Mixed oxide nanoparticles and method of making

DOEpatents

Lauf, Robert J.; Phelps, Tommy J.; Zhang, Chuanlun; Roh, Yul

2002-09-03

Methods and apparatus for producing mixed oxide nanoparticulates are disclosed. Selected thermophilic bacteria cultured with suitable reducible metals in the presence of an electron donor may be cultured under conditions that reduce at least one metal to form a doped crystal or mixed oxide composition. The bacteria will form nanoparticles outside the cell, allowing easy recovery. Selection of metals depends on the redox potentials of the reducing agents added to the culture. Typically hydrogen or glucose are used as electron donors.

Evolving effective behaviours to interact with tag-based populations

NASA Astrophysics Data System (ADS)

Yucel, Osman; Crawford, Chad; Sen, Sandip

2015-07-01

Tags and other characteristics, externally perceptible features that are consistent among groups of animals or humans, can be used by others to determine appropriate response strategies in societies. This usage of tags can be extended to artificial environments, where agents can significantly reduce cognitive effort spent on appropriate strategy choice and behaviour selection by reusing strategies for interacting with new partners based on their tags. Strategy selection mechanisms developed based on this idea have successfully evolved stable cooperation in games such as the Prisoner's Dilemma game but relies upon payoff sharing and matching methods that limit the applicability of the tag framework. Our goal is to develop a general classification and behaviour selection approach based on the tag framework. We propose and evaluate alternative tag matching and adaptation schemes for a new, incoming individual to select appropriate behaviour against any population member of an existing, stable society. Our proposed approach allows agents to evolve both the optimal tag for the environment as well as appropriate strategies for existing agent groups. We show that these mechanisms will allow for robust selection of optimal strategies by agents entering a stable society and analyse the various environments where this approach is effective.

Non-dopaminergic treatments for motor control in Parkinson's disease.

PubMed

Fox, Susan H

2013-09-01

The pathological processes underlying Parkinson's disease (PD) involve more than dopamine cell loss within the midbrain. These non-dopaminergic neurotransmitters include noradrenergic, serotonergic, glutamatergic, and cholinergic systems within cortical, brainstem and basal ganglia regions. Several non-dopaminergic treatments are now in clinical use to treat motor symptoms of PD, or are being evaluated as potential therapies. Agents for symptomatic monotherapy and as adjunct to dopaminergic therapies for motor symptoms include adenosine A2A antagonists and the mixed monoamine-B inhibitor (MAO-BI) and glutamate release agent safinamide. The largest area of potential use for non-dopaminergic drugs is as add-on therapy for motor fluctuations. Thus adenosine A2A antagonists, safinamide, and the antiepileptic agent zonisamide can extend the duration of action of levodopa. To reduce levodopa-induced dyskinesia, drugs that target overactive glutamatergic neurotransmission can be used, and include the non-selective N-methyl D-aspartate antagonist amantadine. More recently, selective metabotropic glutamate receptor (mGluR₅) antagonists are being evaluated in phase II randomized controlled trials. Serotonergic agents acting as 5-HT2A/2C antagonists, such as the atypical antipsychotic clozapine, may also reduce dyskinesia. 5-HT1A agonists theoretically can reduce dyskinesia, but in practice, may also worsen PD motor symptoms, and so clinical applicability has not yet been shown. Noradrenergic α2A antagonism using fipamezole can potentially reduce dyskinesia. Several non-dopaminergic agents have also been investigated to reduce non-levodopa-responsive motor symptoms such as gait and tremor. Thus the cholinesterase inhibitor donepezil showed mild benefit in gait, while the predominantly noradrenergic re-uptake inhibitor methylphenidate had conflicting results in advanced PD subjects. Tremor in PD may respond to muscarinic M4 cholinergic antagonists (anticholinergics), but tolerability is often poor. Alternatives include β-adrenergic antagonists such as propranolol. Other options include 5-HT2A antagonists, and drugs that have mixed binding properties involving serotonin and acetylcholine, such as clozapine and the antidepressant mirtazapine, can be effective in reducing PD tremor. Many other non-dopaminergic agents are in preclinical and phase I/II early stages of study, and the reader is directed to recent reviews. While levodopa remains the most effective agent to treat motor symptoms in PD, the overall approach to using non-dopaminergic drugs in PD is to reduce reliance on levodopa and to target non-levodopa-responsive symptoms.

Effect and removal mechanisms of 6 different washing agents for building wastes containing chromium.

PubMed

Xing-run, Wang; Yan-xia, Zhang; Qi, Wang; Jian-min, Shu

2012-01-01

With the building wastes contaminated by chromium in Haibei Chemical Plan in China as objects, we studied the contents of total Cr and Cr (VI) of different sizes, analyzed the effect of 6 different washing agents, discussed the removal mechanisms of 6 different washing agents for Cr in various forms, and finally selected applicable washing agent. As per the results, particle size had little impact on the contents of total Cr and Cr (VI); after one washing with water, the removal rate of total Cr and Cr (VI) was 75% and 78%, respectively, and after the second washing with 6 agents, the removal rate of citric acid was the highest, above 90% for total Cr and above 99% for hexavalent chromium; the pH of building wastes were reduced by citric acid, and under acid condition, hexavalent chromium was reduced to trivalent chromium spontaneously by organic acid, which led to better removal rate of acid soluble Cr and reducible Cr; due to the complexing action, citric acid had best removal rate for oxidizable trivalent chromium. In conclusion, citric acid is the most applicable second washing agent for building wastes.

Method for selectively reducing plutonium values by a photochemical process

DOEpatents

Friedman, Horace A.; Toth, Louis M.; Bell, Jimmy T.

1978-01-01

The rate of reduction of Pu(IV) to Pu(III) in nitric acid solution containing a reducing agent is enhanced by exposing the solution to 200-500 nm electromagnetic radiation. Pu values are recovered from an organic extractant solution containing Pu(IV) values and U(VI) values by the method of contacting the extractant solution with an aqueous nitric acid solution in the presence of a reducing agent and exposing the aqueous solution to electromagnetic radiation having a wavelength of 200-500 nm. Under these conditions, Pu values preferentially distribute to the aqueous phase and U values preferentially distribute to the organic phase.

Method and reaction pathway for selectively oxidizing organic compounds

DOEpatents

Camaioni, Donald M.; Lilga, Michael A.

1998-01-01

A method of selectively oxidizing an organic compound in a single vessel comprises: a) combining an organic compound, an acid solution in which the organic compound is soluble, a compound containing two oxygen atoms bonded to one another, and a metal ion reducing agent capable of reducing one of such oxygen atoms, and thereby forming a mixture; b) reducing the compound containing the two oxygen atoms by reducing one of such oxygen atoms with the metal ion reducing agent to, 1) oxidize the metal ion reducing agent to a higher valence state, and 2) produce an oxygen containing intermediate capable of oxidizing the organic compound; c) reacting the oxygen containing intermediate with the organic compound to oxidize the organic compound into an oxidized organic intermediate, the oxidized organic intermediate having an oxidized carbon atom; d) reacting the oxidized organic intermediate with the acid counter ion and higher valence state metal ion to bond the acid counter ion to the oxidized carbon atom and thereby produce a quantity of an ester incorporating the organic intermediate and acid counter ion; and e) reacting the oxidized organic intermediate with the higher valence state metal ion and water to produce a quantity of alcohol which is less than the quantity of ester, the acid counter ion incorporated in the ester rendering the carbon atom bonded to the counter ion less reactive with the oxygen containing intermediate in the mixture than is the alcohol with the oxygen containing intermediate.

Genetic Modification of Oncolytic Newcastle Disease Virus for Cancer Therapy.

PubMed

Cheng, Xing; Wang, Weijia; Xu, Qi; Harper, James; Carroll, Danielle; Galinski, Mark S; Suzich, JoAnn; Jin, Hong

2016-06-01

Clinical development of a mesogenic strain of Newcastle disease virus (NDV) as an oncolytic agent for cancer therapy has been hampered by its select agent status due to its pathogenicity in avian species. Using reverse genetics, we have generated a lead candidate oncolytic NDV based on the mesogenic NDV-73T strain that is no longer classified as a select agent for clinical development. This recombinant NDV has a modification at the fusion protein (F) cleavage site to reduce the efficiency of F protein cleavage and an insertion of a 198-nucleotide sequence into the HN-L intergenic region, resulting in reduced viral gene expression and replication in avian cells but not in mammalian cells. In mammalian cells, except for viral polymerase (L) gene expression, viral gene expression is not negatively impacted or increased by the HN-L intergenic insertion. Furthermore, the virus can be engineered to express a foreign gene while still retaining the ability to grow to high titers in cell culture. The recombinant NDV selectively replicates in and kills tumor cells and is able to drive potent tumor growth inhibition following intratumoral or intravenous administration in a mouse tumor model. The candidate is well positioned for clinical development as an oncolytic virus. Avian paramyxovirus type 1, NDV, has been an attractive oncolytic agent for cancer virotherapy. However, this virus can cause epidemic disease in poultry, and concerns about the potential environmental and economic impact of an NDV outbreak have precluded its clinical development. Here we describe generation and characterization of a highly potent oncolytic NDV variant that is unlikely to cause Newcastle disease in its avian host, representing an essential step toward moving NDV forward as an oncolytic agent. Several attenuation mechanisms have been genetically engineered into the recombinant NDV that reduce chicken pathogenicity to a level that is acceptable worldwide without impacting viral production in cell culture. The selective tumor replication of this recombinant NDV, both in vitro and in vivo, along with efficient tumor cell killing makes it an attractive oncolytic virus candidate that may provide clinical benefit to patients. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

77 FR 497 - Control of Emissions From New Nonroad Compression-Ignition Engines: Approval of New Scheduled...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-05

... replenishment of the nitrogen-containing reducing agent for selective catalytic reduction (SCR) technologies... NO X reduction requirements for their diesel engines. SCR systems use a nitrogen-containing reducing... balance between the dictates of operating nonroad equipment (which requires DEF tanks of small enough...

Monochloramine Inactivation of Bacterial Select Agents▿

PubMed Central

Rose, Laura J.; Rice, Eugene W.; Hodges, Lisa; Peterson, Alicia; Arduino, Matthew J.

2007-01-01

Seven species of bacterial select agents were tested for susceptibility to monochloramine. Under test conditions, the monochloramine routinely maintained in potable water would reduce six of the species by 2 orders of magnitude within 4.2 h. Bacillus anthracis spores would require up to 3.5 days for the same inactivation with monochloramine. PMID:17400782

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

PubMed Central

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

2015-01-01

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

Selective catalytic reduction system and process using a pre-sulfated zirconia binder

DOEpatents

Sobolevskiy, Anatoly; Rossin, Joseph A.

2010-06-29

A selective catalytic reduction (SCR) process with a palladium catalyst for reducing NOx in a gas, using hydrogen as a reducing agent is provided. The process comprises contacting the gas stream with a catalyst system, the catalyst system comprising (ZrO.sub.2)SO.sub.4, palladium, and a pre-sulfated zirconia binder. The inclusion of a pre-sulfated zirconia binder substantially increases the durability of a Pd-based SCR catalyst system. A system for implementing the disclosed process is further provided.

Investigational opioid antagonists for treating opioid-induced bowel dysfunction.

PubMed

Mozaffari, Shilan; Nikfar, Shekoufeh; Abdollahi, Mohammad

2018-03-01

Opioids have been highlighted for their role in pain relief among cancer and non-cancer patients. Novel agents have been investigated to reduce opioid-induced constipation (OIC) as the main adverse effect that may lead to treatment discontinuation. Development of peripherally acting mu-opioid receptor antagonists (PAMORA) has resulted in a novel approach to preserve the efficacy of pain control along with less OIC. Areas covered: Clinical evidence for investigational PAMORAs was reviewed and clinical trials on investigational agents to reduce OIC were included. TD-1211 is currently being evaluated in Phase II clinical trial. Oxycodone-naltrexone and ADL-5945 went through Phase III clinical trials, but have been discontinued. Expert opinion: There is a substantial need to develop agents with specific pharmacokinetic properties to meet the needs of patients with underlying diseases. Holding the efficacy of a medicine with the highest selectivity on targeted receptors and the least adverse effects is the main approach in upcoming investigations to improve patients' quality of life (QoL). Novel agents to reduce opioid-induced bowel dysfunction (OIBD) that do not reverse peripherally mediated pain analgesia are of great interest. Direct comparison of available agents in this field is lacking in the literature.

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.

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

Tertiary nitrogen heterocyclic material to reduce moisture-induced damage in asphalt-aggregate mixtures

DOEpatents

Plancher, Henry; Petersen, Joseph C.

1982-01-01

Asphalt-aggregate roads crack when subjected to freezing and thawing cycles. Herein, the useful life of asphalts are substantially improved by a minor amount of a moisture damage inhibiting agent selected from compounds having a pyridine moiety, including acid salts of such compounds. A shale oil fraction may serve as the source of the improving agent and may simply be blended with conventional petroleum asphalts.

Does Environmental Knowledge Inhibit Hominin Dispersal?

PubMed

Wren, Colin D; Costopoulos, Andre

2015-07-01

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

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

PubMed

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

2013-02-01

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

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

PubMed Central

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

2013-01-01

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

Selective functionalization of the mesopores of SBA-15

DOE PAGES

Webb, Jonathan D.; Seki, Tomohiro; Goldston, Jennifer F.; ...

2014-10-23

In this study, a method has been developed that permits the highly selective functionalization of the interior and exterior surfaces of the ubiquitous mesoporous material, SBA-15. The key step is reloading the as-synthesized material with structure-directing agent, Pluronic ® P123, prior to selective functionalization of the external surface with a silylating agent. This new approach represents a significant improvement over literature procedures. Results from physisorption analyses as well as solid-state NMR permit a detailed, quantitative assessment of functionalized SBA-15. This work also provides insight into the stability of the silyl layer during extraction procedures – an issue often neglected inmore » other studies but of significant importance as decomposition of this layer could result in the introduction of new silanols and reduce the effectiveness of any selective grafting procedure.« less

Non-target effects of an introduced biological control agent on deer mouse ecology.

PubMed

Pearson, D E; McKelvey, K S; Ruggiero, L F

2000-01-01

Release of exotic insects as biological control agents is a common approach to controlling exotic plants. Though controversy has ensued regarding the deleterious direct effects of biological control agents to non-target species, few have examined the indirect effects of a "well-behaved" biological control agent on native fauna. We studied a grassland in west-central Montana infested with spotted knapweed (Centaurea maculosa) to examine the effects of knapweed invasion and two gall flybiological control agents (Urophora affinis and U. quadrifasciata) on the native deer mouse (Peromyscus maniculatus). Stomach-content analysis revealed that Urophora were the primary food item in Peromyscus diets for most of the year and made up 84-86% of the winter diet. Stomach contents indicated that wild-caught mice consumed on average up to 247 Urophora larvae mouse -1 day -1 , while feeding trials revealed that deer mice could depredate nearly 5 times as many larvae under laboratory conditions. In feeding trials, deer mice selected knapweed seedheads with greater numbers of galls while avoiding uninfested seedheads. When Urophora larvae were present in knapweed seedheads, deer mice selected microhabitats with moderately high (31-45% cover) and high knapweed infestation (≥46% cover). After Urophora emerged and larvae were unavailable to Peromyscus, mice reversed habitat selection to favor sites dominated by native-prairie with low knapweed infestation (0-15%). Establishment of the biological control agent, Urophora spp., has altered deer mouse diets and habitat selection by effecting changes in foraging strategies. Deer mice and other predators may reduce Urophora populations below a threshold necessary to effectively control spotted knapweed.

Niobium(V) saponite clay for the catalytic oxidative abatement of chemical warfare agents.

PubMed

Carniato, Fabio; Bisio, Chiara; Psaro, Rinaldo; Marchese, Leonardo; Guidotti, Matteo

2014-09-15

A Nb(V)-containing saponite clay was designed to selectively transform toxic organosulfur chemical warfare agents (CWAs) under extremely mild conditions into nontoxic products with reduced environmental impact. Thanks to the insertion of Nb(V) sites within the saponite framework, a bifunctional catalyst with strong oxidizing and acid properties was obtained. Remarkable activity and high selectivity were observed for the oxidative abatement of (2-chloroethyl)ethyl sulfide (CEES), a simulant of sulfur mustard, at room temperature with aqueous hydrogen peroxide. This performance was significantly better compared to a conventional commercial decontamination powder. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Decolonization in Prevention of Health Care-Associated Infections

PubMed Central

Schweizer, Marin L.

2016-01-01

SUMMARY Colonization with health care-associated pathogens such as Staphylococcus aureus, enterococci, Gram-negative organisms, and Clostridium difficile is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on S. aureus decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for S. aureus nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin-containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as Candida. Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram-negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections. PMID:26817630

Effect of reducing agents on low-temperature synthesis of nanostructured LiFePO4

NASA Astrophysics Data System (ADS)

Kulka, Andrzej; Walczak, Katarzyna; Zając, Wojciech; Molenda, Janina

2017-09-01

Simple co-precipitation synthesis procedure yielding nanometric LiFePO4 with enhanced electrochemical properties without any post-synthesis heat treatment is presented. XRD, SEM and TEM analysis of the obtained powders revealed platelet crystallites and well crystalized bulk structure. Effective way of decreasing amount of Fe3+ containing phases by addition of reducing agents (KI, (NH4)2S2O3, glucose and the atmosphere of 5%H2-95%Ar) during low-temperature (107 °C) synthesis is described. The traditional analytical chemistry methods or the Mӧssbauer spectroscopy methods revealed that utilization of selected reducing agents diminished Fe3+ concentration from 25 to 12 at%. The constructed cells with optimized LiFePO4 as a cathode material showed superior electrochemical performances, including high reversible capacity up to 162 mAh/g at C/10 current discharge rate, flat voltage plateau with a value close to 3.45 V vs. Li0/+.

Application of insoluble fibers in the fining of wine phenolics.

PubMed

Guerrero, Raúl F; Smith, Paul; Bindon, Keren A

2013-05-08

The application of animal-derived proteins as wine fining agents has been subject to increased regulation in recent years. As an alternative to protein-based fining agents, insoluble plant-derived fibers have the capacity to adsorb red wine tannins. Changes in red wine tannin were analyzed following application of fibers derived from apple and grape and protein-based fining agents. Other changes in wine composition, namely, color, monomeric phenolics, metals, and turbidity, were also determined. Wine tannin was maximally reduced by application of an apple pomace fiber and a grape pomace fiber (G4), removing 42 and 38%, respectively. Potassium caseinate maximally removed 19% of wine tannin, although applied at a lower dose. Fibers reduced anthocyanins, total phenolics, and wine color density, but changes in wine hue were minor. Proteins and apple fiber selectively removed high molecular mass phenolics, whereas grape fibers removed those of both high and low molecular mass. The results show that insoluble fibers may be considered as alternative fining agents for red wines.

42 CFR 73.11 - Security.

Code of Federal Regulations, 2010 CFR

2010-10-01

... select agent or toxin against unauthorized access, theft, loss, or release. (b) The security plan must be... activities, loss or theft of select agents or toxins, release of select agents or toxins, or alteration of... of select agents or toxins, (iv) Any release of a select agent or toxin, and (v) Any sign that...

9 CFR 121.11 - Security.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the select agent or toxin against unauthorized access, theft, loss, or release. (b) The security plan... activities, loss or theft of select agents or toxins, release of select agents or toxins, or alteration of... of select agents or toxins; (iv) Any release of a select agent or toxin; and (v) Any sign that...

Frequency-Agile LIDAR Receiver for Chemical and Biological Agent Sensing

DTIC Science & Technology

2010-06-01

transimpedance preamplifier architecture was optimized around the selected IR detector diode – Input-referenced noise density of 0.8 nV/ Hz0.5  A portion of...objectives: • Reduce baseline (background) photon flux on detector : Tunable Fabry-Perot etalon in optical train • Reduce input-referenced amplifier noise ...custom amplifier • Reduce detector dark current: High impedance detector  Performance Metrics: – Noise equivalent power of receiver system (NEP

Role of ivabradine and heart rate lowering in chronic heart failure: guideline update.

PubMed

Chow, Sheryl L; Page, Robert Lee; Depre, Christophe

2018-06-14

This review summarizes the current management of heart failure (HF) in patients with reduced ejection fraction and the potential role of heart rate lowering agents in select populations, as recommended in the updated guidelines. Areas covered: PubMed was searched for studies that evaluated the role of heart rate lowering or ivabradine in HF management. Expert commentary: Targeting heart rate may offer benefit when added to renin-angiotensin aldosterone antagonists, and beta-blockers. Ivabradine is a heart rate lowering agent that acts on the funny current (I f ) in the sinoatrial node, thereby reducing heart rate without directly affecting cardiac contraction and relaxation. Clinical data from a phase 3 trial demonstrated that ivabradine reduced the composite endpoint of cardiovascular death or hospital admission for worsening systolic HF, while maintaining an acceptable safety profile in patients receiving standard of care therapy. These data, in addition to more recently published guidelines, suggest ivabradine as a promising new treatment option for lowering heart rate after optimizing standard therapy in select patients with chronic HF.

Differential mobility spectroscopy for chemical agent detection

NASA Astrophysics Data System (ADS)

Griffin, M. Todd

2006-05-01

General Dynamics ATP (GDATP) and Sionex Corporation (Sionex) are carrying out a cooperative development for a handheld chemical agent detector, being called JUNO TM, which will have lower false positives, higher sensitivity, and improved interference rejection compared with presently available detectors. This enhanced performance is made possible by the use of a new principle of ion separation called Differential Mobility Spectrometry (DMS). The enhanced selectivity is provided by the field tunable nature of the Sionex differential mobility technology (microDMxTM) which forms the analytical heart of the JUNO system and enables fingerprinting of molecules by characterization of the ionized molecular behavior under multiple electric field conditions. This enhanced selectivity is valuable in addressing not only the traditional list of chemical warfare agents (CWA) but also the substantial list of Toxic Industrial Compounds (TICs) and Toxic Industrial Materials (TIMs) which may be released in warfare or terrorist situations. Experimental results showing the ability of the microDMx to reject interferences, detect and resolve live agents are presented. An additional breakthrough in the technology was realized by operating the device at a reduced pressure of around 0.5 atmospheres. This reduced pressure operation resulted in roughly doubling the spectrometers resolution over what has previously been reported [1]. Advances have also been made in power consumption and packaging leading to a device suitable for portable, handheld, applications. Experimental results illustrating the performance of the microDMx technology employed in JUNO are highlighted.

76 FR 62412 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... for Registration, (2) Request to Transfer Select Agent or Toxin, (3) Report of Theft, Loss, or Release..., or Release of Select Agent and Toxin, (4) Report of Identification of Select Agent or Toxin. There... Release of Select Agent or Toxin; (4) Report of Identification of Select Agent or Toxin; and (5) Request...

Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery.

PubMed

Erstad, B L

2001-09-01

To review the use of systemic hemostatic medications for reducing bleeding and transfusion requirements with cardiac surgery. Articles were obtained through computerized searches involving MEDLINE (from 1966 to September 2000). Additionally, several textbooks containing information on the diagnosis and management of bleeding associated with cardiac surgery were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. Due to the large number of randomized investigations involving systemic hemostatic medications for reducing bleeding associated with cardiac surgery, the article selection process focused on recent randomized controlled trials, metaanalyses and pharmacoeconomic evaluations. The primary outcomes extracted from the literature were blood loss and associated transfusion requirements, although other outcome measures such as mortality were extracted when available. Although the majority of investigations for reducing cardiac bleeding and transfusion requirements have involved aprotinin, evidence from recent meta-analyses and randomized trials indicates that the synthetic antifibrinolytic agents, aminocaproic acid and tranexamic acid, have similar clinical efficacy. Additionally, aminocaproic acid (and to a lesser extent tranexamic acid) is much less costly. More comparative information of hemostatic agents is needed retative to other outcomes (eg., reoperation rates, myocardial infarction, stroke). There is insufficient evidence to recommend the use of desmopressin for reducing bleeding and transfusion requirements in cardiac surgery, although certain subsets of patients may benefit from its use. Of the medications that have been used to reduce bleeding and transfusion requirements with cardiac surgery, the antifibrinolytic agents have the best evidence supporting their use. Aminocaproic acid is the least costly therapy based on medication costs and transfusion requirements.

In vitro Comparative Evaluation of Tensile Bond Strength of 6(th), 7(th) and 8(th) Generation Dentin Bonding Agents.

PubMed

Kamble, Suresh S; Kandasamy, Baburajan; Thillaigovindan, Ranjani; Goyal, Nitin Kumar; Talukdar, Pratim; Seal, Mukut

2015-05-01

Newer dentin bonding agents were developed to improve the quality of composite restoration and to reduce time consumption in its application. The aim of the present study was to evaluate tensile bond strength of 6(th), 7(th) and 8(th) generation bonding agents by in vitro method. Selected 60 permanent teeth were assigned into 20 in each group (Group I: 6(th) generation bonding agent-Adper SE plus 3M ESPE, Group II: 7(th) generation bonding agent-G-Bond GC Corp Japan and Group III: 8(th) generation dentin adhesives-FuturaBond, DC, Voco, Germany). With high-speed diamond disc, coronal dentin was exposed, and selected dentin bonding agents were applied, followed by composite restoration. All samples were saved in saline for 24 h and tensile bond strength testing was done using a universal testing machine. The obtained data were tabulated and statistically analyzed using ANOVA test. The tensile bond strength readings for 6(th) generation bonding agent was 32.2465, for 7(th) generation was 31.6734, and for 8(th)-generation dentine bonding agent was 34.74431. The highest tensile bond strength was seen in 8(th) generation bonding agent compared to 6(th) and 7(th) generation bonding agents. From the present study it can be conclude that 8(th) generation dentine adhesive (Futura DC, Voco, Germany) resulted in highest tensile bond strength compared to 6(th) (Adper SE plus, 3M ESPE) and 7(th) generation (G-Bond) dentin bonding agents.

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

... select agent or toxin to APHIS or CDC. (i) The seizure of any of the following overlap select agents and.... This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after seizure of the overlap select agent or toxin. (ii) For all other overlap select agents or toxins, APHIS/CDC Form...

Characterization of effectors from Fusarium graminearum

USDA-ARS?s Scientific Manuscript database

Fusarium graminearum is the causal agent of Fusarium head blight (FHB), which reduces crop yield and quality by producing various mycotoxins. Effectors play an important role in the pathogenesis of many bacterial and fungal pathogens. In this study, 26 effector candidates were selected for investiga...

Changing perspectives of stress gastritis prophylaxis.

PubMed

Smythe, M A; Zarowitz, B J

1994-09-01

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

[Evaluation on a fast weight reduction model in vitro].

PubMed

Li, Songtao; Li, Ying; Wen, Ying; Sun, Changhao

2010-03-01

To establish a fast and effective model in vitro for screening weight-reducing drugs and taking preliminary evaluation of the model. Mature adipocytes of SD rat induced by oleic acid were used to establish a obesity model in vitro. Isoprel, genistein, caffeine were selected as positive agents and curcumine as negative agent to evaluate the obesity model. Lipolysis of adipocytes was stimulated significantly by isoprel, genistein and caffeine rather than curcumine. This model could be used efficiently for screening weight-losing drugs.

77 FR 71702 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

... of Select Agents and Toxins; Biennial Review AGENCY: Centers for Disease Control and Prevention (CDC... designated certain select agents and toxins as Tier 1 agents. DATES: Effective Date: Effective December 4, 2012. FOR FURTHER INFORMATION CONTACT: Robbin Weyant, Director, Division of Select Agents and Toxins...

In vivo detection of cucurbit[6]uril, a hyperpolarized xenon contrast agent for a xenon magnetic resonance imaging biosensor

PubMed Central

Hane, Francis T.; Li, Tao; Smylie, Peter; Pellizzari, Raiili M.; Plata, Jennifer A.; DeBoef, Brenton; Albert, Mitchell S.

2017-01-01

The Hyperpolarized gas Chemical Exchange Saturation Transfer (HyperCEST) Magnetic Resonance (MR) technique has the potential to increase the sensitivity of a hyperpolarized xenon-129 MRI contrast agent. Signal enhancement is accomplished by selectively depolarizing the xenon within a cage molecule which, upon exchange, reduces the signal in the dissolved phase pool. Herein we demonstrate the in vivo detection of the cucurbit[6]uril (CB6) contrast agent within the vasculature of a living rat. Our work may be used as a stepping stone towards using the HyperCEST technique as a molecular imaging modality. PMID:28106110

Reactive Oxygen Species (ROS) Inducible DNA Cross-Linking Agents and Their Effect on Cancer Cells and Normal Lymphocytes

PubMed Central

2015-01-01

Reducing host toxicity is one of the main challenges of cancer chemotherapy. Many tumor cells contain high levels of ROS that make them distinctively different from normal cells. We report a series of ROS-activated aromatic nitrogen mustards that selectively kill chronic lymphocytic leukemia (CLL) over normal lymphocytes. These agents showed powerful DNA cross-linking abilities when coupled with H2O2, one of the most common ROS in cancer cells, whereas little DNA cross-linking was detected without H2O2. Consistent with chemistry observation, in vitro cytotoxicity assay demonstrated that these agents induced 40–80% apoptosis in primary leukemic lymphocytes isolated from CLL patients but less than 25% cell death to normal lymphocytes from healthy donors. The IC50 for the most potent compound (2) was ∼5 μM in CLL cells, while the IC50 was not achieved in normal lymphocytes. Collectively, these data provide utility and selectivity of these agents that will inspire further and effective applications. PMID:24801734

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

NASA Technical Reports Server (NTRS)

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

2004-01-01

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

Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma

PubMed Central

Sareddy, Gangadhara R.; Li, Xiaonan; Liu, Jinyou; Viswanadhapalli, Suryavathi; Garcia, Lauren; Gruslova, Aleksandra; Cavazos, David; Garcia, Mike; Strom, Anders M.; Gustafsson, Jan-Ake; Tekmal, Rajeshwar Rao; Brenner, Andrew; Vadlamudi, Ratna K.

2016-01-01

Glioblastomas (GBM), deadly brain tumors, have greater incidence in males than females. Epidemiological evidence supports a tumor suppressive role of estrogen; however, estrogen as a potential therapy for GBM is limited due to safety concerns. Since GBM express ERβ, a second receptor for estrogen, targeting ERβ with a selective agonist may be a potential novel GBM therapy. In the present study, we examined the therapeutic effect of the selective synthetic ERβ agonist LY500307 using in vitro and in vivo GBM models. Treatment with LY500307 significantly reduced the proliferation of GBM cells with no activity on normal astrocytes in vitro. ERβ agonists promoted apoptosis of GBM cells, and mechanistic studies using RNA sequencing revealed that LY500307 modulated several pathways related to apoptosis, cell cycle, and DNA damage response. Further, LY500307 sensitized GBM cells to several FDA-approved chemotherapeutic drugs including cisplatin, lomustine and temozolomide. LY500307 treatment significantly reduced the in vivo tumor growth and promoted apoptosis of GBM tumors in an orthotopic model and improved the overall survival of tumor-bearing mice in the GL26 syngeneic glioma model. Our results demonstrate that LY500307 has potential as a therapeutic agent for GBM. PMID:27126081

Chemiluminescence evidence supporting the selective role of ligands in the permanganate oxidation of micropollutants.

PubMed

Roderick, Mark S; Adcock, Jacqui L; Terry, Jessica M; Smith, Zoe M; Parry, Samuel; Linton, Stuart M; Thornton, Megan T; Barrow, Colin J; Francis, Paul S

2013-10-10

The selective increase in the oxidation rate of certain organic compounds with permanganate in the presence of environmental "ligands" and reduced species has been ascribed to the different reactivity of the target compounds toward Mn(III), which bears striking similarities to recent independent investigations into the use of permanganate as a chemiluminescence reagent. In spite of the importance of Mn(III) in the light-producing pathway, the dependence of the oxidation mechanism for any given compound on this intermediate could not be determined solely through the emission intensity. However, target compounds susceptible to single-electron oxidation by Mn(III) (such as bisphenol A and triclosan) can be easily distinguished by the dramatic increase in chemiluminescence intensity when a permanganate reagent containing high, stable concentrations of Mn(III) is used. The differences are accentuated under the low pH conditions that favor the chemiluminescence emission due to the greater reactivity of Mn(III) and the greater influence of complexing agents. This study supports the previously postulated selective role of ligands and reducing agents in permanganate oxidations and demonstrates a new approach to explore the chemistry of environmental manganese redox processes.

Genomic selection exploits within-family genetic variation for disease resistance in rainbow trout

USDA-ARS?s Scientific Manuscript database

Flavobacterium psychrophilum is the etiological agent causing bacterial cold water disease (BCWD) in salmonid fish. Previous breeding strategies to reduce losses due to BCWD involve testing and determining phenotypic differences between multiple families of rainbow trout. These results were used to ...

Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine clinical isolates of Mannheimia haemolytica.

PubMed

Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J J; Hesje, C E

2012-11-09

Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin. Copyright © 2012 Elsevier B.V. All rights reserved.

Selection and Transmission of Antibiotic-Resistant Bacteria.

PubMed

Andersson, Dan I; Hughes, Diarmaid

2017-07-01

Ever since antibiotics were introduced into human and veterinary medicine to treat and prevent bacterial infections there has been a steady selection and increase in the frequency of antibiotic resistant bacteria. To be able to reduce the rate of resistance evolution, we need to understand how various biotic and abiotic factors interact to drive the complex processes of resistance emergence and transmission. We describe several of the fundamental factors that underlay resistance evolution, including rates and niches of emergence and persistence of resistant bacteria, time- and space-gradients of various selective agents, and rates and routes of transmission of resistant bacteria between humans, animals and other environments. Furthermore, we discuss the options available to reduce the rate of resistance evolution and/ or transmission and their advantages and disadvantages.

Decolonization in Prevention of Health Care-Associated Infections.

PubMed

Septimus, Edward J; Schweizer, Marin L

2016-04-01

Colonization with health care-associated pathogens such as Staphylococcus aureus, enterococci, Gram-negative organisms, and Clostridium difficile is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on S. aureus decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for S. aureus nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin-containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as Candida. Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram-negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Compaction agent clarification of microbial lysates

NASA Technical Reports Server (NTRS)

DeWalt, Brad W.; Murphy, Jason C.; Fox, George E.; Willson, Richard C.

2003-01-01

Recombinant proteins are often purified from microbial lysates containing high concentrations of nucleic acids. Pre-purification steps such as nuclease addition or precipitation with polyethyleneimine or ammonium sulfate are normally required to reduce viscosity and to eliminate competing polyanions before anion exchange chromatography. We report that small polycationic compaction agents such as spermine selectively precipitate nucleic acids during or after Escherichia coli lysis, allowing DNA and RNA to be pelleted with the insoluble cell debris. Analysis by spectrophotometry and protein assay confirmed a significant reduction in the concentration of nucleic acids present, with preservation of protein. Lysate viscosity is greatly reduced, facilitating subsequent processing. We have used 5mM spermine to remove nucleic acids from E. coli lysate in the purification of a hexahistidine-tagged HIV reverse transcriptase.

76 FR 30092 - Notice of Request for Extension of Approval of an Information Collection; Select Agent Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

...] Notice of Request for Extension of Approval of an Information Collection; Select Agent Registration... . FOR FURTHER INFORMATION CONTACT: For information regarding the select agent registration process... Dr. Charles Divan, Branch Chief, Agriculture Select Agent Program, RIPPS, PPQ, APHIS, 4700 River Road...

75 FR 23223 - Multi-Agency Informational Meeting Concerning Compliance With the Federal Select Agent Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

...] Multi-Agency Informational Meeting Concerning Compliance With the Federal Select Agent Program; Public... Select Agent Program established under the Public Health Security and Bioterrorism Preparedness and... Roberson, Veterinary Permit Examiner, APHIS Select Agent Program, VS, ASAP, APHIS, 4700 River Road Unit 2...

76 FR 14896 - Multi-Agency Informational Meeting Concerning Compliance With the Federal Select Agent Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

...] Multi-Agency Informational Meeting Concerning Compliance With the Federal Select Agent Program; Public... specific regulatory guidance related to the Federal Select Agent Program established under the Public.... Sarah Kwiatkowski, Veterinary Program Assistant, APHIS Select Agent Program, APHIS, 4700 River Road Unit...

76 FR 17617 - Multi-Agency Informational Meeting Concerning Compliance With the Federal Select Agent Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

...] Multi-Agency Informational Meeting Concerning Compliance With the Federal Select Agent Program; Public... specific regulatory guidance related to the Federal Select Agent Program established under the Public.... Sarah Kwiatkowski, Veterinary Program Assistant, APHIS Select Agent Program, APHIS, 4700 River Road Unit...

77 FR 56845 - Multi-Agency Informational Meeting Concerning Compliance With the Federal Select Agent Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-14

... Informational Meeting Concerning Compliance With the Federal Select Agent Program; Public Webcast AGENCY... with the Federal Select Agent Program. The purpose of this notice is to notify all interested parties... changes to the select agent regulations; occupational health, information and physical security; personnel...

78 FR 56234 - Multi-Agency Informational Meeting Concerning Compliance with the Select Agent Regulations...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-12

... Informational Meeting Concerning Compliance with the Select Agent Regulations; Public Webcast AGENCY: Centers... purpose of the webcast is to provide guidance related to the select agent regulations established under... Justice Information Services. Changes to Section 11(Security) of the select agent regulations including...

Growth kinetics and efficacy as parameters for ranking and selecting biocontrol agents that reduce pink rot in stored potatoes

USDA-ARS?s Scientific Manuscript database

Increased production of organic agricultural products and the relative ineffectiveness of traditional control measures support development of new biocontrol technologies for use against pink rot infections in storage. The microbiota of 84 different agricultural soils was individually transferred to...

77 FR 488 - Control of Emissions From New Highway Vehicles and Engines; Approval of New Scheduled Maintenance...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-05

... and engine manufacturers began planning to meet those requirements by optimizing engine designs for low emissions and adding high-efficiency aftertreatment systems. Manufacturers examined the use of... recirculation, and selective catalytic reduction (SCR). SCR systems use a nitrogen-containing reducing agent...

Catalytic epoxidation activity of keplerate polyoxomolybdate nanoball toward aqueous suspension of olefins under mild aerobic conditions.

PubMed

Rezaeifard, Abdolreza; Haddad, Reza; Jafarpour, Maasoumeh; Hakimi, Mohammad

2013-07-10

Catalytic efficiency of a sphere-shaped nanosized polyoxomolybdate {Mo132} in the aerobic epoxidation of olefins in water at ambient temperature and pressure in the absence of reducing agent is exploited which resulted good-to-high yields and desired selectivity.

Pharmacological management of osteogenesis

PubMed Central

Nardone, Valeria; D'Asta, Federica; Brandi, Maria Luisa

2014-01-01

Osteogenesis and bone remodeling are complex biological processes that are essential for the formation of new bone tissue and its correct functioning. When the balance between bone resorption and formation is disrupted, bone diseases and disorders such as Paget's disease, fibrous dysplasia, osteoporosis and fragility fractures may result. Recent advances in bone cell biology have revealed new specific targets for the treatment of bone loss that are based on the inhibition of bone resorption by osteoclasts or the stimulation of bone formation by osteoblasts. Bisphosphonates, antiresorptive agents that reduce bone resorption, are usually recommended as first-line therapy in women with postmenopausal osteoporosis. Numerous studies have shown that bisphosphonates are able to significantly reduce the risk of femoral and vertebral fractures. Other antiresorptive agents indicated for the treatment of osteoporosis include selective estrogen receptor modulators, such as raloxifene. Denosumab, a human monoclonal antibody, is another antiresorptive agent that has been approved in Europe and the USA. This agent blocks the RANK/RANKL/OPG system, which is responsible for osteoclastic activation, thus reducing bone resorption. Other approved agents include bone anabolic agents, such as teriparatide, a recombinant parathyroid hormone that improves bone microarchitecture and strength, and strontium ranelate, considered to be a dual-action drug that acts by both osteoclastic inhibition and osteoblastic stimulation. Currently, anti-catabolic drugs that act through the Wnt-β catenin signaling pathway, serving as Dickkopf-related protein 1 inhibitors and sclerostin antagonists, are also in development. This concise review provides an overview of the drugs most commonly used for the control of osteogenesis in bone diseases. PMID:24964310

Hypolipidemic, anti-obesity, anti-inflammatory, anti-osteoporotic, and anti-neoplastic properties of amine carboxyboranes.

PubMed Central

Hall, I H; Chen, S Y; Rajendran, K G; Sood, A; Spielvogel, B F; Shih, J

1994-01-01

The amine-carboxyborane derivatives were shown to be effective antineoplastic/cytotoxic agents with selective activity against single-cell and solid tumors derived from murine and human leukemias, lymphomas, sarcomas, and carcinomas. The agents inhibited DNA and RNA synthesis in preference to protein synthesis in L1210 lymphoid leukemia cells. Inosine-monophosphate dehydrogenase apparently is a target site of the compounds; similar effects on phosphoribosyl-pyrophosphate amido transferase, orotidine-monophosphate decarboxylase, and both nucleoside and nucleotide kinases were observed. Deoxyribonucleotide pool levels were reduced in the cells; DNA strand scission was observed with the agents. In rodents, the amine carboxyboranes were potent hypolipidemic agents, lowering both serum cholesterol and triglyceride concentrations, in addition to lowering cholesterol content of very low-density lipoprotein and low-density lipoprotein (LDL) and elevating high-density lipoprotein (HDL) cholesterol concentrations. De novo regulatory enzymes involved in lipid synthesis were also inhibited (e.g., hypocholesterolemic 3-hydroxy-3-methyl-Coenzyme A reductase, acyl-Coenzyme A cholesterol acyltransferase, and sn-glycerol-3-phosphate acyltransferase). Concurrently, the agents modulated LDL and HDL receptor binding, internalization, and degradation, so that less cholesterol was delivered to the plaques and more broken down from esters and conducted to the liver for biliary excretion. Tissue lipids in the aorta wall of the rat were reduced and fewer atherosclerotic morphologic lesions were present in quail aortas after treatment with the agents. Cholesterol resorption from the rat intestine was reduced in the presence of drug. Genetic hyperlipidemic mice demonstrated the same types of reduction after treatment with the agents. The agents would effectively lower lipids in tissue based on the inhibition of regulatory enzymes in pigs. These findings should help improve domestic meat supplies from fowl and pigs. The amine-carboxyboranes were effective anti-inflammatory agents against septic shock, induced edema, pleurisy, and chronic arthritis at 2.5 to 8 mg/kg. Lysosomal and proteolytic enzyme activities were also inhibited. More significantly, the agents were dual inhibitors of prostaglandin cyclooxygenase and 5'-lipoxygenase activities. These compounds also affected cytokine release and white cell migration. Subsequent studies showed that the amine-carboxyboranes were potent anti-osteoporotic agents reducing calcium resorption as well as increasing calcium and proline incorporation into mouse pup calvaria and rat UMR-106 collagen. PMID:7889876

76 FR 62312 - Multi-Agency Informational Meeting Concerning Compliance With the Federal Select Agent Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... Select Agent Program; Public Meeting AGENCIES: Animal and Plant Health Inspection Service, USDA. ACTION... will be held to provide specific regulatory guidance related to the Federal Select Agent Program... Select Agent Program, APHIS, 4700 River Road, Unit 2, Riverdale, MD 20737; (301) 734-5960. CDC: Dr...

Polymer-based lanthanide luminescent sensor for detection of the hydrolysis product of the nerve agent Soman in water.

PubMed

Jenkins, A L; Uy, O M; Murray, G M

1999-01-15

The techniques of molecular imprinting and sensitized lanthanide luminescence have been combined to create the basis for a sensor that can selectively measure the hydrolysis product of the nerve agent Soman in water. The sensor functions by selectively and reversibly binding the phosphonate hydrolysis product of this agent to a functionality-imprinted copolymer possessing a coordinatively bound luminescent lanthanide ion, Eu3+. Instrumental support for this device is designed to monitor the appearance of a narrow luminescence band in the 610-nm region of the Eu3+ spectrum that results when the analyte is coordinated to the copolymer. The ligand field shifted luminescence was excited using 1 mW of the 465.8-nm line of an argon ion laser and monitored via an optical fiber using a miniature spectrometer. For this configuration, the limit of detection for the hydrolysis product is 7 parts per trillion (ppt) in solution with a linear range from 10 ppt to 10 ppm. Chemical and spectroscopic selectivities have been combined to reduce the likelihood of false positive analyses. Chemically analogous organophosphorus pesticides tested against the sensor have been shown to not interfere with determination.

Sunscreening Agents

PubMed Central

Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

2013-01-01

The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

Group Cooperation without Group Selection: Modest Punishment Can Recruit Much Cooperation.

PubMed

Krasnow, Max M; Delton, Andrew W; Cosmides, Leda; Tooby, John

2015-01-01

Humans everywhere cooperate in groups to achieve benefits not attainable by individuals. Individual effort is often not automatically tied to a proportionate share of group benefits. This decoupling allows for free-riding, a strategy that (absent countermeasures) outcompetes cooperation. Empirically and formally, punishment potentially solves the evolutionary puzzle of group cooperation. Nevertheless, standard analyses appear to show that punishment alone is insufficient, because second-order free riders (those who cooperate but do not punish) can be shown to outcompete punishers. Consequently, many have concluded that other processes, such as cultural or genetic group selection, are required. Here, we present a series of agent-based simulations that show that group cooperation sustained by punishment easily evolves by individual selection when you introduce into standard models more biologically plausible assumptions about the social ecology and psychology of ancestral humans. We relax three unrealistic assumptions of past models. First, past models assume all punishers must punish every act of free riding in their group. We instead allow punishment to be probabilistic, meaning punishers can evolve to only punish some free riders some of the time. This drastically lowers the cost of punishment as group size increases. Second, most models unrealistically do not allow punishment to recruit labor; punishment merely reduces the punished agent's fitness. We instead realistically allow punished free riders to cooperate in the future to avoid punishment. Third, past models usually restrict agents to interact in a single group their entire lives. We instead introduce realistic social ecologies in which agents participate in multiple, partially overlapping groups. Because of this, punitive tendencies are more expressed and therefore more exposed to natural selection. These three moves toward greater model realism reveal that punishment and cooperation easily evolve by direct selection--even in sizeable groups.

New insights into the formation mechanism of Ag, Au and AgAu nanoparticles in aqueous alkaline media: alkoxides from alcohols, aldehydes and ketones as universal reducing agents.

PubMed

Gomes, Janaina F; Garcia, Amanda C; Ferreira, Eduardo B; Pires, Cleiton; Oliveira, Vanessa L; Tremiliosi-Filho, Germano; Gasparotto, Luiz H S

2015-09-07

In this report we present new insights into the formation mechanism of Ag, Au and AgAu nanoparticles with alcohols, aldehydes and ketones in alkaline medium at room temperature. We selected methanol, ethanol, glycerol, formaldehyde, acetaldehyde and acetone to demonstrate their capability of reducing gold and silver ions under the above-mentioned conditions. We showed that the particles are also formed with potassium tert-butoxide in the absence of hydroxides. Our results strongly suggest that alkoxides, formed from any molecule containing a hydroxyl or a functional group capable of generating them in alkaline medium, are the actual and universal reducing agent of silver and gold ions, in opposition to the currently accepted mechanisms. The universality of the reaction mechanism proposed in this work may impact on the production of noble nanoparticles with simple chemicals normally found in standard laboratories.

Effect of organic complexing agents on the interactions of Cs(+), Sr(2+) and UO(2)(2+) with silica and natural sand.

PubMed

Reinoso-Maset, Estela; Worsfold, Paul J; Keith-Roach, Miranda J

2013-05-01

Sorption processes play a key role in controlling radionuclide migration through subsurface environments and can be affected by the presence of anthropogenic organic complexing agents found at contaminated sites. The effect of these complexing agents on radionuclide-solid phase interactions is not well known. Therefore the aim of this study was to examine the processes by which EDTA, NTA and picolinate affect the sorption kinetics and equilibria of Cs(+), Sr(2+) and UO2(2+) onto natural sand. The caesium sorption rate and equilibrium were unaffected by the complexing agents. Strontium however showed greater interaction with EDTA and NTA in the presence of desorbed matrix cations than geochemical modelling predicted, with SrNTA(-) enhancing sorption and SrEDTA(2-) showing lower sorption than Sr(2+). Complexing agents reduced UO2(2+) sorption to silica and enhanced the sorption rate in the natural sand system. Elevated concentrations of picolinate reduced the sorption of Sr(2+) and increased the sorption rate of UO2(2+), demonstrating the potential importance of this complexing agent. These experiments provide a direct comparison of the sorption behaviour of Cs(+), Sr(2+) and UO2(2+)onto natural sand and an assessment of the relative effects of EDTA, NTA and picolinate on the selected elements. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antitumor Efficacy Testing in Rodents

PubMed Central

2008-01-01

The preclinical research and human clinical trials necessary for developing anticancer therapeutics are costly. One contributor to these costs is preclinical rodent efficacy studies, which, in addition to the costs associated with conducting them, often guide the selection of agents for clinical development. If inappropriate or inaccurate recommendations are made on the basis of these preclinical studies, then additional costs are incurred. In this commentary, I discuss the issues associated with preclinical rodent efficacy studies. These include the identification of proper preclinical efficacy models, the selection of appropriate experimental endpoints, and the correct statistical evaluation of the resulting data. I also describe important experimental design considerations, such as selecting the drug vehicle, optimizing the therapeutic treatment plan, properly powering the experiment by defining appropriate numbers of replicates in each treatment arm, and proper randomization. Improved preclinical selection criteria can aid in reducing unnecessary human studies, thus reducing the overall costs of anticancer drug development. PMID:18957675

Tangential Flow Filtration of Colloidal Silver Nanoparticles: A "Green" Laboratory Experiment for Chemistry and Engineering Students

ERIC Educational Resources Information Center

Dorney, Kevin M.; Baker, Joshua D.; Edwards, Michelle L.; Kanel, Sushil R.; O'Malley, Matthew; Pavel Sizemore, Ioana E.

2014-01-01

Numerous nanoparticle (NP) fabrication methodologies employ "bottom-up" syntheses, which may result in heterogeneous mixtures of NPs or may require toxic capping agents to reduce NP polydispersity. Tangential flow filtration (TFF) is an alternative "green" technique for the purification, concentration, and size-selection of…

Trimodel Mammography with Perfect Coregistration

DTIC Science & Technology

2017-02-01

background, the major confounding factor in reading mammography; the imaging characteristics suggest that this contrast mechanism would be preferable...image with enhanced edges and reduced anatomical background, the major confounding factor in reading mammography; the imaging characteristics suggest...subjects, vertebrate animals , biohazards, and/or select agents Describe significant deviations, unexpected outcomes, or changes in approved protocols

75 FR 7548 - Amendments to the Select Agents Controls in Export Control Classification Number (ECCN) 1C360 on...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

...-91434-01] RIN 0694-AE67 Amendments to the Select Agents Controls in Export Control Classification Number... controls on certain select agents identified in Export Control Classification Number (ECCN) 1C360 on the...) list of select agents and toxins. The changes made by APHIS were part of a biennial review and...

Solving "Smart City" Transport Problems by Designing Carpooling Gamification Schemes with Multi-Agent Systems: The Case of the So-Called "Mordor of Warsaw".

PubMed

Olszewski, Robert; Pałka, Piotr; Turek, Agnieszka

2018-01-06

To reduce energy consumption and improve residents' quality of life, "smart cities" should use not only modern technologies, but also the social innovations of the "Internet of Things" (IoT) era. This article attempts to solve transport problems in a smart city's office district by utilizing gamification that incentivizes the carpooling system. The goal of the devised system is to significantly reduce the number of cars, and, consequently, to alleviate traffic jams, as well as to curb pollution and energy consumption. A representative sample of the statistical population of people working in one of the biggest office hubs in Poland (the so-called "Mordor of Warsaw") was surveyed. The collected data were processed using spatial data mining methods, and the results were a set of parameters for the multi-agent system. This approach made it possible to run a series of simulations on a set of 100,000 agents and to select an effective gamification methodology that supports the carpooling process. The implementation of the proposed solutions (a "serious game" variation of urban games) would help to reduce the number of cars by several dozen percent, significantly reduce energy consumption, eliminate traffic jams, and increase the activity of the smart city residents.

Utility negotiating strategies for end-users

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

Studebaker, J.M.

This exciting new book discusses how retail electricity and natural gas consumers can learn to negotiate a concessionary rate with their utility service -- new, and post-deregulation. This includes survey resources that are available to the retail customer and negotiation processes that one should become familiar with in the electric utility industry. The contents include: Electricity -- an overview; Regulation of electricity -- now; Basic procedures for reducing electricity costs; Negotiation of electricity costs; Negotiation on electricity that is provided by marketers; The retail wheeling transaction; The retail wheeling contract process; Natural gas negotiation strategies; Regulation of natural gas utilities;more » Developing a strategy for reducing natural gas costs; Process of getting the natural gas to the customer; How to select an agent; and Negotiating with an agent.« less

An evaluation of smear layer with various desensitizing agents after tooth preparation.

PubMed

Zaimoglu, A; Aydin, A K

1992-09-01

According to hydrodynamics, any agent blocking the dentinal tubules reduces the flow of fluids and diminishes hypersensitivity. The properties of the desensitizing agents that sponsor tubular occlusion and the barrier efficiency resulting from the interaction of the smear layer with test materials were examined with the scanning electron microscope and energy-dispersive x-ray microanalysis. Selected dentinal desensitizing was accomplished with burnishing procedures, cavity varnish, calcium hydroxide, and topical fluoride. Subjective evaluations were also recorded clinically after tooth preparation. This investigation indicated that the smear layer did not protect against zinc phosphate cement, and that cavity varnish prevented the formation of the smear plugs. The smear layer and plugs were basically composed of calcium and phosphorus, the major ingredients of dentin.

Implementation of a new technology for point detection

NASA Astrophysics Data System (ADS)

Petinarides, John; Griffin, M. Todd; Miller, Ranaan A.; Nazarov, Erkinjon G.; Bashall, Anthony D.

2005-05-01

General Dynamics ATP (GDATP) and Sionex Corporation (Sionex) are carrying out a cooperative development for a handheld chemical agent detector, being called JUNO, which will have lower false positives, higher sensitivity, and improved interference rejection compared with presently available detectors. This enhanced performance is made possible by the use of a new principle of ion separation called Differential Mobility Spectrometry (DMS). The enhanced selectivity is provided by the field tunable nature of the Sionex differential mobility technology (microDMxTM) which forms the analytical heart of the JUNO system and enables fingerprinting of molecules by characterization of the ionized molecular behavior under multiple electric field conditions. This enhanced selectivity is valuable in addressing not only the traditional list of chemical warfare agents (CWA) but also the substantial list of Toxic Industrial Compounds (TICs) and Toxic Industrial Materials (TIMs) which may be released in warfare or terrorist situations. Experimental results showing the ability of the microDMx to reject interferences, detect and resolve live agents are presented. An additional breakthrough in the technology was realized by operating the device at a reduced pressure of around 0.5 atmospheres. This reduced pressure operation resulted in roughly doubling the spectrometers resolution over what has previously been reported [1]. Advances have also been made in power consumption and packaging leading to a device suitable for portable, handheld, applications. Experimental results illustrating the performance of the microDMx technology employed in JUNO are highlighted.

Role of ivabradine in management of stable angina in patients with different clinical profiles

PubMed Central

Kaski, Juan Carlos; Gloekler, Steffen; Ferrari, Roberto; Fox, Kim; Lévy, Bernard I; Komajda, Michel; Vardas, Panos; Camici, Paolo G

2018-01-01

In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the I f current, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD. PMID:29632676

Polymer-assisted deposition of films and preparation of carbon nanotube arrays using the films

DOEpatents

Luo, Hongmei; Li, Qingwen; Bauer, Eve; Burrell, Anthony Keiran; McCleskey, Thomas Mark; Jia, Quanxi

2013-07-16

Carbon nanotubes were prepared by coating a substrate with a coating solution including a suitable solvent, a soluble polymer, a metal precursor having a first metal selected from iron, nickel, cobalt, and molybdenum, and optionally a second metal selected from aluminum and magnesium, and also a binding agent that forms a complex with the first metal and a complex with the second metal. The coated substrate was exposed to a reducing atmosphere at elevated temperature, and then to a hydrocarbon in the reducing atmosphere. The result was decomposition of the polymer and formation of carbon nanotubes on the substrate. The carbon nanotubes were often in the form of an array on the substrate.

Pathogen security-help or hindrance?

PubMed

Morse, Stephen A

2014-01-01

Events over the past 15 years have resulted in the promulgation of regulations in the United States to enhance biosecurity by restricting the access to pathogens and toxins (i.e., biological select agents and toxins [BSATs]), which pose a severe threat to human being, animal, or plant health or to animal or plant products, to qualified institutions, laboratories, and scientists. These regulations also reduce biosafety concerns by imposing specific requirements on laboratories working with BSATs. Furthermore, they provide a legal framework for prosecuting someone who possesses a BSAT illegally. With the implementation of these regulations has come discussion in the scientific community about the potential of these regulations to affect the cost of doing BSAT research, hamper research and international collaborations, or whether it would stop someone with a microbiological background from isolating many of the select agents from nature.

Pathogen Security-Help or Hindrance?

PubMed Central

Morse, Stephen A.

2015-01-01

Events over the past 15 years have resulted in the promulgation of regulations in the United States to enhance biosecurity by restricting the access to pathogens and toxins (i.e., biological select agents and toxins [BSATs]), which pose a severe threat to human being, animal, or plant health or to animal or plant products, to qualified institutions, laboratories, and scientists. These regulations also reduce biosafety concerns by imposing specific requirements on laboratories working with BSATs. Furthermore, they provide a legal framework for prosecuting someone who possesses a BSAT illegally. With the implementation of these regulations has come discussion in the scientific community about the potential of these regulations to affect the cost of doing BSAT research, hamper research and international collaborations, or whether it would stop someone with a microbiological background from isolating many of the select agents from nature. PMID:25610829

76 FR 29754 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-23

... Agent or Toxin, (3) Report of Theft, Loss, or Release of Select Agent and Toxin, (4) Report of..., Use, and Transfer of Select Agents and Toxins (OMB Control No. 0920-0576)--Revision--Office of Public Health Preparedness and Response (OPHPR), Division of Select Agents and Toxins, Centers for Disease...

GC-MS and LC-MS analysis of nerve agents in body fluids: intra-laboratory verification test using spiked plasma and urine samples.

PubMed

Koller, Marianne; Becker, Christian; Thiermann, Horst; Worek, Franz

2010-05-15

The purpose of this study was to check the applicability of different analytical methods for the identification of unknown nerve agents in human body fluids. Plasma and urine samples were spiked with nerve agents (plasma) or with their metabolites (urine) or were left blank. Seven random samples (35% of all samples) were selected for the verification test. Plasma was worked up for unchanged nerve agents and for regenerated nerve agents after fluoride-induced reactivation of nerve agent-inhibited butyrylcholinesterase. Both extracts were analysed by GC-MS. Metabolites were extracted from plasma and urine, respectively, and were analysed by LC-MS. The urinary metabolites and two blank samples could be identified without further measurements, plasma metabolites and blanks were identified in six of seven samples. The analysis of unchanged nerve agent provided five agents/blanks and the sixth agent after further investigation. The determination of the regenerated agents also provided only five clear findings during the first screening because of a rather noisy baseline. Therefore, the sample preparation was extended by a size exclusion step performed before addition of fluoride which visibly reduced baseline noise and thus improved identification of the two missing agents. The test clearly showed that verification should be performed by analysing more than one biomarker to ensure identification of the agent(s). Copyright (c) 2010 Elsevier B.V. All rights reserved.

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.

Emergence of social structures via preferential selection

NASA Astrophysics Data System (ADS)

Lipowski, Adam; Lipowska, Dorota; Ferreira, Antonio Luis

2014-09-01

We examine a weighted-network multiagent model with preferential selection such that agents choose partners with probability p (w), where w is the number of their past selections. When p (w) increases sublinearly with the number of past selections [p(w)˜wα,α<1], agents develop a uniform preference for all other agents. At α =1, this state loses stability and more complex structures form. For a superlinear increase (α>1), strong heterogeneities emerge and agents make selections mainly within small and sometimes asymmetric clusters. Even in a few-agent case, the formation of such clusters resembles phase transitions with spontaneous symmetry breaking.

42 CFR 73.3 - HHS select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria are... Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses...

Deterring Online Advertising Fraud through Optimal Payment in Arrears

NASA Astrophysics Data System (ADS)

Edelman, Benjamin

Online advertisers face substantial difficulty in selecting and supervising small advertising partners: Fraud can be well-hidden, and limited reputation systems reduce accountability. But partners are not paid until after their work is complete, and advertisers can extend this delay both to improve detection of improper partner practices and to punish partners who turn out to be rule-breakers. I capture these relationships in a screening model with delayed payments and probabilistic delayed observation of agents’ types. I derive conditions in which an advertising principal can set its payment delay to deter rogue agents and to attract solely or primarily good-type agents. Through the savings from excluding rogue agents, the principal can increase its profits while offering increased payments to good-type agents. I estimate that a leading affiliate network could have invoked an optimal payment delay to eliminate 71% of fraud without decreasing profit.

Intelligent agent-based intrusion detection system using enhanced multiclass SVM.

PubMed

Ganapathy, S; Yogesh, P; Kannan, A

2012-01-01

Intrusion detection systems were used in the past along with various techniques to detect intrusions in networks effectively. However, most of these systems are able to detect the intruders only with high false alarm rate. In this paper, we propose a new intelligent agent-based intrusion detection model for mobile ad hoc networks using a combination of attribute selection, outlier detection, and enhanced multiclass SVM classification methods. For this purpose, an effective preprocessing technique is proposed that improves the detection accuracy and reduces the processing time. Moreover, two new algorithms, namely, an Intelligent Agent Weighted Distance Outlier Detection algorithm and an Intelligent Agent-based Enhanced Multiclass Support Vector Machine algorithm are proposed for detecting the intruders in a distributed database environment that uses intelligent agents for trust management and coordination in transaction processing. The experimental results of the proposed model show that this system detects anomalies with low false alarm rate and high-detection rate when tested with KDD Cup 99 data set.

Intelligent Agent-Based Intrusion Detection System Using Enhanced Multiclass SVM

PubMed Central

Ganapathy, S.; Yogesh, P.; Kannan, A.

2012-01-01

Intrusion detection systems were used in the past along with various techniques to detect intrusions in networks effectively. However, most of these systems are able to detect the intruders only with high false alarm rate. In this paper, we propose a new intelligent agent-based intrusion detection model for mobile ad hoc networks using a combination of attribute selection, outlier detection, and enhanced multiclass SVM classification methods. For this purpose, an effective preprocessing technique is proposed that improves the detection accuracy and reduces the processing time. Moreover, two new algorithms, namely, an Intelligent Agent Weighted Distance Outlier Detection algorithm and an Intelligent Agent-based Enhanced Multiclass Support Vector Machine algorithm are proposed for detecting the intruders in a distributed database environment that uses intelligent agents for trust management and coordination in transaction processing. The experimental results of the proposed model show that this system detects anomalies with low false alarm rate and high-detection rate when tested with KDD Cup 99 data set. PMID:23056036

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

PubMed Central

Tsutsumi, Lissa S.; Owusu, Yaw B.; Hurdle, Julian G.; Sun, Dianqing

2014-01-01

Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance. PMID:24236721

Selective Attention and Control of Action: Comparative Psychology of an Artificial, Evolved Agent and People

ERIC Educational Resources Information Center

Ward, Robert; Ward, Ronnie

2008-01-01

This study examined the selective attention abilities of a simple, artificial, evolved agent and considered implications of the agent's performance for theories of selective attention and action. The agent processed two targets in continuous time, catching one and then the other. This task required many cognitive operations, including prioritizing…

The Akt signaling pathway

PubMed Central

Madhunapantula, SubbaRao V; Mosca, Paul J

2011-01-01

Studies using cultured melanoma cells and patient tumor biopsies have demonstrated deregulated PI3 kinase-Akt3 pathway activity in ∼70% of melanomas. Furthermore, targeting Akt3 and downstream PRAS40 has been shown to inhibit melanoma tumor development in mice. Although these preclinical studies and several other reports using small interfering RNAs and pharmacological agents targeting key members of this pathway have been shown to retard melanoma development, analysis of early Phase I and Phase II clinical trials using pharmacological agents to target this pathway demonstrate the need for (1) selection of patients whose tumors have PI3 kinase-Akt pathway deregulation, (2) further optimization of therapeutic agents for increased potency and reduced toxicity, (3) the identification of additional targets in the same pathway or in other signaling cascades that synergistically inhibit the growth and progression of melanoma, and (4) better methods for targeted delivery of pharmaceutical agents inhibiting this pathway. In this review we discuss key potential targets in PI3K-Akt3 signaling, the status of pharmacological agents targeting these proteins, drugs under clinical development, and strategies to improve the efficacy of therapeutic agents targeting this pathway. PMID:22157148

Efficacy of Biocides Used in the Modern Food Industry To Control Salmonella enterica, and Links between Biocide Tolerance and Resistance to Clinically Relevant Antimicrobial Compounds

PubMed Central

Condell, Orla; Iversen, Carol; Cooney, Shane; Power, Karen A.; Walsh, Ciara; Burgess, Catherine

2012-01-01

Biocides play an essential role in limiting the spread of infectious disease. The food industry is dependent on these agents, and their increasing use is a matter for concern. Specifically, the emergence of bacteria demonstrating increased tolerance to biocides, coupled with the potential for the development of a phenotype of cross-resistance to clinically important antimicrobial compounds, needs to be assessed. In this study, we investigated the tolerance of a collection of susceptible and multidrug-resistant (MDR) Salmonella enterica strains to a panel of seven commercially available food-grade biocide formulations. We explored their abilities to adapt to these formulations and their active biocidal agents, i.e., triclosan, chlorhexidine, hydrogen peroxide, and benzalkonium chloride, after sequential rounds of in vitro selection. Finally, cross-tolerance of different categories of biocidal formulations, their active agents, and the potential for coselection of resistance to clinically important antibiotics were investigated. Six of seven food-grade biocide formulations were bactericidal at their recommended working concentrations. All showed a reduced activity against both surface-dried and biofilm cultures. A stable phenotype of tolerance to biocide formulations could not be selected. Upon exposure of Salmonella strains to an active biocidal compound, a high-level of tolerance was selected for a number of Salmonella serotypes. No cross-tolerance to the different biocidal agents or food-grade biocide formulations was observed. Most tolerant isolates displayed changes in their patterns of susceptibility to antimicrobial compounds. Food industry biocides are effective against planktonic Salmonella. When exposed to sublethal concentrations of individual active biocidal agents, tolerant isolates may emerge. This emergence was associated with changes in antimicrobial susceptibilities. PMID:22367085

Efficacy of biocides used in the modern food industry to control salmonella enterica, and links between biocide tolerance and resistance to clinically relevant antimicrobial compounds.

PubMed

Condell, Orla; Iversen, Carol; Cooney, Shane; Power, Karen A; Walsh, Ciara; Burgess, Catherine; Fanning, Séamus

2012-05-01

Biocides play an essential role in limiting the spread of infectious disease. The food industry is dependent on these agents, and their increasing use is a matter for concern. Specifically, the emergence of bacteria demonstrating increased tolerance to biocides, coupled with the potential for the development of a phenotype of cross-resistance to clinically important antimicrobial compounds, needs to be assessed. In this study, we investigated the tolerance of a collection of susceptible and multidrug-resistant (MDR) Salmonella enterica strains to a panel of seven commercially available food-grade biocide formulations. We explored their abilities to adapt to these formulations and their active biocidal agents, i.e., triclosan, chlorhexidine, hydrogen peroxide, and benzalkonium chloride, after sequential rounds of in vitro selection. Finally, cross-tolerance of different categories of biocidal formulations, their active agents, and the potential for coselection of resistance to clinically important antibiotics were investigated. Six of seven food-grade biocide formulations were bactericidal at their recommended working concentrations. All showed a reduced activity against both surface-dried and biofilm cultures. A stable phenotype of tolerance to biocide formulations could not be selected. Upon exposure of Salmonella strains to an active biocidal compound, a high-level of tolerance was selected for a number of Salmonella serotypes. No cross-tolerance to the different biocidal agents or food-grade biocide formulations was observed. Most tolerant isolates displayed changes in their patterns of susceptibility to antimicrobial compounds. Food industry biocides are effective against planktonic Salmonella. When exposed to sublethal concentrations of individual active biocidal agents, tolerant isolates may emerge. This emergence was associated with changes in antimicrobial susceptibilities.

Considerations in detecting CDC select agents under field conditions

NASA Astrophysics Data System (ADS)

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

2008-04-01

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

Inheritance of evolved resistance to a novel herbicide (pyroxasulfone).

PubMed

Busi, Roberto; Gaines, Todd A; Vila-Aiub, Martin M; Powles, Stephen B

2014-03-01

Agricultural weeds have rapidly adapted to intensive herbicide selection and resistance to herbicides has evolved within ecological timescales. Yet, the genetic basis of broad-spectrum generalist herbicide resistance is largely unknown. This study aims to determine the genetic control of non-target-site herbicide resistance trait(s) that rapidly evolved under recurrent selection of the novel lipid biosynthesis inhibitor pyroxasulfone in Lolium rigidum. The phenotypic segregation of pyroxasulfone resistance in parental, F1 and back-cross (BC) families was assessed in plants exposed to a gradient of pyroxasulfone doses. The inheritance of resistance to chemically dissimilar herbicides (cross-resistance) was also evaluated. Evolved resistance to the novel selective agent (pyroxasulfone) is explained by Mendelian segregation of one semi-dominant allele incrementally herbicide-selected at higher frequency in the progeny. In BC families, cross-resistance is conferred by an incompletely dominant single major locus. This study confirms that herbicide resistance can rapidly evolve to any novel selective herbicide agents by continuous and repeated herbicide use. The results imply that the combination of herbicide options (rotation, mixtures or combinations) to exploit incomplete dominance can provide acceptable control of broad-spectrum generalist resistance-endowing monogenic traits. Herbicide diversity within a set of integrated management tactics can be one important component to reduce the herbicide selection intensity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Synthesis of gold nanochains via photoactivation technique and their catalytic applications.

PubMed

Sinha, Arun Kumar; Basu, Mrinmoyee; Sarkar, Sougata; Pradhan, Mukul; Pal, Tarasankar

2013-05-15

The article reports a simple photoactivation technique for the synthesis of chain like assembly of spherical Au nanocrystals using a nontoxic biochemical, β-cyclodextrin under ~365 nm UV-light irradiation. Under UV irradiation, β-cyclodextrin acts as a reducing as well as capping agent and eventually becomes a stabilizing linker for Au nanoparticles. The UV-visible spectroscopy, transmission electron microscopy (TEM), selected area electron diffraction (SAED), X-ray diffraction (XRD), and X-ray photoelectron spectroscopic techniques are employed to systematically characterize the Au nanochains. Additionally, it is shown that the Au nanocrystals act as an effective catalyst for the reduction in nitrobenzene to aniline and methylene blue to leuco methylene blue in presence of suitable reducing agent. The catalytic reduction reactions and kinetic parameters are evaluated from UV-visible spectroscopy. Copyright © 2013 Elsevier Inc. All rights reserved.

Use of local anaesthetic agents among New Zealand plastic surgeons--their practices and philosophies.

PubMed

Porter, C J; Frizelle, F A

2000-01-01

Skin lesions are treated by a variety of medical practitioners. To describe the method and techniques of use of local anaesthetic (LA) for excision of skin lesions amongst a group of surgeons who are frequent users. An open-ended questionnaire was designed to investigate the way LA was used for local excision and reasons behind the practice. All registered Plastic and Reconstructive Surgeons in New Zealand were sent the questionnaire. This group was chosen because they are high frequency users of local anaesthetic for excision of skin lesions. Questionnaires were sent to all 28 Plastic and Reconstructive Surgeons in New Zealand of which twenty-three (82%) responded. The reasons for selection of specific products relate to convenience of product (14), speed of onset (6), effect duration (4), ease to add bicarbonate (3), others (5). Lignocaine and bupivicaine were the most popular LA agent used except when there was concern about cardiac toxicity when Prilocaine was used instead. Adrenaline was used for vasoconstriction induced haemostasis, and avoided in anatomical areas with end arteries due to the risk of tissue ischaemia. This complication was identified as medicolegally indefensible despite a lack of scientific evidence in the literature. The techniques used to reduce patient discomfort of local anaesthetic infiltration relate to patient oriented techniques (15), injection related techniques (25), LA agent related techniques (19). Details of these specific techniques are presented in detail. LA uses vary according to the specific surgical situation, patient risk factors and according to the individual surgeon. The main reason for selection of a specific LA agent relates to convenience and not pharmacokinetics. Injection related techniques are the most common method to reduce pain from LA.

Enhancement of anion-exchange chromatography of DNA using compaction agents

NASA Technical Reports Server (NTRS)

Murphy, Jason C.; Fox, George E.; Willson, Richard C.

2003-01-01

The use of adsorptive chromatography for preparative nucleic acid separations is often limited by low capacity. The possibility that the adsorbent surface area sterically accessible to nucleic acid molecules could be increased by reducing their radius of gyration with compaction agents has been investigated. The equilibrium adsorption capacity of Q Sepharose anion-exchange matrix for plasmid DNA at 600 mM NaCl was enhanced by up to ca. 40% in the presence of 2.5 mM spermine. In addition, compaction agent selectivity has been demonstrated. Spermine, for example, enhances the adsorption of both plasmid and genomic DNA, spermidine enhances binding only of plasmid, and hexamine cobalt enhances only the binding of genomic DNA. Compaction may be generally useful for enhancing adsorptive separations of nucleic acids.

Second generation antipsychotics for schizophrenia.

PubMed

Feltus, M S; Gardner, D M

1999-01-01

To provide a narrative review based on clinically relevant evidence specific to the issues surrounding the use of the second generation antipsychotics in schizophrenia. MEDLINE and Cochrane Library searches were performed to identify literature pertinent to the available and anticipated novel antipsychotics in North America. Articles that were selected included clinical trials, clinical practice guidelines, reviews and pharmacoeconomic analyses researching the efficacy and safety of the second generation antipsychotics including comparative studies among these agents. Related editorials, letters and newsletter commentaries were reviewed from a variety of sources to provide enhanced depth. Following the advent of clozapine in the 1980s, three other second generation antipsychotics (risperidone, olanzapine and quetiapine) have become available, with others (eg, ziprasidone) expected in the near future. The single major advance with these agents is their reduced propensity for extrapyramidal side effects and tardive dyskinesia. However, clinicians should be aware of the differential risk for these side effects. The purported advantage for negative symptoms compared with conventional agents has been inconsistent and may not be clinically important. The availability of a wide selection of antipsychotics has heralded the possibility of more effective management of the complex symptoms of schizophrenia. However, this has also made the choice of optimal treatment difficult. It is essential that practitioners understand how these agents compare with each other and with conventional antipsychotics.

Selective attention and control of action: comparative psychology of an artificial, evolved agent and people.

PubMed

Ward, Robert; Ward, Ronnie

2008-10-01

This study examined the selective attention abilities of a simple, artificial, evolved agent and considered implications of the agent's performance for theories of selective attention and action. The agent processed two targets in continuous time, catching one and then the other. This task required many cognitive operations, including prioritizing the first target (T1) over the second (T2); selectively focusing responses on T1, while preventing T2 from interfering with responses; creating a memory for the unselected T2 item, so that it could be efficiently processed later; and reallocating processing towards T2 after catching T1. The evolved agent demonstrated all these abilities. Analysis shows that the agent used reactive inhibition to selectively focus behavior. That is, the more salient T2, the more strongly responses towards T2 were inhibited and the slower the agent was to subsequently reallocate processing towards T2. Reactive inhibition was also suggested in two experiments with people, performing a virtually identical catch task. The presence of reactive inhibition in the simple agent and in people suggests that it is an important mechanism for selective processing.

Multi-agent Reinforcement Learning Model for Effective Action Selection

NASA Astrophysics Data System (ADS)

Youk, Sang Jo; Lee, Bong Keun

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

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

Solving “Smart City” Transport Problems by Designing Carpooling Gamification Schemes with Multi-Agent Systems: The Case of the So-Called “Mordor of Warsaw”

PubMed Central

Turek, Agnieszka

2018-01-01

To reduce energy consumption and improve residents’ quality of life, “smart cities” should use not only modern technologies, but also the social innovations of the “Internet of Things” (IoT) era. This article attempts to solve transport problems in a smart city’s office district by utilizing gamification that incentivizes the carpooling system. The goal of the devised system is to significantly reduce the number of cars, and, consequently, to alleviate traffic jams, as well as to curb pollution and energy consumption. A representative sample of the statistical population of people working in one of the biggest office hubs in Poland (the so-called “Mordor of Warsaw”) was surveyed. The collected data were processed using spatial data mining methods, and the results were a set of parameters for the multi-agent system. This approach made it possible to run a series of simulations on a set of 100,000 agents and to select an effective gamification methodology that supports the carpooling process. The implementation of the proposed solutions (a “serious game” variation of urban games) would help to reduce the number of cars by several dozen percent, significantly reduce energy consumption, eliminate traffic jams, and increase the activity of the smart city residents. PMID:29316643

76 FR 77914 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Amendments to the Select Agent and Toxin Regulations AGENCY: Animal and Plant Health Inspection Service, USDA... proposed rule that would amend and republish the list of select agents and toxins that have the potential...

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

PubMed Central

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

2014-01-01

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

Aggressive treatment of early rheumatoid arthritis: recognizing the window of opportunity and treating to target goals.

PubMed

Resman-Targoff, Beth H; Cicero, Marco P

2010-11-01

Evidence supports the use of aggressive therapy for patients with early rheumatoid arthritis (RA). Clinical outcomes in patients with early RA can improve with a treat-to-target approach that sets the goal at disease remission. The current selection of antirheumatic therapies, including conventional and biologic disease-modifying antirheumatic drugs (DMARDs), has made disease remission a realistic target for patients with early RA. The challenge is selecting the optimal antirheumatic drug or combination of drugs for initial and subsequent therapy to balance the clinical benefits, risks, and economic considerations. In some cases, the use of biologic agents as part of the treatment regimen has shown superior results compared with conventional DMARDs alone in halting the progression of disease, especially in reducing radiographic damage. However, the use of biologic agents as initial therapy is challenged by cost-effectiveness analyses, which favor the use of conventional DMARDs. The use of biologic agents may be justified in certain patients with poor prognostic factors or those who experience an inadequate response to conventional DMARDs as a means to slow or halt disease progression and its associated disability. In these cases, the higher cost of treatment with biologic agents may be offset by decreased societal costs, such as lost work productivity, and increased health-related quality of life. Further research is needed to understand optimal strategies for balancing costs, benefits, and risks of antirheumatic drugs. Some key questions are (1) when biologic agents are appropriate for initial therapy, and (2) when to conclude that response to conventional DMARDs is inadequate and biologic agents should be initiated.

Method of preparing size-selected metal clusters

DOEpatents

Elam, Jeffrey W.; Pellin, Michael J.; Stair, Peter C.

2010-05-11

The invention provides a method for depositing catalytic clusters on a surface, the method comprising confining the surface to a controlled atmosphere; contacting the surface with catalyst containing vapor for a first period of time; removing the vapor from the controlled atmosphere; and contacting the surface with a reducing agent for a second period of time so as to produce catalyst-containing nucleation sites.

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

PubMed

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

2008-01-01

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

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

PubMed

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

2008-01-01

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

The Real-Time ObjectAgent Software Architecture for Distributed Satellite Systems

DTIC Science & Technology

2001-01-01

real - time operating system selection are also discussed. The fourth section describes a simple demonstration of real-time ObjectAgent. Finally, the...experience with C++. After selecting the programming language, it was necessary to select a target real - time operating system (RTOS) and embedded...ObjectAgent software to run on the OSE Real Time Operating System . In addition, she is responsible for the integration of ObjectAgent

A feeding protocol for delivery of agents to assess development in Varroa mites

PubMed Central

2017-01-01

A novel feeding protocol for delivery of bio-active agents to Varroa mites was developed by providing mites with honey bee larva hemolymph supplemented with cultured insect cells and selected materials delivered on a fibrous cotton substrate. Mites were starved, fed on treated hemolymph to deliver selected agents and then returned to bee larvae. Transcript levels of two reference genes, actin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as well as for nine selected genes involved in reproductive processes showed that the starvation and feeding protocol periods did not pose a high level of stress to the mites as transcript levels remained comparable between phoretic mites and those completing the protocol. The feeding protocol was used to deliver molecules such as hormone analogs or plasmids. Mites fed with Tebufenozide, an ecdysone analog, had higher transcript levels of shade than untreated or solvent treated mites. In order to extend this feeding protocol, cultured insect cells were incorporated to a final ratio of 1 part cells and 2 parts hemolymph. Although supplementation with Bombyx mori Bm5 cells increased the amount of hemolymph consumed per mite, there was a significant decrease in the percentage of mites that fed and survived. On the other hand, Drosophila melanogaster S2 cells reduced significantly the percentage of mites that fed and survived as well as the amount of hemolymph consumed. The feeding protocol provides a dynamic platform with which to challenge the Varroa mite to establish efficacy of control agents for this devastating honey bee pest. PMID:28448606

Select Agent and Toxin Regulations: Beyond the Eighth Edition of the Guide for the Care and Use of Laboratory Animals

PubMed Central

Kastenmayer, Robin J; Moore, Rashida M; Bright, Allison L; Torres-Cruz, Rafael; Elkins, William R

2012-01-01

In the interval between the publication of the seventh and eighth editions of the Guide for the Care and Use of Laboratory Animals (Guide), much has changed with regard to the regulation and funding of highly pathogenic biologic agents and toxins (Select Agents). Funding of research involving highly pathogenic agents has increased dramatically during this time, thus increasing the demand for facilities capable of supporting this work. The eighth edition of the Guide briefly mentions Select Agents and provides a limited set of references. Here we provide some background information regarding the relevant laws and regulations, as well as an overview of the programmatic requirements pertaining to the use of Select Agents, with a focus on use in animals. PMID:22776191

9 CFR 121.3 - VS select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-01-01

... genetically modified. (d) VS select agents or toxins that meet any of the following criteria are excluded from... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND... recombinant organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses...

Lysosomotropic properties of weakly basic anticancer agents promote cancer cell selectivity in vitro.

PubMed

Ndolo, Rosemary A; Luan, Yepeng; Duan, Shaofeng; Forrest, M Laird; Krise, Jeffrey P

2012-01-01

Drug distribution in cells is a fundamentally important, yet often overlooked, variable in drug efficacy. Many weakly basic anticancer agents accumulate extensively in the acidic lysosomes of normal cells through ion trapping. Lysosomal trapping reduces the activity of anticancer drugs, since anticancer drug targets are often localized in the cell cytosol or nucleus. Some cancer cells have defective acidification of lysosomes, which causes a redistribution of trapped drugs from the lysosomes to the cytosol. We have previously established that such differences in drug localization between normal and cancer cells can contribute to the apparent selectivity of weakly basic drugs to cancer cells in vitro. In this work, we tested whether this intracellular distribution-based drug selectivity could be optimized based on the acid dissociation constant (pKa) of the drug, which is one of the determinants of lysosomal sequestration capacity. We synthesized seven weakly basic structural analogs of the Hsp90 inhibitor geldanamycin (GDA) with pKa values ranging from 5 to 12. The selectivity of each analog was expressed by taking ratios of anti-proliferative IC(50) values of the inhibitors in normal fibroblasts to the IC(50) values in human leukemic HL-60 cells. Similar selectivity assessments were performed in a pair of cancer cell lines that differed in lysosomal pH as a result of siRNA-mediated alteration of vacuolar proton ATPase subunit expression. Optimal selectivity was observed for analogs with pKa values near 8. Similar trends were observed with commercial anticancer agents with varying weakly basic pKa values. These evaluations advance our understanding of how weakly basic properties can be optimized to achieve maximum anticancer drug selectivity towards cancer cells with defective lysosomal acidification in vitro. Additional in vivo studies are needed to examine the utility of this approach for enhancing selectivity.

Lysosomotropic Properties of Weakly Basic Anticancer Agents Promote Cancer Cell Selectivity In Vitro

PubMed Central

Ndolo, Rosemary A.; Luan, Yepeng; Duan, Shaofeng; Forrest, M. Laird; Krise, Jeffrey P.

2012-01-01

Drug distribution in cells is a fundamentally important, yet often overlooked, variable in drug efficacy. Many weakly basic anticancer agents accumulate extensively in the acidic lysosomes of normal cells through ion trapping. Lysosomal trapping reduces the activity of anticancer drugs, since anticancer drug targets are often localized in the cell cytosol or nucleus. Some cancer cells have defective acidification of lysosomes, which causes a redistribution of trapped drugs from the lysosomes to the cytosol. We have previously established that such differences in drug localization between normal and cancer cells can contribute to the apparent selectivity of weakly basic drugs to cancer cells in vitro. In this work, we tested whether this intracellular distribution-based drug selectivity could be optimized based on the acid dissociation constant (pKa) of the drug, which is one of the determinants of lysosomal sequestration capacity. We synthesized seven weakly basic structural analogs of the Hsp90 inhibitor geldanamycin (GDA) with pKa values ranging from 5 to 12. The selectivity of each analog was expressed by taking ratios of anti-proliferative IC50 values of the inhibitors in normal fibroblasts to the IC50 values in human leukemic HL-60 cells. Similar selectivity assessments were performed in a pair of cancer cell lines that differed in lysosomal pH as a result of siRNA-mediated alteration of vacuolar proton ATPase subunit expression. Optimal selectivity was observed for analogs with pKa values near 8. Similar trends were observed with commercial anticancer agents with varying weakly basic pKa values. These evaluations advance our understanding of how weakly basic properties can be optimized to achieve maximum anticancer drug selectivity towards cancer cells with defective lysosomal acidification in vitro. Additional in vivo studies are needed to examine the utility of this approach for enhancing selectivity. PMID:23145164

42 CFR 73.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION... its naturally occurring environment provided that the select agent or toxin has not been intentionally... such agent or toxin or destroys the agent or toxin by a recognized sterilization or inactivation...

Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies.

PubMed

Dodson, Shontelle; Baracos, Vickie E; Jatoi, Aminah; Evans, William J; Cella, David; Dalton, James T; Steiner, Mitchell S

2011-01-01

Cancer cachexia is a complex metabolic condition characterized by loss of skeletal muscle. Common clinical manifestations include muscle wasting, anemia, reduced caloric intake, and altered immune function, which contribute to increased disability, fatigue, diminished quality of life, and reduced survival. The prevalence of cachexia and the impact of this disorder on the patient and family underscore the need for effective management strategies. Dietary supplementation and appetite stimulation alone are inadequate to reverse the underlying metabolic abnormalities of cancer cachexia and have limited long-term impact on patient quality of life and survival. Therapies that can increase muscle mass and physical performance may be a promising option; however, there are currently no drugs approved for the prevention or treatment of cancer cachexia. Several agents are in clinical development, including anabolic agents, such as selective androgen receptor modulators and drugs targeting inflammatory cytokines that promote skeletal muscle catabolism.

Idiopathic pulmonary fibrosis: a holistic approach to disease management in the antifibrotic age.

PubMed

Shaw, Jonathon; Marshall, Tracey; Morris, Helen; Hayton, Conal; Chaudhuri, Nazia

2017-11-01

Idiopathic pulmonary fibrosis (IPF) is the most common cause of interstitial lung disease (ILD) and carries a worse prognosis than many cancers. Until recently, there were no active treatment options available for patients with IPF, meaning palliation or lung transplantation in selected patients were the only options. The management of IPF has changed dramatically over the last decade with the advent of two antifibrotic agents; pirfenidone and nintedanib. These new agents have been shown to reduce decline in lung function and pirfenidone has been shown to reduce mortality. The changing landscape of IPF diagnosis and management present a number of issues that may be encountered including management of side effects related to antifibrotic therapy. This article aims to give an overview of the holistic approach to the management of patients with IPF, including antifibrotic management, symptom management and the invaluable role of the ILD specialist nurse.

Idiopathic pulmonary fibrosis: a holistic approach to disease management in the antifibrotic age

PubMed Central

Shaw, Jonathon; Marshall, Tracey; Morris, Helen; Chaudhuri, Nazia

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is the most common cause of interstitial lung disease (ILD) and carries a worse prognosis than many cancers. Until recently, there were no active treatment options available for patients with IPF, meaning palliation or lung transplantation in selected patients were the only options. The management of IPF has changed dramatically over the last decade with the advent of two antifibrotic agents; pirfenidone and nintedanib. These new agents have been shown to reduce decline in lung function and pirfenidone has been shown to reduce mortality. The changing landscape of IPF diagnosis and management present a number of issues that may be encountered including management of side effects related to antifibrotic therapy. This article aims to give an overview of the holistic approach to the management of patients with IPF, including antifibrotic management, symptom management and the invaluable role of the ILD specialist nurse. PMID:29268540

URANIUM PRECIPITATION PROCESS

DOEpatents

Thunaes, A.; Brown, E.A.; Smith, H.W.; Simard, R.

1957-12-01

A method for the recovery of uranium from sulfuric acid solutions is described. In the present process, sulfuric acid is added to the uranium bearing solution to bring the pH to between 1 and 1.8, preferably to about 1.4, and aluminum metal is then used as a reducing agent to convert hexavalent uranium to the tetravalent state. As the reaction proceeds, the pH rises amd a selective precipitation of uranium occurs resulting in a high grade precipitate. This process is an improvement over the process using metallic iron, in that metallic aluminum reacts less readily than metallic iron with sulfuric acid, thus avoiding consumption of the reducing agent and a raising of the pH without accomplishing the desired reduction of the hexavalent uranium in the solution. Another disadvantage to the use of iron is that positive ferric ions will precipitate with negative phosphate and arsenate ions at the pH range employed.

Water Quality Research Program: Recent Developments in the Analysis of Metals in Water, Wastewater, and Other Matrices.

DTIC Science & Technology

1987-11-01

for various types of samples and acids. The system features PFA -closed vessels that will tolerate up to 100 psi, a Teflon-lined cavity that reduces...complexes. Selec- tivity is accomplished by masking agents and pH adjustment and sorption on a small XAD-4 resin column. Evaporation of solvent 119...same pH, Cr(VI) is selectively reduced to Cr(III) and accumulated by adsorption at -0.3 V versus SCE (Batley and Matousek 1980). 150. Sorption , ion

Selective catalytic reduction system and process for treating NOx emissions using a zinc or titanium promoted palladium-zirconium catalyst

DOEpatents

Sobolevskiy, Anatoly [Orlando, FL; Rossin, Joseph A [Columbus, OH; Knapke, Michael J [Columbus, OH

2011-08-02

A process and system (18) for reducing NO.sub.x in a gas using hydrogen as a reducing agent is provided. The process comprises contacting the gas stream (29) with a catalyst system (38) comprising sulfated zirconia washcoat particles (41), palladium, a pre-sulfated zirconia binder (44), and a promoter (45) comprising at least one of titanium, zinc, or a mixture thereof. The presence of zinc or titanium increases the resistance of the catalyst system to a sulfur and water-containing gas stream.

42 CFR 73.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION... its naturally occurring environment provided that the select agent or toxin has not been intentionally... an entity eligible to receive such agent or toxin or destroys the agent or toxin by a recognized...

Alpha-beta coordination method for collective search

DOEpatents

Goldsmith, Steven Y.

2002-01-01

The present invention comprises a decentralized coordination strategy called alpha-beta coordination. The alpha-beta coordination strategy is a family of collective search methods that allow teams of communicating agents to implicitly coordinate their search activities through a division of labor based on self-selected roles and self-determined status. An agent can play one of two complementary roles. An agent in the alpha role is motivated to improve its status by exploring new regions of the search space. An agent in the beta role is also motivated to improve its status, but is conservative and tends to remain aggregated with other agents until alpha agents have clearly identified and communicated better regions of the search space. An agent can select its role dynamically based on its current status value relative to the status values of neighboring team members. Status can be determined by a function of the agent's sensor readings, and can generally be a measurement of source intensity at the agent's current location. An agent's decision cycle can comprise three sequential decision rules: (1) selection of a current role based on the evaluation of the current status data, (2) selection of a specific subset of the current data, and (3) determination of the next heading using the selected data. Variations of the decision rules produce different versions of alpha and beta behaviors that lead to different collective behavior properties.

FTIR gas analysis with improved sensitivity and selectivity for CWA and TIC detection

NASA Astrophysics Data System (ADS)

Phillips, Charles M.; Tan, Huwei

2010-04-01

This presentation describes the use of an FTIR (Fourier Transform Infrared)-based spectrometer designed to continuously monitor ambient air for the presence of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). The necessity of a reliable system capable of quickly and accurately detecting very low levels of CWAs and TICs while simultaneously retaining a negligible false alarm rate will be explored. Technological advancements in FTIR sensing have reduced noise while increasing selectivity and speed of detection. These novel analyzer design characteristics are discussed in detail and descriptions are provided which show how optical throughput, gas cell form factor, and detector response are optimized. The hardware and algorithms described here will explain why this FTIR system is very effective for the simultaneous detection and speciation of a wide variety of toxic compounds at ppb concentrations. Analytical test data will be reviewed demonstrating the system's sensitivity to and selectivity for specific CWAs and TICs; this will include recent data acquired as part of the DHS ARFCAM (Autonomous Rapid Facility Chemical Agent Monitor) project. These results include analyses of the data from live agent testing for the determination of CWA detection limits, immunity to interferences, detection times, residual noise analysis and false alarm rates. Sensing systems such as this are critical for effective chemical hazard identification which is directly relevant to the CBRNE community.

7 CFR 331.10 - Restricting access to select agents and toxins; security risk assessments.

Code of Federal Regulations, 2010 CFR

2010-01-01

...; security risk assessments. 331.10 Section 331.10 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE POSSESSION, USE, AND TRANSFER OF SELECT AGENTS AND TOXINS § 331.10 Restricting access to select agents and toxins; security risk...

42 CFR 73.5 - Exemptions for HHS select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other HHS select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

42 CFR 73.5 - Exemptions for HHS select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other HHS select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

9 CFR 121.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... select agent or toxin that is contained in a specimen presented for proficiency testing will be exempt...

9 CFR 121.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... select agent or toxin that is contained in a specimen presented for proficiency testing will be exempt...

Regulatory Myeloid Cells in Transplantation

PubMed Central

Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

2013-01-01

Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention.

PubMed

Fajardo, Alexandra M; Piazza, Gary A

2015-07-15

Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. Copyright © 2015 the American Physiological Society.

Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention

PubMed Central

Piazza, Gary A.

2015-01-01

Colorectal cancer (CRC) is one of the most common human malignancies and a leading cause of cancer-related deaths in developed countries. Identifying effective preventive strategies aimed at inhibiting the development and progression of CRC is critical for reducing the incidence and mortality of this malignancy. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action. This review will discuss the molecular mechanisms being studied for the CRC chemopreventive activity of NSAIDs (i.e., aspirin, sulindac, and ibuprofen), COX-2 inhibitors (i.e., celecoxib), natural products (i.e., curcumin, resveratrol, EGCG, genistein, and baicalein), and metformin. A deeper understanding of how these anti-inflammatory agents inhibit CRC will provide insight into the development of potentially safer and more effective chemopreventive drugs. PMID:26021807

Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention

ERIC Educational Resources Information Center

Hayes, Spencer J.; Andrew, Matthew; Elliott, Digby; Gowen, Emma; Bennett, Simon J.

2016-01-01

We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only…

Carboxylesterase inhibitors

PubMed Central

Hatfield, M. Jason; Potter, Philip M.

2011-01-01

Introduction Carboxylesterases play major roles in the hydrolysis of numerous therapeutically active compounds. This is, in part, due to the prevalence of the ester moiety in these small molecules. However, the impact these enzymes may play on drug stability and pharmacokinetics is rarely considered prior to molecule development. Therefore, the application of selective inhibitors of this class of proteins may have utility in modulating the metabolism, distribution and toxicity of agents that are subjected to enzyme hydrolysis. Areas covered This review details the development of all such compounds dating back to 1986, but principally focuses on the very recent identification of selective human carboxylesterases inhibitors. Expert opinion The implementation of carboxylesterase inhibitors may significantly revolutionize drug discovery. Such molecules may allow for improved efficacy of compounds inactivated by this class of enzymes and/or reduce the toxicity of agents that are activated by these proteins. Furthermore, since lack of carboxylesterase activity appears to have no obvious biological consequence, these compounds could be applied in combination with virtually any esterified drug. Therefore, inhibitors of these proteins may have utility in altering drug hydrolysis and distribution in vivo. The characteristics, chemical and biological properties, and potential uses of such agents, are discussed here. PMID:21609191

Agent Reward Shaping for Alleviating Traffic Congestion

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian

2006-01-01

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

Influence of Selected Personal Characteristics and County Situational Factors on Time Allocated to Dairy Subjects by Extension Agents in Selected Tennessee Counties.

ERIC Educational Resources Information Center

Northcutt, Sherwin Dean; And Others

The study deals with various predictors of time spent on dairy subjects by Extension agents and predictors of contacts made by agents with dairy clientele. Purposes were to determine the relationships, if any, between various independent variables and groups of independent variables (agents' background and training, county dairy situation, agents'…

75 FR 42363 - Public Health Security and Bioterrorism Preparedness and Response Act of 2002; Biennial Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... Bioterrorism Preparedness and Response Act of 2002; Biennial Review and Republication of the Select Agent and... Act) requires the biennial review and republication of the HHS list of select agents and toxins. Accordingly, we are soliciting public comment on the current HHS list of select agents and toxins, including...

75 FR 50730 - Public Health Security and Bioterrorism Preparedness and Response Act of 2002: Biennial Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-17

... Bioterrorism Preparedness and Response Act of 2002: Biennial Review and Republication of the Select Agent and... public comment on the current HHS list of select agents and toxins. This document is extending the... changes to the list of select agents and toxins'' and mailed to: Centers for Disease Control and...

Contribution of Selective Conditions to Microbial Competition in Four Listeria Selective Enrichment Formulations

PubMed Central

Keys, Ashley L.; Hitchins, Anthony D.; Smiley, R. Derike

2017-01-01

Microbial competition during selective enrichment negatively affects Listeria monocytogenes populations and may hinder the subsequent detection or recovery of this organism. Competition assays among 10 selected strains of Listeria and Citrobacter braakii were performed in buffered Listeria enrichment broth, 3-(N-morpholino)propanesulfonic acid–buffered Listeria enrichment broth, University of Vermont medium–modified Listeria enrichment broth, and Fraser broth. The individual contributions of each selective agent in these media were also assessed, as well as the contribution of incubation temperature. Acriflavine hydrochloride and sodium nalidixate were ineffective at preventing the overgrowth of C. braakii; this resulted in substantially lower populations of Listeria than when the competitor was absent. At the higher levels, both of these selective agents were detrimental to Listeria populations. The highest enrichment populations of Listeria were observed when either NaCl or LiCl was present. In the absence of selective agents, the final populations of Listeria following competitive growth with C. braakii were not substantially affected by temperature; however, in the presence of selective agents, the Listeria populations were statistically higher at the higher incubation temperature. There are a limited number of selective agents available for use in Listeria-specific enrichment media, resulting in formulations that are only somewhat selective for this species. The optimization of current formulations may help researchers to improve Listeria recovery, particularly from products with a high microbial load. The understanding of the behavior and interactions between target and nontarget microorganisms in the presence of these available selective agents is a necessary step in the optimization of Listeria selective enrichment formulations. PMID:28221922

Contribution of Selective Conditions to Microbial Competition in Four Listeria Selective Enrichment Formulations.

PubMed

Keys, Ashley L; Hitchins, Anthony D; Smiley, R Derike

2016-11-01

Microbial competition during selective enrichment negatively affects Listeria monocytogenes populations and may hinder the subsequent detection or recovery of this organism. Competition assays among 10 selected strains of Listeria and Citrobacter braakii were performed in buffered Listeria enrichment broth, 3-(N-morpholino)propanesulfonic acid-buffered Listeria enrichment broth, University of Vermont medium-modified Listeria enrichment broth, and Fraser broth. The individual contributions of each selective agent in these media were also assessed, as well as the contribution of incubation temperature. Acriflavine hydrochloride and sodium nalidixate were ineffective at preventing the overgrowth of C. braakii ; this resulted in substantially lower populations of Listeria than when the competitor was absent. At the higher levels, both of these selective agents were detrimental to Listeria populations. The highest enrichment populations of Listeria were observed when either NaCl or LiCl was present. In the absence of selective agents, the final populations of Listeria following competitive growth with C. braakii were not substantially affected by temperature; however, in the presence of selective agents, the Listeria populations were statistically higher at the higher incubation temperature. There are a limited number of selective agents available for use in Listeria -specific enrichment media, resulting in formulations that are only somewhat selective for this species. The optimization of current formulations may help researchers to improve Listeria recovery, particularly from products with a high microbial load. The understanding of the behavior and interactions between target and nontarget microorganisms in the presence of these available selective agents is a necessary step in the optimization of Listeria selective enrichment formulations.

Immobilizer-assisted management of metal-contaminated agricultural soils for safer food production.

PubMed

Kim, Kwon-Rae; Kim, Jeong-Gyu; Park, Jeong-Sik; Kim, Min-Suk; Owens, Gary; Youn, Gyu-Hoon; Lee, Jin-Su

2012-07-15

Production of food crops on metal contaminated agricultural soils is of concern because consumers are potentially exposed to hazardous metals via dietary intake of such crops or crop derived products. Therefore, the current study was conducted to develop management protocols for crop cultivation to allow safer food production. Metal uptake, as influenced by pH change-induced immobilizing agents (dolomite, steel slag, and agricultural lime) and sorption agents (zeolite and compost), was monitored in three common plants representative of leafy (Chinese cabbage), root (spring onion) and fruit (red pepper) vegetables, in a field experiment. The efficiency of the immobilizing agents was assessed by their ability to decrease the phytoavailability of metals (Cd, Pb, and Zn). The fruit vegetable (red pepper) showed the least accumulation of Cd (0.16-0.29 mgkg(-1) DW) and Pb (0.2-0.9 mgkg(-1) DW) in edible parts regardless of treatment, indicating selection of low metal accumulating crops was a reasonable strategy for safer food production. However, safer food production was more likely to be achievable by combining crop selection with immobilizing agent amendment of soils. Among the immobilizing agents, pH change-induced immobilizers were more effective than sorption agents, showing decreases in Cd and Pb concentrations in each plant well below standard limits. The efficiency of pH change-induced immobilizers was also comparable to reductions obtained by 'clean soil cover' where the total metal concentrations of the plow layer was reduced via capping the surface with uncontaminated soil, implying that pH change-induced immobilizers can be practically applied to metal contaminated agricultural soils for safer food production. Copyright © 2012 Elsevier Ltd. All rights reserved.

Salivary hypofunction and xerostomia: diagnosis and treatment.

PubMed

Atkinson, Jane C; Grisius, Margaret; Massey, Ward

2005-04-01

Salivary gland hypofunction and complaints of xerostomia are common in elderly patients, irrespective of their living situation. Medication use is frequently related to dry mouth symptoms and reductions in salivary flow rates. Patients with reduced salivary flow are at increased risk for caries, oral fungal infections, swallowing problems, and diminished or altered taste. Oral health care providers should institute aggressive preventive measures and recommend palliative care for patients with significant reduction in salivary gland function. The systemic agents pilocarpine and cevimeline may help selected patients. Selective use of fluoride-releasing restorative materials and conservative treatment plans are recommended for this patient group.

SEPARATION OF URANIUM, PLUTONIUM, AND FISSION PRODUCTS

DOEpatents

Spence, R.; Lister, M.W.

1958-12-16

Uranium and plutonium can be separated from neutron-lrradiated uranium by a process consisting of dissolvlng the lrradiated material in nitric acid, saturating the solution with a nitrate salt such as ammonium nitrate, rendering the solution substantially neutral with a base such as ammonia, adding a reducing agent such as hydroxylamine to change plutonium to the trivalent state, treating the solution with a substantially water immiscible organic solvent such as dibutoxy diethylether to selectively extract the uranium, maklng the residual aqueous solutlon acid with nitric acid, adding an oxidizing agent such as ammonlum bromate to oxidize the plutonium to the hexavalent state, and selectlvely extracting the plutonium by means of an immlscible solvent, such as dibutoxy dlethyletber.

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

PubMed

Rehm, Susan J; Tice, Alan

2010-09-15

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

Two-agent cooperative search using game models with endurance-time constraints

NASA Astrophysics Data System (ADS)

Sujit, P. B.; Ghose, Debasish

2010-07-01

In this article, the problem of two Unmanned Aerial Vehicles (UAVs) cooperatively searching an unknown region is addressed. The search region is discretized into hexagonal cells and each cell is assumed to possess an uncertainty value. The UAVs have to cooperatively search these cells taking limited endurance, sensor and communication range constraints into account. Due to limited endurance, the UAVs need to return to the base station for refuelling and also need to select a base station when multiple base stations are present. This article proposes a route planning algorithm that takes endurance time constraints into account and uses game theoretical strategies to reduce the uncertainty. The route planning algorithm selects only those cells that ensure the agent will return to any one of the available bases. A set of paths are formed using these cells which the game theoretical strategies use to select a path that yields maximum uncertainty reduction. We explore non-cooperative Nash, cooperative and security strategies from game theory to enhance the search effectiveness. Monte-Carlo simulations are carried out which show the superiority of the game theoretical strategies over greedy strategy for different look ahead step length paths. Within the game theoretical strategies, non-cooperative Nash and cooperative strategy perform similarly in an ideal case, but Nash strategy performs better than the cooperative strategy when the perceived information is different. We also propose a heuristic based on partitioning of the search space into sectors to reduce computational overhead without performance degradation.

Review of Restricted Experiment Requests, Division of Select Agents and Toxins, Centers for Disease Control and Prevention, 2006-2013.

PubMed

Smith, Jacinta; Gangadharan, Denise; Weyant, Robbin

2015-01-01

The Centers for Disease Control and Prevention (CDC) Division of Select Agents and Toxins (DSAT) regulates laboratories that possess, use, or transfer select agents and toxins in the United States. DSAT also mitigates biosafety risks through the review of "restricted experiments," which under the select agent regulations are experiments that pose heightened biosafety risks. From January 2006 through December 2013, DSAT received 618 requests from 109 entities to perform potentially restricted experiments. Of these requests, 85% were determined not to meet the regulatory definition of a restricted experiment, while 15% of the requests met the definition of a restricted experiment. Of the 91 restricted experiments proposed, DSAT approved 31 (34%) requests because the biosafety conditions proposed were commensurate with the experiments' biosafety risk. All 31 approved restricted experiments were for work with select toxins. DSAT did not approve 60 restricted experiment requests due to potentially serious biosafety risks to public health and safety. All 60 denied restricted experiments proposed inserting drug resistance traits into select agents that could compromise the control of disease. The select agents and toxins associated most frequently with requests that met the regulatory definition of a restricted experiment are Shiga toxin (n = 16), Burkholderia mallei (n = 15), Botulinum neurotoxin (n = 14), and Brucella abortus (n = 14). In general, all restricted experiment decisions are determined on a case-by-case basis. This article describes the trends and characteristics of the data associated with restricted experiment requests among select agents that have an impact on public health and safety (HHS only agents) or both public health and safety and animal health or products (overlap agents). The information presented here, coupled with the information published in the restricted experiment guidance document ( www.selectagents.gov ), is intended to promote awareness among the research community of the type of experiments that meet the regulatory definition of a restricted experiment as well as to provide a greater understanding of the restricted experiment review process.

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

USDA-ARS?s Scientific Manuscript database

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

A computer program for fast and easy typing of partial endoglucanase gene sequence into phylotypes and sequevars 1&2 (select agents) of Ralstonia solanacearum

USDA-ARS?s Scientific Manuscript database

The phytopathogen Ralstonia solanacearum is a species complex that contains a subset of strains that are quarantined or select agent pathogens. An unidentified R. solanacearum strain is considered a select agent in the US until proven otherwise, which can be done by phylogenetic analysis of a partia...

Co-Selection of Resistance to Antibiotics, Biocides and Heavy Metals, and Its Relevance to Foodborne Pathogens

PubMed Central

Wales, Andrew D.; Davies, Robert H.

2015-01-01

Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There is indeed experimental and observational evidence that exposure to these non-antibiotic antimicrobial agents can induce or select for bacterial adaptations that result in decreased susceptibility to one or more antibiotics. This may occur via cellular mechanisms that are protective across multiple classes of antimicrobial agents or by selection of genetic determinants for resistance to non-antibiotic agents that are linked to genes for antibiotic resistance. There may also be relevant effects of these antimicrobial agents on bacterial community structure and via non-specific mechanisms such as mobilization of genetic elements or mutagenesis. Notably, some co-selective adaptations have adverse effects on fitness in the absence of a continued selective pressure. The present review examines the evidence for the significance of these phenomena, particularly in respect of bacterial zoonotic agents that commonly occur in livestock and that may be transmitted, directly or via the food chain, to human populations. PMID:27025641

Requirements for facilities transferring or receiving select agents. Final rule.

PubMed

2001-08-31

CDC administers regulations that govern the transfer of certain biological agents and toxins ("select agents"). These regulations require entities that transfer or receive select agents to register with CDC and comply with biosafety standards contained in the Third Edition of the CDC/NIH publication "Biosafety in Microbiological and Biomedical Laboratories ("BMBL")." On October 28,1999, CDC published a Notice of Proposed Rulemaking ("NPRM") seeking both to revise the biosafety standards facilities must follow when handling select agents and to provide new biosecurity standards for such facilities. These new standards are contained in the Fourth Edition of BMBL, which the NPRM proposed to incorporate by reference, thereby replacing the Third Edition. No comments were received in response to this proposal. CDC is therefore amending its regulations to incorporate the Fourth Edition.

The Quinone Based Antitumor Agent Sepantronium Bromide (YM155) Causes Oxygen Independent Redox Activated Oxidative DNA Damage.

PubMed

Wani, Tasaduq Hussain; Surendran, Sreeraj; Jana, Anal; Chakrabarty, Anindita; Chowdhury, Goutam

2018-06-13

Sepantronium bromide (YM155) is a small molecule antitumor agent currently in phase II clinical trials. Although developed as survivin suppressor, YM155's primary mode of action has recently been found to be DNA damage. However, the mechanism of DNA damage by YM155 is still unknown. Knowing the mechanism of action of an anticancer drug is necessary to formulate a rational drug combination and select a cancer type for achieving maximum clinical efficacy. Using cell-based assays we showed that YM155 cause extensive DNA cleavage and reactive oxygen species generation. DNA cleavage by YM155 was found to be inhibited by radical scavengers and desferal. The reducing agent DTT and the cellular reducing system xanthine/xanthine oxidase were found to reductively activate YM155 and cause DNA cleavage. Unlike quinones, DNA cleavage by YM155 occurs in the presence of catalase and under hypoxic conditions indicating that hydrogen peroxide and oxygen is not necessary. Although YM155 is a quinone, it does not follow a typical quinone mechanism. Consistent with these observations a mechanism has been proposed that suggests that YM155 can cause oxidative DNA cleavage upon two electron reductive activation.

The Use of Calcimimetics for the Treatment of Secondary Hyperparathyroidism: A 10 Year Evidence Review.

PubMed

Rodríguez, Mariano; Goodman, William G; Liakopoulos, Vassilios; Messa, Piergiorgio; Wiecek, Andrzej; Cunningham, John

2015-01-01

Until the discovery of calcimimetics, the management of secondary hyperparathyroidism (SHPT) relied exclusively on treatment with phosphate binders, vitamin D derivatives or surgical parathyroidectomy with limited success. The therapeutic use of calcimimetic agents, together with a better understanding of the pivotal role of the calcium-sensing receptor (CaSR) in the physiological regulation of parathyroid gland function, substantially advanced the management of hyperparathyroidism in dialysis practice. Calcimimetics bind selectively to the CaSR receptor in parathyroid tissue and enhance the inhibitory effect of extracellular calcium ions on parathyroid hormone (PTH) secretion, thereby reducing PTH levels even when serum calcium concentrations are normal or low. The availability of calcimimetic agents for clinical use has opened a new era in the management of patients with SHPT. Indeed, calcimimetic compounds have been shown to reduce PTH levels and to lower serum calcium concentrations in all forms of hyperparathyroidism, including primary hyperparathyroidism (PHPT) and parathyroid carcinoma. Such findings underscore the critical importance of the CaSR as a therapeutic target in this family of clinical disorders. New calcimimetic agents are being developed that have the potential to offer improved efficacy and safety compared with currently available calcimimetic compounds. © 2015 Wiley Periodicals, Inc.

Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases.

PubMed

Moral, Mario E G; Siahaan, Teruna J

2017-01-01

Overexpressed cell-surface receptors are hallmarks of many disease states and are often used as markers for targeting diseased cells over healthy counterparts. Cell adhesion peptides, which are often derived from interacting regions of these receptor-ligand proteins, mimic surfaces of intact proteins and, thus, have been studied as targeting agents for various payloads to certain cell targets for cancers and autoimmune diseases. Because many cytotoxic agents in the free form are often harmful to healthy cells, the use of cell adhesion peptides in targeting their delivery to diseased cells has been studied to potentially reduce required effective doses and associated harmful side-effects. In this review, multiple cell adhesion peptides from extracellular matrix and ICAM proteins were used to selectively direct drug payloads, signal-inhibitor peptides, and diagnostic molecules, to diseased cells over normal counterparts. RGD constructs have been used to improve the selectivity and efficacy of diagnostic and drug-peptide conjugates against cancer cells. From this precedent, novel conjugates of antigenic and cell adhesion peptides, called Bifunctional Peptide Inhibitors (BPIs), have been designed to selectively regulate immune cells and suppress harmful inflammatory responses in autoimmune diseases. Similar peptide conjugations with imaging agents have delivered promising diagnostic methods in animal models of rheumatoid arthritis. BPIs have also been shown to generate immune tolerance and suppress autoimmune diseases in animal models of type-1 diabetes, rheumatoid arthritis, and multiple sclerosis. Collectively, these studies show the potential of cell adhesion peptides in improving the delivery of drugs and diagnostic agents to diseased cells in clinical settings. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characterization of the unique function of a reduced amide bond in a cytolytic peptide that acts on phospholipid membranes.

PubMed Central

Oh, J E; Lee, K H

2000-01-01

The incorporation of a reduced amide bond, psi(CH(2)NH), into peptide results in an increase in the net positive charge and the perturbation of alpha-helical structure. By using this characteristic of the reduced amide bond, we designed and synthesized novel pseudopeptides containing reduced amide bonds, which had a great selectivity between bacterial and mammalian cells. A structure-activity relationship study on pseudopeptides indicated that the decrease in alpha-helicity and the increase in net positive charge in the backbone, caused by the incorporation of a reduced amide bond into the peptide, both contributed to an improvement in the selectivity between lipid membranes with various surface charges. However, activity results in vitro indicated that a perturbation of alpha-helical structure rather than an increase in net positive charge in the backbone is more important in the selectivity between bacterial and mammalian cells. The present result revealed that the backbone of membrane-active peptides were important not only in maintaining the secondary structure for the interactions with lipid membranes but also in direct interactions with lipid membranes. The present study showed the unique function of a reduced amide bond in cytolytic peptides and a direction for developing novel anti-bacterial agents from cytolytic peptides that act on the lipid membrane of micro-organisms. PMID:11104671

Microbubbles in Ultrasound-Triggered Drug and Gene Delivery

PubMed Central

Hernot, Sophie; Klibanov, Alexander L.

2008-01-01

Ultrasound contrast agents, in the form of gas-filled microbubbles, are becoming popular in perfusion monitoring; they are employed as molecular imaging agents. Microbubbles are manufactured from biocompatible materials, they can be injected intravenously, and some are approved for clinical use. Microbubbles can be destroyed by ultrasound irradiation. This destruction phenomenon can be applied to targeted drug delivery and enhancement of drug action. The ultrasonic field can be focused at the target tissues and organs; thus, selectivity of the treatment can be improved, reducing undesirable side effects. Microbubbles enhance ultrasound energy deposition in the tissues and serve as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection is observed in the areas of the body where ultrasound is applied after intravascular administration of microbubbles and plasmid DNA. Accelerated blood clot dissolution in the areas of insonation by cooperative action of thrombolytic agents and microbubbles is demonstrated in several clinical trials. PMID:18486268

Design, Synthesis and Bio-evaluation of an EphA2-based Targeted Delivery System

PubMed Central

Barile, Elisa; Wang, Si; Das, Swadesh K.; Noberini, Roberta; Dahl, Russell; Stebbins, John L.; Pasquale, Elena B.; Fisher, Paul B.; Pellecchia, Maurizio

2014-01-01

We recently described a new targeted delivery system based on specific EphA2 receptor targeting peptides conjugated with the chemotherapeutic agent paclitaxel. In this manuscript we investigate the chemical determinants responsible for the stability and degradation of these agents in plasma. Introducing modifications in both the peptide and the linker between the peptide and paclitaxel, resulted in drug conjugates that are both long-lived in rat plasma and that markedly reduced tumor size in a prostate cancer xenograft model compared to paclitaxel alone treatment. These studies identify critical rate-limiting degradation sites on the peptide-drug conjugates, enabling the design of agents with increased stability and efficacy. These results provide support for our central hypothesis that peptide-drug conjugates targeting the EphA2 receptor represent an innovative and potentially effective strategy to selectively deliver cytotoxic drugs to cancer cells. PMID:24677792

Determination of trace amounts of chemical warfare agent degradation products in decontamination solutions with NMR spectroscopy.

PubMed

Koskela, Harri; Rapinoja, Marja-Leena; Kuitunen, Marja-Leena; Vanninen, Paula

2007-12-01

Decontamination solutions are used for an efficient detoxification of chemical warfare agents (CWAs). As these solutions can be composed of strong alkaline chemicals with hydrolyzing and oxidizing properties, the analysis of CWA degradation products in trace levels from these solutions imposes a challenge for any analytical technique. Here, we present results of application of nuclear magnetic resonance spectroscopy for analysis of trace amounts of CWA degradation products in several untreated decontamination solutions. Degradation products of the nerve agents sarin, soman, and VX were selectively monitored with substantially reduced interference of background signals by 1D 1H-31P heteronuclear single quantum coherence (HSQC) spectrometry. The detection limit of the chemicals was at the low part-per-million level (2-10 microg/mL) in all studied solutions. In addition, the concentration of the degradation products was obtained with sufficient confidence with external standards.

Lorcaserin: drug profile and illustrative model of the regulatory challenges of weight-loss drug development.

PubMed

Bays, Harold E

2011-03-01

Lorcaserin is a selective 5-hydroxytryptamine receptor 2c agonist developed as a weight-loss drug. Phase II and III clinical trials support lorcaserin as not only reducing adiposity (i.e., fat mass), but also as improving the metabolic diseases commonly associated with adiposopathy (i.e., fat dysfunction). At the time of this writing, regulatory processes continue towards evaluating lorcaserin as a potentially marketed weight-loss and weight-maintenance agent. Some of the challenges facing lorcaserin are similar to the difficulties encountered by all investigational weight-loss therapeutic agents, which include evolving paths towards approval. While important for clinicians to understand approval hurdles for all therapeutics, it is especially critical for researchers and developers to grasp the unique regulatory complexities of anti-obesity agents. This article profiles lorcaserin as an illustrative example of general drug development regulatory processes, and specifically details the unique challenge of weight-loss drug development.

Virtual screening of selective multitarget kinase inhibitors by combinatorial support vector machines.

PubMed

Ma, X H; Wang, R; Tan, C Y; Jiang, Y Y; Lu, T; Rao, H B; Li, X Y; Go, M L; Low, B C; Chen, Y Z

2010-10-04

Multitarget agents have been increasingly explored for enhancing efficacy and reducing countertarget activities and toxicities. Efficient virtual screening (VS) tools for searching selective multitarget agents are desired. Combinatorial support vector machines (C-SVM) were tested as VS tools for searching dual-inhibitors of 11 combinations of 9 anticancer kinase targets (EGFR, VEGFR, PDGFR, Src, FGFR, Lck, CDK1, CDK2, GSK3). C-SVM trained on 233-1,316 non-dual-inhibitors correctly identified 26.8%-57.3% (majority >36%) of the 56-230 intra-kinase-group dual-inhibitors (equivalent to the 50-70% yields of two independent individual target VS tools), and 12.2% of the 41 inter-kinase-group dual-inhibitors. C-SVM were fairly selective in misidentifying as dual-inhibitors 3.7%-48.1% (majority <20%) of the 233-1,316 non-dual-inhibitors of the same kinase pairs and 0.98%-4.77% of the 3,971-5,180 inhibitors of other kinases. C-SVM produced low false-hit rates in misidentifying as dual-inhibitors 1,746-4,817 (0.013%-0.036%) of the 13.56 M PubChem compounds, 12-175 (0.007%-0.104%) of the 168 K MDDR compounds, and 0-84 (0.0%-2.9%) of the 19,495-38,483 MDDR compounds similar to the known dual-inhibitors. C-SVM was compared to other VS methods Surflex-Dock, DOCK Blaster, kNN and PNN against the same sets of kinase inhibitors and the full set or subset of the 1.02 M Zinc clean-leads data set. C-SVM produced comparable dual-inhibitor yields, slightly better false-hit rates for kinase inhibitors, and significantly lower false-hit rates for the Zinc clean-leads data set. Combinatorial SVM showed promising potential for searching selective multitarget agents against intra-kinase-group kinases without explicit knowledge of multitarget agents.

Comparison of the White-Nose Syndrome Agent Pseudogymnoascus destructans to Cave-Dwelling Relatives Suggests Reduced Saprotrophic Enzyme Activity

PubMed Central

Reynolds, Hannah T.; Barton, Hazel A.

2014-01-01

White-nose Syndrome (WNS) is an emerging infectious mycosis that has impacted multiple species of North American bats since its initial discovery in 2006, yet the physiology of the causal agent, the psychrophilic fungus Pseudogymnoascus destructans ( = Geomyces destructans), is not well understood. We investigated the ability of P. destructans to secrete enzymes that could permit environmental growth or affect pathogenesis and compared enzyme activity across several Pseudogymnoascus species isolated from both hibernating bats and cave sediments. We found that P. destructans produced enzymes that could be beneficial in either a pathogenic or saprotrophic context, such as lipases, hemolysins, and urease, as well as chitinase and cellulases, which could aid in saprotrophic growth. The WNS pathogen showed significantly lower activity for urease and endoglucanase compared to con-generic species (Pseudogymnoascus), which may indicate a shift in selective pressure to the detriment of P. destructans’ saprotrophic ability. Based on the positive function of multiple saprotrophic enzymes, the causal agent of White-nose Syndrome shows potential for environmental growth on a variety of substrates found in caves, albeit at a reduced level compared to environmental strains. Our data suggest that if P. destructans emerged as an opportunistic infection from an environmental source, co-evolution with its host may have led to a reduced capacity for saprotrophic growth. PMID:24466096

Comparison of the white-nose syndrome agent Pseudogymnoascus destructans to cave-dwelling relatives suggests reduced saprotrophic enzyme activity.

PubMed

Reynolds, Hannah T; Barton, Hazel A

2014-01-01

White-nose Syndrome (WNS) is an emerging infectious mycosis that has impacted multiple species of North American bats since its initial discovery in 2006, yet the physiology of the causal agent, the psychrophilic fungus Pseudogymnoascus destructans ( = Geomyces destructans), is not well understood. We investigated the ability of P. destructans to secrete enzymes that could permit environmental growth or affect pathogenesis and compared enzyme activity across several Pseudogymnoascus species isolated from both hibernating bats and cave sediments. We found that P. destructans produced enzymes that could be beneficial in either a pathogenic or saprotrophic context, such as lipases, hemolysins, and urease, as well as chitinase and cellulases, which could aid in saprotrophic growth. The WNS pathogen showed significantly lower activity for urease and endoglucanase compared to con-generic species (Pseudogymnoascus), which may indicate a shift in selective pressure to the detriment of P. destructans' saprotrophic ability. Based on the positive function of multiple saprotrophic enzymes, the causal agent of White-nose Syndrome shows potential for environmental growth on a variety of substrates found in caves, albeit at a reduced level compared to environmental strains. Our data suggest that if P. destructans emerged as an opportunistic infection from an environmental source, co-evolution with its host may have led to a reduced capacity for saprotrophic growth.

Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model.

PubMed

Ando, Shiori; Funato, Michinori; Ohuchi, Kazuki; Kameyama, Tsubasa; Inagaki, Satoshi; Seki, Junko; Kawase, Chizuru; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kaneko, Hideo; Hara, Hideaki

2017-11-05

Spinal muscular atrophy (SMA) is an intractable disease characterized by a progressive loss of spinal motor neurons, which leads to skeletal muscle weakness and atrophy. Currently, there are no curative agents for SMA, although it is understood to be caused by reduced levels of survival motor neuron (SMN) protein. Additionally, why reduced SMN protein level results in selective apoptosis in spinal motor neurons is still not understood. Our purpose in this study was to evaluate the therapeutic potential of edaravone, a free radical scavenger, by using induced pluripotent stem cells from an SMA patient (SMA-iPSCs) and to address oxidative stress-induced apoptosis in spinal motor neurons. We first found that edaravone could improve impaired neural development of SMA-iPSCs-derived spinal motor neurons with limited effect on nuclear SMN protein expression. Furthermore, edaravone inhibited the generation of reactive oxygen species and mitochondrial reactive oxygen species upregulated in SMA-iPSCs-derived spinal motor neurons, and reversed oxidative-stress induced apoptosis. In this study, we suggest that oxidative stress might be partly the reason for selective apoptosis in spinal motor neurons in SMA pathology, and that oxidative stress-induced apoptosis might be the therapeutic target of SMA. Copyright © 2017 Elsevier B.V. All rights reserved.

System and process for producing fuel with a methane thermochemical cycle

DOEpatents

Diver, Richard B.

2015-12-15

A thermochemical process and system for producing fuel are provided. The thermochemical process includes reducing an oxygenated-hydrocarbon to form an alkane and using the alkane in a reforming reaction as a reducing agent for water, a reducing agent for carbon dioxide, or a combination thereof. Another thermochemical process includes reducing a metal oxide to form a reduced metal oxide, reducing an oxygenated-hydrocarbon with the reduced metal oxide to form an alkane, and using the alkane in a reforming reaction as a reducing agent for water, a reducing agent for carbon dioxide, or a combination thereof. The system includes a reformer configured to perform a thermochemical process.

Pain expressiveness and altruistic behavior: an exploration using agent-based modeling.

PubMed

de C Williams, Amanda C; Gallagher, Elizabeth; Fidalgo, Antonio R; Bentley, Peter J

2016-03-01

Predictions which invoke evolutionary mechanisms are hard to test. Agent-based modeling in artificial life offers a way to simulate behaviors and interactions in specific physical or social environments over many generations. The outcomes have implications for understanding adaptive value of behaviors in context. Pain-related behavior in animals is communicated to other animals that might protect or help, or might exploit or predate. An agent-based model simulated the effects of displaying or not displaying pain (expresser/nonexpresser strategies) when injured and of helping, ignoring, or exploiting another in pain (altruistic/nonaltruistic/selfish strategies). Agents modeled in MATLAB interacted at random while foraging (gaining energy); random injury interrupted foraging for a fixed time unless help from an altruistic agent, who paid an energy cost, speeded recovery. Environmental and social conditions also varied, and each model ran for 10,000 iterations. Findings were meaningful in that, in general, contingencies that evident from experimental work with a variety of mammals, over a few interactions, were replicated in the agent-based model after selection pressure over many generations. More energy-demanding expression of pain reduced its frequency in successive generations, and increasing injury frequency resulted in fewer expressers and altruists. Allowing exploitation of injured agents decreased expression of pain to near zero, but altruists remained. Decreasing costs or increasing benefits of helping hardly changed its frequency, whereas increasing interaction rate between injured agents and helpers diminished the benefits to both. Agent-based modeling allows simulation of complex behaviors and environmental pressures over evolutionary time.

A novel orally available small molecule that inhibits hepatitis B virus expression.

PubMed

Mueller, Henrik; Wildum, Steffen; Luangsay, Souphalone; Walther, Johanna; Lopez, Anaïs; Tropberger, Philipp; Ottaviani, Giorgio; Lu, Wenzhe; Parrott, Neil John; Zhang, Jitao David; Schmucki, Roland; Racek, Tomas; Hoflack, Jean-Christophe; Kueng, Erich; Point, Floriane; Zhou, Xue; Steiner, Guido; Lütgehetmann, Marc; Rapp, Gianna; Volz, Tassilo; Dandri, Maura; Yang, Song; Young, John A T; Javanbakht, Hassan

2018-03-01

The hallmarks of chronic HBV infection are a high viral load (HBV DNA) and even higher levels (>100-fold in excess of virions) of non-infectious membranous particles containing the tolerogenic viral S antigen (HBsAg). Currently, standard treatment effectively reduces viremia but only rarely results in a functional cure (defined as sustained HBsAg loss). There is an urgent need to identify novel therapies that reduce HBsAg levels and restore virus-specific immune responsiveness in patients. We report the discovery of a novel, potent and orally bioavailable small molecule inhibitor of HBV gene expression (RG7834). RG7834 antiviral characteristics and selectivity against HBV were evaluated in HBV natural infection assays and in a urokinase-type plasminogen activator/severe combined immunodeficiency humanized mouse model of HBV infection, either alone or in combination with entecavir. Unlike nucleos(t)ide therapies, which reduce viremia but do not lead to an effective reduction in HBV antigen expression, RG7834 significantly reduced the levels of viral proteins (including HBsAg), as well as lowering viremia. Consistent with its proposed mechanism of action, time course RNA-seq analysis revealed a fast and selective reduction in HBV mRNAs in response to RG7834 treatment. Furthermore, oral treatment of HBV-infected humanized mice with RG7834 led to a mean HBsAg reduction of 1.09 log 10 compared to entecavir, which had no significant effect on HBsAg levels. Combination of RG7834, entecavir and pegylated interferon α-2a led to significant reductions of both HBV DNA and HBsAg levels in humanized mice. We have identified a novel oral HBV viral gene expression inhibitor that blocks viral antigen and virion production, that is highly selective for HBV, and has a unique antiviral profile that is clearly differentiated from nucleos(t)ide analogues. We discovered a novel small molecule viral expression inhibitor that is highly selective for HBV and unlike current therapy inhibits the expression of viral proteins by specifically reducing HBV mRNAs. RG7834 can therefore potentially provide anti-HBV benefits and increase HBV cure rates, by direct reduction of viral agents needed to complete the viral life cycle, as well as a reduction of viral agents involved in evasion of the host immune responses. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients: a meta-analysis of randomized controlled trials.

PubMed

Wein, Lironne; Wein, Sara; Haas, Steven Joseph; Shaw, James; Krum, Henry

2007-07-23

There is uncertainty regarding which pharmacological agents most effectively prevent venous thromboembolism in hospitalized medical patients. We therefore performed a meta-analysis to determine this. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1950, 1966, and 1800, respectively, through June 30, 2006, for randomized controlled trials that involved medical patients comparing unfractionated heparin (UFH) or low-molecular-weight heparin or heparinoid (LMWH) with a control, LMWH with UFH, or selective factor Xa inhibitors with a comparator. Study selection, validity assessment, and data abstraction were performed by 2 independent reviewers (L.W. and S.W.). Data synthesis was undertaken by 1 blinded investigator (S.J.H.). Thirty-six studies were included. Compared with the control, UFH was associated with a reduced risk of deep venous thrombosis (DVT) (risk ratio [RR], 0.33; 95% confidence interval [CI], 0.26-0.42) and pulmonary embolism (RR, 0.64; 95% CI, 0.50-0.82), as was LMWH (RR, 0.56; 95% CI, 0.45-0.70; and RR, 0.37; 95% CI, 0.21-0.64, respectively). A UFH dosage of 5000 U 3 times daily was more effective in preventing DVT than a UFH dosage of 5000 U twice daily when compared with the control (RR, 0.27; 95% CI, 0.20-0.36; vs RR, 0.52; 95% CI, 0.28-0.96). Neither UFH nor LMWH reduced mortality. When directly compared with UFH, LMWH was associated with a lower risk of DVT (RR, 0.68; 95% CI, 0.52-0.88) and injection site hematoma (RR, 0.47; 95% CI, 0.36-0.62), but no difference was seen between the 2 agents in the risk of bleeding or thrombocytopenia. Both UFH and LMWH reduce venous thromboembolic risk in hospitalized medical patients, but neither agent alters mortality. When directly compared, LMWH is more effective in preventing DVT.

Peptide-based protein capture agents with high affinity, selectivity, and stability as antibody replacements in biodetection assays

NASA Astrophysics Data System (ADS)

Coppock, Matthew B.; Farrow, Blake; Warner, Candice; Finch, Amethist S.; Lai, Bert; Sarkes, Deborah A.; Heath, James R.; Stratis-Cullum, Dimitra

2014-05-01

Current biodetection assays that employ monoclonal antibodies as primary capture agents exhibit limited fieldability, shelf life, and performance due to batch-to-batch production variability and restricted thermal stability. In order to improve upon the detection of biological threats in fieldable assays and systems for the Army, we are investigating protein catalyzed capture (PCC) agents as drop-in replacements for the existing antibody technology through iterative in situ click chemistry. The PCC agent oligopeptides are developed against known protein epitopes and can be mass produced using robotic methods. In this work, a PCC agent under development will be discussed. The performance, including affinity, selectivity, and stability of the capture agent technology, is analyzed by immunoprecipitation, western blotting, and ELISA experiments. The oligopeptide demonstrates superb selectivity coupled with high affinity through multi-ligand design, and improved thermal, chemical, and biochemical stability due to non-natural amino acid PCC agent design.

Polymorphism at the defensin gene in the Anopheles gambiae complex: testing different selection hypotheses

PubMed Central

Simard, Frédéric; Licht, Monica; Besansky, Nora J.; Lehmann, Tovi

2007-01-01

Genetic variation in defensin, a gene encoding a major effector molecule of insects immune response was analyzed within and between populations of three members of the Anopheles gambiae complex. The species selected included the two anthropophilic species, An. gambiae and An. arabiensis and the most zoophilic species of the complex, An. quadriannulatus. The first species was represented by four populations spanning its extreme genetic and geographical ranges, whereas each of the other two species was represented by a single population. We found (i) reduced overall polymorphism in the mature peptide region and in the total coding region, together with specific reductions in rare and moderately frequent mutations (sites) in the coding region compared with non coding regions, (ii) markedly reduced rate of nonsynonymous diversity compared with synonymous variation in the mature peptide and virtually identical mature peptide across the three species, and (iii) increased divergence between species in the mature peptide together with reduced differentiation between populations of An. gambiae in the same DNA region. These patterns suggest a strong purifying selection on the mature peptide and probably the whole coding region. Because An. quadriannulatus is not exposed to human pathogens, identical mature peptide and similar pattern of polymorphism across species implies that human pathogens played no role as selective agents on this peptide. PMID:17161659

[Effect of amount of silane coupling agent on flexural strength of dental composite resins reinforced with aluminium borate whisker].

PubMed

Zhu, Ming-yi; Zhang, Xiu-yin

2015-06-01

To evaluate the effect of amount of silane coupling agent on flexural strength of dental composite resins reinforced with aluminium borate whisker (ABW). ABW was surface-treated with 0%, 1%, 2%, 3% and 4% silan coupling agent (γ-MPS), and mixed with resin matrix to synthesize 5 groups of composite resins. After heat-cured at 120 degrees centigrade for 1 h, specimens were tested in three-point flexure to measure strength according to ISO-4049. One specimen was selected randomly from each group and observed under scanning electron microscope (SEM). The data was analyzed with SAS 9.2 software package. The flexural strength (117.93±11.9 Mpa) of the group treated with 2% silane coupling agent was the highest, and significantly different from that of the other 4 groups (α=0.01). The amount of silane coupling agent has impact on the flexural strength of dental composite resins reinforced with whiskers; The flexual strength will be reduced whenever the amount is higher or lower than the threshold. Supported by Research Fund of Science and Technology Committee of Shanghai Municipality (08DZ2271100).

Emerging drugs for head and neck cancer

PubMed Central

Wen, Yihui; Grandis, Jennifer R

2017-01-01

Introduction Despite improvements in treatment, survival rates of head and neck squamous cell carcinoma (HNSCC) are stagnant. The existing chemotherapeutic agents are non-selective and associated with toxicities. Combinations of the only the US FDA-approved epidermal growth factor receptor (EGFR)-targeted agent, cetuximab, with chemotherapy or radiation improves overall survival. However, the response rates to cetuximab are modest. Thus, there is an urgent need for new agents that can be safely integrated into current treatment regimens to improve outcome. Areas covered Current EGFR-targeted drugs under clinical development include mAbs and tyrosine kinase inhibitors. The modest efficacy of these drugs implicates intrinsic or acquired resistance. Novel molecular agents inhibiting alternative targets to overcome anti-EGFR resistance in HNSCC are under investigation. Gene therapy and immunotherapy are also promising strategies to improve efficacy and reduce toxicity. Expert opinion To date, only six drugs have been FDA-approved for the treatment of head and neck cancer. Cetuximab is the only approved molecular targeting agent for HNSCC and despite ubiquitous expression of EGFR in HNSCC tumors, clinical responses are limited. Genetic and epigenetic characterization of HNSCC tumors, coupled with improved preclinical models, should facilitate the development of more effective drugs. PMID:25826749

Future immunosuppressive agents in solid-organ transplantation.

PubMed

Gabardi, Steven; Cerio, Jeffrey

2004-06-01

To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium, everolimus, and FTY720. Clinical trials and abstracts evaluating mycophenolate sodium, everolimus, and FTY720 in solid-organ transplantation were considered for evaluation. English-language studies and published abstracts were selected for inclusion. Mycophenolate sodium has recently been approved by the Food and Drug Adminstration for marketing in the United States; everolimus and FTY720 are immunosuppressive agents that may soon be available in the United States. These agents have proven efficacy in reducing the incidence of acute rejection in solid-organ transplantation. Clinical trials have shown that these newer agents are relatively well tolerated. The most common adverse events associated with these agents were gastrointestinal and hematologic effects (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and hematologic effects (everolimus): and gastrointestinal effects, headache, and bradycardia (FTY720). Mycophenolate sodium has been approved in some European countries and the United States. Everolimus has been approved in some European countries and a new drug application has been submitted to the Food and Drug Administration. FTY720 is currently in phase III clinical trials and submission to the Food and Drug Administration for approval is a few years away. The approval of these agents will furnish the transplant practitioner with even more options for immunosuppression.

Synergistic effects of nucleating agents and plasticizers on the crystallization behavior of poly(lactic acid).

PubMed

Shi, Xuetao; Zhang, Guangcheng; Phuong, Thanh Vu; Lazzeri, Andrea

2015-01-19

The synergistic effect of nucleating agents and plasticizers on the thermal and mechanical performance of PLA nanocomposites was investigated with the objective of increasing the crystallinity and balancing the stiffness and toughness of PLA mechanical properties. Calcium carbonate, halloysite nanotubes, talc and LAK (sulfates) were compared with each other as heterogeneous nucleating agents. Both the DSC isothermal and non-isothermal studies indicated that talc and LAK were the more effective nucleating agents among the selected fillers. Poly(D-lactic acid) (PDLA) acted also as a nucleating agent due to the formation of the PLA stereocomplex. The half crystallization time was reduced by the addition of talc to about 2 min from 37.5 min of pure PLA by the isothermal crystallization study. The dynamic mechanical thermal study (DMTA) indicated that nanofillers acted as both reinforcement fillers and nucleating agents in relation to the higher storage modulus. The plasticized PLA studied by DMTA indicated a decreasing glass transition temperature with the increasing of the PEG content. The addition of nanofiller increased the Young's modulus. PEG had the plasticization effect of increasing the break deformation, while sharply decreasing the stiffness and strength of PLA. The synergistic effect of nanofillers and plasticizer achieved the balance between stiffness and toughness with well-controlled crystallization.

New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463.

PubMed

Zhu, Yi; Doornebal, Ewald J; Pirtskhalava, Tamar; Giorgadze, Nino; Wentworth, Mark; Fuhrmann-Stroissnigg, Heike; Niedernhofer, Laura J; Robbins, Paul D; Tchkonia, Tamara; Kirkland, James L

2017-03-08

Senescent cells accumulate with aging and at sites of pathology in multiple chronic diseases. Senolytics are drugs that selectively promote apoptosis of senescent cells by temporarily disabling the pro-survival pathways that enable senescent cells to resist the pro-apoptotic, pro-inflammatory factors that they themselves secrete. Reducing senescent cell burden by genetic approaches or by administering senolytics delays or alleviates multiple age- and disease-related adverse phenotypes in preclinical models. Reported senolytics include dasatinib, quercetin, navitoclax (ABT263), and piperlongumine. Here we report that fisetin, a naturally-occurring flavone with low toxicity, and A1331852 and A1155463, selective BCL-X L inhibitors that may have less hematological toxicity than the less specific BCL-2 family inhibitor navitoclax, are senolytic. Fisetin selectively induces apoptosis in senescent but not proliferating human umbilical vein endothelial cells (HUVECs). It is not senolytic in senescent IMR90 cells, a human lung fibroblast strain, or primary human preadipocytes. A1331852 and A1155463 are senolytic in HUVECs and IMR90 cells, but not preadipocytes. These agents may be better candidates for eventual translation into clinical interventions than some existing senolytics, such as navitoclax, which is associated with hematological toxicity.

Ultrasensitive and Selective Organic FET-type Nonenzymatic Dopamine Sensor Based on Platinum Nanoparticles-Decorated Reduced Graphene Oxide.

PubMed

Oh, Jungkyun; Lee, Jun Seop; Jun, Jaemoon; Kim, Sung Gun; Jang, Jyongsik

2017-11-15

Dopamine (DA), a catecholamine hormone, is an important neurotransmitter that controls renal and cardiovascular organizations and regulates physiological activities. Abnormal concentrations of DA cause unfavorable neuronal illnesses such as Parkinson's disease, schizophrenia, and attention deficit hyperactivity disorder/attention deficit disorder. However, the DA concentration is exceedingly low in patients and difficult to detect with existing biosensors. In this study, we developed an organic field-effect-transistor-type (OFET) nonenzyme biosensor using platinum nanoparticle-decorated reduced graphene oxide (Pt_rGO) for ultrasensitive and selective DA detection. The Pt_rGOs were fabricated by reducing GO aqueous solution-containing Pt precursors (PtCl 4 ) with a chemical reducing agent. The Pt_rGOs were immobilized on a graphene substrate by π-π interactions and a conducting-polymer source-drain electrode was patterned on the substrate to form the DA sensor. The resulting OFET sensor showed a high sensitivity to remarkably low DA concentrations (100 × 10 -18 M) and selectivity among interfering molecules. Good stability was expected for the OFET sensor because it was fabricated without an enzymatic receptor, and π-π conjugation is a part of the immobilization process. Furthermore, the OFET sensors are flexible and offer the possibility of wide application as wearable and portable sensors.

Selective Reversible Inhibition of Liver Carnitine Palmitoyl-Transferase 1 by Teglicar Reduces Gluconeogenesis and Improves Glucose Homeostasis

PubMed Central

Conti, Roberto; Mannucci, Edoardo; Pessotto, Pompeo; Tassoni, Emanuela; Carminati, Paolo; Giannessi, Fabio; Arduini, Arduino

2011-01-01

OBJECTIVE We have developed a new antihyperglycemic agent (teglicar) through the selective and reversible inhibition of the liver isoform of carnitine palmitoyl-transferase 1 (L-CPT1). RESEARCH DESIGN AND METHODS Glucose production was investigated in isolated hepatocytes and during pancreatic clamps in healthy rats. Chronic treatments on C57BL/6J, db/db, high-fat fed mice, and rats were performed to understand glucose metabolism and insulin sensitivity. RESULTS In isolated hepatocytes, teglicar concentration dependently reduced ketone bodies and glucose production up to 72 and 50%, respectively. In rats, teglicar reduced the endogenous glucose production (−62%) without affecting peripheral glucose utilization. Heart 2-[3H]deoxyglucose uptake in mice was also not affected, confirming in vivo the drug selectivity toward L-CPT1. Chronic treatment in db/db mice (50 mg/kg/bid; 45 days) reduced postabsorptive glycemia (−38%), water consumption (−31%), and fructosamine (−30%). Such antidiabetic activity was associated with an improved insulin sensitivity assessed by the insulin tolerance test. A significant 50% increase in hepatic triglyceride content (HTGC) was found, although plasma alanineaminotransferase was not altered. In addition, long-term teglicar administration to high-fat fed C57BL/6J mice normalized glycemia (−19%) and insulinemia (−53%). Long-term teglicar administration (30 days, 80 mg/kg) in healthy overnight-fasted rats slightly reduced basal glycemia (−20%, ns), reduced basal insulin levels by 60%, doubled triglycerides, and increased free-fatty acids (+53%). HTGC was markedly increased, but liver and peripheral insulin sensitivity assessed by hyperinsulinemiceuglycemic clamp were not affected. CONCLUSIONS Teglicar, in vitro and in animal models, reduces gluconeogenesis and improves glucose homeostasis, refreshing the interest in selective and reversible L-CPT1 inhibition as a potential antihyperglycemic approach. PMID:21270274

Lorcaserin in Obese and Overweight Patients Taking Prohibited Serotonergic Agents: A Retrospective Analysis.

PubMed

Nguyen, Charles T; Zhou, Sharon; Shanahan, William; Fain, Randi

2016-06-01

Lorcaserin is a selective serotonin 2C receptor (5-HT2C) agonist approved in the United States for use in chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Its pharmacologic activity is limited to 5-HT subtype 2 receptors. The potency of lorcaserin for the 5-HT2C receptor is 14-fold greater than its potency for the 5-HT2A receptor and 61-fold greater than its potency for the 5-HT2B receptor. Although 5-HT receptors have been implicated in serotonin syndrome, the precise pathogenesis is unknown. Given a theoretic risk for this syndrome in patients administered lorcaserin either alone or in combination with certain serotonergic agents (eg, selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), patients taking prohibited serotonergic agents were excluded from the Phase III clinical trials. This retrospective analysis evaluated the tolerability of lorcaserin in patients who took protocol-allowed or proscribed serotonergic agents for varying durations of up to 1 year during the BLOOM, BLOSSOM, and BLOOM-DM studies. Patients randomly assigned to receive either lorcaserin 10 mg QD, lorcaserin 10 mg BID, or placebo and who took a spectrum of serotonergic agents were evaluated at week 52 of treatment (814 and 624 patients receiving lorcaserin and placebo, respectively, were found to have taken allowed or prohibited serotonergic agents during these trials). After the use of a proscribed serotonergic agent was discovered, these patients were discontinued from the trial and followed. None of the patients in the serotonergic agent subpopulation or in the overall safety population met the clinical criteria of serotonin syndrome. The proportions of patients experiencing any adverse event (AE) were balanced in the lorcaserin and placebo groups in the prohibited serotonergic agent subpopulation. The prevalences of the most common AEs were similar between the serotonergic agent subpopulation and the overall safety population. The concurrent use of lorcaserin and prohibited or allowed serotonergic agents did not appear to have increased the spectrum or intensity of AEs potentially associated with serotonin excess in this limited dataset. However, the sample population was too small to rule out an effect on a rare event such as serotonin syndrome. ClinicalTrials.gov identifiers: NCT00395135, NCT00603902, and NCT00603291. Published by Elsevier Inc.

Quinol derivatives as potential trypanocidal agents

PubMed Central

Capes, Amy; Patterson, Stephen; Wyllie, Susan; Hallyburton, Irene; Collie, Iain T.; McCarroll, Andrew J.; Stevens, Malcolm F.G.; Frearson, Julie A.; Wyatt, Paul G.; Fairlamb, Alan H.; Gilbert, Ian H.

2012-01-01

Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. PMID:22264753

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).

Comparative Analysis of Two Biological Warfare Air Samplers Using Live Surrogate Agents

DTIC Science & Technology

2012-03-01

extensively for Phosphate Buffer Saline (PBS) solution and water , and, to a very limited degree in AF evaluations, for virus preserving media, specifically...or water . Furthermore, viral studies have been conducted comparing the effectiveness of utilizing the reduced secondary flow rate on the XMX/2L...with using bioagent aerosols rated BSL-2 or higher. Male Specific Coliphage 2 (MS2), American Type Culture Collection (ATCC) 15597-B1, was selected

Hydrogen as a New Class of Radioprotective Agent

PubMed Central

Qian, Liren; Shen, Jianliang; Chuai, Yunhai; Cai, Jianming

2013-01-01

It is well known that most of the ionizing radiation-induced damage is caused by hydroxyl radicals (·OH) follows radiolysis of H2O. Molecular hydrogen (H2) has antioxidant activities by selectively reducing ·OH and peroxynitrite(ONOO-). We firstly hypothesized and demonstrated the radioprotective effect of H2 in vitro and in vivo, which was also repeated on different experimental animal models by different departments. A randomized, placebo-controlled study showed that consumption of hydrogen-rich water reduces the biological reaction to radiation-induced oxidative stress without compromising anti-tumor effects. These encouraging results suggested that H2 represents a potentially novel preventative strategy for radiation-induced oxidative injuries. H2 is explosive. Therefore, administration of hydrogen-rich solution (physiological saline/pure water/other solutions saturated with H2) may be more practical in daily life and more suitable for daily consumption. This review focuses on major scientific and clinical advances of hydrogen-rich solution/H2 as a new class of radioprotective agent. PMID:24155664

Synthesis and growth mechanism of sponge-like nickel using a hydrothermal method

NASA Astrophysics Data System (ADS)

Shao, Bin; Yin, Xueguo; Hua, Weidong; Ma, Yilong; Sun, Jianchun; Li, Chunhong; Chen, Dengming; Guo, Donglin; Li, Kejian

2018-05-01

Sponge-like nickel composed of micro-chains with a diameter of 1-5 μm was selectively synthesized by the hydrothermal method, using sodium hydroxide (NaOH) as the alkaline reagent, aqueous hydrazine as reducing agent and citric acid as a coordination agent. The time-dependent samples prepared at different NaOH concentrations were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectrometer (FTIR). The results showed that the agglomerates of nickel citrate hydrazine complex nanoplates were first precipitated and then reduced to prickly nickel micro-chains at a lower NaOH concentration, which played a role in the further formation of sponge-like nickel. Also, the probable growth mechanism of the sponge-like nickel was proposed. The magnetic properties of sponge-like nickel were studied using a vibrating sample magnetometer. The sponge-like nickel exhibited a ferromagnetic behavior with a saturation magnetization value of 43.8 emu g-1 and a coercivity value of 120.7 Oe.

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.

Review of Restricted Experiment Requests, Division of Select Agents and Toxins, Centers for Disease Control and Prevention, 2006-2013

PubMed Central

Smith, Jacinta; Weyant, Robbin

2015-01-01

The Centers for Disease Control and Prevention (CDC) Division of Select Agents and Toxins (DSAT) regulates laboratories that possess, use, or transfer select agents and toxins in the United States. DSAT also mitigates biosafety risks through the review of “restricted experiments,” which under the select agent regulations are experiments that pose heightened biosafety risks. From January 2006 through December 2013, DSAT received 618 requests from 109 entities to perform potentially restricted experiments. Of these requests, 85% were determined not to meet the regulatory definition of a restricted experiment, while 15% of the requests met the definition of a restricted experiment. Of the 91 restricted experiments proposed, DSAT approved 31 (34%) requests because the biosafety conditions proposed were commensurate with the experiments' biosafety risk. All 31 approved restricted experiments were for work with select toxins. DSAT did not approve 60 restricted experiment requests due to potentially serious biosafety risks to public health and safety. All 60 denied restricted experiments proposed inserting drug resistance traits into select agents that could compromise the control of disease. The select agents and toxins associated most frequently with requests that met the regulatory definition of a restricted experiment are Shiga toxin (n = 16), Burkholderia mallei (n = 15), Botulinum neurotoxin (n = 14), and Brucella abortus (n = 14). In general, all restricted experiment decisions are determined on a case-by-case basis. This article describes the trends and characteristics of the data associated with restricted experiment requests among select agents that have an impact on public health and safety (HHS only agents) or both public health and safety and animal health or products (overlap agents). The information presented here, coupled with the information published in the restricted experiment guidance document (www.selectagents.gov), is intended to promote awareness among the research community of the type of experiments that meet the regulatory definition of a restricted experiment as well as to provide a greater understanding of the restricted experiment review process. PMID:26347984

Group Cooperation without Group Selection: Modest Punishment Can Recruit Much Cooperation

PubMed Central

Cosmides, Leda; Tooby, John

2015-01-01

Humans everywhere cooperate in groups to achieve benefits not attainable by individuals. Individual effort is often not automatically tied to a proportionate share of group benefits. This decoupling allows for free-riding, a strategy that (absent countermeasures) outcompetes cooperation. Empirically and formally, punishment potentially solves the evolutionary puzzle of group cooperation. Nevertheless, standard analyses appear to show that punishment alone is insufficient, because second-order free riders (those who cooperate but do not punish) can be shown to outcompete punishers. Consequently, many have concluded that other processes, such as cultural or genetic group selection, are required. Here, we present a series of agent-based simulations that show that group cooperation sustained by punishment easily evolves by individual selection when you introduce into standard models more biologically plausible assumptions about the social ecology and psychology of ancestral humans. We relax three unrealistic assumptions of past models. First, past models assume all punishers must punish every act of free riding in their group. We instead allow punishment to be probabilistic, meaning punishers can evolve to only punish some free riders some of the time. This drastically lowers the cost of punishment as group size increases. Second, most models unrealistically do not allow punishment to recruit labor; punishment merely reduces the punished agent’s fitness. We instead realistically allow punished free riders to cooperate in the future to avoid punishment. Third, past models usually restrict agents to interact in a single group their entire lives. We instead introduce realistic social ecologies in which agents participate in multiple, partially overlapping groups. Because of this, punitive tendencies are more expressed and therefore more exposed to natural selection. These three moves toward greater model realism reveal that punishment and cooperation easily evolve by direct selection—even in sizeable groups. PMID:25893241

Varied exposure to carcinogenic, mutagenic, and reprotoxic (CMR) chemicals in occupational settings in France.

PubMed

Havet, Nathalie; Penot, Alexis; Morelle, Magali; Perrier, Lionel; Charbotel, Barbara; Fervers, Béatrice

2017-02-01

To explore varied exposure to carcinogenic, mutagenic, and reprotoxic chemicals (CMR) for French employees. Our study assessed data from the French national cross-sectional survey of occupational risks (SUMER) that was conducted in 2010 in a national representative sample of employees. We selected 28 CMR agents that were classified by the International Agency for Research on Cancer or European Union as being known or presumed to have CMR potential in humans. The association of individual and job characteristics with exposure prevalence, duration, and intensity of the CMR agents during a 1-week period was examined using multilevel logistic regression analysis. Overall, 10.4% of employees in 2010 were exposed to one or more CMR agents at their workplace, and 3.4% were subjected to multiple CMR exposures. Blue-collar workers, night-shift workers and workers with short-term employment contracts experienced higher exposure prevalence (p < 0.01) and intensity (p < 0.05). Blue-collar workers and shift workers experienced also longer exposure duration (p < 0.001). Conversely, managers, workers of large companies, and women were less exposed to CMR agents (p < 0.001). The presence of a Committee for Health, Safety, and Working Conditions, and intervention by Occupational Health and Safety officers were significantly associated with reduced exposure intensities (p < 0.001 and p < 0.05). Establishment of European CMR regulations and the existence of an applicable substitution principle reduced the exposure duration (p < 0.001) and intensity (p < 0.05). Our results point out disparities in CMR exposure and identify high-priority targets for prevention measures to help reducing social health discrepancies.

"Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy.

PubMed

Kemp, Jessica A; Shim, Min Suk; Heo, Chan Yeong; Kwon, Young Jik

2016-03-01

The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

Controllable reductive method for synthesizing metal-containing particles

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

Moon, Ji-Won; Jung, Hyunsung; Phelps, Tommy Joe

The invention is directed to a method for producing metal-containing particles, the method comprising subjecting an aqueous solution comprising a metal salt, E.sub.h, lowering reducing agent, pH adjusting agent, and water to conditions that maintain the E.sub.h value of the solution within the bounds of an E.sub.h-pH stability field corresponding to the composition of the metal-containing particles to be produced, and producing said metal-containing particles in said aqueous solution at a selected E.sub.h value within the bounds of said E.sub.h-pH stability field. The invention is also directed to the resulting metal-containing particles as well as devices in which they aremore » incorporated.« less

Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Shan, Liang; Gu, Xinbin; Wang, Paul

2013-09-01

Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

Adaptive consensus of scale-free multi-agent system by randomly selecting links

NASA Astrophysics Data System (ADS)

Mou, Jinping; Ge, Huafeng

2016-06-01

This paper investigates an adaptive consensus problem for distributed scale-free multi-agent systems (SFMASs) by randomly selecting links, where the degree of each node follows a power-law distribution. The randomly selecting links are based on the assumption that every agent decides to select links among its neighbours according to the received data with a certain probability. Accordingly, a novel consensus protocol with the range of the received data is developed, and each node updates its state according to the protocol. By the iterative method and Cauchy inequality, the theoretical analysis shows that all errors among agents converge to zero, and in the meanwhile, several criteria of consensus are obtained. One numerical example shows the reliability of the proposed methods.

Housing Interventions and Control of Asthma-Related Indoor Biologic Agents: A Review of the Evidence

PubMed Central

Krieger, James; Jacobs, David E.; Ashley, Peter J.; Baeder, Andrea; Chew, Ginger L.; Dearborn, Dorr; Hynes, H. Patricia; Miller, J. David; Morley, Rebecca; Rabito, Felicia; Zeldin, DC

2014-01-01

Subject matter experts systematically reviewed evidence on the effectiveness of housing interventions that affect health outcomes, primarily asthma, associated with exposure to moisture, mold, and allergens. Three of the 11 interventions reviewed had sufficient evidence for implementation: multifaceted, in-home, tailored interventions for reducing asthma morbidity; integrated pest management to reduce cockroach allergen; and combined elimination of moisture intrusion and leaks and removal of moldy items to reduce mold and respiratory symptoms. Four interventions needed more field evaluation, one needed formative research, and three either had no evidence of effectiveness or were ineffective. The three interventions with sufficient evidence all applied multiple, integrated strategies. This evidence review shows that selected interventions that improve housing conditions will reduce morbidity from asthma and respiratory allergies. PMID:20689369

Housing interventions and control of asthma-related indoor biologic agents: a review of the evidence.

PubMed

Krieger, James; Jacobs, David E; Ashley, Peter J; Baeder, Andrea; Chew, Ginger L; Dearborn, Dorr; Hynes, H Patricia; Miller, J David; Morley, Rebecca; Rabito, Felicia; Zeldin, Darryl C

2010-01-01

Subject matter experts systematically reviewed evidence on the effectiveness of housing interventions that affect health outcomes, primarily asthma, associated with exposure to moisture, mold, and allergens. Three of the 11 interventions reviewed had sufficient evidence for implementation: multifaceted, in-home, tailored interventions for reducing asthma morbidity; integrated pest management to reduce cockroach allergen; and combined elimination of moisture intrusion and leaks and removal of moldy items to reduce mold and respiratory symptoms. Four interventions needed more field evaluation, 1 needed formative research, and 3 either had no evidence of effectiveness or were ineffective. The 3 interventions with sufficient evidence all applied multiple, integrated strategies. This evidence review shows that selected interventions that improve housing conditions will reduce morbidity from asthma and respiratory allergies.

Biomass Pyrolysis Solids as Reducing Agents: Comparison with Commercial Reducing Agents.

PubMed

Adrados, Aitziber; De Marco, Isabel; López-Urionabarrenechea, Alexander; Solar, Jon; Caballero, Blanca M; Gastelu, Naia

2015-12-23

Biomass is one of the most suitable options to be used as renewable energy source due to its extensive availability and its contribution to reduce greenhouse gas emissions. Pyrolysis of lignocellulosic biomass under appropriate conditions (slow heating rate and high temperatures) can produce a quality solid product, which could be applicable to several metallurgical processes as reducing agent (biocoke or bioreducer). Two woody biomass samples (olives and eucalyptus) were pyrolyzed to produce biocoke. These biocokes were characterized by means of proximate and ultimate analysis, real density, specific surface area, and porosity and were compared with three commercial reducing agents. Finally, reactivity tests were performed both with the biocokes and with the commercial reducing agents. Bioreducers have lower ash and sulfur contents than commercial reducers, higher surface area and porosity, and consequently, much higher reactivity. Bioreducers are not appropriate to be used as top burden in blast furnaces, but they can be used as fuel and reducing agent either tuyére injected at the lower part of the blast furnace or in non-ferrous metallurgical processes where no mechanical strength is needed as, for example, in rotary kilns.

Microbial Resistance to Triclosan: A Case Study in Natural Selection

ERIC Educational Resources Information Center

Serafini, Amanda; Matthews, Dorothy M.

2009-01-01

Natural selection is the mechanism of evolution caused by the environmental selection of organisms most fit to reproduce, sometimes explained as "survival of the fittest." An example of evolution by natural selection is the development of bacteria that are resistant to antimicrobial agents as a result of exposure to these agents. Triclosan, which…

Evaluating food additives as antifungal agents against Monilinia fructicola in vitro and in hydroxypropyl methylcellulose-lipid composite edible coatings for plums.

PubMed

Karaca, Hakan; Pérez-Gago, María B; Taberner, Verònica; Palou, Lluís

2014-06-02

Common food preservative agents were evaluated in in vitro tests for their antifungal activity against Monilinia fructicola, the most economically important pathogen causing postharvest disease of stone fruits. Radial mycelial growth was measured in Petri dishes of PDA amended with three different concentrations of the agents (0.01-0.2%, v/v) after 7 days of incubation at 25 °C. Thirteen out of fifteen agents tested completely inhibited the radial growth of the fungus at various concentrations. Among them, ammonium carbonate, ammonium bicarbonate and sodium bicarbonate were the most effective while sodium acetate and sodium formate were the least effective. The effective agents and concentrations were tested as ingredients of hydroxypropyl methylcellulose (HPMC)-lipid edible coatings against brown rot disease on plums previously inoculated with M. fructicola (curative activity). 'Friar' and 'Larry Ann' plums were inoculated with the pathogen, coated with stable edible coatings about 24h later, and incubated at 20 °C and 90% RH. Disease incidence (%) and severity (lesion diameter) were determined after 4, 6, and 8 days of incubation and the 'area under the disease progress stairs' (AUDPS) was calculated. Coatings containing bicarbonates and parabens significantly reduced brown rot incidence in plums, but potassium sorbate, used at 1.0% in the coating formulation, was the most effective agent with a reduction rate of 28.6%. All the tested coatings reduced disease severity to some extent, but coatings containing 0.1% sodium methylparaben or sodium ethylparaben or 0.2% ammonium carbonate or ammonium bicarbonate were superior to the rest, with reduction rates of 45-50%. Overall, the results showed that most of the agents tested in this study had significant antimicrobial activity against M. fructicola and the application of selected antifungal edible coatings is a promising alternative for the control of postharvest brown rot in plums. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of different classes of beta-antagonists on clinical and experimental hypertension.

PubMed

Fitzgerald, J D

1982-01-01

The reference beta adrenoceptor antagonist propranolol reduces blood pressure in about 60% of patients with essential hypertension. Pressure is reduced in the supine, and erect positions without postural hypotension as well as during exercise. The average extent of pressure reduction is approximately 26/16 mm.Hg. Though all clinically available beta antagonists reduce blood pressure, the profile may be modified by both adrenotropic and non-adrenotropic ancillary properties. Of the adrenotropic properties, potency influences dose frequency and total body burden of drug. Selective beta 1 antagonism may enhance safety without reducing efficacy in patients with obstructive airways disease. Selective beta 2 blockade does not reduce blood pressure in experimental models or normal subjects, but the response in patients is unknown. Partial agonism may reduce efficacy if the degree of stimulant activity is too great. Of the non-adrenotropic properties, membrane stabilising properties are of relevance only in so far as such agents undergo extensive biotransformation resulting in either reduced efficacy when drugs are used at fixed doses or the formation of biologically active metabolites. The additional properties of either alpha adrenergic blockade or inhibition of vascular smooth muscle tone modify both the speed of onset and the haemodynamic profile. The interaction of these ancillary pharmacological properties is evaluated in this review.

Biocontrol Ability and Action Mechanism of Starmerella bacillaris (Synonym Candida zemplinina) Isolated from Wine Musts against Gray Mold Disease Agent Botrytis cinerea on Grape and Their Effects on Alcoholic Fermentation

PubMed Central

Lemos Junior, Wilson José Fernandes; Bovo, Barbara; Nadai, Chiara; Crosato, Giulia; Carlot, Milena; Favaron, Francesco; Giacomini, Alessio; Corich, Viviana

2016-01-01

Gray mold is one of the most important diseases of grapevine in temperate climates. This plant pathogen affects plant growth and reduces wine quality. The use of yeasts as biocontrol agents to apply in the vineyard have been investigated in recent years as an alternative to agrochemicals. In this work, fermenting musts obtained from overripe grape berries, therefore more susceptible to infection by fungal pathogens such as Botrytis cinerea, were considered for the selection of yeasts carrying antifungal activity. Thirty-six isolates were identified as Starmerella bacillaris, a species recently proven to be of enological interest. Among them 14 different strains were studied and antifungal activity against B. cinerea was demonstrated, for the first time, to be present in S. bacillaris species. The production of volatile organic compounds (VOCs), tested in vitro, was found to be the main responsible of S. bacillaris antifungal effects. All the strains were able to reduce B. cinerea decay on wounded grape berries artificially inoculated with gray mold. The colonization level of wound was very high reaching, after 5 days, a concentration of 106 cells per ml of grape juice obtained after berry crushing. At this cell concentration S. bacillaris strains were used to ferment synthetic and natural musts. The sequential yeast inoculation, performed by adding S. cerevisiae 48 h after S. bacillaris, was needed to complete sugar consumption and determined a significant increase in glicerol content and a reduction of ethanol and acetic acid concentrations. The high wound colonization ability, found in this work, together with the propensity to colonize grape berry and the interesting enological traits possessed by the selected S. bacillaris strains allow the use of this yeast as biocontrol agent on vine and grape berries with possible positive effects on must fermentation, although the presence of S. cerevisiae is needed to complete the fermentation process. This work introduces new possibilities in wine yeast selection programs in order to identify innovative wine yeasts that are simultaneously antifungal agents in vineyards and alternative wine starters for grape must fermentation and open new perspective to a more integrated strategy for increasing wine quality. PMID:27574517

Biological interactions to select biocontrol agents against toxigenic strains of Aspergillus flavus and Fusarium verticillioides from maize.

PubMed

Etcheverry, Miriam G; Scandolara, Andrea; Nesci, Andrea; Vilas Boas Ribeiro, Marta Sofia; Pereira, Paola; Battilani, Paola

2009-05-01

Biological control represent an alternative to the use of pesticides in crop protection. A key to progress in biological control to protect maize against Fusarium verticillioides and Aspergillus flavus maize pathogens are, to select in vitro, the best agent to be applied in the field. The aim of this study was to examine the antagonistic activity of bacterial and yeast isolates against F.verticillioides and A. flavus toxigenic strains. The first study showed the impact of Bacillus amyloliquefaciens BA-S13, Microbacterium oleovorans DMS 16091, Enterobacter hormomaechei EM-562T, and Kluyveromyces spp. L14 and L16 isolates on mycelial growth of two strains of A. flavus MPVPA 2092, 2094 and three strains of F. verticillioides MPVPA 285, 289, and 294 on 3% maize meal extract agar at different water activities (0.99, 0.97, 0.95, and 0.93). From this first assay antagonistics isolates M. oleovorans, B. amyloliquefaciens and Kluyveromyces sp. (L16) produced an increase of lag phase of growth and decreased a growth rate of all fungal strains. These isolates were selected for futher studies. In vitro non-rhizospheric maize soil (centrally and sprayed inoculated) and in vitro maize (ears apex and base inoculated) were treated with antagonistics and pathogenic strains alone in co-inoculated cultures. Bacillus amyloliquefaciens significantly reduced F. verticillioides and A. flavus count in maize soil inoculated centrally. Kluyveromyces sp. L16 reduced F. verticillioides and A. flavus count in maize soil inoculated by spray. Kluyveromyces sp. L16 was the most effective treatment limiting percent infections by F. verticillioides on the maize ears.

Reducing agent can be omitted in the incubation medium of the batch in vitro fermentation model of the pig intestines.

PubMed

Poelaert, C; Nollevaux, G; Boudry, C; Taminiau, B; Nezer, C; Daube, G; Schneider, Y-J; Portetelle, D; Théwis, A; Bindelle, J

2018-06-01

Over the past decade, in vitro methods have been developed to study intestinal fermentation in pigs and its influence on the digestive physiology and health. In these methods, ingredients are fermented by a bacterial inoculum diluted in a mineral buffer solution. Generally, a reducing agent such as Na2S or cysteine-HCl generates the required anaerobic environment by releasing metabolites similar to those produced when protein is fermented, possibly inducing a dysbiosis. An experiment was conducted to study the impact of two reducing agents on results yielded by such in vitro fermentation models. Protein (soybean proteins, casein) and carbohydrate (potato starch, cellulose) ingredients were fermented in vitro by bacteria isolated from fresh feces obtained from three sows in three carbonate-based incubation media differing in reducing agent: (i) Na2S, (ii) cysteine-HCl and (iii) control with a mere saturation with CO2 and devoid of reducing agent. The gas production during fermentation was recorded over 72 h. Short-chain fatty acids (SCFA) production after 24 and 72 h and microbial composition of the fermentation broth after 24 h were compared between ingredients and between reducing agents. The fermentation residues after 24 h were also evaluated in terms of cytotoxicity using Caco-2 cell monolayers. Results showed that the effect of the ingredient induced higher differences than the reducing agent. Among the latter, cysteine-HCl induced the strongest differences compared with the control, whereas Na2S was similar to the control for most parameters. For all ingredients, final gas produced per g of substrate was similar (P>0.10) for the three reducing agents whereas the maximum rate of gas production (R max) was reduced (P0.10) after 24 h of fermentation with Na2S and in the control without reducing agent. Molar ratios of branched chain-fatty acids were higher (P<0.05) for protein (36.5% and 9.7% for casein and soybean proteins, respectively) than for carbohydrate (<4%) ingredients. Only fermentation residues of casein showed a possible cytotoxic effect regardless of the reducing agent (P<0.05). Concerning the microbial composition of the fermentation broth, most significant differences in phyla and in genera ascribable to the reducing agent were found with potato starch and casein. In conclusion, saturating the incubation media with CO2 seems sufficient to generate a suitable anaerobic environment for intestinal microbes and the use of a reducing agent can be omitted.

Fluorination utilizing thermodynamically unstable fluorides and fluoride salts thereof

DOEpatents

Bartlett, Neil; Whalen, J. Marc; Chacon, Lisa

2000-12-12

A method for fluorinating a carbon compound or cationic carbon compound utilizes a fluorination agent selected from thermodynamically unstable nickel fluorides and salts thereof in liquid anhydrous hydrogen fluoride. The desired carbon compound or cationic organic compound to undergo fluorination is selected and reacted with the fluorination agent by contacting the selected organic or cationic organic compound and the chosen fluorination agent in a reaction vessel for a desired reaction time period at room temperature or less.

Treatment with biologic agents improves the prognosis of patients with rheumatoid arthritis and amyloidosis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

2012-07-01

Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy. One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated. Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance. Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate.

Non-aflatoxigenic Aspergillus flavus as potential biocontrol agents to reduce aflatoxin contamination in peanuts harvested in Northern Argentina.

PubMed

Alaniz Zanon, María Silvina; Barros, Germán Gustavo; Chulze, Sofía Noemí

2016-08-16

Biological control is one of the most promising strategies for preventing aflatoxin contamination in peanuts at field stage. A population of 46 native Aspergillus flavus nonaflatoxin producers were analysed based on phenotypic, physiological and genetic characteristics. Thirty-three isolates were characterized as L strain morphotype, 3 isolates as S strain morphotype, and 10 isolates did not produce sclerotia. Only 11 of 46 non-aflatoxigenic isolates did not produce cyclopiazonic acid. The vegetative compatibility group (VCG) diversity index for the population was 0.37. For field trials we selected the non-aflatoxigenic A. flavus AR27, AR100G and AFCHG2 strains. The efficacy of single and mixed inocula as potential biocontrol agents in Northern Argentina was evaluated through a 2-year study (2014-2015). During the 2014 peanut growing season, most of the treatments reduced the incidence of aflatoxigenic strains in both soil and peanut kernel samples, and no aflatoxin was detected in kernels. During the 2015 growing season, there was a reduction of aflatoxigenic strains in kernel samples from the plots treated with the potential biocontrol agents. Reductions of aflatoxin contamination between 78.36% and 89.55% were observed in treated plots in comparison with the un-inoculated control plots. This study provides the first data on aflatoxin biocontrol based on competitive exclusion in the peanut growing region of Northern Argentina, and proposes bioproducts with potential use as biocontrol agents. Copyright © 2016. Published by Elsevier B.V.

Carotid Artery Stenting, Endarterectomy, or Medical Treatment Alone: The Debate Is Not Over

PubMed Central

Kassaian, Seyed Ebrahim; Goodarzynejad, Hamidreza

2011-01-01

The management of carotid artery stenosis reduces the risk of stroke and its related deaths. Management options include risk factor modification and medical therapy, carotid endarterectomy (CEA), and carotid artery stenting (CAS). Although several randomized controlled trials (RCTs), mostly conducted in late-1980s and mid-1990s, have proved CEA to be effective in the prevention of ipsilateral ischemic events in selected patients with carotid artery stenosis, aggressive risk factor modification and medical therapy with recently introduced antiplatelet agents, statins, and more effective antihypertensive medications may have reduced compelling indications for immediate surgery in asymptomatic populations. Also recently, due to improvements in percutaneous techniques and carotid stents, CAS has received wide attention as a potential alternative to CEA. Herein, we review the recent data on the management options of carotid artery stenosis and seek to identify the most appropriate treatment strategy in selected patients with carotid artery stenosis. PMID:23074598

75 FR 44724 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Reorganization of the Select Agent and Toxin List AGENCY: Animal and Plant Health Inspection Service, USDA... Agricultural Bioterrorism Protection Act of 2002, we are soliciting public comment regarding the list of select...

Limiting the protein corona: A successful strategy for in vivo active targeting of anti-HER2 nanobody-functionalized nanostars.

PubMed

D'Hollander, Antoine; Jans, Hilde; Velde, Greetje Vande; Verstraete, Charlotte; Massa, Sam; Devoogdt, Nick; Stakenborg, Tim; Muyldermans, Serge; Lagae, Liesbet; Himmelreich, Uwe

2017-04-01

Gold nanoparticles hold great promise as anti-cancer theranostic agents against cancer by actively targeting the tumor cells. As this potential has been supported numerously during in vitro experiments, the effective application is hampered by our limited understanding and control of the interactions within complex in vivo biological systems. When these nanoparticles are exposed to a biological environment, their surfaces become covered with proteins and biomolecules, referred to as the protein corona, reducing the active targeting capabilities. We demonstrate a chemical strategy to overcome this issue by reducing the protein corona's thickness by blocking the active groups of the self-assembled monolayer on gold nanostars. An optimal blocking agent, 2-mercapto ethanol, has been selected based on charge and length of the carbon chain. By using a nanobody as a biological ligand of the human epidermal growth factor 2 receptor (HER2), the active targeting is demonstrated in vitro and in vivo in an experimental tumor model by using darkfield microscopy and photoacoustic imaging. In this study, we have established gold nanostars as a conceivable theranostic agent with a specificity for HER2-positive tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Biological Select Agents and Toxins: Risk-Based Assessment Management and Oversight.

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

Burnett, LouAnn Crawford; Brodsky, Benjamin H.

Sandia National Laboratories' International Biological and Chemical Threat Reduction (SNL/IBCTR) conducted, on behalf of the Federal Select Agent Program (FSAP), a review of risk assessment in modern select agent laboratories. This review and analysis consisted of literature review, interviews of FSAP staff, entities regulated by FSAP, and deliberations of an expert panel. Additionally, SNL/IBCTR reviewed oversight mechanisms used by industries, US agencies, and other countries for high-consequence risks (e.g, nuclear, chemical, or biological materials, aviation, off-shore drilling, etc.) to determine if alternate oversight mechanisms existed that might be applicable to FSAP oversight of biological select agents and toxins. This reportmore » contains five findings, based on these reviews and analyses, with recommendations and suggested actions for FSAP to consider.« less

Pollinator-mediated natural selection in Penstemon digitalis.

PubMed

Parachnowitsch, Amy; Kessler, André

2010-12-01

Measuring the agents of natural selection is important because it allows us to understand not only which traits are expected to evolve but also why they will evolve. Natural selection by pollinators on floral traits is often assumed because in outcrossing animal-pollinated plants flowers are generally thought to function as advertisements of rewards directed at pollinators. We tested the role of bee pollinators in selection on Penstemon digitalis and found that pollinators were driving selection for larger and more flowers. However, what makes our publication unique is the additional information we gained from reviewing the few other studies that also directly tested whether pollinators were agents of selection on floral traits. As we would expect if pollinators are important agents of selection, selection on floral traits was significantly stronger when pollinators were present than when they were experimentally removed. Taken together, these results suggest that pollinators can be important drivers of selection in contemporary populations.

The selective estrogen receptor modulators in breast cancer prevention.

PubMed

Li, Fangxuan; Dou, Jinli; Wei, Lijuan; Li, Shixia; Liu, Juntian

2016-05-01

Persistently increased blood levels of estrogens are associated with an increased risk of breast cancer. Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor (ER). Several clinical trials have demonstrated the effectiveness of its prophylactic administration. Incidence of invasive ER-positive breast cancer was reduced by SERMs treatment, especially for those women with high risk of developing breast cancer. In this study, we reviewed the clinical application of SERMs in breast cancer prevention. To date, four prospective randomized clinical trials had been performed to test the efficacy of tamoxifen for this purpose. Concerning on the benefit and cost of tamoxifen, various studies from different countries demonstrated that chemoprevention with tamoxifen seemed to be cost-effective for women with a high risk of invasive breast cancer. Based above, tamoxifen was approved for breast cancer prevention by the US Food and Drug Administration in 1998. Raloxifene was also approved for postmenopausal women in 2007 for breast cancer prevention which reduces the risk of invasive breast cancer with a lower risk of unwanted stimulation of endometrium. Thus, raloxifene is considered to have a better clinical possesses as prophylactic agent. Several other agents, such as arzoxifene and lasofoxifene, are currently being investigated in clinic. The American Society of Clinical Oncology and National Comprehensive Cancer Network had published guidelines on breast cancer chemoprevention by SERMs. However, use of tamoxifen and raloxifene for primary breast cancer prevention was still low. A broader educational effort is needed to alert women and primary care physicians that SERMs are available to reduce breast cancer risk.

Information security for compliance with select agent regulations.

PubMed

Lewis, Nick; Campbell, Mark J; Baskin, Carole R

2015-01-01

The past decade has seen a significant rise in research on high-consequence human and animal pathogens, many now known as "select agents." While physical security around these agents is tightly regulated, information security standards are still lagging. The understanding of the threats unique to the academic and research environment is still evolving, in part due to poor communication between the various stakeholders. Perhaps as a result, information security guidelines published by select agent regulators lack the critical details and directives needed to achieve even the lowest security level of the Federal Information Security Management Act (FISMA). While only government agencies are currently required to abide by the provisions of FISMA (unless specified as preconditions for obtaining government grants or contracts--still a relatively rare or narrowly scoped occurrence), the same strategies were recently recommended by executive order for others. We propose that information security guidelines for select agent research be updated to promulgate and detail FISMA standards and processes and that the latter be ultimately incorporated into select agent regulations. We also suggest that information security in academic and research institutions would greatly benefit from active efforts to improve communication among the biosecurity, security, and information technology communities, and from a secure venue for exchange of timely information on emerging threats and solutions in the research environment.

Information Security for Compliance with Select Agent Regulations

PubMed Central

Lewis, Nick; Campbell, Mark J.

2015-01-01

The past decade has seen a significant rise in research on high-consequence human and animal pathogens, many now known as “select agents.” While physical security around these agents is tightly regulated, information security standards are still lagging. The understanding of the threats unique to the academic and research environment is still evolving, in part due to poor communication between the various stakeholders. Perhaps as a result, information security guidelines published by select agent regulators lack the critical details and directives needed to achieve even the lowest security level of the Federal Information Security Management Act (FISMA). While only government agencies are currently required to abide by the provisions of FISMA (unless specified as preconditions for obtaining government grants or contracts—still a relatively rare or narrowly scoped occurrence), the same strategies were recently recommended by executive order for others. We propose that information security guidelines for select agent research be updated to promulgate and detail FISMA standards and processes and that the latter be ultimately incorporated into select agent regulations. We also suggest that information security in academic and research institutions would greatly benefit from active efforts to improve communication among the biosecurity, security, and information technology communities, and from a secure venue for exchange of timely information on emerging threats and solutions in the research environment. PMID:26042864

Method for photo-altering a biological system to improve biological effect

DOEpatents

Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

2000-08-01

Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

Synthesis of Cryptophycin Affinity Labels and Tubulin Labeling

DTIC Science & Technology

2004-05-01

isolated from blue-green algae ( Nostoc sp.), are a new and potent tumor-selective class of tubulin-binding antimitotic agents that show excellent activity... Nostoc sp.3𔃾 and displays IC 50 values in the pM range. Of special importance is the reduced susceptibility of the cryptophycins to P-glycoprotein...also named arenastatin A), isolated from the Okinawan marine sponge Dysidea arenaria5 and later from Nostoc sp. strain GSV 224,6 is also a potent

Synthesis of Cryptophycin Affinity Labels and Tubulin Labeling

DTIC Science & Technology

2005-05-01

isolated from blue-green algae ( Nostoc sp.), are a new and potent tumor-selective class of tubulin-binding antimitotic agents’ that show excellent activity... Nostoc sp. 4𔃿 and displays IC 5 0 values in the pM range. Of special importance is the reduced susceptibility of the cryptophycins to P-glycoprotein...also named arenastatin A), isolated from the Okinawan marine sponge Dysidea arenaria6 and later from Nostoc sp. strain GSV 224,7 is also a potent

Toward the Realization of a Compact Chemical Sensor Platform using Quantum Cascade Lasers

DTIC Science & Technology

2015-09-01

bromide (KBr) beamsplitter and a mercury cadmium telluride ( MCT )-A (narrow band – 650 cm-1 cutoff) detector . Each spectrum was acquired at a resolution...focuses on increasing speed, sensitivity, and selectivity, while reducing size and cost. Although the current state-of-the-art vapor detector (Joint...Chemical Agent Detector (JCAD)) is lightweight, handheld, and easily attaches to a belt, it still provides added bulk to a soldier on foot patrol. Both

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.

Relative toxicity and residual activity of insecticides used in blueberry pest management: mortality of natural enemies.

PubMed

Roubos, Craig R; Rodriguez-Saona, Cesar; Holdcraft, Robert; Mason, Keith S; Isaacs, Rufus

2014-02-01

A series of bioassays were conducted to determine the relative toxicities and residual activities of insecticides labeled for use in blueberry (Vaccinium corymbosum L.) on natural enemies, to identify products with low toxicity or short duration effects on biological control agents. In total, 14 insecticides were evaluated using treated petri dishes and four commercially available natural enemies (Aphidius colemani Viereck, Orius insidiosus [Say], Chrysoperla rufilabris [Burmeister], and Hippodamia convergens [Guérin-Menéville]). Dishes were aged under greenhouse conditions for 0, 3, 7, or 14 d before introducing insects to test residual activity. Acute effects (combined mortality and knockdown) varied by insecticide, residue age, and natural enemy species. Broad-spectrum insecticides caused high mortality to all biocontrol agents, whereas products approved for use in organic agriculture had little effect. The reduced-risk insecticide acetamiprid consistently caused significant acute effects, even after aging for 14 d. Methoxyfenozide, novaluron, and chlorantraniliprole, which also are classified as reduced-risk insecticides, had low toxicity, and along with the organic products could be compatible with biological control. This study provides information to guide blueberry growers in their selection of insecticides. Further research will be needed to determine whether adoption of a pest management program based on the use of more selective insecticides will result in higher levels of biological control in blueberry.

General and specialized media routinely employed for primary isolation of bacterial pathogens of fishes

USGS Publications Warehouse

Starliper, C.E.

2008-01-01

There are a number of significant diseases among cultured and free-ranging freshwater fishes that have a bacterial etiology; these represent a variety of gram-negative and gram-positive genera. Confirmatory diagnosis of these diseases involves primary isolation of the causative bacterium on bacteriologic media. Frequently used "general" bacteriologic media simply provide the essential nutrients for growth. For most of the major pathogens, however, there are differential and/or selective media that facilitate primary recovery. Some specialized media are available as "ready-to-use" from suppliers, while others must be prepared. Differential media employ various types of indicator systems, such as pH indicators, that allow diagnosticians to observe assimilation of selected substrates. An advantage to the use of differential media for primary isolation is that they hasten bacterial characterization by yielding the appropriate positive or negative result for a particular substrate, often leading to a presumptive identification. Selective media also incorporate agent(s) that inhibit the growth of contaminants typically encountered with samples from aquatic environments. Media that incorporate differential and/or selective components are ideally based on characters that are unique to the targeted bacterium, and their use can reduce the time associated with diagnosis and facilitate early intervention in affected fish populations. In this review, the concepts of general and differential/selective bacteriologic media and their use and development for fish pathogens are discussed. The media routinely employed for primary isolation of the significant bacterial pathogens of fishes are presented. ?? Wildlife Disease Association 2008.

The roles of the cyclo-oxygenases types one and two in prostaglandin synthesis in human fetal membranes at term.

PubMed

Sawdy, R J; Slater, D M; Dennes, W J; Sullivan, M H; Bennett, P R

2000-01-01

The aim of this study was to determine the relative contributions of cyclo-oxygenase (COX) types 1 and 2 to prostaglandin synthesis at term. Fetal membranes were collected from 6 pregnancies after elective caesarean section at term, prior to labour. The presence of COX-1 and COX-2 protein was determined using Western analysis. The relative contributions of the two isoforms of COX to prostaglandin synthesis were determined by incubation of fetal membrane discs with either a COX-2 selective inhibitor, SC236, or a COX-1 selective inhibitor, SC560, and measurement of prostaglandin release during 24 h using enzyme-linked immuno-sorbent assay (ELISA). Both COX-1 and COX-2 protein were demonstrated in amnion and chorion-decidua. The COX-2 selective inhibitor, SC-236, significantly reduced prostaglandin synthesis, both in its COX-2 specific and higher, non-specific concentration ranges. The COX-1 selective inhibitor, SC-560, had no effect upon prostaglandin synthesis in its COX-1 specific concentration range, but did significantly reduce prostaglandin synthesis at higher, non-selective concentrations. Fetal membranes contain both COX-1 and COX-2 at term, but only COX-2 contributes towards prostaglandin synthesis. COX-2 selective NSAI drugs will be as effective as non-selective agents in inhibition of fetal membrane prostaglandin synthesis and may represent a new strategy for tocolysis. Copyright 2000 Harcourt Publishers Ltd.

Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Infections

DTIC Science & Technology

1987-10-01

observed with free MTP-PE. In addition to our observations on peritoneal and alveolar macrophages, we also examined the effect of MTP-PE treatment on liver...Ir OIC FILE COPY C2 ILn 00 NM AD _____ N SELECTIVE TARGETING OF ANTIVIRAL AND IMMUNOMODULATING AGENTS IN THE TREATMENT OF ARENAVIRUS INFECTIONS "Kc...Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Injections 12. PERSONAL AUTHOR(S) J. David Gangemi 13a. TYPE OF

Bioremediation potential of hydrocarbon-utilizing fungi from select marine niches of India.

PubMed

Barnes, Natasha Maria; Khodse, Vishwas B; Lotlikar, Nikita P; Meena, Ram Murti; Damare, Samir R

2018-01-01

Ten fungal isolates with an ability to degrade crude oil were isolated from select marine substrates, such as mangrove sediments, Arabian Sea sediments, and tarballs. Out of the ten isolates, six belonged to Aspergillus , two to Fusarium and one each to Penicillium and Acremonium as identified using ITS rDNA sequencing. The selected ten fungal isolates were found to degrade the long-chain n -alkanes as opposed to short-chain n -alkanes from the crude oil. Mangrove fungus #NIOSN-M126 ( Penicillium citrinum ) was found to be highly efficient in biodegradation of crude oil, reducing the total crude oil content by 77% and the individual n -alkane fraction by an average of 95.37%, indicating it to be a potential candidate for the development into a bioremediation agent.

Drug therapies for reducing gastric acidity in people with cystic fibrosis.

PubMed

Ng, Sze May; Francini, Angelo J

2012-04-18

Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 15 February 2012. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. Thirty-eight trials were identified from the searches. Sixteen trials, with 256 participants, were suitable for inclusion. Seven trials were limited to children and three trials enrolled only adults. Meta-analysis was not performed. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.

Targeting Histone Deacetylases in Diseases: Where Are We?

PubMed Central

Benedetti, Rosaria; Conte, Mariarosaria

2015-01-01

Abstract Significance: Epigenetic inactivation of pivotal genes involved in cell growth is a hallmark of human pathologies, in particular cancer. Histone acetylation balance obtained through opposing actions of histone deacetylases (HDACs) and histone acetyltransferases is one epigenetic mechanism controlling gene expression and is, thus, associated with disease etiology and progression. Interfering pharmacologically with HDAC activity can correct abnormalities in cell proliferation, migration, vascularization, and death. Recent Advances: Histone deacetylase inhibitors (HDACi) represent a new class of cytostatic agents that interfere with the function of HDACs and are able to increase gene expression by indirectly inducing histone acetylation. Several HDACi, alone or in combination with DNA-demethylating agents, chemopreventive, or classical chemotherapeutic drugs, are currently being used in clinical trials for solid and hematological malignancies, and are, thus, promising candidates for cancer therapy. Critical Issues: (i) Non-specific (off-target) HDACi effects due to activities unassociated with HDAC inhibition. (ii) Advantages/disadvantages of non-selective or isoform-directed HDACi. (iii) Limited number of response-predictive biomarkers. (iv) Toxicity leading to dysfunction of critical biological processes. Future Directions: Selective HDACi could achieve enhanced clinical utility by reducing or eliminating the serious side effects associated with current first-generation non-selective HDACi. Isoform-selective and pan-HDACi candidates might benefit from the identification of biomarkers, enabling better patient stratification and prediction of response to treatment. Antioxid. Redox Signal. 23, 99–126. PMID:24382114

Biomass Pyrolysis Solids as Reducing Agents: Comparison with Commercial Reducing Agents

PubMed Central

Adrados, Aitziber; De Marco, Isabel; López-Urionabarrenechea, Alexander; Solar, Jon; Caballero, Blanca M.; Gastelu, Naia

2015-01-01

Biomass is one of the most suitable options to be used as renewable energy source due to its extensive availability and its contribution to reduce greenhouse gas emissions. Pyrolysis of lignocellulosic biomass under appropriate conditions (slow heating rate and high temperatures) can produce a quality solid product, which could be applicable to several metallurgical processes as reducing agent (biocoke or bioreducer). Two woody biomass samples (olives and eucalyptus) were pyrolyzed to produce biocoke. These biocokes were characterized by means of proximate and ultimate analysis, real density, specific surface area, and porosity and were compared with three commercial reducing agents. Finally, reactivity tests were performed both with the biocokes and with the commercial reducing agents. Bioreducers have lower ash and sulfur contents than commercial reducers, higher surface area and porosity, and consequently, much higher reactivity. Bioreducers are not appropriate to be used as top burden in blast furnaces, but they can be used as fuel and reducing agent either tuyére injected at the lower part of the blast furnace or in non-ferrous metallurgical processes where no mechanical strength is needed as, for example, in rotary kilns. PMID:28787805

Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis

PubMed Central

Tonelli, Marcello; Hemmelgarn, Brenda; Reiman, Tony; Manns, Braden; Reaume, M. Neil; Lloyd, Anita; Wiebe, Natasha; Klarenbach, Scott

2009-01-01

Background Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy. Methods We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment. We included RCTs involving anemic adults with cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and assessed clinical outcomes (all-cause mortality, cardiovascular events and hypertension, health-related quality of life, blood transfusions and tumour response) and harms (serious adverse events) between groups. Results We identified 52 trials (n = 12 006) that met our selection criteria. The pooled all-cause mortality during treatment was significantly higher in the group receiving erythropoiesis-stimulating therapy than in the control group (relative risk [RR] 1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use of erythropoiesis-stimulating agents led to clinically detectable improvements in disease-specific measures of quality of life. It also reduced the use of blood transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events (RR 1.16, 95% CI 1.08 to 1.25). Interpretation Use of erythropoiesis-stimulating agents in patients with cancer-related anemia improved some disease-specific measures of quality of life and decreased the use of blood transfusions. However, it increased the risk of death and serious adverse events. Our findings suggest that such therapy not be used routinely as an alternative to blood transfusion in patients with anemia related to cancer. PMID:19407261

9 CFR 121.5 - Exemptions for VS select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... agent or toxin that is contained in a specimen presented for proficiency testing will be exempt from the...

9 CFR 121.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... presented for proficiency testing will be exempt from the requirements of this part for such agent or toxin...

9 CFR 121.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... presented for proficiency testing will be exempt from the requirements of this part for such agent or toxin...

9 CFR 121.5 - Exemptions for VS select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... agent or toxin that is contained in a specimen presented for proficiency testing will be exempt from the...

9 CFR 121.5 - Exemptions for VS select agents and toxins.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... agent or toxin that is contained in a specimen presented for proficiency testing will be exempt from the...

9 CFR 121.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Exemptions for overlap select agents and toxins. 121.6 Section 121.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... presented for proficiency testing will be exempt from the requirements of this part for such agent or toxin...

Evolving therapies for the management of chronic and acute decompensated heart failure.

PubMed

Cook, Jennifer C; Tran, Richard H; Patterson, J Herbert; Rodgers, Jo E

2016-11-01

The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high. In response to a demand for novel pharmacologic agents, several therapeutic compounds have recently gained approval or are currently under review by the Food and Drug Administration. Sacubitril-valsartan has demonstrated benefit in reducing cardiovascular mortality and HF-related hospitalizations in clinical trials, while ivabradine and ferric carboxymaltose have proven efficacious in reducing HF-related hospitalizations. Lastly, the role of serelaxin in ADHF is currently under investigation in an ongoing Phase III study. While large, outcome-driven clinical trials are fundamental in informing the clinical application of these therapeutic agents, careful patient selection is imperative to ensuring similar outcomes postmarketing. In addition, optimization of current guideline-directed medical therapy remains essential as new therapies emerge and are incorporated into guideline recommendations. Additional therapeutic agents currently undergoing investigation include bucindolol hydrochloride, cimaglermin alfa, nitroxyl, omecamtiv mecarbil, TRV027, and ularitide. Clinical practitioners should remain abreast of emerging literature so that new therapeutic entities are optimally applied and positive patient outcomes are achieved. Recently introduced agents for the treatment of patients with HF include sacubitril-valsartan, ivabradine, and ferric carboxymaltose. Additional agents worthy of attention include serelaxin and other therapies currently under investigation. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models.

PubMed

Lin, Jie; Sampath, Deepak; Nannini, Michelle A; Lee, Brian B; Degtyarev, Michael; Oeh, Jason; Savage, Heidi; Guan, Zhengyu; Hong, Rebecca; Kassees, Robert; Lee, Leslie B; Risom, Tyler; Gross, Stefan; Liederer, Bianca M; Koeppen, Hartmut; Skelton, Nicholas J; Wallin, Jeffrey J; Belvin, Marcia; Punnoose, Elizabeth; Friedman, Lori S; Lin, Kui

2013-04-01

We describe the preclinical pharmacology and antitumor activity of GDC-0068, a novel highly selective ATP-competitive pan-Akt inhibitor currently in clinical trials for the treatment of human cancers. The effect of GDC-0068 on Akt signaling was characterized using specific biomarkers of the Akt pathway, and response to GDC-0068 was evaluated in human cancer cell lines and xenograft models with various genetic backgrounds, either as a single agent or in combination with chemotherapeutic agents. GDC-0068 blocked Akt signaling both in cultured human cancer cell lines and in tumor xenograft models as evidenced by dose-dependent decrease in phosphorylation of downstream targets. Inhibition of Akt activity by GDC-0068 resulted in blockade of cell-cycle progression and reduced viability of cancer cell lines. Markers of Akt activation, including high-basal phospho-Akt levels, PTEN loss, and PIK3CA kinase domain mutations, correlate with sensitivity to GDC-0068. Isogenic PTEN knockout also sensitized MCF10A cells to GDC-0068. In multiple tumor xenograft models, oral administration of GDC-0068 resulted in antitumor activity ranging from tumor growth delay to regression. Consistent with the role of Akt in a survival pathway, GDC-0068 also enhanced antitumor activity of classic chemotherapeutic agents. GDC-0068 is a highly selective, orally bioavailable Akt kinase inhibitor that shows pharmacodynamic inhibition of Akt signaling and robust antitumor activity in human cancer cells in vitro and in vivo. Our preclinical data provide a strong mechanistic rationale to evaluate GDC-0068 in cancers with activated Akt signaling. ©2012 AACR.

Topical Microbicides and HIV Prevention in the Female Genital Tract

PubMed Central

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

2014-01-01

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

Minimizing potential resistance: the molecular view--a comment on Courvalin and Trieu-Cuot.

PubMed

Hooper, D C

2001-09-15

The complexity of bacterial resistance to antimicrobial agents is driven by the interplay of many mechanistic and epidemiologic factors. Mechanistically, resistance by target alteration, reduced permeation, and drug inactivation can occur by both chromosomal mutation and acquisition of new genetic elements. Epidemiologically, exposure to antimicrobial agents provides a growth or persistence advantage for any existing resistant bacteria, generally irrespective of the mechanism. When a single chromosomal mutation is sufficient to cause resistance, any such exposure provides a risk of selection, as long as a sufficiently large bacterial population is exposed. Transmission of resistant bacteria can also amplify resistance of any type, but it is particularly important for complex resistance mechanisms that have evolved over time and for mechanisms that depend on infrequent biological events in nature. Because true biological barriers to the development of resistance are likely to be elusive, multiple approaches that address both the use of antimicrobial agents and transmission are necessary to slow the advance of resistance.

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...

42 CFR 73.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1...

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...

System and method for regeneration and recirculation of a reducing agent using highly exothermic reactions induced by mixed industrial slags

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

Nakano, Jinichiro; Bennett, James P.; Nakano, Anna

Embodiments relate to systems and methods for regenerating and recirculating a CO, H.sub.2 or combinations thereof utilized for metal oxide reduction in a reduction furnace. The reduction furnace receives the reducing agent, reduces the metal oxide, and generates an exhaust of the oxidized product. The oxidized product is transferred to a mixing vessel, where the oxidized product, a calcium oxide, and a vanadium oxide interact to regenerate the reducing agent from the oxidized product. The regenerated reducing agent is transferred back to the reduction furnace for continued metal oxide reductions.

Antibiotics in Serbian Households: a Source of Potential Health and Environmental Threats?

PubMed

Kusturica, Milica Paut; Tomić, Zdenko; Bukumirić, Zoran; Horvat, Olga; Pavlović, Nebojša; Mikov, Momir; Sabo, Ana

2015-06-01

Worldwide data indicate that antibiotics are frequently used inappropriately. The objective of this study was to investigate the extent of storage and wastage of antibacterial agents in households in Novi Sad, Serbia. The study was performed in 8 months period (December 2011-July 2012) in households in Novi Sad, Serbia. The households were randomly selected from the telephone directory. The interviewer performed the survey visiting each household. The total number of antibacterial agents in the 383 surveyed households was 318, constituting 7.3% of the total stored medications. From 383 families included in the study antibiotics were found in 178 (46.5%). In 13 (7.3%) families were found more than one pack of the same antibiotics. The median number of antibacterial agents per household was 1 (range 1-5). The most common antibacterial agents that were not in current use were cephalexin (22.1%) and amoxicillin (16.6%), followed by doxycycline (11.4%), sulfamethoxazole/trimethoprim (11.4%) and amoxicillin/clavulanic acid (9.2%). The percentage of expired antibacterial agents was 20.8%, while 85.2% were not currently in use. Antibacterial agents were commonly encountered in Serbian households, and a relatively large percentage was wasted. Informational and educational activities aimed at improving the public knowledge about antimicrobials play the leading role in reducing imprudent use of antibiotics. Copyright© by the National Institute of Public Health, Prague 2015.

The chemistry and applications of antimicrobial polymers: a state-of-the-art review.

PubMed

Kenawy, El-Refaie; Worley, S D; Broughton, Roy

2007-05-01

Microbial infection remains one of the most serious complications in several areas, particularly in medical devices, drugs, health care and hygienic applications, water purification systems, hospital and dental surgery equipment, textiles, food packaging, and food storage. Antimicrobials gain interest from both academic research and industry due to their potential to provide quality and safety benefits to many materials. However, low molecular weight antimicrobial agents suffer from many disadvantages, such as toxicity to the environment and short-term antimicrobial ability. To overcome problems associated with the low molecular weight antimicrobial agents, antimicrobial functional groups can be introduced into polymer molecules. The use of antimicrobial polymers offers promise for enhancing the efficacy of some existing antimicrobial agents and minimizing the environmental problems accompanying conventional antimicrobial agents by reducing the residual toxicity of the agents, increasing their efficiency and selectivity, and prolonging the lifetime of the antimicrobial agents. Research concerning the development of antimicrobial polymers represents a great a challenge for both the academic world and industry. This article reviews the state of the art of antimicrobial polymers primarily since the last comprehensive review by one of the authors in 1996. In particular, it discusses the requirements of antimicrobial polymers, factors affecting the antimicrobial activities, methods of synthesizing antimicrobial polymers, major fields of applications, and future and perspectives in the field of antimicrobial polymers.

Effect of Anesthesia Carrier Gas on In-Vivo Circulation Times of Ultrasound Microbubble Contrast Agents in Rats

PubMed Central

Mullin, Lee; Gessner, Ryan; Kwan, James; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. PMID:21246710

Visual discrimination of dihydroxybenzene isomers based on a nitrogen-doped graphene quantum dot-silver nanoparticle hybrid

NASA Astrophysics Data System (ADS)

Shi, Bingfang; Su, Yubin; Zhao, Jingjin; Liu, Rongjun; Zhao, Yan; Zhao, Shulin

2015-10-01

A room temperature reducing agent-free strategy for the synthesis of a nitrogen-doped graphene quantum dot-silver nanoparticle (N-GQD/AgNP) hybrid was presented. In this strategy, N-GQDs were used as a reducing agent and stabilizer for the formation of the N-GQD/AgNP hybrid, and the formation of the N-GQD/AgNP hybrid may result from the extraordinary reduction properties of N-GQDs, which are attributed to the nature of the surface oxygen-containing functional groups. The N-GQD/AgNP hybrid exhibits good dispersity and outstanding catalytic ability toward the oxidation of catechol (CC) and hydroquinone (HQ) by Ag+. In the presence of the N-GQD/AgNP hybrid, the reduction of Ag+ by CC and HQ was improved. CC enhanced the absorbance of the N-GQD/AgNP-Ag+ system the most, and HQ followed, while resorcinol (RC) had only a little effect on the absorption intensity of the system. Thus, a sensitive and selective colorimetric sensing method based on the N-GQD/AgNP-Ag+ system was developed for the discrimination of CC, HQ and RC. A good linear relationship was obtained from 0.1 to 15.0 μM for CC and from 0.3 to 20.0 μM for HQ. The detection limits of CC and HQ were 0.03 and 0.1 μM, respectively. In addition, the proposed method also shows a high selectivity for the detection of CC and HQ, and appreciable changes in color of the N-GQD/AgNP-Ag+ system toward CC, RC and HQ were observed.A room temperature reducing agent-free strategy for the synthesis of a nitrogen-doped graphene quantum dot-silver nanoparticle (N-GQD/AgNP) hybrid was presented. In this strategy, N-GQDs were used as a reducing agent and stabilizer for the formation of the N-GQD/AgNP hybrid, and the formation of the N-GQD/AgNP hybrid may result from the extraordinary reduction properties of N-GQDs, which are attributed to the nature of the surface oxygen-containing functional groups. The N-GQD/AgNP hybrid exhibits good dispersity and outstanding catalytic ability toward the oxidation of catechol (CC) and hydroquinone (HQ) by Ag+. In the presence of the N-GQD/AgNP hybrid, the reduction of Ag+ by CC and HQ was improved. CC enhanced the absorbance of the N-GQD/AgNP-Ag+ system the most, and HQ followed, while resorcinol (RC) had only a little effect on the absorption intensity of the system. Thus, a sensitive and selective colorimetric sensing method based on the N-GQD/AgNP-Ag+ system was developed for the discrimination of CC, HQ and RC. A good linear relationship was obtained from 0.1 to 15.0 μM for CC and from 0.3 to 20.0 μM for HQ. The detection limits of CC and HQ were 0.03 and 0.1 μM, respectively. In addition, the proposed method also shows a high selectivity for the detection of CC and HQ, and appreciable changes in color of the N-GQD/AgNP-Ag+ system toward CC, RC and HQ were observed. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04659a

Novel Medical Strategies Combating Nonmelanoma Skin Cancer

PubMed Central

Bhandari, Prasan R; Pai, Varadraj V

2014-01-01

The incidence of nonmelanoma skin cancer (NMSC) continues to rise, partly because of aging, the frequency of early childhood sunburns, and sporadic extreme recreational sun exposure. A nonsurgical approach to selected cutaneous malignancy could possibly reduce the cost as well as morbidity of surgical treatment for NMSC. There has been growing interest in isolating compounds that could suppress or reverse the biochemical changes necessary for cutaneous malignancies to progress by pharmacologic intervention. By targeting diverse pathways recognized as important in the pathogenesis of nonmelanoma skin cancers, a combination approach with multiple agents or addition of chemopreventative agents to topical sunscreens may offer the potential for novel and synergistic therapies in treating nonmelanoma skin cancer. This preliminary information will expand to include more therapeutic options for NMSC in the future. PMID:25484380

Metabotropic Glutamate Receptors for Parkinson's Disease Therapy

PubMed Central

Gasparini, Fabrizio; Di Paolo, Thérèse; Gomez-Mancilla, Baltazar

2013-01-01

Excessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson's disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate glutamatergic signalling via glutamate receptors, as treatments for PD and L-DOPA-induced dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate receptor antagonists showed antiparkinsonian and antidyskinetic activity, their clinical use was limited due to psychiatric adverse effects, with the exception of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor) modulators were considered to have a more favourable side-effect profile, and several agents have been studied in preclinical models of PD. The most promising results have been seen clinically with selective antagonists of mGlu5 receptor and preclinically with selective positive allosteric modulators of mGlu4 receptor. The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD. PMID:23853735

Febuxostat for the treatment of gout.

PubMed

Bridgeman, Mary Barna; Chavez, Benjamin

2015-02-01

Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues. The xanthine oxidase inhibitor, allopurinol, has historically been the principle agent utilized for reducing elevated uric acid levels and treating underlying cause of gout symptoms; the availability of febuxostat, a newer non-purine selective xanthine oxidase inhibitor, represents an alternative therapy for those patients with contraindications or intolerance to allopurinol. This article reviews the published literature on the pharmacologic characteristics and clinical safety and efficacy data on the use of febuxostat in the treatment of gout. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-November 2014) was conducted utilizing the key words 'febuxostat', 'allopurinol', and 'gout'. All published articles regarding febuxostat were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. Febuxostat has shown benefit with respect to symptomatic relief and uric acid level reduction. The safety profile of this agent makes it an ideal alternative in those patients with contraindications to or who are intolerant of allopurinol.

The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

PubMed

Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

2018-01-15

Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

Size-controlled synthesis of Pd nanocrystals using a specific multifunctional peptide

NASA Astrophysics Data System (ADS)

Chiu, Chin-Yi; Li, Yujing; Huang, Yu

2010-06-01

Here we report a peptide-mediated synthesis of Pd NCs in aqueous solution with controllable size in the sub-10 nanometre regime. The specific multifunctional peptide Q7 selected using the phage display technique can bind to the Pd NC surface and act as a stabilizer to mediate Pd crystal nucleation and growth. At the nucleation stage, Q7 bound to and helped stabilize the different-sized small Pd NC nuclei achieved using different concentrations of the external reducing agent, NaBH4. At the growth stage, Q7 played the dual role of binding to and reducing the precursor onto the existing nuclei, which led to the further controllable growth of the Pd NCs. By using the variable sizes of nuclei as seeds, and by introducing different amounts of precursors Pd NCs with tunable sizes from 2.6 to 6.6 nm were achieved with good size distribution.Here we report a peptide-mediated synthesis of Pd NCs in aqueous solution with controllable size in the sub-10 nanometre regime. The specific multifunctional peptide Q7 selected using the phage display technique can bind to the Pd NC surface and act as a stabilizer to mediate Pd crystal nucleation and growth. At the nucleation stage, Q7 bound to and helped stabilize the different-sized small Pd NC nuclei achieved using different concentrations of the external reducing agent, NaBH4. At the growth stage, Q7 played the dual role of binding to and reducing the precursor onto the existing nuclei, which led to the further controllable growth of the Pd NCs. By using the variable sizes of nuclei as seeds, and by introducing different amounts of precursors Pd NCs with tunable sizes from 2.6 to 6.6 nm were achieved with good size distribution. Electronic Supplementary Information (ESI) available. Experimental details for peptide selection, peptide synthesis and Pd NCs synthesis; Q7 peptide sequence molecular structure and characterization; TEM images of Pd NCs. See DOI: 10.1039/c0nr00194e/

Toxic industrial chemicals and chemical weapons: exposure, identification, and management by syndrome.

PubMed

Tomassoni, Anthony J; French, Robert N E; Walter, Frank G

2015-02-01

Toxidromes aid emergency care providers in the context of the patient presenting with suspected poisoning, unexplained altered mental status, unknown hazardous materials or chemical weapons exposure, or the unknown overdose. The ability to capture an adequate chemical exposure history and to recognize toxidromes may reduce dependence on laboratory tests, speed time to delivery of specific antidote therapy, and improve selection of supportive care practices tailored to the etiologic agent. This article highlights elements of the exposure history and presents selected toxidromes that may be caused by toxic industrial chemicals and chemical weapons. Specific antidotes for toxidromes and points regarding their use, and special supportive measures, are presented. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of the Effectiveness of Five Odor Reducing Agents for Sewer System Odors Using an On-Line Total Reduced Sulfur Analyzer

PubMed Central

Choi, Il; Lee, Hyunjoo; Shin, Joungdu; Kim, Hyunook

2012-01-01

Sewer odors have been a concern to citizens of the Metropolitan Seoul region, which has installed combined sewer systems (CSSs) in 86% of its area. Although a variety of odorants are released from sewers, volatile sulfur compounds (VSCs) have been recognized as major ones. A number of technologies have been proposed to monitor or control odors from sewers. One of the most popular strategies adopted for the control of sewage odor is by applying a commercial odor-reducing agent into the sewer. In this study, the effectiveness of five different commercial odor-reducing agents (i.e., an odor masking agent, an alkaline solution, two microbial agents, and a chemical oxidant) was evaluated by continuously monitoring VSCs released from the sewer with an on-line total reduced sulfur (TRS) analyzer before and after each agent was sprayed into CSSs at five different locations of the city. In short, when the effectiveness of odor treatment was tested in the sewer system using five commercial odor reducing treatments, only the chemical oxidant was good enough to reduce the odor in terms of TRS levels measured before and after the application (p < 0.01). PMID:23223148

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (b) of this section that have been genetically modified. (d) Select agents or toxins that meet any of..., and recombinant and/or synthetic organisms: (1) Nucleic acids that can produce infectious forms of any...

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (b) of this section that have been genetically modified. (d) Select agents or toxins that meet any of..., and recombinant and/or synthetic organisms: (1) Nucleic acids that can produce infectious forms of any...

Clean process to destroy arsenic-containing organic compounds with recovery of arsenic

DOEpatents

Upadhye, R.S.; Wang, F.T.

1996-08-13

A reduction method is provided for the treatment of arsenic-containing organic compounds with simultaneous recovery of pure arsenic. Arsenic-containing organic compounds include pesticides, herbicides, and chemical warfare agents such as Lewisite. The arsenic-containing compound is decomposed using a reducing agent. Arsine gas may be formed directly by using a hydrogen-rich reducing agent, or a metal arsenide may be formed using a pure metal reducing agent. In the latter case, the arsenide is reacted with an acid to form arsine gas. In either case, the arsine gas is then reduced to elemental arsenic. 1 fig.

Clean process to destroy arsenic-containing organic compounds with recovery of arsenic

DOEpatents

Upadhye, Ravindra S.; Wang, Francis T.

1996-01-01

A reduction method is provided for the treatment of arsenic-containing organic compounds with simultaneous recovery of pure arsenic. Arsenic-containing organic compounds include pesticides, herbicides, and chemical warfare agents such as Lewisite. The arsenic-containing compound is decomposed using a reducing agent. Arsine gas may be formed directly by using a hydrogen-rich reducing agent, or a metal arsenide may be formed using a pure metal reducing agent. In the latter case, the arsenide is reacted with an acid to form arsine gas. In either case, the arsine gas is then reduced to elemental arsenic.

Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated

PubMed Central

Ayala, Jennifer E.; Niswender, Colleen M.; Luo, Qingwei; Banko, Jessica L.; Conn, P. Jeffrey

2008-01-01

Summary Group III metabotropic glutamate receptors (mGluRs) reduce synaptic transmission at the Schaffer collateral-CA1 (SC-CA1) synapse in rats by a presynaptic mechanism. Previous studies show that low concentrations of the group III-selective agonist, L-AP4, reduce synaptic transmission in slices from neonatal but not adult rats, whereas high micromolar concentrations reduce transmission in both age groups. L-AP4 activates mGluRs 4 and 8 at much lower concentrations than those required to activate mGluR7, suggesting that the group III mGluR subtype modulating transmission is a high affinity receptor in neonates and a low affinity receptor in adults. The previous lack of subtype selective ligands has made it difficult to test this hypothesis. We have measured fEPSPs in the presence of novel subtype selective agents to address this question. We show that the effects of L-AP4 can be blocked by LY341495 in both neonates and adults, verifying that these effects are mediated by mGluRs. In addition, the selective mGluR8 agonist, DCPG, has a significant effect in slices from neonatal rats but does not reduce synaptic transmission in adult slices. The mGluR4 selective allosteric potentiator, PHCCC, is unable to potentiate the L-AP4-induced effects at either age. Taken together, our data suggest that group III mGluRs regulate transmission at the SC-CA1 synapse throughout development but there is a developmental regulation of the subtypes involved so that that both mGluR8 serves this role in neonates but not adults whereas mGluR7 is involved in regulating transmission at this synapse in throughout postnatal development. PMID:18255102

Effects of agents that inactivate free radical NO (NO•) on nitroxyl anion-mediated relaxations, and on the detection of NO• released from the nitroxyl anion donor Angeli's salt

PubMed Central

Ellis, Anthie; Lu, Hong; Li, Chun Guang; Rand, Michael J

2001-01-01

The effects of agents that inactivate free radical nitric oxide (carboxy-PTIO, hydroxocobalamin and pyrogallol) were tested on relaxations produced by the nitroxyl anion (NO−) donor Angeli's salt in rat aortic rings and anococcygeus muscles. The amount of NO• generated from Angeli's salt in the presence of these agents was measured using a NO•-selective electrode sensor. Carboxy-PTIO (100, 300 μM), hydroxocobalamin (30, 100 μM) and pyrogallol (10, 30 μM) significantly reduced relaxations produced by Angeli's salt (0.3 μM) in aortic rings but not in anococcygeus muscles. NO• generated from Angeli's salt (0.1 – 10 μM), as detected by the sensor electrode, was less than 0.5% of the amount of Angeli's salt added. Carboxy-PTIO (100 μM) and hydroxocobalamin (30 μM), but not pyrogallol significantly increased the amount of NO• detected. In the presence of an oxidizing agent copper [II] (as CuSO4 100 μM), the amount of NO• detected from 0.3 μM of Angeli's salt increased from an undetectable level of 142.7±15.7 nM (equivalent to 47.6% of Angeli's salt added). Under these conditions, carboxy-PTIO, hydroxocobalamin and pyrogallol significantly reduced the amount of NO• detected from Angeli's salt as well as the signal generated by an equivalent amount of authentic NO (0.33 μM). The difference in effects of these agents on relaxations to Angeli's salt in the aorta and the anococcygeus muscle may be explained by the ready conversion of NO− to NO• in the aorta through an unidentified mechanism, which makes NO− susceptible to inactivation by these agents. Furthermore, in addition to inactivating NO•, carboxy-PTIO and hydroxocobalamin may themselves oxidize NO− to NO•, albeit slightly. PMID:11588105

$1.8 Million and counting: how volatile agent education has decreased our spending $1000 per day.

PubMed

Miller, Scott A; Aschenbrenner, Carol A; Traunero, Justin R; Bauman, Loren A; Lobell, Samuel S; Kelly, Jeffrey S; Reynolds, John E

2016-12-01

Volatile anesthetic agents comprise a substantial portion of every hospital's pharmacy budget. Challenged with an initiative to lower anesthetic drug expenditures, we developed an education-based intervention focused on reducing volatile anesthetic costs while preserving access to all available volatile anesthetics. When postintervention evaluation demonstrated a dramatic year-over-year reduction in volatile agent acquisition costs, we undertook a retrospective analysis of volatile anesthetic purchasing data using time series analysis to determine the impact of our educational initiative. We obtained detailed volatile anesthetic purchasing data from the Central Supply of Wake Forest Baptist Health from 2007 to 2014 and integrated these data with the time course of our educational intervention. Aggregate volatile anesthetic purchasing data were analyzed for 7 consecutive fiscal years. The educational initiative emphasized tissue partition coefficients of volatile anesthetics in adipose tissue and muscle and their impact on case management. We used an interrupted time series analysis of monthly cost per unit data using autoregressive integrated moving average modeling, with the monthly cost per unit being the amount spent per bottle of anesthetic agent per month. The cost per unit decreased significantly after the intervention (t=-6.73, P<.001). The autoregressive integrated moving average model predicted that the average cost per unit decreased $48 after the intervention, with 95% confidence interval of $34 to $62. As evident from the data, the purchasing of desflurane and sevoflurane decreased, whereas that of isoflurane increased. An educational initiative focused solely on the selection of volatile anesthetic agent per case significantly reduced volatile anesthetic expense at a tertiary medical center. This approach appears promising for application in other hospitals in the rapidly evolving, value-added health care environment. We were able to accomplish this with instruction on tissue partition coefficients and each agent's individual cost per MAC-hour delivered. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical use and applications of histone deacetylase inhibitors in multiple myeloma

PubMed Central

Tandon, Nidhi; Ramakrishnan, Vijay; Kumar, Shaji K

2016-01-01

The incorporation of various novel therapies has resulted in a significant survival benefit in newly diagnosed and relapsed patients with multiple myeloma (MM) over the past decade. Despite these advances, resistance to therapy leads to eventual relapse and fatal outcomes in the vast majority of patients. Hence, there is an unmet need for new safe and efficacious therapies for continued improvement in outcomes. Given the role of epigenetic aberrations in the pathogenesis and progression of MM and the success of histone deacetylase inhibitors (HDACi) in other malignancies, many HDACi have been tried in MM. Various preclinical studies helped us to understand the antimyeloma activity of different HDACi in MM as a single agent or in combination with conventional, novel, and immune therapies. The early clinical trials of HDACi depicted only modest single-agent activity, but recent studies have revealed encouraging clinical response rates in combination with other antimyeloma agents, especially proteasome inhibitors. This led to the approval of the combination of panobinostat and bortezomib for the treatment of relapsed/refractory MM patients with two prior lines of treatment by the US Food and Drug Administration. However, it remains yet to be defined how we can incorporate HDACi in the current therapeutic paradigms for MM that will help to achieve longer disease control and significant survival benefits. In addition, isoform-selective and/or class-selective HDAC inhibition to reduce unfavorable side effects needs further evaluation. PMID:27226735

The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development

ERIC Educational Resources Information Center

Baker, Lauri M.; Hadley, Gregg

2014-01-01

The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…

Burnout among Extension Agents in the Ohio Cooperative Extension Service.

ERIC Educational Resources Information Center

Igodan, O. Chris; Newcomb, L. H.

A study examined the extent and causes of burnout among extension agents in Ohio. From the 241 extension agents working in the 88 counties of Ohio, researchers selected a random sample of 101 agents. Included in the sample were 34 agriculture agents, 33 home economics agents. Included in the sample agents were asked to complete a survey…

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.

Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

PubMed

Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; Lőbenberg, Raimar; Doschak, Michael R

2015-12-01

Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation. In the following review, we evaluate transdermal drug delivery systems, with a particular focus on delivering therapeutic agents to treat superficial bone pain, notably stress fractures. We further introduce and discuss several small peptide hormones active in bone (such as calcitonins and parathyroid hormone) that have shown potential for transdermal delivery, often under the added augmentation of transdermal drug delivery systems that employ lipo/hydrophilicity, electric charge, and/or microprojection facilitation across the skin barrier.

Efficiency of Composite Binders with Antifreezing Agents

NASA Astrophysics Data System (ADS)

Ogurtsova, Y. N.; Zhernovsky, I. V.; Botsman, L. N.

2017-11-01

One of the non-heating methods of cold-weather concreting is using concretes hardening at negative temperatures. This method consists in using chemical additives which reduce the freezing temperature of the liquid phase and provide for concrete hardening at negative temperatures. The non-heating cold-weather concreting, due to antifreezing agents, allows saving heat and electric energy at the more flexible work performance technology. At selecting the antifreezing components, the possibility of concreting at temperatures up to minus 20 °C and combination with a plasticizer contained in the composite binder were taken into account. The optimal proportions of antifreezing and complex agents produced by MC-Bauchemie Russia for fine-grained concretes were determined. So, the introduction of antifreezing and complex agents allows obtaining a structure of composite characteristic for cement stone in the conditions of below zero temperatures at using different binders; the hydration of such composite proceeded naturally. Low-water-demand binders (LWDB) based composites are characterized by a higher density and homogeneity due to a high dispersity of a binder and its complicated surface providing for a lot of crystallization centers. LWDB contains small pores keeping water in a liquid form and promoting a more complete hydration process.

Laser-induced copper deposition with weak reducing agents

NASA Astrophysics Data System (ADS)

Kochemirovsky, V. A.; Fateev, S. A.; Logunov, L. S.; Tumkin, I. I.; Safonov, S. V.; Khairullina, E. M.

2013-11-01

The study showed that organic alcohols with 1,2,3,5,6 hydroxyl groups can be used as reducing agents for laser-induced copper deposition from solutions (LCLD).Multiatomic alcohols, sorbitol, xylitol, and glycerol, are shown to be effective reducing agents for performing LCLD at glass-ceramic surfaces. High-conductivity copper tracks with good topology were synthesized.

76 FR 12118 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... that come to CDC for Select Agents. The term select agents is used to describe a limited group of... bioterrorism, inflicting significant morbidity and mortality on susceptible populations. In light of current...

Guidelines for Contracting Microfilming Services.

ERIC Educational Resources Information Center

Byrne, Sherry

1986-01-01

Outlines the process involved in selecting an outside filming agent for the purpose of preserving a library's or archive's holdings. Guidelines include project planning, selecting a filming agent, and contract preparation and maintenance. A sample contract is included. (Author/EM)

Drug therapies for reducing gastric acidity in people with cystic fibrosis.

PubMed

Ng, Sze May; Franchini, Angelo J

2014-07-13

Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 17 March 2014. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.

PREPARATION OF HIGH PURITY UF$sub 4$

DOEpatents

Magner, J.E.; Long, R.S.; Ellis, D.A.; Grinstead, R.R.

1962-04-17

S>A process for preparing very highly pure uranous tetrafluoride from impure uranium laden solvent extraction strip solutions, ion exchange process and resin-inpulp process eluate solutions which are at least 8M in hydrochloric acid is described. The process first comprises treating any of the above-mentioned solutions with a reducing agent to reduce the uranium to the + 4 oxidation state, and then contacting the reduced solution with an extractant phase comprising about 10 to 70% of tri-butyl phosphate in an organic solvent-diluent selected from benzene, ethyl-benzene, chlorobenzene, xylene, kerosene, or the like. The uranium is extracted into the extractant phase and is subsequently precipitated by treating the extractant with an aqueous fluoride solution. The highly pure uranous tetrafluoride precipitate is separated from the phases and recovered for subsequent utilization. (AEC)

An Expression of Periodic Phenomena of Fashion on Sexual Selection Model with Conformity Genes and Memes

NASA Astrophysics Data System (ADS)

Mutoh, Atsuko; Tokuhara, Shinya; Kanoh, Masayoshi; Oboshi, Tamon; Kato, Shohei; Itoh, Hidenori

It is generally thought that living things have trends in their preferences. The mechanism of occurrence of another trends in successive periods is concerned in their conformity. According to social impact theory, the minority is always exists in the group. There is a possibility that the minority make the transition to the majority by conforming agents. Because of agent's promotion of their conform actions, the majority can make the transition. We proposed an evolutionary model with both genes and memes, and elucidated the interaction between genes and memes on sexual selection. In this paper, we propose an agent model for sexual selection imported the concept of conformity. Using this model we try an environment where male agents and female agents are existed, we find that periodic phenomena of fashion are expressed. And we report the influence of conformity and differentiation on the transition of their preferences.

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.

Hydrocarbon extraction agents and microbiological processes for their production

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

Zajic, J.E.; Gerson, D.F.

1987-02-03

A process is described for producing extraction agents useful in the separation of hydrocarbon values from mineral deposits. It comprises cultivating by an aerobic fermentation, in a growth promoting medium and under growth promoting conditions, and on a liquid hydrocarbon substrate, a selected microbial strain of a species of microorganism selected from the group consisting of Arthrobacter terregens, Arthrobacter xerosis, Bacillus megaterium, Corynebacterium lepus, Corynebacterium xerosis, Nocardia petroleophila, and Vibrio ficheri. This is done to produce an extraction agent of microbiological origin in the fermentation medium, subsequently recovering the extraction agent from the fermentation medium and drying the agent tomore » powdered form.« less

Benzoin Radicals as Reducing Agent for Synthesizing Ultrathin Copper Nanowires.

PubMed

Cui, Fan; Dou, Letian; Yang, Qin; Yu, Yi; Niu, Zhiqiang; Sun, Yuchun; Liu, Hao; Dehestani, Ahmad; Schierle-Arndt, Kerstin; Yang, Peidong

2017-03-01

In this work, we report a new, general synthetic approach that uses heat driven benzoin radicals to grow ultrathin copper nanowires with tunable diameters. This is the first time carbon organic radicals have been used as a reducing agent in metal nanowire synthesis. In-situ temperature dependent electron paramagnetic resonance (EPR) spectroscopic studies show that the active reducing agent is the free radicals produced by benzoins under elevated temperature. Furthermore, the reducing power of benzoin can be readily tuned by symmetrically decorating functional groups on the two benzene rings. When the aromatic rings are modified with electron donating (withdrawing) groups, the reducing power is promoted (suppressed). The controllable reactivity gives the carbon organic radical great potential as a versatile reducing agent that can be generalized in other metallic nanowire syntheses.

Dosimeter and method for using the same

DOEpatents

Warner, Benjamin P.; Johns, Deidre M.

2003-06-24

A very sensitive dosimeter that detects ionizing radiation is described. The dosimeter includes a breakable sealed container. A solution of a reducing agent is inside the container. The dosimeter has an air-tight dosimeter body with a transparent portion and an opaque portion. The transparent portion includes a transparent chamber that holds the breakable container with the reducing agent. The opaque portion includes an opaque chamber that holds an emulsion of silver salt (AgX) selected from silver chloride, silver bromide, silver iodide, and combinations of them. A passageway in the dosimeter provides fluid communication between the transparent chamber and the opaque chamber. The dosimeter may also include a chemical pH indicator in the breakable container that provides a detectable color change to the solution for a pH of about 3-10. The invention also includes a method of detecting ionizing radiation that involves producing the dosimeter, breaking the breakable container, allowing the solution to flow through the passageway and contact the emulsion, detecting any color change in the solution and using the color change to determine a radiation dosage.

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.

Implementing the water framework directive: contract design and the cost of measures to reduce nitrogen pollution from agriculture.

PubMed

Bartolini, Fabio; Gallerani, Vittorio; Raggi, Meri; Viaggi, Davide

2007-10-01

The performance of different policy design strategies is a key issue in evaluating programmes for water quality improvement under the Water Framework Directive (60/2000). This issue is emphasised by information asymmetries between regulator and agents. Using an economic model under asymmetric information, the aim of this paper is to compare the cost-effectiveness of selected methods of designing payments to farmers in order to reduce nitrogen pollution in agriculture. A principal-agent model is used, based on profit functions generated through farm-level linear programming. This allows a comparison of flat rate payments and a menu of contracts developed through mechanism design. The model is tested in an area of Emilia Romagna (Italy) in two policy contexts: Agenda 2000 and the 2003 Common Agricultural Policy (CAP) reform. The results show that different policy design options lead to differences in policy costs as great as 200-400%, with clear advantages for the menu of contracts. However, different policy scenarios may strongly affect such differences. Hence, the paper calls for greater attention to the interplay between CAP scenarios and water quality measures.

Implementing the Water Framework Directive: Contract Design and the Cost of Measures to Reduce Nitrogen Pollution from Agriculture

NASA Astrophysics Data System (ADS)

Bartolini, Fabio; Gallerani, Vittorio; Raggi, Meri; Viaggi, Davide

2007-10-01

The performance of different policy design strategies is a key issue in evaluating programmes for water quality improvement under the Water Framework Directive (60/2000). This issue is emphasised by information asymmetries between regulator and agents. Using an economic model under asymmetric information, the aim of this paper is to compare the cost-effectiveness of selected methods of designing payments to farmers in order to reduce nitrogen pollution in agriculture. A principal-agent model is used, based on profit functions generated through farm-level linear programming. This allows a comparison of flat rate payments and a menu of contracts developed through mechanism design. The model is tested in an area of Emilia Romagna (Italy) in two policy contexts: Agenda 2000 and the 2003 Common Agricultural Policy (CAP) reform. The results show that different policy design options lead to differences in policy costs as great as 200-400%, with clear advantages for the menu of contracts. However, different policy scenarios may strongly affect such differences. Hence, the paper calls for greater attention to the interplay between CAP scenarios and water quality measures.

Remediation mechanisms of mercapto-grafted palygorskite for cadmium pollutant in paddy soil.

PubMed

Liang, Xuefeng; Qin, Xu; Huang, Qingqing; Huang, Rong; Yin, Xiuling; Cai, Yanming; Wang, Lin; Sun, Yuebing; Xu, Yingming

2017-10-01

The immobilization agent was the key factor that determined the success of remediation of heavy metal polluted soil. In this study, mercapto-grafted palygorskite (MP) as a novel and efficient immobilization agent was utilized for the remediation of Cd-polluted paddy soil in pot trials, and the remediation mechanisms were investigated in the aspect of soil chemistry and plant physiology with different rice cultivars as model plants. Mercapto-grafted palygorskite at applied doses of 0.1-0.3% could reduce Cd contents of brown rice and straws of different cultivars significantly. Both reduced DTPA-extractable Cd contents in rhizosphere and non-rhizosphere soil and decreasing Cd contents in iron plaques on rice root surfaces confirmed that MP was an efficient immobilization agent for Cd pollutant in paddy soil. In the aspect of soil chemistry, the pH values of rhizosphere and non-rhizosphere soils had no statistical changes in the MP treatment groups, but their zeta potentials decreased obviously, indicating that MP could enhance the fixation or sorption of Cd on soil compositions. In the aspect of antioxidant system, MP could increase POD activity of rice roots significantly to alleviate the stress of Cd to roots, and resulted in the decrease of T-AOC, SOD, and CAT activities of rice roots of the selected cultivars. MP had no inhabitation or enhancement effects on TSH of rice roots but enhance the contents of MTs and NPT to binding Cd to complete detoxification process. MP as a novel and efficient immobilization agent could complete the remediation effects through soil chemistry and plant physiological mechanisms.

Situ formation of apatite for sequestering radionuclides and heavy metals

DOEpatents

Moore, Robert C.

2003-07-15

Methods for in situ formation in soil of a permeable reactive barrier or zone comprising a phosphate precipitate, such as apatite or hydroxyapatite, which is capable of selectively trapping and removing radionuclides and heavy metal contaminants from the soil, while allowing water or other compounds to pass through. A preparation of a phosphate reagent and a chelated calcium reagent is mixed aboveground and injected into the soil. Subsequently, the chelated calcium reagent biodegrades and slowly releases free calcium. The free calcium reacts with the phosphate reagent to form a phosphate precipitate. Under the proper chemical conditions, apatite or hydroxyapatite can form. Radionuclide and heavy metal contaminants, including lead, strontium, lanthanides, and uranium are then selectively sequestered by sorbing them onto the phosphate precipitate. A reducing agent can be added for reduction and selective sequestration of technetium or selenium contaminants.

Collagenase Santyl ointment: a selective agent for wound debridement.

PubMed

Shi, Lei; Carson, Dennis

2009-01-01

Enzymatic debridement is a frequently used technique for removal of necrotic tissue from wounds. Proteases with specificity to break down the collagenous materials in necrotic tissues can achieve selective debridement, digesting denatured collagen in eschar while sparing nonnecrotic tissues. This article provides information about the selectivity of a collagenase-based debriding agent, including evidence of its safe and efficacious uses. Recent research has been conducted, investigating the chemical and biological properties of collagenase ointment, including healing in animal models, digestion power on different collagen types, cell migration activity from collagen degradation products, and compatibility with various wound dressings and metal ions. Evidence presented demonstrates that collagenase ointment is an effective, selective, and safe wound debriding agent.

Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats.

PubMed

Kleven, Mark S; Barret-Grévoz, Catherine; Bruins Slot, Liesbeth; Newman-Tancredi, Adrian

2005-08-01

Compounds possessing 5-HT(1A) agonist properties attenuate catalepsy induced by D(2) receptor blockade. Here we examined the role of 5-HT(1A) receptor agonism in the reduced cataleptogenic potential of several novel antipsychotic agents in the crossed leg position (CLP) and the bar catalepsy tests in rats. When administered alone, ziprasidone produced marked catalepsy, whereas aripiprazole, bifeprunox, SLV313, SSR181507 and sarizotan did not. However, when 5-HT(1A) receptors were blocked with the selective antagonist, WAY100635 (0.63 mg/kg, SC), robust cataleptogenic properties of SLV313, bifeprunox and sarizotan were unmasked and the catalepsy induced by ziprasidone was accentuated. In contrast, only modest catalepsy was induced by aripiprazole and SSR181507, even following a higher dose of WAY100635 (2.5 mg/kg). This suggests that these compounds possess other anti-cataleptic properties, such as partial agonism at dopamine D(2) receptors. The capacity to reverse neuroleptic-induced catalepsy was investigated in interaction studies with haloperidol (2.5 mg/kg, SC). Whereas ziprasidone and aripiprazole did not markedly reduce the effects of haloperidol, SLV313 and sarizotan attenuated CLP catalepsy. In contrast, SSR181507 and bifeprunox potently inhibited both CLP and bar catalepsy. Taken together, these data show that 5-HT(1A) receptor activation reduces the cataleptogenic potential of novel antipsychotic agents but indicate marked diversity in the contribution of 5-HT(1A) and/or other mechanisms to the profiles of the drugs.

The anorexic agents, sibutramine and fenfluramine, depress GABAB-induced inhibitory postsynaptic potentials in rat mesencephalic dopaminergic cells

PubMed Central

Ledonne, Ada; Sebastianelli, Luca; Federici, Mauro; Bernardi, Giorgio; Mercuri, Nicola Biagio

2009-01-01

Background and purpose Nutrition is the result of a complex interaction among environmental, homeostatic and reward-related processes. Accumulating evidence supports key roles for the dopaminergic neurons of the ventral midbrain in regulating feeding behaviour. For this reason, in the present study, we have investigated the electrophysiological effects of two centrally acting anorexic agents, fenfluramine and sibutramine, on these cells. Experimental approach Rat midbrain slices were used to make intracellular recordings from dopaminergic neurons of the substantia nigra and the ventral tegmental area. Gamma-aminobutyric acid (GABA)-mediated synaptic transmission was assessed from the inhibitory postsynaptic potentials (IPSPs) mediated by GABAA and GABAB receptors. Key results Fenfluramine and sibutramine reduced, concentration-dependently, the GABAB IPSPs, without affecting the GABAA-mediated potentials. This effect is presynaptic, as postsynaptic membrane responses induced by application of a GABAB receptor agonist, baclofen, were not affected by the two drugs. Furthermore, the selective 5-hydroxytriptamine 1B (5-HT1B) receptor antagonist, SB216641, blocked the reduction of GABAB IPSPs caused by fenfluramine and sibutramine, indicating that the receptor mediating this effect is 5-HT1B. Conclusions and implications Two anorexic agents, fenfluramine and sibutramine, induced the activation of 5-HT1B receptors located on presynaptic GABAergic terminals, thus reducing the release of GABA. This action can alter the strength of synaptic afferents that modify the activity of dopaminergic neurons, inducing neuronal excitation. Our results reveal an additional mechanism of action for fenfluramine and sibutramine that might contribute to reducing food intake, by influencing the pleasurable and motor aspects of feeding behaviour. PMID:19298257

42 CFR 73.10 - Restricting access to select agents and toxins; security risk assessments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING SELECT AGENTS AND TOXINS § 73.10 Restricting... or intelligence agency of committing a crime specified in 18 U.S.C. 2332b(g)(5), knowing involvement...

Treatments for Tinnitus

PubMed Central

Noble, William

2008-01-01

The various forms of treatment for tinnitus that have been tested in properly controlled trials can be classified as pharmacological, acoustic-physical, and psychological. In clinical trials, no pharmacological agent has been shown to have lasting effect on the presence or severity of tinnitus, although there are promising signs in an animal model. Acoustic devices do not seem to influence tinnitus, although appropriately fitted hearing aids may slightly reduce its prominence. Of physical treatments, cortical implantation may hold some promise of being effective for tinnitus suppression in selected cases. A psychological treatment that has emerged as consistently beneficial is cognitive-behavior therapy in terms of affecting overall well-being and reducing level of tinnitus annoyance. PMID:18635586

Novel potential for the management of Alzheimer disease.

PubMed

Ginter, E; Simko, V; Weinrebova, D; Ladecka, Z

2015-01-01

Pathologic characteristics of Alzheimer disease (AD) are β-amyloid (Aβ) plaques, neurofibrillary tangles (NFT) and neurodegeneration. Currently, there is no cure for AD. Cilostazol, a selective inhibitor of type 3 phosphodiesterase, is likely to be a promising agent for AD. In the brain of the experimental animals it significantly reduced the Aβ amyloid plaques. Initial clinical reports on the effect of Cilostazol in AD patients are promising. In mice, stem cells favourably influence the pathogenetic process critical in AD, by reducing deposits of Aβ plaques. Clinical trials of the drug, called Betablock, are already underway in Britain. Successful management and resolution of AD in man will still require further intensive research (Fig. 4, Ref. 11).

Poliovirus Mutants Resistant to Neutralization with Soluble Cell Receptors

NASA Astrophysics Data System (ADS)

Kaplan, Gerardo; Peters, David; Racaniello, Vincent R.

1990-12-01

Poliovirus mutants resistant to neutralization with soluble cellular receptor were isolated. Replication of soluble receptor-resistant (srr) mutants was blocked by a monoclonal antibody directed against the HeLa cell receptor for poliovirus, indicating that the mutants use this receptor to enter cells. The srr mutants showed reduced binding to HeLa cells and cell membranes. However, the reduced binding phenotype did not have a major impact on viral replication, as judged by plaque size and one-step growth curves. These results suggest that the use of soluble receptors as antiviral agents could lead to the selection of neutralization-resistant mutants that are able to bind cell surface receptors, replicate, and cause disease.

Oligo-branched peptides for tumor targeting: from magic bullets to magic forks.

PubMed

Falciani, Chiara; Pini, Alessandro; Bracci, Luisa

2009-02-01

Selective targeting of tumor cells is the final goal of research and drug discovery for cancer diagnosis, imaging and therapy. After the invention of hybridoma technology, the concept of magic bullet was introduced into the field of oncology, referring to selective killing of tumor cells, by specific antibodies. More recently, small molecules and peptides have also been proposed as selective targeting agents. We analyze the state of the art of tumor-selective agents that are presently available and tested in clinical settings. A novel approach based on 'armed' oligo-branched peptides as tumor targeting agents, is discussed and compared with existing tumor-selective therapies mediated by antibodies, small molecules or monomeric peptides. Oligo-branched peptides could be novel drugs that combine the advantages of antibodies and small molecules.

Sensitivity Analysis in Agent-Based Models of Socio-Ecological Systems: An Example in Agricultural Land Conservation for Lake Water Quality Improvement

NASA Astrophysics Data System (ADS)

Ligmann-Zielinska, A.; Kramer, D. B.; Spence Cheruvelil, K.; Soranno, P.

2012-12-01

Socio-ecological systems are dynamic and nonlinear. To account for this complexity, we employ agent-based models (ABMs) to study macro-scale phenomena resulting from micro-scale interactions among system components. Because ABMs typically have many parameters, it is challenging to identify which parameters contribute to the emerging macro-scale patterns. In this paper, we address the following question: What is the extent of participation in agricultural land conservation programs given heterogeneous landscape, economic, social, and individual decision making criteria in complex lakesheds? To answer this question, we: [1] built an ABM for our model system; [2] simulated land use change resulting from agent decision making, [3] estimated the uncertainty of the model output, decomposed it and apportioned it to each of the parameters in the model. Our model system is a freshwater socio-ecological system - that of farmland and lake water quality within a region containing a large number of lakes and high proportions of agricultural lands. Our study focuses on examining how agricultural land conversion from active to fallow reduces freshwater nutrient loading and improves water quality. Consequently, our ABM is composed of farmer agents who make decisions related to participation in a government-sponsored Conservation Reserve Program (CRP) managed by the Farm Service Agency (FSA). We also include an FSA agent, who selects enrollment offers made by farmers and announces the signup results leading to land use change. The model is executed in a Monte Carlo simulation framework to generate a distribution of maps of fallow lands that are used for calculating nutrient loading to lakes. What follows is a variance-based sensitivity analysis of the results. We compute sensitivity indices for individual parameters and their combinations, allowing for identification of the most influential as well as the insignificant inputs. In the case study, we observe that farmland conservation is first and foremost driven by the FSA signup choices. Environmental criteria used in FSA offer selection play a secondary role in farmland-to-fallow-land conversion. Farmer decision making is mainly influenced by the willingness to reduce the potential annual rental payments. As the case study demonstrates, our approach leads to ABM simplification without the loss of outcome variability. It also shows how to represent the magnitude of ABM complexity and isolate the effects of the interconnected explanatory variables on the simulated emergent phenomena. More importantly, the results of our research indicate that some of the parameters exert influence on model outcomes only if analyzed in combination with other parameters. Without evaluating the interaction effects among inputs, we risk losing important functional relationships among ABM components and, consequently, we potentially reduce its explanatory power.

Serotonin Transporter-Independent Actions of the Antidepressant Vortioxetine As Revealed Using the SERT Met172 Mouse.

PubMed

Nackenoff, Alex G; Simmler, Linda D; Baganz, Nicole L; Pehrson, Alan L; Sánchez, Connie; Blakely, Randy D

2017-05-17

Selective serotonin (5-HT, SERT) reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression. However, they have delayed efficacy and can induce side-effects that can encourage discontinuation. Recently, agents have been developed, including vortioxetine (Trintellix), that augment SERT blockade with interactions at other targets. At therapeutic doses, vortioxetine interacts with SERT as well as 5-HT 1A , 5-HT 1B , 5-HT 3 , and 5-HT 7 receptors. We assessed the SERT-dependency of vortioxetine action using the SERT Met172 mouse model, which disrupts high-affinity interactions of many antidepressants with the transporter. We demonstrate that the SERT Met172 substitution induces an ∼19-fold loss in vortioxetine potency for SERT inhibition in midbrain synaptosomes. Moreover, in these mice, we observed reduced SERT occupancy, a diminished ability to prolong 5-HT clearance, and a reduced capacity to elevate extracellular 5-HT. Despite reduced interactions with SERT, vortioxetine maintained its ability to enhance mobility in tail suspension and forced swim tests, reduce consumption latency in the novelty induced hypophagia test, and promoted proliferation and survival of subgranular zone hippocampal stem cells. Our findings suggest that the antidepressant actions of vortioxetine may be SERT-independent, and encourage consideration of agents that mimic one or more actions of the drug in the development of improved depression treatments.

A novel method of reducing agent contacting pattern for metal ceramic composite membrane fabrication

NASA Astrophysics Data System (ADS)

Agarwal, Amrita; Pujari, Murali; Uppaluri, Ramgopal; Verma, Anil

2014-11-01

Deliberating upon process modifications for surfactant induced electroless plating (SIEP), this article highlights the plating bath performance characteristics for two distinct reducing agent contacting modes (bulk and drop wise). Eventually, the effect of reducing agent concentration (50, 100, 200% excess) suitable for electroless plating bath for a nickel concentration of 0.08 mol/L was investigated. Finally, the compatibility of variation in nickel concentration (0.08-0.24 mol/L) with respect to variation in reducing agent concentration (50, 100, 200% excess) was investigated. LPSA, BET, FTIR, XRD, FESEM and nitrogen permeation experiments were used for surface and physical characterization. It was observed that for the bulk addition of reducing agent, the PPD values were 84.5% which increased to 89.3% for dropwise addition case. Thus the optimal combinations of SIEP process parameters were identified as 0.08 mol/L of nickel metal solution concentration with 100% excess drop-wise reducing agent. These conditions provided a plating rate of 5.5 × 10-5 mol/m2 s, PPD of 89.3% and a metal film thickness of 15.7 μm respectively after 12 h of sequential plating.

Select phytochemicals suppress human T-lymphocytes and mouse splenocytes suggesting their use in autoimmunity and transplantation

PubMed Central

Hushmendy, Shazaan; Jayakumar, Lalithapriya; Hahn, Amy B.; Bhoiwala, Devang; Bhoiwala, Dipti L.; Crawford, Dana R.

2009-01-01

We have considered a novel “rational” gene targeting approach for treating pathologies whose genetic bases are defined using select phytochemicals. We reason that one such potential application of this approach would be conditions requiring immunosuppression such as autoimmune disease and transplantation, where the genetic target is clearly defined; i.e., interleukin-2 and associated T-cell activation. Therefore, we hypothesized that select phytochemicals can suppress T-lymphocyte proliferation both in vitro and in vivo. The immunosuppressive effects of berry extract, curcumin, quercetin, sulforaphane, epigallocatechin gallate (EGCG), resveratrol, α-tocopherol, vitamin C and sucrose were tested on anti-CD3 plus anti-CD28-activated primary human T-lymphocytes in culture. Curcumin, sulforaphane, quercetin, berry extract and EGCG all significantly inhibited T-cell proliferation, and this effect was not due to toxicity. IL-2 production was also reduced by these agents, implicating this important T-cell cytokine in proliferation suppression. Except for berry extract, these same agents also inhibited mouse splenic T-cell proliferation and IL-2 production. Subsequent in vivo studies revealed that quercetin (but not sulforaphane) modestly suppressed mouse splenocyte proliferation following supplementation of BALB/c mice diets. This effect was especially prominent if corrected for the loss of supplement “recall” as observed in cultured T-cells. These results suggest the potential use of these select phytochemicals for treating autoimmune and transplant patients, and support our strategy of using select phytochemicals to treat genetically-defined pathologies, an approach that we believe is simple, healthy, and cost-effective. PMID:19761891

Biomimetic synthesis of silver nanoparticles using the fish scales of Labeo rohita and their application as catalysts for the reduction of aromatic nitro compounds

NASA Astrophysics Data System (ADS)

Sinha, Tanur; Ahmaruzzaman, M.; Sil, A. K.; Bhattacharjee, Archita

2014-10-01

In this article, a cleaner, greener, cheaper and environment friendly method for the generation of self assembled silver nanoparticles (Ag NPs) applying a simple irradiation technique using the aqueous extract of the fish scales (which is considered as a waste material) of Labeo rohita is described. Gelatin is considered as the major ingredient responsible for the reduction as well as stabilisation of the self assembled Ag NPs. The size and morphology of the individual Ag NPs can be tuned by controlling the various reaction parameters, such as temperature, concentration, and pH. Studies showed that on increasing concentration and pH Ag NPs size decreases, while on increasing temperature, Ag NPs size increases. The present process does not need any external reducing agent, like sodium borohydride or hydrazine or others and gelatin itself can play a dual role: a ‘reducing agent' and ‘stabilisation agent' for the formation of gelatin-Ag NPs colloidal dispersion. The synthesized Ag NPs were characterised by Ultraviolet-Visible spectroscopy (UV-Vis), Transmission electron microscopy (TEM) and Selected area electron diffraction (SAED) analyses. The synthesized Ag NPs was used to study the catalytic reduction of various aromatic nitro compounds in aqueous and three different micellar media. The hydrophobic and electrostatic interaction between the micelle and the substrate is responsible for the catalytic activity of the nanoparticles in micelle.

Interactive machine learning for health informatics: when do we need the human-in-the-loop?

PubMed

Holzinger, Andreas

2016-06-01

Machine learning (ML) is the fastest growing field in computer science, and health informatics is among the greatest challenges. The goal of ML is to develop algorithms which can learn and improve over time and can be used for predictions. Most ML researchers concentrate on automatic machine learning (aML), where great advances have been made, for example, in speech recognition, recommender systems, or autonomous vehicles. Automatic approaches greatly benefit from big data with many training sets. However, in the health domain, sometimes we are confronted with a small number of data sets or rare events, where aML-approaches suffer of insufficient training samples. Here interactive machine learning (iML) may be of help, having its roots in reinforcement learning, preference learning, and active learning. The term iML is not yet well used, so we define it as "algorithms that can interact with agents and can optimize their learning behavior through these interactions, where the agents can also be human." This "human-in-the-loop" can be beneficial in solving computationally hard problems, e.g., subspace clustering, protein folding, or k-anonymization of health data, where human expertise can help to reduce an exponential search space through heuristic selection of samples. Therefore, what would otherwise be an NP-hard problem, reduces greatly in complexity through the input and the assistance of a human agent involved in the learning phase.

Older partner selection promotes the prevalence of cooperation in evolutionary games.

PubMed

Yang, Guoli; Huang, Jincai; Zhang, Weiming

2014-10-21

Evolutionary games typically come with the interplays between evolution of individual strategy and adaptation to network structure. How these dynamics in the co-evolution promote (or obstruct) the cooperation is regarded as an important topic in social, economic, and biological fields. Combining spatial selection with partner choice, the focus of this paper is to identify which neighbour should be selected as a role to imitate during the process of co-evolution. Age, an internal attribute and kind of local piece of information regarding the survivability of the agent, is a significant consideration for the selection strategy. The analysis and simulations presented, demonstrate that older partner selection for strategy imitation could foster the evolution of cooperation. The younger partner selection, however, may decrease the level of cooperation. Our model highlights the importance of agent׳s age on the promotion of cooperation in evolutionary games, both efficiently and effectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

Gutierrez, Maria G; Warawa, Jonathan M

2016-05-01

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

Selection of fluxing agent for coal ash and investigation of fusion mechanism: a first-principles study

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

Jie Li; Mei-Fang Du; Zhong-Xiao Zhang

2009-01-15

An approach based on the ab initio quantum chemical modeling (CASTEP, generalized gradient approximation (GGA), and density functional theory (DFT)) was first employed to guide the selection of the appropriate fluxing agent to reduce the coal ash melting temperature. Two kinds of typical Chinese coal ash A and B with a high-melting temperature were chosen as the investigated subjects. Result of the calculation shows that mullite mineral, which is the main component of coal ash, is easier to combine with an electron acceptor than with an electron donor. Because the cations of borax (Na{sub 2}B{sub 4}O{sub 7}10H{sub 2}O) and limestonemore » can act as electron acceptors, borax and limestone were selected as the fluxing agents in our experiment. Results of the experiment show that the melting temperatures of coal ash A and B are both decreased by borax and limestone, respectively. Moreover, borax has a better fluxing effect than limestone under the same conditions. The further numerical study on the coal ash fusing mechanism indicates that the Na{sup +} and Ca{sup 2+} cations, as acceptors, can enter into the crystal lattice of mullite mainly through O(7) and O(8) and then cause the Al(6)-O(8) and Al(5)-O(7) bonds to rupture in the (AlO{sub 6})-octahedron. From this, mullite is forced to transform to feldspar and corundum minerals that have a low binding energy. Because of the phase change of minerals in the coal ash, the coal ash melting temperature is decreased by adding borax and limestone. 27 refs., 8 figs., 3 tabs.« less

An efficient and high-throughput protocol for Agrobacterium-mediated transformation based on phosphomannose isomerase positive selection in Japonica rice (Oryza sativa L.).

PubMed

Duan, Yongbo; Zhai, Chenguang; Li, Hao; Li, Juan; Mei, Wenqian; Gui, Huaping; Ni, Dahu; Song, Fengshun; Li, Li; Zhang, Wanggen; Yang, Jianbo

2012-09-01

A number of Agrobacterium-mediated rice transformation systems have been developed and widely used in numerous laboratories and research institutes. However, those systems generally employ antibiotics like kanamycin and hygromycin, or herbicide as selectable agents, and are used for the small-scale experiments. To address high-throughput production of transgenic rice plants via Agrobacterium-mediated transformation, and to eliminate public concern on antibiotic markers, we developed a comprehensive efficient protocol, covering from explant preparation to the acquisition of low copy events by real-time PCR analysis before transplant to field, for high-throughput production of transgenic plants of Japonica rice varieties Wanjing97 and Nipponbare using Escherichia coli phosphomannose isomerase gene (pmi) as a selectable marker. The transformation frequencies (TF) of Wanjing97 and Nipponbare were achieved as high as 54.8 and 47.5%, respectively, in one round of selection of 7.5 or 12.5 g/L mannose appended with 5 g/L sucrose. High-throughput transformation from inoculation to transplant of low copy events was accomplished within 55-60 days. Moreover, the Taqman assay data from a large number of transformants showed 45.2% in Wanjing97 and 31.5% in Nipponbare as a low copy rate, and the transformants are fertile and follow the Mendelian segregation ratio. This protocol facilitates us to perform genome-wide functional annotation of the open reading frames and utilization of the agronomically important genes in rice under a reduced public concern on selectable markers. We describe a comprehensive protocol for large scale production of transgenic Japonica rice plants using non-antibiotic selectable agent, at simplified, cost- and labor-saving manners.

Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy.

PubMed

Yang, Yuhui; Karakhanova, Svetlana; Hartwig, Werner; D'Haese, Jan G; Philippov, Pavel P; Werner, Jens; Bazhin, Alexandr V

2016-12-01

Mitochondria are indispensable for energy metabolism, apoptosis regulation, and cell signaling. Mitochondria in malignant cells differ structurally and functionally from those in normal cells and participate actively in metabolic reprogramming. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression, and participating in signaling pathways. Mitochondrial and nuclear DNA mutations caused by oxidative damage that impair the oxidative phosphorylation process will result in further mitochondrial ROS production, completing the "vicious cycle" between mitochondria, ROS, genomic instability, and cancer development. The multiple essential roles of mitochondria have been utilized for designing novel mitochondria-targeted anticancer agents. Selective drug delivery to mitochondria helps to increase specificity and reduce toxicity of these agents. In order to reduce mitochondrial ROS production, mitochondria-targeted antioxidants can specifically accumulate in mitochondria by affiliating to a lipophilic penetrating cation and prevent mitochondria from oxidative damage. In consistence with the oncogenic role of ROS, mitochondria-targeted antioxidants are found to be effective in cancer prevention and anticancer therapy. A better understanding of the role played by mitochondria in cancer development will help to reveal more therapeutic targets, and will help to increase the activity and selectivity of mitochondria-targeted anticancer drugs. In this review we summarized the impact of mitochondria on cancer and gave summary about the possibilities to target mitochondria for anticancer therapies. J. Cell. Physiol. 231: 2570-2581, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of selected food phytochemicals in reducing the toxic actions of TCDD and p,p′-DDT in U937 macrophages

PubMed Central

Sciullo, Eric M.; Vogel, Christoph F.; Wu, Dalei; Murakami, Akira; Ohigashi, Hajime

2010-01-01

To assess the effectiveness of selected food phytochemicals in reducing the toxic effects of the environmental toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and p,p′-DDT (DDT), we tested the potencies of auraptene, nobiletin, zerumbone, and (±)-13-hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) in reversing the inflammatory action of these toxicants in U937 human macrophages. Using quantitative RT–PCR as the initial screening assay, we identified antagonistic actions of zerumbone and auraptene against the action of TCDD and DDT in up-regulating the mRNA expressions of COX-2 and VEGF. The functional significance of the inhibitory action of zerumbone on COX-2 expression was confirmed by demonstrating its suppression of TCDD-induced activation of COX-2 gene expression in mouse MMDD1 cells. We tested auraptene on DDT-induced reactive oxygen species (ROS) formation in U937 macrophages and found that auraptene is a powerful agent antagonizing this action of DDT. To confirm the significance of these actions of zerumbone and auraptene at the cellular level, we assessed their influence on TCDD-induced apoptosis resistance in intact U937 macrophages and found that they are capable of reversing this action of TCDD. In conclusion, zerumbone and auraptene were identified to be the most effective agents in protecting U937 macrophages from developing these cell toxic effects of TCDD and DDT. PMID:20865247

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

PubMed Central

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

2014-01-01

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

Efficiency Improvement of Action Acquisition in Two-Link Robot Arm Using Fuzzy ART with Genetic Algorithm

NASA Astrophysics Data System (ADS)

Kotani, Naoki; Taniguchi, Kenji

An efficient learning method using Fuzzy ART with Genetic Algorithm is proposed. The proposed method reduces the number of trials by using a policy acquired in other tasks because a reinforcement learning needs a lot of the number of trials until an agent acquires appropriate actions. Fuzzy ART is an incremental unsupervised learning algorithm in responce to arbitrary sequences of analog or binary input vectors. Our proposed method gives a policy by crossover or mutation when an agent observes unknown states. Selection controls the category proliferation problem of Fuzzy ART. The effectiveness of the proposed method was verified with the simulation of the reaching problem for the two-link robot arm. The proposed method achieves a reduction of both the number of trials and the number of states.

A Systematic Review of the Effectiveness of Antianxiety and Antidepressive Agents for Functional Dyspepsia.

PubMed

Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Shimada, Yuji; Sasaki, Hitoshi; Matsumoto, Kohei; Takeda, Tsutomu; Ueyama, Hiroya; Matsumoto, Kenshi; Watanabe, Sumio

2017-12-01

Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective.

A Systematic Review of the Effectiveness of Antianxiety and Antidepressive Agents for Functional Dyspepsia

PubMed Central

Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Shimada, Yuji; Sasaki, Hitoshi; Matsumoto, Kohei; Takeda, Tsutomu; Ueyama, Hiroya; Matsumoto, Kenshi; Watanabe, Sumio

2017-01-01

Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective. PMID:29021437

Natural selection of memory-one strategies for the iterated prisoner's dilemma.

PubMed

Kraines, D P; Kraines, V Y

2000-04-21

In the iterated Prisoner's Dilemma, mutually cooperative behavior can become established through Darwinian natural selection. In simulated interactions of stochastic memory-one strategies for the Iterated Prisoner's Dilemma, Nowak and Sigmund discovered that cooperative agents using a Pavlov (Win-Stay Lose-Switch) type strategy eventually dominate a random population. This emergence follows more directly from a deterministic dynamical system based on differential reproductive success or natural selection. When restricted to an environment of memory-one agents interacting in iterated Prisoner's Dilemma games with a 1% noise level, the Pavlov agent is the only cooperative strategy and one of very few others that cannot be invaded by a similar strategy. Pavlov agents are trusting but no suckers. They will exploit weakness but repent if punished for cheating. Copyright 2000 Academic Press.

Direct manipulation of insect reproduction by agents of parasite origin

PubMed Central

Webb, T. J.; Hurd, H.

1999-01-01

Reproductive output of female Tenebrio molitor beetles is reduced upon infection with metacestodes of the rat tapeworm, Hymenolepis diminuta. We are using this as a model to investigate the adaptive significance of parasite-induced curtailment of insect reproduction. Production of the yolk protein vitellogenin (Vg) in the insect fat body is significantly reduced both in vitro and in vivo by metacestodes. Synthesis can be measured by using [14C]L-leucine incorporation, followed by immunoprecipitation. In this paper we demonstrate that a significant decrease in [14C]Vg can be produced by an acetic acid extract of the parasite. Conclusive evidence is presented that the active component(s) originate from the metacestodes: an extract of parasites grown entirely axenically has similar deleterious effects. The developmental stage of the metacestode is important: immature (stage I to II) parasites had greater capacity to suppress Vg synthesis than mature ones (stage V to VI). Examination of the chemical nature of the effector molecule(s) revealed that acetic-acid-extractable, boiling-resistant, pronase-sensitive agents in the molecular mass range 10 to 50 kDa reduced Vg synthesis by 47.4%. These data suggest that metacestodes produce a modulator molecule that directly affects insect vitellogenesis and, therefore, that reduction of host fitness may confer a selective advantage upon the parasite.

Effect of hydrophobic additive on oxygen transport in catalyst layer of proton exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Wang, Shunzhong; Li, Xiaohui; Wan, Zhaohui; Chen, Yanan; Tan, Jinting; Pan, Mu

2018-03-01

Oxygen transport resistance (OTR) is a critical factor influencing the performance of proton exchange membrane fuel cells (PEMFCs). In this paper, an effective method to reduce the OTR of catalyst layers (CLs) by introducing a hydrophobic additive into traditional CLs is proposed. A low-molecular-weight polytetrafluoroethylene (PTFE) is selected for its feasibility to prepare an emulsion, which is mixed with a traditional catalyst ink to successfully fabricate the CL with PTFE of 10 wt%. The PTFE film exists in the mesopores between the carbon particles. The limiting current of the hydrophobic CL was almost 4000 mA/cm2, which is 500 mA/cm2 higher than that of the traditional CL. PTFE reduces the OTR of the CL in the dry region by as much as 24 s/m compared to the traditional CL and expands the dry region from 2000 mA/cm2 in the traditional CL to 2500 mA/cm2. Furthermore, the CL with the hydrophobic agent can improve the oxygen transport in the wet region (>2000 mA/cm2) more effectively than that in the dry region. All these results indicate that the CL with the hydrophobic agent shows a superior performance in terms of optimizing water management and effectively reduces the OTR in PEMFCs.

The effect of antimicrobial agents on bond strength of orthodontic adhesives: a meta-analysis of in vitro studies.

PubMed

Altmann, A S P; Collares, F M; Leitune, V C B; Samuel, S M W

2016-02-01

Antimicrobial orthodontic adhesives aim to reduce white spot lesions' incidence in orthodontic patients, but they should not jeopardizing its properties. Systematic review and meta-analysis were performed to answer the question whether the association of antimicrobial agents with orthodontic adhesives compromises its mechanical properties and whether there is a superior antimicrobial agent. PubMed and Scopus databases. In vitro studies comparing shear bond strength of conventional photo-activated orthodontic adhesives to antimicrobial photo-activated orthodontic adhesives were considered eligible. Search terms included the following: orthodontics, orthodontic, antimicrobial, antibacterial, bactericidal, adhesive, resin, resin composite, bonding agent, bonding system, and bond strength. The searches yielded 494 citations, which turned into 467 after duplicates were discarded. Titles and abstracts were read and 13 publications were selected for full-text reading. Twelve studies were included in the meta-analysis. The global analysis showed no statistically significant difference between control and experimental groups. In the subgroup analysis, only the chlorhexidine subgroup showed a statistically significant difference, where the control groups had higher bond strength than the experimental groups. Many studies on in vitro orthodontic bond strength fail to report test conditions that could affect their outcomes. The pooled in vitro data suggest that adding an antimicrobial agent to an orthodontic adhesive system does not influence bond strength to enamel. It is not possible to state which antimicrobial agent is better to be associated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Digital PCR assessment of MGMT promoter methylation coupled with reduced protein expression optimises prediction of response to alkylating agents in metastatic colorectal cancer patients.

PubMed

Sartore-Bianchi, Andrea; Pietrantonio, Filippo; Amatu, Alessio; Milione, Massimo; Cassingena, Andrea; Ghezzi, Silvia; Caporale, Marta; Berenato, Rosa; Falcomatà, Chiara; Pellegrinelli, Alessio; Bardelli, Alberto; Nichelatti, Michele; Tosi, Federica; De Braud, Filippo; Di Nicolantonio, Federica; Barault, Ludovic; Siena, Salvatore

2017-01-01

O(6)-methylguanine-DNA-methyltransferase (MGMT) is a repair protein, and its deficiency makes tumours more susceptible to the cytotoxic effect of alkylating agents. Five clinical trials with temozolomide or dacarbazine have been performed in metastatic colorectal cancer (mCRC) with selection based on methyl-specific PCR (MSP) testing with modest results. We hypothesised that mitigated results are consequences of unspecific patient selection and that alternative methodologies for MGMT testing such as immunohistochemistry (IHC) and digital polymerase chain reaction (PCR) could enhance patient enrolment. Formalin-fixed paraffin embedded archival tumour tissue samples from four phase II studies of temozolomide or dacarbazine in MGMT MSP-positive mCRCs were analysed by IHC for MGMT protein expression and by methyl-BEAMing (MB) for percentage of promoter methylation. Pooled data were then retrospectively analysed according to objective response rate, progression-free survival (PFS) and overall survival (OS). One hundred and five patients were included in the study. Twelve had achieved partial response (PR) (11.4%), 24 stable disease (SD; 22.9%) and 69 progressive disease (PD; 65.7%). Patients with PR/SD had lower IHC scores and higher MB levels than those with PD. MGMT expression by IHC was negatively and MB levels positively associated with PFS (p < 0.001 and 0.004, respectively), but not with OS. By combining both assays, IHC low/MB high patients displayed an 87% reduction in the hazard of progression (p < 0.001) and a 77% in the hazard for death (p = 0.001). In mCRC selected for MGMT deficiency by MSP, IHC and MB testing improve clinical outcome to alkylating agents. Their combination could enhance patient selection in this setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization and competitive ability of non-aflatoxigenic Aspergillus flavus isolated from the maize agro-ecosystem in Argentina as potential aflatoxin biocontrol agents.

PubMed

Alaniz Zanon, María Silvina; Clemente, María Paz; Chulze, Sofía Noemí

2018-07-20

Aspergillus flavus is an opportunistic pathogen and may produce aflatoxins in maize, one of the most important crops in Argentina. A promising strategy to reduce aflatoxin accumulation is the biological control based on competitive exclusion. In order to select potential biocontrol agents among isolates from the maize growing region in Argentina, a total of 512 A. flavus strains were isolated from maize kernels and soil samples. Thirty-six per cent of the isolates from maize kernels did not produce detectable levels of aflatoxins, while 73% of the isolates from soil were characterized as non-aflatoxin producers. Forty percent and 49% of the isolates from maize kernels and soil samples, respectively, were not producers of cyclopiazonic acid (CPA). Sclerotia morphology was evaluated using Czapek Dox media. Eighty-six per cent of the isolates from maize kernels and 85% of the isolates from soil samples were L sclerotia morphotype (average diameter > 400 μm). The remaining isolates did not produce sclerotia. All isolates had MAT 1-1 idiomorph. The competitive ability of 9 non aflatoxigenic strains, 4 CPA(+) and 5 CPA(-), was evaluated in co-inoculations of maize kernels with an aflatoxigenic strain. All evaluated strains significantly (p < 0.05) reduced aflatoxin contamination in maize kernels. The aflatoxin B 1 (AFB 1 ) reduction ranged from 6 to 60%. The strain A. flavus ARG5/30 isolated from maize kernels would be a good candidate as a potential biocontrol agent to be used in maize, since it was characterized as neither aflatoxin nor CPA producer, morphotype L, MAT 1-1 idiomorph, and reduced AFB 1 content in maize kernels by 59%. This study showed the competitive ability of potential aflatoxin biocontrol agents to be evaluated under field trials in a maize agro-ecosystem in Argentina. Copyright © 2018 Elsevier B.V. All rights reserved.

Experimental Evaluation of Suitability of Selected Multi-Criteria Decision-Making Methods for Large-Scale Agent-Based Simulations.

PubMed

Tučník, Petr; Bureš, Vladimír

2016-01-01

Multi-criteria decision-making (MCDM) can be formally implemented by various methods. This study compares suitability of four selected MCDM methods, namely WPM, TOPSIS, VIKOR, and PROMETHEE, for future applications in agent-based computational economic (ACE) models of larger scale (i.e., over 10 000 agents in one geographical region). These four MCDM methods were selected according to their appropriateness for computational processing in ACE applications. Tests of the selected methods were conducted on four hardware configurations. For each method, 100 tests were performed, which represented one testing iteration. With four testing iterations conducted on each hardware setting and separated testing of all configurations with the-server parameter de/activated, altogether, 12800 data points were collected and consequently analyzed. An illustrational decision-making scenario was used which allows the mutual comparison of all of the selected decision making methods. Our test results suggest that although all methods are convenient and can be used in practice, the VIKOR method accomplished the tests with the best results and thus can be recommended as the most suitable for simulations of large-scale agent-based models.

Structural characterization of chemical warfare agent degradation products in decontamination solutions with proton band-selective (1)H-(31)P NMR spectroscopy.

PubMed

Koskela, Harri; Hakala, Ullastiina; Vanninen, Paula

2010-06-15

Decontamination solutions, which are usually composed of strong alkaline chemicals, are used for efficient detoxification of chemical warfare agents (CWAs). The analysis of CWA degradation products directly in decontamination solutions is challenging due to the nature of the matrix. Furthermore, occasionally an unforeseen degradation pathway can result in degradation products which could be eluded to in standard analyses. Here, we present the results of the application of proton band-selective (1)H-(31)P NMR spectroscopy, i.e., band-selective 1D (1)H-(31)P heteronuclear single quantum coherence (HSQC) and band-selective 2D (1)H-(31)P HSQC-total correlation spectroscopy (TOCSY), for ester side chain characterization of organophosphorus nerve agent degradation products in decontamination solutions. The viability of the approach is demonstrated with a test mixture of typical degradation products of nerve agents sarin, soman, and VX. The proton band-selective (1)H-(31)P NMR spectroscopy is also applied in characterization of unusual degradation products of VX in GDS 2000 solution.

Antibiosis and bmyB Gene Presence As Prevalent Traits for the Selection of Efficient Bacillus Biocontrol Agents against Crown Gall Disease.

PubMed

Frikha-Gargouri, Olfa; Ben Abdallah, Dorra; Bhar, Ilhem; Tounsi, Slim

2017-01-01

This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates. Moreover, potential in vitro biocontrol traits were investigated including biofilm formation, motility, hemolytic activity, detection of lipopeptide biosynthetic genes ( sfp, ituC and bmyB ) and production of antibacterial compounds. The obtained results indicated high correlations of the efficiency of the biocontrol with the reduction of gall weight ( p = 0.000) and the antibacterial activity in vitro ( p = 0.000). Moreover, there was strong correlations of the efficiency of the biocontrol ( p = 0.004) and the reduction in gall weight ( p = 0.000) with the presence of the bmyB gene. This gene directs the synthesis of the lipopeptide bacillomycin belonging to the iturinic family of lipopeptides. These results were also confirmed by the two-way hierarchical cluster analysis and the correspondence analysis showing the relatedness of these four variables. According to the obtained results a new screening procedure of Bacillus biocontrol agents against crown gall disease could be advanced consisting on two step selection procedure. The first consists on selecting strains with high antibacterial activity in vitro or those harbouring the bmyB gene. Further selection has to be performed on tomato plants in vivo . Moreover, based on the results of the biocontrol assay, five potent strains exhibiting high biocontrol abilities were selected. They were identified as Bacillus subtilis or Bacillus amyloliquefaciens . These strains were found to produce either surfactin or surfactin and iturin lipopeptides. In conclusion, our study presented a new and effective method to evaluate the biocontrol ability of antagonistic Bacillus strains against crown gall disease that could increase the efficiency of screening method of biocontrol agents. Besides, the selected strains could be used as novel biocontrol agents against pathogenic Agrobacterium tumefaciens strains.

Antibiosis and bmyB Gene Presence As Prevalent Traits for the Selection of Efficient Bacillus Biocontrol Agents against Crown Gall Disease

PubMed Central

Frikha-Gargouri, Olfa; Ben Abdallah, Dorra; Bhar, Ilhem; Tounsi, Slim

2017-01-01

This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates. Moreover, potential in vitro biocontrol traits were investigated including biofilm formation, motility, hemolytic activity, detection of lipopeptide biosynthetic genes (sfp, ituC and bmyB) and production of antibacterial compounds. The obtained results indicated high correlations of the efficiency of the biocontrol with the reduction of gall weight (p = 0.000) and the antibacterial activity in vitro (p = 0.000). Moreover, there was strong correlations of the efficiency of the biocontrol (p = 0.004) and the reduction in gall weight (p = 0.000) with the presence of the bmyB gene. This gene directs the synthesis of the lipopeptide bacillomycin belonging to the iturinic family of lipopeptides. These results were also confirmed by the two-way hierarchical cluster analysis and the correspondence analysis showing the relatedness of these four variables. According to the obtained results a new screening procedure of Bacillus biocontrol agents against crown gall disease could be advanced consisting on two step selection procedure. The first consists on selecting strains with high antibacterial activity in vitro or those harbouring the bmyB gene. Further selection has to be performed on tomato plants in vivo. Moreover, based on the results of the biocontrol assay, five potent strains exhibiting high biocontrol abilities were selected. They were identified as Bacillus subtilis or Bacillus amyloliquefaciens. These strains were found to produce either surfactin or surfactin and iturin lipopeptides. In conclusion, our study presented a new and effective method to evaluate the biocontrol ability of antagonistic Bacillus strains against crown gall disease that could increase the efficiency of screening method of biocontrol agents. Besides, the selected strains could be used as novel biocontrol agents against pathogenic Agrobacterium tumefaciens strains. PMID:28855909

3 CFR 13546 - Executive Order 13546 of July 2, 2010. Optimizing the Security of Biological Select Agents and...

Code of Federal Regulations, 2011 CFR

2011-01-01

... discourage research or other legitimate activities. (c) Understanding that research and laboratory work on... consultation, as needed, on topics of relevance to the SAP. Sec. 8. Sharing of Select Agent Program Information...

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-01-01

... in paragraph (b) of this section that have been genetically modified. (d) Overlap select agents or... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE... elements, recombinant nucleic acids, and recombinant organisms: (1) Nucleic acids that can produce...

Development of biocontrol agents from food microbial isolates for controlling post-harvest peach brown rot caused by Monilinia fructicola.

PubMed

Zhou, Ting; Schneider, Karin E; Li, Xiu-Zhen

2008-08-15

An unconventional strategy of screening food microbes for biocontrol activity was used to develop biocontrol agents for controlling post-harvest peach brown rot caused by Monilinia fructicola. Forty-four microbial isolates were first screened for their biocontrol activity on apple fruit. Compared with the pathogen-only check, seven of the 44 isolates reduced brown rot incidence by >50%, including four bacteria: Bacillus sp. C06, Lactobacillus sp. C03-b and Bacillus sp. T03-c, Lactobacillus sp. P02 and three yeasts: Saccharomyces delbrueckii A50, S. cerevisiae YE-5 and S. cerevisiae A41. Eight microbial isolates were selected for testing on peaches by wound co-inoculation with mixtures of individual microbial cultures and conidial suspension of M. fructicola. Only two of them showed significant biocontrol activity after five days of incubation at 22 degrees C. Bacillus sp. C06 suppressed brown rot incidence by 92% and reduced lesion diameter by 88% compared to the pathogen-only check. Bacillus sp.T03-c reduced incidence and lesion diameter by 40% and 62%, respectively. The two isolates were compared with Pseudomonas syringae MA-4, a biocontrol agent for post-harvest peach diseases, by immersing peaches in an aliquot containing individual microbial isolates and the pathogen conidia. Treatments with isolates MA-4, C06 and T03-c significantly controlled brown rot by 91, 100, and 100% respectively. However, only isolates MA-4 and C06 significantly reduced brown rot by 80% and 15%, respectively when bacterial cells alone were applied. On naturally infected peaches, both the bacterial culture and its cell-free filtrate of the isolate C06 significantly controlled peach decay resulting in 77 and 90% reduction, respectively, whereas the treatment using only the bacterial cells generally had no effect. Isolate C06 is a single colony isolate obtained from a mesophilic cheese starter, and has been identified belonging to Bacillus amyloliquefaciens. The results have clearly demonstrated that isolate C06 has a great potential for being developed into a biocontrol agent.

Inhibition of class IA PI3K enzymes in non-small cell lung cancer cells uncovers functional compensation among isoforms.

PubMed

Stamatkin, Christopher; Ratermann, Kelley L; Overley, Colleen W; Black, Esther P

2015-01-01

Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies while normal cell proliferation requires pathway functionality. Although inhibitors of the PI3K pathway are in clinical trials or approved for therapy, an understanding of the functional activities of pathway members in specific malignancies is needed. In lung cancers, the PI3K pathway is often aberrantly activated by mutation of genes encoding EGFR, KRAS, and PIK3CA proteins. We sought to understand whether class IA PI3K enzymes represent rational therapeutic targets in cells of non-squamous lung cancers by exploring pharmacological and genetic inhibitors of PI3K enzymes in a non-small cell lung cancer (NSCLC) cell line system. We found that class IA PI3K enzymes were expressed in all cell lines tested, but treatment of NSCLC lines with isoform-selective inhibitors (A66, TGX-221, CAL-101 and IC488743) had little effect on cell proliferation or prolonged inhibition of AKT activity. Inhibitory pharmacokinetic and pharmacodynamic responses were observed using these agents at non-isoform selective concentrations and with the pan-class I (ZSTK474) agent. Response to pharmacological inhibition suggested that PI3K isoforms may functionally compensate for one another thus limiting efficacy of single agent treatment. However, combination of ZSTK474 and an EGFR inhibitor (erlotinib) in NSCLC resistant to each single agent reduced cellular proliferation. These studies uncovered unanticipated cellular responses to PI3K isoform inhibition in NSCLC that does not correlate with PI3K mutations, suggesting that patients bearing tumors with wildtype EGFR and KRAS are unlikely to benefit from inhibitors of single isoforms but may respond to pan-isoform inhibition.

Synergistic Antiproliferative Effects of a New Cucurbitacin B Derivative and Chemotherapy Drugs on Lung Cancer Cell Line A549.

PubMed

Marostica, Lucas Lourenço; Silva, Izabella Thaís; Kratz, Jadel Müller; Persich, Lara; Geller, Fabiana Cristina; Lang, Karen Luise; Caro, Miguel Soriano Balparda; Durán, Fernando Javier; Schenkel, Eloir Paulo; Simões, Cláudia Maria Oliveira

2015-10-19

Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer.

Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1.

PubMed

Fanfone, Deborah; Despretz, Nadège; Stanicki, Dimitri; Rubio-Magnieto, Jenifer; Fossépré, Mathieu; Surin, Mathieu; Rorive, Sandrine; Salmon, Isabelle; Vander Elst, Luce; Laurent, Sophie; Muller, Robert N; Saussez, Sven; Burtea, Carmen

2017-10-06

The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1.

Effect of temperature in the selective reduction process of limonite nickel ore

NASA Astrophysics Data System (ADS)

Mayangsari, W.; Febriana, Eni; Prasetyo, A. B.

2018-05-01

Temperature is the main factor for the reduction process that influence to reduction degree, phase and morphology transformation. In order to determine these effects which is caused by reduction temperature, this study was conducted. Limoniticnickel ore was prepared by drying and size reduction. A part of prepared limonitewas characterized with XRF to determine the chemical composition. The other part was mixed with reducing agent and CaSO4 to produce pellet. A series of selective reduction processes were conducted to the pellet by using graphite crucible in the muffle furnace carbolite at 800° - 1100°C for 60 minutes. Reduced ore characterized by using XRD and SEM analysis. Based on the result study, weight loss and reduction degree increase as temperature raised along with CaSO4 addition. Moreover, it caused decomposition and transformation to the metallic phase of kamacite and iron up to 7.51% and 41.44% respectively in the reduction process at 1100°C for 60 minutes. Furthermore, particle size growth as metallic phase content increased.

New drugs for the treatment of rheumatoid arthritis.

PubMed

Schuna, A A; Megeff, C

2000-02-01

New pharmacologic treatment options for rheumatoid arthritis (RA) are described. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for RA but are limited by the risk of adverse effects, especially gastrointestinal and renal toxicity. The therapeutic effects of these agents are mediated primarily through inhibition of cyclooxygenase (COX) and prevention of subsequent formation of prostaglandins and related inflammatory mediators. Nonspecific COX inhibition appears to be responsible for much of the toxicity of NSAIDs. Agents have been developed that can selectively inhibit the COX-2 isoform, while sparing COX-1. Celecoxib and other COX-2 inhibitors appear to be no more efficacious than conventional NSAIDs, but offer superior safety. COX-2 inhibitors should be considered for patients who are candidates for NSAID therapy but at risk for GI bleeding. Unlike disease-modifying antirheumatic drugs (DMARDs), these agents do not alter underlying disease progression. Leflunomide is a newer DMARD that reduces pyrimidine synthesis, thus decreasing rheumatoid inflammation. Leflunomide appears to be as effective as methotrexate but, unlike that drug, does not necessitate monitoring for bone marrow toxicity. Etanercept, the first biological agent with FDA-approved labeling for use in RA, has shown efficacy and minimal toxicity, except for injection-site reactions. Other biologicals that have been investigated for use in RA include infliximab and interleukin-1-receptor antagonist. COX-2 inhibitors, leflunomide, and etanercept are promising new drugs available for treating RA. Other agents are under development.

Non-antibiotic selection systems for soybean somatic embryos: the lysine analog aminoethyl-cysteine as a selection agent

PubMed Central

2009-01-01

Background In soybean somatic embryo transformation, the standard selection agent currently used is hygromycin. It may be preferable to avoid use of antibiotic resistance genes in foods. The objective of these experiments was to develop a selection system for producing transgenic soybean somatic embryos without the use of antibiotics such as hygromycin. Results When tested against different alternate selection agents our studies show that 0.16 μg/mL glufosinate, 40 mg/L isopropylamine-glyphosate, 0.5 mg/mL (S-(2 aminoethyl)-L-cysteine) (AEC) and the acetolactate synthase (ALS) inhibitors Exceed® and Synchrony® both at 150 μg/mL inhibited soybean somatic embryo growth. Even at the concentration of 2 mg/mL, lysine+threonine (LT) were poor selection agents. The use of AEC may be preferable since it is a natural compound. Unlike the plant enzyme, dihydrodipicolinate synthase (DHPS) from E. coli is not feed-back inhibited by physiological concentrations of lysine. The dapA gene which codes for E. coli DHPS was expressed in soybean somatic embryos under the control of the CaMV 35S promoter. Following introduction of the construct into embryogenic tissue of soybean, transgenic events were recovered by incubating the tissue in liquid medium containing AEC at a concentration of 5 mM. Only transgenic soybeans were able to grow at this concentration of AEC; no escapes were observed. Conclusion Genetically engineered soybeans expressing a lysine insensitive DHPS gene can be selected with the non-antibiotic selection agent AEC. We also report here the inhibitory effects of glufosinate, (isopropylamine-glyphosate) (Roundup®), AEC and the ALS inhibitors Exceed® and Synchrony® against different tissues of soybean PMID:19922622

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-01-01

... this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE...) Genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic organisms...

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-01-01

... this section that have been genetically modified. (d) Overlap select agents or toxins that meet any of... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE...) Genetic elements, recombinant and/or synthetic nucleic acids, and recombinant and/or synthetic organisms...

42 CFR 73.9 - Responsible Official.

Code of Federal Regulations, 2012 CFR

2012-10-01

... toxins must be immediately reported by telephone, facsimile, or e-mail: Bacillus anthracis, Botulinum... SELECT AGENTS AND TOXINS § 73.9 Responsible Official. (a) An individual or entity required to register...) Ensure that annual inspections are conducted for each laboratory where select agents or toxins are stored...

The Scarlet Letter of Alkylation: A Mini Review of Selective Alkylating Agents

PubMed Central

Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J

2012-01-01

If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to “tame” the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it is referred to herein, constitutes an extremely nascent and dynamic field in oncology. The pharmacodynamic response to this selective strategy depends on a delicate kinetic balance between specificity and the rate and extent of binding. Three representative compounds are presented: RRx-001, 3-bromopyruvate, and TH-302. The main impetus for the development of these compounds has been the avoidance of the serious complications of traditional alkylating agents; therefore, it is the thesis of this review that they should not experience stigma by association. PMID:22937173

Neural Modularity Helps Organisms Evolve to Learn New Skills without Forgetting Old Skills

PubMed Central

Ellefsen, Kai Olav; Mouret, Jean-Baptiste; Clune, Jeff

2015-01-01

A long-standing goal in artificial intelligence is creating agents that can learn a variety of different skills for different problems. In the artificial intelligence subfield of neural networks, a barrier to that goal is that when agents learn a new skill they typically do so by losing previously acquired skills, a problem called catastrophic forgetting. That occurs because, to learn the new task, neural learning algorithms change connections that encode previously acquired skills. How networks are organized critically affects their learning dynamics. In this paper, we test whether catastrophic forgetting can be reduced by evolving modular neural networks. Modularity intuitively should reduce learning interference between tasks by separating functionality into physically distinct modules in which learning can be selectively turned on or off. Modularity can further improve learning by having a reinforcement learning module separate from sensory processing modules, allowing learning to happen only in response to a positive or negative reward. In this paper, learning takes place via neuromodulation, which allows agents to selectively change the rate of learning for each neural connection based on environmental stimuli (e.g. to alter learning in specific locations based on the task at hand). To produce modularity, we evolve neural networks with a cost for neural connections. We show that this connection cost technique causes modularity, confirming a previous result, and that such sparsely connected, modular networks have higher overall performance because they learn new skills faster while retaining old skills more and because they have a separate reinforcement learning module. Our results suggest (1) that encouraging modularity in neural networks may help us overcome the long-standing barrier of networks that cannot learn new skills without forgetting old ones, and (2) that one benefit of the modularity ubiquitous in the brains of natural animals might be to alleviate the problem of catastrophic forgetting. PMID:25837826

Neural modularity helps organisms evolve to learn new skills without forgetting old skills.

PubMed

Ellefsen, Kai Olav; Mouret, Jean-Baptiste; Clune, Jeff

2015-04-01

A long-standing goal in artificial intelligence is creating agents that can learn a variety of different skills for different problems. In the artificial intelligence subfield of neural networks, a barrier to that goal is that when agents learn a new skill they typically do so by losing previously acquired skills, a problem called catastrophic forgetting. That occurs because, to learn the new task, neural learning algorithms change connections that encode previously acquired skills. How networks are organized critically affects their learning dynamics. In this paper, we test whether catastrophic forgetting can be reduced by evolving modular neural networks. Modularity intuitively should reduce learning interference between tasks by separating functionality into physically distinct modules in which learning can be selectively turned on or off. Modularity can further improve learning by having a reinforcement learning module separate from sensory processing modules, allowing learning to happen only in response to a positive or negative reward. In this paper, learning takes place via neuromodulation, which allows agents to selectively change the rate of learning for each neural connection based on environmental stimuli (e.g. to alter learning in specific locations based on the task at hand). To produce modularity, we evolve neural networks with a cost for neural connections. We show that this connection cost technique causes modularity, confirming a previous result, and that such sparsely connected, modular networks have higher overall performance because they learn new skills faster while retaining old skills more and because they have a separate reinforcement learning module. Our results suggest (1) that encouraging modularity in neural networks may help us overcome the long-standing barrier of networks that cannot learn new skills without forgetting old ones, and (2) that one benefit of the modularity ubiquitous in the brains of natural animals might be to alleviate the problem of catastrophic forgetting.

Green route for synthesis of multifunctional fluorescent carbon dots from Tulsi leaves and its application as Cr(VI) sensors, bio-imaging and patterning agents.

PubMed

Bhatt, Shreya; Bhatt, Madhuri; Kumar, Anshu; Vyas, Gaurav; Gajaria, Tejal; Paul, Parimal

2018-07-01

We report a one pot green strategy for the synthesis of carbon dots using tulsi leaves and their potential application in sensing of Cr(VI) selectively. The detection mechanism is based on the phenomenon called inner filter effect (IFE) and a good linear static quenching was observed in the range of 1.6 μM to 50 μM with a detection limit of 4.5 ppb. The reversible switching in fluorescence has been tested and a good recovery in fluorescence was observed up to three consecutive cycles upon addition of ascorbic acid as reducing agent. Also the low toxicity, high fluorescence and photostabilty of the CDs make them excellent imaging and patterning agent. The acid and alkali resistant property of these CDs makes it suitable for real sample analysis. The fluorescent CDs were applied for successful detection of Cr(VI) in water with spike-recoveries ranging from 93 to 99%. Copyright © 2018 Elsevier B.V. All rights reserved.

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation

PubMed Central

Mendez-Enriquez, E; Melendez, Y; Martinez, F; Baay, G; Huerta-Yepez, S; Gonzalez-Bonilla, C; Fortoul, T I; Soldevila, G; García-Zepeda, E A

2008-01-01

Airway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides. PMID:18336592

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation.

PubMed

Mendez-Enriquez, E; Melendez, Y; Martinez, F; Baay, G; Huerta-Yepez, S; Gonzalez-Bonilla, C; Fortoul, T I; Soldevila, G; García-Zepeda, E A

2008-05-01

Airway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides.

How Do Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of Arterial Blood Pressure

PubMed Central

Digne-Malcolm, Holly; Frise, Matthew C.; Dorrington, Keith L.

2016-01-01

Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, some Ca++-channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors). These findings provide insights into the actions of antihypertensive drugs, and challenge misconceptions about the mechanisms underlying the therapeutic efficacy of many of the agents. PMID:27524972

Micro-Level Adaptation, Macro-Level Selection, and the Dynamics of Market Partitioning

PubMed Central

García-Díaz, César; van Witteloostuijn, Arjen; Péli, Gábor

2015-01-01

This paper provides a micro-foundation for dual market structure formation through partitioning processes in marketplaces by developing a computational model of interacting economic agents. We propose an agent-based modeling approach, where firms are adaptive and profit-seeking agents entering into and exiting from the market according to their (lack of) profitability. Our firms are characterized by large and small sunk costs, respectively. They locate their offerings along a unimodal demand distribution over a one-dimensional product variety, with the distribution peak constituting the center and the tails standing for the peripheries. We found that large firms may first advance toward the most abundant demand spot, the market center, and release peripheral positions as predicted by extant dual market explanations. However, we also observed that large firms may then move back toward the market fringes to reduce competitive niche overlap in the center, triggering nonlinear resource occupation behavior. Novel results indicate that resource release dynamics depend on firm-level adaptive capabilities, and that a minimum scale of production for low sunk cost firms is key to the formation of the dual structure. PMID:26656107

Novel morphology change of Au-Methotrexate conjugates: From nanochains to discrete nanoparticles.

PubMed

Wang, Wei-Yuan; Zhao, Xiu-Fen; Ju, Xiao-Han; Wang, Yu; Wang, Lin; Li, Shu-Ping; Li, Xiao-Dong

2016-12-30

A novel morphology change of Au-methotrexate (Au-MTX) conjugates that could transform from nanochains to discrete nanoparticles was achieved by a simple, one-pot, and hydrothermal growth method. Herein, MTX was used efficiently as a complex-forming agent, reducing agent, capping agent, and importantly a targeting anticancer drug. The formation mechanism suggested a similarity with the molecular imprinting technology. The Au-MTX complex induced the MTX molecules to selectively adsorb on different crystal facets of gold nanoparticles (AuNPs) and then formed gold nanospheres. Moreover, the abundantly binding MTX molecules promoted directional alignment of these gold nanospheres to further form nanochains. More interestingly, the linear structures gradually changed into discrete nanoparticles by adding different amount of ethylene diamine tetra (methylene phosphonic acid) (EDTMPA) into the initial reaction solution, which likely arose from the strong electrostatic effect of the negatively charged phosphonic acid groups. Compared with the as-prepared nanochains, the resultant discrete nanoparticles showed almost equal drug loading capacity but with higher drug release control, colloidal stability, and in vitro anticancer activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Micro-Level Adaptation, Macro-Level Selection, and the Dynamics of Market Partitioning.

PubMed

García-Díaz, César; van Witteloostuijn, Arjen; Péli, Gábor

2015-01-01

This paper provides a micro-foundation for dual market structure formation through partitioning processes in marketplaces by developing a computational model of interacting economic agents. We propose an agent-based modeling approach, where firms are adaptive and profit-seeking agents entering into and exiting from the market according to their (lack of) profitability. Our firms are characterized by large and small sunk costs, respectively. They locate their offerings along a unimodal demand distribution over a one-dimensional product variety, with the distribution peak constituting the center and the tails standing for the peripheries. We found that large firms may first advance toward the most abundant demand spot, the market center, and release peripheral positions as predicted by extant dual market explanations. However, we also observed that large firms may then move back toward the market fringes to reduce competitive niche overlap in the center, triggering nonlinear resource occupation behavior. Novel results indicate that resource release dynamics depend on firm-level adaptive capabilities, and that a minimum scale of production for low sunk cost firms is key to the formation of the dual structure.

Multifunctional mesoporous silica nanoparticles for combined therapeutic, diagnostic and targeted action in cancer treatment.

PubMed

Rosenholm, Jessica M; Sahlgren, Cecilia; Lindén, Mika

2011-07-01

The main objective in the development of nanomedicine is to obtain delivery platforms for targeted delivery of drugs or imaging agents for improved therapeutic efficacy, reduced side effects and increased diagnostic sensitivity. A (nano)material class that has been recognized for its controllable properties on many levels is ordered mesoporous inorganic materials, typically in the form of amorphous silica (SiO2). Characteristics for this class of materials include mesoscopic order, tunable pore dimensions in the (macro)molecular size range, a high pore volume and surface area, the possibility for selective surface functionality as well as morphology control. The robust but biodegradable ceramic matrix moreover provides shelter for incorporated agents (drugs, proteins, imaging agents, photosensitizers) leaving the outer particle surface free for further modification. The unique features make these materials particularly amenable to modular design, whereby functional moieties and features may be interchanged or combined to produce multifunctional nanodelivery systems combining targeting, diagnostic, and therapeutic actions. This review covers the latest developments related to the use of mesoporous silica nanoparticles (MSNs) as nanocarriers in biomedical applications, with special focus on cancer therapy and diagnostics.

Cytotoxicity and Antineoplastic Activities of Alkylamines and Their Borane Derivatives

PubMed Central

Tse, Elaine Y.; Muhammad, Rosallah A.

1996-01-01

The alkylamines and their related boron derivatives demonstrated potent cytotoxicity against the growth of murine and human tissue cultured cells. These agents did not necessarily require the boron atom to possess potent cytotoxic action in certain tumor lines. Their ability to suppress tumor cell growth was based on their inhibition of DNA and protein syntheses. DNA synthesis was reduced because purine synthesis was blocked at the enzyme site of IMP dehydrogenase by the agents. In addition ribonucleotide reductase and nucleoside kinase activities were reduced by the agents which would account for the reduced d[NTP] pools. The DNA template or molecule may be a target of the drugs with regard to binding of the drug to nucleoside bases or intercalaction of the drug between DNA base pairs. Only some Of the agents caused DNA fragmentation with reduced DNA viscosity. These effects would contribute to overall cell death afforded by the agents. PMID:18472803

A biotin-conjugated pyridine-based isatoic anhydride, a selective room temperature RNA-acylating agent for the nucleic acid separation.

PubMed

Ursuegui, S; Yougnia, R; Moutin, S; Burr, A; Fossey, C; Cailly, T; Laayoun, A; Laurent, A; Fabis, F

2015-03-28

Isatoic anhydride derivatives, including a biotin and a disulfide linker were specifically designed for nucleic acid separation. 2'-OH selective RNA acylation, capture of biotinylated RNA adducts by streptavidin-coated magnetic beads and disulfide chemical cleavage led to isolation of highly enriched RNA samples from an initial 9/1 DNA-RNA mixture. Starting from the parent compound N-methylisatoic anhydride A which was used at 65 °C, we improved the extraction process by designing a new generation of isatoic anhydrides that are able to react under smoother conditions. Among them, a pyridine-based isatoic anhydride derivative 15f was found to be reactive at room temperature, leading to enhance the efficiency and selectivity of the extraction process by significantly reducing DNA side extraction. The extracted and purified RNAs can then be detected by RT-PCR.

42 CFR 73.9 - Responsible Official.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SELECT AGENTS AND TOXINS § 73.9 Responsible Official. (a) An individual or entity required to register... onsite incidents involving select agents and toxins in accordance with the entity's incident response... toxins are stored or used in order to determine compliance with the requirements of this part. The...

42 CFR 73.9 - Responsible Official.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SELECT AGENTS AND TOXINS § 73.9 Responsible Official. (a) An individual or entity required to register... onsite incidents involving select agents and toxins in accordance with the entity's incident response... toxins are stored or used in order to determine compliance with the requirements of this part. The...

Selective disulfide reduction for labeling and enhancement of Fab antibody fragments

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

Kirley, Terence L., E-mail: terry.kirley@uc.edu; Greis, Kenneth D.; Norman, Andrew B.

Many methods have been developed for chemical labeling and enhancement of the properties of antibodies and their common fragments, including the Fab and F(ab’){sub 2} fragments. Somewhat selective reduction of some antibody disulfide bonds has been previously achieved, yielding antibodies and antibody fragments that can be labeled at defined sites, enhancing their utility and properties. Selective reduction of the two hinge disulfide bonds present in F(ab’){sub 2} fragments using mild reduction has been useful. However, such reduction is often not quantitative and results in the reduction of multiple disulfide bonds, and therefore subsequent multiple labeling or conjugation sites are neithermore » homogenous nor stoichiometric. Here, a simple and efficient selective reduction of the single disulfide bond linking the partial heavy chain and the intact light chain which compose the Fab fragment is accomplished utilizing tris(2-carboxyethyl)phosphine (TCEP) immobilized on agarose beads. The resultant reduced cysteine residues were labeled with several cysteine-selective fluorescent reagents, as well as by cysteine-directed PEGylation. These two cysteine residues can also be re-ligated by means of a bifunctional cysteine cross-linking agent, dibromobimane, thereby both restoring a covalent linkage between the heavy and light chains at this site, far removed from the antigen binding site, and also introducing a fluorescent probe. There are many other research and clinical uses for these selectively partially reduced Fab fragments, including biotinylation, toxin and drug conjugation, and incorporation of radioisotopes, and this technique enables simple generation of very useful Fab fragment derivatives with many potential applications. - Highlights: • TCEP agarose is effective for selective reduction of a single Fab disulfide bond. • This disulfide is solvent accessible and distant from the antigen binding site. • A variety of buffers of varying pHs can be used, simplifying subsequent steps. • The methods used are simple, easily verifiable, reproducible, and quantitative. • The selectively reduced Fab has many experimental and clinical applications.« less

Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data.

PubMed

Kurosaki, Eiji; Ogasawara, Hideaki

2013-07-01

Sodium-glucose cotransporter-2 (SGLT2) is expressed in the proximal tubules of the kidneys and plays a key role in renal glucose reabsorption. A novel class of antidiabetic medications, SGLT2-selective inhibitors attempt to improve glycemic control in diabetics by preventing glucose from being reabsorbed through SGLT2 and re-entering circulation. Ipragliflozin is an SGLT2 inhibitor in Phase 3 clinical development for the treatment of type 2 diabetes mellitus (T2DM). In this review, we summarize recent animal and human studies on ipragliflozin and other SGLT2 inhibitors including dapagliflozin, canagliflozin, empagliflozin, tofogliflozin, and luseogliflozin. These agents all show potent and selective SGLT2 inhibition in vitro and reduce blood glucose levels and HbA1c in both diabetic animal models and patients with T2DM. SGLT2 inhibitors offer several advantages over other classes of hypoglycemic agents. Due to their insulin-independent mode of action, SGLT2 inhibitors provide steady glucose control without major risk for hypoglycemia and may also reverse β-cell dysfunction and insulin resistance. Other favorable effects of SGLT2 inhibitors include a reduction in both body weight and blood pressure. SGLT2 inhibitors are safe and well tolerated and can easily be combined with other classes of antidiabetic medications to achieve tighter glycemic control. The long-term safety and efficacy of these agents are under evaluation. Copyright © 2013 Elsevier Inc. All rights reserved.

alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.

PubMed

Tomasetti, M; Strafella, E; Staffolani, S; Santarelli, L; Neuzil, J; Guerrieri, R

2010-04-13

A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death. The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected. These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.

Workload-Based Automated Interface Mode Selection

DTIC Science & Technology

2012-03-22

Process . . . . . . . . . . . . . . . . . . . . . 31 3.5.10 Agent Reward Function . . . . . . . . . . . . . . . . 31 3.5.11 Accelerated Learning... Strategies . . . . . . . . . . . . 31 4. Experimental Methodology . . . . . . . . . . . . . . . . . . . . . . . . 33 4.1 System Engineering Methodology...26 5. Agent state function. . . . . . . . . . . . . . . . . . . . . . . . . . . 28 6. Agent reward function

Efficacy of commercially available wipes for disinfection of pulse oximeter sensors.

PubMed

Nandy, Poulomi; Lucas, Anne D; Gonzalez, Elizabeth A; Hitchins, Victoria M

2016-03-01

This study examined the effectiveness of commercially available disinfecting wipes and cosmetic wipes in disinfecting pulse oximeter sensors contaminated with pathogenic bacterial surrogates. Surrogates of potential biological warfare agents and bacterial pathogens associated with hospital-acquired infections (HAIs) were spotted on test surfaces, with and without an artificial test soil (sebum), allowed to dry, and then cleaned with different commercially available cleaning and disinfecting wipes or sterile gauze soaked in water, bleach (diluted 1:10), or 70% isopropanol. The percentage of microbial survival and an analytical estimation of remaining test soil on devices were determined. Wipes containing sodium hypochlorite as the active ingredient and gauze soaked in bleach (1:10) were the most effective in removing both vegetative bacteria and spores. In the presence of selective disinfectants, sebum had a protective effect on vegetative bacteria, but not on spores. The presence of sebum reduces the cleaning efficiency of some commercially available wipes for some select microbes. Various commercial wipes performed significantly better than the designated cleaning agent (70% isopropanol) in disinfecting the oximetry sensor. Cosmetic wipes were not more effective than the disinfecting wipes in removing sebum. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Ecology and Evolution of the Human Microbiota: Fire, Farming and Antibiotics

PubMed Central

Gillings, Michael R.; Paulsen, Ian T.; Tetu, Sasha G.

2015-01-01

Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention of agriculture, and the increasing availability of processed foods after the Industrial Revolution. However, no factor has had a faster or more direct effect than antimicrobial agents. Biocides, disinfectants and antibiotics select for individual cells that carry resistance genes, immediately reducing both overall microbial diversity and within-species genetic diversity. Treated individuals may never recover their original diversity, and repeated treatments lead to a series of genetic bottlenecks. The sequential introduction of diverse antimicrobial agents has selected for increasingly complex DNA elements that carry multiple resistance genes, and has fostered their spread through the human microbiota. Practices that interfere with microbial colonization, such as sanitation, Caesarian births and bottle-feeding, exacerbate the effects of antimicrobials, generating species-poor and less resilient microbial assemblages in the developed world. More and more evidence is accumulating that these perturbations to our internal ecosystems lie at the heart of many diseases whose frequency has shown a dramatic increase over the last half century. PMID:26371047

Ecology and Evolution of the Human Microbiota: Fire, Farming and Antibiotics.

PubMed

Gillings, Michael R; Paulsen, Ian T; Tetu, Sasha G

2015-09-08

Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention of agriculture, and the increasing availability of processed foods after the Industrial Revolution. However, no factor has had a faster or more direct effect than antimicrobial agents. Biocides, disinfectants and antibiotics select for individual cells that carry resistance genes, immediately reducing both overall microbial diversity and within-species genetic diversity. Treated individuals may never recover their original diversity, and repeated treatments lead to a series of genetic bottlenecks. The sequential introduction of diverse antimicrobial agents has selected for increasingly complex DNA elements that carry multiple resistance genes, and has fostered their spread through the human microbiota. Practices that interfere with microbial colonization, such as sanitation, Caesarian births and bottle-feeding, exacerbate the effects of antimicrobials, generating species-poor and less resilient microbial assemblages in the developed world. More and more evidence is accumulating that these perturbations to our internal ecosystems lie at the heart of many diseases whose frequency has shown a dramatic increase over the last half century.

Pyropheophorbide 2-deoxyglucosamide: a new photosensitizer targeting glucose transporters.

PubMed

Zhang, Min; Zhang, Zhihong; Blessington, Dana; Li, Hui; Busch, Theresa M; Madrak, Vanessa; Miles, Jeremy; Chance, Britton; Glickson, Jerry D; Zheng, Gang

2003-01-01

To prepare near-infrared fluorescence imaging and photodynamic therapy agents targeted at glucose transporters, pyropheophorbide 2-deoxyglucosamide (Pyro-2DG) was synthesized and evaluated in a 9L glioma rat model. Fluorescence imaging studies demonstrate that Pyro-2DG is selectively accumulated in the tumor. Upon its photoactivation, we demonstrate that this agent efficiently causes selective mitochondrial damage to the region of a tumor that was photoirradiated after administration of this agent, but does not affect tissues photoirradiated in the absence of the agent or tissues treated with the agent that are not photoirradiated. Preliminary confocal microscopy studies suggest that Pyro-2DG is delivered and trapped in tumor cells via the GLUT/hexokinase pathway and therefore is useful both as a tumor-targeted NIR fluorescence imaging probe and as a PDT agent for the destruction of cancer.

Synthetic applications of hypophosphite derivatives in reduction.

PubMed

Guyon, Carole; Métay, Estelle; Popowycz, Florence; Lemaire, Marc

2015-08-07

The development of new tools for the reduction of organic functions to reach high chemo- and stereo-selectivity is an important research domain. Although, aluminum and boron hydrides are commonly used, they suffer from environmentally and safety issues. In particular, at industrial scale, the search for more specific and efficient reagents with a lower ecological impact remains one of the main objectives of organic chemists. This review captures highlights from literature concerning phosphonic and phosphinic acid derivatives as reducing agents and evaluates their potential as alternatives, in particular to boron and aluminum hydrides.

Samarium Diiodide-Mediated Reactions in Total Synthesis

PubMed Central

Nicolaou, K. C.; Ellery, Shelby P.; Chen, Jason S.

2009-01-01

Introduced by Henri Kagan more than three decades ago, samarium diiodide (SmI2) has found increasing applications in chemical synthesis. This single-electron reducing agent has been particularly useful in C–C bond formations, including those found in total synthesis endeavors. This Review highlights selected applications of SmI2 in total synthesis, with special emphasis on novel transformations and mechanistic considerations. The examples discussed are both illustrative of the power of this reagent in complex molecule construction and inspirational for the design of synthetic strategies toward such targets, both natural and designed. PMID:19714695

Dehydration of plutonium or neptunium trichloride hydrate

DOEpatents

Foropoulos, Jr., Jerry; Avens, Larry R.; Trujillo, Eddie A.

1992-01-01

A process of preparing anhydrous actinide metal trichlorides of plutonium or neptunium by reacting an aqueous solution of an actinide metal trichloride selected from the group consisting of plutonium trichloride or neptunium trichloride with a reducing agent capable of converting the actinide metal from an oxidation state of +4 to +3 in a resultant solution, evaporating essentially all the solvent from the resultant solution to yield an actinide trichloride hydrate material, dehydrating the actinide trichloride hydrate material by heating the material in admixture with excess thionyl chloride, and recovering anhydrous actinide trichloride is provided.

Dehydration of plutonium or neptunium trichloride hydrate

DOEpatents

Foropoulos, J. Jr.; Avens, L.R.; Trujillo, E.A.

1992-03-24

A process is described for preparing anhydrous actinide metal trichlorides of plutonium or neptunium by reacting an aqueous solution of an actinide metal trichloride selected from the group consisting of plutonium trichloride or neptunium trichloride with a reducing agent capable of converting the actinide metal from an oxidation state of +4 to +3 in a resultant solution, evaporating essentially all the solvent from the resultant solution to yield an actinide trichloride hydrate material, dehydrating the actinide trichloride hydrate material by heating the material in admixture with excess thionyl chloride, and recovering anhydrous actinide trichloride.

One-Electron Reduction of Penicillins in Relation to the Oxidative Stress Phenomenon

PubMed Central

Szabó, László; Tóth, Tünde; Takács, Erzsébet; Wojnárovits, László

2015-01-01

Certain bactericidal antibiotics target mitochondrial components and, due to the leakage of electrons from the electron transport chain, one-electron reduction might occur that can lead to intermediates passing the electron to suitable acceptors. This study aimed at investigating the one-electron reduction mechanism of selected penicillin derivatives using pulse radiolysis techniques. Penicillins can accommodate the electron on each of their carbonyl carbon. Ketyl radicals are thus produced, which are reducing agents with possibility to interact with suitable biomolecules. A detailed mechanism of the reduction is reported. PMID:26690427

Carbon Monoxide and Nitric Oxide Mediate Cytoskeletal Reorganization in Microvascular Cells via Vasodilator-Stimulated Phosphoprotein Phosphorylation

PubMed Central

Li Calzi, Sergio; Purich, Daniel L.; Chang, Kyung Hee; Afzal, Aqeela; Nakagawa, Takahiko; Busik, Julia V.; Agarwal, Anupam; Segal, Mark S.; Grant, Maria B.

2008-01-01

OBJECTIVE— We examined the effect of the vasoactive agents carbon monoxide (CO) and nitric oxide (NO) on the phosphorylation and intracellular redistribution of vasodilator-stimulated phosphoprotein (VASP), a critical actin motor protein required for cell migration that also controls vasodilation and platelet aggregation. RESEARCH DESIGN AND METHODS— We examined the effect of donor-released CO and NO in endothelial progenitor cells (EPCs) and platelets from nondiabetic and diabetic subjects and in human microvascular endothelial cells (HMECs) cultured under low (5.5 mmol/l) or high (25 mmol/l) glucose conditions. VASP phosphorylation was evaluated using phosphorylation site-specific antibodies. RESULTS— In control platelets, CO selectively promotes phosphorylation at VASP Ser-157, whereas NO promotes phosphorylation primarily at Ser-157 and also at Ser-239, with maximal responses at 1 min with both agents on Ser-157 and at 15 min on Ser-239 with NO treatment. In diabetic platelets, neither agent resulted in VASP phosphorylation. In nondiabetic EPCs, NO and CO increased phosphorylation at Ser-239 and Ser-157, respectively, but this response was markedly reduced in diabetic EPCs. In endothelial cells cultured under low glucose conditions, both CO and NO induced phosphorylation at Ser-157 and Ser-239; however, this response was completely lost when cells were cultured under high glucose conditions. In control EPCs and in HMECs exposed to low glucose, VASP was redistributed to filopodia-like structures following CO or NO exposure; however, redistribution was dramatically attenuated under high glucose conditions. CONCLUSIONS— Vasoactive gases CO and NO promote cytoskeletal changes through site- and cell type–specific VASP phosphorylation, and in diabetes, blunted responses to these agents may lead to reduced vascular repair and tissue perfusion. PMID:18559661

Feasibility of dual-low scheme combined with iterative reconstruction technique in acute cerebral infarction volume CT whole brain perfusion imaging.

PubMed

Wang, Tao; Gong, Yi; Shi, Yibing; Hua, Rong; Zhang, Qingshan

2017-07-01

The feasibility of application of low-concentration contrast agent and low tube voltage combined with iterative reconstruction in whole brain computed tomography perfusion (CTP) imaging of patients with acute cerebral infarction was investigated. Fifty-nine patients who underwent whole brain CTP examination and diagnosed with acute cerebral infarction from September 2014 to March 2016 were selected. Patients were randomly divided into groups A and B. There were 28 cases in group A [tube voltage, 100 kV; contrast agent, iohexol (350 mg I/ml), reconstructed by filtered back projection] and 31 cases in group B [tube voltage, 80 kV; contrast agent, iodixanol (270 mg I/ml), reconstructed by algebraic reconstruction technique]. The artery CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), dose length product, effective dose (ED) of radiation and brain iodine intake of both groups were measured and statistically analyzed. Two physicians carried out kappa (κ) analysis on the consistency of image quality evaluation. The difference in subjective image quality evaluation between the groups was tested by χ 2 . The differences in CT value, SNR, CNR, CTP and CT angiography subjective image quality evaluation between both groups were not statistically significant (P>0.05); the diagnosis rate of the acute infarcts between the two groups was not significantly different; while the ED and iodine intake in group B (dual low-dose group) were lower than group A. In conclusion, combination of low tube voltage and iterative reconstruction technique, and application of low-concentration contrast agent (270 mg I/ml) in whole brain CTP examination reduced ED and iodine intake without compromising image quality, thereby reducing the risk of contrast-induced nephropathy.

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

Hamilton, Terry F.; Martinelli, Roger E.; Kehl, Steven R.

A series of K d tracer batch experiments were conducted in this paper to assess the absorptive-desorption properties of Biochar as a potential agent to selectively sequester labile soil Cs or otherwise help reduce the uptake of Cs isotopes into plants. A parallel experiment was conducted for strontium. Fine-grained fractionated Woodlands tree Biochar was found to have a relatively high affinity for Cs ions (K d > 100) relative to coral soil (K d < 10) collected from the Marshall Islands. The Biochar material also contains an abundance of K (and Mg). Finally, these findings support a hypothesis that themore » addition of Biochar as a soil amendment may provide a simple yet effective method for reducing soil-to-plant transfer of Cs isotopes in contaminated environments.« less

[Microflora of damaged ferroconcrete structures under the conditions of inhibitory protection].

PubMed

Kopteva, Zh P; Zanina, V V; Purish, L M; Piliashenko-Novokhatnyĭ, A I; Kozlova, I A

2004-01-01

Thionic, sulphate-reducing, denitrifying and ammonifying bacteria widely distributed in the sewer system on various structure elements have been isolated from damaged ferroconcrete samples. Effect of protective materials on microbe-induced corrosion of metal famework of concrete samples has been studied. Selective effect of corrosion inhibitors and coatings on the growth of corrosion-active bacteria of sulphur and nitrogen cycle has been revealed. It is shown that acid medium formed by thionic bacteria is more aggressive than ammonium-hydrosulphide one formed by denitrifying and sulphate-reducing bacteria. It has been established that the corrosion inhibitor--pyrquin, organosilicon coating CO-FMI and epoxyorganosilicon coating 4sk are most effective materials as to the action of thionic bacteria--dangerous agents of ferroconcrete aerobic corrosion.

Trace contaminant studies of HSC adsorbent. M.S. Thesis

NASA Technical Reports Server (NTRS)

Yieh, D. T. N.

1978-01-01

The adsorption and desorption of fifteen trace contaminants on HSC (polyethylenimine coated acrylic ester) adsorbent were experimentally investigated with the following two objectives: to test the removal potential and the adsorption reversibility of the selected trace contaminants, and to test the effect a preadsorbed trace contaminant has on the CO2 adsorption capacity. The experimental method for acquiring the adsorption equilibrium data used is based on the volumetric (or displacement) concept of vacuum adsorption. From the experimental results, it was found that the HSC adsorbent has good adsorption potential for contaminants of alcohol compounds, esters, and benzene compounds; whereas, adsorption of ketone compounds, oxidizing and reducing agents are detrimental to the adsorbent. In addition, all liquid contaminants reduce the CO2 capacity of HSC adsorbent.

Simultaneous removal of nitrogen oxides and sulfur oxides from combustion gases

DOEpatents

Clay, David T.; Lynn, Scott

1976-10-19

A process for the simultaneous removal of sulfur oxides and nitrogen oxides from power plant stack gases comprising contacting the stack gases with a supported iron oxide catalyst/absorbent in the presence of sufficient reducing agent selected from the group consisting of carbon monoxide, hydrogen, and mixtures thereof, to provide a net reducing atmosphere in the SO.sub.x /NO.sub.x removal zone. The sulfur oxides are removed by absorption substantially as iron sulfide, and nitrogen oxides are removed by catalytic reduction to nitrogen and ammonia. The spent iron oxide catalyst/absorbent is regenerated by oxidation and is recycled to the contacting zone. Sulfur dioxide is also produced during regeneration and can be utilized in the production of sulfuric acid and/or sulfur.

The aerosphere as a network connector of organisms and their diseases

USGS Publications Warehouse

Ross, Jeremy D.; Bridge, Eli S.; Prosser, Diann J.; Takekawa, John Y.

2018-01-01

Aeroecological processes, especially powered flight of animals, can rapidly connect biological communities across the globe. This can have profound consequences for evolutionary diversification, energy and nutrient transfers, and the spread of infectious diseases. The latter is of particular consequence for human populations, since migratory birds are known to host diseases which have a history of transmission into domestic poultry or even jumping to human hosts. In this chapter, we present a scenario under which a highly pathogenic avian influenza (HPAI) strain enters North America from East Asia via post-molting waterfowl migration. We use an agent-based model (ABM) to simulate the movement and disease transmission among 106 generalized waterfowl agents originating from ten molting locations in eastern Siberia, with the HPAI seeded in only ~102 agents at one of these locations. Our ABM tracked the disease dynamics across a very large grid of sites as well as individual agents, allowing us to examine the spatiotemporal patterns of change in virulence of the HPAI infection as well as waterfowl host susceptibility to the disease. We concurrently simulated a 12-station disease monitoring network in the northwest USA and Canada in order to assess the potential efficacy of these sites to detect and confirm the arrival of HPAI. Our findings indicated that HPAI spread was initially facilitated but eventually subdued by the migration of host agents. Yet, during the 90-day simulation, selective pressures appeared to have distilled the HPAI strain to its most virulent form (i.e., through natural selection), which was counterbalanced by the host susceptibility being conversely reduced (i.e., through genetic predisposition and acquired immunity). The monitoring network demonstrated wide variation in the utility of sites; some were clearly better at providing early warnings of HPAI arrival, while sites further from the disease origin exposed the selective dynamics which slowed the spread of the disease albeit with the result of passing highly virulent strains into southern wintering locales (where human impacts are more likely). Though the ABM presented had generalized waterfowl migration and HPAI disease dynamics, this exercise demonstrates the power of such simulations to examine the extremely large and complex processes which comprise aeroecology. We offer insights into how such models could be further parameterized to represent HPAI transmission risks as well as how ABMs could be applied to other aeroecological questions pertaining to individual-based connectivity.

Scopolamine provocation-based pharmacological MRI model for testing procognitive agents.

PubMed

Hegedűs, Nikolett; Laszy, Judit; Gyertyán, István; Kocsis, Pál; Gajári, Dávid; Dávid, Szabolcs; Deli, Levente; Pozsgay, Zsófia; Tihanyi, Károly

2015-04-01

There is a huge unmet need to understand and treat pathological cognitive impairment. The development of disease modifying cognitive enhancers is hindered by the lack of correct pathomechanism and suitable animal models. Most animal models to study cognition and pathology do not fulfil either the predictive validity, face validity or construct validity criteria, and also outcome measures greatly differ from those of human trials. Fortunately, some pharmacological agents such as scopolamine evoke similar effects on cognition and cerebral circulation in rodents and humans and functional MRI enables us to compare cognitive agents directly in different species. In this paper we report the validation of a scopolamine based rodent pharmacological MRI provocation model. The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam, alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on the blood-oxygen-level dependent responses and also linked to rodent cognitive models. These drugs revealed significant effect on scopolamine induced blood-oxygen-level dependent change except for piracetam. In the water labyrinth test only PNU-120596 did not show a significant effect. This provocational model is suitable for testing procognitive compounds. These functional MR imaging experiments can be paralleled with human studies, which may help reduce the number of false cognitive clinical trials. © The Author(s) 2015.

Maintenance therapy for colorectal cancer: which regimen and which patients?

PubMed

Mikhail, Sameh; Bekaii-Saab, Tanios

2015-11-01

The introduction of therapeutic agents such as irinotecan, oxaliplatin, and more recently biologic agents such as vascular endothelial growth factor and epidermal growth factor receptor (EGFR) inhibitors has significantly improved survival of patients with metastatic colorectal cancer. These novel agents have also contributed to added toxicities. Therefore, several studies have evaluated the role of maintenance therapy with less intensive regimens in patients who experienced stable disease or treatment response following induction therapy as a strategy to reduce toxicity and improve quality of life. The success of such strategies, however, requires assurance that their survival would not be compromised. We therefore reviewed studies that have explored the various strategies of treatment de-escalation with an emphasis on survival and toxicity outcomes. Recent studies evaluated the role of maintenance therapy with chemotherapy only, chemotherapy plus bevcizumab, bevacizumab only, and EGFR inhibitors. Current evidence suggests that maintenance strategies offer significant benefit to patients by providing continuous clinical benefit while minimizing the risks associated with continuous therapy. Strategies to improve selection of patients for maintenance therapy versus identifying subgroups of patients that will benefit from a chemotherapy-free interval need to continue to be studied. Finally, as our understanding of the molecular and genetic drivers of colorectal cancer continues to expand, refining these strategies to include more target-specific agents should become more routine.

Optimal inverse functions created via population-based optimization.

PubMed

Jennings, Alan L; Ordóñez, Raúl

2014-06-01

Finding optimal inputs for a multiple-input, single-output system is taxing for a system operator. Population-based optimization is used to create sets of functions that produce a locally optimal input based on a desired output. An operator or higher level planner could use one of the functions in real time. For the optimization, each agent in the population uses the cost and output gradients to take steps lowering the cost while maintaining their current output. When an agent reaches an optimal input for its current output, additional agents are generated in the output gradient directions. The new agents then settle to the local optima for the new output values. The set of associated optimal points forms an inverse function, via spline interpolation, from a desired output to an optimal input. In this manner, multiple locally optimal functions can be created. These functions are naturally clustered in input and output spaces allowing for a continuous inverse function. The operator selects the best cluster over the anticipated range of desired outputs and adjusts the set point (desired output) while maintaining optimality. This reduces the demand from controlling multiple inputs, to controlling a single set point with no loss in performance. Results are demonstrated on a sample set of functions and on a robot control problem.

Application of Grazing-Inspired Guidance Laws to Autonomous Information Gathering

DTIC Science & Technology

2014-09-01

paths by expressing it as the Selective Traveling Salesman Problem subject to dynamic constraints. Tisdale et al. [11] utilized a receding horizon ap...vehicle failures by halving the initial fuel level on selected agents. Note that simulations start with agents 50s travel time away from where they

Drug therapies for reducing gastric acidity in people with cystic fibrosis.

PubMed

Ng, Sze May; Moore, Helen S

2016-08-22

Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 12 May 2016. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.

Experimental Evaluation of Suitability of Selected Multi-Criteria Decision-Making Methods for Large-Scale Agent-Based Simulations

PubMed Central

2016-01-01

Multi-criteria decision-making (MCDM) can be formally implemented by various methods. This study compares suitability of four selected MCDM methods, namely WPM, TOPSIS, VIKOR, and PROMETHEE, for future applications in agent-based computational economic (ACE) models of larger scale (i.e., over 10 000 agents in one geographical region). These four MCDM methods were selected according to their appropriateness for computational processing in ACE applications. Tests of the selected methods were conducted on four hardware configurations. For each method, 100 tests were performed, which represented one testing iteration. With four testing iterations conducted on each hardware setting and separated testing of all configurations with the–server parameter de/activated, altogether, 12800 data points were collected and consequently analyzed. An illustrational decision-making scenario was used which allows the mutual comparison of all of the selected decision making methods. Our test results suggest that although all methods are convenient and can be used in practice, the VIKOR method accomplished the tests with the best results and thus can be recommended as the most suitable for simulations of large-scale agent-based models. PMID:27806061

What Influences Agents to Pursue a Career in Extension?

ERIC Educational Resources Information Center

Arnold, Shannon; Place, Nick

2010-01-01

The qualitative study reported here explored why agricultural agents pursue an Extension career. A purposive sample was used to select twelve Florida agricultural agents. Interviews investigated positive and negative influences that affected agents' employment decisions. Grounded theory was used as the primary data analysis method (Strauss &…

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.

Effect of selective catalytic reduction (SCR) on fine particle emission from two coal-fired power plants in China

NASA Astrophysics Data System (ADS)

Li, Zhen; Jiang, Jingkun; Ma, Zizhen; Wang, Shuxiao; Duan, Lei

2015-11-01

Nitrogen oxides (NOx) emission abatement of coal-fired power plants (CFPPs) requires large-scaled installation of selective catalytic reduction (SCR), which would reduce secondary fine particulate matter (PM2.5) (by reducing nitrate aerosol) in the atmosphere. However, our field measurement of two CFPPs equipped with SCR indicates a significant increase of SO42- and NH4+ emission in primary PM2.5, due to catalytic enhancement of SO2 oxidation to SO3 and introducing of NH3 as reducing agent. The subsequent formation of (NH4)2SO4 or NH4HSO4 aerosol is commonly concentrated in sub-micrometer particulate matter (PM1) with a bimodal pattern. The measurement at the inlet of stack also showed doubled primary PM2.5 emission by SCR operation. This effect should therefore be considered when updating emission inventory of CFPPs. By rough estimation, the enhanced primary PM2.5 emission from CFPPs by SCR operation would offset 12% of the ambient PM2.5 concentration reduction in cities as the benefit of national NOx emission abatement, which should draw attention of policy-makers for air pollution control.

Pain-relieving agents for infantile colic.

PubMed

Biagioli, Elena; Tarasco, Valentina; Lingua, Carla; Moja, Lorenzo; Savino, Francesco

2016-09-16

Infantile colic is a common disorder in the first months of life, affecting somewhere between 4% and 28% of infants worldwide, depending on geography and definitions used. Although it is self limiting and resolves by four months of age, colic is perceived by parents as a problem that requires action. Pain-relieving agents, such as drugs, sugars and herbal remedies, have been suggested as interventions to reduce crying episodes and severity of symptoms. To assess the effectiveness and safety of pain-relieving agents for reducing colic in infants younger than four months of age. We searched the following databases in March 2015 and again in May 2016: CENTRAL, Ovid MEDLINE, Embase and PsycINFO, along with 11 other databases. We also searched two trial registers, four thesis repositories and the reference lists of relevant studies to identify unpublished and ongoing studies. We included randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of pain-relieving agents given to infants with colic. We used the standard methodological procedures of The Cochrane Collaboration. We included 18 RCTs involving 1014 infants. All studies were small and at high risk of bias, often presenting major shortcomings across multiple design factors (e.g. selection, performance, attrition, lack of washout period).Three studies compared simethicone with placebo, and one with Mentha piperita; four studies compared herbal agents with placebo; two compared sucrose or glucose with placebo; five compared dicyclomine with placebo; and two compared cimetropium - one against placebo and the other at two different dosages. One multiple-arm study compared sucrose and herbal tea versus no treatment. Simethicone. Comparison with placebo revealed no difference in daily hours of crying reported for simethicone at the end of treatment in one small, low-quality study involving 27 infants. A meta-analysis of data from two cross-over studies comparing simethicone with placebo showed no difference in the number of of infants who responded positively to treatment (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.73 to 1.23; 110 infants, low-quality evidence).One small study (30 participants) compared simethicone with Mentha piperita and found no difference in crying duration, number of crying episodes or number of responders. Herbal agents. We found low-quality evidence suggesting that herbal agents reduce the duration of crying compared with placebo (mean difference (MD) 1.33, 95% CI 0.71 to 1.96; three studies, 279 infants), with different magnitude of benefit noted across studies (I² = 96%). We found moderate-quality evidence indicating that herbal agents increase response over placebo (RR 2.05, 95% CI 1.56 to 2.70; three studies, 277 infants). Sucrose. One very low-quality study involving 35 infants reported that sucrose reduced hours spent crying compared with placebo (MD 1.72, 95% CI 1.38 to 2.06). Dicyclomine. We could consider only one of the five studies of dicyclomine (48 infants) for the primary comparison. In this study, more of the infants given dicyclomine responded than than those given placebo (RR 2.50, 95% CI 1.17 to 5.34). Cimetropium bromide. Data from one very low-quality study comparing cimetropium bromide with placebo showed reduced crying duration among infants treated with cimetropium bromide (MD -30.20 minutes per crisis, 95% CI -39.51 to -20.89; 86 infants). The same study reported that cimetropium increased the number of responders (RR 2.29, 95% CI 1.44 to 3.64).No serious adverse events were reported for all of the agents considered, with the exception of dicyclomine, for which two of five studies reported relevant adverse effects (longer sleep 4%, wide-eyed state 4%, drowsiness 13%). At the present time, evidence of the effectiveness of pain-relieving agents for the treatment of infantile colic is sparse and prone to bias. The few available studies included small sample sizes, and most had serious limitations. Benefits, when reported, were inconsistent.We found no evidence to support the use of simethicone as a pain-relieving agent for infantile colic.Available evidence shows that herbal agents, sugar, dicyclomine and cimetropium bromide cannot be recommended for infants with colic.Investigators must conduct RCTs using standardised measures that allow comparisons among pain-relieving agents and pooling of results across studies. Parents, who most often provide the intervention and assess the outcome, should always be blinded.

Proanthocyanidin-rich extracts from cranberry fruit (Vaccinium macrocarpon Ait.) selectively inhibit the growth of human pathogenic fungi Candida spp. and Cryptococcus neoformans.

PubMed

Patel, Kunal D; Scarano, Frank J; Kondo, Miwako; Hurta, Robert A R; Neto, Catherine C

2011-12-28

Cranberry ( Vaccinium macrocarpon ) has been shown in clinical studies to reduce infections caused by Escherichia coli and other bacteria, and proanthocyanidins are believed to play a role. The ability of cranberry to inhibit the growth of opportunistic human fungal pathogens that cause oral, skin, respiratory, and systemic infections has not been well-studied. Fractions from whole cranberry fruit were screened for inhibition of five Candida species and Cryptococcus neoformans , a causative agent of fungal meningitis. Candida glabrata , Candida lusitaniae , Candida krusei , and Cryptococcus neoformans showed significant susceptibility to treatment with cranberry proanthocyanidin fractions in a broth microdilution assay, with minimum inhibitory concentrations as low as 1 μg/mL. MALDI-TOF MS analysis of subfractions detected epicatechin oligomers of up to 12 degrees of polymerization. Those containing larger oligomers caused the strongest inhibition. This study suggests that cranberry has potential as an antifungal agent.

A hybrid, auto-adaptive and rule-based multi-agent approach using evolutionary algorithms for improved searching

NASA Astrophysics Data System (ADS)

Izquierdo, Joaquín; Montalvo, Idel; Campbell, Enrique; Pérez-García, Rafael

2016-08-01

Selecting the most appropriate heuristic for solving a specific problem is not easy, for many reasons. This article focuses on one of these reasons: traditionally, the solution search process has operated in a given manner regardless of the specific problem being solved, and the process has been the same regardless of the size, complexity and domain of the problem. To cope with this situation, search processes should mould the search into areas of the search space that are meaningful for the problem. This article builds on previous work in the development of a multi-agent paradigm using techniques derived from knowledge discovery (data-mining techniques) on databases of so-far visited solutions. The aim is to improve the search mechanisms, increase computational efficiency and use rules to enrich the formulation of optimization problems, while reducing the search space and catering to realistic problems.

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

PubMed

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

2013-12-01

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

Effects of vascularization on cancer nanochemotherapy outcomes

NASA Astrophysics Data System (ADS)

Paiva, L. R.; Ferreira, S. C.; Martins, M. L.

2016-08-01

Cancer therapy requires anticancer agents capable of efficient and uniform systemic delivery. One promising route to their development is nanotechnology. Here, a previous model for cancer chemotherapy based on a nanosized drug carrier (Paiva et al., 2011) is extended by including tissue vasculature and a three-dimensional growth. We study through computer simulations the therapy against tumors demanding either large or small nutrient supplies growing under different levels of tissue vascularization. Our results indicate that highly vascularized tumors demand more aggressive therapies (larger injected doses administrated at short intervals) than poorly vascularized ones. Furthermore, nanoparticle endocytic rate by tumor cells, not its selectivity, is the major factor that determines the therapeutic success. Finally, our finds indicate that therapies combining cytotoxic agents with antiangiogenic drugs that reduce the abnormal tumor vasculature, instead of angiogenic drugs that normalize it, can lead to successful treatments using feasible endocytic rates and administration intervals.

Antimutagenicity of amifostine against the anticancer drug fotemustine in the Drosophila somatic mutation and recombination (SMART) test.

PubMed

Aydemir, N; Sevim, N; Celikler, S; Vatan, O; Bilaloglu, R

2009-01-01

Amifostine (WR-2721), a phosphorylated aminothiol pro-drug, is a selective cytoprotective agent in normal tissue against the toxicities associated with chemotherapy and irradiation. Fotemustine is a cancer chemotherapeutic agent that belongs to an extremely active class of alkylating compounds. Amifostine was tested for antimutagenicity against fotemustine in the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Third-instar larvae that were trans-heterozygous for the two genetic markers mwh and flr were treated at different concentrations (2, 4, and 8 microg/ml for fotemustine and, 1, 2, and 4 microg/ml for amifostine) of the test compounds; for the antimutagenicity study, 8 microg/ml fotemustine plus 1 and 2 microg/ml amifostine were tested. Fotemustine showed mutagenic and recombinagenic effects in both genotypes in the wing-spot test. Amifostine significantly reduced the mutagenic and recombinagenic effects of fotemustine.

Chemotherapeutic agents for the treatment of metastatic breast cancer: An update.

PubMed

Abotaleb, Mariam; Kubatka, Peter; Caprnda, Martin; Varghese, Elizabeth; Zolakova, Barbora; Zubor, Pavol; Opatrilova, Radka; Kruzliak, Peter; Stefanicka, Patrik; Büsselberg, Dietrich

2018-05-01

Breast cancer is the second greatest cause of death among women worldwide; it comprises a group of heterogeneous diseases that evolves due to uncontrolled cellular growth and differentiation and the loss of normal programmed cell death. There are different molecular sub-types of breast cancer; therefore, various options are selected for treatment of different forms of metastatic breast cancer. However, the use of chemotherapeutic drugs is usually accompanied by deleterious side effects and the development of drug resistance when applied for a longer period. This review offers a classification of these chemotherapeutic agents according to their modes of action and therefore improves the understanding of molecular targets that are affected during treatment. Overall, it will allow the clinician to identify more specific targets to increase the effectiveness of a drug and to reduce general toxicity, resistance and other side effects. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pancreatic Cancer Therapy Review: From Classic Therapeutic Agents to Modern Nanotechnologies.

PubMed

Rebelo, Ana; Molpeceres, Jesus; Rijo, Patrícia; Reis, Catarina Pinto

2017-01-01

Pancreatic cancer remains one of the most lethal cancers worldwide, with an extremely poor prognosis. This cancer is considered the 5th leading cause of cancer related death. The median survival after diagnosis is generally 2-8 months and five-year survival rate is less than 5%. In recent years, nanotechnology is emerging as a rising approach for drug delivery since it has opened up new landscapes in medicine through introduction of smart nanocarrier systems that can selectively deliver the therapeutic agent in a specific region and in appropriate levels, reducing the adverse side effects. This review covers the main delivery systems developed so far for anticancer drug delivery to the pancreas over a period of 20 years, from polymeric to lipidic-based nanosystems, with a particular emphasis on albumin as core material. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Kinetics and Mechanisms of Chemical and Biological Agents Release from Biopolymeric Microcapsules.

PubMed

Vinceković, Marko; Jurić, Slaven; Đermić, Edyta; Topolovec-Pintarić, Snježana

2017-11-08

Kinetics and mechanisms of copper cations and Trichoderma viride spores release from uncoated and chitosan coated alginate microcapsules were investigated. The gelation of a fixed amount of sodium alginate at different concentrations of copper ion solutions resulted in distinct kinetics and release mechanisms. The increase in copper cation concentration promoted, but the presence of the chitosan layer on the microcapsule surface and the increase in microcapsule size reduced the rate of active agent release. Fitting to simple Korsmeyer-Peppas empirical model revealed that the underlying release mechanism (Fickian diffusion or a combination of the diffusion and erosion mechanisms) depends on the copper cation concentration and presence of T. viride spores. The investigation pointed out that the proper selection of formulation variables helps in designing microcapsules with the desirable release of copper ions and T. viride for plant protection and nutrition.

A Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular Disease Risk in the Era of Precision Medicine.

PubMed

Patel, Kershaw V; Pandey, Ambarish; de Lemos, James A

2018-04-11

Until recently, therapies to mitigate atherosclerotic cardiovascular disease (ASCVD) risk have been limited to lifestyle interventions, blood pressure lowering medications, high intensity statin therapy, antiplatelet agents, and in select patients, coronary artery revascularization. Despite administration of these evidence-based therapies, substantial residual risk for cardiovascular events persists, particularly among individuals with known ASCVD. Moreover, the current guideline-based approach does not adequately account for patient-specific, causal pathways that lead to ASCVD progression and complications. In the past few years, multiple new pharmacological agents, targeting conceptually distinct pathophysiological targets, have been shown in large and well-conducted clinical trials to lower cardiovascular risk among patients with established ASCVD receiving guideline directed medical care. These evidenced-based therapies reduce event rates, and in some cases all-cause and cardiovascular mortality; these benefits confirm important new disease targets and challenge the adequacy of the current "standard of care" for secondary prevention.

Effect of selection agents to Chrysanthemum (Chrysanthemum morifolium) callus growth after Agrobacterium-mediated genetic transformation

NASA Astrophysics Data System (ADS)

Sjahril, R.; Jamaluddin, I.; Nadir, M.; Asman; Dungga, N. E.

2018-05-01

Genetic transformation mediated by Agrobacterium tumefaciens requires an efficient selection method for successful progress of transformation. This study aims to determine the concentration and kind of antibiotics and selection agents used during transformation to formulate standard protocol of chrysanthemum in the process of propagating disease resistant Chrysanthemum mediated by Agrobacterium tumefaciens EHA105 (pEKB-WD). The experiments were performed by planting chrysanthemum explants leaf cutting (5 mm diameter on NAA medium 2 mg L-1 BAP 2 mg L-1) with addition of Kanamycin: 25, 50, 100, 150 and 200 (mg L-1); Hygromycin: 5, 10, 25, 50 and 75 (mg L-1); Paromomycin: 10, 25, 50, 75 and 100 (mg L-1). Experiment was arranged in a Completely Randomized Design (CRD). Each treatment was repeated five times thus 75 bottles of culture were used; each bottle consists of 5 pieces of leaf cuttings, resulted in total of 375 pieces. The results showed that selection agent had a critical value for Hygromycin 25 mg L-1 and Kanamycin 100 mg L-1 which can make explant experienced necrosis better than Paromomycin. Paromomycin at 100 mg L-1 was only able to kill explant’s periphery. Remained callus stayed fresh more than 50% so that when used as the selection agent could produce more escape cell. The optimum transformation with concentration of 10% Agrobacterium (vol/vol) with 30 minutes co-cultivation can produce more efficient transformed callus. Considering the high price of Hygromycin, it was best to use Kanamycin as selective agents.

ATVB Council Statement: Non-statin LDL-lowering Therapy and Cardiovascular Risk Reduction

PubMed Central

Hegele, Robert A.; Gidding, Samuel S.; Ginsberg, Henry N.; McPherson, Ruth; Raal, Frederick J.; Rader, Daniel J.; Robinson, Jennifer G.; Welty, Francine K.

2015-01-01

Pharmacologic reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here we consider the place of non-statin therapies that also reduce LDL cholesterol in prevention of CVD. Among conventional non-statins, placebo-controlled randomized clinical trials showed that bile acid sequestrants, niacin and fibrates given as monotherapy each reduce CVD end points. From trials in which patients’ LDL cholesterol was already well-controlled on a statin, adding ezetimibe incrementally reduced CVD end points, while adding a fibrate or niacin showed no incremental benefit. Among emerging non-statins, monoclonal antibodies against proprotein convertase subtilisin kexin type 9 (PCSK9) added to a statin and given for up to 78 weeks showed preliminary evidence of reductions in CVD outcomes. While these promising early findings contributed to the recent approval of these agents in Europe and the US, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits. Other non-statin agents recently approved in the US include lomitapide and mipomersen, which both act via distinctive LDL-receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift towards more assertive LDL-lowering treatment, using both statins and non-statins initiated earlier in appropriately selected patients. PMID:26376908

Method development for comprehensive extraction and analysis of marine toxins: Liquid-liquid extraction and tandem liquid chromatography separations coupled to electrospray tandem mass spectrometry

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

Wunschel, David S.; Valenzuela, Blandina R.; Kaiser, Brooke L. Deatherage

Toxins from biological sources are recognized as potential chemical weapon threats, with saxitoxin and ricin listed by the chemical weapons convention (CWC) as schedule one agents (CWC reference). These two toxins represent a metabolite (saxitoxin) and protein (ricin) from algal and plant sources, respectively. An array of toxins have been listed as "select agents" by the Health and Human Services (HHS) select agent program, including ricin, abrin, saxitoxin, tetrodotoxin, specific paralytic alpha conotoxin peptides, T-2 toxin, diacetoxyscirpenols, botulinum toxins, and staphylococcal enterotoxins [1]. The quantities of these toxins dictate whether they are considered select agents with federal oversight of theirmore » storage and use. While this list captures some of the naturally occurring toxins that may pose a threat to the public, there are a number of other naturally occurring toxins that may also be a concern.« less

Social dilemma structure hidden behind traffic flow with route selection

NASA Astrophysics Data System (ADS)

Tanimoto, Jun; Nakamura, Kousuke

2016-10-01

Several traffic flows contain social dilemma structures. Herein, we explored a route-selection problem using a cellular automaton simulation dovetailed with evolutionary game theory. In our model, two classes of driver-agents coexist: D agents (defective strategy), which refer to traffic information for route selection to move fast, and C agents (cooperative strategy), which are insensitive to information and less inclined to move fast. Although no evidence suggests that the social dilemma structure in low density causes vehicles to move freely and that in high density causes traffic jams, we found a structure that corresponds to an n-person (multiplayer) Chicken (n-Chicken) game if the provided traffic information is inappropriate. If appropriate traffic information is given to the agents, the n-Chicken game can be solved. The information delivered to vehicles is crucial for easing the social dilemma due to urban traffic congestion when developing technologies to support the intelligent transportation system (ITS).

Containment of antimicrobial resistance due to use of antimicrobial agents in animals intended for food: WHO perspective.

PubMed

Aidara-Kane, A

2012-04-01

The use of antimicrobial agents in humans and food-producing animals has important consequences for human and animal health, as it can lead to the development of resistant bacteria (pathogens and/or commensals with resistance genes). Moreover, resistant bacteria in animals can be transferred to people--usually through the consumption of food, but also through direct contact with food-producing animals or through environmental spread. Ultimately, this can result in human infections with bacteria that are resistant to antimicrobial agents and that can therefore be difficult or impossible to cure. Of special concern is resistance to antimicrobial agents classified by the World Health Organization (WHO) as critically important for human medicine, such as fluoroquinolones, third- and fourth-generation cephalosporins, and macrolides. WHO encourages the agricultural, food, veterinary and health sectors to work together to eliminate the burden of antimicrobial resistance arising from the use of antimicrobial agents in food-producing animals. Joint efforts should be made to reduce the inappropriate use of antimicrobial agents (e.g. the use of antimicrobials as growth promoters) and limit the spread of bacteria resistant to antimicrobial agents. WHO will continueto address this issue in conjunction with the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health, the animal health/production industry and other important stakeholders. It will also continue to enhance the capacity of its Member States (through training courses and sentinel studies), particularly developing countries, to conduct integrated surveillance of antimicrobial use and resistance, to carry out risk assessments to support the selection of risk management options and to implement strategies for the containment of antimicrobial resistance.

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

PubMed

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

2017-11-01

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

Aspirin and the prevention of venous thromboembolism following total joint arthroplasty

PubMed Central

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

2017-01-01

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

Kit for providing a technetium medical radioimaging agent

DOEpatents

Wildung, Raymond E.; Garland, Thomas R.; Li, Shu-Mei W.

2000-01-01

The present invention is directed toward a kit for microbial reduction of a technetium compound to form other compounds of value in medical imaging. The technetium compound is combined in a mixture with non-growing microbial cells which contain a technetium-reducing enzyme system, a stabilizing agent and an electron donor in a saline solution under anaerobic conditions. The mixture is substantially free of an inorganic technetium reducing agent and its reduction products. The resulting product is Tc of lower oxidation states, the form of which can be partially controlled by the stabilizing agent. It has been discovered that the microorganisms Shewanella alga, strain Bry and Shewanella putrifacians, strain CN-32 contain the necessary enzyme systems for technetium reduction and can form both mono nuclear and polynuclear reduced Tc species depending on the stabilizing agent.

Production of sintered porous metal fluoride pellets

DOEpatents

Anderson, L.W.; Stephenson, M.J.

1973-12-25

Porous pellets characterized by a moderately reactive crust and a softer core of higher reactivity are produced by forming agglomerates containing a metal fluoride powder and a selected amount ofwater. The metal fluoride is selected to be sinterable and essentially non-reactive with gaseous fluorinating agents. The agglomerates are contacted with a gaseous fluorinating agent under controlled conditions whereby the heat generated by localized reaction of the agent and water is limited to values effccting bonding by localized sintering. Porous pellets composed of cryolite (Na/sub 3/AlF/sub 6/) can be used to selectively remove trace quantities of niobium pentafluoride from a feed gas consisting predominantly of uranium hexafluoride. (Official Gazette)

Further development of high temperature-resistant graphite fiber coupling agents

NASA Technical Reports Server (NTRS)

Griffin, R. N.

1976-01-01

Potential coupling agents for graphite fibers were screened by their effect on the weight losses of Thornel 300, HMS, and HTS fibers at 588K for 200 and 400 hours. Unidirectional laminates were made from HMS and HTS fibers, untreated, and treated with each of the seven coupling agents. The matrix of all laminates was PMR polyimide (PMR-PR). On the basis of the best overall retention of elevated temperature interlaminar shear strength after 200 hours at 588K, composite weight after 200 hours at 588K, and fiber weight after 400 hours at 588K, ventromer T-1 applied from aqueous solution and pyrolyzed PPQ were selected for further evaluation as coupling agents for HTS fiber while ventromer T-2 and pyrolyzed PPQ were selected as coupling agents for HMS fiber. It was shown that pyrolyzed PPQ as a coupling agent improves the oxidative stability of HTS/PMR-PI composites.

In vivo antimicrobial activity of silver nanoparticles produced via a green chemistry synthesis using Acacia rigidula as a reducing and capping agent.

PubMed

Escárcega-González, Carlos Enrique; Garza-Cervantes, J A; Vázquez-Rodríguez, A; Montelongo-Peralta, Liliana Zulem; Treviño-González, M T; Díaz Barriga Castro, E; Saucedo-Salazar, E M; Chávez Morales, R M; Regalado Soto, D I; Treviño González, F M; Carrazco Rosales, J L; Cruz, Rocío Villalobos; Morones-Ramírez, José Rubén

2018-01-01

One of the main issues in the medical field and clinical practice is the development of novel and effective treatments against infections caused by antibiotic-resistant bacteria. One avenue that has been approached to develop effective antimicrobials is the use of silver nanoparticles (Ag-NPs), since they have been found to exhibit an efficient and wide spectrum of antimicrobial properties. Among the main drawbacks of using Ag-NPs are their potential cytotoxicity against eukaryotic cells and the latent environmental toxicity of their synthesis methods. Therefore, diverse green synthesis methods, which involve the use of environmentally friendly plant extracts as reductive and capping agents, have become attractive to synthesize Ag-NPs that exhibit antimicrobial effects against resistant bacteria at concentrations below toxicity thresholds for eukaryotic cells. In this study, we report a green one-pot synthesis method that uses Acacia rigidula extract as a reducing and capping agent, to produce Ag-NPs with applications as therapeutic agents to treat infections in vivo. The Ag-NPs were characterized using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction, energy-dispersive spectroscopy, ultraviolet-visible, and Fourier transform infrared. We show that Ag-NPs are spherical with a narrow size distribution. The Ag-NPs show antimicrobial activities in vitro against Gram-negative ( Escherichia coli , Pseudomonas aeruginosa , and a clinical multidrug-resistant strain of P. aeruginosa ) and Gram-positive ( Bacillus subtilis ) bacteria. Moreover, antimicrobial effects of the Ag-NPs, against a resistant P. aeruginosa clinical strain, were tested in a murine skin infection model. The results demonstrate that the Ag-NPs reported in this work are capable of eradicating pathogenic resistant bacteria in an infection in vivo. In addition, skin, liver, and kidney damage profiles were monitored in the murine infection model, and the results demonstrate that Ag-NPs can be used safely as therapeutic agents in animal models. Together, these results suggest the potential use of Ag-NPs, synthesized by green chemistry methods, as therapeutic agents against infections caused by resistant and nonresistant strains.

In vivo antimicrobial activity of silver nanoparticles produced via a green chemistry synthesis using Acacia rigidula as a reducing and capping agent

PubMed Central

Escárcega-González, Carlos Enrique; Garza-Cervantes, JA; Vázquez-Rodríguez, A; Montelongo-Peralta, Liliana Zulem; Treviño-González, MT; Díaz Barriga Castro, E; Saucedo-Salazar, EM; Chávez Morales, RM; Regalado Soto, DI; Treviño González, FM; Carrazco Rosales, JL; Cruz, Rocío Villalobos; Morones-Ramírez, José Rubén

2018-01-01

Introduction One of the main issues in the medical field and clinical practice is the development of novel and effective treatments against infections caused by antibiotic-resistant bacteria. One avenue that has been approached to develop effective antimicrobials is the use of silver nanoparticles (Ag-NPs), since they have been found to exhibit an efficient and wide spectrum of antimicrobial properties. Among the main drawbacks of using Ag-NPs are their potential cytotoxicity against eukaryotic cells and the latent environmental toxicity of their synthesis methods. Therefore, diverse green synthesis methods, which involve the use of environmentally friendly plant extracts as reductive and capping agents, have become attractive to synthesize Ag-NPs that exhibit antimicrobial effects against resistant bacteria at concentrations below toxicity thresholds for eukaryotic cells. Purpose In this study, we report a green one-pot synthesis method that uses Acacia rigidula extract as a reducing and capping agent, to produce Ag-NPs with applications as therapeutic agents to treat infections in vivo. Materials and methods The Ag-NPs were characterized using transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction, energy-dispersive spectroscopy, ultraviolet–visible, and Fourier transform infrared. Results We show that Ag-NPs are spherical with a narrow size distribution. The Ag-NPs show antimicrobial activities in vitro against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, and a clinical multidrug-resistant strain of P. aeruginosa) and Gram-positive (Bacillus subtilis) bacteria. Moreover, antimicrobial effects of the Ag-NPs, against a resistant P. aeruginosa clinical strain, were tested in a murine skin infection model. The results demonstrate that the Ag-NPs reported in this work are capable of eradicating pathogenic resistant bacteria in an infection in vivo. In addition, skin, liver, and kidney damage profiles were monitored in the murine infection model, and the results demonstrate that Ag-NPs can be used safely as therapeutic agents in animal models. Conclusion Together, these results suggest the potential use of Ag-NPs, synthesized by green chemistry methods, as therapeutic agents against infections caused by resistant and nonresistant strains. PMID:29713166

Effects of antimicrobial treatment on fiberglass-acrylic filters.

PubMed

Cecchini, C; Verdenelli, M C; Orpianesi, C; Dadea, G M; Cresci, A

2004-01-01

The aims of the present study were to: (i) analyse a group of antimicrobial agents and to select the most active against test microbial strains; (ii) test the effect of the antimicrobial treatment on air filters in order to reduce microbial colonization. Different kinds of antimicrobial agents were analysed to assess their compatibility with the production process of air filter media. The minimal inhibitory concentration for each antimicrobial agent was determined against a defined list of microbial strains, and an antimicrobial activity assay of filter prototypes was developed to determine the most active agent among the compatible antimicrobials. Then, the most active was chosen and added directly to the filter during the production process. The microbial colonization of treated and untreated filter media was assessed at different working times for different incubation times by stereomicroscope and scanning electron microscope analysis. Some of the antimicrobial agents analysed were more active against microbial test strains and compatible with the production process of the filter media. Filter sections analysis of treated filter media showed a significantly lower microbial colonization than those untreated, a reduction of species both in density and varieties and of the presence of bacteria and fungal hyphae with reproductive structures. This study demonstrated the ability of antimicrobial treatments to inhibit the growth of micro-organisms in filter media and subsequently to increase indoor air quality (IAQ), highlighting the value of adding antimicrobials to filter media. To make a contribution to solving the problem of microbial contamination of air filters, by demonstrating the efficacy of incorporating antimicrobial agents in the filter media to improve IAQ and health.

Synthesis of silver nanoparticles using reducing agents obtained from natural sources (Rumex hymenosepalus extracts)

PubMed Central

2013-01-01

We have synthesized silver nanoparticles from silver nitrate solutions using extracts of Rumex hymenosepalus, a plant widely found in a large region in North America, as reducing agent. This plant is known to be rich in antioxidant molecules which we use as reducing agents. Silver nanoparticles grow in a single-step method, at room temperature, and with no addition of external energy. The nanoparticles have been characterized by ultraviolet-visible spectroscopy and transmission electron microscopy, as a function of the ratio of silver ions to reducing agent molecules. The nanoparticle diameters are in the range of 2 to 40 nm. High-resolution transmission electron microscopy and fast Fourier transform analysis show that two kinds of crystal structures are obtained: face-centered cubic and hexagonal. PMID:23841946

Microbial methods of reducing technetium

DOEpatents

Wildung, Raymond E [Richland, WA; Garland, Thomas R [Greybull, WY; Gorby, Yuri A [Richland, WA; Hess, Nancy J [Benton City, WA; Li, Shu-Mei W [Richland, WA; Plymale, Andrew E [Richland, WA

2001-01-01

The present invention is directed toward a method for microbial reduction of a technetium compound to form other compounds of value in medical imaging. The technetium compound is combined in a mixture with non-growing microbial cells which contain a technetium-reducing enzyme system, a stabilizing agent and an electron donor in a saline solution under anaerobic conditions. The mixture is substantially free of an inorganic technetium reducing agent and its reduction products. The resulting product is Tc of lower oxidation states, the form of which can be partially controlled by the stabilizing agent. It has been discovered that the microorganisms Shewanella alga, strain Bry and Shewanelia putrifacians, strain CN-32 contain the necessary enzyme systems for technetium reduction and can form both mono nuclear and polynuclear reduced Tc species depending on the stabilizing agent.

Use of Natural Antimicrobial Peptides and Bacterial Biopolymers for Cultured Pearl Production

PubMed Central

Simon-Colin, Christelle; Gueguen, Yannick; Bachere, Evelyne; Kouzayha, Achraf; Saulnier, Denis; Gayet, Nicolas; Guezennec, Jean

2015-01-01

Cultured pearls are the product of grafting and rearing of Pinctada margaritifera pearl oysters in their natural environment. Nucleus rejections and oyster mortality appear to result from bacterial infections or from an inappropriate grafting practice. To reduce the impact of bacterial infections, synthetic antibiotics have been applied during the grafting practice. However, the use of such antibiotics presents a number of problems associated with their incomplete biodegradability, limited efficacy in some cases, and an increased risk of selecting for antimicrobial resistant bacteria. We investigated the application of a marine antimicrobial peptide, tachyplesin, which is present in the Japanese horseshoe crab Tachypleus tridentatus, in combination with two marine bacterial exopolymers as alternative treatment agents. In field studies, the combination treatment resulted in a significant reduction in graft failures vs. untreated controls. The combination of tachyplesin (73 mg/L) with two bacterial exopolysaccharides (0.5% w/w) acting as filming agents, reduces graft-associated bacterial contamination. The survival data were similar to that reported for antibiotic treatments. These data suggest that non-antibiotic treatments of pearl oysters may provide an effective means of improving oyster survival following grafting procedures. PMID:26110895

Detection of abrin holotoxin using novel monoclonal antibodies

USDA-ARS?s Scientific Manuscript database

Abrin, a member of ribosome-inactivating protein family, is produced by the Abrus precatorius plant. It has been determined to have the potential to pose a severe threat to both human and animal health and is listed as a select agent by the U.S. Federal Select Agent Program. However, an immunoassay ...

42 CFR 73.5 - Exemptions for HHS select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... minor (Alastrim), or Yersinia pestis. This report must be followed by submission of APHIS/CDC Form 4.../CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2011 CFR

2011-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2010 CFR

2010-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within seven calendar days after...

42 CFR 73.5 - Exemptions for HHS select agents and toxins.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... minor (Alastrim), or Yersinia pestis. This report must be followed by submission of APHIS/CDC Form 4.../CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent...

42 CFR 73.5 - Exemptions for HHS select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the select agent or toxin is reported to CDC or APHIS and to other appropriate authorities when... minor (Alastrim), or Yersinia pestis. This report must be followed by submission of APHIS/CDC Form 4.../CDC Form 4 must be submitted within seven calendar days after identification. (iii) Less stringent...

9 CFR 121.5 - Exemptions for VS select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... toxin that is contained in a specimen presented for proficiency testing will be exempt from the...

9 CFR 121.5 - Exemptions for VS select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Exemptions for VS select agents and toxins. 121.5 Section 121.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... toxin that is contained in a specimen presented for proficiency testing will be exempt from the...

Production of an ion-exchange membrane-catalytic electrode bonded material for electrolytic cells

NASA Technical Reports Server (NTRS)

Takenaka, H.; Torikai, E.

1986-01-01

A good bond is achieved by placing a metal salt in solution on one side of a membrane and a reducing agent on the other side so that the reducing agent penetrates the membrane and reduces the metal. Thus, a solution containing Pt, Rh, etc., is placed on one side of the membrane and a reducing agent such as NaBH, is placed on the other side. The bonded metal layer obtained is superior in catalytic activity and is suitable as an electrode in a cell such as for solid polymer electrolyte water electrolysis.

Dosimetry using silver salts

DOEpatents

Warner, Benjamin P.

2003-06-24

The present invention provides a method for detecting ionizing radiation. Exposure of silver salt AgX to ionizing radiation results in the partial reduction of the salt to a mixture of silver salt and silver metal. The mixture is further reduced by a reducing agent, which causes the production of acid (HX) and the oxidized form of the reducing agent (R). Detection of HX indicates that the silver salt has been exposed to ionizing radiation. The oxidized form of the reducing agent (R) may also be detected. The invention also includes dosimeters employing the above method for detecting ionizing radiation.

Genome Sequencing and Comparative Analysis of Stenotrophomonas acidaminiphila Reveal Evolutionary Insights Into Sulfamethoxazole Resistance.

PubMed

Huang, Yao-Ting; Chen, Jia-Min; Ho, Bing-Ching; Wu, Zong-Yen; Kuo, Rita C; Liu, Po-Yu

2018-01-01

Stenotrophomonas acidaminiphila is an aerobic, glucose non-fermentative, Gram-negative bacterium that been isolated from various environmental sources, particularly aquatic ecosystems. Although resistance to multiple antimicrobial agents has been reported in S. acidaminiphila , the mechanisms are largely unknown. Here, for the first time, we report the complete genome and antimicrobial resistome analysis of a clinical isolate S. acidaminiphila SUNEO which is resistant to sulfamethoxazole. Comparative analysis among closely related strains identified common and strain-specific genes. In particular, comparison with a sulfamethoxazole-sensitive strain identified a mutation within the sulfonamide-binding site of folP in SUNEO, which may reduce the binding affinity of sulfamethoxazole. Selection pressure analysis indicated folP in SUNEO is under purifying selection, which may be owing to long-term administration of sulfonamide against Stenotrophomonas .

Aging, Clonality and Rejuvenation of Hematopoietic Stem Cells

PubMed Central

Akunuru, Shailaja; Geiger, Hartmut

2016-01-01

Aging is associated with reduced organ function and increased disease incidence. Hematopoietic stem cell (HSC) aging driven by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration, aging-associated immune remodeling, and increased leukemia incidence. Compromised DNA damage responses and increased production of reactive oxygen species have been previously causatively attributed to HSC aging. However, recent paradigm-shifting concepts such as global epigenetic and cytoskeletal polarity shifts, cellular senescence, as well as clonal selection of HSCs upon aging provide new insights into HSC aging mechanisms. Rejuvenating agents that can reprogram the epigenetic status of aged HSCs or senolytic drugs that selectively deplete senescent cells provide promising translational avenues for attenuating hematopoietic aging and potentially, alleviating aging-associated immune remodeling and myeloid malignancies. PMID:27380967

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

Schizophrenia: multi-attribute utility theory approach to selection of atypical antipsychotics.

PubMed

Bettinger, Tawny L; Shuler, Garyn; Jones, Donnamaria R; Wilson, James P

2007-02-01

Current guidelines/algorithms recommend atypical antipsychotics as first-line agents for the treatment of schizophrenia. Because there are extensive healthcare costs associated with the treatment of schizophrenia, many institutions and health systems are faced with making restrictive formulary decisions regarding the use of atypical antipsychotics. Often, medication acquisition costs are the driving force behind formulary decisions, while other treatment factors are not considered. To apply a multi-attribute utility theory (MAUT) analysis to aid in the selection of a preferred agent among the atypical antipsychotics for the treatment of schizophrenia. Five atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) were selected as the alternative agents to be included in the MAUT analysis. The attributes identified for inclusion in the analysis were efficacy, adverse effects, cost, and adherence, with relative weights of 35%, 35%, 20%, and 10%, respectively. For each agent, attribute scores were calculated, weighted, and then summed to generate a total utility score. The agent with the highest total utility score was considered the preferred agent. Aripiprazole, with a total utility score of 75.8, was the alternative agent with the highest total utility score in this model. This was followed by ziprasidone, risperidone, and quetiapine, with total utility scores of 71.8, 69.0, and 65.9, respectively. Olanzapine received the lowest total utility score. A sensitivity analysis was performed and failed to displace aripiprazole as the agent with the highest total utility score. This model suggests that aripiprazole should be considered a preferred agent for the treatment of schizophrenia unless found to be otherwise inappropriate.

Contrast enhanced spectroscopic optical coherence tomography

NASA Technical Reports Server (NTRS)

Xu, Chenyang (Inventor); Boppart, Stephen A. (Inventor)

2010-01-01

A method of forming an image of a sample includes performing SOCT on a sample. The sample may include a contrast agent, which may include an absorbing agent and/or a scattering agent. A method of forming an image of tissue may include selecting a contrast agent, delivering the contrast agent to the tissue, acquiring SOCT data from the tissue, and converting the SOCT data into an image. The contributions to the SOCT data of an absorbing agent and a scattering agent in a sample may be quantified separately.

Dispatching power system for preventive and corrective voltage collapse problem in a deregulated power system

NASA Astrophysics Data System (ADS)

Alemadi, Nasser Ahmed

Deregulation has brought opportunities for increasing efficiency of production and delivery and reduced costs to customers. Deregulation has also bought great challenges to provide the reliability and security customers have come to expect and demand from the electrical delivery system. One of the challenges in the deregulated power system is voltage instability. Voltage instability has become the principal constraint on power system operation for many utilities. Voltage instability is a unique problem because it can produce an uncontrollable, cascading instability that results in blackout for a large region or an entire country. In this work we define a system of advanced analytical methods and tools for secure and efficient operation of the power system in the deregulated environment. The work consists of two modules; (a) contingency selection module and (b) a Security Constrained Optimization module. The contingency selection module to be used for voltage instability is the Voltage Stability Security Assessment and Diagnosis (VSSAD). VSSAD shows that each voltage control area and its reactive reserve basin describe a subsystem or agent that has a unique voltage instability problem. VSSAD identifies each such agent. VS SAD is to assess proximity to voltage instability for each agent and rank voltage instability agents for each contingency simulated. Contingency selection and ranking for each agent is also performed. Diagnosis of where, why, when, and what can be done to cure voltage instability for each equipment outage and transaction change combination that has no load flow solution is also performed. A security constrained optimization module developed solves a minimum control solvability problem. A minimum control solvability problem obtains the reactive reserves through action of voltage control devices that VSSAD determines are needed in each agent to obtain solution of the load flow. VSSAD makes a physically impossible recommendation of adding reactive generation capability to specific generators to allow a load flow solution to be obtained. The minimum control solvability problem can also obtain solution of the load flow without curtailing transactions that shed load and generation as recommended by VSSAD. A minimum control solvability problem will be implemented as a corrective control, that will achieve the above objectives by using minimum control changes. The control includes; (1) voltage setpoint on generator bus voltage terminals; (2) under load tap changer tap positions and switchable shunt capacitors; and (3) active generation at generator buses. The minimum control solvability problem uses the VSSAD recommendation to obtain the feasible stable starting point but completely eliminates the impossible or onerous recommendation made by VSSAD. This thesis reviews the capabilities of Voltage Stability Security Assessment and Diagnosis and how it can be used to implement a contingency selection module for the Open Access System Dispatch (OASYDIS). The OASYDIS will also use the corrective control computed by Security Constrained Dispatch. The corrective control would be computed off line and stored for each contingency that produces voltage instability. The control is triggered and implemented to correct the voltage instability in the agent experiencing voltage instability only after the equipment outage or operating changes predicted to produce voltage instability have occurred. The advantages and the requirements to implement the corrective control are also discussed.

The Subset Sum game.

PubMed

Darmann, Andreas; Nicosia, Gaia; Pferschy, Ulrich; Schauer, Joachim

2014-03-16

In this work we address a game theoretic variant of the Subset Sum problem, in which two decision makers (agents/players) compete for the usage of a common resource represented by a knapsack capacity. Each agent owns a set of integer weighted items and wants to maximize the total weight of its own items included in the knapsack. The solution is built as follows: Each agent, in turn, selects one of its items (not previously selected) and includes it in the knapsack if there is enough capacity. The process ends when the remaining capacity is too small for including any item left. We look at the problem from a single agent point of view and show that finding an optimal sequence of items to select is an [Formula: see text]-hard problem. Therefore we propose two natural heuristic strategies and analyze their worst-case performance when (1) the opponent is able to play optimally and (2) the opponent adopts a greedy strategy. From a centralized perspective we observe that some known results on the approximation of the classical Subset Sum can be effectively adapted to the multi-agent version of the problem.

The Subset Sum game☆

PubMed Central

Darmann, Andreas; Nicosia, Gaia; Pferschy, Ulrich; Schauer, Joachim

2014-01-01

In this work we address a game theoretic variant of the Subset Sum problem, in which two decision makers (agents/players) compete for the usage of a common resource represented by a knapsack capacity. Each agent owns a set of integer weighted items and wants to maximize the total weight of its own items included in the knapsack. The solution is built as follows: Each agent, in turn, selects one of its items (not previously selected) and includes it in the knapsack if there is enough capacity. The process ends when the remaining capacity is too small for including any item left. We look at the problem from a single agent point of view and show that finding an optimal sequence of items to select is an NP-hard problem. Therefore we propose two natural heuristic strategies and analyze their worst-case performance when (1) the opponent is able to play optimally and (2) the opponent adopts a greedy strategy. From a centralized perspective we observe that some known results on the approximation of the classical Subset Sum can be effectively adapted to the multi-agent version of the problem. PMID:25844012

Evolutionary game theory using agent-based methods.

PubMed

Adami, Christoph; Schossau, Jory; Hintze, Arend

2016-12-01

Evolutionary game theory is a successful mathematical framework geared towards understanding the selective pressures that affect the evolution of the strategies of agents engaged in interactions with potential conflicts. While a mathematical treatment of the costs and benefits of decisions can predict the optimal strategy in simple settings, more realistic settings such as finite populations, non-vanishing mutations rates, stochastic decisions, communication between agents, and spatial interactions, require agent-based methods where each agent is modeled as an individual, carries its own genes that determine its decisions, and where the evolutionary outcome can only be ascertained by evolving the population of agents forward in time. While highlighting standard mathematical results, we compare those to agent-based methods that can go beyond the limitations of equations and simulate the complexity of heterogeneous populations and an ever-changing set of interactors. We conclude that agent-based methods can predict evolutionary outcomes where purely mathematical treatments cannot tread (for example in the weak selection-strong mutation limit), but that mathematics is crucial to validate the computational simulations. Copyright © 2016 Elsevier B.V. All rights reserved.

A preliminary assessment on the use of biochar as a soil additive for reducing soil-to-plant uptake of cesium isotopes in radioactively contaminated environments

DOE PAGES

Hamilton, Terry F.; Martinelli, Roger E.; Kehl, Steven R.; ...

2015-10-19

A series of K d tracer batch experiments were conducted in this paper to assess the absorptive-desorption properties of Biochar as a potential agent to selectively sequester labile soil Cs or otherwise help reduce the uptake of Cs isotopes into plants. A parallel experiment was conducted for strontium. Fine-grained fractionated Woodlands tree Biochar was found to have a relatively high affinity for Cs ions (K d > 100) relative to coral soil (K d < 10) collected from the Marshall Islands. The Biochar material also contains an abundance of K (and Mg). Finally, these findings support a hypothesis that themore » addition of Biochar as a soil amendment may provide a simple yet effective method for reducing soil-to-plant transfer of Cs isotopes in contaminated environments.« less

Reducing Interaction Costs for Self-interested Agents

NASA Astrophysics Data System (ADS)

Zhang, Yunqi; Larson, Kate

In many multiagent systems, agents are not able to freely interact with each other or with a centralized mechanism. They may be limited in their interactions by cost or by the inherent structure of the system. Using a combinatorial auction application as motivation, we study the impact of interaction costs and structure on the strategic behaviour of self-interested agents. We present a particular model of costly agent-interaction, and argue that self-interested agents may wish to coordinate their actions with their neighbours so as to reduce their individual costs. We highlight the issues that arise in such a setting, propose a cost-sharing mechanism that agents can use, and discuss group coordination procedures. Experimental work validates our model.

Distribution and decline of human pathogenic bacteria in soil after application in irrigation water and the potential for soil-splash-mediated dispersal onto fresh produce.

PubMed

Monaghan, J M; Hutchison, M L

2012-05-01

To improve our understanding of the survival and splash-mediated transfer of zoonotic agents and faecal indicator bacteria introduced into soils used for crop cultivation via contaminated irrigation waters. Zoonotic agents and an Escherichia coli marker bacterium were inoculated into borehole water, which was applied to two different soil types in early-, mid- and late summer. Decline of the zoonotic agents was influenced by soil type. Marker bacteria applied to columns of two soil types in irrigation water did not concentrate at the surface of the soils. Decline of zoonotic agents at the surface was influenced by soil type and environmental conditions. Typically, declines were rapid and bacteria were not detectable after 5 weeks. Selective agar strips were used to determine that the impact of water drops 24-87 μl could splash marker bacteria from soil surfaces horizontal distances of at least 25 cm and heights of 20 cm. Soil splash created by rain-sized water droplets can transfer enteric bacteria from soil to ready-to-eat crops. Persistence of zoonotic agents was reduced at the hottest part of the growing season when irrigation is most likely. Soil splash can cause crop contamination. We report the penetration depths and seasonally influenced declines of bacteria applied in irrigation water into two soil types. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

INTEROCC case–control study: lack of association between glioma tumors and occupational exposure to selected combustion products, dusts and other chemical agents

PubMed Central

2013-01-01

Background The aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide). Methods The INTEROCC study included cases diagnosed with glioma during 2000–2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure. Results The study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose–response relationships with cumulative exposure or with duration of exposure. Conclusion Thus, there was no evidence that these exposures influence risk of glioma. PMID:23587105

INTEROCC case-control study: lack of association between glioma tumors and occupational exposure to selected combustion products, dusts and other chemical agents.

PubMed

Lacourt, Aude; Cardis, Elisabeth; Pintos, Javier; Richardson, Lesley; Kincl, Laurel; Benke, Geza; Fleming, Sarah; Hours, Martine; Krewski, Daniel; McLean, Dave; Parent, Marie-Elise; Sadetzki, Siegal; Schlaefer, Klaus; Schlehofer, Brigitte; Lavoue, Jerome; van Tongeren, Martie; Siemiatycki, Jack

2013-04-12

The aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide). The INTEROCC study included cases diagnosed with glioma during 2000-2004 in sub-regions of seven countries. Population controls, selected from various sampling frames in different centers, were frequency or individually matched to cases by sex, age and center. Face-to-face interviews with the subject or a proxy respondent were conducted by trained interviewers. Detailed information was collected on socio-economic and lifestyle characteristics, medical history and work history. Occupational exposure to the 10 selected agents was assessed by a job exposure matrix (JEM) which provides estimates of the probability and level of exposure for different occupations. Using a 25% probability of exposure in a given occupation in the JEM as the threshold for considering a worker exposed, the lifetime prevalence of exposure varied from about 1% to about 15% for the different agents. Associations between glioma and each of the 10 agents were estimated by conditional logistic regression, and using three separate exposure indices: i) ever vs. never; ii) lifetime cumulative exposure; iii) total duration of exposure. The study sample consisted of 1,800 glioma cases and 5,160 controls. Most odds ratio estimates were close to the null value. None of the ten agents displayed a significantly increased odds ratio nor any indication of dose-response relationships with cumulative exposure or with duration of exposure. Thus, there was no evidence that these exposures influence risk of glioma.

9 CFR 121.10 - Restricting access to select agents and toxins; security risk assessments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... education, training, and/or experience to handle or use such agents or toxins. (d) To apply for access... other organization that engages in intentional crimes of violence; or being an agent of a foreign power...

Esophageal Cancer Prevention

MedlinePlus

... agents to try to reduce the risk of cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin and other drugs ... agents to try to reduce the risk of cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin and other drugs ...

Metal and alloy nanoparticles by amine-borane reduction of metal salts by solid-phase synthesis: atom economy and green process.

PubMed

Sanyal, Udishnu; Jagirdar, Balaji R

2012-12-03

A new solid state synthetic route has been developed toward metal and bimetallic alloy nanoparticles from metal salts employing amine-boranes as the reducing agent. During the reduction, amine-borane plays a dual role: acts as a reducing agent and reduces the metal salts to their elemental form and simultaneously generates a stabilizing agent in situ which controls the growth of the particles and stabilizes them in the nanosize regime. Employing different amine-boranes with differing reducing ability (ammonia borane (AB), dimethylamine borane (DMAB), and triethylamine borane (TMAB)) was found to have a profound effect on the particle size and the size distribution. Usage of AB as the reducing agent provided the smallest possible size with best size distribution. Employment of TMAB also afforded similar results; however, when DMAB was used as the reducing agent it resulted in larger sized nanoparticles that are polydisperse too. In the AB mediated reduction, BNH(x) polymer generated in situ acts as a capping agent whereas, the complexing amine of the other amine-boranes (DMAB and TMAB) play the same role. Employing the solid state route described herein, monometallic Au, Ag, Cu, Pd, and Ir and bimetallic CuAg and CuAu alloy nanoparticles of <10 nm were successfully prepared. Nucleation and growth processes that control the size and the size distribution of the resulting nanoparticles have been elucidated in these systems.

Effects of Knowledge, Attitudes, and Practices of Primary Care Providers on Antibiotic Selection, United States

PubMed Central

Roberts, Rebecca M.; Albert, Alison P.; Johnson, Darcia D.; Hicks, Lauri A.

2014-01-01

Appropriate selection of antibiotic drugs is critical to optimize treatment of infections and limit the spread of antibiotic resistance. To better inform public health efforts to improve prescribing of antibiotic drugs, we conducted in-depth interviews with 36 primary care providers in the United States (physicians, nurse practitioners, and physician assistants) to explore knowledge, attitudes, and self-reported practices regarding antibiotic drug resistance and antibiotic drug selection for common infections. Participants were generally familiar with guideline recommendations for antibiotic drug selection for common infections, but did not always comply with them. Reasons for nonadherence included the belief that nonrecommended agents are more likely to cure an infection, concern for patient or parent satisfaction, and fear of infectious complications. Providers inconsistently defined broad- and narrow-spectrum antibiotic agents. There was widespread concern for antibiotic resistance; however, it was not commonly considered when selecting therapy. Strategies to encourage use of first-line agents are needed in addition to limiting unnecessary prescribing of antibiotic drugs. PMID:25418868

The effect of friend selection on social influences in obesity.

PubMed

Trogdon, Justin G; Allaire, Benjamin T

2014-12-01

We present an agent-based model of weight choice and peer selection that simulates the effect of peer selection on social multipliers for weight loss interventions. The model generates social clustering around weight through two mechanisms: a causal link from others' weight to an individual's weight and the propensity to select peers based on weight. We simulated weight loss interventions and tried to identify intervention targets that maximized the spillover of weight loss from intervention participants to nonparticipants. Social multipliers increase with the number of intervention participants' friends. For example, when friend selection was based on a variable exogenous to weight, the weight lost among non-participants increased by 23% (14.3lb vs. 11.6lb) when targeting the most popular obese. Holding constant the number of participants' friends, multipliers increase with increased weight clustering due to selection, up to a point. For example, among the most popular obese, social multipliers when matching on a characteristic correlated with weight (1.189) were higher than when matching on the exogenous characteristic (1.168) and when matching on weight (1.180). Increased weight clustering also implies more obese "friends of friends" of participants, who reduce social multipliers. Copyright © 2014 Elsevier B.V. All rights reserved.

Targeting of phage particles towards endothelial cells by antibodies selected through a multi-parameter selection strategy.

PubMed

Mandrup, Ole A; Lykkemark, Simon; Kristensen, Peter

2017-02-10

One of the hallmarks of cancer is sustained angiogenesis. Here, normal endothelial cells are activated, and their formation of new blood vessels leads to continued tumour growth. An improved patient condition is often observed when angiogenesis is prevented or normalized through targeting of these genomically stable endothelial cells. However, intracellular targets constitute a challenge in therapy, as the agents modulating these targets have to be delivered and internalized specifically to the endothelial cells. Selection of antibodies binding specifically to certain cell types is well established. It is nonetheless a challenge to ensure that the binding of antibodies to the target cell will mediate internalization. Previously selection of such antibodies has been performed targeting cancer cell lines; most often using either monovalent display or polyvalent display. In this article, we describe selections that isolate internalizing antibodies by sequential combining monovalent and polyvalent display using two types of helper phages, one which increases display valence and one which reduces background. One of the selected antibodies was found to mediate internalization into human endothelial cells, although our results confirms that the single stranded nature of the DNA packaged into phage particles may limit applications aimed at targeting nucleic acids in mammalian cells.

7 CFR 331.3 - PPQ select agents and toxins.

Code of Federal Regulations, 2011 CFR

2011-01-01

... listed in paragraph (b) of this section if the nucleic acids: (i) Can be expressed in vivo or in vitro; or (ii) Are in a vector or recombinant host genome and can be expressed in vivo or in vitro. (3... select agents and toxins. (a) Except as provided in paragraphs (d) and (e) of this section, the...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2013 CFR

2013-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... pseudomallei. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within...

42 CFR 73.6 - Exemptions for overlap select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-10-01

... reported to CDC or APHIS and to other appropriate authorities when required by Federal, State, or local law... pseudomallei. This report must be followed by submission of APHIS/CDC Form 4 within seven calendar days after identification. (ii) For all other overlap select agents or toxins, APHIS/CDC Form 4 must be submitted within...

A multiplex PCR assay to detect and differentiate select agent strains of Ralstonia solanacearum

USDA-ARS?s Scientific Manuscript database

Ralstonia solanacearum causes bacterial wilt in a variety of cash crops. R. solanacearum race 3 biovar 2 strains are considered select agents by the U.S. Government because they are not endemic to the U.S. and have the potential to cause brown rot disease in our potato production fields. Simple and...

The good, the bad, and the timely: how temporal order and moral judgment influence causal selection

PubMed Central

Reuter, Kevin; Kirfel, Lara; van Riel, Raphael; Barlassina, Luca

2014-01-01

Causal selection is the cognitive process through which one or more elements in a complex causal structure are singled out as actual causes of a certain effect. In this paper, we report on an experiment in which we investigated the role of moral and temporal factors in causal selection. Our results are as follows. First, when presented with a temporal chain in which two human agents perform the same action one after the other, subjects tend to judge the later agent to be the actual cause. Second, the impact of temporal location on causal selection is almost canceled out if the later agent did not violate a norm while the former did. We argue that this is due to the impact that judgments of norm violation have on causal selection—even if the violated norm has nothing to do with the obtaining effect. Third, moral judgments about the effect influence causal selection even in the case in which agents could not have foreseen the effect and did not intend to bring it about. We discuss our findings in connection to recent theories of the role of moral judgment in causal reasoning, on the one hand, and to probabilistic models of temporal location, on the other. PMID:25477851

Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents.

PubMed

Jonsson, Colleen B; Cole, Kelly Stefano; Roy, Chad J; Perlin, David S; Byrne, Gerald

2013-04-29

Select agent research in the United States must meet federally-mandated biological surety guidelines and rules which are comprised of two main components: biosecurity and biosafety. Biosecurity is the process employed for ensuring biological agents are properly safeguarded against theft, loss, diversion, unauthorized access or use/release. Biosafety is those processes that ensure that operations with such agents are conducted in a safe, secure and reliable manner. As such, a biological surety program is generally concerned with biological agents that present high risk for adverse medical and/or agricultural consequences upon release outside of proper containment. The U.S. Regional and National Biocontainment Laboratories (RBL, NBL) represent expertise in this type of research, and are actively engaged in the development of programs to address these critical needs and federal requirements. While this comprises an ongoing activity for the RBLs, NBLs and other facilities that handle select agents as new guidelines and regulations are implemented, the present article is written with the goal of presenting a simplified yet comprehensive review of these requirements. Herein, we discuss the requirements and the various activities that the RBL/NBL programs have implemented to achieve these metrics set forth by various agencies within the U.S. Federal government.

Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents

PubMed Central

Jonsson, Colleen B.; Cole, Kelly Stefano; Roy, Chad J.; Perlin, David S.; Byrne, Gerald

2014-01-01

Select agent research in the United States must meet federally-mandated biological surety guidelines and rules which are comprised of two main components: biosecurity and biosafety. Biosecurity is the process employed for ensuring biological agents are properly safeguarded against theft, loss, diversion, unauthorized access or use/release. Biosafety is those processes that ensure that operations with such agents are conducted in a safe, secure and reliable manner. As such, a biological surety program is generally concerned with biological agents that present high risk for adverse medical and/or agricultural consequences upon release outside of proper containment. The U.S. Regional and National Biocontainment Laboratories (RBL, NBL) represent expertise in this type of research, and are actively engaged in the development of programs to address these critical needs and federal requirements. While this comprises an ongoing activity for the RBLs, NBLs and other facilities that handle select agents as new guidelines and regulations are implemented, the present article is written with the goal of presenting a simplified yet comprehensive review of these requirements. Herein, we discuss the requirements and the various activities that the RBL/NBL programs have implemented to achieve these metrics set forth by various agencies within the U.S. Federal government. PMID:24900945

Control of oxidation-reduction potential during Cheddar cheese ripening and its effect on the production of volatile flavour compounds.

PubMed

Caldeo, Veronica; Hannon, John A; Hickey, Dara-Kate; Waldron, Dave; Wilkinson, Martin G; Beresford, Thomas P; McSweeney, Paul L H

2016-11-01

In cheese, a negative oxidation-reduction (redox) potential is required for the stability of aroma, especially that associated with volatile sulphur compounds. To control the redox potential during ripening, redox agents were added to the salted curd of Cheddar cheese before pressing. The control cheese contained only salt, while different oxidising or reducing agents were added with the NaCl to the experimental cheeses. KIO3 (at 0·05, 0·1 and 1%, w/w) was used as the oxidising agent while cysteine (at 2%, w/w) and Na2S2O4 (at 0·05 and 0·1%, w/w) were used as reducing agents. During ripening the redox potential of the cheeses made with the reducing agents did not differ significantly from the control cheese (E h ≈ -120 mV) while the cheeses made with 0·1 and 0·05% KIO3 had a significantly higher and positive redox potential in the first month of ripening. Cheese made with 1% KIO3 had positive values of redox potential throughout ripening but no starter lactic acid bacteria survived in this cheese; however, numbers of starter organisms in all other cheeses were similar. Principal component analysis (PCA) of the volatile compounds clearly separated the cheeses made with the reducing agents from cheeses made with the oxidising agents at 2 month of ripening. Cheeses with reducing agents were characterized by the presence of sulphur compounds whereas cheeses made with KIO3 were characterized mainly by aldehydes. At 6 month of ripening, separation by PCA was less evident. These findings support the hypothesis that redox potential could be controlled during ripening and that this parameter has an influence on the development of cheese flavour.

A Method to Administer Agents to the Larynx in an Awake Large Animal

ERIC Educational Resources Information Center

Durkes, Abigail; Sivasankar, M. Preeti

2017-01-01

Purpose: This research note describes an adapted experimental methodology to administer an exogenous agent to the larynx and upper airway of awake animals. The exogenous agent could be a perturbation. In the current study, the agent was isotonic saline. Isotonic saline was selected because it is safe, of similar composition to extracellular fluid,…

Hydroxypyridonate chelating agents and synthesis thereof

DOEpatents

Raymond, K.N.; Scarrow, R.C.; White, D.L.

1985-11-12

Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

Effects of Spousal Satisfaction and Selected Career Factors on Job Satisfaction of Extension Agents.

ERIC Educational Resources Information Center

Hebert, Michael; Kotrlik, Joe W.

1990-01-01

A survey of extension agents and their spouses (n=127, 83 percent) found that the strongest predictor of job satisfaction was spousal satisfaction. Four-H agents had lower job satisfaction, related to long, irregular working hours. Agents had low extrinsic satisfaction related to recognition, salary, policies, and decision-making power. Spouses…

Synthesis and characterization of a smart contrast agent sensitive to calcium.

PubMed

Dhingra, Kirti; Maier, Martin E; Beyerlein, Michael; Angelovski, Goran; Logothetis, Nikos K

2008-08-07

A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows approximately 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.

Selective disulfide reduction for labeling and enhancement of Fab antibody fragments.

PubMed

Kirley, Terence L; Greis, Kenneth D; Norman, Andrew B

2016-11-25

Many methods have been developed for chemical labeling and enhancement of the properties of antibodies and their common fragments, including the Fab and F(ab') 2 fragments. Somewhat selective reduction of some antibody disulfide bonds has been previously achieved, yielding antibodies and antibody fragments that can be labeled at defined sites, enhancing their utility and properties. Selective reduction of the two hinge disulfide bonds present in F(ab') 2 fragments using mild reduction has been useful. However, such reduction is often not quantitative and results in the reduction of multiple disulfide bonds, and therefore subsequent multiple labeling or conjugation sites are neither homogenous nor stoichiometric. Here, a simple and efficient selective reduction of the single disulfide bond linking the partial heavy chain and the intact light chain which compose the Fab fragment is accomplished utilizing tris(2-carboxyethyl)phosphine (TCEP) immobilized on agarose beads. The resultant reduced cysteine residues were labeled with several cysteine-selective fluorescent reagents, as well as by cysteine-directed PEGylation. These two cysteine residues can also be re-ligated by means of a bifunctional cysteine cross-linking agent, dibromobimane, thereby both restoring a covalent linkage between the heavy and light chains at this site, far removed from the antigen binding site, and also introducing a fluorescent probe. There are many other research and clinical uses for these selectively partially reduced Fab fragments, including biotinylation, toxin and drug conjugation, and incorporation of radioisotopes, and this technique enables simple generation of very useful Fab fragment derivatives with many potential applications. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

Ding, Hui; Wang, Rongyu; Wang, Xiao; Ji, Wenhua

2018-06-21

Molecularly imprinted covalent organic polymers were constructed by an imine-linking reaction between 1,3,5-triformylphloroglucinol and 2,6-diaminopyridine and used for the selective solid-phase extraction of benzoxazole fluorescent whitening agents from food samples. Binding experiments showed that imprinting sites on molecularly imprinted polymers had higher selectivity for targets compared with those of the corresponding non-imprinted polymers. Parameters affecting the solid-phase extraction procedure were examined. Under optimal conditions, actual samples were treated and the eluent was analyzed with high-performance liquid chromatography with diode-array detection. The results showed that the established method owned the wide linearity, satisfactory detection limits and quantification limits, and acceptable recoveries. Thus, this developed method possesses the practical potential to the selectively determine benzoxazole fluorescent whitening agents in complex food samples. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

PubMed

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

2002-12-06

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

RECONDITIONING FUEL ELEMENTS

DOEpatents

Brandt, H.L.

1962-02-20

A process is given for decanning fuel elements that consist of a uranium core, an intermediate section either of bronze, silicon, Al-Si, and uranium silicide layers or of lead, Al-Si, and uranium silicide layers around said core, and an aluminum can bonded to said intermediate section. The aluminum can is dissolved in a solution of sodium hydroxide (9 to 20 wt%) and sodium nitrate (35 to 12 wt %), and the layers of the intermediate section are dissolved in a boiling sodium hydroxide solution of a minimum concentration of 50 wt%. (AEC) A method of selectively reducing plutonium oxides and the rare earth oxides but not uranium oxides is described which comprises placing the oxides in a molten solvent of zinc or cadmium and then adding metallic uranium as a reducing agent. (AEC)

[Impact of HLA mismatch on transplant outcomes].

PubMed

Kanda, Junya

Human leukocyte antigen (HLA) mismatch increases the risk of severe graft-versus-host disease (GVHD) and transplant-related mortality. However, the variety of stem cell sources such as cord blood units or the improvements in GVHD prophylaxis makes the interpretation of HLA mismatch more complex. In unrelated transplantation, the locus of HLA mismatch has a great impact on the donor candidate selection, whereas in related transplantation, it has an impact on the intensity of GVHD prophylaxis because donor availability is limited. Anti-thymocyte globulin and post-transplant cyclophosphamide are attractive GVHD prophylactic agents to reduce the risk of immune-associated complications in HLA-mismatched transplantations. HLA mismatch has a reduced impact in adult cord blood transplantation. In this review article, the impact of HLA mismatch based on graft sources is discussed.

Reduced-risk pest management programs for eastern U.S. peach orchards: effects on arthropod predators, parasitoids, and select pests.

PubMed

Biddinger, David J; Leslie, Timothy W; Joshi, Neelendra K

2014-06-01

We developed new integrated pest management programs for eastern U.S. peaches with minimal use of organophosphates. From 2002-2005, we assessed the ecological impacts of these reduced-risk programs versus grower standard conventional programs that still relied primarily on the use of organophosphorous and carbamate insecticides. Using a split-plot design replicated at four commercial Pennsylvania peach orchards, we quantified pesticide rates, environmental impact, and arthropod community response. We used Environmental Impact Quotient (EIQ) analysis based on the growers' pesticide records from each orchard to calculate seasonal cumulative EIQ field ratings for all years. Ecological effects of the reduced-risk and conventional program were also measured as the abundance and diversity of nontarget arthropod predators, parasitoids, and selected pest taxa. Pesticide inputs and EIQ values were substantially lower in reduced-risk programs compared with conventional spray programs. Arthropod arrays differed significantly between pest management programs: most beneficial predator and parasitoid taxa were positively associated with the reduced-risk program and negatively associated with the standard grower program. Regardless of the pest management program, we observed significant differences in species arrays in the peach tree canopy compared with the ground cover of the orchards, but the arthropod community did not differ among the field sites or based on distance from the edge of the orchard. We conclude that reduced-risk programs not only provide control comparable with that of conventional programs, but they also reduce negative environmental effects while conserving key arthropod biological control agents within eastern U.S. peach orchards.

Spin-on metal oxide materials with high etch selectivity and wet strippability

NASA Astrophysics Data System (ADS)

Yao, Huirong; Mullen, Salem; Wolfer, Elizabeth; McKenzie, Douglas; Rahman, Dalil; Cho, JoonYeon; Padmanaban, Munirathna; Petermann, Claire; Hong, SungEun; Her, YoungJun

2016-03-01

Metal oxide or metal nitride films are used as hard mask materials in semiconductor industry for patterning purposes due to their excellent etch resistances against the plasma etches. Chemical vapor deposition (CVD) or atomic layer deposition (ALD) techniques are usually used to deposit the metal containing materials on substrates or underlying films, which uses specialized equipment and can lead to high cost-of-ownership and low throughput. We have reported novel spin-on coatings that provide simple and cost effective method to generate metal oxide films possessing good etch selectivity and can be removed by chemical agents. In this paper, new spin-on Al oxide and Zr oxide hard mask formulations are reported. The new metal oxide formulations provide higher metal content compared to previously reported material of specific metal oxides under similar processing conditions. These metal oxide films demonstrate ultra-high etch selectivity and good pattern transfer capability. The cured films can be removed by various chemical agents such as developer, solvents or wet etchants/strippers commonly used in the fab environment. With high metal MHM material as an underlayer, the pattern transfer process is simplified by reducing the number of layers in the stack and the size of the nano structure is minimized by replacement of a thicker film ACL. Therefore, these novel AZ® spinon metal oxide hard mask materials can potentially be used to replace any CVD or ALD metal, metal oxide, metal nitride or spin-on silicon-containing hard mask films in 193 nm or EUV process.

Selected Pathogens of Concern to Industrial Food Processors: Infectious, Toxigenic, Toxico-Infectious, Selected Emerging Pathogenic Bacteria

NASA Astrophysics Data System (ADS)

Behling, Robert G.; Eifert, Joseph; Erickson, Marilyn C.; Gurtler, Joshua B.; Kornacki, Jeffrey L.; Line, Erick; Radcliff, Roy; Ryser, Elliot T.; Stawick, Bradley; Yan, Zhinong

This chapter, written by several contributing authors, is devoted to discussing selected microbes of contemporary importance. Microbes from three categories are described by the following: (1) infectious invasive agents like Salmonella, Listeria monocytogenes, and Campylobacter; (2) toxigenic pathogens such as Staphylococcus aureus, Bacillus cereus, and Clostridium botulinum; and (3) toxico-infectious agents like enterohemorrhagic Escherichia coli and Clostridium perfringens. In addition, emerging pathogens, like Cronobacter (Enterobacter) sakazakii, Arcobacter spp., and Mycobacterium avium subspecies paratuberculosis are also described.

A Targeted Mulifunctional Platform for Imaging and Treatment of Breast Cancer and Its Metastases Based on Adenoviral Vectors and Magnetic Nanoparticles

DTIC Science & Technology

2008-02-01

tu- mor cells. In this regard, herpesvirus samiri (HVS) was de- monstrated to be naturally selectively oncolytic for the pancreatic cancer line PANC-1...the hexon virus. Therefore, Ad can provide a versatile platform for selective binding of AuNPs, resulting in a multifunctional agent capable of...utility remained unaffected. Therefore, Ad can provide a versatile platform for selective binding of nanoparticles, resulting in a multifunctional agent

Dyadic brain modelling, mirror systems and the ontogenetic ritualization of ape gesture

PubMed Central

Arbib, Michael; Ganesh, Varsha; Gasser, Brad

2014-01-01

The paper introduces dyadic brain modelling, offering both a framework for modelling the brains of interacting agents and a general framework for simulating and visualizing the interactions generated when the brains (and the two bodies) are each coded up in computational detail. It models selected neural mechanisms in ape brains supportive of social interactions, including putative mirror neuron systems inspired by macaque neurophysiology but augmented by increased access to proprioceptive state. Simulation results for a reduced version of the model show ritualized gesture emerging from interactions between a simulated child and mother ape. PMID:24778382

Dyadic brain modelling, mirror systems and the ontogenetic ritualization of ape gesture.

PubMed

Arbib, Michael; Ganesh, Varsha; Gasser, Brad

2014-01-01

The paper introduces dyadic brain modelling, offering both a framework for modelling the brains of interacting agents and a general framework for simulating and visualizing the interactions generated when the brains (and the two bodies) are each coded up in computational detail. It models selected neural mechanisms in ape brains supportive of social interactions, including putative mirror neuron systems inspired by macaque neurophysiology but augmented by increased access to proprioceptive state. Simulation results for a reduced version of the model show ritualized gesture emerging from interactions between a simulated child and mother ape.

Bacteriocins - exploring alternatives to antibiotics in mastitis treatment.

PubMed

Pieterse, Reneé; Todorov, Svetoslav D

2010-07-01

Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease.

Structure–Activity Relationship Studies of the Tricyclic Indoline Resistance-Modifying Agent

PubMed Central

2015-01-01

Previously we discovered a tricyclic indoline, N-[2-(6-bromo-4-methylidene-2,3,4,4a,9,9a-hexahydro-1H-carbazol-4a-yl)ethyl]-4-chlorobenzene-1-sulfonamide (1, Of1), from bioinspired synthesis of a highly diverse polycyclic indoline alkaloid library, that selectively resensitizes methicillin-resistant Staphylococcus aureus strains to β-lactam antibiotics. Herein, we report a thorough structure–activity relationship investigation of 1, which identified regions of 1 that tolerate modifications without compromising activity and afforded the discovery of a more potent analogue with reduced mammalian toxicity. PMID:24694192

Pretreatment of solid carbonaceous material with dicarboxylic aromatic acids to prevent scale formation

DOEpatents

Brunson, Roy J.

1982-01-01

Scale formation during the liquefaction of lower ranking coals and similar carbonaceous materials is significantly reduced and/or prevented by pretreatment with a pretreating agent selected from the group consisting of phthalic acid, phthalic anhydride, pyromellitic acid and pyromellitic anhydride. The pretreatment is believed to convert the scale-forming components to the corresponding phthalate and/or pyromellitate prior to liquefaction. The pretreatment is accomplished at a total pressure within the range from about 1 to about 2 atmospheres. Temperature during pretreatment will generally be within the range from about 5.degree. to about 80.degree. C.

Salvaging and Conserving Water Damaged Photographic Materials

NASA Astrophysics Data System (ADS)

Suzuki, Ryuji

Degradation of water damaged photographic materials is discussed; the most vulnerable elements are gelatin layers and silver image. A simple and inexpensive chemical treatment is proposed, consisting of a bath containing a gelatin-protecting biocide and a silver image protecting agent. These ingredients were selected among those used in manufacturing of silver halide photographic emulsions or processing chemicals. Experiments confirmed that this treatment significantly reduced oxidative attacks to silver image and bacterial degradation of gelatin layers. The treated material was also stable under intense light fading test. Method of hardening gelatin to suppress swelling is also discussed.

Lyme disease: a selective medium for isolation of the suspected etiological agent, a spirochete.

PubMed Central

Johnson, S E; Klein, G C; Schmid, G P; Bowen, G S; Feeley, J C; Schulze, T

1984-01-01

A simple procedure with a new selective culture medium for the isolation of the suspected etiological agent of Lyme disease from ticks is described. Live ticks (Ixodes dammini) were ground with a mortar and pestle, and the suspensions were inoculated into a selective and nonselective medium. The selective medium, which contained kanamycin and 5-fluorouracil, yielded positive spirochete cultures from 100% of the pooled ticks and from 79% of the single tick specimens. The isolation rate for the nonselective medium was 0% from the tick pools and 58% from the single tick specimens. PMID:6361065

Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease.

PubMed

Argaw, Azeb Tadesse; Asp, Linnea; Zhang, Jingya; Navrazhina, Kristina; Pham, Trinh; Mariani, John N; Mahase, Sean; Dutta, Dipankar J; Seto, Jeremy; Kramer, Elisabeth G; Ferrara, Napoleone; Sofroniew, Michael V; John, Gareth R

2012-07-01

In inflammatory CNS conditions such as multiple sclerosis (MS), current options to treat clinical relapse are limited, and more selective agents are needed. Disruption of the blood-brain barrier (BBB) is an early feature of lesion formation that correlates with clinical exacerbation, leading to edema, excitotoxicity, and entry of serum proteins and inflammatory cells. Here, we identify astrocytic expression of VEGF-A as a key driver of BBB permeability in mice. Inactivation of astrocytic Vegfa expression reduced BBB breakdown, decreased lymphocyte infiltration and neuropathology in inflammatory and demyelinating lesions, and reduced paralysis in a mouse model of MS. Knockdown studies in CNS endothelium indicated activation of the downstream effector eNOS as the principal mechanism underlying the effects of VEGF-A on the BBB. Systemic administration of the selective eNOS inhibitor cavtratin in mice abrogated VEGF-A-induced BBB disruption and pathology and protected against neurologic deficit in the MS model system. Collectively, these data identify blockade of VEGF-A signaling as a protective strategy to treat inflammatory CNS disease.

Evaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE Inhibitory Activities

PubMed Central

Abdullah, Noorlidah; Ismail, Siti Marjiana; Aminudin, Norhaniza; Shuib, Adawiyah Suriza; Lau, Beng Fye

2012-01-01

Considering the importance of diet in prevention of oxidative stress-related diseases including hypertension, this study was undertaken to evaluate the in vitro antioxidant and ACE inhibitory activities of selected culinary-medicinal mushrooms extracted by boiling in water for 30 min. Antioxidant capacity was measured using the following assays: DPPH free radical scavenging activity, β-carotene bleaching, inhibition of lipid peroxidation, reducing power ability, and cupric ion reducing antioxidant capacity (CUPRAC). Antioxidant potential of each mushroom species was calculated based on the average percentages relative to quercetin and summarized as Antioxidant Index (AI). Ganoderma lucidum (30.1%), Schizophyllum commune (27.6%), and Hericium erinaceus (17.7%) showed relatively high AI. Total phenolics in these mushrooms varied between 6.19 to 63.51 mg GAE/g extract. In the ACE inhibitory assay, G. lucidum was shown to be the most potent species (IC50 = 50 μg/mL). Based on our findings, culinary-medicinal mushrooms can be considered as potential source of dietary antioxidant and ACE inhibitory agents. PMID:21716693

The Impact of Weight Gain on Motivation, Compliance, and Metabolic Control in Patients with Type 2 Diabetes Mellitus

PubMed Central

Pi-Sunyer, F. Xavier

2010-01-01

Patients with type 2 diabetes, approximately 85% of whom are overweight or obese, often have an increased incidence of cardiovascular disease (CVD) risk factors such as hypertension and dyslipidemia. Both type 2 diabetes and obesity are independent risk factors for CVD. Unfortunately, many therapies aimed at maintaining and improving glucose control are associated with weight gain. Among the older antidiabetes agents, most, including the insulin secretagogues and sensitizers, can lead to weight gain, except for metformin, which is weight-neutral. Among the newer agents, the dipeptidyl peptidase-4 inhibitors generally are weight-neutral in addition to lowering glucose, while the glucagon-like peptide–1 receptor agonists lead to weight reduction. Patients with type 2 diabetes are at an increased risk for both diabetes-and CV-related outcomes, and weight reduction is an important component of diabetes management. Weight gain in patients with type 2 diabetes can contribute to patient frustration and may negatively impact their compliance to therapeutic regimens. The selection of antidiabetes agents that not only improve glucose control but reduce or have a neutral effect on weight with beneficial effects on lipids are ideal options for managing patients with type 2 diabetes. PMID:19820278

Alginate edible films containing microencapsulated lemongrass oil or citral: effect of encapsulating agent and storage time on physical and antimicrobial properties.

PubMed

Alarcón-Moyano, Jessica K; Bustos, Rubén O; Herrera, María Lidia; Matiacevich, Silvia B

2017-08-01

Active edible films have been proposed as an alternative to extend shelf life of fresh foods. Most essential oils have antimicrobial properties; however, storage conditions could reduce their activity. To avoid this effect the essential oil (EO) can be microencapsulated prior to film casting. The aim of this study was to determine the effects of the type of encapsulating agent (EA), type of EO and storage time on physical properties and antimicrobial activity of alginate-based films against Escherichia coli ATCC 25922. Trehalose (TH), Capsul ® (CAP) and Tween 20 (Tw20) were used as EA. Lemongrass essential oil (LMO) and citral were used as active agents. The results showed that the type of EA affected the stability of the film forming-emulsions as well as the changes in opacity and colour of the films during storage but not the antimicrobial activity of them. Both microencapsulated EOs showed a prolonged release from the alginate films during the 28 days of storage. Trehalose was selected to encapsulate both active compounds because the films made with this microencapsulated EA showed the greatest physical stability and the lowest color variation among all the films studied.

SCH 43478 and analogs: in vitro activity and in vivo efficacy of novel agents for herpesvirus type 2.

PubMed

Albin, R; Chase, R; Risano, C; Lieberman, M; Ferrari, E; Skelton, A; Buontempo, P; Cox, S; DeMartino, J; Wright-Minogue, J; Jirau-Lucca, G; Kelly, J; Afonso, A; Kwong, A D; Rozhon, E J; O'Connell, J F

1997-08-01

SCH 43478 and analogs are a class of non-nucleoside antiviral agents that have potent and selective activity against herpes simplex virus type 2 (HSV-2). The IC50 for these compounds in plaque reduction analysis using Vero cells ranges from 0.8 to 2.0 microg/ml. All compounds have a LC50 > 100 microg/ml in cytotoxicity analysis. Mechanism of action studies suggest that these molecules have an effect on the transactivation of viral immediate early (alpha) gene expression. Time of addition studies indicate that antiviral activity of these analogs is limited to the initial 2-3 h after infection and is not due to inhibition of viral adsorption or penetration. Analysis of HSV protein expression demonstrates that SCH 49286 inhibits the accumulation of viral immediate early (alpha) gene products. SCH 43478 demonstrates statistically significant efficacy (P < 0.05) in the guinea pig genital model of HSV infection. Following subcutaneous administration in a therapeutic treatment regimen, SCH 43478 (90 mg/kg/day) is efficacious in reducing the number and severity of lesions and the neurological complications of acute HSV infection. Thus, SCH 43478 and analogs are anti-herpesvirus agents with a unique mechanism of action.

Selection of the distributional rule as an alternative tool to foster cooperation in a Public Good Game

NASA Astrophysics Data System (ADS)

Colasante, Annarita

2017-02-01

This paper presents an investigation about cooperation in a Public Good Game using an Agent Based Model calibrated on experimental data. Starting from the experiment proposed in Colasante and Russo (2016), we analyze the dynamic of cooperation in a Public Good Game where agents receive an heterogeneous income and choose both the level of contribution and the distribution rule. The starting point is the calibration and the output validation of the model using the experimental results. Once tested the goodness of fit of the Agent Based Model, we run some policy experiment in order to verify how each distribution rule, i.e. equidistribution, proportional to contribution and progressive, affects the level of contribution in the simulated model. We find out that the share of cooperators decreases over time if we exogenously set the equidistribution rule. On the contrary, the share of cooperators converges to 100 % if we impose the progressive rule. Finally, the most interesting result refers to the effect of the progressive rule. We observe that, in the case of high inequality, this rule is not able to reduce the heterogeneity of income.

Discovery and evaluation of triple inhibitors of VEGFR-2, TIE-2 and EphB4 as anti-angiogenic and anti-cancer agents

PubMed Central

Zhang, Lin; Shan, Yuanyuan; Ji, Xingyue; Zhu, Mengyuan; Li, Chuansheng; Sun, Ying; Si, Ru; Pan, Xiaoyan; Wang, Jinfeng; Ma, Weina; Dai, Bingling; Wang, Binghe; Zhang, Jie

2017-01-01

Receptor tyrosine kinases (RTKs), especially VEGFR-2, TIE-2, and EphB4, play a crucial role in both angiogenesis and tumorigenesis. Moreover, complexity and heterogeneity of angiogenesis make it difficult to treat such pathological traits with single-target agents. Herein, we developed two classes of multi-target RTK inhibitors (RTKIs) based on the highly conserved ATP-binding pocket of VEGFR-2/TIE-2/EphB4, using previously reported BPS-7 as a lead compound. These multi-target RTKIs exhibited considerable potential as novel anti-angiogenic and anticancer agents. Among them, QDAU5 displayed the most promising potency and selectivity. It significantly suppressed viability of EA.hy926 and proliferation of several cancer cells. Further investigations indicated that QDAU5 showed high affinity to VEGFR-2 and reduced the phosphorylation of VEGFR-2. We identified QDAU5 as a potent multiple RTKs inhibitor exhibiting prominent anti-angiogenic and anticancer potency both in vitro and in vivo. Moreover, quinazolin-4(3H)-one has been identified as an excellent hinge binding moiety for multi-target inhibitors of angiogenic VEGFR-2, Tie-2, and EphB4. PMID:29285210

Chemical agents for the control of plaque and plaque microflora: an overview.

PubMed

Gaffar, A; Afflitto, J; Nabi, N

1997-10-01

This presentation provides an overview of the technologies available for the chemical control of plaque. It is generally accepted that the formation of dental plaque at the interfaces of tooth/gingiva is one of the major causes of gingival inflammation and dental caries. Several therapeutic approaches have been used to control dental plaque and supragingival infections. These include fluoride preparations such as stannous fluoride, oxygenating agents, anti-attachment agents, and cationic and non-cationic antibacterial agents. Among the fluoride preparations, stable stannous fluoride pastes and gels have been shown to reduce supragingival plaque, gingivitis, hypersensitivity and caries. The effect of the oxygenating agents on the supragingival plaque has been equivocal, but recent data indicate that a stable agent which provides sustained active oxygen release is effective in controlling plaque. A polymer, PVPA, which reduced attachment of bacteria to teeth was shown to significantly reduce plaque formation in humans. A new generation of antibacterials includes non-ionics such as triclosan, which in combination with a special polymer delivery system, has been shown to reduce plaque, gingivitis, supragingival calculus and dental caries in long-term studies conducted around the world. Unlike the first generation of agents, the triclosan/copolymer/sodium fluoride system is effective in long-term clinicals and does not cause staining of teeth, increase in calculus, or disturbance in the oral microbial ecology.

Enhancement of the Musca domestica hytrosavirus infection with orally delivered reducing agents.

PubMed

Boucias, D; Baniszewski, J; Prompiboon, P; Lietze, V; Geden, C

2015-01-01

House flies (Musca domestica L.) throughout the world are infected with the salivary gland hypertrophy virus MdSGHV (Hytrosaviridae). Although the primary route of infection is thought to be via ingestion, flies that are old enough to feed normally are resistant to infection per os, suggesting that the peritrophic matrix (PM) is a barrier to virus transmission. Histological examination of the peritrophic matrix of healthy flies revealed a multilaminate structure produced by midgut cells located near the proventriculus. SEM revealed the PM to form a confluent sheet surrounding the food bolus with pores/openings less than 10nm in diameter. TEM revealed the PM to be multilayered, varying in width from 350 to 900 nm, and generally thinner in male than in female flies. When flies were fed on the reducing agents dithiothetriol (DTT) or tris (2-caboxyethyl)phosphine hydrochloride (TCEP) for 48 h before per os exposure to the virus, infection rates increased 10- to 20-fold compared with flies that did not receive the reducing agent treatments. PM's from flies treated with DTT and TCEP displayed varying degrees of disruption, particularly in the outer layer, and lacked the electron-dense inner layer facing the ectoperitrophic space. Both drugs were somewhat toxic to the flies, resulting in>40% mortality at doses greater than 10mM (DTT) or 5 mM (TCEP). DTT increased male fly susceptibility (55.1% infected) more than that of females (7.8%), whereas TCEP increased susceptibility of females (42.9%) more than that of males (26.2%). The cause for the sex differences in response to oral exposure the reducing agents is unclear. Exposing flies to food treated with virus and the reducing agents at the same time, rather than pretreating flies with the drugs, had no effect on susceptibility to the virus. Presumably, the reducing agent disrupted the enveloped virus and acted as a viricidal agent. In summary, it is proposed that the reducing agents influence integrity of the PM barrier and increase the susceptibility of flies to infection by MdSGHV. Copyright © 2014 Elsevier Inc. All rights reserved.

Preferential partner selection in an evolutionary study of Prisoner's Dilemma.

PubMed

Ashlock, D; Smucker, M D; Stanley, E A; Tesfatsion, L

1996-01-01

Partner selection is an important process in many social interactions, permitting individuals to decrease the risks associated with cooperation. In large populations, defectors may escape punishment by roving from partner to partner, but defectors in smaller populations risk social isolation. We investigate these possibilities for an evolutionary Prisoner's Dilemma in which agents use expected payoffs to choose and refuse partners. In comparison to random or round-robin partner matching, we find that the average payoffs attained with preferential partner selection tend to be more narrowly confined to a few isolated payoff regions. Most ecologies evolve to essentially full cooperative behavior, but when agents are intolerant of defections, or when the costs of refusal and social isolation are small, we also see the emergence of wallflower ecologies in which all agents are socially isolated. Between these two extremes, we see the emergence of ecologies whose agents tend to engage in a small number of defections followed by cooperation thereafter. The latter ecologies exhibit a plethora of interesting social interaction patterns.

5-Amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel and selective 5-hydroxytryptamine4 receptor partial agonist: pharmacological profile in vitro and gastroprokinetic effect in conscious dogs.

PubMed

Mikami, Tadayoshi; Ochi, Yasuo; Suzuki, Keiko; Saito, Toshiyuki; Sugie, Yutaka; Sakakibara, Minoru

2008-04-01

5-Hydroxytryptamine (5-HT) receptors and dopamine(2) (D(2)) receptor modulate gastrointestinal motility. Gastroprokinetic agents that act on several 5-HT receptor subtypes and/or D(2) receptors are used clinically. Although the 5-HT(4) receptor is known to mediate the gastroprokinetic effects of these agents, the absence of highly selective 5-HT(4) receptor agonists has made it difficult to confirm the physiological consequences of selective 5-HT(4) receptor stimulation. In this study, we report the in vitro pharmacological profiles and the in vivo gastroprokinetic effects of 5-amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel, potent, and selective 5-HT(4) partial agonist. Compared with preceding 5-HT(4) agonists such as cisapride, mosapride, and tegaserod, CJ-033,466 had a superior in vitro profile, with nanomolar agonistic activities for the 5-HT(4) receptor and 1000-fold greater selectivity for the 5-HT(4) receptor over other 5-HT and D(2) receptors. In vivo studies in conscious dogs showed that CJ-033,466 dose-dependently stimulated gastric antral motility in both the fasted and postprandial states at the same dose range and that it was 30 times more potent than cisapride. Furthermore, CJ-033,466 accelerated the gastric emptying rate in a gastroparesis dog model at the minimally effective dose established in the gastric motility study. In conclusion, CJ-033,466 is a potent and highly selective 5-HT(4) agonist that stimulates physiologically coordinated gastric motility, and it has no activity on other 5-HT receptor subtypes and D(2) receptors. Therefore, CJ-033,466 could be used to treat gastroparesis, providing better gastroprokinetics and reduced side effects mediated by the other receptors.

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

PubMed Central

Welliver, Mark; McDonough, John; Kalynych, Nicholas; Redfern, Robert

2008-01-01

Neuromuscular blockade, induced by neuromuscular blocking agents, has allowed prescribed immobility, improved surgical exposure, optimal airway management conditions, and facilitated mechanical ventilation. However, termination of the effects of neuromuscular blocking agents has, until now, remained limited. A novel cyclodextrin encapsulation process offers improved termination of the paralytic effects of aminosteroidal non-depolarizing neuromuscular blocking agents. Sugammadex sodium is the first in a new class of drug called selective relaxant binding agents. Currently, in clinical trials, sugammadex, a modified gamma cyclodextrin, has shown consistent and rapid termination of neuromuscular blockade with few side effects. The pharmacology of cyclodextrins in general and sugammadex in particular, together with the results of current clinical research are reviewed. The ability of sugammadex to terminate the action of neuromuscular blocking agents by direct encapsulation is compared to the indirect competitive antagonism of their effects by cholinesterase inhibitors. Also discussed are the clinical implications that extend beyond fast, effective reversal, including numerous potential perioperative benefits. PMID:19920893

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.

S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity.

PubMed

Zvejniece, Liga; Svalbe, Baiba; Vavers, Edijs; Makrecka-Kuka, Marina; Makarova, Elina; Liepins, Vilnis; Kalvinsh, Ivars; Liepinsh, Edgars; Dambrova, Maija

2017-09-01

S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents. Copyright © 2017. Published by Elsevier Inc.

An enhanced performance through agent-based secure approach for mobile ad hoc networks

NASA Astrophysics Data System (ADS)

Bisen, Dhananjay; Sharma, Sanjeev

2018-01-01

This paper proposes an agent-based secure enhanced performance approach (AB-SEP) for mobile ad hoc network. In this approach, agent nodes are selected through optimal node reliability as a factor. This factor is calculated on the basis of node performance features such as degree difference, normalised distance value, energy level, mobility and optimal hello interval of node. After selection of agent nodes, a procedure of malicious behaviour detection is performed using fuzzy-based secure architecture (FBSA). To evaluate the performance of the proposed approach, comparative analysis is done with conventional schemes using performance parameters such as packet delivery ratio, throughput, total packet forwarding, network overhead, end-to-end delay and percentage of malicious detection.

The investigation of antibacterial activity of selected native plants from North of Iran.

PubMed

Koohsari, H; Ghaemi, E A; Sadegh Sheshpoli, M; Jahedi, M; Zahiri, M

2015-01-01

Plant derived products have been used for medicinal purposes during centuries. Bacterial resistance to currently used antibiotics has become a concern to public health. The development of bacterial super resistant strains has resulted in the currently used antibiotic agents failing to end many bacterial infections. For this reason, the search is ongoing for new antimicrobial agents, both by the design and by the synthesis of new agents, or through the search of natural sources for yet undiscovered antimicrobial agents. Herbal medications in particular have seen a revival of interest due to a perception that there is a lower incidence of adverse reactions to plant preparations compared to synthetic pharmaceuticals. Coupled with the reduced costs of plant preparations, this makes the search for natural therapeutics an attractive option. This research was carried out to assess the antibacterial activity aqueous and ethanolic extracts of six Azadshahr township Native plants in north of Iran against six species of pathogen bacteria by using three methods of Disk diffusion, Well method and MBC. The results of this research indicated that the effect of ethanol extracts were more than aqueous extract and among six plants, Lippia citriodora and Plantago major ethanol extract had the most antibacterial activity in any of the three methods. Gram-positive bacteria were more sensitive than gram-negative bacteria. Staphylococcus epidermidis and Staphylococcus aureus were the most susceptible Gram-positive bacteria.

Continuing Professional Education of Insurance and Risk Management Practitioners: A Comparative Case Study of Customer Service Representatives, Insurance Agents and Risk Managers

ERIC Educational Resources Information Center

Krauss, George E.

2009-01-01

The purpose of this study is to understand how selected insurance practitioners learn and developed in their practices setting. The selected insurance practitioners (collectively customer service representatives, insurance agents, and risk managers) are responsible for the counseling and placement of insurance products and the implementation of…

Imaging of vaporised sub-micron phase change contrast agents with high frame rate ultrasound and optics

NASA Astrophysics Data System (ADS)

Lin, Shengtao; Zhang, Ge; Jamburidze, Akaki; Chee, Melisse; Hau Leow, Chee; Garbin, Valeria; Tang, Meng-Xing

2018-03-01

Phase-change ultrasound contrast agent (PCCA), or nanodroplet, shows promise as an alternative to the conventional microbubble agent over a wide range of diagnostic applications. Meanwhile, high-frame-rate (HFR) ultrasound imaging with microbubbles enables unprecedented temporal resolution compared to traditional contrast-enhanced ultrasound imaging. The combination of HFR ultrasound imaging and PCCAs can offer the opportunity to observe and better understand PCCA behaviour after vaporisation captures the fast phenomenon at a high temporal resolution. In this study, we utilised HFR ultrasound at frame rates in the kilohertz range (5-20 kHz) to image native and size-selected PCCA populations immediately after vaporisation in vitro within clinical acoustic parameters. The size-selected PCCAs through filtration are shown to preserve a sub-micron-sized (mean diameter  <  200 nm) population without micron-sized outliers (>1 µm) that originate from native PCCA emulsion. The results demonstrate imaging signals with different amplitudes and temporal features compared to that of microbubbles. Compared with the microbubbles, both the B-mode and pulse-inversion (PI) signals from the vaporised PCCA populations were reduced significantly in the first tens of milliseconds, while only the B-mode signals from the PCCAs were recovered during the next 400 ms, suggesting significant changes to the size distribution of the PCCAs after vaporisation. It is also shown that such recovery in signal over time is not evident when using size-selective PCCAs. Furthermore, it was found that signals from the vaporised PCCA populations are affected by the amplitude and frame rate of the HFR ultrasound imaging. Using high-speed optical camera observation (30 kHz), we observed a change in particle size in the vaporised PCCA populations exposed to the HFR ultrasound imaging pulses. These findings can further the understanding of PCCA behaviour under HFR ultrasound imaging.

Pharmacokinetic and pharmacodynamic profile of dronedarone , a new antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Rosa, Gian Marco; Bianco, Daniele; Parodi, Antonello; Valbusa, Alberto; Zawaideh, Camilla; Bizzarri, Nicolò; Ferrero, Simone; Brunelli, Claudio

2014-12-01

Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.

[Guidelines for the treatment of constipation].

PubMed

Park, Moo In; Shin, Jeong Eun; Myung, Seung Jae; Huh, Kyu Chan; Choi, Chang Hwan; Jung, Sung Ae; Choi, Suck Chei; Sohn, Chong Il; Choi, Myung Gyu

2011-02-01

While constipation is a common symptom in Korea, there are no existing treatment guidelines. Although constipation may occur as a result of organic cause, there is no obstructive mucosal or structural cause in the vast majority of patients with constipation. The present paper deals with only the management of functional constipation: lifestyle changes; bulking agents and stool softeners; osmotic agents; stimulant laxatives; prokinetics; biofeedback and surgical treatments. Exercise and dietary fiber are helpful in some patients with constipation. Laxatives including bulking agents, stool softeners, osmotic agents, and stimulant laxatives have been found to be more effective than placebo at relieving symptoms of constipation. New enterokinetic agents that affect peristalsis through selective interaction with 5-hydroxytryptamine-4 receptors can be effective in patients with constipation who cannot get adequate relief from current laxatives. Biofeedback can relieve symptoms in selected patients with pelvic floor dyssynergia. Surgical treatments can be helpful in some patients with refractory constipation.

Equine Airway Mast Cells are Sensitive to Cell Death Induced by Lysosomotropic Agents.

PubMed

Wernersson, S; Riihimäki, M; Pejler, G; Waern, I

2017-01-01

Mast cells are known for their detrimental effects in various inflammatory conditions. Regimens that induce selective mast cell apoptosis may therefore be of therapeutic significance. Earlier studies have demonstrated that murine- and human-cultured mast cells are highly sensitive to apoptosis induced by the lysosomotropic agent LeuLeuOMe (LLME). However, the efficacy of lysosomotropic agents for inducing apoptosis of in vivo-derived airway mast cells and the impact on mast cells in other species have not been assessed. Here we addressed whether lysosomotropic agents can induce cell death of equine in vivo-derived mast cells. Bronchoalveolar lavage (BAL) fluids from horses were incubated with LLME at 15-100 μm for up to 48 h. The overall cell viability was unaffected by 15 μm LLME up to 48 h, whereas a relatively modest drop in total cell counts (~30%) was seen at the highest LLME dose used. In contrast to the relatively low effect on total cell counts, LLME efficiently and dose dependently reduced the number of mast cells in BAL fluids, with an almost complete depletion (96%) of mast cells after 24 h of incubation with 100 μm LLME. A significant but less dramatic reduction (up to ~45%) of lymphocytes was also seen, whereas macrophages and neutrophils were essentially resistant. The appearance of apoptotic bodies suggested a mechanism involving apoptosis rather than necrosis. These findings suggest that equine airway mast cells are highly sensitive to lysosomotropic agents. Possibly, lysosomotropic agents could be of therapeutic value to treat disorders involving harmful accumulation of mast cells in the airways. © 2016 The Foundation for the Scandinavian Journal of Immunology.

Quantitative comparison of topical aluminum salt solution efficacy for management of sweating: a randomized, controlled trial.

PubMed

Swary, Jillian H; West, Dennis P; Kakar, Rohit; Ortiz, Sara; Schaeffer, Matthew R; Veledar, Emir; Alam, Murad

2015-12-01

There is a lack of studies objectively comparing the efficacy of topical antiperspirants in reducing sweat. To objectively and quantitatively compare the efficacy of two aluminum salt solutions for the reduction of induced sweating. A subject, rater, and statistician-blinded, randomized, controlled trial. Nineteen subjects were exposed to a standardized heat challenge for 3 h. Topical agent A (20% aluminum chloride hexahydrate) was randomized to either axilla, and topical agent B (1% aluminum acetate) assigned to the contralateral side. A sauna suit induced sweating during three 30-min heat intervals: (1) with no study agents (pre); (2) with both study agents, one on each side; and (3) after the agents were washed off (post). Sweat levels were measured by securing Whatman(®) filter paper to each axilla and measuring the paper weight after each heat interval. The difference in paper weight following each heat interval between Study Agent A and Study Agent B was measured by a gravimetric scale. Topical agent A had a significantly greater effect at reducing axillary sweating than B (P = 0.0002). In a sweating simulation, 20% aluminum chloride hexahydrate quantitatively and objectively appeared to reduce sweat more effectively than 1% aluminum acetate. © 2015 Wiley Periodicals, Inc.

Method for distinguishing normal and transformed cells using G1 kinase inhibitors

DOEpatents

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

1993-01-01

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

Method for distinguishing normal and transformed cells using G1 kinase inhibitors

DOEpatents

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

1993-02-09

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

Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention.

PubMed

Hayes, Spencer J; Andrew, Matthew; Elliott, Digby; Gowen, Emma; Bennett, Simon J

2016-02-01

We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only neurotypical adults imitated atypical biological kinematics. Adults with autism did, however, become significantly more accurate at imitating movement time. This confirmed they engaged in the task, and that sensorimotor adaptation was self-regulated. The attentional bias to movement time suggests the attenuation in imitating kinematics might be a compensatory strategy due to deficits in lower-level visuomotor processes associated with self-other mapping, or selective attention modulated the processes that represent biological kinematics.

Discovery of ((4R,5S)-5-amino-4-(2,4,5- trifluorophenyl)cyclohex-1-enyl)-(3- (trifluoromethyl)-5,6-dihydro- [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a highly potent, selective, orally efficacious, and safe dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

PubMed

Pei, Zhonghua; Li, Xiaofeng; von Geldern, Thomas W; Madar, David J; Longenecker, Kenton; Yong, Hong; Lubben, Thomas H; Stewart, Kent D; Zinker, Bradley A; Backes, Bradley J; Judd, Andrew S; Mulhern, Mathew; Ballaron, Stephen J; Stashko, Michael A; Mika, Amanda K; Beno, David W A; Reinhart, Glenn A; Fryer, Ryan M; Preusser, Lee C; Kempf-Grote, Anita J; Sham, Hing L; Trevillyan, James M

2006-11-02

Dipeptidyl peptidase IV (DPP4) deactivates glucose-regulating hormones such as GLP-1 and GIP, thus, DPP4 inhibition has become a useful therapy for type 2 diabetes. Optimization of the high-throughput screening lead 6 led to the discovery of 25 (ABT-341), a highly potent, selective, and orally bioavailable DPP4 inhibitor. When dosed orally, 25 dose-dependently reduced glucose excursion in ZDF rats. Amide 25 is safe in a battery of in vitro and in vivo tests and may represent a new therapeutic agent for the treatment of type 2 diabetes.

Development of an enzyme free glucose sensor based on copper oxide-graphene composite by using green reducing agent ascorbic acid

NASA Astrophysics Data System (ADS)

Palve, Yogesh Pandit; Jha, Neetu

2018-05-01

In this research work we have developed high sensitive and selective glucose sensor based on copper oxide-graphene composite which is prepared by green synthesis method and used for nonenzymatic glucose sensor. In present paper we report that present method highly selective, simple, efficient, accurate, ecofriendly, less toxic. The prepared composite were characterized by material characterization like SEM, XRD and also by electrochemical characterization like CV, chronoamperometry represents that copper oxide-graphene shows excellent electrocatalytic activity towards glucose, exhibiting a good sensitivity of 103.84 µA mM-1 cm-2, a fast response time 2s, a low detection limit 0.00033µM and linear range from 10 µM-3000 µM. The present sensor can successfully apply for determination of glucose concentration in human blood sample.

Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention.

PubMed

Leake, A; Ferrier, I N

1993-01-01

Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.

Novel treatment options for the management of heterozygous familial hypercholesterolemia.

PubMed

Polychronopoulos, Georgios; Tziomalos, Konstantinos

2017-12-01

Even though statins represent the mainstay of treatment of heterozygous familial hypercholesterolemia (FH), their low-density lipoprotein cholesterol (LDL-C) lowering efficacy is finite and most patients with FH will not achieve LDL-C targets with statin monotherapy. Addition of ezetimibe with or without bile acid sequestrants will also not lead to treatment goals in many of these patients, particularly in those with established cardiovascular disease. In this selected subgroup of the FH population, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide substantial reductions in LDL-C levels, reduce cardiovascular morbidity and appear to be safe. Mipomersen, an antisense single-strand oligonucleotide that inhibits the production of apoB by binding to the mRNA that encodes the synthesis of apoB, and lomitapide, an inhibitor of microsomal triglyceride transfer protein, also reduce LDL-C levels but are currently indicated only for the management of homozygous FH. Areas covered: In the present review, the role of PCSK9 inhibitors, mipomersen and lomitapide in the management of FH is briefly discussed. Other LDL-C-lowering agents under evaluation include inclisiran, a small interference RNA molecule that induces long-term inhibition of PSCK9 synthesis, anacetrapib, a cholesterol ester-transfer protein inhibitor, ETC-1002 (bempedoic acid), an inhibitor of adenosine triphosphate citrate lyase, and gemcabene, which reduces hepatic apolipoprotein C-III mRNA. The safety and efficacy of these agents are also reviewed. Expert Commentary: Even though several novel treatment options for heterozygous FH are under development, it remains to be shown whether these treatments will also reduce cardiovascular morbidity in these high-risk patients.