Targeting stemness is an effective strategy to control EML4-ALK+ non-small cell lung cancer cells

PubMed Central

Oh, Se Jin; Noh, Kyung Hee; Lee, Young-Ho; Hong, Soon-Oh; Song, Kwon-Ho; Lee, Hyo-Jung; Kim, Soyeon; Kim, Tae Min; Jeon, Ju-Hong; Seo, Jae Hong; Kim, Dong-Wan; Kim, Tae Woo

2015-01-01

The fusion between anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) is a causative factor in a unique subset of patients with non-small cell lung carcinoma (NSCLC). Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS. Cancer stem cell (CSC) theory provides a plausible explanation for acquisition of tumorigenesis and resistance. However, the question as to whether EML4-ALK-driven tumorigenesis is linked with the stem-like property and whether the stemness is an effective target in controlling EML4-ALK+ NSCLC including crizotinib-resistant NSCLC cells has not been addressed. Here, we report that stem-like properties stem from ALK activity in EML4-ALK+ NSCLC cells. Notably, treatment with rapamycin, a CSC targeting agent, attenuates stem-like phenotypes of the EML4-ALK+ cells, which increased capability of tumor formation and higher expression of stemness-associated molecules such as ALDH, NANOG, and OCT4. Importantly, combinational treatment with rapamycin and crizotinib leads to synergistic anti-tumor effects on EML4-ALK+ NSCLC cells as well as on those resistant to crizotinib. Thus, we provide a proof of principle that targeting stemness would be a novel strategy to control intractable EML4-ALK+ NSCLC. PMID:26517679

Targeting stemness is an effective strategy to control EML4-ALK+ non-small cell lung cancer cells.

PubMed

Oh, Se Jin; Noh, Kyung Hee; Lee, Young-Ho; Hong, Soon-Oh; Song, Kwon-Ho; Lee, Hyo-Jung; Kim, Soyeon; Kim, Tae Min; Jeon, Ju-Hong; Seo, Jae Hong; Kim, Dong-Wan; Kim, Tae Woo

2015-11-24

The fusion between anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) is a causative factor in a unique subset of patients with non-small cell lung carcinoma (NSCLC). Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS. Cancer stem cell (CSC) theory provides a plausible explanation for acquisition of tumorigenesis and resistance. However, the question as to whether EML4-ALK-driven tumorigenesis is linked with the stem-like property and whether the stemness is an effective target in controlling EML4-ALK+ NSCLC including crizotinib-resistant NSCLC cells has not been addressed. Here, we report that stem-like properties stem from ALK activity in EML4-ALK+ NSCLC cells. Notably, treatment with rapamycin, a CSC targeting agent, attenuates stem-like phenotypes of the EML4-ALK+ cells, which increased capability of tumor formation and higher expression of stemness-associated molecules such as ALDH, NANOG, and OCT4. Importantly, combinational treatment with rapamycin and crizotinib leads to synergistic anti-tumor effects on EML4-ALK+ NSCLC cells as well as on those resistant to crizotinib. Thus, we provide a proof of principle that targeting stemness would be a novel strategy to control intractable EML4-ALK+ NSCLC.

Are national targets the right way to improve infection control practice?

PubMed

Millar, M

2009-12-01

The 'right way to improve infection control practice' should be cost-effective and lead to a fair distribution of infection control resources. Cost-effectiveness is a measure of aggregate 'good', and fairness emphasises similar treatment for individuals under similar circumstances. The UK national meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) target encourages National Health Service trusts to prioritise strategies aimed at MRSA BSI prevention. Under resource-limited conditions, the MRSA BSI target inevitably encourages deprioritisation of patients at risk of non-target healthcare-associated infection (HCAI), some of which are associated with an equal or larger burden of adverse outcome. Established healthcare improvement strategies, such as the Plan, Do, Study, Act (PDSA) cycle advocated by the Health Foundation, require the setting of aims (or targets). If we are to improve infection control practice then we need to decide on what to measure, how to measure it, and what the improvement (target) should be. In selecting targets for infection prevention, account should be taken of the contribution of HCAI to adverse health outcomes overall. Human risk compensation behaviour and microbial adaptation may both counteract the overall benefit of infection targets isolated from overall outcomes. Risk taking is part of a healthy healthcare system. We must be careful not to isolate HCAI outcomes from overall outcomes or to isolate 'risk takers' from 'risk controllers'. We must try to limit the scope for human risk compensation and we must watch out for microbial adaptation. Targets should be set locally, taking account of fairness and cost-effectiveness. Locally relevant information is key; positive incentives work best.

Mass Media Strategies Targeting High Sensation Seekers: What Works and Why

ERIC Educational Resources Information Center

Stephenson, Michael T.

2003-01-01

Objectives: To examine strategies for using the mass media effectively in drug prevention campaigns targeting high sensation seekers. Methods: Both experimental lab and field studies were used to develop a comprehensive audience segmentation strategy targeting high sensation seekers. Results: A 4-pronged targeting strategy employed in an…

Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages.

PubMed

Qian, Yuan; Qiao, Sha; Dai, Yanfeng; Xu, Guoqiang; Dai, Bolei; Lu, Lisen; Yu, Xiang; Luo, Qingming; Zhang, Zhihong

2017-09-26

Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8 + T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8 + T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

Intercepting a moving target: On-line or model-based control?

PubMed

Zhao, Huaiyong; Warren, William H

2017-05-01

When walking to intercept a moving target, people take an interception path that appears to anticipate the target's trajectory. According to the constant bearing strategy, the observer holds the bearing direction of the target constant based on current visual information, consistent with on-line control. Alternatively, the interception path might be based on an internal model of the target's motion, known as model-based control. To investigate these two accounts, participants walked to intercept a moving target in a virtual environment. We degraded the target's visibility by blurring the target to varying degrees in the midst of a trial, in order to influence its perceived speed and position. Reduced levels of visibility progressively impaired interception accuracy and precision; total occlusion impaired performance most and yielded nonadaptive heading adjustments. Thus, performance strongly depended on current visual information and deteriorated qualitatively when it was withdrawn. The results imply that locomotor interception is normally guided by current information rather than an internal model of target motion, consistent with on-line control.

Target marketing strategies for occupational therapy entrepreneurs.

PubMed

Kautzmann, L N; Kautzmann, F N; Navarro, F H

1989-01-01

Understanding marketing techniques is one of the skills needed by successful entre renews. Target marketing is an effective method for occupational therapy entrepreneurs to use in determining when and where to enter the marketplace. The two components of target marketing, market segmentation and the development of marketing mix strategies for each identified market segment, are described. The Profife of Attitudes Toward Health Care (PATH) method of psychographic market segmentation of health care consumers is presented. Occupational therapy marketing mix strategies for each PATH consumer group are delineated and compatible groupings of market segments are suggested.

Target Control in Logical Models Using the Domain of Influence of Nodes.

PubMed

Yang, Gang; Gómez Tejeda Zañudo, Jorge; Albert, Réka

2018-01-01

Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system's state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins, and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in Boolean network models of biomolecular networks. Specifically, we define the domain of influence (DOI) of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence (LDOI) of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose DOI can cover the desired target node states. We perform greedy randomized adaptive search in node state space to find such solutions. We apply our strategy to in silico biological network models of real systems to demonstrate its effectiveness.

Targeting microbial biofilms: current and prospective therapeutic strategies

PubMed Central

Koo, Hyun; Allan, Raymond N; Howlin, Robert P; Hall-Stoodley, Luanne; Stoodley, Paul

2017-01-01

Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections. The multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials, and indicates the need for multi-targeted or combinatorial therapies. In this review, we focus on current therapeutic strategies and those that are under development that target vital structural and functional traits of microbial biofilms and drug tolerance mechanisms, including the extracellular matrix and dormant cells. We emphasize strategies that are supported by in vivo or ex vivo studies, highlight emerging biofilm-targeting technologies, and provide a rationale for multi-targeted therapies that are aimed at disrupting the complex biofilm microenvironment. PMID:28944770

Proteolysis targeting peptide (PROTAP) strategy for protein ubiquitination and degradation.

PubMed

Zheng, Jing; Tan, Chunyan; Xue, Pengcheng; Cao, Jiakun; Liu, Feng; Tan, Ying; Jiang, Yuyang

2016-02-19

Ubiquitination proteasome pathway (UPP) is the most important and selective way to degrade proteins in vivo. Here, a novel proteolysis targeting peptide (PROTAP) strategy, composed of a target protein binding peptide, a linker and a ubiquitin E3 ligase recognition peptide, was designed to recruit both target protein and E3 ligase and then induce polyubiquitination and degradation of the target protein through UPP. In our study, the PROTAP strategy was proved to be a general method with high specificity using Bcl-xL protein as model target in vitro and in cells, which indicates that the strategy has great potential for in vivo application. Copyright © 2016 Elsevier Inc. All rights reserved.

Maneuver Analysis and Targeting Strategy for the Stardust Re-Entry Capsule

NASA Technical Reports Server (NTRS)

Helfrich, Cliff; Bhat, Ramachand S.; Kangas, Julie A.; Wilson, Roby S.; Wong, Mau C.; Potts, Christopher L.; Williams, Kenneth E.

2006-01-01

The Stardust Sample Return Capsule (SRC) returned to Earth on January 15, 2006 after seven years of collecting interstellar and comet particles over three heliocentric revolutions, as shown in Figure 1. The SRC was carried on board the Stardust spacecraft, as shown in Figure 2. Because the spacecraft was built with unbalanced thrusters, turns and attitude control maintenance resulted in undesirable delta-v being imparted to the trajectory. As a result, a carefully planned maneuver strategy was devised to accurately target the Stardust capsule to the Utah Test and Training Range (UTTR). This paper provides an overview of the Stardust spacecraft and mission and describes the maneuver strategy that was employed to achieve the stringent targeting requirements for landing in Utah. In addition, an overview of Stardust maneuver analysis tools and techniques will also be presented.

Prodrug strategy for cancer cell-specific targeting: A recent overview.

PubMed

Zhang, Xian; Li, Xiang; You, Qidong; Zhang, Xiaojin

2017-10-20

The increasing development of targeted cancer therapy provides extensive possibilities in clinical trials, and numerous strategies have been explored. The prodrug is one of the most promising strategies in targeted cancer therapy to improve the selectivity and efficacy of cytotoxic compounds. Compared with normal tissues, cancer cells are characterized by unique aberrant markers, thus inactive prodrugs targeting these markers are excellent therapeutics to release active drugs, killing cancer cells without damaging normal tissues. In this review, we explore an integrated view of potential prodrugs applied in targeted cancer therapy based on aberrant cancer specific markers and some examples are provided for inspiring new ideas of prodrug strategy for cancer cell-specific targeting. Copyright © 2017. Published by Elsevier Masson SAS.

Voyager 1 Saturn targeting strategy

NASA Technical Reports Server (NTRS)

Cesarone, R. J.

1980-01-01

A trajectory targeting strategy for the Voyager 1 Saturn encounter has been designed to accomodate predicted uncertainties in Titan's ephemeris while maximizing spacecraft safety and science return. The encounter is characterized by a close Titan flyby 18 hours prior to Saturn periapse. Retargeting of the nominal trajectory to account for late updates in Titan's estimated position can disperse the ascending node location, which is nominally situated at a radius of low expected particle density in Saturn's ring plane. The strategy utilizes a floating Titan impact vector magnitude to minimize this dispersion. Encounter trajectory characteristics and optimal tradeoffs are presented.

Nanomedicine Strategies to Target Tumor-Associated Macrophages

PubMed Central

Binnemars-Postma, Karin; Storm, Gert; Prakash, Jai

2017-01-01

In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail. PMID:28471401

[The development of novel tumor targeting delivery strategy].

PubMed

Gao, Hui-le; Jiang, Xin-guo

2016-02-01

Tumor is one of the most serious threats for human being. Although many anti-tumor drugs are approved for clinical use, the treatment outcome is still modest because of the poor tumor targeting efficiency and low accumulation in tumor. Therefore, it is important to deliver anti-tumor drug into tumor efficiently, elevate drug concentration in tumor tissues and reduce the drug distribution in normal tissues. And it has been one of the most attractive directions of pharmaceutical academy and industry. Many kinds of strategies, especially various nanoparticulated drug delivery systems, have been developed to address the critical points of complex tumor microenvironment, which are partially or mostly satisfied for tumor treatment. In this paper, we carefully reviewed the novel targeting delivery strategies developed in recent years. The most powerful method is passive targeting delivery based on the enhanced permeability and retention(EPR) effect, and most commercial nanomedicines are based on the EPR effect. However, the high permeability and retention require different particle sizes, thus several kinds of size-changeable nanoparticles are developed, such as size reducible particles and assemble particles, to satisfy the controversial requirement for particle size and enhance both tumor retention and penetration. Surface charge reversible nanoparticles also shows a high efficiency because the anionic charge in blood circulation and normal organs decrease the unintended internalization. The charge can change into positive in tumor microenvironment, facilitating drug uptake by tumor cells. Additionally, tumor microenvironment responsive drug release is important to decrease drug side effect, and many strategies are developed, such as p H sensitive release and enzyme sensitive release. Except the responsive nanoparticles, shaping tumor microenvironment could attenuate the barriers in drug delivery, for example, decreasing tumor collagen intensity and normalizing tumor

Control of Maillard Reactions in Foods: Strategies and Chemical Mechanisms.

PubMed

Lund, Marianne N; Ray, Colin A

2017-06-14

Maillard reactions lead to changes in food color, organoleptic properties, protein functionality, and protein digestibility. Numerous different strategies for controlling Maillard reactions in foods have been attempted during the past decades. In this paper, recent advances in strategies for controlling the Maillard reaction and subsequent downstream reaction products in food systems are critically reviewed. The underlying mechanisms at play are presented, strengths and weaknesses of each strategy are discussed, and reasonable reaction mechanisms are proposed to reinforce the evaluations. The review includes strategies involving addition of functional ingredients, such as plant polyphenols and vitamins, as well as enzymes. The resulting trapping or modification of Maillard targets, reactive intermediates, and advanced glycation endproducts (AGEs) are presented with their potential unwanted side effects. Finally, recent advances in processing for control of Maillard reactions are discussed.

A Novel Energy-Efficient Multi-Sensor Fusion Wake-Up Control Strategy Based on a Biomimetic Infectious-Immune Mechanism for Target Tracking.

PubMed

Zhou, Jie; Liang, Yan; Shen, Qiang; Feng, Xiaoxue; Pan, Quan

2018-04-18

A biomimetic distributed infection-immunity model (BDIIM), inspired by the immune mechanism of an infected organism, is proposed in order to achieve a high-efficiency wake-up control strategy based on multi-sensor fusion for target tracking. The resultant BDIIM consists of six sub-processes reflecting the infection-immunity mechanism: occurrence probabilities of direct-infection (DI) and cross-infection (CI), immunity/immune-deficiency of DI and CI, pathogen amount of DI and CI, immune cell production, immune memory, and pathogen accumulation under immunity state. Furthermore, a corresponding relationship between the BDIIM and sensor wake-up control is established to form the collaborative wake-up method. Finally, joint surveillance and target tracking are formulated in the simulation, in which we show that the energy cost and position tracking error are reduced to 50.8% and 78.9%, respectively. Effectiveness of the proposed BDIIM algorithm is shown, and this model is expected to have a significant role in guiding the performance improvement of multi-sensor networks.

Near-Nash targeting strategies for heterogeneous teams of autonomous combat vehicles

NASA Astrophysics Data System (ADS)

Galati, David G.; Simaan, Marwan A.

2008-04-01

Military strategists are currently seeking methodologies to control large numbers of autonomous assets. Automated planners based upon the Nash equilibrium concept in non-zero sum games are one option. Because such planners inherently consider possible adversarial actions, assets are able to adapt to, and to some extent predict, potential enemy actions. However, these planners must function properly both in cases in which a pure Nash strategy does not exist and in scenarios possessing multiple Nash equilibria. Another issue that needs to be overcome is the scalability of the Nash equilibrium. That is, as the dimensionality of the problem increases, the Nash strategies become unfeasible to compute using traditional methodologies. In this paper we introduce the concept of near-Nash strategies as a mechanism to overcome these difficulties. We then illustrate this concept by deriving the near-Nash strategies and using these strategies as the basis for an intelligent battle plan for heterogeneous teams of autonomous combat air vehicles in the Multi-Team Dynamic Weapon Target Assignment model.

Engineering tolerance using biomaterials to target and control antigen presenting cells.

PubMed

Tostanoski, Lisa H; Gosselin, Emily A; Jewell, Christopher M

2016-05-01

Autoimmune diseases occur when cells of the adaptive immune system incorrectly recognize and attack "self" tissues. Importantly, the proliferation and differentiation of these cells is triggered and controlled by interactions with antigen presenting cells (APCs), such as dendritic cells. Thus, modulating the signals transduced by APCs (e.g., cytokines, costimulatory surface proteins) has emerged as a promising strategy to promote tolerance for diseases such as multiple sclerosis, type 1 diabetes, and lupus. However, many approaches have been hindered by non-specific activity of immunosuppressive or immunoregulatory cues, following systemic administration of soluble factors via traditional injections routes (e.g., subcutaneous, intravenous). Biomaterials offer a unique opportunity to control the delivery of tolerogenic signals in vivo via properties such as controlled particle size, tunable release kinetics, and co-delivery of multiple classes of cargo. In this review, we highlight recent reports that exploit these properties of biomaterials to target APCs and promote tolerance via three strategies, i) passive or active targeting of particulate carriers to APCs, ii) biomaterial-mediated control over antigen localization and processing, and iii) targeted delivery of encapsulated or adsorbed immunomodulatory signals. These reports represent exciting advances toward the goal of more effective therapies for autoimmune diseases, without the broad suppressive effects associated with current clinically-approved therapies.

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.

PubMed

Lo, Nathan C; Gurarie, David; Yoon, Nara; Coulibaly, Jean T; Bendavid, Eran; Andrews, Jason R; King, Charles H

2018-01-23

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA. Copyright © 2018 the Author(s). Published by PNAS.

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis

PubMed Central

Yoon, Nara; Coulibaly, Jean T.; Bendavid, Eran; Andrews, Jason R.; King, Charles H.

2018-01-01

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5–20%) and high-prevalence (25–50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, “hot spots” of transmission, and noncompliance to MDA. PMID:29301964

Target discrimination strategies in optics detection

NASA Astrophysics Data System (ADS)

Sjöqvist, Lars; Allard, Lars; Henriksson, Markus; Jonsson, Per; Pettersson, Magnus

2013-10-01

Detection and localisation of optical assemblies used for weapon guidance or sniper rifle scopes has attracted interest for security and military applications. Typically a laser system is used to interrogate a scene of interest and the retro-reflected radiation is detected. Different system approaches for area coverage can be realised ranging from flood illumination to step-and-stare or continuous scanning schemes. Independently of the chosen approach target discrimination is a crucial issue, particularly if a complex scene such as in an urban environment and autonomous operation is considered. In this work target discrimination strategies in optics detection are discussed. Typical parameters affecting the reflected laser radiation from the target are the wavelength, polarisation properties, temporal effects and the range resolution. Knowledge about the target characteristics is important to predict the target discrimination capability. Two different systems were used to investigate polarisation properties and range resolution information from targets including e.g. road signs, optical reflexes, rifle sights and optical references. The experimental results and implications on target discrimination will be discussed. If autonomous operation is required target discrimination becomes critical in order to reduce the number of false alarms.

A Convenient Cas9-based Conditional Knockout Strategy for Simultaneously Targeting Multiple Genes in Mouse.

PubMed

Chen, Jiang; Du, Yinan; He, Xueyan; Huang, Xingxu; Shi, Yun S

2017-03-31

The most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.

Identification of control targets in Boolean molecular network models via computational algebra.

PubMed

Murrugarra, David; Veliz-Cuba, Alan; Aguilar, Boris; Laubenbacher, Reinhard

2016-09-23

Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network. Supplementary data is available online and our code in Macaulay2 and Matlab are available via http://www.ms.uky.edu/~dmu228/ControlAlg . This paper presents a novel method for the identification of intervention targets in Boolean network models. The results in this paper show that the proposed methods are useful and efficient for moderately large networks.

Do biological-based strategies hold promise to biofouling control in MBRs?

PubMed

Malaeb, Lilian; Le-Clech, Pierre; Vrouwenvelder, Johannes S; Ayoub, George M; Saikaly, Pascal E

2013-10-01

Biofouling in membrane bioreactors (MBRs) remains a primary challenge for their wider application, despite the growing acceptance of MBRs worldwide. Research studies on membrane fouling are extensive in the literature, with more than 200 publications on MBR fouling in the last 3 years; yet, improvements in practice on biofouling control and management have been remarkably slow. Commonly applied cleaning methods are only partially effective and membrane replacement often becomes frequent. The reason for the slow advancement in successful control of biofouling is largely attributed to the complex interactions of involved biological compounds and the lack of representative-for-practice experimental approaches to evaluate potential effective control strategies. Biofouling is driven by microorganisms and their associated extra-cellular polymeric substances (EPS) and microbial products. Microorganisms and their products convene together to form matrices that are commonly treated as a black box in conventional control approaches. Biological-based antifouling strategies seem to be a promising constituent of an effective integrated control approach since they target the essence of biofouling problems. However, biological-based strategies are in their developmental phase and several questions should be addressed to set a roadmap for translating existing and new information into sustainable and effective control techniques. This paper investigates membrane biofouling in MBRs from the microbiological perspective to evaluate the potential of biological-based strategies in offering viable control alternatives. Limitations of available control methods highlight the importance of an integrated anti-fouling approach including biological strategies. Successful development of these strategies requires detailed characterization of microorganisms and EPS through the proper selection of analytical tools and assembly of results. Existing microbiological/EPS studies reveal a number of

Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor.

PubMed

Yoon, Hong Yeol; Shin, Min Lee; Shim, Man Kyu; Lee, Sangmin; Na, Jin Hee; Koo, Heebeom; Lee, Hyukjin; Kim, Jong-Ho; Lee, Kuen Yong; Kim, Kwangmeyung; Kwon, Ick Chan

2017-05-01

Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-CNPs) and integrin α v β 3 with cyclic RGD-conjugated CNPs (cRGD-CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN-CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD-CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN-CNPs could bind artificial azide reporters on tumor cells more uniformly (∼92.9%) compared to cRGD-CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy.

RNA interference: a new strategy in the evolutionary arms race between human control strategies and insect pests.

PubMed

Machado, Vilmar; Rodríguez-García, María Juliana; Sánchez-García, Francisco Javier; Galan, Jose

2014-01-01

The relationship between humans and the insect pests of cultivated plants may be considered to be an indirect coevolutionary process, i.e., an arms race. Over time, humans have developed several strategies to minimize the negative impacts of insects on agricultural production. However, insects have made adaptive responses via the evolution of resistance to insecticides, and more recently against Bacillus thuriengiensis. Thus, we need to continuously invest resources in the development of new strategies for crop protection. Recent advances in genomics have demonstrated the possibility of a new weapon or strategy in this war, i.e., gene silencing, which involves blocking the expression of specific genes via mRNA inactivation. In the last decade, several studies have demonstrated the effectiveness of this strategy in the control of different species of insects. However, several technical difficulties need to be overcome to transform this potential into reality, such as the selection of target genes, the concentration of dsRNA, the nucleotide sequence of the dsRNA, the length of dsRNA, persistence in the insect body, and the life stage of the target species where gene silencing is most efficient. This study analyzes several aspects related to the use of gene silencing in pest control and it includes an overview of the inactivation process, as well as the problems that need to be resolved to transform gene silencing into an effective pest control method.

Neuromuscular mechanisms and neural strategies in the control of time-varying muscle contractions.

PubMed

Erimaki, Sophia; Agapaki, Orsalia M; Christakos, Constantinos N

2013-09-01

The organization of the neural input to motoneurons that underlies time-varying muscle force is assumed to depend on muscle transfer characteristics and neural strategies or control modes utilizing sensory signals. We jointly addressed these interlinked, but previously studied individually and partially, issues for sinusoidal (range 0.5-5.0 Hz) force-tracking contractions of a human finger muscle. Using spectral and correlation analyses of target signal, force signal, and motor unit (MU) discharges, we studied 1) patterns of such discharges, allowing inferences on the motoneuronal input; 2) transformation of MU population activity (EMG) into quasi-sinusoidal force; and 3) relation of force oscillation to target, carrying information on the input's organization. A broad view of force control mechanisms and strategies emerged. Specifically, synchronized MU and EMG modulations, reflecting a frequency-modulated motoneuronal input, accompanied the force variations. Gain and delay drops between EMG modulation and force oscillation, critical for the appropriate organization of this input, occurred with increasing target frequency. According to our analyses, gain compensation was achieved primarily through rhythmical activation/deactivation of higher-threshold MUs and secondarily through the adaptation of the input's strength expected during tracking tasks. However, the input's timing was not adapted to delay behaviors and seemed to depend on the control modes employed. Thus, for low-frequency targets, the force oscillation was highly coherent with, but led, a target, this timing error being compatible with predictive feedforward control partly based on the target's derivatives. In contrast, the force oscillation was weakly coherent, but in phase, with high-frequency targets, suggesting control mainly based on a target's rhythm.

Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

PubMed

Arrue, Lily; Ratjen, Lars

2017-12-07

The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

PubMed

Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

2014-11-21

In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

Systematic Assessment of Strategies for Lung-targeted Delivery of MicroRNA Mimics

PubMed Central

Schlosser, Kenny; Taha, Mohamad; Stewart, Duncan J.

2018-01-01

There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A). Intravenous (IV; via jugular vein), intraperitoneal (IP) and subcutaneous (SC) delivery served as controls. Relative levels of cel-miR-39 were quantified by RT-qPCR. Results: At 2 h post delivery, IT-L showed the highest lung mimic level, which was significantly higher than levels achieved by all other methods (from ~10- to 10,000-fold, p<0.05). Mimic levels remained detectable in the lung 24 h after delivery, but were 10- to 100-fold lower. The intrapulmonary distribution of cel-miR-39 was comparable when delivered as either a liquid or aerosol, with evidence of mimic distribution to both the left and right lung lobes and penetration to distal regions. All lung-targeted strategies showed lung-selective mimic uptake, with mimic levels 10- to 100-fold lower in heart and 100- to 10,000-fold lower in liver, kidney and spleen. In contrast, IV, SC and IP routes showed comparable or higher mimic levels in non-pulmonary tissues. Conclusions: miRNA uptake in the lungs differed markedly by up to 4 orders of magnitude, demonstrating that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of mi

Drug-targeting strategies in cancer therapy.

PubMed

Huang, P S; Oliff, A

2001-02-01

Genetic changes in cell-cycle, apoptotic, and survival pathways cause tumorigenesis, leading to significant phenotypic changes in transformed cells. These changes in the tumor environment - elevated expression of surface proteases, increased angiogenesis and glucuronidase activity - can be taken advantage of to improve the therapeutic index of existing cancer therapies. Targeting cytotoxics to tumor cells by enzymatic activation is a promising strategy for improving chemotherapeutics.

Considerations for biomarker-targeted intervention strategies for tuberculosis disease prevention.

PubMed

Fiore-Gartland, Andrew; Carpp, Lindsay N; Naidoo, Kogieleum; Thompson, Ethan; Zak, Daniel E; Self, Steve; Churchyard, Gavin; Walzl, Gerhard; Penn-Nicholson, Adam; Scriba, Thomas J; Hatherill, Mark

2018-03-01

Current diagnostic tests for Mycobacterium tuberculosis (MTB) infection have low prognostic specificity for identifying individuals who will develop tuberculosis (TB) disease, making mass preventive therapy strategies targeting all MTB-infected individuals impractical in high-burden TB countries. Here we discuss general considerations for a risk-targeted test-and-treat strategy based on a highly specific transcriptomic biomarker that can identify individuals who are most likely to progress to active TB disease as well as individuals with TB disease who have not yet presented for medical care. Such risk-targeted strategies may offer a rapid, ethical and cost-effective path towards decreasing the burden of TB disease and interrupting transmission and would also be critical to achieving TB elimination in countries nearing elimination. We also discuss design considerations for a Correlate of Risk Targeted Intervention Study (CORTIS), which could provide proof-of-concept for the strategy. One such study in South Africa is currently enrolling 1500 high-risk and 1700 low-risk individuals, as defined by biomarker status, and is randomizing high-risk participants to TB preventive therapy or standard of care treatment. All participants are monitored for progression to active TB with primary objectives to assess efficacy of the treatment and performance of the biomarker. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Improved targeted immunization strategies based on two rounds of selection

NASA Astrophysics Data System (ADS)

Xia, Ling-Ling; Song, Yu-Rong; Li, Chan-Chan; Jiang, Guo-Ping

2018-04-01

In the case of high degree targeted immunization where the number of vaccine is limited, when more than one node associated with the same degree meets the requirement of high degree centrality, how can we choose a certain number of nodes from those nodes, so that the number of immunized nodes will not exceed the limit? In this paper, we introduce a new idea derived from the selection process of second-round exam to solve this problem and then propose three improved targeted immunization strategies. In these proposed strategies, the immunized nodes are selected through two rounds of selection, where we increase the quotas of first-round selection according the evaluation criterion of degree centrality and then consider another characteristic parameter of node, such as node's clustering coefficient, betweenness and closeness, to help choose targeted nodes in the second-round selection. To validate the effectiveness of the proposed strategies, we compare them with the degree immunizations including the high degree targeted and the high degree adaptive immunizations using two metrics: the size of the largest connected component of immunized network and the number of infected nodes. Simulation results demonstrate that the proposed strategies based on two rounds of sorting are effective for heterogeneous networks and their immunization effects are better than that of the degree immunizations.

Comparison of smallpox outbreak control strategies using a spatial metapopulation model.

PubMed

Hall, I M; Egan, J R; Barrass, I; Gani, R; Leach, S

2007-10-01

To determine the potential benefits of regionally targeted mass vaccination as an adjunct to other smallpox control strategies we employed a spatial metapopulation patch model based on the administrative districts of Great Britain. We counted deaths due to smallpox and to vaccination to identify strategies that minimized total deaths. Results confirm that case isolation, and the tracing, vaccination and observation of case contacts can be optimal for control but only for optimistic assumptions concerning, for example, the basic reproduction number for smallpox (R0=3) and smaller numbers of index cases ( approximately 10). For a wider range of scenarios, including larger numbers of index cases and higher reproduction numbers, the addition of mass vaccination targeted only to infected districts provided an appreciable benefit (5-80% fewer deaths depending on where the outbreak started with a trigger value of 1-10 isolated symptomatic individuals within a district).

Evaluating Internal Model Strength and Performance of Myoelectric Prosthesis Control Strategies.

PubMed

Shehata, Ahmed W; Scheme, Erik J; Sensinger, Jonathon W

2018-05-01

On-going developments in myoelectric prosthesis control have provided prosthesis users with an assortment of control strategies that vary in reliability and performance. Many studies have focused on improving performance by providing feedback to the user but have overlooked the effect of this feedback on internal model development, which is key to improve long-term performance. In this paper, the strength of internal models developed for two commonly used myoelectric control strategies: raw control with raw feedback (using a regression-based approach) and filtered control with filtered feedback (using a classifier-based approach), were evaluated using two psychometric measures: trial-by-trial adaptation and just-noticeable difference. The performance of both strategies was also evaluated using Schmidt's style target acquisition task. Results obtained from 24 able-bodied subjects showed that although filtered control with filtered feedback had better short-term performance in path efficiency ( ), raw control with raw feedback resulted in stronger internal model development ( ), which may lead to better long-term performance. Despite inherent noise in the control signals of the regression controller, these findings suggest that rich feedback associated with regression control may be used to improve human understanding of the myoelectric control system.

Anti-tumour strategies aiming to target tumour-associated macrophages

PubMed Central

Tang, Xiaoqiang; Mo, Chunfen; Wang, Yongsheng; Wei, Dandan; Xiao, Hengyi

2013-01-01

Tumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy. PMID:23113570

Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

PubMed Central

Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

2012-01-01

Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

Sensory-Targeted Ankle Rehabilitation Strategies for Chronic Ankle Instability.

PubMed

McKeon, Patrick O; Wikstrom, Erik A

2016-05-01

Deficient sensory input from damaged ankle ligament receptors is thought to contribute to sensorimotor deficits in those with chronic ankle instability (CAI). Targeting other viable sensory receptors may then enhance sensorimotor control in these patients. The purpose of this randomized controlled trial was to evaluate the effects of 2 wk of sensory-targeted ankle rehabilitation strategies (STARS) on patient- and clinician-oriented outcomes in those with CAI. Eighty patients with self-reported CAI participated. All patients completed patient-oriented questionnaires capturing self-reported function as well as the weight-bearing lunge test and an eyes-closed single-limb balance test. After baseline testing, patients were randomly allocated to four STARS groups: joint mobilization, plantar massage, triceps surae stretching, or control. Each patient in the intervention groups received six 5-min treatments of their respective STARS over 2 wk. All subjects were reassessed on patient- and clinician-oriented measures immediately after the intervention and completed a 1-month follow-up that consisted of patient-oriented measures. Change scores of the three STARS groups were compared with the control using independent t-tests and Hedges' g effect sizes with 95% confidence intervals. The joint mobilization group had the greatest weight-bearing lunge test improvement. Plantar massage had the most meaningful single-limb balance improvement. All STARS groups improved patient-oriented outcomes with joint mobilization having the most meaningful effect immediately after the intervention and plantar massage at the 1-month follow-up. Each STARS treatment offers unique contributions to the patient- and clinician-oriented rehabilitation outcomes of those with CAI. Both joint mobilization and plantar massage appear to demonstrate the greatest potential to improve sensorimotor function in those with CAI.

Drug Target Interference in Immunogenicity Assays: Recommendations and Mitigation Strategies.

PubMed

Zhong, Zhandong Don; Clements-Egan, Adrienne; Gorovits, Boris; Maia, Mauricio; Sumner, Giane; Theobald, Valerie; Wu, Yuling; Rajadhyaksha, Manoj

2017-11-01

Sensitive and specific methodology is required for the detection and characterization of anti-drug antibodies (ADAs). High-quality ADA data enables the evaluation of potential impact of ADAs on the drug pharmacokinetic profile, patient safety, and efficacious response to the drug. Immunogenicity assessments are typically initiated at early stages in preclinical studies and continue throughout the drug development program. One of the potential bioanalytical challenges encountered with ADA testing is the need to identify and mitigate the interference mediated by the presence of soluble drug target. A drug target, when present at sufficiently high circulating concentrations, can potentially interfere with the performance of ADA and neutralizing antibody (NAb) assays, leading to either false-positive or, in some cases, false-negative ADA and NAb assay results. This publication describes various mechanisms of assay interference by soluble drug target, as well as strategies to recognize and mitigate such target interference. Pertinent examples are presented to illustrate the impact of target interference on ADA and NAb assays as well as several mitigation strategies, including the use of anti-target antibodies, soluble versions of the receptors, target-binding proteins, lectins, and solid-phase removal of targets. Furthermore, recommendations for detection and mitigation of such interference in different formats of ADA and NAb assays are provided.

Active control strategy for the running attitude of high-speed train under strong crosswind condition

NASA Astrophysics Data System (ADS)

Li, Decang; Meng, Jianjun; Bai, Huan; Xu, Ruxun

2018-07-01

This paper focuses on the safety of high-speed trains under strong crosswind conditions. A new active control strategy is proposed based on the adaptive predictive control theory. The new control strategy aims at adjusting the attitudes of a train by controlling the new-type intelligent giant magnetostrictive actuator (GMA). It combined adaptive control with dynamic matrix control; parameters of predictive controller was real-time adjusted by online distinguishing to enhance the robustness of the control algorithm. On this basis, a correction control algorithm is also designed to regulate the parameters of predictive controller based on the step response of a controlled objective. Finally, the simulation results show that the proposed control strategy can adjust the running attitudes of high-speed trains under strong crosswind conditions; they also indicate that the new active control strategy is effective and applicable in improving the safety performance of a train based on a host-target computer technology provided by Matlab/Simulink.

Identification of the feedforward component in manual control with predictable target signals.

PubMed

Drop, Frank M; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus M; Mulder, Max

2013-12-01

In the manual control of a dynamic system, the human controller (HC) often follows a visible and predictable reference path. Compared with a purely feedback control strategy, performance can be improved by making use of this knowledge of the reference. The operator could effectively introduce feedforward control in conjunction with a feedback path to compensate for errors, as hypothesized in literature. However, feedforward behavior has never been identified from experimental data, nor have the hypothesized models been validated. This paper investigates human control behavior in pursuit tracking of a predictable reference signal while being perturbed by a quasi-random multisine disturbance signal. An experiment was done in which the relative strength of the target and disturbance signals were systematically varied. The anticipated changes in control behavior were studied by means of an ARX model analysis and by fitting three parametric HC models: two different feedback models and a combined feedforward and feedback model. The ARX analysis shows that the experiment participants employed control action on both the error and the target signal. The control action on the target was similar to the inverse of the system dynamics. Model fits show that this behavior can be modeled best by the combined feedforward and feedback model.

Constrained target controllability of complex networks

NASA Astrophysics Data System (ADS)

Guo, Wei-Feng; Zhang, Shao-Wu; Wei, Ze-Gang; Zeng, Tao; Liu, Fei; Zhang, Jingsong; Wu, Fang-Xiang; Chen, Luonan

2017-06-01

It is of great theoretical interest and practical significance to study how to control a system by applying perturbations to only a few driver nodes. Recently, a hot topic of modern network researches is how to determine driver nodes that allow the control of an entire network. However, in practice, to control a complex network, especially a biological network, one may know not only the set of nodes which need to be controlled (i.e. target nodes), but also the set of nodes to which only control signals can be applied (i.e. constrained control nodes). Compared to the general concept of controllability, we introduce the concept of constrained target controllability (CTC) of complex networks, which concerns the ability to drive any state of target nodes to their desirable state by applying control signals to the driver nodes from the set of constrained control nodes. To efficiently investigate the CTC of complex networks, we further design a novel graph-theoretic algorithm called CTCA to estimate the ability of a given network to control targets by choosing driver nodes from the set of constrained control nodes. We extensively evaluate the CTC of numerous real complex networks. The results indicate that biological networks with a higher average degree are easier to control than biological networks with a lower average degree, while electronic networks with a lower average degree are easier to control than web networks with a higher average degree. We also show that our CTCA can more efficiently produce driver nodes for target-controlling the networks than existing state-of-the-art methods. Moreover, we use our CTCA to analyze two expert-curated bio-molecular networks and compare to other state-of-the-art methods. The results illustrate that our CTCA can efficiently identify proven drug targets and new potentials, according to the constrained controllability of those biological networks.

Stakeholder analysis and mapping as targeted communication strategy.

PubMed

Shirey, Maria R

2012-09-01

This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. With the goal of presenting practical approaches helpful to nurse leaders advancing organizational change, content includes evidence-based projects, tools, and resources that mobilize and sustain organizational change initiatives. In this article, the author highlights the importance of stakeholder theory and discusses how to apply the theory to conduct a stakeholder analysis. This article also provides an explanation of how to use related stakeholder mapping techniques with targeted communication strategies.

Mixed-Strategy Chance Constrained Optimal Control

NASA Technical Reports Server (NTRS)

Ono, Masahiro; Kuwata, Yoshiaki; Balaram, J.

2013-01-01

This paper presents a novel chance constrained optimal control (CCOC) algorithm that chooses a control action probabilistically. A CCOC problem is to find a control input that minimizes the expected cost while guaranteeing that the probability of violating a set of constraints is below a user-specified threshold. We show that a probabilistic control approach, which we refer to as a mixed control strategy, enables us to obtain a cost that is better than what deterministic control strategies can achieve when the CCOC problem is nonconvex. The resulting mixed-strategy CCOC problem turns out to be a convexification of the original nonconvex CCOC problem. Furthermore, we also show that a mixed control strategy only needs to "mix" up to two deterministic control actions in order to achieve optimality. Building upon an iterative dual optimization, the proposed algorithm quickly converges to the optimal mixed control strategy with a user-specified tolerance.

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

PubMed Central

Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde B; Uhlig, Till; Fremstad, Hallvard; Madland, Tor Magne; Lexberg, Åse Stavland; Haukeland, Hilde; Rødevand, Erik; Høili, Christian; Stray, Hilde; Noraas, Anne; Hansen, Inger Johanne Widding; Bakland, Gunnstein; Nordberg, Lena Bugge; van der Heijde, Désirée; Kvien, Tore K

2016-01-01

Objective To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the

Effects of Flood Control Strategies on Flood Resilience Under Sociohydrological Disturbances

NASA Astrophysics Data System (ADS)

Sung, Kyungmin; Jeong, Hanseok; Sangwan, Nikhil; Yu, David J.

2018-04-01

A community capacity to cope with flood hazards, or community flood resilience, emerges from the interplay of hydrological and social processes. This interplay can be significantly influenced by the flood control strategy adopted by a society, i.e., how a society sets its desired flood protection level and strives to achieve this goal. And this interplay can be further complicated by rising land-sea level differences, seasonal water level fluctuations, and economic change. But not much research has been done on how various forms of flood control strategies affect human-flood interactions under these disturbances and therefore flood resilience in the long run. The current study is an effort to address these issues by developing a conceptual model of human-flood interaction mediated by flood control strategies. Our model extends the existing model of Yu et al. (2017), who investigated the flood resilience of a community-based flood protection system in coastal Bangladesh. The major extensions made in this study are inclusions of various forms of flood control strategies (both adaptive and nonadaptive ones), the challenge of rising land-sea level differences, and various high tide level scenarios generated from modifying the statistical variances and averages. Our results show that adaptive forms of flood control strategies tend to outperform nonadaptive ones for maintaining the model community's flood protection system. Adaptive strategies that dynamically adjust target flood protection levels through close monitoring of flood damages and social memories of flood risk can help the model community deal with various disturbances.

A Prosthetic Hand Body Area Controller Based on Efficient Pattern Recognition Control Strategies.

PubMed

Benatti, Simone; Milosevic, Bojan; Farella, Elisabetta; Gruppioni, Emanuele; Benini, Luca

2017-04-15

Poliarticulated prosthetic hands represent a powerful tool to restore functionality and improve quality of life for upper limb amputees. Such devices offer, on the same wearable node, sensing and actuation capabilities, which are not equally supported by natural interaction and control strategies. The control in state-of-the-art solutions is still performed mainly through complex encoding of gestures in bursts of contractions of the residual forearm muscles, resulting in a non-intuitive Human-Machine Interface (HMI). Recent research efforts explore the use of myoelectric gesture recognition for innovative interaction solutions, however there persists a considerable gap between research evaluation and implementation into successful complete systems. In this paper, we present the design of a wearable prosthetic hand controller, based on intuitive gesture recognition and a custom control strategy. The wearable node directly actuates a poliarticulated hand and wirelessly interacts with a personal gateway (i.e., a smartphone) for the training and personalization of the recognition algorithm. Through the whole system development, we address the challenge of integrating an efficient embedded gesture classifier with a control strategy tailored for an intuitive interaction between the user and the prosthesis. We demonstrate that this combined approach outperforms systems based on mere pattern recognition, since they target the accuracy of a classification algorithm rather than the control of a gesture. The system was fully implemented, tested on healthy and amputee subjects and compared against benchmark repositories. The proposed approach achieves an error rate of 1.6% in the end-to-end real time control of commonly used hand gestures, while complying with the power and performance budget of a low-cost microcontroller.

A Prosthetic Hand Body Area Controller Based on Efficient Pattern Recognition Control Strategies

PubMed Central

Benatti, Simone; Milosevic, Bojan; Farella, Elisabetta; Gruppioni, Emanuele; Benini, Luca

2017-01-01

Poliarticulated prosthetic hands represent a powerful tool to restore functionality and improve quality of life for upper limb amputees. Such devices offer, on the same wearable node, sensing and actuation capabilities, which are not equally supported by natural interaction and control strategies. The control in state-of-the-art solutions is still performed mainly through complex encoding of gestures in bursts of contractions of the residual forearm muscles, resulting in a non-intuitive Human-Machine Interface (HMI). Recent research efforts explore the use of myoelectric gesture recognition for innovative interaction solutions, however there persists a considerable gap between research evaluation and implementation into successful complete systems. In this paper, we present the design of a wearable prosthetic hand controller, based on intuitive gesture recognition and a custom control strategy. The wearable node directly actuates a poliarticulated hand and wirelessly interacts with a personal gateway (i.e., a smartphone) for the training and personalization of the recognition algorithm. Through the whole system development, we address the challenge of integrating an efficient embedded gesture classifier with a control strategy tailored for an intuitive interaction between the user and the prosthesis. We demonstrate that this combined approach outperforms systems based on mere pattern recognition, since they target the accuracy of a classification algorithm rather than the control of a gesture. The system was fully implemented, tested on healthy and amputee subjects and compared against benchmark repositories. The proposed approach achieves an error rate of 1.6% in the end-to-end real time control of commonly used hand gestures, while complying with the power and performance budget of a low-cost microcontroller. PMID:28420135

A driver-adaptive stability control strategy for sport utility vehicles

NASA Astrophysics Data System (ADS)

Zhu, Shenjin; He, Yuping

2017-08-01

Conventional vehicle stability control (VSC) systems are designed for average drivers. For a driver with a good driving skill, the VSC systems may be redundant; for a driver with a poor driving skill, the VSC intervention may be inadequate. To increase safety of sport utility vehicles (SUVs), this paper proposes a novel driver-adaptive VSC (DAVSC) strategy based on scaling the target yaw rate commanded by the driver. The DAVSC system is adaptive to drivers' driving skills. More control effort would be exerted for drivers with poor driving skills, and vice versa. A sliding mode control (SMC)-based differential braking (DB) controller is designed using a three degrees of freedom (DOF) yaw-plane model. An eight DOF nonlinear yaw-roll model is used to simulate the SUV dynamics. Two driver models, namely longitudinal and lateral, are used to 'drive' the virtual SUV. By integrating the virtual SUV, the DB controller, and the driver models, the performance of the DAVSC system is investigated. The simulations demonstrate the effectiveness of the DAVSC strategy.

Heat shock proteins as potential targets for protective strategies in neurodegeneration.

PubMed

Kampinga, Harm H; Bergink, Steven

2016-06-01

Protein aggregates are hallmarks of nearly all age-related neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and several polyglutamine diseases such as Huntington's disease and different forms of spinocerebellar ataxias (SCA; SCA1-3, SCA6, and SCA7). The collapse of cellular protein homoeostasis can be both a cause and a consequence of this protein aggregation. Boosting components of the cellular protein quality control system has been widely investigated as a strategy to counteract protein aggregates or their toxic consequences. Heat shock proteins (HSPs) play a central part in regulating protein quality control and contribute to protein aggregation and disaggregation. Therefore, HSPs are viable targets for the development of drugs aimed at reducing pathogenic protein aggregates that are thought to contribute to the development of so many neurodegenerative disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeting male mosquito swarms to control malaria vector density

PubMed Central

Sawadogo, Simon Peguedwinde; Niang, Abdoulaye; Bilgo, Etienne; Millogo, Azize; Maïga, Hamidou; Dabire, Roch K.; Tripet, Frederic; Diabaté, Abdoulaye

2017-01-01

Malaria control programs are being jeopardized by the spread of insecticide resistance in mosquito vector populations. It has been estimated that the spread of resistance could lead to an additional 120000 deaths per year, and interfere with the prospects for sustained control or the feasibility of achieving malaria elimination. Another complication for the development of resistance management strategies is that, in addition to insecticide resistance, mosquito behavior evolves in a manner that diminishes the impact of LLINs and IRS. Mosquitoes may circumvent LLIN and IRS control through preferential feeding and resting outside human houses and/or being active earlier in the evening before people go to sleep. Recent developments in our understanding of mosquito swarming suggest that new tools targeting mosquito swarms can be designed to cut down the high reproductive rate of malaria vectors. Targeting swarms of major malaria vectors may provide an effective control method to counteract behavioral resistance developed by mosquitoes. Here, we evaluated the impact of systematic spraying of swarms of Anopheles gambiae s.l. using a mixed carbamate and pyrethroid aerosol. The impact of this intervention on vector density, female insemination rates and the age structure of males was measured. We showed that the resulting mass killing of swarming males and some mate-seeking females resulted in a dramatic 80% decrease in population size compared to a control population. A significant decrease in female insemination rate and a significant shift in the age structure of the male population towards younger males incapable of mating were observed. This paradigm-shift study therefore demonstrates that targeting primarily males rather than females, can have a drastic impact on mosquito population. PMID:28278212

Start-Stop Moment Optimization of Range Extender and Control Strategy Design for Extended -Range Electric Vehicle

NASA Astrophysics Data System (ADS)

Zhao, Jing-bo; Han, Bing-yuan; Bei, Shao-yi

2017-10-01

Range extender is the core component of E-REV, its start-stop control determines the operation modes of vehicle. This paper based on a certain type of E-REV, researched constant power control strategy of range extender in extended-range model, to target range as constraint condition, combined with different driving cycle conditions, by correcting battery SOC for range extender start-stop moment, optimized the control strategy of range extender, and established the vehicle and range extender start-stop control simulation model. Selected NEDC and UDDS conditions simulation results show that: under certain target mileage, the range extender running time reduced by 37.2% and 28.2% in the NEDC condition, and running time UDDS conditions were reduced by 40.6% and 33.5% in the UDDS condition, reached the purpose of meeting the vehicle mileage and reducing consumption and emission.

40 CFR 52.07 - Control strategies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategies. 52.07 Section 52.07... PROMULGATION OF IMPLEMENTATION PLANS General Provisions § 52.07 Control strategies. (a) Each subpart specifies in what respects the control strategies are approved or disapproved. Where emission limitations with...

40 CFR 52.07 - Control strategies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategies. 52.07 Section 52.07... PROMULGATION OF IMPLEMENTATION PLANS General Provisions § 52.07 Control strategies. (a) Each subpart specifies in what respects the control strategies are approved or disapproved. Where emission limitations with...

40 CFR 52.07 - Control strategies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategies. 52.07 Section 52.07... PROMULGATION OF IMPLEMENTATION PLANS General Provisions § 52.07 Control strategies. (a) Each subpart specifies in what respects the control strategies are approved or disapproved. Where emission limitations with...

40 CFR 52.07 - Control strategies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategies. 52.07 Section 52.07... PROMULGATION OF IMPLEMENTATION PLANS General Provisions § 52.07 Control strategies. (a) Each subpart specifies in what respects the control strategies are approved or disapproved. Where emission limitations with...

40 CFR 52.07 - Control strategies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategies. 52.07 Section 52.07... PROMULGATION OF IMPLEMENTATION PLANS General Provisions § 52.07 Control strategies. (a) Each subpart specifies in what respects the control strategies are approved or disapproved. Where emission limitations with...

Big brown bats (Eptesicus fuscus) reveal diverse strategies for sonar target tracking in clutter.

PubMed

Mao, Beatrice; Aytekin, Murat; Wilkinson, Gerald S; Moss, Cynthia F

2016-09-01

Bats actively adjust the acoustic features of their sonar calls to control echo information specific to a given task and environment. A previous study investigated how bats adapted their echolocation behavior when tracking a moving target in the presence of a stationary distracter at different distances and angular offsets. The use of only one distracter, however, left open the possibility that a bat could reduce the interference of the distracter by turning its head. Here, bats tracked a moving target in the presence of one or two symmetrically placed distracters to investigate adaptive echolocation behavior in a situation where vocalizing off-axis would result in increased interference from distracter echoes. Both bats reduced bandwidth and duration but increased sweep rate in more challenging distracter conditions, and surprisingly, made more head turns in the two-distracter condition compared to one, but only when distracters were placed at large angular offsets. However, for most variables examined, subjects showed distinct strategies to reduce clutter interference, either by (1) changing spectral or temporal features of their calls, or (2) producing large numbers of sonar sound groups and consistent head-turning behavior. The results suggest that individual bats can use different strategies for target tracking in cluttered environments.

Strategies for enhancing the implementation of school-based policies or practices targeting risk factors for chronic disease.

PubMed

Wolfenden, Luke; Nathan, Nicole K; Sutherland, Rachel; Yoong, Sze Lin; Hodder, Rebecca K; Wyse, Rebecca J; Delaney, Tessa; Grady, Alice; Fielding, Alison; Tzelepis, Flora; Clinton-McHarg, Tara; Parmenter, Benjamin; Butler, Peter; Wiggers, John; Bauman, Adrian; Milat, Andrew; Booth, Debbie; Williams, Christopher M

2017-11-29

consulted with experts in the field to identify other relevant research. 'Implementation' was defined as the use of strategies to adopt and integrate evidence-based health interventions and to change practice patterns within specific settings. We included any trial (randomised or non-randomised) conducted at any scale, with a parallel control group that compared a strategy to implement policies or practices to address diet, physical activity, overweight or obesity, tobacco or alcohol use by school staff to 'no intervention', 'usual' practice or a different implementation strategy. Citation screening, data extraction and assessment of risk of bias was performed by review authors in pairs. Disagreements between review authors were resolved via consensus, or if required, by a third author. Considerable trial heterogeneity precluded meta-analysis. We narratively synthesised trial findings by describing the effect size of the primary outcome measure for policy or practice implementation (or the median of such measures where a single primary outcome was not stated). We included 27 trials, 18 of which were conducted in the USA. Nineteen studies employed randomised controlled trial (RCT) designs. Fifteen trials tested strategies to implement healthy eating policies, practice or programs; six trials tested strategies targeting physical activity policies or practices; and three trials targeted tobacco policies or practices. Three trials targeted a combination of risk factors. None of the included trials sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. All trials examined multi-strategic implementation strategies and no two trials examined the same combinations of implementation strategies. The most common implementation strategies included educational materials, educational outreach and educational meetings. For all outcomes, the overall quality of evidence was very low and the risk of bias was high for the majority of

Comparison of provider and plan-based targeting strategies for disease management.

PubMed

Annis, Ann M; Holtrop, Jodi Summers; Tao, Min; Chang, Hsiu-Ching; Luo, Zhehui

2015-05-01

We aimed to describe and contrast the targeting methods and engagement outcomes for health plan-delivered disease management with those of a provider-delivered care management program. Health plan epidemiologists partnered with university health services researchers to conduct a quasi-experimental, mixed-methods study of a 2-year pilot. We used semi-structured interviews to assess the characteristics of program-targeting strategies, and calculated target and engagement rates from clinical encounter data. Five physician organizations (POs) with 51 participating practices implemented care management. Health plan member lists were sent monthly to the practices to accept patients, and then the practices sent back data reports regarding targeting and engagement in care management. Among patients accepted by the POs, we compared those who were targeted and engaged by POs with those who met health plan targeting criteria. The health plan's targeting process combined claims algorithms and employer group preferences to identify candidates for disease management; on the other hand, several different factors influenced PO practices' targeting approaches, including clinical and personal knowledge of the patients, health assessment information, and availability of disease-relevant programs. Practices targeted a higher percentage of patients for care management than the health plan (38% vs 16%), where only 7% of these patients met the targeting criteria of both. Practices engaged a higher percentage of their targeted patients than the health plan (50% vs 13%). The health plan's claims-driven targeting approach and the clinically based strategies of practices both provide advantages; an optimal model may be to combine the strengths of each approach to maximize benefits in care management.

Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting.

PubMed

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Gupta, Biki; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2017-10-01

In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circulating Magnetic Microbubbles for Localized Real-Time Control of Drug Delivery by Ultrasonography-Guided Magnetic Targeting and Ultrasound

PubMed Central

Chertok, Beata; Langer, Robert

2018-01-01

Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time. Unfortunately, challenges in fabricating magnetic microbubbles with such characteristics have limited progress in this field. In this report, we develop magnetic microbubbles (MagMB) that display strong magnetic and acoustic activities, while also preserving the ability to circulate systemically and evade pulmonary entrapment. Methods: We systematically evaluated the characteristics of MagMB including their pharmacokinetics, biodistribution, visibility to ultrasonography and amenability to magneto-acoustic modulation in tumor-bearing mice. We further assessed the applicability of MagMB for ultrasonography-guided control of drug targeting. Results: Following intravenous injection, MagMB exhibited a 17- to 90-fold lower pulmonary entrapment compared to previously reported magnetic microbubbles and mimicked circulation persistence of the clinically utilized Definity microbubbles (>10 min). In addition, MagMB could be accumulated in tumor vasculature by magnetic targeting, monitored by ultrasonography and collapsed by focused ultrasound on demand to activate drug deposition at the target. Furthermore, drug delivery to target tumors could be enhanced by adjusting the magneto-acoustic modulation based on ultrasonographic monitoring of MagMB in real-time. Conclusions: Circulating MagMB in conjunction with ultrasonography-guided magneto-acoustic modulation may provide a strategy for tailored minimally

Wellness at work. Boost wellness center participation with target marketing strategies.

PubMed

DeMoranville, C W; Schoenbachler, D D; Przytulski, J

1998-01-01

By using target marketing strategies, corporate wellness programs can increase employee participation rates and tailor activities to meet employee needs. The authors examined this issue through a research survey that segmented a university's staff and employee population into three wellness program groups: High Participators, Moderate Participators, and Low Participators. Participators' views on the following issues were analyzed: health management programs, exercise programs, wellness center use inhibitors, wellness center use incentives, wellness center communications, and willingness to pay for the wellness center. The results identified unique lifestyle characteristics for each group that can help make target marketing strategies effective.

78 FR 14121 - Notice of Availability of Funds and Solicitation for Grant Applications for Strategies Targeting...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

... Solicitation for Grant Applications for Strategies Targeting Characteristics Common to Female Ex-Offenders... will be targeted to females, but must also be open to eligible male ex-offenders. Strategies Targeting Characteristics Common to Female Ex-Offenders grants [[Page 14122

The n-by-T Target Discharge Strategy for Inpatient Units.

PubMed

Parikh, Pratik J; Ballester, Nicholas; Ramsey, Kylie; Kong, Nan; Pook, Nancy

2017-07-01

Ineffective inpatient discharge planning often causes discharge delays and upstream boarding. While an optimal discharge strategy that works across all units at a hospital is likely difficult to identify and implement, a strategy that provides a reasonable target to the discharge team appears feasible. We used observational and retrospective data from an inpatient trauma unit at a Level 2 trauma center in the Midwest US. Our proposed novel n-by-T strategy-discharge n patients by the Tth hour-was evaluated using a validated simulation model. Outcome measures included 2 measures: time-based (mean discharge completion and upstream boarding times) and capacity-based (increase in annual inpatient and upstream bed hours). Data from the pilot implementation of a 2-by-12 strategy at the unit was obtained and analyzed. The model suggested that the 1-by-T and 2-by-T strategies could advance the mean completion times by over 1.38 and 2.72 h, respectively (for 10 AM ≤ T ≤ noon, occupancy rate = 85%); the corresponding mean boarding time reductions were nearly 11% and 15%. These strategies could increase the availability of annual inpatient and upstream bed hours by at least 2,469 and 500, respectively. At 100% occupancy rate, the hospital-favored 2-by-12 strategy reduced the mean boarding time by 26.1%. A pilot implementation of the 2-by-12 strategy at the unit corroborated with the model findings: a 1.98-h advancement in completion times (P<0.0001) and a 14.5% reduction in boarding times (P = 0.027). Target discharge strategies, such as the n-by-T, can help substantially reduce discharge lateness and upstream boarding, especially during high unit occupancy. To sustain implementation, necessary commitment from the unit staff and physicians is vital, and may require some training.

Pakistan needs to speed up its human immunodeficiency virus control strategy to achieve targets in fast-track acquired immune deficiency syndrome response.

PubMed

Waheed, Yasir; Waheed, Hasnain

2017-05-12

In last fifteen years remarkable success in the fight against human immunodeficiency virus (HIV) is achieved globally. The number of HIV infections has decreased and the number of people on antiretroviral therapy is increased. This all is possible by strong political commitments and heavy investments in the fight against HIV. Pakistan is among few Asian countries in which HIV cases are increasing year by year since 1990. There are 94000 cases of HIV in Pakistan and only 14000 are registered with government. The main source of HIV infection in Pakistan is the use of contaminated injection equipment among people who inject drugs (PWID). The overall prevalence of HIV among PWID in Pakistan is 27.2%. There are five cities in Pakistan in which HIV prevalence is above 40% in PWIDs. In June 2016, United Nations political declaration on acquired immune deficiency syndrome (AIDS) provided a global mandate to fast-track the AIDS response over the next five years to achieve the targets in Sustainable Development Goals. To achieve the targets in fast-track AIDS response, the global leaders showed strong commitments to invest $ 26 billion per year by 2020. Pakistan needs to speed up its HIV control program. There is a dire need to locate all HIV positive people and enroll them in the treatment program. Pakistan also needs to calculate exact number of people living with HIV, increase HIV treatment centers and increase HIV awareness. Recently, Global Fund invested handsome money in the fight against HIV. Let's hope the country will have effective HIV control strategy to achieve the HIV elimination target by 2030.

Inverse targeting —An effective immunization strategy

NASA Astrophysics Data System (ADS)

Schneider, C. M.; Mihaljev, T.; Herrmann, H. J.

2012-05-01

We propose a new method to immunize populations or computer networks against epidemics which is more efficient than any continuous immunization method considered before. The novelty of our method resides in the way of determining the immunization targets. First we identify those individuals or computers that contribute the least to the disease spreading measured through their contribution to the size of the largest connected cluster in the social or a computer network. The immunization process follows the list of identified individuals or computers in inverse order, immunizing first those which are most relevant for the epidemic spreading. We have applied our immunization strategy to several model networks and two real networks, the Internet and the collaboration network of high-energy physicists. We find that our new immunization strategy is in the case of model networks up to 14%, and for real networks up to 33% more efficient than immunizing dynamically the most connected nodes in a network. Our strategy is also numerically efficient and can therefore be applied to large systems.

Point target detection utilizing super-resolution strategy for infrared scanning oversampling system

NASA Astrophysics Data System (ADS)

Wang, Longguang; Lin, Zaiping; Deng, Xinpu; An, Wei

2017-11-01

To improve the resolution of remote sensing infrared images, infrared scanning oversampling system is employed with information amount quadrupled, which contributes to the target detection. Generally the image data from double-line detector of infrared scanning oversampling system is shuffled to a whole oversampled image to be post-processed, whereas the aliasing between neighboring pixels leads to image degradation with a great impact on target detection. This paper formulates a point target detection method utilizing super-resolution (SR) strategy concerning infrared scanning oversampling system, with an accelerated SR strategy proposed to realize fast de-aliasing of the oversampled image and an adaptive MRF-based regularization designed to achieve the preserving and aggregation of target energy. Extensive experiments demonstrate the superior detection performance, robustness and efficiency of the proposed method compared with other state-of-the-art approaches.

Current status and strategies for viral hepatitis control in Korea.

PubMed

Sinn, Dong Hyun; Cho, Eun Ju; Kim, Ji Hoon; Kim, Do Young; Kim, Yoon Jun; Choi, Moon Seok

2017-09-01

Viral hepatitis is one of major global health challenges with increasing disease burden worldwide. Hepatitis B virus and hepatitis C virus infections are major causes of chronic liver diseases. They can lead to cirrhosis, hepatocellular carcinoma, and death in significant portion of affected people. Transmission of hepatitis B virus can be blocked by vaccination. Progression of hepatitis B virus-related liver diseases can be prevented by long-term viral suppression with effective drugs. Although vaccine for hepatitis C virus is currently unavailable, hepatitis C virus infection can be eradicated by oral direct antiviral agents. To eliminate viral hepatitis, World Health Organization (WHO) has urged countries to develop national goals and targets through reducing 90% of new infections and providing universal access to key treatment services up to 80%. This can lead to 65% reduction of viral hepatitis-related mortality. Here, we discuss some key features of viral hepatitis, strategies to control viral hepatitis suggested by WHO, and current status and strategies for viral hepatitis control in South Korea. To achieve the goal of viral hepatitis elimination by 2030 in South Korea, an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention (CDC) needs to be established to organize and execute comprehensive strategy for the management of viral hepatitis in South Korea.

[Improvement in zinc nutrition due to zinc transporter-targeting strategy].

PubMed

Kambe, Taiho

2016-07-01

Adequate intake of zinc from the daily diet is indispensable to maintain health. However, the dietary zinc content often fails to fulfill the recommended daily intake, leading to zinc deficiency and also increases the risk of developing chronic diseases, particularly in elderly individuals. Therefore, increased attention is required to overcome zinc deficiency and it is important to improve zinc nutrition in daily life. In the small intestine, the zinc transporter, ZIP4, functions as a component that is essential for zinc absorption. In this manuscript, we present a brief overview regarding zinc deficiency. Moreover, we review a novel strategy, called "ZIP4-targeting", which has the potential to enable efficient zinc absorption from the diet. ZIP4-targeting strategy is possibly a major step in preventing zinc deficiency and improving human health.

Global investment targets for malaria control and elimination between 2016 and 2030

PubMed Central

Patouillard, Edith; Griffin, Jamie; Bhatt, Samir; Ghani, Azra; Cibulskis, Richard

2017-01-01

Background Access to malaria control interventions falls short of universal health coverage. The Global Technical Strategy for malaria targets at least 90% reduction in case incidence and mortality rates, and elimination in 35 countries by 2030. The potential to reach these targets will be determined in part by investments in malaria. This study estimates the financing required for malaria control and elimination over the 2016–2030 period. Methods A mathematical transmission model was used to explore the impact of increasing intervention coverage on burden and costs. The cost analysis took a public provider perspective covering all 97 malaria endemic countries and territories in 2015. All control interventions currently recommended by the WHO were considered. Cost data were sourced from procurement databases, the peer-reviewed literature, national malaria strategic plans, the WHO-CHOICE project and key informant interviews. Results Annual investments of $6.4 billion (95% uncertainty interval (UI $4.5–$9.0 billion)) by 2020, $7.7 billion (95% UI $5.4–$10.9 billion) by 2025 and $8.7 billion (95% UI $6.0–$12.3 billion) by 2030 will be required to reach the targets set in the Global Technical Strategy. These are equivalent to annual investment per person at risk of malaria of US$3.90 by 2020, US$4.30 by 2025 and US$4.40 by 2030, compared with US$2.30 if interventions were sustained at current coverage levels. The 20 countries with the highest burden in 2015 will require 88% of the total investment. Conclusions Given the challenges in increasing domestic and international funding, the efficient use of currently available resources should be a priority. PMID:29242750

Global investment targets for malaria control and elimination between 2016 and 2030.

PubMed

Patouillard, Edith; Griffin, Jamie; Bhatt, Samir; Ghani, Azra; Cibulskis, Richard

2017-01-01

Access to malaria control interventions falls short of universal health coverage. The Global Technical Strategy for malaria targets at least 90% reduction in case incidence and mortality rates, and elimination in 35 countries by 2030. The potential to reach these targets will be determined in part by investments in malaria. This study estimates the financing required for malaria control and elimination over the 2016-2030 period. A mathematical transmission model was used to explore the impact of increasing intervention coverage on burden and costs. The cost analysis took a public provider perspective covering all 97 malaria endemic countries and territories in 2015. All control interventions currently recommended by the WHO were considered. Cost data were sourced from procurement databases, the peer-reviewed literature, national malaria strategic plans, the WHO-CHOICE project and key informant interviews. Annual investments of $6.4 billion (95% uncertainty interval (UI $4.5-$9.0 billion)) by 2020, $7.7 billion (95% UI $5.4-$10.9 billion) by 2025 and $8.7 billion (95% UI $6.0-$12.3 billion) by 2030 will be required to reach the targets set in the Global Technical Strategy. These are equivalent to annual investment per person at risk of malaria of US$3.90 by 2020, US$4.30 by 2025 and US$4.40 by 2030, compared with US$2.30 if interventions were sustained at current coverage levels. The 20 countries with the highest burden in 2015 will require 88% of the total investment. Given the challenges in increasing domestic and international funding, the efficient use of currently available resources should be a priority.

Strategies that Target Leukocyte Traffic in IBD: Recent Developments

PubMed Central

Rivera-Nieves, Jesús

2015-01-01

Purpose of review We review the most recent developments regarding the targeting of molecules involved in the traffic of leukocytes for the treatment of IBD. Recent Findings We discuss the most important findings of one published phase II trial that targeted the β7 integrin (Etrolizumab), two phase II trials that targeted the α4β7 integrin ligand: Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1, PF-00547659), a phase II targeting the chemokine IP-10 (CXCL10) in Crohn’s and a phase II trial that targeted the sphingosine-1-phosphate receptor-1 (S1P1): ozanimod in patients with ulcerative colitis (UC). Summary Targeting molecules involved in leukocyte traffic has recently become an effective and safe strategy for the treatment of IBD. Novel approaches now not only target the integrins on the lymphocyte surface, but also its endothelial ligand: MAdCAM-1. As with vedolizumab, antibodies against MAdCAM-1 appear most effective in ulcerative colitis rather than in Crohn’s. Targeting chemokines or their receptors does not appear to have the same efficacy as those that target the most stable integrin:immunoglobulin superfamily interactions between the lymphocyte and endothelium. Preliminary results also suggest that the sphingosine-1-phosphate pathway might also be targeted therapeutically in IBD, no longer with parenterally administered antibodies but with orally administered small molecules. PMID:26398681

A strategy for actualization of active targeting nanomedicine practically functioning in a living body.

PubMed

Lee, Kyoung Jin; Shin, Seol Hwa; Lee, Jae Hee; Ju, Eun Jin; Park, Yun-Yong; Hwang, Jung Jin; Suh, Young-Ah; Hong, Seung-Mo; Jang, Se Jin; Lee, Jung Shin; Song, Si Yeol; Jeong, Seong-Yun; Choi, Eun Kyung

2017-10-01

Designing nanocarriers with active targeting has been increasingly emphasized as for an ideal delivery mechanism of anti-cancer therapeutic agents, but the actualization has been constrained by lack of reliable strategy ultimately applicable. Here, we designed and verified a strategy to achieve active targeting nanomedicine that works in a living body, utilizing animal models bearing a patient's tumor tissue and subjected to the same treatments that would be used in the clinic. The concept for this strategy was that a novel peptide probe and its counterpart protein, which responded to a therapy, were identified, and then the inherent ability of the peptide to target the designated tumor protein was used for active targeting in vivo. An initial dose of ionizing radiation was locally delivered to the gastric cancer (GC) tumor of a patient-derived xenograft mouse model, and phage-displayed peptide library was intravenously injected. The peptides tightly bound to the tumor were recovered, and the counterpart protein was subsequently identified. Peptide-conjugated liposomal drug showed dramatically improved therapeutic efficacy and possibility of diagnostic imaging with radiation. These results strongly suggested the potential of our strategy to achieve in vivo functional active targeting and to be applied clinically for human cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Performance and strategy comparisons of human listeners and logistic regression in discriminating underwater targets.

PubMed

Yang, Lixue; Chen, Kean

2015-11-01

To improve the design of underwater target recognition systems based on auditory perception, this study compared human listeners with automatic classifiers. Performances measures and strategies in three discrimination experiments, including discriminations between man-made and natural targets, between ships and submarines, and among three types of ships, were used. In the experiments, the subjects were asked to assign a score to each sound based on how confident they were about the category to which it belonged, and logistic regression, which represents linear discriminative models, also completed three similar tasks by utilizing many auditory features. The results indicated that the performances of logistic regression improved as the ratio between inter- and intra-class differences became larger, whereas the performances of the human subjects were limited by their unfamiliarity with the targets. Logistic regression performed better than the human subjects in all tasks but the discrimination between man-made and natural targets, and the strategies employed by excellent human subjects were similar to that of logistic regression. Logistic regression and several human subjects demonstrated similar performances when discriminating man-made and natural targets, but in this case, their strategies were not similar. An appropriate fusion of their strategies led to further improvement in recognition accuracy.

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

PubMed Central

Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

2018-01-01

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

National Drug Control Strategy, 2011

ERIC Educational Resources Information Center

Office of National Drug Control Policy, 2011

2011-01-01

In May of 2010, President Obama released the Administration's inaugural "National Drug Control Strategy". Based on the premise that drug use and its consequences pose a threat not just to public safety, but also to public health, the 2010 "Strategy" represented the first comprehensive rebalancing of Federal drug control policy in the nearly 40…

Overview on the target fabrication facilities at ELI-NP and ongoing strategies

NASA Astrophysics Data System (ADS)

Gheorghiu, C. C.; Leca, V.; Popa, D.; Cernaianu, M. O.; Stutman, D.

2016-10-01

Along with the development of petawatt class laser systems, the interaction between high power lasers and matter flourished an extensive research, with high-interest applications like: laser nuclear physics, proton radiography or cancer therapy. The new ELI-NP (Extreme Light Infrastructure - Nuclear Physics) petawatt laser facility, with 10PW and ~ 1023W/cm2 beam intensity, is one of the innovative projects that will provide novel research of fundamental processes during light-matter interaction. As part of the ELI-NP facility, Targets Laboratory will provide the means for in-house manufacturing and characterization of the required targets (mainly solid ones) for the experiments, in addition to the research activity carried out in order to develop novel target designs with improved performances. A description of the Targets Laboratory with the main pieces of equipment and their specifications are presented. Moreover, in view of the latest progress in the target design, one of the proposed strategies for the forthcoming experiments at ELI-NP is also described, namely: ultra-thin patterned foil of diamond-like carbon (DLC) coated with a carbon-based ultra-low density layer. The carbon foam which behaves as a near-critical density plasma, will allow the controlled-shaping of the laser pulse before the main interaction with the solid foil. Particular emphasis will be directed towards the target's design optimization, by simulation tests and tuning the key-properties (thickness/length, spacing, density foam, depth, periodicity etc.) which are expected to have a crucial effect on the laser-matter interaction process.

Targeting cancer’s weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model

PubMed Central

Lineweaver, Charles H.; Davies, Paul C.W.; Vincent, Mark D.

2014-01-01

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target-the-weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target-the-weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. PMID:25043755

Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.

PubMed

Li, Lin; Di, Xingsheng; Wu, Mingrui; Sun, Zhisu; Zhong, Lu; Wang, Yongjun; Fu, Qiang; Kan, Qiming; Sun, Jin; He, Zhonggui

2017-04-01

Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of active-targeting nanosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Strategies to target non-T-cell HIV reservoirs.

PubMed

Sacha, Jonah B; Ndhlovu, Lishomwa C

2016-07-01

A central question for the HIV cure field is to determine new ways to target clinically relevant, latently and actively replicating HIV-infected cells beyond resting memory CD4 T cells, particularly in anatomical areas of low drug penetrability. HIV eradication strategies being positioned for targeting HIV for extinction in the CD4 T-cell compartment may also show promise in non-CD4 T-cells reservoirs. Furthermore, several exciting novel therapeutic approaches specifically focused on HIV clearance from non-CD4 T-cell populations are being developed. Although reservoir validity in these non-CD4 T cells continues to remain debated, this review will highlight recent advances and make an argument as to their clinical relevancy as we progress towards an HIV cure.

40 CFR 52.582 - Control strategy: Ozone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Ozone. 52.582 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Georgia> § 52.582 Control strategy: Ozone. Link to an... of the user, the added text is set forth as follows: § 52.582 Control strategy: Ozone. (d...

Construction and applications of exon-trapping gene-targeting vectors with a novel strategy for negative selection.

PubMed

Saito, Shinta; Ura, Kiyoe; Kodama, Miho; Adachi, Noritaka

2015-06-30

Targeted gene modification by homologous recombination provides a powerful tool for studying gene function in cells and animals. In higher eukaryotes, non-homologous integration of targeting vectors occurs several orders of magnitude more frequently than does targeted integration, making the gene-targeting technology highly inefficient. For this reason, negative-selection strategies have been employed to reduce the number of drug-resistant clones associated with non-homologous vector integration, particularly when artificial nucleases to introduce a DNA break at the target site are unavailable or undesirable. As such, an exon-trap strategy using a promoterless drug-resistance marker gene provides an effective way to counterselect non-homologous integrants. However, constructing exon-trapping targeting vectors has been a time-consuming and complicated process. By virtue of highly efficient att-mediated recombination, we successfully developed a simple and rapid method to construct plasmid-based vectors that allow for exon-trapping gene targeting. These exon-trap vectors were useful in obtaining correctly targeted clones in mouse embryonic stem cells and human HT1080 cells. Most importantly, with the use of a conditionally cytotoxic gene, we further developed a novel strategy for negative selection, thereby enhancing the efficiency of counterselection for non-homologous integration of exon-trap vectors. Our methods will greatly facilitate exon-trapping gene-targeting technologies in mammalian cells, particularly when combined with the novel negative selection strategy.

Rethinking volitional control over task choice in multitask environments: use of a stimulus set selection strategy in voluntary task switching.

PubMed

Arrington, Catherine M; Weaver, Starla M

2015-01-01

Under conditions of volitional control in multitask environments, subjects may engage in a variety of strategies to guide task selection. The current research examines whether subjects may sometimes use a top-down control strategy of selecting a task-irrelevant stimulus dimension, such as location, to guide task selection. We term this approach a stimulus set selection strategy. Using a voluntary task switching procedure, subjects voluntarily switched between categorizing letter and number stimuli that appeared in two, four, or eight possible target locations. Effects of stimulus availability, manipulated by varying the stimulus onset asynchrony between the two target stimuli, and location repetition were analysed to assess the use of a stimulus set selection strategy. Considered across position condition, Experiment 1 showed effects of both stimulus availability and location repetition on task choice suggesting that only in the 2-position condition, where selection based on location always results in a target at the selected location, subjects may have been using a stimulus set selection strategy on some trials. Experiment 2 replicated and extended these findings in a visually more cluttered environment. These results indicate that, contrary to current models of task selection in voluntary task switching, the top-down control of task selection may occur in the absence of the formation of an intention to perform a particular task.

Win–Win strategies to promote air pollutant control policies and non-fossil energy target regulation in China

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

Wang, Lining; Patel, Pralit L.; Yu, Sha

The rapid growth of energy consumption in China has led to increased emissions of air pollutants. As a response, in its 12th Five Year Plan the Chinese government proposed mitigation targets for SO2 and NOx emissions. Herein we have investigated mitigation measures taken in different sectors and their corresponding impacts on the energy system. Additionally, as non-fossil energy development has gained traction in addressing energy and environmental challenges in China, we further investigated the impact of non-fossil energy development on air pollutant emissions, and then explored interactions and co-benefits between these two types of policies. An extended Global Change Assessmentmore » Model (GCAM) was used in this study, which includes an additional air pollutant emissions control module coupling multiple end-of-pipe (EOP) control technologies with energy technologies, as well as more detailed end-use sectors in China. We find that implementing EOP control technologies would reduce air pollution in the near future, but with little room left to implement these EOP technologies, other cleaner and more efficient technologies are also effective. These technologies would reduce final energy consumption, increase electricity’s share in final energy, and increase the share of non-fossil fuels in primary energy and electricity consumption. Increasing non-fossil energy usage at China’s proposed adoption rate would in turn also reduce SO2 and NOx emissions, however, the reductions from this policy alone still lag behind the targeted requirements of air pollutant reduction. Fortunately, a combination of air pollutant controls and non-fossil energy development could synergistically help realize the respective individual targets, and would result in lower costs than would addressing these issues separately.« less

The use of modelling to evaluate and adapt strategies for animal disease control.

PubMed

Saegerman, C; Porter, S R; Humblet, M F

2011-08-01

Disease is often associated with debilitating clinical signs, disorders or production losses in animals and/or humans, leading to severe socio-economic repercussions. This explains the high priority that national health authorities and international organisations give to selecting control strategies for and the eradication of specific diseases. When a control strategy is selected and implemented, an effective method of evaluating its efficacy is through modelling. To illustrate the usefulness of models in evaluating control strategies, the authors describe several examples in detail, including three examples of classification and regression tree modelling to evaluate and improve the early detection of disease: West Nile fever in equids, bovine spongiform encephalopathy (BSE) and multifactorial diseases, such as colony collapse disorder (CCD) in the United States. Also examined are regression modelling to evaluate skin test practices and the efficacy of an awareness campaign for bovine tuberculosis (bTB); mechanistic modelling to monitor the progress of a control strategy for BSE; and statistical nationwide modelling to analyse the spatio-temporal dynamics of bTB and search for potential risk factors that could be used to target surveillance measures more effectively. In the accurate application of models, an interdisciplinary rather than a multidisciplinary approach is required, with the fewest assumptions possible.

Nonspecific Organelle-Targeting Strategy with Core-Shell Nanoparticles of Varied Lipid Components/Ratios.

PubMed

Zhang, Lu; Sun, Jiashu; Wang, Yilian; Wang, Jiancheng; Shi, Xinghua; Hu, Guoqing

2016-07-19

We report a nonspecific organelle-targeting strategy through one-step microfluidic fabrication and screening of a library of surface charge- and lipid components/ratios-varied lipid shell-polymer core nanoparticles. Different from the common strategy relying on the use of organelle-targeted moieties conjugated onto the surface of nanoparticles, here, we program the distribution of hybrid nanoparticles in lysosomes or mitochondria by tuning the lipid components/ratios in shell. Hybrid nanoparticles with 60% 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 20% 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) can intracellularly target mitochondria in both in vitro and in vivo models. While replacing DOPE with the same amount of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), the nanoparticles do not show mitochondrial targeting, indicating an incremental effect of cationic and fusogenic lipids on lysosomal escape which is further studied by molecular dynamics simulations. This work unveils the lipid-regulated subcellular distribution of hybrid nanoparticles in which target moieties and complex synthetic steps are avoided.

Avian influenza control strategies

USDA-ARS?s Scientific Manuscript database

Control strategies for avian influenza in poultry vary depending on whether the goal is prevention, management, or eradication. Components used in control programs include: 1) education which includes communication, public awareness, and behavioral change, 2) changes to production and marketing sys...

Optimal control of anthracnose using mixed strategies.

PubMed

Fotsa Mbogne, David Jaures; Thron, Christopher

2015-11-01

In this paper we propose and study a spatial diffusion model for the control of anthracnose disease in a bounded domain. The model is a generalization of the one previously developed in [15]. We use the model to simulate two different types of control strategies against anthracnose disease. Strategies that employ chemical fungicides are modeled using a continuous control function; while strategies that rely on cultivational practices (such as pruning and removal of mummified fruits) are modeled with a control function which is discrete in time (though not in space). For comparative purposes, we perform our analyses for a spatially-averaged model as well as the space-dependent diffusion model. Under weak smoothness conditions on parameters we demonstrate the well-posedness of both models by verifying existence and uniqueness of the solution for the growth inhibition rate for given initial conditions. We also show that the set [0, 1] is positively invariant. We first study control by impulsive strategies, then analyze the simultaneous use of mixed continuous and pulse strategies. In each case we specify a cost functional to be minimized, and we demonstrate the existence of optimal control strategies. In the case of pulse-only strategies, we provide explicit algorithms for finding the optimal control strategies for both the spatially-averaged model and the space-dependent model. We verify the algorithms for both models via simulation, and discuss properties of the optimal solutions. Copyright © 2015 Elsevier Inc. All rights reserved.

A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology

PubMed Central

Durrant, Jacob D.; Amaro, Rommie E.; Xie, Lei; Urbaniak, Michael D.; Ferguson, Michael A. J.; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E.; McCammon, J. Andrew

2010-01-01

Conventional drug design embraces the “one gene, one drug, one disease” philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology. PMID:20098496

A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology.

PubMed

Durrant, Jacob D; Amaro, Rommie E; Xie, Lei; Urbaniak, Michael D; Ferguson, Michael A J; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E; McCammon, J Andrew

2010-01-22

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology.

Attentional Control via Parallel Target-Templates in Dual-Target Search

PubMed Central

Barrett, Doug J. K.; Zobay, Oliver

2014-01-01

Simultaneous search for two targets has been shown to be slower and less accurate than independent searches for the same two targets. Recent research suggests this ‘dual-target cost’ may be attributable to a limit in the number of target-templates than can guide search at any one time. The current study investigated this possibility by comparing behavioural responses during single- and dual-target searches for targets defined by their orientation. The results revealed an increase in reaction times for dual- compared to single-target searches that was largely independent of the number of items in the display. Response accuracy also decreased on dual- compared to single-target searches: dual-target accuracy was higher than predicted by a model restricting search guidance to a single target-template and lower than predicted by a model simulating two independent single-target searches. These results are consistent with a parallel model of dual-target search in which attentional control is exerted by more than one target-template at a time. The requirement to maintain two target-templates simultaneously, however, appears to impose a reduction in the specificity of the memory representation that guides search for each target. PMID:24489793

A review of the ligands and related targeting strategies for active targeting of paclitaxel to tumours.

PubMed

Li, Juan; Wang, Fengshan; Sun, Deqing; Wang, Rongmei

2016-08-01

It has been 30 years since the discovery of the anti-tumour property of paclitaxel (PTX), which has been successfully applied in clinic for the treatment of carcinomas of the lungs, breast and ovarian. However, PTX is poorly soluble in water and has no targeting and selectivity to tumour tissue. Recent advances in active tumour targeting of PTX delivery vehicles have addressed some of the issues related to lack of solubility in water and non-specific toxicities associated with PTX. These PTX delivery vehicles are designed for active targeting to specific cancer cells by the addition of ligands for recognition by specific receptors/antigens on cancer cells. This article will focus on various ligands and related targeting strategies serving as potential tools for active targeting of PTX to tumour tissues, illustrating their use in different tumour models. This review also highlights the need of further studies on the discovery of receptors in different cells of specific organ and ligands with binding efficiency to these specific receptors.

Strategies for target identification of antimicrobial natural products.

PubMed

Farha, Maya A; Brown, Eric D

2016-05-04

Covering: 2000 to 2015Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical-based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs.

Dual peptide conjugation strategy for improved cellular uptake and mitochondria targeting.

PubMed

Lin, Ran; Zhang, Pengcheng; Cheetham, Andrew G; Walston, Jeremy; Abadir, Peter; Cui, Honggang

2015-01-21

Mitochondria are critical regulators of cellular function and survival. Delivery of therapeutic and diagnostic agents into mitochondria is a challenging task in modern pharmacology because the molecule to be delivered needs to first overcome the cell membrane barrier and then be able to actively target the intracellular organelle. Current strategy of conjugating either a cell penetrating peptide (CPP) or a subcellular targeting sequence to the molecule of interest only has limited success. We report here a dual peptide conjugation strategy to achieve effective delivery of a non-membrane-penetrating dye 5-carboxyfluorescein (5-FAM) into mitochondria through the incorporation of both a mitochondrial targeting sequence (MTS) and a CPP into one conjugated molecule. Notably, circular dichroism studies reveal that the combined use of α-helix and PPII-like secondary structures has an unexpected, synergistic contribution to the internalization of the conjugate. Our results suggest that although the use of positively charged MTS peptide allows for improved targeting of mitochondria, with MTS alone it showed poor cellular uptake. With further covalent linkage of the MTS-5-FAM conjugate to a CPP sequence (R8), the dually conjugated molecule was found to show both improved cellular uptake and effective mitochondria targeting. We believe these results offer important insight into the rational design of peptide conjugates for intracellular delivery.

Hospital protocols for targeted glycemic control: Development, implementation, and models for cost justification.

PubMed

Magee, Michelle F

2007-05-15

Evolving elements of best practices for providing targeted glycemic control in the hospital setting, clinical performance measurement, basal-bolus plus correction-dose insulin regimens, components of standardized subcutaneous (s.c.) insulin order sets, and strategies for implementation and cost justification of glycemic control initiatives are discussed. Best practices for targeted glycemic control should address accurate documentation of hyperglycemia, initial patient assessment, management plan, target blood glucose range, blood glucose monitoring frequency, maintenance of glycemic control, criteria for glucose management consultations, and standardized insulin order sets and protocols. Establishing clinical performance measures, including desirable processes and outcomes, can help ensure the success of targeted hospital glycemic control initiatives. The basal-bolus plus correction-dose regimen for insulin administration will be used to mimic the normal physiologic pattern of endogenous insulin secretion. Standardized insulin order sets and protocols are being used to minimize the risk of error in insulin therapy. Components of standardized s.c. insulin order sets include specification of the hyperglycemia diagnosis, finger stick blood glucose monitoring frequency and timing, target blood glucose concentration range, cutoff values for excessively high or low blood glucose concentrations that warrant alerting the physician, basal and prandial or nutritional (i.e., bolus) insulin, correction doses, hypoglycemia treatment, and perioperative or procedural dosage adjustments. The endorsement of hospital administrators and key physician and nursing leaders is needed for glycemic control initiatives. Initiatives may be cost justified on the basis of the billings for clinical diabetes management services and/or the return- on-investment accrued to reductions in hospital length of stay, readmissions, and accurate documentation and coding of unrecognized or uncontrolled

MTTE: an innovative strategy for the evaluation of targeted/exome enrichment efficiency

PubMed Central

Klonowska, Katarzyna; Handschuh, Luiza; Swiercz, Aleksandra; Figlerowicz, Marek; Kozlowski, Piotr

2016-01-01

Although currently available strategies for the preparation of exome-enriched libraries are well established, a final validation of the libraries in terms of exome enrichment efficiency prior to the sequencing step is of considerable importance. Here, we present a strategy for the evaluation of exome enrichment, i.e., the Multipoint Test for Targeted-enrichment Efficiency (MTTE), PCR-based approach utilizing multiplex ligation-dependent probe amplification with capillary electrophoresis separation. We used MTTE for the analysis of subsequent steps of the Illumina TruSeq Exome Enrichment procedure. The calculated values of enrichment-associated parameters (i.e., relative enrichment, relative clearance, overall clearance, and fold enrichment) and the comparison of MTTE results with the actual enrichment revealed the high reliability of our assay. Additionally, the MTTE assay enabled the determination of the sequence-associated features that may confer bias in the enrichment of different targets. Importantly, the MTTE is low cost method that can be easily adapted to the region of interest important for a particular project. Thus, the MTTE strategy is attractive for post-capture validation in a variety of targeted/exome enrichment NGS projects. PMID:27572310

MTTE: an innovative strategy for the evaluation of targeted/exome enrichment efficiency.

PubMed

Klonowska, Katarzyna; Handschuh, Luiza; Swiercz, Aleksandra; Figlerowicz, Marek; Kozlowski, Piotr

2016-10-11

Although currently available strategies for the preparation of exome-enriched libraries are well established, a final validation of the libraries in terms of exome enrichment efficiency prior to the sequencing step is of considerable importance. Here, we present a strategy for the evaluation of exome enrichment, i.e., the Multipoint Test for Targeted-enrichment Efficiency (MTTE), PCR-based approach utilizing multiplex ligation-dependent probe amplification with capillary electrophoresis separation. We used MTTE for the analysis of subsequent steps of the Illumina TruSeq Exome Enrichment procedure. The calculated values of enrichment-associated parameters (i.e., relative enrichment, relative clearance, overall clearance, and fold enrichment) and the comparison of MTTE results with the actual enrichment revealed the high reliability of our assay. Additionally, the MTTE assay enabled the determination of the sequence-associated features that may confer bias in the enrichment of different targets. Importantly, the MTTE is low cost method that can be easily adapted to the region of interest important for a particular project. Thus, the MTTE strategy is attractive for post-capture validation in a variety of targeted/exome enrichment NGS projects.

[Aedes aegypti control strategies: a review].

PubMed

Zara, Ana Laura de Sene Amâncio; Santos, Sandra Maria Dos; Fernandes-Oliveira, Ellen Synthia; Carvalho, Roberta Gomes; Coelho, Giovanini Evelim

2016-01-01

to describe the main strategies to control Aedes aegypti, with emphasis on promising technological innovations for use in Brazil. this study is a non-systematic review of the literature. several technologies have been developed as alternatives in the control of Ae. aegypti, using different mechanisms of action, such as selective monitoring of the infestation, social interventions, dispersing insecticides, new biological control agents and molecular techniques for population control of mosquitoes, also considering the combination between them. Evolving technologies require evaluation of the effectiveness, feasibility and costs of implementation strategies as complementary to the actions already recommended by the National Program for Dengue Control. the integration of different compatible and effective vector control strategies, considering the available technologies and regional characteristics, appears to be a viable method to try to reduce the infestation of mosquitoes and the incidence of arbovirus transmitted by them.

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies.

PubMed

Mangraviti, Antonella; Gullotti, David; Tyler, Betty; Brem, Henry

2016-10-28

Despite recent technological advancements and promising preclinical experiments, brain tumor patients are still met with limited treatment options. Some of the barriers to clinical improvements include the systemic toxicity of cytotoxic compounds, the impedance of the blood brain barrier (BBB), and the lack of therapeutic agents that can selectively target the intracranial tumor environment. To overcome such barriers, a number of chemotherapeutic agents and nucleic acid-based therapies are rapidly being synthesized and tested as new brain tumor-targeted delivery strategies. Novel carriers include liposomal and polymeric nanoparticles, wafers, microchips, microparticle-based nanoplatforms and cells-based vectors. Strong preclinical results suggest that these nanotechnologies are set to transform the therapeutic paradigm for brain tumor treatment. In addition to new tumoricidal agents, parallel work is also being conducted on the BBB front. Preclinical testing of chemical and physical modulation strategies is yielding improved intracranial concentrations. New diagnostic and therapeutic imaging techniques, such as high-intensity focused ultrasound and MRI-guided focused ultrasound, are being used to modulate the BBB in a more precise and non-invasive manner. This review details some of the tremendous advances that are being explored in current brain tumor targeted therapies, including local implant development, nanobiotechnology-based delivery strategies, and techniques of BBB manipulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacological and Physical Vessel Modulation Strategies to Improve EPR-mediated Drug Targeting to Tumors

PubMed Central

Ojha, Tarun; Pathak, Vertika; Shi, Yang; Hennink, Wim; Moonen, Chrit; Storm, Gert; Kiessling, Fabian; Lammers, Twan

2018-01-01

The performance of nanomedicine formulations depends on the Enhanced Permeability and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems, such as liposomes, polymers and micelles, aim to exploit the EPR effect to accumulate at pathological sites, to thereby improve the balance between drug efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not yet managed to achieve convincing therapeutic results, at least not in large cohorts of patients. This is likely mostly due to high inter- and intra-patient heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and predict EPR, another strategy to address this heterogeneity is the establishment of vessel modulation strategies to homogenize and improve EPR. Over the years, several pharmacological and physical co-treatments have been evaluated to improve EPR-mediated tumor targeting. These include pharmacological strategies, such as vessel permeabilization, normalization, disruption and promotion, as well as physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and phototherapy. In the present manuscript, we summarize exemplary studies showing that pharmacological and physical vessel modulation strategies can be used to improve tumor-targeted drug delivery, and we discuss how these advanced combination regimens can be optimally employed to enhance the (pre-) clinical performance of tumor-targeted nanomedicines. PMID:28697952

Pharmacological and physical vessel modulation strategies to improve EPR-mediated drug targeting to tumors.

PubMed

Ojha, Tarun; Pathak, Vertika; Shi, Yang; Hennink, Wim E; Moonen, Chrit T W; Storm, Gert; Kiessling, Fabian; Lammers, Twan

2017-09-15

The performance of nanomedicine formulations depends on the Enhanced Permeability and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems, such as liposomes, polymers and micelles, aim to exploit the EPR effect to accumulate at pathological sites, to thereby improve the balance between drug efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not yet managed to achieve convincing therapeutic results, at least not in large cohorts of patients. This is likely mostly due to high inter- and intra-patient heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and predict EPR, another strategy to address this heterogeneity is the establishment of vessel modulation strategies to homogenize and improve EPR. Over the years, several pharmacological and physical co-treatments have been evaluated to improve EPR-mediated tumor targeting. These include pharmacological strategies, such as vessel permeabilization, normalization, disruption and promotion, as well as physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and phototherapy. In the present manuscript, we summarize exemplary studies showing that pharmacological and physical vessel modulation strategies can be used to improve tumor-targeted drug delivery, and we discuss how these advanced combination regimens can be optimally employed to enhance the (pre-) clinical performance of tumor-targeted nanomedicines. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrated control strategy for autonomous decentralized conveyance systems based on distributed MEMS arrays

NASA Astrophysics Data System (ADS)

Zhou, Lingfei; Chapuis, Yves-Andre; Blonde, Jean-Philippe; Bervillier, Herve; Fukuta, Yamato; Fujita, Hiroyuki

2004-07-01

In this paper, the authors proposed to study a model and a control strategy of a two-dimensional conveyance system based on the principles of the Autonomous Decentralized Microsystems (ADM). The microconveyance system is based on distributed cooperative MEMS actuators which can produce a force field onto the surface of the device to grip and move a micro-object. The modeling approach proposed here is based on a simple model of a microconveyance system which is represented by a 5 x 5 matrix of cells. Each cell is consisted of a microactuator, a microsensor, and a microprocessor to provide actuation, autonomy and decentralized intelligence to the cell. Thus, each cell is able to identify a micro-object crossing on it and to decide by oneself the appropriate control strategy to convey the micro-object to its destination target. The control strategy could be established through five simple decision rules that the cell itself has to respect at each calculate cycle time. Simulation and FPGA implementation results are given in the end of the paper in order to validate model and control approach of the microconveyance system.

Temperature Controller System for Gas Gun Targets

NASA Astrophysics Data System (ADS)

Bucholtz, Scott; Sheffield, Stephen

2005-07-01

A temperature controller system capable of heating and cooling gas gun targets over the range -75 C to +200 C was designed and tested. The system uses cold nitrogen gas from a liquid nitrogen Dewar for cooling and compressed air for heating. Two gas flow heaters control the gas temperature for both heating and cooling. One heater controls the temperature of the target mounting plate and the other the temperature of a copper tubing coil surrounding the target. Each heater is separately adjustable, so the target material will achieve a uniform temperature throughout its volume. A magnetic gauge with integrated thermocouples was developed to measure the internal temperature of the target. Using this system shock experiments, including equation-of-state measurements and shock initiation of high explosives, can be performed over a range of initial temperatures. Successful tests were completed on Teflon samples. This work was supported by the NNSA Enhanced Surveillance Campaign through contract DE-ACO4-01AL66850.

Temperature Controller System for Gas Gun Targets

NASA Astrophysics Data System (ADS)

Bucholtz, S. M.; Gehr, R. J.; Rupp, T. D.; Sheffield, S. A.; Robbins, D. L.

2006-07-01

A temperature controller system capable of heating and cooling gas gun targets over the range -75°C to +120°C was designed and tested. The system uses cold nitrogen gas from a liquid nitrogen Dewar for cooling and compressed air for heating. Two gas flow heaters control the gas temperature for both heating and cooling. One heater controls the temperature of the target mounting plate and the other the temperature of a copper tubing coil surrounding the target. Each heater is separately adjustable, so the target material will achieve a uniform temperature throughout its volume. A magnetic gauge membrane with integrated thermocouples was developed to measure the internal temperature of the target. Using this system, multiple magnetic gauge shock experiments, including equation-of-state measurements and shock initiation of high explosives, can be performed over a range of initial temperatures. Successful heating and cooling tests were completed on Teflon samples.

Quantitative proteomics in cardiovascular research: global and targeted strategies

PubMed Central

Shen, Xiaomeng; Young, Rebeccah; Canty, John M.; Qu, Jun

2014-01-01

Extensive technical advances in the past decade have substantially expanded quantitative proteomics in cardiovascular research. This has great promise for elucidating the mechanisms of cardiovascular diseases (CVD) and the discovery of cardiac biomarkers used for diagnosis and treatment evaluation. Global and targeted proteomics are the two major avenues of quantitative proteomics. While global approaches enable unbiased discovery of altered proteins via relative quantification at the proteome level, targeted techniques provide higher sensitivity and accuracy, and are capable of multiplexed absolute quantification in numerous clinical/biological samples. While promising, technical challenges need to be overcome to enable full utilization of these techniques in cardiovascular medicine. Here we discuss recent advances in quantitative proteomics and summarize applications in cardiovascular research with an emphasis on biomarker discovery and elucidating molecular mechanisms of disease. We propose the integration of global and targeted strategies as a high-throughput pipeline for cardiovascular proteomics. Targeted approaches enable rapid, extensive validation of biomarker candidates discovered by global proteomics. These approaches provide a promising alternative to immunoassays and other low-throughput means currently used for limited validation. PMID:24920501

Drug discovery strategies to outer membrane targets in Gram-negative pathogens.

PubMed

Brown, Dean G

2016-12-15

This review will cover selected recent examples of drug discovery strategies which target the outer membrane (OM) of Gram-negative bacteria either by disruption of outer membrane function or by inhibition of essential gene products necessary for outer membrane assembly. Significant advances in pathway elucidation, structural biology and molecular inhibitor designs have created new opportunities for drug discovery within this target-class space. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fortification of foods with vitamin D in India: strategies targeted at children.

PubMed

G, Ritu; Gupta, Ajay

2015-01-01

Vitamin D deficiency is endemic in India, despite abundant sunshine, due to several socioeconomic and cultural constraints. Fortification of staple foods with vitamin D is a viable population-based strategy for the general population in India. These strategies are discussed in the review article entitled, "Fortification of Foods With Vitamin D in India" [1]. The quantity of foods consumed by children is much smaller compared to adults. Therefore, children need energy-dense and micronutrient-dense foods to meet their daily nutritional requirements. Targeted food fortification programs are needed to meet the special needs of children. This review explores potential strategies that could be used for fortification of foods with vitamin D for children in India. Sattu has the potential to be a valuable vehicle for vitamin D fortification in India. The salient characteristics and merits of sattu as an ideal food to be fortified with micronutrients, especially vitamin D, are reviewed here. Key teaching points: • Fortification of foods with vitamin D, specifically targeted towards the nutritional requirements of infants and children, is a viable strategy in the Indian scenario. •Government programs targeting the nutritional needs of children in India, especially via midday meal programs in schools, should incorporate indigenous ready-to-eat foods fortified with micronutrients including vitamin D. These foods would need to have longer shelf life, require minimal preparation, and have economic and technological feasibility. • Sattu, a protein rich Indian fast food, comprised of roasted flour made from cereals and legumes, has immense potential to serve as an economically and technologically feasible fortification vehicle for vitamin D fortification strategies.

Control Strategy Tool (CoST)

EPA Pesticide Factsheets

The EPA Control Strategy Tool (CoST) is a software tool for projecting potential future control scenarios, their effects on emissions and estimated costs. This tool uses the NEI and the Control Measures Dataset as key inputs. CoST outputs are projections of future control scenarios.

Hantavirus Gc induces long-term immune protection via LAMP-targeting DNA vaccine strategy.

PubMed

Jiang, Dong-Bo; Zhang, Jin-Peng; Cheng, Lin-Feng; Zhang, Guan-Wen; Li, Yun; Li, Zi-Chao; Lu, Zhen-Hua; Zhang, Zi-Xin; Lu, Yu-Chen; Zheng, Lian-He; Zhang, Fang-Lin; Yang, Kun

2018-02-01

Hemorrhagic fever with renal syndrome (HFRS) occurs widely throughout Eurasia. Unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (HTNV), which is an Old World hantavirus. However, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated HFRS vaccine. Previous studies revealed that a lysosome-associated membrane protein 1 (LAMP1)-targeting strategy involving a DNA vaccine based on the HTNV glycoprotein Gn successfully conferred long-term immunity, and indicated that further research on Gc, another HTNV antigen, was warranted. Plasmids encoding Gc and lysosome-targeted Gc, designated pVAX-Gc and pVAX-LAMP/Gc, respectively, were constructed. Proteins of interest were identified by fluorescence microscopy following cell line transfection. Five groups of 20 female BALB/c mice were subjected to the following inoculations: inactivated HTNV vaccine, pVAX-LAMP/Gc, pVAX-Gc, and, as the negative controls, pVAX-LAMP or the blank vector pVAX1. Humoral and cellular immunity were assessed by enzyme-linked immunosorbent assays (ELISAs) and 15-mer peptide enzyme-linked immunospot (ELISpot) epitope mapping assays. Repeated immunization with pVAX-LAMP/Gc enhanced adaptive immune responses, as demonstrated by the specific and neutralizing antibody titers and increased IFN-γ production. The inactivated vaccine induced a comparable humoral reaction, but the negative controls only elicited insignificant responses. Using a mouse model of HTNV challenge, the in vivo protection conferred by the inactivated vaccine and Gc-based constructs (with/without LAMP recombination) was confirmed. Evidence of pan-epitope reactions highlighted the long-term cellular response to the LAMP-targeting strategy, and histological observations indicated the safety of the LAMP-targeting vaccines. The long-term protective immune responses induced by pVAX-LAMP/Gc may be

An innovative pre-targeting strategy for tumor cell specific imaging and therapy

NASA Astrophysics Data System (ADS)

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-08-01

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging

ACCELERATOR TARGET POSITIONER AND CONTROL CIRCUIT THEREFOR

DOEpatents

Stone, K.F.; Force, R.J.; Olson, W.W.; Cagle, D.S.

1959-12-15

An apparatus is described for inserting and retracting a target material with respect to the internal beam of a charged particle accelerator and to circuitry for controlling the timing and motion of the target placement. Two drive coils are mounted on the shaft of a target holder arm and disposed within the accelerator magnetic field with one coil at right angles to the other. Control circuitry alternately connects each coil to a current source and to a varying shorting resistance whereby the coils interchangeably produce driving and braking forces which swing the target arm within a ninety degree arc. The target is thus moved into the beam and away from it at high speeds and is brought to rest after each movement without whiplash or vibration.

Targeted Screening Strategies to Detect Trypanosoma cruzi Infection in Children

PubMed Central

Levy, Michael Z.; Kawai, Vivian; Bowman, Natalie M.; Waller, Lance A.; Cabrera, Lilia; Pinedo-Cancino, Viviana V.; Seitz, Amy E.; Steurer, Frank J.; Cornejo del Carpio, Juan G.; Cordova-Benzaquen, Eleazar; Maguire, James H.; Gilman, Robert H.; Bern, Caryn

2007-01-01

Background Millions of people are infected with Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Anti-trypanosomal drug therapy can cure infected individuals, but treatment efficacy is highest early in infection. Vector control campaigns disrupt transmission of T. cruzi, but without timely diagnosis, children infected prior to vector control often miss the window of opportunity for effective chemotherapy. Methods and Findings We performed a serological survey in children 2–18 years old living in a peri-urban community of Arequipa, Peru, and linked the results to entomologic, spatial and census data gathered during a vector control campaign. 23 of 433 (5.3% [95% CI 3.4–7.9]) children were confirmed seropositive for T. cruzi infection by two methods. Spatial analysis revealed that households with infected children were very tightly clustered within looser clusters of households with parasite-infected vectors. Bayesian hierarchical mixed models, which controlled for clustering of infection, showed that a child's risk of being seropositive increased by 20% per year of age and 4% per vector captured within the child's house. Receiver operator characteristic (ROC) plots of best-fit models suggest that more than 83% of infected children could be identified while testing only 22% of eligible children. Conclusions We found evidence of spatially-focal vector-borne T. cruzi transmission in peri-urban Arequipa. Ongoing vector control campaigns, in addition to preventing further parasite transmission, facilitate the collection of data essential to identifying children at high risk of T. cruzi infection. Targeted screening strategies could make integration of diagnosis and treatment of children into Chagas disease control programs feasible in lower-resource settings. PMID:18160979

Target of physiological gait: Realization of speed adaptive control for a prosthetic knee during swing flexion.

PubMed

Cao, Wujing; Yu, Hongliu; Zhao, Weiliang; Li, Jin; Wei, Xiaodong

2018-01-01

Prosthetic knee is the most important component of lower limb prosthesis. Speed adaptive for prosthetic knee during swing flexion is the key method to realize physiological gait. This study aims to discuss the target of physiological gait, propose a speed adaptive control method during swing flexion and research the damping adjustment law of intelligent hydraulic prosthetic knee. According to the physiological gait trials of healthy people, the control target during swing flexion is defined. A new prosthetic knee with fuzzy logical control during swing flexion is designed to realize the damping adjustment automatically. The function simulation and evaluation system of intelligent knee prosthesis is provided. Speed adaptive control test of the intelligent prosthetic knee in different velocities are researched. The maximum swing flexion of the knee angle is set between sixty degree and seventy degree as the target of physiological gait. Preliminary experimental results demonstrate that the prosthetic knee with fuzzy logical control is able to realize physiological gait under different speeds. The faster the walking, the bigger the valve closure percentage of the hydraulic prosthetic knee. The proposed fuzzy logical control strategy and intelligent hydraulic prosthetic knee are effective for the amputee to achieve physiological gait.

Characterizing Types of Human Mobility to Inform Differential and Targeted Malaria Elimination Strategies in Northeast Cambodia

PubMed Central

Peeters Grietens, Koen; Gryseels, Charlotte; Dierickx, Susan; Bannister-Tyrrell, Melanie; Trienekens, Suzan; Uk, Sambunny; Phoeuk, Pisen; Suon, Sokha; Set, Srun; Gerrets, René; Hoibak, Sarah; Muela Ribera, Joan; Hausmann-Muela, Susanna; Tho, Sochantha; Durnez, Lies; Sluydts, Vincent; d’Alessandro, Umberto; Coosemans, Marc; Erhart, Annette

2015-01-01

Human population movements currently challenge malaria elimination in low transmission foci in the Greater Mekong Subregion. Using a mixed-methods design, combining ethnography (n = 410 interviews), malariometric data (n = 4996) and population surveys (n = 824 indigenous populations; n = 704 Khmer migrants) malaria vulnerability among different types of mobile populations was researched in the remote province of Ratanakiri, Cambodia. Different structural types of human mobility were identified, showing differential risk and vulnerability. Among local indigenous populations, access to malaria testing and treatment through the VMW-system and LLIN coverage was high but control strategies failed to account for forest farmers’ prolonged stays at forest farms/fields (61% during rainy season), increasing their exposure (p = 0.002). The Khmer migrants, with low acquired immunity, active on plantations and mines, represented a fundamentally different group not reached by LLIN-distribution campaigns since they were largely unregistered (79%) and unaware of the local VMW-system (95%) due to poor social integration. Khmer migrants therefore require control strategies including active detection, registration and immediate access to malaria prevention and control tools from which they are currently excluded. In conclusion, different types of mobility require different malaria elimination strategies. Targeting mobility without an in-depth understanding of malaria risk in each group challenges further progress towards elimination. PMID:26593245

40 CFR 52.2584 - Control strategy; Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy; Particulate matter... Control strategy; Particulate matter. (a) Part D—Disapproval—USEPA disapproves Regulation NR 154.11(7)(b... control strategy to attain and maintain the standards for particulate matter, because it does not contain...

40 CFR 52.2584 - Control strategy; Particulate matter.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy; Particulate matter... Control strategy; Particulate matter. (a) Part D—Disapproval—USEPA disapproves Regulation NR 154.11(7)(b... control strategy to attain and maintain the standards for particulate matter, because it does not contain...

40 CFR 52.2584 - Control strategy; Particulate matter.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy; Particulate matter... Control strategy; Particulate matter. (a) Part D—Disapproval—USEPA disapproves Regulation NR 154.11(7)(b... control strategy to attain and maintain the standards for particulate matter, because it does not contain...

40 CFR 52.2584 - Control strategy; Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy; Particulate matter... Control strategy; Particulate matter. (a) Part D—Disapproval—USEPA disapproves Regulation NR 154.11(7)(b... control strategy to attain and maintain the standards for particulate matter, because it does not contain...

40 CFR 52.2584 - Control strategy; Particulate matter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy; Particulate matter... Control strategy; Particulate matter. (a) Part D—Disapproval—USEPA disapproves Regulation NR 154.11(7)(b... control strategy to attain and maintain the standards for particulate matter, because it does not contain...

Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer

PubMed Central

Chavez-Gonzalez, Antonieta; Bakhshinejad, Babak; Pakravan, Katayoon

2018-01-01

Background Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are characterized by high self-renewal and multi-lineage differentiation capacities. CSCs are thought to play indispensable roles in the initiation, progression and metastasis of many types of cancer. Leukemias are thought to be initiated and maintained by a specific sub-type of CSC, the leukemia stem cell (LSC). An important feature of LSCs is their resistance to standard therapy, which may lead to relapse. Increasing efforts are aimed at developing novel therapeutic strategies that selectively target LSCs, while sparing their normal counterparts and, thus, minimizing adverse treatment-associated side-effects. These LSC targeting therapies aim to eradicate LSCs through affecting mechanisms that control their survival, self-renewal, differentiation, proliferation and cell cycle progression. Some LSC targeting therapies have already been proven successful in pre-clinical studies and they are now being tested in clinical studies, mainly in combination with conventional treatment regimens. Conclusions A growing body of evidence indicates that the selective targeting of LSCs represents a promising approach to improve disease outcome. Beyond doubt, the CSC hypothesis has added a new dimension to the area of anticancer research, thereby paving the way for shaping a new trend in cancer therapy. PMID:27678246

Conformational stability as a design target to control protein aggregation.

PubMed

Costanzo, Joseph A; O'Brien, Christopher J; Tiller, Kathryn; Tamargo, Erin; Robinson, Anne Skaja; Roberts, Christopher J; Fernandez, Erik J

2014-05-01

Non-native protein aggregation is a prevalent problem occurring in many biotechnological manufacturing processes and can compromise the biological activity of the target molecule or induce an undesired immune response. Additionally, some non-native aggregation mechanisms lead to amyloid fibril formation, which can be associated with debilitating diseases. For natively folded proteins, partial or complete unfolding is often required to populate aggregation-prone conformational states, and therefore one proposed strategy to mitigate aggregation is to increase the free energy for unfolding (ΔGunf) prior to aggregation. A computational design approach was tested using human γD crystallin (γD-crys) as a model multi-domain protein. Two mutational strategies were tested for their ability to reduce/increase aggregation rates by increasing/decreasing ΔGunf: stabilizing the less stable domain and stabilizing the domain-domain interface. The computational protein design algorithm, RosettaDesign, was implemented to identify point variants. The results showed that although the predicted free energies were only weakly correlated with the experimental ΔGunf values, increased/decreased aggregation rates for γD-crys correlated reasonably well with decreases/increases in experimental ΔGunf, illustrating improved conformational stability as a possible design target to mitigate aggregation. However, the results also illustrate that conformational stability is not the sole design factor controlling aggregation rates of natively folded proteins.

Understanding L2 French Teaching Strategies in a Non-Target Language Classroom Context

ERIC Educational Resources Information Center

Sun, Peijian; Yuan, Rui; Teng, Lin

2015-01-01

This research explored the congruence and disparity between teachers' and students' attitudes towards French as a second language (L2) teaching strategies in a non-target language classroom context in the USA. The findings suggest students' and teachers' attitudes towards the direct and indirect teaching strategies were generally consistent, but…

The study on the control strategy of micro grid considering the economy of energy storage operation

NASA Astrophysics Data System (ADS)

Ma, Zhiwei; Liu, Yiqun; Wang, Xin; Li, Bei; Zeng, Ming

2017-08-01

To optimize the running of micro grid to guarantee the supply and demand balance of electricity, and to promote the utilization of renewable energy. The control strategy of micro grid energy storage system is studied. Firstly, the mixed integer linear programming model is established based on the receding horizon control. Secondly, the modified cuckoo search algorithm is proposed to calculate the model. Finally, a case study is carried out to study the signal characteristic of micro grid and batteries under the optimal control strategy, and the convergence of the modified cuckoo search algorithm is compared with others to verify the validity of the proposed model and method. The results show that, different micro grid running targets can affect the control strategy of energy storage system, which further affect the signal characteristics of the micro grid. Meanwhile, the convergent speed, computing time and the economy of the modified cuckoo search algorithm are improved compared with the traditional cuckoo search algorithm and differential evolution algorithm.

The strategic framework of tuberculosis control and prevention in the elderly: a scoping review towards End TB targets.

PubMed

Li, Jun; Chung, Pui-Hong; Leung, Cyrus L K; Nishikiori, Nobuyuki; Chan, Emily Y Y; Yeoh, Eng-Kiong

2017-06-01

With the rapid pace of population ageing, tuberculosis (TB) in the elderly increasingly becomes a public health challenge. Despite the increasing burden and high risks for TB in the elderly, targeted strategy has not been well understood and evaluated. We undertook a scoping review to identify current TB strategies, research and policy gaps in the elderly and summarized the results within a strategic framework towards End TB targets. Databases of Embase, MEDLINE, Global health and EBM reviews were searched for original studies, review articles, and policy papers published in English between January 1990 and December 2015. Articles examining TB strategy, program, guideline or intervention in the elderly from public health perspective were included.Nineteen articles met the inclusion criteria. Most of them were qualitative studies, issued in high- and middle-income countries and after 2000. To break the chain of TB transmission and reactivation in the elderly, infection control, interventions of avoiding delay in diagnosis and containment are essential for preventing transmission, especially in elderly institutions and aged immigrants; screening of latent TB infection and preventive therapy had effective impacts on reducing the risk of reactivation and should be used less reluctantly in older people; optimizing early case-finding with a high index of suspicion, systematic screening for prioritized high-risk groups, initial empirical and adequate follow-up treatment with close monitoring and evaluation, as well as enhanced programmatic management are fundamental pillars for active TB elimination. Evaluation of TB epidemiology, risk factors, impacts and cost-effectiveness of interventions, adopting accurate and rapid diagnostic tools, shorter and less toxic preventive therapy, are critical issues for developing strategy in the elderly towards End TB targets.TB control strategies in the elderly were comprehensively mapped in a causal link pathway. The framework and

Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

PubMed

Tkatch, Tatiana; Greotti, Elisa; Baranauskas, Gytis; Pendin, Diana; Roy, Soumitra; Nita, Luliaoana I; Wettmarshausen, Jennifer; Prigge, Matthias; Yizhar, Ofer; Shirihai, Orian S; Fishman, Daniel; Hershfinkel, Michal; Fleidervish, Ilya A; Perocchi, Fabiana; Pozzan, Tullio; Sekler, Israel

2017-06-27

Key mitochondrial functions such as ATP production, Ca 2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH + ) across the inner membrane. Although several drugs can modulate ΔμH + , their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψ m ) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca 2+ dynamics, and respiratory metabolism. By directly modulating Δψ m , the mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and 'hard-to-reach' patients.

PubMed

Quaife, Samantha L; Ruparel, Mamta; Beeken, Rebecca J; McEwen, Andy; Isitt, John; Nolan, Gary; Sennett, Karen; Baldwin, David R; Duffy, Stephen W; Janes, Samuel M; Wardle, Jane

2016-04-20

Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60-75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led 'lung health check' hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. If effective at improving informed uptake of screening and reducing bias in participation, this invitation

Trajectory Control of Rendezvous with Maneuver Target Spacecraft

NASA Technical Reports Server (NTRS)

Zhou, Zhinqiang

2012-01-01

In this paper, a nonlinear trajectory control algorithm of rendezvous with maneuvering target spacecraft is presented. The disturbance forces on the chaser and target spacecraft and the thrust forces on the chaser spacecraft are considered in the analysis. The control algorithm developed in this paper uses the relative distance and relative velocity between the target and chaser spacecraft as the inputs. A general formula of reference relative trajectory of the chaser spacecraft to the target spacecraft is developed and applied to four different proximity maneuvers, which are in-track circling, cross-track circling, in-track spiral rendezvous and cross-track spiral rendezvous. The closed-loop differential equations of the proximity relative motion with the control algorithm are derived. It is proven in the paper that the tracking errors between the commanded relative trajectory and the actual relative trajectory are bounded within a constant region determined by the control gains. The prediction of the tracking errors is obtained. Design examples are provided to show the implementation of the control algorithm. The simulation results show that the actual relative trajectory tracks the commanded relative trajectory tightly. The predicted tracking errors match those calculated in the simulation results. The control algorithm developed in this paper can also be applied to interception of maneuver target spacecraft and relative trajectory control of spacecraft formation flying.

Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases

PubMed Central

Forte, Maurizio; Damato, Antonio; Ambrosio, Mariateresa; Puca, Annibale A.; Sciarretta, Sebastiano; Frati, Giacomo; Vecchione, Carmine

2016-01-01

Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases. PMID:27651855

A summary of the new GINA strategy: a roadmap to asthma control

PubMed Central

Bateman, Eric D.; Becker, Allan; Boulet, Louis-Philippe; Cruz, Alvaro A.; Drazen, Jeffrey M.; Haahtela, Tari; Hurd, Suzanne S.; Inoue, Hiromasa; de Jongste, Johan C.; Lemanske, Robert F.; Levy, Mark L.; O'Byrne, Paul M.; Paggiaro, Pierluigi; Pedersen, Soren E.; Pizzichini, Emilio; Soto-Quiroz, Manuel; Szefler, Stanley J.; Wong, Gary W.K.; FitzGerald, J. Mark

2015-01-01

Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence. This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations. PMID:26206872

Targeting International Terrorism with the Law of Armed Conflict: An Alternative Strategy

DTIC Science & Technology

1991-02-11

AD-A236 582 D TIC III IBII IH IH JUNI 1. 1991. (Unclassified Paper) NAVAL WAR COLLEGE Newport, R.I. TARGETING INTERNATIONAL TERRORISM WITH THE LAW OF...11. TITLE OWN11110 Secrty Ceu4ifction) TARGETING INTERNATIONAL TERRORISM WITH THE LAW OF ARMED CONFLICT: AN ALTERNATIVE STRATEGY (1.) 12, PERSONAL...lawegieforcoperatiosb re forcdaigwt nes.nItiofurther rorimmendgfral rbetos msesnt ofte thkede easuc-tresa en ocnrotadrsodttate-sponsored terrorism . Ti a

The impact of molecular targets in cancer drug development: major hurdles and future strategies.

PubMed

Hebar, Alexandra; Valent, Peter; Selzer, Edgar

2013-01-01

The last decades were characterized by enormous technological advances resulting in a better understanding of disease pathologies and improvement of treatment strategies. The development of targeted drugs, whose beginning can be traced back to Paul Ehrlich's theory of the 'magic bullet' approximately 100 years ago, is today widely appraised as a promising strategy to combat benign, as well as malignant, diseases. Over 40 years after US President Nixon declared the 'war on cancer', treatment outcome, especially of solid tumors in the advanced stages of disease, still lies far behind expectations. In this perspective article, the authors discuss the recent development of targeted cancer drugs and identify major hurdles. The authors further highlight future strategies that might improve and accelerate the drug-development process.

Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

PubMed

Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

2016-12-01

Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

Targeting ticks for control of selected hemoparasitic diseases of cattle.

PubMed

Kocan, K M

1995-03-01

Development in and transmission of hemoparasites by tick vectors are phenomena closely synchronized with the tick feeding cycle. In all known life cycles, initial infection of tick tissues occurs in midgut epithelial cells and transmission is effected as ticks feed after parasites have developed and multiplied in salivary glands. Many factors reviewed affect development and transmission of hemoparasites by ticks including age of ticks, artificial temperature, climate and/or season, tick stage or sex, hemoparasite variation, concurrent infection of ticks with other pathogens, host cell susceptibility, transovarial transmission, effect of hemoparasites on tick biology, and the effect of infecting parasitemia level in cattle on infection rates in ticks. Four hemoparasites of cattle, Anaplasma marginale, Cowdria ruminantium, Theileria parva, and Babesia spp., are all dependent on ticks for biological transmission. Babesia is transmitted transovarially whereas the other three are transmitted transstadially. Mechanical transfer of infective blood via fomites and mouthparts of biting arthropods is also a major means of transmission for Anaplasma marginale but not of the others. Potential control methods for hemoparasites that target parasites as they are developing in their respective tick hosts include tick control, vaccines (against ticks and parasites), and drugs (against ticks and parasites). Successful application of control strategies will be dependent upon thorough understanding of parasite developmental cycles, biology of the tick vectors and the immune response of cattle to ticks and to hemoparasites. The most effective control measures will be those that are targeted against both ticks and the hemoparasites they vector.

Exposure control strategies in the carbonaceous nanomaterial industry.

PubMed

Dahm, Matthew M; Yencken, Marianne S; Schubauer-Berigan, Mary K

2011-06-01

Little is known about exposure control strategies currently being implemented to minimize exposures during the production or use of nanomaterials in the United States. Our goal was to estimate types and quantities of materials used and factors related to workplace exposure reductions among companies manufacturing or using engineered carbonaceous nanomaterials (ECNs). Information was collected through phone surveys on work practices and exposure control strategies from 30 participating producers and users of ECN. The participants were classified into three groups for further examination. We report here the use of exposure control strategies. Observed patterns suggest that large-scale manufacturers report greater use of nanospecific exposure control strategies particularly for respiratory protection. Workplaces producing or using ECN generally report using engineering and administrative controls as well as personal protective equipment to control workplace employee exposure.

40 CFR 52.573 - Control strategy: General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: General. 52.573 Section 52.573 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Georgia> § 52.573 Control strategy: General...

Comparison of individual pitch and smart rotor control strategies for load reduction

NASA Astrophysics Data System (ADS)

Plumley, C.; Leithead, W.; Jamieson, P.; Bossanyi, E.; Graham, M.

2014-06-01

Load reduction is increasingly seen as an essential part of controller and wind turbine design. On large multi-MW wind turbines that experience high levels of wind shear and turbulence across the rotor, individual pitch control and smart rotor control are being considered. While individual pitch control involves adjusting the pitch of each blade individually to reduce the cyclic loadings on the rotor, smart rotor control involves activating control devices distributed along the blades to alter the local aerodynamics of the blades. Here we investigate the effectiveness of using a DQ-axis control and a distributed (independent) control for both individual pitch and trailing edge flap smart rotor control. While load reductions are similar amongst the four strategies across a wide range of variables, including blade root bending moments, yaw bearing and shaft, the pitch actuator requirements vary. The smart rotor pitch actuator has reduced travel, rates, accelerations and power requirements than that of the individual pitch controlled wind turbines. This benefit alone however would be hard to justify the added design complexities of using a smart rotor, which can be seen as an alternative to upgrading the pitch actuator and bearing. In addition, it is found that the independent control strategy is apt at roles that the collective pitch usually targets, such as tower motion and speed control, and it is perhaps here, in supplementing other systems, that the future of the smart rotor lies.

40 CFR 52.1025 - Control strategy: Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Particulate matter. 52.1025 Section 52.1025 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... strategy: Particulate matter. (a) The revisions to the control strategy resulting from the modification to...

40 CFR 52.1025 - Control strategy: Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy: Particulate matter. 52.1025 Section 52.1025 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... strategy: Particulate matter. (a) The revisions to the control strategy resulting from the modification to...

40 CFR 52.1025 - Control strategy: Particulate matter.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Particulate matter. 52.1025 Section 52.1025 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... strategy: Particulate matter. (a) The revisions to the control strategy resulting from the modification to...

40 CFR 52.1025 - Control strategy: Particulate matter.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Particulate matter. 52.1025 Section 52.1025 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... strategy: Particulate matter. (a) The revisions to the control strategy resulting from the modification to...

40 CFR 52.527 - Control strategy: General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: General. 52.527 Section 52.527 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Florida § 52.527 Control strategy: General. (a...

Effective motion planning strategy for space robot capturing targets under consideration of the berth position

NASA Astrophysics Data System (ADS)

Zhang, Xin; Liu, Jinguo

2018-07-01

Although many motion planning strategies for missions involving space robots capturing floating targets can be found in the literature, relatively little has discussed how to select the berth position where the spacecraft base hovers. In fact, the berth position is a flexible and controllable factor, and selecting a suitable berth position has a great impact on improving the efficiency of motion planning in the capture mission. Therefore, to make full use of the manoeuvrability of the space robot, this paper proposes a new viewpoint that utilizes the base berth position as an optimizable parameter to formulate a more comprehensive and effective motion planning strategy. Considering the dynamic coupling, the dynamic singularities, and the physical limitations of space robots, a unified motion planning framework based on the forward kinematics and parameter optimization technique is developed to convert the planning problem into the parameter optimization problem. For getting rid of the strict grasping position constraints in the capture mission, a new conception of grasping area is proposed to greatly simplify the difficulty of the motion planning. Furthermore, by utilizing the penalty function method, a new concise objective function is constructed. Here, the intelligent algorithm, Particle Swarm Optimization (PSO), is worked as solver to determine the free parameters. Two capturing cases, i.e., capturing a two-dimensional (2D) planar target and capturing a three-dimensional (3D) spatial target, are studied under this framework. The corresponding simulation results demonstrate that the proposed method is more efficient and effective for planning the capture missions.

An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

PubMed

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-09-21

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.

40 CFR 52.2033 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Sulfur oxides. 52.2033 Section 52.2033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... strategy: Sulfur oxides. (a) The revision to the control strategy resulting from the modification to the...

40 CFR 52.2033 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy: Sulfur oxides. 52.2033 Section 52.2033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... strategy: Sulfur oxides. (a) The revision to the control strategy resulting from the modification to the...

40 CFR 52.2033 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy: Sulfur oxides. 52.2033 Section 52.2033 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... strategy: Sulfur oxides. (a) The revision to the control strategy resulting from the modification to the...

Efficient community-based control strategies in adaptive networks

NASA Astrophysics Data System (ADS)

Yang, Hui; Tang, Ming; Zhang, Hai-Feng

2012-12-01

Most studies on adaptive networks concentrate on the properties of steady state, but neglect transient dynamics. In this study, we pay attention to the emergence of community structure in the transient process and the effects of community-based control strategies on epidemic spreading. First, by normalizing the modularity, we investigate the evolution of community structure during the transient process, and find that a strong community structure is induced by the rewiring mechanism in the early stage of epidemic dynamics, which, remarkably, delays the outbreak of disease. We then study the effects of control strategies started at different stages on the prevalence. Both immunization and quarantine strategies indicate that it is not ‘the earlier, the better’ for the implementation of control measures. And the optimal control effect is obtained if control measures can be efficiently implemented in the period of a strong community structure. For the immunization strategy, immunizing the susceptible nodes on susceptible-infected links and immunizing susceptible nodes randomly have similar control effects. However, for the quarantine strategy, quarantining the infected nodes on susceptible-infected links can yield a far better result than quarantining infected nodes randomly. More significantly, the community-based quarantine strategy performs better than the community-based immunization strategy. This study may shed new light on the forecast and the prevention of epidemics among humans.

40 CFR 52.350 - Control strategy: Ozone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Ozone. 52.350 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Colorado § 52.350 Control strategy: Ozone. (a) Revisions to the Colorado State Implementation Plan, 1-hour ozone NAAQS Redesignation Request and Maintenance...

40 CFR 52.350 - Control strategy: Ozone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Ozone. 52.350 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Colorado § 52.350 Control strategy: Ozone. (a) Revisions to the Colorado State Implementation Plan, 1-hour ozone NAAQS Redesignation Request and Maintenance...

40 CFR 52.350 - Control strategy: Ozone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Ozone. 52.350 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Colorado § 52.350 Control strategy: Ozone. (a) Revisions to the Colorado State Implementation Plan, 1-hour ozone NAAQS Redesignation Request and Maintenance...

40 CFR 52.350 - Control strategy: Ozone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Ozone. 52.350 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Colorado § 52.350 Control strategy: Ozone. (a) Revisions to the Colorado State Implementation Plan, 1-hour ozone NAAQS Redesignation Request and Maintenance...

40 CFR 52.350 - Control strategy: Ozone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Ozone. 52.350 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Colorado § 52.350 Control strategy: Ozone. (a) Revisions to the Colorado State Implementation Plan, 1-hour ozone NAAQS Redesignation Request and Maintenance...

40 CFR 52.2236 - Control strategy; lead.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy; lead. 52.2236 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Tennessee § 52.2236 Control strategy; lead... SIP on October 6, 1994. These revisions address the requirements necessary to change a lead...

40 CFR 52.2236 - Control strategy; lead.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy; lead. 52.2236 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Tennessee § 52.2236 Control strategy; lead... on October 6, 1994. These revisions address the requirements necessary to change a lead nonattainment...

40 CFR 52.2236 - Control strategy; lead.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy; lead. 52.2236 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Tennessee § 52.2236 Control strategy; lead... on October 6, 1994. These revisions address the requirements necessary to change a lead nonattainment...

40 CFR 52.2236 - Control strategy; lead.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy; lead. 52.2236 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Tennessee § 52.2236 Control strategy; lead... SIP on October 6, 1994. These revisions address the requirements necessary to change a lead...

40 CFR 52.2236 - Control strategy; lead.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy; lead. 52.2236 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Tennessee § 52.2236 Control strategy; lead... on October 6, 1994. These revisions address the requirements necessary to change a lead nonattainment...

Compensatory mechanisms in Great Lakes sea lamprey populations: implications for alternative control strategies

USGS Publications Warehouse

Jones, Michael L.; Bergstedt, R.A.; Twohey, Michael B.; Fodale, Michael F.; Cuddy, Douglas W.; Slade, Jeffrey W.

2003-01-01

Compensatory mechanisms are demographic processes that tend to increase population growth rates at lower population density. These processes will tend to reduce the effectiveness of actions that use controls on reproductive success to suppress sea lamprey (Petromyzon marinus), an economically important pest in the Great Lakes. Historical evidence for compensatory mechanisms in sea lamprey populations was reviewed, and revealed: (1) strong evidence for shifts in sex ratios as sea lamprey abundance was reduced in the early years of the control program; (2) weak and equivocal evidence for increased growth rates of sea lamprey cohorts re-colonizing streams following a lampricide treatment; and (3) suggestions of other compensatory processes, such as earlier ages at metamorphosis, but with little empirical evidence. Larval size distribution data for cohorts in the first and second years following a lampricide treatment (26 pairs of cohorts in 20 streams) was analyzed and did not indicate a consistent pattern of more rapid growth of the first colonizing cohort (only 11 of 33 cases). To test for compensation between spawning and age-1 in sea lamprey populations, data were analyzed for 49 stream-years for which spawning female abundance was known and age-1 abundance was estimated in the following year. A fit of these data to a Ricker stock-recruitment function showed evidence for compensation, measured as reduced survival to age 1 at higher abundance of spawning females. More obvious, however, was a large amount of density-independent variation in survival, which tends to mask evidence for compensatory survival. The results were applied to a simple model that simulates sea lamprey populations and their control in a hypothetical lake. Control strategies that targeted reproductive success performed far less well than comparable strategies that targeted larval populations, because density-independent recruitment variation leads to occasional strong year classes even when

Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization.

PubMed

Wang, Sheng; Huang, Peng; Chen, Xiaoyuan

2016-09-01

Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy].

PubMed

Ilyas, Muhammad; Khaqan, Ali; Iqbal, Jamshed; Riaz, Raja Ali

Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy.

PubMed

Ilyas, Muhammad; Khaqan, Ali; Iqbal, Jamshed; Riaz, Raja Ali

Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Targeting Hispanic populations: future research and prevention strategies.

PubMed Central

Ramirez, A G; McAlister, A; Gallion, K J; Villarreal, R

1995-01-01

Minority populations face a wide variety of economic, institutional, and cultural barriers to health care. These barriers and low levels of education and income pose significant challenges for health professionals in developing cancer research and prevention-control strategies. It is suggested that specific segments of Hispanic populations fit the model of an underdeveloped country in the intermediate stage of epidemiological transition. Since noncommunicable diseases have not yet fully emerged in some of these Hispanic population segments, the opportunity exists to apply primordial prevention strategies. Such campaigns would focus on dissuading members of these populations from adopting negative health behaviors while promoting positive lifestyle choices. Optimal programs would increase cancer screening participation and discourage risk behaviors through community-oriented, population-based interventions. Future directions in prevention and control efforts for minority populations should include expanded health insurance coverage, improved access to health care, greater emphasis on minority recruitment in health care fields, focused epidemiologic and clinical research, and identification and replication of effective components within existing prevention-control programs. PMID:8741800

Strategies that target leukocyte traffic in inflammatory bowel diseases: recent developments.

PubMed

Rivera-Nieves, Jesús

2015-11-01

We review the most recent developments regarding the targeting of molecules involved in the traffic of leukocytes for the treatment of inflammatory bowel diseases (IBD). We discuss the most important findings of one published phase II trial that targeted the β7 integrin (etrolizumab), two phase II trials that targeted the α4β7 integrin ligand: mucosal addressin cell adhesion molecule 1 (MAdCAM-1, PF-00547659), a phase II trial targeting the chemokine IP-10 (CXCL10) in Crohn's, and a phase II trial that targeted the sphingosine-1-phosphate receptor-1: ozanimod in patients with ulcerative colitis. Targeting molecules involved in leukocyte traffic has recently become an effective and well tolerated strategy for the treatment of IBD. Novel approaches now not only target the integrins on the lymphocyte surface, but also its endothelial ligand: MAdCAM-1. As with vedolizumab, antibodies against MAdCAM-1 appear most effective in ulcerative colitis rather than in Crohn's. Targeting chemokines or their receptors does not appear to have the same efficacy as those that target the most stable integrin: immunoglobulin superfamily interactions between the lymphocyte and endothelium. Preliminary results also suggest that the sphingosine-1-phosphate pathway might also be targeted therapeutically in IBD, no longer with parenterally administered antibodies but with orally administered small molecules.

40 CFR 52.1126 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Sulfur oxides. 52... strategy: Sulfur oxides. (a) The revisions to the control strategy resulting from the modification to the..., which allows a relaxation of sulfur in fuel limitations under certain conditions, is approved for the...

40 CFR 52.1126 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Sulfur oxides. 52... strategy: Sulfur oxides. (a) The revisions to the control strategy resulting from the modification to the..., which allows a relaxation of sulfur in fuel limitations under certain conditions, is approved for the...

40 CFR 52.2059 - Control strategy: Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy: Particulate matter... Control strategy: Particulate matter. (a) Pennsylvania has committed to undertake a comprehensive program... Investigating and Controlling Nontraditional Particulate Matter Emissions Task Completion date Scheduled tasks...

40 CFR 52.2059 - Control strategy: Particulate matter.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy: Particulate matter... Control strategy: Particulate matter. (a) Pennsylvania has committed to undertake a comprehensive program... Investigating and Controlling Nontraditional Particulate Matter Emissions Task Completion date Scheduled tasks...

40 CFR 52.2059 - Control strategy: Particulate matter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy: Particulate matter... Control strategy: Particulate matter. (a) Pennsylvania has committed to undertake a comprehensive program... Investigating and Controlling Nontraditional Particulate Matter Emissions Task Completion date Scheduled tasks...

40 CFR 52.2059 - Control strategy: Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Particulate matter... Control strategy: Particulate matter. (a) Pennsylvania has committed to undertake a comprehensive program... Investigating and Controlling Nontraditional Particulate Matter Emissions Task Completion date Scheduled tasks...

Research on particulate filter simulation and regeneration control strategy

NASA Astrophysics Data System (ADS)

Dawei, Qu; Jun, Li; Yu, Liu

2017-03-01

This paper reports a DPF (Diesel Particulate Filter) collection mathematical model for a new regeneration control strategy. The new strategy is composed by main parts, such as regeneration time capturing, temperature rising strategy and regeneration control strategy. In the part of regeneration time capturing, a multi-level regeneration capturing method is put forward based on the combined effect of the PM (Particulate Matter) loading, pressure drop and fuel consumption. The temperature rising strategy proposes the global temperature for all operating conditions. The regeneration control process considers the particle loading density, temperature and oxygen respectively. Based on the analysis of the initial overheating, runaway temperature and local hot spot, the final control strategy is established.

40 CFR 52.930 - Control strategy: Ozone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Ozone. 52.930 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.930 Control strategy: Ozone. (a) The VOC..., Campbell and Kenton Counties) ozone nonattainment area. The demonstration of attainment of the ozone...

40 CFR 52.930 - Control strategy: Ozone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Ozone. 52.930 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.930 Control strategy: Ozone. (a) The VOC..., Campbell and Kenton Counties) ozone nonattainment area. The demonstration of attainment of the ozone...

40 CFR 52.930 - Control strategy: Ozone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Ozone. 52.930 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.930 Control strategy: Ozone. (a) The VOC..., Campbell and Kenton Counties) ozone nonattainment area. The demonstration of attainment of the ozone...

40 CFR 52.523 - Control strategy: Ozone

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Ozone 52.523 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Florida § 52.523 Control strategy: Ozone (a) Disapproval. EPA is disapproving portions of Florida's infrastructure SIP for the 1997 8-hour ozone NAAQS regarding...

40 CFR 52.930 - Control strategy: Ozone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Ozone. 52.930 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.930 Control strategy: Ozone. (a) The VOC..., Campbell and Kenton Counties) ozone nonattainment area. The demonstration of attainment of the ozone...

40 CFR 52.523 - Control strategy: Ozone

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Ozone 52.523 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Florida § 52.523 Control strategy: Ozone (a) Disapproval. EPA is disapproving portions of Florida's infrastructure SIP for the 1997 8-hour ozone NAAQS regarding...

40 CFR 52.930 - Control strategy: Ozone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Ozone. 52.930 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.930 Control strategy: Ozone. (a) The VOC..., Campbell and Kenton Counties) ozone nonattainment area. The demonstration of attainment of the ozone...

40 CFR 52.1375 - Control strategy: Lead.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy: Lead. 52.1375 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1375 Control strategy: Lead. Determination—EPA has determined that the East Helena Lead nonattainment area has attained the lead national...

40 CFR 52.1375 - Control strategy: Lead.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Lead. 52.1375 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1375 Control strategy: Lead. Determination—EPA has determined that the East Helena Lead nonattainment area has attained the lead national...

40 CFR 52.1375 - Control strategy: Lead.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Lead. 52.1375 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1375 Control strategy: Lead. Determination—EPA has determined that the East Helena Lead nonattainment area has attained the lead national...

40 CFR 52.1375 - Control strategy: Lead.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Lead. 52.1375 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1375 Control strategy: Lead. Determination—EPA has determined that the East Helena Lead nonattainment area has attained the lead national...

40 CFR 52.1375 - Control strategy: Lead.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy: Lead. 52.1375 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1375 Control strategy: Lead. Determination—EPA has determined that the East Helena Lead nonattainment area has attained the lead national...

Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success

PubMed Central

Lemoine, Jean Frantz; Desormeaux, Anne Marie; Monestime, Franck; Fayette, Carl Renad; Desir, Luccene; Direny, Abdel Nasser; Carciunoiu, Sarah; Miller, Lior; Knipes, Alaine; Lammie, Patrick; Smith, Penelope; Stockton, Melissa; Trofimovich, Lily; Bhandari, Kalpana; Reithinger, Richard; Crowley, Kathryn; Ottesen, Eric; Baker, Margaret

2016-01-01

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti’s neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a “directly observed treatment” strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained– 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH—and the significant reduction in burden of infection– 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti’s very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of “best practices” for

Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success.

PubMed

Lemoine, Jean Frantz; Desormeaux, Anne Marie; Monestime, Franck; Fayette, Carl Renad; Desir, Luccene; Direny, Abdel Nasser; Carciunoiu, Sarah; Miller, Lior; Knipes, Alaine; Lammie, Patrick; Smith, Penelope; Stockton, Melissa; Trofimovich, Lily; Bhandari, Kalpana; Reithinger, Richard; Crowley, Kathryn; Ottesen, Eric; Baker, Margaret

2016-10-01

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a "directly observed treatment" strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained- 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH-and the significant reduction in burden of infection- 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti's very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of "best practices" for NTD control but

National Drug Control Strategy. Update

ERIC Educational Resources Information Center

Office of National Drug Control Policy, 2005

2005-01-01

The first National Drug Control Strategy set ambitious two and five-year performance based goals: (1) to lower the rate of drug use by 10 percent over 2 years among both youth and adults; and (2) to lower the rate by 25 percent over 5 years. The chapters in this updated version are keyed to the strategies three priorities: (1) Stopping Use Before…

Nonrandom Intrafraction Target Motions and General Strategy for Correction of Spine Stereotactic Body Radiotherapy

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

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Hossain, Sabbir

2009-11-15

Purpose: To characterize nonrandom intrafraction target motions for spine stereotactic body radiotherapy and to develop a method of correction via image guidance. The dependence of target motions, as well as the effectiveness of the correction strategy for lesions of different locations within the spine, was analyzed. Methods and Materials: Intrafraction target motions for 64 targets in 64 patients treated with a total of 233 fractions were analyzed. Based on the target location, the cases were divided into three groups, i.e., cervical (n = 20 patients), thoracic (n = 20 patients), or lumbar-sacrum (n = 24 patients) lesions. For each case,more » time-lag autocorrelation analysis was performed for each degree of freedom of motion that included both translations (x, y, and z shifts) and rotations (roll, yaw, and pitch). A general correction strategy based on periodic interventions was derived to determine the time interval required between two adjacent interventions, to overcome the patient-specific target motions. Results: Nonrandom target motions were detected for 100% of cases regardless of target locations. Cervical spine targets were found to possess the highest incidence of nonrandom target motion compared with thoracic and lumbar-sacral lesions (p < 0.001). The average time needed to maintain the target motion to within 1 mm of translation or 1 deg. of rotational deviation was 5.5 min, 5.9 min, and 7.1 min for cervical, thoracic, and lumbar-sacrum locations, respectively (at 95% confidence level). Conclusions: A high incidence of nonrandom intrafraction target motions was found for spine stereotactic body radiotherapy treatments. Periodic interventions at approximately every 5 minutes or less were needed to overcome such motions.« less

An Energy-Efficient Target-Tracking Strategy for Mobile Sensor Networks.

PubMed

Mahboubi, Hamid; Masoudimansour, Walid; Aghdam, Amir G; Sayrafian-Pour, Kamran

2017-02-01

In this paper, an energy-efficient strategy is proposed for tracking a moving target in an environment with obstacles, using a network of mobile sensors. Typically, the most dominant sources of energy consumption in a mobile sensor network are sensing, communication, and movement. The proposed algorithm first divides the field into a grid of sufficiently small cells. The grid is then represented by a graph whose edges are properly weighted to reflect the energy consumption of sensors. The proposed technique searches for near-optimal locations for the sensors in different time instants to route information from the target to destination, using a shortest path algorithm. Simulations confirm the efficacy of the proposed algorithm.

40 CFR 52.66 - Control Strategy: Ozone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control Strategy: Ozone. 52.66 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.66 Control Strategy: Ozone. (a) The redesignation request submitted by the State of Alabama, on March 16, 1995 for the Birmingham marginal ozone...

40 CFR 52.66 - Control Strategy: Ozone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control Strategy: Ozone. 52.66 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.66 Control Strategy: Ozone. (a) The redesignation request submitted by the State of Alabama, on March 16, 1995 for the Birmingham marginal ozone...

40 CFR 52.582 - Control strategy: Ozone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Ozone. 52.582 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Georgia § 52.582 Control strategy: Ozone. (a) Approval... area has attaining data for the 1997 8-hour ozone NAAQS. This determination, in accordance with 40 CFR...

40 CFR 52.476 - Control strategy: ozone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: ozone. 52.476 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS District of Columbia § 52.476 Control strategy: ozone. (a... of Progress Plan for the District of Columbia's portion of the Metropolitan Washington, D.C. ozone...

40 CFR 52.66 - Control Strategy: Ozone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control Strategy: Ozone. 52.66 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.66 Control Strategy: Ozone. (a) The redesignation request submitted by the State of Alabama, on March 16, 1995 for the Birmingham marginal ozone...

40 CFR 52.476 - Control strategy: ozone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: ozone. 52.476 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS District of Columbia § 52.476 Control strategy: ozone. (a... of Progress Plan for the District of Columbia's portion of the Metropolitan Washington, D.C. ozone...

40 CFR 52.66 - Control Strategy: Ozone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control Strategy: Ozone. 52.66 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.66 Control Strategy: Ozone. (a) The redesignation request submitted by the State of Alabama, on March 16, 1995 for the Birmingham marginal ozone...

40 CFR 52.476 - Control strategy: ozone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: ozone. 52.476 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS District of Columbia § 52.476 Control strategy: ozone. (a... of Progress Plan for the District of Columbia's portion of the Metropolitan Washington, D.C. ozone...

40 CFR 52.726 - Control strategy: Ozone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Ozone. 52.726 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.726 Control strategy: Ozone. Link to an... State of Illinois to satisfy the condition of approval to the ozone State Implementation Plan listed in...

40 CFR 52.377 - Control strategy: Ozone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Ozone. 52.377 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.377 Control strategy: Ozone. Link to an... Air Act, for the Greater Hartford serious ozone nonattainment area, and the Connecticut portion of the...

40 CFR 52.476 - Control strategy: ozone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: ozone. 52.476 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS District of Columbia § 52.476 Control strategy: ozone. (a... of Progress Plan for the District of Columbia's portion of the Metropolitan Washington, D.C. ozone...

40 CFR 52.476 - Control strategy: ozone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: ozone. 52.476 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS District of Columbia § 52.476 Control strategy: ozone. (a... of Progress Plan for the District of Columbia's portion of the Metropolitan Washington, D.C. ozone...

40 CFR 52.726 - Control strategy: Ozone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Ozone. 52.726 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.726 Control strategy: Ozone. Link to an... State of Illinois to satisfy the condition of approval to the ozone State Implementation Plan listed in...

40 CFR 52.582 - Control strategy: Ozone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Ozone. 52.582 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Georgia § 52.582 Control strategy: Ozone. (a) Approval... area has attaining data for the 1997 8-hour ozone NAAQS. This determination, in accordance with 40 CFR...

40 CFR 52.582 - Control strategy: Ozone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Ozone. 52.582 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Georgia § 52.582 Control strategy: Ozone. (a) Approval... area has attaining data for the 1997 8-hour ozone NAAQS. This determination, in accordance with 40 CFR...

40 CFR 52.377 - Control strategy: Ozone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Ozone. 52.377 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.377 Control strategy: Ozone. Link to an... the Greater Hartford serious ozone nonattainment area, and the Connecticut portion of the NY-NJ-CT...

40 CFR 52.797 - Control strategy: Lead.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Lead. 52.797 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.797 Control strategy: Lead. (a)-(b... request to redesignate the County to attainment of the lead standard. (e) On April 1, 2009, Indiana...

40 CFR 52.797 - Control strategy: Lead.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Lead. 52.797 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.797 Control strategy: Lead. (a)-(b... request to redesignate the County to attainment of the lead standard. (e) On April 1, 2009, Indiana...

40 CFR 52.58 - Control strategy: Lead.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Lead. 52.58 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.58 Control strategy: Lead. The lead plan... the lead standard throughout Alabama. The lead plan submitted by the State on October 7, 1985, and...

40 CFR 52.58 - Control strategy: Lead.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Lead. 52.58 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.58 Control strategy: Lead. The lead plan... the lead standard throughout Alabama. The lead plan submitted by the State on October 7, 1985, and...

40 CFR 52.797 - Control strategy: Lead.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Lead. 52.797 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.797 Control strategy: Lead. (a)-(b... request to redesignate the County to attainment of the lead standard. (e) On April 1, 2009, Indiana...

40 CFR 52.58 - Control strategy: Lead.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Lead. 52.58 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.58 Control strategy: Lead. The lead plan... the lead standard throughout Alabama. The lead plan submitted by the State on October 7, 1985, and...

40 CFR 52.58 - Control strategy: Lead.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Lead. 52.58 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.58 Control strategy: Lead. The lead plan... the lead standard throughout Alabama. The lead plan submitted by the State on October 7, 1985, and...

40 CFR 52.58 - Control strategy: Lead.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Lead. 52.58 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.58 Control strategy: Lead. The lead plan... the lead standard throughout Alabama. The lead plan submitted by the State on October 7, 1985, and...

Feature extraction and selection strategies for automated target recognition

NASA Astrophysics Data System (ADS)

Greene, W. Nicholas; Zhang, Yuhan; Lu, Thomas T.; Chao, Tien-Hsin

2010-04-01

Several feature extraction and selection methods for an existing automatic target recognition (ATR) system using JPLs Grayscale Optical Correlator (GOC) and Optimal Trade-Off Maximum Average Correlation Height (OT-MACH) filter were tested using MATLAB. The ATR system is composed of three stages: a cursory regionof- interest (ROI) search using the GOC and OT-MACH filter, a feature extraction and selection stage, and a final classification stage. Feature extraction and selection concerns transforming potential target data into more useful forms as well as selecting important subsets of that data which may aide in detection and classification. The strategies tested were built around two popular extraction methods: Principal Component Analysis (PCA) and Independent Component Analysis (ICA). Performance was measured based on the classification accuracy and free-response receiver operating characteristic (FROC) output of a support vector machine(SVM) and a neural net (NN) classifier.

Targeted intervention strategies to optimise diversion of BMW in the Dublin, Ireland region

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

Purcell, M., E-mail: mary.purcell@cit.ie; Centre for Water Resources Research, School of Architecture, Landscape and Civil Engineering, University College Dublin, Newstead, Belfield, Dublin 4; Magette, W.L.

Highlights: > Previous research indicates that targeted strategies designed for specific areas should lead to improved diversion. > Survey responses and GIS model predictions from previous research were the basis for goal setting. > Then logic modelling and behavioural research were employed to develop site-specific management intervention strategies. > Waste management initiatives can be tailored to specific needs of areas rather than one size fits all means currently used. - Abstract: Urgent transformation is required in Ireland to divert biodegradable municipal waste (BMW) from landfill and prevent increases in overall waste generation. When BMW is optimally managed, it becomes amore » resource with value instead of an unwanted by-product requiring disposal. An analysis of survey responses from commercial and residential sectors for the Dublin region in previous research by the authors proved that attitudes towards and behaviour regarding municipal solid waste is spatially variable. This finding indicates that targeted intervention strategies designed for specific geographic areas should lead to improved diversion rates of BMW from landfill, a requirement of the Landfill Directive 1999/31/EC. In the research described in this paper, survey responses and GIS model predictions from previous research were the basis for goal setting, after which logic modelling and behavioural research were employed to develop site-specific waste management intervention strategies. The main strategies devised include (a) roll out of the Brown Bin (Organics) Collection and Community Workshops in Dun Laoghaire Rathdown, (b) initiation of a Community Composting Project in Dublin City (c) implementation of a Waste Promotion and Motivation Scheme in South Dublin (d) development and distribution of a Waste Booklet to promote waste reduction activities in Fingal (e) region wide distribution of a Waste Booklet to the commercial sector and (f) Greening Irish Pubs Initiative. Each of these

Advanced strategies for quality control of Chinese medicines.

PubMed

Zhao, Jing; Ma, Shuang-Cheng; Li, Shao-Ping

2018-01-05

Quality control is always the critical issue for Chinese medicines (CMs) with their worldwide increasing use. Different from western medicine, CMs are usually considered that multiple constituents are responsible for the therapeutic effects. Therefore, quality control of CMs is a challenge. In 2011, the strategies for quantification, related to the markers, reference compounds and approaches, in quality control of CMs were reviewed (Li, et al., J. Pharm. Biomed. Anal., 2011, 55, 802-809). Since then, some new strategies have been proposed in these fields. Therefore, the review on the strategies for quality control of CMs should be updated to improve the safety and efficacy of CMs. Herein, novel strategies related to quality marker discovery, reference compound development and advanced approaches (focused on glyco-analysis) for quality control, during 2011-2016, were summarized and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel model-based control strategy for aerobic filamentous fungal fed-batch fermentation processes.

PubMed

Mears, Lisa; Stocks, Stuart M; Albaek, Mads O; Cassells, Benny; Sin, Gürkan; Gernaey, Krist V

2017-07-01

A novel model-based control strategy has been developed for filamentous fungal fed-batch fermentation processes. The system of interest is a pilot scale (550 L) filamentous fungus process operating at Novozymes A/S. In such processes, it is desirable to maximize the total product achieved in a batch in a defined process time. In order to achieve this goal, it is important to maximize both the product concentration, and also the total final mass in the fed-batch system. To this end, we describe the development of a control strategy which aims to achieve maximum tank fill, while avoiding oxygen limited conditions. This requires a two stage approach: (i) calculation of the tank start fill; and (ii) on-line control in order to maximize fill subject to oxygen transfer limitations. First, a mechanistic model was applied off-line in order to determine the appropriate start fill for processes with four different sets of process operating conditions for the stirrer speed, headspace pressure, and aeration rate. The start fills were tested with eight pilot scale experiments using a reference process operation. An on-line control strategy was then developed, utilizing the mechanistic model which is recursively updated using on-line measurements. The model was applied in order to predict the current system states, including the biomass concentration, and to simulate the expected future trajectory of the system until a specified end time. In this way, the desired feed rate is updated along the progress of the batch taking into account the oxygen mass transfer conditions and the expected future trajectory of the mass. The final results show that the target fill was achieved to within 5% under the maximum fill when tested using eight pilot scale batches, and over filling was avoided. The results were reproducible, unlike the reference experiments which show over 10% variation in the final tank fill, and this also includes over filling. The variance of the final tank fill is

Efficient Nonlocal M-Control and N-Target Controlled Unitary Gate Using Non-symmetric GHZ States

NASA Astrophysics Data System (ADS)

Chen, Li-Bing; Lu, Hong

2018-03-01

Efficient local implementation of a nonlocal M-control and N-target controlled unitary gate is considered. We first show that with the assistance of two non-symmetric qubit(1)-qutrit(N) Greenberger-Horne-Zeilinger (GHZ) states, a nonlocal 2-control and N-target controlled unitary gate can be constructed from 2 local two-qubit CNOT gates, 2 N local two-qutrit conditional SWAP gates, N local qutrit-qubit controlled unitary gates, and 2 N single-qutrit gates. At each target node, the two third levels of the two GHZ target qutrits are used to expose one and only one initial computational state to the local qutrit-qubit controlled unitary gate, instead of being used to hide certain states from the conditional dynamics. This scheme can be generalized straightforwardly to implement a higher-order nonlocal M-control and N-target controlled unitary gate by using M non-symmetric qubit(1)-qutrit(N) GHZ states as quantum channels. Neither the number of the additional levels of each GHZ target particle nor that of single-qutrit gates needs to increase with M. For certain realistic physical systems, the total gate time may be reduced compared with that required in previous schemes.

40 CFR 52.377 - Control strategy: Ozone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Ozone. 52.377 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.377 Control strategy: Ozone. (a... requirements of sections 172(c)(9) and 182(c)(9) of the Clean Air Act, for the Greater Hartford serious ozone...

40 CFR 52.377 - Control strategy: Ozone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Ozone. 52.377 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.377 Control strategy: Ozone. (a... requirements of sections 172(c)(9) and 182(c)(9) of the Clean Air Act, for the Greater Hartford serious ozone...

40 CFR 52.1681 - Control strategy: Lead.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Lead. 52.1681 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New York § 52.1681 Control strategy: Lead. As part of the attainment demonstration for lead, the State of New York has committed to rate all sources...

40 CFR 52.1681 - Control strategy: Lead.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Lead. 52.1681 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New York § 52.1681 Control strategy: Lead. As part of the attainment demonstration for lead, the State of New York has committed to rate all sources...

40 CFR 52.1681 - Control strategy: Lead.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Lead. 52.1681 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New York § 52.1681 Control strategy: Lead. As part of the attainment demonstration for lead, the State of New York has committed to rate all sources...

40 CFR 52.1681 - Control strategy: Lead.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy: Lead. 52.1681 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New York § 52.1681 Control strategy: Lead. As part of the attainment demonstration for lead, the State of New York has committed to rate all sources...

40 CFR 52.795 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.795 Control strategy: Sulfur dioxide. (a) Revised APC-13 (December 5, 1974 submission) of Indiana's Air Pollution Control regulations...

40 CFR 52.795 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.795 Control strategy: Sulfur dioxide. (a) Revised APC-13 (December 5, 1974 submission) of Indiana's Air Pollution Control regulations...

40 CFR 52.795 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.795 Control strategy: Sulfur dioxide. (a) Revised APC-13 (December 5, 1974 submission) of Indiana's Air Pollution Control regulations...

40 CFR 52.795 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.795 Control strategy: Sulfur dioxide. (a) Revised APC-13 (December 5, 1974 submission) of Indiana's Air Pollution Control regulations...

40 CFR 52.795 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.795 Control strategy: Sulfur dioxide. (a) Revised APC-13 (December 5, 1974 submission) of Indiana's Air Pollution Control regulations...

Bioinspired Gold Nanorod Functionalization Strategies for MUC1-Targeted Imaging and Photothermal Therapy

NASA Astrophysics Data System (ADS)

Zelasko-Leon, Daria Cecylia

The majority of cancers diagnosed in 2016 are epithelial in origin, constituting 85% of all new cases and predicted to account for 78% of all cancer deaths this year. Given these statistics, improving patient outcomes by providing personalized, multimodal, and minimally invasive medical interventions is critically needed. Mucin 1 (MUC1), a transmembrane glycoprotein, extends over 100 nm from cell membranes and is a key marker promoting epithelial carcinogenesis. Due to its antenna-like manifestation, MUC1 is a unique yet underexplored candidate for targeted cancer therapy, with overexpression in >64% of epithelial cancers. To overcome the limitations of existing treatment strategies for epithelial cancer, this dissertation describes a novel platform for nanomedicine, highlighting bioinspired modifications of gold nanorod (AuNR) surfaces for diagnostic cancer imaging and photothermal therapy. An ongoing challenge in the field of nanomedicine is the need for simple and effective strategies for simple surface modification of nanoparticles to facilitate targeting and enhance efficacy. Here, biofunctionalization of AuNRs was achieved with polydopamine (PD) and tannic acid (TA), polyphenolic compounds found in the marine mussel and throughout the plant kingdom that exhibit promiscuous interfacial binding properties. AuNR stabilization was achieved via PD or TA coatings followed by secondary modification with the serum protein, bovine serum albumin (BSA), or glycoprotein-mimetic polymers. The resultant constructs demonstrated good biocompatibility, enabled diagnostic imaging, and facilitated MUC1-specific photothermal treatment of breast and oral cancer cells. The in vivo performance of BSA and PD modified AuNRs was evaluated in two orthotopic animal models of breast cancer. Clinically relevant hyperthermia and high response rates with MUC1-targeted formulations were found, with significant enhancement of progression-free survival and several complete tumor regressions

Tumor-targeted inhibition by a novel strategy - mimoretrovirus expressing siRNA targeting the Pokemon gene.

PubMed

Tian, Zhiqiang; Wang, Huaizhi; Jia, Zhengcai; Shi, Jinglei; Tang, Jun; Mao, Liwei; Liu, Hongli; Deng, Yijing; He, Yangdong; Ruan, Zhihua; Li, Jintao; Wu, Yuzhang; Ni, Bing

2010-12-01

Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)β(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.

[Strategies for sustainable management of commensal rodents. Definitions of control objectives at communal level].

PubMed

Plenge-Bönig, A; Schmolz, E

2014-05-01

The German Act on the Prevention and Control of Infectious Diseases in Man (Infektionsschutzgesetz, IfSG) provides a legal framework for activities and responsibilities concerning communal rodent control. However, actual governance of communal rodent control is relatively heterogeneous, as federal states (Bundesländer) have different or even no regulations for prevention and management of commensal rodent infestations (e.g. brown rats, roof rats and house mice). Control targets and control requirements are rarely precisely defined and often do not go beyond general measures and objectives. Although relevant regulations provide information about agreed preventive measures against rodents, the concept of sustainability is not expressed as such. A centrally managed database-supported municipal rodent control is a key factor for sustainability because it allows a systematic and analytical approach to identify and reduce rodent populations. The definition of control objectives and their establishment in legal decrees is mandatory for the implementation of a sustainable management strategy of rodent populations at a local level. Systematic recording of rodent infestations through municipal-operated monitoring provides the essential data foundation for a targeted rodent management which is already implemented in some German and European cities and nationwide in Denmark. A sustainable rodent management includes a more targeted rodenticide application which in the long-term will lead to an overall reduction of rodenticide use. Thus, the benefits of sustainable rodent management will be a reduction of rodenticide exposure to the environment, prevention of resistance and long-term economical savings.

Analysis of pilot control strategy

NASA Technical Reports Server (NTRS)

Heffley, R. K.; Hanson, G. D.; Jewell, W. F.; Clement, W. F.

1983-01-01

Methods for nonintrusive identification of pilot control strategy and task execution dynamics are presented along with examples based on flight data. The specific analysis technique is Nonintrusive Parameter Identification Procedure (NIPIP), which is described in a companion user's guide (NASA CR-170398). Quantification of pilot control strategy and task execution dynamics is discussed in general terms followed by a more detailed description of how NIPIP can be applied. The examples are based on flight data obtained from the NASA F-8 digital fly by wire airplane. These examples involve various piloting tasks and control axes as well as a demonstration of how the dynamics of the aircraft itself are identified using NIPIP. Application of NIPIP to the AFTI/F-16 flight test program is discussed. Recommendations are made for flight test applications in general and refinement of NIPIP to include interactive computer graphics.

National Drug Control Strategy. 2008 Annual Report

ERIC Educational Resources Information Center

Office of National Drug Control Policy, 2008

2008-01-01

This report presents the 2008 National Drug Control Strategy of the White House Office of National Drug Control Policy. The overarching goal of the President's Strategy is to reduce drug use in America through a balanced approach that focuses on stopping use before it starts, healing America's drug users, and disrupting the market for illegal…

SP-100 initial startup and restart control strategy

NASA Astrophysics Data System (ADS)

Halfen, Frank J.; Wong, Kwok K.; Switick, Dennis M.; Shukla, Jaikaran N.

Startup control strategies for SP-100 are described. Revised control and operating strategies are discussed which have been developed and tested using the SP-100 dynamic simulation model Aries-GFS (Generic Flight System).

Targeting Key Transporters in Tumor Glycolysis as a Novel Anticancer Strategy.

PubMed

Shi, Yunli; Liu, Shengnan; Ahmad, Shabir; Gao, Qingzhi

2018-05-22

Increased glycolysis has been one of the metabolic characteristics known as the Warburg effect. The functional and therapeutic importance of the Warburg effect in targeted therapy is scientifically recognized and the glucose metabolic pathway has become a desirable target of anticancer strategies. Glucose transporters (GLUTs) play an important role in cancer glycolysis to sustain cancer cell proliferation, metastasis and survival. Utilizing the knowledge of differential expression and biological functions of GLUTs offers us the possibility of designing and delivering chemotherapeutics toward targeted tumor tissues for improved cancer selectivity. Inhibition of glucose uptake or glycolysis may effectively kill hypoxic cancer cells. Facilitative drug uptake via active transportation provides the potential opportunity to circumvent the drug resistance in chemotherapy. GLUTs as the hallmarks and biotargets of cancer metabolism enable the design and development of novel targeted theranostic agents. In this updated review, we examine the current scenario of the GLUTs as strategic targets in cancer and the unique concepts for discovery and development of GLUTs-targeted anticancer agents. We highlight the recent progresses on structural biology and underlying mechanism studies of GLUTs, with a brief introduction to the computational approaches in GLUT-mediated drug transport and tumor targeting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies

PubMed Central

Thaker, Nikhil G; Pollack, Ian F

2010-01-01

Median survival of patients with malignant glioma (MG) from time of diagnosis is approximately 1 year, despite surgery, irradiation and conventional chemotherapy. Improving patient outcome relies on our ability to develop more effective therapies that are directed against the unique molecular aberrations within a patient’s tumor. Such molecularly targeted therapies may provide novel treatments that are more effective than conventional chemotherapeutics. Recently developed therapeutic strategies have focused on targeting several core glioma signaling pathways, including pathways mediated by growth-factors, PI3K/Akt/PTEN/mTOR, Ras/Raf/MEK/MAPK and other vital pathways. However, given the molecular diversity, heterogeneity and diverging and converging signaling pathways associated with MG, it is unlikely that any single agent will have efficacy in more than a subset of tumors. Overcoming these therapeutic barriers will require multiple agents that can simultaneously inhibit these processes, providing a rationale for combination therapies. This review summarizes the currently implemented single-agent and combination molecularly targeted therapies for MG. PMID:19951140

An improved PID switching control strategy for type 1 diabetes.

PubMed

Marchetti, Gianni; Barolo, Massimiliano; Jovanovic, Lois; Zisser, Howard; Seborg, Dale E

2006-01-01

In order for an "artificial pancreas" to become a reality for ambulatory use, a practical closed-loop control strategy must be developed and critically evaluated. In this paper, an improved PID control strategy for blood glucose control is proposed and evaluated in silico using a physiologic model of Hovorka et al. The key features of the proposed control strategy are: (i) a switching strategy for initiating PID control after a meal and insulin bolus; (ii) a novel time-varying setpoint trajectory, (iii) noise and derivative filters to reduce sensitivity to sensor noise, and (iv) a systematic controller tuning strategy. Simulation results demonstrate that the proposed control strategy compares favorably to alternatives for realistic conditions that include meal challenges, incorrect carbohydrate meal estimates, changes in insulin sensitivity, and measurement noise.

Emerging strategies for EphA2 receptor targeting for cancer therapeutics.

PubMed

Tandon, Manish; Vemula, Sai Vikram; Mittal, Suresh K

2011-01-01

High mortality rates with cancers warrant further development of earlier diagnostics and better treatment strategies. Membrane-bound erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EphA2) is overexpressed in breast, prostate, urinary bladder, skin, lung, ovary and brain cancers. EphA2 overexpression in cancers, its signaling mechanisms and strategies to target its deregulation. High EphA2 expression in cancer cells is correlated with a poor prognosis associated with recurrence due to enhanced metastasis. Interaction of the EphA2 receptor with its ligand (e.g., ephrinA1) triggers events that are deregulated and implicated in carcinogenesis. EphrinA1-independent oncogenic activity and ephrinA1-dependent tumor suppressor roles for EphA2 are described. Molecular interactions of EphA2 with signaling proteins are associated with the modulation of cytoskeleton dynamics, cell adhesion, proliferation, differentiation and metastasis. The deregulated signaling by EphA2 and its involvement in oncogenesis provide multiple avenues for the rational design of intervention approaches. EphA2 has been tested as a drug target using multiple approaches such as agonist antibodies, RNA interference, immunotherapy, virus vector-mediated gene transfer, small-molecule inhibitors and nanoparticles. With over a decade of research, encouraging results with targeting of EphA2 expression in various pre-clinical cancer models necessitate further studies.

Capacity value of energy storage considering control strategies.

PubMed

Shi, Nian; Luo, Yi

2017-01-01

In power systems, energy storage effectively improves the reliability of the system and smooths out the fluctuations of intermittent energy. However, the installed capacity value of energy storage cannot effectively measure the contribution of energy storage to the generator adequacy of power systems. To achieve a variety of purposes, several control strategies may be utilized in energy storage systems. The purpose of this paper is to study the influence of different energy storage control strategies on the generation adequacy. This paper presents the capacity value of energy storage to quantitatively estimate the contribution of energy storage on the generation adequacy. Four different control strategies are considered in the experimental method to study the capacity value of energy storage. Finally, the analysis of the influence factors on the capacity value under different control strategies is given.

Pac-Man for biotechnology: co-opting degrons for targeted protein degradation to control and alter cell function.

PubMed

Yu, Geng; Rosenberg, Julian N; Betenbaugh, Michael J; Oyler, George A

2015-12-01

Protein degradation in normal living cells is precisely regulated to match the cells' physiological requirements. The selectivity of protein degradation is determined by an elaborate degron-tagging system. Degron refers to an amino acid sequence that encodes a protein degradation signal, which is oftentimes a poly-ubiquitin chain that can be transferred to other proteins. Current understanding of ubiquitination dependent and independent protein degradation processes has expanded the application of degrons for targeted protein degradation and novel cell engineering strategies. Recent findings suggest that small molecules inducing protein association can be exploited to create degrons that target proteins for degradation. Here, recent applications of degron-based targeted protein degradation in eukaryotic organisms are reviewed. The degron mediated protein degradation represents a rapidly tunable methodology to control protein abundance, which has broad application in therapeutics and cellular function control and monitoring. Copyright © 2015. Published by Elsevier Ltd.

Application of capability indices and control charts in the analytical method control strategy.

PubMed

Oliva, Alexis; Llabres Martinez, Matías

2017-08-01

In this study, we assessed the usefulness of control charts in combination with the process capability indices, C pm and C pk , in the control strategy of an analytical method. The traditional X-chart and moving range chart were used to monitor the analytical method over a 2-year period. The results confirmed that the analytical method is in-control and stable. Different criteria were used to establish the specifications limits (i.e. analyst requirements) for fixed method performance (i.e. method requirements). If the specification limits and control limits are equal in breadth, the method can be considered "capable" (C pm  = 1), but it does not satisfy the minimum method capability requirements proposed by Pearn and Shu (2003). Similar results were obtained using the C pk index. The method capability was also assessed as a function of method performance for fixed analyst requirements. The results indicate that the method does not meet the requirements of the analytical target approach. A real-example data of a SEC with light-scattering detection method was used as a model whereas previously published data were used to illustrate the applicability of the proposed approach. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Feature Extraction and Selection Strategies for Automated Target Recognition

NASA Technical Reports Server (NTRS)

Greene, W. Nicholas; Zhang, Yuhan; Lu, Thomas T.; Chao, Tien-Hsin

2010-01-01

Several feature extraction and selection methods for an existing automatic target recognition (ATR) system using JPLs Grayscale Optical Correlator (GOC) and Optimal Trade-Off Maximum Average Correlation Height (OT-MACH) filter were tested using MATLAB. The ATR system is composed of three stages: a cursory region of-interest (ROI) search using the GOC and OT-MACH filter, a feature extraction and selection stage, and a final classification stage. Feature extraction and selection concerns transforming potential target data into more useful forms as well as selecting important subsets of that data which may aide in detection and classification. The strategies tested were built around two popular extraction methods: Principal Component Analysis (PCA) and Independent Component Analysis (ICA). Performance was measured based on the classification accuracy and free-response receiver operating characteristic (FROC) output of a support vector machine(SVM) and a neural net (NN) classifier.

EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers

PubMed Central

Wilson, Joanna B.; Manet, Evelyne; Fahraeus, Robin

2018-01-01

The presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controlling viral gene expression and without EBNA1, the virus cannot persist. EBNA1 itself has been linked to cell transformation but the underlying mechanism of its oncogenic activity has been unclear. However, recent data are starting to shed light on its growth-promoting pathways, suggesting that targeting EBNA1 can have a direct growth suppressing effect. In order to carry out its tasks, EBNA1 interacts with cellular factors and these interactions are potential therapeutic targets, where the aim would be to cripple the virus and thereby rid the tumour cells of any oncogenic activity related to the virus. Another strategy to target EBNA1 is to interfere with its expression. Controlling the rate of EBNA1 synthesis is critical for the virus to maintain a sufficient level to support viral functions, while at the same time, restricting expression is equally important to prevent the immune system from detecting and destroying EBNA1-positive cells. To achieve this balance EBNA1 has evolved a unique repeat sequence of glycines and alanines that controls its own rate of mRNA translation. As the underlying molecular mechanisms for how this repeat suppresses its own rate of synthesis in cis are starting to be better understood, new therapeutic strategies are emerging that aim to modulate the translation of the EBNA1 mRNA. If translation is induced, it could increase the amount of EBNA1-derived antigenic peptides that are presented to the major histocompatibility (MHC) class I pathway and thus, make EBV-carrying cancers better targets for the immune system. If translation is further suppressed, this would provide another means to cripple

Capacity value of energy storage considering control strategies

PubMed Central

Luo, Yi

2017-01-01

In power systems, energy storage effectively improves the reliability of the system and smooths out the fluctuations of intermittent energy. However, the installed capacity value of energy storage cannot effectively measure the contribution of energy storage to the generator adequacy of power systems. To achieve a variety of purposes, several control strategies may be utilized in energy storage systems. The purpose of this paper is to study the influence of different energy storage control strategies on the generation adequacy. This paper presents the capacity value of energy storage to quantitatively estimate the contribution of energy storage on the generation adequacy. Four different control strategies are considered in the experimental method to study the capacity value of energy storage. Finally, the analysis of the influence factors on the capacity value under different control strategies is given. PMID:28558027

Differential response to targeted recruitment strategies to fitness promotion research by African-American women of varying body mass index.

PubMed

Yancey, A K; Miles, O L; McCarthy, W J; Sandoval, G; Hill, J; Leslie, J J; Harrison, G G

2001-01-01

To assess patterns of recruitment into a community-based NCI-funded physical activity and dietary lifestyle change program targeting African-American women. Acquisition of a convenience sample to be screened for participation in a randomized, controlled prevention intervention. African-American-owned and -operated health club located in an area of Los Angeles in which African Americans are concentrated. 893 African-American women. RECRUITMENT STRATEGIES: Social networking/word-of-mouth, staff presentations, mass and targeted media, and physician referral. Completion of screening questionnaire indicating a desire to enroll in the study. Screening questionnaire domains included self-reported height and weight, recent participation in organized weight loss programs, ability to walk one mile unassisted, current medication use, smoking status, personal medical history of cancer, sociodemographic variables, and recruitment source. Sociodemographic and anthropometric characteristics distinguished between respondents obtained through different recruitment strategies. In particular, women with a higher body mass index (BMI) were more likely than those with lower BMIs (P = .014) to be recruited through more personalized methods (eg, social networking). Culturally tailored recruitment strategies are critical in securing the participation of members of "hard-to-reach" populations, who are both under-represented in health promotion research and at high risk for chronic diseases.

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy.

PubMed

Tirados, Inaki; Esterhuizen, Johan; Kovacic, Vanja; Mangwiro, T N Clement; Vale, Glyn A; Hastings, Ian; Solano, Philippe; Lehane, Michael J; Torr, Steve J

2015-01-01

Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised.

Cellular Strategies of Protein Quality Control

PubMed Central

Chen, Bryan; Retzlaff, Marco; Roos, Thomas; Frydman, Judith

2011-01-01

Eukaryotic cells must contend with a continuous stream of misfolded proteins that compromise the cellular protein homeostasis balance and jeopardize cell viability. An elaborate network of molecular chaperones and protein degradation factors continually monitor and maintain the integrity of the proteome. Cellular protein quality control relies on three distinct yet interconnected strategies whereby misfolded proteins can either be refolded, degraded, or delivered to distinct quality control compartments that sequester potentially harmful misfolded species. Molecular chaperones play a critical role in determining the fate of misfolded proteins in the cell. Here, we discuss the spatial and temporal organization of cellular quality control strategies and their implications for human diseases linked to protein misfolding and aggregation. PMID:21746797

Adaptive Control Strategies for Flexible Robotic Arm

NASA Technical Reports Server (NTRS)

Bialasiewicz, Jan T.

1996-01-01

The control problem of a flexible robotic arm has been investigated. The control strategies that have been developed have a wide application in approaching the general control problem of flexible space structures. The following control strategies have been developed and evaluated: neural self-tuning control algorithm, neural-network-based fuzzy logic control algorithm, and adaptive pole assignment algorithm. All of the above algorithms have been tested through computer simulation. In addition, the hardware implementation of a computer control system that controls the tip position of a flexible arm clamped on a rigid hub mounted directly on the vertical shaft of a dc motor, has been developed. An adaptive pole assignment algorithm has been applied to suppress vibrations of the described physical model of flexible robotic arm and has been successfully tested using this testbed.

Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy.

PubMed

Wang, Yi; Wei, Guoqing; Zhang, Xiaobin; Huang, Xuehui; Zhao, Jingya; Guo, Xing; Zhou, Shaobing

2018-03-01

Mitochondrial-targeting therapy is an emerging strategy for enhanced cancer treatment. In the present study, a multistage targeting strategy using doxorubicin-loaded magnetic composite nanoparticles is developed for enhanced efficacy of photothermal and chemical therapy. The nanoparticles with a core-shell-SS-shell architecture are composed of a core of Fe 3 O 4 colloidal nanocrystal clusters, an inner shell of polydopamine (PDA) functionalized with triphenylphosphonium (TPP), and an outer shell of methoxy poly(ethylene glycol) linked to the PDA by disulfide bonds. The magnetic core can increase the accumulation of nanoparticles at the tumor site for the first stage of tumor tissue targeting. After the nanoparticles enter the tumor cells, the second stage of mitochondrial targeting is realized as the mPEG shell is detached from the nanoparticles by redox responsiveness to expose the TPP. Using near-infrared light irradiation at the tumor site, a photothermal effect is generated from the PDA photosensitizer, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the loaded doxorubicin can rapidly enter the mitochondria and subsequently damage the mitochondrial DNA, resulting in cell apoptosis. Thus, the synergism of photothermal therapy and chemotherapy targeting the mitochondria significantly enhances the cancer treatment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two-phase strategy of neural control for planar reaching movements: I. XY coordination variability and its relation to end-point variability.

PubMed

Rand, Miya K; Shimansky, Yury P

2013-03-01

A quantitative model of optimal transport-aperture coordination (TAC) during reach-to-grasp movements has been developed in our previous studies. The utilization of that model for data analysis allowed, for the first time, to examine the phase dependence of the precision demand specified by the CNS for neurocomputational information processing during an ongoing movement. It was shown that the CNS utilizes a two-phase strategy for movement control. That strategy consists of reducing the precision demand for neural computations during the initial phase, which decreases the cost of information processing at the expense of lower extent of control optimality. To successfully grasp the target object, the CNS increases precision demand during the final phase, resulting in higher extent of control optimality. In the present study, we generalized the model of optimal TAC to a model of optimal coordination between X and Y components of point-to-point planar movements (XYC). We investigated whether the CNS uses the two-phase control strategy for controlling those movements, and how the strategy parameters depend on the prescribed movement speed, movement amplitude and the size of the target area. The results indeed revealed a substantial similarity between the CNS's regulation of TAC and XYC. First, the variability of XYC within individual trials was minimal, meaning that execution noise during the movement was insignificant. Second, the inter-trial variability of XYC was considerable during the majority of the movement time, meaning that the precision demand for information processing was lowered, which is characteristic for the initial phase. That variability significantly decreased, indicating higher extent of control optimality, during the shorter final movement phase. The final phase was the longest (shortest) under the most (least) challenging combination of speed and accuracy requirements, fully consistent with the concept of the two-phase control strategy. This paper

2011 National Drug Control Strategy. Executive Summary

ERIC Educational Resources Information Center

Office of National Drug Control Policy, 2011

2011-01-01

In May of 2010, President Obama released the Administration's inaugural "National Drug Control Strategy", a comprehensive approach to combat the public health and safety consequences posed by drug use. Now, a year later, the Administration is releasing its update building upon that initial "Strategy". The "Strategy" establishes ambitious goals to…

Control Law Design for Propofol Infusion to Regulate Depth of Hypnosis: A Nonlinear Control Strategy.

PubMed

Khaqan, Ali; Bilal, Muhammad; Ilyas, Muhammad; Ijaz, Bilal; Ali Riaz, Raja

2015-01-01

Maintaining the depth of hypnosis (DOH) during surgery is one of the major objectives of anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but increases the undue load of an anesthetist in operating room working in a multitasking setup. Manual and target controlled infusion (TCI) systems are not good at handling instabilities like blood pressure changes and heart rate variability arising due to interpatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors to motivate automation in anesthesia. The idea of automated system for Propofol infusion excites the control engineers to come up with a more sophisticated and safe system that handles optimum delivery of drug during surgery and avoids postoperative effects. In contrast to most of the investigations with linear control strategies, the originality of this research work lies in employing a nonlinear control technique, backstepping, to track the desired hypnosis level of patients during surgery. This effort is envisioned to unleash the true capabilities of this nonlinear control technique for anesthesia systems used today in biomedical field. The working of the designed controller is studied on the real dataset of five patients undergoing surgery. The controller tracks the desired hypnosis level within the acceptable range for surgery.

Control Law Design for Propofol Infusion to Regulate Depth of Hypnosis: A Nonlinear Control Strategy

PubMed Central

Khaqan, Ali; Bilal, Muhammad; Ilyas, Muhammad; Ijaz, Bilal; Ali Riaz, Raja

2016-01-01

Maintaining the depth of hypnosis (DOH) during surgery is one of the major objectives of anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but increases the undue load of an anesthetist in operating room working in a multitasking setup. Manual and target controlled infusion (TCI) systems are not good at handling instabilities like blood pressure changes and heart rate variability arising due to interpatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors to motivate automation in anesthesia. The idea of automated system for Propofol infusion excites the control engineers to come up with a more sophisticated and safe system that handles optimum delivery of drug during surgery and avoids postoperative effects. In contrast to most of the investigations with linear control strategies, the originality of this research work lies in employing a nonlinear control technique, backstepping, to track the desired hypnosis level of patients during surgery. This effort is envisioned to unleash the true capabilities of this nonlinear control technique for anesthesia systems used today in biomedical field. The working of the designed controller is studied on the real dataset of five patients undergoing surgery. The controller tracks the desired hypnosis level within the acceptable range for surgery. PMID:27293475

40 CFR 52.2429 - Control strategy: Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Particulate matter. 52.2429 Section 52.2429 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.477 - Control strategy: Particulate matter.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Particulate matter. 52.477 Section 52.477 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.477 - Control strategy: Particulate matter.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Particulate matter. 52.477 Section 52.477 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.1081 - Control strategy: Particulate matter.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Particulate matter. 52.1081 Section 52.1081 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) Determination of Attainment. EPA has determined, as of January...

40 CFR 52.2429 - Control strategy: Particulate matter.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy: Particulate matter. 52.2429 Section 52.2429 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.1131 - Control strategy: Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Particulate matter. 52.1131 Section 52.1131 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) Revisions to the following regulations submitted on March 30...

40 CFR 52.1131 - Control strategy: Particulate matter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy: Particulate matter. 52.1131 Section 52.1131 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) Revisions to the following regulations submitted on March 30...

40 CFR 52.477 - Control strategy: Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Particulate matter. 52.477 Section 52.477 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.1081 - Control strategy: Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy: Particulate matter. 52.1081 Section 52.1081 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) Determination of Attainment. EPA has determined, as of January...

40 CFR 52.2429 - Control strategy: Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy: Particulate matter. 52.2429 Section 52.2429 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.1131 - Control strategy: Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy: Particulate matter. 52.1131 Section 52.1131 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) Revisions to the following regulations submitted on March 30...

40 CFR 52.477 - Control strategy: Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Particulate matter. 52.477 Section 52.477 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.1081 - Control strategy: Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Particulate matter. 52.1081 Section 52.1081 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) Determination of Attainment. EPA has determined, as of January...

40 CFR 52.1081 - Control strategy: Particulate matter.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Particulate matter. 52.1081 Section 52.1081 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) Determination of Attainment. EPA has determined, as of January...

40 CFR 52.2429 - Control strategy: Particulate matter.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy: Particulate matter. 52.2429 Section 52.2429 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.1081 - Control strategy: Particulate matter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy: Particulate matter. 52.1081 Section 52.1081 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) Determination of Attainment. EPA has determined, as of January...

40 CFR 52.2429 - Control strategy: Particulate matter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy: Particulate matter. 52.2429 Section 52.2429 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

40 CFR 52.477 - Control strategy: Particulate matter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Particulate matter. 52.477 Section 52.477 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. Determination of Attainment. EPA has determined, as of January 12...

THE CHOICE OF REAL-TIME CONTROL STRATEGY FOR COMBINED SEWER OVERFLOW CONTROL

EPA Science Inventory

This paper focuses on the strategies used to operate a collection system in real-time control (RTC) in order to optimize use of system capacity and to reduce the cost of long-term combined sewer overflow (CSO) control. Three RTC strategies were developed and analyzed based on the...

Alternative Dual Mode Network Control Strategies

DOT National Transportation Integrated Search

1972-03-01

From a literature survey a qualitative evaluation was made of four network control strategies for the fundamental control philosophy of the moving synchronous slot. In the literature concerning automated transportation systems, such as dual mode, a g...

Development of a targeted transgenesis strategy in highly differentiated cells: a powerful tool for functional genomic analysis.

PubMed

Puttini, Stefania; Ouvrard-Pascaud, Antoine; Palais, Gael; Beggah, Ahmed T; Gascard, Philippe; Cohen-Tannoudji, Michel; Babinet, Charles; Blot-Chabaud, Marcel; Jaisser, Frederic

2005-03-16

Functional genomic analysis is a challenging step in the so-called post-genomic field. Identification of potential targets using large-scale gene expression analysis requires functional validation to identify those that are physiologically relevant. Genetically modified cell models are often used for this purpose allowing up- or down-expression of selected targets in a well-defined and if possible highly differentiated cell type. However, the generation of such models remains time-consuming and expensive. In order to alleviate this step, we developed a strategy aimed at the rapid and efficient generation of genetically modified cell lines with conditional, inducible expression of various target genes. Efficient knock-in of various constructs, called targeted transgenesis, in a locus selected for its permissibility to the tet inducible system, was obtained through the stimulation of site-specific homologous recombination by the meganuclease I-SceI. Our results demonstrate that targeted transgenesis in a reference inducible locus greatly facilitated the functional analysis of the selected recombinant cells. The efficient screening strategy we have designed makes possible automation of the transfection and selection steps. Furthermore, this strategy could be applied to a variety of highly differentiated cells.

Anti-tobacco control industry strategies in Turkey.

PubMed

Keklik, Seda; Gultekin-Karakas, Derya

2018-02-26

Transnational tobacco companies (TTCs) penetrated the Turkish cigarette market due to trade and investment liberalization in the post-1980 period and eventually secured full control. Despite tobacco control policies put in place in reaction to accelerating consumption, TTCs reinforced their market power through a variety of strategies. This paper explores industry strategies that counteract tobacco control policies in Turkey. The study employs both qualitative and quantitative analyses to explore industry strategies in Turkey. Besides the content analyses of industry and market reports, descriptive analyses were conducted for the sub-periods of 1999-2015. The analyses focus on the market strategies of product innovation, advertisement-promotion, cost management and pricing. Rising sales of low tar, ultra-low tar, slim, super-slim and flavoured cigarettes indicate that product innovation served to sustain consumption. Besides, the tobacco industry, using its strong distribution channels, the Internet, and CSR projects, were found to have promoted smoking indirectly. The industry also rationalized manufacturing facilities and reduced the cost of tobacco, making Turkey a cigarette-manufacturing base. Tobacco manufacturers, moreover, offered cigarettes in different price segments and adjusted net prices both up and down according to price categories and market conditions. In response to the successful effect of shifts in price margins, the market share of mid-priced cigarettes expanded while those within the economy category maintained the highest market share. As a result of pricing strategies, net sales revenues increased. Aside from official cigarette sales, the upward trends in the registered and unregistered sales of cigarette substitutes indicate that the demand-side tobacco control efforts remain inadequate. The Turkish case reveals that the resilience of the tobacco industry vis-à-vis mainstream tobacco control efforts necessitates a new policy perspective

A cost-controlling treatment strategy of adding liraglutide to insulin in type 2 diabetes.

PubMed

de Wit, H M; Vervoort, G M M; de Galan, B E; Tack, C J

2017-09-01

Addition of the GLP-1 receptor agonist liraglutide to insulin can reverse insulin-associated weight gain, improve HbA1c and decrease the need for insulin, but is expensive. From a cost perspective, such treatment should be discontinued when it is clear that treatment targets will not be achieved. Our aim was to find the best cost-controlling treatment strategy: the shortest possible trial period needed to discriminate successfully treated patients from those failing to achieve predefined targets of treatment success. We used data from the 'Effect of Liraglutide on insulin-associated wEight GAiN in patients with Type 2 diabetes' (ELEGANT) trial, comparing additional liraglutide (n = 47) and standard insulin therapy (n = 24) during 26 weeks, to calculate the costs associated with different trial periods. Treatment success after 26 weeks was defined by having achieved ≥ 2 of the following: ≥ 4% weight loss, HbA1c ≤ 53 mmol/mol (7%), and/or discontinuation of insulin. The additional direct costs of adding liraglutide for 26 weeks were € 699 per patient, or € 137 per 1 kg weight loss, compared with standard therapy. The best cost-controlling treatment strategy (identifying 21 of 23 responders, treating four non-responders) was to continue treatment in patients showing ≥ 3% weight loss or ≥ 60% decrease in insulin dose at 8 weeks, with a total cost of € 246 for this t rial period, saving € 453 in case of early discontinuation. An 8-week trial period of adding liraglutide to insulin in patients with insulin-associated weight gain is an effective cost-controlling treatment strategy if the liraglutide is discontinued in patients not showing an early response regarding weight loss or insulin reduction.

A comparison of WEC control strategies

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

Wilson, David G.; Bacelli, Giorgio; Coe, Ryan Geoffrey

2016-04-01

The operation of Wave Energy Converter (WEC) devices can pose many challenging problems to the Water Power Community. A key research question is how to significantly improve the performance of these WEC devices through improving the control system design. This report summarizes an effort to analyze and improve the performance of WEC through the design and implementation of control systems. Controllers were selected to span the WEC control design space with the aim of building a more comprehensive understanding of different controller capabilities and requirements. To design and evaluate these control strategies, a model scale test-bed WEC was designed formore » both numerical and experimental testing (see Section 1.1). Seven control strategies have been developed and applied on a numerical model of the selected WEC. This model is capable of performing at a range of levels, spanning from a fully-linear realization to varying levels of nonlinearity. The details of this model and its ongoing development are described in Section 1.2.« less

Multisensory Integration Strategy for Modality-Specific Loss of Inhibition Control in Older Adults.

PubMed

Lee, Ahreum; Ryu, Hokyoung; Kim, Jae-Kwan; Jeong, Eunju

2018-04-11

Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standar Desviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition.

Multisensory Integration Strategy for Modality-Specific Loss of Inhibition Control in Older Adults

PubMed Central

Ryu, Hokyoung; Kim, Jae-Kwan; Jeong, Eunju

2018-01-01

Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standard Deviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition. PMID:29641462

Targeting strategies of mHealth interventions for maternal health in low and middle-income countries: a systematic review protocol

PubMed Central

Abejirinde, Ibukun-Oluwa Omolade; Dieleman, Marjolein; Bardají, Azucena; Broerse, Jacqueline E W; Van Belle, Sara

2018-01-01

Introduction Recently, there has been a steady increase in mobile health (mHealth) interventions aimed at improving maternal health of women in low-income and middle-income countries. While there is evidence indicating that these interventions contribute to improvements in maternal health outcomes, other studies indicate inconclusive results. This uncertainty has raised additional questions, one of which pertains to the role of targeting strategies in implementing mHealth interventions and the focus on pregnant women and health workers as target groups. This review aims to assess who is targeted in different mHealth interventions and the importance of targeting strategies in maternal mHealth interventions. Methods and analysis We will search for peer-reviewed, English-language literature published between 1999 and July 2017 in PubMed, Web of Knowledge (Science Direct, EMBASE) and Cochrane Central Registers of Controlled Trials. The study scope is defined by the Population, Intervention, Comparison and Outcomes framework: P, community members with maternal or reproductive needs; I, electronic health or mHealth programmes geared at improving maternal or reproductive health; C, other non-electronic health or mHealth-based interventions; O, maternal health measures including family planning, antenatal care attendance, health facility delivery and postnatal care attendance. Ethics and dissemination This study is a review of already published or publicly available data and needs no ethical approval. Review results will be published in a peer-reviewed journal and presented at international conferences. PROSPERO registration number CRD42017072280. PMID:29478019

Emerging strategies for EphA2 receptor targeting for cancer therapeutics

PubMed Central

Tandon, Manish; Vemula, Sai Vikram; Mittal, Suresh K.

2010-01-01

Importance of the field High mortality rates with cancers warrant further development of earlier diagnostics and better treatment strategies. Membrane-bound hepatocellular receptor tyrosine kinase class A2 (EphA2) is overexpressed in breast, prostate, urinary bladder, skin, lung, ovary and brain cancers. Areas covered in this review This review describes EphA2 overexpression in cancers, its signaling mechanisms and strategies to target its deregulation. What will the reader will gain High EphA2 expression in cancer cells is correlated to a poor prognosis associated with recurrence due to enhanced metastasis. Interaction of the EphA2 receptor with its ligand (e.g., EphrinA1) triggers events that are deregulated and implicated in carcinogenesis. Both EphrinA1-independent oncogenic activity and EphrinA1-dependent tumor suppressor roles for EphA2 are described. Molecular interactions of EphA2 with signaling proteins are associated with the modulation of cytoskeleton dynamics, cell adhesion, proliferation, differentiation and metastasis. The deregulated signaling by EphA2 and its involvement in oncogenesis provide multiple avenues for the rational design of intervention approaches. Take home message EphA2 has been tested as a drug target using multiple approaches such as agonist antibodies, RNA interference, immunotherapy, virus vectors-mediated gene transfer, small molecule inhibitors and nanoparticles. With over a decade of research, encouraging results with successful targeting of EphA2 expression in various pre-clinical cancer models necessitate further studies. PMID:21142802

40 CFR 52.785 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Carbon monoxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.785 Control strategy: Carbon... for attainment and maintenance of the national standards for carbon monoxide in the Metropolitan...

40 CFR 52.65 - Control Strategy: Nitrogen oxides.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control Strategy: Nitrogen oxides. 52.65 Section 52.65 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.65 Control Strategy: Nitrogen...

40 CFR 52.2353 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy: Carbon monoxide. 52.2353 Section 52.2353 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Utah § 52.2353 Control strategy...

40 CFR 52.1340 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Carbon monoxide. 52.1340 Section 52.1340 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Missouri § 52.1340 Control strategy...

40 CFR 52.1340 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy: Carbon monoxide. 52.1340 Section 52.1340 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Missouri § 52.1340 Control strategy...

40 CFR 52.2353 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Carbon monoxide. 52.2353 Section 52.2353 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Utah § 52.2353 Control strategy...

40 CFR 52.2526 - Control strategy: Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Particulate matter. 52.2526 Section 52.2526 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) EPA approves West Virginia's November 15, 1991 SIP submittal for...

40 CFR 52.1374 - Control strategy: Particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Particulate matter. 52.1374 Section 52.1374 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) On July 8, 1997, the Governor of Montana submitted minor...

40 CFR 52.1374 - Control strategy: Particulate matter.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Particulate matter. 52.1374 Section 52.1374 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) On July 8, 1997, the Governor of Montana submitted minor...

40 CFR 52.1374 - Control strategy: Particulate matter.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Particulate matter. 52.1374 Section 52.1374 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) On July 8, 1997, the Governor of Montana submitted minor...

40 CFR 52.1341 - Control strategy: particulate matter.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: particulate matter. 52.1341 Section 52.1341 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: particulate matter. Determination of Attainment. EPA has determined, as of May 23, 2011...

40 CFR 52.2526 - Control strategy: Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy: Particulate matter. 52.2526 Section 52.2526 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) EPA approves West Virginia's November 15, 1991 SIP submittal for...

40 CFR 52.2526 - Control strategy: Particulate matter.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy: Particulate matter. 52.2526 Section 52.2526 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) EPA approves West Virginia's November 15, 1991 SIP submittal for...

40 CFR 52.2526 - Control strategy: Particulate matter.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy: Particulate matter. 52.2526 Section 52.2526 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) EPA approves West Virginia's November 15, 1991 SIP submittal for...

40 CFR 52.1374 - Control strategy: Particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy: Particulate matter. 52.1374 Section 52.1374 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) On July 8, 1997, the Governor of Montana submitted minor...

40 CFR 52.1374 - Control strategy: Particulate matter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy: Particulate matter. 52.1374 Section 52.1374 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) On July 8, 1997, the Governor of Montana submitted minor...

40 CFR 52.1341 - Control strategy: particulate matter.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 4 2012-07-01 2012-07-01 false Control strategy: particulate matter. 52.1341 Section 52.1341 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: particulate matter. Determination of Attainment. EPA has determined, as of May 23, 2011...

40 CFR 52.2526 - Control strategy: Particulate matter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy: Particulate matter. 52.2526 Section 52.2526 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Control strategy: Particulate matter. (a) EPA approves West Virginia's November 15, 1991 SIP submittal for...

40 CFR 52.65 - Control Strategy: Nitrogen oxides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control Strategy: Nitrogen oxides. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.65 Control Strategy: Nitrogen... using to implement provisions of the Prevention of Significant Deterioration regulations for nitrogen...

40 CFR 52.65 - Control Strategy: Nitrogen oxides.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control Strategy: Nitrogen oxides. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.65 Control Strategy: Nitrogen... using to implement provisions of the Prevention of Significant Deterioration regulations for nitrogen...

40 CFR 52.65 - Control Strategy: Nitrogen oxides.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control Strategy: Nitrogen oxides. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.65 Control Strategy: Nitrogen... using to implement provisions of the Prevention of Significant Deterioration regulations for nitrogen...

40 CFR 52.65 - Control Strategy: Nitrogen oxides.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control Strategy: Nitrogen oxides. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.65 Control Strategy: Nitrogen... using to implement provisions of the Prevention of Significant Deterioration regulations for nitrogen...

40 CFR 52.349 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Carbon monoxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Colorado § 52.349 Control strategy: Carbon monoxide. (a) Revisions to the Colorado State Implementation Plan, Carbon Monoxide Redesignation Request...

40 CFR 52.724 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.724 Control strategy: Sulfur... Board necessary to insure attainment and maintenance of the sulfur dioxide standard, and the...

40 CFR 52.834 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Sulfur dioxide. 52.834 Section 52.834 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Iowa § 52.834 Control strategy: Sulfur dioxide...

40 CFR 52.928 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Sulfur oxides. 52.928 Section 52.928 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.928 Control strategy: Sulfur...

40 CFR 52.928 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Sulfur oxides. 52.928 Section 52.928 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.928 Control strategy: Sulfur...

40 CFR 52.724 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.724 Control strategy: Sulfur... Board necessary to insure attainment and maintenance of the sulfur dioxide standard, and the...

40 CFR 52.724 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.724 Control strategy: Sulfur... Board necessary to insure attainment and maintenance of the sulfur dioxide standard, and the...

40 CFR 52.834 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Sulfur dioxide. 52.834 Section 52.834 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Iowa § 52.834 Control strategy: Sulfur dioxide...

40 CFR 52.834 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Sulfur dioxide. 52.834 Section 52.834 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Iowa § 52.834 Control strategy: Sulfur dioxide...

40 CFR 52.724 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.724 Control strategy: Sulfur... Board necessary to insure attainment and maintenance of the sulfur dioxide standard, and the...

40 CFR 52.834 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Sulfur dioxide. 52.834 Section 52.834 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Iowa § 52.834 Control strategy: Sulfur dioxide...

40 CFR 52.928 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Sulfur oxides. 52.928 Section 52.928 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.928 Control strategy: Sulfur...

40 CFR 52.834 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Sulfur dioxide. 52.834 Section 52.834 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Iowa § 52.834 Control strategy: Sulfur dioxide...

40 CFR 52.928 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Sulfur oxides. 52.928 Section 52.928 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.928 Control strategy: Sulfur...

40 CFR 52.928 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Sulfur oxides. 52.928 Section 52.928 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.928 Control strategy: Sulfur...

40 CFR 52.724 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Sulfur dioxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.724 Control strategy: Sulfur... Board necessary to insure attainment and maintenance of the sulfur dioxide standard, and the...

Four-Week Strategy-Based Training to Enhance Prospective Memory in Older Adults: Targeting Intention Retention Is More Beneficial than Targeting Intention Formation.

PubMed

Ihle, Andreas; Albiński, Rafal; Gurynowicz, Kamila; Kliegel, Matthias

2018-01-01

So far, training of prospective memory (PM) focused on very short instances (single sessions) and targeted the intention-formation phase only. We aimed to compare the effectiveness of 2 different 4-week strategy-based PM training types, namely imagery training (targeting the encoding of the PM intention in the intention-formation phase) versus rehearsal training (targeting the maintenance of the PM intention in the intention-retention phase) in older adults. We used a 4-week training protocol (8 sessions in total, 2 sessions per week). From the 44 participants, 21 were randomly assigned to the imagery training (vividly imagining a mental picture to memorize the connection between the PM cue words and related actions during intention formation) and 23 to the rehearsal training (rehearsing the PM cue words during intention retention). The criterion PM task was assessed before and after the training. Comparing the effectiveness of both training types, we found a significant time by training type interaction on PM accuracy in terms of PM cue detection, F(1, 42) = 6.07, p = 0.018, η2p = 0.13. Subsequent analyses revealed that the rehearsal training was more effective in enhancing PM accuracy in terms of PM cue detection than the imagery training. Strategy-based PM training in older adults targeting the maintenance of the PM intention in the intention-retention phase may be more effective in enhancing PM accuracy in terms of PM cue detection than the strategy targeting the encoding of the PM intention in the intention-formation phase. This suggests that for successful prospective remembering, older adults may need more support to keep the PM cues active in memory while working on the ongoing task than to initially encode the PM intention. © 2018 S. Karger AG, Basel.

Strategies to diagnose and control microbial souring in natural gas storage reservoirs and produced water systems

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

Morris, E.A.; Derr, R.M.; Pope, D.H.

1995-12-31

Hydrogen sulfide production (souring) in natural gas storage reservoirs and produced water systems is a safety and environmental problem that can lead to operational shutdown when local hydrogen sulfide standards are exceeded. Systems affected by microbial souring have historically been treated using biocides that target the general microbial community. However, requirements for more environmentally friendly solutions have led to treatment strategies in which sulfide production can be controlled with minimal impact to the system and environment. Some of these strategies are based on microbial and/or nutritional augmentation of the sour environment. Through research sponsored by the Gas Research Institute (GRI)more » in Chicago, Illinois, methods have been developed for early detection of microbial souring in natural gas storage reservoirs, and a variety of mitigation strategies have been evaluated. The effectiveness of traditional biocide treatment in gas storage reservoirs was shown to depend heavily on the methods by which the chemical is applied. An innovative strategy using nitrate was tested and proved ideal for produced water and wastewater systems. Another strategy using elemental iodine was effective for sulfide control in evaporation ponds and is currently being tested in microbially sour natural gas storage wells.« less

A real-time comparison between direct control, sequential pattern recognition control and simultaneous pattern recognition control using a Fitts’ law style assessment procedure

PubMed Central

2014-01-01

Background Pattern recognition (PR) based strategies for the control of myoelectric upper limb prostheses are generally evaluated through offline classification accuracy, which is an admittedly useful metric, but insufficient to discuss functional performance in real time. Existing functional tests are extensive to set up and most fail to provide a challenging, objective framework to assess the strategy performance in real time. Methods Nine able-bodied and two amputee subjects gave informed consent and participated in the local Institutional Review Board approved study. We designed a two-dimensional target acquisition task, based on the principles of Fitts’ law for human motor control. Subjects were prompted to steer a cursor from the screen center of into a series of subsequently appearing targets of different difficulties. Three cursor control systems were tested, corresponding to three electromyography-based prosthetic control strategies: 1) amplitude-based direct control (the clinical standard of care), 2) sequential PR control, and 3) simultaneous PR control, allowing for a concurrent activation of two degrees of freedom (DOF). We computed throughput (bits/second), path efficiency (%), reaction time (second), and overshoot (%)) and used general linear models to assess significant differences between the strategies for each metric. Results We validated the proposed methodology by achieving very high coefficients of determination for Fitts’ law. Both PR strategies significantly outperformed direct control in two-DOF targets and were more intuitive to operate. In one-DOF targets, the simultaneous approach was the least precise. The direct control was efficient in one-DOF targets but cumbersome to operate in two-DOF targets through a switch-depended sequential cursor control. Conclusions We designed a test, capable of comprehensively describing prosthetic control strategies in real time. When implemented on control subjects, the test was able to capture

A real-time comparison between direct control, sequential pattern recognition control and simultaneous pattern recognition control using a Fitts' law style assessment procedure.

PubMed

Wurth, Sophie M; Hargrove, Levi J

2014-05-30

Pattern recognition (PR) based strategies for the control of myoelectric upper limb prostheses are generally evaluated through offline classification accuracy, which is an admittedly useful metric, but insufficient to discuss functional performance in real time. Existing functional tests are extensive to set up and most fail to provide a challenging, objective framework to assess the strategy performance in real time. Nine able-bodied and two amputee subjects gave informed consent and participated in the local Institutional Review Board approved study. We designed a two-dimensional target acquisition task, based on the principles of Fitts' law for human motor control. Subjects were prompted to steer a cursor from the screen center of into a series of subsequently appearing targets of different difficulties. Three cursor control systems were tested, corresponding to three electromyography-based prosthetic control strategies: 1) amplitude-based direct control (the clinical standard of care), 2) sequential PR control, and 3) simultaneous PR control, allowing for a concurrent activation of two degrees of freedom (DOF). We computed throughput (bits/second), path efficiency (%), reaction time (second), and overshoot (%)) and used general linear models to assess significant differences between the strategies for each metric. We validated the proposed methodology by achieving very high coefficients of determination for Fitts' law. Both PR strategies significantly outperformed direct control in two-DOF targets and were more intuitive to operate. In one-DOF targets, the simultaneous approach was the least precise. The direct control was efficient in one-DOF targets but cumbersome to operate in two-DOF targets through a switch-depended sequential cursor control. We designed a test, capable of comprehensively describing prosthetic control strategies in real time. When implemented on control subjects, the test was able to capture statistically significant differences (p < 0

Economic analysis of HPAI control in the Netherlands II: comparison of control strategies.

PubMed

Longworth, N; Mourits, M C M; Saatkamp, H W

2014-06-01

A combined epidemiological-economic modelling approach was used to analyse strategies for highly pathogenic avian influenza (HPAI) control for the Netherlands. The modelling framework used was InterSpread Plus (ISP), a spatially based, stochastic and dynamic simulation model. A total of eight control strategies were analysed, including pre-emptive depopulation and vaccination strategies. The analysis was carried out for three different regions in the Netherlands: high-, medium- and low-density areas (HDA, MDA and LDA, respectively). The analysis included the veterinary impact (e.g. number of infected premises and duration), but was particularly focused on the impact on direct costs (DC) and direct consequential costs. The efficient set of control strategies for HDA and MDA included strategies based on either pre-emptive depopulation only or combined vaccination and pre-emptive depopulation: D2 (pre-emptive depopulation within a radius of 2 km), RV3 + D1 (ring vaccination within a radius of 3 km and additional pre-emptive depopulation within a radius of 1 km) and PV + D1 (preventive vaccination in non-affected HDAs and pre-emptive depopulation within a radius of 1 km in the affected HDA). Although control solely based on depopulation in most cases showed to be effective for LDA, pre-emptive depopulation showed to have an additional advantage in these areas, that is, prevention of 'virus jumps' to other areas. The pros and cons of the efficient control strategies were discussed, for example, public perception and risk of export restrictions. It was concluded that for the Netherlands control of HPAI preferably should be carried out using strategies including pre-emptive depopulation with or without vaccination. Particularly, the short- and long-term implications on export, that is, indirect consequential costs (ICC) and aftermath costs of these strategies, should be analysed further. © 2012 Blackwell Verlag GmbH.

The insect ecdysone receptor is a good potential target for RNAi-based pest control.

PubMed

Yu, Rong; Xu, Xinping; Liang, Yongkang; Tian, Honggang; Pan, Zhanqing; Jin, Shouheng; Wang, Na; Zhang, Wenqing

2014-01-01

RNA interference (RNAi) has great potential for use in insect pest control. However, some significant challenges must be overcome before RNAi-based pest control can become a reality. One challenge is the proper selection of a good target gene for RNAi. Here, we report that the insect ecdysone receptor (EcR) is a good potential target for RNAi-based pest control in the brown planthopper Nilaparvata lugens, a serious insect pest of rice plants. We demonstrated that the use of a 360 bp fragment (NlEcR-c) that is common between NlEcR-A and NlEcR-B for feeding RNAi experiments significantly decreased the relative mRNA expression levels of NlEcR compared with those in the dsGFP control. Feeding RNAi also resulted in a significant reduction in the number of offspring per pair of N. lugens. Consequently, a transgenic rice line expressing NlEcR dsRNA was constructed by Agrobacterium- mediated transformation. The results of qRT-PCR showed that the total copy number of the target gene in all transgenic rice lines was 2. Northern blot analysis showed that the small RNA of the hairpin dsNlEcR-c was successfully expressed in the transgenic rice lines. After newly hatched nymphs of N. lugens fed on the transgenic rice lines, effective RNAi was observed. The NlEcR expression levels in all lines examined were decreased significantly compared with the control. In all lines, the survival rate of the nymphs was nearly 90%, and the average number of offspring per pair in the treated groups was significantly less than that observed in the control, with a decrease of 44.18-66.27%. These findings support an RNAi-based pest control strategy and are also important for the management of rice insect pests.

40 CFR 52.376 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Carbon monoxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.376 Control strategy: Carbon... submitted a revision to the carbon monoxide State Implementation Plan for the 1990 base year emission...

40 CFR 52.378 - Control strategy: PM10

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: PM10 52.378 Section 52.378 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.378 Control strategy: PM10 (a) Approval...

40 CFR 52.1132 - Control strategy: Carbon Monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Carbon Monoxide. 52.1132 Section 52.1132 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Massachusetts § 52.1132 Control strategy: Carbon Monoxide. (a)...

40 CFR 52.1132 - Control strategy: Carbon Monoxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Carbon Monoxide. 52.1132 Section 52.1132 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Massachusetts § 52.1132 Control strategy: Carbon Monoxide. (a)...

40 CFR 52.1132 - Control strategy: Carbon Monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Carbon Monoxide. 52.1132 Section 52.1132 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Massachusetts § 52.1132 Control strategy: Carbon Monoxide. (a)...

40 CFR 52.376 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.376 Control strategy: Carbon... submitted a revision to the carbon monoxide State Implementation Plan for the 1990 base year emission...

40 CFR 52.376 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.376 Control strategy: Carbon... submitted a revision to the carbon monoxide State Implementation Plan for the 1990 base year emission...

40 CFR 52.376 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Carbon monoxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.376 Control strategy: Carbon... submitted a revision to the carbon monoxide State Implementation Plan for the 1990 base year emission...

40 CFR 52.376 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Carbon monoxide. 52... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Connecticut § 52.376 Control strategy: Carbon... submitted a revision to the carbon monoxide State Implementation Plan for the 1990 base year emission...

On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry.

PubMed

Long, Marcus J C; Poganik, Jesse R; Aye, Yimon

2016-03-23

Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is "tethering"-a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein-protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: "multifunctional scaffolding" versus "on-demand targeting". By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms.

Using cost-effectiveness analysis to evaluate targeting strategies: the case of vitamin A supplementation.

PubMed

Loevinsohn, B P; Sutter, R W; Costales, M O

1997-03-01

Given the demonstrated efficacy of vitamin A supplements in reducing childhood mortality, health officials now have to decide whether it would be efficient to target the supplements to high risk children. Decisions about targeting are complex because they depend on a number of factors; the degree of clustering of preventable deaths, the cost of the intervention, the side-effects of the intervention, the cost of identifying the high risk group, and the accuracy of the 'diagnosis' of risk. A cost-effectiveness analysis was used in the Philippines to examine whether vitamin A supplements should be given universally to all children 6-59 months, targeted broadly to children suffering from mild, moderate, or severe malnutrition, or targeted narrowly to pre-schoolers with moderate and severe malnutrition. The first year average cost of the universal approach was US$67.21 per death averted compared to $144.12 and $257.20 for the broad and narrow targeting approaches respectively. When subjected to sensitivity analysis the conclusion about the most cost-effective strategy was robust to changes in underlying assumptions such as the efficacy of supplements, clustering of deaths, and toxicity. Targeting vitamin A supplements to high risk children is not an efficient use of resources. Based on the results of this cost-effectiveness analysis and a consideration of alternate strategies, it is apparent that vitamin A, like immunization, should be provided to all pre-schoolers in the developing world. Issues about targeting public health interventions can usefully be addressed by cost-effectiveness analysis.

Managing Air Quality - Control Strategies to Achieve Air Pollution Reduction

EPA Pesticide Factsheets

Considerations in designing an effective control strategy related to air quality, controlling pollution sources, need for regional or national controls, steps to developing a control strategy, and additional EPA resources.

Hierarchical Control Strategy for the Cooperative Braking System of Electric Vehicle.

PubMed

Peng, Jiankun; He, Hongwen; Liu, Wei; Guo, Hongqiang

2015-01-01

This paper provides a hierarchical control strategy for cooperative braking system of an electric vehicle with separated driven axles. Two layers are defined: the top layer is used to optimize the braking stability based on two sliding mode control strategies, namely, the interaxle control mode and signal-axle control strategies; the interaxle control strategy generates the ideal braking force distribution in general braking condition, and the single-axle control strategy can ensure braking safety in emergency braking condition; the bottom layer is used to maximize the regenerative braking energy recovery efficiency with a reallocated braking torque strategy; the reallocated braking torque strategy can recovery braking energy as much as possible in the premise of meeting battery charging power. The simulation results show that the proposed hierarchical control strategy is reasonable and can adapt to different typical road surfaces and load cases; the vehicle braking stability and safety can be guaranteed; furthermore, the regenerative braking energy recovery efficiency can be improved.

Hierarchical Control Strategy for the Cooperative Braking System of Electric Vehicle

PubMed Central

Peng, Jiankun; He, Hongwen; Guo, Hongqiang

2015-01-01

This paper provides a hierarchical control strategy for cooperative braking system of an electric vehicle with separated driven axles. Two layers are defined: the top layer is used to optimize the braking stability based on two sliding mode control strategies, namely, the interaxle control mode and signal-axle control strategies; the interaxle control strategy generates the ideal braking force distribution in general braking condition, and the single-axle control strategy can ensure braking safety in emergency braking condition; the bottom layer is used to maximize the regenerative braking energy recovery efficiency with a reallocated braking torque strategy; the reallocated braking torque strategy can recovery braking energy as much as possible in the premise of meeting battery charging power. The simulation results show that the proposed hierarchical control strategy is reasonable and can adapt to different typical road surfaces and load cases; the vehicle braking stability and safety can be guaranteed; furthermore, the regenerative braking energy recovery efficiency can be improved. PMID:26236772

Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy.

PubMed

Zhu, Bo; Tang, Liming; Chen, Shuyang; Yin, Chengqian; Peng, Shiguang; Li, Xin; Liu, Tongzheng; Liu, Wei; Han, Changpeng; Stawski, Lukasz; Xu, Zhi-Xiang; Zhou, Guangbiao; Chen, Xiang; Gao, Xiumei; Goding, Colin R; Xu, Nan; Cui, Rutao; Cao, Peng

2018-05-22

Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2). Depletion of NRF2 significantly induces tumor infiltration by both CD8 + and CD4 + T cells to suppress melanoma progression, and combining NRF2 inhibition with anti-PD-1 treatment enhanced its anti-tumor function. Our studies identify a critical and targetable PD-L1 upstream regulator and provide an alternative strategy to inhibit the PD-1/PD-L1 signaling in melanoma treatment.

Bowel Retraining: Strategies for Establishing Bowel Control

MedlinePlus

... Us Search Bowel Retraining: Strategies for Establishing Bowel Control Home Bowel Retraining Details Treatment Last Updated: 29 ... help people with bowel disorders establish or reestablish control. Individuals with symptoms of inability to control bowel ...

40 CFR 52.1340 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.1340 Section 52.1340 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Missouri § 52.1340 Control strategy: Carbon monoxide. Approval—A...

40 CFR 52.1179 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.1179 Section 52.1179 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Michigan § 52.1179 Control strategy: Carbon monoxide. (a) Approval—On...

40 CFR 52.2353 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.2353 Section 52.2353 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Utah § 52.2353 Control strategy: Carbon monoxide. Determination. EPA has...

40 CFR 52.729 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.729 Section 52.729 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.729 Control strategy: Carbon monoxide. The following source specific...

40 CFR 52.1528 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.1528 Section 52.1528 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Hampshire § 52.1528 Control strategy: Carbon monoxide. (a)...

40 CFR 52.2353 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.2353 Section 52.2353 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Utah § 52.2353 Control strategy: Carbon monoxide. Determination. EPA has...

40 CFR 52.729 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.729 Section 52.729 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.729 Control strategy: Carbon monoxide. The following source specific...

40 CFR 52.1179 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.1179 Section 52.1179 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Michigan § 52.1179 Control strategy: Carbon monoxide. (a) Approval—On...

40 CFR 52.1528 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.1528 Section 52.1528 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Hampshire § 52.1528 Control strategy: Carbon monoxide. (a)...

40 CFR 52.729 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Carbon monoxide. 52.729 Section 52.729 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Illinois> § 52.729 Control strategy: Carbon monoxide. The following source specific...

40 CFR 52.1185 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.1185 Section 52.1185 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Michigan § 52.1185 Control strategy: Carbon monoxide. (a) Approval—On...

40 CFR 52.1340 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.1340 Section 52.1340 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Missouri § 52.1340 Control strategy: Carbon monoxide. Approval—A...

40 CFR 52.1185 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.1185 Section 52.1185 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Michigan § 52.1185 Control strategy: Carbon monoxide. (a) Approval—On...

40 CFR 52.57 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Sulfur oxides. 52.57... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.57 Control strategy: Sulfur oxides... for attainment and maintenance of the national standards for sulfur oxides in the vicinity of the...

40 CFR 52.57 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Sulfur oxides. 52.57... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.57 Control strategy: Sulfur oxides... for attainment and maintenance of the national standards for sulfur oxides in the vicinity of the...

40 CFR 52.57 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Sulfur oxides. 52.57... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.57 Control strategy: Sulfur oxides... for attainment and maintenance of the national standards for sulfur oxides in the vicinity of the...

40 CFR 52.57 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Control strategy: Sulfur oxides. 52.57... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.57 Control strategy: Sulfur oxides... for attainment and maintenance of the national standards for sulfur oxides in the vicinity of the...

40 CFR 52.57 - Control strategy: Sulfur oxides.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Sulfur oxides. 52.57... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Alabama § 52.57 Control strategy: Sulfur oxides... for attainment and maintenance of the national standards for sulfur oxides in the vicinity of the...

Control strategies for robots in contact

NASA Astrophysics Data System (ADS)

Park, Jaeheung

In the field of robotics, there is a growing need to provide robots with the ability to interact with complex and unstructured environments. Operations in such environments pose significant challenges in terms of sensing, planning, and control. In particular, it is critical to design control algorithms that account for the dynamics of the robot and environment at multiple contacts. The work in this thesis focuses on the development of a control framework that addresses these issues. The approaches are based on the operational space control framework and estimation methods. By accounting for the dynamics of the robot and environment, modular and systematic methods are developed for robots interacting with the environment at multiple locations. The proposed force control approach demonstrates high performance in the presence of uncertainties. Building on this basic capability, new control algorithms have been developed for haptic teleoperation, multi-contact interaction with the environment, and whole body motion of non-fixed based robots. These control strategies have been experimentally validated through simulations and implementations on physical robots. The results demonstrate the effectiveness of the new control structure and its robustness to uncertainties. The contact control strategies presented in this thesis are expected to contribute to the needs in advanced controller design for humanoid and other complex robots interacting with their environments.

Model-based development of low-level control strategies for transient operation of solid oxide fuel cell systems

NASA Astrophysics Data System (ADS)

Sorrentino, Marco; Pianese, Cesare

The exploitation of an SOFC-system model to define and test control and energy management strategies is presented. Such a work is motivated by the increasing interest paid to SOFC technology by industries and governments due to its highly appealing potentialities in terms of energy savings, fuel flexibility, cogeneration, low-pollution and low-noise operation. The core part of the model is the SOFC stack, surrounded by a number of auxiliary devices, i.e. air compressor, regulating pressure valves, heat exchangers, pre-reformer and post-burner. Due to the slow thermal dynamics of SOFCs, a set of three lumped-capacity models describes the dynamic response of fuel cell and heat exchangers to any operation change. The dynamic model was used to develop low-level control strategies aimed at guaranteeing targeted performance while keeping stack temperature derivative within safe limits to reduce stack degradation due to thermal stresses. Control strategies for both cold-start and warmed-up operations were implemented by combining feedforward and feedback approaches. Particularly, the main cold-start control action relies on the precise regulation of methane flow towards anode and post-burner via by-pass valves; this strategy is combined with a cathode air-flow adjustment to have a tight control of both stack temperature gradient and warm-up time. Results are presented to show the potentialities of the proposed model-based approach to: (i) serve as a support to control strategies development and (ii) solve the trade-off between fast SOFC cold-start and avoidance of thermal-stress caused damages.

Implicit proactive interference, age, and automatic versus controlled retrieval strategies.

PubMed

Ikier, Simay; Yang, Lixia; Hasher, Lynn

2008-05-01

We assessed the extent to which implicit proactive interference results from automatic versus controlled retrieval among younger and older adults. During a study phase, targets (e.g., "ALLERGY") either were or were not preceded by nontarget competitors (e.g., "ANALOGY"). After a filled interval, the participants were asked to complete word fragments, some of which cued studied words (e.g., "A_L_ _GY"). Retrieval strategies were identified by the difference in response speed between a phase containing fragments that cued only new words and a phase that included a mix of fragments cuing old and new words. Previous results were replicated: Proactive interference was found in implicit memory, and the negative effects were greater for older than for younger adults. Novel findings demonstrate two retrieval processes that contribute to interference: an automatic one that is age invariant and a controlled process that can reduce the magnitude of the automatic interference effects. The controlled process, however, is used effectively only by younger adults. This pattern of findings potentially explains age differences in susceptibility to proactive interference.

Targeted Recovery as an Effective Strategy against Epidemic Spreading.

PubMed

Böttcher, L; Andrade, J S; Herrmann, H J

2017-10-30

We propose a targeted intervention protocol where recovery is restricted to individuals that have the least number of infected neighbours. Our recovery strategy is highly efficient on any kind of network, since epidemic outbreaks are minimal when compared to the baseline scenario of spontaneous recovery. In the case of spatially embedded networks, we find that an epidemic stays strongly spatially confined with a characteristic length scale undergoing a random walk. We demonstrate numerically and analytically that this dynamics leads to an epidemic spot with a flat surface structure and a radius that grows linearly with the spreading rate.

Hepatitis B control in the World Health Organization's Western Pacific Region: targets, strategies, status.

PubMed

Hennessey, Karen; Mendoza-Aldana, Jorge; Bayutas, Benjamin; Lorenzo-Mariano, Kayla Mae; Diorditsa, Sergey

2013-12-27

WHO's Western Pacific Region has the highest rates of hepatitis B virus (HBV) infection in the world; most countries have >8% prevalence of HBV chronic infection in their adult population. In 2005, Member States of the Region adopted a resolution to reduce chronic hepatitis B infection prevalence to less than 2% among children by 2012 as an interim milestone toward a regional goal of less than 1% prevalence. Country commitments to hepatitis B control and successes represent a remarkable public health achievement by preventing over 1 million chronic infections and 300,000 HBV-related deaths per birth cohort. Reported here is a review of the process and strategies for translating this public health initiative into practice including such activities as setting up an Expert Resource Panel, developing implementation guidelines, focusing on facility births while supporting efforts to reach home births, providing guidance for conducting seroprevalence surveys, and establishing a verification process. Copyright © 2012. Published by Elsevier Ltd.

40 CFR 52.2059 - Control strategy: Particulate matter.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy: Particulate matter... Control strategy: Particulate matter. (a) [Reserved] (b) EPA approves the PM-10 attainment demonstration...-Wilmington, PA-NJ-DE fine particulate matter (PM2.5) nonattainment area has attained the 2006 24-hour PM2.5...

40 CFR 52.1682 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.1682 Section 52.1682 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New York § 52.1682 Control strategy: Carbon monoxide. (a) Approval—The...

40 CFR 52.1373 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.1373 Section 52.1373 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1373 Control strategy: Carbon monoxide. (a) On July 8, 1997...

40 CFR 52.1682 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.1682 Section 52.1682 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New York § 52.1682 Control strategy: Carbon monoxide. (a) Approval—The...

40 CFR 52.1581 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 4 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.1581 Section 52.1581 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Jersey § 52.1581 Control strategy: Carbon monoxide. (a) Approval—The...

40 CFR 52.1581 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.1581 Section 52.1581 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) New Jersey § 52.1581 Control strategy: Carbon monoxide. (a) Approval—The...

40 CFR 52.785 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Control strategy: Carbon monoxide. 52.785 Section 52.785 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.785 Control strategy: Carbon monoxide. (a) The requirements of subpart G...

40 CFR 52.2089 - Control strategy: carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy: carbon monoxide. 52.2089 Section 52.2089 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Rhode Island § 52.2089 Control strategy: carbon monoxide. (a) Approval—O...

40 CFR 52.785 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.785 Section 52.785 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.785 Control strategy: Carbon monoxide. (a) The requirements of subpart G...

40 CFR 52.2089 - Control strategy: carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy: carbon monoxide. 52.2089 Section 52.2089 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Rhode Island § 52.2089 Control strategy: carbon monoxide. (a) Approval—O...

40 CFR 52.1373 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 4 2013-07-01 2013-07-01 false Control strategy: Carbon monoxide. 52.1373 Section 52.1373 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Montana § 52.1373 Control strategy: Carbon monoxide. (a) On July 8, 1997...

40 CFR 52.785 - Control strategy: Carbon monoxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Control strategy: Carbon monoxide. 52.785 Section 52.785 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.785 Control strategy: Carbon monoxide. (a) The requirements of subpart G...

40 CFR 52.2575 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy: Sulfur dioxide. 52... strategy: Sulfur dioxide. (a) Part D—Approval—With the exceptions set forth in this subpart, the Administrator approved the Wisconsin sulfur dioxide control plan. (1) Part D—No action—USEPA takes no action on...

40 CFR 52.2575 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy: Sulfur dioxide. 52... strategy: Sulfur dioxide. (a) Part D—Approval—With the exceptions set forth in this subpart, the Administrator approved the Wisconsin sulfur dioxide control plan. (1) Part D—No action—USEPA takes no action on...

40 CFR 52.2575 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy: Sulfur dioxide. 52... strategy: Sulfur dioxide. (a) Part D—Approval—With the exceptions set forth in this subpart, the Administrator approved the Wisconsin sulfur dioxide control plan. (1) Part D—No action—USEPA takes no action on...

40 CFR 52.2575 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Control strategy: Sulfur dioxide. 52... strategy: Sulfur dioxide. (a) Part D—Approval—With the exceptions set forth in this subpart, the Administrator approved the Wisconsin sulfur dioxide control plan. (1) Part D—No action—USEPA takes no action on...

40 CFR 52.2575 - Control strategy: Sulfur dioxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy: Sulfur dioxide. 52... strategy: Sulfur dioxide. (a) Part D—Approval—With the exceptions set forth in this subpart, the Administrator approved the Wisconsin sulfur dioxide control plan. (1) Part D—No action—USEPA takes no action on...

Complex background suppression using global-local registration strategy for the detection of small-moving target on moving platform

NASA Astrophysics Data System (ADS)

Zou, Tianhao; Zuo, Zhengrong

2018-02-01

Target detection is a very important and basic problem of computer vision and image processing. The most often case we meet in real world is a detection task for a moving-small target on moving platform. The commonly used methods, such as Registration-based suppression, can hardly achieve a desired result. To crack this hard nut, we introduce a Global-local registration based suppression method. Differ from the traditional ones, the proposed Global-local Registration Strategy consider both the global consistency and the local diversity of the background, obtain a better performance than normal background suppression methods. In this paper, we first discussed the features about the small-moving target detection on unstable platform. Then we introduced a new strategy and conducted an experiment to confirm its noisy stability. In the end, we confirmed the background suppression method based on global-local registration strategy has a better perform in moving target detection on moving platform.

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy

PubMed Central

Kovacic, Vanja; Mangwiro, T. N. Clement; Vale, Glyn A.; Hastings, Ian; Solano, Philippe; Lehane, Michael J.; Torr, Steve J.

2015-01-01

Background Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. Methods and Findings The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. Interpretation The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised. PMID:26267814

Target prioritization and strategy selection for active case-finding of pulmonary tuberculosis: a tool to support country-level project planning.

PubMed

Nishikiori, Nobuyuki; Van Weezenbeek, Catharina

2013-02-02

Despite the progress made in the past decade, tuberculosis (TB) control still faces significant challenges. In many countries with declining TB incidence, the disease tends to concentrate in vulnerable populations that often have limited access to health care. In light of the limitations of the current case-finding approach and the global urgency to improve case detection, active case-finding (ACF) has been suggested as an important complementary strategy to accelerate tuberculosis control especially among high-risk populations. The present exercise aims to develop a model that can be used for county-level project planning. A simple deterministic model was developed to calculate the number of estimated TB cases diagnosed and the associated costs of diagnosis. The model was designed to compare cost-effectiveness parameters, such as the cost per case detected, for different diagnostic algorithms when they are applied to different risk populations. The model was transformed into a web-based tool that can support national TB programmes and civil society partners in designing ACF activities. According to the model output, tuberculosis active case-finding can be a costly endeavor, depending on the target population and the diagnostic strategy. The analysis suggests the following: (1) Active case-finding activities are cost-effective only if the tuberculosis prevalence among the target population is high. (2) Extensive diagnostic methods (e.g. X-ray screening for the entire group, use of sputum culture or molecular diagnostics) can be applied only to very high-risk groups such as TB contacts, prisoners or people living with human immunodeficiency virus (HIV) infection. (3) Basic diagnostic approaches such as TB symptom screening are always applicable although the diagnostic yield is very limited. The cost-effectiveness parameter was sensitive to local diagnostic costs and the tuberculosis prevalence of target populations. The prioritization of appropriate target

Targeting vacuolar H+-ATPases as a new strategy against cancer.

PubMed

Fais, Stefano; De Milito, Angelo; You, Haiyan; Qin, Wenxin

2007-11-15

Growing evidence suggests a key role of tumor acidic microenvironment in cancer development, progression, and metastasis. As a consequence, the need for compounds that specifically target the mechanism(s) responsible for the low pH of tumors is increasing. Among the key regulators of the tumor acidic microenvironment, vacuolar H(+)-ATPases (V-ATPases) play an important role. These proteins cover a number of functions in a variety of normal as well as tumor cells, in which they pump ions across the membranes. We discuss here some recent results showing that a molecular inhibition of V-ATPases by small interfering RNA in vivo as well as a pharmacologic inhibition through proton pump inhibitors led to tumor cytotoxicity and marked inhibition of human tumor growth in xenograft models. These results propose V-ATPases as a key target for new strategies in cancer treatment.

Membrane-targeted strategies for modulating APP and Aβ-mediated toxicity

PubMed Central

Price, Katherine A; Crouch, Peter J; Donnelly, Paul S; Masters, Colin L; White, Anthony R; Curtain, Cyril C

2009-01-01

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by numerous pathological features including the accumulation of neurotoxic amyloid-β (Aβ) peptide. There is currently no effective therapy for AD, but the development of therapeutic strategies that target the cell membrane is gaining increased interest. The amyloid precursor protein (APP) from which Aβ is formed is a membrane-bound protein, and Aβ production and toxicity are both membrane mediated events. This review describes the critical role of cell membranes in AD with particular emphasis on how the composition and structure of the membrane and its specialized regions may influence toxic or benign Aβ/APP pathways in AD. The putative role of copper (Cu) in AD is also discussed, and we highlight how targeting the cell membrane with Cu complexes has therapeutic potential in AD. PMID:19278455

Changing attitudes toward smoking and smoking susceptibility through peer crowd targeting: more evidence from a controlled study.

PubMed

Moran, Meghan Bridgid; Sussman, Steve

2015-01-01

Peer crowd identification consistently predicts an adolescent's smoking behavior. As such, several interventions have targeted adolescents and young adults based on their identification with a specific crowd (e.g., Hipsters). This study uses a controlled experimental design to isolate and test the effect of peer crowd targeting in an antismoking ad on antismoking attitudes and smoking susceptibility. Two hundred and thirty-nine adolescents, age 13-15 years, completed a baseline survey and then viewed an antismoking ad targeting one of eight crowds; 1 week later they completed a posttest. Participants were assessed on antismoking attitudes and smoking susceptibility. Adolescents who strongly identified with the crowd targeted by the ad reported stronger antismoking attitudes and lower levels of smoking susceptibility. Those who disidentified with the crowd targeted in the ad exhibited not statistically significant increases in smoking susceptibility and weaker antismoking attitudes at posttest. These findings indicate that targeting youths based on their peer crowd is a useful strategy for antismoking interventions. Additional research should further examine whether youths who disidentify with the targeted crowd in an ad exhibit reactance against the message.

National Drug Control Strategy. FY 2009 Budget Summary

ERIC Educational Resources Information Center

The White House, 2008

2008-01-01

The National Drug Control Budget Summary identifies resources and performance indicators for programs within the Executive Branch that are integral to the President's National Drug Control Strategy. The Strategy, which is the Administration's plan for reducing drug use and availability, is based on three pillars: (1) Stopping Use Before It Starts,…

Neuromodulation as a Robot Controller: A Brain Inspired Strategy for Controlling Autonomous Robots

DTIC Science & Technology