone (21% and 150%) when compared to Formulation A; presence of both ingredients in Formulation B further increased their permeation (36% and 23%) in comparison to its single counterparts. Overall permeation of oxybenzone through LDPE was significantly higher by 26%-628% than that through human skin; overall permeation of DEET through human skin was significantly higher by 64%-338% than that through LDPE.

Optimization of HAART with genetic algorithms and agent-based models of HIV infection.

PubMed

Castiglione, F; Pappalardo, F; Bernaschi, M; Motta, S

2007-12-15

Highly Active AntiRetroviral Therapies (HAART) can prolong life significantly to people infected by HIV since, although unable to eradicate the virus, they are quite effective in maintaining control of the infection. However, since HAART have several undesirable side effects, it is considered useful to suspend the therapy according to a suitable schedule of Structured Therapeutic Interruptions (STI). In the present article we describe an application of genetic algorithms (GA) aimed at finding the optimal schedule for a HAART simulated with an agent-based model (ABM) of the immune system that reproduces the most significant features of the response of an organism to the HIV-1 infection. The genetic algorithm helps in finding an optimal therapeutic schedule that maximizes immune restoration, minimizes the viral count and, through appropriate interruptions of the therapy, minimizes the dose of drug administered to the simulated patient. To validate the efficacy of the therapy that the genetic algorithm indicates as optimal, we ran simulations of opportunistic diseases and found that the selected therapy shows the best survival curve among the different simulated control groups. A version of the C-ImmSim simulator is available at http://www.iac.cnr.it/~filippo/c-ImmSim.html

Theranostics and metabolotheranostics for precision medicine in oncology

NASA Astrophysics Data System (ADS)

Bhujwalla, Zaver M.; Kakkad, Samata; Chen, Zhihang; Jin, Jiefu; Hapuarachchige, Sudath; Artemov, Dmitri; Penet, Marie-France

2018-06-01

Most diseases, especially cancer, would significantly benefit from precision medicine where treatment is shaped for the individual. The concept of theragnostics or theranostics emerged around 2002 to describe the incorporation of diagnostic assays into the selection of therapy for this purpose. Increasingly, theranostics has been used for strategies that combine noninvasive imaging-based diagnostics with therapy. Within the past decade theranostic imaging has transformed into a rapidly expanding field that is located at the interface of diagnosis and therapy. A critical need in cancer treatment is to minimize damage to normal tissue. Molecular imaging can be applied to identify targets specific to cancer with imaging, design agents against these targets to visualize their delivery, and monitor response to treatment, with the overall purpose of minimizing collateral damage. Genomic and proteomic profiling can provide an extensive 'fingerprint' of each tumor. With this cancer fingerprint, theranostic agents can be designed to personalize treatment for precision medicine of cancer, and minimize damage to normal tissue. Here, for the first time, we have introduced the term 'metabolotheranostics' to describe strategies where disease-based alterations in metabolic pathways detected by MRS are specifically targeted with image-guided delivery platforms to achieve disease-specific therapy. The versatility of MRI and MRS in molecular and functional imaging makes these technologies especially important in theranostic MRI and 'metabolotheranostics'. Our purpose here is to provide insights into the capabilities and applications of this exciting new field in cancer treatment with a focus on MRI and MRS.

Optimal use of novel agents in chronic lymphocytic leukemia.

PubMed

Smith, Mitchell R; Weiss, Robert F

2018-05-07

Novel agents are changing therapy for patients with CLL, but their optimal use remains unclear. We model the clinical situation in which CLL responds to therapy, but resistant clones, generally carrying del17p, progress and lead to relapse. Sub-clones of varying growth rates and treatment sensitivity affect predicted therapy outcomes. We explore effects of different approaches to starting novel agent in relation to bendamustine-rituximab induction therapy: at initiation of therapy, at the end of chemo-immunotherapy, at molecular relapse, or at clinical detection of relapse. The outcomes differ depending on the underlying clonal architecture, raising the concept that personalized approaches based on clinical evaluation of each patient's clonal architecture might optimize outcomes while minimizing toxicity and cost. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fracture toughness for copper oxide superconductors

DOEpatents

Goretta, Kenneth C.; Kullberg, Marc L.

1993-01-01

An oxide-based strengthening and toughening agent, such as tetragonal Zro.sub.2 particles, has been added to copper oxide superconductors, such as superconducting YBa.sub.2 Cu.sub.3 O.sub.x (123) to improve its fracture toughness (K.sub.IC). A sol-gel coating which is non-reactive with the superconductor, such as Y.sub.2 BaCuO.sub.5 (211) on the ZrO.sub.2 particles minimized the deleterious reactions between the superconductor and the toughening agent dispersed therethrough. Addition of 20 mole percent ZrO.sub.2 coated with 211 yielded a 123 composite with a K.sub.IC of 4.5 MPa(m).sup.0.5.

Extending MAM5 Meta-Model and JaCalIV E Framework to Integrate Smart Devices from Real Environments.

PubMed

Rincon, J A; Poza-Lujan, Jose-Luis; Julian, V; Posadas-Yagüe, Juan-Luis; Carrascosa, C

2016-01-01

This paper presents the extension of a meta-model (MAM5) and a framework based on the model (JaCalIVE) for developing intelligent virtual environments. The goal of this extension is to develop augmented mirror worlds that represent a real and virtual world coupled, so that the virtual world not only reflects the real one, but also complements it. A new component called a smart resource artifact, that enables modelling and developing devices to access the real physical world, and a human in the loop agent to place a human in the system have been included in the meta-model and framework. The proposed extension of MAM5 has been tested by simulating a light control system where agents can access both virtual and real sensor/actuators through the smart resources developed. The results show that the use of real environment interactive elements (smart resource artifacts) in agent-based simulations allows to minimize the error between simulated and real system.

Extending MAM5 Meta-Model and JaCalIV E Framework to Integrate Smart Devices from Real Environments

PubMed Central

2016-01-01

This paper presents the extension of a meta-model (MAM5) and a framework based on the model (JaCalIVE) for developing intelligent virtual environments. The goal of this extension is to develop augmented mirror worlds that represent a real and virtual world coupled, so that the virtual world not only reflects the real one, but also complements it. A new component called a smart resource artifact, that enables modelling and developing devices to access the real physical world, and a human in the loop agent to place a human in the system have been included in the meta-model and framework. The proposed extension of MAM5 has been tested by simulating a light control system where agents can access both virtual and real sensor/actuators through the smart resources developed. The results show that the use of real environment interactive elements (smart resource artifacts) in agent-based simulations allows to minimize the error between simulated and real system. PMID:26926691

Sensitive and comprehensive detection of chemical warfare agents in air by atmospheric pressure chemical ionization ion trap tandem mass spectrometry with counterflow introduction.

PubMed

Seto, Yasuo; Sekiguchi, Hiroshi; Maruko, Hisashi; Yamashiro, Shigeharu; Sano, Yasuhiro; Takayama, Yasuo; Sekioka, Ryoji; Yamaguchi, Shintaro; Kishi, Shintaro; Satoh, Takafumi; Sekiguchi, Hiroyuki; Iura, Kazumitsu; Nagashima, Hisayuki; Nagoya, Tomoki; Tsuge, Kouichiro; Ohsawa, Isaac; Okumura, Akihiko; Takada, Yasuaki; Ezawa, Naoya; Watanabe, Susumu; Hashimoto, Hiroaki

2014-05-06

A highly sensitive and specific real-time field-deployable detection technology, based on counterflow air introduction atmospheric pressure chemical ionization, has been developed for a wide range of chemical warfare agents (CWAs) comprising gaseous (two blood agents, three choking agents), volatile (six nerve gases and one precursor agent, five blister agents), and nonvolatile (three lachrymators, three vomiting agents) agents in air. The approach can afford effective chemical ionization, in both positive and negative ion modes, for ion trap multiple-stage mass spectrometry (MS(n)). The volatile and nonvolatile CWAs tested provided characteristic ions, which were fragmented into MS(3) product ions in positive and negative ion modes. Portions of the fragment ions were assigned by laboratory hybrid mass spectrometry (MS) composed of linear ion trap and high-resolution mass spectrometers. Gaseous agents were detected by MS or MS(2) in negative ion mode. The limits of detection for a 1 s measurement were typically at or below the microgram per cubic meter level except for chloropicrin (submilligram per cubic meter). Matrix effects by gasoline vapor resulted in minimal false-positive signals for all the CWAs and some signal suppression in the case of mustard gas. The moisture level did influence the measurement of the CWAs.

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

PubMed Central

Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon

2015-01-01

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy. PMID:26078967

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review.

PubMed

Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; Gonçalez, Maíra Lima; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon; Chorilli, Marlus

2015-01-01

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

Developing High-Affinity Protein Capture Agents and Nanotechnology-Based Platforms for In Vitro Diagnostics

NASA Astrophysics Data System (ADS)

Rohde, Rosemary Dyane

In this thesis, I describe projects that were aimed at improving ways to capture proteins for clinical diagnostics. Nanoelectronic sensors, such as silicon nanowires (SiNWs), can provide label-free quantitative measurements of protein biomarkers in real time. One technical challenge for SiNWs is to develop chemistry that can be applied for selectively encoding the nanowire surfaces with capture agents, thus making them sensors that have selectivity for specific proteins. Furthermore, because of the nature of how the sensor works, it is desirable to achieve this spatially selective chemical functionalization without having the silicon undergo oxidation. This method is described here and provides a general platform that can incorporate organic and biological molecules on Si (111) with minimal oxidation of the silicon surface. The development of these devices is, in part, driven by early diagnosis, treatment, monitoring, and personalized medicine---all of which are increasingly requiring quantitative, rapid, and multiparameter measurements. To begin achieving this goal, a large number of protein biomarkers need to be captured and quantitatively measured to create a diagnostic panel. One of the greatest challenges towards making protein-biomarker-based in vitro diagnostics inexpensive involves developing capture agents to detect the proteins. A major thrust of this thesis is to develop multi-valent, high-affinity and high-selectivity protein capture agents using in situ click chemistry. In situ click chemistry is a tool that utilizes the protein itself to catalyze the formation of a biligand from individual azide and alkyne ligands that are co-localized. Large one-bead one-compound (OBOC) libraries of peptides are used to form the body of these ligands, also providing high chemical diversity with minimal synthetic effort. This process can be repeated to identify a triligand, tetraligand, and so forth. Moreover, the resulting multiligand protein capture agents can be produced in gram-scale quantities with designed control over chemical and biochemical stability and water solubility. This is a general and robust method for inexpensive, high-throughput capture agent discovery that can be utilized to capture the relevant biomarker proteins for blood protein diagnostics.

ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

PubMed

Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

2014-10-01

Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

Injectable thermosensitive chitosan/glycerophosphate-based hydrogels for tissue engineering and drug delivery applications: a review.

PubMed

Tahrir, Farzaneh G; Ganji, Fariba; Ahooyi, Taha M

2015-01-01

Recently, great attention has been paid to in situ gel-forming chitosan/glycerophosphate (CS/Gp) formulation due to its high biocompatibility with incorporated cells and medical agents, biodegradability and sharp thermosensitive gelation. CS/Gp is in liquid state at room temperature and after minimally invasive administration into the desired tissue, it forms a solid-like gel as a response to temperature increase. The overview of various recently patented strategies on injectable delivery systems indicates the significance of this formulation in biomedical applications. This thermosensitive hydrogel has a great potential as scaffold material in tissue engineering, due to its good biocompatibility, minimal immune reaction, high antibacterial nature, good adhesion to cells and the ability to be molded in various geometries. Moreover, CS/Gp hydrogel has been utilized as a smart drug delivery system to increase patient compliance by maintaining the drug level in the therapeutic window for a long time while avoiding the need for frequent injections of the therapeutic agent. This review paper highlights the recent patents and investigations on different formulations of CS/Gp hydrogels as tissue engineering scaffolds and carriers for therapeutic agents. Additionally, the dominant mechanism of sol-gel transition in those systems as well as their physicochemical properties and biocompatibility are discussed in detail.

Peripheral Artery Disease

MedlinePlus

... This minimally invasive imaging exam relies on a contrast agent and x-rays to show blood flow in ... pinpoint any blockages that may be present. The contrast agent is injected through a tube or catheter that ...

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

NASA Astrophysics Data System (ADS)

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

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

Antifungal Indole and Pyrrolidine-2,4-Dione Derivative Peptidomimetic Lead Design Based on In Silico Study of Bioactive Peptide Families

PubMed Central

Moradi, Shoeib; Azerang, Parisa; Khalaj, Vahid; Sardari, Soroush

2013-01-01

Background The rise of opportunistic fungal infections highlights the need for development of new antimicrobial agents. Antimicrobial Peptides (AMPs) and Antifungal Peptides (AFPs) are among the agents with minimal resistance being developed against them, therefore they can be used as structural templates for design of new antimicrobial agents. Methods In the present study four antifungal peptidomimetic structures named C1 to C4 were designed based on plant defensin of Pisum sativum. Minimum inhibitory concentrations (MICs) for these structures were determined against Aspergillus niger N402, Candida albicans ATCC 10231, and Saccharomyces cerevisiae PTCC 5052. Results C1 and C2 showed more potent antifungal activity against these fungal strains compared to C3 and C4. The structure C2 demonstrated a potent antifungal activity among them and could be used as a template for future study on antifungal peptidomemetics design. Sequences alignments led to identifying antifungal decapeptide (KTCENLADTY) named KTC-Y, which its MIC was determined on fungal protoplast showing 25 (µg/ml) against Aspergillus fumigatus Af293. Conclusion The present approach to reach the antifungal molecules seems to be a powerful approach in design of bioactive agents based on AMP mimetic identification. PMID:23626876

Bactericidal activity of antibiotics against Legionella micdadei (Pittsburgh pneumonia agent).

PubMed Central

Dowling, J N; Weyant, R S; Pasculle, A W

1982-01-01

The bactericidal activity of five antibiotics for Legionella micdadei was determined by the construction of time-kill curves. Erythromycin, rifampin, penicillin G, cephalothin, and gentamicin were bactericidal for L. micdadei at readily achievable concentrations. The minimal bactericidal concentrations, defined as those producing 99.9% killing within 24 h, were: erythromycin, 4.6; rifampin, 0.13; penicillin G, 0.25; cephalothin, 2.5; and gentamicin, 0.25 micrograms/ml. The ratios of the minimal bactericidal to minimal inhibitory concentrations for these antibiotics ranged from 1 to 8. Thus, the poor in vivo activity of beta-lactam and aminoglycoside antibiotics against L. micdadei cannot be ascribed to a lack of killing by these agents. PMID:6927637

Minimal Representation and Decision Making for Networked Autonomous Agents

DTIC Science & Technology

2015-08-27

to a multi-vehicle version of the Travelling Salesman Problem (TSP). We further provided a direct formula for computing the number of robots...the sensor. As a first stab at this, the two-agent rendezvous problem is considered where one agent (the target) is equipped with no sensors and is...by the total distance traveled by all agents. For agents with limited sensing and communication capabilities, we give a formula that computes the

Model-based Executive Control through Reactive Planning for Autonomous Rovers

NASA Technical Reports Server (NTRS)

Finzi, Alberto; Ingrand, Felix; Muscettola, Nicola

2004-01-01

This paper reports on the design and implementation of a real-time executive for a mobile rover that uses a model-based, declarative approach. The control system is based on the Intelligent Distributed Execution Architecture (IDEA), an approach to planning and execution that provides a unified representational and computational framework for an autonomous agent. The basic hypothesis of IDEA is that a large control system can be structured as a collection of interacting agents, each with the same fundamental structure. We show that planning and real-time response are compatible if the executive minimizes the size of the planning problem. We detail the implementation of this approach on an exploration rover (Gromit an RWI ATRV Junior at NASA Ames) presenting different IDEA controllers of the same domain and comparing them with more classical approaches. We demonstrate that the approach is scalable to complex coordination of functional modules needed for autonomous navigation and exploration.

Effects of antihypertensive agents on sexual function.

PubMed

Weiss, R J

1991-12-01

Patient compliance with antihypertensive therapy can be improved by minimizing drug-induced sexual dysfunction. Impotence, decreased libido, impaired ejaculation and gynecomastia are potential side effects, depending on the agent prescribed. Centrally acting antihypertensive agents such as methyldopa and clonidine, nonselective beta-adrenergic blockers and potassium-sparing diuretics are the drugs most often associated with sexual dysfunction. Thiazide diuretics cause impotence but may otherwise play a minimal role in sexual dysfunction. Alpha-adrenergic blockers, angiotensin converting enzyme inhibitors and calcium channel blockers have little adverse effect on sexual function. It is important to obtain an adequate history before and after initiating therapy. If sexual dysfunction develops in a patient, a different class of medication can be tried.

Contrast-enhanced peripheral MRA: technique and contrast agents.

PubMed

Nielsen, Yousef W; Thomsen, Henrik S

2012-09-01

In the last decade contrast-enhanced magnetic resonance angiography (CE-MRA) has gained wide acceptance as a valuable tool in the diagnostic work-up of patients with peripheral arterial disease. This review presents current concepts in peripheral CE-MRA with emphasis on MRI technique and contrast agents. Peripheral CE-MRA is defined as an MR angiogram of the arteries from the aortic bifurcation to the feet. Advantages of CE-MRA include minimal invasiveness and lack of ionizing radiation. The basic technique employed for peripheral CE-MRA is the bolus-chase method. With this method a paramagnetic MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic field strength of the MRI system, receiver coil configuration, use of parallel imaging, contrast bolus timing technique, and k-space filling strategies. Furthermore, it is possible to optimize peripheral CE-MRA using venous compression techniques, hybrid scan protocols, time-resolved imaging, and steady-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Using optimized technique and a stable MRI contrast agent, peripheral CE-MRA is a safe procedure with diagnostic accuracy close to that of conventional catheter X-ray angiography.

Wains: a pattern-seeking artificial life species.

PubMed

de Buitléir, Amy; Russell, Michael; Daly, Mark

2012-01-01

We describe the initial phase of a research project to develop an artificial life framework designed to extract knowledge from large data sets with minimal preparation or ramp-up time. In this phase, we evolved an artificial life population with a new brain architecture. The agents have sufficient intelligence to discover patterns in data and to make survival decisions based on those patterns. The species uses diploid reproduction, Hebbian learning, and Kohonen self-organizing maps, in combination with novel techniques such as using pattern-rich data as the environment and framing the data analysis as a survival problem for artificial life. The first generation of agents mastered the pattern discovery task well enough to thrive. Evolution further adapted the agents to their environment by making them a little more pessimistic, and also by making their brains more efficient.

High char yield epoxy curing agents

NASA Technical Reports Server (NTRS)

Delvigs, P.; Serafini, T. T.; Vanucci, R. D.

1981-01-01

Class of imide-amine curing agents preserves structural integrity, prevents fiber release, and is fully compatible with conventional epoxy resins; agents do not detract from composite properties while greatly reducing char yield. Materials utilizing curing are used in aerospace, automotive, and other structural components where deterioration must be minimized and fiber release avoided in event of fire.

Pre-release biological control agent recommendations for swallow-wort (Vincetoxicum spp.) informed by demographic matrix models

USDA-ARS?s Scientific Manuscript database

Weed biological control workers have advocated for the advance assessment of agent efficacy in order to minimize the release of host-specific but ineffective agents. One method involves demographic matrix modeling of target weed populations in order to identify plant life stage transitions that cont...

Current and emerging treatment options in the management of lupus

PubMed Central

Jordan, Natasha; D’Cruz, David

2016-01-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058

Defining the frontiers between antifungal resistance, tolerance and the concept of persistence.

PubMed

Delarze, Eric; Sanglard, Dominique

2015-11-01

A restricted number of antifungal agents are available for the therapy of fungal diseases. With the introduction of epidemiological cut-off values for each agent in important fungal pathogens based on the distribution of minimal inhibitory concentration (MIC), the distinction between wild type and drug-resistant populations has been facilitated. Antifungal resistance has been described for all currently available antifungal agents in several pathogens and most of the associated resistance mechanisms have been deciphered at the molecular level. Clinical breakpoints for some agents have been proposed and can have predictive value for the success or failure of therapy. Tolerance to antifungals has been a much more ignored area. By definition, tolerance operates at antifungal concentrations above individual intrinsic inhibitory values. Important is that tolerance to antifungal agents favours the emergence of persister cells, which are able to survive antifungal therapy and can cause relapses. Here we will review the current knowledge on antifungal tolerance, its potential mechanisms and also evaluate the role of antifungal tolerance in the efficacy of drug treatments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emerging Drugs for Uveitis

PubMed Central

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

2010-01-01

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

Internalization of fresh produce by foodborne pathogens.

PubMed

Erickson, Marilyn C

2012-01-01

Recent studies addressing the internalization of fresh produce by foodborne pathogens arose in response to the growing number of recent and high profile outbreaks involving fresh produce. Because chemical sanitizing agents used during harvest and minimal processing are unlikely to reach enteric pathogens residing within plant tissue, it is imperative that paths for pathogen entry be recognized and minimized. Using both microscopy and microbial enumeration tools, enteric pathogens have been shown to enter plant tissues through both natural apertures (stomata, lateral junctions of roots, flowers) and damaged (wounds, cut surfaces) tissue. In studies revealing preharvest internalization via plant roots or leaf stomata, experimental conditions have primarily involved exposure of plants to high pathogen concentrations (≥ 6 log g⁻¹ soil or 6 log ml⁻¹ water), but those pathogens internalized appear to have short-term persistence. Postharvest internalization of pathogens via cut surfaces may be minimized by maintaining effective levels of sanitizing agents in waters during harvesting and minimal processing.

Closed-mill delignification by design using polyoxometalates

Treesearch

C. J. Houtman; R. S. Reiner; S. E. Reichel; M. J. Birchmeier; C. E. Sullivan; L. A. Weinstock; R. H. Atalla

1999-01-01

Polyoxometalates (POMs) are a class of delignification agents that promise to provide the basis for a new closed-mill bleaching technology. The results presented here are based on the use of Na6SiV2W10O40, which is effective in reducing the Kappa number of softwood Kraft pulp from 30 to below 10 with minimal loss in viscosity. A critical part of a viable POM process is...

Evaluation of percutaneous permeation of repellent DEET and sunscreen oxybenzone from emulsion-based formulations in artificial membrane and human skin

PubMed Central

Wang, Tao; Miller, Donald; Burczynski, Frank; Gu, Xiaochen

2014-01-01

Insect repellent DEET and sunscreen ingredient oxybenzone play an essential role in minimizing vector-borne diseases and skin cancers. The purpose of this study was to investigate the effects of emulsion type, addition of thickening agent and droplet size in three emulsion-based lotions on percutaneous permeation of DEET and oxybenzone using in vitro diffusion experiments, in order to minimize overall systemic permeation of the substances. Formulation C (water-in-oil emulsion) significantly increased overall permeation of DEET through human skin (56%) compared to Formulation A (oil-in-water emulsion). Formulation B (oil-in-water emulsion with thickening agent xanthan gum) significantly decreased the size of oil droplet containing DEET (16%), but no effect on oil droplets containing oxybenzone. Adding xanthan gum also increased overall permeation of DEET and oxybenzone (21% and 150%) when compared to Formulation A; presence of both ingredients in Formulation B further increased their permeation (36% and 23%) in comparison to its single counterparts. Overall permeation of oxybenzone through LDPE was significantly higher by 26%–628% than that through human skin; overall permeation of DEET through human skin was significantly higher by 64%–338% than that through LDPE. PMID:26579363

Minimizing human infection from Escherichia coli O157:H7 using GUMBOS

PubMed Central

Cole, Marsha R.; Li, Min; Jadeja, Ravirajsinh; El-Zahab, Bilal; Hayes, Daniel; Hobden, Jeffery A.; Janes, Marlene E.; Warner, Isiah M.

2013-01-01

Objectives Reduction in faecal shedding of Shiga toxin-producing enterohaemorrhagic Escherichia coli (EHEC) in food-producing animals is a viable strategy to minimize human disease initiated by exposure to these microorganisms. To this end, an intervention strategy involving the electrostatic hybridization of two commonly used anti-infective agents for veterinary practice (i.e. chlorhexidine and ampicillin) was evaluated to curtail EHEC-transmitted disease from ruminant sources. Chlorhexidine di-ampicillin is a novel group of uniform material based on organic salts (GUMBOS) with inherent in vitro antibacterial activity that comes from its parent antimicrobial ions, chlorhexidine and ampicillin. Methods Antibacterial activities for chlorhexidine diacetate, sodium ampicillin, chlorhexidine di-ampicillin and stoichiometrically equivalent 1 : 2 chlorhexidine diacetate : sodium ampicillin were assessed using the serial 2-fold dilution method and time–kill studies against seven isolates of E. coli O157:H7 and one non-pathogenic E. coli 25922. Further studies to investigate synergistic interactions of reacted and stoichiometrically equivalent unreacted antimicrobial agents at MICs and possible mechanisms were also investigated. Results Synergism and in vitro antibacterial activities against EHEC were observed in this study, which suggests chlorhexidine di-ampicillin could be a useful reagent in reducing EHEC transmission and minimizing EHEC-associated infections. Likewise, chlorhexidine di-ampicillin reduced HeLa cell toxicity as compared with chlorhexidine diacetate or the stoichiometric combination of antimicrobial agents. Further results suggest that the mechanisms of action of chlorhexidine di-ampicillin and chlorhexidine diacetate against E. coli O157:H7 are similar. Conclusions Reacting antimicrobial GUMBOS as indicated in this study may enhance the approach to current combination drug therapeutic strategies for EHEC disease control and prevention. PMID:23447139

Minimizing human infection from Escherichia coli O157:H7 using GUMBOS.

PubMed

Cole, Marsha R; Li, Min; Jadeja, Ravirajsinh; El-Zahab, Bilal; Hayes, Daniel; Hobden, Jeffery A; Janes, Marlene E; Warner, Isiah M

2013-06-01

Reduction in faecal shedding of Shiga toxin-producing enterohaemorrhagic Escherichia coli (EHEC) in food-producing animals is a viable strategy to minimize human disease initiated by exposure to these microorganisms. To this end, an intervention strategy involving the electrostatic hybridization of two commonly used anti-infective agents for veterinary practice (i.e. chlorhexidine and ampicillin) was evaluated to curtail EHEC-transmitted disease from ruminant sources. Chlorhexidine di-ampicillin is a novel group of uniform material based on organic salts (GUMBOS) with inherent in vitro antibacterial activity that comes from its parent antimicrobial ions, chlorhexidine and ampicillin. Antibacterial activities for chlorhexidine diacetate, sodium ampicillin, chlorhexidine di-ampicillin and stoichiometrically equivalent 1 : 2 chlorhexidine diacetate : sodium ampicillin were assessed using the serial 2-fold dilution method and time-kill studies against seven isolates of E. coli O157:H7 and one non-pathogenic E. coli 25922. Further studies to investigate synergistic interactions of reacted and stoichiometrically equivalent unreacted antimicrobial agents at MICs and possible mechanisms were also investigated. Synergism and in vitro antibacterial activities against EHEC were observed in this study, which suggests chlorhexidine di-ampicillin could be a useful reagent in reducing EHEC transmission and minimizing EHEC-associated infections. Likewise, chlorhexidine di-ampicillin reduced HeLa cell toxicity as compared with chlorhexidine diacetate or the stoichiometric combination of antimicrobial agents. Further results suggest that the mechanisms of action of chlorhexidine di-ampicillin and chlorhexidine diacetate against E. coli O157:H7 are similar. Reacting antimicrobial GUMBOS as indicated in this study may enhance the approach to current combination drug therapeutic strategies for EHEC disease control and prevention.

Buses of Cuernavaca—an agent-based model for universal random matrix behavior minimizing mutual information

NASA Astrophysics Data System (ADS)

Warchoł, Piotr

2018-06-01

The public transportation system of Cuernavaca, Mexico, exhibits random matrix theory statistics. In particular, the fluctuation of times between the arrival of buses on a given bus stop, follows the Wigner surmise for the Gaussian unitary ensemble. To model this, we propose an agent-based approach in which each bus driver tries to optimize his arrival time to the next stop with respect to an estimated arrival time of his predecessor. We choose a particular form of the associated utility function and recover the appropriate distribution in numerical experiments for a certain value of the only parameter of the model. We then investigate whether this value of the parameter is otherwise distinguished within an information theoretic approach and give numerical evidence that indeed it is associated with a minimum of averaged pairwise mutual information.

Fracture toughness for copper oxide superconductors

DOEpatents

Goretta, K.C.; Kullberg, M.L.

1993-04-13

An oxide-based strengthening and toughening agent, such as tetragonal ZrO[sub 2] particles, has been added to copper oxide superconductors, such as superconducting YBa[sub 2]Cu[sub 3]O[sub x] (123) to improve its fracture toughness (K[sub IC]). A sol-gel coating which is non-reactive with the superconductor, such as Y[sub 2]BaCuO[sub 5] (211) on the ZrO[sub 2] particles minimized the deleterious reactions between the superconductor and the toughening agent dispersed therethrough. Addition of 20 mole percent ZrO[sub 2] coated with 211 yielded a 123 composite with a K[sub IC] of 4.5 MPa(m)[sup 0.5].

Investigating the feasibility of a BCI-driven robot-based writing agent for handicapped individuals

NASA Astrophysics Data System (ADS)

Syan, Chanan S.; Harnarinesingh, Randy E. S.; Beharry, Rishi

2014-07-01

Brain-Computer Interfaces (BCIs) predominantly employ output actuators such as virtual keyboards and wheelchair controllers to enable handicapped individuals to interact and communicate with their environment. However, BCI-based assistive technologies are limited in their application. There is minimal research geared towards granting disabled individuals the ability to communicate using written words. This is a drawback because involving a human attendant in writing tasks can entail a breach of personal privacy where the task entails sensitive and private information such as banking matters. BCI-driven robot-based writing however can provide a safeguard for user privacy where it is required. This study investigated the feasibility of a BCI-driven writing agent using the 3 degree-of- freedom Phantom Omnibot. A full alphanumerical English character set was developed and validated using a teach pendant program in MATLAB. The Omnibot was subsequently interfaced to a P300-based BCI. Three subjects utilised the BCI in the online context to communicate words to the writing robot over a Local Area Network (LAN). The average online letter-wise classification accuracy was 91.43%. The writing agent legibly constructed the communicated letters with minor errors in trajectory execution. The developed system therefore provided a feasible platform for BCI-based writing.

Antimicrobial edible films and coatings for fresh and minimally processed fruits and vegetables: a review.

PubMed

Valencia-Chamorro, Silvia A; Palou, Lluís; Del Río, Miguel A; Pérez-Gago, María B

2011-01-01

The use of edible films and coatings is an environmentally friendly technology that offers substantial advantages for shelf-life increase of many food products including fruits and vegetables. The development of new natural edible films and coatings with the addition of antimicrobial compounds to preserve fresh and minimally processed fruits and vegetables is a technological challenge for the industry and a very active research field worldwide. Antimicrobial agents have been successfully added to edible composite films and coatings based on polysaccharides or proteins such as starch, cellulose derivatives, chitosan, alginate, fruit puree, whey protein isolated, soy protein, egg albumen, wheat gluten, or sodium caseinate. This paper reviews the development of edible films and coatings with antimicrobial activity, typically through the incorporation of antimicrobial food additives as ingredients, the effect of these edible films on the control of target microorganisms, the influence of antimicrobial agents on mechanical and barrier properties of stand-alone edible films, and the effect of the application of antimicrobial edible coatings on the quality of fresh and fresh-cut fruits and vegetables.

A minimally sufficient model for rib proximal-distal patterning based on genetic analysis and agent-based simulations

PubMed Central

Mah, In Kyoung

2017-01-01

For decades, the mechanism of skeletal patterning along a proximal-distal axis has been an area of intense inquiry. Here, we examine the development of the ribs, simple structures that in most terrestrial vertebrates consist of two skeletal elements—a proximal bone and a distal cartilage portion. While the ribs have been shown to arise from the somites, little is known about how the two segments are specified. During our examination of genetically modified mice, we discovered a series of progressively worsening phenotypes that could not be easily explained. Here, we combine genetic analysis of rib development with agent-based simulations to conclude that proximal-distal patterning and outgrowth could occur based on simple rules. In our model, specification occurs during somite stages due to varying Hedgehog protein levels, while later expansion refines the pattern. This framework is broadly applicable for understanding the mechanisms of skeletal patterning along a proximal-distal axis. PMID:29068314

Degreasing of titanium to minimize stress corrosion

NASA Technical Reports Server (NTRS)

Carpenter, S. R.

1967-01-01

Stress corrosion of titanium and its alloys at elevated temperatures is minimized by replacing trichloroethylene with methanol or methyl ethyl ketone as a degreasing agent. Wearing cotton gloves reduces stress corrosion from perspiration before the metal components are processed.

A Distributed Trajectory-Oriented Approach to Managing Traffic Complexity

NASA Technical Reports Server (NTRS)

Idris, Husni; Wing, David J.; Vivona, Robert; Garcia-Chico, Jose-Luis

2007-01-01

In order to handle the expected increase in air traffic volume, the next generation air transportation system is moving towards a distributed control architecture, in which ground-based service providers such as controllers and traffic managers and air-based users such as pilots share responsibility for aircraft trajectory generation and management. While its architecture becomes more distributed, the goal of the Air Traffic Management (ATM) system remains to achieve objectives such as maintaining safety and efficiency. It is, therefore, critical to design appropriate control elements to ensure that aircraft and groundbased actions result in achieving these objectives without unduly restricting user-preferred trajectories. This paper presents a trajectory-oriented approach containing two such elements. One is a trajectory flexibility preservation function, by which aircraft plan their trajectories to preserve flexibility to accommodate unforeseen events. And the other is a trajectory constraint minimization function by which ground-based agents, in collaboration with air-based agents, impose just-enough restrictions on trajectories to achieve ATM objectives, such as separation assurance and flow management. The underlying hypothesis is that preserving trajectory flexibility of each individual aircraft naturally achieves the aggregate objective of avoiding excessive traffic complexity, and that trajectory flexibility is increased by minimizing constraints without jeopardizing the intended ATM objectives. The paper presents conceptually how the two functions operate in a distributed control architecture that includes self separation. The paper illustrates the concept through hypothetical scenarios involving conflict resolution and flow management. It presents a functional analysis of the interaction and information flow between the functions. It also presents an analytical framework for defining metrics and developing methods to preserve trajectory flexibility and minimize its constraints. In this framework flexibility is defined in terms of robustness and adaptability to disturbances and the impact of constraints is illustrated through analysis of a trajectory solution space with limited degrees of freedom and in simple constraint situations involving meeting multiple times of arrival and resolving a conflict.

Robust model-based 3d/3D fusion using sparse matching for minimally invasive surgery.

PubMed

Neumann, Dominik; Grbic, Sasa; John, Matthias; Navab, Nassir; Hornegger, Joachim; Ionasec, Razvan

2013-01-01

Classical surgery is being disrupted by minimally invasive and transcatheter procedures. As there is no direct view or access to the affected anatomy, advanced imaging techniques such as 3D C-arm CT and C-arm fluoroscopy are routinely used for intra-operative guidance. However, intra-operative modalities have limited image quality of the soft tissue and a reliable assessment of the cardiac anatomy can only be made by injecting contrast agent, which is harmful to the patient and requires complex acquisition protocols. We propose a novel sparse matching approach for fusing high quality pre-operative CT and non-contrasted, non-gated intra-operative C-arm CT by utilizing robust machine learning and numerical optimization techniques. Thus, high-quality patient-specific models can be extracted from the pre-operative CT and mapped to the intra-operative imaging environment to guide minimally invasive procedures. Extensive quantitative experiments demonstrate that our model-based fusion approach has an average execution time of 2.9 s, while the accuracy lies within expert user confidence intervals.

Catheter-related thrombosis: biological and clinical evidence for risk with currently available anticoagulants.

PubMed

Montalescot, Gilles; Walenga, Jeanine M

2009-01-01

Anticoagulants used during percutaneous coronary intervention (PCI) should not only prevent coronary events, but also minimize the risk of periprocedural complications. Current anticoagulation therapies for PCI include unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have good efficacy and safety profiles in PCI; furthermore, associated periprocedural complications such as catheter thrombosis are rare. Although newer anticoagulants seem safe and effective in patients with acute coronary syndrome, clinical trial data suggest that some pure factor Xa (FXa) inhibitors are associated with increased rates of catheter thrombosis, compared with heparin-based agents. Experimental systems show that polytherapeutic agents, including UFH and enoxaparin, are more effective anticoagulants than certain single-target agents. More studies are needed to assess whether catheter thrombosis is a class-, drug-, or dose-related effect, and how best to prevent it. Future trials should report the rates of periprocedural complications when assessing the safety of novel anticoagulation therapies in PCI.

Spiral bacterial foraging optimization method: Algorithm, evaluation and convergence analysis

NASA Astrophysics Data System (ADS)

Kasaiezadeh, Alireza; Khajepour, Amir; Waslander, Steven L.

2014-04-01

A biologically-inspired algorithm called Spiral Bacterial Foraging Optimization (SBFO) is investigated in this article. SBFO, previously proposed by the same authors, is a multi-agent, gradient-based algorithm that minimizes both the main objective function (local cost) and the distance between each agent and a temporary central point (global cost). A random jump is included normal to the connecting line of each agent to the central point, which produces a vortex around the temporary central point. This random jump is also suitable to cope with premature convergence, which is a feature of swarm-based optimization methods. The most important advantages of this algorithm are as follows: First, this algorithm involves a stochastic type of search with a deterministic convergence. Second, as gradient-based methods are employed, faster convergence is demonstrated over GA, DE, BFO, etc. Third, the algorithm can be implemented in a parallel fashion in order to decentralize large-scale computation. Fourth, the algorithm has a limited number of tunable parameters, and finally SBFO has a strong certainty of convergence which is rare in existing global optimization algorithms. A detailed convergence analysis of SBFO for continuously differentiable objective functions has also been investigated in this article.

Development and Sequential Analysis of a New Multi-Agent, Anti-Acne Formulation Based on Plant-Derived Antimicrobial and Anti-Inflammatory Compounds.

PubMed

Saviuc, Crina; Ciubucă, Bianca; Dincă, Gabriela; Bleotu, Coralia; Drumea, Veronica; Chifiriuc, Mariana-Carmen; Popa, Marcela; Gradisteanu Pircalabioru, Gratiela; Marutescu, Luminita; Lazăr, Veronica

2017-01-17

The antibacterial and anti-inflammatory potential of natural, plant-derived compounds has been reported in many studies. Emerging evidence indicates that plant-derived essential oils and/or their major compounds may represent a plausible alternative treatment for acne, a prevalent skin disorder in both adolescent and adult populations. Therefore, the purpose of this study was to develop and subsequently analyze the antimicrobial activity of a new multi-agent, synergic formulation based on plant-derived antimicrobial compounds (i.e., eugenol, β-pinene, eucalyptol, and limonene) and anti-inflammatory agents for potential use in the topical treatment of acne and other skin infections. The optimal antimicrobial combinations selected in this study were eugenol/β-pinene/salicylic acid and eugenol/β-pinene/2-phenoxyethanol/potassium sorbate. The possible mechanisms of action revealed by flow cytometry were cellular permeabilization and inhibition of efflux pumps activity induced by concentrations corresponding to sub-minimal inhibitory (sub-MIC) values. The most active antimicrobial combination represented by salycilic acid/eugenol/β-pinene/2-phenoxyethanol/potassium sorbate was included in a cream base, which demonstrated thermodynamic stability and optimum microbiological characteristics.

Distributed Power Allocation for Wireless Sensor Network Localization: A Potential Game Approach.

PubMed

Ke, Mingxing; Li, Ding; Tian, Shiwei; Zhang, Yuli; Tong, Kaixiang; Xu, Yuhua

2018-05-08

The problem of distributed power allocation in wireless sensor network (WSN) localization systems is investigated in this paper, using the game theoretic approach. Existing research focuses on the minimization of the localization errors of individual agent nodes over all anchor nodes subject to power budgets. When the service area and the distribution of target nodes are considered, finding the optimal trade-off between localization accuracy and power consumption is a new critical task. To cope with this issue, we propose a power allocation game where each anchor node minimizes the square position error bound (SPEB) of the service area penalized by its individual power. Meanwhile, it is proven that the power allocation game is an exact potential game which has one pure Nash equilibrium (NE) at least. In addition, we also prove the existence of an ϵ -equilibrium point, which is a refinement of NE and the better response dynamic approach can reach the end solution. Analytical and simulation results demonstrate that: (i) when prior distribution information is available, the proposed strategies have better localization accuracy than the uniform strategies; (ii) when prior distribution information is unknown, the performance of the proposed strategies outperforms power management strategies based on the second-order cone program (SOCP) for particular agent nodes after obtaining the estimated distribution of agent nodes. In addition, proposed strategies also provide an instructional trade-off between power consumption and localization accuracy.

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

PubMed

Witkowski, Olaf; Ikegami, Takashi

2016-01-01

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

Nanotechnology based approaches for anti-diabetic drugs delivery.

PubMed

Kesharwani, Prashant; Gorain, Bapi; Low, Siew Yeng; Tan, Siew Ann; Ling, Emily Chai Siaw; Lim, Yin Khai; Chin, Chuan Ming; Lee, Pei Yee; Lee, Chun Mey; Ooi, Chun Haw; Choudhury, Hira; Pandey, Manisha

2018-02-01

Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management. Copyright © 2017 Elsevier B.V. All rights reserved.

Real-Time Agent-Based Modeling Simulation with in-situ Visualization of Complex Biological Systems: A Case Study on Vocal Fold Inflammation and Healing.

PubMed

Seekhao, Nuttiiya; Shung, Caroline; JaJa, Joseph; Mongeau, Luc; Li-Jessen, Nicole Y K

2016-05-01

We present an efficient and scalable scheme for implementing agent-based modeling (ABM) simulation with In Situ visualization of large complex systems on heterogeneous computing platforms. The scheme is designed to make optimal use of the resources available on a heterogeneous platform consisting of a multicore CPU and a GPU, resulting in minimal to no resource idle time. Furthermore, the scheme was implemented under a client-server paradigm that enables remote users to visualize and analyze simulation data as it is being generated at each time step of the model. Performance of a simulation case study of vocal fold inflammation and wound healing with 3.8 million agents shows 35× and 7× speedup in execution time over single-core and multi-core CPU respectively. Each iteration of the model took less than 200 ms to simulate, visualize and send the results to the client. This enables users to monitor the simulation in real-time and modify its course as needed.

Standoff detection of explosives and chemical agents using broadly tuned external-cavity quantum cascade lasers (EC-QCLs)

NASA Astrophysics Data System (ADS)

Takeuchi, Eric B.; Rayner, Timothy; Weida, Miles; Crivello, Salvatore; Day, Timothy

2007-10-01

Civilian soft targets such as transportation systems are being targeted by terrorists using IEDs and suicide bombers. Having the capability to remotely detect explosives, precursors and other chemicals would enable these assets to be protected with minimal interruption of the flow of commerce. Mid-IR laser technology offers the potential to detect explosives and other chemicals in real-time and from a safe standoff distance. While many of these agents possess "fingerprint" signatures in the mid-IR (i.e. in the 3-20 micron regime), their effective interrogation by a practical, field-deployable system has been limited by size, complexity, reliability and cost constraints of the base laser technology. Daylight Solutions has addressed these shortcomings by developing compact, portable, broadly tunable mid-IR laser sources based upon external-cavity quantum cascade technology. This technology is now being applied by Daylight in system level architectures for standoff and remote detection of explosives, precursors and chemical agents. Several of these architectures and predicted levels of performance will be presented.

GOLD NANOPARTICLES: A REVIVAL IN PRECIOUS METAL ADMINISTRATION TO PATIENTS

PubMed Central

Thakor, AS; Jokerst, J; Zaveleta, C; Massoud, TF; Gambhir, SS

2011-01-01

Gold has been used as a therapeutic agent to treat a wide variety of rheumatic diseases including psoriatic arthritis, juvenile arthritis and discoid lupus erythematosus. Although the use of gold has been largely superseded by newer drugs, gold nanoparticles are being used effectively in laboratory based clinical diagnostic methods whilst concurrently showing great promise in vivo either as a diagnostic imaging agent or a therapeutic agent. For these reasons, gold nanoparticles are therefore well placed to enter mainstream clinical practice in the near future. Hence, the present review summarizes the chemistry, pharmacokinetics, bio-distribution, metabolism and toxicity of bulk gold in humans based on decades of clinical observation and experiments in which gold was used to treat patients with rheumatoid arthritis. The beneficial attributes of gold nanoparticles, such as their ease of synthesis, functionalization and shape control are also highlighted demonstrating why gold nanoparticles are an attractive target for further development and optimization. The importance of controlling the size and shape of gold nanoparticles to minimize any potential toxic side effects is also discussed. PMID:21846107

Predicting the host range of Nystalea ebalea: secondary plant chemistry and host selection by a surrogate biological control agent of Schinus terebinthifolia

USDA-ARS?s Scientific Manuscript database

The safety of weed biological control depends upon the selection and utilization of the target weed by the agent while causing minimal harm to non-target species. Selection of weed species by biological control agents is determined by the presence of behavioral cues, generally host secondary plant c...

Distributed Constrained Optimization with Semicoordinate Transformations

NASA Technical Reports Server (NTRS)

Macready, William; Wolpert, David

2006-01-01

Recent work has shown how information theory extends conventional full-rationality game theory to allow bounded rational agents. The associated mathematical framework can be used to solve constrained optimization problems. This is done by translating the problem into an iterated game, where each agent controls a different variable of the problem, so that the joint probability distribution across the agents moves gives an expected value of the objective function. The dynamics of the agents is designed to minimize a Lagrangian function of that joint distribution. Here we illustrate how the updating of the Lagrange parameters in the Lagrangian is a form of automated annealing, which focuses the joint distribution more and more tightly about the joint moves that optimize the objective function. We then investigate the use of "semicoordinate" variable transformations. These separate the joint state of the agents from the variables of the optimization problem, with the two connected by an onto mapping. We present experiments illustrating the ability of such transformations to facilitate optimization. We focus on the special kind of transformation in which the statistically independent states of the agents induces a mixture distribution over the optimization variables. Computer experiment illustrate this for &sat constraint satisfaction problems and for unconstrained minimization of NK functions.

RBC micromotors carrying multiple cargos towards potential theranostic applications

NASA Astrophysics Data System (ADS)

Wu, Zhiguang; Esteban-Fernández de Ávila, Berta; Martín, Aída; Christianson, Caleb; Gao, Weiwei; Thamphiwatana, Soracha Kun; Escarpa, Alberto; He, Qiang; Zhang, Liangfang; Wang, Joseph

2015-08-01

Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic resonance imaging. The simultaneous encapsulation of the imaging nanoparticles and therapeutic payloads within the same RBC micromotor has a minimal effect upon its propulsion behavior. The ability of the RBC micromotors to transport imaging and therapeutic agents at high speed and spatial precision through a complex microchannel network is also demonstrated. Such ability to load and transport diagnostic imaging agents and therapeutic drugs within a single cell-based motor, in addition to a lower toxicity observed once the drug is encapsulated within the multicargo RBC motor, opens the door to the development of theranostic micromotors that may simultaneously treat and monitor diseases.Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic resonance imaging. The simultaneous encapsulation of the imaging nanoparticles and therapeutic payloads within the same RBC micromotor has a minimal effect upon its propulsion behavior. The ability of the RBC micromotors to transport imaging and therapeutic agents at high speed and spatial precision through a complex microchannel network is also demonstrated. Such ability to load and transport diagnostic imaging agents and therapeutic drugs within a single cell-based motor, in addition to a lower toxicity observed once the drug is encapsulated within the multicargo RBC motor, opens the door to the development of theranostic micromotors that may simultaneously treat and monitor diseases. Electronic supplementary information (ESI) available: Videos of the propulsion of the multicargo-loaded, RBC-based micromotors and more data are available in the ESI. See DOI: 10.1039/c5nr03730a

Spacecraft surgical scrub system

NASA Technical Reports Server (NTRS)

Abbate, M.

1980-01-01

Ease of handling and control in zero gravity and minimizing the quantity of water required were prime considerations. The program tasks include the selection of biocidal agent from among the variety used for surgical scrub, formulation of a dispensing system, test, and delivery of flight dispensers. The choice of an iodophore was based on effectiveness on single applications, general familiarity among surgeons, and previous qualification for space use. The delivery system was a choice between the squeeze foamer system and impregnated polyurethane foam pads. The impregnated foam pad was recommended because it is a simpler system since the squeeze foamer requires some applicator to effectively clean the skin surfaces, whereas the form pad is the applicator and agent combined. Testing demonstrated that both systems are effective for use as surgical scrubs.

The potential for neurovascular intravenous angiography using K-edge digital subtraction angiography

NASA Astrophysics Data System (ADS)

Schültke, E.; Fiedler, S.; Kelly, M.; Griebel, R.; Juurlink, B.; LeDuc, G.; Estève, F.; Le Bas, J.-F.; Renier, M.; Nemoz, C.; Meguro, K.

2005-08-01

Background: Catheterization of small-caliber blood vessels in the central nervous system can be extremely challenging. Alternatively, intravenous (i.v.) administration of contrast agent is minimally invasive and therefore carries a much lower risk for the patient. With conventional X-ray equipment, volumes of contrast agent that could be safely administered to the patient do not allow acquisition of high-quality images after i.v. injection, because the contrast bolus is extremely diluted by passage through the heart. However, synchrotron-based digital K-edge subtraction angiography does allow acquisition of high-quality images after i.v. administration of relatively small doses of contrast agent. Materials and methods: Eight adult male New Zealand rabbits were used for our experiments. Animals were submitted to both angiography with conventional X-ray equipment and synchrotron-based digital subtraction angiography. Results: With conventional X-ray equipment, no contrast was seen in either cerebral or spinal blood vessels after i.v. injection of iodinated contrast agent. However, using K-edge digital subtraction angiography, as little as 1 ml iodinated contrast agent, when administered as i.v. bolus, yielded images of small-caliber blood vessels in the central nervous system (both brain and spinal cord). Conclusions: If it would be possible to image blood vessels of the same diameter in the central nervous system of human patients, the synchrotron-based technique could yield high-quality images at a significantly lower risk for the patient than conventional X-ray imaging. Images could be acquired where catheterization of feeding blood vessels has proven impossible.

Sequential Nonlinear Learning for Distributed Multiagent Systems via Extreme Learning Machines.

PubMed

Vanli, Nuri Denizcan; Sayin, Muhammed O; Delibalta, Ibrahim; Kozat, Suleyman Serdar

2017-03-01

We study online nonlinear learning over distributed multiagent systems, where each agent employs a single hidden layer feedforward neural network (SLFN) structure to sequentially minimize arbitrary loss functions. In particular, each agent trains its own SLFN using only the data that is revealed to itself. On the other hand, the aim of the multiagent system is to train the SLFN at each agent as well as the optimal centralized batch SLFN that has access to all the data, by exchanging information between neighboring agents. We address this problem by introducing a distributed subgradient-based extreme learning machine algorithm. The proposed algorithm provides guaranteed upper bounds on the performance of the SLFN at each agent and shows that each of these individual SLFNs asymptotically achieves the performance of the optimal centralized batch SLFN. Our performance guarantees explicitly distinguish the effects of data- and network-dependent parameters on the convergence rate of the proposed algorithm. The experimental results illustrate that the proposed algorithm achieves the oracle performance significantly faster than the state-of-the-art methods in the machine learning and signal processing literature. Hence, the proposed method is highly appealing for the applications involving big data.

78 FR 24207 - Request for Information About Diethanolamine (CAS No. 111-42-2)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

.... engineering controls, work practices, personal protective equipment, exposure data before and after... agent in agricultural chemicals, a corrosion inhibitor and wetting agent in metalworking fluids. The...., engineering controls, work practices, PPE) being taken to minimize worker exposure to diethanolamine. (8...

Distributed optimization system and method

DOEpatents

Hurtado, John E.; Dohrmann, Clark R.; Robinett, III, Rush D.

2003-06-10

A search system and method for controlling multiple agents to optimize an objective using distributed sensing and cooperative control. The search agent can be one or more physical agents, such as a robot, and can be software agents for searching cyberspace. The objective can be: chemical sources, temperature sources, radiation sources, light sources, evaders, trespassers, explosive sources, time dependent sources, time independent sources, function surfaces, maximization points, minimization points, and optimal control of a system such as a communication system, an economy, a crane, and a multi-processor computer.

Distributed Optimization System

DOEpatents

Hurtado, John E.; Dohrmann, Clark R.; Robinett, III, Rush D.

2004-11-30

A search system and method for controlling multiple agents to optimize an objective using distributed sensing and cooperative control. The search agent can be one or more physical agents, such as a robot, and can be software agents for searching cyberspace. The objective can be: chemical sources, temperature sources, radiation sources, light sources, evaders, trespassers, explosive sources, time dependent sources, time independent sources, function surfaces, maximization points, minimization points, and optimal control of a system such as a communication system, an economy, a crane, and a multi-processor computer.

Optimal control in microgrid using multi-agent reinforcement learning.

PubMed

Li, Fu-Dong; Wu, Min; He, Yong; Chen, Xin

2012-11-01

This paper presents an improved reinforcement learning method to minimize electricity costs on the premise of satisfying the power balance and generation limit of units in a microgrid with grid-connected mode. Firstly, the microgrid control requirements are analyzed and the objective function of optimal control for microgrid is proposed. Then, a state variable "Average Electricity Price Trend" which is used to express the most possible transitions of the system is developed so as to reduce the complexity and randomicity of the microgrid, and a multi-agent architecture including agents, state variables, action variables and reward function is formulated. Furthermore, dynamic hierarchical reinforcement learning, based on change rate of key state variable, is established to carry out optimal policy exploration. The analysis shows that the proposed method is beneficial to handle the problem of "curse of dimensionality" and speed up learning in the unknown large-scale world. Finally, the simulation results under JADE (Java Agent Development Framework) demonstrate the validity of the presented method in optimal control for a microgrid with grid-connected mode. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia.

PubMed

Cramer, Paula; von Tresckow, Julia; Bahlo, Jasmin; Engelke, Anja; Langerbeins, Petra; Fink, Anna-Maria; Fischer, Kirsten; Wendtner, Clemens-Martin; Kreuzer, Karl-Anton; Stilgenbauer, Stephan; Böttcher, Sebastian; Eichhorst, Barbara; Hallek, Michael

2018-03-01

Four Phase II trials (clinical trials numbers: NCT02345863, NCT02401503, NCT02445131 and NCT02689141) evaluate a different combination of targeted agents in an all-comer population of approximately 60 patients with chronic lymphocytic leukemia irrespective of prior treatment, physical fitness and genetic risk factors. Patients with a higher tumor load start with a debulking treatment with bendamustine. The subsequent induction and maintenance treatment with an anti-CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib, idelalisib or venetoclax) are continued until achievement of a complete response and minimal residual disease negativity. This strategy represents a new era of chronic lymphocytic leukemia therapy where chemotherapy is increasingly replaced by targeted agents and treatment duration is tailored to the patient's individual tumor load and response.

Production and characterization of curcumin microcrystals and evaluation of the antimicrobial and sensory aspects in minimally processed carrots.

PubMed

Silva, Anderson Clayton da; Santos, Priscila Dayane de Freitas; Palazzi, Nicole Campezato; Leimann, Fernanda Vitória; Fuchs, Renata Hernandez Barros; Bracht, Lívia; Gonçalves, Odinei Hess

2017-05-24

Nontoxic conserving agents are in demand by the food industry due to consumers concern about synthetic conservatives, especially in minimally processed food. The antimicrobial activity of curcumin, a natural phenolic compound, has been extensively investigated but hydrophobicity is an issue when applying curcumin to foodstuff. The objective of this work was to evaluate curcumin microcrystals as an antimicrobial agent in minimally processed carrots. The antimicrobial activity of curcumin microcrystals was evaluated in vitro against Gram-positive (Bacillus cereus and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) microorganisms, showing a statistically significant (p < 0.05) decrease in the minimum inhibitory concentration compared to in natura, pristine curcumin. Curcumin microcrystals were effective in inhibiting psychrotrophic and mesophile microorganisms in minimally processed carrots. Sensory analyses were carried out showing no significant difference (p < 0.05) between curcumin microcrystal-treated carrots and non-treated carrots in triangular and tetrahedral discriminative tests. Sensory tests also showed that curcumin microcrystals could be added as a natural preservative in minimally processed carrots without causing noticeable differences that could be detected by the consumer. One may conclude that the analyses of the minimally processed carrots demonstrated that curcumin microcrystals are a suitable natural compound to inhibit the natural microbiota of carrots from a statistical point of view.

Application of a micro-aerosolized disinfectant to clear Mycoplasma gallisepticum from contaminated facilities

USDA-ARS?s Scientific Manuscript database

Infectious agents and their associated diseases can be significant barriers in the production of poultry and zoonotic agents associated with poultry flocks can ultimately endanger consumers. To this end, poultry producers employ a variety of strategies to minimize associated risks. Disinfectants a...

Hybrid Exploration Agent Platform and Sensor Web System

NASA Technical Reports Server (NTRS)

Stoffel, A. William; VanSteenberg, Michael E.

2004-01-01

A sensor web to collect the scientific data needed to further exploration is a major and efficient asset to any exploration effort. This is true not only for lunar and planetary environments, but also for interplanetary and liquid environments. Such a system would also have myriad direct commercial spin-off applications. The Hybrid Exploration Agent Platform and Sensor Web or HEAP-SW like the ANTS concept is a Sensor Web concept. The HEAP-SW is conceptually and practically a very different system. HEAP-SW is applicable to any environment and a huge range of exploration tasks. It is a very robust, low cost, high return, solution to a complex problem. All of the technology for initial development and implementation is currently available. The HEAP Sensor Web or HEAP-SW consists of three major parts, The Hybrid Exploration Agent Platforms or HEAP, the Sensor Web or SW and the immobile Data collection and Uplink units or DU. The HEAP-SW as a whole will refer to any group of mobile agents or robots where each robot is a mobile data collection unit that spends most of its time acting in concert with all other robots, DUs in the web, and the HEAP-SWs overall Command and Control (CC) system. Each DU and robot is, however, capable of acting independently. The three parts of the HEAP-SW system are discussed in this paper. The Goals of the HEAP-SW system are: 1) To maximize the amount of exploration enhancing science data collected; 2) To minimize data loss due to system malfunctions; 3) To minimize or, possibly, eliminate the risk of total system failure; 4) To minimize the size, weight, and power requirements of each HEAP robot; 5) To minimize HEAP-SW system costs. The rest of this paper discusses how these goals are attained.

Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

PubMed

Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

2014-06-01

Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

Biotechnology Research Requirements for Aeronautical Systems through the Year 2000. Volume 1

DTIC Science & Technology

1982-07-30

signature. Reducing the aero contain radic.?z,:"ve fallout. vehicle’s detectibility by reducing the optical, electro, acoustic, and infrared 0 Pulsed...arsenal devoted to agent doses. At this time, basic biochemical and chemical agents, reported use of mycotoxins and pharmacological data are minimal and...mass spectroscopy , quartz chemical agents must be developed. This research microbalances, Industrial hygiene dosimetry, damp should quantify human

Common drug-drug interactions in antifungal treatments for superficial fungal infections.

PubMed

Gupta, Aditya K; Versteeg, Sarah G; Shear, Neil H

2018-04-01

Antifungal agents can be co-administered alongside several other medications for a variety of reasons such as the presence of comorbidities. Pharmacodynamic interactions such as synergistic and antagonistic interactions could be the result of co-administered medications. Pharmacokinetic interactions could also transpire through the inhibition of metabolizing enzymes and drug transport systems, altering the absorption, metabolism and excretion of co-administered medications. Both pharmacodynamic and pharmacokinetic interactions can result in hospitalization due to serious adverse effects associated with antifungal agents, lower therapeutic doses required to achieve desired antifungal activity, and prevent antifungal resistance. Areas covered: The objective of this review is to summarize pharmacodynamic and pharmacokinetic interactions associated with common antifungal agents used to treat superficial fungal infections. Pharmacodynamic and pharmacokinetic interactions that impact the therapeutic effects of antifungal agents and drugs that are influenced by the presence of antifungal agents was the context to which these antifungal agents were addressed. Expert opinion: The potential for drug-drug interactions is minimal for topical antifungals as opposed to oral antifungals as they have minimal exposure to other co-administered medications. Developing non-lipophilic antifungals that have unique metabolizing pathways and are topical applied are suggested properties that could help limit drug-drug interactions associated with future treatments.

Radioprotection and contrast agent use in pediatrics: what, how, and when.

PubMed

Lancharro Zapata, Á M; Rodríguez, C Marín

2016-05-01

It is essential to minimize exposure to ionizing radiation in children for various reasons. The risk of developing a tumor from exposure to a given dose of radiation is greater in childhood. Various strategies can be used to reduce exposure to ionizing radiation. It is fundamental to avoid unnecessary tests and tests that are not indicated, to choose an alternative test that does not use ionizing radiation, and/or to take a series of measures that minimize the dose of radiation that the patient receives, such as avoiding having to repeat tests, using the appropriate projections, using shields, adjusting the protocol (mAs, Kv, or pitch) to the patient's body volume, etc… When contrast agents are necessary, intracavitary ultrasound agents can be used, although the use of ultrasound agents is also being extended to include intravenous administration. In fluoroscopy, contrast agents with low osmolarity must be used, as in CT where we must adjust the dose and speed of injection to the patient's weight and to the caliber of the peripheral line, respectively. In MRI, only three types of contrast agents have been approved for pediatric use. It is sometimes necessary to use double doses or organ-specific contrast agents in certain clinical situations; the safety of contrast agents for these indications has not been proven, so they must be used off label. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Composite starch-based coatings applied to strawberries (Fragaria ananassa).

PubMed

García, M A; Martino, M N; Zaritzky, N E

2001-08-01

Starch-based coatings were used to the extend storage life of strawberries (Fragaria ananassa) stored at 0 degree C and 84.8% relative humidity. Effects of coating formulation (including starch type, plasticizer, lipid and antimicrobial agent) were analysed with respect to fruit quality. Plasticizer addition was necessary for film and coating integrity to avoid pores and cracks. Plasticizer presence reduced weight losses and maintained surface colour of fruits. Amylomaize coatings showed lower water vapour and gas permeabilities and decreased weight losses for longer periods than corn starch ones. Coatings with sorbitol showed lower permeabilities than glycerol ones. Coatings with antimicrobial agents decreased microbial counts, extending storage life of coated fruits by 10 to 14 days in comparison to the control. The addition of 2 g/l sunflower oil to the formulations decreased the water vapour permeability of starch-based films, maintained the surface colour of coated fruits and controlled effectively fruit weight losses during storage. Lipid addition minimized the effects of starch and plasticizer types. Composite starch-based coatings showed selective gas permeability (CO2 higher than O2) which helps to delay senescence of fruits.

Agent-Based Models of Strategies for the Emergence and Evolution of Grammatical Agreement

PubMed Central

Beuls, Katrien; Steels, Luc

2013-01-01

Grammatical agreement means that features associated with one linguistic unit (for example number or gender) become associated with another unit and then possibly overtly expressed, typically with morphological markers. It is one of the key mechanisms used in many languages to show that certain linguistic units within an utterance grammatically depend on each other. Agreement systems are puzzling because they can be highly complex in terms of what features they use and how they are expressed. Moreover, agreement systems have undergone considerable change in the historical evolution of languages. This article presents language game models with populations of agents in order to find out for what reasons and by what cultural processes and cognitive strategies agreement systems arise. It demonstrates that agreement systems are motivated by the need to minimize combinatorial search and semantic ambiguity, and it shows, for the first time, that once a population of agents adopts a strategy to invent, acquire and coordinate meaningful markers through social learning, linguistic self-organization leads to the spontaneous emergence and cultural transmission of an agreement system. The article also demonstrates how attested grammaticalization phenomena, such as phonetic reduction and conventionalized use of agreement markers, happens as a side effect of additional economizing principles, in particular minimization of articulatory effort and reduction of the marker inventory. More generally, the article illustrates a novel approach for studying how key features of human languages might emerge. PMID:23527055

Health Care Decision Support System for the Pediatric Emeregency Department Management.

PubMed

Ben Othman, Sarah; Hammadi, Slim; Quilliot, Alain; Martinot, Alain; Renard, Jean-Marie

2015-01-01

Health organization management is facing a high amount of complexity due to the inherent dynamics of the processes and the distributed organization of hospitals. It is therefore necessary for health care institutions to focus on this issue in order to deal with patients' requirements and satisfy their needs. The main objective of this study is to develop and implement a Decision Support System which can help physicians to better manage their organization, to anticipate the overcrowding feature, and to establish avoidance proposals for it. This work is a part of HOST project (Hospital: Optimization, Simulation, and Crowding Avoidance) of the French National Research Agency (ANR). It aims to optimize the functioning of the Pediatric Emergency Department characterized by stochastic arrivals of patients which leads to its overcrowding and services overload. Our study is a set of tools to smooth out patient flows, enhance care quality and minimize long waiting times and costs due to resources allocation. So we defined a decision aided tool based on Multi-agent Systems where actors negotiate and cooperate under some constraints in a dynamic environment. These entities which can be either physical agents representing real actors in the health care institution or software agents allowing the implementation of optimizing tools, cooperate to satisfy the demands of patients while respecting emergency degrees. This paper is concerned with agents' negotiation. It proposes a new approach for multi-skill tasks scheduling based on interactions between agents.

Effective Treatment of Advanced Human Melanoma Metastasis in Immunodeficient Mice Using Combination Metronomic Chemotherapy Regimens

PubMed Central

Cruz-Munoz, William; Man, Shan; Kerbel, Robert S.

2009-01-01

Statement of translational relevance Despite significant efforts over the last two decades aimed at improving the efficacy of standard treatment (maximum tolerated dose (MTD) of dacarbazine), there has been no significant increase in the median survival of patients suffering from metastatic melanoma. Given the lack of success achieved, a rethinking of alternative treatment strategies is needed. Using preclinical models of advanced melanoma metastasis, we show that metronomic chemotherapeutic combinations results in improved survival, which is achieved with minimal toxicity. These results compare favorably with minimal effectiveness achieved by MTD dacarbazine therapy (alone or in combination with other chemotherapeutic agents or a VEGFR-blocking antibody), often accompanied by higher toxicity. Successes in preclinical setting of metastatic breast cancer have led to a clinical trial to examine the efficacy of metronomic therapy. A similar extension of the metronomic chemotherapeutic combinations presented here into the clinical setting of melanoma metastasis may be warranted. Purpose The development of effective therapeutic approaches for treatment of metastatic melanoma remains an immense challenge. Present therapies offer minimal benefit. While dacarbazine (DTIC) chemotherapy remains the standard therapy, it mediates only low response rates, usually of short duration, even when combined with other chemotherapeutic agents. Thus, new therapeutic strategies are urgently needed. Experimental design Using a newly developed preclinical model, we evaluated the efficacy of various doublet metronomic combination chemotherapy against established, advanced melanoma metastasis and compared these to the standard maximum tolerated dose (MTD) DTIC (alone or in combination with chemotherapeutic agents or VEGFR-blocking antibody) Results Whereas MTD DTIC therapy did not cause significant improvement in median survival, a doublet combination of low-dose metronomic (LDM) vinblastine (Vbl) and LDM cyclophosphamide (CTX) induced a significant increase in survival with only minimal toxicity. Furthermore, we show that the incorporation of the LDM Vbl/LDM CTX combination with a LDM DTIC regimen also results in a significant increase in survival, but not when combined with MTD DTIC therapy. We also show that a combination of metronomic Vbl therapy and a VEGFR2-blocking antibody (DC101) results in significant control of metastatic disease and that the combination of LDM Vbl/DC101 and LDM DTIC induced a significant improvement in median survival. Conclusions The effective control of advanced metastatic melanoma achieved by these metronomic-based chemotherapeutic approaches warrants clinical consideration of this treatment concept given the recent results of a number of metronomic-based chemotherapy clinical trials. PMID:19622578

Information Processing and Dynamics in Minimally Cognitive Agents

ERIC Educational Resources Information Center

Beer, Randall D.; Williams, Paul L.

2015-01-01

There has been considerable debate in the literature about the relative merits of information processing versus dynamical approaches to understanding cognitive processes. In this article, we explore the relationship between these two styles of explanation using a model agent evolved to solve a relational categorization task. Specifically, we…

Exploring Tradeoffs in Demand-side and Supply-side Management of Urban Water Resources using Agent-based Modeling and Evolutionary Computation

NASA Astrophysics Data System (ADS)

Kanta, L.; Berglund, E. Z.

2015-12-01

Urban water supply systems may be managed through supply-side and demand-side strategies, which focus on water source expansion and demand reductions, respectively. Supply-side strategies bear infrastructure and energy costs, while demand-side strategies bear costs of implementation and inconvenience to consumers. To evaluate the performance of demand-side strategies, the participation and water use adaptations of consumers should be simulated. In this study, a Complex Adaptive Systems (CAS) framework is developed to simulate consumer agents that change their consumption to affect the withdrawal from the water supply system, which, in turn influences operational policies and long-term resource planning. Agent-based models are encoded to represent consumers and a policy maker agent and are coupled with water resources system simulation models. The CAS framework is coupled with an evolutionary computation-based multi-objective methodology to explore tradeoffs in cost, inconvenience to consumers, and environmental impacts for both supply-side and demand-side strategies. Decisions are identified to specify storage levels in a reservoir that trigger (1) increases in the volume of water pumped through inter-basin transfers from an external reservoir and (2) drought stages, which restrict the volume of water that is allowed for residential outdoor uses. The proposed methodology is demonstrated for Arlington, Texas, water supply system to identify non-dominated strategies for an historic drought decade. Results demonstrate that pumping costs associated with maximizing environmental reliability exceed pumping costs associated with minimizing restrictions on consumer water use.

Toxicity assessment of individual ingredients of synthetic-based drilling muds (SBMs).

PubMed

Bakhtyar, Sajida; Gagnon, Marthe Monique

2012-09-01

Synthetic-based drilling muds (SBMs) offer excellent technical characteristics while providing improved environmental performance over other drilling muds. The low acute toxicity and high biodegradability of SBMs suggest their discharge at sea would cause minimal impacts on marine ecosystems, however, chronic toxicity testing has demonstrated adverse effects of SBMs on fish health. Sparse environmental monitoring data indicate effects of SBMs on bottom invertebrates. However, no environmental toxicity assessment has been performed on fish attracted to the cutting piles. SBM formulations are mostly composed of synthetic base oils, weighting agents, and drilling additives such as emulsifiers, fluid loss agents, wetting agents, and brine. The present study aimed to evaluate the impact of exposure to individual ingredients of SBMs on fish health. To do so, a suite of biomarkers [ethoxyresorufin-O-deethylase (EROD) activity, biliary metabolites, sorbitol dehydrogenase (SDH) activity, DNA damage, and heat shock protein] have been measured in pink snapper (Pagrus auratus) exposed for 21 days to individual ingredients of SBMs. The primary emulsifier (Emul S50) followed by the fluid loss agent (LSL 50) caused the strongest biochemical responses in fish. The synthetic base oil (Rheosyn) caused the least response in juvenile fish. The results suggest that the impact of Syndrill 80:20 on fish health might be reduced by replacement of the primary emulsifier Emul S50 with an alternative ingredient of less toxicity to aquatic biota. The research provides a basis for improving the environmental performance of SBMs by reducing the environmental risk of their discharge and providing environmental managers with information regarding the potential toxicity of individual ingredients.

A network-based approach for resistance transmission in bacterial populations.

PubMed

Gehring, Ronette; Schumm, Phillip; Youssef, Mina; Scoglio, Caterina

2010-01-07

Horizontal transfer of mobile genetic elements (conjugation) is an important mechanism whereby resistance is spread through bacterial populations. The aim of our work is to develop a mathematical model that quantitatively describes this process, and to use this model to optimize antimicrobial dosage regimens to minimize resistance development. The bacterial population is conceptualized as a compartmental mathematical model to describe changes in susceptible, resistant, and transconjugant bacteria over time. This model is combined with a compartmental pharmacokinetic model to explore the effect of different plasma drug concentration profiles. An agent-based simulation tool is used to account for resistance transfer occurring when two bacteria are adjacent or in close proximity. In addition, a non-linear programming optimal control problem is introduced to minimize bacterial populations as well as the drug dose. Simulation and optimization results suggest that the rapid death of susceptible individuals in the population is pivotal in minimizing the number of transconjugants in a population. This supports the use of potent antimicrobials that rapidly kill susceptible individuals and development of dosage regimens that maintain effective antimicrobial drug concentrations for as long as needed to kill off the susceptible population. Suggestions are made for experiments to test the hypotheses generated by these simulations.

Getting the Gist of Events: Recognition of Two-Participant Actions from Brief Displays

PubMed Central

Hafri, Alon; Papafragou, Anna; Trueswell, John C.

2013-01-01

Unlike rapid scene and object recognition from brief displays, little is known about recognition of event categories and event roles from minimal visual information. In three experiments, we displayed naturalistic photographs of a wide range of two-participant event scenes for 37 ms and 73 ms followed by a mask, and found that event categories (the event gist, e.g., ‘kicking’, ‘pushing’, etc.) and event roles (i.e., Agent and Patient) can be recognized rapidly, even with various actor pairs and backgrounds. Norming ratings from a subsequent experiment revealed that certain physical features (e.g., outstretched extremities) that correlate with Agent-hood could have contributed to rapid role recognition. In a final experiment, using identical twin actors, we then varied these features in two sets of stimuli, in which Patients had Agent-like features or not. Subjects recognized the roles of event participants less accurately when Patients possessed Agent-like features, with this difference being eliminated with two-second durations. Thus, given minimal visual input, typical Agent-like physical features are used in role recognition but, with sufficient input from multiple fixations, people categorically determine the relationship between event participants. PMID:22984951

A Descriptive Overview of Japanese Shipbuilding Surface Preparation and Coating Methods

DTIC Science & Technology

1982-09-01

INORGANIC SHOP PRIMER I Materials I Weight BASE PASTE Total Alkyl-silicate Catalyst Alcohol Special organic resin Tinting pigment Anti-sagging agent... Alcohol Zinc powder 32.0 2.0 6.0 0.5 8.0 40.0 100.0 Shop Primer Composition (Courtesy of Chugoku Marine Paints 51 Limited) 4.2.1 Shop Primer...at a pH of 10 is added to minimize the oxydizing reactions which lead to salt formation and adhesion failure. “Galvanite” is the trade name for the

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

PubMed Central

Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

2012-01-01

Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

Exclusive queueing model including the choice of service windows

NASA Astrophysics Data System (ADS)

Tanaka, Masahiro; Yanagisawa, Daichi; Nishinari, Katsuhiro

2018-01-01

In a queueing system involving multiple service windows, choice behavior is a significant concern. This paper incorporates the choice of service windows into a queueing model with a floor represented by discrete cells. We contrived a logit-based choice algorithm for agents considering the numbers of agents and the distances to all service windows. Simulations were conducted with various parameters of agent choice preference for these two elements and for different floor configurations, including the floor length and the number of service windows. We investigated the model from the viewpoint of transit times and entrance block rates. The influences of the parameters on these factors were surveyed in detail and we determined that there are optimum floor lengths that minimize the transit times. In addition, we observed that the transit times were determined almost entirely by the entrance block rates. The results of the presented model are relevant to understanding queueing systems including the choice of service windows and can be employed to optimize facility design and floor management.

Consensus summary of aerosolized antimicrobial agents: application of guideline criteria. Insights from the Society of Infectious Diseases Pharmacists.

PubMed

Le, Jennifer; Ashley, Elizabeth Dodds; Neuhauser, Melinda M; Brown, Jack; Gentry, Chris; Klepser, Michael E; Marr, Ann Marie; Schiller, Daryl; Schwiesow, Joshua N; Tice, Sally; VandenBussche, Heather L; Wood, G Christopher

2010-06-01

Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital-acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence-based pharmacotherapy. Further research with well-designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.

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.

Influenza virus inactivated by artificial ribonucleases as a prospective killed virus vaccine.

PubMed

Fedorova, Antonina A; Goncharova, Elena P; Kovpak, Mikhail P; Vlassov, Valentin V; Zenkova, Marina A

2012-04-19

The inactivation of viral particles with agents causing minimal damage to the structure of surface epitopes is a well-established approach for the production of killed virus vaccines. Here, we describe new agents for the inactivation of influenza virus, artificial ribonucleases (aRNases), which are chemical compounds capable of cleaving RNA molecules. Several aRNases were identified, exhibiting significant virucidal activity against the influenza A virus and causing a minimal effect on the affinity of monoclonal antibodies for the inactivated virus. Using a murine model of the influenza virus infection, a high protective activity of the aRNase-inactivated virus as a vaccine was demonstrated. The results of the experiments demonstrate the efficacy of novel chemical agents in the preparation of vaccines against influenza and, perhaps, against other infections caused by RNA viruses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Applications of minimal physiologically-based pharmacokinetic models

PubMed Central

Cao, Yanguang

2012-01-01

Conventional mammillary models are frequently used for pharmacokinetic (PK) analysis when only blood or plasma data are available. Such models depend on the quality of the drug disposition data and have vague biological features. An alternative minimal-physiologically-based PK (minimal-PBPK) modeling approach is proposed which inherits and lumps major physiologic attributes from whole-body PBPK models. The body and model are represented as actual blood and tissue usually total body weight) volumes, fractions (fd) of cardiac output with Fick’s Law of Perfusion, tissue/blood partitioning (Kp), and systemic or intrinsic clearance. Analyzing only blood or plasma concentrations versus time, the minimal-PBPK models parsimoniously generate physiologically-relevant PK parameters which are more easily interpreted than those from mam-millary models. The minimal-PBPK models were applied to four types of therapeutic agents and conditions. The models well captured the human PK profiles of 22 selected beta-lactam antibiotics allowing comparison of fitted and calculated Kp values. Adding a classical hepatic compartment with hepatic blood flow allowed joint fitting of oral and intravenous (IV) data for four hepatic elimination drugs (dihydrocodeine, verapamil, repaglinide, midazolam) providing separate estimates of hepatic intrinsic clearance, non-hepatic clearance, and pre-hepatic bioavailability. The basic model was integrated with allometric scaling principles to simultaneously describe moxifloxacin PK in five species with common Kp and fd values. A basic model assigning clearance to the tissue compartment well characterized plasma concentrations of six monoclonal antibodies in human subjects, providing good concordance of predictions with expected tissue kinetics. The proposed minimal-PBPK modeling approach offers an alternative and more rational basis for assessing PK than compartmental models. PMID:23179857

What Does God Know? Supernatural Agents' Access to Socially Strategic and Non-Strategic Information

ERIC Educational Resources Information Center

Purzycki, Benjamin G.; Finkel, Daniel N.; Shaver, John; Wales, Nathan; Cohen, Adam B.; Sosis, Richard

2012-01-01

Current evolutionary and cognitive theories of religion posit that supernatural agent concepts emerge from cognitive systems such as theory of mind and social cognition. Some argue that these concepts evolved to maintain social order by minimizing antisocial behavior. If these theories are correct, then people should process information about…

Post-exposure therapy with recombinant human BuChE following percutaneous VX challenge in guinea-pigs

PubMed Central

Mumford, Helen; Troyer, John K.

2011-01-01

Poisoning by nerve agents via the percutaneous (p.c.) route is an issue because the slow absorption of agent could result in poisoning which outlasts the protection provided by conventional pharmacological therapy. The bioscavenger approach is based on the concept of binding nerve agent in the bloodstream, thus preventing nerve agent from reaching the target tissues and inhibiting acetylcholinesterase activity. One bioscavenger that has been extensively studied is human butyrylcholinesterase (huBuChE). Protexia® is a pegylated form of recombinant huBuChE. We used a guinea-pig model of p.c. nerve agent poisoning, using an implanted telemetry system to collect physiological data. Guinea-pigs were poisoned with the nerve agent VX (0.74 mg/kg) (~2.5×LD50). Two hours following VX exposure, Protexia (72 mg/kg) or saline control was administered intramuscularly. All guinea-pigs treated with Protexia (n=8) survived, compared to no survivors in a saline-treated control group (n=8). Survival following VX and Protexia treatment was associated with minimal incapacitation and observable signs of poisoning, and the mitigation or prevention of the detrimental physiological changes (e.g. seizure, bradycardia and hypothermia) observed in control animals. The opportunity for post-exposure treatment may have utility in both civilian and military scenarios, and this is a promising indication for the use of a bioscavenger. PMID:21620937

Evolution of hemostatic agents in surgical practice

PubMed Central

Sundaram, Chandru P.; Keenan, Alison C.

2010-01-01

Objective: Topical hemostatic agents are used in a wide variety of surgical settings, and the evolution of this class of surgical tools is an interesting topic. We reviewed and outlined the historical progress of topical hemostats into present day surgery and urology, and highlight opportunities for future research. Materials and Methods: A MEDLINE search of all available literature concerning several classes of topical hemostatic agents was performed. Fibrins sealants, Gelatin sponge hemostatics, cyanoacrylate adhesives, oxidized regenerated cellulose, and microfibrillar collagen were included. References were chosen from a broad range of surgical literature. Results: Topical hemostatic agents have historically taken advantage of a wide variety of mechanisms for hemostasis. Fibrin sealants have a rich history and large potential for further applications. Gelatin sponge hemostatics have been widely used since their introduction, but have changed little. Cyanoacrylate adhesives have a unique mechanism and opportunity for novel applications of existing products. Oxidized cellulose was original in the use of plant-based components. Microfibrillar collagen hemostats have evolved to a wide variety of formats. Conclusions: A review of the evolution of topical hemostatic agents highlights opportunities for potential novel research. Fibrin sealants may have the most opportunity for advancement, and understanding the history of these products is useful. With the drive in urology for minimally invasive surgical techniques, adaptation of topical hemostatic agents to this surgical approach would be valuable and offers an opportunity for novel contributions. PMID:21116358

Treatment of Cutaneous Lupus Erythematosus

PubMed Central

Kim, Grace K.; Del Rosso, James Q.

2013-01-01

The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice. PMID:23320123

Accounting for dissociation and photolysis: a review of the algal toxicity of triclosan.

PubMed

Roberts, Jayne; Price, Oliver R; Bettles, Nicola; Rendal, Cecilie; van Egmond, Roger

2014-11-01

Triclosan, an antimicrobial agent commonly used in down-the-drain consumer products, is toxic to freshwater microalgae. However, the rapid photolysis and pH-dependent dissociation of this compound may give rise to uncertainty in growth inhibition tests with freshwater microalgae, if these are not well characterized. Methods are presented to minimize these uncertainties by stabilizing pH with an organic buffering agent (Bis-Tris) and by the application of ultraviolet (UV) covers to remove UV wavelengths. Toxicity tests with these methods were in compliance with the validity criteria of the Organisation for Economic Co-operation and Development test 201, and no negative effects were seen in controls relative to the unmodified method. The methods were used for toxicity tests with triclosan at pH levels of 7.0, 8.0, and 8.5, yielding effective concentration, 10% values of 0.5 µg/L, 0.6 µg/L, and 12.1 µg/L, respectively. The observed change in toxicity with pH was proportional to the change in bioconcentration factor (BCF) as calculated using the cell model (a dynamic flux model based on the Fick-Nernst-Planck equations, in this case parameterized for an algal cell). Effect concentrations produced with the methods presented in the present study offer robust data on which to base risk assessment, and it is suggested that similar approaches be used to minimize uncertainty when other compounds that dissociate and photolyse are tested. © 2014 SETAC.

A threshold model of investor psychology

NASA Astrophysics Data System (ADS)

Cross, Rod; Grinfeld, Michael; Lamba, Harbir; Seaman, Tim

2005-08-01

We introduce a class of agent-based market models founded upon simple descriptions of investor psychology. Agents are subject to various psychological tensions induced by market conditions and endowed with a minimal ‘personality’. This personality consists of a threshold level for each of the tensions being modeled, and the agent reacts whenever a tension threshold is reached. This paper considers an elementary model including just two such tensions. The first is ‘cowardice’, which is the stress caused by remaining in a minority position with respect to overall market sentiment and leads to herding-type behavior. The second is ‘inaction’, which is the increasing desire to act or re-evaluate one's investment position. There is no inductive learning by agents and they are only coupled via the global market price and overall market sentiment. Even incorporating just these two psychological tensions, important stylized facts of real market data, including fat-tails, excess kurtosis, uncorrelated price returns and clustered volatility over the timescale of a few days are reproduced. By then introducing an additional parameter that amplifies the effect of externally generated market noise during times of extreme market sentiment, long-time volatility correlations can also be recovered.

Pervasive surveillance-agent system based on wireless sensor networks: design and deployment

NASA Astrophysics Data System (ADS)

Martínez, José F.; Bravo, Sury; García, Ana B.; Corredor, Iván; Familiar, Miguel S.; López, Lourdes; Hernández, Vicente; Da Silva, Antonio

2010-12-01

Nowadays, proliferation of embedded systems is enhancing the possibilities of gathering information by using wireless sensor networks (WSNs). Flexibility and ease of installation make these kinds of pervasive networks suitable for security and surveillance environments. Moreover, the risk for humans to be exposed to these functions is minimized when using these networks. In this paper, a virtual perimeter surveillance agent, which has been designed to detect any person crossing an invisible barrier around a marked perimeter and send an alarm notification to the security staff, is presented. This agent works in a state of 'low power consumption' until there is a crossing on the perimeter. In our approach, the 'intelligence' of the agent has been distributed by using mobile nodes in order to discern the cause of the event of presence. This feature contributes to saving both processing resources and power consumption since the required code that detects presence is the only system installed. The research work described in this paper illustrates our experience in the development of a surveillance system using WNSs for a practical application as well as its evaluation in real-world deployments. This mechanism plays an important role in providing confidence in ensuring safety to our environment.

Genomic Alterations in Advanced Esophageal Cancer May Lead to Subtype-Specific Therapies

PubMed Central

Forde, Patrick M.

2013-01-01

The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8–12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease. PMID:23853247

Shape-Memory Polymers for Biomedical Applications

NASA Astrophysics Data System (ADS)

Yakacki, Christopher M.; Gall, Ken

Shape-memory polymers (SMPs) are a class of mechanically functional "smart" materials that have generated substantial interest for biomedical applications. SMPs offer the ability to promote minimally invasive surgery, provide structural support, exert stabilizing forces, elute therapeutic agents, and biodegrade. This review focuses on several areas of biomedicine including vascular, orthopedic, and neuronal applications with respect to the progress and potential for SMPs to improve the standard of treatment in these areas. Fundamental studies on proposed biomedical SMP systems are discussed with regards to biodegradability, tailorability, sterilization, and biocompatibility. Lastly, a proposed research and development pathway for SMP-based biomedical devices is proposed based on trends in the recent literature.

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis.

PubMed

Cremolini, Chiara; Antoniotti, Carlotta; Pietrantonio, Filippo; Berenato, Rosa; Tampellini, Marco; Baratelli, Chiara; Salvatore, Lisa; Marmorino, Federica; Borelli, Beatrice; Nichetti, Federico; Bironzo, Paolo; Sonetto, Cristina; Bartolomeo, Maria Di; Braud, Filippo de; Loupakis, Fotios; Falcone, Alfredo; Di Maio, M

2017-07-01

The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC). A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R 2 ). Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, -2.4 to 3.4) for the median PFS and 0.7 months (range, -5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R 2 =0.539, p < 0.001) and poor correlation (R=0.169, R 2 =0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident. Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.

The SOS Chromotest applied for screening plant antigenotoxic agents against ultraviolet radiation.

PubMed

Fuentes, J L; García Forero, A; Quintero Ruiz, N; Prada Medina, C A; Rey Castellanos, N; Franco Niño, D A; Contreras García, D A; Córdoba Campo, Y; Stashenko, E E

2017-09-13

In this work, we investigated the usefulness of the SOS Chromotest for screening plant antigenotoxic agents against ultraviolet radiation (UV). Fifty Colombian plant extracts obtained by supercritical fluid (CO 2 ) extraction, twelve plant extract constituents (apigenin, carvacrol, β-caryophyllene, 1,8-cineole, citral, p-cymene, geraniol, naringenin, pinocembrin, quercetin, squalene, and thymol) and five standard antioxidant and/or photoprotective agents (curcumin, epigallocatechin gallate, resveratrol, α-tocopherol, and Trolox®) were evaluated for their genotoxicity and antigenotoxicity against UV using the SOS Chromotest. None of the plant extracts, constituents or agents were genotoxic in the SOS Chromotest at tested concentrations. Based on the minimal extract concentration that significantly inhibited UV-genotoxicity (CIG), five plant extracts were antigenotoxic against UV as follows: Baccharis nítida (16 μg mL -1 ) = Solanum crotonifolium (16 μg mL -1 ) > Hyptis suaveolens (31 μg mL -1 ) = Persea caerulea (31 μg mL -1 ) > Lippia origanoides (62 μg mL -1 ). Based on CIG values, the flavonoid compounds showed the highest antigenotoxic potential as follows: apigenin (7 μM) > pinocembrin (15 μM) > quercetin (26 μM) > naringenin (38 μM) > epigallocatechin gallate (108 μM) > resveratrol (642 μM). UV-genotoxicity inhibition with epigallocatechin gallate, naringenin and resveratrol was related to its capability for inhibiting protein synthesis. A correlation analysis between compound antigenotoxicity estimates and antioxidant activity evaluated by the oxygen radical absorbance capacity (ORAC) assay showed that these activities were not related. The usefulness of the SOS Chromotest for bioprospecting of plant antigenotoxic agents against UV was discussed.

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 (...

A parallel-machine scheduling problem with two competing agents

NASA Astrophysics Data System (ADS)

Lee, Wen-Chiung; Chung, Yu-Hsiang; Wang, Jen-Ya

2017-06-01

Scheduling with two competing agents has become popular in recent years. Most of the research has focused on single-machine problems. This article considers a parallel-machine problem, the objective of which is to minimize the total completion time of jobs from the first agent given that the maximum tardiness of jobs from the second agent cannot exceed an upper bound. The NP-hardness of this problem is also examined. A genetic algorithm equipped with local search is proposed to search for the near-optimal solution. Computational experiments are conducted to evaluate the proposed genetic algorithm.

Partial Analysis of Insta-Foam

NASA Technical Reports Server (NTRS)

Chou, L. W.

1983-01-01

Insta-Foam, used as a thermal insulator for the non-critical area of the external tank during the prelaunch phase to minimize icing, is a two-component system. Component A has polyisocyanates, blowing agents, and stabilizers; Component B has the polyols, catalysts, blowing agents, stabilizers and fire retardant. The blowing agents are Freon 11 and Freon 12, the stabilizers are silicone surfactants, the catalysts are tertiary amines, and the fire retardant is tri-(beta-chloro-isopropyl) phosphate (PCF). High performance liquid chromatography (HPLC) was quantitatively identified polyols and PFC.

Progress and challenges in the development of physically-based numerical models for prediction of flow and contaminant dispersion in the urban environment

NASA Astrophysics Data System (ADS)

Lien, F. S.; Yee, E.; Ji, H.; Keats, A.; Hsieh, K. J.

2006-06-01

The release of chemical, biological, radiological, or nuclear (CBRN) agents by terrorists or rogue states in a North American city (densely populated urban centre) and the subsequent exposure, deposition and contamination are emerging threats in an uncertain world. The modeling of the transport, dispersion, deposition and fate of a CBRN agent released in an urban environment is an extremely complex problem that encompasses potentially multiple space and time scales. The availability of high-fidelity, time-dependent models for the prediction of a CBRN agent's movement and fate in a complex urban environment can provide the strongest technical and scientific foundation for support of Canada's more broadly based effort at advancing counter-terrorism planning and operational capabilities.The objective of this paper is to report the progress of developing and validating an integrated, state-of-the-art, high-fidelity multi-scale, multi-physics modeling system for the accurate and efficient prediction of urban flow and dispersion of CBRN (and other toxic) materials discharged into these flows. Development of this proposed multi-scale modeling system will provide the real-time modeling and simulation tool required to predict injuries, casualties and contamination and to make relevant decisions (based on the strongest technical and scientific foundations) in order to minimize the consequences of a CBRN incident in a populated centre.

Chitosan-based multifunctional nanomedicines and theranostics for targeted therapy of cancer.

PubMed

Fathi, Marziyeh; Majidi, Sima; Zangabad, Parham Sahandi; Barar, Jaleh; Erfan-Niya, Hamid; Omidi, Yadollah

2018-05-30

Nanotechnology as an emerging field has established inevitable impacts on nano-biomedicine and treatment of formidable diseases, inflammations, and malignancies. In this regard, substantial advances in the design of systems for delivery of therapeutic agents have emerged magnificent and innovative pathways in biomedical applications. Chitosan (CS) is derived via deacetylation of chitin as the second most abundant polysaccharide. Owing to the unique properties of CS (e.g., biocompatibility, biodegradability, bioactivity, mucoadhesion, cationic nature and functional groups), it is an excellent candidate for diverse biomedical and pharmaceutical applications such as drug/gene delivery, transplantation of encapsulated cells, tissue engineering, wound healing, antimicrobial purposes, etc. In this review, we will document, discuss, and provide some key insights toward design and application of miscellaneous nanoplatforms based on CS. The CS-based nanosystems (NSs) can be employed as advanced drug delivery systems (DDSs) in large part due to their remarkable physicochemical and biological characteristics. The abundant functional groups of CS allow the facile functionalization in order to engineer multifunctional NSs, which can simultaneously incorporate therapeutic agents, molecular targeting, and diagnostic/imaging capabilities in particular against malignancies. These multimodal NSs can be literally translated into clinical applications such as targeted diagnosis and therapy of cancer because they offer minimal systemic toxicity and maximal cytotoxicity against cancer cells and tumors. The recent developments in the CS-based NSs functionalized with targeting and imaging agents prove CS as a versatile polymer in targeted imaging and therapy. © 2018 Wiley Periodicals, Inc.

Management of malignancy-associated pleural effusion: current and future treatment strategies.

PubMed

Marchi, Evaldo; Teixeira, Lisete R; Vargas, Francisco S

2003-01-01

Management of recurrent malignant pleural effusion, a common complication of malignancy, poses a challenge to clinicians. Although almost one century has elapsed since the introduction of the pleurodesis procedure, the ideal approach and best agent are still to be defined. Optimally, pleurodesis should be done at the bedside with a minimally invasive procedure, and suitable agents to achieve pleural symphysis should be inexpensive, available worldwide and free of adverse effects. To date, no substance completely fulfills these requirements. Silver nitrate should be considered for pleurodesis because of its low cost and ease of handling. Although talc has been used most frequently to induce pleurodesis, reports of death due to acute respiratory failure have raised concerns about the safety of this agent. Tetracycline, an effective alternative used in the past, is no longer commercially available. This agent has been substituted with derivatives of tetracycline, such as minocycline and doxycycline with success rates similar to those with tetracycline. Several antineoplastic agents have been injected into the pleural space with the aim of producing pleural symphysis, the most representative of this group being bleomycin. Recent knowledge of the molecular mechanisms involved in pleural inflammation has brought into focus new substances, such as transforming growth factor beta and vascular endothelial growth factor, which may be used as pleurodesis agents in the future. Nevertheless, more studies are necessary to better define the potential of these substances in the induction of pleural symphysis.Ideally, a sclerosing agent should be cost-effective, available worldwide and easily administered. Talc will probably stand as the preferred agent to be used for pleurodesis in malignant pleural effusion because of its efficacy, easy manipulation and handling. However, further investigation is necessary to minimize adverse effects related to talc.

Novel probabilistic and distributed algorithms for guidance, control, and nonlinear estimation of large-scale multi-agent systems

NASA Astrophysics Data System (ADS)

Bandyopadhyay, Saptarshi

Multi-agent systems are widely used for constructing a desired formation shape, exploring an area, surveillance, coverage, and other cooperative tasks. This dissertation introduces novel algorithms in the three main areas of shape formation, distributed estimation, and attitude control of large-scale multi-agent systems. In the first part of this dissertation, we address the problem of shape formation for thousands to millions of agents. Here, we present two novel algorithms for guiding a large-scale swarm of robotic systems into a desired formation shape in a distributed and scalable manner. These probabilistic swarm guidance algorithms adopt an Eulerian framework, where the physical space is partitioned into bins and the swarm's density distribution over each bin is controlled using tunable Markov chains. In the first algorithm - Probabilistic Swarm Guidance using Inhomogeneous Markov Chains (PSG-IMC) - each agent determines its bin transition probabilities using a time-inhomogeneous Markov chain that is constructed in real-time using feedback from the current swarm distribution. This PSG-IMC algorithm minimizes the expected cost of the transitions required to achieve and maintain the desired formation shape, even when agents are added to or removed from the swarm. The algorithm scales well with a large number of agents and complex formation shapes, and can also be adapted for area exploration applications. In the second algorithm - Probabilistic Swarm Guidance using Optimal Transport (PSG-OT) - each agent determines its bin transition probabilities by solving an optimal transport problem, which is recast as a linear program. In the presence of perfect feedback of the current swarm distribution, this algorithm minimizes the given cost function, guarantees faster convergence, reduces the number of transitions for achieving the desired formation, and is robust to disturbances or damages to the formation. We demonstrate the effectiveness of these two proposed swarm guidance algorithms using results from numerical simulations and closed-loop hardware experiments on multiple quadrotors. In the second part of this dissertation, we present two novel discrete-time algorithms for distributed estimation, which track a single target using a network of heterogeneous sensing agents. The Distributed Bayesian Filtering (DBF) algorithm, the sensing agents combine their normalized likelihood functions using the logarithmic opinion pool and the discrete-time dynamic average consensus algorithm. Each agent's estimated likelihood function converges to an error ball centered on the joint likelihood function of the centralized multi-sensor Bayesian filtering algorithm. Using a new proof technique, the convergence, stability, and robustness properties of the DBF algorithm are rigorously characterized. The explicit bounds on the time step of the robust DBF algorithm are shown to depend on the time-scale of the target dynamics. Furthermore, the DBF algorithm for linear-Gaussian models can be cast into a modified form of the Kalman information filter. In the Bayesian Consensus Filtering (BCF) algorithm, the agents combine their estimated posterior pdfs multiple times within each time step using the logarithmic opinion pool scheme. Thus, each agent's consensual pdf minimizes the sum of Kullback-Leibler divergences with the local posterior pdfs. The performance and robust properties of these algorithms are validated using numerical simulations. In the third part of this dissertation, we present an attitude control strategy and a new nonlinear tracking controller for a spacecraft carrying a large object, such as an asteroid or a boulder. If the captured object is larger or comparable in size to the spacecraft and has significant modeling uncertainties, conventional nonlinear control laws that use exact feed-forward cancellation are not suitable because they exhibit a large resultant disturbance torque. The proposed nonlinear tracking control law guarantees global exponential convergence of tracking errors with finite-gain Lp stability in the presence of modeling uncertainties and disturbances, and reduces the resultant disturbance torque. Further, this control law permits the use of any attitude representation and its integral control formulation eliminates any constant disturbance. Under small uncertainties, the best strategy for stabilizing the combined system is to track a fuel-optimal reference trajectory using this nonlinear control law, because it consumes the least amount of fuel. In the presence of large uncertainties, the most effective strategy is to track the derivative plus proportional-derivative based reference trajectory, because it reduces the resultant disturbance torque. The effectiveness of the proposed attitude control law is demonstrated by using results of numerical simulation based on an Asteroid Redirect Mission concept. The new algorithms proposed in this dissertation will facilitate the development of versatile autonomous multi-agent systems that are capable of performing a variety of complex tasks in a robust and scalable manner.

Predehydration and Ice Seeding in the Presence of Trehalose Enable Cell Cryopreservation

PubMed Central

2017-01-01

Conventional approaches for cell cryopreservation require the use of toxic membrane-penetrating cryoprotective agents (pCPA), which limits the clinical application of cryopreserved cells. Here, we show intentionally induced ice formation at a high subzero temperature (> −10 °C) during cryopreservation, which is often referred to as ice seeding, could result in significant cell injury in the absence of any pCPA. This issue can be mitigated by predehydrating cells using extracellular trehalose to their minimal volume with minimized osmotically active water before ice seeding. We further observe that ice seeding can minimize the interfacial free energy that drives the devastating ice recrystallization-induced cell injury during warming cryopreserved samples. Indeed, by combining predehydration using extracellular trehalose with ice seeding at high subzero temperatures, high cell viability or recovery is achieved for fibroblasts, adult stem cells, and red blood cells after cryopreservation without using any pCPA. The pCPA-free technology developed in this study may greatly facilitate the long-term storage and ready availability of living cells, tissues, and organs that are of high demand by modern cell-based medicine. PMID:28824959

Microbiological Monitoring for the Constellation Program: Current Requirements and Future Considerations

NASA Technical Reports Server (NTRS)

Ott, C. Mark

2007-01-01

Microbiological requirements for spaceflight are based on assessments of infectious disease risk which could impact crew health or mission success. The determination of risk from infectious disease is composed of several factors including (1) crew susceptibility, (2) crew exposure to the infectious disease agent, (3) the concentration of the infectious agent, and (4) the characteristics of the infectious agent. As a result of the Health Stabilization Program, stringent monitoring, and cleaning protocols, in-flight environmental microbial monitoring is not necessary for short-duration spaceflights. However, risk factors change for long-duration missions, as exemplified by the presence of medically significant organisms in the environments of both the Mir and International Space Station (ISS). Based upon this historical evidence, requirements for short duration usage aboard the Orion Crew Exploration Vehicle and Lunar Lander Vehicle will not require in-flight monitoring; however, as mission duration increases with a Lunar Outpost, an ability to detect microbial hazard will be necessary. The nature of the detection requirements will depend on the maturity of technology in a rapidly evolving marketplace. Regardless, the hardware will still need to maximize information to discipline experts and the crew, while minimizing the size, mass, power consumption, and crew time usage. The refinement of these monitors will be a major goal in our efforts to travel successfully to Mars.

Impact of Various Irrigating Agents on Root Fracture: An in vitro Study.

PubMed

Tiwari, Sukriti; Nikhade, Pradnya; Chandak, Manoj; Sudarshan, C; Shetty, Priyadarshini; Gupta, Naveen K

2016-08-01

Irrigating solutions are used for cleaning and removing dentinal debris, and the other remains from pulpal space during biomechanical preparation. Therefore, we evaluated the impact of various irrigating agents on root fracture at 5-minute time exposure. We sectioned 60 permanent maxillary premolars with fully formed root structures transversely maintaining the root length of approximately 14 mm. Five study groups were made comprising ethylenediaminetetraacetic acid (EDTA), cetrimide, citric acid, and so on as various irrigating agents. A universal force test machine was used to calculate the force which was enough to fracture each root. Analysis of variance (ANOVA) test was used to access the level of significance. About 10% citric acid solution as an irrigating agent showed minimal fracture opposing results, whereas 10% EDTA solution showed the maximum fracture resistance of root portion. Selection of suitable EDTA concentration that has minimal adverse effect on the mechanical properties of the tooth is very important for the successful management of tooth fracture. About 10% EDTA provided the highest fracture resistance, necessitating the use of irrigating solution in root canal therapy (RCT). Further research with higher and different study groups is required to search for more efficient irrigating solution to improve the outcome of RCT.

Application of free energy minimization to the design of adaptive multi-agent teams

NASA Astrophysics Data System (ADS)

Levchuk, Georgiy; Pattipati, Krishna; Fouse, Adam; Serfaty, Daniel

2017-05-01

Many novel DoD missions, from disaster relief to cyber reconnaissance, require teams of humans and machines with diverse capabilities. Current solutions do not account for heterogeneity of agent capabilities, uncertainty of team knowledge, and dynamics of and dependencies between tasks and agent roles, resulting in brittle teams. Most importantly, the state-of-the-art team design solutions are either centralized, imposing role and relation assignment onto agents, or completely distributed, suitable for only homogeneous organizations such as swarms. Centralized design models can't provide insights for team's self-organization, i.e. adapting team structure over time in distributed collaborative manner by team members with diverse expertise and responsibilities. In this paper we present an information-theoretic formalization of team composition and structure adaptation using a minimization of variational free energy. The structure adaptation is obtained in an iterative distributed and collaborative manner without the need for centralized control. We show that our model is lightweight, predictive, and produces team structures that theoretically approximate an optimal policy for team adaptation. Our model also provides a unique coupling between the structure and action policy, and captures three essential processes of learning, perception, and control.

Knowledge focus via software agents

NASA Astrophysics Data System (ADS)

Henager, Donald E.

2001-09-01

The essence of military Command and Control (C2) is making knowledge intensive decisions in a limited amount of time using uncertain, incorrect, or outdated information. It is essential to provide tools to decision-makers that provide: * Management of friendly forces by treating the "friendly resources as a system". * Rapid assessment of effects of military actions againt the "enemy as a system". * Assessment of how an enemy should, can, and could react to friendly military activities. Software agents in the form of mission agents, target agents, maintenance agents, and logistics agents can meet this information challenge. The role of each agent is to know all the details about its assigned mission, target, maintenance, or logistics entity. The Mission Agent would fight for mission resources based on the mission priority and analyze the effect that a proposed mission's results would have on the enemy. The Target Agent (TA) communicates with other targets to determine its role in the system of targets. A system of TAs would be able to inform a planner or analyst of the status of a system of targets, the effect of that status, adn the effect of attacks on that system. The system of TAs would also be able to analyze possible enemy reactions to attack by determining ways to minimize the effect of attack, such as rerouting traffic or using deception. The Maintenance Agent would scheudle maintenance events and notify the maintenance unit. The Logistics Agent would manage shipment and delivery of supplies to maintain appropriate levels of weapons, fuel and spare parts. The central idea underlying this case of software agents is knowledge focus. Software agents are createad automatically to focus their attention on individual real-world entities (e.g., missions, targets) and view the world from that entities perspective. The agent autonomously monitors the entity, identifies problems/opportunities, formulates solutions, and informs the decision-maker. The agent must be able to communicate to receive and disseminate information and provide the decision-maker with assistance via focused knowledge. THe agent must also be able to monitor the state of its own environment and make decisions necessary to carry out its delegated tasks. Agents bring three elements to the C2 domain that offer to improve decision-making. First, they provide higher-quality feedback and provide it more often. In doing so, the feedback loop becomes nearly continuous, reducing or eliminating delays in situation updates to decision-makers. Working with the most current information possible improves the control process, thus enabling effects based operations. Second, the agents accept delegation of actions and perform those actions following an established process. Agents' consistent actions reduce the variability of human input and stabilize the control process. Third, through the delegation of actions, agents ensure 100 percent consideration of plan details.

Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome

PubMed Central

Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Knight, Paul R.; Notter, Robert H.

2009-01-01

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, and there is a significant need for more effective medicinal chemical agents for use in these severe and lethal lung injury syndromes. To facilitate future chemical-based drug discovery research on new agent development, this paper reviews present pharmacotherapy for ALI/ARDS in the context of biological and biochemical drug activities. The complex lung injury pathophysiology of ALI/ARDS offers an array of possible targets for drug therapy, including inflammation, cell and tissue injury, vascular dysfunction, surfactant dysfunction, and oxidant injury. Added targets for pharmacotherapy outside the lungs may also be present, since multiorgan or systemic pathology is common in ALI/ARDS. The biological and physiological complexity of ALI/ARDS requires the consideration of combined-agent treatments in addition to single-agent therapies. A number of pharmacologic agents have been studied individually in ALI/ARDS, with limited or minimal success in improving survival. However, many of these agents have complementary biological/biochemical activities with the potential for synergy or additivity in combination therapy as discussed in this article. PMID:18691048

Continuum Model for Decontamination of Chemical Warfare Agent from a Rubbery Polymer using the Maxwell-Stefan Formulation

NASA Astrophysics Data System (ADS)

Varady, Mark; Bringuier, Stefan; Pearl, Thomas; Stevenson, Shawn; Mantooth, Brent

Decontamination of polymers exposed to chemical warfare agents (CWA) often proceeds by application of a liquid solution. Absorption of some decontaminant components proceed concurrently with extraction of the CWA, resulting in multicomponent diffusion in the polymer. In this work, the Maxwell-Stefan equations were used with the Flory-Huggins model of species activity to mathematically describe the transport of two species within a polymer. This model was used to predict the extraction of the nerve agent O-ethyl S-[2(diisopropylamino)ethyl] methylphosphonothioate (VX) from a silicone elastomer into both water and methanol. Comparisons with experimental results show good agreement with minimal fitting of model parameters from pure component uptake data. Reaction of the extracted VX with sodium hydroxide in the liquid-phase was also modeled and used to predict the overall rate of destruction of VX. Although the reaction proceeds more slowly in the methanol-based solution compared to the aqueous solution, the extraction rate is faster due to increasing VX mobility as methanol absorbs into the silicone, resulting in an overall faster rate of VX destruction.

Naming games in two-dimensional and small-world-connected random geometric networks.

PubMed

Lu, Qiming; Korniss, G; Szymanski, B K

2008-01-01

We investigate a prototypical agent-based model, the naming game, on two-dimensional random geometric networks. The naming game [Baronchelli, J. Stat. Mech.: Theory Exp. (2006) P06014] is a minimal model, employing local communications that captures the emergence of shared communication schemes (languages) in a population of autonomous semiotic agents. Implementing the naming games with local broadcasts on random geometric graphs, serves as a model for agreement dynamics in large-scale, autonomously operating wireless sensor networks. Further, it captures essential features of the scaling properties of the agreement process for spatially embedded autonomous agents. Among the relevant observables capturing the temporal properties of the agreement process, we investigate the cluster-size distribution and the distribution of the agreement times, both exhibiting dynamic scaling. We also present results for the case when a small density of long-range communication links are added on top of the random geometric graph, resulting in a "small-world"-like network and yielding a significantly reduced time to reach global agreement. We construct a finite-size scaling analysis for the agreement times in this case.

The predictive power of zero intelligence in financial markets

NASA Astrophysics Data System (ADS)

Farmer, J. Doyne; Patelli, Paolo; Zovko, Ilija I.

2005-02-01

Standard models in economics stress the role of intelligent agents who maximize utility. However, there may be situations where constraints imposed by market institutions dominate strategic agent behavior. We use data from the London Stock Exchange to test a simple model in which minimally intelligent agents place orders to trade at random. The model treats the statistical mechanics of order placement, price formation, and the accumulation of revealed supply and demand within the context of the continuous double auction and yields simple laws relating order-arrival rates to statistical properties of the market. We test the validity of these laws in explaining cross-sectional variation for 11 stocks. The model explains 96% of the variance of the gap between the best buying and selling prices (the spread) and 76% of the variance of the price diffusion rate, with only one free parameter. We also study the market impact function, describing the response of quoted prices to the arrival of new orders. The nondimensional coordinates dictated by the model approximately collapse data from different stocks onto a single curve. This work is important from a practical point of view, because it demonstrates the existence of simple laws relating prices to order flows and, in a broader context, suggests there are circumstances where the strategic behavior of agents may be dominated by other considerations. double auction market | market microstructure | agent-based models

Effect of an Extra Hydrophobic Resin Layer on Repair Shear Bond Strength of a Silorane-Based Composite Resin

PubMed Central

Mohammadi, Narmin; Bahari, Mahmoud; Kimyai, Soodabeh; Rahbani Nobar, Behnam

2015-01-01

Objectives: Composite repair is a minimally invasive and conservative approach. This study aimed to evaluate the effect of an additional hydrophobic resin layer on the repair shear bond strength of a silorane-based composite repaired with silorane or methacrylate-based composite. Materials and Methods: Sixty bar-shaped composite blocks were fabricated and stored in saline for 72 hours. The surface of the samples were roughened by diamond burs and etched with phosphoric acid; then, they were randomly divided into three groups according to the repairing process: Group 1: Silorane composite-silorane bonding agent-silorane composite; group 2: Silorane composite-silorane bonding agent-hydrophobic resin-silorane composite, and group 3: Silorane composite-silorane bonding agent-hydrophobic resin methacrylate-based composite. Repairing composite blocks measured 2.5×2.5×5mm. After repairing, the samples were stored in saline for 24 hours and thermocycled for 1500 cycles. The repair bond strength was measured at a strain rate of 1mm/min. Twenty additional cylindrical composite blocks (diameter: 2.5mm, height: 6mm) were also fabricated for measuring the cohesive strength of silorane-based composite. The data were analyzed using One-way ANOVA and the post hoc Tukey’s test (α=0.05). Results: Cohesive bond strength of silorane composite was significantly higher than the repair bond strengths in other groups (P<0.001). The repair bond strength of group 3 was significantly higher than that of group 1 (P=0.001). Conclusion: Application of an additional hydrophobic resin layer for repair of silorane-based composite with a methacrylate-based composite enhanced the repair shear bond strength. PMID:27559348

Transcatheter arterial embolization for acute nonvariceal upper gastrointestinal bleeding: Indications, techniques and outcomes.

PubMed

Loffroy, R; Favelier, S; Pottecher, P; Estivalet, L; Genson, P Y; Gehin, S; Cercueil, J P; Krausé, D

2015-01-01

Over the past three decades, transcatheter arterial embolization has become the first-line therapy for the management of acute nonvariceal upper gastrointestinal bleeding that is refractory to endoscopic hemostasis. Advances in catheter-based techniques and newer embolic agents, as well as recognition of the effectiveness of minimally invasive treatment options, have expanded the role of interventional radiology in the treatment of bleeding for a variety of indications. Transcatheter arterial embolization is a fast, safe, and effective minimally invasive alternative to surgery, when endoscopic treatment fails to control acute bleeding from the upper gastrointestinal tract. This article describes the role of arterial embolization in the management of acute nonvariceal upper gastrointestinal bleeding and summarizes the literature evidence on the outcomes of endovascular therapy in such a setting. Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Interactive information retrieval systems with minimalist representation

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

Domeshek, E.; Kedar, S.; Gordon, A.

Almost any information you might want is becoming available on-line. The problem is how to find what you need. One strategy to improve access to existing information sources, is intelligent information agents - an approach based on extensive representation and inference. Another alternative is to simply concentrate on better information organization and indexing. Our systems use a form of conceptual indexing sensitive to users` task-specific information needs. We aim for minimalist representation, coding only select aspects of stored items. Rather than supporting reliable automated inference, the primary purpose of our representations is to provide sufficient discrimination and guidance to amore » user for a given domain and task. This paper argues, using case studies, that minimal representations can make strong contributions to the usefulness and usability of interactive information systems, while minimizing knowledge engineering effort. We demonstrate this approach in several broad spectrum applications including video retrieval and advisory systems.« less

Synthesis and potent in vitro activity of novel 1H-benzimidazoles as anti-MRSA agents.

PubMed

Karataş, Hacer; Alp, Mehmet; Yildiz, Sulhiye; Göker, Hakan

2012-08-01

A new class of 1H-benzimidazolecarboxamidines was synthesized and evaluated for in vitro antibacterial and antifungal activities, including drug-resistant bacterial strains. The most potent compound (32) has the same ratio of anti-MRSA activity as Vancomycin (minimal inhibitory concentrations value 0.78 μg/mL). The mechanism of action for 1H-benzimidazolecarboxamidine appears to be different from existing antibacterial agents. These compounds have potential for development as a new class of potent anti-MRSA agent. © 2012 John Wiley & Sons A/S.

Fire Suppression in Low Gravity Using a Cup Burner

NASA Technical Reports Server (NTRS)

Takahashi, Fumiaki; Linteris, Gregory T.; Katta, Viswanath R.

2004-01-01

Longer duration missions to the moon, to Mars, and on the International Space Station increase the likelihood of accidental fires. The goal of the present investigation is to: (1) understand the physical and chemical processes of fire suppression in various gravity and O2 levels simulating spacecraft, Mars, and moon missions; (2) provide rigorous testing of numerical models, which include detailed combustion suppression chemistry and radiation sub-models; and (3) provide basic research results useful for advances in space fire safety technology, including new fire-extinguishing agents and approaches. The structure and extinguishment of enclosed, laminar, methane-air co-flow diffusion flames formed on a cup burner have been studied experimentally and numerically using various fire-extinguishing agents (CO2, N2, He, Ar, CF3H, and Fe(CO)5). The experiments involve both 1g laboratory testing and low-g testing (in drop towers and the KC-135 aircraft). The computation uses a direct numerical simulation with detailed chemistry and radiative heat-loss models. An agent was introduced into a low-speed coflowing oxidizing stream until extinguishment occurred under a fixed minimal fuel velocity, and thus, the extinguishing agent concentrations were determined. The extinguishment of cup-burner flames, which resemble real fires, occurred via a blowoff process (in which the flame base drifted downstream) rather than the global extinction phenomenon typical of counterflow diffusion flames. The computation revealed that the peak reactivity spot (the reaction kernel) formed in the flame base was responsible for attachment and blowoff of the trailing diffusion flame. Furthermore, the buoyancy-induced flame flickering in 1g and thermal and transport properties of the agents affected the flame extinguishment limits.

Fire Suppression in Low Gravity Using a Cup Burner

NASA Technical Reports Server (NTRS)

Takahashi, Fumiaki; Linteris, Gregory T.; Katta, Viswanath R.

2004-01-01

Longer duration missions to the moon, to Mars, and on the International Space Station increase the likelihood of accidental fires. The goal of the present investigation is to: (1) understand the physical and chemical processes of fire suppression in various gravity and O2 levels simulating spacecraft, Mars, and moon missions; (2) provide rigorous testing of numerical models, which include detailed combustion-suppression chemistry and radiation sub-models; and (3) provide basic research results useful for advances in space fire safety technology, including new fire-extinguishing agents and approaches.The structure and extinguishment of enclosed, laminar, methane-air co-flow diffusion flames formed on a cup burner have been studied experimentally and numerically using various fire-extinguishing agents (CO2, N2, He, Ar, CF3H, and Fe(CO)5). The experiments involve both 1g laboratory testing and low-g testing (in drop towers and the KC-135 aircraft). The computation uses a direct numerical simulation with detailed chemistry and radiative heat-loss models. An agent was introduced into a low-speed coflowing oxidizing stream until extinguishment occurred under a fixed minimal fuel velocity, and thus, the extinguishing agent concentrations were determined. The extinguishment of cup-burner flames, which resemble real fires, occurred via a blowoff process (in which the flame base drifted downstream) rather than the global extinction phenomenon typical of counterflow diffusion flames. The computation revealed that the peak reactivity spot (the reaction kernel) formed in the flame base was responsible for attachment and blowoff of the trailing diffusion flame. Furthermore, the buoyancy-induced flame flickering in 1g and thermal and transport properties of the agents affected the flame extinguishment limits.

Deep Raman spectroscopy for the non-invasive standoff detection of concealed chemical threat agents.

PubMed

Izake, Emad L; Cletus, Biju; Olds, William; Sundarajoo, Shankaran; Fredericks, Peter M; Jaatinen, Esa

2012-05-30

Deep Raman spectroscopy has been utilized for the standoff detection of concealed chemical threat agents from a distance of 15 m under real life background illumination conditions. By using combined time and space resolved measurements, various explosive precursors hidden in opaque plastic containers were identified non-invasively. Our results confirm that combined time and space resolved Raman spectroscopy leads to higher selectivity towards the sub-layer over the surface layer as well as enhanced rejection of fluorescence from the container surface when compared to standoff spatially offset Raman spectroscopy. Raman spectra that have minimal interference from the packaging material and good signal-to-noise ratio were acquired within 5 s of measurement time. A new combined time and space resolved Raman spectrometer has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than picosecond-based laboratory systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Phosphate binder usage in kidney failure patients.

PubMed

Bleyer, Anthony J

2003-06-01

Phosphorus binders are used in patients with kidney failure because of the incomplete removal of phosphorus with dialysis and the inability to exclude phosphorus from the diet. Aluminium was the initial phosphorus binder used, but was replaced by calcium-containing binders because of the development of aluminium toxicity. Calcium-based binders have been the mainstay of therapy for many years, but recent investigations have pointed to increased rates of vascular calcification in patients taking calcium-containing binders. For this reason, alternative agents have been developed. Sevelamer (Renagel), GelTex Pharmaceuticals Inc.) is a polymer which has been found to effectively bind phosphorus. It has resulted in a decreased rate of vascular calcification compared to calcium-containing binders. Other agents under development include lanthanum carbonate and iron-complex preparations. Further research will likely concentrate on identifying binders that bind phosphate more efficiently, have minimal gastrointestinal side effects and provide other benefits to dialysis patients.

Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery.

PubMed

Zarei, Omid; Benvenuti, Silvia; Ustun-Alkan, Fulya; Hamzeh-Mivehroud, Maryam; Dastmalchi, Siavoush

2016-12-01

Cancer is one of the most important life-threatening diseases in the world. The current efforts to combat cancer are being focused on molecular-targeted therapies. The main purpose of such approaches is based on targeting cancer cell-specific molecules to minimize toxicity for the normal cells. RON (Recepteur d'Origine Nantais) tyrosine kinase receptor is one of the promising targets in cancer-targeted therapy and drug delivery. In this review, we will summarize the available agents against extracellular domain of RON with potential antitumor activities. The presented antibodies and antibody drug conjugates against RON in this review showed wide spectrum of in vitro and in vivo antitumor activities promising the hope for them entering the clinical trials. Due to critical role of extracellular domain of RON in receptor activation, the development of therapeutic agents against this region could lead to fruitful outcome in cancer therapy.

Thermal inactivation of infested plants, nursery equipment, and soil is a management option for the treatment of Phytophthora ramorum, causal agent of sudden oak death

Treesearch

Wolfgang Schweigkofler; Vernon Huffman; Karen Suslow; Kathleen Kosta

2017-01-01

Infected nursery plants play an important role in the spread of Phytophthora ramorum , the causal agent of sudden oak death and ramorum blight. In order to minimize the risk for disease transmission to new areas, nurseries are inspected regularly for P. ramorum , and federal regulations require the eradication of...

What does God know? Supernatural agents' access to socially strategic and non-strategic information.

PubMed

Purzycki, Benjamin G; Finkel, Daniel N; Shaver, John; Wales, Nathan; Cohen, Adam B; Sosis, Richard

2012-07-01

Current evolutionary and cognitive theories of religion posit that supernatural agent concepts emerge from cognitive systems such as theory of mind and social cognition. Some argue that these concepts evolved to maintain social order by minimizing antisocial behavior. If these theories are correct, then people should process information about supernatural agents' socially strategic knowledge more quickly than non-strategic knowledge. Furthermore, agents' knowledge of immoral and uncooperative social behaviors should be especially accessible to people. To examine these hypotheses, we measured response-times to questions about the knowledge attributed to four different agents--God, Santa Claus, a fictional surveillance government, and omniscient but non-interfering aliens--that vary in their omniscience, moral concern, ability to punish, and how supernatural they are. As anticipated, participants respond more quickly to questions about agents' socially strategic knowledge than non-strategic knowledge, but only when agents are able to punish. Copyright © 2012 Cognitive Science Society, Inc.

Factors influencing real time internal structural visualization and dynamic process monitoring in plants using synchrotron-based phase contrast X-ray imaging

PubMed Central

Karunakaran, Chithra; Lahlali, Rachid; Zhu, Ning; Webb, Adam M.; Schmidt, Marina; Fransishyn, Kyle; Belev, George; Wysokinski, Tomasz; Olson, Jeremy; Cooper, David M. L.; Hallin, Emil

2015-01-01

Minimally invasive investigation of plant parts (root, stem, leaves, and flower) has good potential to elucidate the dynamics of plant growth, morphology, physiology, and root-rhizosphere interactions. Laboratory based absorption X-ray imaging and computed tomography (CT) systems are extensively used for in situ feasibility studies of plants grown in natural and artificial soil. These techniques have challenges such as low contrast between soil pore space and roots, long X-ray imaging time, and low spatial resolution. In this study, the use of synchrotron (SR) based phase contrast X-ray imaging (PCI) has been demonstrated as a minimally invasive technique for imaging plants. Above ground plant parts and roots of 10 day old canola and wheat seedlings grown in sandy clay loam soil were successfully scanned and reconstructed. Results confirmed that SR-PCI can deliver good quality images to study dynamic and real time processes such as cavitation and water-refilling in plants. The advantages of SR-PCI, effect of X-ray energy, and effective pixel size to study plant samples have been demonstrated. The use of contrast agents to monitor physiological processes in plants was also investigated and discussed. PMID:26183486

Active inference and epistemic value.

PubMed

Friston, Karl; Rigoli, Francesco; Ognibene, Dimitri; Mathys, Christoph; Fitzgerald, Thomas; Pezzulo, Giovanni

2015-01-01

We offer a formal treatment of choice behavior based on the premise that agents minimize the expected free energy of future outcomes. Crucially, the negative free energy or quality of a policy can be decomposed into extrinsic and epistemic (or intrinsic) value. Minimizing expected free energy is therefore equivalent to maximizing extrinsic value or expected utility (defined in terms of prior preferences or goals), while maximizing information gain or intrinsic value (or reducing uncertainty about the causes of valuable outcomes). The resulting scheme resolves the exploration-exploitation dilemma: Epistemic value is maximized until there is no further information gain, after which exploitation is assured through maximization of extrinsic value. This is formally consistent with the Infomax principle, generalizing formulations of active vision based upon salience (Bayesian surprise) and optimal decisions based on expected utility and risk-sensitive (Kullback-Leibler) control. Furthermore, as with previous active inference formulations of discrete (Markovian) problems, ad hoc softmax parameters become the expected (Bayes-optimal) precision of beliefs about, or confidence in, policies. This article focuses on the basic theory, illustrating the ideas with simulations. A key aspect of these simulations is the similarity between precision updates and dopaminergic discharges observed in conditioning paradigms.

Paper-basd surface enhanced Raman spectroscopy of pnenobarbital sodium for point-of-care therapeutic drug monitoring

NASA Astrophysics Data System (ADS)

Yokoyama, Moe; Yamada, Kenji; Nishimura, Takahiro; Kido, Michiko; Jeong, Hieyong; Ohno, Yuko

2015-03-01

Therapeutic drug monitoring (TDM) contributes to safe and effective pharmacotherapy in clinical fields. A simple, rapid, low-cost, and minimally-invasive drug measurement method attracts much interest for point-of-care TDM. Tear fluids can be collected minimally-invasively compared to blood sampling and there is a correlation between a drug concentration in tears and that in bloods. Surface enhanced Raman spectroscopy (SERS) with paper-based substrate is useful for point-of-care TDM owing to inexpensiveness and high-sensitivity. Paper is also a safe tear collection tool. Then we are studying on a paper-based SERS of tear specimen for point-of-care TDM. In this paper, to improve sensitivity in measuring drug concentration in tear fluids, we fabricated a SERS substrate by coating gold nano-rods on a paper substrate and evaluated whether the fabricated substrate can enhance Raman scattering. Sodium phenobarbital (PB), an anti-convulsant agent, was used as a target. In experiment, the fabricated substrate indicated the lower detection limit of PB in a solution than a plain paper substrate. This result showed the potential of the paper based SERS substrate to measure drug concentration in tears simply and inexpensively.

A comparison between metaheuristics as strategies for minimizing cyclic instability in Ambient Intelligence.

PubMed

Romero, Leoncio A; Zamudio, Victor; Baltazar, Rosario; Mezura, Efren; Sotelo, Marco; Callaghan, Vic

2012-01-01

In this paper we present a comparison between six novel approaches to the fundamental problem of cyclic instability in Ambient Intelligence. These approaches are based on different optimization algorithms, Particle Swarm Optimization (PSO), Bee Swarm Optimization (BSO), micro Particle Swarm Optimization (μ-PSO), Artificial Immune System (AIS), Genetic Algorithm (GA) and Mutual Information Maximization for Input Clustering (MIMIC). In order to be able to use these algorithms, we introduced the concept of Average Cumulative Oscillation (ACO), which enabled us to measure the average behavior of the system. This approach has the advantage that it does not need to analyze the topological properties of the system, in particular the loops, which can be computationally expensive. In order to test these algorithms we used the well-known discrete system called the Game of Life for 9, 25, 49 and 289 agents. It was found that PSO and μ-PSO have the best performance in terms of the number of agents locked. These results were confirmed using the Wilcoxon Signed Rank Test. This novel and successful approach is very promising and can be used to remove instabilities in real scenarios with a large number of agents (including nomadic agents) and complex interactions and dependencies among them.

Near Infrared Fluorescence Imaging in Nano-Therapeutics and Photo-Thermal Evaluation

PubMed Central

Vats, Mukti; Mishra, Sumit Kumar; Baghini, Mahdieh Shojaei; Chauhan, Deepak S.; Srivastava, Rohit; De, Abhijit

2017-01-01

The unresolved and paramount challenge in bio-imaging and targeted therapy is to clearly define and demarcate the physical margins of tumor tissue. The ability to outline the healthy vital tissues to be carefully navigated with transection while an intraoperative surgery procedure is performed sets up a necessary and under-researched goal. To achieve the aforementioned objectives, there is a need to optimize design considerations in order to not only obtain an effective imaging agent but to also achieve attributes like favorable water solubility, biocompatibility, high molecular brightness, and a tissue specific targeting approach. The emergence of near infra-red fluorescence (NIRF) light for tissue scale imaging owes to the provision of highly specific images of the target organ. The special characteristics of near infra-red window such as minimal auto-fluorescence, low light scattering, and absorption of biomolecules in tissue converge to form an attractive modality for cancer imaging. Imparting molecular fluorescence as an exogenous contrast agent is the most beneficial attribute of NIRF light as a clinical imaging technology. Additionally, many such agents also display therapeutic potentials as photo-thermal agents, thus meeting the dual purpose of imaging and therapy. Here, we primarily discuss molecular imaging and therapeutic potentials of two such classes of materials, i.e., inorganic NIR dyes and metallic gold nanoparticle based materials. PMID:28452928

A Comparison between Metaheuristics as Strategies for Minimizing Cyclic Instability in Ambient Intelligence

PubMed Central

Romero, Leoncio A.; Zamudio, Victor; Baltazar, Rosario; Mezura, Efren; Sotelo, Marco; Callaghan, Vic

2012-01-01

In this paper we present a comparison between six novel approaches to the fundamental problem of cyclic instability in Ambient Intelligence. These approaches are based on different optimization algorithms, Particle Swarm Optimization (PSO), Bee Swarm Optimization (BSO), micro Particle Swarm Optimization (μ-PSO), Artificial Immune System (AIS), Genetic Algorithm (GA) and Mutual Information Maximization for Input Clustering (MIMIC). In order to be able to use these algorithms, we introduced the concept of Average Cumulative Oscillation (ACO), which enabled us to measure the average behavior of the system. This approach has the advantage that it does not need to analyze the topological properties of the system, in particular the loops, which can be computationally expensive. In order to test these algorithms we used the well-known discrete system called the Game of Life for 9, 25, 49 and 289 agents. It was found that PSO and μ-PSO have the best performance in terms of the number of agents locked. These results were confirmed using the Wilcoxon Signed Rank Test. This novel and successful approach is very promising and can be used to remove instabilities in real scenarios with a large number of agents (including nomadic agents) and complex interactions and dependencies among them. PMID:23112643

Probabilistic sparse matching for robust 3D/3D fusion in minimally invasive surgery.

PubMed

Neumann, Dominik; Grbic, Sasa; John, Matthias; Navab, Nassir; Hornegger, Joachim; Ionasec, Razvan

2015-01-01

Classical surgery is being overtaken by minimally invasive and transcatheter procedures. As there is no direct view or access to the affected anatomy, advanced imaging techniques such as 3D C-arm computed tomography (CT) and C-arm fluoroscopy are routinely used in clinical practice for intraoperative guidance. However, due to constraints regarding acquisition time and device configuration, intraoperative modalities have limited soft tissue image quality and reliable assessment of the cardiac anatomy typically requires contrast agent, which is harmful to the patient and requires complex acquisition protocols. We propose a probabilistic sparse matching approach to fuse high-quality preoperative CT images and nongated, noncontrast intraoperative C-arm CT images by utilizing robust machine learning and numerical optimization techniques. Thus, high-quality patient-specific models can be extracted from the preoperative CT and mapped to the intraoperative imaging environment to guide minimally invasive procedures. Extensive quantitative experiments on 95 clinical datasets demonstrate that our model-based fusion approach has an average execution time of 1.56 s, while the accuracy of 5.48 mm between the anchor anatomy in both images lies within expert user confidence intervals. In direct comparison with image-to-image registration based on an open-source state-of-the-art medical imaging library and a recently proposed quasi-global, knowledge-driven multi-modal fusion approach for thoracic-abdominal images, our model-based method exhibits superior performance in terms of registration accuracy and robustness with respect to both target anatomy and anchor anatomy alignment errors.

Recent advances in endovascular techniques for management of acute nonvariceal upper gastrointestinal bleeding

PubMed Central

Loffroy, Romaric F; Abualsaud, Basem A; Lin, Ming D; Rao, Pramod P

2011-01-01

Over the past two decades, transcatheter arterial embolization has become the first-line therapy for the management of upper gastrointestinal bleeding that is refractory to endoscopic hemostasis. Advances in catheter-based techniques and newer embolic agents, as well as recognition of the effectiveness of minimally invasive treatment options, have expanded the role of interventional radiology in the management of hemorrhage for a variety of indications, such as peptic ulcer bleeding, malignant disease, hemorrhagic Dieulafoy lesions and iatrogenic or trauma bleeding. Transcatheter interventions include the following: selective embolization of the feeding artery, sandwich coil occlusion of the gastroduodenal artery, blind or empiric embolization of the supposed bleeding vessel based on endoscopic findings and coil pseudoaneurysm or aneurysm embolization by three-dimensional sac packing with preservation of the parent artery. Transcatheter embolization is a fast, safe and effective, minimally invasive alternative to surgery when endoscopic treatment fails to control bleeding from the upper gastrointestinal tract. This article reviews the various transcatheter endovascular techniques and devices that are used in a variety of clinical scenarios for the management of hemorrhagic gastrointestinal emergencies. PMID:21860697

RBC micromotors carrying multiple cargos towards potential theranostic applications.

PubMed

Wu, Zhiguang; Esteban-Fernández de Ávila, Berta; Martín, Aída; Christianson, Caleb; Gao, Weiwei; Thamphiwatana, Soracha Kun; Escarpa, Alberto; He, Qiang; Zhang, Liangfang; Wang, Joseph

2015-08-28

Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic resonance imaging. The simultaneous encapsulation of the imaging nanoparticles and therapeutic payloads within the same RBC micromotor has a minimal effect upon its propulsion behavior. The ability of the RBC micromotors to transport imaging and therapeutic agents at high speed and spatial precision through a complex microchannel network is also demonstrated. Such ability to load and transport diagnostic imaging agents and therapeutic drugs within a single cell-based motor, in addition to a lower toxicity observed once the drug is encapsulated within the multicargo RBC motor, opens the door to the development of theranostic micromotors that may simultaneously treat and monitor diseases.

Insights into a microwave susceptible agent for minimally invasive microwave tumor thermal therapy.

PubMed

Shi, Haitang; Liu, Tianlong; Fu, Changhui; Li, Linlin; Tan, Longfei; Wang, Jingzhuo; Ren, Xiangling; Ren, Jun; Wang, Jianxin; Meng, Xianwei

2015-03-01

This work develops a kind of sodium alginate (SA) microcapsules as microwave susceptible agents for in vivo tumor microwave thermal therapy for the first time. Due to the excellent microwave susceptible properties and low bio-toxicity, excellent therapy efficiency can be achieved with the tumor inhibiting ratio of 97.85% after one-time microwave thermal therapy with ultralow power (1.8 W, 450 MHz). Meanwhile, the mechanism of high microwave heating efficiency was confirmed via computer-simulated model in theory, demonstrating that the spatial confinement efficiency of microcapsule walls endows the inside ions with high microwave susceptible properties. This strategy offers tremendous potential applications in clinical tumor treatment with the benefits of safety, reliability, effectiveness and minimally invasiveness. Copyright © 2014 Elsevier Ltd. All rights reserved.

Thymbra capitata essential oil as potential therapeutic agent against Gardnerella vaginalis biofilm-related infections.

PubMed

Machado, Daniela; Gaspar, Carlos; Palmeira-de-Oliveira, Ana; Cavaleiro, Carlos; Salgueiro, Lígia; Martinez-de-Oliveira, José; Cerca, Nuno

2017-04-01

To evaluate the antibacterial activity of Thymbra capitata essential oil and its main compound, carvacrol, against Gardnerella vaginalis grown planktonically and as biofilms, and its effect of vaginal lactobacilli. Minimal inhibitory concentration, minimal lethal concentration determination and flow cytometry analysis were used to assess the antibacterial effect against planktonic cells. Antibiofilm activity was measured through quantification of biomass and visualization of biofilm structure by confocal laser scanning microscopy. T. capitata essential oil and carvacrol exhibited a potent antibacterial activity against G. vaginalis cells. Antibiofilm activity was more evident with the essential oil than carvacrol. Furthermore, vaginal lactobacilli were significantly more tolerant to the essential oil. T. capitata essential oil stands up as a promising therapeutic agent against G. vaginalis biofilm-related infections.

Composition and method for encapsulating photovoltaic devices

DOEpatents

Pern, Fu-Jann

2000-01-01

A composition and method for encapsulating a photovoltaic device which minimizes discoloration of the encapsulant. The composition includes an ethylene-vinyl acetate encapsulant, a curing agent, an optional ultraviolet light stabilizer, and/or an optional antioxidant. The curing agent is preferably 1,1-di-(t-butylperoxy)-3,3,5-trimethylcyclohexane; the ultraviolet light stabilizer is bis-(N-octyloxy-tetramethyl) piperidinyl sebacate and the antioxidant is selected from the group consisting of tris (2,4-di-tert-butylphenyl) phosphite, tetrakis methylene (3,5-di-tert-butyl-4-hydroxyhydrocinnamate) methane, octadecyl 3,5-di-tert-butyl-4-hydroxyhydrocinnamate, and 2,2'-ethylidene bis(4,6-di-t-butylphenyl) fluorophosponite. The composition is applied to a solar cell then cured. The cured product contains a minimal concentration of curing-generated chromophores and resists UV-induced degradation.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).

PubMed

Winthrop, K L; Mariette, X; Silva, J T; Benamu, E; Calabrese, L H; Dumusc, A; Smolen, J S; Aguado, J M; Fernández-Ruiz, M

2018-06-01

The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection. Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Control of muscle relaxation during anesthesia: a novel approach for clinical routine.

PubMed

Stadler, Konrad S; Schumacher, Peter M; Hirter, Sibylle; Leibundgut, Daniel; Bouillon, Thomas W; Glattfelder, Adolf H; Zbinden, Alex M

2006-03-01

During general anesthesia drugs are administered to provide hypnosis, ensure analgesia, and skeletal muscle relaxation. In this paper, the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal train-of-four stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes, a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer-based state feedback controller. Contrary to similar automatic systems described in the literature this controller makes use of two different measures obtained in the train-of-four measurement to maintain the desired level of relaxation. The controller is validated in a clinical study comparing the performance of the controller to the performance of the anesthesiologist. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision while minimizing drug administration. The controller performed at least equally well as the anesthesiologist.

Click chemistry improved wet adhesion strength of mussel-inspired citrate-based antimicrobial bioadhesives

PubMed Central

Guo, Jinshan; Kim, Gloria B.; Shan, Dingying; Kim, Jimin P.; Hu, Jianqing; Wang, Wei; Hamad, Fawzi G.; Qian, Guoying; Rizk, Elias B.; Yang, Jian

2016-01-01

For the first time, a convenient copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was successfully introduced into injectable citrate-based mussel-inspired bioadhesives (iCMBAs, iCs) to improve both cohesive and wet adhesive strengths and elongate the degradation time, providing numerous advantages in surgical applications. The major challenge to developing such an adhesive was the mutual inhibition effect between the oxidant used for crosslinking catechol groups and the Cu(II) reductant used for CuAAC, which was successfully minimized by adding a biocompatible buffering agent typically used in cell culture, 4-(2-hydroxyethyl) -1-piperazineethanesulfonic acid (HEPES), as a copper chelating agent. Among the investigated formulations, the highest adhesion strength achieved (223.11 ± 15.94 kPa) was around 13 times higher than that of a commercially available fibrin glue (15.4 ± 2.8 kPa). In addition, dual-crosslinked (i.e. click crosslinking and mussel-inspired crosslinking) iCMBAs still preserved considerable antibacterial and antifungal capabilities that are beneficial for the bioadhesives used as hemostatic adhesives or sealants for wound management. PMID:27770631

Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.

PubMed

Krukiewicz, Katarzyna; Zak, Jerzy K

2016-05-01

Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Resource Control in Large-Scale Mobile-Agents Systems

DTIC Science & Technology

2005-07-01

wakeup node schedule , much energy can be conserved. We also designed several protocols for global clock synchronization. The most interesting one is...choice as to which remote hosts to visit and in which order. Scheduling mobile-agent migration in a way that minimizes bandwidth and other resource...use, therefore, is both feasible and attractive. Dartmouth considered several variations of the scheduling problem, and devel- oped an algorithm for

Setting standards for product selection: allergy prevention.

PubMed

White, I R

1997-01-01

It is axiomatic to state that if products made of natural rubber latex were not used in health care settings then there would be no problems of acquired hypersensitivity from such products. Although synthetic materials are available they do not currently possess the same technical qualities of elasticity and comfort, nor do they deliver the desired degree of protection against biological agents as gloves made out of natural rubber latex. Selection of gloves either for non-sterile procedures or sterile surgical use should be based on this understanding, and gloves with minimal levels of extractable latex proteins should be used.

Solvent-induced changes in PEDOT:PSS films for organic electrochemical transistors

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

Zhang, Shiming; Kumar, Prajwal; Nouas, Amel Sarah

2015-01-01

Organic electrochemical transistors based on the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS) are of interest for several bioelectronic applications. In this letter, we investigate the changes induced by immersion of PEDOT:PSS films, processed by spin coating from different mixtures, in water and other solvents of different polarities. We found that the film thickness decreases upon immersion in polar solvents, while the electrical conductivity remains unchanged. The decrease in film thickness is minimized via the addition of a cross-linking agent to the mixture used for the spin coating of the films.

Contamination Analyzer

NASA Technical Reports Server (NTRS)

1994-01-01

Measurement of the total organic carbon content in water is important in assessing contamination levels in high purity water for power generation, pharmaceutical production and electronics manufacture. Even trace levels of organic compounds can cause defects in manufactured products. The Sievers Model 800 Total Organic Carbon (TOC) Analyzer, based on technology developed for the Space Station, uses a strong chemical oxidizing agent and ultraviolet light to convert organic compounds in water to carbon dioxide. After ionizing the carbon dioxide, the amount of ions is determined by measuring the conductivity of the deionized water. The new technique is highly sensitive, does not require compressed gas, and maintenance is minimal.

Continual planning and scheduling for managing patient tests in hospital laboratories.

PubMed

Marinagi, C C; Spyropoulos, C D; Papatheodorou, C; Kokkotos, S

2000-10-01

Hospital laboratories perform examination tests upon patients, in order to assist medical diagnosis or therapy progress. Planning and scheduling patient requests for examination tests is a complicated problem because it concerns both minimization of patient stay in hospital and maximization of laboratory resources utilization. In the present paper, we propose an integrated patient-wise planning and scheduling system which supports the dynamic and continual nature of the problem. The proposed combination of multiagent and blackboard architecture allows the dynamic creation of agents that share a set of knowledge sources and a knowledge base to service patient test requests.

Lead selection and characterization of antitubercular compounds using the Nested Chemical Library.

PubMed

Sipos, Anna; Pató, János; Székely, Rita; Hartkoorn, Ruben C; Kékesi, László; Őrfi, László; Szántai-Kis, Csaba; Mikušová, Katarína; Svetlíková, Zuzana; Korduláková, Jana; Nagaraja, Valakunja; Godbole, Adwait Anand; Bush, Natassja; Collin, Frédéric; Maxwell, Anthony; Cole, Stewart T; Kéri, György

2015-06-01

Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based approaches against several validated mycobacterial enzymes and phenotypic screens. We screened more than 17,000 compounds from Vichem's Nested Chemical Library™ using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis, and target-based assays with protein kinases PknA, PknB and PknG as well as other targets such as PimA and bacterial topoisomerases simultaneously. With the help of the target-based approach we have found very potent hits inhibiting the selected target enzymes, but good minimal inhibitory concentrations (MIC) against M. tuberculosis were not achieved. Focussing on the whole cell-based approach several potent hits were found which displayed minimal inhibitory concentrations (MIC) against M. tuberculosis below 10 μM and were non-mutagenic, non-cytotoxic and the targets of some of the hits were also identified. The most active hits represented various scaffolds. Medicinal chemistry-based lead optimization was performed applying various strategies and, as a consequence, a series of novel potent compounds were synthesized. These efforts resulted in some effective potential antitubercular lead compounds which were confirmed in phenotypic assays. Copyright © 2015 Elsevier Ltd. All rights reserved.

A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions

PubMed Central

Rosenberg, Yvonne J.; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

2015-01-01

Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1–2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product. PMID:26268538

A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions.

PubMed

Rosenberg, Yvonne J; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

2015-08-13

Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1-2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product.

A Novel Computer-Based Set-Up to Study Movement Coordination in Human Ensembles

PubMed Central

Alderisio, Francesco; Lombardi, Maria; Fiore, Gianfranco; di Bernardo, Mario

2017-01-01

Existing experimental works on movement coordination in human ensembles mostly investigate situations where each subject is connected to all the others through direct visual and auditory coupling, so that unavoidable social interaction affects their coordination level. Here, we present a novel computer-based set-up to study movement coordination in human groups so as to minimize the influence of social interaction among participants and implement different visual pairings between them. In so doing, players can only take into consideration the motion of a designated subset of the others. This allows the evaluation of the exclusive effects on coordination of the structure of interconnections among the players in the group and their own dynamics. In addition, our set-up enables the deployment of virtual computer players to investigate dyadic interaction between a human and a virtual agent, as well as group synchronization in mixed teams of human and virtual agents. We show how this novel set-up can be employed to study coordination both in dyads and in groups over different structures of interconnections, in the presence as well as in the absence of virtual agents acting as followers or leaders. Finally, in order to illustrate the capabilities of the architecture, we describe some preliminary results. The platform is available to any researcher who wishes to unfold the mechanisms underlying group synchronization in human ensembles and shed light on its socio-psychological aspects. PMID:28649217

Sewage treatment method and apparatus

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

Engelmann, J.A.

1982-07-13

A method and apparatus for treating sewage and converting the sewage into organic fertilizer which utilizes equipment for converting the solid material of the sewage into patties and a mixing apparatus for mixing the patties with bulking agents. The mixture of patties and bulking agents is stored in a pile and subjected to a supply of air to enhance the self-combustion or oxidation of the organic material in the patties. The bulking agents provide the patty-bulking agent mixture with air passages and pockets and minimize compaction of the patties. The selfcombustion of the patties continues until the organic material ismore » burned out, leaving a residual ash. A shaker separator having an elongated longitudinal perforated member is reciprocated to separate the ash from the bulking agents. The ash is collected and utilized as organic fertilizer. The bulking agents are recycled back to the mixing apparatus.« less

Detox agents do not affect the pharmacokinetics of methamphetamine in the rat.

PubMed

Lee, Sang Kyu; Kim, Yoon; Suh, Sungill; Suh, Yong Jun; In, Moon Kyo; Kim, Dong-Hyun; Jin, Changbae; Yoo, Hye Hyun

2009-04-15

Recently, 'detox' agents have been popularly used as forms of diets or nutritional supplements. Especially, several cases have been reported that these detox agents have been used to mask drug tests among drug abusers. In the present study, capsule and drink types of detox agents were evaluated for their ability to alter the elimination of methamphetamine (MA) in rats. For this study, MA and its major metabolite, amphetamine (AP) in urine samples were determined using LC-tandem mass spectrometry after administration of the detox agents to MA-treated rats. As a result, significant differences were not shown between control and detox-dosed groups in the amounts of MA and AP excreted into urine as well as the volume of excreted urine. This result suggests that the detox agents tested may not affect the metabolism or elimination of MA and further might have minimal effect on narcotics detection in the urine samples of drug abusers.

Laboratory security and emergency response guidance for laboratories working with select agents. Centers for Disease Control and Prevention.

PubMed

Richmond, Jonathan Y; Nesby-O'Dell, Shanna L

2002-12-06

In recent years, concern has increased regarding use of biologic materials as agents of terrorism, but these same agents are often necessary tools in clinical and research microbiology laboratories. Traditional biosafety guidelines for laboratories have emphasized use of optimal work practices, appropriate containment equipment, well-designed facilities, and administrative controls to minimize risk of worker injury and to ensure safeguards against laboratory contamination. The guidelines discussed in this report were first published in 1999 (U.S. Department of Health and Human Services/CDC and National Institutes of Health. Biosafety in microbiological and biomedical laboratories [BMBL]. Richmond JY, McKinney RW, eds. 4th ed. Washington, DC: US Department of Health and Human Services, 1999 [Appendix F]). In that report, physical security concerns were addressed, and efforts were focused on preventing unauthorized entry to laboratory areas and preventing unauthorized removal of dangerous biologic agents from the laboratory. Appendix F of BMBL is now being revised to include additional information regarding personnel risk assessments, and inventory controls. The guidelines contained in this report are intended for laboratories working with select agents under biosafety-level 2, 3, or 4 conditions as described in Sections II and III of BMBL. These recommendations include conducting facility risk assessments and developing comprehensive security plans to minimize the probability of misuse of select agents. Risk assessments should include systematic, site-specific reviews of 1) physical security; 2) security of data and electronic technology systems; 3) employee security; 4) access controls to laboratory and animal areas; 5) procedures for agent inventory and accountability; 6) shipping/transfer and receiving of select agents; 7) unintentional incident and injury policies; 8) emergency response plans; and 9) policies that address breaches in security. The security plan should be an integral part of daily operations. All employees should be well-trained and equipped, and the plan should be reviewed annually, at least.

A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive biodegradable macromolecular MRI contrast agent.

PubMed

Ye, Zhen; Zhou, Zhuxian; Ayat, Nadia; Wu, Xueming; Jin, Erlei; Shi, Xiaoyue; Lu, Zheng-Rong

2016-01-01

This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1) at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+) ions, and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging. Copyright © 2015 John Wiley & Sons, Ltd.

Oral Surgical Procedures Performed Safely in Patients With Head and Neck Arteriovenous Malformations: A Retrospective Case Series of 12 Patients.

PubMed

Karim, Abdul Basit; Lindsey, Sean; Bovino, Brian; Berenstein, Alejandro

2016-02-01

This case series describes patients with head and neck arteriovenous malformations who underwent oral and maxillofacial surgical procedures combined with interventional radiology techniques to minimize blood loss. Twelve patients underwent femoral cerebral angiography to visualize the extent of vascular malformation. Before the surgical procedures, surgical sites were devascularized by direct injection of hemostatic or embolic agents. Direct puncture sclerotherapy at the base of surgical sites was performed using Surgiflo or n-butylcyanoacrylate glue. Surgical procedures were carried out in routine fashion. A hemostatic packing of FloSeal, Gelfoam, and Avitene was adapted to the surgical sites. Direct puncture sclerotherapy with Surgiflo or n-butylcyanoacrylate glue resulted in minimal blood loss intraoperatively. Local application of the FloSeal, Gelfoam, and Avitene packing sustained hemostasis and produced excellent healing postoperatively. Patients with arteriovenous malformations can safely undergo routine oral and maxillofacial surgical procedures with minimal blood loss when appropriate endovascular techniques and local hemostatic measures are used by the interventional radiologist and oral and maxillofacial surgeon. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Evolutionary Agent-based Models to design distributed water management strategies

NASA Astrophysics Data System (ADS)

Giuliani, M.; Castelletti, A.; Reed, P. M.

2012-12-01

There is growing awareness in the scientific community that the traditional centralized approach to water resources management, as described in much of the water resources literature, provides an ideal optimal solution, which is certainly useful to quantify the best physically achievable performance, but is generally inapplicable. Most real world water resources management problems are indeed characterized by the presence of multiple, distributed and institutionally-independent decision-makers. Multi-Agent Systems provide a potentially more realistic alternative framework to model multiple and self-interested decision-makers in a credible context. Each decision-maker can be represented by an agent who, being self-interested, acts according to local objective functions and produces negative externalities on system level objectives. Different levels of coordination can potentially be included in the framework by designing coordination mechanisms to drive the current decision-making structure toward the global system efficiency. Yet, the identification of effective coordination strategies can be particularly complex in modern institutional contexts and current practice is dependent on largely ad-hoc coordination strategies. In this work we propose a novel Evolutionary Agent-based Modeling (EAM) framework that enables a mapping of fully uncoordinated and centrally coordinated solutions into their relative "many-objective" tradeoffs using multiobjective evolutionary algorithms. Then, by analysing the conflicts between local individual agent and global system level objectives it is possible to more fully understand the causes, consequences, and potential solution strategies for coordination failures. Game-theoretic criteria have value for identifying the most interesting alternatives from a policy making point of view as well as the coordination mechanisms that can be applied to obtain these interesting solutions. The proposed approach is numerically tested on a synthetic case study, representing a Y-shaped system composed by two regulated lakes, whose releases merge just upstream of a city. Each reservoir is operated by an agent in order to prevent floods along the lake shores (local objective). However, the optimal operation of the reservoirs with respect to the local objectives is conflicting with the minimization of floods in the city (global objective). The evolution of the Agent-based Model from individualistic management strategies of the reservoirs toward a global compromise that reduces the costs for the city is analysed.

Safety in Acute Pain Medicine-Pharmacologic Considerations and the Impact of Systems-Based Gaps.

PubMed

Weingarten, Toby N; Taenzer, Andreas H; Elkassabany, Nabil M; Le Wendling, Linda; Nin, Olga; Kent, Michael L

2018-05-02

In the setting of an expanding prevalence of acute pain medicine services and the aggressive use of multimodal analgesia, an overview of systems-based safety gaps and safety concerns in the setting of aggressive multimodal analgesia is provided below. Expert commentary. Recent evidence focused on systems-based gaps in acute pain medicine is discussed. A focused literature review was conducted to assess safety concerns related to commonly used multimodal pharmacologic agents (opioids, nonsteroidal anti-inflammatory drugs, gabapentanoids, ketamine, acetaminophen) in the setting of inpatient acute pain management. Optimization of systems-based gaps will increase the probability of accurate pain assessment, improve the application of uniform evidence-based multimodal analgesia, and ensure a continuum of pain care. While acute pain medicine strategies should be aggressively applied, multimodal regimens must be strategically utilized to minimize risk to patients and in a comorbidity-specific fashion.

78 FR 9056 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... of automated collection techniques or other forms of information technology to minimize the... agent/brokers provided during training will be used to record their training history through CMS LMS...

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

PubMed Central

Estey, Elihu; Grimwade, David; Amadori, Sergio; Appelbaum, Frederick R.; Büchner, Thomas; Dombret, Hervé; Ebert, Benjamin L.; Fenaux, Pierre; Larson, Richard A.; Levine, Ross L.; Lo-Coco, Francesco; Naoe, Tomoki; Niederwieser, Dietger; Ossenkoppele, Gert J.; Sanz, Miguel; Sierra, Jorge; Tallman, Martin S.; Tien, Hwei-Fang; Wei, Andrew H.; Löwenberg, Bob; Bloomfield, Clara D.

2017-01-01

The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease. PMID:27895058

Coevolution of Epidemics, Social Networks, and Individual Behavior: A Case Study

NASA Astrophysics Data System (ADS)

Chen, Jiangzhuo; Marathe, Achla; Marathe, Madhav

This research shows how a limited supply of antivirals can be distributed optimally between the hospitals and the market so that the attack rate is minimized and enough revenue is generated to recover the cost of the antivirals. Results using an individual based model find that prevalence elastic demand behavior delays the epidemic and change in the social contact network induced by isolation reduces the peak of the epidemic significantly. A microeconomic analysis methodology combining behavioral economics and agent-based simulation is a major contribution of this work. In this paper we apply this methodology to analyze the fairness of the stockpile distribution, and the response of human behavior to disease prevalence level and its interaction with the market.

Formulation and characterization of a compacted multiparticulate system for modified release of water-soluble drugs--part 1--acetaminophen.

PubMed

Cantor, Stuart L; Hoag, Stephen W; Augsburger, Larry L

2009-03-01

The aim of this study was to characterize and evaluate a modified release, multiparticulate tablet formulation consisting of placebo beads and drug-loaded beads. Acetaminophen (APAP) bead formulations containing ethylcellulose (EC) from 40-60% and placebo beads containing 30% calcium silicate and prepared using 0-20% alcohol were developed using extrusion-spheronization and studied using a central composite experimental design. Particle size and true density of beads were measured. Segregation testing was performed using the novel ASTM D6940-04 method on a 50:50 blend of uncoated APAP beads (60%EC) : calcium silicate placebo beads (10% alcohol). Tablets were prepared using an instrumented Stokes-B2 rotary tablet press and evaluated for crushing strength and dissolution rate. Compared with drug beads (60%EC), placebo beads (10% alcohol) were smaller but had higher true densities: 864.8 mum and 1.27 g/cm(3), and 787.1 mum and 1.73 g/cm(3), respectively. Segregation testing revealed that there was approximately a 20% difference in drug content (as measured by the coefficient of variation) between initial and final blend samples. Although calcium silicate-based placebo beads were shown to be ineffective cushioning agents in blends with Surelease(R)-coated APAP beads, they were found to be very compactibile when used alone and gave tablet crushing strength values between 14 and 17 kP. The EC in the APAP bead matrix minimally suppressed the drug release from uncoated beads (t(100%) = 2 h). However, while tablets containing placebo beads reformulated with glycerol monostearate (GMS) showed a slower release rate (t(60%)= 5 h) compared with calcium silicate-based placebos, some coating damage ( approximately 30%) still occurred on compression as release was faster than coated APAP beads alone. While tablets containing coated drug beads can be produced with practical crushing strengths (>8 kP) and low compression pressures (10-35 MPa), dissolution studies revealed that calcium silicate-based placebos are ineffective as cushioning agents. Blend segregation was likely observed due to the particle size and the density differences between APAP beads and calcium silicate-based placebo beads; placebo bead percolation can perhaps be minimized by increasing their size during the extrusion-spheronization process. The GMS- based placebos offer greater promise as cushioning agents for compacted, coated drug beads; however, this requires an optimized compression pressure range and drug bead : placebo bead ratio (i.e., 50:50).

Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

PubMed

Devarbhavi, Harshad; Andrade, Raúl J

2014-05-01

Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

More Opportunities than Wealth: Inequality and Emergent Social Classes in a Network of Power and Frustration

NASA Astrophysics Data System (ADS)

Nisoli, Cristiano; Mahault, Benoit; Saxena, Avadh

We introduce a minimal agent-based model to qualitatively conceptualize the allocation of limited wealth among more abundant opportunities. There the interplay of power, satisfaction and frustration determines the distribution, concentration, and inequality of wealth. Our framework allows us to compare subjective measures of frustration and satisfaction to collective measures of fairness in wealth distribution, such as the Lorenz curve and the Gini index. We find that a completely libertarian, law-of-the-jungle setting, where every agent can acquire wealth from, or lose wealth to, anybody else invariably leads to large inequality. The picture is however dramatically modified when hard constraints are imposed over agents, and they are limited to share wealth with neighbors on a network. We address dynamical societies via an out of equilibrium coevolution of the network, driven by a competition between power and frustration. The ratio between power and frustration controls different dynamical regimes separated by kinetic transitions and characterized by drastically different values of the indices of equality. In particular, it leads to the emergence of three self-organized social classes, lower, middle, and upper class, whose interactions drive a cyclical regime.

SOMM: A New Service Oriented Middleware for Generic Wireless Multimedia Sensor Networks Based on Code Mobility

PubMed Central

Faghih, Mohammad Mehdi; Moghaddam, Mohsen Ebrahimi

2011-01-01

Although much research in the area of Wireless Multimedia Sensor Networks (WMSNs) has been done in recent years, the programming of sensor nodes is still time-consuming and tedious. It requires expertise in low-level programming, mainly because of the use of resource constrained hardware and also the low level API provided by current operating systems. The code of the resulting systems has typically no clear separation between application and system logic. This minimizes the possibility of reusing code and often leads to the necessity of major changes when the underlying platform is changed. In this paper, we present a service oriented middleware named SOMM to support application development for WMSNs. The main goal of SOMM is to enable the development of modifiable and scalable WMSN applications. A network which uses the SOMM is capable of providing multiple services to multiple clients at the same time with the specified Quality of Service (QoS). SOMM uses a virtual machine with the ability to support mobile agents. Services in SOMM are provided by mobile agents and SOMM also provides a t space on each node which agents can use to communicate with each other. PMID:22346646

SOMM: A new service oriented middleware for generic wireless multimedia sensor networks based on code mobility.

PubMed

Faghih, Mohammad Mehdi; Moghaddam, Mohsen Ebrahimi

2011-01-01

Although much research in the area of Wireless Multimedia Sensor Networks (WMSNs) has been done in recent years, the programming of sensor nodes is still time-consuming and tedious. It requires expertise in low-level programming, mainly because of the use of resource constrained hardware and also the low level API provided by current operating systems. The code of the resulting systems has typically no clear separation between application and system logic. This minimizes the possibility of reusing code and often leads to the necessity of major changes when the underlying platform is changed. In this paper, we present a service oriented middleware named SOMM to support application development for WMSNs. The main goal of SOMM is to enable the development of modifiable and scalable WMSN applications. A network which uses the SOMM is capable of providing multiple services to multiple clients at the same time with the specified Quality of Service (QoS). SOMM uses a virtual machine with the ability to support mobile agents. Services in SOMM are provided by mobile agents and SOMM also provides a t space on each node which agents can use to communicate with each other.

Process Management inside ATLAS DAQ

NASA Astrophysics Data System (ADS)

Alexandrov, I.; Amorim, A.; Badescu, E.; Burckhart-Chromek, D.; Caprini, M.; Dobson, M.; Duval, P. Y.; Hart, R.; Jones, R.; Kazarov, A.; Kolos, S.; Kotov, V.; Liko, D.; Lucio, L.; Mapelli, L.; Mineev, M.; Moneta, L.; Nassiakou, M.; Pedro, L.; Ribeiro, A.; Roumiantsev, V.; Ryabov, Y.; Schweiger, D.; Soloviev, I.; Wolters, H.

2002-10-01

The Process Management component of the online software of the future ATLAS experiment data acquisition system is presented. The purpose of the Process Manager is to perform basic job control of the software components of the data acquisition system. It is capable of starting, stopping and monitoring the status of those components on the data acquisition processors independent of the underlying operating system. Its architecture is designed on the basis of a server client model using CORBA based communication. The server part relies on C++ software agent objects acting as an interface between the local operating system and client applications. Some of the major design challenges of the software agents were to achieve the maximum degree of autonomy possible, to create processes aware of dynamic conditions in their environment and with the ability to determine corresponding actions. Issues such as the performance of the agents in terms of time needed for process creation and destruction, the scalability of the system taking into consideration the final ATLAS configuration and minimizing the use of hardware resources were also of critical importance. Besides the details given on the architecture and the implementation, we also present scalability and performance tests results of the Process Manager system.

Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles

PubMed Central

Spyratou, Ellas; Makropoulou, Mersini; Sihver, Lembit

2017-01-01

Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use light e.g., laser irradiation in an extracorporeal or intravenous mode to activate photosensitizer agents with selectivity in the target tissue. Photothermal therapy (PTT) is a minimally invasive technique for cancer treatment which uses laser-activated photoabsorbers to convert photon energy into heat sufficient to induce cells destruction via apoptosis, necroptosis and/or necrosis. During the last decade, PTT has attracted an increased interest since the therapy can be combined with customized functionalized nanoparticles (NPs). Recent advances in nanotechnology have given rise to generation of various types of NPs, like gold NPs (AuNPs), designed to act both as radiosensitizers and photothermal sensitizing agents due to their unique optical and electrical properties i.e., functioning in dual mode. Functionalized AuNPS can be employed in combination with non-ionizing and ionizing radiation to significantly improve the efficacy of cancer treatment while at the same time sparing normal tissues. Here, we first provide an overview of the use of NPs for cancer therapy. Then we review many recent advances on the use of gold NPs in PTT, RT and PTT/RT based on different types of AuNPs, irradiation conditions and protocols. We refer to the interaction mechanisms of AuNPs with cancer cells via the effects of non-ionizing and ionizing radiations and we provide recent existing experimental data as a baseline for the design of optimized protocols in PTT, RT and PTT/RT combined treatment. PMID:29257070

Influence of quenching agent on microstructure, properties and thermal stress of SiC{sub p}/2009 composites

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

He, Tianbing, E-mail: tianbing_1988@sina.com

15% vol. SiC{sub p}/2009 composites prepared by powder metallurgy were quenched in room temperature water and 20% polyethylene glycol (PEG) solution respectively, then aged naturally. The influence of quenching agent on microstructure, properties and thermal stress of SiC{sub p}/2009 composites were investigated by means of scanning/transmission electron microscope, hardness and tensile test. The results showed that the number of precipitated phase in water quenched composites increased, with much finer in size and more homogeneous in distribution compared with 20% PEG quenched one. Meanwhile, the density of dislocation in composites by water quenching was also much higher. Intergranular corrosion did notmore » occur with the two quenching agents. The 20% PEG quenched composites exhibited slight lower hardness and higher electrical conductivity than that of water quenched one. The two quenched composites showed same level in tensile strength, but the yield strength of water-quenched composites was higher (8 MPa, 3%). The usage of 20% PEG reduced thermal stress and minimized warping deformation of the parts, it is a more suitable quenching agent for SiC{sub p}/2009 composites in engineering application fields. - Highlights: •SiC{sub p}/2009 composites quenched by water and 20% PEG solution were investigated. •Aging precipitation behavior of SiC{sub p}/2009 composites is sensitive to quenchant. •Influence of quenching agent on properties of SiC{sub p}/2009 composites are minimal. •Quenching with 20% PEG reduces thermal stress of SiC{sub p}/2009 composites remarkably. •20% PEG is a more suitable quenching agent for SiC{sub p}/2009 composites than water.« less

The role of bacillus-based biological control agents in integrated pest management systems: plant diseases.

PubMed

Jacobsen, B J; Zidack, N K; Larson, B J

2004-11-01

ABSTRACT Bacillus-based biological control agents (BCAs) have great potential in integrated pest management (IPM) systems; however, relatively little work has been published on integration with other IPM management tools. Unfortunately, most research has focused on BCAs as alternatives to synthetic chemical fungicides or bactericides and not as part of an integrated management system. IPM has had many definitions and this review will use the national coalition for IPM definition: "A sustainable approach to managing pests by combining biological, cultural, physical and chemical tools in a way that minimizes economic, health and environmental risks." This review will examine the integrated use of Bacillus-based BCAs with disease management tools, including resistant cultivars, fungicides or bactericides, or other BCAs. This integration is important because the consistency and degree of disease control by Bacillus-based BCAs is rarely equal to the control afforded by the best fungicides or bactericides. In theory, integration of several tools brings stability to disease management programs. Integration of BCAs with other disease management tools often provides broader crop adaptation and both more efficacious and consistent levels of disease control. This review will also discuss the use of Bacillus-based BCAs in fungicide resistance management. Work with Bacillus thuringiensis and insect pest management is the exception to the relative paucity of reports but will not be the focus of this review.

Targeted delivery of cancer-specific multimodal contrast agents for intraoperative detection of tumor boundaries and therapeutic margins

NASA Astrophysics Data System (ADS)

Xu, Ronald X.; Xu, Jeff S.; Huang, Jiwei; Tweedle, Michael F.; Schmidt, Carl; Povoski, Stephen P.; Martin, Edward W.

2010-02-01

Background: Accurate assessment of tumor boundaries and intraoperative detection of therapeutic margins are important oncologic principles for minimal recurrence rates and improved long-term outcomes. However, many existing cancer imaging tools are based on preoperative image acquisition and do not provide real-time intraoperative information that supports critical decision-making in the operating room. Method: Poly lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) were synthesized by a modified double emulsion method. The MB and NB surfaces were conjugated with CC49 antibody to target TAG-72 antigen, a human glycoprotein complex expressed in many epithelial-derived cancers. Multiple imaging agents were encapsulated in MBs and NBs for multimodal imaging. Both one-step and multi-step cancer targeting strategies were explored. Active MBs/NBs were also fabricated for therapeutic margin assessment in cancer ablation therapies. Results: The multimodal contrast agents and the cancer-targeting strategies were tested on tissue simulating phantoms, LS174 colon cancer cell cultures, and cancer xenograft nude mice. Concurrent multimodal imaging was demonstrated using fluorescence and ultrasound imaging modalities. Technical feasibility of using active MBs and portable imaging tools such as ultrasound for intraoperative therapeutic margin assessment was demonstrated in a biological tissue model. Conclusion: The cancer-specific multimodal contrast agents described in this paper have the potential for intraoperative detection of tumor boundaries and therapeutic margins.

Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

NASA Astrophysics Data System (ADS)

Subramaniam, Prasad

Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on the synthesis and use of a biodegradable dendritic polypeptide-based nanocarrier for the delivery of multiple anticancer drugs and siRNA to brain tumor cells. The co-delivery of important anticancer agents using a single platform was shown to increase the efficacy of the drugs manyfold, ensuring the cancer cell-specific delivery and minimizing dose limiting toxicities of the individual drugs. This would be of immense importance when used in vivo.

Apparent competition can compromise the safety of highly specific biocontrol agents.

PubMed

Carvalheiro, Luisa G; Buckley, Yvonne M; Ventim, Rita; Fowler, Simon V; Memmott, Jane

2008-07-01

Despite current concern about the safety of biological control of weeds, assessing the indirect impacts of introduced agents is not common practice. Using 17 replicate food webs, we demonstrate that the use of a highly host-plant specific weed biocontrol agent, recently introduced into Australia, is associated with declines of local insect communities. The agent shares natural enemies (predators and parasitoids) with seed herbivore species from native plants, so apparent competition is the most likely cause for these losses. Both species richness and abundance in insect communities (seed herbivores and their parasitoids) were negatively correlated with the abundance of the biocontrol agent. Local losses of up to 11 species (dipteran seed herbivores and parasitoids) took place as the biocontrol agent abundance increased. Ineffective biocontrol agents that remain highly abundant in the community are most likely to have persistent, indirect negative effects. Our findings suggest that more investment is required in pre-release studies on the effectiveness of biocontrol agents, as well as in post-release studies assessing indirect impacts, to avoid or minimize the release of potentially damaging species.

Fire suppression in human-crew spacecraft

NASA Technical Reports Server (NTRS)

Friedman, Robert; Dietrich, Daniel L.

1991-01-01

Fire extinguishment agents range from water and foam in early-design spacecraft (Halon 1301 in the present Shuttle) to carbon dioxide proposed for the Space Station Freedom. The major challenge to spacecraft fire extinguishment design and operations is from the micro-gravity environment, which minimizes natural convection and profoundly influences combustion and extinguishing agent effectiveness, dispersal, and post-fire cleanup. Discussed here are extinguishment in microgravity, fire-suppression problems anticipated in future spacecraft, and research needs and opportunities.

In vitro Comparison of Impact of Different Bleaching Agents on the Microhardness of Enamel.

PubMed

Dey, Subhra; Pandey, Vinisha; Kumar, Anuj; Awasthi, Neha; Sahu, Anshu; Pujari, Sudarshan C

2016-03-01

Various agents are used these days for increasing the esthetics. One such procedure is bleaching that offers various advantages, as it is minimal invasive and cheap option to color the teeth and remove stain. The altered enamel after the bleaching process shows surface demineralization and porosities. The present study aimed to evaluate the effect of different bleaching agents on the microhardness of enamel. A total of 100 freshly human extracted maxillary premolar teeth were selected for the study. Teeth with sound tooth structure were included for the study. All the specimens were randomly divided into four groups with 25 specimens in each group depending upon the type of bleaching agent used: Group A, artificial saliva (Control group); Group B, 35% hydrogen peroxide (HP); Group C, 25% HP; Group D, 10% carbamide peroxide (CP). Knoop Hardness Number (KHN) was calculated at 24, 48-hour, and 7-week interval. Results showed no statistical significant differences between the microhardness of enamel of different groups (p < 0.005). A slight fall in the value of KHN was seen in all the groups, except for the control group, although the results were statistically nonsignificant (p > 0.005). Although nonsignificantly, all the bleaching solutions produced some amount of alterations in the microstructure of enamel. More studies with higher study groups and more advanced estimation technologies are required to minimize microstructure alterations and promote for better outcome of bleaching procedures.

Scaling laws of strategic behavior and size heterogeneity in agent dynamics

NASA Astrophysics Data System (ADS)

Vaglica, Gabriella; Lillo, Fabrizio; Moro, Esteban; Mantegna, Rosario N.

2008-03-01

We consider the financial market as a model system and study empirically how agents strategically adjust the properties of large orders in order to meet their preference and minimize their impact. We quantify this strategic behavior by detecting scaling relations between the variables characterizing the trading activity of different institutions. We also observe power-law distributions in the investment time horizon, in the number of transactions needed to execute a large order, and in the traded value exchanged by large institutions, and we show that heterogeneity of agents is a key ingredient for the emergence of some aggregate properties characterizing this complex system.

Production of xanthan gum from a chemically defined medium introduction

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

Weisrock, W.P.; Klein, H.S.

1983-02-22

Heteropolysaccharides produced by the action of Xanthomonas bacteria on carbohydrate media have a potential application as film forming agents, as thickeners in oil field drilling fluids and fracturing liquids and as emulsifying, stabilizing, and sizing agents. Heteropolysaccharides, particularly, xanthan gum, have a significant potential as mobility control agents in micellar polymer flooding. Xanthan gum has excellent viscosifying properties at low concentration, is resistant to shear degradation and exhibits only minimal losses in viscosity as a function of temperature, pH, and ionic strength. For these reasons, xanthan gum is an attractive alternative to synthetic polyacrylamides for enhanced oil recovery operations. 15more » claims.« less

Vesicants and nerve agents in chemical warfare. Decontamination and treatment strategies for a changed world.

PubMed

Devereaux, Asha; Amundson, Dennis E; Parrish, J S; Lazarus, Angeline A

2002-10-01

Vesicants and nerve agents have been used in chemical warfare for ages. They remain a threat in today's altered political climate because they are relatively simple to produce, transport, and deploy. Vesicants, such as mustard and lewisite, can affect the skin, eyes, respiratory system, and gastrointestinal system. They leave affected persons at risk for long-term effects. Nerve agents, such as tabun, sarin, soman, and VX, hyperstimulate the muscarinic and nicotinic receptors of the nervous system. Physicians need to familiarize themselves with the clinical findings of such exposures and the decontamination and treatment strategies necessary to minimize injuries and deaths.

Regeneration of anion exchange resins by catalyzed electrochemical reduction

DOEpatents

Gu, Baohua; Brown, Gilbert M.

2002-01-01

Anion exchange resins sorbed with perchlorate may be regenerated by a combination of chemical reduction of perchlorate to chloride using a reducing agent and an electrochemical reduction of the oxidized reducing agent. Transitional metals including Ti, Re, and V are preferred chemical reagents for the reduction of perchlorate to chloride. Complexing agents such as oxalate are used to prevent the precipitation of the oxidized Ti(IV) species, and ethyl alcohol may be added to accelerate the reduction kinetics of perchlorate. The regeneration may be performed by continuously recycling the regenerating solution through the resin bed and an electrochemical cell so that the secondary waste generation is minimized.

Extended Neural Metastability in an Embodied Model of Sensorimotor Coupling

PubMed Central

Aguilera, Miguel; Bedia, Manuel G.; Barandiaran, Xabier E.

2016-01-01

The hypothesis that brain organization is based on mechanisms of metastable synchronization in neural assemblies has been popularized during the last decades of neuroscientific research. Nevertheless, the role of body and environment for understanding the functioning of metastable assemblies is frequently dismissed. The main goal of this paper is to investigate the contribution of sensorimotor coupling to neural and behavioral metastability using a minimal computational model of plastic neural ensembles embedded in a robotic agent in a behavioral preference task. Our hypothesis is that, under some conditions, the metastability of the system is not restricted to the brain but extends to the system composed by the interaction of brain, body and environment. We test this idea, comparing an agent in continuous interaction with its environment in a task demanding behavioral flexibility with an equivalent model from the point of view of “internalist neuroscience.” A statistical characterization of our model and tools from information theory allow us to show how (1) the bidirectional coupling between agent and environment brings the system closer to a regime of criticality and triggers the emergence of additional metastable states which are not found in the brain in isolation but extended to the whole system of sensorimotor interaction, (2) the synaptic plasticity of the agent is fundamental to sustain open structures in the neural controller of the agent flexibly engaging and disengaging different behavioral patterns that sustain sensorimotor metastable states, and (3) these extended metastable states emerge when the agent generates an asymmetrical circular loop of causal interaction with its environment, in which the agent responds to variability of the environment at fast timescales while acting over the environment at slow timescales, suggesting the constitution of the agent as an autonomous entity actively modulating its sensorimotor coupling with the world. We conclude with a reflection about how our results contribute in a more general way to current progress in neuroscientific research. PMID:27721746

Extended Neural Metastability in an Embodied Model of Sensorimotor Coupling.

PubMed

Aguilera, Miguel; Bedia, Manuel G; Barandiaran, Xabier E

2016-01-01

The hypothesis that brain organization is based on mechanisms of metastable synchronization in neural assemblies has been popularized during the last decades of neuroscientific research. Nevertheless, the role of body and environment for understanding the functioning of metastable assemblies is frequently dismissed. The main goal of this paper is to investigate the contribution of sensorimotor coupling to neural and behavioral metastability using a minimal computational model of plastic neural ensembles embedded in a robotic agent in a behavioral preference task. Our hypothesis is that, under some conditions, the metastability of the system is not restricted to the brain but extends to the system composed by the interaction of brain, body and environment. We test this idea, comparing an agent in continuous interaction with its environment in a task demanding behavioral flexibility with an equivalent model from the point of view of "internalist neuroscience." A statistical characterization of our model and tools from information theory allow us to show how (1) the bidirectional coupling between agent and environment brings the system closer to a regime of criticality and triggers the emergence of additional metastable states which are not found in the brain in isolation but extended to the whole system of sensorimotor interaction, (2) the synaptic plasticity of the agent is fundamental to sustain open structures in the neural controller of the agent flexibly engaging and disengaging different behavioral patterns that sustain sensorimotor metastable states, and (3) these extended metastable states emerge when the agent generates an asymmetrical circular loop of causal interaction with its environment, in which the agent responds to variability of the environment at fast timescales while acting over the environment at slow timescales, suggesting the constitution of the agent as an autonomous entity actively modulating its sensorimotor coupling with the world. We conclude with a reflection about how our results contribute in a more general way to current progress in neuroscientific research.

Toxicity Minimized Cryoprotectant Addition and Removal Procedures for Adherent Endothelial Cells

PubMed Central

Davidson, Allyson Fry; Glasscock, Cameron; McClanahan, Danielle R.; Benson, James D.; Higgins, Adam Z.

2015-01-01

Ice-free cryopreservation, known as vitrification, is an appealing approach for banking of adherent cells and tissues because it prevents dissociation and morphological damage that may result from ice crystal formation. However, current vitrification methods are often limited by the cytotoxicity of the concentrated cryoprotective agent (CPA) solutions that are required to suppress ice formation. Recently, we described a mathematical strategy for identifying minimally toxic CPA equilibration procedures based on the minimization of a toxicity cost function. Here we provide direct experimental support for the feasibility of these methods when applied to adherent endothelial cells. We first developed a concentration- and temperature-dependent toxicity cost function by exposing the cells to a range of glycerol concentrations at 21°C and 37°C, and fitting the resulting viability data to a first order cell death model. This cost function was then numerically minimized in our state constrained optimization routine to determine addition and removal procedures for 17 molal (mol/kg water) glycerol solutions. Using these predicted optimal procedures, we obtained 81% recovery after exposure to vitrification solutions, as well as successful vitrification with the relatively slow cooling and warming rates of 50°C/min and 130°C/min. In comparison, conventional multistep CPA equilibration procedures resulted in much lower cell yields of about 10%. Our results demonstrate the potential for rational design of minimally toxic vitrification procedures and pave the way for extension of our optimization approach to other adherent cell types as well as more complex systems such as tissues and organs. PMID:26605546

Development of a QDots 800 based fluorescent solid phantom for validation of NIRF imaging platforms

NASA Astrophysics Data System (ADS)

Zhu, Banghe; Sevick-Muraca, Eva M.

2013-02-01

Over the past decade, we developed near-infrared fluorescence (NIRF) devices for non-invasive lymphatic imaging using microdosages of ICG in humans and for detection of lymph node metastasis in animal models mimicking metastatic human prostate cancer. To validate imaging, a NIST traceable phantom is needed so that developed "first-inhumans" drugs may be used with different luorescent imaging platforms. In this work, we developed a QDots 800 based fluorescent solid phantom for installation and operational qualification of clinical and preclinical, NIRF imaging devices. Due to its optical clearance, polyurethane was chosen as the base material. Titanium dioxide was used as the scattering agent because of its miscibility in polyurethane. QDots 800 was chosen owing to its stability and NIR emission spectra. A first phantom was constructed for evaluation of the noise floor arising from excitation light leakage, a phenomenon that can be minimized during engineering and design of fluorescent imaging systems. A second set of phantoms were constructed to enable quantification of device sensitivity associated with our preclinical and clinical devices. The phantoms have been successfully applied for installation and operational qualification of our preclinical and clinical devices. Assessment of excitation light leakage provides a figure of merit for "noise floor" and imaging sensitivity can be used to benchmark devices for specific imaging agents.

Treating pain on skin graft donor sites: Review and clinical recommendations.

PubMed

Sinha, Sarthak; Schreiner, Amanda J; Biernaskie, Jeff; Nickerson, Duncan; Gabriel, Vincent A

2017-11-01

Split-thickness skin grafting is the most common reconstructive procedure in managing burn injuries. Harvesting split-thickness skin creates a new partial thickness wound referred to as the donor site. Pain at the donor site is reported to be one of the most distressing symptoms during the early postoperative period. Here, we (a) identify strategies for managing donor site pain, (b) assess the quality of individual studies, and (c) formulate evidence-based recommendations based on the amount and consistency of evidence. Our analysis revealed five distinct approaches to minimize donor site pain. These include: continuous subcutaneous local anesthetic infusion (three studies), subcutaneous anesthetic injection (five studies), topical agents (six studies), nonpharmacological interventions (three studies), and wound dressings (18 studies). Available randomized control trials typically evaluated pain on standardized scales (i.e. Visual Analog Scale, Numerical Rating Scale), and compared the experimental group with standard care. Recommended treatments include: (a) subcutaneous anesthetic injection of adrenaline-lidocaine; (b) ice application; (c) topical agents, such as lidocaine and bupivacaine; and (d) hydrocolloid- and polyurethane-based wound dressings accompanied with fibrin sealant. Methodologically sound randomized control trials examining the efficacy of modified tumescent solution, ropivacaine, plasma therapy, noncontact ultrasound, and morphine gels are lacking and should be a priority for future research.

Reactive hydroxyapatite fillers for pectin biocomposites.

PubMed

Munarin, Fabiola; Petrini, Paola; Barcellona, Giulia; Roversi, Tommaso; Piazza, Laura; Visai, Livia; Tanzi, Maria Cristina

2014-12-01

In this work, a novel injectable biocomposite hydrogel is produced by internal gelation, using pectin as organic matrix and hydroxyapatite either as crosslinking agent and inorganic reinforcement. Tunable gelling kinetics and rheological properties are obtained varying the hydrogels' composition, with the final aim of developing systems for cell immobilization. The reversibility by dissolution of pectin-hydroxyapatite hydrogels is achieved with saline solutions, to possibly accelerate the release of the cells or active agents immobilized. Texture analysis confirms the possibility of extruding the biocomposites from needles with diameters from 20 G to 30 G, indicating that they can be implanted with minimally-invasive approaches, minimizing the pain during injection and the side effects of the open surgery. L929 fibroblasts entrapped in the hydrogels survive to the immobilization procedure and exhibit high cell viability. On the overall, these systems result to be suitable supports for the immobilization of cells for tissue regeneration applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Innovative Ingredients and Emerging Technologies for Controlling Ice Recrystallization, Texture, and Structure Stability in Frozen Dairy Desserts: A Review.

PubMed

Soukoulis, Christos; Fisk, Ian

2016-11-17

Over the past decade, ice cream manufacturers have developed a strong understanding of the functionality of key ingredients and processing, developing effective explanations for the link between structure forming agents, stability mechanisms, and perceived quality. Increasing demand for products perceived as healthier/more natural with minimal processing has identified a number of new tools to improve quality and storage stability of frozen dairy desserts. Ingredients such as dietary fiber, polysaccharides, prebiotics, alternate sweeteners, fat sources rich in unsaturated fatty acids and ice strucsturing proteins (ISP) have been successfully applied as cryoprotective, texturizing, and structuring agents. Emerging minimal processing technologies including hydrostatic pressure processing, ultrasonic or high pressure assisted freezing, low temperature extrusion and enzymatically induced biopolymers crosslinking have been evaluated for their ability to improve colloidal stability, texture and sensory quality. It is therefore timely for a comprehensive review.

Safety of the breast-feeding infant after maternal anesthesia.

PubMed

Dalal, Priti G; Bosak, Jodi; Berlin, Cheston

2014-04-01

There has been an increase in breast-feeding supported by the recommendations of the American Academy of Pediatrics and the World Health Organization. An anesthesiologist may be presented with a well-motivated breast-feeding mother who wishes to breast-feed her infant in the perioperative period. Administration of anesthesia entails acute administration of drugs with potential for sedation and respiratory effects on the nursing infant. The short-term use of these drugs minimizes the possibility of these effects. The aim should be to minimize the use of narcotics and benzodiazepines, use shorter acting agents, use regional anesthesia where possible and avoid agents with active metabolites. Frequent clinical assessments of the nursing infant are important. Available literature does suggest that although the currently available anesthetic and analgesic drugs are transferred in the breast milk, the amounts transferred are almost always clinically insignificant and pose little or no risk to the nursing infant. © 2013 John Wiley & Sons Ltd.

Molecular dynamics simulation analysis of Focal Adhesive Kinase (FAK) docked with solanesol as an anti-cancer agent

PubMed Central

Daneial, Betty; Joseph, Jacob Paul Vazhappilly; Ramakrishna, Guruprasad

2017-01-01

Focal adhesion kinase (FAK) plays a primary role in regulating the activity of many signaling molecules. Increased FAK expression has been associated in a series of cellular processes like cell migration and survival. FAK inhibition by an anti cancer agent is critical. Therefore, it is of interest to identify, modify, design, improve and develop molecules to inhibit FAK. Solanesol is known to have inhibitory activity towards FAK. However, the molecular principles of its binding with FAK is unknown. Solanesol is a highly flexible ligand (25 rotatable bonds). Hence, ligand-protein docking was completed using AutoDock with a modified contact based scoring function. The FAK-solanesol complex model was further energy minimized and simulated in GROMOS96 (53a6) force field followed by post simulation analysis such as Root mean square deviation (RMSD), root mean square fluctuations (RMSF) and solvent accessible surface area (SASA) calculations to explain solanesol-FAK binding. PMID:29081606

Coordinated single-phase control scheme for voltage unbalance reduction in low voltage network.

PubMed

Pullaguram, Deepak; Mishra, Sukumar; Senroy, Nilanjan

2017-08-13

Low voltage (LV) distribution systems are typically unbalanced in nature due to unbalanced loading and unsymmetrical line configuration. This situation is further aggravated by single-phase power injections. A coordinated control scheme is proposed for single-phase sources, to reduce voltage unbalance. A consensus-based coordination is achieved using a multi-agent system, where each agent estimates the averaged global voltage and current magnitudes of individual phases in the LV network. These estimated values are used to modify the reference power of individual single-phase sources, to ensure system-wide balanced voltages and proper power sharing among sources connected to the same phase. Further, the high X / R ratio of the filter, used in the inverter of the single-phase source, enables control of reactive power, to minimize voltage unbalance locally. The proposed scheme is validated by simulating a LV distribution network with multiple single-phase sources subjected to various perturbations.This article is part of the themed issue 'Energy management: flexibility, risk and optimization'. © 2017 The Author(s).

Controversies in Alzheimer's disease drug development.

PubMed

Cummings, Jeffrey L

2008-08-01

Understanding of the pathophysiological basis of Alzheimer's disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer's disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described.

Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients.

PubMed

Mehta-Shah, Neha; Bartlett, Nancy L

2018-04-12

Addition of brentuximab vedotin, a CD30-targeted antibody-drug conjugate, and the programmed death 1 (PD-1) inhibitors nivolumab and pembrolizumab to the armamentarium for transplant-ineligible relapsed/refractory classical Hodgkin lymphoma has resulted in improved outcomes, including the potential for cure in a small minority of patients. For patients who have failed prior transplant or are unsuitable for dose-intense approaches based on age or comorbidities, an individualized approach with sequential use of single agents such as brentuximab vedotin, PD-1 inhibitors, everolimus, lenalidomide, or conventional agents such as gemcitabine or vinorelbine may result in prolonged survival with a minimal or modest effect on quality of life. Participation in clinical trials evaluating new approaches such as combination immune checkpoint inhibition, novel antibody-drug conjugates, or cellular therapies such as Epstein-Barr virus-directed cytotoxic T lymphocytes and chimeric antigen receptor T cells offer additional options for eligible patients. © 2018 by The American Society of Hematology.

Molecular dynamics simulation analysis of Focal Adhesive Kinase (FAK) docked with solanesol as an anti-cancer agent.

PubMed

Daneial, Betty; Joseph, Jacob Paul Vazhappilly; Ramakrishna, Guruprasad

2017-01-01

Focal adhesion kinase (FAK) plays a primary role in regulating the activity of many signaling molecules. Increased FAK expression has been associated in a series of cellular processes like cell migration and survival. FAK inhibition by an anti cancer agent is critical. Therefore, it is of interest to identify, modify, design, improve and develop molecules to inhibit FAK. Solanesol is known to have inhibitory activity towards FAK. However, the molecular principles of its binding with FAK is unknown. Solanesol is a highly flexible ligand (25 rotatable bonds). Hence, ligand-protein docking was completed using AutoDock with a modified contact based scoring function. The FAK-solanesol complex model was further energy minimized and simulated in GROMOS96 (53a6) force field followed by post simulation analysis such as Root mean square deviation (RMSD), root mean square fluctuations (RMSF) and solvent accessible surface area (SASA) calculations to explain solanesol-FAK binding.

Intravenous Imaging Contrast Media Complications: The Basics That Every Clinician Needs to Know.

PubMed

Rose, Trevor A; Choi, Jung W

2015-09-01

Intravenous contrast is commonly used in noninvasive imaging procedures such as magnetic resonance imaging and computed tomography and can evaluate blood vessels and better characterize soft-tissue lesions. Although the incidence of adverse events after administration of contrast is low, it is important that clinicians and radiologists minimize risks and respond quickly and effectively when reactions occur. We will discuss a range of adverse events to iodinated and gadolinium-based contrast agents, including allergic-like reactions, nephrotoxicity, extravasation, and nephrogenic systemic fibrosis. We will review risk stratification for patients, as well as premedication and treatment of adverse events. Copyright © 2015 Elsevier Inc. All rights reserved.

Fleet Assignment Using Collective Intelligence

NASA Technical Reports Server (NTRS)

Antoine, Nicolas E.; Bieniawski, Stefan R.; Kroo, Ilan M.; Wolpert, David H.

2004-01-01

Airline fleet assignment involves the allocation of aircraft to a set of flights legs in order to meet passenger demand, while satisfying a variety of constraints. Over the course of the day, the routing of each aircraft is determined in order to minimize the number of required flights for a given fleet. The associated flow continuity and aircraft count constraints have led researchers to focus on obtaining quasi-optimal solutions, especially at larger scales. In this paper, the authors propose the application of an agent-based integer optimization algorithm to a "cold start" fleet assignment problem. Results show that the optimizer can successfully solve such highly- constrained problems (129 variables, 184 constraints).

QSAR models for describing the toxicological effects of ILs against Staphylococcus aureus based on norm indexes.

PubMed

He, Wensi; Yan, Fangyou; Jia, Qingzhu; Xia, Shuqian; Wang, Qiang

2018-03-01

The hazardous potential of ionic liquids (ILs) is becoming an issue of great concern due to their important role in many industrial fields as green agents. The mathematical model for the toxicological effects of ILs is useful for the risk assessment and design of environmentally benign ILs. The objective of this work is to develop QSAR models to describe the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of ILs against Staphylococcus aureus (S. aureus). A total of 169 and 101 ILs with MICs and MBCs, respectively, are used to obtain multiple linear regression models based on matrix norm indexes. The norm indexes used in this work are proposed by our research group and they are first applied to estimate the antibacterial toxicity of these ILs against S. aureus. These two models precisely and reliably calculated the IL toxicities with a square of correlation coefficient (R 2 ) of 0.919 and a standard error of estimate (SE) of 0.341 (in log unit of mM) for pMIC, and an R 2 of 0.913 and SE of 0.282 for pMBC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

NASA Astrophysics Data System (ADS)

Shalviri, Alireza

The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in controlled delivery applications of larger molecular size compounds. The starch based hydrogels, polymers and nanoparticles developed in this work have shown great potentials for controlled drug delivery and biomedical imaging applications.

Gold-nanoparticle-based theranostic agents for radiotherapy of malignant solid tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina

Radiation therapy is one of the three major methods of cancer treatment. The fundamental goal of radiotherapy is to deliver high radiation doses to targets while simultaneously minimizing doses to critical structures and healthy normal tissues. The aim of this study is to develop a general, practical, and facile method to prepare nanoscale theranostic agents for more efficacious radiation therapy with less adverse side effects. First, a novel type of gold nanoparticle, hollow Au nanoparticles (HAuNPs) which was synthesized using the unique bubble template synthesis method developed in our lab, are studied in vitro and in vivo to investigate their effect as radiosensitizing agents to enhance the radiation dose during external radiotherapy. The results showed the promising potential of using HAuNPs as radiosensitization agents for efficacious treatment of breast cancer. Second, a novel radiolabeling method is developed to incorporate medical radioisotopes to gold nanoparticles. We incorporate palladium-103 (103Pd), a radioisotope currently in clinical brachytherapy, into a hollow gold nanoparticle. The resulting 103Pd Au nanoparticles in the form of a colloidal suspension can be administered by direct injection into tumors, serving as internal radiation sources (nanoseeds) for radiation therapy. The size of the nanoseed, 150nm in diameter, is large enough to prevent nanoseeds from diffusing into other areas while still small enough to allow them to homogeneously distribute inside the tumor. The therapeutic efficacy of 103Pd Au nanoseeds have been tested when intratumorally injected into a prostate cancer xenograft model. The findings showed that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors. Finally, to make real clinical application more plausible, multi-functional magnetic nanoseeds nanoparticles for imaging-guided radiotherapy are synthesized and characterized.

Natural-product-based chromenes as a novel class of potential termiticides.

PubMed

Meepagala, Kumudini M; Osbrink, Weste; Burandt, Charles; Lax, Alan; Duke, Stephen O

2011-11-01

Among the termite infestations in the United States, the Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), is considered to be the most devastating termite pest. This pest most likely invaded North America as a result of the disembarkation of wooden military cargo at the port of New Orleans that arrived from Asia during and after World War II. It has now spread over other states, including Texas, Florida, South Carolina and California. Devastation caused by C. formosanus in North America has been estimated to cost $ US 1 billion a year. Over the past decades, organochlorines and organophosphates, the two prominent classes of termite control agents, have been banned owing to environmental and human health concerns. At the present time, phenylpyrazoles, pyrethroids, chloronicotinyls and pyrroles are being used as termite control agents. Mammalian toxicity and seeping of these compounds into groundwater are some of the drawbacks associated with these treatments. The instruction for the application of these termiticides indicate ground water advisory. Hence, with the increasing spread of termite infestation there is an increased need to discover effective, environmentally friendly and safe termite control agents with minimal mammalian toxicity. Chromene analogs derived from a natural-product-based chromene amide isolated from Amyris texana were tested in a collaborative discovery program for effective, environmentally friendly termite control agents. Several chromene derivatives were synthesized and characterized as a novel class of potential termiticides, followed by bioassays. These compounds exhibited significantly higher mortalities compared with untreated controls in laboratory bioassays. Chromene derivatives have been shown to be a potential novel class of termiticides against Formosan subterranean termites. Copyright © 2011 Society of Chemical Industry.

The efficacy of eutectic mixture of local anesthetics as a topical anesthetic agent used for dental procedures: A brief review

PubMed Central

Daneshkazemi, Alireza; Abrisham, Seyyed Mohammad; Daneshkazemi, Pedram; Davoudi, Amin

2016-01-01

Dental pain management is one of the most critical aspects of modern dentistry which might affect patient's quality of life. Several methods are suggested to provide a painless situation for patients. Desensitization of the oral site using topical anesthetics is one of those methods. The improvements of topical anesthetic agents are probably one of the most important advances in dental science in the past 100 years. Most of them are safe and can be applied on oral mucosa with minimal irritation and allergic reactions. At present, these agents are various with different potent and indications. Eutectic mixture of local anesthetics (EMLA) (lidocaine + prilocaine) is a commercial anesthetic agent which has got acceptance among dental clinicians. This article provides a brief review about the efficacy of EMLA as a topical anesthetic agent when used during dental procedures. PMID:27746520

The efficacy of eutectic mixture of local anesthetics as a topical anesthetic agent used for dental procedures: A brief review.

PubMed

Daneshkazemi, Alireza; Abrisham, Seyyed Mohammad; Daneshkazemi, Pedram; Davoudi, Amin

2016-01-01

Dental pain management is one of the most critical aspects of modern dentistry which might affect patient's quality of life. Several methods are suggested to provide a painless situation for patients. Desensitization of the oral site using topical anesthetics is one of those methods. The improvements of topical anesthetic agents are probably one of the most important advances in dental science in the past 100 years. Most of them are safe and can be applied on oral mucosa with minimal irritation and allergic reactions. At present, these agents are various with different potent and indications. Eutectic mixture of local anesthetics (EMLA) (lidocaine + prilocaine) is a commercial anesthetic agent which has got acceptance among dental clinicians. This article provides a brief review about the efficacy of EMLA as a topical anesthetic agent when used during dental procedures.

Complexity Management Using Metrics for Trajectory Flexibility Preservation and Constraint Minimization

NASA Technical Reports Server (NTRS)

Idris, Husni; Shen, Ni; Wing, David J.

2011-01-01

The growing demand for air travel is increasing the need for mitigating air traffic congestion and complexity problems, which are already at high levels. At the same time new surveillance, navigation, and communication technologies are enabling major transformations in the air traffic management system, including net-based information sharing and collaboration, performance-based access to airspace resources, and trajectory-based rather than clearance-based operations. The new system will feature different schemes for allocating tasks and responsibilities between the ground and airborne agents and between the human and automation, with potential capacity and cost benefits. Therefore, complexity management requires new metrics and methods that can support these new schemes. This paper presents metrics and methods for preserving trajectory flexibility that have been proposed to support a trajectory-based approach for complexity management by airborne or ground-based systems. It presents extensions to these metrics as well as to the initial research conducted to investigate the hypothesis that using these metrics to guide user and service provider actions will naturally mitigate traffic complexity. The analysis showed promising results in that: (1) Trajectory flexibility preservation mitigated traffic complexity as indicated by inducing self-organization in the traffic patterns and lowering traffic complexity indicators such as dynamic density and traffic entropy. (2)Trajectory flexibility preservation reduced the potential for secondary conflicts in separation assurance. (3) Trajectory flexibility metrics showed potential application to support user and service provider negotiations for minimizing the constraints imposed on trajectories without jeopardizing their objectives.

Structure Dependence of Lysosomal Transit of Chitosan-Based Polyplexes for Gene Delivery.

PubMed

Thibault, Marc; Lavertu, Marc; Astolfi, Mélina; Buschmann, Michael D

2016-10-01

Chitosan-based polyplexes are known to traffic through lysosomes for a relatively long time, independent of the degree of deacetylation (DDA) and the number average molecular weight (Mn) of the polymer, even though both of these parameters have profound effects on polyplex stability and transfection efficiency. A better understanding of the lysosomal barrier is paramount to the rational design of vectors capable of overcoming obstacles to transgene expression. The aim of the present study was to investigate if lysosomal transit affects chitosan-based polyplex transfection efficiency in a structure-dependent (DDA, Mn) manner. Toward this end, we analyzed the effects of intracellular trafficking modifying agents on transfection efficiency and intracellular vesicular trafficking of polyplexes with different structural properties and stabilities or nucleic acid binding affinity. The use of agents that modify endosome/lysosome acidification and transit processes by distinct mechanisms and their effect on cell viability, polyplex uptake, vesicular trafficking, and transfection efficiency revealed novel and strong chitosan structure-dependent consequences of lysosomal transit. Inhibiting lysosomal transit using chloroquine significantly increased the efficiency of unstable polyplexes, while having minimal effects for polyplexes with intermediate or high stability. In parallel, specifically inhibiting the acidification of vesicles abrogated transfection for all formulations, suggesting that vesicular acidification is essential to promote transfection, most probably by facilitating lysosomal escape. These results provide novel insights into the structure-performance relationship of chitosan-based gene delivery systems.

Toxic-Waste Disposal by Combustion in Containers

NASA Technical Reports Server (NTRS)

Houseman, J.; Stephens, J. B.; Moynihan, P. I.; Compton, L. E.; Kalvinskas, J. J.

1986-01-01

Chemical wastes burned with minimal handling in storage containers. Technique for disposing of chemical munitions by burning them inside shells applies to disposal of toxic materials stored in drums. Fast, economical procedure overcomes heat-transfer limitations of conventional furnace designs by providing direct contact of oxygenrich combustion gases with toxic agent. No need to handle waste material, and container also decontaminated in process. Oxygen-rich torch flame cuts burster well and causes vaporization and combustion of toxic agent contained in shell.

Relativistic quantum cryptography

NASA Astrophysics Data System (ADS)

Kaniewski, Jedrzej

Special relativity states that information cannot travel faster than the speed of light, which means that communication between agents occupying distinct locations incurs some minimal delay. Alternatively, we can see it as temporary communication constraints between distinct agents and such constraints turn out to be useful for cryptographic purposes. In relativistic cryptography we consider protocols in which interactions occur at distinct locations at well-defined times and we investigate why such a setting allows to implement primitives which would not be possible otherwise. (Abstract shortened by UMI.).

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

PubMed

Döhner, Hartmut; Estey, Elihu; Grimwade, David; Amadori, Sergio; Appelbaum, Frederick R; Büchner, Thomas; Dombret, Hervé; Ebert, Benjamin L; Fenaux, Pierre; Larson, Richard A; Levine, Ross L; Lo-Coco, Francesco; Naoe, Tomoki; Niederwieser, Dietger; Ossenkoppele, Gert J; Sanz, Miguel; Sierra, Jorge; Tallman, Martin S; Tien, Hwei-Fang; Wei, Andrew H; Löwenberg, Bob; Bloomfield, Clara D

2017-01-26

The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease. © 2017 by The American Society of Hematology.

Photodynamic characterization and optimization using multifunctional nanoparticles for brain cancer treatment

NASA Astrophysics Data System (ADS)

Herrmann, Kristen; Lee Koo, Yong-Eun; Orringer, Daniel A.; Sagher, Oren; Philbert, Martin; Kopelman, Raoul

2013-03-01

Photosensitizer-conjugated polyacrylamide nanoparticles were prepared for in vivo characterization of the minimally invasive and localized treatment of photodynamic therapy (PDT) on brain tumors. By incorporating a variety of nanoparticle matrixes, choosing methylene blue as a photosensitizer, and targeting the nanoparticle by the use of F3 peptide we have made nanoparticle-based PDT improvements to current PDT efficiency. Quantitative growth patterns were determined through visual observation of the tumorigenic response to various treatments by the use of an animal cranial window model. PDT treatments with methylene blue-polyacrylamide (MB-PAA) nanoparticles produced significant adjournment of tumor growth over control groups, clearly demonstrating the advantages of nanoparticle-based PDT agents for the eradication of local tumors, leading to the potential palliation of the advancing disease.

Effect of Two Cancer Chemotherapeutic Agents on the Antibacterial Activity of Three Antimicrobial Agents

PubMed Central

Moody, Marcia R.; Morris, Maureen J.; Young, Viola Mae; Moyé, Lemuel A.; Schimpff, Stephen C.; Wiernik, Peter H.

1978-01-01

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli. This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside. PMID:103494

Optimum shape control of flexible beams by piezo-electric actuators

NASA Technical Reports Server (NTRS)

Baz, A.; Poh, S.

1987-01-01

The utilization of piezoelectric actuators in controlling the static deformation and shape of flexible beams is examined. An optimum design procedure is presented to enable the selection of the optimal location, thickness and excitation voltage of the piezoelectric actuators in a way that would minimize the deflection of the beam to which these actuators are bonded. Numerical examples are presented to illustrate the application of the developed optimization procedure in minimizing structural deformation of beams using ceramic and polymeric piezoelectric actuators bonded to the beams with a typical bonding agent. The obtained results emphasize the importance of the devised rational produce in designing beam-actuator systems with minimal elastic distortions.

Minimally invasive convection-enhanced delivery of biologics into dorsal root ganglia: validation in the pig model and prospective modeling in humans. Technical note.

PubMed

Pleticha, Josef; Maus, Timothy P; Christner, Jodie A; Marsh, Michael P; Lee, Kendall H; Hooten, W Michael; Beutler, Andreas S

2014-10-01

Dorsal root ganglia (DRG) are critical anatomical structures involved in nociception. Intraganglionic (IG) drug delivery is therefore an important route of administration for novel analgesic therapies. Although IG injection in large animal models is highly desirable for preclinical biodistribution and toxicology studies of new drugs, no method to deliver pharmaceutical agents into the DRG has been reported in any large species. The present study describes a minimally invasive technique of IG agent delivery in domestic swine, one of the most common large animal models. The technique utilizes CT guidance for DRG targeting and a custom-made injection assembly for convection enhanced delivery (CED) of therapeutic agents directly into DRG parenchyma. The DRG were initially visualized by CT myelography to determine the optimal access route to the DRG. The subsequent IG injection consisted of 3 steps. First, a commercially available guide needle was advanced to a position dorsolateral to the DRG, and the dural root sleeve was punctured, leaving the guide needle contiguous with, but not penetrating, the DRG. Second, the custom-made stepped stylet was inserted through the guide needle into the DRG parenchyma. Third, the stepped stylet was replaced by the custom-made stepped needle, which was used for the IG CED. Initial dye injections performed in pig cadavers confirmed the accuracy of DRG targeting under CT guidance. Intraganglionic administration of adeno-associated virus in vivo resulted in a unilateral transduction of the injected DRG, with 33.5% DRG neurons transduced. Transgene expression was also found in the dorsal root entry zones at the corresponding spinal levels. The results thereby confirm the efficacy of CED by the stepped needle and a selectivity of DRG targeting. Imaging-based modeling of the procedure in humans suggests that IG CED may be translatable to the clinical setting.

Anaerobic Toxicity of Cationic Silver Nanoparticles

EPA Science Inventory

The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag⁺ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged p...

On the application of copula in modeling maintenance contract

NASA Astrophysics Data System (ADS)

Iskandar, B. P.; Husniah, H.

2016-02-01

This paper deals with the application of copula in maintenance contracts for a nonrepayable item. Failures of the item are modeled using a two dimensional approach where age and usage of the item and this requires a bi-variate distribution to modelling failures. When the item fails then corrective maintenance (CM) is minimally repaired. CM can be outsourced to an external agent or done in house. The decision problem for the owner is to find the maximum total profit whilst for the agent is to determine the optimal price of the contract. We obtain the mathematical models of the decision problems for the owner as well as the agent using a Nash game theory formulation.

Susceptibility of Pittsburgh pneumonia agent (Legionella micdadei) and other newly recognized members of the genus Legionella to nineteen antimicrobial agents.

PubMed Central

Pasculle, A W; Dowling, J N; Weyant, R S; Sniffen, J M; Cordes, L G; Gorman, G M; Feeley, J C

1981-01-01

The susceptibilities of 11 strains representing the five recognized species of Legionella were determined by agar dilution testing on buffered charcoal-yeast extract agar. All of the legionellae tested were susceptible to rifampin, erythromycin, rosaramycin, chloramphenicol, and the aminoglycosides and were resistant to clindamycin and vancomycin. Susceptibilities to penicillins and cephalosporins were variable. Legionella micdadei, Legionella bozemanii, and Legionella gormanii were susceptible to these agents, but minimal inhibitory concentrations for each species were different. Legionella dumoffii resembled Legionella pneumophila in being resistant to penicillin, cephalothin, and cephamandole and susceptible to moxalactam and cefoxitin. All species except L. micdadei produced beta-lactamase. PMID:7325645

A New Method of Comparing Forcing Agents in Climate Models

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

Kravitz, Benjamin S.; MacMartin, Douglas; Rasch, Philip J.

We describe a new method of comparing different climate forcing agents (e.g., CO2, CH4, and solar irradiance) that avoids many of the ambiguities introduced by temperature-related climate feedbacks. This is achieved by introducing an explicit feedback loop external to the climate model that adjusts one forcing agent to balance another while keeping global mean surface temperature constant. Compared to current approaches, this method has two main advantages: (i) the need to define radiative forcing is bypassed and (ii) by maintaining roughly constant global mean temperature, the effects of state dependence on internal feedback strengths are minimized. We demonstrate this approachmore » for several different forcing agents and derive the relationships between these forcing agents in two climate models; comparisons between forcing agents are highly linear in concordance with predicted functional forms. Transitivity of the relationships between the forcing agents appears to hold within a wide range of forcing. The relationships between the forcing agents obtained from this method are consistent across both models but differ from relationships that would be obtained from calculations of radiative forcing, highlighting the importance of controlling for surface temperature feedback effects when separating radiative forcing and climate response.« less

Optimal Routing and Control of Multiple Agents Moving in a Transportation Network and Subject to an Arrival Schedule and Separation Constraints

NASA Technical Reports Server (NTRS)

Sadovsky, A. V.; Davis, D.; Isaacson, D. R.

2012-01-01

We address the problem of navigating a set of moving agents, e.g. automated guided vehicles, through a transportation network so as to bring each agent to its destination at a specified time. Each pair of agents is required to be separated by a minimal distance, generally agent-dependent, at all times. The speed range, initial position, required destination, and required time of arrival at destination for each agent are assumed provided. The movement of each agent is governed by a controlled differential equation (state equation). The problem consists in choosing for each agent a path and a control strategy so as to meet the constraints and reach the destination at the required time. This problem arises in various fields of transportation, including Air Traffic Management and train coordination, and in robotics. The main contribution of the paper is a model that allows to recast this problem as a decoupled collection of problems in classical optimal control and is easily generalized to the case when inertia cannot be neglected. Some qualitative insight into solution behavior is obtained using the Pontryagin Maximum Principle. Sample numerical solutions are computed using a numerical optimal control solver.

Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Feng, Yi

Macromolecular contrast agents have been shown to be superior to small molecular weight contrast agents for MRI in blood pool imaging, tumor diagnosis and grading. However, none has been approved by the FDA because they circulate in the bloodstream much longer than small molecular weight contrast agents and result in high tissue accumulation of toxic Gd(III) ions. Biodegradable macromolecular contrast agents (BMCA) were invented to alleviate the toxic accumulation. They have a cleavable disulfide bond based backbone that can be degraded in vivo and excreted out of the body via renal filtration. Furthermore, the side chain of the backbone can be modified to achieve various degradation rates. Three BMCA, (Gd-DTPA)-cystamine copolymers (GDCC), Gd-DTPA cystine copolymers (GDCP), and Gd-DTPA cystine diethyl ester copolymers (GDCEP), were evaluated as blood pool contrast agents in a rat model. They have excellent blood pool enhancement, preferred pharmacokinetics, and only minimal long-term tissue retention of toxic Gd(III) ions. GDCC and GDCP, the lead agents with desired degradation rates, with molecular weights of 20 KDa and 70 KDa, were chosen for dynamic contrast enhanced MRI (DCE-MRI) to differentiate human prostate tumor models of different malignancy and growth rates. GDCC and GDCP could differentiate these tumor models, providing more accurate estimations of plasma volume, flow leakage rate, and permeability surface area product than a small molecular weight contrast agent Gd-DTPA-BMA when compared to the prototype macromolecular contrast agent albumin-Gd-DTPA. GDCC was favored for its neutral charge side chain and reasonable uptake rate by the tumors. GDCC with a molecular weight of 40 KDa (GDCC-40, above the renal filtration cutoff size) was used to assess the efficacy of two photothermal therapies (interstitial and indocyanine green enhanced). GDCC-40 provided excellent tumor enhancement shortly after its injection. Acute tumor response (4 hr) after therapies was revealed by DCE-MRI using GDCC-40. The region of the tumor with suspicious uptake of GDCC-40 could be correlated to the residual tumor. With only minimum tissue accumulation, BMCA have applications in blood pool imaging, cancer diagnosis, and efficacy assessment of anticancer treatment. Therefore, BMCA are promising for clinical applications.

Using Business Process Specification and Agent to Integrate a Scenario Driven Supply Chain

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

Cho, Hyunbo; Kulvatunyou, Boonserm; Jeong, Hanil

2004-07-01

In today's increasingly competitive global market, most enterprises place high priority on reducing order-fulfillment costs, minimizing time-to-market, and maximizing product quality. The desire of businesses to achieve these goals has seen a shift from a make-to-stock paradigm to a make-to-order paradigm. The success of this new paradigm requires robust and efficient supply chain integration and the ability to operate in the business-to-business (B2B) environment. Recent internet-based approaches have enabled instantaneous and secure information sharing among trading partners (i.e., customers, manufacturers, and suppliers). In this paper, we present a framework that enables both integration and B2B operations. This framework uses pre-definedmore » business process specifications (BPS) and agent technologies. The BPS, which specifies a message choreography among the trading partners, is modeled using a modified Unified Modeling Language (UML). The behavior of the enterprise applications within each trading partner -- how they respond to external events specified in the BPS -- is modeled using Petri-nets and implemented as a collection of agents. The concepts and models proposed in this paper should provide the starting point for the formulation of a structured approach to B2B supply chain integration and implementation.« less

Updates on smart polymeric carrier systems for protein delivery.

PubMed

El-Sherbiny, Ibrahim; Khalil, Islam; Ali, Isra; Yacoub, Magdi

2017-10-01

Smart materials are those materials that are responsive to chemical (organic molecules, chemical agents or specific agents), biochemical (protein, enzymes, growth factors, substrates or ligands), physical (electric field, magnetic field, temperature, pH, ionic strength or radiation) or mechanical (pressure or mechanical stress) signals. These responsive materials interact with the stimuli by changing their properties or conformational structures in a predictable manner. Recently, smart polymers have been utilized in various biomedical applications. Particularly, they have been used as a platform to synthesize stimuli-responsive systems that could deliver therapeutics to a specific site for a specific period with minimal adverse effects. For instance, stimuli-responsive polymers-based systems have been recently reported to deliver different bioactive molecules such as carbohydrates (heparin), chemotherapeutic agents (doxorubicin), small organic molecules (anti-coagulants), nucleic acids (siRNA), and proteins (growth factors and hormones). Protein therapeutics played a fundamental role in treatment of various chronic and some autoimmune diseases. For instance insulin has been used in treatment of diabetes. However, being a protein in nature, insulin delivery is limited by its instability, short half-life, and easy denaturation when administered orally. To overcome these challenges, and as highlighted in this review article, much research efforts have been recently devoted to design and develop convenient smart controlled nanosystems for protein therapeutics delivery.

Dynamics of Complex Systems Built as Coupled Physical, Communication and Decision Layers

PubMed Central

Kühnlenz, Florian; Nardelli, Pedro H. J.

2016-01-01

This paper proposes a simple model to capture the complexity of multilayer systems where their constituent layers affect, and are affected by, each other. The physical layer is a circuit composed by a power source and resistors in parallel. Every individual agent aims at maximizing its own delivered power by adding, removing or keeping the resistors it has; the delivered power is in turn a non-linear function that depends on the other agents’ behavior, its own internal state, its global state perception, the information received from its neighbors via the communication network and a randomized selfishness. We develop an agent-based simulation to analyze the effects of number of agents (system size), communication network topology, communication errors and the minimum power gain that triggers a behavioral change on the system dynamic. Our results show that a wave-like behavior at macro-level (caused by individual changes in the decision layer) can only emerge for a specific system size. The ratio between cooperators and defectors depends on the minimum gain assumed—lower minimal gains lead to less cooperation, and vice-versa. Different communication network topologies imply different levels of power utilization and fairness at the physical layer, and a certain level of error in the communication layer induces more cooperation. PMID:26730590

Multi-Agent Flight Simulation with Robust Situation Generation

NASA Technical Reports Server (NTRS)

Johnson, Eric N.; Hansman, R. John, Jr.

1994-01-01

A robust situation generation architecture has been developed that generates multi-agent situations for human subjects. An implementation of this architecture was developed to support flight simulation tests of air transport cockpit systems. This system maneuvers pseudo-aircraft relative to the human subject's aircraft, generating specific situations for the subject to respond to. These pseudo-aircraft maneuver within reasonable performance constraints, interact in a realistic manner, and make pre-recorded voice radio communications. Use of this system minimizes the need for human experimenters to control the pseudo-agents and provides consistent interactions between the subject and the pseudo-agents. The achieved robustness of this system to typical variations in the subject's flight path was explored. It was found to successfully generate specific situations within the performance limitations of the subject-aircraft, pseudo-aircraft, and the script used.

Standardized Review and Approval Process for High-Cost Medication Use Promotes Value-Based Care in a Large Academic Medical System.

PubMed

Durvasula, Raghu; Kelly, Janet; Schleyer, Anneliese; Anawalt, Bradley D; Somani, Shabir; Dellit, Timothy H

2018-04-01

As healthcare costs rise and reimbursements decrease, healthcare organization leadership and clinical providers must collaborate to provide high-value healthcare. Medications are a key driver of the increasing cost of healthcare, largely as a result of the proliferation of expensive specialty drugs, including biologic agents. Such medications contribute significantly to the inpatient diagnosis-related group payment system, often with minimal or unproved benefit over less-expensive therapies. To describe a systematic review process to reduce non-evidence-based inpatient use of high-cost medications across a large multihospital academic health system. We created a Pharmacy & Therapeutics subcommittee consisting of clinicians, pharmacists, and an ethics representative. This committee developed a standardized process for a timely review (<48 hours) and approval of high-cost medications based on their clinical effectiveness, safety, and appropriateness. The engagement of clinical experts in the development of the consensus-based guidelines for the use of specific medications facilitated the clinicians' acceptance of the review process. Over a 2-year period, a total of 85 patient-specific requests underwent formal review. All reviews were conducted within 48 hours. This review process has reduced the non-evidence-based use of specialty medications and has resulted in a pharmacy savings of $491,000 in fiscal year 2016, with almost 80% of the savings occurring in the last 2 quarters, because our process has matured. The creation of a collaborative review process to ensure consistent, evidence-based utilization of high-cost medications provides value-based care, while minimizing unnecessary practice variation and reducing the cost of inpatient care.

Guidelines for safe handling of hazardous drugs: A systematic review

PubMed Central

Bernabeu-Martínez, Mari A.; Ramos Merino, Mateo; Santos Gago, Juan M.; Álvarez Sabucedo, Luis M.; Wanden-Berghe, Carmina

2018-01-01

Objective To review the scientific literature related to the safe handling of hazardous drugs (HDs). Method Critical analysis of works retrieved from MEDLINE, the Cochrane Library, Scopus, CINHAL, Web of Science and LILACS using the terms "Hazardous Substances", "Antineoplastic Agents" and "Cytostatic Agents", applying "Humans" and "Guidelines" as filters. Date of search: January 2017. Results In total, 1100 references were retrieved, and from those, 61 documents were selected based on the inclusion and exclusion criteria: 24 (39.3%) documents related to recommendations about HDs; 27 (44.3%) about antineoplastic agents, and 10 (33.3%) about other types of substances (monoclonal antibodies, gene medicine and other chemical and biological agents). In 14 (23.3%) guides, all the stages in the manipulation process involving a risk due to exposure were considered. Only one guide addressed all stages of the handling process of HDs (including stages with and without the risk of exposure). The most described stages were drug preparation (41 guides, 67.2%), staff training and/or patient education (38 guides, 62.3%), and administration (37 guides, 60.7%). No standardized informatics system was found that ensured quality management, traceability and minimization of the risks associated with these drugs. Conclusions Most of the analysed guidelines limit their recommendations to the manipulation of antineoplastics. The most frequently described activities were preparation, training, and administration. It would be convenient to apply ICTs (Information and Communications Technologies) to manage processes involving HDs in a more complete and simpler fashion. PMID:29750798

Methodological assessment of the reduction of the content of impurities in nimodipine emulsion via the use of 21 amino acid protection

PubMed Central

Xie, Yiqiao; Zhuang, Zhiquan; Zhang, Shu; Xia, Zihua; Chen, De; Fan, Kaiyan; Ren, Jialin; Lin, CuiCui; Chen, Yanzhong; Yang, Fan

2017-01-01

Purpose The present study examined the factors affecting the content of impurities of nimodipine (NMP) emulsion and the associated methods of compound protection. Methods Destructive testing of NMP emulsion and its active pharmaceutical ingredient (API) were conducted, and ultracentrifugation was used to study the content of impurities in two phases. The impurity of NMP was measured under different potential of hydrogen (pH) conditions, antioxidants and pH-adjusting agents. Results Following destruction, the degradation of NMP notably occurred in the basic environment. The consumption of the pH-adjusting agent NaOH was proportional to the production of impurities since the inorganic base and/or acid promoted the degradation of NMP. The organic antioxidants, notably amino acids with an appropriate length of intermediate chain and electron-donating side group, exhibited improved antioxidant effects compared with inorganic antioxidants. The minimal amount of impurities was produced following addition of 0.04% lysine and 0.06% leucine in the aqueous phase and adjustment of the pH to a range of 7.5–8.0 in the presence of acetic acid solution. Conclusion NMP was more prone to degradation in an oxidative environment, in an aqueous phase and/or in the presence of inorganic pH-adjusting agents and antioxidants. The appropriate antioxidant and pH-adjusting agent should be selected according to the chemical structure, while destructive testing of the drug is considered to play the optimal protective effect. PMID:28490879

Guidelines for safe handling of hazardous drugs: A systematic review.

PubMed

Bernabeu-Martínez, Mari A; Ramos Merino, Mateo; Santos Gago, Juan M; Álvarez Sabucedo, Luis M; Wanden-Berghe, Carmina; Sanz-Valero, Javier

2018-01-01

To review the scientific literature related to the safe handling of hazardous drugs (HDs). Critical analysis of works retrieved from MEDLINE, the Cochrane Library, Scopus, CINHAL, Web of Science and LILACS using the terms "Hazardous Substances", "Antineoplastic Agents" and "Cytostatic Agents", applying "Humans" and "Guidelines" as filters. Date of search: January 2017. In total, 1100 references were retrieved, and from those, 61 documents were selected based on the inclusion and exclusion criteria: 24 (39.3%) documents related to recommendations about HDs; 27 (44.3%) about antineoplastic agents, and 10 (33.3%) about other types of substances (monoclonal antibodies, gene medicine and other chemical and biological agents). In 14 (23.3%) guides, all the stages in the manipulation process involving a risk due to exposure were considered. Only one guide addressed all stages of the handling process of HDs (including stages with and without the risk of exposure). The most described stages were drug preparation (41 guides, 67.2%), staff training and/or patient education (38 guides, 62.3%), and administration (37 guides, 60.7%). No standardized informatics system was found that ensured quality management, traceability and minimization of the risks associated with these drugs. Most of the analysed guidelines limit their recommendations to the manipulation of antineoplastics. The most frequently described activities were preparation, training, and administration. It would be convenient to apply ICTs (Information and Communications Technologies) to manage processes involving HDs in a more complete and simpler fashion.

Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation

PubMed Central

Burke, Caitlin W.; Price, Richard J.

2010-01-01

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas. PMID:21206463

Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

PubMed

Burke, Caitlin W; Price, Richard J

2010-12-15

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

Effect of asphalt rejuvenating agent on aged reclaimed asphalt pavement and binder properties.

DOT National Transportation Integrated Search

2016-11-01

Hot in-place recycling (HIR) preserves distressed asphalt pavements while minimizing use of virgin binder : and aggregates. The final quality of an HIR mixture depends on the characteristics of the original binder, aging of the : pavement surface dur...

PERFORMANCE OF OZONE AS A DISINFECTANT FOR COMBINED SEWER OVERFLOW

EPA Science Inventory

Disinfection of combined sewer overflow (CSO) minimizes the amount of disease-causing microorganisms (pathogens) released into receiving waters. Currently, the primary disinfecting agent used in the US for wastewater treatment is chlorine (Cl2); however, Cl2 produces problems in ...

What magnitude are observed non-target impacts from weed biocontrol?

PubMed

Suckling, David Maxwell; Sforza, René François Henri

2014-01-01

A systematic review focused by plant on non-target impacts from agents deliberately introduced for the biological control of weeds found significant non-target impacts to be rare. The magnitude of direct impact of 43 biocontrol agents on 140 non-target plants was retrospectively categorized using a risk management framework for ecological impacts of invasive species (minimal, minor, moderate, major, massive). The vast majority of agents introduced for classical biological control of weeds (>99% of 512 agents released) have had no known significant adverse effects on non-target plants thus far; major effects suppressing non-target plant populations could be expected to be detectable. Most direct non-target impacts on plants (91.6%) were categorized as minimal or minor in magnitude with no known adverse long-term impact on non-target plant populations, but a few cacti and thistles are affected at moderate (n = 3), major (n = 7) to massive (n = 1) scale. The largest direct impacts are from two agents (Cactoblastis cactorum on native cacti and Rhinocyllus conicus on native thistles), but these introductions would not be permitted today as more balanced attitudes exist to plant biodiversity, driven by both society and the scientific community. Our analysis shows (as far as is known), weed biological control agents have a biosafety track record of >99% of cases avoiding significant non-target impacts on plant populations. Some impacts could have been overlooked, but this seems unlikely to change the basic distribution of very limited adverse effects. Fewer non-target impacts can be expected in future because of improved science and incorporation of wider values. Failure to use biological control represents a significant opportunity cost from the certainty of ongoing adverse impacts from invasive weeds. It is recommended that a simple five-step scale be used to better communicate the risk of consequences from both action (classical biological control) and no action (ongoing impacts from invasive weeds).

What Magnitude Are Observed Non-Target Impacts from Weed Biocontrol?

PubMed Central

Suckling, David Maxwell; Sforza, René François Henri

2014-01-01

A systematic review focused by plant on non-target impacts from agents deliberately introduced for the biological control of weeds found significant non-target impacts to be rare. The magnitude of direct impact of 43 biocontrol agents on 140 non-target plants was retrospectively categorized using a risk management framework for ecological impacts of invasive species (minimal, minor, moderate, major, massive). The vast majority of agents introduced for classical biological control of weeds (>99% of 512 agents released) have had no known significant adverse effects on non-target plants thus far; major effects suppressing non-target plant populations could be expected to be detectable. Most direct non-target impacts on plants (91.6%) were categorized as minimal or minor in magnitude with no known adverse long-term impact on non-target plant populations, but a few cacti and thistles are affected at moderate (n = 3), major (n = 7) to massive (n = 1) scale. The largest direct impacts are from two agents (Cactoblastis cactorum on native cacti and Rhinocyllus conicus on native thistles), but these introductions would not be permitted today as more balanced attitudes exist to plant biodiversity, driven by both society and the scientific community. Our analysis shows (as far as is known), weed biological control agents have a biosafety track record of >99% of cases avoiding significant non-target impacts on plant populations. Some impacts could have been overlooked, but this seems unlikely to change the basic distribution of very limited adverse effects. Fewer non-target impacts can be expected in future because of improved science and incorporation of wider values. Failure to use biological control represents a significant opportunity cost from the certainty of ongoing adverse impacts from invasive weeds. It is recommended that a simple five-step scale be used to better communicate the risk of consequences from both action (classical biological control) and no action (ongoing impacts from invasive weeds). PMID:24454755

Modeling the Impact of Motivation, Personality, and Emotion on Social Behavior

NASA Astrophysics Data System (ADS)

Miller, Lynn C.; Read, Stephen J.; Zachary, Wayne; Rosoff, Andrew

Models seeking to predict human social behavior must contend with multiple sources of individual and group variability that underlie social behavior. One set of interrelated factors that strongly contribute to that variability - motivations, personality, and emotions - has been only minimally incorporated in previous computational models of social behavior. The Personality, Affect, Culture (PAC) framework is a theory-based computational model that addresses this gap. PAC is used to simulate social agents whose social behavior varies according to their personalities and emotions, which, in turn, vary according to their motivations and underlying motive control parameters. Examples involving disease spread and counter-insurgency operations show how PAC can be used to study behavioral variability in different social contexts.

The assessment of the antibacterial and antifungal activities of aspirin, EDTA and aspirin-EDTA combination and their effectiveness as antibiofilm agents.

PubMed

Al-Bakri, A G; Othman, G; Bustanji, Y

2009-07-01

To evaluate the antimicrobial activities of aspirin, EDTA and an aspirin-EDTA (A-EDTA) combination against Pseudomonas aeruginosa, Escherichia coli and Candida albicans in planktonic and biofilm cultures. Minimal inhibitory concentrations (MIC) and minimal biocidal concentrations (MBC) were determined using twofold broth microdilution and viable counting methods, respectively. Aspirin's recorded MIC values ranged from 1.2 to 2.7 mg ml(-1). Checkerboard assay demonstrated a synergism in antimicrobial activity upon combination. Aspirin's minimal biofilm eradication concentration values (MBEC) against the established biofilms ranged between 1.35 and 3.83 mg ml(-1). A complete eradication of bacterial biofilms was achieved after a 4-h treatment with the A-EDTA combination. Both aspirin and EDTA possess broad-spectrum antimicrobial activity for both planktonic and biofilm cultures. Aspirin used at the MBEC for 24 h was successful in eradicating P. aeruginosa, E. coli and C. albicans biofilms established on abiotic surfaces. Moreover, the exposure to the A-EDTA combination (4 h) effected complete bacterial biofilm eradication. There is a continuous need for the discovery of new antimicrobial agents. Aspirin and EDTA are 'nonantibiotic drugs', the combination of which can be used successfully to treat and eradicate biofilms established on abiotic surfaces.

Using Ant Colony Optimization for Routing in VLSI Chips

NASA Astrophysics Data System (ADS)

Arora, Tamanna; Moses, Melanie

2009-04-01

Rapid advances in VLSI technology have increased the number of transistors that fit on a single chip to about two billion. A frequent problem in the design of such high performance and high density VLSI layouts is that of routing wires that connect such large numbers of components. Most wire-routing problems are computationally hard. The quality of any routing algorithm is judged by the extent to which it satisfies routing constraints and design objectives. Some of the broader design objectives include minimizing total routed wire length, and minimizing total capacitance induced in the chip, both of which serve to minimize power consumed by the chip. Ant Colony Optimization algorithms (ACO) provide a multi-agent framework for combinatorial optimization by combining memory, stochastic decision and strategies of collective and distributed learning by ant-like agents. This paper applies ACO to the NP-hard problem of finding optimal routes for interconnect routing on VLSI chips. The constraints on interconnect routing are used by ants as heuristics which guide their search process. We found that ACO algorithms were able to successfully incorporate multiple constraints and route interconnects on suite of benchmark chips. On an average, the algorithm routed with total wire length 5.5% less than other established routing algorithms.

Management of irritable bowel syndrome in primary care: feasibility randomised controlled trial of mebeverine, methylcellulose, placebo and a patient self-management cognitive behavioural therapy website. (MIBS trial).

PubMed

Everitt, Hazel A; Moss-Morris, Rona E; Sibelli, Alice; Tapp, Laura; Coleman, Nicholas S; Yardley, Lucy; Smith, Peter W; Little, Paul S

2010-11-18

IBS affects 10-22% of the UK population. Abdominal pain, bloating and altered bowel habit affect quality of life, social functioning and time off work. Current GP treatment relies on a positive diagnosis, reassurance, lifestyle advice and drug therapies, but many suffer ongoing symptoms.A recent Cochrane review highlighted the lack of research evidence for IBS drugs. Neither GPs, nor patients have good evidence to inform prescribing decisions. However, IBS drugs are widely used: In 2005 the NHS costs were nearly £10 million for mebeverine and over £8 million for fibre-based bulking agents. CBT and self-management can be helpful, but poor availability in the NHS restricts their use. We have developed a web-based CBT self-management programme, Regul8, based on an existing evidence based self-management manual and in partnership with patients. This could increase access with minimal increased costs. The aim is to undertake a feasibility factorial RCT to assess the effectiveness of the commonly prescribed medications in UK general practice for IBS: mebeverine (anti-spasmodic) and methylcellulose (bulking-agent) and Regul8, the CBT based self-management website.135 patients aged 16 to 60 years with IBS symptoms fulfilling Rome III criteria, recruited via GP practices, will be randomised to 1 of 3 levels of the drug condition: mebeverine, methylcellulose or placebo for 6 weeks and to 1 of 3 levels of the website condition, Regul8 with a nurse telephone session and email support, Regul8 with minimal email support, or no website, thus creating 9 groups. Irritable bowel symptom severity scale and IBS-QOL will be measured at baseline, 6 and 12 weeks as the primary outcomes. An intention to treat analysis will be undertaken by ANCOVA for a factorial trial. This pilot will provide valuable information for a larger trial. Determining the effectiveness of commonly used drug treatments will help patients and doctors make informed treatment decisions regarding drug management of IBS symptoms, enabling better targeting of treatment. A web-based self-management CBT programme for IBS developed in partnership with patients has the potential to benefit large numbers of patients with low cost to the NHS. Assessment of the amount of email or therapist support required for the website will enable economic analysis to be undertaken.

Fish Viruses: Buffers and Methods for Plaquing Eight Agents Under Normal Atmosphere

PubMed Central

Wolf, Ken; Quimby, M. C.

1973-01-01

A universal procedure was sought for plaque assay of eight fish viruses (bluegill myxovirus, channel catfish virus, eel virus, Egtved virus, infectious hematopoietic necrosis virus, infectious pancreatic necrosis virus, lymphocystis virus, and the agent of spring viremia of carp (Rhabdovirus carpio), in dish cultures of various fish cells. Eagle minimal essential medium with sodium bicarbonate-CO2 buffer (Earle’s salt solution) was compared with minimal essential medium buffered principally with tris (hydroxymethyl)aminomethane or N-2-hydroxyethylpiperazine-N′-2′-ethanesulfonic acid at a pH or in the range of 7.6 to 8.0 depending upon temperature. Five fish cell lines collectively capable of replicating all fish viruses thus far isolated were tested and quantitatively found to grow comparably well in the three media. Two-phase (gel-liquid) media incorporating the various buffer systems allowed plaquing at 15 to 33 C either in partial pressures of CO2 or in normal atmosphere, but greater efficiency and sensitivity were obtained with the organic buffers, and, overall, the best results were obtained with tris(hydroxymethyl)aminomethane. Epizootiological data, specific fish cell line response, and plaque morphology permit presumptive identification of most of the agents. At proper pH, use of organic buffers obviates the need for CO2 incubators. Images PMID:4349252

Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy.

PubMed

Chen, Tao; Li, Mian; Zhang, Ruiwen; Wang, Hui

2009-07-01

The present study was designed to determine the effects of artemisinin (ARS) and its derivatives on human ovarian cancer cells, to evaluate their potential as novel chemotherapeutic agents used alone or in combination with a conventional cancer chemotherapeutic agent, and to investigate their underlying mechanisms of action. Human ovarian cancer cells (A2780 and OVCAR-3), and immortalized non-tumourigenic human ovarian surface epithelial cells (IOSE144), were exposed to four ARS compounds for cytotoxicity testing. The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells. ARS compounds exerted potent cytotoxicity to human ovarian carcinoma cells, with minimal effects on non-tumourigenic ovarian surface epithelial (OSE) cells. DHA inhibited ovarian cancer cell growth when administered alone or in combination with carboplatin, presumably through the death receptor- and, mitochondrion-mediated caspase-dependent apoptotic pathway. These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models. In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy.

Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy

PubMed Central

Chen, Tao; Li, Mian; Zhang, Ruiwen; Wang, Hui

2009-01-01

The present study was designed to determine the effects of artemisinin (ARS) and its derivatives on human ovarian cancer cells, to evaluate their potential as novel chemotherapeutic agents used alone or in combination with a conventional cancer chemotherapeutic agent, and to investigate their underlying mechanisms of action. Human ovarian cancer cells (A2780 and OVCAR-3), and immortalized non-tumourigenic human ovarian surface epithelial cells (IOSE144), were exposed to four ARS compounds for cytotoxicity testing. The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells. ARS compounds exerted potent cytotoxicity to human ovarian carcinoma cells, with minimal effects on non-tumourigenic ovarian surface epithelial (OSE) cells. DHA inhibited ovarian cancer cell growth when administered alone or in combination with carboplatin, presumably through the death receptor- and, mitochondrion-mediated caspase-dependent apoptotic pathway. These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models. In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy. PMID:18466355

[Antiangiogenic agents in ARMD treatment].

PubMed

Coroi, Mihaela-Cristiana; Demea, Sorina; Todor, Meda; Apopei, Emmanuela

2012-01-01

The aim of antiangiogenic agents in the treatment of age related senile macular degeneration is to destroy coroidian neoformation vessels by minimally affecting the central vision. We present a case of important central vision recovery after 3 intravitreal injections of Avastin. The therapeutic decision and patient monitoring have been made using imaging studies, such as OCT and AFG. A modern therapeutic approach of neovascular forms of age related macular degeneration, backed up by AFG and OCT is a modern treatment method of this disabling illness which brings patients optimal functional and structural improvement.

The multi-criteria optimization for the formation of the multiple-valued logic model of a robotic agent

NASA Astrophysics Data System (ADS)

Bykovsky, A. Yu; Sherbakov, A. A.

2016-08-01

The C-valued Allen-Givone algebra is the attractive tool for modeling of a robotic agent, but it requires the consensus method of minimization for the simplification of logic expressions. This procedure substitutes some undefined states of the function for the maximal truth value, thus extending the initially given truth table. This further creates the problem of different formal representations for the same initially given function. The multi-criteria optimization is proposed for the deliberate choice of undefined states and model formation.

Constant Price of Anarchy in Network Creation Games via Public Service Advertising

NASA Astrophysics Data System (ADS)

Demaine, Erik D.; Zadimoghaddam, Morteza

Network creation games have been studied in many different settings recently. These games are motivated by social networks in which selfish agents want to construct a connection graph among themselves. Each node wants to minimize its average or maximum distance to the others, without paying much to construct the network. Many generalizations have been considered, including non-uniform interests between nodes, general graphs of allowable edges, bounded budget agents, etc. In all of these settings, there is no known constant bound on the price of anarchy. In fact, in many cases, the price of anarchy can be very large, namely, a constant power of the number of agents. This means that we have no control on the behavior of network when agents act selfishly. On the other hand, the price of stability in all these models is constant, which means that there is chance that agents act selfishly and we end up with a reasonable social cost.

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

PubMed

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

2013-03-01

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

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.

Target drug delivery system as a new scarring modulation after glaucoma filtration surgery

PubMed Central

2011-01-01

Background Excessive wound healing following glaucoma filtration surgery is the main determinant of surgical failure, resulting from the activation of human Tenon's capsule fibroblasts (HTFs). To mitigate the excessive wound healing, the topicall use of antiproliferative agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), has increased the surgery success rate, but the traditional administration of these agents can result in a variety of toxicities with nonspecific damage. However, modulation of the wound healing process to prevent excessive fibroblast proliferation and scar formation can play a major role in improving the outcome of surgery. Therefore, the search for alternative modes of drug delivery and new agents is needed to minimize the ocular complications and improve the success of surgery. We have shown that there is a postoperative overexpression of the LDL receptor (LDLr) in the activated HTFs may provide a novel target for drug delivery systems. Presentation of the Hypothesis We hypothesize that antifibrotic agents (MMC) encapsulated in LDLr targeting drug delivery system (LDL-MMC-chitosan nanoparticles) may be proposed in anti-scarring therapy to increase the safety and effectiveness and to reduce toxicity. Testing the Hypothesis A chitosan-based polymeric predrug of MMC was synthesized and its cytotoxicity was proved to be low. In addition, we propose hyaluronic acid film as a container to release LDL-MMC-chitosan nanoparticles gradually at subconjunctival filtering site after glaucoma filtration surgery to eliminate the LDL-MMC-chitosan nanoparticles. Implications of the Hypothesis and discussion This strategy can be applicable to anti-scarring therapy during excessive conjunctival wound healing. This hypothesis integrates advantages of the targeting drug delivery and antifibrotic agents, such as high efficiency, convenience, and lower the toxicity. PMID:21736763

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

Maternal drug use: evaluation of risks to breast-fed infants.

PubMed

Kirksey, A; Groziak, S M

1984-01-01

This paper, based on a review of the literature, evaluates the risks to infants of maternal drug use during lactation. The potential harm of a particular drug to the breastfed infant is related both to the complex mechanism of milk synthesis and secretion and the mode of passage of the drug from plasma into milk. The 1st part of the paper discusses mammary cell and milk synthesis, milk secretion and composition, the mode of passage of drugs into milk, and factors influencing drug concentrations in milk. Drug concentrations in milk are dependent on 6 major factors: drug dosage, proportion bound in plasma, molecular weight, lipid solubility, degree of ionization, and pH difference between plasma and milk. Drugs that are weak acids are ionized to a greater extent and are more protein-bound than weak alkaline drugs. The 2nd part of the paper evaluates the risks to breastfed infants of selected pharmacons. Some categories of drugs that contain pharmacons that should be limited or avoided by nursing mothers are alkylating agents, analgesics and anti-inflammatory agents, anticoagulants, anticonvulsants, anti-infective agents, central nervous system stimulants, hormones, laxatives, minerals, provitamins, psychotherapeutic agents, thyroid affecting agents, and vitamins. The following precautions are suggested to minimize the risks of potentially harmful pharmacons: 1) all unnecessary medications should be avoided by nrusing mothers; 2) if medication is necessary during lactation, drug dosage should be controlled and the infant should be monitored for adverse symptoms; 3) drugs should be administered shortly after breastfeeding and the interval prolonged before the next feeding; and 4) if the infant must be fed soon after a potentially harmful drug has been taken by the mother, bottle feeding is recommended.

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung

PubMed Central

Murphy, Sean V.; Hale, Austin; Reid, Tanya; Olson, John; Kidiyoor, Amritha; Tan, Josh; Zhou, Zhiguo; Jackson, John; Atala, Anthony

2016-01-01

Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a ‘proof-of-concept’ experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course. PMID:26546729

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung.

PubMed

Murphy, Sean V; Hale, Austin; Reid, Tanya; Olson, John; Kidiyoor, Amritha; Tan, Josh; Zhou, Zhiguo; Jackson, John; Atala, Anthony

2016-04-15

Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the ​in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a 'proof-of-concept' experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-IL-23 Phase II Data for Psoriasis: A Review.

PubMed

Beroukhim, Kourosh; Danesh, Melissa J; Nguyen, Catherine; Austin, Annemieke; Koo, John; Levin, Ethan

2015-10-01

Monoclonal antibodies that target both Interleukin (IL)-12 and IL-23 have shown great efficacy in the treatment of psoriasis. Recent evidence suggests that IL-23 serves a more critical role than IL-12 in the pathogenesis of psoriasis, leading to the development of monoclonal antibodies that specifically target IL-23. We reviewed the results of the phase II clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab, in order to assess the efficacy and safety profile of each agent. By week 16, the proportion of patients achieving Physician Global Assessment (PGA) score of clear (0) or minimal (1) and Psoriasis Area and Severity Index (PASI 75) was above 70% among the most efficacious dosage of each agent (P < 0.001 compared to placebo for all agents). The safety profiles of the agents were similar, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, cough, and headache. The anti-IL-23 agents demonstrated a rapid clinical improvement and favorable short-term safety profile. The results of the phase II trials support IL-23 as an essential target in psoriasis treatment.

Effect of asphalt rejuvenating agent on aged reclaimed asphalt pavement and binder properties : technical summary.

DOT National Transportation Integrated Search

2016-11-01

Hot in-place recycling (HIR) preserves distressed asphalt pavements while minimizing use of virgin binder and aggregates. The final quality of an HIR mixture depends on the characteristics of the original binder, aging of the pavement surface during ...

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

PubMed

El-Dawayati, Maiada M

2017-01-01

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

Optimization of isolation and cultivation of bacterial endophytes through addition of plant extract to nutrient media

PubMed Central

Eevers, N; Gielen, M; Sánchez-López, A; Jaspers, S; White, J C; Vangronsveld, J; Weyens, N

2015-01-01

Many endophytes have beneficial effects on plants and can be exploited in biotechnological applications. Studies hypothesize that only 0.001–1% of all plant-associated bacteria are cultivable. Moreover, even after successful isolations, many endophytic bacteria often show reduced regrowth capacity. This research aimed to optimize isolation processes and culturing these bacteria afterwards. We compared several minimal and complex media in a screening. Beside the media themselves, two gelling agents and adding plant extract to media were investigated to enhance the number and diversity of endophytes as well as the growth capacity when regrown after isolation. In this work, 869 medium delivered the highest numbers of cultivable bacteria, as well as the highest diversity. When comparing gelling agents, no differences were observed in the numbers of bacteria. Adding plant extract to the media lead to a slight increase in diversity. However, when adding plant extract to improve the regrowth capacity, sharp increases of viable bacteria occurred in both rich and minimal media. PMID:25997013

Nonsurgical Outpatient Therapies for the Management of Female Stress Urinary Incontinence: Long-Term Effectiveness and Durability

PubMed Central

Davila, G. Willy

2011-01-01

Objective. To evaluate long-term effectiveness and safety of conservative and minimally invasive outpatient treatments for female stress urinary incontinence (SUI) through a review of the literature. Methods. PubMed was searched for reports on prospective clinical trials with at least 12-month follow-up of minimally invasive treatments, pelvic floor rehabilitation, or pharmacotherapy in women with SUI. Each report was examined for long-term rates of effectiveness and safety. Results. Thirty-two clinical trial reports were included. Prospective long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months. Poor initial tolerability with duloxetine resulted in substantial discontinuation. Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements, generally good tolerability, and safety. Conclusions. Conservative therapy is an appropriate initial approach for female SUI, but if therapy fails, radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery. PMID:21738529

Processing Characteristics and Properties of the Cellular Products Made by Using Special Foaming Agents

NASA Astrophysics Data System (ADS)

Garbacz, Tomasz; Dulebova, Ludmila

2012-12-01

The paper describes the manufacturing process of extruded products by the cellular extrusion method, and presents specifications of the blowing agents used in the extrusion process as well as process conditions. The process of cellular extrusion of thermoplastic materials is aimed at obtaining cellular shapes and coats with reduced density, presenting no hollows on the surface of extruder product and displaying minimal contraction under concurrent maintenance of properties similar to properties of products extruded by means of the conventional method. In order to obtain cellular structure, the properties of extruded product are modified by applying suitable plastic or inserting auxiliary agents.

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.

Oxidative decontamination of chemical and biological warfare agents using L-Gel.

PubMed

Raber, Ellen; McGuire, Raymond

2002-08-05

A decontamination method has been developed using a single reagent that is effective both against chemical warfare (CW) and biological warfare (BW) agents. The new reagent, "L-Gel", consists of an aqueous solution of a mild commercial oxidizer, Oxone, together with a commercial fumed silica gelling agent, Cab-O-Sil EH-5. L-Gel is non-toxic, environmentally friendly, relatively non-corrosive, maximizes contact time because of its thixotropic nature, clings to walls and ceilings, and does not harm carpets or painted surfaces. The new reagent also addresses the most demanding requirements for decontamination in the civilian sector, including availability, low maintenance, ease of application and deployment by a variety of dispersal mechanisms, minimal training and acceptable expense. Experiments to test the effectiveness of L-Gel were conducted at Lawrence Livermore National Laboratory and independently at four other locations. L-Gel was tested against all classes of chemical warfare agents and against various biological warfare agent surrogates, including spore-forming bacteria and non-virulent strains of real biological agents. Testing showed that L-Gel is as effective against chemical agents and biological materials, including spores, as the best military decontaminants.

Representation in dynamical agents.

PubMed

Ward, Ronnie; Ward, Robert

2009-04-01

This paper extends experiments by Beer [Beer, R. D. (1996). Toward the evolution of dynamical neural networks for minimally cognitive behavior. In P. Maes, M. Mataric, J. Meyer, J. Pollack, & S. Wilson (Eds.), From animals to animats 4: Proceedings of the fourth international conference on simulation of adaptive behavior (pp. 421-429). MIT Press; Beer, R. D. (2003). The dynamics of active categorical perception in an evolved model agent (with commentary and response). Adaptive Behavior, 11 (4), 209-243] with an evolved, dynamical agent to further explore the question of representation in cognitive systems. Beer's environmentally-situated visual agent was controlled by a continuous-time recurrent neural network, and evolved to perform a categorical perception task, discriminating circles from diamonds. Despite the agent's high levels of discrimination performance, Beer found no evidence of internal representation in the best-evolved agent's nervous system. Here we examine the generality of this result. We evolved an agent for shape discrimination, and performed extensive behavioral analyses to test for representation. In this case we find that agents developed to discriminate equal-width shapes exhibit what Clark [Clark, A. (1997). The dynamical challenge. Cognitive Science, 21 (4), 461-481] calls "weak-substantive representation". The agent had internal configurations that (1) were understandably related to the object in the environment, and (2) were functionally used in a task relevant way when the target was not visible to the agent.

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

Simulation and Prediction of the Drug-Drug Interaction Potential of Naloxegol by Physiologically Based Pharmacokinetic Modeling.

PubMed

Zhou, D; Bui, K; Sostek, M; Al-Huniti, N

2016-05-01

Naloxegol, a peripherally acting μ-opioid receptor antagonist for the treatment of opioid-induced constipation, is a substrate for cytochrome P450 (CYP) 3A4/3A5 and the P-glycoprotein (P-gp) transporter. By integrating in silico, preclinical, and clinical pharmacokinetic (PK) findings, minimal and full physiologically based pharmacokinetic (PBPK) models were developed to predict the drug-drug interaction (DDI) potential for naloxegol. The models reasonably predicted the observed changes in naloxegol exposure with ketoconazole (increase of 13.1-fold predicted vs. 12.9-fold observed), diltiazem (increase of 2.8-fold predicted vs. 3.4-fold observed), rifampin (reduction of 76% predicted vs. 89% observed), and quinidine (increase of 1.2-fold predicted vs. 1.4-fold observed). The moderate CYP3A4 inducer efavirenz was predicted to reduce naloxegol exposure by ∼50%, whereas weak CYP3A inhibitors were predicted to minimally affect exposure. In summary, the PBPK models reasonably estimated interactions with various CYP3A modulators and can be used to guide dosing in clinical practice when naloxegol is coadministered with such agents. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A mind map for managing minimal residual disease in acute myeloid leukemia.

PubMed

Benton, Christopher B; Ravandi, Farhad

2017-11-01

Advances in detecting traces of leukemia that were previously unidentifiable have increasingly led to the incorporation of information about residual disease into clinical decision making for patients with leukemia in both the postinduction and consolidation settings. This review discusses current concepts related to minimal residual disease (MRD), which is defined as submicroscopic disease detected during morphologic complete remission. The focus is on acute myeloid leukemia (AML). Basic methods for detecting MRD include flow cytometry, reverse transcription-polymerase chain reaction, and mutation analysis. Several studies using these assays have demonstrated prognostic implications based on MRD-positive vs MRD-negative status. As our understanding of the biological factors responsible for MRD in AML evolves, residual disease should be evaluated in the context of other prognostic markers. Current therapeutic options for managing MRD in AML are limited, and the clinical implications of a positive MRD test result can be significant. Regarding individual patients, an evidence-based approach must be applied while the institution- and assay-specific differences that currently exist are considered. Challenges associated with MRD assessment, such as the limited standardization of available assays and the paucity of effective agents to eradicate MRD, will need to be overcome before physicians who treat leukemia can use MRD as a tool for clinical management.

Biological control agents elevate hantavirus by subsidizing deer mouse populations.

PubMed

Pearson, Dean E; Callaway, Ragan M

2006-04-01

Biological control of exotic invasive plants using exotic insects is practiced under the assumption that biological control agents are safe if they do not directly attack non-target species. We tested this assumption by evaluating the potential for two host-specific biological control agents (Urophora spp.), widely established in North America for spotted knapweed (Centaurea maculosa) control, to indirectly elevate Sin Nombre hantavirus by providing food subsidies to populations of deer mice (Peromyscus maniculatus), the primary reservoir for the virus. We show that seropositive deer mice (mice testing positive for hantavirus) were over three times more abundant in the presence of the biocontrol food subsidy. Elevating densities of seropositive mice may increase risk of hantavirus infection in humans and significantly alter hantavirus ecology. Host specificity alone does not ensure safe biological control. To minimize indirect risks to non-target species, biological control agents must suppress pest populations enough to reduce their own numbers.

Application of the HeartLander Crawling Robot for Injection of a Thermally Sensitive Anti-Remodeling Agent for Myocardial Infarction Therapy

PubMed Central

Chapman, Michael P.; López González, Jose L.; Goyette, Brina E.; Fujimoto, Kazuro L.; Ma, Zuwei; Wagner, William R.; Zenati, Marco A.; Riviere, Cameron N.

2011-01-01

The injection of a mechanical bulking agent into the left ventricular (LV) wall of the heart has shown promise as a therapy for maladaptive remodeling of the myocardium after myocardial infarct (MI). The HeartLander robotic crawler presented itself as an ideal vehicle for minimally-invasive, highly accurate epicardial injection of such an agent. Use of the optimal bulking agent, a thermosetting hydrogel developed by our group, presents a number of engineering obstacles, including cooling of the miniaturized injection system while the robot is navigating in the warm environment of a living patient. We present herein a demonstration of an integrated miniature cooling and injection system in the HeartLander crawling robot, that is fully biocompatible and capable of multiple injections of a thermosetting hydrogel into dense animal tissue while the entire system is immersed in a 37°C water bath. PMID:21096276

In Vivo Recording of Neural and Behavioral Correlates of Anesthesia Induction, Reversal, and Euthanasia in Cephalopod Molluscs.

PubMed

Butler-Struben, Hanna M; Brophy, Samantha M; Johnson, Nasira A; Crook, Robyn J

2018-01-01

Cephalopod molluscs are among the most behaviorally and neurologically complex invertebrates. As they are now included in research animal welfare regulations in many countries, humane and effective anesthesia is required during invasive procedures. However, currently there is no evidence that agents believed to act as anesthetics produce effects beyond immobility. In this study we demonstrate, for the first time, that two of the most commonly used agents in cephalopod general anesthesia, magnesium chloride and ethanol, are capable of producing strong and reversible blockade of afferent and efferent neural signal; thus they are genuine anesthetics, rather than simply sedating agents that render animals immobile but not insensible. Additionally, we demonstrate that injected magnesium chloride and lidocaine are effective local anesthetic agents. This represents a considerable advance for cephalopod welfare. Using a reversible, minimally invasive recording procedure, we measured activity in the pallial nerve of cuttlefish ( Sepia bandensis ) and octopus ( Abdopus aculeatus, Octopus bocki ), during induction and reversal for five putative general anesthetic and two local anesthetic agents. We describe the temporal relationship between loss of behavioral responses (immobility), loss of efferent neural signal (loss of "consciousness") and loss of afferent neural signal (anesthesia) for general anesthesia, and loss of afferent signal for local anesthesia. Both ethanol and magnesium chloride were effective as bath-applied general anesthetics, causing immobility, complete loss of behavioral responsiveness and complete loss of afferent and efferent neural signal. Cold seawater, diethyl ether, and MS-222 (tricaine) were ineffective. Subcutaneous injection of either lidocaine or magnesium chloride blocked behavioral and neural responses to pinch in the injected area, and we conclude that both are effective local anesthetic agents for cephalopods. Lastly, we demonstrate that a standard euthanasia protocol-immersion in isotonic magnesium chloride followed by surgical decerebration-produced no behavioral response and no neural activity during surgical euthanasia. Based on these data, we conclude that both magnesium chloride and ethanol can function as general anesthetic agents, and lidocaine and magnesium chloride can function as local anesthetic agents for cephalopod molluscs.

In Vivo Recording of Neural and Behavioral Correlates of Anesthesia Induction, Reversal, and Euthanasia in Cephalopod Molluscs

PubMed Central

Butler-Struben, Hanna M.; Brophy, Samantha M.; Johnson, Nasira A.; Crook, Robyn J.

2018-01-01

Cephalopod molluscs are among the most behaviorally and neurologically complex invertebrates. As they are now included in research animal welfare regulations in many countries, humane and effective anesthesia is required during invasive procedures. However, currently there is no evidence that agents believed to act as anesthetics produce effects beyond immobility. In this study we demonstrate, for the first time, that two of the most commonly used agents in cephalopod general anesthesia, magnesium chloride and ethanol, are capable of producing strong and reversible blockade of afferent and efferent neural signal; thus they are genuine anesthetics, rather than simply sedating agents that render animals immobile but not insensible. Additionally, we demonstrate that injected magnesium chloride and lidocaine are effective local anesthetic agents. This represents a considerable advance for cephalopod welfare. Using a reversible, minimally invasive recording procedure, we measured activity in the pallial nerve of cuttlefish (Sepia bandensis) and octopus (Abdopus aculeatus, Octopus bocki), during induction and reversal for five putative general anesthetic and two local anesthetic agents. We describe the temporal relationship between loss of behavioral responses (immobility), loss of efferent neural signal (loss of “consciousness”) and loss of afferent neural signal (anesthesia) for general anesthesia, and loss of afferent signal for local anesthesia. Both ethanol and magnesium chloride were effective as bath-applied general anesthetics, causing immobility, complete loss of behavioral responsiveness and complete loss of afferent and efferent neural signal. Cold seawater, diethyl ether, and MS-222 (tricaine) were ineffective. Subcutaneous injection of either lidocaine or magnesium chloride blocked behavioral and neural responses to pinch in the injected area, and we conclude that both are effective local anesthetic agents for cephalopods. Lastly, we demonstrate that a standard euthanasia protocol—immersion in isotonic magnesium chloride followed by surgical decerebration—produced no behavioral response and no neural activity during surgical euthanasia. Based on these data, we conclude that both magnesium chloride and ethanol can function as general anesthetic agents, and lidocaine and magnesium chloride can function as local anesthetic agents for cephalopod molluscs. PMID:29515454

In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Zuo, Guo-Ying; Zhang, Xin-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

2015-12-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen posing a serious therapeutic challenge in the clinic. It is often multidrug-resistant (MDR) to conventional classes of antibacterial agents and there is an urgent need to develop new agents or strategies for treatment. Magnolol (ML) and honokiol (HL) are two naturally occurring diallylbiphenols which have been reported to show inhibition of MRSA. In this study their synergistic effects with antibacterial agents were further evaluated via checkerboard and time-kill assays. The susceptibility spectrum of clinical MRSA strains was tested by the disk diffusion method. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ML and HL were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and time-killing experiments. ML and HL showed similar activity against both MSSA and MRSA with MIC/MBC at 16 ~ 64 mg/L, with potency similar to amikacin (AMK) and gentamicin (GEN). When they were used in combination with conventional antibacterial agents, they showed bacteriostatic synergy with FICIs between 0.25 ~ 0.5, leading to the combined MICs decreasing to as low as 1 ~ 2 and 1 ~ 16 mg/L for ML (HL) and the agents, respectively. MIC50 of the combinations decreased from 16 mg/L to 1 ~ 4 mg/L for ML (HL) and 8 ~ 128 mg/L to 2 ~ 64 mg/L for the antibacterial agents, which exhibited a broad spectrum of synergistic action with aminoglycosides (AMK, etilmicin (ETM) and GEN), floroquinolones (levofloxacin (LEV), ciprofloxacin and norfloxacin), fosfomycin (FOS) and piperacillin. The times of dilution (TOD, the extent of decreasing in MIC value) were determined up to 16 for the combined MIC. A more significant synergy after combining was determined as ML (HL) with AMK, ETM, GEN and FOS. ML (HL) combined with antibacterial agents did not show antagonistic effects on any of the ten MRSA strains. Reversal effects of MRSA resistance to AMK and GEN by ML and HL were also observed, respectively. All the combinations also showed better dynamic bactericidal activity against MRSA than any of single ML (HL) or the agents at 24 h incubation. The more significant synergy of combinations were determined as HL (ML) + ETM, HL + LEV and HL + AMK (GEN or FOS), with △LC24 of 2.02 ~ 2.25. ML and HL showed synergistic potentiation of antibacterial agents against clinical isolates of MRSA and warrant further pharmacological investigation.

PDT-based combinations in overcoming chemoresistance from stromal and heterotypic cellular communication (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rizvi, Imran; Bulin, Anne-Laure; Anbil, Sriram R.; Briars, Emma A.; Vecchio, Daniela; Celli, Jonathan P.; Broekgaarden, Mans; Hasan, Tayyaba

2017-02-01

Targeting the molecular and cellular cues that influence treatment resistance in tumors is critical to effectively treating unresponsive populations of stubborn disease. The informed design of mechanism-based combinations is emerging as increasingly important to targeting resistance and improving the efficacy of conventional treatments, while minimizing toxicity. Photodynamic therapy (PDT) has been shown to synergize with conventional agents and to overcome the evasion pathways that cause resistance. Increasing evidence shows that PDT-based combinations cooperate mechanistically with, and improve the therapeutic index of, traditional chemotherapies. These and other findings emphasize the importance of including PDT as part of comprehensive treatment plans for cancer, particularly in complex disease sites. Identifying effective combinations requires a multi-faceted approach that includes the development of bioengineered cancer models and corresponding image analysis tools. The molecular and phenotypic basis of verteporfin-mediated PDT-based enhancement of chemotherapeutic efficacy and predictability in complex 3D models for ovarian cancer will be presented.

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

PubMed

Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q

2015-02-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

Choosing the best treatment strategy for chronic myeloid leukemia patients resistant to imatinib: weighing the efficacy and safety of individual drugs with BCR-ABL mutations and patient history.

PubMed

Jabbour, E; Hochhaus, A; Cortes, J; La Rosée, P; Kantarjian, H M

2010-01-01

For patients with chronic myeloid leukemia who become or are inherently resistant to imatinib therapy, including dose escalation, several important factors must be considered when deciding which strategy to attempt next. The second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib offer improved potency and a high likelihood of success for these patients. Overall, the efficacy data are comparable for these two agents, and so physicians should consider the BCR-ABL mutation profile and the patient's history to make an educated decision on the best choice. Only a few BCR-ABL mutations seem to be less responsive to either nilotinib or dasatinib and it is recommended to choose the second-line TKI that has shown clinical activity against the specific mutation in these cases. For patients with all other mutations, and for patients with no mutations, it is recommended to choose the second-generation TKI based on the patient's disease history. It is important to choose an agent that minimizes the likelihood of exacerbating the patient's past tolerability issues to imatinib, or comorbid conditions. Here, we propose a treatment algorithm for imatinib-resistant patients based on BCR-ABL mutation status and patient history.

Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles in vitro

NASA Astrophysics Data System (ADS)

Luo, Fanghong; Li, Yang; Jia, Mengmeng; Cui, Fei; Wu, Hongjie; Yu, Fei; Lin, Jinyan; Yang, Xiangrui; Hou, Zhenqing; Zhang, Qiqing

2014-07-01

Recently, methotrexate (MTX) has been used to target to folate (FA) receptor-overexpressing cancer cells for targeted drug delivery. However, the systematic evaluation of MTX as a Janus-like agent has not been reported before. Here, we explored the validity of using MTX playing an early-phase cancer-specific targeting ligand cooperated with a late-phase therapeutic anticancer agent based on the PEGylated chitosan (CS) nanoparticles (NPs) as drug carriers. Some advantages of these nanoscaled drug delivery systems are as follows: (1) the NPs can ensure minimal premature release of MTX at off-target site to reduce the side effects to normal tissue; (2) MTX can function as a targeting ligand at target site prior to cellular uptake; and (3) once internalized by the target cell, the NPs can function as a prodrug formulation, releasing biologically active MTX inside the cells. The (MTX + PEG)-CS-NPs presented a sustained/proteases-mediated drug release. More importantly, compared with the PEG-CS-NPs and (FA + PEG)-CS-NPs, the (MTX + PEG)-CS-NPs showed a greater cellular uptake. Furthermore, the (MTX + PEG)-CS-NPs demonstrated a superior cytotoxicity compare to the free MTX. Our findings therefore validated that the MTX-loaded PEGylated CS-NPs can simultaneously target and treat FA receptor-overexpressing cancer cells.

Anthracnose disease of switchgrass caused by the novel fungal species Colletotrichum navitas.

PubMed

Crouch, Jo Anne; Beirn, Lisa A; Cortese, Laura M; Bonos, Stacy A; Clarke, Bruce B

2009-12-01

In recent years perennial grasses such as the native tallgrass prairie plant Panicum virgatum (switchgrass) have taken on a new role in the North American landscape as a plant-based source of renewable energy. Because switchgrass is a native plant, it has been suggested that disease problems will be minimal, but little research in this area has been conducted. Recently, outbreaks of switchgrass anthracnose disease have been reported from the northeastern United States. Incidences of switchgrass anthracnose are known in North America since 1886 through herbarium specimens and disease reports, but the causal agent of this disease has never been experimentally determined or taxonomically evaluated. In the present work, we evaluate the causal agent of switchgrass anthracnose, a new species we describe as Colletotrichum navitas (navitas=Latin for energy). Multilocus molecular phylogenetics and morphological characters show C. navitas is a novel species in the falcate-spored graminicolous group of the genus Colletotrichum; it is most closely related to the corn anthracnose pathogen Colletotrichum graminicola. We present a formal description and illustrations for C. navitas and provide experimental confirmation that this organism is responsible for switchgrass anthracnose disease.

Immunotherapy for lung cancer: advances and prospects.

PubMed

Yang, Li; Wang, Liping; Zhang, Yi

2016-01-01

Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment.

In vitro and in silico investigation of electrospun terbinafine hydrochloride-loaded buccal nanofibrous sheets.

PubMed

Szabó, Péter; Daróczi, Tünde Beáta; Tóth, Gergő; Zelkó, Romána

2016-11-30

Terbinafine hydrochloride-loaded nanofibrous buccal films were formulated with the aim to improve the solubility and dissolution behavior; thus, the local effectiveness of the antifungal agent. Poly(vinyl alcohol) and chitosan polymer composites were selected as delivery base in order to enhance the mucoadhesion of the fibrous films. The dissolution of terbinafine hydrochloride was carried out applying a stainless steel disc assembly and the terbinafine concentration was determined by HPLC-MS in selective ion monitoring mode. The prediction of the absorption behavior of the prepared fibrous samples in the human oral cavity was modeled using GastroPlus™ software. The result indicates that the fibrous films enabled fast and complete dissolution of the active agent. The drug absorption from the oral cavity could be minimized by the employment of the proper oral transit model. Because of the limited absorption of terbinafine hydrochloride from the oral mucosa the formulation can be beneficial in local administration in the case of hold and expectorate administration mode. Copyright © 2016 Elsevier B.V. All rights reserved.

A Heuristic Bioinspired for 8-Piece Puzzle

NASA Astrophysics Data System (ADS)

Machado, M. O.; Fabres, P. A.; Melo, J. C. L.

2017-10-01

This paper investigates a mathematical model inspired by nature, and presents a Meta-Heuristic that is efficient in improving the performance of an informed search, when using strategy A * using a General Search Tree as data structure. The work hypothesis suggests that the investigated meta-heuristic is optimal in nature and may be promising in minimizing the computational resources required by an objective-based agent in solving high computational complexity problems (n-part puzzle) as well as In the optimization of objective functions for local search agents. The objective of this work is to describe qualitatively the characteristics and properties of the mathematical model investigated, correlating the main concepts of the A * function with the significant variables of the metaheuristic used. The article shows that the amount of memory required to perform this search when using the metaheuristic is less than using the A * function to evaluate the nodes of a general search tree for the eight-piece puzzle. It is concluded that the meta-heuristic must be parameterized according to the chosen heuristic and the level of the tree that contains the possible solutions to the chosen problem.

Bupivacaine, levobupivacaine and ropivacaine: are they clinically different?

PubMed

Casati, Andrea; Putzu, Marta

2005-06-01

Two new, long-acting local anaesthetics have been developed after the evidence of bupivacaine-related severe toxicity: levobupivacaine and ropivacaine. Both these agents are pure left-isomers and, based on their three-dimensional structure, they have less toxic potential both on the central nervous system and on the heart. Several clinical studies have evaluated their toxicology and clinical profiles: theoretically and experimentally, some differences can be seen, but the reflections of these characteristics into clinical practice have not been evident. Evaluating randomised, controlled trials that have compared these three local anaesthetics, this chapter supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences observed between the three agents are mainly related to the slightly different anaesthetic potency, with racemic bupivacaine>levobupivacaine>ropivacaine. However, the reduced toxic potential of the two pure left-isomers supports their use in those clinical situations in which the risk of systemic toxicity related to either overdosing or unwanted intravascular injection is high, such as during epidural or peripheral nerve blocks.

Controversies in Alzheimer’s disease drug development

PubMed Central

Cummings, Jeffrey L.

2010-01-01

Understanding of the pathophysiological basis of Alzheimer’s disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer’s disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described. PMID:18925488

Melasma: systematic review of the systemic treatments.

PubMed

Zhou, Linghong Linda; Baibergenova, Akerke

2017-09-01

Currently available treatment options for melasma include prevention of UV radiation, topical lightening agents, chemical peels, and light-based and laser therapies. However, none have shown effective and sustained results, with incomplete clearance and frequent recurrences. There has been increasing interest recently in oral medications and dietary supplements in improving melasma. We sought to evaluate the efficacy and safety/tolerability of oral medications and dietary supplements for the treatment of melasma. Multiple databases were systematically searched for randomized clinical trials (RCTs) evaluating the use of oral medication for treatment of melasma alone or in combination with other treatments. A total of eight RCTs met inclusion criteria. Oral medications and dietary supplements evaluated include tranexamic acid, Polypodium leucotomos extract, beta-carotenoid, melatonin, and procyanidin. These agents appear to have a beneficial effect on melasma improvement. In conclusion, oral medications have a role in melasma treatment and have been shown to be efficacious and tolerable with a minimal number and severity of adverse events. Therefore, dermatologists should keep oral medications and dietary supplements in their armamentarium for the treatment of melasma. © 2017 The International Society of Dermatology.

Potential of predatory bacteria as biocontrol agents for foodborne and plant pathogens

USDA-ARS?s Scientific Manuscript database

Foodborne pathogens such as Escherichia coli O157:H7, Salmonella spp., Listeria monocytogenes, Shigella are responsible for frequent occurrences of illnesses and mortality in humans and produce losses. Pre-harvest yield losses and post-harvest decay on minimally processed produce (fruits, vegetables...

Controlled release of metronidazole from composite poly-ε-caprolactone/alginate (PCL/alginate) rings for dental implants.

PubMed

Lan, Shih-Feng; Kehinde, Timilehin; Zhang, Xiangming; Khajotia, Sharukh; Schmidtke, David W; Starly, Binil

2013-06-01

Dental implants provide support for dental crowns and bridges by serving as abutments for the replacement of missing teeth. To prevent bacterial accumulation and growth at the site of implantation, solutions such as systemic antibiotics and localized delivery of bactericidal agents are often employed. The objective of this study was to demonstrate a novel method of controlled localized delivery of antibacterial agents to an implant site using a biodegradable custom fabricated ring. The study involved incorporating a model antibacterial agent (metronidazole) into custom designed poly-ε-caprolactone/alginate (PCL/alginate) composite rings to produce the intended controlled release profile. The rings can be designed to fit around the body of any root form dental implants of various diameters, shapes and sizes. In vitro release studies indicate that pure (100%) alginate rings exhibited an expected burst release of metronidazole in the first few hours, whereas Alginate/PCL composite rings produced a medium burst release followed by a sustained release for a period greater than 4 weeks. By varying the PCL/alginate weight ratios, we have shown that we can control the amount of antibacterial agents released to provide the minimal inhibitory concentration (MIC) needed for adequate protection. The fabricated composite rings have achieved a 50% antibacterial agent release profile over the first 48 h and the remaining amount slowly released over the remainder of the study period. The PCL/alginate agent release characteristic fits the Ritger-Peppas model indicating a diffusion-based mechanism during the 30-day study period. The developed system demonstrates a controllable drug release profile and the potential for the ring to inhibit bacterial biofilm growth for the prevention of diseases such as peri-implantitis resulting from bacterial infection at the implant site. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties.

PubMed

Herold, Karl F; Sanford, R Lea; Lee, William; Andersen, Olaf S; Hemmings, Hugh C

2017-03-21

General anesthetics have revolutionized medicine by facilitating invasive procedures, and have thus become essential drugs. However, detailed understanding of their molecular mechanisms remains elusive. A mechanism proposed over a century ago involving unspecified interactions with the lipid bilayer known as the unitary lipid-based hypothesis of anesthetic action, has been challenged by evidence for direct anesthetic interactions with a range of proteins, including transmembrane ion channels. Anesthetic concentrations in the membrane are high (10-100 mM), however, and there is no experimental evidence ruling out a role for the lipid bilayer in their ion channel effects. A recent hypothesis proposes that anesthetic-induced changes in ion channel function result from changes in bilayer lateral pressure that arise from partitioning of anesthetics into the bilayer. We examined the effects of a broad range of chemically diverse general anesthetics and related nonanesthetics on lipid bilayer properties using an established fluorescence assay that senses drug-induced changes in lipid bilayer properties. None of the compounds tested altered bilayer properties sufficiently to produce meaningful changes in ion channel function at clinically relevant concentrations. Even supra-anesthetic concentrations caused minimal bilayer effects, although much higher (toxic) concentrations of certain anesthetic agents did alter lipid bilayer properties. We conclude that general anesthetics have minimal effects on bilayer properties at clinically relevant concentrations, indicating that anesthetic effects on ion channel function are not bilayer-mediated but rather involve direct protein interactions.

Standardized Review and Approval Process for High-Cost Medication Use Promotes Value-Based Care in a Large Academic Medical System

PubMed Central

Durvasula, Raghu; Kelly, Janet; Schleyer, Anneliese; Anawalt, Bradley D.; Somani, Shabir; Dellit, Timothy H.

2018-01-01

Background As healthcare costs rise and reimbursements decrease, healthcare organization leadership and clinical providers must collaborate to provide high-value healthcare. Medications are a key driver of the increasing cost of healthcare, largely as a result of the proliferation of expensive specialty drugs, including biologic agents. Such medications contribute significantly to the inpatient diagnosis-related group payment system, often with minimal or unproved benefit over less-expensive therapies. Objective To describe a systematic review process to reduce non–evidence-based inpatient use of high-cost medications across a large multihospital academic health system. Methods We created a Pharmacy & Therapeutics subcommittee consisting of clinicians, pharmacists, and an ethics representative. This committee developed a standardized process for a timely review (<48 hours) and approval of high-cost medications based on their clinical effectiveness, safety, and appropriateness. The engagement of clinical experts in the development of the consensus-based guidelines for the use of specific medications facilitated the clinicians' acceptance of the review process. Results Over a 2-year period, a total of 85 patient-specific requests underwent formal review. All reviews were conducted within 48 hours. This review process has reduced the non–evidence-based use of specialty medications and has resulted in a pharmacy savings of $491,000 in fiscal year 2016, with almost 80% of the savings occurring in the last 2 quarters, because our process has matured. Conclusion The creation of a collaborative review process to ensure consistent, evidence-based utilization of high-cost medications provides value-based care, while minimizing unnecessary practice variation and reducing the cost of inpatient care.

Managing Campus Security: Issues for Police Officers at Public Institutions.

ERIC Educational Resources Information Center

Dwyer, William O.; And Others

1994-01-01

To maximize the effectiveness of their campus security systems while minimizing the institution's exposure to liability, campus administrators must understand the legal context in which their police or security personnel are operating as agents of authority. Some of these policy and behavior issues are explained. (MSE)

Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound.

PubMed

Sheeran, Paul S; Luois, Samantha; Dayton, Paul A; Matsunaga, Terry O

2011-09-06

Recent efforts in the area of acoustic droplet vaporization with the objective of designing extravascular ultrasound contrast agents has led to the development of stabilized, lipid-encapsulated nanodroplets of the highly volatile compound decafluorobutane (DFB). We developed two methods of generating DFB droplets, the first of which involves condensing DFB gas (boiling point from -1.1 to -2 °C) followed by extrusion with a lipid formulation in HEPES buffer. Acoustic droplet vaporization of micrometer-sized lipid-coated droplets at diagnostic ultrasound frequencies and mechanical indices were confirmed optically. In our second formulation methodology, we demonstrate the formulation of submicrometer-sized lipid-coated nanodroplets based upon condensation of preformed microbubbles containing DFB. The droplets are routinely in the 200-300 nm range and yield microbubbles on the order of 1-5 μm once vaporized, consistent with ideal gas law expansion predictions. The simple and effective nature of this methodology allows for the development of a variety of different formulations that can be used for imaging, drug and gene delivery, and therapy. This study is the first to our knowledge to demonstrate both a method of generating ADV agents by microbubble condensation and formulation of primarily submicrometer droplets of decafluorobutane that remain stable at physiological temperatures. Finally, activation of DFB nanodroplets is demonstrated using pressures within the FDA guidelines for diagnostic imaging, which may minimize the potential for bioeffects in humans. This methodology offers a new means of developing extravascular contrast agents for diagnostic and therapeutic applications. © 2011 American Chemical Society

Peptide-based pharmacomodulation of a cancer-targeted optical imaging and photodynamic therapy agent

PubMed Central

Stefflova, Klara; Li, Hui; Chen, Juan; Zheng, Gang

2008-01-01

We designed and synthesized a folate receptor-targeted, water soluble, and pharmacomodulated photodynamic therapy (PDT) agent that selectively detects and destroys the targeted cancer cells while sparing normal tissue. This was achieved by minimizing the normal organ uptake (e.g., liver and spleen) and by discriminating between tumors with different levels of folate receptor (FR) expression. This construct (Pyro-peptide-Folate, PPF) is comprised of three components: 1) Pyropheophorbide a (Pyro) as an imaging and therapeutic agent, 2) peptide sequence as a stable linker and modulator improving the delivery efficiency, and 3) Folate as a homing molecule targeting FR-expressing cancer cells. We observed an enhanced accumulation of PPF in KB cancer cells (FR+) compared to HT 1080 cancer cells (FR-), resulting in a more effective post-PDT killing of KB cells over HT 1080 or normal CHO cells. The accumulation of PPF in KB cells can be up to 70% inhibited by an excess of free folic acid. The effect of Folate on preferential accumulation of PPF in KB tumors (KB vs. HT 1080 tumors 2.5:1) was also confirmed in vivo. In contrast to that, no significant difference between the KB and HT 1080 tumor was observed in case of the untargeted probe (Pyro-peptide, PP), eliminating the potential influence of Pyro’s own nonspecific affinity to cancer cells. More importantly, we found that incorporating a short peptide sequence considerably improved the delivery efficiency of the probe – a process we attributed to a possible peptide-based pharmacomodulation – as was demonstrated by a 50-fold reduction in PPF accumulation in liver and spleen when compared to a peptide-lacking probe (Pyro-K-Folate, PKF). This approach could potentially be generalized to improve the delivery efficiency of other targeted molecular imaging and photodynamic therapy agents. PMID:17298029

Gaseous emissions from management of solid waste: a systematic review

PubMed Central

Pardo, Guillermo; Moral, Raúl; Aguilera, Eduardo; del Prado, Agustín

2015-01-01

The establishment of sustainable soil waste management practices implies minimizing their environmental losses associated with climate change (greenhouse gases: GHGs) and ecosystems acidification (ammonia: NH3). Although a number of management strategies for solid waste management have been investigated to quantify nitrogen (N) and carbon (C) losses in relation to varied environmental and operational conditions, their overall effect is still uncertain. In this context, we have analyzed the current scientific information through a systematic review. We quantified the response of GHG emissions, NH3 emissions, and total N losses to different solid waste management strategies (conventional solid storage, turned composting, forced aerated composting, covering, compaction, addition/substitution of bulking agents and the use of additives). Our study is based on a meta-analysis of 50 research articles involving 304 observations. Our results indicated that improving the structure of the pile (waste or manure heap) via addition or substitution of certain bulking agents significantly reduced nitrous oxide (N2O) and methane (CH4) emissions by 53% and 71%, respectively. Turned composting systems, unlike forced aerated composted systems, showed potential for reducing GHGs (N2O: 50% and CH4: 71%). Bulking agents and both composting systems involved a certain degree of pollution swapping as they significantly promoted NH3 emissions by 35%, 54%, and 121% for bulking agents, turned and forced aerated composting, respectively. Strategies based on the restriction of O2 supply, such as covering or compaction, did not show significant effects on reducing GHGs but substantially decreased NH3 emissions by 61% and 54% for covering and compaction, respectively. The use of specific additives significantly reduced NH3 losses by 69%. Our meta-analysis suggested that there is enough evidence to refine future Intergovernmental Panel on Climate Change (IPCC) methodologies from solid waste, especially for solid waste composting practices. More holistic and integrated approaches are therefore required to develop more sustainable solid waste management systems. PMID:25393229

Gaseous emissions from management of solid waste: a systematic review.

PubMed

Pardo, Guillermo; Moral, Raúl; Aguilera, Eduardo; Del Prado, Agustín

2015-03-01

The establishment of sustainable soil waste management practices implies minimizing their environmental losses associated with climate change (greenhouse gases: GHGs) and ecosystems acidification (ammonia: NH3 ). Although a number of management strategies for solid waste management have been investigated to quantify nitrogen (N) and carbon (C) losses in relation to varied environmental and operational conditions, their overall effect is still uncertain. In this context, we have analyzed the current scientific information through a systematic review. We quantified the response of GHG emissions, NH3 emissions, and total N losses to different solid waste management strategies (conventional solid storage, turned composting, forced aerated composting, covering, compaction, addition/substitution of bulking agents and the use of additives). Our study is based on a meta-analysis of 50 research articles involving 304 observations. Our results indicated that improving the structure of the pile (waste or manure heap) via addition or substitution of certain bulking agents significantly reduced nitrous oxide (N2 O) and methane (CH4 ) emissions by 53% and 71%, respectively. Turned composting systems, unlike forced aerated composted systems, showed potential for reducing GHGs (N2 O: 50% and CH4 : 71%). Bulking agents and both composting systems involved a certain degree of pollution swapping as they significantly promoted NH3 emissions by 35%, 54%, and 121% for bulking agents, turned and forced aerated composting, respectively. Strategies based on the restriction of O2 supply, such as covering or compaction, did not show significant effects on reducing GHGs but substantially decreased NH3 emissions by 61% and 54% for covering and compaction, respectively. The use of specific additives significantly reduced NH3 losses by 69%. Our meta-analysis suggested that there is enough evidence to refine future Intergovernmental Panel on Climate Change (IPCC) methodologies from solid waste, especially for solid waste composting practices. More holistic and integrated approaches are therefore required to develop more sustainable solid waste management systems. © 2014 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

Propagation, cascades, and agreement dynamics in complex communication and social networks

NASA Astrophysics Data System (ADS)

Lu, Qiming

Many modern and important technological, social, information and infrastructure systems can be viewed as complex systems with a large number of interacting components. Models of complex networks and dynamical interactions, as well as their applications are of fundamental interests in many aspects. Here, several stylized models of multiplex propagation and opinion dynamics are investigated on complex and empirical social networks. We first investigate cascade dynamics in threshold-controlled (multiplex) propagation on random geometric networks. We find that such local dynamics can serve as an efficient, robust, and reliable prototypical activation protocol in sensor networks in responding to various alarm scenarios. We also consider the same dynamics on a modified network by adding a few long-range communication links, resulting in a small-world network. We find that such construction can further enhance and optimize the speed of the network's response, while keeping energy consumption at a manageable level. We also investigate a prototypical agent-based model, the Naming Game, on two-dimensional random geometric networks. The Naming Game [A. Baronchelli et al., J. Stat. Mech.: Theory Exp. (2006) P06014.] is a minimal model, employing local communications that captures the emergence of shared communication schemes (languages) in a population of autonomous semiotic agents. Implementing the Naming Games with local broadcasts on random geometric graphs, serves as a model for agreement dynamics in large-scale, autonomously operating wireless sensor networks. Further, it captures essential features of the scaling properties of the agreement process for spatially-embedded autonomous agents. Among the relevant observables capturing the temporal properties of the agreement process, we investigate the cluster-size distribution and the distribution of the agreement times, both exhibiting dynamic scaling. We also present results for the case when a small density of long-range communication links are added on top of the random geometric graph, resulting in a "small-world"-like network and yielding a significantly reduced time to reach global agreement. We construct a finite-size scaling analysis for the agreement times in this case. When applying the model of Naming Game on empirical social networks, this stylized agent-based model captures essential features of agreement dynamics in a network of autonomous agents, corresponding to the development of shared classification schemes in a network of artificial agents or opinion spreading and social dynamics in social networks. Our study focuses on the impact that communities in the underlying social graphs have on the outcome of the agreement process. We find that networks with strong community structure hinder the system from reaching global agreement; the evolution of the Naming Game in these networks maintains clusters of coexisting opinions indefinitely. Further, we investigate agent-based network strategies to facilitate convergence to global consensus.

Towards the implementation of a spectral database for the detection of biological warfare agents

NASA Astrophysics Data System (ADS)

Carestia, M.; Pizzoferrato, R.; Gelfusa, M.; Cenciarelli, O.; D'Amico, F.; Malizia, A.; Scarpellini, D.; Murari, A.; Vega, J.; Gaudio, P.

2014-10-01

The deliberate use of biological warfare agents (BWA) and other pathogens can jeopardize the safety of population, fauna and flora, and represents a concrete concern from the military and civil perspective. At present, the only commercially available tools for fast warning of a biological attack can perform point detection and require active or passive sampling collection. The development of a stand-off detection system would be extremely valuable to minimize the risk and the possible consequences of the release of biological aerosols in the atmosphere. Biological samples can be analyzed by means of several optical techniques, covering a broad region of the electromagnetic spectrum. Strong evidence proved that the informative content of fluorescence spectra could provide good preliminary discrimination among those agents and it can also be obtained through stand-off measurements. Such a system necessitates a database and a mathematical method for the discrimination of the spectral signatures. In this work, we collected fluorescence emission spectra of the main BWA simulants, to implement a spectral signature database and apply the Universal Multi Event Locator (UMEL) statistical method. Our preliminary analysis, conducted in laboratory conditions with a standard UV lamp source, considers the main experimental setups influencing the fluorescence signature of some of the most commonly used BWA simulants. Our work represents a first step towards the implementation of a spectral database and a laser-based biological stand-off detection and identification technique.

Method for distinguishing normal and transformed cells using G1 kinase inhibitors

DOEpatents

Crissman, Harry A.; Gadbois, Donna M.; Tobey, Robert A.; Bradbury, E. Morton

1993-01-01

A G.sub.1 phase kinase inhibitor is applied in a low concentration to a population of normal and transformed mammalian cells. The concentration of G.sub.1 phase kinase inhibitor is selected to reversibly arrest normal mammalian cells in the G.sub.1 cell cycle without arresting growth of transformed cells. The transformed cells may then be selectively identified and/or cloned for research or diagnostic purposes. The transformed cells may also be selectively killed by therapeutic agents that do not affect normal cells in the G.sub.1 phase, suggesting that such G.sub.1 phase kinase inhibitors may form an effective adjuvant for use with chemotherapeutic agents in cancer therapy for optimizing the killing dose of chemotherapeutic agents while minimizing undesirable side effects on normal cells.

Method for distinguishing normal and transformed cells using G1 kinase inhibitors

DOEpatents

Crissman, H.A.; Gadbois, D.M.; Tobey, R.A.; Bradbury, E.M.

1993-02-09

A G[sub 1] phase kinase inhibitor is applied in a low concentration to a population of normal and transformed mammalian cells. The concentration of G[sub 1] phase kinase inhibitor is selected to reversibly arrest normal mammalian cells in the G[sub 1] cell cycle without arresting growth of transformed cells. The transformed cells may then be selectively identified and/or cloned for research or diagnostic purposes. The transformed cells may also be selectively killed by therapeutic agents that do not affect normal cells in the G[sub 1] phase, suggesting that such G[sub 1] phase kinase inhibitors may form an effective adjuvant for use with chemotherapeutic agents in cancer therapy for optimizing the killing dose of chemotherapeutic agents while minimizing undesirable side effects on normal cells.

Eliminating extravasation events: a multidisciplinary approach.

PubMed

Coyle, Christine E; Griffie, Julie; Czaplewski, Lynn M

2014-01-01

Administration of chemotherapy agents can give rise to many safety issues. Extravasation of a vesicant agent causes tissue blistering and necrosis. This complication of chemotherapy administration causes additional pain and suffering in patients who are already suffering with a diagnosis of cancer. Nurses hold key responsibilities for educating patients about administration issues and following practice standards to minimize the risk of extravasation. Defining a path of shared responsibilities among team members is a critical step in assuring the safe administration of drugs classified as vesicants. This article describes a clinical practice change that is used at a large midwestern academic medical cancer center. This practice and policy change has resulted in a 90% reduction in the administration of vesicant agents peripherally, with no occurrence of extravasations in the first 6 months of implementation.

Eliminating Extravasation Events: A Multidisciplinary Approach.

PubMed

Coyle, Christine E; Griffie, Julie; Czaplewski, Lynn M

2015-01-01

Administration of chemotherapy agents can give rise to many safety issues. Extravasation of a vesicant agent causes tissue blistering and necrosis. This complication of chemotherapy administration causes additional pain and suffering in patients who are already suffering with a diagnosis of cancer. Nurses hold key responsibilities for educating patients about administration issues and following practice standards to minimize the risk of extravasation. Defining a path of shared responsibilities among team members is a critical step in assuring the safe administration of drugs classified as vesicants. This article describes a clinical practice change that is used at a large midwestern academic medical cancer center. This practice and policy change has resulted in a 90% reduction in the administration of vesicant agents peripherally, with no occurrence of extravasations in the first 6 months of implementation.

Host Specificity of Epiplema albida: A Potential Biological Control Agent for Sri Lankan Privet in the Mascarene Islands

PubMed Central

Shaw, Richard H.

2017-01-01

Epiplema albida (Hampson) (Lepidoptera: Uraniidae, Epipleminae) from Sri Lanka, was studied to assess its safety for use as a biological control agent for Sri Lankan privet, Ligustrum robustum subsp. walkeri (Oleaceae) in La Réunion and other Mascarene Islands. Larval no-choice feeding tests using newly hatched larvae, larval development tests, and multiple choice oviposition tests were used. Adult females of E. albida are shown to have highly selective oviposition behaviour and the species is physiologically restricted to very few hosts for feeding and development. The risk to key test plants in La Réunion is minimal, so this species can be considered for use as a biological control agent there, but would need further evaluation for potential use elsewhere. PMID:28788086

An economic model of friendship and enmity for measuring social balance in networks

NASA Astrophysics Data System (ADS)

Lee, Kyu-Min; Shin, Euncheol; You, Seungil

2017-12-01

We propose a dynamic economic model of networks where agents can be friends or enemies with one another. This is a decentralized relationship model in that agents decide whether to change their relationships so as to minimize their imbalanced triads. In this model, there is a single parameter, which we call social temperature, that captures the degree to which agents care about social balance in their relationships. We show that the global structure of relationship configuration converges to a unique stationary distribution. Using this stationary distribution, we characterize the maximum likelihood estimator of the social temperature parameter. Since the estimator is computationally challenging to calculate from real social network datasets, we provide a simple simulation algorithm and verify its performance with real social network datasets.

Supportive Care in Hemato-Oncology: A Review in Light of the Latest Guidelines

PubMed Central

Gündüz, Eren; Gülbaş, Zafer

2012-01-01

Recent developments in cancer therapy have resulted in increases in treatment success rates and survival. One of thebasic goals of such therapy is improving patient quality of life. Chemotherapy protocols for solid or hematologicalmalignancies-most of which include multiple agents-negatively impact patient quality of life. Additionally, there havebeen developments in supportive care, which seeks to ameliorate or minimize the negative effects of chemotherapy.Herein we present a review and brief summarization of some of the agents used for supportive care in cancer patientsin light of the latest guidelines. PMID:24744617

Antibacterial, antifungal, and antiviral effects of three essential oil blends.

PubMed

Brochot, Amandine; Guilbot, Angèle; Haddioui, Laïla; Roques, Christine

2017-08-01

New agents that are effective against common pathogens are needed particularly for those resistant to conventional antimicrobial agents. Essential oils (EOs) are known for their antimicrobial activity. Using the broth microdilution method, we showed that (1) two unique blends of Cinnamomum zeylanicum, Daucus carota, Eucalyptus globulus and Rosmarinus officinalis EOs (AB1 and AB2; cinnamon EOs from two different suppliers) were active against the fourteen Gram-positive and -negative bacteria strains tested, including some antibiotic-resistant strains. Minimal inhibitory concentrations (MICs) ranged from 0.01% to 3% v/v with minimal bactericidal concentrations from <0.01% to 6.00% v/v; (2) a blend of Cinnamomum zeylanicum, Daucus carota, Syzygium aromaticum, Origanum vulgare EOs was antifungal to the six Candida strains tested, with MICs ranging from 0.01% to 0.05% v/v with minimal fungicidal concentrations from 0.02% to 0.05% v/v. Blend AB1 was also effective against H1N1 and HSV1 viruses. With this dual activity, against H1N1 and against S. aureus and S. pneumoniae notably, AB1 may be interesting to treat influenza and postinfluenza bacterial pneumonia infections. These blends could be very useful in clinical practice to combat common infections including those caused by microorganisms resistant to antimicrobial drugs. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

CE: Preventing Contrast-Induced Acute Kidney Injury.

PubMed

Gallegos, Yvonne; Taha, Asma Ali; Rutledge, Dana N

2016-12-01

: Diagnostic radiographic imaging scans using intravascular iodinated contrast media can lead to various complications. The most salient of these is contrast-induced acute kidney injury (CI-AKI) or contrast-induced nephropathy, a potentially costly and serious patient safety concern. Prevention strategies are the cornerstone of evidence-based clinical management for patients receiving contrast agents. These include preprocedure screening, stratification of patients based on risk factors, and protective interventions, the most important of which is hydration both before and after the radiographic imaging scan. There is a gap, however, between best evidence and clinical practice in terms of exact hydration protocols. Nurses play an important role in nephropathy prevention and need to be familiar with CI-AKI as a potential complication of radiographic imaging scans. In order to ensure safe, high-quality care, nurses must be involved in efforts to prevent CI-AKI as well as interventions that minimize patients' risk of kidney injury.

New technology for early detection of health threats

NASA Astrophysics Data System (ADS)

Southern, Šárka O.; Lilienthal, Gerald W.

2008-04-01

Governmental agencies charged with protecting the health of the population and agriculture have several main strategic objectives including the detection of harmful agents, the identification of vulnerable biological targets, the prediction of health outcomes and the development of countermeasures. New technologies are urgently needed in several critical areas of bio-chemical defense: economical and minimally invasive biosensors for field use in humans and other species important for agriculture and infrastructure, universal analytical platforms for broad-based, early warnings of threats and technologies guiding the development of countermeasures. A new technology called Stress Response Profiling (SRP) was recently developed by the Gaia Medical Institute. SRP provides a universal analytical platform for monitoring health status based on measurements of physiological stress. The platform is implemented through handheld devices that can be used for noninvasive detection of early-stage health problems. This paper summarizes SRP features, advantages and potential benefits for critical areas of homeland defense.

Self-* properties through gossiping.

PubMed

Babaoglu, Ozalp; Jelasity, Márk

2008-10-28

As computer systems have become more complex, numerous competing approaches have been proposed for these systems to self-configure, self-manage, self-repair, etc. such that human intervention in their operation can be minimized. In ubiquitous systems, this has always been a central issue as well. In this paper, we overview techniques to implement self-* properties in large-scale, decentralized networks through bio-inspired techniques in general, and gossip-based algorithms in particular. We believe that gossip-based algorithms could be an important inspiration for solving problems in ubiquitous computing as well. As an example, we outline a novel approach to arrange large numbers of mobile agents (e.g. vehicles, rescue teams carrying mobile devices) into different formations in a totally decentralized manner. The approach is inspired by the biological mechanism of cell sorting via differential adhesion, as well as by our earlier work in self-organizing peer-to-peer overlay networks.

Effect of 2',3'-didehydro-3'-deoxythymidine in an in vitro hollow-fiber pharmacodynamic model system correlates with results of dose-ranging clinical studies.

PubMed Central

Bilello, J A; Bauer, G; Dudley, M N; Cole, G A; Drusano, G L

1994-01-01

We sought to validate an in vitro system which could predict the minimal effect dose of antiretroviral agents. Mixtures of uninfected CEM cells and CEM cells chronically infected with human immunodeficiency virus (HIV) type 1 MN were exposed to 2',3'-didehydro-3'-deoxythymidine (D4T) in vitro in a hollow-fiber model which simulates the plasma concentration-time profile of D4T in patients. Drug concentration was adjusted to simulate continuous intravenous infusion, or an intravenous bolus administered twice daily. The effect of the dosing regimen was measured with viral infectivity, p24 antigen, and reverse transcriptase or PCR for unintegrated HIV DNA. Dose deescalation studies on a twice-daily dosing schedule predicted a minimum effect dose of 0.5 mg/kg of body weight per day which correlated with the results of a clinical trial. Antiviral effect was demonstrated to be independent of schedule for every 12-h dosing versus continuous infusion. Finally, at or near the minimal effect dose, efficacy appeared to depend on the viral load. The ability of this in vitro pharmacodynamic model to assess the response of HIV-infected cells to different doses and schedules of antiviral agents may be useful in the design of optimal dosing regimens for clinical trials but requires validation with other types of antiretroviral agents. PMID:8092842

Clinical evaluation of a new 10% carbamide peroxide tooth-whitening agent.

PubMed

Barnes, D M; Kihn, P W; Romberg, E; George, D; DePaola, L; Medina, E

1998-10-01

NUPRO Gold Tooth Whitening System was evaluated for efficacy according to the proposed ADA guidelines for acceptance. Sixty participants with discolored anterior teeth participated in a 14-day, double-blind, clinical trial. The participants were matched for age, gender, and oral health status and were given either a placebo gel without the active agent or the NUPRO Gold active gel, which they wore in a custom-fabricated mouth guard for home use. The shade of each participant's maxillary anterior teeth was evaluated using a value-oriented Vita Lumin Vacuum Shade Guide before the study. The same shade guide was used to determine shade changes. Time of use of the agent and potential side effects, such as tooth and gingival hypersensitivity and tissue irritation, were assessed at all recall examinations and were recorded by participants in daily diaries. The average shade change for the placebo users was less than one shade. The average shade change for the NUPRO Gold users was 6.96 shades. Tooth hypersensitivity varied from none to severe. Tissue irritation was minimal. The results of these evaluations indicate that NUPRO Gold is effective as a tooth-whitening system, when administered properly under the supervision of a dentist, with commonly reported side effects of transient tooth sensitivity and minimal gingival sensitivity. Little or no change in tissue health was noted. This study was supported by Dentsply Preventive Care (York, Pennsylvania).

Distinct mobilization of leukocytes and hematopoietic stem cells by CXCR4 peptide antagonist LY2510924 and monoclonal antibody LY2624587

PubMed Central

Peng, Sheng-Bin; Van Horn, Robert D.; Yin, Tinggui; Brown, Robin M.; Roell, William C.; Obungu, Victor H.; Ruegg, Charles; Wroblewski, Victor J.; Raddad, Eyas; Stille, John R.

2017-01-01

Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 play a critical role in mobilization and redistribution of immune cells and hematopoietic stem cells (HSCs). We evaluated effects of two CXCR4-targeting agents, peptide antagonist LY2510924 and monoclonal antibody LY2624587, on mobilizing HSCs and white blood cells (WBCs) in humans, monkeys, and mice. Biochemical analysis showed LY2510924 peptide blocked SDF-1/CXCR4 binding in all three species; LY2624587 antibody blocked binding in human and monkey, with minimal activity in mouse. Cellular analysis showed LY2624587 antibody, but not LY2510924 peptide, down-regulated cell surface CXCR4 and induced hematological tumor cell death; both agents have been shown to inhibit SDF-1/CXCR4 interaction and downstream signaling. In animal models, LY2510924 peptide induced robust, prolonged, dose- and time-dependent WBC and HSC increases in mice and monkeys, whereas LY2624587 antibody induced only moderate, transient increases in monkeys. In clinical trials, similar pharmacodynamic effects were observed in patients with advanced cancer: LY2510924 peptide induced sustained WBC and HSC increases, while LY2624587 antibody induced only minimal, transient WBC changes. These distinct pharmacodynamic effects in two different classes of CXCR4 inhibitors are clinically important and should be carefully considered when designing combination studies with immune checkpoint inhibitors or other agents for cancer therapy. PMID:29212254

Diffusion and Localization of Relative Strategy Scores in The Minority Game

NASA Astrophysics Data System (ADS)

Granath, Mats; Perez-Diaz, Alvaro

2016-10-01

We study the equilibrium distribution of relative strategy scores of agents in the asymmetric phase (α ≡ P/N≳ 1) of the basic Minority Game using sign-payoff, with N agents holding two strategies over P histories. We formulate a statistical model that makes use of the gauge freedom with respect to the ordering of an agent's strategies to quantify the correlation between the attendance and the distribution of strategies. The relative score xin Z of the two strategies of an agent is described in terms of a one dimensional random walk with asymmetric jump probabilities, leading either to a static and asymmetric exponential distribution centered at x=0 for fickle agents or to diffusion with a positive or negative drift for frozen agents. In terms of scaled coordinates x/√{N} and t / N the distributions are uniquely given by α and in quantitative agreement with direct simulations of the game. As the model avoids the reformulation in terms of a constrained minimization problem it can be used for arbitrary payoff functions with little calculational effort and provides a transparent and simple formulation of the dynamics of the basic Minority Game in the asymmetric phase.

Effects of iodinated contrast agent, xylocaine and gadolinium concentration on the signal emitted in magnetic resonance arthrography: a samples study*

PubMed Central

da Silva, Yvana Lopes Pinheiro; Costa, Rita Zanlorensi Visneck; Pinho, Kátia Elisa Prus; Ferreira, Ricardo Rabello; Schuindt, Sueliton Miyamoto

2015-01-01

Objective To investigate the effects of dilution of paramagnetic contrast agent with iodinated contrast and xylocaine on the signal intensity during magnetic resonance arthrography, and to improve the paramagnetic contrast agent concentration utilized in this imaging modality. Materials and Methods Samples specially prepared for the study with three different concentrations of paramagnetic contrast agent diluted in saline, iodinated contrast agent and xylocaine were imaged with fast spin echo T1-weighted sequences with fat saturation. The samples were placed into flasks and graphical analysis of the signal intensity was performed as a function of the paramagnetic contrast concentration. Results As compared with samples of equal concentrations diluted only with saline, the authors have observed an average signal intensity decrease of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the increased gadolinium concentration in the samples caused decrease in signal intensity with all the dilutions. Conclusion Minimizing the use of iodinated contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5 mmol/L diluted in saline will improve the sensitivity of magnetic resonance arthrography. PMID:25987746

The Risk of Some Veterinary Antimicrobial Agents on Public Health Associated with Antimicrobial Resistance and their Molecular Basis

PubMed Central

Hao, Haihong; Sander, Pascal; Iqbal, Zahid; Wang, Yulian; Cheng, Guyue; Yuan, Zonghui

2016-01-01

The risk of antimicrobial agents used in food-producing animals on public health associated with antimicrobial resistance continues to be a current topic of discussion as related to animal and human public health. In the present review, resistance monitoring data, and risk assessment results of some important antimicrobial agents were cited to elucidate the possible association of antimicrobial use in food animals and antimicrobial resistance in humans. From the selected examples, it was apparent from reviewing the published scientific literature that the ban on use of some antimicrobial agents (e.g., avoparcin, fluoroquinolone, tetracyclines) did not change drug resistance patterns and did not mitigate the intended goal of minimizing antimicrobial resistance. The use of some antimicrobial agents (e.g., virginiamycin, macrolides, and cephalosporins) in food animals may have an impact on the antimicrobial resistance in humans, but it was largely depended on the pattern of drug usage in different geographical regions. The epidemiological characteristics of resistant bacteria were closely related to molecular mechanisms involved in the development, fitness, and transmission of antimicrobial resistance. PMID:27803693

L-β-N-methylamino-l-alanine (BMAA) nitrosation generates a cytotoxic DNA damaging alkylating agent: An unexplored mechanism for neurodegenerative disease.

PubMed

Potjewyd, G; Day, P J; Shangula, S; Margison, G P; Povey, A C

2017-03-01

L-β-N-methylamino-l-alanine (BMAA) is a non-proteinic amino acid, that is neurotoxic in vitro and in animals, and is implicated in the causation of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC) on Guam. Given that natural amino acids can be N-nitrosated to form toxic alkylating agents and the structural similarity of BMAA to other amino acids, our hypothesis was that N-nitrosation of BMAA might result in a toxic alkylating agent, providing a novel mechanistic hypothesis for BMAA action. We have chemically nitrosated BMAA with sodium nitrite to produce nitrosated BMAA (N-BMAA) which was shown to react with the alkyl-trapping agent, 4-(p-nitrobenzyl)pyridine, cause DNA strand breaks in vitro and was toxic to the human neuroblastoma cell line SH-SY5Y under conditions in which BMAA itself was minimally toxic. Our results indicate that N-BMAA is an alkylating agent and toxin suggesting a plausible and previously unrecognised mechanism for the neurotoxic effects of BMAA. Copyright © 2017 Elsevier B.V. All rights reserved.

Minimally Invasive Monitoring of Chronic Central Venous Catheter Patency in Mice Using Digital Subtraction Angiography (DSA)

PubMed Central

Figueiredo, Giovanna; Fiebig, Teresa; Kirschner, Stefanie; Nikoubashman, Omid; Kabelitz, Lisa; Othman, Ahmed; Nonn, Andrea; Kramer, Martin; Brockmann, Marc A.

2015-01-01

Background Repetitive administration of medication or contrast agents is frequently performed in mice. The introduction of vascular access mini-ports (VAMP) for mice allows long-term vascular catheterization, hereby eliminating the need for repeated vessel puncture. With catheter occlusion being the most commonly reported complication of chronic jugular vein catheterization, we tested whether digital subtraction angiography (DSA) can be utilized to evaluate VAMP patency in mice. Methods Twenty-three mice underwent catheterization of the jugular vein and subcutaneous implantation of a VAMP. The VAMP was flushed every second day with 50 μL of heparinized saline solution (25 IU/ml). DSA was performed during injection of 100 μL of an iodine based contrast agent using an industrial X-ray inspection system intraoperatively, as well as 7±2 and 14±2 days post implantation. Results DSA allowed localization of catheter tip position, to rule out dislocation, kinking or occlusion of a microcatheter, and to evaluate parent vessel patency. In addition, we observed different ante- and retrograde collateral flow patterns in case of jugular vein occlusion. More exactly, 30% of animals showed parent vessel occlusion after 7±2 days in our setting. At this time point, nevertheless, all VAMPs verified intravascular contrast administration. After 14±2 days, intravascular contrast injection was verified in 70% of the implanted VAMPs, whereas at this point of time 5 animals had died or were sacrificed and in 2 mice parent vessel occlusion hampered intravascular contrast injection. Notably, no occlusion of the catheter itself was observed. Conclusion From our observations we conclude DSA to be a fast and valuable minimally invasive tool for investigation of catheter and parent vessel patency and for anatomical studies of collateral blood flow in animals as small as mice. PMID:26098622

Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats.

PubMed

Bloch-Shilderman, E; Rabinovitz, I; Egoz, I; Yacov, G; Allon, N; Nili, U

2018-02-01

VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure. Characterization of such a threshold is crucial for dealing with unresolved operative dilemmas such as when it is safe enough to resettle a population that has been evacuated from a VX-contaminated area. Rats, continuously exposed to various doses of VX (0.225-45 µg/kg/day) for 4 weeks via implanted mini-osmotic pumps, showed a dose-dependent and continuous decrease in ChE activity in whole blood, brain and muscles, ranging between 20 and 100%. Exposure to 13.5 µg/kg/day led to a stable low ChE activity level (~ 20%), accompanied by transient and negligible electrocorticogram spectral power transformations, especially in the theta and alpha brain wave frequencies, and a significant decrease in total brain M2 receptor density. These changes were neither accompanied by observable signs of intoxication nor by changes in motor function, circadian rhythm or TSPO level (a reliable marker of brain damage). Following exposure to lower doses of 2.25 and 0.225 µg/kg/day, the only change measured was a reduction in ChE activity of 60 and 20%, respectively. Based on these results, we delineate ChE inhibition as the physiological measure most susceptible to alterations following prolonged VX exposure, and determine for the first time the threshold sub-acute VX dose for minimal physiological effects (up to 20% reduction in ChE activity) in the rat as 0.225 µg/kg/day.

Cooperative mobile agents search using beehive partitioned structure and Tabu Random search algorithm

NASA Astrophysics Data System (ADS)

Ramazani, Saba; Jackson, Delvin L.; Selmic, Rastko R.

2013-05-01

In search and surveillance operations, deploying a team of mobile agents provides a robust solution that has multiple advantages over using a single agent in efficiency and minimizing exploration time. This paper addresses the challenge of identifying a target in a given environment when using a team of mobile agents by proposing a novel method of mapping and movement of agent teams in a cooperative manner. The approach consists of two parts. First, the region is partitioned into a hexagonal beehive structure in order to provide equidistant movements in every direction and to allow for more natural and flexible environment mapping. Additionally, in search environments that are partitioned into hexagons, mobile agents have an efficient travel path while performing searches due to this partitioning approach. Second, we use a team of mobile agents that move in a cooperative manner and utilize the Tabu Random algorithm to search for the target. Due to the ever-increasing use of robotics and Unmanned Aerial Vehicle (UAV) platforms, the field of cooperative multi-agent search has developed many applications recently that would benefit from the use of the approach presented in this work, including: search and rescue operations, surveillance, data collection, and border patrol. In this paper, the increased efficiency of the Tabu Random Search algorithm method in combination with hexagonal partitioning is simulated, analyzed, and advantages of this approach are presented and discussed.

Developing an effective breast cancer vaccine.

PubMed

Soliman, Hatem

2010-07-01

Harnessing the immune response in treating breast cancer would potentially offer a less toxic, more targeted approach to eradicating residual disease. Breast cancer vaccines are being developed to effectively train cytotoxic T cells to recognize and kill transformed cells while sparing normal ones. However, achieving this goal has been problematic due to the ability of established cancers to suppress and evade the immune response. A review of the literature on vaccines and breast cancer treatment was conducted, specifically addressing strategies currently available, as well as appropriate settings, paradigms for vaccine development and response monitoring, and challenges with immunosuppression. Multiple issues need to be addressed in order to optimize the benefits offered by breast cancer vaccines. Primary issues include the following: (1) cancer vaccines will likely work better in a minimal residual disease state, (2) clinical trial design for immunotherapy should incorporate recommendations from expert groups such as the Cancer Vaccine Working Group and use standardized immune response measurements, (3) the presently available cancer vaccine approaches, including dendritic cell-based, tumor-associated antigen peptide-based, and whole cell-based, have various pros and cons, (4) to date, no one approach has been shown to be superior to another, and (5) vaccines will need to be combined with immunoregulatory agents to overcome tumor-related immunosuppression. Combining a properly optimized cancer vaccine with novel immunomodulating agents that overcome tumor-related immunosuppression in a well-designed clinical trial offers the best hope for developing an effective breast cancer vaccine strategy.

Laser photoacoustic spectroscopy helps fight terrorism: High sensitivity detection of chemical Warfare Agent and explosives

NASA Astrophysics Data System (ADS)

Patel, C. K. N.

2008-01-01

Tunable laser photoacoustic spectroscopy is maturing rapidly in its applications to real world problems. One of the burning problems of the current turbulent times is the threat of terrorist acts against civilian population. This threat appears in two distinct forms. The first is the potential release of chemical warfare agents (CWA), such as the nerve agents, in a crowded environment. An example of this is the release of Sarin by Aum Shinrikyo sect in a crowded Tokyo subway in 1995. An example of the second terrorist threat is the ever-present possible suicide bomber in crowded environment such as airports, markets and large buildings. Minimizing the impact of both of these threats requires early detection of the presence of the CWAs and explosives. Photoacoustic spectroscopy is an exquisitely sensitive technique for the detection of trace gaseous species, a property that Pranalytica has extensively exploited in its CO2 laser based commercial instrumentation for the sub-ppb level detection of a number of industrially important gases including ammonia, ethylene, acrolein, sulfur hexafluoride, phosphine, arsine, boron trichloride and boron trifluoride. In this presentation, I will focus, however, on our recent use of broadly tunable single frequency high power room temperature quantum cascade lasers (QCL) for the detection of the CWAs and explosives. Using external grating cavity geometry, we have developed room temperature QCLs that produce continuously tunable single frequency CW power output in excess of 300 mW at wavelengths covering 5 μm to 12 μm. I will present data that show a CWA detection capability at ppb levels with false alarm rates below 1:108. I will also show the capability of detecting a variety of explosives at a ppb level, again with very low false alarm rates. Among the explosives, we have demonstrated the capability of detecting homemade explosives such as triacetone triperoxide and its liquid precursor, acetone which is a common household liquid. This capability, deployed at airports and other public places, will go a long way towards increasing public safety and minimizing inconveniences faced in airline travel.

50 CFR 21.51 - Depredation order for resident Canada geese at agricultural facilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... management of resident Canada geese, as defined in § 21.3. (b) What is the depredation order for resident... producers (or their employees or agents) to conduct and implement various components of the depredation... goose management tools to the extent they deem appropriate. To minimize lethal take, agricultural...

Agent Regeneration and Hazardous Waste Minimization and Teaching Note. IBM Case Study. Doc #93-1.

ERIC Educational Resources Information Center

Oliker, L. Richard; And Others

The manufacturing process used to produce printbands for International Business Machines, Inc. involves a photolithographic process in which the stainless steel panels are chemically machined using strong ferric chloride etching solution containing hydrochloric acid. The waste material that results from this chemical reaction is a solution…

Minimal heat treatments reduce Shiga toxin-producing Escherichia coli (STEC)and Salmonella on the surface of fresh beef

USDA-ARS?s Scientific Manuscript database

Washing and sanitizing agents have been effective in reducing bacterial populations and pathogen presence on carcasses. Thermal interventions consistently provide the greatest pathogen reductions and can be applied during slaughter in a number of different forms, either as a whole carcass wash, or t...

Upper-Limb Exercises for Stroke Patients through the Direct Engagement of an Embodied Agent

DTIC Science & Technology

2011-03-01

hemiparesis . To alleviate impairments, pa- tients pursue therapy services at the acute, sub-acute, and chronic phases as necessary. Patients need...year-old male who suffered from a stroke 15 years ago. He has right hemiparesis and ambu- lates with a quad cane. He has limited scapula and minimal

A biomedical solicitation examination of nanoparticles as drug agents to minimize the hemodynamics of a stenotic channel

NASA Astrophysics Data System (ADS)

Ijaz, S.; Nadeem, S.

2017-11-01

A theoretical examination is presented in this analysis to study the flow of a bio-nanofluid through a curved stenotic channel. The curved channel is considered with an overlapping stenotic region. The effect of convective conditions is incorporated to discuss the heat transfer characteristic. The mathematical problem of a curved stenotic channel is formulated and then solved by using the exact technique. To discuss the hemodynamics of a curved stenotic channel the expression of resistance to blood is evaluated by dividing the channel into pre-stenotic, stenotic and post stenotic region. In this investigation gold, silver and copper nanoparticles are used as drug carriers. The outcomes of the graphical illustration reveal that with an increase in nanoparticle concentration hemodynamics effects of stenosed curved channel are reduced and they also conclude that the drug Au nanoparticles are more effective to minimize hemodynamics when compared to the drug Ag and Cu nanoparticles. This analysis finds valuable theoretical information for nanoparticles used as drug agents in the field of bio-inspired applications.

[Cefazolin efficacy and antibiotic sensitivity against pathogenic bacteria in pediatric with acute upper urinary tract infection].

PubMed

Fuke, Toshiya; Abe, Yoshifusa; Hoshino, Akihiro; Oto, Hideyasu; Sakai, Naho; Murayama, Junichiro; Yoshida, Koichiro; Itabashi, Kazuo

2010-05-01

Acute upper urinary tract infection may cause sepsis, especially in neonates and infants, mandating the choice of appropriate, effective antibacterials minimizing increasing bacterial resistance. Frequently prescribing broad-spectrum cephalosporinin is one such example. Different antibacterial therapies are initiated clinically due to treatment protocol differences among institutions, disease severity, etc. We studied the efficacy of cefazolin (CEZ), a first-generation cephalosporin, as first-line parenteral treatment in acute upper urinary tract infection. We found that 88.9% of microbial infections have indications for CEZ. CEZ efficacy is 91.3%, and 97.2% of urine cultures show negative results. Escherichia coli sensitivity to antibacterial agents is 90.9% of the minimal inhibitory concentration (MIC) < 4 for CEZ, 93.9% of MIC < 1 for ceftazidime (CAZ), 63.6% of MIC < 4 for ampicillin, and 81.8% of MIC < 2 for gentamicin. CEZ thus has the same efficacy as CAZ and is more effective than other antibacterial agents against E. coli. We concluded that CEZ is an effective antibacterial in initial antibacterial pediatric therapy in acute upper urinary tract infection.

Simple procedures to obtain exogenous internal controls for use in RT-PCR detection of bovine pestiviruses.

PubMed

Golemba, Marcelo D; Parreño, Viviana; Jones, Leandro R

2008-06-01

Pestiviruses are ubiquitous pathogens of cattle and frequent adventitious viruses in biologicals. Furthermore, it has been suggested that these agents might be related to infantile gastroenteritis and microencephaly. Since the virus is highly prevalent in fetal bovine serum, the risk of contamination is high in most laboratories. Thus, the implementation of detection methods in all laboratories is of worth. Despite continuous surveillance, these agents have been detected in cell lines, fetal bovine serum, live and inactivated animal and human vaccines and interferon for human use. In this report, DNA and RNA internal controls (ICs) which can be implemented in laboratories with minimal equipment are described. The developed standards can be added before RNA purification, allowing to monitor all steps of the protocol (viral RNA extraction, reverse transcription and cDNA amplification). It is shown that inhibitory effects that could lead to decreased sensitivity can be minimized by controlling the amount of mimic molecules added to the samples. A method to avoid the problem of DNA traces present in in vitro transcribed RNA preparations is provided.

Comparative molecular field analysis to derive pharmacophore maps for induction doses of intravenous anaesthetic agents.

PubMed

Sear, J W

2011-03-01

The present study examines the molecular basis of induction of anaesthesia by i.v. hypnotic agents using comparative molecular field analysis (CoMFA). ED(50) induction doses for 14 i.v. anaesthetics in human subjects (expressed as molar dose per kilogram body weight) were obtained from the literature. Immobilizing potency data for the same 14 agents (expressed as the EC(50) plasma free drug concentrations that abolish movement in response to a noxious stimulus in 50% patients) were taken from our previous publication. These data were used to form CoMFA models for the two aspects of anaesthetic activity. Molecular alignment was achieved by field-fit minimization techniques. The lead structure for both models was eltanolone. The final CoMFA model for the ED(50) induction dose was based on two latent variables, and explained 99.3% of the variance in observed activities. It showed good intrinsic predictability (cross-validated q(2)=0.849). The equivalent model for immobilizing activity was also based on two latent variables, with r(2)=0.988 and q(2)=0.852. Although there was a correlation between -log ED(50) and -log EC(50) (r(2)=0.779), comparison of the pharmacophore maps showed poor correlation for both electrostatic and steric regions when isocontours were constructed by linking lattice grid points, making the greatest 40% contributions; the relative contributions of electrostatic and steric interactions differing between the models (induction dose: 2.5:1; immobilizing activity 1.8:1). Comparison of two CoMFA activity models shows only small elements of commonality, suggesting that different molecular features may be responsible for these two properties of i.v. anaesthetics.

Evidence-based clinical update: Which local anesthetic drug for pediatric caudal block provides optimal efficacy with the fewest side effects?

PubMed

Dobereiner, Elisabeth F A; Cox, Robin G; Ewen, Alastair; Lardner, David R

2010-12-01

The purpose of this evidence-based clinical update is to identify the best evidence when selecting a long-acting local anesthetic agent for single-shot pediatric caudal anesthesia in children. A structured literature search was conducted using PubMed and Medline (OVID) using the terms "caudal" and combinations of at least two of "bupivacaine", "ropivacaine", and "levobupivacaine". The search limits included "randomized controlled trials" (RCTs), "meta-analysis", "evidence-based reviews" or "reviews", "human", and "all child: 0-18 yr". Seventeen RCTs were identified that concerned single-shot pediatric caudal anesthesia with at least two of the three drugs in question. Data were extracted for the areas of clinical efficacy and side effects. Study findings were assigned levels of evidence, and grades of recommendation were made according to Centre for Evidence-Based Medicine criteria. The three drugs investigated were found to be equivalent in terms of efficacy. Evidence showed bupivacaine with the highest incidence of motor block and ropivacaine with the lowest. Adverse effects were rare and unrelated to the choice of drug. There were no serious adverse events. None of the three agents was shown to be superior in terms of efficacy. Bupivacaine is preferred if motor block is desired, ropivacaine is preferred if motor block is to be minimized. Adverse effects in human studies are rare, mild, and unrelated to the choice of drug. Despite encountering the absence of serious adverse events in each of the studies reviewed, it is noted that animal studies suggest a safer profile with ropivacaine or levobupivacaine than with bupivacaine.

Bactericidal action of binary and ternary mixtures of carvacrol, thymol, and eugenol against Listeria innocua.

PubMed

García-García, Rebeca; López-Malo, Aurelio; Palou, Enrique

2011-03-01

The bactericidal effect of 3 natural agents (carvacrol, thymol, and eugenol) was evaluated as well as their binary and ternary mixtures on Listeria innocua inactivation in liquid model systems. Minimal bactericidal concentrations (MBC) of these agents were determined, and then binary and ternary mixtures were evaluated. Culture media were inoculated with L. innocua and incubated for 72 h at 35 °C. Turbidity of studied systems were determined every 24 h. The most effective individual antimicrobial agent was carvacrol, followed by thymol and then eugenol with MBCs of 150, 250, and 450 mg kg(-1), respectively. It was observed that the most effective binary mixture was 75 mg kg(-1) carvacrol and 62.5 mg kg(-1) thymol. Furthermore, the ternary mixture carvacrol-thymol-eugenol in concentrations of 75, 31.25, and 56.25 mg kg(-1), correspondingly, was the most effective for L. innocua inactivation. Several binary and ternary mixtures of these 3 natural antimicrobial agents worked adequately to inactivate L. innocua.

All Natural and Clean-Label Preservatives and Antimicrobial Agents Used during Poultry Processing and Packaging.

PubMed

Grant, Ar'quette; Parveen, Salina

2017-04-01

The poultry industry is faced with compounding pressures of maintaining product safety and wholesomeness while keeping up with consumer trends of all-natural foods and label accuracy. Consumers are increasingly demanding that their foods be minimally processed and contain compounds that are easily read and recognized, i.e., products must be clean labeled. The purpose of this review is to briefly describe several natural antimicrobial agents that can be incorporated into poultry processing. These compounds and their essential oils were included in this mini-review because they are generally recognized as safe by the U.S. Food and Drug Administration and are considered clean label: thyme extract, rosemary extract, garlic, and oregano. This list of natural antimicrobial agents by no means includes all of the options available to poultry processors. Rather, this review provides a brief glance at the potential these natural antimicrobial agents have in terms of reduced pathogenicity, increased shelf stability, and sensory acceptability through direct product application or as part of the product packaging.

Consensus in evolving networks of mobile agents

NASA Astrophysics Data System (ADS)

Baronchelli, Andrea; Díaz-Guilera, Albert

2012-02-01

Populations of mobile and communicating agents describe a vast array of technological and natural systems, ranging from sensor networks to animal groups. Here, we investigate how a group-level agreement may emerge in the continuously evolving networks defined by the local interactions of the moving individuals. We adopt a general scheme of motion in two dimensions and we let the individuals interact through the minimal naming game, a prototypical scheme to investigate social consensus. We distinguish different regimes of convergence determined by the emission range of the agents and by their mobility, and we identify the corresponding scaling behaviors of the consensus time. In the same way, we rationalize also the behavior of the maximum memory used during the convergence process, which determines the minimum cognitive/storage capacity needed by the individuals. Overall, we believe that the simple and general model presented in this talk can represent a helpful reference for a better understanding of the behavior of populations of mobile agents.

Consensus in networks of mobile communicating agents

NASA Astrophysics Data System (ADS)

Baronchelli, Andrea; Díaz-Guilera, Albert

2012-01-01

Populations of mobile and communicating agents describe a vast array of technological and natural systems, ranging from sensor networks to animal groups. Here, we investigate how a group-level agreement may emerge in the continuously evolving network defined by the local interactions of the moving individuals. We adopt a general scheme of motion in two dimensions and we let the individuals interact through the minimal naming game, a prototypical scheme to investigate social consensus. We distinguish different regimes of convergence determined by the emission range of the agents and by their mobility, and we identify the corresponding scaling behaviors of the consensus time. In the same way, we rationalize also the behavior of the maximum memory used during the convergence process, which determines the minimum cognitive/storage capacity needed by the individuals. Overall, we believe that the simple and general model presented in this paper can represent a helpful reference for a better understanding of the behavior of populations of mobile agents.

New aspects of boar semen freezing strategies.

PubMed

Grossfeld, R; Sieg, B; Struckmann, C; Frenzel, A; Maxwell, W M C; Rath, D

2008-11-01

Although cryopreserved boar semen has been available since 1975, a major breakthrough in commercial application has not yet occurred. There is ongoing research to improve sperm survival after thawing, to limit the damage occurring to spermatozoa during freezing, and to further minimize the number of spermatozoa needed to establish a pregnancy. Boar spermatozoa are exposed to lipid peroxidation during freezing and thawing, which causes damage to the sperm membranes and impairs energy metabolism. The addition of antioxidants or chelating agents (e.g. catalase, vitamin E, glutathione, butylated hydroxytoluene or superoxide dismutase) to the still standard egg-yolk based cooling and freezing media for boar semen, effectively prevented this damage. In general, final glycerol concentrations of 2-3% in the freezing media, cooling rates of -30 to -50 degrees C/min, and thawing rates of 1200-1800 degrees C/min resulted in the best sperm survival. However, cooling and thawing rates individually optimized for sub-standard freezing boars have substantially improved their sperm quality after cryopreservation. With deep intrauterine insemination, the sperm dose has been decreased from 6 to 1x10(9) spermatozoa without compromising farrowing rate or litter size. Minimizing insemination-to-ovulation intervals, based either on estimated or determined ovulation, have also improved the fertility after AI with cryopreserved boar semen. With this combination of different approaches, acceptable fertility with cryopreserved boar semen can be achieved, facilitating the use of cryopreserved boar semen in routine AI programs.

Equilibria, prudent compromises, and the "waiting" game.

PubMed

Sim, Kwang Mong

2005-08-01

While evaluation of many e-negotiation agents are carried out through empirical studies, this work supplements and complements existing literature by analyzing the problem of designing market-driven agents (MDAs) in terms of equilibrium points and stable strategies. MDAs are negotiation agents designed to make prudent compromises taking into account factors such as time preference, outside option, and rivalry. This work shows that 1) in a given market situation, an MDA negotiates optimally because it makes minimally sufficient concession, and 2) by modeling negotiation of MDAs as a game gamma of incomplete information, it is shown that the strategies adopted by MDAs are stable. In a bilateral negotiation, it is proven that the strategy pair of two MDAs forms a sequential equilibrium for gamma. In a multilateral negotiation, it is shown that the strategy profile of MDAs forms a market equilibrium for gamma.

Information processing and dynamics in minimally cognitive agents.

PubMed

Beer, Randall D; Williams, Paul L

2015-01-01

There has been considerable debate in the literature about the relative merits of information processing versus dynamical approaches to understanding cognitive processes. In this article, we explore the relationship between these two styles of explanation using a model agent evolved to solve a relational categorization task. Specifically, we separately analyze the operation of this agent using the mathematical tools of information theory and dynamical systems theory. Information-theoretic analysis reveals how task-relevant information flows through the system to be combined into a categorization decision. Dynamical analysis reveals the key geometrical and temporal interrelationships underlying the categorization decision. Finally, we propose a framework for directly relating these two different styles of explanation and discuss the possible implications of our analysis for some of the ongoing debates in cognitive science. Copyright © 2014 Cognitive Science Society, Inc.

[Epidemiologic diagnostic of nosocomial suppurative-septic infections of Pseudomonas etiology based on intraspecies typing of causative agent].

PubMed

Fel'dblium, I V; Zakharova, Iu A; Nikolaeva, A M; Fedotova, O S

2013-01-01

Scientific justification of optimization of epidemiologic diagnostic of suppurative-septic infection (SSI) caused by Pseudomonas aeruginosa based on comparability of antibiotic sensitivity and beta-lactamase production. Intraspecies typing of 37 P. aeruginosa strains isolated during microbiological monitoring of 106 patients and 131 objects of clinical environment of surgical and obstetrician hospitals by using a complex ofphenotypic and molecular-biological methods including determination of sensitivity to antibiotics by serial dilutions method and PCR-diagnostics with determination of TEM, SHV, CTX, OXA, MBL, VIM genes was performed. P. aeruginosa strains combined into groups by isolation location during studies turned out to be heterogeneous by sensitivity to antibiotics and beta-lactamase production that allowed to form subgroups of strains by focality attribute. Isolates recovered from different SSI foci had significant differences in minimal inhibitory concentration (MIC) reaching 1024 times. MIC parameter within subgroups did not exceed 8 - 16 consequent dilutions. Use of a complex of phenotypic and molecular-biologic methods of causative agent typing including determination of sensitivity to antibiotics by serial dilutions method and evaluation of beta-lactamase production allowed to establish a mechanism of development of SSI epidemic process caused by P. aeruginosa, detect origins and reservoirs of infection in hospital, modes and factors of transmission and reach maximum justification of epidemiologic control and prophylaxis measures of localization of foci of nosocomial infections of pseudomonas etiology.

Alternative Agents to Prevent Fogging in Head and Neck Endoscopy

PubMed Central

Piromchai, Patorn; Kasemsiri, Pornthep; Thanaviratananich, Sanguansak

2011-01-01

Background: The essential factor for diagnosis and treatment of diseases in head and neck endoscopy is the visibility of the image. An anti-fogging agent can reduce this problem by minimizing surface tension to prevent the condensation of water in the form of small droplets on a surface. There is no report on the use of hibiscrub® or baby shampoo to reduce fogging in the literature. The objective of this study was to compare the efficacy between commercial anti-fogging agent, hibiscrub® and baby shampoo to reduce fogging for the use in head and neck endoscopy. Methods: The study was conducted at the Department of Otorhinolaryngology, Faculty of Medicine, Khon Kaen University in August 2010. Commercial anti-fogging agent, baby shampoo and hibiscrub® were applied on rigid endoscope lens before putting them into a mist generator. The images were taken at baseline, 15 seconds, 30 seconds and 1 minute. The images’ identifiers were removed before they were sent to two evaluators. A visual analogue scale (VAS) was used to rate the image quality from 0 to 10. Results: The difference in mean VAS score between anti-fogging agent, baby shampoo and hibiscrub® versus no agent were 5.46, 4.45 and 2.1 respectively. The commercial anti-fogging agent and baby shampoo had most protective benefit and performed significantly better than no agent (P = 0.05). Conclusions: Baby shampoo is an effective agent to prevent fogging during head and neck endoscopy and compares favourably with commercial anti-fogging agent. PMID:24179399

Operant conditioning: a minimal components requirement in artificial spiking neurons designed for bio-inspired robot's controller

PubMed Central

Cyr, André; Boukadoum, Mounir; Thériault, Frédéric

2014-01-01

In this paper, we investigate the operant conditioning (OC) learning process within a bio-inspired paradigm, using artificial spiking neural networks (ASNN) to act as robot brain controllers. In biological agents, OC results in behavioral changes learned from the consequences of previous actions, based on progressive prediction adjustment from rewarding or punishing signals. In a neurorobotics context, virtual and physical autonomous robots may benefit from a similar learning skill when facing unknown and unsupervised environments. In this work, we demonstrate that a simple invariant micro-circuit can sustain OC in multiple learning scenarios. The motivation for this new OC implementation model stems from the relatively complex alternatives that have been described in the computational literature and recent advances in neurobiology. Our elementary kernel includes only a few crucial neurons, synaptic links and originally from the integration of habituation and spike-timing dependent plasticity as learning rules. Using several tasks of incremental complexity, our results show that a minimal neural component set is sufficient to realize many OC procedures. Hence, with the proposed OC module, designing learning tasks with an ASNN and a bio-inspired robot context leads to simpler neural architectures for achieving complex behaviors. PMID:25120464

Modeling perspectives on echolocation strategies inspired by bats flying in groups.

PubMed

Lin, Yuan; Abaid, Nicole

2015-12-21

Bats navigating with echolocation - which is a type of active sensing achieved by interpreting echoes resulting from self-generated ultrasonic pulses - exhibit unique behaviors during group flight. While bats may benefit from eavesdropping on their peers׳ echolocation, they also potentially suffer from confusion between their own and peers׳ pulses, caused by an effect called frequency jamming. This hardship of group flight is supported by experimental observations of bats simplifying their sound-scape by shifting their pulse frequencies or suppressing echolocation altogether. Here, we investigate eavesdropping and varying pulse emission rate from a modeling perspective to understand these behaviors׳ potential benefits and detriments. We define an agent-based model of echolocating bats avoiding collisions in a three-dimensional tunnel. Through simulation, we show that bats with reasonably accurate eavesdropping can reduce collisions compared to those neglecting information from peers. In large populations, bats minimize frequency jamming by decreasing pulse emission rate, while collision risk increases; conversely, increasing pulse emission rate minimizes collisions by allowing more sensing information generated per bat. These strategies offer benefits for both biological and engineered systems, since frequency jamming is a concern in systems using active sensing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Trial Watch

PubMed Central

Galluzzi, Lorenzo; Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Herve´; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido

2012-01-01

During the last two decades, several approaches for the activation of the immune system against cancer have been developed. These include rather unselective maneuvers such as the systemic administration of immunostimulatory agents (e.g., interleukin-2) as well as targeted interventions, encompassing highly specific monoclonal antibodies, vaccines and cell-based therapies. Among the latter, adoptive cell transfer (ACT) involves the selection of autologous lymphocytes with antitumor activity, their expansion/activation ex vivo, and their reinfusion into the patient, often in the context of lymphodepleting regimens (to minimize endogenous immunosuppression). Such autologous cells can be isolated from tumor-infiltrating lymphocytes or generated by manipulating circulating lymphocytes for the expression of tumor-specific T-cell receptors. In addition, autologous lymphocytes can be genetically engineered to prolong their in vivo persistence, to boost antitumor responses and/or to minimize side effects. ACT has recently been shown to be associated with a consistent rate of durable regressions in melanoma and renal cell carcinoma patients and holds great promises in several other oncological settings. In this Trial Watch, we will briefly review the scientific rationale behind ACT and discuss the progress of recent clinical trials evaluating the safety and effectiveness of adoptive cell transfer as an anticancer therapy. PMID:22737606

Deciphering minimal antigenic epitopes associated with Burkholderia pseudomallei and Burkholderia mallei lipopolysaccharide O-antigens.

PubMed

Tamigney Kenfack, Marielle; Mazur, Marcelina; Nualnoi, Teerapat; Shaffer, Teresa L; Ngassimou, Abba; Blériot, Yves; Marrot, Jérôme; Marchetti, Roberta; Sintiprungrat, Kitisak; Chantratita, Narisara; Silipo, Alba; Molinaro, Antonio; AuCoin, David P; Burtnick, Mary N; Brett, Paul J; Gauthier, Charles

2017-07-24

Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. Studies have highlighted the importance of Bp and Bm lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis of seven oligosaccharides as the minimal structures featuring all of the reported acetylation/methylation patterns associated with Bp and Bm LPS O-antigens (OAgs). Our approach is based on the conversion of an L-rhamnose into a 6-deoxy-L-talose residue at a late stage of the synthetic sequence. Using biochemical and biophysical methods, we demonstrate the binding of several Bp and Bm LPS-specific monoclonal antibodies with terminal OAg residues. Mice immunized with terminal disaccharide-CRM197 constructs produced high-titer antibody responses that crossreacted with Bm-like OAgs. Collectively, these studies serve as foundation for the development of novel therapeutics, diagnostics, and vaccine candidates to combat diseases caused by Bp and Bm.Melioidosis and glanders are multifaceted infections caused by gram-negative bacteria. Here, the authors synthesize a series of oligosaccharides that mimic the lipopolysaccharides present on the pathogens' surface and use them to develop novel glycoconjugates for vaccine development.

Operant conditioning: a minimal components requirement in artificial spiking neurons designed for bio-inspired robot's controller.

PubMed

Cyr, André; Boukadoum, Mounir; Thériault, Frédéric

2014-01-01

In this paper, we investigate the operant conditioning (OC) learning process within a bio-inspired paradigm, using artificial spiking neural networks (ASNN) to act as robot brain controllers. In biological agents, OC results in behavioral changes learned from the consequences of previous actions, based on progressive prediction adjustment from rewarding or punishing signals. In a neurorobotics context, virtual and physical autonomous robots may benefit from a similar learning skill when facing unknown and unsupervised environments. In this work, we demonstrate that a simple invariant micro-circuit can sustain OC in multiple learning scenarios. The motivation for this new OC implementation model stems from the relatively complex alternatives that have been described in the computational literature and recent advances in neurobiology. Our elementary kernel includes only a few crucial neurons, synaptic links and originally from the integration of habituation and spike-timing dependent plasticity as learning rules. Using several tasks of incremental complexity, our results show that a minimal neural component set is sufficient to realize many OC procedures. Hence, with the proposed OC module, designing learning tasks with an ASNN and a bio-inspired robot context leads to simpler neural architectures for achieving complex behaviors.

Progress in defining clinically meaningful changes for clinical trials in nonrenal manifestations of SLE disease activity.

PubMed

Choi, Chan-Bum; Liang, Matthew H; Bae, Sang-Cheol

2016-01-06

Since the 2002 Dusseldorf meeting, one new agent, Benlysta, has been approved by the US Food and Drug Administration for systemic lupus erythematosus. Experiences from the field in conducting trials of all the agents tested during this period have provided valuable practical insights. There has been incremental progress in defining the minimal clinically important difference (MCID) of key disease manifestations and the view is largely that of the health care providers and not that of the person suffering the disease. This basic methodological work on the MCID should improve the efficiency and the clinical relevance of future trials and their design.

Iodinated contrast media and their adverse reactions.

PubMed

Singh, Jagdish; Daftary, Aditya

2008-06-01

Cross-use of technology between nuclear medicine and radiology technologists is expanding. The growth of PET/CT and the increasing use of intravenous contrast agents during these procedures bring the nuclear medicine technologist into direct contact with these agents and their associated complications. A basic understanding of the occurrence, risk factors, clinical features, and management of these procedures is of increasing importance to the nuclear medicine technologist. After reading this article, the technologist will be able to list the factors that increase the risk of contrast reactions; understand ways to minimize the occurrence of contrast reactions; and develop a plan to identify, treat, and manage the reactions effectively.

Nanotechnology: A Valuable Strategy to Improve Bacteriocin Formulations

PubMed Central

Fahim, Hazem A.; Khairalla, Ahmed S.; El-Gendy, Ahmed O.

2016-01-01

Bacteriocins are proteinaceous antibacterial compounds, produced by diverse bacteria, which have been successfully used as: (i) food biopreservative; (ii) anti-biofilm agents; and (iii) additives or alternatives to the currently existing antibiotics, to minimize the risk of emergence of resistant strains. However, there are several limitations that challenge the use of bacteriocins as biopreservatives/antibacterial agents. One of the most promising avenues to overcome these limitations is the use of nanoformulations. This review highlights the practical difficulties with using bacteriocins to control pathogenic microorganisms, and provides an overview on the role of nanotechnology in improving the antimicrobial activity and the physicochemical properties of these peptides. PMID:27695440

Feasibility study for the manufacture of zero gravity pharmaceuticles, immunological, and viral agents

NASA Technical Reports Server (NTRS)

1974-01-01

The feasibility of extracting, isolating, purifying, separating, or preparing medical and biological products of high socio-economic value in space was studied. In particular, the study was designed to concentrate on the isolation or purification of virals, pharmaceutical and immunological agents by means of electrophoresis, as the Apollo 16 flight demonstrated that a mixed population of latex spheres (.2 and .8 microns) could be successfully separated by electrophoresis in space and without sedimentation with minimal convection. This prompted NASA scientists to look into the possibility of carrying out types of biochemical experiments that would utilize space for medical purposes.

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods

PubMed Central

Abreu, D. P. B.; Almeida-Paes, R.; Brilhante, R. S. N.; Chakrabarti, A.; Córdoba, S.; Gonzalez, G. M.; Guarro, J.; Johnson, E. M.; Kidd, S. E.; Pereira, S. A.; Rozental, S.; Szeszs, M. W.; Ballesté Alaniz, R.; Bonifaz, A.; Bonfietti, L. X.; Borba-Santos, L. P.; Capilla, J.; Colombo, A. L.; Dolande, M.; Isla, M. G.; Melhem, M. S. C.; Mesa-Arango, A. C.; Oliveira, M. M. E.; Panizo, M. M.; Pires de Camargo, Z.; Zancope-Oliveira, R. M.; Turnidge, J.

2017-01-01

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrix schenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 μg/ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana. These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy. PMID:28739796

Sea-dumped chemical weapons: environmental risk, occupational hazard.

PubMed

Greenberg, M I; Sexton, K J; Vearrier, D

2016-01-01

Chemical weapons dumped into the ocean for disposal in the twentieth century pose a continuing environmental and human health risk. In this review we discuss locations, quantity, and types of sea-dumped chemical weapons, related environmental concerns, and human encounters with sea-dumped chemical weapons. We utilized the Ovid (http://ovidsp.tx.ovid.com) and PubMed (http://www.pubmed.org) search engines to perform MEDLINE searches for the terms 'sea-dumped chemical weapons', 'chemical warfare agents', and 'chemical munitions'. The searches returned 5863 articles. Irrelevant and non-English articles were excluded. A review of the references for these articles yielded additional relevant sources, with a total of 64 peer-reviewed articles cited in this paper. History and geography of chemical weapons dumping at sea: Hundreds of thousands of tons of chemical munitions were disposed off at sea following World War II. European, Russian, Japanese, and United States coasts are the areas most affected worldwide. Several areas in the Baltic and North Seas suffered concentrated large levels of dumping, and these appear to be the world's most studied chemical warfare agent marine dumping areas. Chemical warfare agents: Sulfur mustard, Lewisite, and the nerve agents appear to be the chemical warfare agents most frequently disposed off at sea. Multiple other type of agents including organoarsenicals, blood agents, choking agents, and lacrimators were dumped at sea, although in lesser volumes. Environmental concerns: Numerous geohydrologic variables contribute to the rate of release of chemical agents from their original casings, leading to difficult and inexact modeling of risk of release into seawater. Sulfur mustard and the organoarsenicals are the most environmentally persistent dumped chemical agents. Sulfur mustard in particular has a propensity to form a solid or semi-solid lump with a polymer coating of breakdown products, and can persist in this state on the ocean floor for decades. Rates of solubility and hydrolysis and levels of innate toxicity of a chemical agent are used to predict the risk to the marine environments. The organoarsenicals eventually breakdown into arsenic, and thus present an indefinite timeline for contamination. Generally, studies assaying sediment and water levels of parent chemical agents and breakdown products at dumpsites have found minimal amounts of relevant chemicals, although arsenic levels are typically higher in dumpsites than reference areas. Studies of marine organisms have not shown concerning amounts of chemical agents or breakdown products in tissue, but have shown evidence of chronic toxicity. There is believed to be minimal risk posed by seafood consumption. Microbiota assays of dumpsites are significantly altered in species composition compared to reference sites, which may imply unseen but significant changes to ecosystems of dumpsites. Human health concerns: The major human health risk at this time appears to arise from acute exposure to an agent by either accidental recovery of a chemical weapon on a fishing vessel, or by munitions washed ashore onto beaches. Improving technology continues to make the deep sea more accessible, thus increasing the risk of disturbing munitions lying on or buried in the seabed. Pipe laying, cable burying, drilling, scuba diving, trawling, and undersea scientific research are the activities posing the most risk. The long-term threat to the benthic habitat via increased arsenic concentrations, shifts in microbiota speciation, and chronic toxicity to vertebrates and invertebrates is not currently understood. The risk to the environment of massive release via disturbance remains a distinct possibility. Terrorist recovery and re-weaponization of chemical agents is a remote possibility.

Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties

PubMed Central

Herold, Karl F.; Sanford, R. Lea; Lee, William; Andersen, Olaf S.; Hemmings, Hugh C.

2017-01-01

General anesthetics have revolutionized medicine by facilitating invasive procedures, and have thus become essential drugs. However, detailed understanding of their molecular mechanisms remains elusive. A mechanism proposed over a century ago involving unspecified interactions with the lipid bilayer known as the unitary lipid-based hypothesis of anesthetic action, has been challenged by evidence for direct anesthetic interactions with a range of proteins, including transmembrane ion channels. Anesthetic concentrations in the membrane are high (10–100 mM), however, and there is no experimental evidence ruling out a role for the lipid bilayer in their ion channel effects. A recent hypothesis proposes that anesthetic-induced changes in ion channel function result from changes in bilayer lateral pressure that arise from partitioning of anesthetics into the bilayer. We examined the effects of a broad range of chemically diverse general anesthetics and related nonanesthetics on lipid bilayer properties using an established fluorescence assay that senses drug-induced changes in lipid bilayer properties. None of the compounds tested altered bilayer properties sufficiently to produce meaningful changes in ion channel function at clinically relevant concentrations. Even supra-anesthetic concentrations caused minimal bilayer effects, although much higher (toxic) concentrations of certain anesthetic agents did alter lipid bilayer properties. We conclude that general anesthetics have minimal effects on bilayer properties at clinically relevant concentrations, indicating that anesthetic effects on ion channel function are not bilayer-mediated but rather involve direct protein interactions. PMID:28265069

Enhanced recovery pathways in thoracic surgery from Italian VATS Group: perioperative analgesia protocols.

PubMed

Piccioni, Federico; Segat, Matteo; Falini, Stefano; Umari, Marzia; Putina, Olga; Cavaliere, Lucio; Ragazzi, Riccardo; Massullo, Domenico; Taurchini, Marco; Del Naja, Carlo; Droghetti, Andrea

2018-03-01

Video-assisted thoracoscopic surgery (VATS) is a minimally invasive technique that allows a faster recovery after thoracic surgery. Although enhanced recovery after surgery (ERAS) principles seem reasonably applicable to thoracic surgery, there is little literature on the application of such a strategy in this context. In regard to pain management, ERAS pathways promote the adoption of a multimodal strategy, tailored to the patients. This approach is based on combining systemic and loco-regional analgesia to favour opioid-sparing strategies. Thoracic paravertebral block is considered the first-line loco-regional technique for VATS. Other techniques include intercostal nerve block and serratus anterior plane block. Nonsteroidal anti-inflammatory drugs and paracetamol are essential part of the multimodal treatment of pain. Also, adjuvant drugs can be useful as opioid-sparing agents. Nevertheless, the treatment of postoperative pain must take into account opioid agents too, if necessary. All above is useful for careful planning and execution of a multimodal analgesic treatment to enhance the recovery of patients. This article summarizes the most recent evidences from literature and authors' experiences on perioperative multimodal analgesia principles for implementing an ERAS program after VATS lobectomy.

Enhanced recovery pathways in thoracic surgery from Italian VATS Group: perioperative analgesia protocols

PubMed Central

Piccioni, Federico; Segat, Matteo; Falini, Stefano; Umari, Marzia; Putina, Olga; Cavaliere, Lucio; Ragazzi, Riccardo; Massullo, Domenico; Taurchini, Marco; Droghetti, Andrea

2018-01-01

Video-assisted thoracoscopic surgery (VATS) is a minimally invasive technique that allows a faster recovery after thoracic surgery. Although enhanced recovery after surgery (ERAS) principles seem reasonably applicable to thoracic surgery, there is little literature on the application of such a strategy in this context. In regard to pain management, ERAS pathways promote the adoption of a multimodal strategy, tailored to the patients. This approach is based on combining systemic and loco-regional analgesia to favour opioid-sparing strategies. Thoracic paravertebral block is considered the first-line loco-regional technique for VATS. Other techniques include intercostal nerve block and serratus anterior plane block. Nonsteroidal anti-inflammatory drugs and paracetamol are essential part of the multimodal treatment of pain. Also, adjuvant drugs can be useful as opioid-sparing agents. Nevertheless, the treatment of postoperative pain must take into account opioid agents too, if necessary. All above is useful for careful planning and execution of a multimodal analgesic treatment to enhance the recovery of patients. This article summarizes the most recent evidences from literature and authors’ experiences on perioperative multimodal analgesia principles for implementing an ERAS program after VATS lobectomy. PMID:29629202

Immunogenicity of biologic therapies: causes and consequences.

PubMed

Boehncke, Wolf-Henning; Brembilla, Nicolo Costantino

2018-04-25

Antibodies or fusion proteins termed biologics allow the targeted therapy of diseases. Many of these agents have proven superior efficacy and safety to conventional therapies, and subsequently revolutionized the management of numerous chronic diseases. Repetitive administration of these protein-based therapeutics to immunocompetent patients elicit immune responses in the form of Anti Drug Antibodies (ADAs), which in turn impact their pharmacological properties and may trigger adverse events. Areas covered: Structural characteristics determining the immunogenicity of biologics are reviewed along with strategies to minimize it. Next, the different types of treatment-emerging ADAs, their potential clinical implications, and assays to detect them are addressed. Emphasis is put on the review of data on the immunogenicity of different types of biologics across numerous indications. Finally, practical considerations are discussed on how to manage patients with issues around the immunogenicity of their biologic treatment. Expert commentary: Immunogenicity is a clinically relevant criterion when selecting a biologic. Besides intrinsic properties of the agent (namely its structure), its respective mode of action, dosing regimen, comedication, and the indication treated must be considered. ADA detection assays need to be standardized to improve comparability of available data and to allow clinical decision-making.

Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs

PubMed Central

2005-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective in treating the pain and inflammation associated with osteoarthritis and rheumatoid arthritis, but it is well recognized that these agents are associated with substantial gastrointestinal toxicity. Treatment guidelines suggest that patients with one or more risk factors for NSAID associated ulcers should be prescribed preventive treatment. However, well over 80% of such patients may not receive an appropriate therapeutic intervention. Multiple strategies are available to reduce the risk for NSAID associated gastrointestinal complications. First, risk may be reduced by using non-NSAID analgesics. Second, use of the minimum effective dose of the NSAID may reduce risk. Third, co-therapy with a proton pump inhibitor or misoprostol may be desirable in at-risk patients. Use of cyclo-oxygenase-2 inhibitors may also reduce the risk for gastrointestinal events, although this benefit is eliminated in patients who receive aspirin, and cyclo-oxygenase-2 inhibitors may increase cardiovascular adverse events. The optimal management of NSAID related gastrointestinal complications must be based on the individual patient's risk factors for gastrointestinal and cardiovascular disease, as well as on the efficacy and tolerability of both the NSAID and accompanying gastroprotective agent. PMID:16168078

Uncertainties in endocrine substitution therapy for central hypocortisolism.

PubMed

Swords, Francesca M

2014-01-01

Central hypocortisolism is common, and has multiple potential causes. However, the treatment aims remain the same whatever the cause: to maximize quality of life, while minimizing treatment-related adverse effects. The majority of patients with central hypocortisolism now receive hydrocortisone in two to three divided doses with a total daily dose of 10-20mg, or a weight-based regimen of 8.1mg/m(2)/day. However, various areas of controversy remain: how to assess the patient with suspected hypocortisolism, which is the optimal agent to use, what is the optimal total daily dose, how to administer divided daily doses, how to monitor therapy and individually tailor doses, whether to replace other adrenal androgens, how to approach the patient with adrenal suppression, and how to best educate patients with hypocortisolism and treat them in emergency situations. This chapter will discuss the evidence behind each of these controversial areas in turn. The evidence for newer agents such as prolonged- and delayed-release preparations of hydrocortisone will also be explored, with a discussion on their potential role in the future management of this major clinical problem. © 2014 Elsevier B.V. All rights reserved.

Anti-Streptococcal activity of Brazilian Amazon Rain Forest plant extracts presents potential for preventive strategies against dental caries

PubMed Central

da SILVA, Juliana Paola Corrêa; de CASTILHO, Adriana Lígia; SARACENI, Cíntia Helena Couri; DÍAZ, Ingrit Elida Collantes; PACIÊNCIA, Mateus Luís Barradas; SUFFREDINI, Ivana Barbosa

2014-01-01

Caries is a global public health problem, whose control requires the introduction of low-cost treatments, such as strong prevention strategies, minimally invasive techniques and chemical prevention agents. Nature plays an important role as a source of new antibacterial substances that can be used in the prevention of caries, and Brazil is the richest country in terms of biodiversity. Objective In this study, the disk diffusion method (DDM) was used to screen over 2,000 Brazilian Amazon plant extracts against Streptococcus mutans. Material and Methods Seventeen active plant extracts were identified and fractionated. Extracts and their fractions, obtained by liquid-liquid partition, were tested in the DDM assay and in the microdilution broth assay (MBA) to determine their minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs). The extracts were also subjected to antioxidant analysis by thin layer chromatography. Results EB271, obtained from Casearia spruceana, showed significant activity against the bacterium in the DDM assay (20.67±0.52 mm), as did EB1129, obtained from Psychotria sp. (Rubiaceae) (15.04±2.29 mm). EB1493, obtained from Ipomoea alba, was the only extract to show strong activity against Streptococcus mutans (0.08 mg/mL

Detecting post-fire salvage logging with Landsat change maps and national fire survey data

Treesearch

Todd A. Schroeder; Michael A. Wulder; Sean P. Healey; Gretchen G. Moisen

2012-01-01

In Canadian boreal forests, wildfire is the predominant agent of natural disturbance often with millions of hectares burning annually. In addition to fire, nearly one quarter of Canada's boreal forest is also managed for industrial wood production. Post-fire logging (or salvage harvesting) is increasingly used to minimize economic losses from fire, notwithstanding...

Development and Construct Validation of an Inventory for Assessing the Home Environment for Motor Development

ERIC Educational Resources Information Center

Rodrigues, Luis Paulo; Saraiva, Linda; Gabbard, Carl

2005-01-01

A contemporary view of early childhood motor development considers environmental influences as critical factors in optimal growth and behavior, with the home being the primary agent. However, there has been minimal research examining the relationship between motor development and the home. The present study addresses this gap with the goal of…

Overcoming ocular drug delivery barriers through the use of physical forces.

PubMed

Huang, Di; Chen, Ying-Shan; Rupenthal, Ilva D

2018-02-15

Overcoming the physiological barriers in the eye remains a key obstacle in the field of ocular drug delivery. While ocular barriers naturally have a protective function, they also limit drug entry into the eye. Various pharmaceutical strategies, such as novel formulations and physical force-based techniques, have been investigated to weaken these barriers and transport therapeutic agents effectively to both the anterior and the posterior segments of the eye. This review summarizes and discusses the recent research progress in the field of ocular drug delivery with a focus on the application of physical methods, including electrical fields, sonophoresis, and microneedles, which can enhance penetration efficiency by transiently disrupting the ocular barriers in a minimally or non-invasive manner. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploring the onset of collective motion in self-organised trails of social organisms

NASA Astrophysics Data System (ADS)

Brigatti, E.; Hernández, A.

2018-04-01

We investigate the emergence of self-organised trails between two specific target areas in collective motion of social organisms by means of an agent-based model. We present numerical evidences that an increase in the efficiency of navigation, in dependence of the colony size, exists. Moreover, the shift, from the diffusive to the directed motion can be quantitatively characterised, identifying and measuring a well defined crossover point. This point corresponds to the minimal number of individuals necessary for the onset of collective cooperation. Finally, by means of a finite-size scaling analysis, we describe its scaling behaviour as a function of the environment size. This last result can be of particular interest for interpreting empirical observations or for the design of artificial swarms.

Update on botulinum toxin and dermal fillers.

PubMed

Berbos, Zachary J; Lipham, William J

2010-09-01

The art and science of facial rejuvenation is an ever-evolving field of medicine, as evidenced by the continual development of new surgical and nonsurgical treatment modalities. Over the past 10 years, the use of botulinum toxin and dermal fillers for aesthetic purposes has risen sharply. Herein, we discuss properties of several commonly used injectable products and provide basic instruction for their use toward the goal of achieving facial rejuvenation. The demand for nonsurgical injection-based facial rejuvenation products has risen enormously in recent years. Used independently or concurrently, botulinum toxin and dermal filler agents offer an affordable, minimally invasive approach to facial rejuvenation. Botulinum toxin and dermal fillers can be used to diminish facial rhytides, restore facial volume, and sculpt facial contours, thereby achieving an aesthetically pleasing, youthful facial appearance.

Pharmacogenetics in cardiovascular diseases: State of the art and implementation-recommendations of the French National Network of Pharmacogenetics (RNPGx).

PubMed

Lamoureux, Fabien; Duflot, Thomas

2017-04-01

The use of genomic markers to predict drug response and effectiveness has the potential to improve healthcare by increasing drug efficacy and minimizing adverse effects. Polymorphisms associated with inter-individual variability in drug metabolism, transport, or pharmacodynamics of major cardiovascular drugs have been identified. These include single nucleotide polymorphisms (SNP) affecting clinical outcomes in patients receiving antiplatelet agents, oral anticoagulants and statins. Based on clinical evidence supporting genetic testing in the management of cardiovascular diseases using these drug classes, this short review presents clinical guidance regarding current pharmacogenetics implementation in routine medical practice. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Alpha-hydroxyacid chemical peeling agents: case studies and rationale for safe and effective use.

PubMed

Briden, M Elizabeth

2004-02-01

Chemical peeling is an in-office procedure that involves the application of a chemical agent to the skin to induce controlled destruction or exfoliation of old skin and stimulation of new epidermal growth with more evenly distributed melanin. When peel agents reach the dermal layer, important wound-healing activities occur that cause skin remodeling and skin smoothing, both antiaging benefits. There are a number of key factors in selecting a peeling agent and procedure, and each is discussed. Variables to consider are the peeling agent and its formulation, the concentration of the agent, the patient's skin type, the site to be peeled, the skin preparation procedure prior to and immediately preceding the application of the agent, the application method, the duration of contact, and the patient's medical history and lifestyle. Various types of peels are discussed. Of particular interest are superficial chemical peels, which offer great flexibility over a range of skin types and conditions with minimal to no "downtime." Alpha-hydroxyacid (AHA) peels are superficial and can be combined with other cosmetic procedures in the office to maximize benefits. In addition, AHA peels work well when combined with supportive homecare products including AHAs or polyhydroxy acids (PHAs), topical retinoids, and antiacne/antirosacea treatments. Case studies are presented of patients using AHA peels for the treatment of acne and hyperpigmentation in a variety of skin types, including Asian skin.

Self-organized criticality in a network of economic agents with finite consumption

NASA Astrophysics Data System (ADS)

da Cruz, João P.; Lind, Pedro G.

2012-02-01

We introduce a minimal agent model to explain the emergence of heavy-tailed return distributions as a result of self-organized criticality. The model assumes that agents trade their economic outputs with each other composing a complex network of agents and connections. Further, the incoming degree of an agent is proportional to the demand on its goods, while its outgoing degree is proportional to the supply. The model considers a collection of economic agents which are attracted to establish connections among them to make an exchange at a price formed by supply and demand. With our model we are able to reproduce the evolution of the return of macroscopic quantities (indices) and to correctly retrieve the non-trivial exponent value characterizing the amplitude of drops in several indices in financial markets, relating it to the underlying topology of connections. The distribution of drops in empirical data is obtained by counting the number of successive time-steps for which a decrease in the index value is observed. All eight financial indexes show an exponent m˜5/2. Finally, we present mean-field calculations of the critical exponents, and of the scaling relation m=3/2 γ-1 between the exponent m for the distribution of drops and the topological exponent γ for the degree distribution.

Study of zwitterionic sulfopropylbetaine containing reactive siloxanes for application in antibacterial materials.

PubMed

Chen, Shiguo; Chen, Shaojun; Jiang, Song; Mo, Yangmiao; Luo, Junxuan; Tang, Jiaoning; Ge, Zaochuan

2011-07-01

Antibacterial agents receive a great deal of attention around the world due to the interesting academic problems of how to combat bacteria and of the beneficial health, social and economic effects of successful agents. Scientists are actively developing new antibacterial agents for biomaterial applications. This paper reports the novel antibacterial agent siloxane sulfopropylbetaine (SSPB), which contains reactive alkoxysilane groups. The structure and properties of SSPB were systematically investigated, with the results showing that SSPB contains both quaternary ammonium compounds and reactive siloxane groups. SSPB has good antibacterial activity against both Escherichia coli (E. coli, 8099) and Staphylococcus aureus (S. aureus, ATCC 6538). The minimal inhibition concentration is 70 μmol/ml SSPB against both E. coli and S. aureus. In addition, the SSPB antibacterial agent can be used in both weak acid and weak alkaline environments, functioning within the wide pH range of 4.0-9.0. The SSPB-modified glass surface killed 99.96% of both S. aureus and E. coli organisms within 24 h. No significant decrease was observed in this antibacterial activity after 20 washes. Moreover, SSPB does not induce a skin reaction and is nontoxic to animals. Thus, SSPB is an ideal candidate for future applications as a safe, environmentally friendly antibacterial agent. Copyright © 2011 Elsevier B.V. All rights reserved.

The sticky business of adhesion prevention in minimally invasive gynecologic surgery.

PubMed

Han, Esther S; Scheib, Stacey A; Patzkowsky, Kristin E; Simpson, Khara; Wang, Karen C

2017-08-01

The negative impact of postoperative adhesions has long been recognized, but available options for prevention remain limited. Minimally invasive surgery is associated with decreased adhesion formation due to meticulous dissection with gentile tissue handling, improved hemostasis, and limiting exposure to reactive foreign material; however, there is conflicting evidence on the clinical significance of adhesion-related disease when compared to open surgery. Laparoscopic surgery does not guarantee the prevention of adhesions because longer operative times and high insufflation pressure can promote adhesion formation. Adhesion barriers have been available since the 1980s, but uptake among surgeons remains low and there is no clear evidence that they reduce clinically significant outcomes such as chronic pain or infertility. In this article, we review the ongoing magnitude of adhesion-related complications in gynecologic surgery, currently available interventions and new research toward more effective adhesion prevention. Recent literature provides updated epidemiologic data and estimates of healthcare costs associated with adhesion-related complications. There have been important advances in our understanding of normal peritoneal healing and the pathophysiology of adhesions. Adhesion barriers continue to be tested for safety and effectiveness and new agents have shown promise in clinical studies. Finally, there are many experimental studies of new materials and pharmacologic and biologic prevention agents. There is great interest in new adhesion prevention technologies, but new agents are unlikely to be available for clinical use for many years. High-quality effectiveness and outcomes-related research is still needed.

Advances in analytical technologies for environmental protection and public safety.

PubMed

Sadik, O A; Wanekaya, A K; Andreescu, S

2004-06-01

Due to the increased threats of chemical and biological agents of injury by terrorist organizations, a significant effort is underway to develop tools that can be used to detect and effectively combat chemical and biochemical toxins. In addition to the right mix of policies and training of medical personnel on how to recognize symptoms of biochemical warfare agents, the major success in combating terrorism still lies in the prevention, early detection and the efficient and timely response using reliable analytical technologies and powerful therapies for minimizing the effects in the event of an attack. The public and regulatory agencies expect reliable methodologies and devices for public security. Today's systems are too bulky or slow to meet the "detect-to-warn" needs for first responders such as soldiers and medical personnel. This paper presents the challenges in monitoring technologies for warfare agents and other toxins. It provides an overview of how advances in environmental analytical methodologies could be adapted to design reliable sensors for public safety and environmental surveillance. The paths to designing sensors that meet the needs of today's measurement challenges are analyzed using examples of novel sensors, autonomous cell-based toxicity monitoring, 'Lab-on-a-Chip' devices and conventional environmental analytical techniques. Finally, in order to ensure that the public and legal authorities are provided with quality data to make informed decisions, guidelines are provided for assessing data quality and quality assurance using the United States Environmental Protection Agency (US-EPA) methodologies.

Controlling Hazardous Releases while Protecting Passengers in Civil Infrastructure Systems

NASA Astrophysics Data System (ADS)

Rimer, Sara P.; Katopodes, Nikolaos D.

2015-11-01

The threat of accidental or deliberate toxic chemicals released into public spaces is a significant concern to public safety, and the real-time detection and mitigation of such hazardous contaminants has the potential to minimize harm and save lives. Furthermore, the safe evacuation of occupants during such a catastrophe is of utmost importance. This research develops a comprehensive means to address such scenarios, through both the sensing and control of contaminants, and the modeling of and potential communication to occupants as they evacuate. A computational fluid dynamics model is developed of a simplified public space characterized by a long conduit (e.g. airport terminal) with unidirectional ambient flow that is capable of detecting and mitigating the hazardous contaminant (via boundary ports) over several time horizons using model predictive control optimization. Additionally, a physical prototype is built to test the real-time feasibility of this computational flow control model. The prototype is a blower wind-tunnel with an elongated test section with the capability of sensing (via digital camera) an injected `contaminant' (propylene glycol smoke), and then mitigating that contaminant using actuators (compressed air operated vacuum nozzles) which are operated by a set of pressure regulators and a programmable controller. Finally, an agent-based model is developed to simulate ``agents'' (i.e. building occupants) as they evacuate a public space, and is coupled with the computational flow control model such that agents must interact with a dynamic, threatening environment. NSF-CMMI #0856438.

The Treatment of Primary Orthostatic Hypotension.

PubMed

Hale, Genevieve M; Valdes, Jose; Brenner, Michael

2017-05-01

To review the efficacy and safety of pharmacological and nonpharmacological strategies used to treat primary orthostatic hypotension (OH). A literature review using PubMed and MEDLINE databases searching hypotension, non-pharmacological therapy, midodrine, droxidopa, pyridostigmine, fludrocortisone, atomoxetine, pseudoephedrine, and octreotide was performed. Randomized or observational studies, cohorts, case series, or case reports written in English between January 1970 and November 2016 that assessed primary OH treatment in adult patients were evaluated. Based on the chosen criteria, it was found that OH patients make up approximately 15% of all syncope patients, predominantly as a result of cardiovascular or neurological insults, or offending medication. Nonpharmacological strategies are the primary treatment, such as discontinuing offending medications, switching medication administration to bedtime, avoiding large carbohydrate-rich meals, limiting alcohol, maintaining adequate hydration, adding salt to diet, and so on. If these fail, pharmacotherapy can help ameliorate symptoms, including midodrine, droxidopa, fludrocortisone, pyridostigmine, atomoxetine, sympathomimetic agents, and octreotide. Midodrine and droxidopa possess the most evidence with respect to increasing blood pressure and alleviating symptoms. Pyridostigmine and fludrocortisone can be used in patients who fail to respond to these agents. Emerging evidence with low-dose atomoxetine is promising, especially in those with central autonomic failure, and may prove to be a viable alternative treatment option. Data surrounding other therapies such as sympathomimetic agents or octreotide are minimal. Medication management of primary OH should be guided by patient-specific factors, such as tolerability, adverse effects, and drug-drug and drug-disease interactions.

A hybrid simulation approach for integrating safety behavior into construction planning: An earthmoving case study.

PubMed

Goh, Yang Miang; Askar Ali, Mohamed Jawad

2016-08-01

One of the key challenges in improving construction safety and health is the management of safety behavior. From a system point of view, workers work unsafely due to system level issues such as poor safety culture, excessive production pressure, inadequate allocation of resources and time and lack of training. These systemic issues should be eradicated or minimized during planning. However, there is a lack of detailed planning tools to help managers assess the impact of their upstream decisions on worker safety behavior. Even though simulation had been used in construction planning, the review conducted in this study showed that construction safety management research had not been exploiting the potential of simulation techniques. Thus, a hybrid simulation framework is proposed to facilitate integration of safety management considerations into construction activity simulation. The hybrid framework consists of discrete event simulation (DES) as the core, but heterogeneous, interactive and intelligent (able to make decisions) agents replace traditional entities and resources. In addition, some of the cognitive processes and physiological aspects of agents are captured using system dynamics (SD) approach. The combination of DES, agent-based simulation (ABS) and SD allows a more "natural" representation of the complex dynamics in construction activities. The proposed hybrid framework was demonstrated using a hypothetical case study. In addition, due to the lack of application of factorial experiment approach in safety management simulation, the case study demonstrated sensitivity analysis and factorial experiment to guide future research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cosmetics for acne: indications and recommendations for an evidence-based approach.

PubMed

Dall'oglio, F; Tedeschi, A; Fabbrocini, G; Veraldi, S; Picardo, M; Micali, G

2015-02-01

The aim of this review was to evaluate, by a thorough revision of the literature, the true efficacy of currently available topic and systemic cosmetic acne agents. The efficacy of currently available cosmetic acne agents has been retrospectively evaluated via thorough revision of the literature on matched electronic databases (PubMed). All retrieved studies, either randomized clinical trials or clinical trials, controlled or uncontrolled were considered. Scientific evidence suggests that most cosmetic products for acne may enhance the clinical outcome. Cleansers should be indicated to all acne patients; those containing benzoyl peroxide or azelaic/salicylic acid/triclosan show the best efficacy profile. Sebum-controlling agents containing nicotinamide or zinc acetate may minimize excessive sebum production. Cosmetics with antimicrobial and anti-inflammatory substances such as, respectively, ethyl lactate or phytosphingosine and nicotinamide or resveratrol, may speed acne recovery. Topical corneolytics, including retinaldehyde/glycolic acid or lactic acid, induce a comedolytic effect and may also facilitate skin absorption of topical drugs. Finally, the use of specific moisturizers should be strongly recommended in all acne patients. Cosmetics, if correctly prescribed, may improve the performance of the therapy, whereas wrong procedures and/or inadequate cosmetics may worsen acne. Cosmetological recommendations may allow clinicians to make informed decisions about the role of various cosmetics and to indentify the appropriate indications and precautions. The choice of the most effective product should take into consideration the ongoing pharmacological therapy and acne type/severity as well.

Quantum-Classical Hybrid for Information Processing

NASA Technical Reports Server (NTRS)

Zak, Michail

2011-01-01

Based upon quantum-inspired entanglement in quantum-classical hybrids, a simple algorithm for instantaneous transmissions of non-intentional messages (chosen at random) to remote distances is proposed. The idea is to implement instantaneous transmission of conditional information on remote distances via a quantum-classical hybrid that preserves superposition of random solutions, while allowing one to measure its state variables using classical methods. Such a hybrid system reinforces the advantages, and minimizes the limitations, of both quantum and classical characteristics. Consider n observers, and assume that each of them gets a copy of the system and runs it separately. Although they run identical systems, the outcomes of even synchronized runs may be different because the solutions of these systems are random. However, the global constrain must be satisfied. Therefore, if the observer #1 (the sender) made a measurement of the acceleration v(sub 1) at t =T, then the receiver, by measuring the corresponding acceleration v(sub 1) at t =T, may get a wrong value because the accelerations are random, and only their ratios are deterministic. Obviously, the transmission of this knowledge is instantaneous as soon as the measurements have been performed. In addition to that, the distance between the observers is irrelevant because the x-coordinate does not enter the governing equations. However, the Shannon information transmitted is zero. None of the senders can control the outcomes of their measurements because they are random. The senders cannot transmit intentional messages. Nevertheless, based on the transmitted knowledge, they can coordinate their actions based on conditional information. If the observer #1 knows his own measurements, the measurements of the others can be fully determined. It is important to emphasize that the origin of entanglement of all the observers is the joint probability density that couples their actions. There is no centralized source, or a sender of the signal, because each receiver can become a sender as well. An observer receives a signal by performing certain measurements synchronized with the measurements of the others. This means that the signal is uniformly and simultaneously distributed over the observers in a decentralized way. The signals transmit no intentional information that would favor one agent over another. All the sequence of signals received by different observers are not only statistically equivalent, but are also point-by-point identical. It is important to assume that each agent knows that the other agent simultaneously receives the identical signals. The sequences of the signals are true random, so that no agent could predict the next step with the probability different from those described by the density. Under these quite general assumptions, the entangled observers-agents can perform non-trivial tasks that include transmission of conditional information from one agent to another, simple paradigm of cooperation, etc. The problem of behavior of intelligent agents correlated by identical random messages in a decentralized way has its own significance: it simulates evolutionary behavior of biological and social systems correlated only via simultaneous sensoring sequences of unexpected events.

Design and Simulation of Material-Integrated Distributed Sensor Processing with a Code-Based Agent Platform and Mobile Multi-Agent Systems

PubMed Central

Bosse, Stefan

2015-01-01

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques. PMID:25690550

Design and simulation of material-integrated distributed sensor processing with a code-based agent platform and mobile multi-agent systems.

PubMed

Bosse, Stefan

2015-02-16

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques.

A Green Solvent Induced DNA Package

NASA Astrophysics Data System (ADS)

Satpathi, Sagar; Sengupta, Abhigyan; Hridya, V. M.; Gavvala, Krishna; Koninti, Raj Kumar; Roy, Bibhisan; Hazra, Partha

2015-03-01

Mechanistic details of DNA compaction is essential blue print for gene regulation in living organisms. Many in vitro studies have been implemented using several compaction agents. However, these compacting agents may have some kinds of cytotoxic effects to the cells. To minimize this aspect, several research works had been performed, but people have never focused green solvent, i.e. room temperature ionic liquid as DNA compaction agent. To the best of our knowledge, this is the first ever report where we have shown that guanidinium tris(pentafluoroethyl)trifluorophosphate (Gua-IL) acts as a DNA compacting agent. The compaction ability of Gua-IL has been verified by different spectroscopic techniques, like steady state emission, circular dichroism, dynamic light scattering and UV melting. Notably, we have extensively probed this compaction by Gua-IL through field emission scanning electron microscopy (FE-SEM) and fluorescence microscopy images. We also have discussed the plausible compaction mechanism process of DNA by Gua-IL. Our results suggest that Gua-IL forms a micellar kind of self aggregation above a certain concentration (>=1 mM), which instigates this compaction process. This study divulges the specific details of DNA compaction mechanism by a new class of compaction agent, which is highly biodegradable and eco friendly in nature.

Interferon-alpha in the treatment of multiple myeloma.

PubMed

Khoo, Teh Liane; Vangsted, Annette Juul; Joshua, Douglas; Gibson, John

2011-03-01

Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the haematological malignancy multiple myeloma. Interferon has been used in this clinical practice for over thirty years. However, despite considerable efforts, numerous clinical trials and two large meta-analysis, its exact role in the management of multiple myeloma still remains unclear. Its role in the treatment of multiple myeloma has been as a single induction agent, a co-induction agent with other chemotherapy regimens, and as maintenance therapy after conventional chemotherapy or complete remission after autologous or allogeneic transplantation. Interferon as a single induction agent or co-induction agent with other chemotherapy agents appears only to have minimal benefit in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs"--thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment of multiple myeloma or will interferon be resigned to the history books remains to be seen.

Evolution and anti-evolution in a minimal stock market model

NASA Astrophysics Data System (ADS)

Rothenstein, R.; Pawelzik, K.

2003-08-01

We present a novel microscopic stock market model consisting of a large number of random agents modeling traders in a market. Each agent is characterized by a set of parameters that serve to make iterated predictions of two successive returns. The future price is determined according to the offer and the demand of all agents. The system evolves by redistributing the capital among the agents in each trading cycle. Without noise the dynamics of this system is nearly regular and thereby fails to reproduce the stochastic return fluctuations observed in real markets. However, when in each cycle a small amount of noise is introduced we find the typical features of real financial time series like fat-tails of the return distribution and large temporal correlations in the volatility without significant correlations in the price returns. Introducing the noise by an evolutionary process leads to different scalings of the return distributions that depend on the definition of fitness. Because our realistic model has only very few parameters, and the results appear to be robust with respect to the noise level and the number of agents we expect that our framework may serve as new paradigm for modeling self-generated return fluctuations in markets.

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.

Chemical Computer Man: Chemical Agent Response Simulation (CARS). Technical report, January 1983-September 1985

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

Davis, E.G.; Mioduszewski, R.J.

The Chemical Computer Man: Chemical Agent Response Simulation (CARS) is a computer model and simulation program for estimating the dynamic changes in human physiological dysfunction resulting from exposures to chemical-threat nerve agents. The newly developed CARS methodology simulates agent exposure effects on the following five indices of human physiological function: mental, vision, cardio-respiratory, visceral, and limbs. Mathematical models and the application of basic pharmacokinetic principles were incorporated into the simulation so that for each chemical exposure, the relationship between exposure dosage, absorbed dosage (agent blood plasma concentration), and level of physiological response are computed as a function of time. CARS,more » as a simulation tool, is designed for the users with little or no computer-related experience. The model combines maximum flexibility with a comprehensive user-friendly interactive menu-driven system. Users define an exposure problem and obtain immediate results displayed in tabular, graphical, and image formats. CARS has broad scientific and engineering applications, not only in technology for the soldier in the area of Chemical Defense, but also in minimizing animal testing in biomedical and toxicological research and the development of a modeling system for human exposure to hazardous-waste chemicals.« less

Barbiturate euthanasia solution-induced tissue artifact in nonhuman primates.

PubMed

Grieves, J L; Dick, E J; Schlabritz-Loutsevich, N E; Butler, S D; Leland, M M; Price, S E; Schmidt, C R; Nathanielsz, P W; Hubbard, G B

2008-06-01

Barbiturate euthanasia solutions are a humane and approved means of euthanasia. Overdosing causes significant tissue damage in a variety of laboratory animals. One hundred seventeen non-human primates (NHP) representing 7 species including 12 fetuses euthanized for humane and research reasons by various vascular routes with Euthasol, Sodium Pentobarbital, Fatal Plus, Beuthanasia D, or Euthanasia 5 were evaluated for euthanasia-induced tissue damage. Lungs and livers were histologically graded for hemolysis, vascular damage, edema, and necrosis. Severity of tissue damage was analyzed for differences on the basis of agent, age, sex, dose, and injection route. Severity of tissue damage was directly related to dose and the intracardiac injection route, but did not differ by species, sex, and agent used. When the recommended dose of agent was used, tissue damage was generally reduced, minimal, or undetectable. Barbiturate-induced artifacts in NHPs are essentially the same as in other laboratory species.

Hydrolysis of Nerve Agents by Model Nucleophiles: A Computational Study

PubMed Central

Beck, Jeremy M.

2008-01-01

Density functional theory calculations were employed to study the reaction of five nerve agents with model nucleophiles, including EtX− and EtXH (X = O, S, Se) for serine, cysteine and selenocysteine, respectively. Calculations at the B3LYP/6-311++G(2d,p) level of theory predict an exothermic reaction between ethoxide and all of the nerve agents studied. As compared to EtO− as a nucleophile, these reactions become ~30 kcal/mol more endothermic for EtS−, and by ~40 kcal/mol for EtSe−. The equivalent reactions with the neutral nucleophiles (EtXH) were more endothermic. The effect of solvation on the reaction thermochemistry was determined using a polarizable continuum model simulating the dielectric constant of chloroform. While there was a large exothermic shift for reactions involving charged nucleophiles with solvation modeling, the corresponding shift was minimal for the reaction with neutral nucleophiles. PMID:18538754

Effects of diatrizoate and iopamidol on spermatogenesis.

PubMed

Yaghmai, V; Harapanhalli, R S; Patel, Y D; Baker, S R; Rao, D V

1993-12-01

The biological effects of iodinated contrast media were examined by using spermatogenesis in mouse testis as the experimental model. Spermhead survival and abnormality assays were used as the biological end points. Diatrizoate meglumine/diatrizoate sodium and iopamidol were administered intravenously at equal rates and concentrations. Testicular uptake and clearance of these contrast agents were examined by high-performance liquid chromatography techniques. Appropriate mannitol solutions were employed as osmolality controls. Intravenous administration of the contrast agent or its respective mannitol control resulted in approximately a 30% decrease in spermhead count. A dose-related experiment with mannitol demonstrated that the spermhead count decreased rapidly until 600 mOsm/kg was reached, beyond which this decrease was minimal. Clearance of both contrast media was complete in approximately 4 hours. No significant increase in the induction of spermhead abnormalities was observed. Osmotic substances, such as iodinated contrast agents, affect the process of spermatogenesis.

Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents

PubMed Central

Kim, Jin-Woo; Galanzha, Ekaterina I.; Shashkov, Evgeny V.; Moon, Hyung-Mo; Zharov, Vladimir P.

2012-01-01

Carbon nanotubes have shown promise as contrast agents for photoacoustic and photothermal imaging of tumours and infections because they offer high resolution and allow deep tissue imaging. However, in vivo applications have been limited by the relatively low absorption displayed by nanotubes at near-infrared wavelengths and concerns over toxicity. Here, we show that gold-plated carbon nanotubes—termed golden carbon nanotubes—can be used as photoacoustic and photothermal contrast agents with enhanced near-infrared contrast (~102-fold) for targeting lymphatic vessels in mice using extremely low laser fluence levels of a few mJ cm−2. Antibody-conjugated golden carbon nanotubes were used to map the lymphatic endothelial receptor, and preliminary in vitro viability tests show golden carbon nanotubes have minimal toxicity. This new nanomaterial could be an effective alternative to existing nanoparticles and fluorescent labels for non-invasive targeted imaging of molecular structures in vivo. PMID:19809462

Clinical biomarkers of angiogenesis inhibition

PubMed Central

Brown, Aaron P.; Citrin, Deborah E.; Camphausen, Kevin A.

2009-01-01

Introduction An expanding understanding of the importance of angiogenesis in oncology and the development of numerous angiogenesis inhibitors are driving the search for biomarkers of angiogenesis. We review currently available candidate biomarkers and surrogate markers of anti-angiogenic agent effect. Discussion A number of invasive, minimally invasive, and non-invasive tools are described with their potential benefits and limitations. Diverse markers can evaluate tumor tissue or biological fluids, or specialized imaging modalities. Conclusions The inclusion of these markers into clinical trials may provide insight into appropriate dosing for desired biological effects, appropriate timing of additional therapy, prediction of individual response to an agent, insight into the interaction of chemotherapy and radiation following exposure to these agents, and perhaps most importantly, a better understanding of the complex nature of angiogenesis in human tumors. While many markers have potential for clinical use, it is not yet clear which marker or combination of markers will prove most useful. PMID:18414993

VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer

PubMed Central

Gerstner, Elizabeth R.; Duda, Dan G.; di Tomaso, Emmanuelle; Ryg, Peter A.; Loeffler, Jay S.; Sorensen, A. Gregory; Ivy, Percy; Jain, Rakesh K.; Batchelor, Tracy T.

2016-01-01

Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. Increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate tumor penetration of chemotherapy agents. In addition, edema and the corticosteroids needed to control cerebral edema cause significant morbidity and mortality. Agents that block the VEGF pathway are able to decrease vascular permeability and, thus, cerebral edema, by restoring the abnormal tumor vasculature to a more normal state. Decreasing cerebral edema minimizes the adverse effects of corticosteroids and could improve clinical outcomes. Anti-VEGF agents might also be useful in other cancer-related conditions that increase vascular permeability, such as malignant pleural effusions or ascites. PMID:19333229

New approaches in agent-based modeling of complex financial systems

NASA Astrophysics Data System (ADS)

Chen, Ting-Ting; Zheng, Bo; Li, Yan; Jiang, Xiong-Fei

2017-12-01

Agent-based modeling is a powerful simulation technique to understand the collective behavior and microscopic interaction in complex financial systems. Recently, the concept for determining the key parameters of agent-based models from empirical data instead of setting them artificially was suggested. We first review several agent-based models and the new approaches to determine the key model parameters from historical market data. Based on the agents' behaviors with heterogeneous personal preferences and interactions, these models are successful in explaining the microscopic origination of the temporal and spatial correlations of financial markets. We then present a novel paradigm combining big-data analysis with agent-based modeling. Specifically, from internet query and stock market data, we extract the information driving forces and develop an agent-based model to simulate the dynamic behaviors of complex financial systems.

Four simple rules that are sufficient to generate the mammalian blastocyst

PubMed Central

Nissen, Silas Boye; Perera, Marta; Gonzalez, Javier Martin; Morgani, Sophie M.; Jensen, Mogens H.; Sneppen, Kim; Brickman, Joshua M.

2017-01-01

Early mammalian development is both highly regulative and self-organizing. It involves the interplay of cell position, predetermined gene regulatory networks, and environmental interactions to generate the physical arrangement of the blastocyst with precise timing. However, this process occurs in the absence of maternal information and in the presence of transcriptional stochasticity. How does the preimplantation embryo ensure robust, reproducible development in this context? It utilizes a versatile toolbox that includes complex intracellular networks coupled to cell—cell communication, segregation by differential adhesion, and apoptosis. Here, we ask whether a minimal set of developmental rules based on this toolbox is sufficient for successful blastocyst development, and to what extent these rules can explain mutant and experimental phenotypes. We implemented experimentally reported mechanisms for polarity, cell—cell signaling, adhesion, and apoptosis as a set of developmental rules in an agent-based in silico model of physically interacting cells. We find that this model quantitatively reproduces specific mutant phenotypes and provides an explanation for the emergence of heterogeneity without requiring any initial transcriptional variation. It also suggests that a fixed time point for the cells’ competence of fibroblast growth factor (FGF)/extracellular signal—regulated kinase (ERK) sets an embryonic clock that enables certain scaling phenomena, a concept that we evaluate quantitatively by manipulating embryos in vitro. Based on these observations, we conclude that the minimal set of rules enables the embryo to experiment with stochastic gene expression and could provide the robustness necessary for the evolutionary diversification of the preimplantation gene regulatory network. PMID:28700688

What is Quantum Mechanics? A Minimal Formulation

NASA Astrophysics Data System (ADS)

Friedberg, R.; Hohenberg, P. C.

2018-03-01

This paper presents a minimal formulation of nonrelativistic quantum mechanics, by which is meant a formulation which describes the theory in a succinct, self-contained, clear, unambiguous and of course correct manner. The bulk of the presentation is the so-called "microscopic theory", applicable to any closed system S of arbitrary size N, using concepts referring to S alone, without resort to external apparatus or external agents. An example of a similar minimal microscopic theory is the standard formulation of classical mechanics, which serves as the template for a minimal quantum theory. The only substantive assumption required is the replacement of the classical Euclidean phase space by Hilbert space in the quantum case, with the attendant all-important phenomenon of quantum incompatibility. Two fundamental theorems of Hilbert space, the Kochen-Specker-Bell theorem and Gleason's theorem, then lead inevitably to the well-known Born probability rule. For both classical and quantum mechanics, questions of physical implementation and experimental verification of the predictions of the theories are the domain of the macroscopic theory, which is argued to be a special case or application of the more general microscopic theory.

Effect of gamma irradiation on microbial quality of minimally processed carrot and lettuce: A case study in Greater Accra region of Ghana

NASA Astrophysics Data System (ADS)

Frimpong, G. K.; Kottoh, I. D.; Ofosu, D. O.; Larbi, D.

2015-05-01

The effect of ionizing radiation on the microbiological quality on minimally processed carrot and lettuce was studied. The aim was to investigate the effect of irradiation as a sanitizing agent on the bacteriological quality of some raw eaten salad vegetables obtained from retailers in Accra, Ghana. Minimally processed carrot and lettuce were analysed for total viable count, total coliform count and pathogenic organisms. The samples collected were treated and analysed for a 15 day period. The total viable count for carrot ranged from 1.49 to 14.01 log10 cfu/10 g while that of lettuce was 0.70 to 8.5 7 log10 cfu/10 g. It was also observed that total coliform count for carrot was 1.46-7.53 log10 cfu/10 g and 0.14-7.35 log10 cfu/10 g for lettuce. The predominant pathogenic organisms identified were Bacillus cereus, Cronobacter sakazakii, Staphylococcus aureus, and Klebsiella spp. It was concluded that 2 kGy was most effective for medium dose treatment of minimally processed carrot and lettuce.

Agent-Based Learning Environments as a Research Tool for Investigating Teaching and Learning.

ERIC Educational Resources Information Center

Baylor, Amy L.

2002-01-01

Discusses intelligent learning environments for computer-based learning, such as agent-based learning environments, and their advantages over human-based instruction. Considers the effects of multiple agents; agents and research design; the use of Multiple Intelligent Mentors Instructing Collaboratively (MIMIC) for instructional design for…

Disturbance of DNA conformation by the binding of testosterone-based platinum drugs via groove-face and intercalative interactions: a molecular dynamics simulation study

PubMed Central

2013-01-01

Background To explore novel platinum-based anticancer agents that are distinct from the structure and interaction mode of the traditional cisplatin by forming the bifunctional intrastrand 1,2 GpG adduct, the monofunctional platinum + DNA adducts with extensive non-covalent interactions had been studied. It was reported that the monofunctional testosterone-based platinum(II) agents present the high anticancer activity. Moreover, it was also found that the testosterone-based platinum agents could cause the DNA helix to undergo significant unwinding and bending over the non-testosterone-based platinum agents. However, the interaction mechanisms of these platinum agents with DNA at the atomic level are not yet clear so far. Results In the present work, we used molecular dynamics (MD) simulations and DNA conformational dynamics calculations to study the DNA distortion properties of the testosterone-based platinum + DNA, the improved testosterone-based platinum + DNA and the non-testosterone-based platinum + DNA adducts. The results show that the intercalative interaction of the improved flexible testosterone-based platinum agent with DNA molecule could cause larger DNA conformational distortion than the groove-face interaction of the rigid testosterone-based platinum agent with DNA molecule. Further investigations for the non-testosterone-based platinum agent reveal the occurrence of insignificant change of DNA conformation due to the absence of testosterone ligand in such agent. Based on the DNA dynamics analysis, the DNA base motions relating to DNA groove parameter changes and hydrogen bond destruction of DNA base pairs were also discussed in this work. Conclusions The flexible linker in the improved testosterone-based platinum agent causes an intercalative interaction with DNA in the improved testosterone-based platinum + DNA adduct, which is different from the groove-face interaction caused by a rigid linker in the testosterone-based platinum agent. The present investigations provide useful information of DNA conformation affected by a testosterone-based platinum complex at the atomic level. PMID:23517640

Agent-based self-service technology adoption model for air-travelers: Exploring best operational practices

NASA Astrophysics Data System (ADS)

Ueda, Keiichi; Kurahashi, Setsuya

2018-02-01

The continuous development of the service economy and an aging society with fewer children is expected to lead to a shortage of workers in the near future. In addition, the growth of the service economy would require service providers to meet various service requirements. In this regard, self-service technology (SST) is a promising alternative to securing labor in both developed and emerging countries. SST is expected to coordinate the controllable productive properties in order to optimize resources and minimize consumer stress. As services are characterized by simultaneity and inseparability, a smoother operation in cooperation with the consumer is required to provide a certain level of service. This study focuses on passenger handling in an airport departure lobby with the objective of optimizing multiple service resources comprising interpersonal service staff and self-service kiosks. Our aim is to elucidate the passenger decision- making mechanism of choosing either interpersonal service or self-service as the check-in option, and to apply it to analyze several scenarios to determine the best practice. The experimental space is studied and an agent-based model is proposed to analyze the operational efficiency via a simulation. We expand on a previous SST adoption model, which is enhanced by introducing the concept of individual traits. We focus on the decision-making of individuals who are neutral toward the service option, by tracking the actual activity of passengers and mapping their behavior into the model. A new method of validation that follows a different approach is proposed to ensure that this model approximates real-world situations. A scenario analysis is then carried out with the aim of exploring the best operational practice to minimize the stress experienced by the air travelers and to meet the business needs of the airline managers at the airport. We collected actual data from the Departure Control System of an airline to map the real-world data to the proposed model. Passenger behavior was extracted by front-line service experts and clarified through consecutive on-site observations.

Enhanced visualization of the bile duct via parallel white light and indocyanine green fluorescence laparoscopic imaging

NASA Astrophysics Data System (ADS)

Demos, Stavros G.; Urayama, Shiro

2014-03-01

Despite best efforts, bile duct injury during laparoscopic cholecystectomy is a major potential complication. Precise detection method of extrahepatic bile duct during laparoscopic procedures would minimize the risk of injury. Towards this goal, we have developed a compact imaging instrumentation designed to enable simultaneous acquisition of conventional white color and NIR fluorescence endoscopic/laparoscopic imaging using ICG as contrast agent. The capabilities of this system, which offers optimized sensitivity and functionality, are demonstrated for the detection of the bile duct in an animal model. This design could also provide a low-cost real-time surgical navigation capability to enhance the efficacy of a variety of other image-guided minimally invasive procedures.

Diagnosis and management of Neuromyelitis Optica Spectrum Disorder (NMOSD) in Iran: A consensus guideline and recommendations.

PubMed

Sahraian, Mohammad Ali; Moghadasi, Abdorreza Naser; Azimi, Amir Reza; Asgari, Nasrin; H Akhoundi, Fahimeh; Abolfazli, Roya; Alaie, Shekoofeh; Ashtari, Fereshteh; Ayromlou, Hormoz; Baghbanian, Seyed Mohammad; Moghadam, Nahid Beladi; Fatehi, Farzad; Foroughipour, Mohsen; Langroodi, Hamidreza Ghalyanchi; Majdinasab, Nastaran; Nickseresht, Alireza; Nourian, Abbas; Shaygannejad, Vahid; Torabi, Hamid Reza

2017-11-01

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a relapsing neuro inflammatory disease of the central nervous system that typically presents with optic neuritis or myelitis and may cause severe disability. The diagnostic criteria have been updated and several immunosuppressive agents have been demonstrated to prevent acute exacerbations. As the disease rarely develops in a progressive course, management of acute attacks and proper prevention of exacerbations may change the long term out-come and prevent future disability. Consensus recommendations and guidelines will help the physicians to improve their practice and unify the treatment approaches in different communities. In order to develop a national consensus and recommendations for the diagnosis and management of NMOSD in Iran, a group of neurologists with long term experience in management of NMOSD were gathered to develop this consensus based on available national and international data. The primary draft was prepared and discussed to suggest the most appropriate treatment for these patients. We propose strategies for early diagnosis and treatment for prevention of relapses and minimizing consequences of attacks as a primary therapeutic goal. Attacks are currently treated with intravenous corticosteroids and, in refractory cases, with plasma exchange. All participants agreed on preventive treatment with currently available immunosuppressive agents such as azothioprin, rituximab and mycofenolate mofetil based on previous positive data in NMOSD in order to reduce attack frequency. The current consensus reviews the previous data and provides the clinicians with practical recommendations and advices for the diagnosis and management of NMOSD based on scientific data and clinical experience. Copyright © 2017 Elsevier B.V. All rights reserved.

Silvicultural approaches for management of eastern white pine to minimize impacts of damaging agents

Treesearch

M.E. Ostry; G. Laflamme; S.A. Katovich

2010-01-01

Since the arrival to North America of Cronartium ribicola, management of eastern white pine has been driven by the need to avoid the actual or, in many areas, the perceived damage caused by white pine blister rust. Although white pine has lost much of its former dominance, it remains a valuable species for biotic diversity, aesthetics, wildlife...

Reduced weight decontamination formulation for neutralization of chemical and biological warfare agents

DOEpatents

Tucker, Mark D.

2014-06-03

A reduced weight DF-200 decontamination formulation that is stable under high temperature storage conditions. The formulation can be pre-packed as an all-dry (i.e., no water) or nearly-dry (i.e., minimal water) three-part kit, with make-up water (the fourth part) being added later in the field at the point of use.

KR-12-a5 is a non-cytotoxic agent with potent antimicrobial effects against oral pathogens.

PubMed

Caiaffa, Karina Sampaio; Massunari, Loiane; Danelon, Marcelle; Abuna, Gabriel Flores; Bedran, Telma Blanca Lombardo; Santos-Filho, Norival Alves; Spolidorio, Denise Madalena Palomari; Vizoto, Natalia Leal; Cilli, Eduardo Maffud; Duque, Cristiane

2017-11-01

This study evaluated the cytotoxicity and antimicrobial activity of analogs of cationic peptides against microorganisms associated with endodontic infections. L-929 fibroblasts were exposed to LL-37, KR-12-a5 and hBD-3-1C V and chlorhexidine (CHX, control), and cell metabolism was evaluated with MTT. The minimal inhibitory concentration (MIC) and the minimal bactericidal/fungicidal concentration (MBC/MFC) of the peptides and CHX were determined against oral pathogens associated with endodontic infections. Enterococcus faecalis and Streptococcus mutans biofilms were cultivated in bovine dentin blocks, exposed to different concentrations of the most efficient antimicrobial peptide and analyzed by confocal laser scanning microscopy. CHX and peptides affected the metabolism of L-929 at concentrations > 31.25 and 500 μg ml -1 , respectively. Among the peptides, KR-12-a5 inhibited growth of both the microorganisms tested with the lowest MIC/MBC/MFC values. In addition, KR-12-a5 significantly reduced E. faecalis and S. mutans biofilms inside dentin tubules. In conclusion, KR-12-a5 is a non-cytotoxic agent with potent antimicrobial and anti-biofilm activity against oral pathogens associated with endodontic infections.

Controlled Endolysosomal Release of Agents by pH-responsive Polymer Blend Particles.

PubMed

Zhan, Xi; Tran, Kenny K; Wang, Liguo; Shen, Hong

2015-07-01

A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly(lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity.

Controlled endolysosomal release of agents by pH-responsive polymer blend particles

PubMed Central

Zhan, Xi; Tran, Kenny K.; Wang, Liguo; Shen, Hong

2015-01-01

Purpose A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly (lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. Methods We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. Results We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. Conclusions This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity. PMID:25592550

Drug Delivery Nanosystems for the Localized Treatment of Glioblastoma Multiforme.

PubMed

Nam, L; Coll, C; Erthal, L C S; de la Torre, C; Serrano, D; Martínez-Máñez, R; Santos-Martínez, M J; Ruiz-Hernández, E

2018-05-11

Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood⁻brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood⁻brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the attempts to develop nanostructures as local drug delivery systems able to deliver multiple agents for both therapeutic and diagnostic functions for the management of glioblastoma.

In Vitro Studies on a Microfluidic Sensor with Embedded Obstacles Using New Antibacterial Synthetic Compounds (1-TDPPO) Mixed Prop-2-en-1-one with Difluoro Phenyl.

PubMed

Roh, Changhyun; Lee, Jaewoong; Kinger, Mayank; Kang, Chankyu

2017-04-08

This paper describes the use of an analytical microfluidic sensor for accelerating chemo-repellent response and strong anti-bacterial 1-(Thien-2-yl)-3-(2, 6-difluoro phenyl) prop-2-en-1-one (1-TDPPO). The chemically-synthesized antimicrobial agent, which included prop-2-en-1-one and difluoro phenyl groups, was moving through an optically transparent polydimethylsiloxane (PDMS) microfluidic sensor with circular obstacles arranged evenly. The response, growth and distribution of fluorescent labeling Pseudomonas aeruginosa PAO1 against the antimicrobial agent were monitored by confocal laser scanning microscope (CLSM). The microfluidic sensor along with 1-TDPPOin this study exhibits the following advantages: (i) Real-time chemo-repellent responses of cell dynamics; (ii) Rapid eradication of biofilm by embedded obstacles and powerful antibacterial agents, which significantly reduce the response time compared to classical methods; (iii) Minimal consumption of cells and antimicrobial agents; and (iv) Simplifying the process of the normalization of the fluorescence intensity and monitoring of biofilm by captured images and datasets.

Incentive Control Strategies for Decision Problems with Parametric Uncertainties

NASA Astrophysics Data System (ADS)

Cansever, Derya H.

The central theme of this thesis is the design of incentive control policies in large scale systems with hierarchical decision structures, under the stipulation that the objective functionals of the agents at the lower level of the hierarchy are uncertain to the top-level controller (the leader). These uncertainties are modeled as a finite -dimensional parameter vector whose exact value constitutes private information to the relevant agent at the lower level. The approach we have adopted is to design incentive policies for the leader such that the dependence of the decision of the agents on the uncertain parameter is minimized. We have identified several classes of problems for which this approach is feasible. In particular, we have constructed policies whose performance is arbitrarily close to the solution of a version of the same problem that does not involve uncertainties. We have also shown that for a certain class of problem wherein the leader observes a linear combination of the agents' decisions, the leader can achieve the performance he would obtain if he had observed each decision separately.

Effects of Clove Oil as a Euthanasia Agent on Blood Collection Efficiency and Serum Cortisol Levels in Danio rerio

PubMed Central

Davis, Daniel J; Klug, Jenna; Hankins, Miriam; Doerr, Holly M; Monticelli, Stephanie R; Song, Ava; Gillespie, Catherine H; Bryda, Elizabeth C

2015-01-01

Zebrafish are an important laboratory animal model for biomedical research and are increasingly being used for behavioral neuroscience. Tricaine methanesulfonate (MS222) is the standard agent used for euthanasia of zebrafish. However, recent studies of zebrafish behavior suggest that MS222 may be aversive, and clove oil might be a possible alternative. In this study, we compared the effects of MS222 or clove oil as a euthanasia agent in zebrafish on the volume of blood collected and on serum levels of cortisol. Greater amounts of serum could be collected and lower serum levels of cortisol were present in fish euthanized with clove oil compared with equipotent dose of MS222. Euthanasia with clove oil did not blunt the expected elevation of serum cortisol levels elicited by an acute premortem stress. According to our findings, clove oil is a fast-acting agent that minimizes the cortisol response to euthanasia in zebrafish and allows the collection of large volumes of blood postmortem. These results represent a significant refinement in euthanasia methods for zebrafish. PMID:26424256

Effects of Clove Oil as a Euthanasia Agent on Blood Collection Efficiency and Serum Cortisol Levels in Danio rerio.

PubMed

Davis, Daniel J; Klug, Jenna; Hankins, Miriam; Doerr, Holly M; Monticelli, Stephanie R; Song, Ava; Gillespie, Catherine H; Bryda, Elizabeth C

2015-09-01

Zebrafish are an important laboratory animal model for biomedical research and are increasingly being used for behavioral neuroscience. Tricaine methanesulfonate (MS222) is the standard agent used for euthanasia of zebrafish. However, recent studies of zebrafish behavior suggest that MS222 may be aversive, and clove oil might be a possible alternative. In this study, we compared the effects of MS222 or clove oil as a euthanasia agent in zebrafish on the volume of blood collected and on serum levels of cortisol. Greater amounts of serum could be collected and lower serum levels of cortisol were present in fish euthanized with clove oil compared with equipotent dose of MS222. Euthanasia with clove oil did not blunt the expected elevation of serum cortisol levels elicited by an acute premortem stress. According to our findings, clove oil is a fast-acting agent that minimizes the cortisol response to euthanasia in zebrafish and allows the collection of large volumes of blood postmortem. These results represent a significant refinement in euthanasia methods for zebrafish.

Chemomechanical Caries Removal: A Review & Study of an Indigen-ously Developed Agent (Carie Care (TM) Gel) In Children.

PubMed

Venkataraghavan, Karthik; Kush, Anil; Lakshminarayana, Cs; Diwakar, Latha; Ravikumar, Puja; Patil, Shankargouda; Karthik, Sandhya

2013-08-01

The invention and application of engine driven or rotary instruments in operative treatment of carious lesions has resulted in removal of considerable toothe structure. However, with the introduction of adhesive materials for restorations, and the advent of minimal cavity design this principle has been challenged and is now considered to be too destructive to the tooth structure during caries removal. A number of techniques are available for cutting tooth tissue. The chemo mechanical method of caries removal/treatment is considered to be less painful when compared to the traditional treatment method (use of drill). The present study was carried to study the effect of an indigenously developed caries removal agent viz. Carie Care (TM) & its effectiveness as a chemo mechanical caries removal agent. How to cite this article: Venkataraghavan K, Kush A, Lakshminarayana CS, Diwakar L, Ravikumar P, Patil S, Karthik S. Chemomechanical Caries Removal: A Review & Study of an Indigenously Developed Agent (Carie Care (TM) Gel) In Children. J Int Oral Health 2013; 5(4):84-90.

Minimizing Hemodialysis Catheter Dysfunction: An Ounce of Prevention

PubMed Central

Lee, Timmy; Lok, Charmaine; Vazquez, Miguel; Moist, Louise; Maya, Ivan; Mokrzycki, Michele

2012-01-01

The maintenance of tunneled catheter (TC) patency is critical for the provision of adequate hemodialysis in patients who are TC-dependent. TC dysfunction results in the need for costly and inconvenient interventions, and reduced quality of life. Since the introduction of TCs in the late 1980s, heparin catheter lock has been the standard prophylactic regimen for the prevention of TC dysfunction. More recently, alternative catheter locking agents have emerged, and in some cases have shown to be superior to heparin lock with respect to improving TC patency and reducing TC-associated infections. These include citrate, tissue plasminogen activator, and a novel agent containing sodium citrate, methylene blue, methylparaben, and propylparaben. In addition, prophylaxis using oral anticoagulants/antiplatelet agents, including warfarin, aspirin, ticlodipine, as well as the use of modified heparin-coated catheters have also been studied for the prevention of TC dysfunction with variable results. The use of oral anticoagulants and/or antiplatelet agents as primary or secondary prevention of TC dysfunction must be weighed against their potential adverse effects, and should be individualized for each patient. PMID:22518310

Foraging swarms as Nash equilibria of dynamic games.

PubMed

Özgüler, Arif Bülent; Yildiz, Aykut

2014-06-01

The question of whether foraging swarms can form as a result of a noncooperative game played by individuals is shown here to have an affirmative answer. A dynamic game played by N agents in 1-D motion is introduced and models, for instance, a foraging ant colony. Each agent controls its velocity to minimize its total work done in a finite time interval. The game is shown to have a unique Nash equilibrium under two different foraging location specifications, and both equilibria display many features of a foraging swarm behavior observed in biological swarms. Explicit expressions are derived for pairwise distances between individuals of the swarm, swarm size, and swarm center location during foraging.

Consentaneous Agent-Based and Stochastic Model of the Financial Markets

PubMed Central

Gontis, Vygintas; Kononovicius, Aleksejus

2014-01-01

We are looking for the agent-based treatment of the financial markets considering necessity to build bridges between microscopic, agent based, and macroscopic, phenomenological modeling. The acknowledgment that agent-based modeling framework, which may provide qualitative and quantitative understanding of the financial markets, is very ambiguous emphasizes the exceptional value of well defined analytically tractable agent systems. Herding as one of the behavior peculiarities considered in the behavioral finance is the main property of the agent interactions we deal with in this contribution. Looking for the consentaneous agent-based and macroscopic approach we combine two origins of the noise: exogenous one, related to the information flow, and endogenous one, arising form the complex stochastic dynamics of agents. As a result we propose a three state agent-based herding model of the financial markets. From this agent-based model we derive a set of stochastic differential equations, which describes underlying macroscopic dynamics of agent population and log price in the financial markets. The obtained solution is then subjected to the exogenous noise, which shapes instantaneous return fluctuations. We test both Gaussian and q-Gaussian noise as a source of the short term fluctuations. The resulting model of the return in the financial markets with the same set of parameters reproduces empirical probability and spectral densities of absolute return observed in New York, Warsaw and NASDAQ OMX Vilnius Stock Exchanges. Our result confirms the prevalent idea in behavioral finance that herding interactions may be dominant over agent rationality and contribute towards bubble formation. PMID:25029364

ITOHealth: a multimodal middleware-oriented integrated architecture for discovering medical entities.

PubMed

Alor-Hernández, Giner; Sánchez-Cervantes, José Luis; Juárez-Martínez, Ulises; Posada-Gómez, Rubén; Cortes-Robles, Guillermo; Aguilar-Laserre, Alberto

2012-03-01

Emergency healthcare is one of the emerging application domains for information services, which requires highly multimodal information services. The time of consuming pre-hospital emergency process is critical. Therefore, the minimization of required time for providing primary care and consultation to patients is one of the crucial factors when trying to improve the healthcare delivery in emergency situations. In this sense, dynamic location of medical entities is a complex process that needs time and it can be critical when a person requires medical attention. This work presents a multimodal location-based system for locating and assigning medical entities called ITOHealth. ITOHealth provides a multimodal middleware-oriented integrated architecture using a service-oriented architecture in order to provide information of medical entities in mobile devices and web browsers with enriched interfaces providing multimodality support. ITOHealth's multimodality is based on the use of Microsoft Agent Characters, the integration of natural language voice to the characters, and multi-language and multi-characters support providing an advantage for users with visual impairments.

Suicide prevention by online support groups: an action theory-based model of emotional first aid.

PubMed

Gilat, Itzhak; Shahar, Golan

2009-01-01

In the last two decades, online support groups have become a valuable source of help for individuals in suicidal crisis. Their attractiveness is attributed to features that enhance help-seeking and self-disclosure such as availability, anonymity, and use of written communication. However, online support groups also suffer from limitations and potential risks as agents of suicide prevention. The Israeli Association for Emotional First Aid (ERAN) has developed a practical model that seeks to maximize the benefits and minimize the risks of online suicide prevention. The model applies the Action Theory concepts whereby individuals shape their own environment. The present paper presents the model, which is based on an online support group combined with personal chat and a telephonic help line. The online support group is moderated by paraprofessionals who function as both process regulators and support providers. The principles and practice of the model are described, the theoretical rationale is presented, and directions for future research are suggested.

Toward “Green” Hybrid Materials: Core–Shell Particles with Enhanced Impact Energy Absorbing Ability

PubMed Central

2016-01-01

Restrained properties of “green” degradable products drive the creation of materials with innovative structures and retained eco-attributes. Herein, we introduce the creation of impact modifiers in the form of core–shell (CS) particles toward the creation of “green” composite materials. Particles with CS structure constituted of PLA stereocomplex (PLASC) and a rubbery phase of poly(ε-caprolactone-co-d,l-lactide) (P[CL-co-LA]) were successfully achieved by spray droplet atomization. A synergistic association of the soft P[CL-co-LA] and hard PLASC domains in the core–shell structure induced unique thermo-mechanical effects on the PLA-based composites. The core–shell particles enhanced the crystallization of PLA matrices by acting as nucleating agents. The core–shell particles functioned efficiently as impact modifiers with minimal effect on the composites stiffness and strength. These findings provide a new platform for scalable design of polymeric-based structures to be used in the creation of advanced degradable materials. PMID:29503773

Hydrogel based approaches for cardiac tissue engineering.

PubMed

Saludas, Laura; Pascual-Gil, Simon; Prósper, Felipe; Garbayo, Elisa; Blanco-Prieto, María

2017-05-25

Heart failure still represents the leading cause of death worldwide. Novel strategies using stem cells and growth factors have been investigated for effective cardiac tissue regeneration and heart function recovery. However, some major challenges limit their translation to the clinic. Recently, biomaterials have emerged as a promising approach to improve delivery and viability of therapeutic cells and proteins for the regeneration of the damaged heart. In particular, hydrogels are considered one of the most promising vehicles. They can be administered through minimally invasive techniques while maintaining all the desirable characteristics of drug delivery systems. This review discusses recent advances made in the field of hydrogels for cardiac tissue regeneration in detail, focusing on the type of hydrogel (conventional, injectable, smart or nano- and micro-gel), the biomaterials used for its manufacture (natural, synthetic or hybrid) and the therapeutic agent encapsulated (stem cells or proteins). We expect that these novel hydrogel-based approaches will open up new possibilities in drug delivery and cell therapies. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis, analgesic, anti-inflammatory and anti-ulcerogenic activities of certain novel Schiff's bases as fenamate isosteres.

PubMed

Alafeefy, Ahmed M; Bakht, Mohammed A; Ganaie, Majid A; Ansarie, Mohd N; El-Sayed, Nahed N; Awaad, Amani S

2015-01-15

A series of certain novel Schiff bases as fenamate isosteres (VI:a-k) were synthesized to locate analgesic, anti-inflammatory agent with minimal ulcerogenic potential. The structures of the newly synthesized compounds were elucidated on the basis of their elemental analysis as well as IR, and NMR and mass spectroscopic data. All the compounds were evaluated for their anti-inflammatory activity by carrageenan induced paw oedema method. The compounds possessing good anti-inflammatory activity were further tested for analgesic, ulcerogenic, lipid peroxidation potentials and liver toxicity. Compounds (VI-c), (VI-f), (VI-h) and (VI-i) showed the best anti-inflammatory and significant analgesic activities at doses comparable to that of the standard drug Indomethacin. However, compounds (VI-c) and (VI-f) could be considered the most potent anti-inflammatory and analgesic molecules with maximum reduction in gastro-intestinal ulceration with no hepatocyte necrosis or liver degeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Towards non- and minimally instrumented, microfluidics-based diagnostic devices†

PubMed Central

Weigl, Bernhard; Domingo, Gonzalo; LaBarre, Paul; Gerlach, Jay

2009-01-01

In many health care settings, it is uneconomical, impractical, or unaffordable to maintain and access a fully equipped diagnostics laboratory. Examples include home health care, developing-country health care, and emergency situations in which first responders are dealing with pandemics or biowarfare agent release. In those settings, fully disposable diagnostic devices that require no instrument support, reagent, or significant training are well suited. Although the only such technology to have found widespread adoption so far is the immunochromatographic rapid assay strip test, microfluidics holds promise to expand the range of assay technologies that can be performed in formats similar to that of a strip test. In this paper, we review progress toward development of disposable, low-cost, easy-to-use microfluidics-based diagnostics that require no instrument at all. We also present examples of microfluidic functional elements—including mixers, separators, and detectors—as well as complete microfluidic devices that function entirely without any moving parts and external power sources. PMID:19023463

Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening.

PubMed

Arduino, Daniela M; Wettmarshausen, Jennifer; Vais, Horia; Navas-Navarro, Paloma; Cheng, Yiming; Leimpek, Anja; Ma, Zhongming; Delrio-Lorenzo, Alba; Giordano, Andrea; Garcia-Perez, Cecilia; Médard, Guillaume; Kuster, Bernhard; García-Sancho, Javier; Mokranjac, Dejana; Foskett, J Kevin; Alonso, M Teresa; Perocchi, Fabiana

2017-08-17

The mitochondrial calcium uniporter complex is essential for calcium (Ca 2+ ) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca 2+ signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for targeting uniporter activity. Here we introduce a high-throughput assay that selects for human MCU-specific small-molecule modulators in primary drug screens. Using isolated yeast mitochondria, reconstituted with human MCU, its essential regulator EMRE, and aequorin, and exploiting a D-lactate- and mannitol/sucrose-based bioenergetic shunt that greatly minimizes false-positive hits, we identify mitoxantrone out of more than 600 clinically approved drugs as a direct selective inhibitor of human MCU. We validate mitoxantrone in orthogonal mammalian cell-based assays, demonstrating that our screening approach is an effective and robust tool for MCU-specific drug discovery and, more generally, for the identification of compounds that target mitochondrial functions. Copyright © 2017 Elsevier Inc. All rights reserved.

Neutron-activatable radionuclide cancer therapy using graphene oxide nanoplatelets.

PubMed

Kim, Junghyun; Jay, Michael

2017-09-01

Neutron-activation is a promising method of generating radiotherapeutics with minimal handling of radioactive materials. Graphene oxide nanoplatelets (GONs) were examined as a carrier for neutron-activatable holmium with the purpose of exploiting inherent characteristics for theranostic application. GONs were hypothesized to be an ideal candidate for this application owing to their desirable characteristics such as a rigid structure, high metal loading capacity, low density, heat resistance, and the ability to withstand harsh environments associated with the neutron-activation process. Non-covalently PEGylated GONs (GONs-PEG) offered enhanced dispersibility and biocompatibility, and also exhibited increased holmium loading capacity nearly two-fold greater than GONs. Holmium leaching was investigated over a wide pH range, including conditions that mimic the tumor microenvironment, following neutron irradiation. The in vitro cell-based cytotoxicity analysis of GONs-based formulations with non-radioactive holmium confirmed their safety profile within cells. The results demonstrate the potential of GONs as a carrier of neutron-activatable radiotherapeutic agents. Copyright © 2017 Elsevier Inc. All rights reserved.

A New Approach To Secure Federated Information Bases Using Agent Technology.

ERIC Educational Resources Information Center

Weippi, Edgar; Klug, Ludwig; Essmayr, Wolfgang

2003-01-01

Discusses database agents which can be used to establish federated information bases by integrating heterogeneous databases. Highlights include characteristics of federated information bases, including incompatible database management systems, schemata, and frequently changing context; software agent technology; Java agents; system architecture;…

A CSP-Based Agent Modeling Framework for the Cougaar Agent-Based Architecture

NASA Technical Reports Server (NTRS)

Gracanin, Denis; Singh, H. Lally; Eltoweissy, Mohamed; Hinchey, Michael G.; Bohner, Shawn A.

2005-01-01

Cognitive Agent Architecture (Cougaar) is a Java-based architecture for large-scale distributed agent-based applications. A Cougaar agent is an autonomous software entity with behaviors that represent a real-world entity (e.g., a business process). A Cougaar-based Model Driven Architecture approach, currently under development, uses a description of system's functionality (requirements) to automatically implement the system in Cougaar. The Communicating Sequential Processes (CSP) formalism is used for the formal validation of the generated system. Two main agent components, a blackboard and a plugin, are modeled as CSP processes. A set of channels represents communications between the blackboard and individual plugins. The blackboard is represented as a CSP process that communicates with every agent in the collection. The developed CSP-based Cougaar modeling framework provides a starting point for a more complete formal verification of the automatically generated Cougaar code. Currently it is used to verify the behavior of an individual agent in terms of CSP properties and to analyze the corresponding Cougaar society.

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…

The Setting Time of Polyether Impression Materials after Contact with Conventional and Experimental Gingival Margin Displacement Agents.

PubMed

Nowakowska, Danuta; Raszewski, Zbigniew; Ziętek, Marek; Saczko, Jolanta; Kulbacka, Julita; Więckiewicz, Włodzimierz

2018-02-01

The compatibility of chemical gingival margin displacement agents with polyether impression materials has not been determined. The aim of this study was to evaluate the setting time of polyether impression elastomers after contact with conventional and experimental gingival displacement agents. The study compared the setting time of two polyether impression materials: medium body (Impregum Penta Soft) and light body (Impregum Garant L DuoSoft) after contact with 10 gingival displacement agents, including 5 conventional astringents (10%, 20%, and 25% aluminum chloride, 25% aluminum sulfate, and 15.5% ferric sulfate) and 5 experimental adrenergics (0.1% and 0.01% HCl-epinephrine, 0.05% HCl-tetrahydrozoline, 0.05% HCl-oxymetazoline, and 10% HCl-phenylephrine). As many as 120 specimens (60 light body and 60 medium body) were mixed with 20 μl of each of 10 gingival displacement agents, and the time to achieve maximum viscosity was measured with a viscometer. The setting times of these specimens were compared with the control group of 12 specimens, which were polymerized without contact with the displacement agents. The experiments were performed in two environments: 23°C and 37°C (± 0.1°C). Individual and average polymerization time compatibility indices (PTCI) were calculated. Data were analyzed by 2-way ANOVA (α = 0.05). The evaluated chemical displacement agents from both groups changed the setting time of light- and medium-body PE. The negative individual PTCI values achieved astringent (20% aluminum chloride) with two PE in both temperature environments. The average PTCI values of the experimental displacement agents at laboratory and intraoral temperatures were significantly higher than the conventional agents. The present findings suggest that experimental retraction agents can be recommended clinically as gingival margin displacement agents with minimal effects on the setting time of medium- and light-body polyether impression materials; however, direct contact of chemical displacement agents and polyether impression materials can be avoided. © 2016 by the American College of Prosthodontists.

The highly intelligent virtual agents for modeling financial markets

NASA Astrophysics Data System (ADS)

Yang, G.; Chen, Y.; Huang, J. P.

2016-02-01

Researchers have borrowed many theories from statistical physics, like ensemble, Ising model, etc., to study complex adaptive systems through agent-based modeling. However, one fundamental difference between entities (such as spins) in physics and micro-units in complex adaptive systems is that the latter are usually with high intelligence, such as investors in financial markets. Although highly intelligent virtual agents are essential for agent-based modeling to play a full role in the study of complex adaptive systems, how to create such agents is still an open question. Hence, we propose three principles for designing high artificial intelligence in financial markets and then build a specific class of agents called iAgents based on these three principles. Finally, we evaluate the intelligence of iAgents through virtual index trading in two different stock markets. For comparison, we also include three other types of agents in this contest, namely, random traders, agents from the wealth game (modified on the famous minority game), and agents from an upgraded wealth game. As a result, iAgents perform the best, which gives a well support for the three principles. This work offers a general framework for the further development of agent-based modeling for various kinds of complex adaptive systems.

The formulary process from a risk management perspective.

PubMed

Raber, Jack H

2010-06-01

During their evolution over the past 6 decades, hospital formularies have become more than a list of drugs that an institution keeps in stock. Today, an agent under formulary consideration must be examined not only in light of its relative efficacy, safety, and acquisition cost, but consideration must also be given to the potential indirect costs that accompany its use. Federal regulations have, for some drugs, added layers of administrative actions that must be followed to ensure their appropriate use. Examples of this are risk evaluation and mitigation strategies (REMS) and duties that may be implied or expressly addressed in the black-box warnings associated with some classes of agents and, in isolated instances, specific drugs within a given class. Regulatory interpretation of these programs and warnings has often led to the expectation that the institution providing the agent will implement effective protocols and procedures to minimize the risk of adverse events to a patient in addition to or in accordance with required programs such as REMS. The consequences for failing to meet this expectation can lead to regulatory sanctions; the potential also exists for liability exposure. Risk management principles apply to all levels of the decision-making process for evaluating a new agent for formulary inclusion or when reevaluating an agent's formulary status. Pharmacists play an important role in mitigating these risks by carefully evaluating every agent from a broader perspective.

The chemistry and applications of antimicrobial polymers: a state-of-the-art review.

PubMed

Kenawy, El-Refaie; Worley, S D; Broughton, Roy

2007-05-01

Microbial infection remains one of the most serious complications in several areas, particularly in medical devices, drugs, health care and hygienic applications, water purification systems, hospital and dental surgery equipment, textiles, food packaging, and food storage. Antimicrobials gain interest from both academic research and industry due to their potential to provide quality and safety benefits to many materials. However, low molecular weight antimicrobial agents suffer from many disadvantages, such as toxicity to the environment and short-term antimicrobial ability. To overcome problems associated with the low molecular weight antimicrobial agents, antimicrobial functional groups can be introduced into polymer molecules. The use of antimicrobial polymers offers promise for enhancing the efficacy of some existing antimicrobial agents and minimizing the environmental problems accompanying conventional antimicrobial agents by reducing the residual toxicity of the agents, increasing their efficiency and selectivity, and prolonging the lifetime of the antimicrobial agents. Research concerning the development of antimicrobial polymers represents a great a challenge for both the academic world and industry. This article reviews the state of the art of antimicrobial polymers primarily since the last comprehensive review by one of the authors in 1996. In particular, it discusses the requirements of antimicrobial polymers, factors affecting the antimicrobial activities, methods of synthesizing antimicrobial polymers, major fields of applications, and future and perspectives in the field of antimicrobial polymers.

Pharmacologic management of types 1 and 2 diabetes mellitus and their complications in women of childbearing age.

PubMed

Mukherjee, Mimi S; Coppenrath, Valerie A; Dallinga, Bree A

2015-02-01

The numbers of women of childbearing age with pregestational diabetes mellitus (diabetes existing before pregnancy) are increasing, primarily because more patients are developing type 2 diabetes at younger ages. The teratogenicity associated with hyperglycemia in early pregnancy is well documented, and tight glucose control minimizes the risk of congenital malformation. Preconception planning is essential; thus contraception that does not worsen complications of diabetes is desirable. In addition, because contraceptives are not 100% effective, the treatment of elevated blood glucose levels, hypertension, and dyslipidemia in these women requires consideration of unplanned pregnancy. We summarized the literature to aid clinicians in choosing individualized treatment that minimizes risk in case pregnancy occurs and maximizes benefit in preventing the complications of diabetes. In women with well-controlled diabetes without vascular disease, all contraceptive methods are safe. Intrauterine devices are recommended due to their minimal effects on risk factors for diabetic complications and their lack of reliance on patient adherence for efficacy. Among insulins, the insulin analogs-insulin lispro, insulin aspart, and insulin detemir-offer patients greater convenience than regular insulin and NPH insulin, and they are safe in case of unplanned pregnancy. Of the noninsulin agents, glyburide and metformin are the safest during pregnancy, but many of the other agents pose minimal risk as long as they are withdrawn during early pregnancy. The risks and benefits of angiotensin-converting enzyme inhibitors in women with compelling indications must be weighed individually. In hypertensive patients at a high risk for unplanned pregnancy, nifedipine should be considered due to literature supporting its safety during early pregnancy. Pravastatin is recommended for women with dyslipidemia who are using effective contraception because there have been no reports of birth defects with this statin when used during early pregnancy in humans and animals. © 2015 Pharmacotherapy Publications, Inc.

Darwinism and ethology. The role of natural selection in animals and humans.

PubMed

Gervet, J; Soleilhavoup, M

1997-11-01

The role of behaviour in biological evolution is examined within the context of Darwinism. All Darwinian models are based on the distinction of two mechanisms: one that permits faithful transmission of a feature from one generation to another, and another that differentially regulates the degree of this transmission. Behaviour plays a minimal role as an agent of transmission in the greater part of the animal kingdom; by contrast, the forms it may assume strongly influence the mechanisms of selection regulating the different rates of transmission. We consider the decisive feature of the human species to be the existence of a phenotypical system of cultural coding characterized by precision and reliability which are the distinctive feature of genetic coding in animals. We examine the consequences for the application of the Darwinian model to human history.

Supercritical water gasification of biomass: Thermodynamic constraints.

PubMed

Castello, Daniele; Fiori, Luca

2011-08-01

In the present work, the supercritical water gasification (SCWG) of biomass is analyzed with a view to outlining the possible thermodynamic constraints that must be taken into account to develop this new process. In particular, issues concerning the formation of solid carbon and the process heat duty are discussed. The analysis is conducted by means of a two-phase non-stoichiometric thermodynamic model, based on Gibbs free energy minimization. Results show that char formation at equilibrium only occurs at high biomass concentrations, with a strong dependence on biomass composition. As regards the process heat duty, SCWG is mostly endothermic when biomass concentration is low, although a very small amount of oxidizing agent is able to make the process exothermic, with only a small loss in the heating value of the syngas produced. Copyright © 2011 Elsevier Ltd. All rights reserved.

New Scaffold for Angiogenesis Inhibitors Discovered by Targeted Chemical Transformations of Wondonin Natural Products.

PubMed

Yu, Shuai; Oh, Jedo; Li, Feng; Kwon, Yongseok; Cho, Hyunkyung; Shin, Jongheon; Lee, Sang Kook; Kim, Sanghee

2017-10-12

The structure of wondonin marine natural products was renovated to attain new drug-like scaffolds. Wondonins have novel antiangiogenic properties without overt cytotoxicity. However, the chemical instability and synthetic complexity of wondonins have hindered their development as a new type of antiangiogenesis agent. Using a structure-based bioisosterism, the benzodioxole moiety was changed to benzothiazole, and the imidazole moiety was replaced by 1,2,3-triazole. Our efforts resulted in a new scaffold with enhanced antiangiogenic activity and minimized cytotoxicity. One compound with this scaffold effectively inhibited hyaloid vessel formation in diabetic retinopathy mimic zebrafish model. The biological findings together suggested the potential of the scaffold as a lead structure for development of antiangiogenic drugs with novel functions and as a probe to elucidate new biological mechanisms associated with angiogenesis.

Catalytic destruction of groundwater contaminants in reactive extraction wells

DOEpatents

McNab, Jr., Walt W.; Reinhard, Martin

2002-01-01

A system for remediating groundwater contaminated with halogenated solvents, certain metals and other inorganic species based on catalytic reduction reactions within reactive well bores. The groundwater treatment uses dissolved hydrogen as a reducing agent in the presence of a metal catalyst, such a palladium, to reduce halogenated solvents (as well as other substituted organic compounds) to harmless species (e.g., ethane or methane) and immobilize certain metals to low valence states. The reactive wells function by removing water from a contaminated water-bearing zone, treating contaminants with a well bore using catalytic reduction, and then reinjecting the treated effluent into an adjacent water-bearing zone. This system offers the advantages of a compact design with a minimal surface footprint (surface facilities) and the destruction of a broad suite of contaminants without generating secondary waste streams.

Reduced Zeta potential through use of cationic adhesion promoter for improved resist process performance and minimizing material consumption

NASA Astrophysics Data System (ADS)

Hodgson, Lorna; Thompson, Andrew

2012-03-01

This paper presents the results of a non-HMDS (non-silane) adhesion promoter that was used to reduce the zeta potential for very thin (proprietary) polymer on silicon. By reducing the zeta potential, as measured by the minimum sample required to fully coat a wafer, the amount of polymer required to coat silicon substrates was significantly reduced in the manufacture of X-ray windows used for high transmission of low-energy X-rays. Moreover, this approach used aqueous based adhesion promoter described as a cationic surface active agent that has been shown to improve adhesion of photoresists (positive, negative, epoxy [SU8], e-beam and dry film). As well as reducing the amount of polymer required to coat substrates, this aqueous adhesion promoter is nonhazardous, and contains non-volatile solvents.

Airborne agent concentration analysis

DOEpatents

Gelbard, Fred

2004-02-03

A method and system for inferring airborne contaminant concentrations in rooms without contaminant sensors, based on data collected by contaminant sensors in other rooms of a building, using known airflow interconnectivity data. The method solves a least squares problem that minimizes the difference between measured and predicted contaminant sensor concentrations with respect to an unknown contaminant release time. Solutions are constrained to providing non-negative initial contaminant concentrations in all rooms. The method can be used to identify a near-optimal distribution of sensors within the building, when then number of available sensors is less than the total number of rooms. This is achieved by having a system-sensor matrix that is non-singular, and by selecting that distribution which yields the lowest condition number of all the distributions considered. The method can predict one or more contaminant initial release points from the collected data.

GFP-complementation assay to detect functional CPP and protein delivery into living cells

PubMed Central

Milech, Nadia; Longville, Brooke AC; Cunningham, Paula T; Scobie, Marie N; Bogdawa, Heique M; Winslow, Scott; Anastasas, Mark; Connor, Theresa; Ong, Ferrer; Stone, Shane R; Kerfoot, Maria; Heinrich, Tatjana; Kroeger, Karen M; Tan, Yew-Foon; Hoffmann, Katrin; Thomas, Wayne R; Watt, Paul M; Hopkins, Richard M

2015-01-01

Efficient cargo uptake is essential for cell-penetrating peptide (CPP) therapeutics, which deliver widely diverse cargoes by exploiting natural cell processes to penetrate the cell’s membranes. Yet most current CPP activity assays are hampered by limitations in assessing uptake, including confounding effects of conjugated fluorophores or ligands, indirect read-outs requiring secondary processing, and difficulty in discriminating internalization from endosomally trapped cargo. Split-complementation Endosomal Escape (SEE) provides the first direct assay visualizing true cytoplasmic-delivery of proteins at biologically relevant concentrations. The SEE assay has minimal background, is amenable to high-throughput processes, and adaptable to different transient and stable cell lines. This split-GFP-based platform can be useful to study transduction mechanisms, cellular imaging, and characterizing novel CPPs as pharmaceutical delivery agents in the treatment of disease. PMID:26671759

Optoacoustic sensing of ocular bacterial antigen using targeted gold nanorods

NASA Astrophysics Data System (ADS)

Maswadi, Saher; Page, Leland; Woodward, Lee; Glickman, Randolph D.; Barsalou, Norman

2008-02-01

Bacterial contamination can be detected using a minimally invasive optical method, based on laser-induced optoacoustic spectroscopy, to probe for specific antigens associated with a specific infectious agent. As a model system, we have used a surface antigen (Ag), isolated from Chlamydia trachomatis, and a complementary antibody (Ab). A preparation of 0.2 mg/ml of monoclonal Ab specific to the C. trachomatis surface Ag was conjugated to gold nanorods using standard commercial reagents, in order to produce a targeted contrast agent with a strong optoacoustic signal. The C. trachomatis Ag was absorbed in standard plastic microwells, and the binding of the complementary Ab-nanorod conjugate was tested in an immunoaffinity assay. Optoacoustic signals were elicited from the bound nanorods, using an optical parametric oscillator (OPO) laser system as the optical pump. The wavelength tuneability of the OPO optimized the spectroscopic measurement by exciting the nanorods at their optical absorption maxima. Optoacoustic responses were measured in the microwells using a probe beam deflection technique. Immunoaffinity assays were performed on several dilutions of purified C. trachomatis antigen ranging from 50 μg/ml to 1 pg/ml, in order to determine the detection limit for the optoacoustic-based assay. Only when the antigen was present, and the complementary Ab-NR reagent was introduced into the microwell, was an enhanced optoacoustic signal obtained, which indicated specific binding of the Ab-NR complex. The limit of detection with the current system design is between 1 and 5 pg/ml of bacterial Ag.

Real-time, aptamer-based tracking of circulating therapeutic agents in living animals

PubMed Central

Ferguson, B. Scott; Hoggarth, David A.; Maliniak, Dan; Ploense, Kyle; White, Ryan J.; Woodward, Nick; Hsieh, Kuangwen; Bonham, Andrew J.; Eisenstein, Michael; Kippin, Tod; Plaxco, Kevin W.; Soh, H. Tom

2014-01-01

A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients’ health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at sub-minute temporal resolution. Importantly, we show that MEDIC can also obtain pharmacokineticparameters for individual animals in real-time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters. PMID:24285484

Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders.

PubMed

Mesa, Ruben A

2007-01-01

The diagnosis and management of the BCR-ABL-negative myeloproliferative disorders (MPDs) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are at an explosive crossroads of scientific investigation and evolving paradigms since the discovery of the tyrosine kinase-activating JAK2V617F mutation in 2005. Additional discovery of relevant molecular lesions (JAK2 exon 12 mutations and c-MplW515L/K) have only further enriched our understanding of MPD pathogenesis. The improved diagnostic certainty these molecular markers provide have resulted in the modification, and simplification, of the World Health Organization (WHO) diagnostic algorithms for MPDs. Despite these scientific advances, however, the initial management of MPDs continues to rely upon a risk-based strategy to minimize the risk of vascular events with control of erythrocytosis, targeted antiplatelet therapy, and risk-based myelosuppressive therapy. No current medical therapy has altered the natural trend of the MPDs to lead to overt severe myelofibrosis or acute leukemia. Investigations into targeted therapies for MPDs are proceeding at a brisk pace with agents aimed at immunomodulation, decreasing marrow stromal reaction to the aberrant clone, DNA hypomethylation, or the inhibition of tyrosine kinases. Specific inhibition of JAK2 itself appears promising by in vitro investigations, and clinical trials with multiple agents are planned to commence enrollment in 2007. The potential impact of JAK2 inhibitors on the manifestations of the MPDs is unclear, but is awaited with great interest.

Euthanasia using gaseous agents in laboratory rodents.

PubMed

Valentim, A M; Guedes, S R; Pereira, A M; Antunes, L M

2016-08-01

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously. Nevertheless, its aversive potential has been criticized in terms of animal welfare. The data available regarding the use of carbon dioxide (CO2), inhaled anaesthetics (such as isoflurane, sevoflurane, halothane and enflurane), as well as carbon monoxide and inert gases are discussed throughout this review. Euthanasia of fetuses and neonates is also addressed. A table listing currently available information to ease access to data regarding euthanasia techniques using gaseous agents in laboratory rodents was compiled. Regarding better animal welfare, there is currently insufficient evidence to advocate banning or replacing CO2 in the euthanasia of rodents; however, there are hints that alternative gases are more humane. The exposure to a volatile anaesthetic gas before loss of consciousness has been proposed by some scientific studies to minimize distress; however, the impact of such a measure is not clear. Areas of inconsistency within the euthanasia literature have been highlighted recently and stem from insufficient knowledge, especially regarding the advantages of the administration of isoflurane or sevoflurane over CO2, or other methods, before loss of consciousness. Alternative methods to minimize distress may include the development of techniques aimed at inducing death in the home cage of animals. Scientific outcomes have to be considered before choosing the most suitable euthanasia method to obtain the best results and accomplish the 3Rs (replacement, reduction and refinement). © The Author(s) 2015.

Antitumor agent 25-epi Ritterostatin GN1N induces endoplasmic reticulum stress and autophagy mediated cell death in melanoma cells.

PubMed

Riaz Ahmed, Kausar Begam; Kanduluru, Ananda Kumar; Feng, Li; Fuchs, Philip L; Huang, Peng

2017-05-01

Metastatic melanoma is the most aggressive of all skin cancers and is associated with poor prognosis owing to lack of effective treatments. 25-epi Ritterostatin GN1N is a novel antitumor agent with yet undefined mechanisms of action. We sought to delineate the antitumor mechanisms of 25-epi Ritterostatin GN1N in melanoma cells to determine the potential of this compound as a treatment for melanoma. Activation of the endoplasmic reticulum (ER) stress protein glucose-regulated protein 78 (GRP78) has been associated with increased melanoma progression, oncogenic signaling, drug resistance, and suppression of cell death. We found that 25-epi Ritterostatin GN1N induced cell death in melanoma cells at nanomolar concentrations, and this cell death was characterized by inhibition of GRP78 expression, increased expression of the ER stress marker CHOP, loss of mitochondrial membrane potential, and lipidation of the autophagy marker protein LC3B. Importantly, normal melanocytes exhibited limited sensitivity to 25-epi Ritterostatin GN1N. Subsequent in vivo results demonstrated that 25-epi Ritterostatin GN1N reduced melanoma growth in mouse tumor xenografts and did not affect body weight, suggesting minimal toxicity. In summary, our findings indicate that 25-epi Ritterostatin GN1N causes ER stress and massive autophagy, leading to collapse of mitochondrial membrane potential and cell death in melanoma cells, with minimal effects in normal melanocytes. Thus, 25-epi Ritterostatin GN1N is a promising anticancer agent that warrants further investigation.

Pharmacologic Hemostatic Agents in Total Joint Arthroplasty-A Cost-Effectiveness Analysis.

PubMed

Ramkumar, Dipak B; Ramkumar, Niveditta; Tapp, Stephanie J; Moschetti, Wayne E

2018-03-03

Total knee and hip arthroplasties can be associated with substantial blood loss, affecting morbidity and even mortality. Two pharmacological antifibrinolytics, ε-aminocaproic acid (EACA) and tranexamic acid (TXA) have been used to minimize perioperative blood loss, but both have associated morbidity. Given the added cost of these medications and the risks associated with then, a cost-effectiveness analysis was undertaken to ascertain the best strategy. A cost-effectiveness model was constructed using the payoffs of cost (in United States dollars) and effectiveness (quality-adjusted life expectancy, in days). The medical literature was used to ascertain various complications, their probabilities, utility values, and direct medical costs associated with various health states. A time horizon of 10 years and a willingness to pay threshold of $100,000 was used. The total cost and effectiveness (quality-adjusted life expectancy, in days) was $459.77, $951.22, and $1174.87 and 3411.19, 3248.02, and 3342.69 for TXA, no pharmacologic hemostatic agent, and EACA, respectively. Because TXA is less expensive and more effective than the competing alternatives, it was the favored strategy. One-way sensitivity analyses for probability of transfusion and myocardial infarction for all 3 strategies revealed that TXA remains the dominant strategy across all clinically plausible values. TXA, when compared with no pharmacologic hemostatic agent and with EACA, is the most cost-effective strategy to minimize intraoperative blood loss in hip and knee total joint arthroplasties. These findings are robust to sensitivity analyses using clinically plausible probabilities. Copyright © 2018 Elsevier Inc. All rights reserved.

An Active Learning Exercise for Introducing Agent-Based Modeling

ERIC Educational Resources Information Center

Pinder, Jonathan P.

2013-01-01

Recent developments in agent-based modeling as a method of systems analysis and optimization indicate that students in business analytics need an introduction to the terminology, concepts, and framework of agent-based modeling. This article presents an active learning exercise for MBA students in business analytics that demonstrates agent-based…

Fluorescent ampicillin analogues as multifunctional disguising agents against opsonization

NASA Astrophysics Data System (ADS)

Kotagiri, Nalinikanth; Sakon, Joshua; Han, Haewook; Zharov, Vladimir P.; Kim, Jin-Woo

2016-06-01

Cancer nanomedicines are opening new paradigms in cancer management and recent research points to how they can vastly improve imaging and therapy through multimodality and multifunctionality. However, challenges to achieving optimal efficacy are manifold starting from processing materials and evaluating their intended effectiveness on biological tissue, to developing new strategies aimed at improving transport of these materials through the biological milieu to the target tissue. Here, we report a fluorescent derivative of a beta-lactam antibiotic, ampicillin (termed iAmp) and its multifunctional physicobiochemical characteristics and potential as a biocompatible shielding agent and an effective dispersant. Carbon nanotubes (CNTs) were chosen to demonstrate the efficacy of iAmp. CNTs are known for their versatility and have been used extensively for cancer theranostics as photothermal and photoacoustic agents, but have limited solubility in water and biocompatibility. Traditional dispersants are associated with imaging artifacts and are not fully biocompatible. The chemical structure of iAmp is consistent with a deamination product of ampicillin. Although the four-membered lactam ring is intact, it does not retain the antibiotic properties. The iAmp is an effective dispersant and simultaneously serves as a fluorescent label for single-walled CNTs (SWNTs) with minimal photobleaching. The iAmp also enables bioconjugation of SWNTs to bio-ligands such as antibodies through functional carboxyl groups. Viability tests show that iAmp-coated SWNTs have minimal toxicity. Bio-stability tests under physiological conditions reveal that iAmp coating not only remains stable in a biologically relevant environment with high protein and salt concentrations, but also renders SWNTs transparent against nonspecific protein adsorption, also known as protein corona. Mammalian tissue culture studies with macrophages and opsonins validate that iAmp coating affords immunological resistance to SWNTs. Furthermore, iAmp coating offers protection to SWNTs against their nonspecific adsorption across disparate cell types, which has precluded a targeted strategy, and enables selective molecular targeting. The iAmp can therefore be used as an efficient dispersant, a photostable fluorescent agent, and a biocompatible disguising agent, alleviating CNTs' drawbacks and rendering them suitable for nanotheranostic and drug delivery applications.Cancer nanomedicines are opening new paradigms in cancer management and recent research points to how they can vastly improve imaging and therapy through multimodality and multifunctionality. However, challenges to achieving optimal efficacy are manifold starting from processing materials and evaluating their intended effectiveness on biological tissue, to developing new strategies aimed at improving transport of these materials through the biological milieu to the target tissue. Here, we report a fluorescent derivative of a beta-lactam antibiotic, ampicillin (termed iAmp) and its multifunctional physicobiochemical characteristics and potential as a biocompatible shielding agent and an effective dispersant. Carbon nanotubes (CNTs) were chosen to demonstrate the efficacy of iAmp. CNTs are known for their versatility and have been used extensively for cancer theranostics as photothermal and photoacoustic agents, but have limited solubility in water and biocompatibility. Traditional dispersants are associated with imaging artifacts and are not fully biocompatible. The chemical structure of iAmp is consistent with a deamination product of ampicillin. Although the four-membered lactam ring is intact, it does not retain the antibiotic properties. The iAmp is an effective dispersant and simultaneously serves as a fluorescent label for single-walled CNTs (SWNTs) with minimal photobleaching. The iAmp also enables bioconjugation of SWNTs to bio-ligands such as antibodies through functional carboxyl groups. Viability tests show that iAmp-coated SWNTs have minimal toxicity. Bio-stability tests under physiological conditions reveal that iAmp coating not only remains stable in a biologically relevant environment with high protein and salt concentrations, but also renders SWNTs transparent against nonspecific protein adsorption, also known as protein corona. Mammalian tissue culture studies with macrophages and opsonins validate that iAmp coating affords immunological resistance to SWNTs. Furthermore, iAmp coating offers protection to SWNTs against their nonspecific adsorption across disparate cell types, which has precluded a targeted strategy, and enables selective molecular targeting. The iAmp can therefore be used as an efficient dispersant, a photostable fluorescent agent, and a biocompatible disguising agent, alleviating CNTs' drawbacks and rendering them suitable for nanotheranostic and drug delivery applications. Electronic supplementary information (ESI) available: Details of quantum yield estimation and physicobiochemical analyses to assess the mechanism of iAmp synthesis and its chemical structure as well as the cytotoxicity and bio-stability of iAmp and iAmp-SWNT hybrids. See DOI: 10.1039/c5nr08686h

A Two-Stage Multi-Agent Based Assessment Approach to Enhance Students' Learning Motivation through Negotiated Skills Assessment

ERIC Educational Resources Information Center

Chadli, Abdelhafid; Bendella, Fatima; Tranvouez, Erwan

2015-01-01

In this paper we present an Agent-based evaluation approach in a context of Multi-agent simulation learning systems. Our evaluation model is based on a two stage assessment approach: (1) a Distributed skill evaluation combining agents and fuzzy sets theory; and (2) a Negotiation based evaluation of students' performance during a training…

Blood Glucose Reduction by Diabetic Drugs with Minimal Hypoglycemia Risk for Cardiovascular Outcomes: Evidence from Meta-regression Analysis of Randomized Controlled Trials.

PubMed

Huang, Chi-Jung; Wang, Wei-Ting; Sung, Shih-Hsien; Chen, Chen-Huan; Lip, Gregory Yh; Cheng, Hao-Min; Chiang, Chern-En

2018-05-02

To investigate the effects of blood glucose control with antihyperglycemic agents with minimal hypoglycemia risk on cardiovascular outcomes in patients with type 2 diabetes (T2D). Randomized controlled trials (RCTs) comparing the relative efficacy and safety of antidiabetic drugs with less hypoglycemia risk were comprehensively searched in MEDLINE, Embase, and the Cochrane Library up to January 27, 2018. Mixed-effects meta-regression analysis was conducted to explore the relationship between haemoglobin A1c (HbA1c) reduction and the risk of major adverse cardiovascular events (MACE), myocardial infarction, stroke, cardiovascular death, all-cause death, and hospitalization for heart failure. Ten RCTs comprising 92400 participants with T2D were included and provided information on 9773 MACE during a median follow-up of 2.6 years. The mean HbA1c concentration was 0.42% lower (median, 0.27-0.86%) for participants given antihyperglycemic agents than those given placebo. The meta-regression analysis demonstrated that HbA1c reduction was significantly associated with a decreased risk of MACE (β value, -0.39 to -0.55; P<0.02) even after adjusting for each of the following possible confounding factors including age, sex, baseline HbA1c, duration of follow-up, difference in achieved systolic blood pressure, difference in achieved body weight, or risk difference in hypoglycemia. Lowering HbA1c by 1% conferred a significant risk reduction of 30% (95% CI, 17-40%) for MACE. By contrast, the meta-regression analysis for trials using conventional agents failed to demonstrate a significant relationship between achieved HbA1c difference and MACE risk (P>0.74). Compared with placebo, newer T2D agents with less hypoglycemic hazard significantly reduced the risk of MACE. The MACE reduction seems to be associated with HbA1c reduction in a linear relationship. This article is protected by copyright. All rights reserved.

The Physics of Traffic Congestion and Road Pricing in Transportation Planning

NASA Astrophysics Data System (ADS)

Levinson, David

2010-03-01

This presentation develops congestion theory and congestion pricing theory from its micro- foundations, the interaction of two or more vehicles. Using game theory, with a two- player game it is shown that the emergence of congestion depends on the players' relative valuations of early arrival, late arrival, and journey delay. Congestion pricing can be used as a cooperation mechanism to minimize total costs (if returned to the players). The analysis is then extended to the case of the three- player game, which illustrates congestion as a negative externality imposed on players who do not themselves contribute to it. A multi-agent model of travelers competing to utilize a roadway in time and space is presented. To realize the spillover effect among travelers, N-player games are constructed in which the strategy set includes N+1 strategies. We solve the N-player game (for N = 7) and find Nash equilibria if they exist. This model is compared to the bottleneck model. The results of numerical simulation show that the two models yield identical results in terms of lowest total costs and marginal costs when a social optimum exists. Moving from temporal dynamics to spatial complexity, using consistent agent- based techniques, we model the decision-making processes of users and infrastructure owner/operators to explore the welfare consequence of price competition, capacity choice, and product differentiation on congested transportation networks. Component models include: (1) An agent-based travel demand model wherein each traveler has learning capabilities and unique characteristics (e.g. value of time); (2) Econometric facility provision cost models; and (3) Representations of road authorities making pricing and capacity decisions. Different from small-network equilibrium models in prior literature, this agent- based model is applicable to pricing and investment analyses on large complex networks. The subsequent economic analysis focuses on the source, evolution, measurement, and impact of product differentiation with heterogeneous users on a mixed ownership network (with tolled and untolled roads). Two types of product differentiation in the presence of toll roads, path differentiation and space differentiation, are defined and measured for a base case and several variants with different types of price and capacity competition and with various degrees of user heterogeneity. The findings favor a fixed-rate road pricing policy compared to complete pricing freedom on toll roads. It is also shown that the relationship between net social benefit and user heterogeneity is not monotonic on a complex network with toll roads.

Agent Based Fault Tolerance for the Mobile Environment

NASA Astrophysics Data System (ADS)

Park, Taesoon

This paper presents a fault-tolerance scheme based on mobile agents for the reliable mobile computing systems. Mobility of the agent is suitable to trace the mobile hosts and the intelligence of the agent makes it efficient to support the fault tolerance services. This paper presents two approaches to implement the mobile agent based fault tolerant service and their performances are evaluated and compared with other fault-tolerant schemes.

Antimicrobial Properties of Natural Phenols and Related Compounds

PubMed Central

Jurd, L.; King, A. D.; Mihara, K.; Stanley, W. L.

1971-01-01

Obtusastyrene (4-cinnamylphenol) displays effective antimicrobial activity in vitro against a variety of gram-positive bacteria, yeasts, and molds. The activity of obtusastyrene is not appreciably affected by pH, and its minimal inhibitory concentrations, 12 to 25 μg/ml for bacteria and 12 to 100 μg/ml for fungi, compare favorably with those of a number of synthetic, phenolic antimicrobial agents. PMID:5553287

Minority games and stylized facts

NASA Astrophysics Data System (ADS)

Challet, Damien; Marsili, Matteo; Zhang, Yi-Cheng

2001-10-01

The minority game is a generic model of competing adaptive agents, which is often believed to be a model of financial markets. We discuss to which extent this is a reasonable statement, and present minimal modifications that make this model reproduce stylized facts. The resulting model shows that without speculators, prices follow random walks, and that stylized facts disappear if enough speculators take into account their market impact.

Delivery of drugs, growth factors, genes and stem cells via intrapericardial, epicardial and intramyocardial routes for sustained local targeted therapy of myocardial disease.

PubMed

Maslov, Mikhail; Foianini, Stephan; Lovich, Mark

2017-10-01

Local myocardial delivery (LMD) of therapeutic agents is a promising strategy that aims to treat various myocardial pathologies. It is designed to deliver agents directly to the myocardium and minimize their extracardiac concentrations and side effects. LMD aims to enhance outcomes of existing therapies by broadening their therapeutic window and to utilize new agents that could not be otherwise be implemented systemically. Areas covered: This article provides a historical overview of six decades LMD evolution in terms of the approaches, including intrapericardial, epicardial, and intramyocardial delivery, and the wide array of classes of agents used to treat myocardial pathologies. We examines delivery of pharmaceutical compounds, targeted gene transfection and cell implantation techniques to produce therapeutic effects locally. We outline therapeutic indications, successes and failures as well as technical approaches for LMD. Expert opinion: While LMD is more complicated than conventional oral or intravenous administration, given recent advances in interventional cardiology, it is safe and may provide better therapeutic outcomes. LMD is complex as many factors impact pharmacokinetics and biologic result. The choice between routes of LMD is largely driven not only by the myocardial pathology but also by the nature and physicochemical properties of the therapeutic agents.

Inhibition of Legionella pneumophila multiplication within human macrophages by antimicrobial agents.

PubMed Central

Vildé, J L; Dournon, E; Rajagopalan, P

1986-01-01

The activity of serial concentrations of different antimicrobial agents on the multiplication of Legionella pneumophila within human monocyte-derived macrophages was studied. The results led to the definition of a minimal extracellular concentration inhibiting intracellular multiplication (MIEC). According to the MIECs, the antimicrobial agents tested were classified in three groups: very active (MIEC less than or equal to 0.06 microgram/ml), such as erythromycin, rifampin, and pefloxacin; active (1 microgram/ml greater than or equal to MIEC greater than or equal to 0.1 microgram/ml), such as sulfamethoxazole-trimethoprim or doxycycline; and ineffective, such as cefoxitin, which was not active within macrophages at as high as 64 micrograms/ml despite a low MIC (0.2 microgram/ml) on bacterial charcoal-yeast extract agar. The activity of netilmicin was difficult to assess because of its effect on extracellular legionellae. Combinations of erythromycin with rifampin and pefloxacin with erythromycin, rifampin, doxycycline, or netilmicin showed an additive effect and no antagonism. These results obtained in a cellular model are in agreement with the efficacy of antimicrobial agents in experimental infections and in Legionnaires disease. They sustain clinical interest in the new quinolones, such as pefloxacin, and in combinations of antimicrobial agents for the treatment of Legionnaires disease. PMID:3492176

Modeling of transdermal fluorescence measurements from first-in-human clinical trials for renal function determination using fluorescent tracer agent MB-102

NASA Astrophysics Data System (ADS)

Shultz, Kimberly M.; Debreczeny, Martin P.; Dorshow, Richard B.; Keating, Jennifer E.; Bechtel, Kate L.

2017-02-01

The fluorescent tracer agent 3,6-diamino-2,5-bisN-[(1R)-1-carboxy-2-hydroxyethyl]carbamoylpyrazine, designated MB-102, is cleared from the body solely by the kidneys. A prototype noninvasive fluorescence detection device has been developed for monitoring transdermal fluorescence after bolus intravenous injection of MB-102 in order to measure kidney function. A mathematical model of the detected fluorescence signal was created for evaluation of observed variations in agent kinetics across body locations and for analysis of candidate instrument geometries. The model comprises pharmacokinetics of agent distribution within body compartments, local diffusion of the agent within the skin, Monte Carlo photon transport through tissue, and ray tracing of the instrument optics. Data from eight human subjects with normal renal function and a range of skin colors shows good agreement with simulated data. Body site dependence of equilibration kinetics was explored using the model to find the local vasculature-to-interstitial diffusion time constant, blood volume fraction, and interstitial volume fraction. Finally, candidate instrument geometries were evaluated using the model. While an increase in source-detector separation was found to increase sensitivity to tissue optical properties, it reduced the relative intensity of the background signal with minimal effect on the measured equilibration kinetics.

A distributed agent architecture for real-time knowledge-based systems: Real-time expert systems project, phase 1

NASA Technical Reports Server (NTRS)

Lee, S. Daniel

1990-01-01

We propose a distributed agent architecture (DAA) that can support a variety of paradigms based on both traditional real-time computing and artificial intelligence. DAA consists of distributed agents that are classified into two categories: reactive and cognitive. Reactive agents can be implemented directly in Ada to meet hard real-time requirements and be deployed on on-board embedded processors. A traditional real-time computing methodology under consideration is the rate monotonic theory that can guarantee schedulability based on analytical methods. AI techniques under consideration for reactive agents are approximate or anytime reasoning that can be implemented using Bayesian belief networks as in Guardian. Cognitive agents are traditional expert systems that can be implemented in ART-Ada to meet soft real-time requirements. During the initial design of cognitive agents, it is critical to consider the migration path that would allow initial deployment on ground-based workstations with eventual deployment on on-board processors. ART-Ada technology enables this migration while Lisp-based technologies make it difficult if not impossible. In addition to reactive and cognitive agents, a meta-level agent would be needed to coordinate multiple agents and to provide meta-level control.

Phytotechnologies – Preventing Exposures, Improving Public Health

PubMed Central

Henry, Heather F.; Burken, Joel G.; Maier, Raina M.; Newman, Lee A.; Rock, Steven; Schnoor, Jerald L.; Suk, William A.

2014-01-01

Phytotechnologies have the potential to reduce the amount and/or toxicity of deleterious chemicals/agents, and thereby, prevent human exposures to hazardous substances. As such, phytotechnologies are a tool for primary prevention within the context of public health. Research advances demonstrate that phytotechnologies can be uniquely tailored for effective exposure prevention for a variety of applications. In addition to exposure prevention, phytotechnologists have advanced the use of plants as sensors to delineate environmental contaminants and potential exposures. The applications presented in this paper are at various stages of development and are presented in a framework to reflect how phytotechnologies can help meet basic public health needs for access to clean water, air, and food resources. As plant-based technologies can often be integrated into communities at minimal cost and with low infrastructure needs, their use in improving environmental quality can be applied broadly to minimize potential contaminant exposure. These natural treatment systems concurrently provide ecosystem services of notable value to communities and society. In the future, integration and coordination of phytotechnology activities with public health research will allow technology development that focuses on prevention of environmental exposures. Such an approach will lead to an important role of phytotechnologies in providing sustainable solutions to environmental exposure challenges that improve public health and potentially reduce the burden of disease. PMID:23819283

Innovative technologies to manage aflatoxins in foods and feeds and the profitability of application - A review.

PubMed

Udomkun, Patchimaporn; Wiredu, Alexander Nimo; Nagle, Marcus; Müller, Joachim; Vanlauwe, Bernard; Bandyopadhyay, Ranajit

2017-06-01

Aflatoxins are mainly produced by certain strains of Aspergillus flavus , which are found in diverse agricultural crops. In many lower-income countries, aflatoxins pose serious public health issues since the occurrence of these toxins can be considerably common and even extreme. Aflatoxins can negatively affect health of livestock and poultry due to contaminated feeds. Additionally, they significantly limit the development of international trade as a result of strict regulation in high-value markets. Due to their high stability, aflatoxins are not only a problem during cropping, but also during storage, transport, processing, and handling steps. Consequently, innovative evidence-based technologies are urgently required to minimize aflatoxin exposure. Thus far, biological control has been developed as the most innovative potential technology of controlling aflatoxin contamination in crops, which uses competitive exclusion of toxigenic strains by non-toxigenic ones. This technology is commercially applied in groundnuts maize, cottonseed, and pistachios during pre-harvest stages. Some other effective technologies such as irradiation, ozone fumigation, chemical and biological control agents, and improved packaging materials can also minimize post-harvest aflatoxins contamination in agricultural products. However, integrated adoption of these pre- and post-harvest technologies is still required for sustainable solutions to reduce aflatoxins contamination, which enhances food security, alleviates malnutrition, and strengthens economic sustainability.

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

NASA Astrophysics Data System (ADS)

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

2011-04-01

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

Proceedings 3rd NASA/IEEE Workshop on Formal Approaches to Agent-Based Systems (FAABS-III)

NASA Technical Reports Server (NTRS)

Hinchey, Michael (Editor); Rash, James (Editor); Truszkowski, Walt (Editor); Rouff, Christopher (Editor)

2004-01-01

These preceedings contain 18 papers and 4 poster presentation, covering topics such as: multi-agent systems, agent-based control, formalism, norms, as well as physical and biological models of agent-based systems. Some applications presented in the proceedings include systems analysis, software engineering, computer networks and robot control.

Analyzing the multiple-target-multiple-agent scenario using optimal assignment algorithms

NASA Astrophysics Data System (ADS)

Kwok, Kwan S.; Driessen, Brian J.; Phillips, Cynthia A.; Tovey, Craig A.

1997-09-01

This work considers the problem of maximum utilization of a set of mobile robots with limited sensor-range capabilities and limited travel distances. The robots are initially in random positions. A set of robots properly guards or covers a region if every point within the region is within the effective sensor range of at least one vehicle. We wish to move the vehicles into surveillance positions so as to guard or cover a region, while minimizing the maximum distance traveled by any vehicle. This problem can be formulated as an assignment problem, in which we must optimally decide which robot to assign to which slot of a desired matrix of grid points. The cost function is the maximum distance traveled by any robot. Assignment problems can be solved very efficiently. Solution times for one hundred robots took only seconds on a silicon graphics crimson workstation. The initial positions of all the robots can be sampled by a central base station and their newly assigned positions communicated back to the robots. Alternatively, the robots can establish their own coordinate system with the origin fixed at one of the robots and orientation determined by the compass bearing of another robot relative to this robot. This paper presents example solutions to the multiple-target-multiple-agent scenario using a matching algorithm. Two separate cases with one hundred agents in each were analyzed using this method. We have found these mobile robot problems to be a very interesting application of network optimization methods, and we expect this to be a fruitful area for future research.

Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin.

PubMed

Raju, Jayadev; Mehta, Rekha

2009-01-01

Cancer chemoprevention is a strategy taken to retard, regress, or resist the multistep process of carcinogenesis, including the blockage of its vital morphogenetic milestones viz. normal-preneoplasia-neoplasia-metastasis. For several reasons, including safety, minimal (or no) toxicity and side-effects, and better availability, alternatives such as naturally occurring phytochemicals that are found in foods are becoming increasingly popular over synthetic drugs. Food saponins have been used in complimentary and traditional medicine against a variety of diseases including several cancers. Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a well-known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. Over the past decade, a series of preclinical and mechanistic studies have been conducted to understand the role of diosgenin as a chemopreventive/therapeutic agent against several cancers. This review highlights the biological activity of diosgenin that contributes to cancer chemoprevention and control. The anticancer mode of action of diosgenin has been demonstrated via modulation of multiple cell signaling events involving critical molecular candidates associated with growth, differentiation, apoptosis, and oncogenesis. Altogether, these preclinical and mechanistic findings strongly implicate the use of diosgenin as a novel, multitarget-based chemopreventive or therapeutic agent against several cancer types. Future research in this field will help to establish not only whether diosgenin is safe and efficacious as a chemopreventive agent against several human cancers, but also to develop and evaluate standards of evidence for health claims for diosgenin-containing foods as they become increasingly popular and enter the marketplace labeled as functional foods and nutraceuticals.

Intracochlear administration of steroids with a catheter during human cochlear implantation: a safety and feasibility study.

PubMed

Prenzler, Nils K; Salcher, Rolf; Timm, Max; Gaertner, Lutz; Lenarz, Thomas; Warnecke, Athanasia

2018-05-14

Suppression of foreign body reaction, improvement of electrode-nerve interaction, and preservation of residual hearing are essential research topics in cochlear implantation. Intracochlear pharmaco- or cell-based therapies can open new horizons in this field. Local drug delivery strategies are desirable as higher local concentrations of agents can be realized and side effects can be minimized compared to systemic administrations. When administered locally at accessible, basal parts of the cochlea, drugs reach apical regions later and in much lower concentrations due to poor diffusion patterns in cochlear fluids. Therefore, new devices are needed to warrant rapid distribution of agents into all parts of the cochlea. Five patients received a deep intracochlear injection of triamcinolone with a specifically designed cochlear catheter during cochlear implantation right before inserting a cochlear implant electrode. As a measure for formation of fibrous tissue around the electrode, electrical impedances were measured in the operation room and over 4 months thereafter. No adverse events were observed peri- and postoperatively. The handling of the device was easy. Severe damage to the microstructure of the cochlea was excluded as far as possible by cone beam computed tomography and vestibular testing. A delayed rise of the impedances was seen in the catheter group compared to controls over all regions of the cochlea. A statistical significance, however, was only obtained at the midregion of the cochlea. Consequently, the cochlear catheter is a safe and feasible device for local drug delivery of pharmaceutical agents into deeper regions of the cochlea.

Electroconvulsive therapy-induced persistent retrograde amnesia: could it be minimised by ketamine or other pharmacological approaches?

PubMed

Gregory-Roberts, Emily M; Naismith, Sharon L; Cullen, Karen M; Hickie, Ian B

2010-10-01

Certain pharmacological agents administered during electroconvulsive therapy may have the potential to prevent persistent retrograde amnesia induced during electroconvulsive therapy. This review examines mechanisms for electroconvulsive therapy-induced retrograde amnesia, and evaluates the suitability of the anaesthetic ketamine for preventing this amnestic outcome. A review of human studies, animal models and theoretical models in light of memory dysfunction following electroconvulsive therapy was conducted. MEDLINE was searched from 1950 to April 2009 using the MeSH terms "electroconvulsive therapy", "memory", "memory short term", "memory disorders", "excitatory amino acid antagonists", and "ketamine". PREMEDLINE was searched using the terms "electroconvulsive therapy", "amnesia" and "ketamine". Additional keyword and reference list searches were performed. No language, date constraints or article type constraints were used. Disruption of long term potentiation as a mechanism for electroconvulsive therapy-induced retrograde amnesia is well supported. Based on this putative mechanism, an N-methyl-D-aspartate receptor antagonist would appear suitable for preventing the retrograde amnesia. Available evidence in animals and humans supports the prediction that ketamine, an anaesthetic agent and N-methyl-D-aspartate receptor antagonist, could effectively prevent electroconvulsive therapy-induced persistent retrograde amnesia. Whilst there are concerns about the use of ketamine with electroconvulsive therapy, such as possible psychotomimetic effects, on balance this anaesthetic agent may improve or hasten clinical response to electroconvulsive therapy. A clinical trial is warranted to determine if ketamine anaesthesia during electroconvulsive therapy can lessen persistent retrograde amnesia and improve therapeutic response. Electroconvulsive therapy with ketamine anaesthesia may provide effective antidepressant action with minimal side effects. Copyright 2009 Elsevier B.V. All rights reserved.

Antimicrobial resistance of zoonotic and commensal bacteria in Europe: the missing link between consumption and resistance in veterinary medicine.

PubMed

Garcia-Migura, Lourdes; Hendriksen, Rene S; Fraile, Lorenzo; Aarestrup, Frank M

2014-05-14

The emergence of resistance in food animals has been associated to the consumption of antimicrobials in veterinary medicine. Consequently, monitoring programs have been designed to monitor the occurrence of antimicrobial resistant bacteria. This study analyses the amount of antimicrobial agents used in nine European countries from 2005 to 2011, and compares by univariate analysis the correlations between consumptions of each of the following antimicrobial classes; tetracycline, penicillins, cephalosporins, quinolones and macrolides. An overview of resistance in zoonotic and commensal bacteria in Europe focusing on Salmonella, Escherichia coli, Campylobacter sp. and Enterococcus sp., during the same period of time based on monitoring programs is also assessed. With the exception of cephalosporins, linear regressions showed strong positive associations between the consumption of the four different antimicrobial classes. Substantial differences between countries were observed in the amount of antimicrobials used to produce 1 kg of meat. Moreover, large variations in proportions of resistant bacteria were reported by the different countries, suggesting differences in veterinary practice. Despite the withdrawn of a specific antimicrobial from "on farm" use, persistence over the years of bacteria resistant to this particular antimicrobial agent, was still observed. There were also differences in trends of resistance associated to specific animal species. In order to correlate the use of antimicrobial agents to the presence of resistance, surveillance of antimicrobial consumption by animal species should be established. Subsequently, intervention strategies could be designed to minimize the occurrence of resistance. Copyright © 2014 Elsevier B.V. All rights reserved.

International Patterns of Practice in the Management of Radiation Therapy-induced Nausea and Vomiting

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

Dennis, Kristopher; Zhang Liying; Lutz, Stephen

Purpose: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials: Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately andmore » committed to an initial management approach. Results: In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT){sub 3} receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions: Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk assessment and to refine antiemetic guideline management recommendations.« less

[Antibacterial activity of copper salts against microorganisms isolated from chronic infected wounds].

PubMed

Febré, Naldy; Silva, Viviana; Báez, Andrea; Palza, Humberto; Delgado, Katherine; Aburto, Isabel; Silva, Victor

2016-12-01

The antimicrobial activity of copper (Cu+2) is recognized and used as an antimicrobial agent. To evaluate the antimicrobial activity of copper against microorganisms obtained from chronic cutaneous wound infections. Five chemical products that contained copper particles in their composition were tested (zeolite, silica, acetate, nitrate and nanoparticle of copper). The antimicrobial activity against antibiotic resistant strains usually isolated from chronic cutaneous wound infections was determined for two of the products with better performance in copper release. The minimal inhibitory and minimal bactericidal concentrations of copper acetate and nitrate were similar, fluctuating between 400-2,000 µg/ml. The studied copper salts show great potential to be used to control both gram positive and gram negative, antibiotic resistant bacteria isolated from wound infections.

A hybrid agent-based approach for modeling microbiological systems.

PubMed

Guo, Zaiyi; Sloot, Peter M A; Tay, Joc Cing

2008-11-21

Models for systems biology commonly adopt Differential Equations or Agent-Based modeling approaches for simulating the processes as a whole. Models based on differential equations presuppose phenomenological intracellular behavioral mechanisms, while models based on Multi-Agent approach often use directly translated, and quantitatively less precise if-then logical rule constructs. We propose an extendible systems model based on a hybrid agent-based approach where biological cells are modeled as individuals (agents) while molecules are represented by quantities. This hybridization in entity representation entails a combined modeling strategy with agent-based behavioral rules and differential equations, thereby balancing the requirements of extendible model granularity with computational tractability. We demonstrate the efficacy of this approach with models of chemotaxis involving an assay of 10(3) cells and 1.2x10(6) molecules. The model produces cell migration patterns that are comparable to laboratory observations.

Demeter, persephone, and the search for emergence in agent-based models.

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

North, M. J.; Howe, T. R.; Collier, N. T.

2006-01-01

In Greek mythology, the earth goddess Demeter was unable to find her daughter Persephone after Persephone was abducted by Hades, the god of the underworld. Demeter is said to have embarked on a long and frustrating, but ultimately successful, search to find her daughter. Unfortunately, long and frustrating searches are not confined to Greek mythology. In modern times, agent-based modelers often face similar troubles when searching for agents that are to be to be connected to one another and when seeking appropriate target agents while defining agent behaviors. The result is a 'search for emergence' in that many emergent ormore » potentially emergent behaviors in agent-based models of complex adaptive systems either implicitly or explicitly require search functions. This paper considers a new nested querying approach to simplifying such agent-based modeling and multi-agent simulation search problems.« less