Some single-machine scheduling problems with learning effects and two competing agents.

PubMed

Li, Hongjie; Li, Zeyuan; Yin, Yunqiang

2014-01-01

This study considers a scheduling environment in which there are two agents and a set of jobs, each of which belongs to one of the two agents and its actual processing time is defined as a decreasing linear function of its starting time. Each of the two agents competes to process its respective jobs on a single machine and has its own scheduling objective to optimize. The objective is to assign the jobs so that the resulting schedule performs well with respect to the objectives of both agents. The objective functions addressed in this study include the maximum cost, the total weighted completion time, and the discounted total weighted completion time. We investigate three problems arising from different combinations of the objectives of the two agents. The computational complexity of the problems is discussed and solution algorithms where possible are presented.

An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab

PubMed Central

Lombardi, Giuseppe; Farina, Patrizia; Della Puppa, Alessandro; Cecchin, Diego; Pambuku, Ardi; Bellu, Luisa; Zagonel, Vittorina

2014-01-01

Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas. PMID:24800248

Efficacy of ATR inhibitors as single agents in Ewing sarcoma

PubMed Central

Lecona, Emilio; Murga, Matilde; Callen, Elsa; Azorin, Daniel; Alonso, Javier; Lopez, Andres J.; Nussenzweig, Andre; Fernandez-Capetillo, Oscar

2016-01-01

Ewing sarcomas (ES) are pediatric bone tumors that arise from a driver translocation, most frequently EWS/FLI1. Current ES treatment involves DNA damaging agents, yet the basis for the sensitivity to these therapies remains unknown. Oncogene-induced replication stress (RS) is a known source of endogenous DNA damage in cancer, which is suppressed by ATR and CHK1 kinases. We here show that ES suffer from high endogenous levels of RS, rendering them particularly dependent on the ATR pathway. Accordingly, two independent ATR inhibitors show in vitro toxicity in ES cell lines as well as in vivo efficacy in ES xenografts as single agents. Expression of EWS/FLI1 or EWS/ERG oncogenic translocations sensitizes non-ES cells to ATR inhibitors. Our data shed light onto the sensitivity of ES to genotoxic agents, and identify ATR inhibitors as a potential therapy for Ewing Sarcomas. PMID:27577084

Single agent and synergistic combinatorial efficacy of first-in-class small molecule imipridone ONC201 in hematological malignancies.

PubMed

Prabhu, Varun V; Talekar, Mala K; Lulla, Amriti R; Kline, C Leah B; Zhou, Lanlan; Hall, Junior; Van den Heuvel, A Pieter J; Dicker, David T; Babar, Jawad; Grupp, Stephan A; Garnett, Mathew J; McDermott, Ultan; Benes, Cyril H; Pu, Jeffrey J; Claxton, David F; Khan, Nadia; Oster, Wolfgang; Allen, Joshua E; El-Deiry, Wafik S

2018-01-01

ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples. ONC201 induced caspase-dependent apoptosis that involved activation of the integrated stress response (ATF4/CHOP) pathway, inhibition of Akt phosphorylation, Foxo3a activation, downregulation of cyclin D1, IAP and Bcl-2 family members. ONC201 synergistically reduced cell viability in combination with cytarabine and 5-azacytidine in AML cells. ONC201 combined with cytarabine in a Burkitt's lymphoma xenograft model induced tumor growth inhibition that was superior to either agent alone. ONC201 synergistically combined with bortezomib in MM, MCL and ALCL cells and with ixazomib or dexamethasone in MM cells. ONC201 combined with bortezomib in a Burkitt's lymphoma xenograft model reduced tumor cell density and improved CHOP induction compared to either agent alone. These results serve as a rationale for ONC201 single-agent trials in relapsed/refractory acute leukemia, non-Hodgkin's lymphoma, MM and combination trial with dexamethasone in MM, provide pharmacodynamic biomarkers and identify further synergistic combinatorial regimens that can be explored in the clinic.

Active Brownian agents with concentration-dependent chemotactic sensitivity.

PubMed

Meyer, Marcel; Schimansky-Geier, Lutz; Romanczuk, Pawel

2014-02-01

We study a biologically motivated model of overdamped, autochemotactic Brownian agents with concentration-dependent chemotactic sensitivity. The agents in our model move stochastically and produce a chemical ligand at their current position. The ligand concentration obeys a reaction-diffusion equation and acts as a chemoattractant for the agents, which bias their motion towards higher concentrations of the dynamically altered chemical field. We explore the impact of concentration-dependent response to chemoattractant gradients on large-scale pattern formation, by deriving a coarse-grained macroscopic description of the individual-based model, and compare the conditions for emergence of inhomogeneous solutions for different variants of the chemotactic sensitivity. We focus primarily on the so-called receptor-law sensitivity, which models a nonlinear decrease of chemotactic sensitivity with increasing ligand concentration. Our results reveal qualitative differences between the receptor law, the constant chemotactic response, and the so-called log law, with respect to stability of the homogeneous solution, as well as the emergence of different patterns (labyrinthine structures, clusters, and bubbles) via spinodal decomposition or nucleation. We discuss two limiting cases, where the model can be reduced to the dynamics of single species: (I) the agent density governed by a density-dependent effective diffusion coefficient and (II) the ligand field with an effective bistable, time-dependent reaction rate. In the end, we turn to single clusters of agents, studying domain growth and determining mean characteristics of the stationary inhomogeneous state. Analytical results are confirmed and extended by large-scale GPU simulations of the individual based model.

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

PubMed

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

2016-01-01

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

Method for improved selectivity in photo-activation of molecular agents

DOEpatents

Fisher, Walter G.; Wachter, Eric A.; Dees, H. Craig

1998-01-01

A method for the treatment of a particular volume of plant or animal tissue comprising the steps of treating the plant or animal tissue with at least one photo-active molecular agent, wherein the particular volume of the plant or animal tissue retains at least a portion of the at least one photo-active molecular agent, and then treating the particular volume of the plant or animal tissue with light sufficient to promote a simultaneous two-photon excitation of at least one of the at least one photo-active molecular agent retained in the particular volume of the plant or animal tissue, wherein the at least one photo-active molecular agent becomes active in the particular volume of the plant or animal tissue. There is also disclosed a method for the treatment of cancer in plant or animal tissue and a method for producing at least one photo-activated molecular agent in a particular volume of a material.

Method for improved selectivity in photo-activation of molecular agents

DOEpatents

Fisher, Walter G.; Wachter, Eric A.; Dees, H. Craig

1999-01-01

A method for the treatment of a particular volume of plant or animal tissue comprising the steps of treating the plant or animal tissue with at least one photo-active molecular agent, wherein the particular volume of the plant or animal tissue retains at least a portion of the at least one photo-active molecular agent, and then treating the particular volume of the plant or animal tissue with light sufficient to promote a simultaneous two-photon excitation of at least one of the at least one photo-active molecular agent retained in the particular volume of the plant or animal tissue, wherein the at least one photo-active molecular agent becomes active in the particular volume of the plant or animal tissue. There is also disclosed a method for the treatment of cancer in plant or animal tissue and a method for producing at least one photo-activated molecular agent in a particular volume of a material.

Method for improved selectivity in photo-activation of molecular agents

DOEpatents

Fisher, W.G.; Wachter, E.A.; Dees, H.C.

1998-11-03

A method for the treatment of a particular volume of plant or animal tissue comprising the steps of treating the plant or animal tissue with at least one photo-active molecular agent, wherein the particular volume of the plant or animal tissue retains at least a portion of the at least one photo-active molecular agent, and then treating the particular volume of the plant or animal tissue with light sufficient to promote a simultaneous two-photon excitation of at least one of the at least one photo-active molecular agent retained in the particular volume of the plant or animal tissue, wherein the at least one photo-active molecular agent becomes active in the particular volume of the plant or animal tissue. There is also disclosed a method for the treatment of cancer in plant or animal tissue and a method for producing at least one photo-activated molecular agent in a particular volume of a material. 23 figs.

Single-particle aerosol mass spectrometry for the detection and identification of chemical warfare agent simulants.

PubMed

Martin, Audrey N; Farquar, George R; Frank, Matthias; Gard, Eric E; Fergenson, David P

2007-08-15

Single-particle aerosol mass spectrometry (SPAMS) was used for the real-time detection of liquid nerve agent simulants. A total of 1000 dual-polarity time-of-flight mass spectra were obtained for micrometer-sized single particles each of dimethyl methyl phosphonate, diethyl ethyl phosphonate, diethyl phosphoramidate, and diethyl phthalate using laser fluences between 0.58 and 7.83 nJ/microm2, and mass spectral variation with laser fluence was studied. The mass spectra obtained allowed identification of single particles of the chemical warfare agent (CWA) simulants at each laser fluence used although lower laser fluences allowed more facile identification. SPAMS is presented as a promising real-time detection system for the presence of CWAs.

Activity induced phase transition in mixtures of active and passive agents

NASA Astrophysics Data System (ADS)

Sinha Mahapatra, Pallab; Kulkarni, Ajinkya

2017-11-01

Collective behaviors of self-propelling agents are ubiquitous in nature that produces interesting patterns. The objective of this study is to investigate the phase transition in mixtures of active and inert agents suspended in a liquid. A modified version of the Vicsek Model has been used (see Ref.), where the particles are modeled as soft disks with finite mass, confined in a square domain. The particles are required to align their local motion to their immediate neighborhood, similar to the Vicsek model. We identified the transition from disorganized thermal-like motion to an organized vortical motion. We analyzed the nature of the transition by using different order parameters. Furthermore the switching between the phases has been investigated via artificial nucleation of randomly picked active agents spanning the entire domain. Finally the motivation for this phase transition has been explained via average dissipation and the mean square displacement (MSD) of the agents.

Method for improved selectivity in photo-activation of molecular agents

DOEpatents

Fisher, Walter G.; Wachter, Eric A.; Dees, H. Craig

2000-01-01

An apparatus for the treatment of a particular volume of plant or animal tissue by treating the plant or animal tissue with at least one photo-active molecular agent, wherein the particular volume of the plant or animal tissue retains at least a portion of the at least one photo-active molecular agent, and then treating the particular volume of the plant or animal tissue with light sufficient to promote a simultaneous two-photon excitation of at least one of the at least one photo-active molecular agent retained in the particular volume of the plant or animal tissue, wherein the at least one photo-active molecular agent becomes active in the particular volume of the plant or animal tissue.

Single Agent Polysaccharopeptide Delays Metastases and Improves Survival in Naturally Occurring Hemangiosarcoma

PubMed Central

Brown, Dorothy Cimino; Reetz, Jennifer

2012-01-01

The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP) is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models. Clear evidence of clinically relevant benefits of PSP in cancer patients, however, is lacking. The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality. PMID:22988473

Synthesis and characterization of activated carbon from white lotus via single step chemical activation

NASA Astrophysics Data System (ADS)

Andas, Jeyashelly; Midon, Muhammad Dzulfiqar

2017-08-01

Highly porous activated carbon was successfully fabricated from the stalk of Nymphaea odorata via single step chemical activation. ZnCl2 was used as the chemical activating agent in the activation process. The raw material was preliminary characterized using Fourier Transform Infrared (FTIR), ultimate analysis (CHNS/O Analyzer) and Scanning Electron Microscope (SEM). The percentage yield, iodine number (IN) and the textural properties of the activated carbon were optimized under the influence of several synthesizing parameters such as impregnation ratio, activation temperature and activation time using ZnCl2. High IN (750.11 mg/g - 967.16 mg/g) was obtained from Sodium thiosulphate volumetric method and represents the porosity of the synthesized materials. Reduction in several functional groups was observed in the FTIR spectrum of the synthesized activated carbon. SEM analysis of the activated carbon verified the formation of highly porous surface compared to the raw Nymphaea odorata. This study provides a facile synthesis of activated carbon from waste natural resources at benign condition.

Pharmacokinetics and bioequivalence of a rosuvastatin/ezetimibe fixed-dose combination tablet versus single agents in healthy male subjects
.

PubMed

Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; Na, Sookie; Kim, Hyun-Ju; Yoon, Young-Ran; Lee, Hae Won

2018-01-01

The pharmacokinetic profiles and bioequivalence of a new rosuvastatin/ezetimibe fixed-dose combination (FDC; NVP-1205) vs. rosuvastatin and ezetimibe concomitantly administered as single agents were evaluated. In this open-label, single-dose, crossover study (NCT02029625), eligible subjects were randomly assigned in a 1 : 1 ratio to receive a single dose of rosuvastatin (10 mg) with ezetimibe (10 mg) as either a FDC or as single agents concomitantly administered under fasted conditions, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected predose and up to 96 hours postdose in each period for determination of plasma rosuvastatin and ezetimibe concentrations by liquid-chromatography tandem mass spectroscopy and calculation of pharmacokinetic parameters. The mean C_max and AUC_0-t values of rosuvastatin were 12.5 ng/mL and 115.6 ng×h/mL for the FDC, and 12.2 ng/mL and 115.1 ng×h/mL for the single agents concomitantly administered, respectively. The mean C_max and AUC_0-t values of ezetimibe were 4.7 ng/mL and 67.3 ng×h/mL for the FDC, and 4.5 ng/mL and 68.2 ng×h/mL for the single agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the rosuvastatin C_max and AUC_0-t were 106.20 (96.62 - 116.74) and 102.88 (96.32 - 109.90), respectively. The GMR and 90% CI for the ezetimibe C_max and AUC_0-t were 108.96 (98.56 - 120.51) and 98.13 (92.01 - 104.66), respectively. All treatments were well tolerated during this study, with no serious adverse events reported. The rosuvastatin/ezetimibe (10/10 mg) FDC was bioequivalent to single agents concomitantly administered. A single dose of rosuvastatin/ezetimibe as the FDC or as single agents was well tolerated.
.

Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

PubMed

Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

2018-01-01

The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Single Agents with Designed Combination Chemotherapy Potential: Synthesis and Evaluation of Substituted Pyrimido[4,5-b]indoles as Receptor Tyrosine Kinase and Thymidylate Synthase Inhibitors and as Antitumor Agents

PubMed Central

Gangjee, Aleem; Zaware, Nilesh; Raghavan, Sudhir; Ihnat, Michael; Shenoy, Satyendra; Kisliuk, Roy L.

2010-01-01

Combinations of antiangiogenic agents (AAs) with cytotoxic agents have shown significant promise and several such clinical trials are currently underway. We have designed, synthesized and evaluated two compounds that each inhibit vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet derived growth factor receptor-beta (PDGFR-β) for antiangiogenic effects and also inhibit human thymidylate synthase (hTS) for cytotoxic effects in single agents. The synthesis of these compounds involved the nucleophilic displacement of the common intermediate 5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate benzenethiols. The inhibitory potency of both these single agents against VEGFR-2, PDGFR-β and hTS is better than or close to standards. In a COLO-205 xenograft mouse model one of the analogs significantly decreased tumor growth (TGI = 76% at 35 mg/kg), liver metastases and tumor blood vessels compared to a standard drug and to control and thus demonstrated potent tumor growth inhibition, inhibition of metastasis and antiangiogenic effects in vivo. These compounds afford combination chemotherapeutic potential in single agents. PMID:20092323

Distributed MPC based consensus for single-integrator multi-agent systems.

PubMed

Cheng, Zhaomeng; Fan, Ming-Can; Zhang, Hai-Tao

2015-09-01

This paper addresses model predictive control schemes for consensus in multi-agent systems (MASs) with discrete-time single-integrator dynamics under switching directed interaction graphs. The control horizon is extended to be greater than one which endows the closed-loop system with extra degree of freedom. We derive sufficient conditions on the sampling period and the interaction graph to achieve consensus by using the property of infinite products of stochastic matrices. Consensus can be achieved asymptotically if the sampling period is selected such that the interaction graph among agents has a directed spanning tree jointly. Significantly, if the interaction graph always has a spanning tree, one can select an arbitrary large sampling period to guarantee consensus. Finally, several simulations are conducted to illustrate the effectiveness of the theoretical results. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Quantum Speedup for Active Learning Agents

NASA Astrophysics Data System (ADS)

Paparo, Giuseppe Davide; Dunjko, Vedran; Makmal, Adi; Martin-Delgado, Miguel Angel; Briegel, Hans J.

2014-07-01

Can quantum mechanics help us build intelligent learning agents? A defining signature of intelligent behavior is the capacity to learn from experience. However, a major bottleneck for agents to learn in real-life situations is the size and complexity of the corresponding task environment. Even in a moderately realistic environment, it may simply take too long to rationally respond to a given situation. If the environment is impatient, allowing only a certain time for a response, an agent may then be unable to cope with the situation and to learn at all. Here, we show that quantum physics can help and provide a quadratic speedup for active learning as a genuine problem of artificial intelligence. This result will be particularly relevant for applications involving complex task environments.

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…

Method for improved selectivity in photo-activation and detection of molecular diagnostic agents

DOEpatents

Wachter, Eric A.; Fisher, Walter G.; Dees, H. Craig

1998-01-01

A method for the imaging of a particular volume of plant or animal tissue, wherein the plant or animal tissue contains at least one photo-active molecular agent. The method includes the steps of treating the particular volume of the plant or animal tissue with light sufficient to promote a simultaneous two-photon excitation of the photo-active molecular agent contained in the particular volume of the plant or animal tissue, photo-activating at least one of the at least one photo-active molecular agent in the particular volume of the plant or animal tissue, thereby producing at least one photo-activated molecular agent, wherein the at least one photo-activated molecular agent emits energy, detecting the energy emitted by the at least one photo-activated molecular agent, and producing a detected energy signal which is characteristic of the particular volume of plant or animal tissue. The present invention is also a method for the imaging of a particular volume of material, wherein the material contains at least one photo-active molecular agent.

Method for improved selectivity in photo-activation and detection of molecular diagnostic agents

DOEpatents

Wachter, E.A.; Fisher, W.G.; Dees, H.C.

1998-11-10

A method for the imaging of a particular volume of plant or animal tissue, wherein the plant or animal tissue contains at least one photo-active molecular agent. The method includes the steps of treating the particular volume of the plant or animal tissue with light sufficient to promote a simultaneous two-photon excitation of the photo-active molecular agent contained in the particular volume of the plant or animal tissue, photo-activating at least one of the at least one photo-active molecular agent in the particular volume of the plant or animal tissue, thereby producing at least one photo-activated molecular agent, wherein the at least one photo-activated molecular agent emits energy, detecting the energy emitted by the at least one photo-activated molecular agent, and producing a detected energy signal which is characteristic of the particular volume of plant or animal tissue. The present invention is also a method for the imaging of a particular volume of material, wherein the material contains at least one photo-active molecular agent. 13 figs.

Methods for improved selectivity in photo-activation and detection of molecular diagnostic agents

DOEpatents

Wachter, Eric A [Oak Ridge, TN; Fisher, Walter G [Knoxville, TN; Dees, H Craig [Knoxville, TN

2008-03-18

A method for the imaging of a particular volume of plant or animal tissue, wherein the plant or animal tissue contains at least one photo-active molecular agent. The method comprises the steps of treating the particular volume of the plant or animal tissue with light sufficient to promote a simultaneous two-photon excitation of the photo-active molecular agent contained in the particular volume of the plant or animal tissue, photo-activating at least one of the at least one photo-active molecular agent in the particular volume of the plant or animal tissue, thereby producing at least one photo-activated molecular agent, wherein the at least one photo-activated molecular agent emits energy, detecting the energy emitted by the at least one photo-activated molecular agent, and producing a detected energy signal which is characteristic of the particular volume of plant or animal tissue. The present invention also provides a method for the imaging of a particular volume of material, wherein the material contains at least one photo-active molecular agent.

Activity of 10 antimicrobial agents against intracellular Rhodococcus equi.

PubMed

Giguère, Steeve; Berghaus, Londa J; Lee, Elise A

2015-08-05

Studies with facultative intracellular bacterial pathogens have shown that evaluation of the bactericidal activity of antimicrobial agents against intracellular bacteria is more closely associated with in vivo efficacy than traditional in vitro susceptibility testing. The objective of this study was to determine the relative activity of 10 antimicrobial agents against intracellular Rhodococcus equi. Equine monocyte-derived macrophages were infected with virulent R. equi and exposed to erythromycin, clarithromycin, azithromycin, rifampin, ceftiofur, gentamicin, enrofloxacin, vancomycin, imipenem, or doxycycline at concentrations achievable in plasma at clinically recommended dosages in foals. The number of intracellular R. equi was determined 48h after infection by counting colony forming units (CFUs). The number of R. equi CFUs in untreated control wells were significantly higher than those of monolayers treated with antimicrobial agents. Numbers of R. equi were significantly lower in monolayers treated with enrofloxacin followed by those treated with gentamicin, and vancomycin, when compared to monolayers treated with other antimicrobial agents. Numbers of R. equi in monolayers treated with doxycycline were significantly higher than those of monolayers treated with other antimicrobial agents. Differences in R. equi CFUs between monolayers treated with other antimicrobial agents were not statistically significant. Enrofloxacin, gentamicin, and vancomycin are the most active drugs in equine monocyte-derived macrophages infected with R. equi. Additional studies will be needed to determine if these findings correlate with in vivo efficacy. Copyright © 2015 Elsevier B.V. All rights reserved.

Dacarbazine as single-agent therapy for relapsed lymphoma in dogs.

PubMed

Griessmayr, P C; Payne, S E; Winter, J E; Barber, L G; Shofer, F S

2009-01-01

Multidrug resistance is the most common cause of treatment failure in dogs with multicentric lymphoma. 5-(3,3-Dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is an atypical alkylator used as standard treatment in human Hodgkin's lymphoma, and has been effective in combination treatment to treat resistant lymphoma in dogs. However, no data are available on the use of DTIC as a single agent in the treatment of relapsed canine lymphoma. Single-agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy. Forty client-owned dogs with relapsed lymphoma. Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800-1,000 mg/m(2) every 2-3 weeks as a 4-5-hour IV infusion) and were evaluated for response rate and duration. Hematologic and gastrointestinal toxicity was assessed. The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression-free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7-14 days after the treatment. Treatments were delayed because of thrombocytopenia. DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma.

Preparation of Activated Carbon from Palm Shells Using KOH and ZnCl2 as the Activating Agent

NASA Astrophysics Data System (ADS)

Yuliusman; Nasruddin; Afdhol, M. K.; Amiliana, R. A.; Hanafi, A.

2017-07-01

Palm shell is a potential source of raw materials for the produce of activated carbon as biosorbent for quite large numbers. The purpose of this study is to produce activated carbon qualified Indonesian Industrial Standard (SNI), which will be used as biosorbent to purify the impurities in the off gas petroleum refinery products. Stages of manufacture of activated carbon include carbonization, activation of chemistry and physics. Carbonization of activated carbon is done at a temperature of 400°C followed by chemical activation with active agent KOH and ZnCl2. Then the physical activation is done by flowing N2 gas for 1 hour at 850°C and followed by gas flow through the CO2 for 1 hour at 850°C. Research results indicate that activation of the active agent KOH produce activated carbon is better than using the active agent ZnCl2. The use of KOH as an active agent to produce activated carbon with a water content of 13.6%, ash content of 9.4%, iodine number of 884 mg/g and a surface area of 1115 m2/g. While the use of ZnCl2 as the active agent to produce activated carbon with a water content of 14.5%, total ash content of 9.0%, iodine number 648 mg/g and a surface area of 743 m2/g.

Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents.

PubMed

Lane, D D; Chiu, D Y; Su, F Y; Srinivasan, S; Kern, H B; Press, O W; Stayton, P S; Convertine, A J

2015-02-28

Aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a series of linear copolymers of N,N-dimethylacrylamide (DMA) and 2-hydroxyethylacrylamide (HEAm) with narrow Đ values over a molecular weight range spanning three orders of magnitude (10 3 to 10 6 Da). Trithiocarbonate-based RAFT chain transfer agents (CTAs) were grafted onto these scaffolds using carbodiimide chemistry catalyzed with DMAP. The resultant graft chain transfer agent (gCTA) was subsequently employed to synthesize polymeric brushes with a number of important vinyl monomer classes including acrylamido, methacrylamido, and methacrylate. Brush polymerization kinetics were evaluated for the aqueous RAFT polymerization of DMA from a 10 arm gCTA. Polymeric brushes containing hydroxyl functionality were further functionalized in order to prepare 2nd generation gCTAs which were subsequently employed to prepare polymers with a brushed-brush architecture with molecular weights in excess of 10 6 Da. These resultant single particle nanoparticles (SNPs) were employed as drug delivery vehicles for the anthracycline-based drug doxorubicin via copolymerization of DMA with a protected carbazate monomer (bocSMA). Cell-specific targeting functionality was also introduced via copolymerization with a biotin-functional monomer (bioHEMA). Drug release of the hydrazone linked doxorubicin was evaluated as function of pH and serum and chemotherapeutic activity was evaluated in SKOV3 ovarian cancer cells.

Overcoming resistance to single-agent therapy for oncogenic BRAF gene fusions via combinatorial targeting of MAPK and PI3K/mTOR signaling pathways

PubMed Central

Jain, Payal; Silva, Amanda; Han, Harry J.; Lang, Shih-Shan; Zhu, Yuankun; Boucher, Katie; Smith, Tiffany E.; Vakil, Aesha; Diviney, Patrick; Choudhari, Namrata; Raman, Pichai; Busch, Christine M.; Delaney, Tim; Yang, Xiaodong; Olow, Aleksandra K.; Mueller, Sabine; Haas-Kogan, Daphne; Fox, Elizabeth; Storm, Phillip B.; Resnick, Adam C.; Waanders, Angela J.

2017-01-01

Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies. We demonstrate effectiveness of multiple MEKi against diverse BRAF-fusions with novel N-terminal partners, with trametinib being the most potent. However, resistance to MEKi or PLX8394 develops via increased RTK expression causing activation of PI3K/mTOR pathway in BRAF-fusion expressing resistant clones. To circumvent acquired resistance, we show potency of combinatorial targeting with trametinib and everolimus, an mTOR inhibitor (mTORi) against multiple BRAF-fusions. While single-agent mTORi and MEKi PLGG clinical trials are underway, our study provides preclinical rationales for using MEKi and mTORi combinatorial therapy to stave off or prevent emergent drug-resistance in BRAF-fusion driven PLGGs. PMID:29156677

A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation.

PubMed

Kanda, Atsuhiro; Ishizuka, Erdal Tan; Shibata, Atsushi; Matsumoto, Takahiro; Toyofuku, Hidekazu; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

2017-06-16

The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P)RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines. Moreover, we developed a novel single-strand RNAi agent, proline-modified short hairpin RNA directed against human and mouse (P)RR [(P)RR-PshRNA], and we determined its safety and efficacy in vitro and in vivo. Application of (P)RR-PshRNA in mice caused significant amelioration of acute (uveitic) and chronic (diabetic) models of ocular inflammation with no apparent adverse effects. Our findings demonstrate the significant implication of RAPS in the pathogenesis of human uveitis and the potential usefulness of (P)RR-PshRNA as a therapeutic agent to reduce ocular inflammation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chicken cathelicidin-2-derived peptides with enhanced immunomodulatory and antibacterial activities against biological warfare agents.

PubMed

Molhoek, E Margo; van Dijk, Albert; Veldhuizen, Edwin J A; Dijk-Knijnenburg, Helma; Mars-Groenendijk, Roos H; Boele, Linda C L; Kaman-van Zanten, Wendy E; Haagsman, Henk P; Bikker, Floris J

2010-09-01

Host defence peptides (HDPs) are considered to be excellent candidates for the development of novel therapeutic agents. Recently, it was demonstrated that the peptide C1-15, an N-terminal segment of chicken HDP cathelicidin-2, exhibits potent antibacterial activity while lacking cytotoxicity towards eukaryotic cells. In the present study, we report that C1-15 is active against bacteria such as Bacillus anthracis and Yersinia pestis that may potentially be used by bioterrorists. Substitution of single and multiple phenylalanine (Phe) residues to tryptophan (Trp) in C1-15 resulted in variants with improved antibacterial activity against B. anthracis and Y. pestis as well as decreased salt sensitivity. In addition, these peptides exhibited enhanced neutralisation of lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs). The antibacterial and LPS-neutralising activities of these C1-15-derived peptides are exerted at concentrations far below the concentrations that are toxic to human PBMCs. Taken together, we show that Phe-->Trp substitutions in C1-15 variants enhances the antibacterial and LPS-neutralising activities against pathogenic bacteria, including those that may potentially be used as biological warfare agents. Copyright (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Outcomes of matched sibling donor bone marrow transplantation in children using single-agent calcineurin inhibitors as prophylaxis for graft versus host disease.

PubMed

Elgarten, Caitlin W; Arnold, Danielle E; Bunin, Nancy J; Seif, Alix E

2018-01-01

Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI may be sufficient prophylaxis for a defined group of patients. Single-agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes using this prophylactic strategy in a recent cohort. We performed a single-institution chart review and retrospective analysis of consecutive children undergoing MSD BMT who received single-agent CNI for GVHD prophylaxis between January 2002 and December 2014. Fifty-two children with a median age of 6.1 years (interquartile range [IQR] 2.5-8.3) and donor age of 6 years (IQR 3-10), with malignant and nonmalignant diseases (n = 35 and 17, respectively) were evaluated. Forty-three (82.6%) received oral prophylaxis with single-agent tacrolimus after initial intravenous therapy. Rates of GVHD were consistent with reported rates on dual prophylaxis: the overall incidence of grades 2-4 acute GVHD was 25.5%, grades 3-4 GVHD 9.8%, and chronic GVHD 10.4%. The cumulative incidence of relapse among children with malignancy was 20% at a median of 237 days (IQR 194-318) post-transplant. Two-year overall survival was 82.7% (95% confidence interval [CI]: 69.4-90.6%) and event-free survival was 78.9% (95% CI: 65.1-87.7%). No patient experienced graft failure. Single-agent CNI is a safe, effective approach to GVHD prophylaxis in young patients undergoing HLA-identical sibling BMT. Additionally, single-agent oral tacrolimus is a reasonable alternative to cyclosporine in this population. © 2017 Wiley Periodicals, Inc.

SEQUESTERING AGENTS FOR ACTIVE CAPS - REMEDIATION OF METALS AND ORGANICS

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

Knox, A; Michael Paller, M; Danny D. Reible, D

2007-05-10

This research evaluated organoclays, zeolites, phosphates, and a biopolymer as sequestering agents for inorganic and organic contaminants. Batch experiments were conducted to identify amendments and mixtures of amendments for metal and organic contaminants removal and retention. Contaminant removal was evaluated by calculating partitioning coefficients. Metal retention was evaluated by desorption studies in which residue from the removal studies was extracted with 1 M MgCl{sub 2} solution. The results indicated that phosphate amendments, some organoclays, and the biopolymer, chitosan, were very effective sequestering agents for metals in fresh and salt water. Organoclays were very effective sorbents for phenanthrene, pyrene, and benzo(a)pyrene.more » Partitioning coefficients for the organoclays were 3000-3500 ml g{sup -1} for benzo(a)pyrene, 400-450 ml g{sup -1} for pyrene, and 50-70 ml g{sup -1} for phenanthrene. Remediation of sites with a mixture of contaminants is more difficult than sites with a single contaminant because metals and organic contaminants have different fate and transport mechanisms in sediment and water. Mixtures of amendments (e.g., organoclay and rock phosphate) have high potential for remediating both organic and inorganic contaminants under a broad range of environmental conditions, and have promise as components in active caps for sediment remediation.« less

Durable clinical activity of single-agent bevacizumab in a nonagenarian patient with metastatic alveolar soft part sarcoma.

PubMed

Mir, Olivier; Boudou-Rouquette, Pascaline; Larousserie, Frédérique; Blanchet, Benoit; Babinet, Antoine; Anract, Philippe; Goldwasser, François

2012-08-01

Alveolar soft part sarcoma is a rare malignancy usually considered resistant to conventional chemotherapy, but recent data suggest that the multikinase inhibitors sunitinib and cediranib could be active in this setting. A 90-year-old lady with alveolar soft part sarcoma of the leg and lung metastases was started on sunitinib 37.5 mg daily. The treatment was poorly tolerated with grade 3 hypertension and grade 3 thrombocytopenia, which persisted after dose reduction to 25 mg daily. The patient was subsequently started on bevacizumab 10 mg/kg every 2 weeks, resulting in a marked improvement in pain and a partial response on lung metastases for 16 months and ongoing. Agents targeting the vascular endothelial growth factor-signalling pathway seem to exert clinically relevant and prolonged activity against alveolar soft part sarcoma and deserve further evaluation in the treatment of this rare soft tissue sarcoma.

6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib.

PubMed

Liu, Yanning; Lou, Guohua; Norton, John T; Wang, Chen; Kandela, Irawati; Tang, Shuai; Shank, Nathaniel I; Gupta, Pankaj; Huang, Min; Avram, Michael J; Green, Richard; Mazar, Andrew; Appella, Daniel; Chen, Zhi; Huang, Sui

2017-12-01

Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC. Treatment by MEAN at an effective dose for 6 wk was well tolerated by animals. Combined therapy using both sorafenib and MEAN enhanced tumor growth inhibition over monotherapy with either agent. Additional experiments revealed that MEAN inhibited tumor growth through mechanisms distinct from those of either its parent compound, amonafide, or sorafenib. MEAN suppressed C-MYC expression and increased expression of several tumor suppressor genes, including Src homology region 2 domain-containing phosphatase-1 ( SHP-1 ) and TXNIP (thioredoxin-interacting protein). As an encouraging feature for envisioned clinical application, the IC 50 of MEAN was not significantly changed in several drug-resistant cell lines with activated P-glycoprotein drug efflux pumps compared to drug-sensitive parent cells, demonstrating the ability of MEAN to be effective in cells resistant to existing chemotherapy regimens. MEAN is a promising candidate for clinical development as a single-agent therapy or in combination with sorafenib for the management of HCC.-Liu, Y., Lou, G., Norton, J. T., Wang, C., Kandela, I., Tang, S., Shank, N. I., Gupta, P., Huang, M., Avram, M. J., Green, R., Mazar, A., Appella, D., Chen, Z., Huang, S. 6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib. © FASEB.

[In vitro activity of voriconazole and three other antifungal agents against dermatophytes].

PubMed

Serrano-Martino, María del Carmen; Chávez-Caballero, Mónica; Valverde-Conde, Anastasio; Claro, Rosa María; Pemán, Javier; Martín-Mazuelos, Estrella

2003-11-01

The increase in infections due to dermatophytes in recent years led us to study the effectiveness of new antifungal formulations against these microorganisms. The in vitro activity of a new antifungal agent, voriconazole, was compared with three other antifungal agents, itraconazole, fluconazole and terbinafine, against 120 dermatophytes belonging to four species (61 Trichophyton mentagrophytes, 34 Microsporum canis, 13 M. gypseum and 12 T. rubrum). A broth microdilution method was used following the recommendations of the NCCLS document M38-P with some modifications. Terbinafine was the most active agent against the dermatophytes studied (MIC90 < or = 0.03 mg/ml), followed by voriconazole (MIC90, 0.25 micro g/ml) and itraconazole (MIC90, 0.5 micro g/ml). Fluconazole was the least active antifungal agent. The most susceptible species was M. canis. Voriconazole was found to have effective activity against dermatophytes.

Keratin sponge/hydrogel II, active agent delivery

USDA-ARS?s Scientific Manuscript database

Keratin sponge/hydrogels from oxidation and reduction hydrolysis of fine and coarse wool fibers were formed to behave as cationic hydrogels to swell and release active agents in the specific region of the gastro-intestinal (GI) tract. Their porous, interpenetrating networks (IPN) were effective for...

Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

USDA-ARS?s Scientific Manuscript database

Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...

Synthesis and biological activity of imidazopyridine anticoccidial agents: part I.

PubMed

Scribner, Andrew; Dennis, Richard; Hong, Jean; Lee, Shuliang; McIntyre, Donald; Perrey, David; Feng, Dennis; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2007-01-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we present the synthesis and biological activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

The influence of active vision on the exoskeleton of intelligent agents

NASA Astrophysics Data System (ADS)

Smith, Patrice; Terry, Theodore B.

2016-04-01

Chameleonization occurs when a self-learning autonomous mobile system's (SLAMR) active vision scans the surface of which it is perched causing the exoskeleton to changes colors exhibiting a chameleon effect. Intelligent agents having the ability to adapt to their environment and exhibit key survivability characteristics of its environments would largely be due in part to the use of active vision. Active vision would allow the intelligent agent to scan its environment and adapt as needed in order to avoid detection. The SLAMR system would have an exoskeleton, which would change, based on the surface it was perched on; this is known as the "chameleon effect." Not in the common sense of the term, but from the techno-bio inspired meaning as addressed in our previous paper. Active vision, utilizing stereoscopic color sensing functionality would enable the intelligent agent to scan an object within its close proximity, determine the color scheme, and match it; allowing the agent to blend with its environment. Through the use of its' optical capabilities, the SLAMR system would be able to further determine its position, taking into account spatial and temporal correlation and spatial frequency content of neighboring structures further ensuring successful background blending. The complex visual tasks of identifying objects, using edge detection, image filtering, and feature extraction are essential for an intelligent agent to gain additional knowledge about its environmental surroundings.

Agent-based power sharing scheme for active hybrid power sources

NASA Astrophysics Data System (ADS)

Jiang, Zhenhua

The active hybridization technique provides an effective approach to combining the best properties of a heterogeneous set of power sources to achieve higher energy density, power density and fuel efficiency. Active hybrid power sources can be used to power hybrid electric vehicles with selected combinations of internal combustion engines, fuel cells, batteries, and/or supercapacitors. They can be deployed in all-electric ships to build a distributed electric power system. They can also be used in a bulk power system to construct an autonomous distributed energy system. An important aspect in designing an active hybrid power source is to find a suitable control strategy that can manage the active power sharing and take advantage of the inherent scalability and robustness benefits of the hybrid system. This paper presents an agent-based power sharing scheme for active hybrid power sources. To demonstrate the effectiveness of the proposed agent-based power sharing scheme, simulation studies are performed for a hybrid power source that can be used in a solar car as the main propulsion power module. Simulation results clearly indicate that the agent-based control framework is effective to coordinate the various energy sources and manage the power/voltage profiles.

Socialization Agents and Activities of Young Adolescents

ERIC Educational Resources Information Center

Arnon, Sara; Shamai, Shmuel; Ilatov, Zinaida

2008-01-01

Research examined the relative importance of peer groups for young adolescents as compared with diverse adult socialization agents--family, school, and community. The factors involved were teenagers' activities, preferences, feelings, and thoughts as to how they spend their leisure time, their preferences for help providers, and their sense of…

Decontamination of chemical and biological warfare agents with a single multi-functional material.

PubMed

Amitai, Gabi; Murata, Hironobu; Andersen, Jill D; Koepsel, Richard R; Russell, Alan J

2010-05-01

We report the synthesis of new polymers based on a dimethylacrylamide-methacrylate (DMAA-MA) co-polymer backbone that support both chemical and biological agent decontamination. Polyurethanes containing the redox enzymes glucose oxidase and horseradish peroxidase can convert halide ions into active halogens and exert striking bactericidal activity against gram positive and gram negative bacteria. New materials combining those biopolymers with a family of N-alkyl 4-pyridinium aldoxime (4-PAM) halide-acrylate co-polymers offer both nucleophilic activity for the detoxification of organophosphorus nerve agents and internal sources of halide ions for generation of biocidal activity. Generation of free bromine and iodine was observed in the combined material resulting in bactericidal activity of the enzymatically formed free halogens that caused complete kill of E. coli (>6 log units reduction) within 1 h at 37 degrees C. Detoxification of diisopropylfluorophosphate (DFP) by the polyDMAA MA-4-PAM iodide component was dose-dependent reaching 85% within 30 min. A subset of 4-PAM-halide co-polymers was designed to serve as a controlled release reservoir for N-hydroxyethyl 4-PAM (HE 4-PAM) molecules that reactivate nerve agent-inhibited acetylcholinesterase (AChE). Release rates for HE 4-PAM were consistent with hydrolysis of the HE 4-PAM from the polymer backbone. The HE 4-PAM that was released from the polymer reactivated DFP-inhibited AChE at a similar rate to the oxime antidote 4-PAM. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Negotiating on location, timing, duration, and participant in agent-mediated joint activity-travel scheduling

NASA Astrophysics Data System (ADS)

Ma, Huiye; Ronald, Nicole; Arentze, Theo A.; Timmermans, Harry J. P.

2013-10-01

Agent-based simulation has become an important modeling approach in activity-travel analysis. Social activities account for a large amount of travel and have an important effect on activity-travel scheduling. Participants in joint activities usually have various options regarding location, participants, and timing and take different approaches to make their decisions. In this context, joint activity participation requires negotiation among agents involved, so that conflicts among the agents can be addressed. Existing mechanisms do not fully provide a solution when utility functions of agents are nonlinear and non-monotonic. Considering activity-travel scheduling in time and space as an application, we propose a novel negotiation approach, which takes into account these properties, such as continuous and discrete issues, and nonlinear and non-monotonic utility functions, by defining a concession strategy and a search mechanism. The results of experiments show that agents having these properties can negotiate efficiently. Furthermore, the negotiation procedure affects individuals’ choices of location, timing, duration, and participants.

Methods, microfluidic devices, and systems for detection of an active enzymatic agent

DOEpatents

Sommer, Gregory J; Hatch, Anson V; Singh, Anup K; Wang, Ying-Chih

2014-10-28

Embodiments of the present invention provide methods, microfluidic devices, and systems for the detection of an active target agent in a fluid sample. A substrate molecule is used that contains a sequence which may cleave in the presence of an active target agent. A SNAP25 sequence is described, for example, that may be cleaved in the presence of Botulinum Neurotoxin. The substrate molecule includes a reporter moiety. The substrate molecule is exposed to the sample, and resulting reaction products separated using electrophoretic separation. The elution time of the reporter moiety may be utilized to identify the presence or absence of the active target agent.

Nature of the Elimination of the Penicillinase Plasmid from Staphylococcus aureus by Surface-Active Agents

PubMed Central

Sonstein, Stephen A.; Baldwin, J. N.

1972-01-01

Growth of Stapylococcus aureus in various ionic surface-active agents resulted in loss of the ability to produce penicillinase, whereas growth in nonionic surface-active agents had no effect on penicillinase production. The curing effect of various alkyl sulfates was found to be dependent upon the chain length. Curing by surface-active agents could be inhibited by magnesium. Reciprocal transduction experiments showed that curing by a surface-active agent was a property of the plasmid, not of the bacterial strain in which the plasmic resides. PMID:4204903

Use of 99mTc-Tilmanocept as a Single Agent for Sentinel Lymph Node Identification in Breast Cancer: A Retrospective Pilot Study.

PubMed

Unkart, Jonathan T; Wallace, Anne M

2017-09-01

99m Tc-tilmanocept received recent Food and Drug Administration approval for lymphatic mapping in 2013. However, to our knowledge, no prior studies have evaluated the use of 99m Tc-tilmanocept as a single agent in sentinel lymph node (SLN) biopsy in breast cancer. Methods: We executed this retrospective pilot study to assess the ability of 99m Tc-tilmanocept to identify sentinel nodes as a single agent in clinically node-negative breast cancer patients. Patients received a single intradermal injection overlying the tumor of either 18.5 MBq (0.5 mCi) of 99m Tc-tilmanocept on the day of surgery or 74.0 MBq (2.0 mCi) on the day before surgery by a radiologist. Immediate 3-view lymphoscintigraphy was performed. Intraoperatively, SLNs were identified with a portable γ-probe. A node was classified as hot if the count (per second) of the node was more than 3 times the background count. Descriptive statistics are reported. Results: Nineteen patients underwent SLN biopsy with single-agent 99m Tc-tilmanocept. Immediate lymphoscintigraphy identified at least 1 sentinel node in 13 of 17 patients (76.5%). Intraoperatively, at least 1 (mean, 1.7 ± 0.8; range, 1-3) hot node was identified in all patients. Three patients (15.8%) had 1 disease-positive SLN. Conclusion: In this small, retrospective pilot study, 99m Tc-tilmanocept performed well as a single agent for intraoperative sentinel node identification in breast cancer. A larger, randomized clinical trial is warranted to compare 99m Tc-tilmanocept as a single agent with other radiopharmaceuticals for sentinel node identification in breast cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

PubMed

Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Ouvry, Gilles; Perrey, David; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2008-06-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Bispectral index, entropy, and quantitative electroencephalogram during single-agent xenon anesthesia.

PubMed

Laitio, Ruut M; Kaskinoro, Kimmo; Särkelä, Mika O K; Kaisti, Kaike K; Salmi, Elina; Maksimow, Anu; Långsjö, Jaakko W; Aantaa, Riku; Kangas, Katja; Jääskeläinen, Satu; Scheinin, Harry

2008-01-01

The aim was to evaluate the performance of anesthesia depth monitors, Bispectral Index (BIS) and Entropy, during single-agent xenon anesthesia in 17 healthy subjects. After mask induction with xenon and intubation, anesthesia was continued with xenon only. BIS, State Entropy and Response Entropy, and electroencephalogram were monitored throughout induction, steady-state anesthesia, and emergence. The performance of BIS, State Entropy, and Response Entropy were evaluated with prediction probability, sensitivity, and specificity analyses. The power spectrum of the raw electroencephalogram signal was calculated. The mean (SD) xenon concentration during anesthesia was 66.4% (2.4%). BIS, State Entropy, and Response Entropy demonstrated low prediction probability values at loss of response (0.455, 0.656, and 0.619) but 1 min after that the values were high (0.804, 0.941, and 0.929). Thereafter, equally good performance was demonstrated for all indices. At emergence, the prediction probability values to distinguish between steady-state anesthesia and return of response for BIS, State Entropy, and Response Entropy were 0.988, 0.892, and 0.992. No statistical differences between the performances of the monitors were observed. Quantitative electroencephalogram analyses showed generalized increase in total power (P < 0.001), delta (P < 0.001) and theta activity (P < 0.001), and increased alpha activity (P = 0.003) in the frontal brain regions. Electroencephalogram-derived depth of sedation indices BIS and Entropy showed a delay to detect loss of response during induction of xenon anesthesia. Both monitors performed well in distinguishing between conscious and unconscious states during steady-state anesthesia. Xenon-induced changes in electroencephalogram closely resemble those induced by propofol.

Hybrid Compounds as Anti-infective Agents.

PubMed

Sbaraglini, María Laura; Talevi, Alan

2017-01-01

Hybrid drugs are multi-target chimeric chemicals combining two or more drugs or pharmacophores covalently linked in a single molecule. In the field of anti-infective agents, they have been proposed as a possible solution to drug resistance issues, presumably having a broader spectrum of activity and less probability of eliciting high level resistance linked to single gene product. Although less frequently explored, they could also be useful in the treatment of frequently occurring co-infections. Here, we overview recent advances in the field of hybrid antimicrobials. Furthermore, we discuss some cutting-edge approaches to face the development of designed multi-target agents in the era of omics and big data, namely analysis of gene signatures and multitask QSAR models. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

USDA-ARS?s Scientific Manuscript database

Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids were increased against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis, by addition of a methyl, methoxyl or a chloro group at position 4 of the aromatic ri...

Expert Statement on the Single-Agent Use of Inhaled Bronchodilator in the Treatment of Stable Mild-Moderate Chronic Obstructive Pulmonary Disease.

PubMed

Riesco Miranda, Juan Antonio; Alcázar, Bernardino; Alfageme, Inmaculada; Casanova, Ciro; Celli, Bartolomé; de-Torres, Juan P; Jiménez Ruiz, Carlos A

2017-10-01

To describe the evidence- and experience-based expert consensus on the use of single-agent bronchodilators in patients with stable mild-moderate chronic obstructive pulmonary disease (COPD). Using Delphi methodology, a panel of 7 respiratory medicine experts was established, who, in the first nominal group meeting defined the scope, users, and document sections. The panel drew up 14 questions on the use of single-agent bronchodilators in patients with mild-moderate stable COPD to be answered with a systematic review of the literature. The results of the review were discussed in a second nominal group meeting and 17 statements were generated. Agreement/disagreement with the statements was tested among16 different experts including respiratory medicine experts and primary care physicians. Statements were scored from1 (total disagreement) to10 (total agreement). Agreement was considered if at least 70% voted ≥7. The level of evidence and grade of recommendation of the systematic literature review was assessed using the Oxford Centre for Evidence-based Medicine levels. A total of 12 of the 17 statements were selected. Specific statements were generated on different profiles of patients with stable mild-moderate COPD in whom single-agent bronchodilators could be prescribed. These statements on the use of single-agent bronchodilators might improve the outcomes and prognosis of patients with stable mild-moderate COPD. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Isolation, screening, and characterization of surface-active agent-producing, oil-degrading marine bacteria of Mumbai Harbor.

PubMed

Mohanram, Rajamani; Jagtap, Chandrakant; Kumar, Pradeep

2016-04-15

Diverse marine bacterial species predominantly found in oil-polluted seawater produce diverse surface-active agents. Surface-active agents produced by bacteria are classified into two groups based on their molecular weights, namely biosurfactants and bioemulsifiers. In this study, surface-active agent-producing, oil-degrading marine bacteria were isolated using a modified Bushnell-Haas medium with high-speed diesel as a carbon source from three oil-polluted sites of Mumbai Harbor. Surface-active agent-producing bacterial strains were screened using nine widely used methods. The nineteen bacterial strains showed positive results for more than four surface-active agent screening methods; further, these strains were characterized using biochemical and nucleic acid sequencing methods. Based on the results, the organisms belonged to the genera Acinetobacter, Alcanivorax, Bacillus, Comamonas, Chryseomicrobium, Halomonas, Marinobacter, Nesterenkonia, Pseudomonas, and Serratia. The present study confirmed the prevalence of surface-active agent-producing bacteria in the oil-polluted waters of Mumbai Harbor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aptamer-Encoded Nanopore for Ultrasensitive Detection of Bioterrorist Agent Ricin at Single-Molecule Resolution

PubMed Central

Gu, Li-Qun; Ding, Shu; Gao, Changlu

2011-01-01

The molecular-scale pore structure, called nanopore, can be formed from protein ion channels by genetic engineering or fabricated on solid substrates using fashion nanotechnology. Target molecules in interaction with the functionalized lumen of nanopore, can produce characteristic changes in the pore conductance, which act as fingerprints, allowing us to identify single molecules and simultaneously quantify each target species in the mixture. Nanopore sensors have been created for tremendous biomedical detections, with targets ranging from metal ions, drug compounds and cellular second messengers, to proteins and DNAs. Here we will review our recent discoveries with a lab-in-hand glass nanopore: single-molecule discrimination of chiral enantiomers with a trapped cyclodextrin, and sensing of bioterrorist agent ricin. PMID:19964179

Effectiveness of a new non-hydrogen peroxide bleaching agent after single use - a double-blind placebo-controlled short-term study.

PubMed

Bizhang, Mozhgan; Domin, Julia; Danesh, Gholamreza; Zimmer, Stefan

2017-01-01

Tooth whitening represents perhaps the most common aesthetic procedure in dentistry worldwide. The efficacy of bleaching depends on three aspects: bleaching agent, bleaching method, and tooth color. This in vivo study aimed to examine whitening effects on frontal teeth of the upper and lower jaws using an over-the-counter (OTC) non-hydrogen peroxide bleaching agent in comparison to a placebo after one single use. Forty subjects (25 female; 15 male) participated in this double-blind randomized placebo-controlled trial. The subjects were randomly allocated to two groups (n=20). The test group received the OTC product (iWhite Instant) and the placebo group received an identically composed product except for the active agents. Each subject was treated with a prefilled tray containing iWhite Instant or the placebo for 20 minutes. The tooth shade of the front teeth (upper and lower jaws) was assessed before (E_0), immediately after (E_1) and 24 h after treatment (E_2), using a shade guide (VITA classical). Statistical testing was accomplished using the Mann-Whitney U test (p<0.001). The dropout rate was 0%. There were no significant differences at E_0 between placebo and test groups regarding the tooth color. Differences in tooth color changes immediately after (ΔE1_0) and 24 h after treatment (ΔE2_0) were calculated for both groups. The mean values (standard deviations) of tooth color changes for ΔE1_0 were 2.26 (0.92) in the test group and 0.01 (0.21) in the placebo group. The color changes for ΔE2_0 showed mean values of 2.15 (1.10) in the test group and 0.07 (0.35) in the placebo group. For ΔE1_0 and ΔE2_0 significant differences were found between the groups. In this short-term study, the results showed that a non-hydrogen peroxide bleaching agent has significant whitening effects immediately and 24 h after a single-use treatment.

Effects of surface active agents on DNAPL migration and distribution in saturated porous media.

PubMed

Cheng, Zhou; Gao, Bin; Xu, Hongxia; Sun, Yuanyuan; Shi, Xiaoqing; Wu, Jichun

2016-11-15

Dissolved surface active agents such as surfactant and natural organic matter can affect the distribution and fate of dense nonaqueous liquids (DNAPLs) in soil and groundwater systems. This work investigated how two common groundwater surface active agents, humic acid (HA) and Tween 80, affected tetrachloroethylene (PCE) migration and source zone architecture in saturated porous media under environmentally relevant conditions. Batch experiments were first conducted to measure the contact angles and interfacial tensions (IFT) between PCE and quartz surface in water containing different amount of surface active agents. Results showed that the contact angle increased and IFT decreased with concentration of surface active agent increasing, and Tween 80 was much more effective than HA. Five 2-D flow cell experiments were then conducted. Correspondingly, Tween 80 showed strong effects on the migration and distribution of PCE in the porous media due to its ability to change the medium wettability from water-wet into intermediate/NAPL-wet. The downward migration velocities of the PCE in three Tween 80 cells were slower than those in the other two cells. In addition, the final saturation of the PCE in the cells containing surface active agents was higher than that in the water-only cell. Results from this work indicate that the presence of surface active agents in groundwater may strongly affect the fate and distribution of DNAPL through altering porous medium wettability. Copyright © 2016 Elsevier B.V. All rights reserved.

Halloysite clay nanotubes for controlled delivery of chemically active agents

NASA Astrophysics Data System (ADS)

Abdullayev, Elshard

In this work we explored the capabilities of halloysite nanotubes as capsules for encapsulation and controlled delivery of the chemically and biologically active substances. Halloysite is a two-layered aluminosilicate which has a predominantly hollow tubular structure in the submicron range and is chemically similar to kaolinite [1, 2]. In the first section of this work, we analyzed the structure of the halloysite nanotubes as well as its capability to encapsulate and deliver biologically and chemically active agents, similarities and differences between release characteristics of different agents and how these differences relate with their chemical structure. Models were used to describe the release characteristics of the active agents. Study of the interaction between loaded agents and halloysite nanotubes provides better understanding of the release characteristics of the loaded agents and how halloysite can be implemented for technological and medical applications. The second part of the work deals with self-healing coatings produced on the basis of halloysite nanotubes loaded with corrosion inhibitors. Self-healing coatings are one of the effective methods to protect metals from corrosion and deterioration. The difference between self-healing coatings and the usual coatings is the ability of the first to recover after the formation of the damages due to external or internal stresses. High efficiency of the self- healing coatings produced by halloysite nanotubes were demonstrated on 110 Copper alloys and 2024 aluminum alloys. Controlled delivery of the corrosion inhibitors with additional encapsulation of the halloysite nanotubes by synthesizing stoppers at tube endings was also demonstrated. Additional encapsulation of the halloysite nanotubes may be necessary when slow release of the loaded agents is required or rapid convection of the liquid in the surrounding environment takes place (since this may cause rapid release of the loaded agents without additional

A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-β, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort.

PubMed

Werner, Theresa L; Wade, Mark L; Agarwal, Neeraj; Boucher, Kenneth; Patel, Jesal; Luebke, Aaron; Sharma, Sunil

2015-12-01

JI-101 is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor β (PDGFR-β), and ephrin type-B receptor 4 (EphB4). None of the currently approved angiogenesis inhibitors have been reported to inhibit EphB4, and therefore, JI-101 has a novel mechanism of action. We conducted a pilot trial to assess the pharmacokinetics (PK), tolerability, and efficacy of JI-101 in combination with everolimus in advanced cancers, and pharmacodynamics (PD), tolerability, and efficacy of JI-101 in ovarian cancer. This was the first clinical study assessing anti-tumor activity of JI-101 in a combinatorial regimen. In the PK cohort, four patients received single agent 10 mg everolimus on day 1, 10 mg everolimus and 200 mg JI-101 combination on day 8, and single agent 200 mg JI-101 on day 15. In the PD cohort, eleven patients received single agent JI-101 at 200 mg twice daily for 28 day treatment cycles. JI-101 was well tolerated as a single agent and in combination with everolimus. No serious adverse events were observed. Common adverse events were hypertension, nausea, and abdominal pain. JI-101 increased exposure of everolimus by approximately 22%, suggestive of drug-drug interaction. The majority of patients had stable disease at their first set of restaging scans (two months), although no patients demonstrated a response to the drug per RECIST criteria. The novel mechanism of action of JI-101 is promising in ovarian cancer treatment and further prospective studies of this agent may be pursued in a less refractory patient population or in combination with cytotoxic chemotherapy.

Composting of Sewage Sludge Using Recycled Matured Compost as a Single Bulking Agent

NASA Astrophysics Data System (ADS)

Zhang, Xiangyang; Ren, Jian; Niu, Huasi; Wu, Xingwu

2010-11-01

Pretreatment (bulking agent choice and mixing) is an essential phase of dewatered raw sludge (RS) composting affecting its industrialization significantly. In this paper recycled compost (RC) was chosen as a single bulking agent in the composting experiment instead of other agents such as sawdust, rice straw, MSW, and the mixing machine was developed for mixing of SS and RC. According to the mixing experiment, SS and RC can be mixed uniformly and formed into small particles of 10˜15 mm in diameter, which improved the availability of oxygen during composting. The effect of different volumetric ratios of RS to RC, 1:1 (Exp.1), 1:2 (Exp.2) and 1:4 (Exp.3), on the performance of composting was investigated in detail. Temperature, oxygen consumption rate, organic matter, C/N ratio and moisture content were monitored in each experiment. In despite of low initial C/N of the mixture, intensive fermentation happened in all the experiments. Exp.1 and Exp.2 achieved stability and sanitization, but Exp 1 took more days to accomplish the fermentation. Exp 3 maintained thermophilic temperatures for a shortest time and did not satisfy the necessary sanitation requirements because more RC was recycled. In all experiments, the moisture content of their final composts were too high to be used as bulking agents before extra moisture was reduced. RS: RC = 1:2 (v/v) was the optimum and advisable proportion for the industrialization of sewage sludge composting of, the composting period was about 10 days, and the aeration rate 0.05 m3/(m3ṡmin) was appropriate in this study.

Microbicidal activity of octenidine hydrochloride, a new alkanediylbis[pyridine] germicidal agent.

PubMed Central

Sedlock, D M; Bailey, D M

1985-01-01

The potential of octenidine hydrochloride (WIN 41464-2) as a topical microbicide was measured both by in vitro death kinetics and reductions in numbers of bacteria on the skin of cynomolgus monkeys. Semilogarithmic survival curves were plotted to measure the microbicidal activity of various concentrations of octenidine against Staphylococcus aureus. The microbicidal activity of octenidine was also determined for Staphylococcus epidermidis, Proteus mirabilis, Streptococcus pyogenes, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, and Candida albicans. Death rates for the same microbial strains were compared with those obtained by using chlorhexidine gluconate. Octenidine concentrations of less than 1.5 microM (0.94 microgram/ml) caused a greater than 99% reduction of each microbial population within 15 min. Staphylococcus epidermidis was the most susceptible of the test organisms, and E. coli and C. albicans were the least susceptible. Octenidine was more active than chlorhexidine against each test strain. Skin-degerming activities of aqueous and formulated octenidine and formulated chlorhexidine were compared in single and multiple applications of these agents to the hand and foot surfaces of monkeys by using a glove-juice extraction procedure to measure the skin microflora. Aqueous octenidine, at a concentration of 0.2 to 1.6% reduced resident microflora populations from 90 to 99.98%, depending on the concentration and number of applications. Octenidine formulated at 2% in a surfactant-based vehicle exhibited significantly better skin-degerming activity than did either a nonmedicated vehicle or the Hibiclens brand of 4% chlorhexidine gluconate. PMID:3909955

Dual HER2\\PIK3CA targeting overcomes single-agent acquired resistance in HER2 amplified uterine serous carcinoma cell lines in vitro and in vivo

PubMed Central

Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L.; English, Diana P.; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D.

2015-01-01

HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC), and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA mutated and PIK3CA-wild type HER2/neu amplified USC cell lines. Cell viability and cell cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC-xenografts. We found both single agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long lasting growth inhibition in both USC xenografts when compared to single agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA or pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild type PIK3CA resistant to chemotherapy. PMID:26333383

Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo.

PubMed

Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D

2015-11-01

HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu-amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0-G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy. ©2015 American Association for Cancer Research.

Evaluation of patritumab with or without erlotinib in combination with standard cytotoxic agents against pediatric sarcoma xenograft models.

PubMed

Bandyopadhyay, Abhik; Favours, Edward; Phelps, Doris A; Pozo, Vanessa Del; Ghilu, Samson; Kurmashev, Dias; Michalek, Joel; Trevino, Aron; Guttridge, Denis; London, Cheryl; Hirotani, Kenji; Zhang, Ling; Kurmasheva, Raushan T; Houghton, Peter J

2018-02-01

Integrating molecularly targeted agents with cytotoxic drugs used in curative treatment of pediatric cancers is complex. An evaluation was undertaken with the ERBB3/Her3-specific antibody patritumab (P) either alone or with the ERBB1/epidermal growth factor receptor inhibitor erlotinib (E) in combination with standard cytotoxic agents, cisplatin, vincristine, and cyclophosphamide, in pediatric sarcoma xenograft models that express receptors and ligands targeted by these agents. Tumor models were selected based upon ERBB3 expression and phosphorylation, and ligand (heregulin) expression. Patritumab, E, or these agents combined was evaluated without or with concomitant cytotoxic agents using procedures developed by the Pediatric Preclinical Testing Program. Full doses of cytotoxic agents were tolerated when combined with P, whereas dose reductions of 25% (vincristine, cisplatin) or 50% (cyclophosphamide) were required when combined with P + E. Patritumab, E alone, or in combination did not significantly inhibit growth of any tumor model, except for Rh18 xenografts (E alone). Patritumab had no single-agent activity and marginally enhanced the activity of vincristine and cisplatin only in Ewing sarcoma ES-4. P + E did not increase the antitumor activity of vincristine or cisplatin, whereas dose-reduced cyclophosphamide was significantly less active than cyclophosphamide administered at its maximum tolerated dose when combined with P + E. P had no single-agent activity, although it marginally potentiated the activity of vincristine and cisplatin in one of three models studied. However, the addition of E necessitated dose reduction of each cytotoxic agent, abrogating the enhancement observed with P alone. © 2017 Wiley Periodicals, Inc.

Pharmacokinetic parameters explain the therapeutic activity of antimicrobial agents in a silkworm infection model.

PubMed

Paudel, Atmika; Panthee, Suresh; Urai, Makoto; Hamamoto, Hiroshi; Ohwada, Tomohiko; Sekimizu, Kazuhisa

2018-01-25

Poor pharmacokinetic parameters are a major reason for the lack of therapeutic activity of some drug candidates. Determining the pharmacokinetic parameters of drug candidates at an early stage of development requires an inexpensive animal model with few associated ethical issues. In this study, we used the silkworm infection model to perform structure-activity relationship studies of an antimicrobial agent, GPI0039, a novel nitrofuran dichloro-benzyl ester, and successfully identified compound 5, a nitrothiophene dichloro-benzyl ester, as a potent antimicrobial agent with superior therapeutic activity in the silkworm infection model. Further, we compared the pharmacokinetic parameters of compound 5 with a nitrothiophene benzyl ester lacking chlorine, compound 7, that exerted similar antimicrobial activity but had less therapeutic activity in silkworms, and examined the metabolism of these antimicrobial agents in human liver fractions in vitro. Compound 5 had appropriate pharmacokinetic parameters, such as an adequate half-life, slow clearance, large area under the curve, low volume of distribution, and long mean residence time, compared with compound 7, and was slowly metabolized by human liver fractions. These findings suggest that the therapeutic effectiveness of an antimicrobial agent in the silkworms reflects appropriate pharmacokinetic properties.

Evaluation of Foaming Performance of Bitumen Modified with the Addition of Surface Active Agent

NASA Astrophysics Data System (ADS)

Chomicz-Kowalska, Anna; Mrugała, Justyna; Maciejewski, Krzysztof

2017-10-01

The article presents the analysis of the performance of foamed bitumen modified using surface active agents. Although, bitumen foaming permits production of asphalt concrete and other asphalt mix types without using chemical additives in significantly reduced temperatures, the decrease in processing temperatures still impacts the adhesion performance and bitumen coating of aggregates in final mixes. Therefore, in some cases it may be feasible to incorporate adhesion promoters and surface active agents into warm and half-warm mixes with foamed bitumen to increase their service life and resilience. Because of the various nature of the available surface active agents, varying bitumen compatibility and their possible impact on the rheological properties of bitumen, the introduction of surface active agents may significantly alter the bitumen foaming performance. The tests included basic performance tests of bitumen before and after foaming. The two tested bitumen were designated as 35/50 and 50/70 penetration grade binders, which were modified with a surface active agent widely used for improving mixture workability, compactibility and adhesion in a wide range of asphalt mixes and techniques, specifically Warm Mix Asphalt. Alongside to the reference unmodified bitumen, binders with 0.2%, 0.4% and 0.6% surface active agent concentration were tested. The analysis has shown a positive influence of the modifier on the foaming performance of both of the base bitumen increasing their maximum expansion ratio and bitumen foam halflife. In the investigations, it was found that the improvement was dependent on the bitumen type and modifier content. The improved expansion ratio and foam half-life has a positive impact on the aggregate coating and adhesion, which together with the adhesion promoting action of the modifier will have a combined positive effect on the quality of produced final asphalt mixes.

Suspected postpartum endometritis: a controlled clinical trial of single-agent antibiotic therapy with Amox-CA (Augmentin) vs. ampicillin-metronidazole +/- aminoglycoside.

PubMed

Fernandez, H; Claquin, C; Guibert, M; Papiernik, E

1990-01-01

Endometritis is the commonest postpartum complication and is one of the leading causes of maternal morbidity, if not mortality. The object of the present clinical trial was to assess the efficiency of single-agent therapy with Amox-CA (Augmentin) (formulation which includes a beta-lactamase inhibitor), against standard treatment which necessarily combines two or three antibiotics depending on the clinical severity of the case. 101 patients were evaluated in this comparative prospective randomized study. The mild forms were defined by a temperature between 37.9 and 38.4 degrees C and the severe forms by a temperature of more than 38.5 degrees C (which alone required treatment with three antibiotics). The time until the return of apyrexia and the clinical cure rate, as well as duration of treatment, were identical in both groups. Tolerance was good: no side effect requiring discontinuation of treatment occurred. In the population value, the use of a single-agent therapy with amoxycillin/clavulanic acid is not significantly different from a double or triple-agent regimen, and the convenience is increase.

Synthesis, antiproliferative activity and mechanism of gallium(III)-thiosemicarbazone complexes as potential anti-breast cancer agents.

PubMed

Qi, Jinxu; Yao, Qian; Qian, Kun; Tian, Liang; Cheng, Zhen; Yang, Dongmei; Wang, Yihong

2018-05-14

Five thiosemicarbazone ligands were synthesized and characterized by condensation with different aldehydes or ketones by 4-phenylthiosemicarbazone. The representative dichlorido[2-(Di-2-pyridinylmethylene)-Nphenylhydrazinecarbothioamide-N,N,S]-gallium(III) (Ga4) was characterized by X-ray single crystal diffraction, which was 1:1 ligand/Ga(III) complexes. The structure-activity relationship of these ligands and Ga (III) complexes have been investigated, and the results demonstrate that the formation of Ga (III) complexes have significant antiproliferative activity over the corresponding ligands. The anticancer mechanism of gallium (III) complexes has been studied in detail, which is typical agents that effect on the mitochondrial apoptotic pathway. The ability of gallium (III) complexes to inhibit the cell cycle does not enhanced with the increasing concentrations, whereas the ability to promote apoptosis is concentration-dependent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The effect of functional groups on reduction and activation of quinone bioreductive agents by DT-diaphorase.

PubMed

Fourie, Jeanne; Oleschuk, Curtis J; Guziec, Frank; Guziec, Lynn; Fiterman, Derek J; Monterrosa, Cielo; Begleiter, Asher

2002-02-01

Bioreductive antitumor agents are an important class of anticancer drugs that include the clinically used drug, mitomycin C, and new agents such as EO9 and tirapazamine that have recently been tested in clinical trials. These agents require activation by reductive enzymes such as DT-diaphorase or NADPH:cytochrome P450 reductase. A major focus for improving cancer chemotherapy has been to increase the selectivity and targeting of antitumor drugs to tumor cells. Bioreductive antitumor agents are ideally suited to improving tumor selectivity by an enzyme-directed approach to tumor targeting. However, none of the bioreductive agents developed to date has been specific for activation by a single reductive enzyme. This is in part due to a lack of knowledge about structural factors that confer selectivity for activation by reductive enzymes. The purpose of this study was to investigate the ability of specific functional groups to modify reduction and activation of quinone bioreductive agents by DT-diaphorase. We used a series of model benzoquinone mustard (BM) bioreductive agents and compared the parent compound BM to MBM, which has a strong electron-donating methoxy group, MeBM, which has a weaker electron-donating methyl group, CBM, which has an electron-withdrawing chloro group, and PBM and its structural isomer, meta-PBM (m-PBM), which both have sterically bulky benzene rings attached to the quinone moiety. We determined the rate of reduction of these agents by purified human DT-diaphorase under hypoxic and aerobic conditions. We also measured the cytotoxic activity of these agents in human tumor cell lines with and without the DT-diaphorase inhibitor, dicoumarol. Under hypoxic conditions in vitro, the t(1/2) values for reduction of the analogs by purified DT-diaphorase were 4, 6, 8, 9, 10 and 21 min for BM, MeBM, CBM, MBM, PBM and m-PBM, respectively. Under aerobic conditions the rank order of redox cycling after two-electron reduction by DT-diaphorase was MBM > Me

Chemiresistor Devices for Chemical Warfare Agent Detection Based on Polymer Wrapped Single-Walled Carbon Nanotubes

PubMed Central

Fennell, John F.; Hamaguchi, Hitoshi; Yoon, Bora; Swager, Timothy M.

2017-01-01

Chemical warfare agents (CWA) continue to present a threat to civilian populations and military personnel in operational areas all over the world. Reliable measurements of CWAs are critical to contamination detection, avoidance, and remediation. The current deployed systems in United States and foreign militaries, as well as those in the private sector offer accurate detection of CWAs, but are still limited by size, portability and fabrication cost. Herein, we report a chemiresistive CWA sensor using single-walled carbon nanotubes (SWCNTs) wrapped with poly(3,4-ethylenedioxythiophene) (PEDOT) derivatives. We demonstrate that a pendant hexafluoroisopropanol group on the polymer that enhances sensitivity to a nerve agent mimic, dimethyl methylphosphonate, in both nitrogen and air environments to concentrations as low as 5 ppm and 11 ppm, respectively. Additionally, these PEDOT/SWCNT derivative sensor systems experience negligible device performance over the course of two weeks under ambient conditions. PMID:28452929

Chemiresistor Devices for Chemical Warfare Agent Detection Based on Polymer Wrapped Single-Walled Carbon Nanotubes.

PubMed

Fennell, John F; Hamaguchi, Hitoshi; Yoon, Bora; Swager, Timothy M

2017-04-28

Chemical warfare agents (CWA) continue to present a threat to civilian populations and military personnel in operational areas all over the world. Reliable measurements of CWAs are critical to contamination detection, avoidance, and remediation. The current deployed systems in United States and foreign militaries, as well as those in the private sector offer accurate detection of CWAs, but are still limited by size, portability and fabrication cost. Herein, we report a chemiresistive CWA sensor using single-walled carbon nanotubes (SWCNTs) wrapped with poly(3,4-ethylenedioxythiophene) (PEDOT) derivatives. We demonstrate that a pendant hexafluoroisopropanol group on the polymer that enhances sensitivity to a nerve agent mimic, dimethyl methylphosphonate, in both nitrogen and air environments to concentrations as low as 5 ppm and 11 ppm, respectively. Additionally, these PEDOT/SWCNT derivative sensor systems experience negligible device performance over the course of two weeks under ambient conditions.

Redox-activated MRI contrast agents based on lanthanide and transition metal ions.

PubMed

Tsitovich, Pavel B; Burns, Patrick J; McKay, Adam M; Morrow, Janet R

2014-04-01

The reduction/oxidation (redox) potential of tissue is tightly regulated in order to maintain normal physiological processes, but is disrupted in disease states. Thus, the development of new tools to map tissue redox potential may be clinically important for the diagnosis of diseases that lead to redox imbalances. One promising area of chemical research is the development of redox-activated probes for mapping tissue through magnetic resonance imaging (MRI). In this review, we summarize several strategies for the design of redox-responsive MRI contrast agents. Our emphasis is on both lanthanide(III) and transition metal(II/III) ion complexes that provide contrast either as T1 relaxivity MRI contrast agents or as paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents. These agents are redox-triggered by a variety of chemical reactions or switches including redox-activated thiol groups, and heterocyclic groups that interact with the metal ion or influence properties of other ancillary ligands. Metal ion centered redox is an approach which is ripe for development by coordination chemists. Redox-triggered metal ion approaches have great potential for creating large differences in magnetic properties that lead to changes in contrast. An attractive feature of these agents is the ease of fine-tuning the metal ion redox potential over a biologically relevant range. Copyright © 2014 Elsevier Inc. All rights reserved.

Using an agent-based model to simulate children's active travel to school.

PubMed

Yang, Yong; Diez-Roux, Ana V

2013-05-26

Despite the multiple advantages of active travel to school, only a small percentage of US children and adolescents walk or bicycle to school. Intervention studies are in a relatively early stage and evidence of their effectiveness over long periods is limited. The purpose of this study was to illustrate the utility of agent-based models in exploring how various policies may influence children's active travel to school. An agent-based model was developed to simulate children's school travel behavior within a hypothetical city. The model was used to explore the plausible implications of policies targeting two established barriers to active school travel: long distance to school and traffic safety. The percent of children who walk to school was compared for various scenarios. To maximize the percent of children who walk to school the school locations should be evenly distributed over space and children should be assigned to the closest school. In the case of interventions to improve traffic safety, targeting a smaller area around the school with greater intensity may be more effective than targeting a larger area with less intensity. Despite the challenges they present, agent based models are a useful complement to other analytical strategies in studying the plausible impact of various policies on active travel to school.

CATS-based Air Traffic Controller Agents

NASA Technical Reports Server (NTRS)

Callantine, Todd J.

2002-01-01

This report describes intelligent agents that function as air traffic controllers. Each agent controls traffic in a single sector in real time; agents controlling traffic in adjoining sectors can coordinate to manage an arrival flow across a given meter fix. The purpose of this research is threefold. First, it seeks to study the design of agents for controlling complex systems. In particular, it investigates agent planning and reactive control functionality in a dynamic environment in which a variety perceptual and decision making skills play a central role. It examines how heuristic rules can be applied to model planning and decision making skills, rather than attempting to apply optimization methods. Thus, the research attempts to develop intelligent agents that provide an approximation of human air traffic controller behavior that, while not based on an explicit cognitive model, does produce task performance consistent with the way human air traffic controllers operate. Second, this research sought to extend previous research on using the Crew Activity Tracking System (CATS) as the basis for intelligent agents. The agents use a high-level model of air traffic controller activities to structure the control task. To execute an activity in the CATS model, according to the current task context, the agents reference a 'skill library' and 'control rules' that in turn execute the pattern recognition, planning, and decision-making required to perform the activity. Applying the skills enables the agents to modify their representation of the current control situation (i.e., the 'flick' or 'picture'). The updated representation supports the next activity in a cycle of action that, taken as a whole, simulates air traffic controller behavior. A third, practical motivation for this research is to use intelligent agents to support evaluation of new air traffic control (ATC) methods to support new Air Traffic Management (ATM) concepts. Current approaches that use large, human

Modulation of Regulatory T Cell Activity by TNF Receptor Type II-Targeting Pharmacological Agents

PubMed Central

Zou, Huimin; Li, Ruixin; Hu, Hao; Hu, Yuanjia; Chen, Xin

2018-01-01

There is now compelling evidence that tumor necrosis factor (TNF)–TNF receptor type II (TNFR2) interaction plays a decisive role in the activation, expansion, and phenotypical stability of suppressive CD4+Foxp3+ regulatory T cells (Tregs). In an effort to translate this basic research finding into a therapeutic benefit, a number of agonistic or antagonistic TNFR2-targeting biological agents with the capacity to activate or inhibit Treg activity have been developed and studied. Recent studies also show that thalidomide analogs, cyclophosphamide, and other small molecules are able to act on TNFR2, resulting in the elimination of TNFR2-expressing Tregs. In contrast, pharmacological agents, such as vitamin D3 and adalimumab, were reported to induce the expansion of Tregs by promoting the interaction of transmembrane TNF (tmTNF) with TNFR2. These studies clearly show that TNFR2-targeting pharmacological agents represent an effective approach to modulating the function of Tregs and thus may be useful in the treatment of major human diseases such as autoimmune disorders, graft-versus-host disease (GVHD), and cancer. In this review, we will summarize and discuss the latest progress in the study of TNFR2-targeting pharmacological agents and their therapeutic potential based on upregulation or downregulation of Treg activity. PMID:29632537

Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

PubMed

Wysham, Weiya Z; Schaffer, Elisabeth M; Coles, Theresa; Roque, Dario R; Wheeler, Stephanie B; Kim, Kenneth H

2017-05-01

AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

Bolus dose response characteristics of single chain urokinase plasminogen activator and tissue plasminogen activator in a dog model of arterial thrombosis.

PubMed

Badylak, S F; Voytik, S; Klabunde, R E; Henkin, J; Leski, M

1988-11-15

Tissue plasminogen activator (t-PA) and single chain urokinase-plasminogen activator (scu-PA) are relatively "fibrin-specific" thrombolytic drugs with short plasma half lives of 6-8 minutes. Most treatment regimens with these agents utilize a bolus injection followed by continuous drug infusion, usually combined with anticoagulant therapy. The purpose of this study was to establish the dose-response characteristics for scu-PA and t-PA, when given as a single intravenous bolus injection, in a dog model of arterial thrombosis. Eight groups of 6 dogs each were given one of the following doses of scu-PA (mg/kg): 0.20, 0.50, 1.00, 2.00; or t-PA: 0.05, 0.10, 0.20; or an equivalent amount of saline (control group). All doses were given as a single bolus injection 60 minutes after formation of a totally occlusive femoral artery thrombus. Thrombolysis was measured by monitoring the continuous decrement of 125I activity from a radiolabelled thrombus. Ninety minutes after drug injection, all scu-PA treated dogs showed greater thrombolysis (30%, 45%, 56%, and 67%, respectively) than the control group (15%, p less than 0.01). The 0.10 and 0.20 mg/kg t-PA treated dogs showed greater thrombolysis (35% and 49%, respectively) than the control group (15%, p less than 0.01). Both scu-PA and t-PA caused a partial and dose-dependent decrease in alpha 2-antiplasmin activity but scu-PA caused a greater depletion (72% vs. 18%, respectively, p less than 0.05) at 60 minutes after the highest dose of drug administration. Both drugs showed a longer than expected thrombolytic effect based upon the known half lives. Neither drug caused significant changes in the prothrombin time, activated partial thromboplastin time, thrombin time, hematocrit, platelet count, or fibrin degradation product concentration. Single bolus injections of scu-PA and t-PA produce safe and effective thrombolysis in this dog model of arterial thrombosis.

Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.

PubMed

Unger, E C; McCreery, T P; Sweitzer, R H; Caldwell, V E; Wu, Y

1998-12-01

Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

A detailed heterogeneous agent model for a single asset financial market with trading via an order book.

PubMed

Mota Navarro, Roberto; Larralde, Hernán

2017-01-01

We present an agent based model of a single asset financial market that is capable of replicating most of the non-trivial statistical properties observed in real financial markets, generically referred to as stylized facts. In our model agents employ strategies inspired on those used in real markets, and a realistic trade mechanism based on a double auction order book. We study the role of the distinct types of trader on the return statistics: specifically, correlation properties (or lack thereof), volatility clustering, heavy tails, and the degree to which the distribution can be described by a log-normal. Further, by introducing the practice of "profit taking", our model is also capable of replicating the stylized fact related to an asymmetry in the distribution of losses and gains.

Chemical release from single-PMMA microparticles monitored by CARS microscopy

NASA Astrophysics Data System (ADS)

Enejder, Annika; Svedberg, Fredrik; Nordstierna, Lars; Nydén, Magnus

2011-03-01

Microparticles loaded with antigens, proteins, DNA, fungicides, and other functional agents emerge as ideal vehicles for vaccine, drug delivery, genetic therapy, surface- and crop protection. The microscopic size of the particles and their collective large specific surface area enables highly active and localized release of the functional substance. In order to develop designs with release profiles optimized for the specific application, it is desirable to map the distribution of the active substance within the particle and how parameters such as size, material and morphology affect release rates at single particle level. Current imaging techniques are limited in resolution, sensitivity, image acquisition time, or sample treatment, excluding dynamic studies of active agents in microparticles. Here, we demonstrate that the combination of CARS and THG microscopy can successfully be used, by mapping the spatial distribution and release rates of the fungicide and food preservative IPBC from different designs of PMMA microparticles at single-particle level. By fitting a radial diffusion model to the experimental data, single particle diffusion coefficients can be determined. We show that release rates are highly dependent on the size and morphology of the particles. Hence, CARS and THG microscopy provides adequate sensitivity and spatial resolution for quantitative studies on how singleparticle properties affect the diffusion of active agents at microscopic level. This will aid the design of innovative microencapsulating systems for controlled release.

Physical Activity Experiences and Beliefs Among Single Mothers: A Qualitative Study.

PubMed

Dlugonski, Deirdre; Motl, Robert W

2016-09-01

Single motherhood has been associated with negative health consequences such as depression and cardiovascular disease. Physical activity might reduce these consequences, but little is known about physical activity experiences and beliefs that might inform interventions and programs for single mothers. The present study used social-cognitive theory as a framework to explore physical activity beliefs and experiences among single mothers. Single mothers (N = 14) completed a semistructured interview and the International Physical Activity Questionnaire. Participants were categorized into 3 activity levels, and data were analyzed according to these categories. All participants reported barriers to physical activity. Physically active single mothers seemed to be more confident in their ability to overcome these barriers and more likely to plan physical activity in their daily routine, and they more frequently reported having social support compared with low-active single mothers. Across all activity levels, participants focused on the physical outcomes of physical activity participation such as weight loss. These results provide information that is useful for designing and delivering behavioral interventions for increasing physical activity among single mothers.

THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS

PubMed Central

Hirsch, Robert L.; Kellner, Aaron

1956-01-01

Rabbits subjected to subtotal hepatectomy failed to develop increased serum cholesterol levels following parenteral injection of triton WR 1339, the finding indicating that the liver is essential for the establishment of the hypercholesterolemia induced by surface-active agents. The cholesterol content of the livers of rabbits rendered hyperlipemic by means of triton remained unchanged both during the rapid rise of the serum cholesterol levels and during the return to normal values. By contrast, the cholesterol content of the livers of rabbits fed cholesterol rose progressively over a period of 5 weeks, concommittant with the increase in serum cholesterol levels. The findings provide support for the hypothesis that surface-active agents bring about hyperlipemia by altering the circulating lipoproteins in some manner so that they are retained in the circulating body fluids. PMID:13332177

Scoping Planning Agents With Shared Models

NASA Technical Reports Server (NTRS)

Bedrax-Weiss, Tania; Frank, Jeremy D.; Jonsson, Ari K.; McGann, Conor

2003-01-01

In this paper we provide a formal framework to define the scope of planning agents based on a single declarative model. Having multiple agents sharing a single model provides numerous advantages that lead to reduced development costs and increase reliability of the system. We formally define planning in terms of extensions of an initial partial plan, and a set of flaws that make the plan unacceptable. A Flaw Filter (FF) allows us to identify those flaws relevant to an agent. Flaw filters motivate the Plan Identification Function (PIF), which specifies when an agent is is ready hand control to another agent for further work. PIFs define a set of plan extensions that can be generated from a model and a plan request. FFs and PIFs can be used to define the scope of agents without changing the model. We describe an implementation of PIFsand FFswithin the context of EUROPA, a constraint-based planning architecture, and show how it can be used to easily design many different agents.

Direct Single-Enzyme Biomineralization of Catalytically Active Ceria and Ceria–Zirconia Nanocrystals

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

Curran, Christopher D.; Lu, Li; Jia, Yue

Biomineralization is an intriguing approach to the synthesis of functional inorganic materials for energy applications whereby biological systems are engineered to mineralize inorganic materials and control their structure over multiple length scales under mild reaction conditions. Herein we demonstrate a single-enzyme-mediated biomineralization route to synthesize crystalline, catalytically active, quantum-confined ceria (CeO2–x) and ceria–zirconia (Ce1–yZryO2–x) nanocrystals for application as environmental catalysts. In contrast to typical anthropogenic synthesis routes, the crystalline oxide nanoparticles are formed at room temperature from an otherwise inert aqueous solution without the addition of a precipitant or additional reactant. An engineered form of silicatein, rCeSi, as a singlemore » enzyme not only catalyzes the direct biomineralization of the nanocrystalline oxides but also serves as a templating agent to control their morphological structure. The biomineralized nanocrystals of less than 3 nm in diameter are catalytically active toward carbon monoxide oxidation following an oxidative annealing step to remove carbonaceous residue. The introduction of zirconia into the nanocrystals leads to an increase in Ce(III) concentration, associated catalytic activity, and the thermal stability of the nanocrystals.« less

21 CFR 178.3400 - Emulsifiers and/or surface-active agents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... paperboard. α-[p-(1,1,3,3-Tetramethylbutyl)phenyl] omega-hydroxypoly(oxyethylene) produced by the... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Emulsifiers and/or surface-active agents. 178.3400... substances: List of substances Limitations α-Alkyl-, α-alkenyl-, and α-alkylaryl-omega-hydroxypoly...

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

PubMed Central

Lefranc, Florence; Carbone, Marianna; Mollo, Ernesto; Gavagnin, Margherita; Betancourt, Tania; Dasari, Ramesh

2016-01-01

Abstract The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity. PMID:27925266

The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN.

PubMed

Guan, J; Tucker, E R; Wan, H; Chand, D; Danielson, L S; Ruuth, K; El Wakil, A; Witek, B; Jamin, Y; Umapathy, G; Robinson, S P; Johnson, T W; Smeal, T; Martinsson, T; Chesler, L; Palmer, R H; Hallberg, B

2016-09-01

The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer. However, in neuroblastoma, activating mutations in the ALK kinase domain are typically refractory to crizotinib treatment, highlighting the need for more potent inhibitors. The next-generation ALK inhibitor PF-06463922 is predicted to exhibit increased affinity for ALK mutants prevalent in neuroblastoma. We examined PF-06463922 activity in ALK-driven neuroblastoma models in vitro and in vivo In vitro kinase assays and cell-based experiments examining ALK mutations of increasing potency show that PF-06463922 is an effective inhibitor of ALK with greater activity towards ALK neuroblastoma mutants. In contrast to crizotinib, single agent administration of PF-06463922 caused dramatic tumor inhibition in both subcutaneous and orthotopic xenografts as well as a mouse model of high-risk neuroblastoma driven by Th-ALK(F1174L)/MYCN Taken together, our results suggest PF-06463922 is a potent inhibitor of crizotinib-resistant ALK mutations, and highlights an important new treatment option for neuroblastoma patients. © 2016. Published by The Company of Biologists Ltd.

Enhance the anti-microorganism activity of cinnamon oil by xanthan gum as emulsifying agent

NASA Astrophysics Data System (ADS)

Lieu, Dong M.; Dang, Thuy T. K.; Nguyen, Huong T.

2018-04-01

The aim of this study was to evaluate the effect of emulsifying agents (tween 20, DMSO (Dimethyl Sulfoxide) and xanthan gum) to inhibit Escherichia coli; Staphylococcus aureus; Saccharomyces cerevisiae and Aspergillus niger by cinnamon oil (Cinnamomum Cassia). Cinnamon oil was added in the emulsifying agents independently: tween 20 (0.3% v/v). DMSO (0.3% v/v) and xanthan gum (0.3% w/v) at different concentrations and evaluated their anti-microorganism activity by agar disk diffusion, mycelial growth inhibition and growth inhibition in liquid phase. The result indicated that, cinnamon oil diluted in different emulsifying agents showed the difference of the anti-microorganism activity, in which DMSO showed the lowest result. Xanthan gum and tween 20 show good stable emulsion. The anti-microorganism effect of cinnamon oil in tween 20 and xanthan gum was not significant difference. However, cinnamon oil in xanthan gum showed anti-microorganism activity better than tween 20 at low concentration in agar disk diffusion. This suggests that, cinnamon oil could be encapsulated by xanthan gum to enhance the anti-microorganism activity.

Multi-Agent Patrolling under Uncertainty and Threats.

PubMed

Chen, Shaofei; Wu, Feng; Shen, Lincheng; Chen, Jing; Ramchurn, Sarvapali D

2015-01-01

We investigate a multi-agent patrolling problem where information is distributed alongside threats in environments with uncertainties. Specifically, the information and threat at each location are independently modelled as multi-state Markov chains, whose states are not observed until the location is visited by an agent. While agents will obtain information at a location, they may also suffer damage from the threat at that location. Therefore, the goal of the agents is to gather as much information as possible while mitigating the damage incurred. To address this challenge, we formulate the single-agent patrolling problem as a Partially Observable Markov Decision Process (POMDP) and propose a computationally efficient algorithm to solve this model. Building upon this, to compute patrols for multiple agents, the single-agent algorithm is extended for each agent with the aim of maximising its marginal contribution to the team. We empirically evaluate our algorithm on problems of multi-agent patrolling and show that it outperforms a baseline algorithm up to 44% for 10 agents and by 21% for 15 agents in large domains.

21 CFR 178.3400 - Emulsifiers and/or surface-active agents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... paperboard. α-[p-(1,1,3,3-Tetramethylbutyl)phenyl] omega-hydroxypoly(oxyethylene) produced by the... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Emulsifiers and/or surface-active agents. 178.3400...-alkylaryl-omega-hydroxypoly(oxyethylene) mixture consisting of 30 weight pct of α-(2,4,6-triisobutylphenyl...

21 CFR 178.3400 - Emulsifiers and/or surface-active agents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... paperboard. α-[p-(1,1,3,3-Tetramethylbutyl)phenyl] omega-hydroxypoly(oxyethylene) produced by the... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Emulsifiers and/or surface-active agents. 178.3400...-alkylaryl-omega-hydroxypoly(oxyethylene) mixture consisting of 30 weight pct of α-(2,4,6-triisobutylphenyl...

21 CFR 178.3400 - Emulsifiers and/or surface-active agents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... paperboard. α-[p-(1,1,3,3-Tetramethylbutyl)phenyl] omega-hydroxypoly(oxyethylene) produced by the... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Emulsifiers and/or surface-active agents. 178.3400...-alkylaryl-omega-hydroxypoly(oxyethylene) mixture consisting of 30 weight pct of α-(2,4,6-triisobutylphenyl...

21 CFR 178.3400 - Emulsifiers and/or surface-active agents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... paperboard. α-[p-(1,1,3,3-Tetramethylbutyl)phenyl] omega-hydroxypoly(oxyethylene) produced by the... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Emulsifiers and/or surface-active agents. 178.3400...-alkylaryl-omega-hydroxypoly(oxyethylene) mixture consisting of 30 weight pct of α-(2,4,6-triisobutylphenyl...

A detailed heterogeneous agent model for a single asset financial market with trading via an order book

PubMed Central

2017-01-01

We present an agent based model of a single asset financial market that is capable of replicating most of the non-trivial statistical properties observed in real financial markets, generically referred to as stylized facts. In our model agents employ strategies inspired on those used in real markets, and a realistic trade mechanism based on a double auction order book. We study the role of the distinct types of trader on the return statistics: specifically, correlation properties (or lack thereof), volatility clustering, heavy tails, and the degree to which the distribution can be described by a log-normal. Further, by introducing the practice of “profit taking”, our model is also capable of replicating the stylized fact related to an asymmetry in the distribution of losses and gains. PMID:28245251

The application of single particle aerosol mass spectrometry for the detection and identification of high explosives and chemical warfare agents

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

Martin, Audrey Noreen

2006-01-01

Single Particle Aerosol Mass Spectrometry (SPAMS) was evaluated as a real-time detection technique for single particles of high explosives. Dual-polarity time-of-flight mass spectra were obtained for samples of 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitro-1,3,5-triazinane (RDX), and pentaerythritol tetranitrate (PETN); peaks indicative of each compound were identified. Composite explosives, Comp B, Semtex 1A, and Semtex 1H were also analyzed, and peaks due to the explosive components of each sample were present in each spectrum. Mass spectral variability with laser fluence is discussed. The ability of the SPAMS system to identify explosive components in a single complex explosive particle (~1 pg) without the need formore » consumables is demonstrated. SPAMS was also applied to the detection of Chemical Warfare Agent (CWA) simulants in the liquid and vapor phases. Liquid simulants for sarin, cyclosarin, tabun, and VX were analyzed; peaks indicative of each simulant were identified. Vapor phase CWA simulants were adsorbed onto alumina, silica, Zeolite, activated carbon, and metal powders which were directly analyzed using SPAMS. The use of metal powders as adsorbent materials was especially useful in the analysis of triethyl phosphate (TEP), a VX stimulant, which was undetectable using SPAMS in the liquid phase. The capability of SPAMS to detect high explosives and CWA simulants using one set of operational conditions is established.« less

Socialization agents and activities of young adolescents.

PubMed

Arnon, Sara; Shamai, Shmuel; Ilatov, Zinaida

2008-01-01

Research examined the relative importance of peer groups for young adolescents as compared with diverse adult socialization agents--family, school, and community. The factors involved were teenagers' activities, preferences, feelings, and thoughts as to how they spend their leisure time, their preferences for help providers, and their sense of attachment to their community. These comparisons were made with religious and non-religious youngsters, in both rural and urban communities, and in gender subgroups. Questionnaires were administered to teenagers at secondary schools in a northern peripheral region of Israel. Findings showed the primary importance of peer groups and family in leisure activities and support, and the secondary importance of school and community. No evidence was found of a sharp generation gap. Community could also be significant if its organizations accepted youth as a peer group, and not only individually, on an equal and cooperating basis.

Reactive oxygen species-activated nanomaterials as theranostic agents.

PubMed

Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

2015-01-01

Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use.

The incorporation of activities to control dengue by community health agents

PubMed Central

Cazola, Luiza Helena de Oliveira; Tamaki, Edson Mamoru; Pontes, Elenir Rose Jardim Cury; de Andrade, Sonia Maria Oliveira

2014-01-01

OBJECTIVE To evaluate the performance of Community Health Agents when dengue control activities were added to their tasks. METHODS Performance was measured comparing the evolution of selected indicators from the Brazilian National Dengue Control Program and the Family Health Strategy for 2002 to 2008 in the municipality of Sao Gabriel do Oeste, MS, Central Western Brazil, with those of Rio Verde de Mato Grosso, neighboring municipality with demographic, socioeconomic and health services similarities. Data were collected from municipal databases of the Information System for Yellow Fever and Dengue and the Information System for Primary Healthcare of the Mato Grosso do Sul State Health Office. The variables selected for the family health strategy activities were: monthly home visits, pregnant women whose antenatal care began in the first trimester, children under one with up-to-date vaccinations and hypertensive patients. Those selected for the Brazilian National Dengue Control Program were: properties inspected with Aedes aegypti and properties not inspected. RESULTS The two municipalities maintained a similar trend in dengue control indicators in the period studied. With regard to the Family Health Strategy, in 2002 Sao Gabriel do Oeste was better off in three of the four indicators studied, however, this situation was reversed at the end of the period when the county was overtaken by Rio Verde de Mato Grosso in three of the four indicators analyzed, including, the monthly average community health worker visits per registered family, the main activity of a Family Health Strategy agent. CONCLUSIONS: Incorporating the National Dengue Control Program into the Family Health Strategy is viable and developed without prejudice to dengue control activities, however, the same did not occur with the activities of family health in Sao Gabriel do Oeste. The additional workload of the community health workers is the most likely hypothesis for the declining performance of these

Multiple stresses from a single agent: Diverse responses to the experimental acidification of Little Rock Lake, Wisconsin

USGS Publications Warehouse

Frost, T.M.; Montz, P.K.; Kratz, T.K.; Badillo, T.; Brezonik, P.L.; Gonzalez, M.J.; Rada, R.G.; Watras, C.J.; Webster, K.E.; Wiener, J.G.; Williamson, C.E.; Morris, D.P.

1999-01-01

A single stress, acidification with sulfuric acid, was applied to Little Rack Lake in a whole-ecosystem manipulation. We documented a wide range of responses to the acidification, including increases in the concentrations of various chemicals, shifts in microbial processes and a major increase in water clarity to UV-B radiation. Each of these changes could in itself be considered as a separate ecosystem stress that is distinct from the intended manipulation. Acidification in Little Rock Lake was accompanied by a number of substantial changes in the occurrence of organisms. A series of detailed investigations indicates that the mechanisms underlying these organismal changes are varied but cannot usually be tied to the direct effects of acidification. Overall, our results demonstrate how multiple stresses can arise from a single agent operating on an ecosystem and suggest that singly operating stresses may actually be quite rare.

Active Brownian particles escaping a channel in single file.

PubMed

Locatelli, Emanuele; Baldovin, Fulvio; Orlandini, Enzo; Pierno, Matteo

2015-02-01

Active particles may happen to be confined in channels so narrow that they cannot overtake each other (single-file conditions). This interesting situation reveals nontrivial physical features as a consequence of the strong interparticle correlations developed in collective rearrangements. We consider a minimal two-dimensional model for active Brownian particles with the aim of studying the modifications introduced by activity with respect to the classical (passive) single-file picture. Depending on whether their motion is dominated by translational or rotational diffusion, we find that active Brownian particles in single file may arrange into clusters that are continuously merging and splitting (active clusters) or merely reproduce passive-motion paradigms, respectively. We show that activity conveys to self-propelled particles a strategic advantage for trespassing narrow channels against external biases (e.g., the gravitational field).

Active Brownian particles escaping a channel in single file

NASA Astrophysics Data System (ADS)

Locatelli, Emanuele; Baldovin, Fulvio; Orlandini, Enzo; Pierno, Matteo

2015-02-01

Active particles may happen to be confined in channels so narrow that they cannot overtake each other (single-file conditions). This interesting situation reveals nontrivial physical features as a consequence of the strong interparticle correlations developed in collective rearrangements. We consider a minimal two-dimensional model for active Brownian particles with the aim of studying the modifications introduced by activity with respect to the classical (passive) single-file picture. Depending on whether their motion is dominated by translational or rotational diffusion, we find that active Brownian particles in single file may arrange into clusters that are continuously merging and splitting (active clusters) or merely reproduce passive-motion paradigms, respectively. We show that activity conveys to self-propelled particles a strategic advantage for trespassing narrow channels against external biases (e.g., the gravitational field).

In Vitro Antifungal Activity of Hexahydropyrimidine Derivatives against the Causative Agents of Dermatomycosis

PubMed Central

Caneschi, César A.; Senra, Mônica P.; Carvalho, Gustavo S. G.; da Silva, Adilson D.

2017-01-01

Nitrogenated heterocyclic compounds are present in both natural and synthetic drugs, and hexahydropyrimidine derivatives may prove to be efficient in treating dermatomycosis causing fungi. This study evaluated the antifungal activity of four hexahydropyrimidine derivatives against the dermatomycosis causing fungi. These derivatives were synthesized, characterized, and assessed in terms of their activity against Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, Trichophyton rubrum, Fusarium oxysporum, and Epidermophyton floccosum between concentrations 7.8 and 1,000 μg mL−1. Scanning electron micrographs were assessed for the active derivatives and reference drugs, and these micrographs revealed that new agents cause morphological changes in fungi. The derivatives HHP1, HHP3, and HHP4 revealed poor activity against the four fungal strains (MICs range 500–1000 μg mL−1). Compound HHP3 was found to be the best potential antifungal agent among those tested and was the most effective among all the active derivatives that caused morphological changes in the susceptible strains. PMID:29226215

Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.

PubMed

Vogel, Charles L; Cobleigh, Melody A; Tripathy, Debu; Gutheil, John C; Harris, Lyndsay N; Fehrenbacher, Louis; Slamon, Dennis J; Murphy, Maureen; Novotny, William F; Burchmore, Michael; Shak, Steven; Stewart, Stanford J; Press, Michael

2002-02-01

To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.

A framework for the use of agent based modeling to simulate ...

EPA Pesticide Factsheets

Simulation of human behavior in exposure modeling is a complex task. Traditionally, inter-individual variation in human activity has been modeled by drawing from a pool of single day time-activity diaries such as the US EPA Consolidated Human Activity Database (CHAD). Here, an agent-based model (ABM) is used to simulate population distributions of longitudinal patterns of four macro activities (sleeping, eating, working, and commuting) in populations of adults over a period of one year. In this ABM, an individual is modeled as an agent whose movement through time and space is determined by a set of decision rules. The rules are based on the agent having time-varying “needs” that are satisfied by performing actions. Needs are modeled as increasing over time, and taking an action reduces the need. Need-satisfying actions include sleeping (meeting the need for rest), eating (meeting the need for food), and commuting/working (meeting the need for income). Every time an action is completed, the model determines the next action the agent will take based on the magnitude of each of the agent’s needs at that point in time. Different activities advertise their ability to satisfy various needs of the agent (such as food to eat or sleeping in a bed or on a couch). The model then chooses the activity that satisfies the greatest of the agent’s needs. When multiple actions could address a need, the model will choose the most effective of the actions (bed over the couc

Neuronal activity determines distinct gliotransmitter release from a single astrocyte

PubMed Central

Covelo, Ana

2018-01-01

Accumulating evidence indicates that astrocytes are actively involved in brain function by regulating synaptic activity and plasticity. Different gliotransmitters, such as glutamate, ATP, GABA or D-serine, released form astrocytes have been shown to induce different forms of synaptic regulation. However, whether a single astrocyte may release different gliotransmitters is unknown. Here we show that mouse hippocampal astrocytes activated by endogenous (neuron-released endocannabinoids or GABA) or exogenous (single astrocyte Ca2+ uncaging) stimuli modulate putative single CA3-CA1 hippocampal synapses. The astrocyte-mediated synaptic modulation was biphasic and consisted of an initial glutamate-mediated potentiation followed by a purinergic-mediated depression of neurotransmitter release. The temporal dynamic properties of this biphasic synaptic regulation depended on the firing frequency and duration of the neuronal activity that stimulated astrocytes. Present results indicate that single astrocytes can decode neuronal activity and, in response, release distinct gliotransmitters to differentially regulate neurotransmission at putative single synapses. PMID:29380725

Using an agent-based model to simulate children’s active travel to school

PubMed Central

2013-01-01

Background Despite the multiple advantages of active travel to school, only a small percentage of US children and adolescents walk or bicycle to school. Intervention studies are in a relatively early stage and evidence of their effectiveness over long periods is limited. The purpose of this study was to illustrate the utility of agent-based models in exploring how various policies may influence children’s active travel to school. Methods An agent-based model was developed to simulate children’s school travel behavior within a hypothetical city. The model was used to explore the plausible implications of policies targeting two established barriers to active school travel: long distance to school and traffic safety. The percent of children who walk to school was compared for various scenarios. Results To maximize the percent of children who walk to school the school locations should be evenly distributed over space and children should be assigned to the closest school. In the case of interventions to improve traffic safety, targeting a smaller area around the school with greater intensity may be more effective than targeting a larger area with less intensity. Conclusions Despite the challenges they present, agent based models are a useful complement to other analytical strategies in studying the plausible impact of various policies on active travel to school. PMID:23705953

Activated carbon fibers and engineered forms from renewable resources

DOEpatents

Baker, Frederick S

2013-02-19

A method of producing activated carbon fibers (ACFs) includes the steps of providing a natural carbonaceous precursor fiber material, blending the carbonaceous precursor material with a chemical activation agent to form chemical agent-impregnated precursor fibers, spinning the chemical agent-impregnated precursor material into fibers, and thermally treating the chemical agent-impregnated precursor fibers. The carbonaceous precursor material is both carbonized and activated to form ACFs in a single step. The method produces ACFs exclusive of a step to isolate an intermediate carbon fiber.

Activated carbon fibers and engineered forms from renewable resources

DOEpatents

Baker, Frederick S.

2010-06-01

A method of producing activated carbon fibers (ACFs) includes the steps of providing a natural carbonaceous precursor fiber material, blending the carbonaceous precursor material with a chemical activation agent to form chemical agent-impregnated precursor fibers, spinning the chemical agent-impregnated precursor material into fibers, and thermally treating the chemical agent-impregnated precursor fibers. The carbonaceous precursor material is both carbonized and activated to form ACFs in a single step. The method produces ACFs exclusive of a step to isolate an intermediate carbon fiber.

Light-activated nanotube-porphyrin conjugates as effective antiviral agents

NASA Astrophysics Data System (ADS)

Banerjee, Indrani; Douaisi, Marc P.; Mondal, Dhananjoy; Kane, Ravi S.

2012-03-01

Porphyrins have been used for photodynamic therapy (PDT) against a wide range of targets like bacteria, viruses and tumor cells. In this work, we report porphyrin-conjugated multi-walled carbon nanotubes (NT-P) as potent antiviral agents. Specifically, we used Protoporphyrin IX (PPIX), which we attached to acid-functionalized multi-walled carbon nanotubes (MWNTs). We decided to use carbon nanotubes as scaffolds because of their ease of recovery from a solution through filtration. In the presence of visible light, NT-P was found to significantly reduce the ability of Influenza A virus to infect mammalian cells. NT-P may be used effectively against influenza viruses with little or no chance of them developing resistance to the treatment. Furthermore, NT-P can be easily recovered through filtration which offers a facile strategy to reuse the active porphyrin moiety to its fullest extent. Thus NT-P conjugates represent a new approach for preparing ex vivo reusable antiviral agents.

Removal of gadolinium-based contrast agents: adsorption on activated carbon.

PubMed

Elizalde-González, María P; García-Díaz, Esmeralda; González-Perea, Mario; Mattusch, Jürgen

2017-03-01

Three carbon samples were employed in this work, including commercial (1690 m 2  g -1 ), activated carbon prepared from guava seeds (637 m 2  g -1 ), and activated carbon prepared from avocado kernel (1068 m 2  g -1 ), to study the adsorption of the following gadolinium-based contrast agents (GBCAs): gadoterate meglumine Dotarem®, gadopentetate dimeglumine Magnevist®, and gadoxetate disodium Primovist®. The activation conditions with H 3 PO 4 were optimized using a Taguchi methodology to obtain mesoporous materials. The best removal efficiency by square meter in a batch system in aqueous solution and model urine was achieved by avocado kernel carbon, in which mesoporosity prevails over microporosity. The kinetic adsorption curves were described by a pseudo-second-order equation, and the adsorption isotherms in the concentration range 0.5-6 mM fit the Freundlich equation. The chemical characterization of the surfaces shows that materials with a greater amount of phenolic functional groups adsorb the GBCA better. Adsorption strongly depends on the pH due to the combination of the following factors: contrast agent protonated forms and carbon surface charge. The tested carbon samples were able to adsorb 70-90% of GBCA in aqueous solution and less in model urine. This research proposes a method for the elimination of GBCA from patient urine before its discharge into wastewater.

Anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma

PubMed Central

Kwak, Tae Won; Shin, Hee Jae; Jeong, Young-Il; Han, Myoung-Eun; Oh, Sae-Ock; Kim, Hyun-Jung; Kim, Do Hyung; Kang, Dae Hwan

2015-01-01

Background The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. Methods The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse. Results Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight when compared with the control. Conclusion These results reveal that streptochlorin is a promising chemotherapeutic agent to the treatment of cholangiocarcinoma. PMID:25931814

Active extravasation of gadolinium-based contrast agent into the subdural space following lumbar puncture.

PubMed

Kothari, Pranay D; Hanser, Evelyn M; Wang, Harrison; Farid, Nikdokht

2016-01-01

A 38year-old male presented with cauda equina syndrome following multiple lumbar puncture attempts. Lumbar spine magnetic resonance imaging (MRI) showed a subdural hematoma and an area of apparent contrast enhancement in the spinal canal on sagittal post-contrast images. Axial post-contrast images obtained seven minutes later demonstrated an increase in size and change in shape of the region of apparent contrast enhancement, indicating active extravasation of the contrast agent. This is the first reported case of active extravasation of gadolinium-based contrast agent in the spine. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial Control of Cell Transfection Using Soluble or Solid-Phase Redox Agents and a Redox-Active Ferrocenyl Lipid

PubMed Central

Aytar, Burcu S.; Muller, John P. E.; Kondo, Yukishige; Abbott, Nicholas L.; Lynn, David M.

2013-01-01

We report principles for active, user-defined control over the locations and timing with which DNA is expressed in cells. Our approach exploits unique properties of a ferrocenyl cationic lipid that is inactive when oxidized, but active when chemically reduced. We show that methods that exert spatial control over the administration of reducing agents can lead to local activation of lipoplexes and spatial control over gene expression. The versatility of this approach is demonstrated using both soluble and solid-phase reducing agents. These methods provide control over cell transfection, including methods for remote activation and the patterning of expression using solid-phase redox agents, that are difficult to achieve using conventional lipoplexes. PMID:23965341

Spatial control of cell transfection using soluble or solid-phase redox agents and a redox-active ferrocenyl lipid.

PubMed

Aytar, Burcu S; Muller, John P E; Kondo, Yukishige; Abbott, Nicholas L; Lynn, David M

2013-09-11

We report principles for active, user-defined control over the locations and timing with which DNA is expressed in cells. Our approach exploits unique properties of a ferrocenyl cationic lipid that is inactive when oxidized, but active when chemically reduced. We show that methods that exert spatial control over the administration of reducing agents can lead to local activation of lipoplexes and spatial control over gene expression. The versatility of this approach is demonstrated using both soluble and solid-phase reducing agents. These methods provide control over cell transfection, including methods for remote activation and the patterning of expression using solid-phase redox agents, that are difficult to achieve using conventional lipoplexes.

Dynamics of three-agent games

NASA Astrophysics Data System (ADS)

Mungan, Muhittin; Rador, Tonguç

2008-02-01

We study the dynamics and resulting score distribution of three-agent games where after each competition a single agent wins and scores a point. A single competition is described by a triplet of numbers p, t and q denoting the probabilities that the team with the highest, middle or lowest accumulated score wins. The three-agent game can be regarded as a social model where a player can be favored or disfavored for advancement, based on his/her accumulated score. We study the full family of solutions in the regime, where the number of agents and competitions is large, which can be regarded as a hydrodynamic limit. Depending on the parameter values (p, q, t), we find six qualitatively different asymptotic score distributions and we provide a qualitative explanation of these results. We also compare our analytical results against numerical simulations of the microscopic model and find these to be in excellent agreement. It is possible to decide the outcome of a three-agent game through a mini-tournament of two-agent competitions among the participating players and it turns out that the resulting possible score distributions are a subset of those obtained for the general three-agent games. We discuss how one can add a steady and democratic decline rate to the model and present a simple geometric construction that allows one to obtain the score evolution equations for n-agent games.

Single-walled carbon nanotubes-ciprofloxacin nanoantibiotic: strategy to improve ciprofloxacin antibacterial activity.

PubMed

Assali, Mohyeddin; Zaid, Abdel Naser; Abdallah, Farah; Almasri, Motasem; Khayyat, Rasha

2017-01-01

As infectious diseases continue to be one of the greatest health challenges worldwide, the demand toward alternative agents is continuously increasing. Recent advancement in nanotechnology has expanded our ability to design and construct nanomaterials to treat bacterial infections. Carbon nanotubes are one among these nanomaterials. Herein, we describe the covalent functionalization of the single-walled carbon nanotubes (SWCNTs) with multiple molecules of ciprofloxacin. The prepared nanoantibiotics were characterized using different techniques, including transmission electron microscopy, Raman spectroscopy, and thermogravimetric analysis. The characterization of the nanoantibiotics confirmed the successful covalent functionalization of the SWCNTs with 55% of functionalization as has been observed by thermogravimetric analysis. The release profile revealed that 90% of the loaded ciprofloxacin was released within 2.5 h at pH 7.4 showing a first-order release profile with R 2 >0.99. Interestingly, the results of the antibacterial activity indicated that the functionalized SWCNTs have significant increase in the antibacterial activity against the three strains of bacteria - by 16-fold for Staphylococcus aureus and Pseudomonas aeruginosa and by 8-fold for Escherichia coli - in comparison to the ciprofloxacin free drug. Moreover, the synthesized nanoantibiotic showed high hemocompatibility and cytocompatibility over a wide concentration range.

Pharmacological activity and toxicity of some neurotropic agents under conditions of experimental hypodynamia

NASA Technical Reports Server (NTRS)

Kirichek, L. T.

1980-01-01

The indices of pharmacological range, risk coefficients, ED50, LD50, the size of the area of toxic activity, and maximal tolerated and absolute lethal doses were compared in hypodynamic mice. The pharmacological activity of the test neurotropic agents exhibiting a central action underwent change, but their toxicity remained unchanged.

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.

Model reduction for agent-based social simulation: coarse-graining a civil violence model.

PubMed

Zou, Yu; Fonoberov, Vladimir A; Fonoberova, Maria; Mezic, Igor; Kevrekidis, Ioannis G

2012-06-01

Agent-based modeling (ABM) constitutes a powerful computational tool for the exploration of phenomena involving emergent dynamic behavior in the social sciences. This paper demonstrates a computer-assisted approach that bridges the significant gap between the single-agent microscopic level and the macroscopic (coarse-grained population) level, where fundamental questions must be rationally answered and policies guiding the emergent dynamics devised. Our approach will be illustrated through an agent-based model of civil violence. This spatiotemporally varying ABM incorporates interactions between a heterogeneous population of citizens [active (insurgent), inactive, or jailed] and a population of police officers. Detailed simulations exhibit an equilibrium punctuated by periods of social upheavals. We show how to effectively reduce the agent-based dynamics to a stochastic model with only two coarse-grained degrees of freedom: the number of jailed citizens and the number of active ones. The coarse-grained model captures the ABM dynamics while drastically reducing the computation time (by a factor of approximately 20).

Model reduction for agent-based social simulation: Coarse-graining a civil violence model

NASA Astrophysics Data System (ADS)

Zou, Yu; Fonoberov, Vladimir A.; Fonoberova, Maria; Mezic, Igor; Kevrekidis, Ioannis G.

2012-06-01

Agent-based modeling (ABM) constitutes a powerful computational tool for the exploration of phenomena involving emergent dynamic behavior in the social sciences. This paper demonstrates a computer-assisted approach that bridges the significant gap between the single-agent microscopic level and the macroscopic (coarse-grained population) level, where fundamental questions must be rationally answered and policies guiding the emergent dynamics devised. Our approach will be illustrated through an agent-based model of civil violence. This spatiotemporally varying ABM incorporates interactions between a heterogeneous population of citizens [active (insurgent), inactive, or jailed] and a population of police officers. Detailed simulations exhibit an equilibrium punctuated by periods of social upheavals. We show how to effectively reduce the agent-based dynamics to a stochastic model with only two coarse-grained degrees of freedom: the number of jailed citizens and the number of active ones. The coarse-grained model captures the ABM dynamics while drastically reducing the computation time (by a factor of approximately 20).

Time-Extended Policies in Mult-Agent Reinforcement Learning

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian K.

2004-01-01

Reinforcement learning methods perform well in many domains where a single agent needs to take a sequence of actions to perform a task. These methods use sequences of single-time-step rewards to create a policy that tries to maximize a time-extended utility, which is a (possibly discounted) sum of these rewards. In this paper we build on our previous work showing how these methods can be extended to a multi-agent environment where each agent creates its own policy that works towards maximizing a time-extended global utility over all agents actions. We show improved methods for creating time-extended utilities for the agents that are both "aligned" with the global utility and "learnable." We then show how to crate single-time-step rewards while avoiding the pi fall of having rewards aligned with the global reward leading to utilities not aligned with the global utility. Finally, we apply these reward functions to the multi-agent Gridworld problem. We explicitly quantify a utility's learnability and alignment, and show that reinforcement learning agents using the prescribed reward functions successfully tradeoff learnability and alignment. As a result they outperform both global (e.g., team games ) and local (e.g., "perfectly learnable" ) reinforcement learning solutions by as much as an order of magnitude.

Sensitive detection of chemical agents and toxic industrial chemicals using active open-path FTIRs

NASA Astrophysics Data System (ADS)

Walter, William T.

2004-03-01

Active open-path FTIR sensors provide more sensitive detection of chemical agents than passive FTIRs, such as the M21 RSCAAL and JSLSCAD, and at the same time identify and quantify toxic industrial chemicals (TIC). Passive FTIRs are bistatic sensors relying on infrared sources of opportunity. Utilization of earth-based sources of opportunity limits the source temperatures available for passive chemical-agent FTIR sensors to 300° K. Active FTIR chemical-agent sensors utilize silicon carbide sources, which can be operated at 1500° K. The higher source temperature provides more than an 80-times increase in the infrared radiant flux emitted per unit area in the 7 to 14 micron spectral fingerprint region. Minimum detection limits are better than 5 μgm/m3 for GA, GB, GD, GF and VX. Active FTIR sensors can (1) assist first responders and emergency response teams in their assessment of and reaction to a terrorist threat, (2) provide information on the identification of the TIC present and their concentrations and (3) contribute to the understanding and prevention of debilitating disorders analogous to the Gulf War Syndrome for military and civilian personnel.

Towards optical control of single blood platelet activation

NASA Astrophysics Data System (ADS)

Spiryova, Darya V.; Karmatskih, Oleg Yu.; Vorob'ev, Alexei Yu.; Moskalensky, Alexander E.

2018-04-01

Blood platelets play a pivotal role in blood coagulation and in other normal and pathological processes. The understanding of fundamental mechanisms underlying their functions is very important for diagnostics and treatment. Single-cell experiments are needed for this purpose, which are complicated by insufficient spatiotemporal precision of conventional activation protocols. We present an approach to trigger single platelet activation optically, without the need of reagent mixing. This is achieved using photolabile compound, which rapidly delivers epinephrine upon UV irradiation. We demonstrated the applicability of the technique to rapidly induce platelet activation for studying dynamics of activation. The presented method may give novel fundamental knowledge about platelet functions and facilitate current research of their ability to deliver drugs to tumors or vascular injury sites.

Socializing Agents for Sport and Physical Activities in Teenage Students: Comparative Studies in Samples From Costa Rica, Mexico, and Spain.

PubMed

Ruiz-Juan, Francisco; Baena-Extremera, Antonio; Granero-Gallegos, Antonio

2017-01-01

The aim of this study is to analyze a set of socializing agents for sport and physical activities and to establish their relationship with leisure time sport and physical activities behaviors and practice patterns in samples of teenage students with different sociocultural backgrounds. The sample included 2168 students in their first year of secondary education, 423 of them being from Costa Rica, 408 from Mexico, and 1337 from Spain (1052 male students, 1037 female students, and 79 students who did not specify gender) aged 11-16 years old ( M = 12.49; SD = .81). A validated questionnaire with questions about leisure time sport and physical activities and socializing agents was used. Descriptive, inferential, and multinomial logistic regression analyses were carried out with SPSS 17.0 to compare all three countries. Costa Rica had the most active students, best friends' inactivity, and unsupportive parents being the agents predicting inactivity and a low level of sport and physical activities. Mexico has a high dropout rate and inactive students exceed active ones; no agent predicts inactivity or sport and physical activities pattern. Spain has the highest level of sport and physical activities practice, and parents, siblings, and friends are predicting agents of inactivity together with unsupportive parents and friends.

Virucidal activity of chemical biocides against mimivirus, a putative pneumonia agent.

PubMed

Campos, Rafael Kroon; Andrade, Ketyllen Reis; Ferreira, Paulo Cesar Peregrino; Bonjardim, Cláudio Antônio; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

2012-12-01

Acanthamoeba polyphaga mimivirus (APMV), the largest known virus, has been studied as a putative pneumonia agent, especially in hospital environments. Despite the repercussions of the discovery of APMV, there has been no study related to the control of APMV and the susceptibility of this virus to disinfectants. This work investigated the virucidal activity against mimivirus of chemical biocides commonly used in clinical practice for the disinfection of hospital equipment and rooms. APMV was dried on sterilized steel coupons, exposed to different concentrations of alcohols (ethanol, 1-propanol and 2-propanol) and commercial disinfectants (active chlorine, glutaraldehyde and benzalkonium chloride) and titrated in amoebas using the TCID50 value. The stability of APMV on an inanimate surface was also tested in the presence and absence of organic matter for 30 days. APMV showed a high level of resistance to chemical biocides, especially alcohols. Only active chlorine and glutaraldehyde were able to decrease the APMV titers to undetectable levels. Dried APMV showed long-lasting stability on an inanimate surface (30 days), even in the absence of organic matter. The data presented herein may help health and laboratory workers plan the best strategy to control this putative pneumonia agent from surfaces and devices. Copyright © 2012 Elsevier B.V. All rights reserved.

Parenting Outcomes of Single Active Duty Postpartum Women

DTIC Science & Technology

1998-04-15

Single active duty mothers face many of the same stressors as civilian single parents, including role strain, child care issues, and lack of...discretionary time. Child care is a difficult issue for single parents who need care that is flexible, convenient, and available at a reasonable cost...Deployments, work related travel, shift work, and relocations pose additional and unique problems for child care arrangements for military (Wahl & Randall

Single Agent Nanoparticle for Radiotherapy and Radio-Photothermal Therapy in Anaplastic Thyroid Cancer

PubMed Central

Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y.; Li, Chun

2015-01-01

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [64Cu]CuS NPs, in which the radiotherapeutic property of 64Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG[64Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[64Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[64Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC. PMID:25913249

Pharmacological management of anticancer agent extravasation: A single institutional guideline.

PubMed

Kimmel, Jaime; Fleming, Patrick; Cuellar, Sandra; Anderson, Jennifer; Haaf, Christina Mactal

2018-03-01

Although the risk of extravasation of a chemotherapy (anticancer) medication is low, the complications associated with these events can have a significant impact on morbidity and health care costs. Institutions that administer anticancer agents should ideally have a current guideline on the proper management of the inadvertent administration of these toxic medications into tissues surrounding blood vessels. It is imperative that the health care team involved in administering drugs used to treat cancer be educated on the risk factors, preventative strategies and treatment of anticancer extravasations, as well as practice safe and proper administration techniques. Anticancer agents are generally divided into classes based on their ability to cause tissue damage. The review of current published guidelines and available literature reveals a lack of consensus on how these medications should be classified. In addition, many recently approved drugs for the treatment of cancer may lack data to support their classification and management of extravasation events. The treatment of the majority of extravasations of anticancer agents involves nonpharmacological measures, potentially in the ambulatory care setting. Antidotes are available for the extravasation of a minority of vesicant agents in order to mitigate tissue damage. Due to the limited data and lack of consensus in published guidelines, a working group was established to put forth an institutional guideline on the management of anticancer extravasations.

Decontamination of adsorbed chemical warfare agents on activated carbon using hydrogen peroxide solutions.

PubMed

Osovsky, Ruth; Kaplan, Doron; Nir, Ido; Rotter, Hadar; Elisha, Shmuel; Columbus, Ishay

2014-09-16

Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in protective garments and air filters. Better than 95% decomposition of adsorbed sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1-24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD-sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis under these conditions is attributed to the microenvironment of the micropores. Apparently, the reactions are favored due to basic sites on the carbon surface. Our findings suggest a potential environmentally friendly route for decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or activators.

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

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

Halbrook, R.S.; Shugart, L.R.; Watson, A.P.

1992-09-01

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. Amore » framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.« less

Study on the influence of the decoking agent on the activity of limestone in wet flue gas desulfurization

NASA Astrophysics Data System (ADS)

Li, Qianjun; Xu, Dongyang; Wu, Yunxia; Yu, Jin

2017-01-01

Influence of the main components of decoking agent (magnesium nitrate, aluminum nitrate, copper nitrate, ammonium nitrate and actual decoking agent) on the activity of limestone is studied in laboratory by MET method. Results show that magnesium nitrate, ammonium nitrate and copper nitrate almost has no effect on the activity of limestone. With the concentration increasing, aluminum nitrate has an increasing inhibition on the dissolution of limestone. Fly ash has inhibition on dissolution of limestone due to the blockage of limestone pore by fly ash. The actual decoking agent has almost no effect on the limestone.

Tolerance of dormant and active cells in Pseudomonas aeruginosa PA01 biofilm to antimicrobial agents.

PubMed

Kim, Jaeeun; Hahn, Ji-Sook; Franklin, Michael J; Stewart, Philip S; Yoon, Jeyong

2009-01-01

The aim of the study was to determine the susceptibility of active and dormant cell populations from Pseudomonas aeruginosa biofilms to non-antibiotic antimicrobial agents such as chlorine, hydrogen peroxide and silver ions in comparison with antibiotics. Active cells in colony biofilm were differentially labelled by induction of a green fluorescent protein (GFP). Active and dormant cells were sorted in phosphate buffered solution by flow cytometry. Reductions in viability were determined with plate counts. The spatial pattern of metabolic activity in colony biofilm was verified, and the active and dormant cells were successfully sorted according to the GFP intensity. Active cells had bigger cell size and higher intracellular density than dormant cells. While dormant cells were more tolerant to tobramycin and silver ions, active cells were more tolerant to chlorine. Metabolically active cells contain denser intracellular components that can react with highly reactive oxidants such as chlorine, thereby reducing the available concentrations of chlorine. In contrast, the concentrations of silver ions and hydrogen peroxide were constant during treatment. Aerobically grown stationary cells were significantly more tolerant to chlorine unlike other antimicrobial agents. Chlorine was more effective in inactivation of metabolically inactive dormant cells and also more effective under anaerobic conditions. The high oxidative reactivity and rapid decay of chlorine might influence the different antimicrobial actions of chlorine compared with antibiotics. This study contributes to understanding the effects of dormancy and the presence of oxygen on the susceptibility of P. aeruginosa biofilm to a wide range of antimicrobial agents.

Progressing single biomolecule force spectroscopy measurements for the screening of DNA binding agents

NASA Astrophysics Data System (ADS)

Zhang, Wenke; Barbagallo, Romina; Madden, Claire; Roberts, Clive J.; Woolford, Alison; Allen, Stephanie

2005-10-01

Recent studies have indicated that the force-extension properties of single molecules of double stranded (ds) DNA are sensitive to the presence of small molecule DNA binding agents, and also to their mode of binding. These observations raise the possibility of using this approach as a highly sensitive tool for the screening of such agents. However, particularly for studies employing the atomic force microscope (AFM), several non-trivial barriers hinder the progress of this approach to the non-specialist arena and hence also the full realization of this possibility. In this paper, we therefore address a series of key reproducibility and metrological issues associated with this type of measurement. Specifically, we present an improved immobilization method that covalently anchors one end (5' end) of a dual labelled (5'-thiol, 3'-biotin) p53 DNA molecule onto a gold substrate via gold-thiol chemistry, whilst the biotinylated 3' end is available for 'pick-up' using a streptavidin modified AFM tip. We also show that co-surface immobilization of DNA with 6-mercapto-1-hexanol (MCH) can also lead to a further increase the measured contour length. We demonstrate the impact of these improved protocols through the observation of the cooperative transition plateau in a DNA fragment of approximately 118 bp, a significantly smaller fragment than previously investigated. The results of a comparative study of the effects of a model minor groove binder (Hoechst 33258) and an intercalating drug (proflavine), alone, as a mixture and under different buffer conditions, are also presented.

Ginsenosides as Anticancer Agents: In vitro and in vivo Activities, Structure–Activity Relationships, and Molecular Mechanisms of Action

PubMed Central

Nag, Subhasree Ashok; Qin, Jiang-Jiang; Wang, Wei; Wang, Ming-Hai; Wang, Hui; Zhang, Ruiwen

2012-01-01

Conventional chemotherapeutic agents are often toxic not only to tumor cells but also to normal cells, limiting their therapeutic use in the clinic. Novel natural product anticancer compounds present an attractive alternative to synthetic compounds, based on their favorable safety and efficacy profiles. Several pre-clinical and clinical studies have demonstrated the anticancer potential of Panax ginseng, a widely used traditional Chinese medicine. The anti-tumor efficacy of ginseng is attributed mainly to the presence of saponins, known as ginsenosides. In this review, we focus on how ginsenosides exert their anticancer effects by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (c-myc, EGFR, and vascular endothelial growth factor), tumor suppressors (p53 and p21), oncogenes (MDM2), cell death mediators (Bcl-2, Bcl-xL, XIAP, caspases, and death receptors), inflammatory response molecules (NF-κB and COX-2), and protein kinases (JNK, Akt, and AMP-activated protein kinase). We also discuss the structure–activity relationship of various ginsenosides and their potentials in the treatment of various human cancers. In summary, recent advances in the discovery and evaluation of ginsenosides as cancer therapeutic agents support further pre-clinical and clinical development of these agents for the treatment of primary and metastatic tumors. PMID:22403544

Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis.

PubMed

Danese, Silvio; Fiorino, Gionata; Peyrin-Biroulet, Laurent; Lucenteforte, Ersilia; Virgili, Gianni; Moja, Lorenzo; Bonovas, Stefanos

2014-05-20

Biological agents are emerging treatment options for the management of ulcerative colitis (UC). To assess the comparative efficacy and harm of biological agents in adult patients with moderately to severely active UC who are naive to biological agents. MEDLINE, EMBASE, and Cochrane Library from inception through December 2013, without language restrictions, and ClinicalTrials.gov, European Medicines Agency, and U.S. Food and Drug Administration Web sites. Randomized, placebo-controlled or head-to-head trials assessing biological agents as induction or maintenance therapy for moderately to severely active UC. Two reviewers independently abstracted study data and outcomes and rated each trial's risk of bias. There were no head-to-head trials. There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo. Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials. Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.

In Vitro Activities of 35 Double Combinations of Antifungal Agents against Scedosporium apiospermum and Scedosporium prolificans▿

PubMed Central

Cuenca-Estrella, Manuel; Alastruey-Izquierdo, Ana; Alcazar-Fuoli, Laura; Bernal-Martinez, Leticia; Gomez-Lopez, Alicia; Buitrago, Maria J.; Mellado, Emilia; Rodriguez-Tudela, Juan L.

2008-01-01

Activities of 35 combinations of antifungal agents against Scedosporium spp. were analyzed by a checkerboard microdilution design and the summation of fractional concentration index. An average indifferent effect was detected apart from combinations of azole agents and echinocandins against Scedosporium apiospermum. Antagonism was absent for all antifungal combinations against both species. PMID:18195067

Single-walled carbon nanotubes-ciprofloxacin nanoantibiotic: strategy to improve ciprofloxacin antibacterial activity

PubMed Central

Assali, Mohyeddin; Zaid, Abdel Naser; Abdallah, Farah; Almasri, Motasem; Khayyat, Rasha

2017-01-01

As infectious diseases continue to be one of the greatest health challenges worldwide, the demand toward alternative agents is continuously increasing. Recent advancement in nanotechnology has expanded our ability to design and construct nanomaterials to treat bacterial infections. Carbon nanotubes are one among these nanomaterials. Herein, we describe the covalent functionalization of the single-walled carbon nanotubes (SWCNTs) with multiple molecules of ciprofloxacin. The prepared nanoantibiotics were characterized using different techniques, including transmission electron microscopy, Raman spectroscopy, and thermogravimetric analysis. The characterization of the nanoantibiotics confirmed the successful covalent functionalization of the SWCNTs with 55% of functionalization as has been observed by thermogravimetric analysis. The release profile revealed that 90% of the loaded ciprofloxacin was released within 2.5 h at pH 7.4 showing a first-order release profile with R2>0.99. Interestingly, the results of the antibacterial activity indicated that the functionalized SWCNTs have significant increase in the antibacterial activity against the three strains of bacteria – by 16-fold for Staphylococcus aureus and Pseudomonas aeruginosa and by 8-fold for Escherichia coli – in comparison to the ciprofloxacin free drug. Moreover, the synthesized nanoantibiotic showed high hemocompatibility and cytocompatibility over a wide concentration range. PMID:28924348

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

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

[Effect of prokinetic agents on the electrical activity of stomach and duodenum in rats].

PubMed

Li, Fujun; Zou, Yiyou; Huang, Tianhui

2009-07-01

To determine the effect of prokinetic agents such as domperidone, mosapride, clarithromycin, and itopride on the electrical activity of the stomach and duodenum in SD rats,and also to explore the mechanism. The organism functional experiment system BL-420E was used to record the myoelectrical activity in the stomach and duodenum of SD rats in all groups using domperidone, mosapride, itopride, clarithromycin, and physiological saline on the interdigestive phase. The effect of the prokinetic agents on the amplitude and frequency of gastric and duodenal electromyogram in the SD rats was compared. The antagonists such as atropine, phentolamine, and propranolol were added to investigate the mechanism of action with all prokinetic agents. All prokinetic agents increased the amplitude and frequency of gastric and duodenal fast waves in the SD rats(P<0.05). The effect of itopride was the most obvious among the 3 groups (P<0.05),and clarithromycin had the weakest effect(P<0.05). The amplitude and frequency of gastric and duodenal fast waves in the SD rats in the groups of clarithromycin,domperidone,mosapride, itopride, and physiological saline were inhibited by atropine(P<0.05),but not by phentolamine and propranolol. Itopride, mosapride, domperidone, and clarithromycin can increase the amplitude and frequency of gastric and duodenal fast waves in the SD rats. The mechanism may be related to cholinergic receptors, but not adrenergic receptors.

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

Learning Activity Models for Multiple Agents in a Smart Space

NASA Astrophysics Data System (ADS)

Crandall, Aaron; Cook, Diane J.

With the introduction of more complex intelligent environment systems, the possibilities for customizing system behavior have increased dramatically. Significant headway has been made in tracking individuals through spaces using wireless devices [1, 18, 26] and in recognizing activities within the space based on video data (see chapter by Brubaker et al. and [6, 8, 23]), motion sensor data [9, 25], wearable sensors [13] or other sources of information [14, 15, 22]. However, much of the theory and most of the algorithms are designed to handle one individual in the space at a time. Resident tracking, activity recognition, event prediction, and behavior automation becomes significantly more difficult for multi-agent situations, when there are multiple residents in the environment.

Agent Based Intelligence in a Tetrahedral Rover

NASA Technical Reports Server (NTRS)

Phelps, Peter; Truszkowski, Walt

2007-01-01

A tetrahedron is a 4-node 6-strut pyramid structure which is being used by the NASA - Goddard Space Flight Center as the basic building block for a new approach to robotic motion. The struts are extendable; it is by the sequence of activities: strut-extension, changing the center of gravity and falling that the tetrahedron "moves". Currently, strut-extension is handled by human remote control. There is an effort underway to make the movement of the tetrahedron autonomous, driven by an attempt to achieve a goal. The approach being taken is to associate an intelligent agent with each node. Thus, the autonomous tetrahedron is realized as a constrained multi-agent system, where the constraints arise from the fact that between any two agents there is an extendible strut. The hypothesis of this work is that, by proper composition of such automated tetrahedra, robotic structures of various levels of complexity can be developed which will support more complex dynamic motions. This is the basis of the new approach to robotic motion which is under investigation. A Java-based simulator for the single tetrahedron, realized as a constrained multi-agent system, has been developed and evaluated. This paper reports on this project and presents a discussion of the structure and dynamics of the simulator.

A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection*

PubMed Central

Vrentas, Catherine E.; Moayeri, Mahtab; Keefer, Andrea B.; Greaney, Allison J.; Tremblay, Jacqueline; O'Mard, Danielle; Leppla, Stephen H.; Shoemaker, Charles B.

2016-01-01

Infection with Bacillus anthracis, the causative agent of anthrax, can lead to persistence of lethal secreted toxins in the bloodstream, even after antibiotic treatment. VHH single-domain antibodies have been demonstrated to neutralize diverse bacterial toxins both in vitro and in vivo, with protein properties such as small size and high stability that make them attractive therapeutic candidates. Recently, we reported on VHHs with in vivo activity against the protective antigen component of the anthrax toxins. Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to the edema factor (EF) and/or lethal factor (LF) components. Six of these VHHs are cross-reactive against both EF and LF and recognize the N-terminal domain (LFN, EFN) of their target(s) with subnanomolar affinity. The cross-reactive VHHs block binding of EF/LF to the protective antigen C-terminal binding interface, preventing toxin entry into the cell. Another VHH appears to recognize the LF C-terminal domain and exhibits a kinetic effect on substrate cleavage by LF. A subset of the VHHs neutralized against EF and/or LF in murine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spore model of anthrax infection. Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against lethal anthrax spore infection in mice as a single dose. This set of VHHs should facilitate development of new therapeutic VNAs and/or diagnostic agents for anthrax. PMID:27539858

A monofunctional platinum(II)-based anticancer agent from a salicylanilide derivative: Synthesis, antiproliferative activity, and transcription inhibition.

PubMed

Wang, Beilei; Wang, Zhigang; Ai, Fujin; Tang, Wai Kin; Zhu, Guangyu

2015-01-01

Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis-[Pt(NH3)2(N-donor)Cl](+) have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo. Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA-Pt containing a bulky salicylanilide moiety. The antiproliferative activity of SA-Pt was close to that of cisplatin. Mechanism studies revealed that SA-Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes. Copyright © 2014 Elsevier Inc. All rights reserved.

Engineered contrast agents in a single structure for T1-T2 dual magnetic resonance imaging.

PubMed

Cabrera-García, Alejandro; Checa-Chavarria, Elisa; Pacheco-Torres, Jesús; Bernabeu-Sanz, Ángela; Vidal-Moya, Alejandro; Rivero-Buceta, Eva; Sastre, Germán; Fernández, Eduardo; Botella, Pablo

2018-04-05

The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T1-T2 dual-mode relaxivity requires the accurate assembly of T1 and T2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)4[Fe(CN)6] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)4[Fe(CN)6]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T1- and T2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.

Balancing the stability and the catalytic specificities of OP hydrolases with enhanced V-agent activities.

PubMed

Reeves, T E; Wales, M E; Grimsley, J K; Li, P; Cerasoli, D M; Wild, J R

2008-06-01

Rational site-directed mutagenesis and biophysical analyses have been used to explore the thermodynamic stability and catalytic capabilities of organophosphorus hydrolase (OPH) and its genetically modified variants. There are clear trade-offs in the stability of modifications that enhance catalytic activities. For example, the H254R/H257L variant has higher turnover numbers for the chemical warfare agents VX (144 versus 14 s(-1) for the native enzyme (wild type) and VR (Russian VX, 465 versus 12 s(-1) for wild type). These increases are accompanied by a loss in stability in which the total Gibb's free energy for unfolding is 19.6 kcal/mol, which is 5.7 kcal/mol less than that of the wild-type enzyme. X-ray crystallographic studies support biophysical data that suggest amino acid residues near the active site contribute to the chemical and thermal stability through hydrophobic and cation-pi interactions. The cation-pi interactions appear to contribute an additional 7 kcal/mol to the overall global stability of the enzyme. Using rational design, it has been possible to make amino acid changes in this region that restored the stability, yet maintained effective V-agent activities, with turnover numbers of 68 and 36 s(-1) for VX and VR, respectively. This study describes the first rationally designed, stability/activity balance for an OPH enzyme with a legitimate V-agent activity, and its crystal structure.

Molluscicidal properties and selective toxicity of surface-active agents

PubMed Central

Visser, S. A.

1965-01-01

Of over 100 commercially produced surface-active agents tested against the bilharziasis vector snail Biomphalaria sudanica, 13 were found to possess considerable and highly selective molluscicidal properties at concentrations of less than 1 ppm for exposures of 48 hours. Against crustacea, fish, water plants, mosquito larvae, mice, and the eggs of B. sudanica, the toxicities of the 13 surfactants were slight. The chemicals did not appear to be absorbed by organic matter to any appreciable extent. It is thought that the toxicity to B. sudanica is of both a chemical and a physical nature. PMID:5294185

A randomized open-label study of guideline-driven antiemetic therapy versus single agent antiemetic therapy in patients with advanced cancer and nausea not related to anticancer treatment.

PubMed

Hardy, Janet; Skerman, Helen; Glare, Paul; Philip, Jennifer; Hudson, Peter; Mitchell, Geoffrey; Martin, Peter; Spruyt, Odette; Currow, David; Yates, Patsy

2018-05-02

Nausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared. This randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score < 3/10 at 72 h. Nausea scores and distress from nausea improved over time in the majority of the 185 patients randomized. For those who completed each treatment day, a greater response rate was seen in the guideline arm than the single agent arm at 24 h (49% vs 32%; p = 0.02), but not at 48 or 72 h. Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59). Over 80% of all participants reported an improved global impression of change. There were few adverse events worse than baseline in either arm. An etiology-based, guideline-directed approach to antiemetic therapy may offer more rapid benefit, but is no better than single agent treatment with haloperidol at 72 h. Australian New Zealand Clinical Trials Registry: ANZCTRN12610000481077 .

Pharmacology of RG W-2938: a cardiotonic agent with vasodilator activity.

PubMed

Barrett, J A; Woltmann, R F; Swillo, R S; Kasiewski, C; Faith, W C; Campbell, H F; Perrone, M H

1990-10-01

The cardiovascular effects of RG W-2938, 6-[6-(3,4-dihydro-3-methyl-2(1H)-2-oxoquinazolinyl)]-4,5-dihydro-3 (2H-pyridazinone, a new nonglycoside, noncatecholamine cardiotonic/vasodilator agent were examined in vivo in anesthetized and conscious dogs and in vitro in isolated guinea pig hearts; in the latter, RG W-2938 5 nmol-5 mumol increased contractility in a dose-related fashion. RG W-2938 30-300 micrograms/kg administered intravenously (i.v.) to anesthetized dogs increased contractile force while decreasing arterial pressure and total peripheral resistance (TPR) in a dose-related manner. Heart rate (HR) was only slightly increased, and aortic flow was not appreciably altered. A single oral dose of RG W-2938 0.3 mg/kg administered to conscious chronically instrumented dogs produced a marked and sustained increase in contractility 15-240 min after treatment while only slightly increasing HR. The effects of RG W-2938 30-300 micrograms/kg, i.v. were studied in a mecamylamine-propranolol-induced model of heart failure. RG W-2938 effectively reversed the drug-induced heart failure by increasing myocardial contractility and decreasing arterial pressure while only slightly affecting HR. These studies show that RG W-2938 is an orally effective positive inotropic/vasodilator agent.

Conditionally activating optical contrast agent with enhanced sensitivity via gold nanoparticle plasmon energy transfer: feasibility study.

PubMed

Kang, Kyung Aih; Wang, Jianting

2014-12-07

Molecular sensing/imaging utilizing fluorophores has been one of the most frequently used techniques in biomedical research. As for any molecular imaging techniques, fluorescence mediated sensing always seeks for greater specificity and sensitivity. Since fluorophores emit fluorescence while their electron energy state changes, manipulating the local electromagnetic field around the fluorophores may be a way to enhance the specificity and sensitivity. Gold nanoparticles (GNPs) are known to form a very strong electromagnetic field on their surface [i.e., surface plasmon field (SPF)], upon receiving photonic energy. The level of fluorescence change by GNP-SPF may range from complete quenching to extensive enhancement, depending upon the SPF strength, excitation and emission wavelengths, and quantum yield of the fluorophore. Here, we report a novel design that utilizes BOTH fluorescence quenching and enhancement abilities of the GNP in one single nano-entity, providing high specificity and sensitivity. The construct utilizes a specially designed molecular dual-spacer that places the fluorphore at the location with an appropriate GNP-SFP strength before and after exposed to the biomarker. A model system to test the concept was an optical signal mediator activated by urokinase-type plasminogen activator (uPA; breast cancer secreting enzyme). The resulting contrast agent shows less than 10% of the natural fluorescence but, in the presence of uPA, its fluorescence emission is triggered and emits its fluorescence approximately twice of the natural form. This study demonstrated that our novel design of an optical contrast agent can be conditionally activated with enhanced sensitivity, using both quenching and enhancement phenomena of fluorophores in the electromagnetic field of the appropriate strengths (in this case, locally generated by the GNP-SPF). This entity is similar to molecular beacon in terms of specificity but with greater sensitivity. In addition, it is not

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

PubMed

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

2018-06-11

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

Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope

PubMed Central

Cremolini, Chiara; Aprile, Giuseppe; Lonardi, Sara; Orlandi, Armando; Mennitto, Alessia; Berenato, Rosa; Antoniotti, Carlotta; Casagrande, Mariaelena; Marsico, Valentina; Marmorino, Federica; Cardellino, Giovanni Gerardo; Bergamo, Francesca; Tomasello, Gianluca; Formica, Vincenzo; Longarini, Raffaella; Giommoni, Elisa; Caporale, Marta; Di Bartolomeo, Maria; Loupakis, Fotios; de Braud, Filippo

2015-01-01

Background. No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in “frail” elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC. Materials and Methods. Forty elderly patients (aged ≥75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results. The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9–8 months) and 14.3 months (95% CI: 10.9–17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%. Conclusion. Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data. Implications for Practice: Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could

Direct observation of frequency modulated transcription in single cells using light activation

PubMed Central

Larson, Daniel R; Fritzsch, Christoph; Sun, Liang; Meng, Xiuhau; Lawrence, David S; Singer, Robert H

2013-01-01

Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single steroid-responsive gene and follow dynamic synthesis of RNA from the activated locus. DOI: http://dx.doi.org/10.7554/eLife.00750.001 PMID:24069527

Preparation of active antibacterial LDPE surface through multistep physicochemical approach: I. Allylamine grafting, attachment of antibacterial agent and antibacterial activity assessment.

PubMed

Bílek, František; Křížová, Táňa; Lehocký, Marián

2011-11-01

Low-density polyethylene (LDPE) samples were treated in air plasma discharge, coated by polyallyamine brush thought copolymeric grafting surface-from reaction and deposited four common antibacterial agents (benzalkonium chloride, bronopol, chlorhexidine and triclosan) to gain material with active antibacterial properties. Surface characteristics were evaluated by static contact angle measurement with surface energy evaluation ATR-FTIR, X-ray Photoelectron Spectroscopy (XPS) and SEM analysis. Inhibition zone on agar was used as in vitro test of antibacterial properties on two representative gram positive Staphylococcus aureus (S. aureus) and gram negative Escherichia coli (E. coli) strains. It was confirmed, that after grafting of polyallyamine, more antibacterial agent is immobilized on the surface. The highest increase of antibacterial activity was observed by the sample containing triclosan. Samples covered by bronopol did not show significant antibacterial activity. Copyright © 2011 Elsevier B.V. All rights reserved.

Ribonuclease from Bacillus Acts as an Antiviral Agent against Negative- and Positive-Sense Single Stranded Human Respiratory RNA Viruses

PubMed Central

Müller, Christin; Romanova, Yulia; Mostafa, Ahmed; Ulyanova, Vera; Pleschka, Stephan; Ilinskaya, Olga

2017-01-01

Bacillus pumilus ribonuclease (binase) was shown to be a promising antiviral agent in animal models and cell cultures. However, the mode of its antiviral action remains unknown. To assess the binase effect on intracellular viral RNA we have selected single stranded negative- and positive-sense RNA viruses, influenza virus, and rhinovirus, respectively, which annually cause respiratory illnesses and are characterized by high contagious nature, mutation rate, and antigen variability. We have shown that binase exerts an antiviral effect on both viruses at the same concentration, which does not alter the spectrum of A549 cellular proteins and expression of housekeeping genes. The titers of influenza A (H1N1pdm) virus and human rhinovirus serotype 1A were reduced by 40% and 65%, respectively. A preincubation of influenza virus with binase before infection significantly reduced viral titer after single-cycle replication of the virus. Using influenza A virus mini genome system we showed that binase reduced GFP reporter signaling indicating a binase action on the expression of viral mRNA. Binase reduced the level of H1N1pdm viral NP mRNA accumulation in A549 cells by 20%. Since the viral mRNA is a possible target for binase this agent could be potentially applied in the antiviral therapy against both negative- and positive-sense RNA viruses. PMID:28546965

Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents.

PubMed

Cheng, Chia-Yi; Chang, Chun-Ping; Lauderdale, Tsai-Ling Yang; Yu, Guann-Yi; Lee, Jinq-Chyi; Jhang, Yi-Wun; Wu, Chien-Huang; Ke, Yi-Yu; Sadani, Amit A; Yeh, Ching-Fang; Huang, I-Wen; Kuo, Yi-Ping; Tsai, De-Jiun; Yeh, Teng-Kuang; Tseng, Chen-Tso; Song, Jen-Shin; Liu, Yu-Wei; Tsou, Lun K; Shia, Kak-Shan

2016-12-08

Series of N -substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N -substituted carbazoles as potential anti-MRSA agents.

Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents

PubMed Central

2016-01-01

Series of N-substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N-substituted carbazoles as potential anti-MRSA agents. PMID:27994762

Learning Sequences of Actions in Collectives of Autonomous Agents

NASA Technical Reports Server (NTRS)

Turner, Kagan; Agogino, Adrian K.; Wolpert, David H.; Clancy, Daniel (Technical Monitor)

2001-01-01

In this paper we focus on the problem of designing a collective of autonomous agents that individually learn sequences of actions such that the resultant sequence of joint actions achieves a predetermined global objective. We are particularly interested in instances of this problem where centralized control is either impossible or impractical. For single agent systems in similar domains, machine learning methods (e.g., reinforcement learners) have been successfully used. However, applying such solutions directly to multi-agent systems often proves problematic, as agents may work at cross-purposes, or have difficulty in evaluating their contribution to achievement of the global objective, or both. Accordingly, the crucial design step in multiagent systems centers on determining the private objectives of each agent so that as the agents strive for those objectives, the system reaches a good global solution. In this work we consider a version of this problem involving multiple autonomous agents in a grid world. We use concepts from collective intelligence to design goals for the agents that are 'aligned' with the global goal, and are 'learnable' in that agents can readily see how their behavior affects their utility. We show that reinforcement learning agents using those goals outperform both 'natural' extensions of single agent algorithms and global reinforcement, learning solutions based on 'team games'.

Quantifying activation of perfluorocarbon-based phase-change contrast agents using simultaneous acoustic and optical observation.

PubMed

Li, Sinan; Lin, Shengtao; Cheng, Yi; Matsunaga, Terry O; Eckersley, Robert J; Tang, Meng-Xing

2015-05-01

Phase-change contrast agents in the form of nanoscale droplets can be activated into microbubbles by ultrasound, extending the contrast beyond the vasculature. This article describes simultaneous optical and acoustical measurements for quantifying the ultrasound activation of phase-change contrast agents over a range of concentrations. In experiments, decafluorobutane-based nanodroplets of different dilutions were sonicated with a high-pressure activation pulse and two low-pressure interrogation pulses immediately before and after the activation pulse. The differences between the pre- and post-interrogation signals were calculated to quantify the acoustic power scattered by the microbubbles activated over a range of droplet concentrations. Optical observation occurred simultaneously with the acoustic measurement, and the pre- and post-microscopy images were processed to generate an independent quantitative indicator of the activated microbubble concentration. Both optical and acoustic measurements revealed linear relationships to the droplet concentration at a low concentration range <10(8)/mL when measured at body temperature. Further increases in droplet concentration resulted in saturation of the acoustic interrogation signal. Compared with body temperature, room temperature was found to produce much fewer and larger bubbles after ultrasound droplet activation. Copyright © 2015. Published by Elsevier Inc.

Network Interventions on Physical Activity in an Afterschool Program: An Agent-Based Social Network Study

PubMed Central

Zhang, Jun; Shoham, David A.; Tesdahl, Eric

2015-01-01

Objectives. We studied simulated interventions that leveraged social networks to increase physical activity in children. Methods. We studied a real-world social network of 81 children (average age = 7.96 years) who lived in low socioeconomic status neighborhoods, and attended public schools and 1 of 2 structured afterschool programs. The sample was ethnically diverse, and 44% were overweight or obese. We used social network analysis and agent-based modeling simulations to test whether implementing a network intervention would increase children’s physical activity. We tested 3 intervention strategies. Results. The intervention that targeted opinion leaders was effective in increasing the average level of physical activity across the entire network. However, the intervention that targeted the most sedentary children was the best at increasing their physical activity levels. Conclusions. Which network intervention to implement depends on whether the goal is to shift the entire distribution of physical activity or to influence those most adversely affected by low physical activity. Agent-based modeling could be an important complement to traditional project planning tools, analogous to sample size and power analyses, to help researchers design more effective interventions for increasing children’s physical activity. PMID:25689202

In Vitro Activities of the Everninomicin SCH 27899 and Other Newer Antimicrobial Agents against Borrelia burgdorferi

PubMed Central

Dever, Lisa L.; Torigian, Christine V.; Barbour, Alan G.

1999-01-01

The in vitro activity of the everninomicin antibiotic SCH 27899 against 17 isolates of Borrelia spp. was investigated. MICs ranged from 0.06 to 0.5 μg/ml. Time-kill studies with the B31 strain of B. burgdorferi demonstrated ≥3-log10-unit killing after 72 h with concentrations representing four times the MIC. The in vitro activity of four other newer antimicrobial agents, meropenem, cefepime, quinupristin-dalfopristin, and linezolid, was also tested against the B31 strain. Meropenem was the most potent of the latter agents, with an MIC of 0.125 μg/ml. PMID:10390242

Combinatorial synthesis and in vitro evaluation of a biaryl hydroxyketone library as antivirulence agents against MRSA.

PubMed

Yu, Guanping; Kuo, David; Shoham, Menachem; Viswanathan, Rajesh

2014-02-10

Antibiotic resistance coupled with decreased development of new antibiotics necessitates the search for novel antibacterial agents. Antivirulence agents offer an alternative to conventional antibiotics. In this work, we report on a family of small-molecule antivirulence agents against methicillin-resistant Staphylococcus aureus (MRSA), the most widespread bacterial pathogen. Structure-activity relationship studies led to the development of a concise synthesis of a 148-member biarylhydroxyketone library. An acylation bond-forming process afforded resorcinols (1) and aryloxy acetonitriles (2) as synthons. A Lewis-acid-activated Friedel-Crafts' acylation step involving a nitrile functionality of 2 by ZnCl2, followed by nucleophilic attack by 1 was executed to obtain biaryl hydroxyketones in excellent yields. A large number of products crystallized. This strategy affords a range of biarylhydroxyketones in a single step. This is the first collective synthetic study documenting access to this class of compounds through a single synthetic operation. In vitro efficacy of compounds in this library was evaluated by a rabbit erythrocyte hemolysis assay. The most efficacious compound, 4f-12, inhibits hemolysis by 98.1 ± 0.1% compared to control in the absence of the compound.

Iron-montmorillonite clays as active sorbents for the decontamination of hazardous chemical warfare agents.

PubMed

Carniato, F; Bisio, C; Evangelisti, C; Psaro, R; Dal Santo, V; Costenaro, D; Marchese, L; Guidotti, M

2018-02-27

A class of heterogeneous catalysts based on commercial bentonite from natural origin, containing at least 80 wt% of montmorillonite clay, was designed to transform selectively and under mild conditions toxic organosulfur and organophosphorus chemical warfare agents into non-noxious products with a reduced impact on health and environment. The bentonite from the natural origin was modified by introducing iron species and acid sites in the interlayer space, aiming to obtain a sorbent with strong catalytic oxidising and hydrolytic properties. The catalytic performance of these materials was evaluated in the oxidative abatement of (2-chloroethyl)ethyl sulfide (CEES), a simulant of sulfur mustard, in the presence of aqueous hydrogen peroxide as an oxidant. A new decontamination formulation was, moreover, proposed and obtained by mixing sodium perborate, as a solid oxidant, to iron-bentonite catalysts. Solid-phase decontamination tests, performed on a cotton textile support contaminated with organosulfide and organophosphonate simulant agents revealed the good activity of the solid formulation, especially in the in situ detoxification of blistering agents. Tests carried out on the real blistering warfare agent, sulfur mustard (HD agent), showed that, thanks to the co-presence of the iron-based clay together with the solid oxidant component, a good decontamination of the test surface from the real warfare agent could be achieved (80% contaminant degradation, under ambient conditions, in 24 h).

Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience.

PubMed

Suprasert, Prapaporn; Manopunya, Manatsawee; Cheewakriangkrai, Chalong

2014-01-01

Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

NASA Technical Reports Server (NTRS)

Andrews, R. J.

1999-01-01

The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved

Physical Activity Experiences and Beliefs among Single Mothers: A Qualitative Study

ERIC Educational Resources Information Center

Dlugonski, Deirdre; Motl, Robert W.

2016-01-01

Purpose: Single motherhood has been associated with negative health consequences such as depression and cardiovascular disease. Physical activity might reduce these consequences, but little is known about physical activity experiences and beliefs that might inform interventions and programs for single mothers. The present study used…

Strain mapping in single-layer two-dimensional crystals via Raman activity

NASA Astrophysics Data System (ADS)

Yagmurcukardes, M.; Bacaksiz, C.; Unsal, E.; Akbali, B.; Senger, R. T.; Sahin, H.

2018-03-01

By performing density functional theory-based ab initio calculations, Raman-active phonon modes of single-layer two-dimensional (2D) materials and the effect of in-plane biaxial strain on the peak frequencies and corresponding activities of the Raman-active modes are calculated. Our findings confirm the Raman spectrum of the unstrained 2D crystals and provide expected variations in the Raman-active modes of the crystals under in-plane biaxial strain. The results are summarized as follows: (i) frequencies of the phonon modes soften (harden) under applied tensile (compressive) strains; (ii) the response of the Raman activities to applied strain for the in-plane and out-of-plane vibrational modes have opposite trends, thus, the built-in strains in the materials can be monitored by tracking the relative activities of those modes; (iii) in particular, the A peak in single-layer Si and Ge disappears under a critical tensile strain; (iv) especially in mono- and diatomic single layers, the shift of the peak frequencies is a stronger indication of the strain rather than the change in Raman activities; (v) Raman-active modes of single-layer ReX2 (X =S , Se) are almost irresponsive to the applied strain. Strain-induced modifications in the Raman spectrum of 2D materials in terms of the peak positions and the relative Raman activities of the modes could be a convenient tool for characterization.

Regulation of the nitric oxide oxidase activity of myeloperoxidase by pharmacological agents.

PubMed

Maiocchi, Sophie L; Morris, Jonathan C; Rees, Martin D; Thomas, Shane R

2017-07-01

The leukocyte-derived heme enzyme myeloperoxidase (MPO) is released extracellularly during inflammation and impairs nitric oxide (NO) bioavailability by directly oxidizing NO or producing NO-consuming substrate radicals. Here, structurally diverse pharmacological agents with activities as MPO substrates/inhibitors or antioxidants were screened for their effects on MPO NO oxidase activity in human plasma and physiological model systems containing endogenous MPO substrates/antioxidants (tyrosine, urate, ascorbate). Hydrazide-based irreversible/reversible MPO inhibitors (4-ABAH, isoniazid) or the sickle cell anaemia drug, hydroxyurea, all promoted MPO NO oxidase activity. This involved the capacity of NO to antagonize MPO inhibition by hydrazide-derived radicals and/or the ability of drug-derived radicals to stimulate MPO turnover thereby increasing NO consumption by MPO redox intermediates or NO-consuming radicals. In contrast, the mechanism-based irreversible MPO inhibitor 2-thioxanthine, potently inhibited MPO turnover and NO consumption. Although the phenolics acetaminophen and resveratrol initially increased MPO turnover and NO consumption, they limited the overall extent of NO loss by rapidly depleting H 2 O 2 and promoting the formation of ascorbyl radicals, which inefficiently consume NO. The vitamin E analogue trolox inhibited MPO NO oxidase activity in ascorbate-depleted fluids by scavenging NO-consuming tyrosyl and urate radicals. Tempol and related nitroxides decreased NO consumption in ascorbate-replete fluids by scavenging MPO-derived ascorbyl radicals. Indoles or apocynin yielded marginal effects. Kinetic analyses rationalized differences in drug activities and identified criteria for the improved inhibition of MPO NO oxidase activity. This study reveals that widely used agents have important implications for MPO NO oxidase activity under physiological conditions, highlighting new pharmacological strategies for preserving NO bioavailability during

Efficient Agent-Based Cluster Ensembles

NASA Technical Reports Server (NTRS)

Agogino, Adrian; Tumer, Kagan

2006-01-01

Numerous domains ranging from distributed data acquisition to knowledge reuse need to solve the cluster ensemble problem of combining multiple clusterings into a single unified clustering. Unfortunately current non-agent-based cluster combining methods do not work in a distributed environment, are not robust to corrupted clusterings and require centralized access to all original clusterings. Overcoming these issues will allow cluster ensembles to be used in fundamentally distributed and failure-prone domains such as data acquisition from satellite constellations, in addition to domains demanding confidentiality such as combining clusterings of user profiles. This paper proposes an efficient, distributed, agent-based clustering ensemble method that addresses these issues. In this approach each agent is assigned a small subset of the data and votes on which final cluster its data points should belong to. The final clustering is then evaluated by a global utility, computed in a distributed way. This clustering is also evaluated using an agent-specific utility that is shown to be easier for the agents to maximize. Results show that agents using the agent-specific utility can achieve better performance than traditional non-agent based methods and are effective even when up to 50% of the agents fail.

Contraceptive agents from cycloaddition reactions of diarylcyclopropenones and diarylthiirene 1, 1-dioxides.

PubMed

Rosen, M H; Fengler, I; Bonet, G; Steinetz, B G; Giannina, T; Dopick, F R; Butler, M C

1976-03-01

The potential for compounds with antifertility activity from the reactions of diphenylcyclopropernone (1) and 2, 3-diphenylthiirene 1, 1-dioxide (2) with enamines is described. In certain instances, a marked dissociation of antifertility from estrogenic activity was possible. Two series were studied extensively, one was stilbene amides (7) and the other stilbene amino ketones (8). The latter series (8) afforded several materials from which, on further biological work-up, was singled out compound 21 as a potent antifertility agent in rats and hamsters.

Agent-Based Scientific Workflow Composition

NASA Astrophysics Data System (ADS)

Barker, A.; Mann, B.

2006-07-01

Agents are active autonomous entities that interact with one another to achieve their objectives. This paper addresses how these active agents are a natural fit to consume the passive Service Oriented Architecture which is found in Internet and Grid Systems, in order to compose, coordinate and execute e-Science experiments. A framework is introduced which allows an e-Science experiment to be described as a MultiAgent System.

Aptamer-crosslinked microbubbles: smart contrast agents for thrombin-activated ultrasound imaging.

PubMed

Nakatsuka, Matthew A; Mattrey, Robert F; Esener, Sadik C; Cha, Jennifer N; Goodwin, Andrew P

2012-11-27

Thrombosis, or malignant blood clotting, is associated with numerous cardiovascular diseases and cancers. A microbubble contrast agent is presented that produces ultrasound harmonic signal only when exposed to elevated thrombin levels. Initially silent microbubbles are activated in the presence of both thrombin-spiked and freshly clotting blood in three minutes with detection limits of 20 nM thrombin and 2 aM microbubbles. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro evaluation of the activity of two doses of Levofloxacin alone and in combination with other agents against Pseudomonas aeruginosa.

PubMed

Burgess, David S; Hall, Ronald G; Hardin, Thomas C

2003-06-01

P. aeruginosa is one of the most difficult to treat pathogens that generally requires combination therapy to prevent the development of resistance. This study evaluated the in vitro activity of two concentrations of levofloxacin (modeled for the 500 mg and 750 mg daily dose) in combination with ceftazidime, cefepime, piperacillin/tazobactam, imipenem, and tobramycin against P. aeruginosa. MICs and time-kill studies were performed against 12 non-duplicate clinical isolates of P. aeruginosa. The percent susceptible for levofloxacin, ceftazidime, cefepime, piperacillin/tazobactam, imipenem, and tobramycin were 67%, 58%, 58%, 67%, 75%, and 100%, respectively. Tobramycin was the most active single agent, killing and maintaining > or =99.9% killing over a 24 h period against all isolates. Levofloxacin 4 microg/mL(750 mg/day) alone reached 99.9% killing and maintain this killing over the time period more often than levofloxacin 2 microg/mL (500 mg/day). No combination was antagonistic and all combinations with tobramycin were indifferent. Overall, levofloxacin 2 microg/mL plus a beta-lactam was synergistic (65%) more often than levofloxacin 4 microg/mL combinations (46%). This was not unexpected due to the increased activity of levofloxacin 4 microg/mL. However, levofloxacin 4 microg/mL combinations maintained a > or =99.9% killing over the entire 24 h period more often than levofloxacin 2 microg/mL combinations (94% vs 83%). The findings from this work suggest that levofloxacin 750 mg/day in combination with another agent active against P. aeruginosa may prove to be clinically beneficial and superior to combinations using lower doses of levofloxacin. In vivo studies are needed to evaluate the clinical significance of these findings.

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

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

Muramoto, S.; Oki, Y.

1984-10-01

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

Antitumor Agents. 272. Structure–Activity Relationships and In Vivo Selective Anti-Breast Cancer Activity of Novel Neo-tanshinlactone Analogs

PubMed Central

Dong, Yizhou; Shi, Qian; Pai, Huei-Chen; Peng, Chieh-Yu; Pan, Shiow-Lin; Teng, Che-Ming; Nakagawa-Goto, Kyoko; Yu, Donglei; Liu, Yi-Nan; Wu, Pei-Chi; Bastow, Kenneth F.; Morris-Natschke, Susan L.; Brossi, Arnold; Lang, Jing-Yu; Hsu, Jennifer L.; Hung, Mien-Chie; Lee, Eva Y.-H. P.; Lee, Kuo-Hsiung

2010-01-01

Neo-tanshinlactone (1) and its previously reported analogs, such as 2, are potent and selective in vitro anti-breast cancer agents. The synthetic pathway to 2 was optimized from seven to five steps, with a better overall yield. Structure–activity relationships studies on these compounds revealed some key molecular determinants for this family of anti-breast agents. Several derivatives (19-21 and 24) exerted potent and selective anti-breast cancer activity with IC50 values of 0.3, 0.2, 0.1 and 0.1 μg/mL, respectively, against the ZR-75-1 cell lines. Compound 24 was two- to three-fold more potent than 1 against SK-BR-3 and ZR-75-1. Importantly, 21 exhibited high selectivity; it was 23 times more active against ZR-75-1 than MCF-7. Compound 20 had an approximately 12-fold ratio of SK-BR-3/MCF-7 selectivity. In addition, analog 2 showed potent activity against a ZR-75-1 xenograft model, but not PC-3 and MDA-MB-231 xenografts, as well as high selectivity against breast cancer cell line compared with normal breast tissue-derived cell lines. Further development of lead compounds 19-21 and 24 as clinical trial candidates is warranted. PMID:20148565

In vitro activities of 10 antimicrobial agents against bacterial vaginosis-associated anaerobic isolates from pregnant Japanese and Thai women.

PubMed

Puapermpoonsiri, S; Watanabe, K; Kato, N; Ueno, K

1997-10-01

The in vitro activities of 10 antimicrobial agents against 159 bacterial vaginosis-associated anaerobic isolates from pregnant Japanese and Thai women were determined. Clindamycin, imipenem, cefmetazole, amoxicillin, amoxicillin-clavulanate, and metronidazole were highly active against all anaerobic isolates except Prevotella bivia and Mobiluncus species, which were resistant to amoxicillin and metronidazole, respectively. Cefotiam, ceftazidime, and ofloxacin were variably effective, while cefaclor was the least effective agent.

Single-agent estramustine phosphate (EMP) is active in advanced breast cancer after failure with anthracyclines and taxanes.

PubMed

Zelek, L; Barthier, S; Riofrio, M; Sevin, D; Fizazi, K; Spielmann, M

2001-09-01

Estramustine phosphate (EMP) is an oral cytotoxic agent that depolymerizes tubuline, a mechanism of action that has been revisited during the last decade. Because of its lack of haematological toxicity and favourable tolerance profile, EMP is a good candidate for palliative chemotherapy. The aim of the study was to assess its tolerance and efficacy in advanced breast cancer after failure with usual regimens. Patients with a life expectancy of at least 12 weeks and bi-dimensionally measurable disease having received at least 1 line of chemotherapy (including taxanes and/or anthracyclines) for advanced breast cancer (ABC) were eligible. EMP was given daily at a dose of 10 mg/kg until disease progression, unacceptable toxicity or patient refusal to continue chemotherapy. Forty patients were included between June 1998 and December 1999. Patients had previously received one to eight chemotherapy regimens (median is two) for ABC. Twenty-two patients (55%) had visceral involvement and eighteen patients (45%) had osseous, chest wall or soft tissue metastases. Adverse events leading to early interruption of EMP were grade 2 allergy (n = 1), grade 2-3 nausea (n = 6), deep-vein thrombosis (n = 1), grade 3 sepsis (n = 1). One patient died at twenty-four weeks from pulmonary embolism, and another at fourteen weeks from unknown cause. Seven objective responses were observed (17.5%; 95% confidence interval (CI): 6%-30%). Median time to failure was 24 weeks (14-52+) in responding patients. All objective responses but one were observed in patients with visceral metastases. In 10 other patients (25%), disease remained stable with a median time to failure of 27 weeks (16-50); 6 of these experienced a decrease of consumption of analgesics or an improvement of performance status. EMP is an active drug in ABC after failure with taxanes and anthracyclines, whose tolerance profile appears favourable.

A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection.

PubMed

Vrentas, Catherine E; Moayeri, Mahtab; Keefer, Andrea B; Greaney, Allison J; Tremblay, Jacqueline; O'Mard, Danielle; Leppla, Stephen H; Shoemaker, Charles B

2016-10-07

Infection with Bacillus anthracis, the causative agent of anthrax, can lead to persistence of lethal secreted toxins in the bloodstream, even after antibiotic treatment. VHH single-domain antibodies have been demonstrated to neutralize diverse bacterial toxins both in vitro and in vivo, with protein properties such as small size and high stability that make them attractive therapeutic candidates. Recently, we reported on VHHs with in vivo activity against the protective antigen component of the anthrax toxins. Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to the edema factor (EF) and/or lethal factor (LF) components. Six of these VHHs are cross-reactive against both EF and LF and recognize the N-terminal domain (LF N , EF N ) of their target(s) with subnanomolar affinity. The cross-reactive VHHs block binding of EF/LF to the protective antigen C-terminal binding interface, preventing toxin entry into the cell. Another VHH appears to recognize the LF C-terminal domain and exhibits a kinetic effect on substrate cleavage by LF. A subset of the VHHs neutralized against EF and/or LF in murine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spore model of anthrax infection. Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against lethal anthrax spore infection in mice as a single dose. This set of VHHs should facilitate development of new therapeutic VNAs and/or diagnostic agents for anthrax. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Activities of a new oral streptogramin, XRP 2868, compared to those of other agents against Streptococcus pneumoniae and haemophilus species.

PubMed

Pankuch, Glenn A; Kelly, Linda M; Lin, Gengrong; Bryskier, Andre; Couturier, Catherine; Jacobs, Michael R; Appelbaum, Peter C

2003-10-01

MIC methodology was used to test the antibacterial activity of XRP 2868, a new oral combination of two semisynthetic streptogramins, RPR 132552A and RPR 202868, compared to activities of other antibacterial agents against pneumococci, Haemophilus influenzae, and Haemophilus parainfluenzae. For 261 pneumococci, XRP 2868 and pristinamycin MICs were similar, irrespective of penicillin G and erythromycin A susceptibilities (MIC at which 50% of isolates were inhibited [MIC(50)], 0.25 micro g/ml; MIC(90), 0.5 micro g/ml), while quinupristin/dalfopristin had MICs which were 1 to 2 dilutions higher. Single components of both XRP 2868 and quinupristin/dalfopristin had higher MICs. Erythromycin A, azithromycin, clarithromycin, and clindamycin MICs were higher for penicillin G-intermediate and -resistant than -susceptible pneumococci. Against 150 H. influenzae strains, all compounds tested had unimodal MIC distributions. XRP 2868 had an overall MIC(50) of 0.25 micro g/ml and an MIC(90) of 1.0 micro g/ml, with no differences between beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant strains. Of note was the similarly low activity of one of its components, RPR 132552A. Pristinamycin and quinupristin/dalfopristin had MICs of 0.125 to 8.0 micro g/ml; quinupristin alone had MICs of 8.0 to >64.0 micro g/ml, and dalfopristin had MICs of 1.0 to >64.0 micro g/ml. Erythromycin A, azithromycin, and clarithromycin had modal MICs of 4.0, 1.0, and 8.0 micro g/ml, respectively. MICs of all compounds against H. parainfluenzae were 1 to 2 dilutions higher than against H. influenzae. XRP 2868 showed potent activity against pneumococci and Haemophilus strains irrespective of their susceptibility to other agents.

Activities of a New Oral Streptogramin, XRP 2868, Compared to Those of Other Agents against Streptococcus pneumoniae and Haemophilus Species

PubMed Central

Pankuch, Glenn A.; Kelly, Linda M.; Lin, Gengrong; Bryskier, Andre; Couturier, Catherine; Jacobs, Michael R.; Appelbaum, Peter C.

2003-01-01

MIC methodology was used to test the antibacterial activity of XRP 2868, a new oral combination of two semisynthetic streptogramins, RPR 132552A and RPR 202868, compared to activities of other antibacterial agents against pneumococci, Haemophilus influenzae, and Haemophilus parainfluenzae. For 261 pneumococci, XRP 2868 and pristinamycin MICs were similar, irrespective of penicillin G and erythromycin A susceptibilities (MIC at which 50% of isolates were inhibited [MIC50], 0.25 μg/ml; MIC90, 0.5 μg/ml), while quinupristin/dalfopristin had MICs which were 1 to 2 dilutions higher. Single components of both XRP 2868 and quinupristin/dalfopristin had higher MICs. Erythromycin A, azithromycin, clarithromycin, and clindamycin MICs were higher for penicillin G-intermediate and -resistant than -susceptible pneumococci. Against 150 H. influenzae strains, all compounds tested had unimodal MIC distributions. XRP 2868 had an overall MIC50 of 0.25 μg/ml and an MIC90 of 1.0 μg/ml, with no differences between β-lactamase-positive, β-lactamase-negative, and β-lactamase-negative ampicillin-resistant strains. Of note was the similarly low activity of one of its components, RPR 132552A. Pristinamycin and quinupristin/dalfopristin had MICs of 0.125 to 8.0 μg/ml; quinupristin alone had MICs of 8.0 to >64.0 μg/ml, and dalfopristin had MICs of 1.0 to >64.0 μg/ml. Erythromycin A, azithromycin, and clarithromycin had modal MICs of 4.0, 1.0, and 8.0 μg/ml, respectively. MICs of all compounds against H. parainfluenzae were 1 to 2 dilutions higher than against H. influenzae. XRP 2868 showed potent activity against pneumococci and Haemophilus strains irrespective of their susceptibility to other agents. PMID:14506040

Characterization of anticancer agents by their growth inhibitory activity and relationships to mechanism of action and structure.

PubMed

Keskin, O; Bahar, I; Jernigan, R L; Beutler, J A; Shoemaker, R H; Sausville, E A; Covell, D G

2000-04-01

An analysis of the growth inhibitory potency of 122 anticancer agents available from the National Cancer Institute anticancer drug screen is presented. Methods of singular value decomposition (SVD) were applied to determine the matrix of distances between all compounds. These SVD-derived dissimilarity distances were used to cluster compounds that exhibit similar tumor growth inhibitory activity patterns against 60 human cancer cell lines. Cluster analysis divides the 122 standard agents into 25 statistically distinct groups. The first eight groups include structurally diverse compounds with reactive functionalities that act as DNA-damaging agents while the remaining 17 groups include compounds that inhibit nucleic acid biosynthesis and mitosis. Examination of the average activity patterns across the 60 tumor cell lines reveals unique 'fingerprints' associated with each group. A diverse set of structural features are observed for compounds within these groups, with frequent occurrences of strong within-group structural similarities. Clustering of cell types by their response to the 122 anticancer agents divides the 60 cell types into 21 groups. The strongest within-panel groupings were found for the renal, leukemia and ovarian cell panels. These results contribute to the basis for comparisons between log(GI(50)) screening patterns of the 122 anticancer agents and additional tested compounds.

Agent-based modeling of noncommunicable diseases: a systematic review.

PubMed

Nianogo, Roch A; Arah, Onyebuchi A

2015-03-01

We reviewed the use of agent-based modeling (ABM), a systems science method, in understanding noncommunicable diseases (NCDs) and their public health risk factors. We systematically reviewed studies in PubMed, ScienceDirect, and Web of Sciences published from January 2003 to July 2014. We retrieved 22 relevant articles; each had an observational or interventional design. Physical activity and diet were the most-studied outcomes. Often, single agent types were modeled, and the environment was usually irrelevant to the studied outcome. Predictive validation and sensitivity analyses were most used to validate models. Although increasingly used to study NCDs, ABM remains underutilized and, where used, is suboptimally reported in public health studies. Its use in studying NCDs will benefit from clarified best practices and improved rigor to establish its usefulness and facilitate replication, interpretation, and application.

Activation of the chemosensing transient receptor potential channel A1 (TRPA1) by alkylating agents.

PubMed

Stenger, Bernhard; Zehfuss, Franziska; Mückter, Harald; Schmidt, Annette; Balszuweit, Frank; Schäfer, Eva; Büch, Thomas; Gudermann, Thomas; Thiermann, Horst; Steinritz, Dirk

2015-09-01

The transient receptor potential ankyrin 1 (TRPA1) cation channel is expressed in different tissues including skin, lung and neuronal tissue. Recent reports identified TRPA1 as a sensor for noxious substances, implicating a functional role in the molecular toxicology. TRPA1 is activated by various potentially harmful electrophilic substances. The chemical warfare agent sulfur mustard (SM) is a highly reactive alkylating agent that binds to numerous biological targets. Although SM is known for almost 200 years, detailed knowledge about the pathophysiology resulting from exposure is lacking. A specific therapy is not available. In this study, we investigated whether the alkylating agent 2-chloroethyl-ethylsulfide (CEES, a model substance for SM-promoted effects) and SM are able to activate TRPA1 channels. CEES induced a marked increase in the intracellular calcium concentration ([Ca(2+)]i) in TRPA1-expressing but not in TRPA1-negative cells. The TRP-channel blocker AP18 diminished the CEES-induced calcium influx. HEK293 cells permanently expressing TRPA1 were more sensitive toward cytotoxic effects of CEES compared with wild-type cells. At low CEES concentrations, CEES-induced cytotoxicity was prevented by AP18. Proof-of-concept experiments using SM resulted in a pronounced increase in [Ca(2+)]i in HEK293-A1-E cells. Human A549 lung epithelial cells, which express TRPA1 endogenously, reacted with a transient calcium influx in response to CEES exposure. The CEES-dependent calcium response was diminished by AP18. In summary, our results demonstrate that alkylating agents are able to activate TRPA1. Inhibition of TRPA1 counteracted cellular toxicity and could thus represent a feasible approach to mitigate SM-induced cell damage.

Identity Agents: Parents as Active and Reflective Participants in their Children's Identity Formation

ERIC Educational Resources Information Center

Schachter, Elli P.; Ventura, Jonathan J.

2008-01-01

The paper introduces the concept of identity agents. This concept refers to those individuals who actively interact with children and youth with the intention of participating in their identity formation, and who reflectively mediate larger social influences on identity formation. This contrasts with the focus of mainstream research in the…

Efficacy of Antimicrobial Agents for Food Contact Applications: Biological Activity, Incorporation into Packaging, and Assessment Methods: A Review.

PubMed

Mousavi Khaneghah, Amin; Hashemi, Seyed Mohammad Bagher; Eş, Ismail; Fracassetti, Daniela; Limbo, Sara

2018-07-01

Interest in the utilization of antimicrobial active packaging for food products has increased in recent years. Antimicrobial active packaging involves the incorporation of antimicrobial compounds into packaging materials, with the aim of maintaining or extending food quality and shelf life. Plant extracts, essential oils, organic acids, bacteriocins, inorganic substances, enzymes, and proteins are used as antimicrobial agents in active packaging. Evaluation of the antimicrobial activity of packaging materials using different methods has become a critical issue for both food safety and the commercial utilization of such packaging technology. This article reviews the different types of antimicrobial agents used for active food packaging materials, the main incorporation techniques, and the assessment methods used to examine the antimicrobial activity of packaging materials, taking into account their safety as food contact materials.

The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models.

PubMed

Foster, Paul; Yamaguchi, Kyoko; Hsu, Pin P; Qian, Fawn; Du, Xiangnan; Wu, Jianming; Won, Kwang-Ai; Yu, Peiwen; Jaeger, Christopher T; Zhang, Wentao; Marlowe, Charles K; Keast, Paul; Abulafia, Wendy; Chen, Jason; Young, Jenny; Plonowski, Artur; Yakes, F Michael; Chu, Felix; Engell, Kelly; Bentzien, Frauke; Lam, Sanh T; Dale, Stephanie; Yturralde, Olivia; Matthews, David J; Lamb, Peter; Laird, A Douglas

2015-04-01

Dysregulation of PI3K/PTEN pathway components, resulting in hyperactivated PI3K signaling, is frequently observed in various cancers and correlates with tumor growth and survival. Resistance to a variety of anticancer therapies, including receptor tyrosine kinase (RTK) inhibitors and chemotherapeutic agents, has been attributed to the absence or attenuation of downregulating signals along the PI3K/PTEN pathway. Thus, PI3K inhibitors have therapeutic potential as single agents and in combination with other therapies for a variety of cancer indications. XL147 (SAR245408) is a potent and highly selective inhibitor of class I PI3Ks (α, β, γ, and δ). Moreover, broad kinase selectivity profiling of >130 protein kinases revealed that XL147 is highly selective for class I PI3Ks over other kinases. In cellular assays, XL147 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 in multiple tumor cell lines with diverse genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL147 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. In mouse xenograft models, oral administration of XL147 results in dose-dependent inhibition of phosphorylation of AKT, p70S6K, and S6 with a duration of action of at least 24 hours. Repeat-dose administration of XL147 results in significant tumor growth inhibition in multiple human xenograft models in nude mice. Administration of XL147 in combination with chemotherapeutic agents results in antitumor activity in xenograft models that is enhanced over that observed with the corresponding single agents. ©2015 American Association for Cancer Research.

The application of click chemistry in the synthesis of agents with anticancer activity

PubMed Central

Ma, Nan; Wang, Ying; Zhao, Bing-Xin; Ye, Wen-Cai; Jiang, Sheng

2015-01-01

The copper(I)-catalyzed 1,3-dipolar cycloaddition between alkynes and azides (click chemistry) to form 1,2,3-triazoles is the most popular reaction due to its reliability, specificity, and biocompatibility. This reaction has the potential to shorten procedures, and render more efficient lead identification and optimization procedures in medicinal chemistry, which is a powerful modular synthetic approach toward the assembly of new molecular entities and has been applied in anticancer drugs discovery increasingly. The present review focuses mainly on the applications of this reaction in the field of synthesis of agents with anticancer activity, which are divided into four groups: topoisomerase II inhibitors, histone deacetylase inhibitors, protein tyrosine kinase inhibitors, and antimicrotubule agents. PMID:25792812

Activation of aluminum as an effective reducing agent by pitting corrosion for wet-chemical synthesis.

PubMed

Li, Wei; Cochell, Thomas; Manthiram, Arumugam

2013-01-01

Metallic aluminum (Al) is of interest as a reducing agent because of its low standard reduction potential. However, its surface is invariably covered with a dense aluminum oxide film, which prevents its effective use as a reducing agent in wet-chemical synthesis. Pitting corrosion, known as an undesired reaction destroying Al and is enhanced by anions such as F⁻, Cl⁻, and Br⁻ in aqueous solutions, is applied here for the first time to activate Al as a reducing agent for wet-chemical synthesis of a diverse array of metals and alloys. Specifically, we demonstrate the synthesis of highly dispersed palladium nanoparticles on carbon black with stabilizers and the intermetallic Cu₂Sb/C, which are promising candidates, respectively, for fuel cell catalysts and lithium-ion battery anodes. Atomic hydrogen, an intermediate during the pitting corrosion of Al in protonic solvents (e.g., water and ethylene glycol), is validated as the actual reducing agent.

Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity.

PubMed

Awada, Ahmad; Dumez, Herlinde; Aftimos, Philippe G; Costermans, Jo; Bartholomeus, Sylvie; Forceville, Kathleen; Berghmans, Thierry; Meeus, Marie-Anne; Cescutti, Jessica; Munzert, Gerd; Pilz, Korinna; Liu, Dan; Schöffski, Patrick

2015-06-01

This trial evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and activity of volasertib, a selective Polo-like kinase 1 inhibitor that induces mitotic arrest and apoptosis, combined with cisplatin or carboplatin in patients with advanced/metastatic solid tumors (NCT00969761; 1230.6). Sequential patient cohorts (3 + 3 dose-escalation design) received a single infusion of volasertib (100-350 mg) with cisplatin (60-100 mg/m(2)) or carboplatin (area under the concentration versus time curve [AUC]4-AUC6) on day 1 every 3 weeks for up to six cycles. Sixty-one patients received volasertib/cisplatin (n = 30) or volasertib/carboplatin (n = 31) for a median of 3.5 (range, 1-6) and 2.0 (range, 1-6) treatment cycles, respectively. The most common cycle 1 dose-limiting toxicities (DLTs) were thrombocytopenia, neutropenia and fatigue. MTDs (based on cycle 1 DLTs) were determined to be volasertib 300 mg plus cisplatin 100 mg/m(2) and volasertib 300 mg plus carboplatin AUC6. Co-administration did not affect the pharmacokinetics of each drug. Partial responses were observed in two patients in each arm. Stable disease was achieved in 11 and six patients treated with volasertib/cisplatin and volasertib/carboplatin, respectively. Volasertib plus cisplatin or carboplatin at full single-agent doses was generally manageable and demonstrated activity in heavily pretreated patients with advanced solid tumors.

Improved efficiency of budesonide nebulization using surface-active agents.

PubMed

Bouwman, A M; Heijstra, M P; Schaefer, N C; Duiverman, E J; Lesouëf, P N; Devadason, S G

2006-01-01

Our aim was to improve the efficiency of nebulised budesonide using surface-active agents. Cationic, anionic, and nonionic detergents were added to commercial budesonide suspension, and the particle size distribution during nebulization was measured using both cascade impaction and laser diffraction. Our results showed that the emitted dose was increased after addition of cationic (p < 0.001) and nonionic detergents (p < 0.01) compared with the commercial formulation alone. The respirable fraction was increased for all detergent formulations (p < 0.001) compared with the commercial formulation. We concluded that cationic and nonionic detergent increased the total output of budesonide from the Sidestream. All detergent formulations increased the respirable fraction of nebulized budesonide.

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

PubMed

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

2018-06-01

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

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.

Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles

PubMed Central

Chen, Chen; Weir, Michael D.; Cheng, Lei; Lin, Nancy; Lin-Gibson, Sheng; Chow, Laurence C.; Zhou, Xuedong; Xu, Hockin H. K.

2015-01-01

Objectives Recurrent caries at the margins is a primary reason for restoration failure. The objectives of this study were to develop bonding agent with the double benefits of antibacterial and remineralizing capabilities, to investigate the effects of NACP filler level and solution pH on Ca and P ion release from adhesive, and to examine the antibacterial and dentin bond properties. Methods Nanoparticles of amorphous calcium phosphate (NACP) and a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) were synthesized. Scotchbond Multi-Purpose (SBMP) primer and adhesive served as control. DMADDM was incorporated into primer and adhesive at 5% by mass. NACP was incorporated into adhesive at filler mass fractions of 10%, 20%, 30% and 40%. A dental plaque microcosm biofilm model was used to test the antibacterial bonding agents. Calcium (Ca) and phosphate (P) ion releases from the cured adhesive samples were measured vs. filler level and solution pH of 7, 5.5 and 4. Results Adding 5% DMADDM and 10–40% NACP into bonding agent, and water-aging for 28 days, did not affect dentin bond strength, compared to SBMP control at 1 day (p > 0.1). Adding DMADDM into bonding agent substantially decreased the biofilm metabolic activity and lactic acid production. Total microorganisms, total streptococci, and mutans streptococci were greatly reduced for bonding agents containing DMADDM. Increasing NACP filler level from 10% to 40% in adhesive increased the Ca and P ion release by an order of magnitude. Decreasing solution pH from 7 to 4 increased the ion release from adhesive by 6–10 folds. Significance Bonding agents containing antibacterial DMADDM and remineralizer NACP were formulated to have Ca and P ion release, which increased with NACP filler level from 10% to 40% in adhesive. NACP adhesive was “smart” and dramatically increased the ion release at cariogenic pH 4, when these ions would be most-needed to inhibit caries. Therefore, bonding agent

A fluorogenic near-infrared imaging agent for quantifying plasma and local tissue renin activity in vivo and ex vivo

PubMed Central

Zhang, Jun; Preda, Dorin V.; Vasquez, Kristine O.; Morin, Jeff; Delaney, Jeannine; Bao, Bagna; Percival, M. David; Xu, Daigen; McKay, Dan; Klimas, Michael; Bednar, Bohumil; Sur, Cyrille; Gao, David Z.; Madden, Karen; Yared, Wael; Rajopadhye, Milind

2012-01-01

The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near-infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments. PMID:22674025

Surface-Active Agents for Isolation of the Core Component of Avian Myeloblastosis Virus 1

PubMed Central

Stromberg, Kurt

1972-01-01

Sixty-one surface-active agents were evaluated in a procedure designed to assess their ability to remove the envelope from the core component of avian myeloblastosis virus (AMV). The procedure consisted of centrifugation of intact AMV through a series of sucrose gradients each containing an upper layer of agent at one of eight concentrations between 0.01 and 10%. The effectiveness of an agent in producing AMV cores was indicated by (i) the appearance of light-scattering bands in the region of core buoyant density in gradient tubes; (ii) the range of surfactant concentration over which these bands appeared; and (iii) an electron microscopy assessment by the negative-staining technique of the relative proportion of core to non-core material in each of these bands. Six nonionic surfactants were selected by this screening method for comparison in regard to recovery of core protein and endogenous ribonucleic acid (RNA)-dependent deoxyribonucleic acid (DNA) polymerase activity, as well as further morphologic evaluation by electron microscopy. The nonionic surfactants of the polyoxyethylene alcohol class (particularly, Sterox SL) were most effective. Nonionic surfactants of the polyoxyethylene alkylphenol class (particularly, Nonidet P-40) were also effective. Sterox SL and Nonidet P-40 each gave a more than fivefold increase in specific activity of endogenous RNA-dependent DNA polymerase, and each gave a low recovery of core protein. Sterox SL did not interfere to the extent that Nonidet P-40 did in procedures which involved spectrophotometric assay at 260 nm. The use of Sterox SL resulted in the least envelope contamination of core preparations by electron microscopy examination, the most recovery of protein and endogenous RNA-dependent DNA polymerase activity, and a core buoyant density in sucrose of 1.27 g/ml. Images PMID:4112071

A practical approach for active camera coordination based on a fusion-driven multi-agent system

NASA Astrophysics Data System (ADS)

Bustamante, Alvaro Luis; Molina, José M.; Patricio, Miguel A.

2014-04-01

In this paper, we propose a multi-agent system architecture to manage spatially distributed active (or pan-tilt-zoom) cameras. Traditional video surveillance algorithms are of no use for active cameras, and we have to look at different approaches. Such multi-sensor surveillance systems have to be designed to solve two related problems: data fusion and coordinated sensor-task management. Generally, architectures proposed for the coordinated operation of multiple cameras are based on the centralisation of management decisions at the fusion centre. However, the existence of intelligent sensors capable of decision making brings with it the possibility of conceiving alternative decentralised architectures. This problem is approached by means of a MAS, integrating data fusion as an integral part of the architecture for distributed coordination purposes. This paper presents the MAS architecture and system agents.

A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents.

PubMed

Herter, Sylvia; Morra, Laura; Schlenker, Ramona; Sulcova, Jitka; Fahrni, Linda; Waldhauer, Inja; Lehmann, Steffi; Reisländer, Timo; Agarkova, Irina; Kelm, Jens M; Klein, Christian; Umana, Pablo; Bacac, Marina

2017-01-01

The complexity of the tumor microenvironment is difficult to mimic in vitro, particularly regarding tumor-host interactions. To enable better assessment of cancer immunotherapy agents in vitro, we developed a three-dimensional (3D) heterotypic spheroid model composed of tumor cells, fibroblasts, and immune cells. Drug targeting, efficient stimulation of immune cell infiltration, and specific elimination of tumor or fibroblast spheroid areas were demonstrated following treatment with a novel immunocytokine (interleukin-2 variant; IgG-IL2v) and tumor- or fibroblast-targeted T cell bispecific antibody (TCB). Following treatment with IgG-IL2v, activation of T cells, NK cells, and NKT cells was demonstrated by increased expression of the activation marker CD69 and enhanced cytokine secretion. The combination of TCBs with IgG-IL2v molecules was more effective than monotherapy, as shown by enhanced effects on immune cell infiltration; activation; increased cytokine secretion; and faster, more efficient elimination of targeted cells. This study demonstrates that the 3D heterotypic spheroid model provides a novel and versatile tool for in vitro evaluation of cancer immunotherapy agents and allows for assessment of additional aspects of the activity of cancer immunotherapy agents, including analysis of immune cell infiltration and drug targeting.

An agent-based method for simulating porous fluid-saturated structures with indistinguishable components

NASA Astrophysics Data System (ADS)

Kashani, Jamal; Pettet, Graeme John; Gu, YuanTong; Zhang, Lihai; Oloyede, Adekunle

2017-10-01

Single-phase porous materials contain multiple components that intermingle up to the ultramicroscopic level. Although the structures of the porous materials have been simulated with agent-based methods, the results of the available methods continue to provide patterns of distinguishable solid and fluid agents which do not represent materials with indistinguishable phases. This paper introduces a new agent (hybrid agent) and category of rules (intra-agent rule) that can be used to create emergent structures that would more accurately represent single-phase structures and materials. The novel hybrid agent carries the characteristics of system's elements and it is capable of changing within itself, while also responding to its neighbours as they also change. As an example, the hybrid agent under one-dimensional cellular automata formalism in a two-dimensional domain is used to generate patterns that demonstrate the striking morphological and characteristic similarities with the porous saturated single-phase structures where each agent of the ;structure; carries semi-permeability property and consists of both fluid and solid in space and at all times. We conclude that the ability of the hybrid agent to change locally provides an enhanced protocol to simulate complex porous structures such as biological tissues which could facilitate models for agent-based techniques and numerical methods.

Homeostatic Agent for General Environment

NASA Astrophysics Data System (ADS)

Yoshida, Naoto

2018-03-01

One of the essential aspect in biological agents is dynamic stability. This aspect, called homeostasis, is widely discussed in ethology, neuroscience and during the early stages of artificial intelligence. Ashby's homeostats are general-purpose learning machines for stabilizing essential variables of the agent in the face of general environments. However, despite their generality, the original homeostats couldn't be scaled because they searched their parameters randomly. In this paper, first we re-define the objective of homeostats as the maximization of a multi-step survival probability from the view point of sequential decision theory and probabilistic theory. Then we show that this optimization problem can be treated by using reinforcement learning algorithms with special agent architectures and theoretically-derived intrinsic reward functions. Finally we empirically demonstrate that agents with our architecture automatically learn to survive in a given environment, including environments with visual stimuli. Our survival agents can learn to eat food, avoid poison and stabilize essential variables through theoretically-derived single intrinsic reward formulations.

CATS-based Agents That Err

NASA Technical Reports Server (NTRS)

Callantine, Todd J.

2002-01-01

This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

Agent-Based Modeling of Noncommunicable Diseases: A Systematic Review

PubMed Central

Arah, Onyebuchi A.

2015-01-01

We reviewed the use of agent-based modeling (ABM), a systems science method, in understanding noncommunicable diseases (NCDs) and their public health risk factors. We systematically reviewed studies in PubMed, ScienceDirect, and Web of Sciences published from January 2003 to July 2014. We retrieved 22 relevant articles; each had an observational or interventional design. Physical activity and diet were the most-studied outcomes. Often, single agent types were modeled, and the environment was usually irrelevant to the studied outcome. Predictive validation and sensitivity analyses were most used to validate models. Although increasingly used to study NCDs, ABM remains underutilized and, where used, is suboptimally reported in public health studies. Its use in studying NCDs will benefit from clarified best practices and improved rigor to establish its usefulness and facilitate replication, interpretation, and application. PMID:25602871

SUSTAINED HYPERLIPEMIA INDUCED IN RABBITS BY MEANS OF INTRAVENOUSLY INJECTED SURFACE-ACTIVE AGENTS

PubMed Central

Kellner, Aaron; Correll, James W.; Ladd, Anthony T.

1951-01-01

The intravenous injection of the surface-active agents Tween 80 and Triton A20 into rabbits fed a normal diet resulted in marked and sustained elevations of the cholesterol, phospholipid, and total lipid content of their blood. The increase in phospholipid in general paralleled that of the blood cholesterol. The implications of the findings are briefly discussed. PMID:14824409

Fixed-dose combination and single active ingredient drugs: a comparative cost analysis.

PubMed

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2016-01-01

Fixed-dose combination (FDC) drugs are formulations of two or more active ingredients. To assess the pricing structure and price difference of all US FDA-approved FDCs and single drugs included in the combination. Data were collected from the FDA Orange Book and Drugs@FDA. Average Wholesale Price (AWP) unit price data were derived from The Red Book. The FDA approved 117 FDC. The average AWP difference percentage between the FDC and the sum of the single drugs in the FDC is 84.9 ± 26.2%, and varied by therapeutic class (p < 0.001). The FDC AWP averaged 83.3 ± 23.4% of the single drug AWP sum when there are no generics, and 95.1 ± 42.3% (p < 0.01) when there are two generic single active ingredients in the FDC. The price difference between FDC and single active ingredients in the combination is correlated with the therapeutic class, the year of FDC approval, and the number of single ingredients in the combination that have generics.

A comparison of muscular activity during single and double mouse clicks.

PubMed

Thorn, Stefan; Forsman, Mikael; Hallbeck, Susan

2005-05-01

Work-related musculoskeletal disorders (WMSDs) in the neck/shoulder region and the upper extremities are a common problem among computer workers. Occurrences of motor unit (MU) double discharges with very short inter-firing intervals (doublets) have been hypothesised as a potential additional risk for overuse of already exhausted fibres during long-term stereotyped activity. Doublets are reported to be present during double-click mouse work tasks. A few comparative studies have been carried out on overall muscle activities for short-term tasks with single types of actions, but none on occurrences of doublets during double versus single clicks. The main purpose of this study was to compare muscle activity levels of single and double mouse clicks during a long-term combined mouse/keyboard work task. Four muscles were studied: left and right upper trapezius, right extensor digitorum communis (EDC) and right flexor carpi ulnaris. Additionally, MU activity was analysed through intramuscular electromyography in the EDC muscle for a selection of subjects. The results indicate that double clicking produces neither higher median or 90th percentile levels in the trapezius and EDC muscles, nor a higher disposition for MU doublets, than does single clicking. Especially for the 90th percentile levels, the indications are rather the opposite (in the EDC significantly higher during single clicks in 8 of 11 subjects, P < 0.05). Although it cannot be concluded from the present study that double clicks are harmless, there were no signs that double clicks during computer work generally constitute a larger risk factor for WMSDs than do single clicks.

Anatase TiO2 single crystals with dominant {0 0 1} facets: Synthesis, shape-control mechanism and photocatalytic activity

NASA Astrophysics Data System (ADS)

Tong, Huifen; Zhou, Yingying; Chang, Gang; Li, Pai; Zhu, Ruizhi; He, Yunbin

2018-06-01

Anatase TiO2 micro-crystals with 51% surface exposing highly active {0 0 1} facets are prepared by hydrothermal synthesis using TiF4 as Ti resource and HF as morphology control agent. In addition, anatase TiO2 single crystals exposing large {0 0 1} crystal facets are facilely synthesized with "green" NaF plus HCl replacing HF for the morphology control. A series of comparative experiments are carried out for separately studying the effects of F- and H+ concentrations on the growth of TiO2 crystals, which have not been understood very much in depth so far. The results indicate that both F- and H+ synergistically affect the synthesis of truncated anatase octahedrons, where F- is preferentially adsorbed on the {0 0 1} facets resulting in lateral growth of these facets and H+ adjusts the growth rate of anatase TiO2 along different orientations by tuning the hydrolysis rate. Based on this information, anatase TiO2 single crystals with small size (1.3 μm) and large exposure of {0 0 1} facets (45%) are successfully prepared under optimal conditions ([H+]/[F-] = 20:1). Photocatalytic activities of the as-prepared products toward methylene blue photo-degradation are further tested. It is revealed that both crystal size and percentage of {0 0 1} facets are decisive for the photocatalytic performance, and the crystals with a small size (1.3 μm) and large exposure of {0 0 1} facets (45%) are catalytically most active. This work has clarified the main factors that control the growth process and morphology of anatase TiO2 single crystals for achieving superior photocatalytic properties.

Single cell multiplexed assay for proteolytic activity using droplet microfluidics.

PubMed

Ng, Ee Xien; Miller, Miles A; Jing, Tengyang; Chen, Chia-Hung

2016-07-15

Cellular enzymes interact in a post-translationally regulated fashion to govern individual cell behaviors, yet current platform technologies are limited in their ability to measure multiple enzyme activities simultaneously in single cells. Here, we developed multi-color Förster resonance energy transfer (FRET)-based enzymatic substrates and use them in a microfluidics platform to simultaneously measure multiple specific protease activities from water-in-oil droplets that contain single cells. By integrating the microfluidic platform with a computational analytical method, Proteolytic Activity Matrix Analysis (PrAMA), we are able to infer six different protease activity signals from individual cells in a high throughput manner (~100 cells/experimental run). We characterized protease activity profiles at single cell resolution for several cancer cell lines including breast cancer cell line MDA-MB-231, lung cancer cell line PC-9, and leukemia cell line K-562 using both live-cell and in-situ cell lysis assay formats, with special focus on metalloproteinases important in metastasis. The ability to measure multiple proteases secreted from or expressed in individual cells allows us to characterize cell heterogeneity and has potential applications including systems biology, pharmacology, cancer diagnosis and stem cell biology. Copyright © 2016 Elsevier B.V. All rights reserved.

Activity Based Protein Profiling Leads to Identification of Novel Protein Targets for Nerve Agent VX.

PubMed

Carmany, Dan; Walz, Andrew J; Hsu, Fu-Lian; Benton, Bernard; Burnett, David; Gibbons, Jennifer; Noort, Daan; Glaros, Trevor; Sekowski, Jennifer W

2017-04-17

Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and death. The primary mechanism behind these overt symptoms is the disruption of cholinergic pathways. While much is known about the primary toxicity mechanisms of nerve agents, there remains a paucity of information regarding impacts on other pathways and systemic effects. These are important for establishing a comprehensive understanding of the toxic mechanisms of OP nerve agents. To identify novel proteins that interact with VX, and that may give insight into these other mechanisms, we used activity-based protein profiling (ABPP) employing a novel VX-probe on lysates from rat heart, liver, kidney, diaphragm, and brain tissue. By making use of a biotin linked VX-probe, proteins covalently bound by the probe were isolated and enriched using streptavidin beads. The proteins were then digested, labeled with isobarically distinct tandem mass tag (TMT) labels, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Quantitative analysis identified 132 bound proteins, with many proteins found in multiple tissues. As with previously published ABPP OP work, monoacylglycerol lipase associated proteins and fatty acid amide hydrolase (FAAH) were shown to be targets of VX. In addition to these two and other predicted neurotransmitter-related proteins, a number of proteins involved with energy metabolism were identified. Four of these enzymes, mitochondrial isocitrate dehydrogenase 2 (IDH2), isocitrate dehydrogenase 3 (IDH3), malate dehydrogenase (MDH), and succinyl CoA (SCS) ligase, were assayed for VX inhibition. Only IDH2 NADP+ activity was shown to be inhibited directly. This result is consistent with other work reporting animals exposed to OP compounds exhibit

Hypoxia-Activated Alkylating Agents in BRCA1-Mutant Ovarian Serous Carcinoma.

PubMed

Conroy, Michael; Borad, Mitesh J; Bryce, Alan H

2017-07-26

Breast cancer 1 antigen (BRCA 1) and breast cancer 2 antigen (BRCA2) genes play a significant role in deoxyribonucleic acid (DNA) repair by means of interstrand crosslink repair, and deleterious germline mutations of these are responsible for most hereditary breast and ovarian cancers. Therapeutic strategies which specifically target interstrand crosslink repair can therefore be helpful in patients with harmful mutations. We describe two patients with advanced ovarian cancer and deleterious BRCA1 mutations who were treated with TH-302, a hypoxia-activated alkylating agent.

[Effects of nootropic agents on visual functions and lacrimal antioxidative activity in patients with primary open-angle glaucoma].

PubMed

Davydova, N G; Kuznetsova, T P; Borisova, S A; Abdulkadyrova, M Zh

2006-01-01

The paper presents the results of an investigation of the effect of the nootropic agents pantogam and nooclerine on visual functions in patients with primary open-angle glaucoma. These agents have been found to have a beneficial effect on the functional activity of the retina and optic nerve, light sensitivity, hemo- and hydrodynamics of the eye.

Docetaxel-loaded single-wall carbon nanohorns using anti-VEGF antibody as a targeting agent: characterization, in vitro and in vivo antitumor activity

NASA Astrophysics Data System (ADS)

Zhao, Qian; Li, Nannan; Shu, Chang; Li, Ruixin; Ma, Xiaona; Li, Xuequan; Wang, Ran; Zhong, Wenying

2015-05-01

A novel antitumor drug delivery system, docetaxel (DTX)-loaded oxidized single-wall carbon nanohorns (oxSWNHs) with anti-VEGF monoclonal antibody (mAb) as a target agent was constructed. DTX was absorbed onto the oxSWNHs via the physical adsorption or π-π interaction. DSPE-PEG-COOH was non-covalently wrapped to the hydrophobic surface of oxSWNHs to improve its water solubility and biocompatibility. The mAb was bonded to the PEG through amide bond. The DTX@oxSWNHs-PEG-mAb (DDS) exhibited suitable particle size (191.2 ± 2.1 nm), good particle size distribution (PDI: 0.196), and negative zeta potential (-24.3 ± 0.85 mV). These features enhanced permeability and retention (EPR) effect and reduced the drug molecule uptake by the reticuloendothelial system. The in vitro drug release followed non-Fickian diffusion ( n = 0.6857, R = 0.9924) with the cumulative release of DTX 59 ± 1.35 % at 72 h. Compared with free DTX, the DDS enhanced the cytotoxicity in MCF-7 cell lines in vitro efficiently (IC50: 2.96 ± 0.6 μg/ml), and provided higher antitumor efficacy (TGI: 69.88 %) in vivo. The histological analysis indicated that the DDS had no significant side effect. Therefore, the new DDS is promising to attain higher pharmaceutical efficacy and lower side effects than free DTX for cancer therapy. The research demonstrated that DTX@oxSWNHs-PEG-mAb might have promising biomedical applications for future cancer therapy.

BSL-3 laboratory practices in the United States: comparison of select agent and non-select agent facilities.

PubMed

Richards, Stephanie L; Pompei, Victoria C; Anderson, Alice

2014-01-01

New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non-select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non-select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non-select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non-select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non-select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non-select agent laboratories to improve occupational health and safety.

Occurrence of Surface Active Agents in the Environment

PubMed Central

Olkowska, Ewa; Ruman, Marek; Polkowska, Żaneta

2014-01-01

Due to the specific structure of surfactants molecules they are applied in different areas of human activity (industry, household). After using and discharging from wastewater treatment plants as effluent stream, surface active agents (SAAs) are emitted to various elements of the environment (atmosphere, waters, and solid phases), where they can undergo numerous physic-chemical processes (e.g., sorption, degradation) and freely migrate. Additionally, SAAs present in the environment can be accumulated in living organisms (bioaccumulation), what can have a negative effect on biotic elements of ecosystems (e.g., toxicity, disturbance of endocrine equilibrium). They also cause increaseing solubility of organic pollutants in aqueous phase, their migration, and accumulation in different environmental compartments. Moreover, surfactants found in aerosols can affect formation and development of clouds, which is associated with cooling effect in the atmosphere and climate changes. The environmental fate of SAAs is still unknown and recognition of this problem will contribute to protection of living organisms as well as preservation of quality and balance of various ecosystems. This work contains basic information about surfactants and overview of pollution of different ecosystems caused by them (their classification and properties, areas of use, their presence, and behavior in the environment). PMID:24527257

Active temporal multiplexing of indistinguishable heralded single photons

PubMed Central

Xiong, C.; Zhang, X.; Liu, Z.; Collins, M. J.; Mahendra, A.; Helt, L. G.; Steel, M. J.; Choi, D. -Y.; Chae, C. J.; Leong, P. H. W.; Eggleton, B. J.

2016-01-01

It is a fundamental challenge in quantum optics to deterministically generate indistinguishable single photons through non-deterministic nonlinear optical processes, due to the intrinsic coupling of single- and multi-photon-generation probabilities in these processes. Actively multiplexing photons generated in many temporal modes can decouple these probabilities, but key issues are to minimize resource requirements to allow scalability, and to ensure indistinguishability of the generated photons. Here we demonstrate the multiplexing of photons from four temporal modes solely using fibre-integrated optics and off-the-shelf electronic components. We show a 100% enhancement to the single-photon output probability without introducing additional multi-photon noise. Photon indistinguishability is confirmed by a fourfold Hong–Ou–Mandel quantum interference with a 91±16% visibility after subtracting multi-photon noise due to high pump power. Our demonstration paves the way for scalable multiplexing of many non-deterministic photon sources to a single near-deterministic source, which will be of benefit to future quantum photonic technologies. PMID:26996317

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

PubMed

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

2009-08-15

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

Perspective of surface active agents in baking industry: an overview.

PubMed

Ahmad, Asif; Arshad, Nazish; Ahmed, Zaheer; Bhatti, Muhammad Shahbaz; Zahoor, Tahir; Anjum, Nomana; Ahmad, Hajra; Afreen, Asma

2014-01-01

Different researchers have previously used surfactants for improving bread qualities and revealed that these compounds result in improving the quality of dough and bread by influencing dough strength, tolerance, uniform crumb cell size, and improve slicing characteristics and gas retention. The objective of this review is to highlight the areas where surfactants are most widely used particularly in the bread industries, their role and mechanism of interaction and their contribution to the quality characteristics of the dough and bread. This review reveals some aspects of surface-active agents regarding its role physiochemical properties of dough that in turn affect the bread characteristics by improving its sensory quality and storage stability.

Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles.

PubMed

Chen, Chen; Weir, Michael D; Cheng, Lei; Lin, Nancy J; Lin-Gibson, Sheng; Chow, Laurence C; Zhou, Xuedong; Xu, Hockin H K

2014-08-01

Recurrent caries at the margins is a primary reason for restoration failure. The objectives of this study were to develop bonding agent with the double benefits of antibacterial and remineralizing capabilities, to investigate the effects of NACP filler level and solution pH on Ca and P ion release from adhesive, and to examine the antibacterial and dentin bond properties. Nanoparticles of amorphous calcium phosphate (NACP) and a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) were synthesized. Scotchbond Multi-Purpose (SBMP) primer and adhesive served as control. DMADDM was incorporated into primer and adhesive at 5% by mass. NACP was incorporated into adhesive at filler mass fractions of 10%, 20%, 30% and 40%. A dental plaque microcosm biofilm model was used to test the antibacterial bonding agents. Calcium (Ca) and phosphate (P) ion releases from the cured adhesive samples were measured vs. filler level and solution pH of 7, 5.5 and 4. Adding 5% DMADDM and 10-40% NACP into bonding agent, and water-aging for 28 days, did not affect dentin bond strength, compared to SBMP control at 1 day (p>0.1). Adding DMADDM into bonding agent substantially decreased the biofilm metabolic activity and lactic acid production. Total microorganisms, total streptococci, and mutans streptococci were greatly reduced for bonding agents containing DMADDM. Increasing NACP filler level from 10% to 40% in adhesive increased the Ca and P ion release by an order of magnitude. Decreasing solution pH from 7 to 4 increased the ion release from adhesive by 6-10 folds. Bonding agents containing antibacterial DMADDM and remineralizer NACP were formulated to have Ca and P ion release, which increased with NACP filler level from 10% to 40% in adhesive. NACP adhesive was "smart" and dramatically increased the ion release at cariogenic pH 4, when these ions would be most-needed to inhibit caries. Therefore, bonding agent containing DMADDM and NACP may be promising to inhibit

THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS

PubMed Central

Hirsch, Robert L.; Kellner, Aaron

1956-01-01

Mice rendered hyperlipemic by means of intravenous or subcutaneous injections of triton WR 1339 were found to have an increase in the total amount of cholesterol in their bodies. This observation indicates that the injected surface-active agent affects the metabolism of cholesterol and brings about hyperlipemia by augmenting the synthesis of lipides, or by interfering with their degradation or excretion, or by some combination of these factors. The implications of the findings for the pathogenesis of the hyperlipemia induced by triton are discussed further in the accompanying paper (16). PMID:13332176

Towards an agent-oriented programming language based on Scala

NASA Astrophysics Data System (ADS)

Mitrović, Dejan; Ivanović, Mirjana; Budimac, Zoran

2012-09-01

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

Single-Phase Single-Stage Grid Tied Solar PV System with Active Power Filtering Using Power Balance Theory

NASA Astrophysics Data System (ADS)

Singh, Yashi; Hussain, Ikhlaq; Singh, Bhim; Mishra, Sukumar

2018-06-01

In this paper, power quality features such as harmonics mitigation, power factor correction with active power filtering are addressed in a single-stage, single-phase solar photovoltaic (PV) grid tied system. The Power Balance Theory (PBT) with perturb and observe based maximum power point tracking algorithm is proposed for the mitigation of power quality problems in a solar PV grid tied system. The solar PV array is interfaced to a single phase AC grid through a Voltage Source Converter (VSC), which provides active power flow from a solar PV array to the grid as well as to the load and it performs harmonics mitigation using PBT based control. The solar PV array power varies with sunlight and due to this, the solar PV grid tied VSC works only 8-10 h per day. At night, when PV power is zero, the VSC works as an active power filter for power quality improvement, and the load active power is delivered by the grid to the load connected at the point of common coupling. This increases the effective utilization of a VSC. The system is modelled and simulated using MATLAB and simulated responses of the system at nonlinear loads and varying environmental conditions are also validated experimentally on a prototype developed in the laboratory.

Single-Phase Single-Stage Grid Tied Solar PV System with Active Power Filtering Using Power Balance Theory

NASA Astrophysics Data System (ADS)

Singh, Yashi; Hussain, Ikhlaq; Singh, Bhim; Mishra, Sukumar

2018-03-01

In this paper, power quality features such as harmonics mitigation, power factor correction with active power filtering are addressed in a single-stage, single-phase solar photovoltaic (PV) grid tied system. The Power Balance Theory (PBT) with perturb and observe based maximum power point tracking algorithm is proposed for the mitigation of power quality problems in a solar PV grid tied system. The solar PV array is interfaced to a single phase AC grid through a Voltage Source Converter (VSC), which provides active power flow from a solar PV array to the grid as well as to the load and it performs harmonics mitigation using PBT based control. The solar PV array power varies with sunlight and due to this, the solar PV grid tied VSC works only 8-10 h per day. At night, when PV power is zero, the VSC works as an active power filter for power quality improvement, and the load active power is delivered by the grid to the load connected at the point of common coupling. This increases the effective utilization of a VSC. The system is modelled and simulated using MATLAB and simulated responses of the system at nonlinear loads and varying environmental conditions are also validated experimentally on a prototype developed in the laboratory.

Activation of cGAS-dependent antiviral responses by DNA intercalating agents

PubMed Central

Pépin, Geneviève; Nejad, Charlotte; Thomas, Belinda J.; Ferrand, Jonathan; McArthur, Kate; Bardin, Philip G.; Williams, Bryan R.G.; Gantier, Michael P.

2017-01-01

Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells. PMID:27694309

New agents approved for treatment of acute staphylococcal skin infections

PubMed Central

Tatarkiewicz, Jan; Staniszewska, Anna

2016-01-01

Vancomycin has been a predominant treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections for decades. However, growing reservations about its efficacy led to an urgent need for new antibiotics effective against MRSA and other drug-resistant Staphylococcus aureus strains. This review covers three new anti-MRSA antibiotics that have been recently approved by the FDA: dalbavancin, oritavancin, and tedizolid. The mechanism of action, indications, antibacterial activity profile, microbial resistance, pharmacokinetics, clinical efficacy, adverse effects, interactions as well as available formulations and administration of each of these new antibiotics are described. Dalbavancin is a once-a-week, two-dose, long-acting intravenous bactericidal lipoglycopeptide antibiotic. Oritavancin, a lipoglycopeptide with bactericidal activity, was developed as a single-dose intravenous treatment for acute bacterial skin and skin-structure infections (ABSSSI), which offers simplifying treatment of infections. Tedizolid is an oxazolidinone-class bacteriostatic once-daily agent, available for intravenous as well as oral use. Increased ability to overcome bacterial resistance is the main therapeutic advantage of the novel agents over existing antibiotics. PMID:27904526

New agents approved for treatment of acute staphylococcal skin infections.

PubMed

Tatarkiewicz, Jan; Staniszewska, Anna; Bujalska-Zadrożny, Magdalena

2016-12-01

Vancomycin has been a predominant treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections for decades. However, growing reservations about its efficacy led to an urgent need for new antibiotics effective against MRSA and other drug-resistant Staphylococcus aureus strains. This review covers three new anti-MRSA antibiotics that have been recently approved by the FDA: dalbavancin, oritavancin, and tedizolid. The mechanism of action, indications, antibacterial activity profile, microbial resistance, pharmacokinetics, clinical efficacy, adverse effects, interactions as well as available formulations and administration of each of these new antibiotics are described. Dalbavancin is a once-a-week, two-dose, long-acting intravenous bactericidal lipoglycopeptide antibiotic. Oritavancin, a lipoglycopeptide with bactericidal activity, was developed as a single-dose intravenous treatment for acute bacterial skin and skin-structure infections (ABSSSI), which offers simplifying treatment of infections. Tedizolid is an oxazolidinone-class bacteriostatic once-daily agent, available for intravenous as well as oral use. Increased ability to overcome bacterial resistance is the main therapeutic advantage of the novel agents over existing antibiotics.

Effect of ionic detergents, nonionic detergents, and chaotropic agents on polyphenol oxidase activity from dormant saffron (Crocus sativus L.) corms.

PubMed

Saeidian, Shahriar; Keyhani, Ezzatollah; Keyhani, Jacqueline

2007-05-02

Polyphenol oxidase (PPO; EC 1.14.18.1) catalyzes the hydroxylation of monophenols to o-diphenols (cresolase activity) and the oxidation of o-diphenols to o-quinones (catecholase activity), leading to browning in plants and produce. Further interest in the enzyme has been triggered by the active role that it plays in plant defense systems. PPO can be found in latent forms and is activated in vitro by various agents including urea, detergents, and proteases. The activation of PPO from several sources by sodium dodecyl sulfate (SDS) has been extensively investigated, but reports on the effect of other detergents or on the differential effect of detergents on each of PPO's activities are scarce. In addition, investigations on the enzyme in other plant parts besides fruits and vegetables are also scarce. Here, the effect of various detergents and chaotropic agents on PPO from dormant saffron (Crocus sativus L.) corm extract was investigated. SDS and sarkosyl activated the cresolase activity, while only SDS activated the catecholase activity. All other detergents tested, in milli- or micromolar concentrations, inhibited the cresolase activity but barely affected the catecholase activity. In contrast, urea and guanidine-HCl drastically inhibited the catecholase activity but moderately inhibited the cresolase activity. The same effects were obtained on the partially purified enzyme. Results identified a PPO, present in dormant corms, which was activated only by anionic detergents and was inhibited by other reputed activating agents such as urea. Results also emphasized the differences in structure and accessibility of the active sites for cresolase and catecholase activities.

Development of a method to analyze single cell activity by using dielectrophoretic levitation.

PubMed

Hakoda, M; Hachisu, T; Wakizaka, Y; Mii, S; Kitajima, N

2005-01-01

In cell fusion and genetic recombination, although the activity of single cells is extremely important, there is no method to analyze single cell activity. Development of a quick analyzing method for single cell activity is desired in various fields. Dielectrophoresis (DEP) refers to the force exerted on the induced dipole moment of an uncharged dielectric and/or conductive particle by a nonuniform electric field. By applying DEP, we obtained experimentally a relationship between the cell activity and the dielectric property, Re[K(omega)], and examined how to evaluate the single cell activity by measuring Re[K(omega)] of a single cell. A cone and plate electrode geometry was adapted in order to achieve the feedback-controlled DEP levitation. The single cell is exposed to a nonuniform field induced by the cone and plate electrode, and a more polarizable cell is moved to the direction of the cone electrode by the DEP force. The cell settles in the position where the DEP force and gravity are balanced by controlling applied voltage. This settled position, measured on the center axis of the cone electrode, depended on the dielectric constant of the cell. From these results, the relationship between the specific growth rates in cell growth phase and the dielectric properties Re[K(omega)] was obtained. Furthermore, the effect on the cell activity of various stresses, such as concentration of carbon dioxide, temperature, etc., was examined.

Agent oriented programming

NASA Technical Reports Server (NTRS)

Shoham, Yoav

1994-01-01

The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

Photocatalytic thin films coupled with polymeric microcapsules for the controlled-release of volatile agents upon solar activation

NASA Astrophysics Data System (ADS)

Oliveira, L. F.; Marques, J.; Coutinho, P. J. G.; Parpot, P.; Tavares, C. J.

2013-06-01

This work reportson the application of solar-activated photocatalytic thin films that allow the controlled-release of volatile agents (e.g., insecticides, repellents) from the interior of adsorbedpolymericmicrocapsules. In order to standardize the tests, a quantification of the inherent controlled-release of a particular volatile agent is determined by gas chromatography coupled to mass spectroscopy, so that an application can be offered to a wide range of supports from various industrial sectors, such as in textiles (clothing, curtains, mosquito nets). This technology takes advantage of the established photocatalytic property of titanium dioxide (TiO2) for the use as an active surface/site to promote the controlled-release of a specific vapor (volatile agentfrom within the aforementioned microcapsules.

Preserving Charge and Oxidation State of Au(III) Ions in an Agent-Functionalized Nanocrystal Model System

PubMed Central

2011-01-01

Supporting functional molecules on crystal facets is an established technique in nanotechnology. To preserve the original activity of ionic metallorganic agents on a supporting template, conservation of the charge and oxidation state of the active center is indispensable. We present a model system of a metallorganic agent that, indeed, fulfills this design criterion on a technologically relevant metal support with potential impact on Au(III)-porphyrin-functionalized nanoparticles for an improved anticancer-drug delivery. Employing scanning tunneling microscopy and -spectroscopy in combination with photoemission spectroscopy, we clarify at the single-molecule level the underlying mechanisms of this exceptional adsorption mode. It is based on the balance between a high-energy oxidation state and an electrostatic screening-response of the surface (image charge). Modeling with first principles methods reveals submolecular details of the metal–ligand bonding interaction and completes the study by providing an illustrative electrostatic model relevant for ionic metalorganic agent molecules, in general. PMID:21736315

Early-term and mid-term histologic events during single-level posterolateral intertransverse process fusion with rhBMP-2/collagen carrier and a ceramic bulking agent in a nonhuman primate model: implications for bone graft preparation.

PubMed

Khan, Safdar N; Toth, Jeffrey M; Gupta, Kavita; Glassman, Steven D; Gupta, Munish C

2014-06-01

We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic bulking agents in 3 different configurations. rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates. Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/β-tricalcium phosphate ceramic bulking agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic bulking agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. At the early time period, histology showed that bone formation

Laboratory activities involving transmissible spongiform encephalopathy causing agents

PubMed Central

Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

2013-01-01

Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

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

PubMed

Sasaki, S

2001-04-01

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

BSL-3 Laboratory Practices in the United States: Comparison of Select Agent and Non–Select Agent Facilities

PubMed Central

Pompei, Victoria C.; Anderson, Alice

2014-01-01

New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non–select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non–select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non–select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non–select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non–select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non–select agent laboratories to improve occupational health and safety. PMID:24552359

A structure-activity analysis of the variation in oxime efficacy against nerve agents

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

Maxwell, Donald M.; Koplovitz, Irwin; Worek, Franz

2008-09-01

A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k{sub r2}) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and inmore » vitro k{sub r2} decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (< 3.7-fold decrease in PR). The decrease in oxime PR and k{sub r2} as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k{sub r2} {center_dot} [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy.« less

Designing Agent Utilities for Coordinated, Scalable and Robust Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Tumer, Kagan

2005-01-01

Coordinating the behavior of a large number of agents to achieve a system level goal poses unique design challenges. In particular, problems of scaling (number of agents in the thousands to tens of thousands), observability (agents have limited sensing capabilities), and robustness (the agents are unreliable) make it impossible to simply apply methods developed for small multi-agent systems composed of reliable agents. To address these problems, we present an approach based on deriving agent goals that are aligned with the overall system goal, and can be computed using information readily available to the agents. Then, each agent uses a simple reinforcement learning algorithm to pursue its own goals. Because of the way in which those goals are derived, there is no need to use difficult to scale external mechanisms to force collaboration or coordination among the agents, or to ensure that agents actively attempt to appropriate the tasks of agents that suffered failures. To present these results in a concrete setting, we focus on the problem of finding the sub-set of a set of imperfect devices that results in the best aggregate device. This is a large distributed agent coordination problem where each agent (e.g., device) needs to determine whether to be part of the aggregate device. Our results show that the approach proposed in this work provides improvements of over an order of magnitude over both traditional search methods and traditional multi-agent methods. Furthermore, the results show that even in extreme cases of agent failures (i.e., half the agents failed midway through the simulation) the system's performance degrades gracefully and still outperforms a failure-free and centralized search algorithm. The results also show that the gains increase as the size of the system (e.g., number of agents) increases. This latter result is particularly encouraging and suggests that this method is ideally suited for domains where the number of agents is currently in the

Effect of a Single Musical Cakra Activation Manoeuvre on Body Temperature: An Exploratory Study.

PubMed

Sumathy, Sundar; Parmar, Parin N

2016-01-01

Cakra activation/balancing and music therapy are part of the traditional Indian healing system. Little is known about effect of musical (vocal) technique of cakra activation on body temperature. We conducted a single-session exploratory study to evaluate effects of a single musical (vocal) cakra activation manoeuvre on body temperature in controlled settings. Seven healthy adults performed a single musical (vocal) cakra activation manoeuvre for approximately 12 minutes in controlled environmental conditions. Pre- and post-manoeuvre body temperatures were recorded with a clinical mercury thermometer. After a single manoeuvre, increase in body temperature was recorded in all seven subjects. The range of increase in body temperature was from 0.2°F to 1.4°F; with mean temperature rise being 0.5°F and median temperature rise being 0.4°F. We conclude that a single session of musical (vocal) technique of cakra activation elevated body temperatures in all 7 subjects. Further research is required to study effects of various cakra activation techniques on body temperature and other physiological parameters.

Effect of a Single Musical Cakra Activation Manoeuvre on Body Temperature: An Exploratory Study

PubMed Central

Sumathy, Sundar; Parmar, Parin N

2016-01-01

Cakra activation/balancing and music therapy are part of the traditional Indian healing system. Little is known about effect of musical (vocal) technique of cakra activation on body temperature. We conducted a single-session exploratory study to evaluate effects of a single musical (vocal) cakra activation manoeuvre on body temperature in controlled settings. Seven healthy adults performed a single musical (vocal) cakra activation manoeuvre for approximately 12 minutes in controlled environmental conditions. Pre- and post-manoeuvre body temperatures were recorded with a clinical mercury thermometer. After a single manoeuvre, increase in body temperature was recorded in all seven subjects. The range of increase in body temperature was from 0.2°F to 1.4°F; with mean temperature rise being 0.5°F and median temperature rise being 0.4°F. We conclude that a single session of musical (vocal) technique of cakra activation elevated body temperatures in all 7 subjects. Further research is required to study effects of various cakra activation techniques on body temperature and other physiological parameters. PMID:28182030

Chelating agents.

PubMed

Bergan, T; Klaveness, J; Aasen, A J

2001-01-01

The antibacterial activity of metal ions, metal chelates, and molecules with chelating ability for polyvalent cations have been evaluated. The chelator N, N'-ethylenebis[2-(2-hydroxyphenyl)-glycine] (EHPG) exerted moderate-to-good activity against isolates of pathogenic bacteria and fungi. Other chelating agents such as ethylenediamine-tetraacetic acid (EDTA) and diethylene-triamine-pentaacetic acid (DTPA) revealed weak-to-moderate activity. Metal chelation of ligands reduced the activity of EDTA and DTPA. Copyright 2001 S. Karger AG, Basel

Polymeric contrast agents for medical imaging.

PubMed

Torchilin, V P

2000-09-01

Synthetic polymers and co-polymers are described, to be used as carriers of reporter groups for gamma-, magnetic resonance (MR), and computed tomography (CT) imaging. Those compounds include polychelating and amphiphilic polymers and serve as key components of various contrast agents. Single terminus-activated polychelating polymers were synthesized using poly-L-lysine (PLL) as a main chain and chelating moieties (such as diethylene triamine pentaacetic acid or DTPA) as side groups. These polymers were used for the modification of diagnostic monoclonal antibodies to increase their load with reporter metal atoms. As a result, better images within shorter time intervals were obtained in animal experiments. The application of liposomes and micelles as carriers for diagnostic imaging agents in experimental and clinical medicine is considered. The load of liposomes and micelles with contrast agents for gamma- and MR imaging (MRI) was sharply increased by using polychelating polymers additionally modified on one end with a hydrophobic phospholipid residue to give amphiphilic polymers. Such polymers easily incorporate the liposome membrane or micelle core and provide better loading of liposomes and micelles with reporter metals and, consequently, better and faster imaging of various physiological compartments, such as lymphatic and vascular systems. A block-copolymer of methoxy-poly(ethylene glycol) (MPEG) and iodine-substituted PLL was synthesized to prepare long-circulating contrast agent for CT imaging of the blood pool. In the aqueous solution, this copolymer forms stable and heavily loaded with iodine (up to 30% of iodine by weight) micelles. These micelle were successfully used for CT visualization of the vascular network in experimental animals. General trends in developing contrast polymers are discussed.

Hydrolysis of Synthetic Esters by the Antibacterial Agent in Serum

PubMed Central

Yotis, William W.

1966-01-01

Yotis, William W. (Loyola University, Chicago, Ill.). Hydrolysis of synthetic esters by the antibacterial agent in serum. J. Bacteriol. 91:488–493. 1966.—An antistaphylococcal serum agent was assayed colorimetrically, manometrically, and titrimetrically for esterase activity. p-Nitrophenol acetate, triacetin, l-lysine methyl and ethyl ester, and norleucine methyl ester were hydrolyzed by the antistaphylococcal agent. Acetylcholine and benzoylcholine esters, triolein, tristearin, and p-tosylarginine methyl ester were not attacked by this agent. With p-nitrophenol acetate as substrate, optimal activity occurred at pH 7.4. Incubation at 60 C for 30 min reduced drastically the esterase activity of the antistaphylococcal agent, and incubation at 75 C for 30 min abolished the esterase activity of this agent. Almost complete inhibition of esterase activity was observed with 0.001 m HgCl2, ZnSO4, and ethylenediaminetetraacetic acid (EDTA). EDTA inhibition could be reversed by the addition of CaCl2, but not MgCl2. Cysteine reversed the inhibition of HgCl2. NaF, atoxyl, diisopropyl fluorophosphate, quinine, and physostigmine did not influence the esterase activity of the antibacterial agent. The demonstration of esterase activity of both the antistaphylococcal agent and coagulase may shed further light on the reported ability of coagulase to neutralize the antistaphylococcal activity of this agent, or the prevention of absorption of the agent on the staphylococcal cell surface. In addition, the colorimetric procedure described in this report may be a convenient tool in assaying the potency of the antistaphylococcal agent. Images PMID:4956776

Active multispectral reflection fingerprinting of persistent chemical agents

NASA Astrophysics Data System (ADS)

Tholl, H. D.; Münzhuber, F.; Kunz, J.; Raab, M.; Rattunde, M.; Hugger, S.; Gutty, F.; Grisard, A.; Larat, C.; Papillon, D.; Schwarz, M.; Lallier, E.; Kastek, M.; Piatkowski, T.; Brygo, F.; Awanzino, C.; Wilsenack, F.; Lorenzen, A.

2017-10-01

Remote detection of toxic chemicals of very low vapour pressure deposited on surfaces in form of liquid films, droplets or powder is a capability that is needed to protect operators and equipment in chemical warfare scenarios and in industrial environments. Infrared spectroscopy is a suitable means to support this requirement. Available instruments based on passive emission spectroscopy have difficulties in discriminating the infrared emission spectrum of the surface background from that of the contamination. Separation of background and contamination is eased by illuminating the surface with a spectrally tune-able light source and by analyzing the reflectivity spectrum. The project AMURFOCAL (Active Multispectral Reflection Fingerprinting of Persistent Chemical Agents) has the research topic of stand-off detection and identification of chemical warfare agents (CWAs) with amplified quantum cascade laser technology in the long-wave infrared spectral range. The project was conducted under the Joint Investment Programme (JIP) on CBRN protection funded through the European Defence Agency (EDA). The AMURFOCAL instrument comprises a spectrally narrow tune-able light source with a broadband infrared detector and chemometric data analysis software. The light source combines an external cavity quantum cascade laser (EC-QCL) with an optical parametric amplifier (OPA) to boost the peak output power of a short laser pulse tune-able over the infrared fingerprint region. The laser beam is focused onto a target at a distance between 10 and 20 m. A 3D data cube is registered by tuning the wavelength of the laser emission while recording the received signal scattered off the target using a multi-element infrared detector. A particular chemical is identified through the extraction of its characteristic spectral fingerprint out of the measured data. The paper describes the AMURFOCAL instrument, its functional units, and its principles of operation.

In-situ coupling between kinase activities and protein dynamics within single focal adhesions

NASA Astrophysics Data System (ADS)

Wu, Yiqian; Zhang, Kaiwen; Seong, Jihye; Fan, Jason; Chien, Shu; Wang, Yingxiao; Lu, Shaoying

2016-07-01

The dynamic activation of oncogenic kinases and regulation of focal adhesions (FAs) are crucial molecular events modulating cell adhesion in cancer metastasis. However, it remains unclear how these events are temporally coordinated at single FA sites. Therefore, we targeted fluorescence resonance energy transfer (FRET)-based biosensors toward subcellular FAs to report local molecular events during cancer cell adhesion. Employing single FA tracking and cross-correlation analysis, we quantified the dynamic coupling characteristics between biochemical kinase activities and structural FA within single FAs. We show that kinase activations and FA assembly are strongly and sequentially correlated, with the concurrent FA assembly and Src activation leading focal adhesion kinase (FAK) activation by 42.6 ± 12.6 sec. Strikingly, the temporal coupling between kinase activation and individual FA assembly reflects the fate of FAs at later stages. The FAs with a tight coupling tend to grow and mature, while the less coupled FAs likely disassemble. During FA disassembly, however, kinase activations lead the disassembly, with FAK being activated earlier than Src. Therefore, by integrating subcellularly targeted FRET biosensors and computational analysis, our study reveals intricate interplays between Src and FAK in regulating the dynamic life of single FAs in cancer cells.

HeLa Cells Containing a Truncated Form of DNA Polymerase Beta are More Sensitized to Alkylating Agents than to Agents Inducing Oxidative Stress.

PubMed

Khanra, Kalyani; Chakraborty, Anindita; Bhattacharyya, Nandan

2015-01-01

The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta (polβ Δ208-304) specific for ovarian cancer. Pol β Δ208-304 has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays. Polβ Δ208-304 cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards H2O2 and UV when compared with HeLa cells alone. It has been shown that cell death in Pol β Δ208-304 transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach.

A user-system interface agent

NASA Technical Reports Server (NTRS)

Wakim, Nagi T.; Srivastava, Sadanand; Bousaidi, Mehdi; Goh, Gin-Hua

1995-01-01

Agent-based technologies answer to several challenges posed by additional information processing requirements in today's computing environments. In particular, (1) users desire interaction with computing devices in a mode which is similar to that used between people, (2) the efficiency and successful completion of information processing tasks often require a high-level of expertise in complex and multiple domains, (3) information processing tasks often require handling of large volumes of data and, therefore, continuous and endless processing activities. The concept of an agent is an attempt to address these new challenges by introducing information processing environments in which (1) users can communicate with a system in a natural way, (2) an agent is a specialist and a self-learner and, therefore, it qualifies to be trusted to perform tasks independent of the human user, and (3) an agent is an entity that is continuously active performing tasks that are either delegated to it or self-imposed. The work described in this paper focuses on the development of an interface agent for users of a complex information processing environment (IPE). This activity is part of an on-going effort to build a model for developing agent-based information systems. Such systems will be highly applicable to environments which require a high degree of automation, such as, flight control operations and/or processing of large volumes of data in complex domains, such as the EOSDIS environment and other multidisciplinary, scientific data systems. The concept of an agent as an information processing entity is fully described with emphasis on characteristics of special interest to the User-System Interface Agent (USIA). Issues such as agent 'existence' and 'qualification' are discussed in this paper. Based on a definition of an agent and its main characteristics, we propose an architecture for the development of interface agents for users of an IPE that is agent-oriented and whose resources

QUICR-learning for Multi-Agent Coordination

NASA Technical Reports Server (NTRS)

Agogino, Adrian K.; Tumer, Kagan

2006-01-01

Coordinating multiple agents that need to perform a sequence of actions to maximize a system level reward requires solving two distinct credit assignment problems. First, credit must be assigned for an action taken at time step t that results in a reward at time step t > t. Second, credit must be assigned for the contribution of agent i to the overall system performance. The first credit assignment problem is typically addressed with temporal difference methods such as Q-learning. The second credit assignment problem is typically addressed by creating custom reward functions. To address both credit assignment problems simultaneously, we propose the "Q Updates with Immediate Counterfactual Rewards-learning" (QUICR-learning) designed to improve both the convergence properties and performance of Q-learning in large multi-agent problems. QUICR-learning is based on previous work on single-time-step counterfactual rewards described by the collectives framework. Results on a traffic congestion problem shows that QUICR-learning is significantly better than a Q-learner using collectives-based (single-time-step counterfactual) rewards. In addition QUICR-learning provides significant gains over conventional and local Q-learning. Additional results on a multi-agent grid-world problem show that the improvements due to QUICR-learning are not domain specific and can provide up to a ten fold increase in performance over existing methods.

Mobile agent location in distributed environments

NASA Astrophysics Data System (ADS)

Fountoukis, S. G.; Argyropoulos, I. P.

2012-12-01

An agent is a small program acting on behalf of a user or an application which plays the role of a user. Artificial intelligence can be encapsulated in agents so that they can be capable of both behaving autonomously and showing an elementary decision ability regarding movement and some specific actions. Therefore they are often called autonomous mobile agents. In a distributed system, they can move themselves from one processing node to another through the interconnecting network infrastructure. Their purpose is to collect useful information and to carry it back to their user. Also, agents are used to start, monitor and stop processes running on the individual interconnected processing nodes of computer cluster systems. An agent has a unique id to discriminate itself from other agents and a current position. The position can be expressed as the address of the processing node which currently hosts the agent. Very often, it is necessary for a user, a processing node or another agent to know the current position of an agent in a distributed system. Several procedures and algorithms have been proposed for the purpose of position location of mobile agents. The most basic of all employs a fixed computing node, which acts as agent position repository, receiving messages from all the moving agents and keeping records of their current positions. The fixed node, responds to position queries and informs users, other nodes and other agents about the position of an agent. Herein, a model is proposed that considers pairs and triples of agents instead of single ones. A location method, which is investigated in this paper, attempts to exploit this model.

Synergy between antibiotics and natural agents results in increased antimicrobial activity against Staphylococcus epidermidis.

PubMed

Abidi, Syed Hani; Ahmed, Khalid; Sherwani, Sikander Khan; Kazmi, Shahana Urooj

2015-09-27

Staphylococcus epidermidis is one of the most frequent causes of biofilm-associated infections on indwelling medical devices. With the emergence of methicillin-resistant S. epidermidis (MRSE), there is an urgent need to discover novel active agents against a range of Gram-positive pathogens. We screened the clinical isolates of S. epidermidis for susceptibility/resistance against commonly prescribed antibiotics. Furthermore, we tested some natural agents alone and in combination with antibiotics to find possible synergistic antimicrobial effects. S. epidermidis clinical isolates were screened for susceptibility/resistance against vancomycin, erythromycin, tetracycline, chloramphenicol, ampicillin, ofloxacin, cephalexin, and gentamicin using the Kirby-Bauer disk diffusion method. The antimicrobial potential of Camellia sinensis, Juglans regia, and Hippophae rhamnoides alone and in combination with antibiotics were examined using the disk diffusion method, where the antimicrobial potential activity was measured in terms of formation of zones of inhibition. Most S. epidermidis isolates were found to be resistant to one or more antibiotics. Gentamycin and ofloxacin were found to be the most effective antibiotics against S. epidermidis isolates. Extracts of Hippophae rhamnoides, Juglans regia, and Camellia sinensis were found to be equally effective against S. epidermidis isolates. In combination with antibiotics, these extracts exhibited appreciable synergistic activity; the highest synergistic activity was observed with erythromycin and cephalexin. In the case of cephalexin, a reversion in resistance was observed. The plant extracts used in the study exhibited additive and synergistic antibacterial activity against S. epidermidis, hence providing an effective alternative to deal with the problem of multidrug resistance.

Chemical Action of Halogenated Agents in Fire Extinguishing

NASA Technical Reports Server (NTRS)

Belles, Frank E.

1955-01-01

The action of halogenated agents in preventing flame propagation in fuel-air mixtures in laboratory tests is discussed in terms of a possible chemical mechanism. The mechanism chosen is that of chain-breaking reactions between agent and active particles (hydrogen and oxygen atoms and hydroxyl radicsls). Data from the literature on the flammability peaks of n-heptane agent-air mixtures are treated. Ratings of agent effectiveness in terms of the fuel equivalent of the agent, based on both fuel and agent concentrations at the peak, are proposed as preferable to ratings in terms of agent concentration alone. These fuel-equivalent ratings are roughly correlated by reactivities assigned to halogen and hydrogen atoms in the agent molecules. It is concluded that the presence of hydrogen in agent need not reduce its fire-fighting ability, provided there is enough halogen to make the agent nonflammable. A method is presented for estimating from quenching-distance data a rate constant for the reaction of agent with active particles. A quantitative result is obtained for methyl bromide. This rate constant predicts the observed peak concentration of methyl bromide quite well. However, more data are needed to prove the validity of the method. The assumption that hal.ogenatedagents act mainly by chain-bresking reactions with active particles is consistent with the experimental facts and should help guide the selection of agents for further tests.

Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents.

PubMed

Cloonan, Suzanne M; Keating, John J; Butler, Stephen G; Knox, Andrew J S; Jørgensen, Anne M; Peters, Günther H; Rai, Dilip; Corrigan, Desmond; Lloyd, David G; Williams, D Clive; Meegan, Mary J

2009-12-01

The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine transporters. In this study, a novel library of structurally diverse 4-MTA analogues were synthesised with or without N-alkyl and/or C-alpha methyl or ethyl groups so that their potential SERT-dependent antiproliferative activity could be assessed. Many of the compounds displayed SERT-binding activity as well as cytotoxic activity. While there was no direct correlation between these two effects, a number of derivatives displayed anti-tumour effects in lymphoma, leukaemia and breast cancer cell lines, showing further potential to be developed as possible chemotherapeutic agents.

Tumor Cell Gene Expression Changes Following Short-term In vivo Exposure to Single Agent Chemotherapeutics are Related to Survival in Multiple Myeloma

PubMed Central

Burington, Bart; Barlogie, Bart; Zhan, Fenghuang; Crowley, John; Shaughnessy, John D.

2013-01-01

Changes in global gene expression patterns in tumor cells following in vivo therapy may vary by treatment and provide added or synergistic prognostic power over pretherapy gene expression profiles (GEP). This molecular readout of drug-cell interaction may also point to mechanisms of action/resistance. In newly diagnosed patients with multiple myeloma (MM), microarray data were obtained on tumor cells prior to and 48 hours after in vivo treatment using dexamethasone (n = 45) or thalidomide (n = 42); in the case of relapsed MM, microarray data were obtained prior to (n = 36) and after (n = 19) lenalidomide administration. Dexamethasone and thalidomide induced both common and unique GEP changes in tumor cells. Combined baseline and 48-hour changes in GEP in a subset of genes, many related to oxidative stress and cytoskeletal dynamics, were predictive of outcome in newly diagnosed MM patients receiving tandem transplants. Thalidomide-altered genes also changed following lenalidomide exposure and predicted event-free and overall survival in relapsed patients receiving lenalidomide as a single agent. Combined with baseline molecular features, changes in GEP following short-term single-agent exposure may help guide treatment decisions for patients with MM. Genes whose drug-altered expression were found to be related to survival may point to molecular switches related to response and/or resistance to different classes of drugs. PMID:18676754

Single-accelerometer-based daily physical activity classification.

PubMed

Long, Xi; Yin, Bin; Aarts, Ronald M

2009-01-01

In this study, a single tri-axial accelerometer placed on the waist was used to record the acceleration data for human physical activity classification. The data collection involved 24 subjects performing daily real-life activities in a naturalistic environment without researchers' intervention. For the purpose of assessing customers' daily energy expenditure, walking, running, cycling, driving, and sports were chosen as target activities for classification. This study compared a Bayesian classification with that of a Decision Tree based approach. A Bayes classifier has the advantage to be more extensible, requiring little effort in classifier retraining and software update upon further expansion or modification of the target activities. Principal components analysis was applied to remove the correlation among features and to reduce the feature vector dimension. Experiments using leave-one-subject-out and 10-fold cross validation protocols revealed a classification accuracy of approximately 80%, which was comparable with that obtained by a Decision Tree classifier.

Comparison of Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to the Nerve Agents Cyclosarin and Tabun in Freely Moving Guinea Pigs

DTIC Science & Technology

2010-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Comparison of extracellular striatal acetylcholine and brain seizure activity following...lethality; nerve agents; organophosphorus compounds; seizure activity ; tabun 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...acetylcholine and brain seizure activity following acute exposure to the nerve agents cyclosarin and tabun in freely moving guinea pigs John C

Activity of posaconazole and other antifungal agents against Mucorales strains identified by sequencing of internal transcribed spacers.

PubMed

Alastruey-Izquierdo, Ana; Castelli, Maria Victoria; Cuesta, Isabel; Monzon, Araceli; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis

2009-04-01

The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates.

Molecular Imaging and Contrast Agent Database (MICAD): evolution and progress.

PubMed

Chopra, Arvind; Shan, Liang; Eckelman, W C; Leung, Kam; Latterner, Martin; Bryant, Stephen H; Menkens, Anne

2012-02-01

The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov ) to students, researchers, and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, X-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1,000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4,250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration as well as a comma separated values file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, pre-clinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities, and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments, or suggestions for further improvement of the database by writing to the editors at micad@nlm.nih.gov.

Molecular Imaging and Contrast Agent Database (MICAD): Evolution and Progress

PubMed Central

Chopra, Arvind; Shan, Liang; Eckelman, W. C.; Leung, Kam; Latterner, Martin; Bryant, Stephen H.; Menkens, Anne

2011-01-01

The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov) to students, researchers and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, x-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration (FDA) as well as a CSV file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, preclinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments or suggestions for further improvement of the database by writing to the editors at: micad@nlm.nih.gov PMID:21989943

Activation of cGAS-dependent antiviral responses by DNA intercalating agents.

PubMed

Pépin, Geneviève; Nejad, Charlotte; Thomas, Belinda J; Ferrand, Jonathan; McArthur, Kate; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

2017-01-09

Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Joint Chemical Agent Detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.; Owen, Jeffery L.

2002-06-01

The Joint Chemical Agent Detector (JCAD) will provide state of the art chemical warfare agent detection capability to ground vehicle operators. Intelligence sources estimate that over twenty counties have active chemical weapons programs. The spread of chemical weapons to third world nations, coupled with the potential for US involvement in these areas in an operational or support capacity, increases the probability that the Joint Services may encounter chemical agents and toxic industrial materials anywhere in the world. Currently, fielded chemical agent detectors are bulky, labor intensive, and subject to false readings. No legacy detector is sensitive enough to provide detection and warning of the low dose hazards associated with miosis contamination. The JCAD will provide a small, lightweight chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection components across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD will detect, identify, quantify, and warn of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector will provide local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD will also be capable of being upgraded to protect against future chemical agent threats. The JCAD will provide the vehicle operators with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Insect-gene-activity detection system for chemical and biological warfare agents and toxic industrial chemicals

NASA Astrophysics Data System (ADS)

Mackie, Ryan S.; Schilling, Amanda S.; Lopez, Arturo M.; Rayms-Keller, Alfredo

2002-02-01

Detection of multiple chemical and biological weapons (CBW) agents and/or complex mixtures of toxic industrial chemicals (TIC) is imperative for both the commercial and military sectors. In a military scenario, a multi-CBW attack would create confusion, thereby delaying decontamination and therapeutic efforts. In the commercial sector, polluted sites invariably contain a mixture of TIC. Novel detection systems capable of detecting CBW and TIC are sorely needed. While it may be impossible to build a detector capable of discriminating all the possible combinations of CBW, a detection system capable of statistically predicting the most likely composition of a given mixture is within the reach of current emerging technologies. Aquatic insect-gene activity may prove to be a sensitive, discriminating, and elegant paradigm for the detection of CBW and TIC. We propose to systematically establish the expression patterns of selected protein markers in insects exposed to specific mixtures of chemical and biological warfare agents to generate a library of biosignatures of exposure. The predicting capabilities of an operational library of biosignatures of exposures will allow the detection of emerging novel or genetically engineered agents, as well as complex mixtures of chemical and biological weapons agents. CBW and TIC are discussed in the context of war, terrorism, and pollution.

Model-free learning on robot kinematic chains using a nested multi-agent topology

NASA Astrophysics Data System (ADS)

Karigiannis, John N.; Tzafestas, Costas S.

2016-11-01

This paper proposes a model-free learning scheme for the developmental acquisition of robot kinematic control and dexterous manipulation skills. The approach is based on a nested-hierarchical multi-agent architecture that intuitively encapsulates the topology of robot kinematic chains, where the activity of each independent degree-of-freedom (DOF) is finally mapped onto a distinct agent. Each one of those agents progressively evolves a local kinematic control strategy in a game-theoretic sense, that is, based on a partial (local) view of the whole system topology, which is incrementally updated through a recursive communication process according to the nested-hierarchical topology. Learning is thus approached not through demonstration and training but through an autonomous self-exploration process. A fuzzy reinforcement learning scheme is employed within each agent to enable efficient exploration in a continuous state-action domain. This paper constitutes in fact a proof of concept, demonstrating that global dexterous manipulation skills can indeed evolve through such a distributed iterative learning of local agent sensorimotor mappings. The main motivation behind the development of such an incremental multi-agent topology is to enhance system modularity, to facilitate extensibility to more complex problem domains and to improve robustness with respect to structural variations including unpredictable internal failures. These attributes of the proposed system are assessed in this paper through numerical experiments in different robot manipulation task scenarios, involving both single and multi-robot kinematic chains. The generalisation capacity of the learning scheme is experimentally assessed and robustness properties of the multi-agent system are also evaluated with respect to unpredictable variations in the kinematic topology. Furthermore, these numerical experiments demonstrate the scalability properties of the proposed nested-hierarchical architecture, where

Activity of Posaconazole and Other Antifungal Agents against Mucorales Strains Identified by Sequencing of Internal Transcribed Spacers▿

PubMed Central

Alastruey-Izquierdo, Ana; Castelli, Maria Victoria; Cuesta, Isabel; Monzon, Araceli; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis

2009-01-01

The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates. PMID:19171801

Hypoxia-Targeting Drug Evofosfamide (TH-302) Enhances Sunitinib Activity in Neuroblastoma Xenograft Models.

PubMed

Kumar, Sushil; Sun, Jessica D; Zhang, Libo; Mokhtari, Reza Bayat; Wu, Bing; Meng, Fanying; Liu, Qian; Bhupathi, Deepthi; Wang, Yan; Yeger, Herman; Hart, Charles; Baruchel, Sylvain

2018-05-23

Antiangiogenic therapy has shown promising results in preclinical and clinical trials. However, tumor cells acquire resistance to this therapy by gaining ability to survive and proliferate under hypoxia induced by antiangiogenic therapy. Combining antiangiogenic therapy with hypoxia-activated prodrugs can overcome this limitation. Here, we have tested the combination of antiangiogenic drug sunitinib in combination with hypoxia-activated prodrug evofosfamide in neuroblastoma. In vitro, neuroblastoma cell line SK-N-BE(2) was 40-folds sensitive to evofosfamide under hypoxia compared to normoxia. In IV metastatic model, evofosfamide significantly increased mice survival compared to the vehicle (P=.02). In SK-N-BE(2) subcutaneous xenograft model, we tested two different treatment regimens using 30 mg/kg sunitinib and 50 mg/kg evofosfamide. Here, sunitinib therapy when started along with evofosfamide treatment showed higher efficacy compared to single agents in subcutaneous SK-N-BE(2) xenograft model, whereas sunitinib when started 7 days after evofosfamide treatment did not have any advantage compared to treatment with either single agent. Immunofluorescence of tumor sections revealed higher number of apoptotic cells and hypoxic areas compared to either single agent when both treatments were started together. Treatment with 80 mg/kg sunitinib with 50 mg/kg evofosfamide was significantly superior to single agents in both xenograft and metastatic models. This study confirms the preclinical efficacy of sunitinib and evofosfamide in murine models of aggressive neuroblastoma. Sunitinib enhances the efficacy of evofosfamide by increasing hypoxic areas, and evofosfamide targets hypoxic tumor cells. Consequently, each drug enhances the activity of the other. Copyright © 2018. Published by Elsevier Inc.

Plasma gasification of refuse derived fuel in a single-stage system using different gasifying agents.

PubMed

Agon, N; Hrabovský, M; Chumak, O; Hlína, M; Kopecký, V; Masláni, A; Bosmans, A; Helsen, L; Skoblja, S; Van Oost, G; Vierendeels, J

2016-01-01

The renewable evolution in the energy industry and the depletion of natural resources are putting pressure on the waste industry to shift towards flexible treatment technologies with efficient materials and/or energy recovery. In this context, a thermochemical conversion method of recent interest is plasma gasification, which is capable of producing syngas from a wide variety of waste streams. The produced syngas can be valorized for both energetic (heat and/or electricity) and chemical (ammonia, hydrogen or liquid hydrocarbons) end-purposes. This paper evaluates the performance of experiments on a single-stage plasma gasification system for the treatment of refuse-derived fuel (RDF) from excavated waste. A comparative analysis of the syngas characteristics and process yields was done for seven cases with different types of gasifying agents (CO2+O2, H2O, CO2+H2O and O2+H2O). The syngas compositions were compared to the thermodynamic equilibrium compositions and the performance of the single-stage plasma gasification of RDF was compared to that of similar experiments with biomass and to the performance of a two-stage plasma gasification process with RDF. The temperature range of the experiment was from 1400 to 1600 K and for all cases, a medium calorific value syngas was produced with lower heating values up to 10.9 MJ/Nm(3), low levels of tar, high levels of CO and H2 and which composition was in good agreement to the equilibrium composition. The carbon conversion efficiency ranged from 80% to 100% and maximum cold gas efficiency and mechanical gasification efficiency of respectively 56% and 95%, were registered. Overall, the treatment of RDF proved to be less performant than that of biomass in the same system. Compared to a two-stage plasma gasification system, the produced syngas from the single-stage reactor showed more favourable characteristics, while the recovery of the solid residue as a vitrified slag is an advantage of the two-stage set-up. Copyright �

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis.

PubMed

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-05-21

To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents.

GMC oxidoreductase, a highly expressed protein in a potent biocontrol agent Fusarium oxysporum Cong:1-2, is dispensable for biocontrol activity.

PubMed

Kawabe, Masato; Okabe Onokubo, Akiko; Arimoto, Yutaka; Yoshida, Takanobu; Azegami, Koji; Teraoka, Tohru; Arie, Tsutomu

2011-01-01

A spontaneous non-pathogenic variant (Cong:1-2) derived from Fusarium oxysporum f. sp. conglutinans (Cong: 1-1), a causal agent of cabbage yellows, carries biocontrol activity for cabbage yellows. We found a GMC oxidoreductase (ODX1) among the proteins expressed much more in Cong:1-2 than Cong:1-1 by 2D-DIGE comparison. GMC oxidoreductases have been reported to be involved in biocontrol activity of several plant pathogenic fungi. The gene encoding ODX1 in Cong:1-2 was cloned, and targeted disruption of the gene in Cong:1-2 did not affect its biocontrol activity, suggesting that GMC oxidoreductase is dispensable for biocontrol activity in the fungal biocontrol agent.

Impact of single-site axonal GABAergic synaptic events on cerebellar interneuron activity.

PubMed

de San Martin, Javier Zorrilla; Jalil, Abdelali; Trigo, Federico F

2015-12-01

Axonal ionotropic receptors are present in a variety of neuronal types, and their function has largely been associated with the modulation of axonal activity and synaptic release. It is usually assumed that activation of axonal GABA(A)Rs comes from spillover, but in cerebellar molecular layer interneurons (MLIs) the GABA source is different: in these cells, GABA release activates presynaptic GABA(A) autoreceptors (autoRs) together with postsynaptic targets, producing an autoR-mediated synaptic event. The frequency of presynaptic, autoR-mediated miniature currents is twice that of their somatodendritic counterparts, suggesting that autoR-mediated responses have an important effect on interneuron activity. Here, we used local Ca(2+) photolysis in MLI axons of juvenile rats to evoke GABA release from individual varicosities to study the activation of axonal autoRs in single release sites. Our data show that single-site autoR conductances are similar to postsynaptic dendritic conductances. In conditions of high [Cl(-)](i), autoR-mediated conductances range from 1 to 5 nS; this corresponds to ∼30-150 GABA(A) channels per presynaptic varicosity, a value close to the number of channels in postsynaptic densities. Voltage responses produced by the activation of autoRs in single varicosities are amplified by a Na(v)-dependent mechanism and propagate along the axon with a length constant of 91 µm. Immunolabeling determination of synapse location shows that on average, one third of the synapses produce autoR-mediated signals that are large enough to reach the axon initial segment. Finally, we show that single-site activation of presynaptic GABA(A) autoRs leads to an increase in MLI excitability and thus conveys a strong feedback signal that contributes to spiking activity. © 2015 Zorrilla de San Martin et al.

Impact of single-site axonal GABAergic synaptic events on cerebellar interneuron activity

PubMed Central

Zorrilla de San Martin, Javier; Jalil, Abdelali

2015-01-01

Axonal ionotropic receptors are present in a variety of neuronal types, and their function has largely been associated with the modulation of axonal activity and synaptic release. It is usually assumed that activation of axonal GABAARs comes from spillover, but in cerebellar molecular layer interneurons (MLIs) the GABA source is different: in these cells, GABA release activates presynaptic GABAA autoreceptors (autoRs) together with postsynaptic targets, producing an autoR-mediated synaptic event. The frequency of presynaptic, autoR-mediated miniature currents is twice that of their somatodendritic counterparts, suggesting that autoR-mediated responses have an important effect on interneuron activity. Here, we used local Ca2+ photolysis in MLI axons of juvenile rats to evoke GABA release from individual varicosities to study the activation of axonal autoRs in single release sites. Our data show that single-site autoR conductances are similar to postsynaptic dendritic conductances. In conditions of high [Cl−]i, autoR-mediated conductances range from 1 to 5 nS; this corresponds to ∼30–150 GABAA channels per presynaptic varicosity, a value close to the number of channels in postsynaptic densities. Voltage responses produced by the activation of autoRs in single varicosities are amplified by a Nav-dependent mechanism and propagate along the axon with a length constant of 91 µm. Immunolabeling determination of synapse location shows that on average, one third of the synapses produce autoR-mediated signals that are large enough to reach the axon initial segment. Finally, we show that single-site activation of presynaptic GABAA autoRs leads to an increase in MLI excitability and thus conveys a strong feedback signal that contributes to spiking activity. PMID:26621773

Agent-based simulation of a financial market

NASA Astrophysics Data System (ADS)

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

2001-10-01

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

Structure-Activity Relationships of 6- and 8-Gingerol Analogs as Anti-Biofilm Agents.

PubMed

Choi, Hyunsuk; Ham, So-Young; Cha, Eunji; Shin, Yujin; Kim, Han-Shin; Bang, Jeong Kyu; Son, Sang-Hyun; Park, Hee-Deung; Byun, Youngjoo

2017-12-14

Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a master regulator of quorum sensing networks in P. aeruginosa. Structure-activity relationship studies showed that a hydrogen-bonding interaction in the head section, stereochemistry and rotational rigidity in the middle section, and optimal alkyl chain length in the tail section are important factors for the enhancement of LasR-binding affinity and for the inhibition of biofilm formation. The most potent compound 41, an analog of (R)-8-gingerol with restricted rotation, showed stronger LasR-binding affinity and inhibition of biofilm formation than the known LasR antagonist (S)-6-gingerol. This new LasR antagonist can be used as an early lead compound for the development of anti-biofilm agents to treat P. aeruginosa infections.

Joint chemical agent detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.

2003-08-01

The Joint Chemical Agent Detector (JCAD) has continued development through 2002. The JCAD has completed Contractor Validation Testing (CVT) that included chemical warfare agent testing, environmental testing, electromagnetic interferent testing, and platform integration validation. The JCAD provides state of the art chemical warfare agent detection capability to military and homeland security operators. Intelligence sources estimate that over twenty countries have active chemical weapons programs. The spread of weapons of mass destruction (and the industrial capability for manufacture of these weapons) to third world nations and terrorist organizations has greatly increased the chemical agent threat to U.S. interests. Coupled with the potential for U.S. involvement in localized conflicts in an operational or support capacity, increases the probability that the military Joint Services may encounter chemical agents anywhere in the world. The JCAD is a small (45 in3), lightweight (2 lb.) chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection component across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD detects, identifies, quantifies, and warns of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector provides local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew and other personnel in the local area with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD is capable of being upgraded to protect against future chemical agent threats. The JCAD provides the operator with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Process for separating metallic from semiconducting single-walled carbon nanotubes

NASA Technical Reports Server (NTRS)

Sun, Ya-Ping (Inventor)

2008-01-01

A method for separating semiconducting single-walled carbon nanotubes from metallic single-walled carbon nanotubes is disclosed. The method utilizes separation agents that preferentially associate with semiconducting nanotubes due to the electrical nature of the nanotubes. The separation agents are those that have a planar orientation, .pi.-electrons available for association with the surface of the nanotubes, and also include a soluble portion of the molecule. Following preferential association of the separation agent with the semiconducting nanotubes, the agent/nanotubes complex is soluble and can be solubilized with the solution enriched in semiconducting nanotubes while the residual solid is enriched in metallic nanotubes.

New agents for prostate cancer.

PubMed

Agarwal, N; Di Lorenzo, G; Sonpavde, G; Bellmunt, J

2014-09-01

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid

L-DOPA-Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug-Delivery Vehicles.

PubMed

McDonagh, Birgitte Hjelmeland; Singh, Gurvinder; Hak, Sjoerd; Bandyopadhyay, Sulalit; Augestad, Ingrid Lovise; Peddis, Davide; Sandvig, Ioanna; Sandvig, Axel; Glomm, Wilhelm Robert

2016-01-20

Manganese oxide nanoparticles (MONPs) are capable of time-dependent magnetic resonance imaging contrast switching as well as releasing a surface-bound drug. MONPs give T2/T2* contrast, but dissolve and release T1-active Mn(2+) and L-3,4-dihydroxyphenylalanine. Complementary images are acquired with a single contrast agent, and applications toward Parkinson's disease are suggested. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model

NASA Astrophysics Data System (ADS)

Cekanova, Maria; Uddin, Md. Jashim; Legendre, Alfred M.; Galyon, Gina; Bartges, Joseph W.; Callens, Amanda; Martin-Jimenez, Tomas; Marnett, Lawrence J.

2012-11-01

We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1 mg/kg fluorocoxib A. Blood and urine samples collected three days after administration of each dose of fluorocoxib A revealed no evidence of toxicity, and no clinically relevant adverse events were noted on physical examination of exposed dogs over that time period. Pharmacokinetic parameters were assessed in additional research dogs from plasma collected at several time points after i.v. administration of fluorocoxib A using high-performance liquid chromatography analysis. The pharmacokinetic studies using 1 mg/kg showed a peak of fluorocoxib A (92±28 ng/ml) in plasma collected at 0.5 h. Tumor specific uptake of fluorocoxib A was demonstrated using a dog diagnosed with colorectal cancer expressing COX-2. Our data support the safe single-dose administration and in vivo efficacy of fluorocoxib A, suggesting a high potential for successful translation to clinical use as an imaging agent for improved tumor detection in humans.

Meisoindigo is a promising agent with in vitro and in vivo activity against human acute myeloid leukemia.

PubMed

Lee, Chin-Cheng; Lin, Che-Pin; Lee, Yueh-Lun; Wang, Giueng-Chueng; Cheng, Yuan-Chih; Liu, H Eugene

2010-05-01

Meisoindigo, a derivative of Indigo naturalis, has been used in China for chronic myeloid leukemia. In vitro cell line studies have shown that this agent might induce apoptosis and myeloid differentiation of acute myeloid leukemia (AML). In this study, we explored its mechanisms and potential in AML. NB4, HL-60, and U937 cells and primary AML cells were used to examine its effects and the NOD/SCID animal model was used to evaluate its in vivo activity. Meisoindigo inhibited the growth of leukemic cells by inducing marked apoptosis and moderate cell-cycle arrest at the G(0)/G(1) phase. It down-regulated anti-apoptotic Bcl-2, and up-regulated pro-apoptotic Bak and Bax and cell-cycle related proteins, p21and p27. Furthermore, it induced myeloid differentiation, as demonstrated by morphologic changes, up-regulation of CD11b, and increased nitroblue tetrazolium reduction activity in all cell lines tested. In addition, meisoindigo down-regulated the expression of human telomerase reverse transcriptase and enhanced the cytotoxicity of conventional chemotherapeutic agents, cytarabine and idarubicin. As with the results from cell lines, meisoindigo also induced apoptosis, up-regulated p21 and p27, and down-regulated Bcl-2 in primary AML cells. The in vivo anti-leukemic activity of meisoindigo was also demonstrated by decreased spleen size in a dose-dependent manner. Taking these results together, meisoindigo is a potential agent for AML.

Effects of competition and cooperation interaction between agents on networks in the presence of a market capacity

NASA Astrophysics Data System (ADS)

Sonubi, A.; Arcagni, A.; Stefani, S.; Ausloos, M.

2016-08-01

A network effect is introduced taking into account competition, cooperation, and mixed-type interaction among agents along a generalized Verhulst-Lotka-Volterra model. It is also argued that the presence of a market capacity undoubtedly enforces a definite limit on the agent's size growth. The state stability of triadic agents, i.e., the most basic network plaquette, is investigated analytically for possible scenarios, through a fixed-point analysis. It is discovered that: (i) market demand is only satisfied for full competition when one agent monopolizes the market; (ii) growth of agent size is encouraged in full cooperation; (iii) collaboration among agents to compete against one single agent may result in the disappearance of this single agent out of the market; and (iv) cooperating with two rivals may become a growth strategy for an intelligent agent.

Effects of competition and cooperation interaction between agents on networks in the presence of a market capacity.

PubMed

Sonubi, A; Arcagni, A; Stefani, S; Ausloos, M

2016-08-01

A network effect is introduced taking into account competition, cooperation, and mixed-type interaction among agents along a generalized Verhulst-Lotka-Volterra model. It is also argued that the presence of a market capacity undoubtedly enforces a definite limit on the agent's size growth. The state stability of triadic agents, i.e., the most basic network plaquette, is investigated analytically for possible scenarios, through a fixed-point analysis. It is discovered that: (i) market demand is only satisfied for full competition when one agent monopolizes the market; (ii) growth of agent size is encouraged in full cooperation; (iii) collaboration among agents to compete against one single agent may result in the disappearance of this single agent out of the market; and (iv) cooperating with two rivals may become a growth strategy for an intelligent agent.

Active and Inactive Leg Hemodynamics during Sequential Single-Leg Interval Cycling.

PubMed

Gordon, Nicole; Abbiss, Chris R; Ihsan, Mohammed; Maiorana, Andrew J; Peiffer, Jeremiah J

2018-06-01

Leg order during sequential single-leg cycling (i.e., exercising both legs independently within a single session) may affect local muscular responses potentially influencing adaptations. This study examined the cardiovascular and skeletal muscle hemodynamic responses during double-leg and sequential single-leg cycling. Ten young healthy adults (28 ± 6 yr) completed six 1-min double-leg intervals interspersed with 1 min of passive recovery and, on a separate occasion, 12 (six with one leg followed by six with the other leg) 1-min single-leg intervals interspersed with 1 min of passive recovery. Oxygen consumption, heart rate, blood pressure, muscle oxygenation, muscle blood volume, and power output were measured throughout each session. Oxygen consumption, heart rate, and power output were not different between sets of single-leg intervals, but the average of both sets was lower than the double-leg intervals. Mean arterial pressure was higher during double-leg compared with sequential single-leg intervals (115 ± 9 vs 104 ± 9 mm Hg, P < 0.05) and higher during the initial compared with second set of single-leg intervals (108 ± 10 vs 101 ± 10 mm Hg, P < 0.05). The increase in muscle blood volume from baseline was similar between the active single leg and the double leg (267 ± 150 vs 214 ± 169 μM·cm, P = 0.26). The pattern of change in muscle blood volume from the initial to second set of intervals was significantly different (P < 0.05) when the leg was active in the initial (-52.3% ± 111.6%) compared with second set (65.1% ± 152.9%). These data indicate that the order in which each leg performs sequential single-leg cycling influences the local hemodynamic responses, with the inactive muscle influencing the stimulus experienced by the contralateral leg.

The slow cell death response when screening chemotherapeutic agents.

PubMed

Blois, Joseph; Smith, Adam; Josephson, Lee

2011-09-01

To examine the correlation between cell death and a common surrogate of death used in screening assays, we compared cell death responses to those obtained with the sulforhodamine B (SRB) cell protein-based "cytotoxicity" assay. With the SRB assay, the Hill equation was used to obtain an IC50 and final cell mass, or cell mass present at infinite agent concentrations, with eight adherent cell lines and four agents (32 agent/cell combinations). Cells were treated with high agent concentrations (well above the SRB IC50) and the death response determined as the time-dependent decrease in cells failing to bind both annexin V and vital fluorochromes by flow cytometry. Death kinetics were categorized as fast (5/32) (similar to the reference nonadherent Jurkat line), slow (17/32), or none (10/32), despite positive responses in the SRB assay in all cases. With slow cell death, a single exposure to a chemotherapeutic agent caused a slow, progressive increase in dead (necrotic) and dying (apoptotic) cells for at least 72 h. Cell death (defined by annexin and/or fluorochrome binding) did not correlate with the standard SRB "cytotoxicity" assay. With the slow cell death response, a single exposure to an agent caused a slow conversion from vital to apoptotic and necrotic cells over at least 72 h (the longest time point examined). Here, increasing the time of exposure to agent concentrations modestly above the SRB IC50 provides a method of maximizing cell kill. If tumors respond similarly, sustained low doses of chemotherapeutic agents, rather than a log-kill, maximum tolerated dose strategy may be an optimal strategy of maximizing tumor cell death.

Modeling of a production system using the multi-agent approach

NASA Astrophysics Data System (ADS)

Gwiazda, A.; Sękala, A.; Banaś, W.

2017-08-01

The method that allows for the analysis of complex systems is a multi-agent simulation. The multi-agent simulation (Agent-based modeling and simulation - ABMS) is modeling of complex systems consisting of independent agents. In the case of the model of the production system agents may be manufactured pieces set apart from other types of agents like machine tools, conveyors or replacements stands. Agents are magazines and buffers. More generally speaking, the agents in the model can be single individuals, but you can also be defined as agents of collective entities. They are allowed hierarchical structures. It means that a single agent could belong to a certain class. Depending on the needs of the agent may also be a natural or physical resource. From a technical point of view, the agent is a bundle of data and rules describing its behavior in different situations. Agents can be autonomous or non-autonomous in making the decision about the types of classes of agents, class sizes and types of connections between elements of the system. Multi-agent modeling is a very flexible technique for modeling and model creating in the convention that could be adapted to any research problem analyzed from different points of views. One of the major problems associated with the organization of production is the spatial organization of the production process. Secondly, it is important to include the optimal scheduling. For this purpose use can approach multi-purposeful. In this regard, the model of the production process will refer to the design and scheduling of production space for four different elements. The program system was developed in the environment NetLogo. It was also used elements of artificial intelligence. The main agent represents the manufactured pieces that, according to previously assumed rules, generate the technological route and allow preprint the schedule of that line. Machine lines, reorientation stands, conveyors and transport devices also represent the

Design of Protease Activated Optical Contrast Agents That Exploit a Latent Lysosomotropic Effect for Use in Fluorescence-Guided Surgery

PubMed Central

2015-01-01

There is a need for new molecular-guided contrast agents to enhance surgical procedures such as tumor resection that require a high degree of precision. Cysteine cathepsins are highly up-regulated in a wide variety of cancers, both in tumor cells and in the tumor-supporting cells of the surrounding stroma. Therefore, tools that can be used to dynamically monitor their activity in vivo could be used as imaging contrast agents for intraoperative fluorescence image guided surgery (FGS). Although multiple classes of cathepsin-targeted substrate probes have been reported, most suffer from overall fast clearance from sites of protease activation, leading to reduced signal intensity and duration in vivo. Here we describe the design and synthesis of a series of near-infrared fluorogenic probes that exploit a latent cationic lysosomotropic effect (LLE) to promote cellular retention upon protease activation. These probes show tumor-specific retention, fast activation kinetics, and rapid systemic distribution. We demonstrate that they are suitable for detection of diverse cancer types including breast, colon and lung tumors. Most importantly, the agents are compatible with the existing, FDA approved, da Vinci surgical system for fluorescence guided tumor resection. Therefore, our data suggest that the probes reported here can be used with existing clinical instrumentation to detect tumors and potentially other types of inflammatory lesions to guide surgical decision making in real time. PMID:26039341

Multi-agent Reinforcement Learning Model for Effective Action Selection

NASA Astrophysics Data System (ADS)

Youk, Sang Jo; Lee, Bong Keun

Reinforcement learning is a sub area of machine learning concerned with how an agent ought to take actions in an environment so as to maximize some notion of long-term reward. In the case of multi-agent, especially, which state space and action space gets very enormous in compared to single agent, so it needs to take most effective measure available select the action strategy for effective reinforcement learning. This paper proposes a multi-agent reinforcement learning model based on fuzzy inference system in order to improve learning collect speed and select an effective action in multi-agent. This paper verifies an effective action select strategy through evaluation tests based on Robocop Keep away which is one of useful test-beds for multi-agent. Our proposed model can apply to evaluate efficiency of the various intelligent multi-agents and also can apply to strategy and tactics of robot soccer system.

Mitigating active shooter impact: Analysis for policy options based on agent/computer-based modeling.

PubMed

Anklam, Charles; Kirby, Adam; Sharevski, Filipo; Dietz, J Eric

2015-01-01

Active shooting violence at confined settings, such as educational institutions, poses serious security concerns to public safety. In studying the effects of active shooter scenarios, the common denominator associated with all events, regardless of reason/intent for shooter motives, or type of weapons used, was the location chosen and time expended between the beginning of the event and its culmination. This in turn directly correlates to number of casualties incurred in any given event. The longer the event protracts, the more casualties are incurred until law enforcement or another barrier can react and culminate the situation. Using AnyLogic technology, devise modeling scenarios to test multiple hypotheses against free-agent modeling simulation to determine the best method to reduce casualties associated with active shooter scenarios. Test four possible scenarios of responding to active shooter in a public school setting using agent-based computer modeling techniques-scenario 1: basic scenario where no access control or any type of security is used within the school; scenario 2, scenario assumes that concealed carry individual(s) (5-10 percent of the work force) are present in the school; scenario 3, scenario assumes that the school has assigned resource officer; scenario 4, scenario assumes that the school has assigned resource officer and concealed carry individual(s) (5-10 percent) present in the school. Statistical data from modeling scenarios indicating which tested hypothesis resulted in fewer casualties and quicker culmination of event. The use of AnyLogic proved the initial hypothesis that a decrease on response time to an active shooter scenario directly reduced victim casualties. Modeling tests show statistically significant fewer casualties in scenarios where on scene armed responders such as resource officers and concealed carry personnel were present.

Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

PubMed

Taupin, Philippe

2009-05-01

The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

Activation of Phosphoinositide Metabolism by Cholinergic Agents.

DTIC Science & Technology

1992-03-15

most notably calcium. Cholinergic agonist-induced seizures; Brain second messenger systems; Neurotransmitter/ Neuromodulator interactions; RAV; Lab...have been described: modulation by protein kinase C and modulation by neurotransmitter (or neuromodulator ) interactions. Agents which stimulate...phosphoinositide hydrolysis that has been identified consists of interactions among neurotransmitter systems or neuromodulators . Perhaps those most widely

A heating-superfusion platform technology for the investigation of protein function in single cells.

PubMed

Xu, Shijun; Ainla, Alar; Jardemark, Kent; Jesorka, Aldo; Jeffries, Gavin D M

2015-01-06

Here, we report on a novel approach for the study of single-cell intracellular enzyme activity at various temperatures, utilizing a localized laser heating probe in combination with a freely positionable microfluidic perfusion device. Through directed exposure of individual cells to the pore-forming agent α-hemolysin, we have controlled the membrane permeability, enabling targeted delivery of the substrate. Mildly permeabilized cells were exposed to fluorogenic substrates to monitor the activity of intracellular enzymes, while adjusting the local temperature surrounding the target cells, using an infrared laser heating system. We generated quantitative estimates for the intracellular alkaline phosphatase activity at five different temperatures in different cell lines, constructing temperature-response curves of enzymatic activity at the single-cell level. Enzymatic activity was determined rapidly after cell permeation, generating five-point temperature-response curves within just 200 s.

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis

PubMed Central

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-01-01

AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. RESULTS: The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents. PMID:26019471

Instructable autonomous agents. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Huffman, Scott Bradley

1994-01-01

In contrast to current intelligent systems, which must be laboriously programmed for each task they are meant to perform, instructable agents can be taught new tasks and associated knowledge. This thesis presents a general theory of learning from tutorial instruction and its use to produce an instructable agent. Tutorial instruction is a particularly powerful form of instruction, because it allows the instructor to communicate whatever kind of knowledge a student needs at whatever point it is needed. To exploit this broad flexibility, however, a tutorable agent must support a full range of interaction with its instructor to learn a full range of knowledge. Thus, unlike most machine learning tasks, which target deep learning of a single kind of knowledge from a single kind of input, tutorability requires a breadth of learning from a broad range of instructional interactions. The theory of learning from tutorial instruction presented here has two parts. First, a computational model of an intelligent agent, the problem space computational model, indicates the types of knowledge that determine an agent's performance, and thus, that should be acquirable via instruction. Second, a learning technique, called situated explanation specifies how the agent learns general knowledge from instruction. The theory is embodied by an implemented agent, Instructo-Soar, built within the Soar architecture. Instructo-Soar is able to learn hierarchies of completely new tasks, to extend task knowledge to apply in new situations, and in fact to acquire every type of knowledge it uses during task performance - control knowledge, knowledge of operators' effects, state inferences, etc. - from interactive natural language instructions. This variety of learning occurs by applying the situated explanation technique to a variety of instructional interactions involving a variety of types of instructions (commands, statements, conditionals, etc.). By taking seriously the requirements of flexible

Agent independent task planning

NASA Technical Reports Server (NTRS)

Davis, William S.

1990-01-01

Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

Single Event Effect Hardware Trojans with Remote Activation

DTIC Science & Technology

2017-03-01

kinetically as in the SDI approach. These high-energy directed energy weapons have been studied and developed largely for the purpose remote sensing and...Single Event Effect Hardware Trojans with Remote Activation Paul A. Quintana; John McCollum; William A. Hill Microsemi Corporation, San Jose...space qualified semiconductors the use of SEE sensitive circuits may represents a latent and remotely -triggered hardware Trojan which would be

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

PubMed

Daryaei, Iman; Pagel, Mark D

2015-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

Transcriptional activation of short interspersed elements by DNA-damaging agents.

PubMed

Rudin, C M; Thompson, C B

2001-01-01

Short interspersed elements (SINEs), typified by the human Alu repeat, are RNA polymerase III (pol III)-transcribed sequences that replicate within the genome through an RNA intermediate. Replication of SINEs has been extensive in mammalian evolution: an estimated 5% of the human genome consists of Alu repeats. The mechanisms regulating transcription, reverse transcription, and reinsertion of SINE elements in genomic DNA are poorly understood. Here we report that expression of murine SINE transcripts of both the B1 and B2 classes is strongly upregulated after prolonged exposure to cisplatin, etoposide, or gamma radiation. A similar induction of Alu transcripts in human cells occurs under these conditions. This induction is not due to a general upregulation of pol III activity in either species. Genotoxic treatment of murine cells containing an exogenous human Alu element induced Alu transcription. Concomitant with the increased expression of SINEs, an increase in cellular reverse transcriptase was observed after exposure to these same DNA-damaging agents. These findings suggest that genomic damage may be an important activator of SINEs, and that SINE mobility may contribute to secondary malignancy after exposure to DNA-damaging chemotherapy.

Nucleotide cleaving agents and method

DOEpatents

Que, Jr., Lawrence; Hanson, Richard S.; Schnaith, Leah M. T.

2000-01-01

The present invention provides a unique series of nucleotide cleaving agents and a method for cleaving a nucleotide sequence, whether single-stranded or double-stranded DNA or RNA, using and a cationic metal complex having at least one polydentate ligand to cleave the nucleotide sequence phosphate backbone to yield a hydroxyl end and a phosphate end.

Effect of water-ageing on dentine bond strength and anti-biofilm activity of bonding agent containing new monomer dimethylaminododecyl methacrylate

PubMed Central

Zhang, Ke; Cheng, Lei; Wu, Eric J.; Weir, Michael D.; Bai, Yuxing; Xu, Hockin H. K.

2013-01-01

Objectives The objectives of this study were to develop bonding agent containing a new antibacterial monomer dimethylaminododecyl methacrylate (DMADDM) as well as nanoparticles of silver (NAg) and nanoparticles of amorphous calcium phosphate (NACP), and to investigate the effects of water-ageing for 6 months on dentine bond strength and anti-biofilm properties for the first time. Methods Four bonding agents were tested: Scotchbond Multi-Purpose (SBMP) Primer and Adhesive control; SBMP + 5% DMADDM; SBMP + 5% DMADDM + 0.1% NAg; and SBMP + 5% DMADDM + 0.1% NAg with 20% NACP in adhesive. Specimens were water-aged for 1 d and 6 months at 37 °C. Then the dentine shear bond strengths were measured. A dental plaque microcosm biofilm model was used to inoculate bacteria on water-aged specimens and to measure metabolic activity, colony-forming units (CFUs), and lactic acid production. Results Dentine bond strength showed a 35% loss in 6 months of water-ageing for SBMP control (mean ± sd; n = 10); in contrast, the new antibacterial bonding agents showed no strength loss. The DMADDM–NAg–NACP containing bonding agent imparted a strong antibacterial effect by greatly reducing biofilm viability, metabolic activity and acid production. The biofilm CFU was reduced by more than two orders of magnitude, compared to SBMP control. Furthermore, the DMADDM–NAg–NACP bonding agent exhibited a long-term antibacterial performance, with no significant difference between 1 d and 6 months (p > 0.1). Conclusions Incorporating DMADDM–NAg–NACP in bonding agent yielded potent and long-lasting antibacterial properties, and much stronger bond strength after 6 months of water-ageing than a commercial control. The new antibacterial bonding agent is promising to inhibit biofilms and caries at the margins. The method of DMADDM–NAg–NACP incorporation may have a wide applicability to other adhesives, cements and composites. PMID:23583528

NP-184[2-(5-methyl-2-furyl) benzimidazole], a novel orally active antithrombotic agent with dual antiplatelet and anticoagulant activities.

PubMed

Kuo, Heng-Lan; Lien, Jin-Cherng; Chung, Ching-Hu; Chang, Chien-Hsin; Lo, Shyh-Chyi; Tsai, I-Chun; Peng, Hui-Chin; Kuo, Sheng-Chu; Huang, Tur-Fu

2010-06-01

The established antiplatelet and anticoagulant agents show beneficial effects in the treatment of thromboembolic diseases; however, these drugs still have considerable limitations. The effects of NP-184, a synthetic compound, on platelet functions, plasma coagulant activity, and mesenteric venule thrombosis in mice were investigated. NP-184 concentration-dependently inhibited the human platelet aggregation induced by collagen, arachidonic acid (AA), and U46619, a thromboxane (TX)A(2) mimic, with IC(50) values of 4.5 +/- 0.2, 3.9 +/- 0.1, and 9.3 +/- 0.5 microM, respectively. Moreover, NP-184 concentration-dependently suppressed TXA(2) formations caused by collagen and AA. In exploring effects of NP-184 on enzymes involved in TXA(2) synthesis, we found that NP-184 selectively inhibited TXA(2) synthase activity with an IC(50) value of 4.3 +/- 0.2 microM. Furthermore, NP-184 produced a right shift of the concentration-response curve of U46619, indicating a competitive antagonism on TXA(2)/prostaglandin H(2) receptor. Intriguingly, NP-184 also caused a concentration-dependent prolongation of the activated partial thromboplastin time (aPTT) with no changes in the prothrombin and thrombin time, indicating that it selectively impairs the intrinsic coagulation pathway. Oral administration of NP-184 significantly inhibited thrombus formation of the irradiated mesenteric venules in fluorescein sodium-treated mice without affecting the bleeding time induced by tail transection. However, after oral administration, NP-184 inhibited the ex vivo mouse platelet aggregation triggered by collagen and U46619 and also prolonged aPTT. Taken together, the dual antiplatelet and anticoagulant activities of NP-184 may have therapeutic potential as an oral antithrombotic agent in the treatment of thromboembolic disorders.

Dendrimer-encapsulated naphthalocyanine as a single agent-based theranostic nanoplatform for near-infrared fluorescence imaging and combinatorial anticancer phototherapy

NASA Astrophysics Data System (ADS)

Taratula, Olena; Schumann, Canan; Duong, Tony; Taylor, Karmin L.; Taratula, Oleh

2015-02-01

Multifunctional theranostic platforms capable of concurrent near-infrared (NIR) fluorescence imaging and phototherapies are strongly desired for cancer diagnosis and treatment. However, the integration of separate imaging and therapeutic components into nanocarriers results in complex theranostic systems with limited translational potential. A single agent-based theranostic nanoplatform, therefore, was developed for concurrent NIR fluorescence imaging and combinatorial phototherapy with dual photodynamic (PDT) and photothermal (PTT) therapeutic mechanisms. The transformation of a substituted silicon naphthalocyanine (SiNc) into a biocompatible nanoplatform (SiNc-NP) was achieved by SiNc encapsulation into the hydrophobic interior of a generation 5 polypropylenimine dendrimer following surface modification with polyethylene glycol. Encapsulation provides aqueous solubility to SiNc and preserves its NIR fluorescence, PDT and PTT properties. Moreover, an impressive photostability in the dendrimer-encapsulated SiNc has been detected. Under NIR irradiation (785 nm, 1.3 W cm-2), SiNc-NP manifested robust heat generation capability (ΔT = 40 °C) and efficiently produced reactive oxygen species essential for PTT and PDT, respectively, without releasing SiNc from the nanopaltform. By varying the laser power density from 0.3 W cm-2 to 1.3 W cm-2 the therapeutic mechanism of SiNc-NP could be switched from PDT to combinatorial PDT-PTT treatment. In vitro and in vivo studies confirmed that phototherapy mediated by SiNc can efficiently destroy chemotherapy resistant ovarian cancer cells. Remarkably, solid tumors treated with a single dose of SiNc-NP combined with NIR irradiation were completely eradicated without cancer recurrence. Finally, the efficiency of SiNc-NP as an NIR imaging agent was confirmed by recording the strong fluorescence signal in the tumor, which was not photobleached during the phototherapeutic procedure.Multifunctional theranostic platforms capable of

Element-specific spectral imaging of multiple contrast agents: a phantom study

NASA Astrophysics Data System (ADS)

Panta, R. K.; Bell, S. T.; Healy, J. L.; Aamir, R.; Bateman, C. J.; Moghiseh, M.; Butler, A. P. H.; Anderson, N. G.

2018-02-01

This work demonstrates the feasibility of simultaneous discrimination of multiple contrast agents based on their element-specific and energy-dependent X-ray attenuation properties using a pre-clinical photon-counting spectral CT. We used a photon-counting based pre-clinical spectral CT scanner with four energy thresholds to measure the X-ray attenuation properties of various concentrations of iodine (9, 18 and 36 mg/ml), gadolinium (2, 4 and 8 mg/ml) and gold (2, 4 and 8 mg/ml) based contrast agents, calcium chloride (140 and 280 mg/ml) and water. We evaluated the spectral imaging performances of different energy threshold schemes between 25 to 82 keV at 118 kVp, based on K-factor and signal-to-noise ratio and ranked them. K-factor was defined as the X-ray attenuation in the K-edge containing energy range divided by the X-ray attenuation in the preceding energy range, expressed as a percentage. We evaluated the effectiveness of the optimised energy selection to discriminate all three contrast agents in a phantom of 33 mm diameter. A photon-counting spectral CT using four energy thresholds of 27, 33, 49 and 81 keV at 118 kVp simultaneously discriminated three contrast agents based on iodine, gadolinium and gold at various concentrations using their K-edge and energy-dependent X-ray attenuation features in a single scan. A ranking method to evaluate spectral imaging performance enabled energy thresholds to be optimised to discriminate iodine, gadolinium and gold contrast agents in a single spectral CT scan. Simultaneous discrimination of multiple contrast agents in a single scan is likely to open up new possibilities of improving the accuracy of disease diagnosis by simultaneously imaging multiple bio-markers each labelled with a nano-contrast agent.

Agent-Based Modeling of Growth Processes

ERIC Educational Resources Information Center

Abraham, Ralph

2014-01-01

Growth processes abound in nature, and are frequently the target of modeling exercises in the sciences. In this article we illustrate an agent-based approach to modeling, in the case of a single example from the social sciences: bullying.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-02-01

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

Antimicrobial activity of ceftaroline and other anti-infective agents against microbial pathogens recovered from the surgical intensive care patient population: a prevalence analysis.

PubMed

Edmiston, Charles E; Krepel, Candace J; Leaper, David; Ledeboer, Nathan A; Mackey, Tami-Lea; Graham, Mary Beth; Lee, Cheong; Rossi, Peter J; Brown, Kellie R; Lewis, Brian D; Seabrook, Gary R

2014-12-01

Ceftaroline is a new parenteral cephalosporin agent with excellent activity against methicillin-sensitive (MSSA) and resistant strains of Staphylococcus aureus (MRSA). Critically ill surgical patients are susceptible to infection, often by multi-drug-resistant pathogens. The activity of ceftaroline against such pathogens has not been described. Three hundred thirty-five consecutive microbial isolates were collected from surgical wounds or abscesses, respiratory, urine, and blood cultures from patients in the surgical intensive care unit (SICU) of a major tertiary medical center. Using Clinical and Laboratory Standards Institute (CLSI) standard methodology and published breakpoints, all aerobic, facultative anaerobic isolates were tested against ceftaroline and selected comparative antimicrobial agents. All staphylococcal isolates were susceptible to ceftaroline at a breakpoint of ≤1.0 mcg/mL. In addition, ceftaroline exhibited excellent activity against all streptococcal clinical isolates and non-ESBL-producing strains of Enterobacteriaceae (93.5%) recovered from SICU patients. Ceftaroline was inactive against ESBL-producing Enterobacteriaceae, Pseudomonas aeruginosa, vancomycin-resistant enterococci, and selective gram-negative anaerobic bacteria. At present, ceftaroline is the only cephalosporin agent that is active against community and healthcare-associated MRSA. Further studies are needed to validate the benefit of this novel broad-spectrum anti-infective agent for the treatment of susceptible serious infections in the SICU patient population.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

PubMed

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2015-01-01

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

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.

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents.

PubMed

Jimenez-Zepeda, V H; Reece, D E; Trudel, S; Chen, C; Tiedemann, R; Kukreti, V

2015-02-01

The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (<12 months post auto-SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.

Next Generation Remote Agent Planner

NASA Technical Reports Server (NTRS)

Jonsson, Ari K.; Muscettola, Nicola; Morris, Paul H.; Rajan, Kanna

1999-01-01

In May 1999, as part of a unique technology validation experiment onboard the Deep Space One spacecraft, the Remote Agent became the first complete autonomous spacecraft control architecture to run as flight software onboard an active spacecraft. As one of the three components of the architecture, the Remote Agent Planner had the task of laying out the course of action to be taken, which included activities such as turning, thrusting, data gathering, and communicating. Building on the successful approach developed for the Remote Agent Planner, the Next Generation Remote Agent Planner is a completely redesigned and reimplemented version of the planner. The new system provides all the key capabilities of the original planner, while adding functionality, improving performance and providing a modular and extendible implementation. The goal of this ongoing project is to develop a system that provides both a basis for future applications and a framework for further research in the area of autonomous planning for spacecraft. In this article, we present an introductory overview of the Next Generation Remote Agent Planner. We present a new and simplified definition of the planning problem, describe the basics of the planning process, lay out the new system design and examine the functionality of the core reasoning module.

Agents Play Mix-game

NASA Astrophysics Data System (ADS)

Gou, Chengling

In recent years, economics and finance see the shift of paradigm from representative agent models to heterogeneous agent models [1, 2]. More and more economists and physicists made efforts in research on heterogeneous agent models for financial markets. Minority game (MG) proposed by D. Challet, and Y. C. Zhang [3] is an example among such efforts. Challet and Zhang's MG model, together with the original bar model of Arthur, attracts a lot of following studies [4-6]. Given MG's richness and yet underlying simplicity, MG has also received much attention as a financial market model [4]. MG comprises an odd number of agents choosing repeatedly between the options of buying (1) and selling (0) a quantity of a risky asset. The agents continually try to make the minority decision, i.e. buy assets when the majority of other agents are selling, and sell when the majority of other agents are buying. Neil F. Johnson [4, 5] and coworkers extended MG by allowing a variable number of active traders at each timestep— they called their modified game as the Grand Canonical Minority Game (GCMG). GCMG, and to a lesser extent the basic MG itself, can reproduce the stylized facts of financial markets, such as volatility clustering and fat-tail distributions.

Monitoring single protease activities on triple-helical collagen molecules

NASA Astrophysics Data System (ADS)

Harzar, Raj; Froberg, James; Srivastava, D. K.; Choi, Yongki

Matrix metalloproteinases (MMPs), a particular family of proteases, play a pivotal role in degrading the extracellular matrix (ECM). It has been known for more than 40 years that MMPs are closely involved in multiple human cancers during cell growth, invasion, and metastasis. However, the mechanisms of MMP activity are far from being understood. Here, we monitored enzymatic processing of MMPs with two complementary approaches, atomic force microscopy and nanocircuits measurements. AFM measurements demonstrated that incubation of collagen monomers with MMPs resulted in a single position cleavage, producing 3/4 and 1/4 collagen fragments. From electronic monitoring of single MMP nanocircuit measurements, we were able to capture a single cleavage event with a rate of 0.012 Hz, which were in good agreement with fluorescence assay measurements. This work was supported financially by the NIGMS/NIH (P30GM103332-02) and ND NASA EPSCoR RID Grant.

Feedback of Interface Agents on Student Perception: Level, Dialogue, and Emotion

ERIC Educational Resources Information Center

Chen, Zhi-Hong; Chou, Chih-Yueh; Tseng, Shu-Fen; Su, Ying-Chu

2018-01-01

Although feedback from interface agents has recently attracted increasing research attention, most studies emphasize the cognitive influences. Thus, the effect of each feedback type on student perception remains unclear. This study focuses on three types of feedback from interface agents to clarify student perception of single feedback and…

Feasibility of adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 for completely resected non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 1001.

PubMed

Okumura, Norihito; Sonobe, Makoto; Okabe, Kazunori; Nakamura, Hiroshige; Kataoka, Masafumi; Yamashita, Motohiro; Nakata, Masao; Kataoka, Kazuhiko; Yamashita, Yoshinori; Soh, Junichi; Yoshioka, Hiroshige; Hotta, Katsuyuki; Matsuo, Keitaro; Sakamoto, Junichi; Toyooka, Shinichi; Date, Hiroshi

2017-04-01

This multicenter study evaluated the feasibility of novel adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent, long-term maintenance with S-1 in patients with completely resected stage II-IIIA non-small-cell lung cancer (NSCLC). Patients received four cycles of S-1 (80 mg/m 2 /day for 2 weeks, followed by 2 weeks rest) plus carboplatin (area under the curve 5, day 1) followed by S-1 (80 mg/m 2 /day for 2 weeks, followed by a 1-week rest). Patients unable to continue S-1 plus carboplatin because of severe toxicity converted to single-agent S-1 maintenance. The duration of adjuvant chemotherapy was 10 months in both situations. The primary endpoint was feasibility, defined as the proportion of patients who completed four cycles of S-1 plus carboplatin and single-agent S-1 maintenance for 10 months. The treatment completion rate was determined; treatment was considered feasible if the lower 90% confidence interval (CI) was ≥50%. Eighty-nine patients were enrolled, of whom 87 were eligible and assessable. Seventy-eight patients (89.7%) completed four cycles of S-1 plus carboplatin and 55 (63.2%) completed the following S-1 maintenance therapy for a total of 10 months. The treatment completion rate was 63.2% (90% CI, 54.4-71.2%), indicating feasibility. There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (13.8%), thrombocytopenia (11.5%), and anorexia (4.6%). The 2-year relapse-free survival rate was 59.8%. We concluded that adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 is feasible and tolerable in patients with completely resected NSCLC. UMIN000005041.

Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

PubMed

Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

2008-12-01

Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

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

PubMed Central

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

2017-01-01

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

Schistosomin: a pronase-sensitive agent in the hemolymph of Trichobilharzia ocellata-infected Lymnaea stagnalis inhibits the activity of albumen glands in vitro.

PubMed

Joosse, J; van Elk, R; Mosselman, S; Wortelboer, H; van Diepen, J C

1988-01-01

The schistosome parasite, Trichobilharzia ocellata, nearly completely inhibits the reproductive activity of its intermediate host, Lymnaea stagnalis. The synthetic activity of albumen glands of infected snails at day 35 postinfection (p.i.) is only 1% of the control value. The parasite acts by humoral means. We tested the hypothesis that (a) specific humoral agent(s) is (are) involved and refer to this (these) agent(s) as schistosomin. The presence of schistosomin in the hemolymph of infected snails was investigated by using galactogen synthesis in albumen glands as an in vitro bioassay. The synthetic activity of albumen glands of noninfected snails decreased by about 50% during a 1-h incubation in the hemolymph of infected snails. This inhibition is attributed to schistosomin. Based on these results, with the present bioassay schistosomin appears in the hemolymph between days 28-36 p.i. onwards. Schistosomin is heat-stable (100 degrees C) and pronase-sensitive, and therefore it might have a peptide nature. Schistosomin suppresses the stimulating action of the female, gonadotrophic dorsal body hormone at relatively low doses, which suggests that it may compete with this hormone for the same receptors. The development of two other bioassays for schistosomin in our laboratory is discussed.

The spread of Ras activity triggered by activation of a single dendritic spine.

PubMed

Harvey, Christopher D; Yasuda, Ryohei; Zhong, Haining; Svoboda, Karel

2008-07-04

In neurons, individual dendritic spines isolate N-methyl-d-aspartate (NMDA) receptor-mediated calcium ion (Ca2+) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca2+ influx is not known. We combined two-photon fluorescence lifetime imaging with two-photon glutamate uncaging to image the activity of the small guanosine triphosphatase Ras after NMDA receptor activation at individual spines. Induction of long-term potentiation (LTP) triggered robust Ca2+-dependent Ras activation in single spines that decayed in approximately 5 minutes. Ras activity spread over approximately 10 micrometers of dendrite and invaded neighboring spines by diffusion. The spread of Ras-dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite.

Single vector platform vaccine protects against lethal respiratory challenge with Tier 1 select agents of anthrax, plague, and tularemia.

PubMed

Jia, Qingmei; Bowen, Richard; Dillon, Barbara Jane; Masleša-Galić, Saša; Chang, Brennan T; Kaidi, Austin C; Horwitz, Marcus A

2018-05-03

Bacillus anthracis, Yersinia pestis, and Francisella tularensis are the causative agents of Tier 1 Select Agents anthrax, plague, and tularemia, respectively. Currently, there are no licensed vaccines against plague and tularemia and the licensed anthrax vaccine is suboptimal. Here we report F. tularensis LVS ΔcapB (Live Vaccine Strain with a deletion in capB)- and attenuated multi-deletional Listeria monocytogenes (Lm)-vectored vaccines against all three aforementioned pathogens. We show that LVS ΔcapB- and Lm-vectored vaccines express recombinant B. anthracis, Y. pestis, and F. tularensis immunoprotective antigens in broth and in macrophage-like cells and are non-toxic in mice. Homologous priming-boosting with the LVS ΔcapB-vectored vaccines induces potent antigen-specific humoral and T-cell-mediated immune responses and potent protective immunity against lethal respiratory challenge with all three pathogens. Protection against anthrax was far superior to that obtained with the licensed AVA vaccine and protection against tularemia was comparable to or greater than that obtained with the toxic and unlicensed LVS vaccine. Heterologous priming-boosting with LVS ΔcapB- and Lm-vectored B. anthracis and Y. pestis vaccines also induced potent protective immunity against lethal respiratory challenge with B. anthracis and Y. pestis. The single vaccine platform, especially the LVS ΔcapB-vectored vaccine platform, can be extended readily to other pathogens.

Identification of a novel inhibitor of isocitrate lyase as a potent antitubercular agent against both active and non-replicating Mycobacterium tuberculosis.

PubMed

Liu, Yishuang; Zhou, Shuang; Deng, Qi; Li, Xinghua; Meng, Jianzhou; Guan, Yan; Li, Chuanyou; Xiao, Chunling

2016-03-01

Screen and identify novel inhibitors of isocitrate lyase (ICL) as potent antitubercular agents against Mycobacterium tuberculosis and determine their inhibitory characteristics, antitubercular activities and mechanisms of action. Recombinant ICL of M. tuberculosis was expressed and purified, which was used for high-throughput screening (HTS) and the following experiments. A total of 71,765 compounds were screened to identify ICL inhibitors which were then evaluated for their roles as potent antitubercular agents. To determine the inhibitory characteristics of the agents against latent M. tuberculosis in persistent infections, a macrophage model (mouse J774A.1 cell) infected with Mycobacterium marinum BAA-535 strain was built and assessed. The potent antitubercular agents were identified using the macrophage model. Then, the inhibitory intensity and mode of the agents that exhibit on ICL protein of M. tuberculosis were analyzed, and the interaction mechanisms were preliminarily clarified according to the parameters of enzyme kinetics, circular dichroism experiments, fluorescence quenching assay, and molecular docking. The previously established ICL inhibitor screening model was evaluated to be suitable for HTS assay. Of the 71,765 compounds, 13 of them were identified to inhibit ICL effectively and stably. IMBI-3 demonstrated the most significant inhibitory activity with IC50 of 30.9 μmol/L. Its minimum inhibitory concentration (MIC) for M. tuberculosis, including extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant tuberculosis (MDR-TB), were determined in the range of 0.25-1 μg/mL. When IMBI-3 is used in combination with isoniazid, the colony-forming units (CFU) counting of latent M. tuberculosis in J774A.1 macrophage cells decreased significantly as IMBI-3 concentration increased. The inhibition mode of IMBI-3 on ICL was probably competitive inhibition with an inhibition constant (Ki) of approximate 1.85 μmol/L. The interaction between IMBI

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.

PubMed

Albuquerque, Edson X; Pereira, Edna F R; Aracava, Yasco; Fawcett, William P; Oliveira, Maristela; Randall, William R; Hamilton, Tracey A; Kan, Robert K; Romano, James A; Adler, Michael

2006-08-29

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

PubMed Central

Albuquerque, Edson X.; Pereira, Edna F. R.; Aracava, Yasco; Fawcett, William P.; Oliveira, Maristela; Randall, William R.; Hamilton, Tracey A.; Kan, Robert K.; Romano, James A.; Adler, Michael

2006-01-01

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. PMID:16914529

A survey of the sequence-specific interaction of damaging agents with DNA: emphasis on antitumor agents.

PubMed

Murray, V

1999-01-01

This article reviews the literature concerning the sequence specificity of DNA-damaging agents. DNA-damaging agents are widely used in cancer chemotherapy. It is important to understand fully the determinants of DNA sequence specificity so that more effective DNA-damaging agents can be developed as antitumor drugs. There are five main methods of DNA sequence specificity analysis: cleavage of end-labeled fragments, linear amplification with Taq DNA polymerase, ligation-mediated polymerase chain reaction (PCR), single-strand ligation PCR, and footprinting. The DNA sequence specificity in purified DNA and in intact mammalian cells is reviewed for several classes of DNA-damaging agent. These include agents that form covalent adducts with DNA, free radical generators, topoisomerase inhibitors, intercalators and minor groove binders, enzymes, and electromagnetic radiation. The main sites of adduct formation are at the N-7 of guanine in the major groove of DNA and the N-3 of adenine in the minor groove, whereas free radical generators abstract hydrogen from the deoxyribose sugar and topoisomerase inhibitors cause enzyme-DNA cross-links to form. Several issues involved in the determination of the DNA sequence specificity are discussed. The future directions of the field, with respect to cancer chemotherapy, are also examined.

Leaderless consensus for the fractional-order nonlinear multi-agent systems under directed interaction topology

NASA Astrophysics Data System (ADS)

Bai, Jing; Wen, Guoguang; Rahmani, Ahmed

2018-04-01

Leaderless consensus for the fractional-order nonlinear multi-agent systems is investigated in this paper. At the first part, a control protocol is proposed to achieve leaderless consensus for the nonlinear single-integrator multi-agent systems. At the second part, based on sliding mode estimator, a control protocol is given to solve leaderless consensus for the the nonlinear single-integrator multi-agent systems. It shows that the control protocol can improve the systems' convergence speed. At the third part, a control protocol is designed to accomplish leaderless consensus for the nonlinear double-integrator multi-agent systems. To judge the systems' stability in this paper, two classic continuous Lyapunov candidate functions are chosen. Finally, several worked out examples under directed interaction topology are given to prove above results.

Application and Implications of Agent Technology for Librarians.

ERIC Educational Resources Information Center

Nardi, Bonnie A.; O'Day, Vicki L.

1998-01-01

Examines intelligent software agents, presents nine design principles aimed specifically at the technology perspective (to personalize task performance and general principles), and discusses what librarians can do that software agents (agents defined as activity-aware software programs) cannot do. Describes an information ecology that integrates…

Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents.

PubMed

Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

2015-07-09

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents.

Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents

PubMed Central

Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

2015-01-01

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents. PMID:26158513

Quantitative telomerase enzyme activity determination using droplet digital PCR with single cell resolution

PubMed Central

Ludlow, Andrew T.; Robin, Jerome D.; Sayed, Mohammed; Litterst, Claudia M.; Shelton, Dawne N.; Shay, Jerry W.; Wright, Woodring E.

2014-01-01

The telomere repeat amplification protocol (TRAP) for the human reverse transcriptase, telomerase, is a PCR-based assay developed two decades ago and is still used for routine determination of telomerase activity. The TRAP assay can only reproducibly detect ∼2-fold differences and is only quantitative when compared to internal standards and reference cell lines. The method generally involves laborious radioactive gel electrophoresis and is not conducive to high-throughput analyzes. Recently droplet digital PCR (ddPCR) technologies have become available that allow for absolute quantification of input deoxyribonucleic acid molecules following PCR. We describe the reproducibility and provide several examples of a droplet digital TRAP (ddTRAP) assay for telomerase activity, including quantitation of telomerase activity in single cells, telomerase activity across several common telomerase positive cancer cells lines and in human primary peripheral blood mononuclear cells following mitogen stimulation. Adaptation of the TRAP assay to digital format allows accurate and reproducible quantification of the number of telomerase-extended products (i.e. telomerase activity; 57.8 ± 7.5) in a single HeLa cell. The tools developed in this study allow changes in telomerase enzyme activity to be monitored on a single cell basis and may have utility in designing novel therapeutic approaches that target telomerase. PMID:24861623

Single-molecule conductance studies of photo-active and photochromic molecules

NASA Astrophysics Data System (ADS)

Tam, E. S.; Parks, J. J.; Santiago-Berrios, M. B.; Zhong, Y.-W.; Abruna, H. D.; Ralph, D. C.

2010-03-01

We perform statistical measurements of single molecule conductance in repeatedly-formed metal-molecule-metal junctions at room temperature. Our results on diaminoalkanes are consistent with those reported by the Venkataraman group. We focus on photo-active and photochromic molecules, including a series of transition-metal complexes with different metal centers and endgroups. We compare the trend in conductance across the family of complexes with that expected from electrochemical measurements. We will also report initial results on the voltage dependence of single-molecule conductances and the effects of optical excitations.

Detection of single ion channel activity with carbon nanotubes

NASA Astrophysics Data System (ADS)

Zhou, Weiwei; Wang, Yung Yu; Lim, Tae-Sun; Pham, Ted; Jain, Dheeraj; Burke, Peter J.

2015-03-01

Many processes in life are based on ion currents and membrane voltages controlled by a sophisticated and diverse family of membrane proteins (ion channels), which are comparable in size to the most advanced nanoelectronic components currently under development. Here we demonstrate an electrical assay of individual ion channel activity by measuring the dynamic opening and closing of the ion channel nanopores using single-walled carbon nanotubes (SWNTs). Two canonical dynamic ion channels (gramicidin A (gA) and alamethicin) and one static biological nanopore (α-hemolysin (α-HL)) were successfully incorporated into supported lipid bilayers (SLBs, an artificial cell membrane), which in turn were interfaced to the carbon nanotubes through a variety of polymer-cushion surface functionalization schemes. The ion channel current directly charges the quantum capacitance of a single nanotube in a network of purified semiconducting nanotubes. This work forms the foundation for a scalable, massively parallel architecture of 1d nanoelectronic devices interrogating electrophysiology at the single ion channel level.

Decision Facilitator for Launch Operations using Intelligent Agents

NASA Technical Reports Server (NTRS)

Thirumalainambi, Rajkumar; Bardina, Jorge

2005-01-01

Launch operations require millions of micro-decisions which contribute to the macro decision of 'Go/No-Go' for a launch. Knowledge workers"(such as managers and technical professionals) need information in a timely precise manner as it can greatly affect mission success. The intelligent agent (web search agent) uses the words of a hypertext markup language document which is connected through the internet. The intelligent agent's actions are to determine if its goal of seeking a website containing a specified target (e.g., keyword or phrase), has been met. There are few parameters that should be defined for the keyword search like "Go" and "No-Go". Instead of visiting launch and range decision making servers individually, the decision facilitator constantly connects to all servers, accumulating decisions so the final decision can be decided in a timely manner. The facilitator agent uses the singleton design pattern, which ensures that only a single instance of the facilitator agent exists at one time. Negotiations could proceed between many agents resulting in a final decision. This paper describes details of intelligent agents and their interaction to derive an unified decision support system.

Synthesis and structure-activity relationship of amidine derivatives of 3,4-ethylenedioxythiophene as novel antibacterial agents.

PubMed

Stolić, Ivana; Čipčić Paljetak, Hana; Perić, Mihaela; Matijašić, Mario; Stepanić, Višnja; Verbanac, Donatella; Bajić, Miroslav

2015-01-27

Current antibacterial chemotherapeutics are facing an alarming increase in bacterial resistance pressuring the search for novel agents that would expand the available therapeutic arsenal against resistant bacterial pathogens. In line with these efforts, a series of 9 amidine derivatives of 3,4-ethylenedioxythiophene were synthesized and, together with 18 previously synthesized analogs, evaluated for their relative DNA binding affinity, in vitro antibacterial activities and preliminary in vitro safety profile. Encouraging antibacterial activity of several subclasses of tested amidine derivatives against Gram-positive (including resistant MRSA, MRSE, VRE strains) and Gram-negative bacterial strains was observed. The bis-phenyl derivatives were the most antibacterially active, while compound 19 from bis-benzimidazole class exhibited the widest spectrum of activity (with MIC of 4, 2, 0.5 and ≤0.25 μg/ml against laboratory strains of Staphyloccocus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, respectively and 4-32 μg/ml against clinical isolates of sensitive and resistant S. aureus, Staphylococcus epidermidis and Enterococcus faecium) and also demonstrated the strongest DNA binding affinity (ΔTm of 15.4 °C). Asymmetrically designed compounds and carboxamide-amidines were, in general, less active. Molecular docking indicated that the shape of the 3,4-ethylenedioxythiophene derivatives and their ability to form multiple electrostatic and hydrogen bonds with DNA, corresponds to the binding modes of other minor-groove binders. Herein reported results encourage further investigation of this class of compounds as novel antibacterial DNA binding agents. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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.

Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity.

PubMed

Tsuchiya, Hironori

2017-08-18

The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca ( Erythroxylum coca , Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and eugenol contained in thyme ( Thymus vulgaris , Lamiaceae) and clove ( Syzygium aromaticum , Myrtaceae), respectively, both of which are structurally and mechanistically similar to intravenous phenolic anesthetics. This paper reviews different classes of phytochemicals with the anesthetic activity and their characteristic molecular structures that could be lead compounds for anesthetics and anesthesia-related drugs. Phytochemicals in research papers published between 1996 and 2016 were retrieved from the point of view of well-known modes of anesthetic action, that is, the mechanistic interactions with Na⁺ channels, γ-aminobutyric acid type A receptors, N -methyl-d-aspartate receptors and lipid membranes. The searched phytochemicals include terpenoids, alkaloids and flavonoids because they have been frequently reported to possess local anesthetic, general anesthetic, antinociceptive, analgesic or sedative property. Clinical applicability of phytochemicals to local and general anesthesia is discussed by referring to animal in vivo experiments and human pre-clinical trials. This review will give structural suggestions for novel anesthetic agents of plant origin.

Raman-activated cell sorting based on dielectrophoretic single-cell trap and release.

PubMed

Zhang, Peiran; Ren, Lihui; Zhang, Xu; Shan, Yufei; Wang, Yun; Ji, Yuetong; Yin, Huabing; Huang, Wei E; Xu, Jian; Ma, Bo

2015-02-17

Raman-activated cell sorting (RACS) is a promising single-cell technology that holds several significant advantages, as RACS is label-free, information-rich, and potentially in situ. To date, the ability of the technique to identify single cells in a high-speed flow has been limited by inherent weakness of the spontaneous Raman signal. Here we present an alternative pause-and-sort RACS microfluidic system that combines positive dielectrophoresis (pDEP) for single-cell trap and release with a solenoid-valve-suction-based switch for cell separation. This has allowed the integration of trapping, Raman identification, and automatic separation of individual cells in a high-speed flow. By exerting a periodical pDEP field, single cells were trapped, ordered, and positioned individually to the detection point for Raman measurement. As a proof-of-concept demonstration, a mixture of two cell strains containing carotenoid-producing yeast (9%) and non-carotenoid-producing Saccharomyces cerevisiae (91%) was sorted, which enriched the former to 73% on average and showed a fast Raman-activated cell sorting at the subsecond level.

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging

PubMed Central

Daryaei, Iman; Pagel, Mark D

2016-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a “double-agent” approach to molecular imaging. Exogenous T2-exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T1 and T2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as “secret agents” in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging. PMID:27747191

Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

PubMed

Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

2014-11-24

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SINGLE AGENT CARBOPLATIN VERSUS CARBOPLATIN PLUS PEGYLATED LIPOSOMAL DOXORUBICIN IN RECURRENT OVARIAN CANCER: FINAL SURVIVAL RESULTS OF A SWOG (S0200) PHASE 3 RANDOMIZED TRIAL

PubMed Central

Markman, Maurie; Moon, James; Wilczynski, Sharon; Lopez, Ana Maria; Rowland, Kendrith M.; Michelin, David P.; Lanzotti, Victor J.; Anderson, Garnet L.; Alberts, David S.

2009-01-01

Objectives Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent. Methods To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m2) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. Results In the limited number of patients (n=61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p=0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p=0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p=0.0008), with 5 being ≥ grade 3 in severity. Conclusion Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions. PMID:20044128

Antimycoplasmal activity of some plant species from northern Nigeria compared to the currently used therapeutic agent.

PubMed

Muraina, I A; Adaudi, A O; Mamman, M; Kazeem, H M; Picard, J; McGaw, L J; Eloff, J N

2010-10-01

Mycoplasma spp. are obligate parasites of humans and animals. But due to the special requirements needed to culture Mycoplasma in the laboratory, little or no research has been done to evaluate the efficacy of medicinal plants on the organism. To screen medicinal plants traditionally used to treat infections for possible antimycoplasmal and cytotoxic activities. Acetone extracts of 21 Nigerian medicinal plants were analyzed for antimycoplasmal and cytotoxicity activities using the metabolic inhibition and colorimetric methods, respectively. The extract with the best antimycoplasmal activities was also analyzed for its phytochemical constituents using the desktop method. Calotropis procera (Aiton) R.Br (Asclepiadaceae) extract had the best antimycoplasmal effect with a minimum inhibitory concentration (MIC) of 80 µg/mL and minimum mycoplasmacidal concentration (MMC) of 160 µg/mL. This extract contained saponins, tannins, cardiac glycosides, alkaloids, and flavonoids. The extract of Vernonia amygdalina Delile (Compositae) was the most cytotoxic with median lethal concentration (LC(50)) of approximately 17 µg/mL, and that of Anacardium occidentale L. (Anacardiaceae) was the least cytotoxic with an LC(50) of approximately 1919 µg/mL. Calotropis procera is a promising plant for an alternative antimycoplasmal agent because the crude acetone extract had a higher mycoplasmacidal activity than the conventional drug tylosin, which is currently used in treatment of the disease in Nigeria. The crude extract of Calotropis procera is worth investigating for the development of a potent agent against cattle Mycoplasma, which has long defied solution by conventional chemotherapy.

Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib.

PubMed

Ahn, Inhye E; Jerussi, Theresa; Farooqui, Mohammed; Tian, Xin; Wiestner, Adrian; Gea-Banacloche, Juan

2016-10-13

Ibrutinib is not known to confer risk for Pneumocystis jirovecii pneumonia (PCP). We observed 5 cases of PCP in 96 patients receiving single-agent ibrutinib, including 4 previously untreated. Clinical presentations included asymptomatic pulmonary infiltrates, chronic cough, and shortness of breath. The diagnosis was often delayed. Median time from starting ibrutinib to occurrence of PCP was 6 months (range, 2-24). The estimated incidence of PCP was 2.05 cases per 100 patient-years (95% confidence interval, 0.67-4.79). At the time of PCP, all patients had CD4 T-cell count >500/μL (median, 966/μL) and immunoglobulin G (IgG) >500 mg/dL (median, 727 mg/dL). All patients underwent bronchoalveolar lavage. P jirovecii was identified by polymerase chain reaction in all 5 cases; direct fluorescence antibody staining was positive in 1. All events were grade ≤2 and resolved with oral therapy. Secondary prophylaxis was not given to 3 patients; after 61 patient-months of follow up, no recurrence occurred. Lack of correlation with CD4 count and IgG level suggests that susceptibility to PCP may be linked to Bruton tyrosine kinase (BTK) inhibition. If confirmed, this association could result in significant changes in surveillance and/or prophylaxis, possibly extending to other BTK inhibitors. This trial was registered at www.clinicaltrials.gov as #NCT01500733 and #NCT02514083.

Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib

PubMed Central

Ahn, Inhye E.; Jerussi, Theresa; Farooqui, Mohammed; Tian, Xin; Wiestner, Adrian

2016-01-01

Ibrutinib is not known to confer risk for Pneumocystis jirovecii pneumonia (PCP). We observed 5 cases of PCP in 96 patients receiving single-agent ibrutinib, including 4 previously untreated. Clinical presentations included asymptomatic pulmonary infiltrates, chronic cough, and shortness of breath. The diagnosis was often delayed. Median time from starting ibrutinib to occurrence of PCP was 6 months (range, 2-24). The estimated incidence of PCP was 2.05 cases per 100 patient-years (95% confidence interval, 0.67-4.79). At the time of PCP, all patients had CD4 T-cell count >500/μL (median, 966/μL) and immunoglobulin G (IgG) >500 mg/dL (median, 727 mg/dL). All patients underwent bronchoalveolar lavage. P jirovecii was identified by polymerase chain reaction in all 5 cases; direct fluorescence antibody staining was positive in 1. All events were grade ≤2 and resolved with oral therapy. Secondary prophylaxis was not given to 3 patients; after 61 patient-months of follow up, no recurrence occurred. Lack of correlation with CD4 count and IgG level suggests that susceptibility to PCP may be linked to Bruton tyrosine kinase (BTK) inhibition. If confirmed, this association could result in significant changes in surveillance and/or prophylaxis, possibly extending to other BTK inhibitors. This trial was registered at www.clinicaltrials.gov as #NCT01500733 and #NCT02514083. PMID:27503501

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents.

PubMed

Anderson, Christian E; Donnola, Shannon B; Jiang, Yun; Batesole, Joshua; Darrah, Rebecca; Drumm, Mitchell L; Brady-Kalnay, Susann M; Steinmetz, Nicole F; Yu, Xin; Griswold, Mark A; Flask, Chris A

2017-08-16

Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI's ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast - Magnetic Resonance Fingerprinting (DC - MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This "multi-color" MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.

Ice nucleation rates of single protein complexes and single macromolecules

NASA Astrophysics Data System (ADS)

Stratmann, F.; Wex, H.; Niedermeier, D.; Hartmann, S.; Augustin, S.; Clauss, T.; Voigtlaender, J.; Pummer, B.; Grothe, H.

2012-12-01

With our flow-tube LACIS (Leipzig Aerosol cloud Interaction Simulator), we measured immersion freezing of droplets containing biological ice nucleating (IN) agents. From our measurements, we were able to deduce ice nucleation rates for single IN protein complexes (for Snomax) and for IN macromolecules (in the case of Birch pollen). For the measurements, aerosol particles were produced from solutions/suspensions of either Snomax (deadened and partly fractionalized pseudomonas syringae bacteria) or of Birch pollen washing water (BW in the following). All particles were dried and size selected before entering LACIS. In LACIS, particles were activated to droplets, and we measured the fraction of all droplets that froze (F(ice)) as function of temperature. For Snomax, a strong increase in F(ice) was observed around -7 to -10°C, for BW around -19 to -25°C, respectively. After this initial steep increase, F(ice) stayed constant for both examined substances down to -35°C. We found that the values of F(ice) in the plateau region depended on the dry particle size. The initial solution used to generate the particles contained parts of bacteria with ice active protein complexes on them in the case of Snomax, or IN macromolecules in the case of BW (Pummer et al., 2011). We show that the distribution of the IN proteins or IN molecules in the aerosol particles follows the Poisson distribution. With this knowledge, derivation of the ice nucleation rates for single IN protein complexes or for single IN macromolecules is possible. Combining the Poisson distribution with a stochastic model and using the derived nucleation rates, we can reproduce not only our measurements for both examined substances, but also past measurements done for Snomax and even pseudomonas syringae bacteria. As an additional peculiarity, we seem to observe two different macromolecules being ice active for Birch trees growing in Central Europe or Northern Europe, with the latter initiating freezing at

Population pharmacokinetic (PK) analysis of laromustine, an emerging alkylating agent, in cancer patients.

PubMed

Nassar, Ala F; Wisnewski, Adam V; King, Ivan

2017-05-01

1. Alkylating agents are capable of introducing an alkyl group into nucleophilic sites on DNA or RNA through covalent bond. Laromustine is an active member of a relatively new class of sulfonylhydrazine prodrugs under development as antineoplastic alkylating agents, and displays significant single-agent activity. 2. This is the first report of the population pharmacokinetic analysis of laromustine, 106 patients, 66 with hematologic malignancies and 40 with solid tumors, participated in five clinical trials worldwide. Of these, 104 patients were included in the final NONMEM analysis. 3. The population estimates for total clearance (CL) and volume of distribution of the central compartment (V 1 ) were 96.3 L/h and 45.9 L, associated with high inter-patient variability of 52.9% and 79.8% and inter-occasion variability of 26.7% and 49.3%, respectively. The population estimates for Q and V 2 were 73.2 L/h and 29.9 L, and inter-patient variability in V 2 was 63.1%, respectively. 4. The estimate of V ss (75.8 L) exceeds total body water, indicating that laromustine is distributed to tissues. The half-life is short, less than 1 h, reflecting rapid clearance. Population PK analysis showed laromustine pharmacokinetics to be independent of dose and organ function with no effect on subsequent dosing cycles.

Coordinating Learning Agents for Active Information Collection

DTIC Science & Technology

2011-06-30

the experiments were not particularly sensitive to this parameter. By limiting the number of actions that are updated (DANT-L in black/ dark ), the...Bazzan, A. and Ossowski, S. (eds.), Applications of Agent Technology in Traffic and Transportation (Springer, 2005). [19] Mataric , M. J., Coordination...organizing market (1998), preprint cond- mat/9802177. [19] Jones, C. and Mataric , M. J., Adaptive division of labor in large-scale multi-robot systems, in IEEE

Susceptibility of Legionella pneumophila to twenty antimicrobial agents.

PubMed Central

Edelstein, P H; Meyer, R D

1980-01-01

Thirty-three isolates of Legionella pneumophila, all except one of which were clinical isolates, were tested against 20 antimicrobial agents by using an agar dilution technique. Erythromycin, rifamp]in, and rosaramycin were the most active agents tested. Aminoglycosides, chloramphenicol, and cefoxitin also inhibited the organisms at low concentrations. Other agents, including moxalactam, cefoperazone, and cephalosporins, exhibited moderate to little activity. Tetracycline, doxycycline and minocyeline were apparently inactivated by charcoal-yeast extract medium. There was slight inoculum dependence noted with most of the antimicrobials tested, particularly the beta-lactam agents. There was no consistent difference in susceptibility between Center for Disease Control-supplied stock strains and recent clinical isolates, but there were marked differences with some agents. Susceptibility testing needs to be standardized in view of the influence of inoculum size, strain variation, and the medium used. PMID:7425611

Time-Extended Payoffs for Collectives of Autonomous Agents

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian K.

2002-01-01

A collective is a set of self-interested agents which try to maximize their own utilities, along with a a well-defined, time-extended world utility function which rates the performance of the entire system. In this paper, we use theory of collectives to design time-extended payoff utilities for agents that are both aligned with the world utility, and are "learnable", i.e., the agents can readily see how their behavior affects their utility. We show that in systems where each agent aims to optimize such payoff functions, coordination arises as a byproduct of the agents selfishly pursuing their own goals. A game theoretic analysis shows that such payoff functions have the net effect of aligning the Nash equilibrium, Pareto optimal solution and world utility optimum, thus eliminating undesirable behavior such as agents working at cross-purposes. We then apply collective-based payoff functions to the token collection in a gridworld problem where agents need to optimize the aggregate value of tokens collected across an episode of finite duration (i.e., an abstracted version of rovers on Mars collecting scientifically interesting rock samples, subject to power limitations). We show that, regardless of the initial token distribution, reinforcement learning agents using collective-based payoff functions significantly outperform both natural extensions of single agent algorithms and global reinforcement learning solutions based on "team games".

Isospecific propylene polymerization with in situ generated bis(phenoxy-amine)zirconium and hafnium single site catalysts.

PubMed

Makio, Haruyuki; Prasad, Aitha Vishwa; Terao, Hiroshi; Saito, Junji; Fujita, Terunori

2013-07-07

Bis(phenoxy-imine) Zr and Hf complexes were activated with (i)Bu3Al or (i)Bu2AlH in conjunction with Ph3CB(C6F5)4 and tested as catalysts for propylene polymerization with emphasis on the enantioselectivity of the isospecific species and the single site polymerization characteristics. The isoselective species was identified as the in situ generated bis(phenoxy-amine) complex whose isoselectivity was sensitive to subtle changes in ligand structure. By employing specific substituents at certain key positions the isotacticity reached an extremely high level comparable to high-end commercial isotactic polypropylenes (Tm > 160 °C). Single site polymerization characteristics depended upon the efficiency and selectivity of the in situ imine reduction which is sensitive to the substituent on the imine nitrogen and the reaction conditions. By using (i)Bu2AlH as a reducing agent, quantitative imine reduction can be achieved with a stoichiometric amount of the reducing agent. This lower alkylaluminum loading is beneficial for the catalyst and significantly enhances the polymerization activity and the molecular weight of the resultant polymer.

Role of Apollon in Human Melanoma Resistance to Antitumor Agents That Activate the Intrinsic or the Extrinsic Apoptosis Pathways

PubMed Central

Tassi, Elena; Zanon, Marina; Vegetti, Claudia; Molla, Alessandra; Bersani, Ilaria; Perotti, Valentina; Pennati, Marzia; Zaffaroni, Nadia; Milella, Michele; Ferrone, Soldano; Carlo-Stella, Carmelo; Gianni, Alessandro M.; Mortarini, Roberta; Anichini, Andrea

2012-01-01

Purpose To assess the role of Apollon in melanoma resistance to intrinsic and extrinsic pathways of apoptosis and to identify strategies to reduce its expression. Experimental Design Apollon expression was assessed in melanoma cells in vitro and in vivo. Apollon modulation and melanoma apoptosis were evaluated by Western blot and/or flow cytometry in response to cytotoxic drugs, mitogen-activated protein/extracellular signal–regulated kinase (MEK)-, BRAFV600E-, and mTOR-specific inhibitors, TRAIL and anti-HLA class II monoclonal antibodies (mAb). Mitochondrial depolarization, caspase activation, apoptosis assays, and gene expression profiling were used to test effects of Apollon silencing, by siRNA, on melanoma response to antitumor agents. Results Apollon was constitutively expressed by melanoma cells, in vitro and in vivo, and at higher levels than in benign melanocytic lesions. Melanoma apoptosis correlated significantly with Apollon protein downmodulation in response to cytotoxic drugs, MEK, or BRAFV600E-specific inhibitors. Combinatorial treatment with MEK and mTOR inhibitors and HLA class II ligation, by a specific mAb, promoted Apollon downmodulation and enhanced melanoma apoptosis. Apollon downmodulation induced by antitumor agents was caspase independent, but proteasome dependent. Knockdown of Apollon, by siRNA, triggered apoptosis and/or significantly enhanced melanoma cell death in response to cytotoxic drugs, MEK- and BRAFV600E-specific inhibitors, and soluble or membrane-bound TRAIL. Apollon silencing promoted mitochondrial depolarization and caspase-2, caspase-8, caspase-9, and caspase-3 activation in response to different antitumor agents and altered the profile of genes modulated by MEK or BRAFV600E-specific inhibitors. Conclusions Targeting of Apollon may significantly improve melanoma cell death in response to antitumor agents that trigger the intrinsic or the extrinsic apoptosis pathways. PMID:22553342

Different impressions of other agents obtained through social interaction uniquely modulate dorsal and ventral pathway activities in the social human brain.

PubMed

Takahashi, Hideyuki; Terada, Kazunori; Morita, Tomoyo; Suzuki, Shinsuke; Haji, Tomoki; Kozima, Hideki; Yoshikawa, Masahiro; Matsumoto, Yoshio; Omori, Takashi; Asada, Minoru; Naito, Eiichi

2014-09-01

Internal (neuronal) representations in the brain are modified by our experiences, and this phenomenon is not unique to sensory and motor systems. Here, we show that different impressions obtained through social interaction with a variety of agents uniquely modulate activity of dorsal and ventral pathways of the brain network that mediates human social behavior. We scanned brain activity with functional magnetic resonance imaging (fMRI) in 16 healthy volunteers when they performed a simple matching-pennies game with a human, human-like android, mechanical robot, interactive robot, and a computer. Before playing this game in the scanner, participants experienced social interactions with each opponent separately and scored their initial impressions using two questionnaires. We found that the participants perceived opponents in two mental dimensions: one represented "mind-holderness" in which participants attributed anthropomorphic impressions to some of the opponents that had mental functions, while the other dimension represented "mind-readerness" in which participants characterized opponents as intelligent. Interestingly, this "mind-readerness" dimension correlated to participants frequently changing their game tactic to prevent opponents from envisioning their strategy, and this was corroborated by increased entropy during the game. We also found that the two factors separately modulated activity in distinct social brain regions. Specifically, mind-holderness modulated activity in the dorsal aspect of the temporoparietal junction (TPJ) and medial prefrontal and posterior paracingulate cortices, while mind-readerness modulated activity in the ventral aspect of TPJ and the temporal pole. These results clearly demonstrate that activity in social brain networks is modulated through pre-scanning experiences of social interaction with a variety of agents. Furthermore, our findings elucidated the existence of two distinct functional networks in the social human brain

An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

PubMed

Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

2017-04-01

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

C-Cl bond activation and catalytic hydrodechlorination of hexachlorobenzene by cobalt and nickel complexes with sodium formate as a reducing agent.

PubMed

Li, Junye; Li, Xiaoyan; Wang, Lin; Hu, Qingping; Sun, Hongjian

2014-05-14

A benzyne cobalt complex, Co(η(2)-C6Cl4)(PMe3)3 (2), was generated from the reaction of hexachlorobenzene with 2 equiv. of Co(PMe3)4 through selective activation of two C-Cl bonds of hexachlorobenzene. Meanwhile, the byproduct CoCl2(PMe3)3 was also confirmed by IR spectra. The cobalt(II) complex, CoCl(C6Cl5)(PMe3)3 (1), as an intermediate in the formation of aryne complex 2, was also isolated by the reaction of hexachlorobenzene with the stoichiometric amount of Co(PMe3)4. Complex 2 could be obtained by the reaction of 1 with Co(PMe3)4. Under similar reaction conditions, the reaction of Ni(PMe3)4 with hexachlorobenzene afforded only a mono-(C-Cl) bond activation nickel(II) complex, NiCl(C6H5)(PMe3)2 (5). The expected benzyne nickel complex was not formed. The structures of complexes 2 and 5 were determined by X-ray single crystal diffraction. Successful selective hydrodechlorinations of hexachlorobenzene were studied and in the presence of Co(PMe3)4 or Ni(PMe3)4 as catalysts and sodium formate as a reducing agent pentachlorobenzene and 1,2,4,5-tetrachlorobenzene were obtained. The catalytic hydrodechlorination mechanism is proposed and discussed.

Activity inhibition on municipal activated sludge by single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Parise, Alex; Thakor, Harshrajsinh; Zhang, Xiaoqi

2014-01-01

The objective of this study was to evaluate the respiratory activity inhibition of activated sludge used in a typical wastewater treatment plant by single-walled carbon nanotubes (SWCNTs) with different length and functionality. Four types of SWCNTs were evaluated: short, functionalized short, long, and functionalized long. Based on the effective concentration (EC50) values obtained, we determined that functionalized SWCNTs resulted in a higher microbial respiratory inhibition than non-functionalized nanotubes, and long SWCNTs gave a higher microbial respiratory inhibition than their short counterparts. Among the four types of SWCNTs studied, functionalized long exhibited the highest respiration inhibition. Scanning electron microscopy imaging indicates that the long SWCNTs dispersed more favorably after sonication than the short variety. The findings demonstrated that the toxicity of CNTs (exhibited by respiratory inhibition) is related to their physical properties; the length and functionality of SWCNTs affected the toxicity of SWCNTs in a mixed-cultured biologic system.

Voter models with contrarian agents

NASA Astrophysics Data System (ADS)

Masuda, Naoki

2013-11-01

In the voter and many other opinion formation models, agents are assumed to behave as congregators (also called the conformists); they are attracted to the opinions of others. In this study I investigate linear extensions of the voter model with contrarian agents. An agent is either congregator or contrarian and assumes a binary opinion. I investigate three models that differ in the behavior of the contrarian toward other agents. In model 1, contrarians mimic the opinions of other contrarians and oppose (i.e., try to select the opinion opposite to) those of congregators. In model 2, contrarians mimic the opinions of congregators and oppose those of other contrarians. In model 3, contrarians oppose anybody. In all models, congregators are assumed to like anybody. I show that even a small number of contrarians prohibits the consensus in the entire population to be reached in all three models. I also obtain the equilibrium distributions using the van Kampen small-fluctuation approximation and the Fokker-Planck equation for the case of many contrarians and a single contrarian, respectively. I show that the fluctuation around the symmetric coexistence equilibrium is much larger in model 2 than in models 1 and 3 when contrarians are rare.

Human single neuron activity precedes emergence of conscious perception.

PubMed

Gelbard-Sagiv, Hagar; Mudrik, Liad; Hill, Michael R; Koch, Christof; Fried, Itzhak

2018-05-25

Identifying the neuronal basis of spontaneous changes in conscious experience in the absence of changes in the external environment is a major challenge. Binocular rivalry, in which two stationary monocular images lead to continuously changing perception, provides a unique opportunity to address this issue. We studied the activity of human single neurons in the medial temporal and frontal lobes while patients were engaged in binocular rivalry. Here we report that internal changes in the content of perception are signaled by very early (~-2000 ms) nonselective medial frontal activity, followed by selective activity of medial temporal lobe neurons that precedes the perceptual change by ~1000 ms. Such early activations are not found for externally driven perceptual changes. These results suggest that a medial fronto-temporal network may be involved in the preconscious internal generation of perceptual transitions.

Endocrine active agents: implications of adverse and non-adverse changes.

PubMed

Foster, Paul M D; McIntyre, Barry S

2002-01-01

The US Environmental Protection Agency (EPA) is currently in the process of developing screening and testing methodologies for the assessment of agents that may possess endocrine-like activity--the so-called endocrine disruptors. Moreover, the EPA has signaled its intention of placing information arising from such studies on the worldwide web. This has created significant interest in how such information may be used in risk assessment and by policymakers and the public in the potential regulation or deselection of specific chemical agents. The construction of lists of endocrine disruptors, although fulfilling the requirements of some parties, is really of little use when the nature of the response, the dose level employed, and the lifestage of the test species used are not given. Thus, we have already seen positive in vitro information available on the interaction with a receptor being used as a key indicator when the results of large, high quality in vivo studies showing no adverse changes have been ignored. Clearly a number of in vitro systems are available to ascertain chemical interaction with specific (mainly steroid) hormone receptors including a number of reporter gene assays. These assays only provide indicators of potential problems and should not be, in isolation, indicators of toxicity. Likewise, short-term in vivo screens such as the uterotrophic and Hershberger studies are frequently conducted in castrated animals and thus indicate the potential for a pharmacological response in vivo rather than an adverse effect. A number of new end points have been added to standard rodent testing protocols in the belief of providing more sensitivity to detect endocrine related changes. These include the measurement of anogenital distance (AGD), developmental landmarks [vaginal opening (VO), preputial separation (PPS)], and in some studies the counting of nipples and areolae on males. AGD, VO, and PPS are all affected by the size of the pup in which they are measured

Quantitative telomerase enzyme activity determination using droplet digital PCR with single cell resolution.

PubMed

Ludlow, Andrew T; Robin, Jerome D; Sayed, Mohammed; Litterst, Claudia M; Shelton, Dawne N; Shay, Jerry W; Wright, Woodring E

2014-07-01

The telomere repeat amplification protocol (TRAP) for the human reverse transcriptase, telomerase, is a PCR-based assay developed two decades ago and is still used for routine determination of telomerase activity. The TRAP assay can only reproducibly detect ∼ 2-fold differences and is only quantitative when compared to internal standards and reference cell lines. The method generally involves laborious radioactive gel electrophoresis and is not conducive to high-throughput analyzes. Recently droplet digital PCR (ddPCR) technologies have become available that allow for absolute quantification of input deoxyribonucleic acid molecules following PCR. We describe the reproducibility and provide several examples of a droplet digital TRAP (ddTRAP) assay for telomerase activity, including quantitation of telomerase activity in single cells, telomerase activity across several common telomerase positive cancer cells lines and in human primary peripheral blood mononuclear cells following mitogen stimulation. Adaptation of the TRAP assay to digital format allows accurate and reproducible quantification of the number of telomerase-extended products (i.e. telomerase activity; 57.8 ± 7.5) in a single HeLa cell. The tools developed in this study allow changes in telomerase enzyme activity to be monitored on a single cell basis and may have utility in designing novel therapeutic approaches that target telomerase. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Mixed response and time-to-event endpoints for multistage single-arm phase II design.

PubMed

Lai, Xin; Zee, Benny Chung-Ying

2015-06-04

The objective of phase II cancer clinical trials is to determine if a treatment has sufficient activity to warrant further study. The efficiency of a conventional phase II trial design has been the object of considerable debate, particularly when the study regimen is characteristically cytostatic. At the time of development of a phase II cancer trial, we accumulated clinical experience regarding the time to progression (TTP) for similar classes of drugs and for standard therapy. By considering the time to event (TTE) in addition to the tumor response endpoint, a mixed-endpoint phase II design may increase the efficiency and ability of selecting promising cytotoxic and cytostatic agents for further development. We proposed a single-arm phase II trial design by extending the Zee multinomial method to fully use mixed endpoints with tumor response and the TTE. In this design, the dependence between the probability of response and the TTE outcome is modeled through a Gaussian copula. Given the type I and type II errors and the hypothesis as defined by the response rate (RR) and median TTE, such as median TTP, the decision rules for a two-stage phase II trial design can be generated. We demonstrated through simulation that the proposed design has a smaller expected sample size and higher early stopping probability under the null hypothesis than designs based on a single-response endpoint or a single TTE endpoint. The proposed design is more efficient for screening new cytotoxic or cytostatic agents and less likely to miss an effective agent than the alternative single-arm design.

Research on Production Scheduling System with Bottleneck Based on Multi-agent

NASA Astrophysics Data System (ADS)

Zhenqiang, Bao; Weiye, Wang; Peng, Wang; Pan, Quanke

Aimed at the imbalance problem of resource capacity in Production Scheduling System, this paper uses Production Scheduling System based on multi-agent which has been constructed, and combines the dynamic and autonomous of Agent; the bottleneck problem in the scheduling is solved dynamically. Firstly, this paper uses Bottleneck Resource Agent to find out the bottleneck resource in the production line, analyses the inherent mechanism of bottleneck, and describes the production scheduling process based on bottleneck resource. Bottleneck Decomposition Agent harmonizes the relationship of job's arrival time and transfer time in Bottleneck Resource Agent and Non-Bottleneck Resource Agents, therefore, the dynamic scheduling problem is simplified as the single machine scheduling of each resource which takes part in the scheduling. Finally, the dynamic real-time scheduling problem is effectively solved in Production Scheduling System.

Agent Architecture for Aviation Data Integration System

NASA Technical Reports Server (NTRS)

Kulkarni, Deepak; Wang, Yao; Windrem, May; Patel, Hemil; Wei, Mei

2004-01-01

This paper describes the proposed agent-based architecture of the Aviation Data Integration System (ADIS). ADIS is a software system that provides integrated heterogeneous data to support aviation problem-solving activities. Examples of aviation problem-solving activities include engineering troubleshooting, incident and accident investigation, routine flight operations monitoring, safety assessment, maintenance procedure debugging, and training assessment. A wide variety of information is typically referenced when engaging in these activities. Some of this information includes flight recorder data, Automatic Terminal Information Service (ATIS) reports, Jeppesen charts, weather data, air traffic control information, safety reports, and runway visual range data. Such wide-ranging information cannot be found in any single unified information source. Therefore, this information must be actively collected, assembled, and presented in a manner that supports the users problem-solving activities. This information integration task is non-trivial and presents a variety of technical challenges. ADIS has been developed to do this task and it permits integration of weather, RVR, radar data, and Jeppesen charts with flight data. ADIS has been implemented and used by several airlines FOQA teams. The initial feedback from airlines is that such a system is very useful in FOQA analysis. Based on the feedback from the initial deployment, we are developing a new version of the system that would make further progress in achieving following goals of our project.

A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis

PubMed Central

2011-01-01

Background Long-term immunosuppression is often required in myasthenia gravis (MG). There are no published trials using methotrexate (MTX) in MG. The steroid-sparing efficacy of azathioprine (AZA) has been demonstrated after 18-months of starting therapy. However, AZA is considered expensive in Africa. We evaluated the steroid-sparing efficacy of MTX (17.5 mg weekly) compared with AZA (2.5 mg/kg daily) in subjects recently diagnosed with generalized MG by assessing their average monthly prednisone requirements. Methods The primary outcome was the average daily prednisone requirement by month between the two groups. Prednisone was given at the lowest dose to manage MG symptoms and adjusted as required according to protocol. Single-blinded assessments were performed 3-monthly for 2-years to determine the quantitative MG score and the MG activities of daily living score in order to determine those with minimal manifestations of MG. Results Thirty-one subjects (AZA n = 15; MTX n = 16) satisfied the inclusion criteria but only 24 were randomized. Baseline characteristics were similar. There was no difference between the AZA- and MTX-groups in respect of prednisone dosing (apart from months 10 and 12), in quantitative MG Score improvement, proportions in sustained remission, frequencies of MG relapses, or adverse reactions and/or withdrawals. The MTX-group received lower prednisone doses between month 10 (p = 0.047) and month 12 (p = 0.039). At month 12 the prednisone dose per kilogram bodyweight in the MTX-group (0.15 mg/kg) was half that of the AZA-group (0.31 mg/kg)(p = 0.019). Conclusions This study provides evidence that in patients with generalized MG methotrexate is an effective steroid-sparing agent 10 months after treatment initiation. Our data suggests that in generalized MG methotrexate has similar efficacy and tolerability to azathioprine and may be the drug of choice in financially constrained health systems. Trial registration SANCTR:DOH-27-0411-2436 PMID

Some Surface-Active Agents and Their Virucidal Effect on Foot-and-Mouth Disease Virus

PubMed Central

Fellowes, O. N.

1965-01-01

Selected cationic and anionic surface-active compounds were tested to determine their virucidal effect on the foot-and-mouth disease virus, type O, strain M11, propagated in primary calf kidney cells. The chemical inactivation of the virus was tested with 0.5, 1.0, 2.0, and 5.0% concentrations of the selected compounds. Virus controls with pH adjusted to cover the expected range of the mixtures of the chemicals and virus were also tested. The absence of virus from the mixtures of chemical and virus after reaction at 28 C for 2 hr was assayed by inoculating suckling mice with the mixtures. One cationic compound, alkyl methyl isoquinilinium chloride, showed considerable antiviral activity due largely to pH effect. The use of the surface-active agents investigated in this study, in the presence of organic material, would not be recommended as virucides. PMID:4286396

Destruction of chemical warfare agents using metal-organic frameworks

NASA Astrophysics Data System (ADS)

Mondloch, Joseph E.; Katz, Michael J.; Isley, William C., III; Ghosh, Pritha; Liao, Peilin; Bury, Wojciech; Wagner, George W.; Hall, Morgan G.; Decoste, Jared B.; Peterson, Gregory W.; Snurr, Randall Q.; Cramer, Christopher J.; Hupp, Joseph T.; Farha, Omar K.

2015-05-01

Chemical warfare agents containing phosphonate ester bonds are among the most toxic chemicals known to mankind. Recent global military events, such as the conflict and disarmament in Syria, have brought into focus the need to find effective strategies for the rapid destruction of these banned chemicals. Solutions are needed for immediate personal protection (for example, the filtration and catalytic destruction of airborne versions of agents), bulk destruction of chemical weapon stockpiles, protection (via coating) of clothing, equipment and buildings, and containment of agent spills. Solid heterogeneous materials such as modified activated carbon or metal oxides exhibit many desirable characteristics for the destruction of chemical warfare agents. However, low sorptive capacities, low effective active site loadings, deactivation of the active site, slow degradation kinetics, and/or a lack of tailorability offer significant room for improvement in these materials. Here, we report a carefully chosen metal-organic framework (MOF) material featuring high porosity and exceptional chemical stability that is extraordinarily effective for the degradation of nerve agents and their simulants. Experimental and computational evidence points to Lewis-acidic ZrIV ions as the active sites and to their superb accessibility as a defining element of their efficacy.

Destruction of chemical warfare agents using metal-organic frameworks.

PubMed

Mondloch, Joseph E; Katz, Michael J; Isley, William C; Ghosh, Pritha; Liao, Peilin; Bury, Wojciech; Wagner, George W; Hall, Morgan G; DeCoste, Jared B; Peterson, Gregory W; Snurr, Randall Q; Cramer, Christopher J; Hupp, Joseph T; Farha, Omar K

2015-05-01

Chemical warfare agents containing phosphonate ester bonds are among the most toxic chemicals known to mankind. Recent global military events, such as the conflict and disarmament in Syria, have brought into focus the need to find effective strategies for the rapid destruction of these banned chemicals. Solutions are needed for immediate personal protection (for example, the filtration and catalytic destruction of airborne versions of agents), bulk destruction of chemical weapon stockpiles, protection (via coating) of clothing, equipment and buildings, and containment of agent spills. Solid heterogeneous materials such as modified activated carbon or metal oxides exhibit many desirable characteristics for the destruction of chemical warfare agents. However, low sorptive capacities, low effective active site loadings, deactivation of the active site, slow degradation kinetics, and/or a lack of tailorability offer significant room for improvement in these materials. Here, we report a carefully chosen metal-organic framework (MOF) material featuring high porosity and exceptional chemical stability that is extraordinarily effective for the degradation of nerve agents and their simulants. Experimental and computational evidence points to Lewis-acidic Zr(IV) ions as the active sites and to their superb accessibility as a defining element of their efficacy.

Discovery of new anticancer agents from higher plants

PubMed Central

Pan, Li; Chai, Hee-Byung; Kinghorn, A. Douglas

2012-01-01

1. ABSTRACT Small organic molecules derived from higher plants have been one of the mainstays of cancer chemotherapy for approximately the past half a century. In the present review, selected single chemical entity natural products of plant origin and their semi-synthetic derivatives currently in clinical trials are featured as examples of new cancer chemotherapeutic drug candidates. Several more recently isolated compounds obtained from plants showing promising in vivo biological activity are also discussed in terms of their potential as anticancer agents, with many of these obtained from species that grow in tropical regions. Since extracts of only a relatively small proportion of the ca. 300,000 higher plants on earth have been screened biologically to date, bioactive compounds from plants should play an important role in future anticancer drug discovery efforts. PMID:22202049

Behavioral networks as a model for intelligent agents

NASA Technical Reports Server (NTRS)

Sliwa, Nancy E.

1990-01-01

On-going work at NASA Langley Research Center in the development and demonstration of a paradigm called behavioral networks as an architecture for intelligent agents is described. This work focuses on the need to identify a methodology for smoothly integrating the characteristics of low-level robotic behavior, including actuation and sensing, with intelligent activities such as planning, scheduling, and learning. This work assumes that all these needs can be met within a single methodology, and attempts to formalize this methodology in a connectionist architecture called behavioral networks. Behavioral networks are networks of task processes arranged in a task decomposition hierarchy. These processes are connected by both command/feedback data flow, and by the forward and reverse propagation of weights which measure the dynamic utility of actions and beliefs.

Developing of a novel antibacterial agent by functionalization of graphene oxide with guanidine polymer with enhanced antibacterial activity

NASA Astrophysics Data System (ADS)

Li, Ping; Sun, Shiyu; Dong, Alideertu; Hao, Yanping; Shi, Shuangqiang; Sun, Zijia; Gao, Ge; Chen, Yuxin

2015-11-01

New materials with excellent antibacterial activity attract numerous research interests. Herein, a facile synthetic method of polyethylene glycol (PEG) and polyhexamethylene guanidine hydrochloride (PHGC) dual-polymer-functionalized graphene oxide (GO) (GO-PEG-PHGC), a novel antibacterial material, was reported. The as-prepared products were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), X-ray pattern (XRD) and elemental analysis. The antibacterial effect on the bacterial strain was investigated by incubating both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). The results show that GO-PEG-PHGC has enhanced antibacterial activity when compared to GO, GO-PEG or GO-PHGC alone. The improved antibacterial activity was described to be related to a better dispersion of GO-PEG-PHGC in the presence of PEG. This better dispersion leads to a greater contact between the bacteria membrane and nanomaterials, therefore leading to greater cell damage. Not only Gram-negative bacteria but also Gram-positive bacteria are greatly inhibited by this antibacterial agent. With the powerful antibacterial activity as well as its low cost and facile preparation, the GO-PEG-PHGC as a novel antibacterial agent can find potential application in the areas of healthcare and environmental engineering.

[Comparison of basic carboxypeptidases activity in male rats tissues at a single injection of haloperidol].

PubMed

Pravosudova, N A; Bykova, I O

2014-01-01

The influence of a single injection of haloperidol on basic carboxypeptidases (biologically active peptide processing enzymes) activity in rat tissues was studied. Acute exposure to haloperidol increased the activity of carboxypeptidases H (CP H) in hypothalamic-pituitary-adrenal system and cerebellum and reduced such activity in testes. Multidirectional changes of PMSF-inhibited carboxypeptidases activity (PMSF-CP) were observed after a single haloperidol injection in all studied tissues except testes. It is suggested that changes of CP H and PMSF-CP activity might affect levels of regulatory peptides in the brain and blood and thus may be involved in general and side effects of haloperidol on the organism.

A real-time architecture for time-aware agents.

PubMed

Prouskas, Konstantinos-Vassileios; Pitt, Jeremy V

2004-06-01

This paper describes the specification and implementation of a new three-layer time-aware agent architecture. This architecture is designed for applications and environments where societies of humans and agents play equally active roles, but interact and operate in completely different time frames. The architecture consists of three layers: the April real-time run-time (ART) layer, the time aware layer (TAL), and the application agents layer (AAL). The ART layer forms the underlying real-time agent platform. An original online, real-time, dynamic priority-based scheduling algorithm is described for scheduling the computation time of agent processes, and it is shown that the algorithm's O(n) complexity and scalable performance are sufficient for application in real-time domains. The TAL layer forms an abstraction layer through which human and agent interactions are temporally unified, that is, handled in a common way irrespective of their temporal representation and scale. A novel O(n2) interaction scheduling algorithm is described for predicting and guaranteeing interactions' initiation and completion times. The time-aware predicting component of a workflow management system is also presented as an instance of the AAL layer. The described time-aware architecture addresses two key challenges in enabling agents to be effectively configured and applied in environments where humans and agents play equally active roles. It provides flexibility and adaptability in its real-time mechanisms while placing them under direct agent control, and it temporally unifies human and agent interactions.

In vitro susceptibility of Trichomonas vaginalis to 50 antimicrobial agents.

PubMed Central

Sears, S D; O'Hare, J

1988-01-01

We determined the susceptibilities of five strains of Trichomonas vaginalis, one of which was metronidazole resistant, to 50 antimicrobial agents. For the metronidazole-susceptible strains, the most active agents were metronidazole, tinidazole, mebendazole, furazolidone, and anisomycin. Against the resistant strain mebendazole, furazolidone, and anisomycin were the most active. Antifungal agents, beta-lactams, macrolides, aminoglycosides, and folic acid antagonists were ineffective against all strains. PMID:3258142

Comparison of the cidal activity of tea tree oil and terpinen-4-ol against clinical bacterial skin isolates and human fibroblast cells.

PubMed

Loughlin, R; Gilmore, B F; McCarron, P A; Tunney, M M

2008-04-01

The aim of this study was to compare both the antimicrobial activity of terpinen-4-ol and tea tree oil (TTO) against clinical skin isolates of meticillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (CoNS) and their toxicity against human fibroblast cells. Antimicrobial activity was compared by using broth microdilution and quantitative in vitro time-kill test methods. Terpinen-4-ol exhibited significantly greater bacteriostatic and bactericidal activity, as measured by minimum inhibitory and bactericidal concentrations, respectively, than TTO against both MRSA and CoNS isolates. Although not statistically significant, time-kill studies also clearly showed that terpinen-4-ol exhibited greater antimicrobial activity than TTO. Comparison of the toxicity of terpinen-4-ol and TTO against human fibroblasts revealed that neither agent, at the concentrations tested, were toxic over the 24-h test period. Terpinen-4-ol is a more potent antibacterial agent against MRSA and CoNS isolates than TTO with neither agent exhibiting toxicity to fibroblast cells at the concentrations tested. Terpinen-4-ol should be considered for inclusion as a single agent in products formulated for topical treatment of MRSA infection. However, further work would initially be required to ensure that resistance would not develop with the use of terpinen-4-ol as a single agent.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity

NASA Astrophysics Data System (ADS)

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-11-01

The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity.

PubMed

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-11-08

The increasing number of recording electrodes enhances the capability of capturing the network's cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.

Chemical warfare agents. Classes and targets.

PubMed

Schwenk, Michael

2018-09-01

Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation. The present work briefly surveys classes and toxicologically relevant features of chemical warfare agents and describes mechanisms of toxic action. Copyright © 2017 Elsevier B.V. All rights reserved.

A smart drug: a pH-responsive photothermal ablation agent for Golgi apparatus activated cancer therapy.

PubMed

Xue, Fengfeng; Wen, Ying; Wei, Peng; Gao, Yilin; Zhou, Zhiguo; Xiao, Shuzhang; Yi, Tao

2017-06-13

We report a pH-responsive photothermal ablation agent (pH-PTT) based on cyanine dyes for photothermal therapy (PTT). The nanoparticles formed by BSA and pH-PTT preferentially accumulated in the Golgi apparatus of cancer cells compared to normal cells, and thus can be specifically activated by the acidic Golgi apparatus in cancer cells for effective PTT both ex vivo and in vivo.

Structure-Activity Relationships of Orotidine-5′-Monophosphate Decarboxylase Inhibitors as Anticancer Agents

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

Bello, A.; Konforte, D; Poduch, E

2009-01-01

A series of 6-substituted and 5-fluoro-6-substituted uridine derivatives were synthesized and evaluated for their potential as anticancer agents. The designed molecules were synthesized from either fully protected uridine or the corresponding 5-fluorouridine derivatives. The mononucleotide derivatives were used for enzyme inhibition investigations against ODCase. Anticancer activities of all the synthesized derivatives were evaluated using the nucleoside forms of the inhibitors. 5-Fluoro-UMP was a very weak inhibitor of ODCase. 6-Azido-5-fluoro and 5-fluoro-6-iodo derivatives are covalent inhibitors of ODCase, and the active site Lys145 residue covalently binds to the ligand after the elimination of the 6-substitution. Among the synthesized nucleoside derivatives, 6-azido-5-fluoro,more » 6-amino-5-fluoro, and 6-carbaldehyde-5-fluoro derivatives showed potent anticancer activities in cell-based assays against various leukemia cell lines. On the basis of the overall profile, 6-azido-5-fluoro and 6-amino-5-fluoro uridine derivatives exhibited potential for further investigations.« less

Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.

PubMed

Li, Guolin; Slansky, Adam; Dobhal, Mahabeer P; Goswami, Lalit N; Graham, Andrew; Chen, Yihui; Kanter, Peter; Alberico, Ronald A; Spernyak, Joseph; Morgan, Janet; Mazurchuk, Richard; Oseroff, Allan; Grossman, Zachary; Pandey, Ravindra K

2005-01-01

A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important

Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review.

PubMed

Polak, David; Martin, Conchita; Sanz-Sánchez, Ignacio; Beyth, Nurit; Shapira, Lior

2015-04-01

Systematically review the scientific evidence for efficiency of anti-inflammatory agents against gingivitis, either as solo treatments or adjunctive therapies. A protocol was developed aimed to answer the following focused question: "Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies?" RCTs and cohort studies on anti-inflammatory agents against gingivitis studies were searched electronically. Screening, data extraction and quality assessment were conducted. The primary outcome measures were indices of gingival inflammation. A sub-analysis was performed dividing the active agents into anti-inflammatory and other drugs. The search identified 3188 studies, of which 14 RCTs met the inclusion criteria. The use of anti-inflammatory or other agents, in general showed a higher reduction in the test than in the control in terms of gingival indexes and bleeding scores. Only two RCTs on inflammatory drugs could be meta-analysed, showing a statistically significant reduction in the GI in the experimental group [WMD = -0.090; 95% CI (-0.105; -0.074); p = 0.000]. However, the contribution of both studies to the global result was unbalanced (% weight: 99.88 and 0.12 respectively). Most of the tested material showed beneficial effect as anti-inflammatory agents against gingivitis, either as a single treatment modality or as an adjunctive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In vitro evaluation of the antibacterial activity of Arctium lappa as a phytotherapeutic agent used in intracanal dressings.

PubMed

Gentil, Marcelo; Pereira, Juliana Vianna; Sousa, Yara T Corrêa Silva; Pietro, Rosimeire; Neto, Manoel D Sousa; Vansan, Luiz Pascoal; de Castro França, Suzelei

2006-03-01

The discovery of natural biocomponents from plants with antibacterial activity on endodontic microbiota may lead to new therapies. This study evaluated the antibacterial activity of a phytotherapeutic agent prepared from an ethyl acetate fraction (AcOEt) extracted from Arctium lappa. This agent was compared with calcium hydroxide as an intracanal dressing. Twenty-seven maxillary canines were instrumented, sterilized and inoculated with a mixed bacterial suspension of Pseudomonas aeruginosa, Escherichia coli, Lactobacillus acidophilus, Streptococcus mutans and Candida albicans. The teeth were divided into three groups and their canals filled with: group 1, calcium hydroxide and propylene glycol; group 2, a paste containing AcOEt fraction of A. lappa and propylene glycol; group 3, propylene glycol (control). At 7, 14 and 30 days, three teeth from each group were opened and a paper point was placed in the root canal for 5 min. The paper points were transferred to Petri dishes with Brain Heart Infusion (BHI). The bacterial growth was classified. Mild bacterial growth was found in group 1 at all time intervals; in group 2 there was severe growth at 7 days, but no growth at 14 and 30 days. The phytotherapeutic agent extracted from an AcOEt fraction of A. lappa inhibited the growth of all the microorganisms in this study. Copyright 2006 John Wiley & Sons, Ltd.

Increasing Physical Activity Amongst Overweight and Obese Cancer Survivors Using an Alexa-Based Intelligent Agent for Patient Coaching: Protocol for the Physical Activity by Technology Help (PATH) Trial

PubMed Central

Schrack, Jennifer; Naiman, Daniel; Lansey, Dina; Baig, Yasmin; Stearns, Vered; Celentano, David; Martin, Seth; Appel, Lawrence

2018-01-01

Background Physical activity has established health benefits, but motivation and adherence remain challenging. Objective We designed and launched a three-arm randomized trial to test artificial intelligence technology solutions to increase daily physical activity in cancer survivors. Methods A single-center, three-arm randomized clinical trial with an allocation ration of 1:1:1: (A) control, in which participants are provided written materials about the benefits of physical activity; (B) text intervention, where participants receive daily motivation from a fully automated, data-driven algorithmic text message via mobile phone (Coachtext); and (C) Voice Assist intervention, where participants are provided with an in-home on demand autonomous Intelligent Agent using data driven Interactive Digital Voice Assist on the Amazon Alexa/Echo (MyCoach). Results The study runs for 5 weeks: a one-week run-in to establish baseline, followed by 4 weeks of intervention. Data for study outcomes is collected automatically through a wearable sensor, and data are transferred in real-time to the study server. The recruitment goal is 42 participants, 14 in each arm. Electronic health records are used to prescreen candidates, with 39 participants recruited to date. Discussion This study aims to investigate the effects of different types of intelligent technology solutions on promoting physical activity in cancer survivors. This innovative approach can easily be expanded and customized to other interventions. Early lessons from our initial participants are helping us develop additional advanced solutions to improve health outcomes. Trial Registration Retrospectively registered on July 10, 2017 at ClinicalTrials.gov: NCT03212079; https://clinicaltrials.gov/ct2/show/NCT03212079 (Archived by WebCite at http://www.webcitation.org/6wgvqjTji) PMID:29434016

IDEA: Planning at the Core of Autonomous Reactive Agents

NASA Technical Reports Server (NTRS)

Muscettola, Nicola; Dorais, Gregory A.; Fry, Chuck; Levinson, Richard; Plaunt, Christian; Clancy, Daniel (Technical Monitor)

2002-01-01

Several successful autonomous systems are separated into technologically diverse functional layers operating at different levels of abstraction. This diversity makes them difficult to implement and validate. In this paper, we present IDEA (Intelligent Distributed Execution Architecture), a unified planning and execution framework. In IDEA a layered system can be implemented as separate agents, one per layer, each representing its interactions with the world in a model. At all levels, the model representation primitives and their semantics is the same. Moreover, each agent relies on a single model, plan database, plan runner and on a variety of planners, both reactive and deliberative. The framework allows the specification of agents that operate, within a guaranteed reaction time and supports flexible specification of reactive vs. deliberative agent behavior. Within the IDEA framework we are working to fully duplicate the functionalities of the DS1 Remote Agent and extend it to domains of higher complexity than autonomous spacecraft control.

Environmental factors affect the activity of biocontrol agents against ochratoxigenic Aspergillus carbonarius on wine grape.

PubMed

De Curtis, F; de Felice, D V; Ianiri, G; De Cicco, V; Castoria, R

2012-09-17

The influence of temperature and relative humidity (RH) on the activity of three biocontrol agents-the yeast Metschnikowia pulcherrima LS16 and two strains of the yeast-like fungus Aureobasidium pullulans LS30 and AU34-2-against infection by A. carbonarius and ochratoxin A (OTA) accumulation in wine grape berries was investigated in lab-scale experiments. The presence of wounds on grape skin dramatically favored infection of berries by A. carbonarius strain A1102, since unwounded berries showed very low levels of infection at all conditions of RH and temperature tested. Artificially wounded berries pre-treated with the biocontrol agents were inoculated with the ochratoxigenic A. carbonarius strain A1102 and were incubated for 5 days at two levels of RH (60% and 100%) and three different temperatures (20, 25 and 30 °C). The three biocontrol agents were able to prevent infections at 60% RH and 20 °C. At 60% RH and 25 °C only strain AU34-2 achieved some protection on day 5, whereas at 30 °C a limited biocontrol efficacy was evident only up to day 2. At 100% RH, LS16, LS30 and AU34-2 showed effective protection of grape berries at 20 °C until the 5th day of incubation. The three biocontrol agents achieved significant protection at higher temperatures only until the 2nd day after the beginning of the experiment: all three strains at 25 °C, and only strain LS16 at 30 °C. After 5 days, the three biocontrol agents were able to significantly reduce the level of OTA in berries at all the conditions tested. This occurred even when protection from infection was not significant, except at 30 °C and 100% of RH for all the three strains, and at 25 °C and 100% of RH for strain LS16. The biocontrol agents displayed a higher rate of colonization on grape berries at 20 and 25 °C than at 30 °C. The higher value of RH (100%) appeared to increase the rate of colonization, in particular at 20 and 25 °C. Taken together, our results emphasize the significant influence of

Smoke-induced microRNA and related proteome alterations. Modulation by chemopreventive agents.

PubMed

De Flora, Silvio; Balansky, Roumen; D'Agostini, Francesco; Cartiglia, Cristina; Longobardi, Mariagrazia; Steele, Vernon E; Izzotti, Alberto

2012-12-15

Dysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression since a single miRNA targets a number of genes simultaneously. This article provides a review of published data and ongoing studies regarding the effects of cigarette smoke (CS), either mainstream (MCS) or environmental (ECS), on the expression of miRNAs and related proteins. The results generated in mice, rats, and humans provided evidence that exposure to CS results in an intense dysregulation of miRNA expression in the respiratory tract, which is mainly oriented in the sense of downregulation. In parallel, there was an upregulation of proteins targeted by the downregulated miRNAs. These trends reflect an attempt to defend the respiratory tract by means of antioxidant mechanisms, detoxification of carcinogens, DNA repair, anti-inflammatory pathways, apoptosis, etc. However, a long-lasting exposure to CS causes irreversible miRNA alterations that activate carcinogenic mechanisms, such as modulation of oncogenes and oncosuppressor genes, cell proliferation, recruitment of undifferentiated stem cells, inflammation, inhibition of intercellular communications, angiogenesis, invasion, and metastasis. The miRNA alterations induced by CS in the lung of mice and rats are similar to those observed in the human respiratory tract. Since a number of miRNAs that are modulated by CS and/or chemopreventive agents are subjected to single nucleotide polymorphisms in humans, they can be evaluated according to toxicogenomic/pharmacogenomics approaches. A variety of cancer chemopreventive agents tested in our laboratory modulated both baseline and CS-related miRNA and proteome alterations, thus contributing to evaluate both safety and efficacy of dietary and pharmacological agents. Copyright © 2012 UICC.

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity

PubMed Central

Vardi, Roni; Goldental, Amir; Sardi, Shira; Sheinin, Anton; Kanter, Ido

2016-01-01

The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity. PMID:27824075

In-vitro activity of several antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA) isolates expressing aminoglycoside-modifying enzymes: potency of plazomicin alone and in combination with other agents.

PubMed

López Díaz, María Carmen; Ríos, Esther; Rodríguez-Avial, Iciar; Simaluiza, Rosa Janneth; Picazo, Juan José; Culebras, Esther

2017-08-01

This study investigated the in-vitro activity of clinically relevant aminoglycosides and new antimicrobial agents-plazomicin, ceftobiprole and dalbavancin-against 55 methicillin-resistant Staphylococcus aureus (MRSA) isolates producing aminoglycoside-modifying enzymes (AMEs). The checkerboard method was used to assess synergism between plazomicin and four antibiotics (fosfomycin, ceftobiprole, cefoxitin and meropenem), and time-kill assays were performed for the most active combinations. Among the aminoglycosides tested, plazomicin was the most active agent against MRSA, with >90% of isolates being inhibited at a minimum inhibitory concentration (MIC) of ≤1 mg/L. MIC 50 and MIC 90 values for ceftobiprole and dalbavancin were 2 and 4 mg/L, and 0.125 and 0.125 mg/L, respectively. The most prevalent AME gene was aac(6')Ie-aph(2″)Ia (87.3%), followed by ant(4')Ia (52.7%) and aph(3')IIIa (52.7%). Plazomicin activity was not affected by the type or number of enzymes detected. In checkerboard and time-kill assays, indifference was the most common result achieved for the antibiotic combinations. Notably, no antagonism was observed with any combination tested. Overall, plazomicin in combination with meropenem had the highest synergistic effect, demonstrating synergy against seven isolates in the checkerboard assay and three isolates in time-kill curves. In conclusion, plazomicin showed potent activity against aminoglycoside-resistant MRSA isolates, regardless of the number and type of AMEs present. These findings indicate the potential utility of plazomicin in combination with meropenem for the treatment of MRSA infections. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Agents in bioinformatics, computational and systems biology.

PubMed

Merelli, Emanuela; Armano, Giuliano; Cannata, Nicola; Corradini, Flavio; d'Inverno, Mark; Doms, Andreas; Lord, Phillip; Martin, Andrew; Milanesi, Luciano; Möller, Steffen; Schroeder, Michael; Luck, Michael

2007-01-01

The adoption of agent technologies and multi-agent systems constitutes an emerging area in bioinformatics. In this article, we report on the activity of the Working Group on Agents in Bioinformatics (BIOAGENTS) founded during the first AgentLink III Technical Forum meeting on the 2nd of July, 2004, in Rome. The meeting provided an opportunity for seeding collaborations between the agent and bioinformatics communities to develop a different (agent-based) approach of computational frameworks both for data analysis and management in bioinformatics and for systems modelling and simulation in computational and systems biology. The collaborations gave rise to applications and integrated tools that we summarize and discuss in context of the state of the art in this area. We investigate on future challenges and argue that the field should still be explored from many perspectives ranging from bio-conceptual languages for agent-based simulation, to the definition of bio-ontology-based declarative languages to be used by information agents, and to the adoption of agents for computational grids.

HER2 mutated breast cancer responds to treatment with single agent neratinib, a second generation HER2/EGFR tyrosine kinase inhibitor

PubMed Central

Ben–Baruch, Noa Efrat; Bose, Ron; Kavuri, Shyam M.; Ma, Cynthia X.; Ellis, Matthew J.

2015-01-01

Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2 targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. In this case report, we describe a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second generation HER2/EGFR tyrosine kinase inhibitor, neratinib, resulted in partial response and dramatic improvement in the patient’s function status. This partial response lasted 11 months and when the patient’s cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2 amplified breast cancer after disease progression. This case is the first report, to our knowledge, of successful single agent treatment of HER2 mutated breast cancer. Two clinical trials of neratinib for HER2 mutated, metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancer, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2 mutated solid tumors is warranted. PMID:26358790

HER2-Mutated Breast Cancer Responds to Treatment With Single-Agent Neratinib, a Second-Generation HER2/EGFR Tyrosine Kinase Inhibitor.

PubMed

Ben-Baruch, Noa Efrat; Bose, Ron; Kavuri, Shyam M; Ma, Cynthia X; Ellis, Matthew J

2015-09-01

Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2-targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. This case report describes a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second-generation HER2/EGFR tyrosine kinase inhibitor neratinib resulted in partial response and dramatic improvement in the patient's functional status. This partial response lasted 11 months, and when the patient's cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2-amplified breast cancer after disease progression. This case represents the first report, to our knowledge, of successful single-agent treatment of HER2-mutated breast cancer. Two clinical trials of neratinib for HER2-mutated metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancers, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2-mutated solid tumors is warranted. Copyright © 2015 by the National Comprehensive Cancer Network.

Extended Treatment with Single-Agent Ibrutinib at the 420 mg Dose Leads to Durable Responses in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

PubMed

Coutré, Steven E; Furman, Richard R; Flinn, Ian W; Burger, Jan A; Blum, Kristie; Sharman, Jeff; Jones, Jeffrey; Wierda, William; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Tran, Anh; Zhou, Cathy; Bilotti, Elizabeth; James, Danelle F; Byrd, John C; O'Brien, Susan

2017-03-01

Purpose: Ibrutinib, a first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase, promotes apoptosis, and inhibits B-cell proliferation, adhesion, and migration. Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve (TN) or had relapsed/refractory (R/R) CLL after ≥1 prior therapy in a phase Ib/II study (PCYC-1102). Subsequently, the ibrutinib 420 mg dose was approved in CLL. Experimental Design: We report data with 44 months of follow-up on 94 patients with TN and R/R CLL/SLL receiving ibrutinib 420 mg once-daily in PCYC-1102 and the long-term extension study PCYC-1103. Results: Ninety-four CLL/SLL patients (27 TN, 67 R/R) were treated with ibrutinib (420 mg/day). Patients with R/R disease had received a median of four prior therapies (range, 1-12). Responses were rapid and durable and median duration of response was not reached. Best overall response was 91% [85% TN (complete response, CR 26%) and 94% R/R (9% CR)]. Median progression-free survival (PFS) was not reached in either group. The 30-month PFS rate was 96% and 76% for TN and R/R patients, respectively. Ibrutinib was well tolerated with extended follow-up; rates of grade ≥3 cytopenias and fatigue, as well as discontinuations due to toxicities decreased over time. Conclusions: Single-agent ibrutinib at 420 mg once-daily resulted in durable responses and was well tolerated with up to 44 months follow-up in patients with TN and R/R CLL/SLL. Currently, 66% of patients continue on ibrutinib. Clin Cancer Res; 23(5); 1149-55. ©2017 AACR . ©2017 American Association for Cancer Research.

Impact of single anaerobic exercise on delayed activation of endothelial xanthine oxidase in men and women.

PubMed

Wiecek, Magdalena; Maciejczyk, Marcin; Szymura, Jadwiga; Kantorowicz, Malgorzata; Szygula, Zbigniew

2017-11-01

The aim of the study was to evaluate the activity of xanthine oxidase (XO) in the blood of men and women during the first hour following a single anaerobic exercise (AN-EX), and after 24 hours of recovery, and to determine whether the changes in XO activity in the blood after AN-EX are dependent on anaerobic performance. Ten men and ten women performed a single AN-EX. Blood was collected before and five times after completion of the AN-EX. The activity of XO was determined. In both groups, a significant (P < 0.05) increase in blood XO activity was found only 24 hours after the AN-EX. The increased activity of XO in men was significantly lower than in women (P < 0.05). Negative correlations were found between the increase in XO activity in the blood plasma 24 hours after the AN-EX and anaerobic power, the total work performed during the AN-EX and the power decrease. In the first hour after the single AN-EX, XO activity in the blood of women and men did not change, but after 24 hours of recovery, it was significantly higher compared to baseline levels in both sexes. Single AN-EX causes a smaller increase in XO activity in people with higher anaerobic performance.

Method and apparatus for enhanced detection of toxic agents

DOEpatents

Greenbaum, Elias; Rodriguez, Jr., Miguel; Wu, Jie Jayne; Qi, Hairong

2013-10-01

A biosensor based detection of toxins includes enhancing a fluorescence signal by concentrating a plurality of photosynthetic organisms in a fluid into a concentrated region using biased AC electro-osmosis. A measured photosynthetic activity of the photosynthetic organisms is obtained in the concentrated region, where chemical, biological or radiological agents reduce a nominal photosynthetic activity of the photosynthetic organisms. A presence of the chemical, biological and/or radiological agents or precursors thereof, is determined in the fluid based on the measured photosynthetic activity of the concentrated plurality of photosynthetic organisms. A lab-on-a-chip system is used for the concentrating step. The presence of agents is determined from feature vectors, obtained from processing a time dependent signal using amplitude statistics and/or time-frequency analysis, relative to a control signal. A linear discriminant method including support vector machine classification (SVM) is used to identify the agents.

Triggered pore-forming agents

DOEpatents

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

1998-01-01

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

Three-dimensional rearrangement of single atoms using actively controlled optical microtraps.

PubMed

Lee, Woojun; Kim, Hyosub; Ahn, Jaewook

2016-05-02

We propose and demonstrate three-dimensional rearrangements of single atoms. In experiments performed with single ⁸⁷Rb atoms in optical microtraps actively controlled by a spatial light modulator, we demonstrate various dynamic rearrangements of up to N = 9 atoms including rotation, 2D vacancy filling, guiding, compactification, and 3D shuffling. With the capability of a phase-only Fourier mask to generate arbitrary shapes of the holographic microtraps, it was possible to place single atoms at arbitrary geometries of a few μm size and even continuously reconfigure them by conveying each atom. For this purpose, we loaded a series of computer-generated phase masks in the full frame rate of 60 Hz of the spatial light modulator, so the animation of phase mask transformed the holographic microtraps in real time, driving each atom along the assigned trajectory. Possible applications of this method of transformation of single atoms include preparation of scalable quantum platforms for quantum computation, quantum simulation, and quantum many-body physics.

Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents

PubMed Central

Dewal, Mahender B.; Wani, Amit S.; Vidaillac, Celine; Oupicky, David; Rybak, Michael J.

2012-01-01

Several thieno[2,3-d]pyrimidinediones have been synthesized and examined for antibacterial activity against a range of Gram-positive and Gram-negative pathogens. Two compounds displayed potent activity (2–16 mg/L) against multi-drug resistant Gram-positive organisms, including methicillin, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus (MRSA, VISA, VRSA) and vancomycin-resistant enterococci (VRE). Only one of these agents possessed moderate activity (16–32 mg/L) against Gram-negative strains. An examination of the cytotoxicity of these agents revealed that they displayed low toxicity (40–50 mg/L) against mammalian cell and very low hemolytic activity (2–7%). Taken together, these studies suggest that thieno[2,3-d]pyrimidinediones are interesting scaffolds for the development of novel Gram-positive antibacterial agents. PMID:22405289

Single chip camera active pixel sensor

NASA Technical Reports Server (NTRS)

Shaw, Timothy (Inventor); Pain, Bedabrata (Inventor); Olson, Brita (Inventor); Nixon, Robert H. (Inventor); Fossum, Eric R. (Inventor); Panicacci, Roger A. (Inventor); Mansoorian, Barmak (Inventor)

2003-01-01

A totally digital single chip camera includes communications to operate most of its structure in serial communication mode. The digital single chip camera include a D/A converter for converting an input digital word into an analog reference signal. The chip includes all of the necessary circuitry for operating the chip using a single pin.

Lytic agents, cell permeability, and monolayer penetrability.

PubMed

Salton, M R

1968-07-01

Cell lysis induced by lytic agents is the terminal phase of a series of events leading to membrane disorganization and breadkdown with the release of cellular macromolecules. Permeability changes following exposure to lytic systems may range from selective effects on ion fluxes to gross membrane damage and cell leakage. Lysis can be conceived as an interfacial phenomenon, and the action of surface-active agents on erythrocytes has provided a model in which to investigate relationships between hemolysis and chemical structure, ionic charge, surface tension lowering, and ability to penetrate monolayers of membrane lipid components. Evidence suggests that lysis follows the attainment of surface pressures exceeding a "critical collapse" level and could involve membrane cholesterol or phospholipid. Similarities of chemical composition of membranes from various cell types could account for lytic responses observed on interaction with surface-active agents. Cell membranes usually contain about 20-30 % lipid and 50-75 % protein. One or two major phospholipids are present in all cell membranes, but sterols are not detectable in bacterial membranes other than those of the Mycoplasma group. The rigid cell wall in bacteria has an important bearing on their response to treatment with lytic agents. Removal of the wall renders the protoplast membrane sensitive to rapid lysis with surfactants. Isolated membranes of erythrocytes and bacteria are rapidly dissociated by surface-active agents. Products of dissociation of bacterial membranes have uniform behavior in the ultracentrifuge (sedimentation coefficients 2-3S). Dissociation of membrane proteins from lipids and the isolation and characterization of these proteins will provide a basis for investigating the specificity of interaction of lytic agents with biomembranes.

Polarized excitons and optical activity in single-wall carbon nanotubes

NASA Astrophysics Data System (ADS)

Chang, Yao-Wen; Jin, Bih-Yaw

2018-05-01

The polarized excitons and optical activity of single-wall carbon nanotubes (SWNTs) are studied theoretically by π -electron Hamiltonian and helical-rotational symmetry. By taking advantage of the symmetrization, the single-particle energy and properties of a SWNT are characterized with the corresponding helical band structure. The dipole-moment matrix elements, magnetic-moment matrix elements, and the selection rules can also be derived. Based on different selection rules, the optical transitions can be assigned as the parallel-polarized, left-handed circularly-polarized, and right-handed circularly-polarized transitions, where the combination of the last two gives the cross-polarized transition. The absorption and circular dichroism (CD) spectra are simulated by exciton calculation. The calculated results are well comparable with the reported measurements. Built on the foundation, magnetic-field effects on the polarized excitons and optical activity of SWNTs are studied. Dark-bright exciton splitting and interband Faraday effect in the CD spectrum of SWNTs under an axial magnetic field are predicted. The Faraday rotation dispersion can be analyzed according to the selection rules of circular polarizations and the helical band structure.

Plumbago auriculata leaf extract-mediated AgNPs and its activities as antioxidant, anti-TB and dye degrading agents.

PubMed

Jaryal, Neeraj; Kaur, Harpreet

2017-11-01

In the present work, silver nanoparticles have been biosynthesized by utilizing the alcoholic extract of Plumbago auriculata. The optimization of reaction conditions was carried out by monitoring the reactions with the help of UV-Visible absorption spectroscopy. The characterization of AgNP was carried out by infrared spectroscopy, transmission electron microscopy and X-Ray diffraction (XRD) studies. The biogenic AgNPs were tested against Mycobacterium tuberculosis using Microplate Almar Blue assay (MABA) and their antioxidant activity was also evaluated. The silver nanoparticles were also assessed for their reducing activity against organic dyes. The AgNPs were spherical in shape with size ranging from 15 to 45 nm with face centered cubic geometry as revealed by XRD analysis. The AgNPs possessed good antitubercular activity with MIC value of 1.6 μg/ml and these also exhibited promising antioxidant activity with IC 50 value of 28.2. Furthermore, AgNPs also reduced congo red within 2 h and malachite green was degraded within 40 min. The present work demonstrated the utilization of P. auriculata for biosynthesis of AgNP which could be a potential candidate for antitubercular drug development and it could also be used as an antioxidant agent. The application of AgNP in reducing agent can be further extended and evaluated for purification of effluent water from textile industries.

Activation of surface lattice oxygen in single-atom Pt/CeO 2 for low-temperature CO oxidation

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