Statistical methods for identifying and bounding a UXO target area or minefield

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

McKinstry, Craig A.; Pulsipher, Brent A.; Gilbert, Richard O.

2003-09-18

The sampling unit for minefield or UXO area characterization is typically represented by a geographical block or transect swath that lends itself to characterization by geophysical instrumentation such as mobile sensor arrays. New spatially based statistical survey methods and tools, more appropriate for these unique sampling units have been developed and implemented at PNNL (Visual Sample Plan software, ver. 2.0) with support from the US Department of Defense. Though originally developed to support UXO detection and removal efforts, these tools may also be used in current form or adapted to support demining efforts and aid in the development of newmore » sensors and detection technologies by explicitly incorporating both sampling and detection error in performance assessments. These tools may be used to (1) determine transect designs for detecting and bounding target areas of critical size, shape, and density of detectable items of interest with a specified confidence probability, (2) evaluate the probability that target areas of a specified size, shape and density have not been missed by a systematic or meandering transect survey, and (3) support post-removal verification by calculating the number of transects required to achieve a specified confidence probability that no UXO or mines have been missed.« less

Designing divertor targets for uniform power load

NASA Astrophysics Data System (ADS)

Dekeyser, W.; Reiter, D.; Baelmans, M.

2015-08-01

Divertor design for next step fusion reactors heavily relies on 2D edge plasma modeling with codes as e.g. B2-EIRENE. While these codes are typically used in a design-by-analysis approach, in previous work we have shown that divertor design can alternatively be posed as a mathematical optimization problem, and solved very efficiently using adjoint methods adapted from computational aerodynamics. This approach has been applied successfully to divertor target shape design for more uniform power load. In this paper, the concept is further extended to include all contributions to the target power load, with particular focus on radiation. In a simplified test problem, we show the potential benefits of fully including the radiation load in the design cycle as compared to only assessing this load in a post-processing step.

Shock Ignition Target Design for Inertial Fusion Energy

DTIC Science & Technology

2010-01-01

Shock ignition target design for inertial fusion energy Andrew J. Schmitt,1, a) Jason W. Bates,1 Steven P. Obenschain,1 Steven T. Zalesak,2 and David...2010 to 00-00-2010 4. TITLE AND SUBTITLE Shock ignition target design for inertial fusion energy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

Nanogel Carrier Design for Targeted Drug Delivery

PubMed Central

Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

2014-01-01

Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

PubMed

Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

2010-09-01

We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

Soft computing model for optimized siRNA design by identifying off target possibilities using artificial neural network model.

PubMed

Murali, Reena; John, Philips George; Peter S, David

2015-05-15

The ability of small interfering RNA (siRNA) to do posttranscriptional gene regulation by knocking down targeted genes is an important research topic in functional genomics, biomedical research and in cancer therapeutics. Many tools had been developed to design exogenous siRNA with high experimental inhibition. Even though considerable amount of work has been done in designing exogenous siRNA, design of effective siRNA sequences is still a challenging work because the target mRNAs must be selected such that their corresponding siRNAs are likely to be efficient against that target and unlikely to accidentally silence other transcripts due to sequence similarity. In some cases, siRNAs may tolerate mismatches with the target mRNA, but knockdown of genes other than the intended target could make serious consequences. Hence to design siRNAs, two important concepts must be considered: the ability in knocking down target genes and the off target possibility on any nontarget genes. So before doing gene silencing by siRNAs, it is essential to analyze their off target effects in addition to their inhibition efficacy against a particular target. Only a few methods have been developed by considering both efficacy and off target possibility of siRNA against a gene. In this paper we present a new design of neural network model with whole stacking energy (ΔG) that enables to identify the efficacy and off target effect of siRNAs against target genes. The tool lists all siRNAs against a particular target with their inhibition efficacy and number of matches or sequence similarity with other genes in the database. We could achieve an excellent performance of Pearson Correlation Coefficient (R=0. 74) and Area Under Curve (AUC=0.906) when the threshold of whole stacking energy is ≥-34.6 kcal/mol. To the best of the author's knowledge, this is one of the best score while considering the "combined efficacy and off target possibility" of siRNA for silencing a gene. The proposed model

28 CFR 551.162 - Designated smoking areas.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Designated smoking areas. 551.162 Section... MISCELLANEOUS Smoking/No Smoking Areas § 551.162 Designated smoking areas. (a) The Warden must designate a smoking area for use in instances where smoking is part of an authorized inmate religious activity. (b)(1...

28 CFR 551.162 - Designated smoking areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Designated smoking areas. 551.162 Section... MISCELLANEOUS Smoking/No Smoking Areas § 551.162 Designated smoking areas. (a) The Warden must designate a smoking area for use in instances where smoking is part of an authorized inmate religious activity. (b)(1...

28 CFR 551.162 - Designated smoking areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Designated smoking areas. 551.162 Section... MISCELLANEOUS Smoking/No Smoking Areas § 551.162 Designated smoking areas. (a) The Warden must designate a smoking area for use in instances where smoking is part of an authorized inmate religious activity. (b)(1...

28 CFR 551.162 - Designated smoking areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Designated smoking areas. 551.162 Section... MISCELLANEOUS Smoking/No Smoking Areas § 551.162 Designated smoking areas. (a) The Warden must designate a smoking area for use in instances where smoking is part of an authorized inmate religious activity. (b)(1...

28 CFR 551.162 - Designated smoking areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Designated smoking areas. 551.162 Section... MISCELLANEOUS Smoking/No Smoking Areas § 551.162 Designated smoking areas. (a) The Warden must designate a smoking area for use in instances where smoking is part of an authorized inmate religious activity. (b)(1...

Large area thermal target board: An improvement to environmental effects and system parameters characterization

NASA Astrophysics Data System (ADS)

Watkins, Wendell R.; Bean, Brent L.; Munding, Peter D.

1994-06-01

Recent field tests have provided excellent opportunities to use a new characterization tool associated with the Mobile Imaging Spectroscopy Laboratory (MISL) of the Battlefield Environment Directorate, formerly the U.S. Army Atmospheric Sciences Laboratory. The MISL large area (1.8 by 1.8 m, uniform temperature, thermal target) was used for characterization and isolation of phenomena which impact target contrast. By viewing the target board from closeup and distant ranges simultaneously with the MISL thermal imagers, the inherent scene content could be calibrated and the degrading effects of atmospheric propagation could be isolated. The target board is equipped with several spatial frequency bar patterns, but only the largest 3.5-cycle full area bar pattern was used for the distant range of 1.6 km. The quantities measured with the target board include the inherent background change, the contrast transmission, and the atmospheric modulation transfer function. The MISL target board has a unique design which makes it lightweight with near perfect transition between the hot and cold portions of the bar pattern. The heated portion of the target is an elongated rectangular even which is tilted back at a 30 deg angle to form a 1.8 by 1.8 m square when viewed from the front. The cold bars we positioned in front of the heated oven surface and can be oriented in either the vertical or horizontal direction. The oven is mounted on a lightweight trailer for one- or two-man positioning. An attached metal and canvas structure is used to shield the entire target from both solar loading and cooling winds. The target board has a thin aluminum sheet front surface which is insulated from the oven's heating structure.

Targeting targeted agents: open issues for clinical trial design.

PubMed

Bria, Emilio; Di Maio, Massimo; Carlini, Paolo; Cuppone, Federica; Giannarelli, Diana; Cognetti, Francesco; Milella, Michele

2009-05-22

Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

PubMed

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

Distributed watershed modeling of design storms to identify nonpoint source loading areas

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

Endreny, T.A.; Wood, E.F.

1999-03-01

Watershed areas that generate nonpoint source (NPS) polluted runoff need to be identified prior to the design of basin-wide water quality projects. Current watershed-scale NPS models lack a variable source area (VSA) hydrology routine, and are therefore unable to identify spatially dynamic runoff zones. The TOPLATS model used a watertable-driven VSA hydrology routine to identify runoff zones in a 17.5 km{sup 2} agricultural watershed in central Oklahoma. Runoff areas were identified in a static modeling framework as a function of prestorm watertable depth and also in a dynamic modeling framework by simulating basin response to 2, 10, and 25 yrmore » return period 6 h design storms. Variable source area expansion occurred throughout the duration of each 6 h storm and total runoff area increased with design storm intensity. Basin-average runoff rates of 1 mm h{sup {minus}1} provided little insight into runoff extremes while the spatially distributed analysis identified saturation excess zones with runoff rates equaling effective precipitation. The intersection of agricultural landcover areas with these saturation excess runoff zones targeted the priority potential NPS runoff zones that should be validated with field visits. These intersected areas, labeled as potential NPS runoff zones, were mapped within the watershed to demonstrate spatial analysis options available in TOPLATS for managing complex distributions of watershed runoff. TOPLATS concepts in spatial saturation excess runoff modelling should be incorporated into NPS management models.« less

Dual Target Design for CLAS12

NASA Astrophysics Data System (ADS)

Alam, Omair; Gilfoyle, Gerard; Christo, Steve

2015-10-01

An experiment to measure the neutron magnetic form factor (GnM) is planned for the new CLAS12 detector in Hall B at Jefferson Lab. This form factor will be extracted from the ratio of the quasielastic electron-neutron to electron-proton scattering off a liquid deuterium (LD2) target. A collinear liquid hydrogen (LH2) target will be used to measure efficiencies at the same time as production data is collected from the LD2 target. To test target designs we have simulated CLAS12 and the target geometry. Electron-nucleon events are produced first with the QUasiElastic Event Generator (QUEEG) which models the internal motion of the nucleons in deuterium.1 The results are used as input to the CLAS12 Monte Caro code gemc; a Geant4-based program that simulates the particle's interactions with each component of CLAS12 including the target material. The dual target geometry has been added to gemc including support structures and cryogenic transport systems. A Perl script was written to define the target materials and geometries. The output of the script is a set of database entries read by gemc at runtime. An initial study of the impact of this dual-target structure revealed limited effects on the electron momentum and angular resolutions. Work supported by the University of Richmond and the US Department of Energy.

Quantifying design trade-offs of beryllium targets on NIF

NASA Astrophysics Data System (ADS)

Yi, S. A.; Zylstra, A. B.; Kline, J. L.; Loomis, E. N.; Kyrala, G. A.; Shah, R. C.; Perry, T. S.; Kanzleiter, R. J.; Batha, S. H.; MacLaren, S. A.; Ralph, J. E.; Masse, L. P.; Salmonson, J. D.; Tipton, R. E.; Callahan, D. A.; Hurricane, O. A.

2017-10-01

An important determinant of target performance is implosion kinetic energy, which scales with the capsule size. The maximum achievable performance for a given laser is thus related to the largest capsule that can be imploded symmetrically, constrained by drive uniformity. A limiting factor for symmetric radiation drive is the ratio of hohlraum to capsule radii, or case-to-capsule ratio (CCR). For a fixed laser energy, a larger hohlraum allows for driving bigger capsules symmetrically at the cost of reduced peak radiation temperature (Tr). Beryllium ablators may thus allow for unique target design trade-offs due to their higher ablation efficiency at lower Tr. By utilizing larger hohlraum sizes than most modern NIF designs, beryllium capsules thus have the potential to operate in unique regions of the target design parameter space. We present design simulations of beryllium targets with a large CCR = 4.3 3.7 . These are scaled surrogates of large hohlraum low Tr beryllium targets, with the goal of quantifying symmetry tunability as a function of CCR. This work performed under the auspices of the U.S. DOE by LANL under contract DE-AC52- 06NA25396, and by LLNL under Contract DE-AC52-07NA27344.

Evolutionary Multiobjective Design Targeting a Field Programmable Transistor Array

NASA Technical Reports Server (NTRS)

Aguirre, Arturo Hernandez; Zebulum, Ricardo S.; Coello, Carlos Coello

2004-01-01

This paper introduces the ISPAES algorithm for circuit design targeting a Field Programmable Transistor Array (FPTA). The use of evolutionary algorithms is common in circuit design problems, where a single fitness function drives the evolution process. Frequently, the design problem is subject to several goals or operating constraints, thus, designing a suitable fitness function catching all requirements becomes an issue. Such a problem is amenable for multi-objective optimization, however, evolutionary algorithms lack an inherent mechanism for constraint handling. This paper introduces ISPAES, an evolutionary optimization algorithm enhanced with a constraint handling technique. Several design problems targeting a FPTA show the potential of our approach.

Missing marine protected area (MPA) targets: How the push for quantity over quality undermines sustainability and social justice.

PubMed

De Santo, Elizabeth M

2013-07-30

International targets for marine protected areas (MPAs) and networks of MPAs set by the World Summit on Sustainable Development and United Nations Convention on Biological Diversity failed to meet their 2012 deadline and have been extended to 2020. Whilst targets play an important role in building momentum for conservation, they are also responsible for the recent designation of several extremely large no-take MPAs, which pose significant long-term monitoring and enforcement challenges. This paper critically examines the effectiveness of MPA targets, focusing on the underlying risks to achieving Millennium Development Goals posed by the global push for quantity versus quality of MPAs. The observations outlined in this paper have repercussions for international protected area politics with respect to (1) the science-policy interface in environmental decision-making, and (2) social justice concerns in global biodiversity conservation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design Analysis of SNS Target StationBiological Shielding Monoligh with Proton Power Uprate

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

Bekar, Kursat B.; Ibrahim, Ahmad M.

2017-05-01

This report documents the analysis of the dose rate in the experiment area outside the Spallation Neutron Source (SNS) target station shielding monolith with proton beam energy of 1.3 GeV. The analysis implemented a coupled three dimensional (3D)/two dimensional (2D) approach that used both the Monte Carlo N-Particle Extended (MCNPX) 3D Monte Carlo code and the Discrete Ordinates Transport (DORT) two dimensional deterministic code. The analysis with proton beam energy of 1.3 GeV showed that the dose rate in continuously occupied areas on the lateral surface outside the SNS target station shielding monolith is less than 0.25 mrem/h, which compliesmore » with the SNS facility design objective. However, the methods and codes used in this analysis are out of date and unsupported, and the 2D approximation of the target shielding monolith does not accurately represent the geometry. We recommend that this analysis is updated with modern codes and libraries such as ADVANTG or SHIFT. These codes have demonstrated very high efficiency in performing full 3D radiation shielding analyses of similar and even more difficult problems.« less

100-N Area Decision Unit Target Analyte List Development for Soil

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

Ovink, R.

2012-09-18

This report documents the process used to identify source area target analytes in support of the 100-N Area remedial investigation/feasibility study (RI/FS) addendum to the Integrated 100 Area Remedial Investigation/Feasibility Study Work Plan (DOE/RL-2008-46, Rev. 0).

Benchmarking CRISPR on-target sgRNA design.

PubMed

Yan, Jifang; Chuai, Guohui; Zhou, Chi; Zhu, Chenyu; Yang, Jing; Zhang, Chao; Gu, Feng; Xu, Han; Wei, Jia; Liu, Qi

2017-02-15

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based gene editing has been widely implemented in various cell types and organisms. A major challenge in the effective application of the CRISPR system is the need to design highly efficient single-guide RNA (sgRNA) with minimal off-target cleavage. Several tools are available for sgRNA design, while limited tools were compared. In our opinion, benchmarking the performance of the available tools and indicating their applicable scenarios are important issues. Moreover, whether the reported sgRNA design rules are reproducible across different sgRNA libraries, cell types and organisms remains unclear. In our study, a systematic and unbiased benchmark of the sgRNA predicting efficacy was performed on nine representative on-target design tools, based on six benchmark data sets covering five different cell types. The benchmark study presented here provides novel quantitative insights into the available CRISPR tools. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Target surface area effects on hot electron dynamics from high intensity laser–plasma interactions

DOE PAGES

Zulick, C.; Raymond, A.; McKelvey, A.; ...

2016-06-15

Reduced surface area targets were studied using an ultra-high intensity femtosecond laser in order to determine the effect of electron sheath field confinement on electron dynamics. X-ray emission due to energetic electrons was imaged using a K α imaging crystal. Electrons were observed to travel along the surface of wire targets, and were slowed mainly by the induced fields. Targets with reduced surface areas were correlated with increased hot electron densities and proton energies. Furthermore, Hybrid Vlasov–Fokker–Planck simulations demonstrated increased electric sheath field strength in reduced surface area targets.

Geothermal Target Areas in Colorado as Identified by Remote Sensing Techniques

DOE Data Explorer

Khalid Hussein

2012-02-01

This layer contains the areas identified as targets of potential geothermal activity. The Criteria used to identify the target areas include: hot/warm surface exposures modeled from ASTER/Landsat satellite imagery and geological characteristics, alteration mineral commonly associated with hot springs (clays, Si, and FeOx) modeled from ASTER and Landsat data, Colorado Geological Survey (CGS) known thermal hot springs/wells and heat-flow data points, Colorado deep-seated fault zones, weakened basement identified from isostatic gravity data, and Colorado sedimentary and topographic characteristics.

Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

PubMed

Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

2017-08-18

The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation†

PubMed Central

Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M.; Radovic-Moreno, Aleksandar F.; Farokhzad, Omid C.

2013-01-01

Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development

Massively parallel de novo protein design for targeted therapeutics.

PubMed

Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J; Hicks, Derrick R; Vergara, Renan; Murapa, Patience; Bernard, Steffen M; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T; Koday, Merika T; Jenkins, Cody M; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M; Fernández-Velasco, D Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A; Fuller, Deborah H; Baker, David

2017-10-05

De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

Massively parallel de novo protein design for targeted therapeutics

NASA Astrophysics Data System (ADS)

Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J.; Hicks, Derrick R.; Vergara, Renan; Murapa, Patience; Bernard, Steffen M.; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D.; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T.; Koday, Merika T.; Jenkins, Cody M.; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M.; Fernández-Velasco, D. Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A.; Fuller, Deborah H.; Baker, David

2017-10-01

De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

Massively parallel de novo protein design for targeted therapeutics

PubMed Central

Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J.; Hicks, Derrick R.; Vergara, Renan; Murapa, Patience; Bernard, Steffen M.; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D.; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T.; Koday, Merika T.; Jenkins, Cody M.; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M.; Fernández-Velasco, D. Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A.; Fuller, Deborah H.; Baker, David

2018-01-01

De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37–43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing. PMID:28953867

AN EARLY STAGE IN THE PLANT RECOLONIZATION OF A NUCLEAR TARGET AREA

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

Rickard, W.H.; Shields, L.M.

1963-01-01

Vegetational analyses were conducted three years postdetonation in a nuclear target area in a Grayia spinosa-Lycium andersonii community in Yucca Fiat, Nevada. Annual plants dominated the early stage of recolonization and were quantitatively more abundant in the disturbed areas than in an adjacent undisturbed shrub community. Ment zelia albicaulis and Chaenactis steviodes occurred in both disturbed and undisturbed areas, however; Mentzelia was more abundant in disturbed areas while Chaenactis was more abundant in the undisturbed community. Salsola kali was confined to disturbed areas while Phacelia vallismortae was more often encountered in the undisturbed community. The plant recolonization of a mechanicallymore » disturbed area was quantitatively and qualitatively more like that of the interior zone of the nuclear target area than less disturbed habitats. These data support a conclusion that soil displacement presents a more rigorous habitat for plant recolonization than disturbances created by the wider ranging destructive components of a nuclear detonation. (auth)« less

The effects of figure/ground, perceived area, and target saliency on the luminosity threshold.

PubMed

Bonato, F; Cataliotti, J

2000-02-01

Observers adjusted the luminance of a target region until it began to appear self-luminous, or glowing. In Experiment 1, the target was either a face-shaped region (figure) or a non-face-shaped region (ground) of identical area that appeared to be the face's background. In Experiment 2, the target was a square or a trapezoid of identical area that appeared as a tilted rectangle. In Experiment 3, the target was a square surrounded by square, circular, or diamond-shaped elements. Targets that (1) were perceived as figures, (2) were phenomenally small in area, or (3) did not group well with other elements in the array because of shape appeared self-luminous at significantly lower luminance levels. These results indicate that like lightness perception, the luminosity threshold is influenced by perceptual organization and is not based on low-level retinal processes alone.

Measuring the extent of overlaps in protected area designations

PubMed Central

Arnell, Andy; Juffe-Bignoli, Diego; Shi, Yichuan; Bingham, Heather; MacSharry, Brian; Kingston, Naomi

2017-01-01

Over the past decades, a number of national policies and international conventions have been implemented to promote the expansion of the world’s protected area network, leading to a diversification of protected area strategies, types and designations. As a result, many areas are protected by more than one convention, legal instrument, or other effective means which may result in a lack of clarity around the governance and management regimes of particular locations. We assess the degree to which different designations overlap at global, regional and national levels to understand the extent of this phenomenon at different scales. We then compare the distribution and coverage of these multi-designated areas in the terrestrial and marine realms at the global level and among different regions, and we present the percentage of each county’s protected area extent that is under more than one designation. Our findings show that almost a quarter of the world’s protected area network is protected through more than one designation. In fact, we have documented up to eight overlapping designations. These overlaps in protected area designations occur in every region of the world, both in the terrestrial and marine realms, but are more common in the terrestrial realm and in some regions, notably Europe. In the terrestrial realm, the most common overlap is between one national and one international designation. In the marine realm, the most common overlap is between any two national designations. Multi-designations are therefore a widespread phenomenon but its implications are not well understood. This analysis identifies, for the first time, multi-designated areas across all designation types. This is a key step to understand how these areas are managed and governed to then move towards integrated and collaborative approaches that consider the different management and conservation objectives of each designation. PMID:29176888

Measuring the extent of overlaps in protected area designations.

PubMed

Deguignet, Marine; Arnell, Andy; Juffe-Bignoli, Diego; Shi, Yichuan; Bingham, Heather; MacSharry, Brian; Kingston, Naomi

2017-01-01

Over the past decades, a number of national policies and international conventions have been implemented to promote the expansion of the world's protected area network, leading to a diversification of protected area strategies, types and designations. As a result, many areas are protected by more than one convention, legal instrument, or other effective means which may result in a lack of clarity around the governance and management regimes of particular locations. We assess the degree to which different designations overlap at global, regional and national levels to understand the extent of this phenomenon at different scales. We then compare the distribution and coverage of these multi-designated areas in the terrestrial and marine realms at the global level and among different regions, and we present the percentage of each county's protected area extent that is under more than one designation. Our findings show that almost a quarter of the world's protected area network is protected through more than one designation. In fact, we have documented up to eight overlapping designations. These overlaps in protected area designations occur in every region of the world, both in the terrestrial and marine realms, but are more common in the terrestrial realm and in some regions, notably Europe. In the terrestrial realm, the most common overlap is between one national and one international designation. In the marine realm, the most common overlap is between any two national designations. Multi-designations are therefore a widespread phenomenon but its implications are not well understood. This analysis identifies, for the first time, multi-designated areas across all designation types. This is a key step to understand how these areas are managed and governed to then move towards integrated and collaborative approaches that consider the different management and conservation objectives of each designation.

Sustainable Rest Area Design and Operations

DOT National Transportation Integrated Search

2017-10-01

One way in which State Departments of Transportation (DOTs) can modernize their rest areas while reducing operations and maintenance costs is by incorporating sustainable practices into rest area design and operations. Sustainability practices that D...

9 CFR 78.40 - Designation of States/areas.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Designation of Brucellosis Areas § 78.40 Designation of States/areas. The Administrator may amend §§ 78.41 and... Administrator may approve the division of a State into two brucellosis classification areas upon finding that...

9 CFR 78.40 - Designation of States/areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Designation of Brucellosis Areas § 78.40 Designation of States/areas. The Administrator may amend §§ 78.41 and... Administrator may approve the division of a State into two brucellosis classification areas upon finding that...

9 CFR 78.40 - Designation of States/areas.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Designation of Brucellosis Areas § 78.40 Designation of States/areas. The Administrator may amend §§ 78.41 and... Administrator may approve the division of a State into two brucellosis classification areas upon finding that...

9 CFR 78.40 - Designation of States/areas.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Designation of Brucellosis Areas § 78.40 Designation of States/areas. The Administrator may amend §§ 78.41 and... Administrator may approve the division of a State into two brucellosis classification areas upon finding that...

47 CFR 17.9 - Designated antenna farm areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Designated antenna farm areas. 17.9 Section 17... ANTENNA STRUCTURES Federal Aviation Administration Notification Criteria § 17.9 Designated antenna farm areas. The areas described in the following paragraphs of this section are established as antenna farm...

47 CFR 17.9 - Designated antenna farm areas.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Designated antenna farm areas. 17.9 Section 17... ANTENNA STRUCTURES Federal Aviation Administration Notification Criteria § 17.9 Designated antenna farm areas. The areas described in the following paragraphs of this section are established as antenna farm...

47 CFR 17.9 - Designated antenna farm areas.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 1 2013-10-01 2013-10-01 false Designated antenna farm areas. 17.9 Section 17... ANTENNA STRUCTURES Federal Aviation Administration Notification Criteria § 17.9 Designated antenna farm areas. The areas described in the following paragraphs of this section are established as antenna farm...

47 CFR 17.9 - Designated antenna farm areas.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 1 2012-10-01 2012-10-01 false Designated antenna farm areas. 17.9 Section 17... ANTENNA STRUCTURES Federal Aviation Administration Notification Criteria § 17.9 Designated antenna farm areas. The areas described in the following paragraphs of this section are established as antenna farm...

47 CFR 17.9 - Designated antenna farm areas.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false Designated antenna farm areas. 17.9 Section 17... ANTENNA STRUCTURES Federal Aviation Administration Notification Criteria § 17.9 Designated antenna farm areas. The areas described in the following paragraphs of this section are established as antenna farm...

Oak Ridge Spallation Neutron Source (ORSNS) target station design integration

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

McManamy, T.; Booth, R.; Cleaves, J.

1996-06-01

The conceptual design for a 1- to 3-MW short pulse spallation source with a liquid mercury target has been started recently. The design tools and methods being developed to define requirements, integrate the work, and provide early cost guidance will be presented with a summary of the current target station design status. The initial design point was selected with performance and cost estimate projections by a systems code. This code was developed recently using cost estimates from the Brookhaven Pulsed Spallation Neutron Source study and experience from the Advanced Neutron Source Project`s conceptual design. It will be updated and improvedmore » as the design develops. Performance was characterized by a simplified figure of merit based on a ratio of neutron production to costs. A work breakdown structure was developed, with simplified systems diagrams used to define interfaces and system responsibilities. A risk assessment method was used to identify potential problems, to identify required research and development (R&D), and to aid contingency development. Preliminary 3-D models of the target station are being used to develop remote maintenance concepts and to estimate costs.« less

Identification of clinical target areas in the brainstem of prion‐infected mice

PubMed Central

Mirabile, Ilaria; Jat, Parmjit S.; Brandner, Sebastian

2015-01-01

Aims While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. Method We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset). Results We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre‐Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Conclusions Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre‐Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt–Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases. PMID:25311251

Savannah River Plant engineering and design history. Volume 4: 300/700 Areas & general services and facilities

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

Not Available

1957-01-01

The primary function of the 300 Area is the production and preparation of the fuel and target elements required for the 100 Area production reactors. Uranium slugs and lithium-aluminium alloy control and blanket rods are prepared in separate structures. Other facilities include a test pile, a physics assembly laboratory, an office and change house, an electrical substation, and various service facilities such as rail lines, roads, sewers, steam and water distribution lines, etc. The 700 Area contains housing and facilities for plant management, general plant services, and certain technical activities. The technical buildings include the Main Technical Laboratory, the Wastemore » Concentration Building, the Health Physics Headquarters, and the Health Physics Calibration building. Sections of this report describe the following: development of the 300-M Area; selection and description of process; design of main facilities of the 300 Area; development of the 700-A Area; design of the main facilities of the 700 Area; and general services and facilities, including transportation, plant protection, waste disposal and drainage, site work, pilot plants, storage, and furniture and fixtures.« less

Designing application software in wide area network settings

NASA Technical Reports Server (NTRS)

Makpangou, Mesaac; Birman, Ken

1990-01-01

Progress in methodologies for developing robust local area network software has not been matched by similar results for wide area settings. The design of application software spanning multiple local area environments is examined. For important classes of applications, simple design techniques are presented that yield fault tolerant wide area programs. An implementation of these techniques as a set of tools for use within the ISIS system is described.

33 CFR 334.120 - Delaware Bay off Milford Neck; naval aircraft bombing target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Delaware Bay off Milford Neck; naval aircraft bombing target area. 334.120 Section 334.120 Navigation and Navigable Waters CORPS OF....120 Delaware Bay off Milford Neck; naval aircraft bombing target area. (a) The danger zone. A circular...

33 CFR 334.120 - Delaware Bay off Milford Neck; naval aircraft bombing target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Delaware Bay off Milford Neck; naval aircraft bombing target area. 334.120 Section 334.120 Navigation and Navigable Waters CORPS OF....120 Delaware Bay off Milford Neck; naval aircraft bombing target area. (a) The danger zone. A circular...

Philippine protected areas are not meeting the biodiversity coverage and management effectiveness requirements of Aichi Target 11.

PubMed

Mallari, Neil Aldrin D; Collar, Nigel J; McGowan, Philip J K; Marsden, Stuart J

2016-04-01

Aichi Target 11 of the Convention on Biological Diversity urges, inter alia, that nations protect at least 17 % of their land, and that protection is effective and targets areas of importance for biodiversity. Five years before reporting on Aichi targets is due, we assessed the Philippines' current protected area system for biodiversity coverage, appropriateness of management regimes and capacity to deliver protection. Although protected estate already covers 11 % of the Philippines' land area, 64 % of its key biodiversity areas (KBAs) remain unprotected. Few protected areas have appropriate management and governance infrastructures, funding streams, management plans and capacity, and a serious mismatch exists between protected area land zonation regimes and conservation needs of key species. For the Philippines to meet the biodiversity coverage and management effectiveness elements of Aichi Target 11, protected area and KBA boundaries should be aligned, management systems reformed to pursue biodiversity-led targets and effective management capacity created.

Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

NASA Technical Reports Server (NTRS)

Nesnas, Issa A.; Pivtoraiko, Mihail N.; Kelly, Alonzo; Fleder, Michael

2012-01-01

This software controls a rover platform to traverse rocky terrain autonomously, plan paths, and avoid obstacles using its stereo hazard and navigation cameras. It does so while continuously tracking a target of interest selected from 10 20 m away. The rover drives and tracks the target until it reaches the vicinity of the target. The rover then positions itself to approach the target, deploys its robotic arm, and places the end effector instrument on the designated target to within 2-3-cm accuracy of the originally selected target. This software features continuous navigation in a fairly rocky field in an outdoor environment and the ability to enable the rover to avoid large rocks and traverse over smaller ones. Using point-and-click mouse commands, a scientist designates targets in the initial imagery acquired from the rover s mast cameras. The navigation software uses stereo imaging, traversability analysis, path planning, trajectory generation, and trajectory execution. It also includes visual target tracking of a designated target selected from 10 m away while continuously navigating the rocky terrain. Improvements in this design include steering while driving, which uses continuous curvature paths. There are also several improvements to the traversability analyzer, including improved data fusion of traversability maps that result from pose estimation uncertainties, dealing with boundary effects to enable tighter maneuvers, and handling a wider range of obstacles. This work advances what has been previously developed and integrated on the Mars Exploration Rovers by using algorithms that are capable of traversing more rock-dense terrains, enabling tight, thread-the-needle maneuvers. These algorithms were integrated on the newly refurbished Athena Mars research rover, and were fielded in the JPL Mars Yard. Forty-three runs were conducted with targets at distances ranging from 5 to 15 m, and a success rate of 93% was achieved for placement of the instrument within

Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

NASA Technical Reports Server (NTRS)

Felder, Michael; Nesnas, Issa A.; Pivtoraiko, Mihail; Kelly, Alonzo; Volpe, Richard

2011-01-01

Exploring planetary surfaces typically involves traversing challenging and unknown terrain and acquiring in-situ measurements at designated locations using arm-mounted instruments. We present field results for a new implementation of an autonomous capability that enables a rover to traverse and precisely place an arm-mounted instrument on remote targets. Using point-and-click mouse commands, a scientist designates targets in the initial imagery acquired from the rover's mast cameras. The rover then autonomously traverse the rocky terrain for a distance of 10 - 15 m, tracks the target(s) of interest during the traverse, positions itself for approaching the target, and then precisely places an arm-mounted instrument within 2-3 cm from the originally designated target. The rover proceeds to acquire science measurements with the instrument. This work advances what has been previously developed and integrated on the Mars Exploration Rovers by using algorithms that are capable of traversing more rock-dense terrains, enabling tight thread-the-needle maneuvers. We integrated these algorithms on the newly refurbished Athena Mars research rover and fielded them in the JPL Mars Yard. We conducted 43 runs with targets at distances ranging from 5 m to 15 m and achieved a success rate of 93% for placement of the instrument within 2-3 cm.

Selection and trajectory design to mission secondary targets

NASA Astrophysics Data System (ADS)

Victorino Sarli, Bruno; Kawakatsu, Yasuhiro

2017-02-01

Recently, with new trajectory design techniques and use of low-thrust propulsion systems, missions have become more efficient and cheaper with respect to propellant. As a way to increase the mission's value and scientific return, secondary targets close to the main trajectory are often added with a small change in the transfer trajectory. As a result of their large number, importance and facility to perform a flyby, asteroids are commonly used as such targets. This work uses the Primer Vector theory to define the direction and magnitude of the thrust for a minimum fuel consumption problem. The design of a low-thrust trajectory with a midcourse asteroid flyby is not only challenging for the low-thrust problem solution, but also with respect to the selection of a target and its flyby point. Currently more than 700,000 minor bodies have been identified, which generates a very large number of possible flyby points. This work uses a combination of reachability, reference orbit, and linear theory to select appropriate candidates, drastically reducing the simulation time, to be later included in the main trajectory and optimized. Two test cases are presented using the aforementioned selection process and optimization to add and design a secondary flyby to a mission with the primary objective of 3200 Phaethon flyby and 25143 Itokawa rendezvous.

Design of the next generation target at Lujan center, LANSCE.

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

Ferres, Laurent

2016-07-27

This is a presentation given at Los Alamos National Laboratory (LANL) on the design of the next generation target at Lujan center, LANSCE. The motivation for this design is to enable new nuclear physics experiments (defense program applications (DANCE)) that are currently limited by neutron intensity or energy resolution available at LANSCE. The target is being redesigned so that the Flight Paths in the upper tier provide a higher intensity in the epithermal and medium energy ranges.

RobOKoD: microbial strain design for (over)production of target compounds.

PubMed

Stanford, Natalie J; Millard, Pierre; Swainston, Neil

2015-01-01

Sustainable production of target compounds such as biofuels and high-value chemicals for pharmaceutical, agrochemical, and chemical industries is becoming an increasing priority given their current dependency upon diminishing petrochemical resources. Designing these strains is difficult, with current methods focusing primarily on knocking-out genes, dismissing other vital steps of strain design including the overexpression and dampening of genes. The design predictions from current methods also do not translate well-into successful strains in the laboratory. Here, we introduce RobOKoD (Robust, Overexpression, Knockout and Dampening), a method for predicting strain designs for overproduction of targets. The method uses flux variability analysis to profile each reaction within the system under differing production percentages of target-compound and biomass. Using these profiles, reactions are identified as potential knockout, overexpression, or dampening targets. The identified reactions are ranked according to their suitability, providing flexibility in strain design for users. The software was tested by designing a butanol-producing Escherichia coli strain, and was compared against the popular OptKnock and RobustKnock methods. RobOKoD shows favorable design predictions, when predictions from these methods are compared to a successful butanol-producing experimentally-validated strain. Overall RobOKoD provides users with rankings of predicted beneficial genetic interventions with which to support optimized strain design.

A target design for irradiation of NaI at high beam current.

NASA Technical Reports Server (NTRS)

Blue, J. W.; Sodd, V. J.

1972-01-01

A solution to the targetry problems encountered when the iodine nucleus is a target for cyclotron irradiation is given as a new target design. A target based on this design has been used in 30 microampere irradiations of 46 MeV alpha particles for one-half hour without significant damage. Such an irradiation produces 6 to 7 mCi of Cs-129, an isotope useful in nuclear medicine. This target should also be considered for cyclotron production of the radioisotopes Cs-127, I-123, and Xe-127.

High-efficiency-release targets for use at ISOL facilities: computational design

NASA Astrophysics Data System (ADS)

Liu, Y.; Alton, G. D.

1999-12-01

This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat-removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated-vitreous-carbon fiber (RVCF) or carbon-bonded-carbon fiber (CBCF) to form highly permeable composite target matrices. Computational studies that simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation are presented in this report.

Statistical Algorithms Accounting for Background Density in the Detection of UXO Target Areas at DoD Munitions Sites

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

Matzke, Brett D.; Wilson, John E.; Hathaway, J.

2008-02-12

Statistically defensible methods are presented for developing geophysical detector sampling plans and analyzing data for munitions response sites where unexploded ordnance (UXO) may exist. Detection methods for identifying areas of elevated anomaly density from background density are shown. Additionally, methods are described which aid in the choice of transect pattern and spacing to assure with degree of confidence that a target area (TA) of specific size, shape, and anomaly density will be identified using the detection methods. Methods for evaluating the sensitivity of designs to variation in certain parameters are also discussed. Methods presented have been incorporated into the Visualmore » Sample Plan (VSP) software (free at http://dqo.pnl.gov/vsp) and demonstrated at multiple sites in the United States. Application examples from actual transect designs and surveys from the previous two years are demonstrated.« less

33 CFR 334.1160 - San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false San Pablo Bay, Calif.; target... REGULATIONS § 334.1160 San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo. (a..., Mare Island Naval Shipyard, Vallejo, California, will conduct target practice in the area at intervals...

33 CFR 334.1160 - San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false San Pablo Bay, Calif.; target... REGULATIONS § 334.1160 San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo. (a..., Mare Island Naval Shipyard, Vallejo, California, will conduct target practice in the area at intervals...

Targeting legume loci: A comparison of three methods for target enrichment bait design in Leguminosae phylogenomics.

PubMed

Vatanparast, Mohammad; Powell, Adrian; Doyle, Jeff J; Egan, Ashley N

2018-03-01

The development of pipelines for locus discovery has spurred the use of target enrichment for plant phylogenomics. However, few studies have compared pipelines from locus discovery and bait design, through validation, to tree inference. We compared three methods within Leguminosae (Fabaceae) and present a workflow for future efforts. Using 30 transcriptomes, we compared Hyb-Seq, MarkerMiner, and the Yang and Smith (Y&S) pipelines for locus discovery, validated 7501 baits targeting 507 loci across 25 genera via Illumina sequencing, and inferred gene and species trees via concatenation- and coalescent-based methods. Hyb-Seq discovered loci with the longest mean length. MarkerMiner discovered the most conserved loci with the least flagged as paralogous. Y&S offered the most parsimony-informative sites and putative orthologs. Target recovery averaged 93% across taxa. We optimized our targeted locus set based on a workflow designed to minimize paralog/ortholog conflation and thus present 423 loci for legume phylogenomics. Methods differed across criteria important for phylogenetic marker development. We recommend Hyb-Seq as a method that may be useful for most phylogenomic projects. Our targeted locus set is a resource for future, community-driven efforts to reconstruct the legume tree of life.

Methods to enable the design of bioactive small molecules targeting RNA.

PubMed

Disney, Matthew D; Yildirim, Ilyas; Childs-Disney, Jessica L

2014-02-21

RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including structure-activity relationships through sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome.

Test Information Targeting Strategies for Adaptive Multistage Testing Designs.

ERIC Educational Resources Information Center

Luecht, Richard M.; Burgin, William

Adaptive multistage testlet (MST) designs appear to be gaining popularity for many large-scale computer-based testing programs. These adaptive MST designs use a modularized configuration of preconstructed testlets and embedded score-routing schemes to prepackage different forms of an adaptive test. The conditional information targeting (CIT)…

Translating Genetic Research into Preventive Intervention: The Baseline Target Moderated Mediator Design.

PubMed

Howe, George W; Beach, Steven R H; Brody, Gene H; Wyman, Peter A

2015-01-01

In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We use simulated data to illustrate a BTMM, and end with a discussion of some of the advantages and limitations of this approach.

Translating Genetic Research into Preventive Intervention: The Baseline Target Moderated Mediator Design

PubMed Central

Howe, George W.; Beach, Steven R. H.; Brody, Gene H.; Wyman, Peter A.

2016-01-01

In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We use simulated data to illustrate a BTMM, and end with a discussion of some of the advantages and limitations of this approach. PMID:26779062

30 CFR 70.208 - Bimonthly sampling; designated areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Bimonthly sampling; designated areas. 70.208... SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-UNDERGROUND COAL MINES Sampling Procedures § 70.208 Bimonthly sampling; designated areas. (a) Each operator shall take one valid respirable dust sample from...

30 CFR 70.208 - Bimonthly sampling; designated areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Bimonthly sampling; designated areas. 70.208... SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-UNDERGROUND COAL MINES Sampling Procedures § 70.208 Bimonthly sampling; designated areas. (a) Each operator shall take one valid respirable dust sample from...

Designing oral vaccines targeting intestinal dendritic cells.

PubMed

Devriendt, Bert; De Geest, Bruno G; Cox, Eric

2011-04-01

Most pathogens colonize and invade the host at mucosal surfaces, such as the lung and the intestine. To combat intestinal pathogens the induction of local adaptive immune responses is required, which is mainly achieved through oral vaccination. However, most vaccines are ineffective when given orally owing to the hostile environment in the gastrointestinal tract. The encapsulation of antigens in biodegradable microparticulate delivery systems enhances their immunogenicity; however, the uptake of these delivery systems by intestinal immune cells is rather poor. Surface decoration of the particulates with targeting ligands could increase the uptake and mediate the selective targeting of the vaccine to intestinal antigen-presenting cells, including dendritic cells. In this review, current knowledge on dendritic cell subsets is discussed, along with progress in the development of selective antigen targeting to these cells, in addition to focusing on data obtained in mice and, where possible, the pig, as a non-rodent animal model for humans. Moreover, the potential use and benefits of Fcγ receptor-mediated targeting of antigen delivery systems are highlighted. In conclusion, dendritic cell targeting ligands grafted on antigen carrier systems should preferably bind to a conserved endocytotic receptor, facilitating the design of a multispecies vaccine platform, which could elicit robust protective immune responses against enteric pathogens.

Dead-blow hammer design applied to a calibration target mechanism to dampen excessive rebound

NASA Technical Reports Server (NTRS)

Lim, Brian Y.

1991-01-01

An existing rotary electromagnetic driver was specified to be used to deploy and restow a blackbody calibration target inside of a spacecraft infrared science instrument. However, this target was much more massive than any other previously inherited design applications. The target experienced unacceptable bounce when reaching its stops. Without any design modification, the momentum generated by the driver caused the target to bounce back to its starting position. Initially, elastomeric dampers were used between the driver and the target. However, this design could not prevent the bounce, and it compromised the positional accuracy of the calibration target. A design that successfully met all the requirements incorporated a sealed pocket 85 percent full of 0.75 mm diameter stainless steel balls in the back of the target to provide the effect of a dead-blow hammer. The energy dissipation resulting from the collision of balls in the pocket successfully dampened the excess momentum generated during the target deployment. The disastrous effects of new requirements on a design with a successful flight history, the modifications that were necessary to make the device work, and the tests performed to verify its functionality are described.

RobOKoD: microbial strain design for (over)production of target compounds

PubMed Central

Stanford, Natalie J.; Millard, Pierre; Swainston, Neil

2015-01-01

Sustainable production of target compounds such as biofuels and high-value chemicals for pharmaceutical, agrochemical, and chemical industries is becoming an increasing priority given their current dependency upon diminishing petrochemical resources. Designing these strains is difficult, with current methods focusing primarily on knocking-out genes, dismissing other vital steps of strain design including the overexpression and dampening of genes. The design predictions from current methods also do not translate well-into successful strains in the laboratory. Here, we introduce RobOKoD (Robust, Overexpression, Knockout and Dampening), a method for predicting strain designs for overproduction of targets. The method uses flux variability analysis to profile each reaction within the system under differing production percentages of target-compound and biomass. Using these profiles, reactions are identified as potential knockout, overexpression, or dampening targets. The identified reactions are ranked according to their suitability, providing flexibility in strain design for users. The software was tested by designing a butanol-producing Escherichia coli strain, and was compared against the popular OptKnock and RobustKnock methods. RobOKoD shows favorable design predictions, when predictions from these methods are compared to a successful butanol-producing experimentally-validated strain. Overall RobOKoD provides users with rankings of predicted beneficial genetic interventions with which to support optimized strain design. PMID:25853130

78 FR 35612 - Agency Information Collection Activities; Comment Request; Targeted Teacher Shortage Areas...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-13

... address the targeted teacher deferment provision of the Higher Education Act of 1965, as amended. The... DEPARTMENT OF EDUCATION [Docket No. ED-2013-ICCD-0076] Agency Information Collection Activities; Comment Request; Targeted Teacher Shortage Areas Nationwide Listing AGENCY: Office of Postsecondary...

30 CFR 70.208 - Bimonthly sampling; designated areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... each designated area on a production shift during each bimonthly period beginning with the bimonthly... dust sampling of designated areas shall begin on the first production shift during the next bimonthly... on which there is a production shift following the day of receipt of notification. (d) Upon issuance...

30 CFR 70.208 - Bimonthly sampling; designated areas.

Code of Federal Regulations, 2012 CFR

2012-07-01

... each designated area on a production shift during each bimonthly period beginning with the bimonthly... dust sampling of designated areas shall begin on the first production shift during the next bimonthly... on which there is a production shift following the day of receipt of notification. (d) Upon issuance...

30 CFR 70.208 - Bimonthly sampling; designated areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... each designated area on a production shift during each bimonthly period beginning with the bimonthly... dust sampling of designated areas shall begin on the first production shift during the next bimonthly... on which there is a production shift following the day of receipt of notification. (d) Upon issuance...

Methods to enable the design of bioactive small molecules targeting RNA

PubMed Central

Disney, Matthew D.; Yildirim, Ilyas; Childs-Disney, Jessica L.

2014-01-01

RNA is an immensely important target for small molecule therapeutics or chemical probes of function. However, methods that identify, annotate, and optimize RNA-small molecule interactions that could enable the design of compounds that modulate RNA function are in their infancies. This review describes recent approaches that have been developed to understand and optimize RNA motif-small molecule interactions, including Structure-Activity Relationships Through Sequencing (StARTS), quantitative structure-activity relationships (QSAR), chemical similarity searching, structure-based design and docking, and molecular dynamics (MD) simulations. Case studies described include the design of small molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and telomerase RNA. These approaches can be combined to afford a synergistic method to exploit the myriad of RNA targets in the transcriptome. PMID:24357181

Injector design for liner-on-target gas-puff experiments

NASA Astrophysics Data System (ADS)

Valenzuela, J. C.; Krasheninnikov, I.; Conti, F.; Wessel, F.; Fadeev, V.; Narkis, J.; Ross, M. P.; Rahman, H. U.; Ruskov, E.; Beg, F. N.

2017-11-01

We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ˜1 cm radius gas profile that satisfies the theoretical requirement for best performance on ˜1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

Injector design for liner-on-target gas-puff experiments.

PubMed

Valenzuela, J C; Krasheninnikov, I; Conti, F; Wessel, F; Fadeev, V; Narkis, J; Ross, M P; Rahman, H U; Ruskov, E; Beg, F N

2017-11-01

We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ∼1 cm radius gas profile that satisfies the theoretical requirement for best performance on ∼1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.

Beyond cysteine: recent developments in the area of targeted covalent inhibition.

PubMed

Mukherjee, Herschel; Grimster, Neil P

2018-05-29

Over the past decade targeted covalent inhibitors have undergone a renaissance due to the clinical validation and regulatory approval of several small molecule therapeutics that are designed to irreversibly modify their target protein. Invariably, these compounds rely on the serendipitous placement of a cysteine residue proximal to the small molecule binding site; while this strategy has afforded numerous successes, it necessarily limits the number of proteins that can be targeted by this approach. This drawback has led several research groups to develop novel methodologies that target non-cysteine residues for covalent modification. Herein, we survey the current literature of warheads that covalently modify non-cysteine amino acids in proteins. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adaptive waveform optimization design for target detection in cognitive radar

NASA Astrophysics Data System (ADS)

Zhang, Xiaowen; Wang, Kaizhi; Liu, Xingzhao

2017-01-01

The problem of adaptive waveform design for target detection in cognitive radar (CR) is investigated. This problem is analyzed in signal-dependent interference, as well as additive channel noise for extended target with unknown target impulse response (TIR). In order to estimate the TIR accurately, the Kalman filter is used in target tracking. In each Kalman filtering iteration, a flexible online waveform spectrum optimization design taking both detection and range resolution into account is modeled in Fourier domain. Unlike existing CR waveform, the proposed waveform can be simultaneously updated according to the environment information fed back by receiver and radar performance demands. Moreover, the influence of waveform spectral phase to radar performance is analyzed. Simulation results demonstrate that CR with the proposed waveform performs better than a traditional radar system with a fixed waveform and offers more flexibility and suitability. In addition, waveform spectral phase will not influence tracking, detection, and range resolution performance but will greatly influence waveform forming speed and peak-to-average power ratio.

Conceptual design considerations and neutronics of lithium fall laser fusion target chambers

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

Meier, W.R.; Thomson, W.B.

1978-05-31

Atomics International and Lawrence Livermore Laboratory are involved in the conceptual design of a laser fusion power plant incorporating the lithium fall target chamber. In this paper we discuss some of the more important design considerations for the target chamber and evaluate its nuclear performance. Sizing and configuration of the fall, hydraulic effects, and mechanical design considerations are addressed. The nuclear aspects examined include tritium breeding, energy deposition, and radiation damage.

Advances in target design for heavy ion fusion

NASA Astrophysics Data System (ADS)

Callahan, D. A.; Tabak, M.; Bennett, G. R.; Cuneo, M. E.; Vesey, R. A.; Nikroo, A.; Czechowicz, D.; Steinman, D.

2005-12-01

Over the past few years, the emphasis in heavy ion target design has moved from the distributed radiator target to the 'hybrid' target because the hybrid target allows a larger beam focal spot than the distributed radiator (~5 mm radius rather than ~2 mm radius). The larger spot relaxes some of the requirements on the driver, but introduces some new target physics issues. Most notable is the use of shine shields and shims in the hohlraum to achieve symmetry rather than achieving symmetry by beam placement. The shim is a thin layer of material placed on or near the capsule surface to block a small amount of excess radiation. While we have been developing this technique for the heavy ion hybrid target, the technique can also be used in any indirect drive target. We have begun testing the concept of a shim to improve symmetry using a double-ended z-pinch hohlraum on the Sandia Z-machine. Experiments using shimmed thin wall capsules have shown that we can reverse the sign of a P2 asymmetry and significantly reduce the size of a P4 asymmetry. These initial experiments demonstrate the concept of a shim as another method for controlling early time asymmetries in ICF capsules.

Designing an Active Target Test Projection Chamber

NASA Astrophysics Data System (ADS)

Koci, James; Tan Ahn Collaboration, Dr.; Nicolas Dixneuf Collaboration

2015-10-01

The development of instrumentation in nuclear physics is crucial for advancing our ability to measure the properties of exotic nuclei. One limitation of the use of exotic nuclei in experiment is their very low production intensities. Recently, detectors, called active-target dectectors, have been developed to address this issue. Active-target detectors use a gas medium to image charged-particle tracks that are emitted in nuclear reactions. Last semester, I designed a vacuum chamber to be used in developing Micro-Pattern Gas detectors that will upgrade the capabilities of an active-target detector called the Prototype AT-TPC. With the exterior of the chamber complete, I have now been using an electric field modeling program, Garfield, developed by CERN to design a field cage to be placed within the vacuum chamber. The field cage will be a box-like apparatus consisting of two parallel metal plates connected with a resistor chain and attached to wires wrapped between them. The cage will provide a uniform electric field within the chamber to drift electrons from nuclear reactions down to the detector in the bottom of the chamber. These signals are then amplified by a proportional counter, and the data is sent to a computer. For the long term, we would like to incorporate a Micro-Pattern Gas Detectors in the interior of the chamber and eventually use the AT-TPC to examine various nuclei. Dr. Ahn is my advising professor.

Progress in bipolar disorder drug design toward the development of novel therapeutic targets: a clinician's perspective.

PubMed

Fornaro, Michele; Kardash, Lubna; Novello, Stefano; Fusco, Andrea; Anastasia, Annalisa; De Berardis, Domenico; Perna, Giampaolo; Carta, Mauro Giovanni

2018-03-01

Bipolar disorder (BD) is a considerable burden to the affected individual. The need for novel drug targets and improved drug design (DD) in BD is therefore clear. Areas covered: The following article provides a brief, narrative, clinician-oriented overview of the most promising novel pharmacological targets for BD along with a concise overview regarding the general DD process and the unmet needs relevant to BD. Expert opinion: A number of novel potential drug targets have been investigated. With the notable exception of the kynurenine pathway, available evidence is too scarce to highlight a definitive roadmap for forthcoming DD in BD. BD itself may present with different facets, as it is a polymorphic clinical spectrum. Therefore, promoting clinical-case stratification should be based on precision medicine, rather than on novel biological targets. Furthermore, the full release of raw study data to the scientific community and the development of uniform clinical trial standards (including more realistic outcomes) should be promoted to facilitate the DD process in BD.

Introduction to spallation physics and spallation-target design

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

Russell, G.J.; Pitcher, E.J.; Daemen, L.L.

1995-10-01

When coupled with the spallation process in appropriate target materials, high-power accelerators can be used to produce large numbers of neutrons, thus providing an alternate method to the use of nuclear reactors for this purpose. Spallation offers exciting new possibilities for generating intense neutron fluxes for a variety of applications, including: (a) spallation-neutron sources for materials science research; (b) accelerator-based production of tritium; (c) accelerator-based transmutation of waste; (d) accelerator-based destruction of plutonium; and (e) radioisotope production for medical and energy applications. Target design plays a key role in these applications, with neutron production/leakage being strongly dependent on the incidentmore » particle type and energy, and target material and geometry.« less

Decoding Target Distance and Saccade Amplitude from Population Activity in the Macaque Lateral Intraparietal Area (LIP)

PubMed Central

Bremmer, Frank; Kaminiarz, Andre; Klingenhoefer, Steffen; Churan, Jan

2016-01-01

Primates perform saccadic eye movements in order to bring the image of an interesting target onto the fovea. Compared to stationary targets, saccades toward moving targets are computationally more demanding since the oculomotor system must use speed and direction information about the target as well as knowledge about its own processing latency to program an adequate, predictive saccade vector. In monkeys, different brain regions have been implicated in the control of voluntary saccades, among them the lateral intraparietal area (LIP). Here we asked, if activity in area LIP reflects the distance between fovea and saccade target, or the amplitude of an upcoming saccade, or both. We recorded single unit activity in area LIP of two macaque monkeys. First, we determined for each neuron its preferred saccade direction. Then, monkeys performed visually guided saccades along the preferred direction toward either stationary or moving targets in pseudo-randomized order. LIP population activity allowed to decode both, the distance between fovea and saccade target as well as the size of an upcoming saccade. Previous work has shown comparable results for saccade direction (Graf and Andersen, 2014a,b). Hence, LIP population activity allows to predict any two-dimensional saccade vector. Functional equivalents of macaque area LIP have been identified in humans. Accordingly, our results provide further support for the concept of activity from area LIP as neural basis for the control of an oculomotor brain-machine interface. PMID:27630547

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets.

PubMed

Wasko, Michael J; Pellegrene, Kendy A; Madura, Jeffry D; Surratt, Christopher K

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for "growing" the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets

PubMed Central

Wasko, Michael J.; Pellegrene, Kendy A.; Madura, Jeffry D.; Surratt, Christopher K.

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for “growing” the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies. PMID:26441817

Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

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

Strauch, Eva-Maria; Bernard, Steffen M.; La, David

Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein ismore » designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.« less

[Target chemotherapy of intestinal nematode infection in area with low endemicity].

PubMed

Zhang, Tao; Shen, Yi-ping; Liu, Ying; Yang, Wei-ping; Shao, Jing-ou; Ju, Shao-you; Dong, Kai; Xu, Ju-ling; Jiang, Ji-min

2002-01-01

To evaluate the control measures for intestinal nematodiasis in endemic area with low prevalence and intensity of infection. Target chemotherapy was carried out in high-risk population based on the epidemiological characteristics such as age and clinical findings. Albendazole and mebendazole were administered each 200 mg once daily every year for 3 or 5 years. Saturated brine floatation and Kato-Katz thick smear techniques were used for stool examination to evaluate the efficacy of treatment. Two hundred residents from each of the three investigation villages were selected for target chemotherapy once a year for three years. The prevalence of intestinal nematodes decreased from 6.2% in 1995 to 5.4% in 1996 and 3.2% in 1997, and remained at 2.3% after three years in 2000. One control village where only primary school students were treated once a year for 5 years, the prevalence of Ascaris and Trichuris infection also decreased from 1.4% and 4.2% in 1995 to 0.9% and 1.4% in 2000, respectively. The target chemotherapy on the predisposed population to hookworm infection showed that the prevalence in the population above 41 years old was declined from 19.4% to 10.9%. The target chemotherapy is an economical and effective approach for the control of intestinal nematode infection in endemic area with low prevalence and intensity of infection.

Target Surface Area Effects on Hot Electron Dynamics from High Intensity Laser-Plasma Interactions

DTIC Science & Technology

2016-08-19

New J. Phys. 18 (2016) 063020 doi:10.1088/1367-2630/18/6/063020 PAPER Target surface area effects on hot electron dynamics from high intensity laser ...Science, University ofMichigan, AnnArbor,MI 48109-2099, USA E-mail: czulick@umich.edu Keywords: laser -plasma,mass-limited, fast electrons, sheath...field Abstract Reduced surface area targets were studied using an ultra-high intensity femtosecond laser in order to determine the effect of electron

7 CFR 3402.4 - Food and agricultural sciences areas targeted for National Needs Graduate and Postdoctoral...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Food and agricultural sciences areas targeted for..., AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS... sciences areas targeted for National Needs Graduate and Postdoctoral Fellowship Grants Program support...

Target-cancer cell specific activatable fluorescence imaging Probes: Rational Design and in vivo Applications

PubMed Central

Kobayashi, Hisataka; Choyke, Peter L.

2010-01-01

CONSPECTUS Conventional imaging methods, such as angiography, computed tomography, magnetic resonance imaging and radionuclide imaging, rely on contrast agents (iodine, gadolinium, radioisotopes) that are “always on”. While these agents have proven clinically useful, they are not sufficiently sensitive because of the inadequate target to background ratio. A unique aspect of optical imaging is that fluorescence probes can be designed to be activatable, i.e. only “turned on” under certain conditions. These probes can be designed to emit signal only after binding a target tissue, greatly increasing sensitivity and specificity in the detection of disease. There are two basic types of activatable fluorescence probes; 1) conventional enzymatically activatable probes, which exist in the quenched state until activated by enzymatic cleavage mostly outside of the cells, and 2) newly designed target-cell specific activatable probes, which are quenched until activated in targeted cells by endolysosomal processing that results when the probe binds specific cell-surface receptors and is subsequently internalized. Herein, we present a review of the rational design and in vivo applications of target-cell specific activatable probes. Designing these probes based on their photo-chemical (e.g. activation strategy), pharmacological (e.g. biodistribution), and biological (e.g. target specificity) properties has recently allowed the rational design and synthesis of target-cell specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photo-chemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include: self-quenching, homo- and hetero-fluorescence resonance energy transfer (FRET), H-dimer formation and photon-induced electron transfer (PeT). In addition, the repertoire is further expanded by the option for reversibility or irreversibility of the signal

Computational design of nanoparticle drug delivery systems for selective targeting

NASA Astrophysics Data System (ADS)

Duncan, Gregg A.; Bevan, Michael A.

2015-09-01

Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues.Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting

Targeting the dopamine D3 receptor: an overview of drug design strategies.

PubMed

Cortés, Antoni; Moreno, Estefanía; Rodríguez-Ruiz, Mar; Canela, Enric I; Casadó, Vicent

2016-07-01

Dopamine is a neurotransmitter widely distributed in both the periphery and the central nervous system (CNS). Its physiological effects are mediated by five closely related G protein-coupled receptors (GPCRs) that are divided into two major subclasses: the D1-like (D1, D5) and the D2-like (D2, D3, D4) receptors. D3 receptors (D3Rs) have the highest density in the limbic areas of the brain, which are associated with cognitive and emotional functions. These receptors are therefore attractive targets for therapeutic management. This review summarizes the functional and pharmacological characteristics of D3Rs, including the design and clinical relevance of full agonists, partial agonists and antagonists, as well as the capacity of these receptors to form active homodimers, heterodimers or higher order receptor complexes as pharmacological targets in several neurological and neurodegenerative disorders. The high sequence homology between D3R and the D2-type challenges the development of D3R-selective compounds. The design of new D3R-preferential ligands with improved physicochemical properties should provide a better pharmacokinetic/bioavailability profile and lesser toxicity than is found with existing D3R ligands. It is also essential to optimize D3R affinity and, especially, D3R vs. D2-type binding and functional selectivity ratios. Developing allosteric and bitopic ligands should help to improve the D3R selectivity of these drugs. As most evidence points to the ability of GPCRs to form homomers and heteromers, the most promising therapeutic strategy in the future is likely to involve the application of heteromer-selective drugs. These selective ligands would display different affinities for a given receptor depending on the receptor partners within the heteromer. Therefore, designing novel compounds that specifically target and modulate D1R-D3R heteromers would be an interesting approach for the treatment of levodopa (L-DOPA)-induced dyskinesias.

Computational design of high efficiency release targets for use at ISOL facilities

NASA Astrophysics Data System (ADS)

Liu, Y.; Alton, G. D.; Middleton, J. W.

1999-06-01

This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated vitreous carbon fiber (RVCF) or carbon-bonded-carbon-fiber (CBCF) to form highly permeable composite target matrices. Computational studies which simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation will be presented in this report.

36 CFR 212.56 - Identification of designated roads, trails, and areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... roads, trails, and areas. 212.56 Section 212.56 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE TRAVEL MANAGEMENT Designation of Roads, Trails, and Areas for Motor Vehicle Use § 212.56 Identification of designated roads, trails, and areas. Designated roads, trails, and areas...

Preliminary design report, Large Space Telescope OTA/SI Phase B study: High speed area photometer. [systems analysis

NASA Technical Reports Server (NTRS)

1975-01-01

A photometer is examined which combines several features from separate instruments into a single package. The design presented has both point and area photometry capability with provision for inserting filters to provide spectral discrimination. The electronics provide for photon counting mode for the point detectors and both photon counting and analog modes for the area detector. The area detector also serves as a target locating device for the point detectors. Topics discussed include: (1) electronic equipment requirements, (2) optical properties, (3) structural housing for the instrument, (4) motors and other mechanical components, (5) ground support equipment, and (6) environment control for the instrument. Engineering drawings and block diagrams are shown.

Urban-area extraction from polarimetric SAR image using combination of target decomposition and orientation angle

NASA Astrophysics Data System (ADS)

Zou, Bin; Lu, Da; Wu, Zhilu; Qiao, Zhijun G.

2016-05-01

The results of model-based target decomposition are the main features used to discriminate urban and non-urban area in polarimetric synthetic aperture radar (PolSAR) application. Traditional urban-area extraction methods based on modelbased target decomposition usually misclassified ground-trunk structure as urban-area or misclassified rotated urbanarea as forest. This paper introduces another feature named orientation angle to improve urban-area extraction scheme for the accurate mapping in urban by PolSAR image. The proposed method takes randomness of orientation angle into account for restriction of urban area first and, subsequently, implements rotation angle to improve results that oriented urban areas are recognized as double-bounce objects from volume scattering. ESAR L-band PolSAR data of the Oberpfaffenhofen Test Site Area was used to validate the proposed algorithm.

7 CFR 3402.4 - Food and agricultural sciences areas targeted for National Needs Graduate and Postdoctoral...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Food and agricultural sciences areas targeted for... AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Program Description § 3402.4 Food and agricultural sciences areas targeted for National Needs Graduate and...

7 CFR 3402.4 - Food and agricultural sciences areas targeted for National Needs Graduate and Postdoctoral...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 15 2013-01-01 2013-01-01 false Food and agricultural sciences areas targeted for... AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Program Description § 3402.4 Food and agricultural sciences areas targeted for National Needs Graduate and...

7 CFR 3402.4 - Food and agricultural sciences areas targeted for National Needs Graduate and Postdoctoral...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Food and agricultural sciences areas targeted for... AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Program Description § 3402.4 Food and agricultural sciences areas targeted for National Needs Graduate and...

7 CFR 3402.4 - Food and agricultural sciences areas targeted for National Needs Graduate and Postdoctoral...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 15 2012-01-01 2012-01-01 false Food and agricultural sciences areas targeted for... AGRICULTURE FOOD AND AGRICULTURAL SCIENCES NATIONAL NEEDS GRADUATE AND POSTGRADUATE FELLOWSHIP GRANTS PROGRAM Program Description § 3402.4 Food and agricultural sciences areas targeted for National Needs Graduate and...

43 CFR 423.60 - How special use areas are designated.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false How special use areas are designated. 423... Use Areas § 423.60 How special use areas are designated. (a) After making a determination under paragraph (b) of this section, an authorized official may: (1) Establish special use areas within...

43 CFR 423.60 - How special use areas are designated.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false How special use areas are designated. 423... Use Areas § 423.60 How special use areas are designated. (a) After making a determination under paragraph (b) of this section, an authorized official may: (1) Establish special use areas within...

Nutrient cycling Microbial Ecosystems: Assembly, Function and Targeted Design

DTIC Science & Technology

2017-05-05

different chemical transformations, converting potentially harmful chemicals via a series of intermediates, to harmless waste products. This shuttling of...Report: Nutrient-cycling Microbial Ecosystems: Assembly, Function and Targeted Design The views, opinions and/or findings contained in this report...are those of the author(s) and should not contrued as an official Department of the Army position, policy or decision, unless so designated by other

Design and Fabrication of Opacity Targets for the National Ignition Facility

DOE PAGES

Cardenas, Tana; Schmidt, Derek William; Dodd, Evan S.; ...

2017-12-22

Accurate models for opacity of partially ionized atoms are important for modeling and understanding stellar interiors and other high-energy-density phenomena such as inertial confinement fusion. Lawrence Livermore National Laboratory is leading a multilaboratory effort to conduct experiments on the National Ignition Facility (NIF) to try to reproduce recent opacity tests at the Sandia National Laboratory Z-facility. Since 2015, the NIF effort has evolved several hohlraum designs that consist of multiple pieces joined together. The target also has three components attached to the main stalk over a long distance with high tolerances that have resulted in several design iterations. The targetmore » has made use of rapid prototyped features to attach a capsule and collimator under the hohlraum while avoiding interference with the beams. Furthermore, this paper discusses the evolution of the hohlraum and overall target design and the challenges involved with fabricating and assembling these targets.« less

Design and Fabrication of Opacity Targets for the National Ignition Facility

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

Cardenas, Tana; Schmidt, Derek William; Dodd, Evan S.

Accurate models for opacity of partially ionized atoms are important for modeling and understanding stellar interiors and other high-energy-density phenomena such as inertial confinement fusion. Lawrence Livermore National Laboratory is leading a multilaboratory effort to conduct experiments on the National Ignition Facility (NIF) to try to reproduce recent opacity tests at the Sandia National Laboratory Z-facility. Since 2015, the NIF effort has evolved several hohlraum designs that consist of multiple pieces joined together. The target also has three components attached to the main stalk over a long distance with high tolerances that have resulted in several design iterations. The targetmore » has made use of rapid prototyped features to attach a capsule and collimator under the hohlraum while avoiding interference with the beams. Furthermore, this paper discusses the evolution of the hohlraum and overall target design and the challenges involved with fabricating and assembling these targets.« less

33 CFR 334.60 - Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Harbor, Mass.; naval aircraft bombing target area. 334.60 Section 334.60 Navigation and Navigable Waters... REGULATIONS § 334.60 Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area. (a... bombing target hulk James Longstreet in Cape Cod Bay at latitude 41°49′46″, longitude 70°02′54″. (b) The...

33 CFR 334.60 - Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Harbor, Mass.; naval aircraft bombing target area. 334.60 Section 334.60 Navigation and Navigable Waters... REGULATIONS § 334.60 Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area. (a... bombing target hulk James Longstreet in Cape Cod Bay at latitude 41°49′46″, longitude 70°02′54″. (b) The...

Mesophotic depths as refuge areas for fishery-targeted species on coral reefs

NASA Astrophysics Data System (ADS)

Lindfield, Steven J.; Harvey, Euan S.; Halford, Andrew R.; McIlwain, Jennifer L.

2016-03-01

Coral reefs are subjected to unprecedented levels of disturbance with population growth and climate change combining to reduce standing coral cover and stocks of reef fishes. Most of the damage is concentrated in shallow waters (<30 m deep) where humans can comfortably operate and where physical disturbances are most disruptive to marine organisms. Yet coral reefs can extend to depths exceeding 100 m, potentially offering refuge from the threats facing shallower reefs. We deployed baited remote underwater stereo-video systems (stereo-BRUVs) at depths of 10-90 m around the southern Mariana Islands to investigate whether fish species targeted by fishing in the shallows may be accruing benefits from being at depth. We show that biomass, abundance and species richness of fishery-targeted species increased from shallow reef areas to a depth of 60 m, whereas at greater depths, a lack of live coral habitat corresponded to lower numbers of fish. The majority of targeted species were found to have distributions that ranged from shallow depths (10 m) to depths of at least 70 m, emphasising that habitat, not depth, is the limiting factor in their vertical distribution. While the gradient of abundance and biomass versus depth was steepest for predatory species, the first species usually targeted by fishing, we also found that fishery-targeted herbivores prevailed in similar biomass and species richness to 60 m. Compared to shallow marine protected areas, there was clearly greater biomass of fishery-targeted species accrued in mesophotic depths. Particularly some species typically harvested by depth-limited fishing methods (e.g., spearfishing), such as the endangered humphead wrasse Cheilinus undulatus, were found in greater abundance on deeper reefs. We conclude that mesophotic depths provide essential fish habitat and refuge for fishery-targeted species, representing crucial zones for fishery management and research into the resilience of disturbed coral reef ecosystems.

Ground target geolocation based on digital elevation model for airborne wide-area reconnaissance system

NASA Astrophysics Data System (ADS)

Qiao, Chuan; Ding, Yalin; Xu, Yongsen; Xiu, Jihong

2018-01-01

To obtain the geographical position of the ground target accurately, a geolocation algorithm based on the digital elevation model (DEM) is developed for an airborne wide-area reconnaissance system. According to the platform position and attitude information measured by the airborne position and orientation system and the gimbal angles information from the encoder, the line-of-sight pointing vector in the Earth-centered Earth-fixed coordinate frame is solved by the homogeneous coordinate transformation. The target longitude and latitude can be solved with the elliptical Earth model and the global DEM. The influences of the systematic error and measurement error on ground target geolocation calculation accuracy are analyzed by the Monte Carlo method. The simulation results show that this algorithm can improve the geolocation accuracy of ground target in rough terrain area obviously. The geolocation accuracy of moving ground target can be improved by moving average filtering (MAF). The validity of the geolocation algorithm is verified by the flight test in which the plane flies at a geodetic height of 15,000 m and the outer gimbal angle is <47°. The geolocation root mean square error of the target trajectory is <45 and <7 m after MAF.

33 CFR 334.1460 - Atlantic Ocean and Vieques Sound, in vicinity of Culebra Island; bombing and gunnery target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., in vicinity of Culebra Island; bombing and gunnery target area. 334.1460 Section 334.1460 Navigation...; bombing and gunnery target area. (a) The danger zone. From Punta Resaca on the north coast of Culebra at... danger zone is subject to use as a target area for bombing and gunnery practice. It will be open to...

33 CFR 334.1460 - Atlantic Ocean and Vieques Sound, in vicinity of Culebra Island; bombing and gunnery target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., in vicinity of Culebra Island; bombing and gunnery target area. 334.1460 Section 334.1460 Navigation...; bombing and gunnery target area. (a) The danger zone. From Punta Resaca on the north coast of Culebra at... danger zone is subject to use as a target area for bombing and gunnery practice. It will be open to...

Pharmacophore based design of some multi-targeted compounds targeted against pathways of diabetic complications.

PubMed

Chadha, Navriti; Silakari, Om

2017-09-01

Diabetic complications is a complex metabolic disorder developed primarily due to prolonged hyperglycemia in the body. The complexity of the disease state as well as the unifying pathophysiology discussed in the literature reports exhibited that the use of multi-targeted agents with multiple complementary biological activities may offer promising therapy for the intervention of the disease over the single-target drugs. In the present study, novel thiazolidine-2,4-dione analogues were designed as multi-targeted agents implicated against the molecular pathways involved in diabetic complications using knowledge based as well as in-silico approaches such as pharmacophore mapping, molecular docking etc. The hit molecules were duly synthesized and biochemical estimation of these molecules against aldose reductase (ALR2), protein kinase Cβ (PKCβ) and poly (ADP-ribose) polymerase 1 (PARP-1) led to identification of compound 2 that showed good potency against PARP-1 and ALR2 enzymes. These positive results support the progress of a low cost multi-targeted agent with putative roles in diabetic complications. Copyright © 2017 Elsevier Inc. All rights reserved.

GLRS-R 2-colour retroreflector target design and predicted performance

NASA Astrophysics Data System (ADS)

Lund, Glenn

The retroreflector ground target design for the GLRS-R spaceborne dual wavelength laser ranging system is described. The passive design flows down from the requirements of high station autonomy, high global field of view, little or no multiple pulse returns, and adequate optical cross section for most ranging geometries. The solution makes use of five hollow cube corner retroreflectors of which one points to the zenith and the remaining four are inclined from the vertical at uniform azimuthal spacings. The need for large retroreflectors is expected to generate narrow diffraction lobes. A good compromise solution is found by spoiling just one of the retroereflector dihedral angles from 90 deg, thus generating two symmetrically oriented diffraction lobes in the return beam. The required spoil angles are found to have little dependance on ground target latitude. Various link budget analyses are presented. They show the influence of such factors as point ahead optimization, turbulence, ranging angle, atmospheric visibility, and ground target thermal deformations.

New designs of LMJ targets for early ignition experiments

NASA Astrophysics Data System (ADS)

C-Clérouin, C.; Bonnefille, M.; Dattolo, E.; Fremerye, P.; Galmiche, D.; Gauthier, P.; Giorla, J.; Laffite, S.; Liberatore, S.; Loiseau, P.; Malinie, G.; Masse, L.; Poggi, F.; Seytor, P.

2008-05-01

The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 40 laser quads, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness are then designed for this purpose. A first strategy is to use scaled-down cylindrical hohlraums and capsules, taking advantage of our better understanding of the problem, set on theoretical modelling, simulations and experiments. Another strategy is to work specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, which is with parametric instabilities a crucial drawback of indirect drive. An alternative design is proposed, made up of the nominal 60 quads capsule, named A1040, in a rugby-shaped hohlraum. Robustness evaluations of these different targets are in progress.

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. 334.10 Section 334.10 Navigation and Navigable Waters CORPS... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger...

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. 334.10 Section 334.10 Navigation and Navigable Waters CORPS... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger...

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. 334.10 Section 334.10 Navigation and Navigable Waters CORPS... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger...

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. 334.10 Section 334.10 Navigation and Navigable Waters CORPS... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger...

Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction

PubMed Central

2012-01-01

Background Choosing appropriate primers is probably the single most important factor affecting the polymerase chain reaction (PCR). Specific amplification of the intended target requires that primers do not have matches to other targets in certain orientations and within certain distances that allow undesired amplification. The process of designing specific primers typically involves two stages. First, the primers flanking regions of interest are generated either manually or using software tools; then they are searched against an appropriate nucleotide sequence database using tools such as BLAST to examine the potential targets. However, the latter is not an easy process as one needs to examine many details between primers and targets, such as the number and the positions of matched bases, the primer orientations and distance between forward and reverse primers. The complexity of such analysis usually makes this a time-consuming and very difficult task for users, especially when the primers have a large number of hits. Furthermore, although the BLAST program has been widely used for primer target detection, it is in fact not an ideal tool for this purpose as BLAST is a local alignment algorithm and does not necessarily return complete match information over the entire primer range. Results We present a new software tool called Primer-BLAST to alleviate the difficulty in designing target-specific primers. This tool combines BLAST with a global alignment algorithm to ensure a full primer-target alignment and is sensitive enough to detect targets that have a significant number of mismatches to primers. Primer-BLAST allows users to design new target-specific primers in one step as well as to check the specificity of pre-existing primers. Primer-BLAST also supports placing primers based on exon/intron locations and excluding single nucleotide polymorphism (SNP) sites in primers. Conclusions We describe a robust and fully implemented general purpose primer design tool

36 CFR 294.49 - List of designated Colorado Roadless Areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 2 2014-07-01 2014-07-01 false List of designated Colorado... AGRICULTURE SPECIAL AREAS Colorado Roadless Area Management § 294.49 List of designated Colorado Roadless Areas. All National Forest System lands within the State of Colorado listed in this section are hereby...

36 CFR 294.49 - List of designated Colorado Roadless Areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 2 2013-07-01 2013-07-01 false List of designated Colorado... AGRICULTURE SPECIAL AREAS Colorado Roadless Area Management § 294.49 List of designated Colorado Roadless Areas. All National Forest System lands within the State of Colorado listed in this section are hereby...

Novel target design for enhanced laser driven proton acceleration

NASA Astrophysics Data System (ADS)

Dalui, Malay; Kundu, M.; Tata, Sheroy; Lad, Amit D.; Jha, J.; Ray, Krishanu; Krishnamurthy, M.

2017-09-01

We demonstrate a simple method of preparing structured target for enhanced laser-driven proton acceleration under target-normal-sheath-acceleration scheme. A few layers of genetically modified, clinically grown micron sized E. Coli bacteria cell coated on a thin metal foil has resulted in an increase in the maximum proton energy by about 1.5 times and the total proton yield is enhanced by approximately 25 times compared to an unstructured reference foil at a laser intensity of 1019 W/cm2. Particle-in-cell simulations on the system shows that the structures on the target-foil facilitates anharmonic resonance, contributing to enhanced hot electron production which leads to stronger accelerating field. The effect is observed to grow as the number of structures is increased in the focal area of the laser pulse.

Measuring the extent and effectiveness of protected areas as an indicator for meeting global biodiversity targets

PubMed Central

Chape, S; Harrison, J; Spalding, M; Lysenko, I

2005-01-01

There are now over 100 000 protected areas worldwide, covering over 12% of the Earth's land surface. These areas represent one of the most significant human resource use allocations on the planet. The importance of protected areas is reflected in their widely accepted role as an indicator for global targets and environmental assessments. However, measuring the number and extent of protected areas only provides a unidimensional indicator of political commitment to biodiversity conservation. Data on the geographic location and spatial extent of protected areas will not provide information on a key determinant for meeting global biodiversity targets: ‘effectiveness’ in conserving biodiversity. Although tools are being devised to assess management effectiveness, there is no globally accepted metric. Nevertheless, the numerical, spatial and geographic attributes of protected areas can be further enhanced by investigation of the biodiversity coverage of these protected areas, using species, habitats or biogeographic classifications. This paper reviews the current global extent of protected areas in terms of geopolitical and habitat coverage, and considers their value as a global indicator of conservation action or response. The paper discusses the role of the World Database on Protected Areas and collection and quality control issues, and identifies areas for improvement, including how conservation effectiveness indicators may be included in the database to improve the value of protected areas data as an indicator for meeting global biodiversity targets. PMID:15814356

36 CFR 212.51 - Designation of roads, trails, and areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Designation of roads, trails... AGRICULTURE TRAVEL MANAGEMENT Designation of Roads, Trails, and Areas for Motor Vehicle Use § 212.51 Designation of roads, trails, and areas. (a) General. Motor vehicle use on National Forest System roads, on...

A multiplex primer design algorithm for target amplification of continuous genomic regions.

PubMed

Ozturk, Ahmet Rasit; Can, Tolga

2017-06-19

Targeted Next Generation Sequencing (NGS) assays are cost-efficient and reliable alternatives to Sanger sequencing. For sequencing of very large set of genes, the target enrichment approach is suitable. However, for smaller genomic regions, the target amplification method is more efficient than both the target enrichment method and Sanger sequencing. The major difficulty of the target amplification method is the preparation of amplicons, regarding required time, equipment, and labor. Multiplex PCR (MPCR) is a good solution for the mentioned problems. We propose a novel method to design MPCR primers for a continuous genomic region, following the best practices of clinically reliable PCR design processes. On an experimental setup with 48 different combinations of factors, we have shown that multiple parameters might effect finding the first feasible solution. Increasing the length of the initial primer candidate selection sequence gives better results whereas waiting for a longer time to find the first feasible solution does not have a significant impact. We generated MPCR primer designs for the HBB whole gene, MEFV coding regions, and human exons between 2000 bp to 2100 bp-long. Our benchmarking experiments show that the proposed MPCR approach is able produce reliable NGS assay primers for a given sequence in a reasonable amount of time.

24 CFR 598.200 - Who nominates an area for designation?

Code of Federal Regulations, 2012 CFR

2012-04-01

... designation? 598.200 Section 598.200 Housing and Urban Development Regulations Relating to Housing and Urban... DESIGNATIONS Nomination Procedure § 598.200 Who nominates an area for designation? Applicants for empowerment... the area is located, except as provided in §§ 598.500, 598.510, and 598.515. The nomination must be...

24 CFR 598.200 - Who nominates an area for designation?

Code of Federal Regulations, 2013 CFR

2013-04-01

... designation? 598.200 Section 598.200 Housing and Urban Development Regulations Relating to Housing and Urban... DESIGNATIONS Nomination Procedure § 598.200 Who nominates an area for designation? Applicants for empowerment... the area is located, except as provided in §§ 598.500, 598.510, and 598.515. The nomination must be...

24 CFR 598.200 - Who nominates an area for designation?

Code of Federal Regulations, 2014 CFR

2014-04-01

... designation? 598.200 Section 598.200 Housing and Urban Development Regulations Relating to Housing and Urban... DESIGNATIONS Nomination Procedure § 598.200 Who nominates an area for designation? Applicants for empowerment... the area is located, except as provided in §§ 598.500, 598.510, and 598.515. The nomination must be...

Targeted proteins for diabetes drug design

NASA Astrophysics Data System (ADS)

Doan Trang Nguyen, Ngoc; Thi Le, Ly

2012-03-01

Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people.

Design and Implementation of the Automated Rendezvous Targeting Algorithms for Orion

NASA Technical Reports Server (NTRS)

DSouza, Christopher; Weeks, Michael

2010-01-01

The Orion vehicle will be designed to perform several rendezvous missions: rendezvous with the ISS in Low Earth Orbit (LEO), rendezvous with the EDS/Altair in LEO, a contingency rendezvous with the ascent stage of the Altair in Low Lunar Orbit (LLO) and a contingency rendezvous in LLO with the ascent and descent stage in the case of an aborted lunar landing. Therefore, it is not difficult to realize that each of these scenarios imposes different operational, timing, and performance constraints on the GNC system. To this end, a suite of on-board guidance and targeting algorithms have been designed to meet the requirement to perform the rendezvous independent of communications with the ground. This capability is particularly relevant for the lunar missions, some of which may occur on the far side of the moon. This paper will describe these algorithms which are designed to be structured and arranged in such a way so as to be flexible and able to safely perform a wide variety of rendezvous trajectories. The goal of the algorithms is not to merely fly one specific type of canned rendezvous profile. Conversely, it was designed from the start to be general enough such that any type of trajectory profile can be flown.(i.e. a coelliptic profile, a stable orbit rendezvous profile, and a expedited LLO rendezvous profile, etc) all using the same rendezvous suite of algorithms. Each of these profiles makes use of maneuver types which have been designed with dual goals of robustness and performance. They are designed to converge quickly under dispersed conditions and they are designed to perform many of the functions performed on the ground today. The targeting algorithms consist of a phasing maneuver (NC), an altitude adjust maneuver (NH), and plane change maneuver (NPC), a coelliptic maneuver (NSR), a Lambert targeted maneuver, and several multiple-burn targeted maneuvers which combine one of more of these algorithms. The derivation and implementation of each of these

43 CFR 1610.7-2 - Designation of areas of critical environmental concern.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Designation of areas of critical..., PROGRAMMING, BUDGETING Resource Management Planning § 1610.7-2 Designation of areas of critical environmental concern. Areas having potential for Areas of Critical Environmental Concern (ACEC) designation and...

77 FR 42354 - Designation of Transportation Management Areas

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-18

... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Federal Highway Administration Designation of Transportation Management Areas AGENCIES: Federal Transit Administration (FTA), Federal Highway... Management Areas (TMAs). The FTA and FHWA are taking this action in compliance with the agencies' authorizing...

Ligand design for riboswitches, an emerging target class for novel antibiotics.

PubMed

Rekand, Illimar Hugo; Brenk, Ruth

2017-09-01

Riboswitches are cis-acting gene regulatory elements and constitute potential targets for new antibiotics. Recent studies in this field have started to explore these targets for drug discovery. New ligands found by fragment screening, design of analogs of the natural ligands or serendipitously by phenotypic screening have shown antibacterial effects in cell assays against a range of bacteria strains and in animal models. In this review, we highlight the most advanced drug design work of riboswitch ligands and discuss the challenges in the field with respect to the development of antibiotics with a new mechanism of action.

Target-cancer-cell-specific activatable fluorescence imaging probes: rational design and in vivo applications.

PubMed

Kobayashi, Hisataka; Choyke, Peter L

2011-02-15

Conventional imaging methods, such as angiography, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide imaging, rely on contrast agents (iodine, gadolinium, and radioisotopes, for example) that are "always on." Although these indicators have proven clinically useful, their sensitivity is lacking because of inadequate target-to-background signal ratio. A unique aspect of optical imaging is that fluorescence probes can be designed to be activatable, that is, only "turned on" under certain conditions. These probes are engineered to emit signal only after binding a target tissue; this design greatly increases sensitivity and specificity in the detection of disease. Current research focuses on two basic types of activatable fluorescence probes. The first developed were conventional enzymatically activatable probes. These fluorescent molecules exist in the quenched state until activated by enzymatic cleavage, which occurs mostly outside of the cells. However, more recently, researchers have begun designing target-cell-specific activatable probes. These fluorophores exist in the quenched state until activated within targeted cells by endolysosomal processing, which results when the probe binds specific receptors on the cell surface and is subsequently internalized. In this Account, we present a review of the rational design and in vivo applications of target-cell-specific activatable probes. In engineering these probes, researchers have asserted control over a variety of factors, including photochemistry, pharmacological profile, and biological properties. Their progress has recently allowed the rational design and synthesis of target-cell-specific activatable fluorescence imaging probes, which can be conjugated to a wide variety of targeting molecules. Several different photochemical mechanisms have been utilized, each of which offers a unique capability for probe design. These include self-quenching, homo- and hetero-fluorescence resonance

Effects of cost metric on cost-effectiveness of protected-area network design in urban landscapes.

PubMed

Burkhalter, J C; Lockwood, J L; Maslo, B; Fenn, K H; Leu, K

2016-04-01

A common goal in conservation planning is to acquire areas that are critical to realizing biodiversity goals in the most cost-effective manner. The way monetary acquisition costs are represented in such planning is an understudied but vital component to realizing cost efficiencies. We sought to design a protected-area network within a forested urban region that would protect 17 birds of conservation concern. We compared the total costs and spatial structure of the optimal protected-area networks produced using three acquisition-cost surrogates (area, agricultural land value, and tax-assessed land value). Using the tax-assessed land values there was a 73% and 78% cost savings relative to networks derived using area or agricultural land value, respectively. This cost reduction was due to the considerable heterogeneity in acquisition costs revealed in tax-assessed land values, especially for small land parcels, and the corresponding ability of the optimization algorithm to identify lower-cost parcels for inclusion that had equal value to our target species. Tax-assessed land values also reflected the strong spatial differences in acquisition costs (US$0.33/m(2)-$55/m(2)) and thus allowed the algorithm to avoid inclusion of high-cost parcels when possible. Our results add to a nascent but growing literature that suggests conservation planners must consider the cost surrogate they use when designing protected-area networks. We suggest that choosing cost surrogates that capture spatial- and size-dependent heterogeneity in acquisition costs may be relevant to establishing protected areas in urbanizing ecosystems. © 2015 Society for Conservation Biology.

Designing Multi-target Compound Libraries with Gaussian Process Models.

PubMed

Bieler, Michael; Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Kriegl, Jan M; Schneider, Gisbert

2016-05-01

We present the application of machine learning models to selecting G protein-coupled receptor (GPCR)-focused compound libraries. The library design process was realized by ant colony optimization. A proprietary Boehringer-Ingelheim reference set consisting of 3519 compounds tested in dose-response assays at 11 GPCR targets served as training data for machine learning and activity prediction. We compared the usability of the proprietary data with a public data set from ChEMBL. Gaussian process models were trained to prioritize compounds from a virtual combinatorial library. We obtained meaningful models for three of the targets (5-HT2c , MCH, A1), which were experimentally confirmed for 12 of 15 selected and synthesized or purchased compounds. Overall, the models trained on the public data predicted the observed assay results more accurately. The results of this study motivate the use of Gaussian process regression on public data for virtual screening and target-focused compound library design. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

33 CFR 334.200 - Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River... Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U.S. Naval Air...) The regulations. (i) Through navigation of surface craft outside the target areas will be permitted at...

Rational design of chemical genetic probes of RNA function and lead therapeutics targeting repeating transcripts.

PubMed

Disney, Matthew D

2013-12-01

RNA is an important yet vastly underexploited target for small molecule chemical probes or lead therapeutics. Small molecules have been used successfully to modulate the function of the bacterial ribosome, viral RNAs and riboswitches. These RNAs are either highly expressed or can be targeted using substrate mimicry, a mainstay in the design of enzyme inhibitors. However, most cellular RNAs are neither highly expressed nor have a lead small molecule inhibitor, a significant challenge for drug discovery efforts. Herein, I describe the design of small molecules targeting expanded repeating transcripts that cause myotonic muscular dystrophy (DM). These test cases illustrate the challenges of designing small molecules that target RNA and the advantages of targeting repeating transcripts. Lastly, I discuss how small molecules might be more advantageous than oligonucleotides for targeting RNA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mock Target Window OTR and IR Design and Testing

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

Wass, Alexander Joseph

In order to fully verify temperature measurements made on the target window using infrared (IR) optical non-contact methods, actual comparative measurements are made with a real beam distribution as the heat source using Argonne National Laboratory’s (ANL) 35 MeV electron accelerator. Using Monte Carlo N-Particle (MCNP) simulations and thermal Finite Element Analysis (FEA), a cooled mock target window with thermocouple implants is designed to be used in such a test to achieve window temperatures up to 700°C. An uncoated and blackcoated mock window is designed to enhance the IR temperature measurements and verify optical transmitted radiation (OTR) imagery. This allowsmore » us to fully verify and characterize our temperature accuracy with our current IR camera method and any future method we may wish to explore using actual production conditions. This test also provides us with valuable conclusions/concerns regarding the calibration method we developed using our IR test stand at TA-53 in MPF-14.« less

Design principles of water sensitive in settlement area on the river banks

NASA Astrophysics Data System (ADS)

Ryanti, E.; Hasriyanti, N.; Utami, W. D.

2018-03-01

This research will formulate the principle of designing settlement area of Kapuas River Pontianak with the approach of water sensitive concept of urban design (WSUD) the densely populated settlement area. By using a case study the approach that is a dense settlement area located on the banks of the river with literature study techniques to formulate the aspects considered and components that are set in the design, descriptive analysis with the rationalistic paradigm for identification characteristics of the settlement in the river banks areas with consideration of WSUD elements and formulate the principles of designing water-sensitive settlement areas. This research is important to do because the problems related to the water management system in the existing riverside settlement in Pontianak has not been maximal to do. So the primary of this research contains several objectives that will be achieved that is identifying the characteristics of riverside settlement area based on consideration of design aspects of the area that are sensitive to water and the principle of designing the area so that the existing problem structure will be formulated in relation to the community’s need for infrastructure in settlement environment and formulate and develop appropriate technology guidelines for integrated water management systems in riverside settlement areas and design techniques for water-sensitive settlements (WSUD).

Designing Targeted Educational Voucher Schemes for the Poor in Developing Countries

ERIC Educational Resources Information Center

Shafiq, M. Najeeb

2009-01-01

Targeted educational voucher schemes [TEVS] are often proposed for poor children in developing countries. This article explores the design of an effective TEVS using three policy instruments: regulation, support services, and finance. The regulation design addresses the rules that must be adhered to by participating households, children, and…

Targeting the impact of agri-environmental policy - Future scenarios in two less favoured areas in Portugal.

PubMed

Jones, Nadia; Fleskens, Luuk; Stroosnijder, Leo

2016-10-01

Targeting agri-environmental measures (AEM) improves their effectiveness in the delivery of public goods, provided the necessary coordination with other incentives. In less favoured areas (LFA) measures focusing on the conservation of extensive farming contribute to sustainable land management in these areas. In this paper we investigate the implementation of a possible AEM supporting the improvement of permanent pastures coordinated with the extensive livestock and single farm payments actually in place. Through applying a spatially-explicit mixed integer optimisation model we simulate future land use scenarios for two less favoured areas in Portugal (Centro and Alentejo) considering two policy scenarios: a 'targeted AEM', and a 'non-targeted AEM'. We then compare the results with a 'basic policy' option (reflecting a situation without AEM). This is done with regard to landscape-scale effects on the reduction of fire hazard and erosion risk, as well as effects on farm income. The results show that an AEM for permanent pastures would be more cost-effective for erosion and fire hazard mitigation if implemented within a spatially targeted framework. However when cost-effectiveness is assessed with other indicators (e.g. net farm income and share of grazing livestock) 'non-targeted AEM' implementation delivers the best outcome in Alentejo. In Centro the implementation of an AEM involves important losses of income compared to the 'basic policy'. 'Targeted AEM' tends to favour farms in very marginal conditions, i.e. targeting is demonstrated to perform best in landscapes where spatial heterogeneity is higher. The results also show the risk of farm abandonment in the two studied less favoured areas: in all three scenarios more than 30% of arable land is deemed to be abandoned. Copyright © 2016 Elsevier Ltd. All rights reserved.

Area estimation using multiyear designs and partial crop identification

NASA Technical Reports Server (NTRS)

Sielken, R. L., Jr.

1983-01-01

Progress is reported for the following areas: (1) estimating the stratum's crop acreage proportion using the multiyear area estimation model; (2) assessment of multiyear sampling designs; and (3) development of statistical methodology for incorporating partially identified sample segments into crop area estimation.

42 CFR 460.22 - Service area designation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PACE Organization Application and Waiver Process § 460.22 Service area designation. (a) An...

42 CFR 460.22 - Service area designation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PACE Organization Application and Waiver Process § 460.22 Service area designation. (a) An...

The area centralis in the chicken retina contains efferent target amacrine cells

PubMed Central

Weller, Cynthia; Lindstrom, Sarah H.; De Grip, Willem J.; Wilson, Martin

2012-01-01

The retinas of birds receive a substantial efferent, or centrifugal, input from a midbrain nucleus. The function of this input is presently unclear but previous work in the pigeon has shown that efferent input is excluded from the area centralis, suggesting that the functions of the area centralis and the efferent system are incompatible. Using an antibody specific to rods, we have identified the area centralis in another species, the chicken, and mapped the distribution of the unique amacrine cells that are the postsynaptic partners of efferent fibers. Efferent target amacrine cells are found within the chicken area centralis and their density is continuous across the border of the area centralis. In contrast to the pigeon retina then, we conclude that the chicken area centralis receives efferent input. We suggest that the difference between the 2 species is attributable to the presence of a fovea within the area centralis of the pigeon and its absence from that of the chicken. PMID:19296862

CFD Analysis and Design of Detailed Target Configurations for an Accelerator-Driven Subcritical System

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

Kraus, Adam; Merzari, Elia; Sofu, Tanju

2016-08-01

High-fidelity analysis has been utilized in the design of beam target options for an accelerator driven subcritical system. Designs featuring stacks of plates with square cross section have been investigated for both tungsten and uranium target materials. The presented work includes the first thermal-hydraulic simulations of the full, detailed target geometry. The innovative target cooling manifold design features many regions with complex flow features, including 90 bends and merging jets, which necessitate three-dimensional fluid simulations. These were performed using the commercial computational fluid dynamics code STAR-CCM+. Conjugate heat transfer was modeled between the plates, cladding, manifold structure, and fluid. Steady-statemore » simulations were performed but lacked good residual convergence. Unsteady simulations were then performed, which converged well and demonstrated that flow instability existed in the lower portion of the manifold. It was established that the flow instability had little effect on the peak plate temperatures, which were well below the melting point. The estimated plate surface temperatures and target region pressure were shown to provide sufficient margin to subcooled boiling for standard operating conditions. This demonstrated the safety of both potential target configurations during normal operation.« less

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.

Design specification for the European Spallation Source neutron generating target element

NASA Astrophysics Data System (ADS)

Aguilar, A.; Sordo, F.; Mora, T.; Mena, L.; Mancisidor, M.; Aguilar, J.; Bakedano, G.; Herranz, I.; Luna, P.; Magan, M.; Vivanco, R.; Jimenez-Villacorta, F.; Sjogreen, K.; Oden, U.; Perlado, J. M.; Martinez, J. L.; Bermejo, F. J.

2017-06-01

The paper addresses some of the most relevant issues concerning the thermal hydraulics and radiation damage of the neutron generation target to be built at the European Spallation Source as recently approved after a critical design review. The target unit consists of a set of Tungsten blocks placed inside a wheel of 2.5 m diameter which rotates at some 0.5 Hz in order to distribute the heat generated from incoming protons which reach the target in the radial direction. The spallation material elements are composed of an array of Tungsten pieces which rest on a rotating steel support (the cassette) and are distributed in a cross-flow configuration. The thermal, mechanical and radiation effects resulting from the impact of a 2 GeV proton pulse are analysed in detail as well as an evaluation of the inventory of spallation products. The current design is found to conform to specifications and found to be robust enough to deal with several accident scenarios.

36 CFR 212.55 - Criteria for designation of roads, trails, and areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... roads, trails, and areas. 212.55 Section 212.55 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE TRAVEL MANAGEMENT Designation of Roads, Trails, and Areas for Motor Vehicle Use § 212.55 Criteria for designation of roads, trails, and areas. (a) General criteria for designation of...

GLRS-R 2-colour retroreflector target design and predicted performance

NASA Technical Reports Server (NTRS)

Lund, Glenn

1993-01-01

This paper reports on the retroreflector ground-target design for the GLRS-R spaceborne dual-wavelength laser ranging system. The described passive design flows down from the requirements of high station autonomy, high global FOV (up to 60 degrees zenith angle), little or no multiple pulse returns, and adequate optical cross section for most ranging geometries. The proposed solution makes use of 5 hollow cube-corner retroreflectors of which one points to the zenith and the remaining four are inclined from the vertical at uniform azimuthal spacings. The need for fairly large (is approximately 10 cm) retroreflectors is expected (within turbulence limitations) to generate quite narrow diffraction lobes, thus placing non-trivial requirements on the vectorial accuracy of velocity aberration corrections. A good compromise solution is found by appropriately spoiling just one of the retroreflector dihedral angles from 90 degrees, thus generating two symmetrically oriented diffraction lobes in the return beam. The required spoil angles are found to have little dependence on ground target latitude. Various link budget analyses are presented, showing the influence of such factors as point-ahead optimization, turbulence, ranging angle, atmospheric visibility and ground target thermal deformations.

GLRS-R 2-colour retroreflector target design and predicted performance

NASA Astrophysics Data System (ADS)

Lund, Glenn

1993-06-01

This paper reports on the retroreflector ground-target design for the GLRS-R spaceborne dual-wavelength laser ranging system. The described passive design flows down from the requirements of high station autonomy, high global FOV (up to 60 degrees zenith angle), little or no multiple pulse returns, and adequate optical cross section for most ranging geometries. The proposed solution makes use of 5 hollow cube-corner retroreflectors of which one points to the zenith and the remaining four are inclined from the vertical at uniform azimuthal spacings. The need for fairly large (is approximately 10 cm) retroreflectors is expected (within turbulence limitations) to generate quite narrow diffraction lobes, thus placing non-trivial requirements on the vectorial accuracy of velocity aberration corrections. A good compromise solution is found by appropriately spoiling just one of the retroreflector dihedral angles from 90 degrees, thus generating two symmetrically oriented diffraction lobes in the return beam. The required spoil angles are found to have little dependence on ground target latitude. Various link budget analyses are presented, showing the influence of such factors as point-ahead optimization, turbulence, ranging angle, atmospheric visibility and ground target thermal deformations.

Design of nuclease-based target recycling signal amplification in aptasensors.

PubMed

Yan, Mengmeng; Bai, Wenhui; Zhu, Chao; Huang, Yafei; Yan, Jiao; Chen, Ailiang

2016-03-15

Compared with conventional antibody-based immunoassay methods, aptasensors based on nucleic acid aptamer have made at least two significant breakthroughs. One is that aptamers are more easily used for developing various simple and rapid homogeneous detection methods by "sample in signal out" without multi-step washing. The other is that aptamers are more easily employed for developing highly sensitive detection methods by using various nucleic acid-based signal amplification approaches. As many substances playing regulatory roles in physiology or pathology exist at an extremely low concentration and many chemical contaminants occur in trace amounts in food or environment, aptasensors for signal amplification contribute greatly to detection of such targets. Among the signal amplification approaches in highly sensitive aptasensors, the nuclease-based target recycling signal amplification has recently become a research focus because it shows easy design, simple operation, and rapid reaction and can be easily developed for homogenous assay. In this review, we summarized recent advances in the development of various nuclease-based target recycling signal amplification with the aim to provide a general guide for the design of aptamer-based ultrasensitive biosensing assays. Copyright © 2015 Elsevier B.V. All rights reserved.

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

NASA Astrophysics Data System (ADS)

Mullen, Douglas Gurnett

Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules

45 CFR 1321.33 - Designation of area agencies.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING State Agency Responsibilities § 1321.33 Designation of... area agency on aging is designated, the State shall give right of first refusal to a unit of general...

45 CFR 1321.33 - Designation of area agencies.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING State Agency Responsibilities § 1321.33 Designation of... area agency on aging is designated, the State shall give right of first refusal to a unit of general...

45 CFR 1321.33 - Designation of area agencies.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING State Agency Responsibilities § 1321.33 Designation of... area agency on aging is designated, the State shall give right of first refusal to a unit of general...

45 CFR 1321.33 - Designation of area agencies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS GRANTS TO STATE AND COMMUNITY PROGRAMS ON AGING State Agency Responsibilities § 1321.33 Designation of... area agency on aging is designated, the State shall give right of first refusal to a unit of general...

Gateway design specification for fiber optic local area networks

NASA Technical Reports Server (NTRS)

1985-01-01

This is a Design Specification for a gateway to interconnect fiber optic local area networks (LAN's). The internetworking protocols for a gateway device that will interconnect multiple local area networks are defined. This specification serves as input for preparation of detailed design specifications for the hardware and software of a gateway device. General characteristics to be incorporated in the gateway such as node address mapping, packet fragmentation, and gateway routing features are described.

Dose-finding designs for trials of molecularly targeted agents and immunotherapies

PubMed Central

Chiuzan, Cody; Shtaynberger, Jonathan; Manji, Gulam A.; Duong, Jimmy K.; Schwartz, Gary K.; Ivanova, Anastasia; Lee, Shing M.

2017-01-01

Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, only 7.1% of trials use novel designs. PMID:28166468

Rational Design of Cancer-Targeted Benzoselenadiazole by RGD Peptide Functionalization for Cancer Theranostics.

PubMed

Yang, Liye; Li, Wenying; Huang, Yanyu; Zhou, Yangliang; Chen, Tianfeng

2015-09-01

A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5] selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI (polyethylenimine) as a linker is rationally designed and synthesized in the present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous solution with a core-shell nanostructure and high stability under physiological conditions. This rational design effectively enhances the selective cellular uptake and cellular retention of BSeC in human glioma cells, and increases its selectivity between cancer and normal cells. The nanoparticles enter the cells through receptor-mediated endocytosis via clathrin-mediated and nystatin-dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this study provides a strategy for the rational design of selenium-containing cancer-targeted theranostics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of photon converter and photoneutron target for High power electron accelerator based BNCT.

PubMed

Rahmani, Faezeh; Seifi, Samaneh; Anbaran, Hossein Tavakoli; Ghasemi, Farshad

2015-12-01

An electron accelerator, ILU-14, with current of 10 mA and 100 kW in power has been considered as one of the options for neutron source in Boron Neutron Capture Therapy (BNCT). The final design of neutron target has been obtained using MCNPX to optimize the neutron production. Tungsten in strip shape and D2O in cylindrical form have been proposed as the photon converter and the photoneutron target, respectively. In addition calculation of heat deposition in the photon target design has been considered to ensure mechanical stability of target. The results show that about 8.37×10(12) photoneutron/s with average energy of 615 keV can be produced by this neutron source design. In addition, using an appropriate beam shaping assembly an epithermal neutron flux of the order of 1.24×10(8) cm(-2) s(-1) can be obtained for BNCT applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Point design targets, specifications, and requirements for the 2010 NIF ignition campaign

NASA Astrophysics Data System (ADS)

Haan, Steven

2010-11-01

A set of point design targets has been specified for the initial ignition campaign on the National Ignition Facility [G. Miller, E. Moses, and C. Wuest, Opt. Eng. 443, 2841 (2004)]. The targets use an ablator of either Be(Cu) or CH(Ge). They are imploded in a U or Au hohlraum at peak radiation temperature 270 to 300eV. Considerations determining the point design include laser-plasma interactions, hydro stability, laser operations, and target fabrication. Simulations were used to evaluate choices, to define requirements, and to estimate sensitivity to uncertainties. Designs were updated to account for 2009 experimental results. We describe a formalism to evaluate the margin for ignition, in a parameter the Ignition Threshold Factor (ITF). Uncertainty and shot-to-shot variability can be evaluated, as well as sensitivity to systematic uncertainties. The formalism is used to estimate the probability of ignition for each target. In collaboration with J Lindl, D Callahan, D Clark, J Salmonson, B Hammel, L Atherton, R Cook, J Edwards, S Glenzer, A Hamza, S Hatchett, D Hinkel, D Ho, O Jones, O Landen, B MacGowan, M Marinak, E Moses, D Munro, S Pollaine, B Spears, P Springer, L Suter, C Thomas, R Town, S Weber, D Wilson, G Kyrala, M Herrmann, R Olson, R Vesey, A Nikroo, H Huang, and K Moreno.

Adaptable setups for magnetic drug targeting in human muscular arteries: Design and implementation

NASA Astrophysics Data System (ADS)

Hajiaghajani, Amirhossein; Hashemi, Soheil; Abdolali, Ali

2017-09-01

Magnetic drug targeting has been used to steer magnetic therapeutic agents and has received much attention for capillaries and human brain arteries. In this paper, we focus on noninvasive targeting of nanoparticles in muscular arteries, in where the vessel diameter and blood flow are much challengingly higher than brain capillaries. We aim to design a low intensity magnetic field which avoids potential side effects on blood cells while steers particles with high targeting rate. The setup design procedure is considerably flexible to be used in a wide variety of large vessels. Using particle tracing, a new method is proposed to connect the geometry of the vessel under the action of targeting to the required magnetic force. Specifications of the coil which is placed outside the body are derived based on this required force. Mutual effects of coil dimensions on the produced magnetic force are elaborated and summarized in a design flowchart to be used for arbitrary muscular vessel sizes. The performance of the optimized coil is validated by in vitro experiments and it is shown that particles are steered with the average efficiency of 80.2% for various conditions.

[Exploration of the design of media access control layer of wireless body area network for medical healthcare].

PubMed

Liu, Xuemei; Ge, Baofeng

2012-04-01

This paper proposes a media access control (MAC) layer design for wireless body area network (WBAN) systems. WBAN is a technology that targets for wireless networking of wearable and implantable body sensors which monitor vital body signs, such as heart-rate, body temperature, blood pressure, etc. It has been receiving attentions from international organizations, e. g. the Institute of Electrical and Electronics Engineers (IEEE), due to its capability of providing efficient healthcare services and clinical management. This paper reviews the standardization procedure of WBAN and summarizes the challenge of the MAC layer design. It also discusses the methods of improving power consumption performance, which is one of the major issues of WBAN systems.

Mineral target areas in Nevada from geological analysis of LANDSAT-1 imagery

NASA Technical Reports Server (NTRS)

Abdel-Gawad, M.; Tubbesing, L.

1975-01-01

Geological analysis of LANDSAT-1 Scene MSS 1053-17540 suggests that certain known mineral districts in east-central Nevada frequently occur near faults or at faults or lineament intersections and areas of complex deformation and flexures. Seventeen (17) areas of analogous characteristics were identified as favorable targets for mineral exploration. During reconnaissance field trips eleven areas were visited. In three areas evidence was found of mining and/or prospecting not known before the field trips. In four areas favorable structural and alteration features were observed which call for more detailed field studies. In one of the four areas limonitic iron oxide samples were found in the regolith of a brecciated dolomite ridge. This area contains quartz veins, granitic and volcanic rocks and lies near the intersection of two linear fault structures identified in the LANDSAT-1 imagery. Semiquantitative spectroscopic analysis of selected portions of the samples showed abnormal contents of arsenic, molybdenum, copper, lead, zinc, and silver. These limonitic samples found were not in situ and further field studies are required to assess their source and significance.

Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection.

PubMed

Sadekar, S; Figueroa, I; Tabrizi, M

2015-07-01

Antibody drug conjugates (ADCs) are a multi-component modality comprising of an antibody targeting a cell-specific antigen, a potent drug/payload, and a linker that can be processed within cellular compartments to release payload upon internalization. Numerous ADCs are being evaluated in both research and clinical settings within the academic and pharmaceutical industry due to their ability to selectively deliver potent payloads. Hence, there is a clear need to incorporate quantitative approaches during early stages of drug development for effective modality design and target selection. In this review, we describe a quantitative approach and framework for evaluation of the interplay between drug- and systems-dependent properties (i.e., target expression, density, localization, turnover, and affinity) in order to deliver a sufficient amount of a potent payload into the relevant target cells. As discussed, theoretical approaches with particular considerations given to various key properties for the target and modality suggest that delivery of the payload into particular effect cells to be more sensitive to antigen concentrations for targets with slow turnover rates as compared to those with faster internalization rates. Further assessments also suggest that increasing doses beyond the threshold of the target capacity (a function of target internalization and expression) may not impact the maximum amount of payload delivered to the intended effect cells. This article will explore the important application of quantitative sciences in selection of the target and design of ADC modalities.

Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

PubMed

Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

2016-05-05

Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

Design and Preliminary Testing of the International Docking Adapter's Peripheral Docking Target

NASA Technical Reports Server (NTRS)

Foster, Christopher W.; Blaschak, Johnathan; Eldridge, Erin A.; Brazzel, Jack P.; Spehar, Peter T.

2015-01-01

The International Docking Adapter's Peripheral Docking Target (PDT) was designed to allow a docking spacecraft to judge its alignment relative to the docking system. The PDT was designed to be compatible with relative sensors using visible cameras, thermal imagers, or Light Detection and Ranging (LIDAR) technologies. The conceptual design team tested prototype designs and materials to determine the contrast requirements for the features. This paper will discuss the design of the PDT, the methodology and results of the tests, and the conclusions pertaining to PDT design that were drawn from testing.

33 CFR 334.200 - Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U...

Code of Federal Regulations, 2010 CFR

2010-07-01

... damage caused by projectiles, bombs, missiles, or Naval or Coast Guard vessels to fishing structures or... and bombs will be dropped at frequent intervals in the target areas. Hooper and Hannibal target areas...

36 CFR 212.57 - Monitoring of effects of motor vehicle use on designated roads and trails and in designated areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... motor vehicle use on designated roads and trails and in designated areas. 212.57 Section 212.57 Parks... Roads, Trails, and Areas for Motor Vehicle Use § 212.57 Monitoring of effects of motor vehicle use on designated roads and trails and in designated areas. For each administrative unit of the National Forest...

43 CFR 1610.7 - Designation of areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Designation of areas. 1610.7 Section 1610.7 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING Resource Management...

Image-algebraic design of multispectral target recognition algorithms

NASA Astrophysics Data System (ADS)

Schmalz, Mark S.; Ritter, Gerhard X.

1994-06-01

In this paper, we discuss methods for multispectral ATR (Automated Target Recognition) of small targets that are sensed under suboptimal conditions, such as haze, smoke, and low light levels. In particular, we discuss our ongoing development of algorithms and software that effect intelligent object recognition by selecting ATR filter parameters according to ambient conditions. Our algorithms are expressed in terms of IA (image algebra), a concise, rigorous notation that unifies linear and nonlinear mathematics in the image processing domain. IA has been implemented on a variety of parallel computers, with preprocessors available for the Ada and FORTRAN languages. An image algebra C++ class library has recently been made available. Thus, our algorithms are both feasible implementationally and portable to numerous machines. Analyses emphasize the aspects of image algebra that aid the design of multispectral vision algorithms, such as parameterized templates that facilitate the flexible specification of ATR filters.

76 FR 22863 - Designation for the Lewiston, ID Area

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-25

... the Lewiston, ID Area AGENCY: Grain Inspection, Packers and Stockyards Administration, USDA. ACTION... official services in the geographic area previously serviced by Lewiston Grain Inspection Service, Inc. (Lewiston). Applications were due by February 3, 2011. Washington was the sole applicant for designation to...

43 CFR 1610.7-2 - Designation of areas of critical environmental concern.

Code of Federal Regulations, 2014 CFR

2014-10-01

... environmental concern. 1610.7-2 Section 1610.7-2 Public Lands: Interior Regulations Relating to Public Lands..., PROGRAMMING, BUDGETING Resource Management Planning § 1610.7-2 Designation of areas of critical environmental concern. Areas having potential for Areas of Critical Environmental Concern (ACEC) designation and...

43 CFR 1610.7-2 - Designation of areas of critical environmental concern.

Code of Federal Regulations, 2013 CFR

2013-10-01

... environmental concern. 1610.7-2 Section 1610.7-2 Public Lands: Interior Regulations Relating to Public Lands..., PROGRAMMING, BUDGETING Resource Management Planning § 1610.7-2 Designation of areas of critical environmental concern. Areas having potential for Areas of Critical Environmental Concern (ACEC) designation and...

43 CFR 1610.7-2 - Designation of areas of critical environmental concern.

Code of Federal Regulations, 2012 CFR

2012-10-01

... environmental concern. 1610.7-2 Section 1610.7-2 Public Lands: Interior Regulations Relating to Public Lands..., PROGRAMMING, BUDGETING Resource Management Planning § 1610.7-2 Designation of areas of critical environmental concern. Areas having potential for Areas of Critical Environmental Concern (ACEC) designation and...

[Design of sponge city and its inspiration to landscape ecology: A case of Liaodong Bay area of Panjin City, Northeast China].

PubMed

Sui, Jin Ling; Liu, Miao; Li, Chun Lin; Hu, Yuan Man; Wu, Yi Lin; Liu, Chong

2017-03-18

With the expansion of urban area, many cities are facing urban water environment issues, i.e., water resources shortage, lack of groundwater reserves, water pollution, urban waterlogging. For resolving these urban issues, 'sponge city' was proposed in 2015 in China. Liaodong Bay area of Panjin City in Liaoning Province of China was chosen as case study. Based on 'Sponge City Construction Technology Guide: Low Impact Development Rainwater System Building (Trial)', the underlying surface and types of land use in the typical area were analyzed. Sponge city plan of the study area was designed through combining topography, hydrology, rainfall intensity and other factors, and selecting LID measures. The results showed that when the study area reached the ove-rall target control rate (the control rate of the total annual runoff was ＞75%), the subsidence greenbelt rate was 1%-31%, with a total area of 13.73 km 2 ; the pervious pavement rate was 1%-13%, with a total area of 2.29 km 2 . This study could provide a case study for planning and designing of 'sponge city', proposing new ideas and methods for the research on landscape pattern and process.

Design and construction of a time-of-flight wall detector at External Target Facility of HIRFL-CSR

NASA Astrophysics Data System (ADS)

Sun, Y.; Sun, Z. Y.; Yu, Y. H.; Yan, D.; Tang, S. W.; Sun, Y. Z.; Wang, S. T.; Zhang, X. H.; Yue, K.; Fang, F.; Chen, J. L.; Zhang, Y. J.; Hu, B. T.

2018-06-01

A Time-Of-Flight Wall (TOFW) detector has been designed and constructed at the External Target Facility (ETF) of HIRFL-CSR. The detector covers a sensitive area of 1.2 × 1.2 m2 and consists of 30 modules. Each module is composed of a long plastic scintillator bar with two photo-multiplier tubes coupled at both ends for readout. The design and manufacture details are described and the test results are reported. The performance of the TOFW detector has been tested and measured with cosmic rays and a 310 MeV/u 40Ar beam. The results show that the time resolutions of all the TOFW modules are better than 128 ps, satisfying the requirements of the experiments which will be carried out at the ETF.

Optimal Design of Gradient Materials and Bi-Level Optimization of Topology Using Targets (BOTT)

NASA Astrophysics Data System (ADS)

Garland, Anthony

The objective of this research is to understand the fundamental relationships necessary to develop a method to optimize both the topology and the internal gradient material distribution of a single object while meeting constraints and conflicting objectives. Functionally gradient material (FGM) objects possess continuous varying material properties throughout the object, and they allow an engineer to tailor individual regions of an object to have specific mechanical properties by locally modifying the internal material composition. A variety of techniques exists for topology optimization, and several methods exist for FGM optimization, but combining the two together is difficult. Understanding the relationship between topology and material gradient optimization enables the selection of an appropriate model and the development of algorithms, which allow engineers to design high-performance parts that better meet design objectives than optimized homogeneous material objects. For this research effort, topology optimization means finding the optimal connected structure with an optimal shape. FGM optimization means finding the optimal macroscopic material properties within an object. Tailoring the material constitutive matrix as a function of position results in gradient properties. Once, the target macroscopic properties are known, a mesostructure or a particular material nanostructure can be found which gives the target material properties at each macroscopic point. This research demonstrates that topology and gradient materials can both be optimized together for a single part. The algorithms use a discretized model of the domain and gradient based optimization algorithms. In addition, when considering two conflicting objectives the algorithms in this research generate clear 'features' within a single part. This tailoring of material properties within different areas of a single part (automated design of 'features') using computational design tools is a novel benefit

Design and construction of targeted AAVP vectors for mammalian cell transduction.

PubMed

Hajitou, Amin; Rangel, Roberto; Trepel, Martin; Soghomonyan, Suren; Gelovani, Juri G; Alauddin, Mian M; Pasqualini, Renata; Arap, Wadih

2007-01-01

Bacteriophage (phage) evolved as bacterial viruses, but can be adapted to transduce mammalian cells through ligand-directed targeting to a specific receptor. We have recently reported a new generation of hybrid prokaryotic-eukaryotic vectors, which are chimeras of genetic cis-elements of recombinant adeno-associated virus and phage (termed AAVP). This protocol describes the design and construction of ligand-directed AAVP vectors, production of AAVP particles and the methodology to transduce mammalian cells in vitro and to target tissues in vivo after systemic administration. Targeted AAVP particles are made in a two-step process. First, a ligand peptide of choice is displayed on the coat protein to generate a targeted backbone phage vector. Then, a recombinant AAV carrying a mammalian transgene cassette is inserted into an intergenomic region. High-titer suspensions (approximately 10(10)-10(11) transducing units per microl) can be produced within 3 days after vector construction. Transgene expression by targeted AAVP usually reaches maximum levels within 1 week.

7 CFR 25.301 - Selection factors for designation of nominated rural areas.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 1 2012-01-01 2012-01-01 false Selection factors for designation of nominated rural areas. 25.301 Section 25.301 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES... rural areas. In choosing among nominated rural areas eligible for designation as Empowerment Zone...

7 CFR 25.301 - Selection factors for designation of nominated rural areas.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 1 2013-01-01 2013-01-01 false Selection factors for designation of nominated rural areas. 25.301 Section 25.301 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES... rural areas. In choosing among nominated rural areas eligible for designation as Empowerment Zone...

7 CFR 25.301 - Selection factors for designation of nominated rural areas.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 1 2014-01-01 2014-01-01 false Selection factors for designation of nominated rural areas. 25.301 Section 25.301 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES... rural areas. In choosing among nominated rural areas eligible for designation as Empowerment Zone...

7 CFR 25.301 - Selection factors for designation of nominated rural areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Selection factors for designation of nominated rural areas. 25.301 Section 25.301 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES... rural areas. In choosing among nominated rural areas eligible for designation as Empowerment Zone...

7 CFR 25.301 - Selection factors for designation of nominated rural areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 1 2011-01-01 2011-01-01 false Selection factors for designation of nominated rural areas. 25.301 Section 25.301 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES... rural areas. In choosing among nominated rural areas eligible for designation as Empowerment Zone...

Role of Bioreactor Technology in Tissue Engineering for Clinical Use and Therapeutic Target Design.

PubMed

Selden, Clare; Fuller, Barry

2018-04-24

Micro and small bioreactors are well described for use in bioprocess development in pre-production manufacture, using ultra-scale down and microfluidic methodology. However, the use of bioreactors to understand normal and pathophysiology by definition must be very different, and the constraints of the physiological environment influence such bioreactor design. This review considers the key elements necessary to enable bioreactors to address three main areas associated with biological systems. All entail recreation of the in vivo cell niche as faithfully as possible, so that they may be used to study molecular and cellular changes in normal physiology, with a view to creating tissue-engineered grafts for clinical use; understanding the pathophysiology of disease at the molecular level; defining possible therapeutic targets; and enabling appropriate pharmaceutical testing on a truly representative organoid, thus enabling better drug design, and simultaneously creating the potential to reduce the numbers of animals in research. The premise explored is that not only cellular signalling cues, but also mechano-transduction from mechanical cues, play an important role.

Modifications to risk-targeted seismic design maps for subduction and near-fault hazards

USGS Publications Warehouse

Liel, Abbie B.; Luco, Nicolas; Raghunandan, Meera; Champion, C.; Haukaas, Terje

2015-01-01

ASCE 7-10 introduced new seismic design maps that define risk-targeted ground motions such that buildings designed according to these maps will have 1% chance of collapse in 50 years. These maps were developed by iterative risk calculation, wherein a generic building collapse fragility curve is convolved with the U.S. Geological Survey hazard curve until target risk criteria are met. Recent research shows that this current approach may be unconservative at locations where the tectonic environment is much different than that used to develop the generic fragility curve. This study illustrates how risk-targeted ground motions at selected sites would change if generic building fragility curve and hazard assessment were modified to account for seismic risk from subduction earthquakes and near-fault pulses. The paper also explores the difficulties in implementing these changes.

24 CFR 598.200 - Who nominates an area for designation?

Code of Federal Regulations, 2010 CFR

2010-04-01

... HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES URBAN EMPOWERMENT ZONES: ROUND TWO AND THREE DESIGNATIONS Nomination Procedure § 598.200 Who nominates an area for designation? Applicants for empowerment...

24 CFR 598.200 - Who nominates an area for designation?

Code of Federal Regulations, 2011 CFR

2011-04-01

... HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES URBAN EMPOWERMENT ZONES: ROUND TWO AND THREE DESIGNATIONS Nomination Procedure § 598.200 Who nominates an area for designation? Applicants for empowerment...

33 CFR 334.1470 - Caribbean Sea and Vieques Sound, in vicinity of Eastern Vieques; bombing and gunnery target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Caribbean Sea and Vieques Sound, in vicinity of Eastern Vieques; bombing and gunnery target area. 334.1470 Section 334.1470 Navigation...; bombing and gunnery target area. (a) The danger zone. From Punta Conejo on the south coast of Vieques at...

33 CFR 334.1470 - Caribbean Sea and Vieques Sound, in vicinity of Eastern Vieques; bombing and gunnery target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Caribbean Sea and Vieques Sound, in vicinity of Eastern Vieques; bombing and gunnery target area. 334.1470 Section 334.1470 Navigation...; bombing and gunnery target area. (a) The danger zone. From Punta Conejo on the south coast of Vieques at...

Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets

PubMed Central

Clinton, Tracy R; Weinstock, Matthew T; Jacobsen, Michael T; Szabo-Fresnais, Nicolas; Pandya, Maya J; Whitby, Frank G; Herbert, Andrew S; Prugar, Laura I; McKinnon, Rena; Hill, Christopher P; Welch, Brett D; Dye, John M; Eckert, Debra M; Kay, Michael S

2015-01-01

Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify d-peptide inhibitors of ebolavirus entry. PMID:25287718

Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets.

PubMed

Clinton, Tracy R; Weinstock, Matthew T; Jacobsen, Michael T; Szabo-Fresnais, Nicolas; Pandya, Maya J; Whitby, Frank G; Herbert, Andrew S; Prugar, Laura I; McKinnon, Rena; Hill, Christopher P; Welch, Brett D; Dye, John M; Eckert, Debra M; Kay, Michael S

2015-04-01

Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify D-peptide inhibitors of ebolavirus entry. © 2014 The Protein Society.

41 CFR 102-74.325 - Are designated smoking areas authorized in interior space?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Are designated smoking... PROPERTY 74-FACILITY MANAGEMENT Facility Management Smoking § 102-74.325 Are designated smoking areas....320(d). A previous exception for designated smoking areas is being eliminated. All designated interior...

41 CFR 102-74.325 - Are designated smoking areas authorized in interior space?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Are designated smoking... PROPERTY 74-FACILITY MANAGEMENT Facility Management Smoking § 102-74.325 Are designated smoking areas....320(d). A previous exception for designated smoking areas is being eliminated. All designated interior...

41 CFR 102-74.325 - Are designated smoking areas authorized in interior space?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Are designated smoking... PROPERTY 74-FACILITY MANAGEMENT Facility Management Smoking § 102-74.325 Are designated smoking areas....320(d). A previous exception for designated smoking areas is being eliminated. All designated interior...

41 CFR 102-74.325 - Are designated smoking areas authorized in interior space?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Are designated smoking... PROPERTY 74-FACILITY MANAGEMENT Facility Management Smoking § 102-74.325 Are designated smoking areas....320(d). A previous exception for designated smoking areas is being eliminated. All designated interior...

41 CFR 102-74.325 - Are designated smoking areas authorized in interior space?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Are designated smoking... PROPERTY 74-FACILITY MANAGEMENT Facility Management Smoking § 102-74.325 Are designated smoking areas....320(d). A previous exception for designated smoking areas is being eliminated. All designated interior...

40 CFR 55.15 - Specific designation of corresponding onshore areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... corresponding onshore areas. (a) California. (1) The South Coast Air Quality Management District is designated... Air Pollution Control District is designated as the COA for the following OCS facilities: Grace, Gilda, Gail and Gina. (3) The Santa Barbara County Air Pollution Control District is designated as the COA for...

40 CFR 55.15 - Specific designation of corresponding onshore areas.

Code of Federal Regulations, 2012 CFR

2012-07-01

... corresponding onshore areas. (a) California. (1) The South Coast Air Quality Management District is designated... Air Pollution Control District is designated as the COA for the following OCS facilities: Grace, Gilda, Gail and Gina. (3) The Santa Barbara County Air Pollution Control District is designated as the COA for...

40 CFR 55.15 - Specific designation of corresponding onshore areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... corresponding onshore areas. (a) California. (1) The South Coast Air Quality Management District is designated... Air Pollution Control District is designated as the COA for the following OCS facilities: Grace, Gilda, Gail and Gina. (3) The Santa Barbara County Air Pollution Control District is designated as the COA for...

40 CFR 55.15 - Specific designation of corresponding onshore areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... corresponding onshore areas. (a) California. (1) The South Coast Air Quality Management District is designated... Air Pollution Control District is designated as the COA for the following OCS facilities: Grace, Gilda, Gail and Gina. (3) The Santa Barbara County Air Pollution Control District is designated as the COA for...

40 CFR 55.15 - Specific designation of corresponding onshore areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... corresponding onshore areas. (a) California. (1) The South Coast Air Quality Management District is designated... Air Pollution Control District is designated as the COA for the following OCS facilities: Grace, Gilda, Gail and Gina. (3) The Santa Barbara County Air Pollution Control District is designated as the COA for...

Sequence-based design of bioactive small molecules that target precursor microRNAs.

PubMed

Velagapudi, Sai Pradeep; Gallo, Steven M; Disney, Matthew D

2014-04-01

Oligonucleotides are designed to target RNA using base pairing rules, but they can be hampered by poor cellular delivery and nonspecific stimulation of the immune system. Small molecules are preferred as lead drugs or probes but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA hairpin precursors, and it identified bioactive small molecules that inhibit biogenesis by binding nuclease-processing sites (44% hit rate). Among 27 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Markedly, microRNA profiling shows that 1 only affects microRNA-96 biogenesis and is at least as selective as an oligonucleotide.

Sequence-based design of bioactive small molecules that target precursor microRNAs

PubMed Central

Velagapudi, Sai Pradeep; Gallo, Steven M.; Disney, Matthew D.

2014-01-01

Oligonucleotides are designed to target RNA using base pairing rules, however, they are hampered by poor cellular delivery and non-specific stimulation of the immune system. Small molecules are preferred as lead drugs or probes, but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA precursors and identified bioactive small molecules that inhibit biogenesis by binding to nuclease processing sites (41% hit rate). Amongst 29 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Importantly, microRNA profiling shows that 1 only significantly effects microRNA-96 biogenesis and is more selective than an oligonucleotide. PMID:24509821

Automated divertor target design by adjoint shape sensitivity analysis and a one-shot method

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

Dekeyser, W., E-mail: Wouter.Dekeyser@kuleuven.be; Reiter, D.; Baelmans, M.

As magnetic confinement fusion progresses towards the development of first reactor-scale devices, computational tokamak divertor design is a topic of high priority. Presently, edge plasma codes are used in a forward approach, where magnetic field and divertor geometry are manually adjusted to meet design requirements. Due to the complex edge plasma flows and large number of design variables, this method is computationally very demanding. On the other hand, efficient optimization-based design strategies have been developed in computational aerodynamics and fluid mechanics. Such an optimization approach to divertor target shape design is elaborated in the present paper. A general formulation ofmore » the design problems is given, and conditions characterizing the optimal designs are formulated. Using a continuous adjoint framework, design sensitivities can be computed at a cost of only two edge plasma simulations, independent of the number of design variables. Furthermore, by using a one-shot method the entire optimization problem can be solved at an equivalent cost of only a few forward simulations. The methodology is applied to target shape design for uniform power load, in simplified edge plasma geometry.« less

Multiple Target Laser Designator (MTLD)

DTIC Science & Technology

2007-03-01

Optimized Liquid Crystal Scanning Element Optimize the Nonimaging Predictive Algorithm for Target Ranging, Tracking, and Position Estimation...commercial potential. 3.0 PROGRESS THIS QUARTER 3.1 Optimization of Nonimaging Holographic Antenna for Target Tracking and Position Estimation (Task 6) In

Drug target identification in protozoan parasites

PubMed Central

Müller, Joachim; Hemphill, Andrew

2016-01-01

Introduction Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Areas covered Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Expert opinion Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses. PMID:27238605

Recent Developments in the VISRAD 3-D Target Design and Radiation Simulation Code

NASA Astrophysics Data System (ADS)

Macfarlane, Joseph; Golovkin, Igor; Sebald, James

2017-10-01

The 3-D view factor code VISRAD is widely used in designing HEDP experiments at major laser and pulsed-power facilities, including NIF, OMEGA, OMEGA-EP, ORION, Z, and LMJ. It simulates target designs by generating a 3-D grid of surface elements, utilizing a variety of 3-D primitives and surface removal algorithms, and can be used to compute the radiation flux throughout the surface element grid by computing element-to-element view factors and solving power balance equations. Target set-up and beam pointing are facilitated by allowing users to specify positions and angular orientations using a variety of coordinates systems (e.g., that of any laser beam, target component, or diagnostic port). Analytic modeling for laser beam spatial profiles for OMEGA DPPs and NIF CPPs is used to compute laser intensity profiles throughout the grid of surface elements. VISRAD includes a variety of user-friendly graphics for setting up targets and displaying results, can readily display views from any point in space, and can be used to generate image sequences for animations. We will discuss recent improvements to conveniently assess beam capture on target and beam clearance of diagnostic components, as well as plans for future developments.

Design of a secondary ionization target for direct production of a C- beam from CO2 pulses for online AMS.

PubMed

Salazar, Gary; Ognibene, Ted

2013-01-01

We designed and optimized a novel device "target" that directs a CO 2 gas pulse onto a Ti surface where a Cs + beam generates C - from the CO 2 . This secondary ionization target enables an accelerator mass spectrometer to ionize pulses of CO 2 in the negative mode to measure 14 C/ 12 C isotopic ratios in real time. The design of the targets were based on computational flow dynamics, ionization mechanism and empirical optimization. As part of the ionization mechanism, the adsorption of CO 2 on the Ti surface was fitted with the Jovanovic-Freundlich isotherm model using empirical and simulation data. The inferred adsorption constants were in good agreement with other works. The empirical optimization showed that amount of injected carbon and the flow speed of the helium carrier gas improve the ionization efficiency and the amount of 12 C - produced until reaching a saturation point. Linear dynamic range between 150 and 1000 ng of C and optimum carrier gas flow speed of around 0.1 mL/min were shown. It was also shown that the ionization depends on the area of the Ti surface and Cs + beam cross-section. A range of ionization efficiency of 1-2.5% was obtained by optimizing the described parameters.

Target design optimization for an electron accelerator driven subcritical facility with circular and square beam profiles.

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

Gohar, M. Y. A; Sofu, T.; Zhong, Z.

2008-10-30

A subcritical facility driven by an electron accelerator is planned at the Kharkov Institute of Physics and Technology (KIPT) in Ukraine for medical isotope production, materials research, training, and education. The conceptual design of the facility is being pursued through collaborations between ANL and KIPT. As part of the design effort, the high-fidelity analyses of various target options are performed with formulations to reflect the realistic configuration and the three dimensional geometry of each design. This report summarizes the results of target design optimization studies for electron beams with two different beam profiles. The target design optimization is performed viamore » the sequential neutronic, thermal-hydraulic, and structural analyses for a comprehensive assessment of each configuration. First, a target CAD model is developed with proper emphasis on manufacturability to provide a basis for separate but consistent models for subsequent neutronic, thermal-hydraulic, and structural analyses. The optimizations are pursued for maximizing the neutron yield, streamlining the flow field to avoid hotspots, and minimizing the thermal stresses to increase the durability. In addition to general geometric modifications, the inlet/outlet channel configurations, target plate partitioning schemes, flow manipulations and rates, electron beam diameter/width options, and cladding material choices are included in the design optimizations. The electron beam interactions with the target assembly and the neutronic response of the subcritical facility are evaluated using the MCNPX code. the results for the electron beam energy deposition, neutron generation, and utilization in the subcritical pile are then used to characterize the axisymmetric heat generation profiles in the target assembly with explicit simulations of the beam tube, the coolant, the clad, and the target materials. Both tungsten and uranium are considered as target materials. Neutron spectra from

Risk-targeted versus current seismic design maps for the conterminous United States

USGS Publications Warehouse

Luco, Nicolas; Ellingwood, Bruce R.; Hamburger, Ronald O.; Hooper, John D.; Kimball, Jeffrey K.; Kircher, Charles A.

2007-01-01

The probabilistic portions of the seismic design maps in the NEHRP Provisions (FEMA, 2003/2000/1997), and in the International Building Code (ICC, 2006/2003/2000) and ASCE Standard 7-05 (ASCE, 2005a), provide ground motion values from the USGS that have a 2% probability of being exceeded in 50 years. Under the assumption that the capacity against collapse of structures designed for these "uniformhazard" ground motions is equal to, without uncertainty, the corresponding mapped value at the location of the structure, the probability of its collapse in 50 years is also uniform. This is not the case however, when it is recognized that there is, in fact, uncertainty in the structural capacity. In that case, siteto-site variability in the shape of ground motion hazard curves results in a lack of uniformity. This paper explains the basis for proposed adjustments to the uniform-hazard portions of the seismic design maps currently in the NEHRP Provisions that result in uniform estimated collapse probability. For seismic design of nuclear facilities, analogous but specialized adjustments have recently been defined in ASCE Standard 43-05 (ASCE, 2005b). In support of the 2009 update of the NEHRP Provisions currently being conducted by the Building Seismic Safety Council (BSSC), herein we provide examples of the adjusted ground motions for a selected target collapse probability (or target risk). Relative to the probabilistic MCE ground motions currently in the NEHRP Provisions, the risk-targeted ground motions for design are smaller (by as much as about 30%) in the New Madrid Seismic Zone, near Charleston, South Carolina, and in the coastal region of Oregon, with relatively little (<15%) change almost everywhere else in the conterminous U.S.

Design study of 10 kW direct fission target for RISP project

NASA Astrophysics Data System (ADS)

Tshoo, K.; Jang, D. Y.; Woo, H. J.; Kang, B. H.; Kim, G. D.; Hwang, W.; Kim, Y. K.

2014-03-01

We are developing Isotope Separation On-Line (ISOL) target system, which consists of 1.3 mm-thick uranium-carbide multi-disks and cylindrical tantalum heater, to be installed in new facility for Rare Isotope Science Project in Korea. The intense neutron-rich nuclei are produced via the fission process using the uranium carbide targets with a 70 MeV proton beam. The fission rate was estimated to be ˜1.5 × 1013/sec for 10 kW proton beam. The target system has been designed to be operated at a temperature of ˜2000 °C so as to improve the release effciency.

47 CFR 54.203 - Designation of eligible telecommunications carriers for unserved areas.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Designation of eligible telecommunications carriers for unserved areas. 54.203 Section 54.203 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Support § 54.203 Designation of eligible telecommunications carriers for unserved areas. (a) If no common...

47 CFR 54.203 - Designation of eligible telecommunications carriers for unserved areas.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Designation of eligible telecommunications carriers for unserved areas. 54.203 Section 54.203 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Support § 54.203 Designation of eligible telecommunications carriers for unserved areas. (a) If no common...

47 CFR 54.203 - Designation of eligible telecommunications carriers for unserved areas.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Designation of eligible telecommunications carriers for unserved areas. 54.203 Section 54.203 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Support § 54.203 Designation of eligible telecommunications carriers for unserved areas. (a) If no common...

47 CFR 54.203 - Designation of eligible telecommunications carriers for unserved areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Designation of eligible telecommunications carriers for unserved areas. 54.203 Section 54.203 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Support § 54.203 Designation of eligible telecommunications carriers for unserved areas. (a) If no common...

47 CFR 54.203 - Designation of eligible telecommunications carriers for unserved areas.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Designation of eligible telecommunications carriers for unserved areas. 54.203 Section 54.203 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... Support § 54.203 Designation of eligible telecommunications carriers for unserved areas. (a) If no common...

76 FR 37059 - Siuslaw National Forest; Oregon; Oregon Dunes NRA Management Area 10 (C) Route and Area Designation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... the 10 (C) area beyond the 3 year standard and guideline timeframe identified in the Plan; [[Page... Management Area 10 (C) Route and Area Designation AGENCY: Forest Service, USDA. ACTION: Notice of intent to... Off Road Vehicle (ORV) routes within Management Area (MA) 10 (C) of the Oregon Dunes National...

Application of Adjoint Methodology to Supersonic Aircraft Design Using Reversed Equivalent Areas

NASA Technical Reports Server (NTRS)

Rallabhandi, Sriram K.

2013-01-01

This paper presents an approach to shape an aircraft to equivalent area based objectives using the discrete adjoint approach. Equivalent areas can be obtained either using reversed augmented Burgers equation or direct conversion of off-body pressures into equivalent area. Formal coupling with CFD allows computation of sensitivities of equivalent area objectives with respect to aircraft shape parameters. The exactness of the adjoint sensitivities is verified against derivatives obtained using the complex step approach. This methodology has the benefit of using designer-friendly equivalent areas in the shape design of low-boom aircraft. Shape optimization results with equivalent area cost functionals are discussed and further refined using ground loudness based objectives.

The DESI Experiment Part I: Science,Targeting, and Survey Design

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

Aghamousa, Amir; et al.

DESI (Dark Energy Spectroscopic Instrument) is a Stage IV ground-based dark energy experiment that will study baryon acoustic oscillations (BAO) and the growth of structure through redshift-space distortions with a wide-area galaxy and quasar redshift survey. To trace the underlying dark matter distribution, spectroscopic targets will be selected in four classes from imaging data. We will measure luminous red galaxies up tomore » $z=1.0$. To probe the Universe out to even higher redshift, DESI will target bright [O II] emission line galaxies up to $z=1.7$. Quasars will be targeted both as direct tracers of the underlying dark matter distribution and, at higher redshifts ($ 2.1 < z < 3.5$), for the Ly-$$\\alpha$$ forest absorption features in their spectra, which will be used to trace the distribution of neutral hydrogen. When moonlight prevents efficient observations of the faint targets of the baseline survey, DESI will conduct a magnitude-limited Bright Galaxy Survey comprising approximately 10 million galaxies with a median $$z\\approx 0.2$$. In total, more than 30 million galaxy and quasar redshifts will be obtained to measure the BAO feature and determine the matter power spectrum, including redshift space distortions.« less

33 CFR 334.1160 - San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo.

Code of Federal Regulations, 2012 CFR

2012-07-01

... practice area, Mare Island Naval Shipyard, Vallejo. 334.1160 Section 334.1160 Navigation and Navigable... REGULATIONS § 334.1160 San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo. (a) The danger zone. A sector in San Pablo Bay adjacent to the westerly shore of Mare Island with a radius...

33 CFR 334.1160 - San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo.

Code of Federal Regulations, 2013 CFR

2013-07-01

... practice area, Mare Island Naval Shipyard, Vallejo. 334.1160 Section 334.1160 Navigation and Navigable... REGULATIONS § 334.1160 San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo. (a) The danger zone. A sector in San Pablo Bay adjacent to the westerly shore of Mare Island with a radius...

33 CFR 334.1160 - San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo.

Code of Federal Regulations, 2014 CFR

2014-07-01

... practice area, Mare Island Naval Shipyard, Vallejo. 334.1160 Section 334.1160 Navigation and Navigable... REGULATIONS § 334.1160 San Pablo Bay, Calif.; target practice area, Mare Island Naval Shipyard, Vallejo. (a) The danger zone. A sector in San Pablo Bay adjacent to the westerly shore of Mare Island with a radius...

33 CFR 334.200 - Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River... Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River, Maryland, danger zones. (a) Aerial firing range—(1) The danger zone. The waters...

33 CFR 334.200 - Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River... Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River, Maryland, danger zones. (a) Aerial firing range—(1) The danger zone. The waters...

33 CFR 334.200 - Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River... Chesapeake Bay, Point Lookout to Cedar Point; aerial and surface firing range and target area, U.S. Naval Air Station, Patuxent River, Maryland, danger zones. (a) Aerial firing range—(1) The danger zone. The waters...

Target design for materials processing very far from equilibrium

NASA Astrophysics Data System (ADS)

Barnard, John J.; Schenkel, Thomas

2016-10-01

Local heating and electronic excitations can trigger phase transitions or novel material states that can be stabilized by rapid quenching. An example on the few nanometer scale are phase transitions induced by the passage of swift heavy ions in solids where nitrogen-vacancy color centers form locally in diamonds when ions heat the diamond matrix to warm dense matter conditions at 0.5 eV. We optimize mask geometries for target materials such as silicon and diamond to induce phase transitions by intense ion pulses (e. g. from NDCX-II or from laser-plasma acceleration). The goal is to rapidly heat a solid target volumetrically and to trigger a phase transition or local lattice reconstruction followed by rapid cooling. The stabilized phase can then be studied ex situ. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of crystal targets with micro-structured masks. A simple analytical model, that includes ion heating and radial, diffusive cooling, was developed that agrees closely with the HYDRA simulations. The model gives scaling laws that can guide the design of targets over a wide range of parameters including those for NDCX-II and the proposed BELLA-i. This work was performed under the auspices of the U.S. DOE under contracts DE-AC52-07NA27344 (LLNL), DE-AC02-05CH11231 (LBNL) and was supported by the US DOE Office of Science, Fusion Energy Sciences. LLNL-ABS-697271.

43 CFR 420.21 - Procedure for designating areas for off-road vehicle use.

Code of Federal Regulations, 2011 CFR

2011-10-01

... cultural or historic resources of particular areas or trails of the public lands, he shall immediately... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Procedure for designating areas for off... BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR OFF-ROAD VEHICLE USE Designated Areas and Permitted...

42 CFR 5.3 - Procedures for designation of health professional(s) shortage areas.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Procedures for designation of health professional(s... SERVICES GENERAL PROVISIONS DESIGNATION OF HEALTH PROFESSIONAL(S) SHORTAGE AREAS § 5.3 Procedures for designation of health professional(s) shortage areas. (a) Using data available to the Department from national...

A Real-Time Brain-Machine Interface Combining Motor Target and Trajectory Intent Using an Optimal Feedback Control Design

PubMed Central

Shanechi, Maryam M.; Williams, Ziv M.; Wornell, Gregory W.; Hu, Rollin C.; Powers, Marissa; Brown, Emery N.

2013-01-01

Real-time brain-machine interfaces (BMI) have focused on either estimating the continuous movement trajectory or target intent. However, natural movement often incorporates both. Additionally, BMIs can be modeled as a feedback control system in which the subject modulates the neural activity to move the prosthetic device towards a desired target while receiving real-time sensory feedback of the state of the movement. We develop a novel real-time BMI using an optimal feedback control design that jointly estimates the movement target and trajectory of monkeys in two stages. First, the target is decoded from neural spiking activity before movement initiation. Second, the trajectory is decoded by combining the decoded target with the peri-movement spiking activity using an optimal feedback control design. This design exploits a recursive Bayesian decoder that uses an optimal feedback control model of the sensorimotor system to take into account the intended target location and the sensory feedback in its trajectory estimation from spiking activity. The real-time BMI processes the spiking activity directly using point process modeling. We implement the BMI in experiments consisting of an instructed-delay center-out task in which monkeys are presented with a target location on the screen during a delay period and then have to move a cursor to it without touching the incorrect targets. We show that the two-stage BMI performs more accurately than either stage alone. Correct target prediction can compensate for inaccurate trajectory estimation and vice versa. The optimal feedback control design also results in trajectories that are smoother and have lower estimation error. The two-stage decoder also performs better than linear regression approaches in offline cross-validation analyses. Our results demonstrate the advantage of a BMI design that jointly estimates the target and trajectory of movement and more closely mimics the sensorimotor control system. PMID:23593130

The role of protected area wetlands in waterfowl habitat conservation: implications for protected area network design

USGS Publications Warehouse

Beatty, William S.; Kesler, Dylan C.; Webb, Elisabeth B.; Raedeke, Andrew H.; Naylor, Luke W.; Humburg, Dale D.

2014-01-01

The principal goal of protected area networks is biodiversity preservation, but efficacy of such networks is directly linked to animal movement within and outside area boundaries. We examined wetland selection patterns of mallards (Anas platyrhynchos) during non-breeding periods from 2010 to 2012 to evaluate the utility of protected areas to migratory waterfowl in North America. We tracked 33 adult females using global positioning system (GPS) satellite transmitters and implemented a use-availability resource selection design to examine mallard use of wetlands under varying degrees of protection. Specifically, we examined effects of proximities to National Wildlife Refuges, private land, state wildlife management areas, Wetland Reserve Program easements (WRP), and waterfowl sanctuaries on mallard wetland selection. In addition, we included landscape-level variables that measured areas of sanctuary and WRP within the surrounding landscape of each used and available wetland. We developed 8 wetland selection models according to season (autumn migration, winter, spring migration), hunting season (present, absent), and time period (diurnal, nocturnal). Model averaged parameter estimates indicated wetland selection patterns varied across seasons and time periods, but ducks consistently selected wetlands with greater areas of sanctuary and WRP in the surrounding landscape. Consequently, WRP has the potential to supplement protected area networks in the midcontinent region. Additionally, seasonal variation in wetland selection patterns indicated considering the effects of habitat management and anthropogenic disturbances on migratory waterfowl during the non-breeding period is essential in designing protected area networks.

Informing Healthcare Waiting Area Design Using Transparency Attributes: A Comparative Preference Study.

PubMed

Jiang, Shan; Powers, Matthew; Allison, David; Vincent, Ellen

2017-07-01

This study aimed to explore people's visual preference for waiting areas in general hospital environments designed with transparency attributes that fully integrate nature. Waiting can be a tedious and frustrating experience among people seeking healthcare treatments and negatively affect their perception of the quality of care. Positive distractions and supportive designs have gained increasing attraction to improve people's waiting experience. Nature, which has shown therapeutic effects according to a growing amount of evidence, could be a distinguished positive distraction in waiting areas. Additionally, the theory of transparency was operationalized to indicate a spatial continuity between the external nature and the built interiors in general healthcare waiting area design. A survey method was adopted in the study. Twenty-one images of general healthcare waiting areas depicting three design typologies were preselected following a strict procedure, including designs with (a) no window views, (b) limited window views to nature, and (c) transparent spaces with maximum natural views. Ninety-five student participants rated the images based on their visual preference using a Likert-type scale. The results showed that transparent waiting areas were significantly preferred. A significant positive relationship existed between the level of transparency and people's preference scores. The factor analysis indicated additional supportive features that may affect people's preferences, including daylight, perceived warmth, noninstitutional furniture arrangement, visual orientation, and the use of natural materials for interior design. However, these tentative results need to be furthered tested with the real patient population as the next step of this study.

Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

PubMed

Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

2017-10-01

Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

Genome-wide Target Enrichment-aided Chip Design: a 66 K SNP Chip for Cashmere Goat.

PubMed

Qiao, Xian; Su, Rui; Wang, Yang; Wang, Ruijun; Yang, Ting; Li, Xiaokai; Chen, Wei; He, Shiyang; Jiang, Yu; Xu, Qiwu; Wan, Wenting; Zhang, Yaolei; Zhang, Wenguang; Chen, Jiang; Liu, Bin; Liu, Xin; Fan, Yixing; Chen, Duoyuan; Jiang, Huaizhi; Fang, Dongming; Liu, Zhihong; Wang, Xiaowen; Zhang, Yanjun; Mao, Danqing; Wang, Zhiying; Di, Ran; Zhao, Qianjun; Zhong, Tao; Yang, Huanming; Wang, Jian; Wang, Wen; Dong, Yang; Chen, Xiaoli; Xu, Xun; Li, Jinquan

2017-08-17

Compared with the commercially available single nucleotide polymorphism (SNP) chip based on the Bead Chip technology, the solution hybrid selection (SHS)-based target enrichment SNP chip is not only design-flexible, but also cost-effective for genotype sequencing. In this study, we propose to design an animal SNP chip using the SHS-based target enrichment strategy for the first time. As an update to the international collaboration on goat research, a 66 K SNP chip for cashmere goat was created from the whole-genome sequencing data of 73 individuals. Verification of this 66 K SNP chip with the whole-genome sequencing data of 436 cashmere goats showed that the SNP call rates was between 95.3% and 99.8%. The average sequencing depth for target SNPs were 40X. The capture regions were shown to be 200 bp that flank target SNPs. This chip was further tested in a genome-wide association analysis of cashmere fineness (fiber diameter). Several top hit loci were found marginally associated with signaling pathways involved in hair growth. These results demonstrate that the 66 K SNP chip is a useful tool in the genomic analyses of cashmere goats. The successful chip design shows that the SHS-based target enrichment strategy could be applied to SNP chip design in other species.

Systems Engineering Approach for Conceptual Design of Frigate

DTIC Science & Technology

2015-09-01

ejection area. Topside designers should also take note of the gun maintenance required area (e.g., barrel swabbing area), which requires significant...Figure 9. Range-to-Target Plot (BlueIntercept Missile vs. RedFire) ........................34 Figure 10. Range-to-Target Plot (Main Gun System vs...and the secondary anti-air weapon will be the main gun system. The frigates shall also be equipped with an area terminal type defense (ATTD

Designing Targeted Educational Voucher Schemes for the Poor in Developing Countries

ERIC Educational Resources Information Center

Shafiq, M. Najeeb

2010-01-01

A targeted educational voucher scheme (TEVS) is often proposed for the poor in developing countries. Essentially, TEVS involves issuing vouchers to poor households, thus enabling them to pay tuition and fees for their children's schooling at participating non-public schools. However, little is known about TEVS' design in developing countries. This…

33 CFR 334.10 - Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Gulf of Maine off Seal Island... REGULATIONS § 334.10 Gulf of Maine off Seal Island, Maine; naval aircraft bombing target area. (a) The danger zone. A circular area with a radius of 1.5 nautical miles, having its center just easterly of Seal...

The choice of the energy embedding law in the design of heavy ionic fusion cylindrical targets

NASA Astrophysics Data System (ADS)

Dolgoleva, GV; Zykova, A. I.

2017-10-01

The paper considers the numerical design of heavy ion fusion (FIHIF) targets, which is one of the branches of controlled thermonuclear fusion (CTF). One of the important tasks in the targets design for controlled thermonuclear fusion is the energy embedding selection whereby it is possible to obtain “burning” (the presence of thermonuclear reactions) of the working DT region. The work is devoted to the rapid ignition of FIHIF targets by means of an additional short-term energy contribution to the DT substance already compressed by massively more longer by energy embedding. This problem has been fairly well studied for laser targets, but this problem is new for heavy ion fusion targets. Maximum momentum increasing is very technically difficult and expensive on modern FIHIF installations. The work shows that the additional energy embedding (“igniting” impulse) reduces the requirements to the maximum impulse. The purpose of this work is to research the ignition impulse effect on the FIHIF target parameters.

45 CFR 1321.33 - Designation of area agencies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Designation of area agencies. 1321.33 Section 1321.33 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS PROGRAMS...

A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.

PubMed

Li, Shiliang; Song, Yuwei; Liu, Xiaofeng; Li, Honglin

2016-01-01

The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.

78 FR 19005 - Notice of Service Area Designation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... regulations have full force and effect when extending the BIA financial assistance and/or social services into... notice, under the regulations, of the service area designation for the Pit River Tribe that is recognized... . SUPPLEMENTARY INFORMATION: In accordance with 25 CFR part 20, Financial Assistance and Social Services Programs...

Design of targeted libraries against the human Chk1 kinase using PGVL Hub.

PubMed

Peng, Zhengwei; Hu, Qiyue

2011-01-01

PGVL Hub is a Pfizer internal desktop tool for chemical library and singleton design. In this chapter, we give a short introduction to PGVL Hub, the core workflow it supports, and the rich design capabilities it provides. By re-creating two legacy targeted libraries against the human checkpoint kinase 1 (Chk1) as a showcase, we illustrate how PGVL Hub could be used to help library designers carry out the steps in library design and realize design objectives such as SAR expansion and improvement in both kinase selectivity and compound aqueous solubility. Finally we share several tips about library design and usage of PGVL Hub.

Modern prodrug design for targeted oral drug delivery.

PubMed

Dahan, Arik; Zimmermann, Ellen M; Ben-Shabat, Shimon

2014-10-14

The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options.

NIF Target Designs and OMEGA Experiments for Shock-Ignition Inertial Confinement Fusion

NASA Astrophysics Data System (ADS)

Anderson, K. S.

2012-10-01

Shock ignition (SI)footnotetextR. Betti et al., Phys. Rev. Lett. 98, 155001 (2007). is being pursued as a viable option to achieve ignition on the National Ignition Facility (NIF). Shock-ignition target designs require the addition of a high-intensity (˜5 x 10^15 W/cm^2) laser spike at the end of a low-adiabat assembly pulse to launch a spherically convergent strong shock to ignite the imploding capsule. Achieving ignition with SI requires the laser spike to generate an ignitor shock with a launching pressure typically in excess of ˜300 Mbar. At the high laser intensities required during the spike pulse, stimulated Raman (SRS) and Brillouin scattering (SBS) could reflect a significant fraction of the incident light. In addition, SRS and the two-plasmon-decay instability can accelerate hot electrons into the shell and preheat the fuel. Since the high-power spike occurs at the end of the pulse when the areal density of the shell is several tens of mg/cm^2, shock-ignition fuel layers are shielded against hot electrons with energies below 150 keV. This paper will present data for a set of OMEGA experiments that were designed to study laser--plasma interactions during the spike pulse. In addition, these experiments were used to demonstrate that high-pressure shocks can be produced in long-scale-length plasmas with SI-relevant intensities. Within the constraints imposed by the hydrodynamics of strong shock generation and the laser--plasma instabilities, target designs for SI experiments on the NIF will be presented. Two-dimensional radiation--hydrodynamic simulations of SI target designs for the NIF predict ignition in the polar-drive beam configuration at sub-MJ laser energies. Design robustness to various 1-D effects and 2-D nonuniformities has been characterized. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302.

Measurement of the distribution of radiation in the area surrounding the target mass using optically stimulated luminescence technique.

PubMed

Tanır, A Güneş; Yedek, Hatice; Koç, Kemal; Bölükdemir, M Hicabi

2017-01-01

The scattered doses received by the area surrounding the target that has been subjected to x-rays were investigated. Two experiments were carried out: 1- Al 2 O 3 : C was used as dosimeter and the luminescence counts was measured using both the RisØ TL/OSL system and an ion chamber. 2- BeO aliquots were used and the counts were read using the IBEOX/OSL system. According to the results, the doses absorbed by the area surrounding the target are significantly amount. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lujan Center Mark-IV Target Neutronics Design Internal Review Report

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

Lisowski, Paul W.; Gallmeier, Franz; Guber, Klaus

The 1L Target Moderator Reflector System (TMRS) at the Lujan Center will need to be replaced before the CY 2020 operating cycle. A Physics Division design team investigated options for improving the overall target performance for nuclear science research with minimal reduction in performance for materials science. This review concluded that devoting an optimized arrangement of the Lujan TMRS upper tier to nuclear science and using the lower tier for materials science can achieve those goals. This would open the opportunity for enhanced nuclear science research in an important neutron energy range for NNSA. There will be no other facilitymore » in the US that will compete in the keV energy range provided flight paths and instrumentation are developed to take advantage of the neutron flux and resolution.« less

Design of a liquid membrane target for high repetition rate neutron generation

NASA Astrophysics Data System (ADS)

Poole, Patrick; Andereck, C. David; Storm, Mike; Schumacher, Douglass

2013-10-01

Ultra-bright, pulsed, spatially-small sources of energetic neutrons have applications in radiography and non-destructive remote sensing. Neutrons can be generated by a process wherein ions accelerated from a laser-irradiated primary target subsequently bombard a converter material, causing neutron-producing nuclear reactions, such as 7Li(d,n)8Be. Deuterons from this process are suppressed by contamination that builds up on the rear of the solid primary target. To eliminate this issue we propose a self-replenishing liquid membrane target consisting of heavy water and deuterated surfactant, formed in-vacuum within a moveable wire frame. In addition to removing issues associated with solid target positioning and collateral damage, this apparatus provides flow rate and target thickness control, and allows for the high repetition rates required to generate desired neutron fluxes with a portable laser-based system. The apparatus design will be presented, as well as a novel interferometric method that measures the membrane thickness using tightly-focused light. This work was performed with support from DARPA.

Rockfall catchment area design guide : metric edition : appendices.

DOT National Transportation Integrated Search

2001-12-01

The appendices belong to "Rockfall catchment area design guide : metric edition". : The data gathered from an exhaustive research project consisting of rolling a total of approximately 11,250 rocks off vertical; 4V:1H;2V;1H;1.33V:1H;1.0V:1.0H slopes ...

36 CFR 212.57 - Monitoring of effects of motor vehicle use on designated roads and trails and in designated areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Monitoring of effects of motor vehicle use on designated roads and trails and in designated areas. 212.57 Section 212.57 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE TRAVEL MANAGEMENT Designation of Roads, Trails, and Areas for Motor Vehicle Use...

Rational Design of Small Molecules Targeting Oncogenic Noncoding RNAs from Sequence.

PubMed

Disney, Matthew D; Angelbello, Alicia J

2016-12-20

The discovery of RNA catalysis in the 1980s and the dissemination of the human genome sequence at the start of this century inspired investigations of the regulatory roles of noncoding RNAs in biology. In fact, the Encyclopedia of DNA Elements (ENCODE) project has shown that only 1-2% of the human genome encodes protein, yet 75% is transcribed into RNA. Functional studies both preceding and following the ENCODE project have shown that these noncoding RNAs have important roles in regulating gene expression, developmental timing, and other critical functions. RNA's diverse roles are often a consequence of the various folds that it adopts. The single-stranded nature of the biopolymer enables it to adopt intramolecular folds with noncanonical pairings to lower its free energy. These folds can be scaffolds to bind proteins or to form frameworks to interact with other RNAs. Not surprisingly, dysregulation of certain noncoding RNAs has been shown to be causative of disease. Given this as the background, it is easy to see why it would be useful to develop methods that target RNA and manipulate its biology in rational and predictable ways. The antisense approach has afforded strategies to target RNAs via Watson-Crick base pairing and has typically focused on targeting partially unstructured regions of RNA. Small molecule strategies to target RNA would be desirable not only because compounds could be lead optimized via medicinal chemistry but also because structured regions within an RNA of interest could be targeted to directly interfere with RNA folds that contribute to disease. Additionally, small molecules have historically been the most successful drug candidates. Until recently, the ability to design small molecules that target non-ribosomal RNAs has been elusive, creating the perception that they are "undruggable". In this Account, approaches to demystify targeting RNA with small molecules are described. Rather than bulk screening for compounds that bind to singular

Area efficient layout design of CMOS circuit for high-density ICs

NASA Astrophysics Data System (ADS)

Mishra, Vimal Kumar; Chauhan, R. K.

2018-01-01

Efficient layouts have been an active area of research to accommodate the greater number of devices fabricated on a given chip area. In this work a new layout of CMOS circuit is proposed, with an aim to improve its electrical performance and reduce the chip area consumed. The study shows that the design of CMOS circuit and SRAM cells comprising tapered body reduced source fully depleted silicon on insulator (TBRS FD-SOI)-based n- and p-type MOS devices. The proposed TBRS FD-SOI n- and p-MOSFET exhibits lower sub-threshold slope and higher Ion to Ioff ratio when compared with FD-SOI MOSFET and FinFET technology. Other parameters like power dissipation, delay time and signal-to-noise margin of CMOS inverter circuits show improvement when compared with available inverter designs. The above device design is used in 6-T SRAM cell so as to see the effect of proposed layout on high density integrated circuits (ICs). The SNM obtained from the proposed SRAM cell is 565 mV which is much better than any other SRAM cell designed at 50 nm gate length MOS device. The Sentaurus TCAD device simulator is used to design the proposed MOS structure.

Changes in Extremely Hot Summers over the Global Land Area under Various Warming Targets.

PubMed

Wang, Lei; Huang, Jianbin; Luo, Yong; Yao, Yao; Zhao, Zongci

2015-01-01

Summer temperature extremes over the global land area were investigated by comparing 26 models of the fifth phase of the Coupled Model Intercomparison Project (CMIP5) with observations from the Goddard Institute for Space Studies (GISS) and the Climate Research Unit (CRU). Monthly data of the observations and models were averaged for each season, and statistics were calculated for individual models before averaging them to obtain ensemble means. The summers with temperature anomalies (relative to 1951-1980) exceeding 3σ (σ is based on the local internal variability) are defined as "extremely hot". The models well reproduced the statistical characteristics evolution, and partly captured the spatial distributions of historical summer temperature extremes. If the global mean temperature increases 2°C relative to the pre-industrial level, "extremely hot" summers are projected to occur over nearly 40% of the land area (multi-model ensemble mean projection). Summers that exceed 5σ warming are projected to occur over approximately 10% of the global land area, which were rarely observed during the reference period. Scenarios reaching warming levels of 3°C to 5°C were also analyzed. After exceeding the 5°C warming target, "extremely hot" summers are projected to occur throughout the entire global land area, and summers that exceed 5σ warming would become common over 70% of the land area. In addition, the areas affected by "extremely hot" summers are expected to rapidly expand by more than 25%/°C as the global mean temperature increases by up to 3°C before slowing to less than 16%/°C as the temperature continues to increase by more than 3°C. The area that experiences summers with warming of 5σ or more above the warming target of 2°C is likely to maintain rapid expansion of greater than 17%/°C. To reduce the impacts and damage from severely hot summers, the global mean temperature increase should remain low.

Changes in Extremely Hot Summers over the Global Land Area under Various Warming Targets

PubMed Central

Wang, Lei; Huang, Jianbin; Luo, Yong; Yao, Yao; Zhao, Zongci

2015-01-01

Summer temperature extremes over the global land area were investigated by comparing 26 models of the fifth phase of the Coupled Model Intercomparison Project (CMIP5) with observations from the Goddard Institute for Space Studies (GISS) and the Climate Research Unit (CRU). Monthly data of the observations and models were averaged for each season, and statistics were calculated for individual models before averaging them to obtain ensemble means. The summers with temperature anomalies (relative to 1951–1980) exceeding 3σ (σ is based on the local internal variability) are defined as “extremely hot”. The models well reproduced the statistical characteristics evolution, and partly captured the spatial distributions of historical summer temperature extremes. If the global mean temperature increases 2°C relative to the pre-industrial level, “extremely hot” summers are projected to occur over nearly 40% of the land area (multi-model ensemble mean projection). Summers that exceed 5σ warming are projected to occur over approximately 10% of the global land area, which were rarely observed during the reference period. Scenarios reaching warming levels of 3°C to 5°C were also analyzed. After exceeding the 5°C warming target, “extremely hot” summers are projected to occur throughout the entire global land area, and summers that exceed 5σ warming would become common over 70% of the land area. In addition, the areas affected by “extremely hot” summers are expected to rapidly expand by more than 25%/°C as the global mean temperature increases by up to 3°C before slowing to less than 16%/°C as the temperature continues to increase by more than 3°C. The area that experiences summers with warming of 5σ or more above the warming target of 2°C is likely to maintain rapid expansion of greater than 17%/°C. To reduce the impacts and damage from severely hot summers, the global mean temperature increase should remain low. PMID:26090931

Full-Carpet Design of a Low-Boom Demonstrator Concept

NASA Technical Reports Server (NTRS)

Ordaz, Irian; Wintzer, Mathias; Rallabhandi, Sriram K.

2015-01-01

The Cart3D adjoint-based design framework is used to mitigate the undesirable o -track sonic boom properties of a demonstrator concept designed for low-boom directly under the flight path. First, the requirements of a Cart3D design mesh are determined using a high-fidelity mesh adapted to minimize the discretization error of the CFD analysis. Low-boom equivalent area targets are then generated at the under-track and one off-track azimuthal position for the baseline configuration. The under-track target is generated using a trim- feasible low-boom target generation process, ensuring that the final design is not only low-boom, but also trimmed at the specified flight condition. The o -track equivalent area target is generated by minimizing the A-weighted loudness using an efficient adjoint-based approach. The configuration outer mold line is then parameterized and optimized to match the off-body pressure distributions prescribed by the low-boom targets. The numerical optimizer uses design gradients which are calculated using the Cart3D adjoint- based design capability. Optimization constraints are placed on the geometry to satisfy structural feasibility. The low-boom properties of the final design are verified using the adaptive meshing approach. This analysis quantifies the error associated with the CFD mesh that is used for design. Finally, an alternate mesh construction and target positioning approach offering greater computational efficiency is demonstrated and verified.

SEDIMENT HABITAT ASSESSMENT FOR TARGETED NEAR-COASTAL AREAS OF THE GULF OF MEXICO: A SUMMARY

EPA Science Inventory

Lewis, Michael A. In press. Sediment Habitat Assessment for Targeted Near-Coastal Areas of the Gulf of Mexico: A Summary. In: Estuarine Indicators Workshop Proceedings. CRC Press, Boca Raton, FL. 25 p. (ERL,GB 1201).

Sediment chemical and biological quality is summarized ...

75 FR 52780 - Designation of Nine Counties as High Intensity Drug Trafficking Areas

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-27

... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Nine Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated nine additional counties as High Drug Trafficking Areas pursuant to...

75 FR 21368 - Designation of Five Counties as High Intensity Drug Trafficking Areas

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-23

... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Five Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated five additional counties as High Drug Trafficking Areas pursuant to...

Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity.

PubMed

Lee, Ciaran M; Davis, Timothy H; Bao, Gang

2018-04-01

What is the topic of this review? In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity. What advances does it highlight? Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power. The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design, these studies have spawned a plethora of guide RNA (gRNA) design tools with algorithms based solely on direct or indirect sequence features. Here, we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Computational and Pharmacological Target of Neurovascular Unit for Drug Design and Delivery

PubMed Central

2015-01-01

The blood-brain barrier (BBB) is a dynamic and highly selective permeable interface between central nervous system (CNS) and periphery that regulates the brain homeostasis. Increasing evidences of neurological disorders and restricted drug delivery process in brain make BBB as special target for further study. At present, neurovascular unit (NVU) is a great interest and highlighted topic of pharmaceutical companies for CNS drug design and delivery approaches. Some recent advancement of pharmacology and computational biology makes it convenient to develop drugs within limited time and affordable cost. In this review, we briefly introduce current understanding of the NVU, including molecular and cellular composition, physiology, and regulatory function. We also discuss the recent technology and interaction of pharmacogenomics and bioinformatics for drug design and step towards personalized medicine. Additionally, we develop gene network due to understand NVU associated transporter proteins interactions that might be effective for understanding aetiology of neurological disorders and new target base protective therapies development and delivery. PMID:26579539

Assessing protected area effectiveness using surrounding (buffer) areas environmentally similar to the target area.

PubMed

Mas, Jean-François

2005-06-01

Many studies are based on the assumption that an area and its surrounding (buffer) area present similar environmental conditions and can be compared. For example, in order to assess the effectiveness of a protected area, the land use/cover changes are compared inside the park with its surroundings. However, the heterogeneity in spatial variables can bias this assessment: we have shown that most of the protected areas in Mexico present significant environmental differences between their interior and their surroundings. Therefore, a comparison that aims at assessing the effectiveness of conservation strategies, must be cautioned. In this paper, a simple method which allows the generation of a buffer area that presents similar conditions with respect to a set of environmental variables is presented. The method was used in order to assess the effectiveness of the Calakmul Biosphere Reserve, a protected area located in the south-eastern part of Mexico. The annual rate of deforestation inside the protected area, the standard buffer area (based upon distance from the protected area only) and the similar buffer area (taking into account distance along with some environmental variables) were 0.3, 1.3 and 0.6%, respectively. These results showed that the protected area was effective in preventing land clearing, but that the comparison with the standard buffer area gave an over-optimistic vision of its effectiveness.

Designated "no smoking" areas provide from partial to no protection from environmental tobacco smoke.

PubMed

Cains, T; Cannata, S; Poulos, R; Ferson, M J; Stewart, B W

2004-03-01

To determine the efficacy of designated "no smoking" areas in the hospitality industry as a means of providing protection from environmental tobacco smoke (ETS), and whether certain design features assist in achieving this end. In the greater metropolitan region of Sydney, a representative group of 17 social and gaming clubs, licensed to serve alcoholic beverages and in which, apart from designated areas, smoking occurs, agreed to participate. In each establishment, simultaneous single measurements of atmospheric nicotine, particulate matter (10 microm; PM10) and carbon dioxide (CO2) levels were measured in a general use area and in a designated "no smoking" area during times of normal operation, together with the levels in outdoor air (PM10 and CO2 only). Analyses were made of these data to assess the extent to which persons using the "no smoking" areas were protected from exposure to ETS. By comparison with levels in general use areas, nicotine and particulate matter levels were significantly less in the "no smoking" areas, but were still readily detectable at higher than ambient levels. For nicotine, mean (SD) levels were 100.5 (45.3) microg/m3 in the areas where smoking occurred and 41.3 (16.1) microg/m3 in the "no smoking" areas. Corresponding PM10 levels were 460 (196) microg/m3 and 210 (210) microg/m3, while outdoor levels were 61 (23) microg/m3. The reduction in pollutants achieved through a separate room being designated "no smoking" was only marginally better than the reduction achieved when a "no smoking" area was contiguous with a smoking area. CO2 levels were relatively uninformative. Provision of designated "no smoking" areas in licensed (gaming) clubs in New South Wales, Australia, provides, at best, partial protection from ETS-typically about a 50% reduction in exposure. The protection afforded is less than users might reasonably have understood and is not comparable with protection afforded by prohibiting smoking on the premises.

Tucson Diversion Channel. Phase I. Sport Fields & Picnic Area. Feature Design Memorandum Number 3.

DTIC Science & Technology

1983-04-01

opportunities for picnicking, a variety of field sports and court games , archery, jogging, and bicycling. d. Rapid urban growth in the Tucson metropolitan area...AD’A136 927 TUCSON DIVERSION CHANNEL PHASE I SPORT FIELDS A PICNI IC J AREA FEATURE DESIGN MEMORANDUM NUMBER 3(U) ARMY ENGINEER DISTRICT LOS ANGELES...TUCSON DIVERSION CHMNEL DESIGN EIORANDUK NO. 3 FEATURE DESIGN MNRORANDIJ PHASE I SPORT FIELDS & PICNIC AREA APRIL 1983 t1 US AM CORPS OF

INTERIOR SECOND FLOOR EAST ENGINEERING DESIGN AREA DETAIL VIEW, FACING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

INTERIOR SECOND FLOOR EAST ENGINEERING DESIGN AREA DETAIL VIEW, FACING NORTH. - NASA Industrial Plant, Systems Integration & Checkout Facility, 12214 Lakewood Boulevard, Downey, Los Angeles County, CA

Vector design for liver specific expression of multiple interfering RNAs that target hepatitis B virus transcripts

PubMed Central

Snyder, Lindsey L.; Esser, Jonathan M.; Pachuk, Catherine J.; Steel, Laura F.

2008-01-01

RNA interference (RNAi) is a process that can target intracellular RNAs for degradation in a highly sequence specific manner, making it a powerful tool that is being pursued in both research and therapeutic applications. Hepatitis B virus (HBV) is a serious public health problem in need of better treatment options, and aspects of its life cycle make it an excellent target for RNAi-based therapeutics. We have designed a vector that expresses interfering RNAs that target HBV transcripts, including both viral RNA replicative intermediates and mRNAs encoding viral proteins. Our vector design incorporates many features of endogenous microRNA (miRNA) gene organization that are proving useful for the development of reagents for RNAi. In particular, our vector contains an RNA pol II driven gene cassette that leads to tissue specific expression and efficient processing of multiple interfering RNAs from a single transcript, without the co-expression of any protein product. This vector shows potent silencing of HBV targets in cell culture models of HBV infection. The vector design will be applicable to silencing of additional cellular or disease-related genes. PMID:18499277

The stimulus integration area for horizontal vergence.

PubMed

Allison, Robert S; Howard, Ian P; Fang, Xueping

2004-06-01

Over what region of space are horizontal disparities integrated to form the stimulus for vergence? The vergence system might be expected to respond to disparities within a small area of interest to bring them into the range of precise stereoscopic processing. However, the literature suggests that disparities are integrated over a fairly large parafoveal area. We report the results of six experiments designed to explore the spatial characteristics of the stimulus for vergence. Binocular eye movements were recorded using magnetic search coils. Each dichoptic display consisted of a central target stimulus that the subject attempted to fuse, and a competing stimulus with conflicting disparity. In some conditions the target was stationary, providing a fixation stimulus. In other conditions, the disparity of the target changed to provide a vergence-tracking stimulus. The target and competing stimulus were combined in a variety of conditions including those in which (1) a transparent textured-disc target was superimposed on a competing textured background, (2) a textured-disc target filled the centre of a competing annular background, and (3) a small target was presented within the centre of a competing annular background of various inner diameters. In some conditions the target and competing stimulus were separated in stereoscopic depth. The results are consistent with a disparity integration area with a diameter of about 5 degrees. Stimuli beyond this integration area can drive vergence in their own right, but they do not appear to be summed or averaged with a central stimulus to form a combined disparity signal. A competing stimulus had less effect on vergence when separated from the target by a disparity pedestal. As a result, we propose that it may be more useful to think in terms of an integration volume for vergence rather than a two-dimensional retinal integration area.

Maximize, minimize or target - optimization for a fitted response from a designed experiment

DOE PAGES

Anderson-Cook, Christine Michaela; Cao, Yongtao; Lu, Lu

2016-04-01

One of the common goals of running and analyzing a designed experiment is to find a location in the design space that optimizes the response of interest. Depending on the goal of the experiment, we may seek to maximize or minimize the response, or set the process to hit a particular target value. After the designed experiment, a response model is fitted and the optimal settings of the input factors are obtained based on the estimated response model. Furthermore, the suggested optimal settings of the input factors are then used in the production environment.

The National Spallation Neutron Source Target Station.

NASA Astrophysics Data System (ADS)

Gabriel, T. A.

1997-05-01

The technologies that are being utilized to design and build a state-of-the-art high powered (>= 1 MW), short pulsed (<= 1 μsec), and reliable spallation neutron source target station are discussed. The protons which directly and indirectly produce the neutrons will be obtained from a 1 GeV proton accelerator composed of an ion gun, rfq, linac, and storage ring. Many scientific and technical disciplines are required to produce a successful target station. These disciplines include engineering, remote handling, neutronics, materials, thermal hydraulics, shock analysis, etc. In the areas of engineering and remote handling special emphasis is being given to rapid and efficient assembly and disassembly of critical parts of the target station. In the neutronics area, emphasis is being given to neutron yield and pulse optimization from the moderators, and heating and activation rates throughout the station. Development of structural materials to withstand aggressive radiation environments and that are compatible with other materials is also an important area. Thermal hydraulics and shock analysis are being closely studied since large amounts of energy are being deposited in small volumes in relatively short time periods (< 1 μsec). These areas will be expanded upon in the paper.

Design Considerations for a New Terminal Area Arrival Scheduler

NASA Technical Reports Server (NTRS)

Thipphavong, Jane; Mulfinger, Daniel

2010-01-01

Design of a terminal area arrival scheduler depends on the interrelationship between throughput, delay and controller intervention. The main contribution of this paper is an analysis of the above interdependence for several stochastic behaviors of expected system performance distributions in the aircraft s time of arrival at the meter fix and runway. Results of this analysis serve to guide the scheduler design choices for key control variables. Two types of variables are analyzed, separation buffers and terminal delay margins. The choice for these decision variables was tested using sensitivity analysis. Analysis suggests that it is best to set the separation buffer at the meter fix to its minimum and adjust the runway buffer to attain the desired system performance. Delay margin was found to have the least effect. These results help characterize the variables most influential in the scheduling operations of terminal area arrivals.

Designer interface peptide grafts target estrogen receptor alpha dimerization

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

Chakraborty, S.; Asare, B.K.; Biswas, P.K., E-mail: pbiswas@tougaloo.edu

The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization.more » Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

A Designed Peptide Targets Two Types of Modifications of p53 with Anti-cancer Activity.

PubMed

Liang, Lunxi; Wang, Huanbin; Shi, Hubing; Li, Zhaoli; Yao, Han; Bu, Zhigao; Song, Ningning; Li, Chushu; Xiang, Dabin; Zhang, Yao; Wang, Jilin; Hu, Ye; Xu, Qi; Ma, Yanlei; Cheng, Zhongyi; Wang, Yingchao; Zhao, Shuliang; Qian, Jin; Chen, Yingxuan; Fang, Jing-Yuan; Xu, Jie

2018-06-21

Many cancer-related proteins are controlled by composite post-translational modifications (PTMs), but prevalent strategies only target one type of modification. Here we describe a designed peptide that controls two types of modifications of the p53 tumor suppressor, based on the discovery of a protein complex that suppresses p53 (suppresome). We found that Morn3, a cancer-testis antigen, recruits different PTM enzymes, such as sirtuin deacetylase and ubiquitin ligase, to confer composite modifications on p53. The molecular functions of Morn3 were validated through in vivo assays and chemico-biological intervention. A rationally designed Morn3-targeting peptide (Morncide) successfully activated p53 and suppressed tumor growth. These findings shed light on the regulation of protein PTMs and present a strategy for targeting two modifications with one molecule. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rational Design of Iron Oxide Nanoparticles as Targeted Nanomedicines for Cancer Therapy

NASA Astrophysics Data System (ADS)

Kievit, Forrest M.

2011-07-01

Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired biological response. Of the nanomaterials studied, superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as one of top candidates for cancer therapy due to their intrinsic superparamagnetism that enables non-invasive magnetic resonance imaging (MRI) and biodegradability favorable for in vivo application. This dissertation is aimed at development of SPION-based nanomedicines to overcome the current limitations in cancer therapy. These limitations include non-specificity of therapy which can harm healthy tissue, the difficulty in delivering nucleic acids for gene therapy, the formation of drug resistance, and the inability to detect and treat micrometastases. First, a SPION-based non-viral gene delivery vehicle was developed through functionalization of the SPION core with a co-polymer designed to provide stable binding of DNA and low toxicity which showed excellent gene delivery in vitro and in vivo. This SPION-based non-viral gene delivery vehicle was then activated with a targeting agent to improve gene delivery throughout a xenograft tumor of brain cancer. It was found that targeting did not promote the accumulation of SPIONs at the tumor site, but rather improved the distribution of SPIONs throughout the tumor so a higher proportion of cells received treatment. Next, the high surface area of SPIONs was utilized for loading large amounts of drug which was shown to overcome the multidrug resistance acquired by many cancer cells. Drug bound to SPIONs showed significantly higher multidrug resistant cell uptake as compared to free drug which translated into improved cell kill. Also, an antibody activated SPION was developed and was shown to be able to target micrometastases in a transgenic animal model of metastatic breast cancer. These SPION-based nanomedicines

High-resolution imaging and target designation through clouds or smoke

DOEpatents

Perry, Michael D.

2003-01-01

A method and system of combining gated intensifiers and advances in solid-state, short-pulse laser technology, compact systems capable of producing high resolution (i.e., approximately less than 20 centimeters) optical images through a scattering medium such as dense clouds, fog, smoke, etc. may be achieved from air or ground based platforms. Laser target designation through a scattering medium is also enabled by utilizing a short pulse illumination laser and a relatively minor change to the detectors on laser guided munitions.

Membrane-spanning α-helical barrels as tractable protein-design targets.

PubMed

Niitsu, Ai; Heal, Jack W; Fauland, Kerstin; Thomson, Andrew R; Woolfson, Derek N

2017-08-05

The rational ( de novo ) design of membrane-spanning proteins lags behind that for water-soluble globular proteins. This is due to gaps in our knowledge of membrane-protein structure, and experimental difficulties in studying such proteins compared to water-soluble counterparts. One limiting factor is the small number of experimentally determined three-dimensional structures for transmembrane proteins. By contrast, many tens of thousands of globular protein structures provide a rich source of 'scaffolds' for protein design, and the means to garner sequence-to-structure relationships to guide the design process. The α-helical coiled coil is a protein-structure element found in both globular and membrane proteins, where it cements a variety of helix-helix interactions and helical bundles. Our deep understanding of coiled coils has enabled a large number of successful de novo designs. For one class, the α-helical barrels-that is, symmetric bundles of five or more helices with central accessible channels-there are both water-soluble and membrane-spanning examples. Recent computational designs of water-soluble α-helical barrels with five to seven helices have advanced the design field considerably. Here we identify and classify analogous and more complicated membrane-spanning α-helical barrels from the Protein Data Bank. These provide tantalizing but tractable targets for protein engineering and de novo protein design.This article is part of the themed issue 'Membrane pores: from structure and assembly, to medicine and technology'. © 2017 The Author(s).

US EPA Nonattainment Areas and Designations

EPA Pesticide Factsheets

This web service contains the following state level layers:Ozone 8-hr (1997 standard), Ozone 8-hr (2008 standard), Lead (2008 standard), SO2 1-hr (2010 standard), PM2.5 24hr (2006 standard), PM2.5 Annual (1997 standard), PM2.5 Annual (2012 standard), and PM10 (1987 standard). Full FGDC metadata records for each layer may be found by clicking the layer name at the web service endpoint (https://gispub.epa.gov/arcgis/rest/services/OAR_OAQPS/NonattainmentAreas/MapServer) and viewing the layer description. These layers identify areas in the U.S. where air pollution levels have not met the National Ambient Air Quality Standards (NAAQS) for criteria air pollutants and have been designated nonattainment?? areas (NAA). The data are updated weekly from an OAQPS internal database. However, that does not necessarily mean the data have changed. The EPA Office of Air Quality Planning and Standards (OAQPS) has set National Ambient Air Quality Standards for six principal pollutants, which are called criteria pollutants. Under provisions of the Clean Air Act, which is intended to improve the quality of the air we breathe, EPA is required to set National Ambient Air Quality Standards for six common air pollutants. These commonly found air pollutants (also known as criteria pollutants) are found all over the United States. They are particle pollution (often referred to as particulate matter), ground-level ozone, carbon monoxide, sulfur oxides, nitrogen oxides, and lead. For each

High speed fiber optics local area networks: Design and implementation

NASA Technical Reports Server (NTRS)

Tobagi, Fouad A.

1988-01-01

The design of high speed local area networks (HSLAN) for communication among distributed devices requires solving problems in three areas: (1) the network medium and its topology; (2) the medium access control; and (3) the network interface. Considerable progress has been made in all areas. Accomplishments are divided into two groups according to their theoretical or experimental nature. A brief summary is given in Section 2, including references to papers which appeared in the literature, as well as to Ph.D. dissertations and technical reports published at Stanford University.

Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

PubMed Central

Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

2016-01-01

The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

Size Matters: Developing Design Rules to Engineer Nanoparticles for Solid Tumour Targeting

NASA Astrophysics Data System (ADS)

Sykes, Edward Alexander

Nanotechnology enables the design of highly customizable platforms for producing minimally invasive and programmable strategies for cancer diagnosis and treatment. Advances in this field have demonstrated that nanoparticles can enhance specificity of anti-cancer agents, respond to tumour-specific cues, and direct the visualization of biological targets in vivo. . Nanoparticles can be synthesized within the 1 to 100 nm range to achieve different electromagnetic properties and specifically interact with biological tissues by tuning their size, shape, and surface chemistry. However, it remains unclear which physicochemical parameters are critical for delivering nanomaterials to the tumour site. With less than 5% of administered nanoparticles reaching the tumour, engineering of nanoparticles for effective delivery to solid tumours remains a critical challenge to cancer nanomedicine. A more comprehensive understanding of the interplay between the nanomaterial physicochemical properties and biological systems is necessary to enhance the efficacy of nanoparticle tumour targeting. This thesis explores how nanoparticle size and functionalization with cancer cell specific agents impact nanoparticle delivery to tumours. Furthermore, this doctoral work (i) discusses how tumour structure evolves with growth, (ii) elucidates how such changes modulate nanoparticle accumulation, and (iii) identifies how the skin serves as a significant off-target site for nanoparticle uptake. This thesis also demonstrates the utility of empirically-derived parametric models, Monte Carlo simulations, and decision matrices for mechanistically understanding and predicting the impact of nanomaterial features and tumour biology on nanoparticle fate in vivo. These topics establish key design considerations to tailor nanoparticles for enhanced tumour targeting. Collectively, the concepts presented herein form a fundamental framework for the development of personalized nanomedicine and nano

Mechanical design of experimental apparatus for FIREX cryo-target cooling

NASA Astrophysics Data System (ADS)

Iwamoto, A.; Norimatsu, T.; Nakai, M.; Sakagami, H.; Fujioka, S.; Shiraga, H.; Azechi, H.

2016-05-01

Mechanical design of an experimental apparatus for FIREX cryo-target cooling is described. Gaseous helium (GHe) sealing system at a cryogenic environment is an important issue for laser fusion experiments. The dedicated loading system was designed for a metal gasket. We take U-TIGHTSEAL® (Usui Kokusai Sangyo Kaisha. Ltd.) with an indium plated copper jacket as an example. According to its specification, a linear load of 110 N/m along its circumference is the optimum compression; however a lower load would still maintain helium (He) leak below the required level. Its sealing performance was investigated systematically. Our system demanded 27 N/mm of the load to keep He leak tightness in a cryogenic environment. Once leak tightness was obtained, it could be reduced to 9.5 N/mm.

Spatial analysis of ecosystem service relationships to improve targeting of payments for hydrological services

PubMed Central

Manson, Robert H.; Ricketts, Taylor H.; Geissert, Daniel

2018-01-01

Payment for hydrological services (PHS) are popular tools for conserving ecosystems and their water-related services. However, improving the spatial targeting and impacts of PHS, as well as their ability to foster synergies with other ecosystem services (ES), remain challenging. We aimed at using spatial analyses to evaluate the targeting performance of México’s National PHS program in central Veracruz. We quantified the effectiveness of areas targeted for PHS in actually covering areas of high HS provision and social priority during 2003–2013. First, we quantified provisioning and spatial distributions of two target (water yield and soil retention), and one non-target ES (carbon storage) using InVEST. Subsequently, pairwise relationships among ES were quantified by using spatial correlation and overlap analyses. Finally, we evaluated targeting by: (i) prioritizing areas of individual and overlapping ES; (ii) quantifying spatial co-occurrences of these priority areas with those targeted by PHS; (iii) evaluating the extent to which PHS directly contribute to HS delivery; and (iv), testing if PHS targeted areas disproportionately covered areas with high ecological and social priority. We found that modelled priority areas exhibited non-random distributions and distinct spatial patterns. Our results show significant pairwise correlations between all ES suggesting synergistic relationships. However, our analysis showed a significantly lower overlap than expected and thus significant mismatches between PHS targeted areas and all types of priority areas. These findings suggest that the targeting of areas with high HS provisioning and social priority by Mexico’s PHS program could be improved significantly. This study underscores: (1) the importance of using maps of HS provisioning as main targeting criteria in PHS design to channel payments towards areas that require future conservation, and (2) the need for future research that helps balance ecological and

Assessment of wadeable stream resources in the driftless area ecoregion in Western Wisconsin using a probabilistic sampling design.

PubMed

Miller, Michael A; Colby, Alison C C; Kanehl, Paul D; Blocksom, Karen

2009-03-01

The Wisconsin Department of Natural Resources (WDNR), with support from the U.S. EPA, conducted an assessment of wadeable streams in the Driftless Area ecoregion in western Wisconsin using a probabilistic sampling design. This ecoregion encompasses 20% of Wisconsin's land area and contains 8,800 miles of perennial streams. Randomly-selected stream sites (n = 60) equally distributed among stream orders 1-4 were sampled. Watershed land use, riparian and in-stream habitat, water chemistry, macroinvertebrate, and fish assemblage data were collected at each true random site and an associated "modified-random" site on each stream that was accessed via a road crossing nearest to the true random site. Targeted least-disturbed reference sites (n = 22) were also sampled to develop reference conditions for various physical, chemical, and biological measures. Cumulative distribution function plots of various measures collected at the true random sites evaluated with reference condition thresholds, indicate that high proportions of the random sites (and by inference the entire Driftless Area wadeable stream population) show some level of degradation. Study results show no statistically significant differences between the true random and modified-random sample sites for any of the nine physical habitat, 11 water chemistry, seven macroinvertebrate, or eight fish metrics analyzed. In Wisconsin's Driftless Area, 79% of wadeable stream lengths were accessible via road crossings. While further evaluation of the statistical rigor of using a modified-random sampling design is warranted, sampling randomly-selected stream sites accessed via the nearest road crossing may provide a more economical way to apply probabilistic sampling in stream monitoring programs.

MRPrimerW: a tool for rapid design of valid high-quality primers for multiple target qPCR experiments

PubMed Central

Kim, Hyerin; Kang, NaNa; An, KyuHyeon; Koo, JaeHyung; Kim, Min-Soo

2016-01-01

Design of high-quality primers for multiple target sequences is essential for qPCR experiments, but is challenging due to the need to consider both homology tests on off-target sequences and the same stringent filtering constraints on the primers. Existing web servers for primer design have major drawbacks, including requiring the use of BLAST-like tools for homology tests, lack of support for ranking of primers, TaqMan probes and simultaneous design of primers against multiple targets. Due to the large-scale computational overhead, the few web servers supporting homology tests use heuristic approaches or perform homology tests within a limited scope. Here, we describe the MRPrimerW, which performs complete homology testing, supports batch design of primers for multi-target qPCR experiments, supports design of TaqMan probes and ranks the resulting primers to return the top-1 best primers to the user. To ensure high accuracy, we adopted the core algorithm of a previously reported MapReduce-based method, MRPrimer, but completely redesigned it to allow users to receive query results quickly in a web interface, without requiring a MapReduce cluster or a long computation. MRPrimerW provides primer design services and a complete set of 341 963 135 in silico validated primers covering 99% of human and mouse genes. Free access: http://MRPrimerW.com. PMID:27154272

From laptop to benchtop to bedside: Structure-based Drug Design on Protein Targets

PubMed Central

Chen, Lu; Morrow, John K.; Tran, Hoang T.; Phatak, Sharangdhar S.; Du-Cuny, Lei; Zhang, Shuxing

2013-01-01

As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting protein-ligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches. PMID:22316152

7 CFR 301.85-2 - Authorization to designate, and terminate designation of, regulated areas and suppressive or...

Code of Federal Regulations, 2014 CFR

2014-01-01

... DOMESTIC QUARANTINE NOTICES Golden Nematode Quarantine and Regulations § 301.85-2 Authorization to... nematode has been found or in which there is reason to believe that golden nematode is present, or which it... nematode. (b) Temporary designation of regulated areas and suppressive or generally infested areas. The...

7 CFR 301.85-2 - Authorization to designate, and terminate designation of, regulated areas and suppressive or...

Code of Federal Regulations, 2012 CFR

2012-01-01

... DOMESTIC QUARANTINE NOTICES Golden Nematode Quarantine and Regulations § 301.85-2 Authorization to... nematode has been found or in which there is reason to believe that golden nematode is present, or which it... nematode. (b) Temporary designation of regulated areas and suppressive or generally infested areas. The...

7 CFR 301.85-2 - Authorization to designate, and terminate designation of, regulated areas and suppressive or...

Code of Federal Regulations, 2013 CFR

2013-01-01

... DOMESTIC QUARANTINE NOTICES Golden Nematode Quarantine and Regulations § 301.85-2 Authorization to... nematode has been found or in which there is reason to believe that golden nematode is present, or which it... nematode. (b) Temporary designation of regulated areas and suppressive or generally infested areas. The...

7 CFR 301.85-2 - Authorization to designate, and terminate designation of, regulated areas and suppressive or...

Code of Federal Regulations, 2011 CFR

2011-01-01

... DOMESTIC QUARANTINE NOTICES Golden Nematode Quarantine and Regulations § 301.85-2 Authorization to... nematode has been found or in which there is reason to believe that golden nematode is present, or which it... nematode. (b) Temporary designation of regulated areas and suppressive or generally infested areas. The...

7 CFR 301.85-2 - Authorization to designate, and terminate designation of, regulated areas and suppressive or...

Code of Federal Regulations, 2010 CFR

2010-01-01

... DOMESTIC QUARANTINE NOTICES Golden Nematode Quarantine and Regulations § 301.85-2 Authorization to... nematode has been found or in which there is reason to believe that golden nematode is present, or which it... nematode. (b) Temporary designation of regulated areas and suppressive or generally infested areas. The...

45 CFR 1321.35 - Withdrawal of area agency designation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Withdrawal of area agency designation. 1321.35 Section 1321.35 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS...

Colon-targeted oral drug delivery systems: design trends and approaches.

PubMed

Amidon, Seth; Brown, Jack E; Dave, Vivek S

2015-08-01

Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

Constant-Envelope Waveform Design for Optimal Target-Detection and Autocorrelation Performances

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

Sen, Satyabrata

2013-01-01

We propose an algorithm to directly synthesize in time-domain a constant-envelope transmit waveform that achieves the optimal performance in detecting an extended target in the presence of signal-dependent interference. This approach is in contrast to the traditional indirect methods that synthesize the transmit signal following the computation of the optimal energy spectral density. Additionally, we aim to maintain a good autocorrelation property of the designed signal. Therefore, our waveform design technique solves a bi-objective optimization problem in order to simultaneously improve the detection and autocorrelation performances, which are in general conflicting in nature. We demonstrate this compromising characteristics of themore » detection and autocorrelation performances with numerical examples. Furthermore, in the absence of the autocorrelation criterion, our designed signal is shown to achieve a near-optimum detection performance.« less

The impact of target site accessibility on the design of effective siRNAs.

PubMed

Tafer, Hakim; Ameres, Stefan L; Obernosterer, Gregor; Gebeshuber, Christoph A; Schroeder, Renée; Martinez, Javier; Hofacker, Ivo L

2008-05-01

Small-interfering RNAs (siRNAs) assemble into RISC, the RNA-induced silencing complex, which cleaves complementary mRNAs. Despite their fluctuating efficacy, siRNAs are widely used to assess gene function. Although this limitation could be ascribed, in part, to variations in the assembly and activation of RISC, downstream events in the RNA interference (RNAi) pathway, such as target site accessibility, have so far not been investigated extensively. In this study we present a comprehensive analysis of target RNA structure effects on RNAi by computing the accessibility of the target site for interaction with the siRNA. Based on our observations, we developed a novel siRNA design tool, RNAxs, by combining known siRNA functionality criteria with target site accessibility. We calibrated our method on two data sets comprising 573 siRNAs for 38 genes, and tested it on an independent set of 360 siRNAs targeting four additional genes. Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs.

Design Automation in Synthetic Biology.

PubMed

Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

2017-04-03

Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

[sgRNA design for the CRISPR/Cas9 system and evaluation of its off-target effects].

PubMed

Xie, Sheng-song; Zhang, Yi; Zhang, Li-sheng; Li, Guang-lei; Zhao, Chang-zhi; Ni, Pan; Zhao, Shu-hong

2015-11-01

The third generation of CRISPR/Cas9-mediated genome editing technology has been successfully applied to genome modification of various species including animals, plants and microorganisms. How to improve the efficiency of CRISPR/Cas9 genome editing and reduce its off-target effects has been extensively explored in this field. Using sgRNA (Small guide RNA) with high efficiency and specificity is one of the critical factors for successful genome editing. Several software have been developed for sgRNA design and/or off-target evaluation, which have advantages and disadvantages respectively. In this review, we summarize characters of 16 kinds online and standalone software for sgRNA design and/or off-target evaluation and conduct a comparative analysis of these different kinds of software through developing 38 evaluation indexes. We also summarize 11 experimental approaches for testing genome editing efficiency and off-target effects as well as how to screen highly efficient and specific sgRNA.

Statistical inference on censored data for targeted clinical trials under enrichment design.

PubMed

Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

Closure Report for Corrective Action Unit 408: Bomblet Target Area Tonopah Test Range (TTR), Nevada, Revision 0

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

Mark Krauss

2010-09-01

This Closure Report (CR) presents information supporting the closure of Corrective Action Unit (CAU) 408: Bomblet Target Area (TTR), Tonopah Test Range, Nevada. This CR complies with the requirements of the Federal Facility Agreement and Consent Order that was agreed to by the State of Nevada; U.S. Department of Energy (DOE), Environmental Management; U.S. Department of Defense; and DOE, Legacy Management. Corrective Action Unit 408 is located at the Tonopah Test Range, Nevada, and consists of Corrective Action Site (CAS) TA-55-002-TAB2, Bomblet Target Areas. This CAS includes the following seven target areas: • Mid Target • Flightline Bomblet Location •more » Strategic Air Command (SAC) Target Location 1 • SAC Target Location 2 • South Antelope Lake • Tomahawk Location 1 • Tomahawk Location 2 The purpose of this CR is to provide documentation supporting the completed corrective actions and data confirming that the closure objectives for the CAS within CAU 408 were met. To achieve this, the following actions were performed: • Review the current site conditions, including the concentration and extent of contamination. • Implement any corrective actions necessary to protect human health and the environment. • Properly dispose of corrective action and investigation wastes. • Document Notice of Completion and closure of CAU 408 issued by the Nevada Division of Environmental Protection. From July 2009 through August 2010, closure activities were performed as set forth in the Streamlined Approach for Environmental Restoration Plan for CAU 408: Bomblet Target Area, Tonopah Test Range (TTR), Nevada. The purposes of the activities as defined during the data quality objectives process were as follows: • Identify and remove munitions of explosive concern (MEC) associated with DOE activities. • Investigate potential disposal pit locations. • Remove depleted uranium-contaminated fragments and soil. • Determine whether contaminants of concern

Impact of target area selection in 125 Iodine seed brachytherapy on locoregional recurrence in patients with non-small cell lung cancer.

PubMed

Yan, Wei-Liang; Lv, Jin-Shuang; Guan, Zhi-Yu; Wang, Li-Yang; Yang, Jing-Kui; Liang, Ji-Xiang

2017-05-01

Computed tomography (CT)-guided percutaneous implantation of 125 Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT. Target areas in group 2 (n = 42) were extended by 0.5 cm in all dimensions outside tumor margins. Preoperative plans for both groups were based on a treatment plan system, which guided 125 I seed implantation. Six months later, patients underwent chest CT to evaluate treatment efficacy (per Response Evaluation Criteria in Solid Tumors version 1). We compared locoregional recurrences between the groups after a year of follow-up. We then used the treatment plan system to extend target areas for group 1 patients by 0.5 cm (defined as group 3 data) and compared these hypothetical group 3 planned seeds with the actual seed numbers used in group 1 patients. All patients successfully underwent implantation; none died during the follow-up period. Recurrence was significantly lower in group 2 than in group 1 ( P  < 0.05). Group 1 patients and group 3 data significantly differed in seed numbers ( P  < 0.01). Our results imply that extending the implantation area for 125 I seeds can decrease recurrence risk by eradicating cancerous lymph-duct blockades within the extended areas. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Designing an Intervention for Women with Systemic Lupus Erythematosus from Medically Underserved Areas to Improve Care: A Qualitative Study

PubMed Central

Feldman, Candace H; Bermas, Bonnie L; Zibit, Melanie; Fraser, Patricia; Todd, Derrick J; Fortin, Paul R; Massarotti, Elena; Costenbader, Karen H

2013-01-01

Objective Systemic lupus erythematosus (lupus) disproportionately affects women, racial/ethnic minorities and low-income populations. We held focus groups for women from medically underserved communities to discuss interventions to improve care. Methods From our Lupus Registry, we invited 282 women, > 18 years, residing in urban, medically underserved areas. Hospital-based clinics and support groups also recruited participants. Women were randomly assigned to 3 focus groups. 75-minute sessions were recorded, transcribed and coded thematically using interpretative phenomenologic analysis and single counting methods. We categorized interventions by benefits, limitations, target populations and implementation questions. Results 29 women with lupus participated in 3 focus groups, (n=9, 9, 11). 80% were African American and 83% were from medically underserved zip codes. Themes included the desire for lupus education, isolation at the time of diagnosis, emotional and physical barriers to care, and the need for assistance navigating the healthcare system. 20 of 29 participants (69%) favored a peer support intervention; 17 (59%) also supported a lupus health passport. Newly diagnosed women were optimal intervention targets. Improvements in quality of life and mental health were proposed outcome measures. Conclusion Women with lupus from medically underserved areas have unique needs best addressed with an intervention designed through collaboration between community members and researchers. PMID:23087258

49 CFR 1560.105 - Denial of transport or sterile area access; designation for enhanced screening.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Denial of transport or sterile area access... Matching § 1560.105 Denial of transport or sterile area access; designation for enhanced screening. (a...-traveling individuals, including denial of transport or sterile area access or designation for enhanced...

Policy for Establishing Separate Air Quality Designations for Areas of Indian Country Memorandum

EPA Pesticide Factsheets

This 2011 memorandum provides EPA's policy regarding designating areas of Indian country separately from adjacent areas for the National Ambient Air Quality Standards (NAAQS), when requested by the relevant tribe for a particular area of Indian country.

Targeting cancer with kinase inhibitors

PubMed Central

Gross, Stefan; Rahal, Rami; Stransky, Nicolas; Lengauer, Christoph; Hoeflich, Klaus P.

2015-01-01

Kinase inhibitors have played an increasingly prominent role in the treatment of cancer and other diseases. Currently, more than 25 oncology drugs that target kinases have been approved, and numerous additional therapeutics are in various stages of clinical evaluation. In this Review, we provide an in-depth analysis of activation mechanisms for kinases in cancer, highlight recent successes in drug discovery, and demonstrate the clinical impact of selective kinase inhibitors. We also describe the substantial progress that has been made in designing next-generation inhibitors to circumvent on-target resistance mechanisms, as well as ongoing strategies for combining kinase inhibitors in the clinic. Last, there are numerous prospects for the discovery of novel kinase targets, and we explore cancer immunotherapy as a new and promising research area for studying kinase biology. PMID:25932675

Bacteriological quality evaluation of seawater and oysters from the Jaranman-Saryangdo area, a designated shellfish growing area in Korea: Impact of inland pollution sources.

PubMed

Mok, Jong Soo; Lee, Ka Jeong; Kim, Poong Ho; Lee, Tae Seek; Lee, Hee Jung; Jung, Yeoun Joong; Kim, Ji Hoe

2016-07-15

From 2011 to 2013, we conducted a full sanitary survey of pollution sources in proximity to a designated shellfish growing area in Korea, and their impact on the sea area therein. From this area, 836 seawater samples and 93 oyster samples were examined to evaluate their bacteriological quality. There were 483 potential pollution sources in the drainage area of the Jaranman-Saryangdo area, including 38 sources discharging water. It demonstrates that while many pollution sources have been identified, no significant impact occurred within the designated shellfish growing area. Variations in fecal coliform (FC) levels in seawater were closely related to rainfall. The FC levels of seawater and oysters from the designated area met the regulation limits set by various countries. Our study indicates that the oysters produced in this area are apparently safe for raw consumption based on their bacterial quality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rational design of micro-RNA-like bifunctional siRNAs targeting HIV and the HIV coreceptor CCR5.

PubMed

Ehsani, Ali; Saetrom, Pål; Zhang, Jane; Alluin, Jessica; Li, Haitang; Snøve, Ola; Aagaard, Lars; Rossi, John J

2010-04-01

Small-interfering RNAs (siRNAs) and micro-RNAs (miRNAs) are distinguished by their modes of action. SiRNAs serve as guides for sequence-specific cleavage of complementary mRNAs and the targets can be in coding or noncoding regions of the target transcripts. MiRNAs inhibit translation via partially complementary base-pairing to 3' untranslated regions (UTRs) and are generally ineffective when targeting coding regions of a transcript. In this study, we deliberately designed siRNAs that simultaneously direct cleavage and translational suppression of HIV RNAs, or cleavage of the mRNA encoding the HIV coreceptor CCR5 and suppression of translation of HIV. These bifunctional siRNAs trigger inhibition of HIV infection and replication in cell culture. The design principles have wide applications throughout the genome, as about 90% of genes harbor sites that make the design of bifunctional siRNAs possible.

Design of a multisensor data fusion system for target detection

NASA Astrophysics Data System (ADS)

Thomopoulos, Stelios C.; Okello, Nickens N.; Kadar, Ivan; Lovas, Louis A.

1993-09-01

The objective of this paper is to discuss the issues that are involved in the design of a multisensor fusion system and provide a systematic analysis and synthesis methodology for the design of the fusion system. The system under consideration consists of multifrequency (similar) radar sensors. However, the fusion design must be flexible to accommodate additional dissimilar sensors such as IR, EO, ESM, and Ladar. The motivation for the system design is the proof of the fusion concept for enhancing the detectability of small targets in clutter. In the context of down-selecting the proper configuration for multisensor (similar and dissimilar, and centralized vs. distributed) data fusion, the issues of data modeling, fusion approaches, and fusion architectures need to be addressed for the particular application being considered. Although the study of different approaches may proceed in parallel, the interplay among them is crucial in selecting a fusion configuration for a given application. The natural sequence for addressing the three different issues is to begin from the data modeling, in order to determine the information content of the data. This information will dictate the appropriate fusion approach. This, in turn, will lead to a global fusion architecture. Both distributed and centralized fusion architectures are used to illustrate the design issues along with Monte-Carlo simulation performance comparison of a single sensor versus a multisensor centrally fused system.

Optical design of the National Ignition Facility main laser and switchyard/target area beam transport systems

NASA Astrophysics Data System (ADS)

Miller, John L.; English, R. Edward, Jr.; Korniski, Ronald J.; Rodgers, J. Michael

1999-07-01

The optical design of the main laser and transport mirror sections of the National Ignition Facility are described. For the main laser the configuration, layout constraints, multiple beam arrangement, pinhole layout and beam paths, clear aperture budget, ray trace models, alignment constraints, lens designs, wavefront performance, and pupil aberrations are discussed. For the transport mirror system the layout, alignment controls and clear aperture budget are described.

MRPrimerW: a tool for rapid design of valid high-quality primers for multiple target qPCR experiments.

PubMed

Kim, Hyerin; Kang, NaNa; An, KyuHyeon; Koo, JaeHyung; Kim, Min-Soo

2016-07-08

Design of high-quality primers for multiple target sequences is essential for qPCR experiments, but is challenging due to the need to consider both homology tests on off-target sequences and the same stringent filtering constraints on the primers. Existing web servers for primer design have major drawbacks, including requiring the use of BLAST-like tools for homology tests, lack of support for ranking of primers, TaqMan probes and simultaneous design of primers against multiple targets. Due to the large-scale computational overhead, the few web servers supporting homology tests use heuristic approaches or perform homology tests within a limited scope. Here, we describe the MRPrimerW, which performs complete homology testing, supports batch design of primers for multi-target qPCR experiments, supports design of TaqMan probes and ranks the resulting primers to return the top-1 best primers to the user. To ensure high accuracy, we adopted the core algorithm of a previously reported MapReduce-based method, MRPrimer, but completely redesigned it to allow users to receive query results quickly in a web interface, without requiring a MapReduce cluster or a long computation. MRPrimerW provides primer design services and a complete set of 341 963 135 in silico validated primers covering 99% of human and mouse genes. Free access: http://MRPrimerW.com. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future.

PubMed

Hol, Wim G J

2015-05-01

Parasitic protozoa cause a range of diseases which threaten billions of human beings. They are responsible for tremendous mortality and morbidity in the least-developed areas of the world. Presented here is an overview of the evolution over the last three to four decades of structure-guided design of inhibitors, leads and drug candidates aiming at targets from parasitic protozoa. Target selection is a crucial and multi-faceted aspect of structure-guided drug design. The major impact of advances in molecular biology, genome sequencing and high-throughput screening is touched upon. The most advanced crystallographic techniques, including XFEL, have already been applied to structure determinations of drug targets from parasitic protozoa. Even cryo-electron microscopy is contributing to our understanding of the mode of binding of inhibitors to parasite ribosomes. A number of projects have been selected to illustrate how structural information has assisted in arriving at promising compounds that are currently being evaluated by pharmacological, pharmacodynamic and safety tests to assess their suitability as pharmaceutical agents. Structure-guided approaches are also applied to incorporate properties into compounds such that they are less likely to become the victim of resistance mechanisms. A great increase in the number of novel antiparasitic compounds will be needed in the future. These should then be combined into various multi-compound therapeutics to circumvent the diverse resistance mechanisms that render single-compound, or even multi-compound, drugs ineffective. The future should also see (i) an increase in the number of projects with a tight integration of structural biology, medicinal chemistry, parasitology and pharmaceutical sciences; (ii) the education of more `medicinal structural biologists' who are familiar with the properties that compounds need to have for a high probability of success in the later steps of the drug-development process; and (iii) the

Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future

PubMed Central

Hol, Wim G. J.

2015-01-01

Parasitic protozoa cause a range of diseases which threaten billions of human beings. They are responsible for tremendous mortality and morbidity in the least-developed areas of the world. Presented here is an overview of the evolution over the last three to four decades of structure-guided design of inhibitors, leads and drug candidates aiming at targets from parasitic protozoa. Target selection is a crucial and multi-faceted aspect of structure-guided drug design. The major impact of advances in molecular biology, genome sequencing and high-throughput screening is touched upon. The most advanced crystallographic techniques, including XFEL, have already been applied to structure determinations of drug targets from parasitic protozoa. Even cryo-electron microscopy is contributing to our understanding of the mode of binding of inhibitors to parasite ribosomes. A number of projects have been selected to illustrate how structural information has assisted in arriving at promising compounds that are currently being evaluated by pharmacological, pharmacodynamic and safety tests to assess their suitability as pharmaceutical agents. Structure-guided approaches are also applied to incorporate properties into compounds such that they are less likely to become the victim of resistance mechanisms. A great increase in the number of novel antiparasitic compounds will be needed in the future. These should then be combined into various multi-compound therapeutics to circumvent the diverse resistance mechanisms that render single-compound, or even multi-compound, drugs ineffective. The future should also see (i) an increase in the number of projects with a tight integration of structural biology, medicinal chemistry, parasitology and pharmaceutical sciences; (ii) the education of more ‘medicinal structural biologists’ who are familiar with the properties that compounds need to have for a high probability of success in the later steps of the drug-development process; and (iii

Design study of a raster scanning system for moving target irradiation in heavy-ion radiotherapy.

PubMed

Furukawa, Takuji; Inaniwa, Taku; Sato, Shinji; Tomitani, Takehiro; Minohara, Shinichi; Noda, Koji; Kanai, Tatsuaki

2007-03-01

A project to construct a new treatment facility as an extension of the existing heavy-ion medical accelerator in chiba (HIMAC) facility has been initiated for further development of carbon-ion therapy. The greatest challenge of this project is to realize treatment of a moving target by scanning irradiation. For this purpose, we decided to combine the rescanning technique and the gated irradiation method. To determine how to avoid hot and/or cold spots by the relatively large number of rescannings within an acceptable irradiation time, we have studied the scanning strategy, scanning magnets and their control, and beam intensity dynamic control. We have designed a raster scanning system and carried out a simulation of irradiating moving targets. The result shows the possibility of practical realization of moving target irradiation with pencil beam scanning. We describe the present status of our design study of the raster scanning system for the HIMAC new treatment facility.

Lifting wavelet method of target detection

NASA Astrophysics Data System (ADS)

Han, Jun; Zhang, Chi; Jiang, Xu; Wang, Fang; Zhang, Jin

2009-11-01

Image target recognition plays a very important role in the areas of scientific exploration, aeronautics and space-to-ground observation, photography and topographic mapping. Complex environment of the image noise, fuzzy, all kinds of interference has always been to affect the stability of recognition algorithm. In this paper, the existence of target detection in real-time, accuracy problems, as well as anti-interference ability, using lifting wavelet image target detection methods. First of all, the use of histogram equalization, the goal difference method to obtain the region, on the basis of adaptive threshold and mathematical morphology operations to deal with the elimination of the background error. Secondly, the use of multi-channel wavelet filter wavelet transform of the original image de-noising and enhancement, to overcome the general algorithm of the noise caused by the sensitive issue of reducing the rate of miscarriage of justice will be the multi-resolution characteristics of wavelet and promotion of the framework can be designed directly in the benefits of space-time region used in target detection, feature extraction of targets. The experimental results show that the design of lifting wavelet has solved the movement of the target due to the complexity of the context of the difficulties caused by testing, which can effectively suppress noise, and improve the efficiency and speed of detection.

30 CFR 905.764 - Process for designating areas unsuitable for surface coal mining operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface coal mining operations. 905.764 Section 905.764 Mineral Resources OFFICE OF SURFACE MINING... WITHIN EACH STATE CALIFORNIA § 905.764 Process for designating areas unsuitable for surface coal mining operations. Part 764 of this chapter, State Processes for Designating Areas Unsuitable for Surface Coal...

30 CFR 910.764 - Process for designating areas unsuitable for surface coal mining operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface coal mining operations. 910.764 Section 910.764 Mineral Resources OFFICE OF SURFACE MINING... WITHIN EACH STATE GEORGIA § 910.764 Process for designating areas unsuitable for surface coal mining operations. Part 764 of this chapter, State Processes for Designating Areas Unsuitable for Surface Coal...

30 CFR 912.764 - Process for designating areas unsuitable for surface coal mining operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface coal mining operations. 912.764 Section 912.764 Mineral Resources OFFICE OF SURFACE MINING... WITHIN EACH STATE IDAHO § 912.764 Process for designating areas unsuitable for surface coal mining operations. Part 764 of this chapter, State Processes for Designating Areas Unsuitable for Surface Coal...

30 CFR 903.764 - Process for designating areas unsuitable for surface coal mining operations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface coal mining operations. 903.764 Section 903.764 Mineral Resources OFFICE OF SURFACE MINING... WITHIN EACH STATE ARIZONA § 903.764 Process for designating areas unsuitable for surface coal mining operations. Part 764 of this chapter, State Processes for Designating Areas Unsuitable for Surface Coal...

Stereotactically Standard Areas: Applied Mathematics in the Service of Brain Targeting in Deep Brain Stimulation.

PubMed

Mavridis, Ioannis N

2017-12-11

The concept of stereotactically standard areas (SSAs) within human brain nuclei belongs to the knowledge of the modern field of stereotactic brain microanatomy. These are areas resisting the individual variability of the nuclear location in stereotactic space. This paper summarizes the current knowledge regarding SSAs. A mathematical formula of SSAs was recently invented, allowing for their robust, reproducible, and accurate application to laboratory studies and clinical practice. Thus, SSAs open new doors for the application of stereotactic microanatomy to highly accurate brain targeting, which is mainly useful for minimally invasive neurosurgical procedures, such as deep brain stimulation.

Designating wilderness areas: A framework for examining lessons from the States

Treesearch

Gary Bryner

2007-01-01

Although wilderness designations require congressional action, state-level political decisions usually determine whether and when Congress formally acts to designate new wilderness areas. In some cases, such as in Alaska, the issue of wilderness protection becomes nationalized and a wide range of interests beyond the borders of the state shape the eventual policy. But...

SRP engineering and design history, Vol III, 200 F and H Areas

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

Banick, C.J.

2000-04-17

This volume combines the record of events relating to the development of design for both the 200-F and H Areas. Chronologically, the definition of plant facilities was first established for the 200-F Area. The second area, 200-H, was projected initially to be a supplementary plutonium separations facility. This history explains the differences in character and capacity of the manufacturing facilities in both areas as production requirements and experience with separations processes advanced.

Package design and nutritional profile of foods targeted at children in supermarkets in Montevideo, Uruguay.

PubMed

Giménez, Ana; Saldamando, Luis de; Curutchet, María Rosa; Ares, Gastón

2017-06-12

Marketing of unhealthy products has been identified as one of the main characteristics of the food environment that negatively affects children's eating patterns. Restrictions on advertising of unhealthy foods to children have already been imposed in different countries. However, marketing strategies are not limited to broadcast and digital advertising, but also include package design. In this context, the current study aimed to describe the food products targeted at children and sold in supermarkets in Montevideo, Uruguay, in terms of package design and nutrient profile. Two supermarkets in Montevideo were selected for data collection. In each supermarket, all products targeted at children were identified. Products were analyzed in terms of package design and nutritional profile, considering the Pan American Health Organization Nutrient Profile Model. A total of 180 unique products were identified, which included a wide range of product categories. The great majority of the products corresponded to ultra-processed products with excessive amounts of sodium, free sugars, total fat, saturated fat, and/or trans fat, which are not recommended for frequent consumption. Several marketing strategies were identified in the design of packages to attract children's attention and drive their preferences. The most common strategies were the inclusion of cartoon characters, bright colors, childish lettering, and a wide range of claims related to health and nutrition, as well as the products' sensory and hedonic characteristics. The study's findings provide additional evidence on the need to regulate packaging of products targeted at children.

Designing for Wide-Area Situation Awareness in Future Power Grid Operations

NASA Astrophysics Data System (ADS)

Tran, Fiona F.

Power grid operation uncertainty and complexity continue to increase with the rise of electricity market deregulation, renewable generation, and interconnectedness between multiple jurisdictions. Human operators need appropriate wide-area visualizations to help them monitor system status to ensure reliable operation of the interconnected power grid. We observed transmission operations at a control centre, conducted critical incident interviews, and led focus group sessions with operators. The results informed a Work Domain Analysis of power grid operations, which in turn informed an Ecological Interface Design concept for wide-area monitoring. I validated design concepts through tabletop discussions and a usability evaluation with operators, earning a mean System Usability Scale score of 77 out of 90. The design concepts aim to support an operator's complete and accurate understanding of the power grid state, which operators increasingly require due to the critical nature of power grid infrastructure and growing sources of system uncertainty.

A multiple-alignment based primer design algorithm for genetically highly variable DNA targets

PubMed Central

2013-01-01

Background Primer design for highly variable DNA sequences is difficult, and experimental success requires attention to many interacting constraints. The advent of next-generation sequencing methods allows the investigation of rare variants otherwise hidden deep in large populations, but requires attention to population diversity and primer localization in relatively conserved regions, in addition to recognized constraints typically considered in primer design. Results Design constraints include degenerate sites to maximize population coverage, matching of melting temperatures, optimizing de novo sequence length, finding optimal bio-barcodes to allow efficient downstream analyses, and minimizing risk of dimerization. To facilitate primer design addressing these and other constraints, we created a novel computer program (PrimerDesign) that automates this complex procedure. We show its powers and limitations and give examples of successful designs for the analysis of HIV-1 populations. Conclusions PrimerDesign is useful for researchers who want to design DNA primers and probes for analyzing highly variable DNA populations. It can be used to design primers for PCR, RT-PCR, Sanger sequencing, next-generation sequencing, and other experimental protocols targeting highly variable DNA samples. PMID:23965160

Design and optimal control of on-orbit servicing trajectory for target vehicle in non-coplanar elliptical orbit

NASA Astrophysics Data System (ADS)

Zhou, Wenyong; Yuan, Jianping; Luo, Jianjun

2005-11-01

Autonomous on-orbit servicing provides flexibility to space systems and has great value both in civil and in military. When a satellite performs on-orbit servicing tasks, flying around is the basic type of motion. This paper is concerned with the design and control problems of a chaser satellite flying around a target spacecraft in non-coplanar elliptical orbit for a long time. At first, a mathematical model used to design a long-term flying around trajectory is presented, which is applicable to the situation that the target spacecraft flies in an elliptical orbit. The conditions of the target at the centre of the flying around path are deduced. Considering the safety and task requirements, a long-term flying around trajectory is designed. Taking into account perturbations and navigation errors which can cause the trajectory unstable and mission impossible, a two-impulse control method is put forward. Genetic algorithm is used to minimize the cost function which considers fuel consumption and bias simultaneously. Some simulation works are carried out and the results indicate the flying around mathematical model and the trajectory control method can be used in the design and control of a long-term flying around trajectory.

Design Strategies for Aptamer-Based Biosensors

PubMed Central

Han, Kun; Liang, Zhiqiang; Zhou, Nandi

2010-01-01

Aptamers have been widely used as recognition elements for biosensor construction, especially in the detection of proteins or small molecule targets, and regarded as promising alternatives for antibodies in bioassay areas. In this review, we present an overview of reported design strategies for the fabrication of biosensors and classify them into four basic modes: target-induced structure switching mode, sandwich or sandwich-like mode, target-induced dissociation/displacement mode and competitive replacement mode. In view of the unprecedented advantages brought about by aptamers and smart design strategies, aptamer-based biosensors are expected to be one of the most promising devices in bioassay related applications. PMID:22399891

Design and engineering of a target for x-ray Thomson scattering measurements on matter at extreme densities and gigabar pressures

DOE PAGES

Boehm, K. -J.; Hash, N.; Barker, D.; ...

2016-06-24

Reconciling the experimental and system requirements during the development of a new target system is one of the most challenging tasks in the design and engineering of targets used in the National Ignition Facility. Targets for the GigaBar 3 campaign were meant to allow the detection of extremely weak Thomson scattering from matter at extreme densities in the face of very bright backlighter and laser entry hole plasma emissions. The problem was to shield the detector sufficiently while maintaining beamline and view clearances, and observing target mass restrictions. A new construction process, based on a rapid prototype frame structure, wasmore » used to develop this target. As a result, details of the design process for these targets are described, and lessons from this development for production and target assembly teams are discussed.« less

Lunar Orbit Insertion Targeting and Associated Outbound Mission Design for Lunar Sortie Missions

NASA Technical Reports Server (NTRS)

Condon, Gerald L.

2007-01-01

This report details the Lunar Orbit Insertion (LOI) arrival targeting and associated mission design philosophy for Lunar sortie missions with up to a 7-day surface stay and with global Lunar landing site access. It also documents the assumptions, methodology, and requirements validated by TDS-04-013, Integrated Transit Nominal and Abort Characterization and Sensitivity Study. This report examines the generation of the Lunar arrival parking orbit inclination and Longitude of the Ascending Node (LAN) targets supporting surface missions with global Lunar landing site access. These targets support the Constellation Program requirement for anytime abort (early return) by providing for a minimized worst-case wedge angle [and an associated minimum plane change delta-velocity (V) cost] between the Crew Exploration Vehicle (CEV) and the Lunar Surface Access Module (LSAM) for an LSAM launch anytime during the Lunar surface stay.

Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10.

PubMed

Yang, Wang-Yong; Gao, Rui; Southern, Mark; Sarkar, Partha S; Disney, Matthew D

2016-06-01

RNA is an important target for chemical probes of function and lead therapeutics; however, it is difficult to target with small molecules. One approach to tackle this problem is to identify compounds that target RNA structures and utilize them to multivalently target RNA. Here we show that small molecules can be identified to selectively bind RNA base pairs by probing a library of RNA-focused small molecules. A small molecule that selectively binds AU base pairs informed design of a dimeric compound (2AU-2) that targets the pathogenic RNA, expanded r(AUUCU) repeats, that causes spinocerebellar ataxia type 10 (SCA10) in patient-derived cells. Indeed, 2AU-2 (50 nM) ameliorates various aspects of SCA10 pathology including improvement of mitochondrial dysfunction, reduced activation of caspase 3, and reduction of nuclear foci. These studies provide a first-in-class chemical probe to study SCA10 RNA toxicity and potentially define broadly applicable compounds targeting RNA AU base pairs in cells.

Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

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

Gardner, Shea N.; Jaing, Crystal J.; Elsheikh, Maher M.

Background . Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results . A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Eachmore » group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions . This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.« less

Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

DOE PAGES

Gardner, Shea N.; Jaing, Crystal J.; Elsheikh, Maher M.; ...

2014-01-01

Background . Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results . A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Eachmore » group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions . This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.« less

Off-design performance loss model for radial turbines with pivoting, variable-area stators

NASA Technical Reports Server (NTRS)

Meitner, P. L.; Glassman, A. J.

1980-01-01

An off-design performance loss model was developed for variable stator (pivoted vane), radial turbines through analytical modeling and experimental data analysis. Stator loss is determined by a viscous loss model; stator vane end-clearance leakage effects are determined by a clearance flow model. Rotor loss coefficient were obtained by analyzing the experimental data from a turbine rotor previously tested with six stators having throat areas from 20 to 144 percent of design area and were correlated with stator-to-rotor throat area ratio. An incidence loss model was selected to obtain best agreement with experimental results. Predicted turbine performance is compared with experimental results for the design rotor as well as with results for extended and cutback versions of the rotor. Sample calculations were made to show the effects of stator vane end-clearance leakage.

Target selection and mass estimation for manned NEO exploration using a baseline mission design

NASA Astrophysics Data System (ADS)

Boden, Ralf C.; Hein, Andreas M.; Kawaguchi, Junichiro

2015-06-01

In recent years Near-Earth Objects (NEOs) have received an increased amount of interest as a target for human exploration. NEOs offer scientifically interesting targets, and at the same time function as a stepping stone for achieving future Mars missions. The aim of this research is to identify promising targets from the large number of known NEOs that qualify for a manned sample-return mission with a maximum duration of one year. By developing a baseline mission design and a mass estimation model, mission opportunities are evaluated based on on-orbit mass requirements, safety considerations, and the properties of the potential targets. A selection of promising NEOs is presented and the effects of mission requirements and restrictions are discussed. Regarding safety aspects, the use of free-return trajectories provides the lowest on-orbit mass, when compared to an alternative design that uses system redundancies to ensure return of the spacecraft to Earth. It is discovered that, although a number of targets are accessible within the analysed time frame, no NEO offers both easy access and high incentive for its exploration. Under the discussed aspects a first human exploration mission going beyond the vicinity of Earth will require a trade off between targets that provide easy access and those that are of scientific interest. This lack of optimal mission opportunities can be seen in the small number of only 4 NEOs that meet all requirements for a sample-return mission and remain below an on-orbit mass of 500 metric Tons (mT). All of them require a mass between 315 and 492 mT. Even less ideal, smaller asteroids that are better accessible require an on-orbit mass that exceeds the launch capability of future heavy lift vehicles (HLV) such as SLS by at least 30 mT. These mass requirements show that additional efforts are necessary to increase the number of available targets and reduce on-orbit mass requirements through advanced mission architectures. The need for on

Targeted repression of AXIN2 and MYC gene expression using designer TALEs

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

Rennoll, Sherri A.; Scott, Samantha A.; Yochum, Gregory S., E-mail: gsy3@psu.edu

Highlights: • We designed TALE–SID fusion proteins to target AXIN2 and MYC. • TALE–SIDs bound the chromosomal AXIN2 and MYC genes and repressed their expression. • TALE–SIDs repress β-catenin{sup S45F}-dependent AXIN2 and MYC transcription. - Abstract: Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered to regulate gene expression in mammalian cells. Whether dTALEs can block gene transcription downstream of signal transduction cascades, however, has yet to be fully explored. Here we tested whether dTALEs can be used to target genes whose expression is controlled by Wnt/β-catenin signaling. TALE DNA binding domains were engineered to recognize sequences adjacentmore » to Wnt responsive enhancer elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A interaction domain (SID) to generate TALE–SID chimeric repressors. The TALE–SIDs repressed luciferase reporter activity, bound their genomic target sites, and repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293 cell line to determine whether the TALE–SIDs could function downstream of oncogenic Wnt/β-catenin signaling. Treating these cells with doxycycline and tamoxifen stimulates nuclear accumulation of a stabilized form of β-catenin found in a subset of colorectal cancers. The TALE–SIDs repressed AXIN2 and MYC expression in these cells, which suggests that dTALEs could offer an effective therapeutic strategy for the treatment of colorectal cancer.« less

36 CFR 212.55 - Criteria for designation of roads, trails, and areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., conflicts among uses of National Forest System lands, the need for maintenance and administration of roads... roads, trails, and areas. 212.55 Section 212.55 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE TRAVEL MANAGEMENT Designation of Roads, Trails, and Areas for Motor Vehicle Use...

45 CFR 670.29 - Designation of Antarctic Specially Protected Areas, Specially Managed Areas and Historic Sites...

Code of Federal Regulations, 2011 CFR

2011-10-01

... for special management and are hereby designated as Antarctic Specially Managed Areas (ASMA). Detailed..., Arlington, Virginia 22230. ASMA 1Admiralty Bay, King George Island, South Shetland Islands ASMA 2McMurdo Dry Valleys, Southern Victoria Land ASMA 3Cape Denison, Commonwealth Bay, George V Land ASMA 4Deception Island...

45 CFR 670.29 - Designation of Antarctic Specially Protected Areas, Specially Managed Areas and Historic Sites...

Code of Federal Regulations, 2010 CFR

2010-10-01

... for special management and are hereby designated as Antarctic Specially Managed Areas (ASMA). Detailed..., Arlington, Virginia 22230. ASMA 1Admiralty Bay, King George Island, South Shetland Islands ASMA 2McMurdo Dry Valleys, Southern Victoria Land ASMA 3Cape Denison, Commonwealth Bay, George V Land ASMA 4Deception Island...

Closing the door on flaviviruses: entry as a target for antiviral drug design.

PubMed

Perera, Rushika; Khaliq, Mansoora; Kuhn, Richard J

2008-10-01

With the emergence and rapid spread of West Nile virus in the United States since 1999, and the 50-100 million infections per year caused by dengue virus globally, the threat of flaviviruses as re-emerging human pathogens has become a reality. To support the efforts that are currently being pursued to develop effective vaccines against these viruses, researchers are also actively pursuing the development of small molecule compounds that target various aspects of the virus life cycle. Recent advances in the structural characterization of the flaviviruses have provided a strong foundation towards these efforts. These studies have provided the pseudo-atomic structures of virions from several members of the genus as well as atomic resolution structures of several viral proteins. Most importantly, these studies have highlighted specific structural rearrangements that occur within the virion that are necessary for the virus to complete its life cycle. These rearrangements occur when the virus must transition from immature, to mature, to fusion-active states and rely heavily on the conformational flexibility of the envelope (E) protein that forms the outer glycoprotein shell of the virus. Analysis of these conformational changes can suggest promising targets for structure-based antiviral design. For instance, by targeting the flexibility of the E protein, it might be possible to inhibit required rearrangements of this protein and trap the virus in a specific state. This would interfere with a productive flaviviral infection. This review presents a structural perspective of the flavivirus life cycle and focuses on the role of the E protein as an opportune target for structure-based antiviral drug design.

Thermal hydraulic design and decay heat removal of a solid target for a spallation neutron source

NASA Astrophysics Data System (ADS)

Takenaka, N.; Nio, D.; Kiyanagi, Y.; Mishima, K.; Kawai, M.; Furusaka, M.

2005-08-01

Thermal hydraulic design and thermal stress calculations were conducted for a water-cooled solid target irradiated by a MW-class proton beam for a spallation neutron source. Plate type and rod bundle type targets were examined. The thickness of the plate and the diameter of the rod were determined based on the maximum and the wall surface temperature. The thermal stress distributions were calculated by a finite element method (FEM). The neutronics performance of the target is roughly proportional to its average density. The averaged densities of the designed targets were calculated for tungsten plates, tantalum clad tungsten plates, tungsten rods sheathed by tantalum and Zircaloy and they were compared with mercury density. It was shown that the averaged density was highest for the tungsten plates and was high for the tantalum cladding tungsten plates, the tungsten rods sheathed by tantalum and Zircaloy in order. They were higher than or equal to that of mercury for the 1 2 MW proton beams. Tungsten target without the cladding or the sheath is not practical due to corrosion by water under irradiation condition. Therefore, the tantalum cladding tungsten plate already made successfully by HIP and the sheathed tungsten rod are the candidate of high performance solid targets. The decay heat of each target was calculated. It was low enough low compared to that of ISIS for the target without tantalum but was about four times as high as that of ISIS when the thickness of the tantalum cladding was 0.5 mm. Heat removal methods of the decay heat with tantalum were examined. It was shown that a special cooling system was required for the target exchange when tantalum was used for the target. It was concluded that the tungsten rod target sheathed with stainless steel or Zircaloy was the most reliable from the safety considerations and had similar neutronics performance to that of mercury.

The Design of New HIV-IN Tethered Bifunctional Inhibitors using Multiple Microdomain Targeted Docking.

PubMed

Ciubotaru, Mihai; Musat, Mihaela Georgiana; Surleac, Marius; Ionita, Elena; Petrescu, Andrei Jose; Abele, Edgars; Abele, Ramona

2018-04-05

Currently used antiretroviral HIV therapy drugs exclusively target critical groups in the enzymes essential for the viral life cycle. Increased mutagenesis of their genes, changes these viral enzymes which once mutated can evade therapeutic targeting, effects which confer drug resistance. To circumvent this, our review addresses a strategy to design and derive HIV-Integrase (HIV-IN) inhibitors which simultaneously target two IN functional domains, rendering it inactive even if the enzyme accumulates many mutations. First we review the enzymatic role of IN to insert the copied viral DNA into a chromosome of the host T lymphocyte, highlighting its main functional and structural features to be subjected to inhibitory action. From a functional and structural perspective we present all classes of HIV-IN inhibitors with their most representative candidates. For each chosen compound we also explain its mechanism of IN inhibition. We use the recently resolved cryo EM IN tetramer intasome DNA complex [1] onto which we dock various reference IN inhibitory chemical scaffolds such as to target adjacent functional IN domains. Pairing compounds with complementary activity, which dock in the vicinity of a IN structural microdomain, we design bifunctional new drugs which may not only be more resilient to IN mutations but also may be more potent inhibitors than their original counterparts. In the end of our review we propose synthesis pathways to link such paired compounds with enhanced synergistic IN inhibitory effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Poughkeepsie Survey. A Report on Employment and Unemployment in a "Target Area" under the Model Cities Program.

ERIC Educational Resources Information Center

Kuper, Irvin, Ed.

Located in the heart of the Mid-Hudson area, Poughkeepsie is in one of the fastest growing regions of New York State, but the city itself has grown very little in the last five decades. The local Model Cities agency has created a target area which includes most of the older part of the city. In July 1967, the population was 35,970. A total of…

Photoaffinity labeling in target- and binding-site identification

PubMed Central

Smith, Ewan; Collins, Ian

2015-01-01

Photoaffinity labeling (PAL) using a chemical probe to covalently bind its target in response to activation by light has become a frequently used tool in drug discovery for identifying new drug targets and molecular interactions, and for probing the location and structure of binding sites. Methods to identify the specific target proteins of hit molecules from phenotypic screens are highly valuable in early drug discovery. In this review, we summarize the principles of PAL including probe design and experimental techniques for in vitro and live cell investigations. We emphasize the need to optimize and validate probes and highlight examples of the successful application of PAL across multiple disease areas. PMID:25686004

Open Targets: a platform for therapeutic target identification and validation

PubMed Central

Koscielny, Gautier; An, Peter; Carvalho-Silva, Denise; Cham, Jennifer A.; Fumis, Luca; Gasparyan, Rippa; Hasan, Samiul; Karamanis, Nikiforos; Maguire, Michael; Papa, Eliseo; Pierleoni, Andrea; Pignatelli, Miguel; Platt, Theo; Rowland, Francis; Wankar, Priyanka; Bento, A. Patrícia; Burdett, Tony; Fabregat, Antonio; Forbes, Simon; Gaulton, Anna; Gonzalez, Cristina Yenyxe; Hermjakob, Henning; Hersey, Anne; Jupe, Steven; Kafkas, Şenay; Keays, Maria; Leroy, Catherine; Lopez, Francisco-Javier; Magarinos, Maria Paula; Malone, James; McEntyre, Johanna; Munoz-Pomer Fuentes, Alfonso; O'Donovan, Claire; Papatheodorou, Irene; Parkinson, Helen; Palka, Barbara; Paschall, Justin; Petryszak, Robert; Pratanwanich, Naruemon; Sarntivijal, Sirarat; Saunders, Gary; Sidiropoulos, Konstantinos; Smith, Thomas; Sondka, Zbyslaw; Stegle, Oliver; Tang, Y. Amy; Turner, Edward; Vaughan, Brendan; Vrousgou, Olga; Watkins, Xavier; Martin, Maria-Jesus; Sanseau, Philippe; Vamathevan, Jessica; Birney, Ewan; Barrett, Jeffrey; Dunham, Ian

2017-01-01

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org. PMID:27899665

An advanced wide area chemical sensor testbed

NASA Astrophysics Data System (ADS)

Seeley, Juliette A.; Kelly, Michael; Wack, Edward; Ryan-Howard, Danette; Weidler, Darryl; O'Brien, Peter; Colonero, Curtis; Lakness, John; Patel, Paras

2005-11-01

In order to meet current and emerging needs for remote passive standoff detection of chemical agent threats, MIT Lincoln Laboratory has developed a Wide Area Chemical Sensor (WACS) testbed. A design study helped define the initial concept, guided by current standoff sensor mission requirements. Several variants of this initial design have since been proposed to target other applications within the defense community. The design relies on several enabling technologies required for successful implementation. The primary spectral component is a Wedged Interferometric Spectrometer (WIS) capable of imaging in the LWIR with spectral resolutions as narrow as 4 cm-1. A novel scanning optic will enhance the ability of this sensor to scan over large areas of concern with a compact, rugged design. In this paper, we shall discuss our design, development, and calibration process for this system as well as recent testbed measurements that validate the sensor concept.

Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive.

PubMed

Childs-Disney, Jessica L; Hoskins, Jason; Rzuczek, Suzanne G; Thornton, Charles A; Disney, Matthew D

2012-05-18

RNA is an important drug target, but it is difficult to design or discover small molecules that modulate RNA function. In the present study, we report that rationally designed, modularly assembled small molecules that bind the RNA that causes myotonic dystrophy type 1 (DM1) are potently bioactive in cell culture models. DM1 is caused when an expansion of r(CUG) repeats, or r(CUG)(exp), is present in the 3' untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) mRNA. r(CUG)(exp) folds into a hairpin with regularly repeating 5'CUG/3'GUC motifs and sequesters muscleblind-like 1 protein (MBNL1). A variety of defects are associated with DM1, including (i) formation of nuclear foci, (ii) decreased translation of DMPK mRNA due to its nuclear retention, and (iii) pre-mRNA splicing defects due to inactivation of MBNL1, which controls the alternative splicing of various pre-mRNAs. Previously, modularly assembled ligands targeting r(CUG)(exp) were designed using information in an RNA motif-ligand database. These studies showed that a bis-benzimidazole (H) binds the 5'CUG/3'GUC motif in r(CUG)(exp.) Therefore, we designed multivalent ligands to bind simultaneously multiple copies of this motif in r(CUG)(exp). Herein, we report that the designed compounds improve DM1-associated defects including improvement of translational and pre-mRNA splicing defects and the disruption of nuclear foci. These studies may establish a foundation to exploit other RNA targets in genomic sequence.

Design and implementation of an inexpensive target scanner for the growth of thin films by the laser-ablation process

NASA Astrophysics Data System (ADS)

Rao, A. M.; Moodera, J. S.

1991-04-01

The design of a target scanner that is inexpensive and easy to construct is described. Our target scanner system does not require an expensive personal computer to raster the laser beam uniformily over the target material, unlike the computer driven target scanners that are currently being used in the thin-film industry. The main components of our target scanner comprise a bidirectional motor, a two-position switch, and a standard optical mirror mount.

Teacher Shortage Areas Nationwide Listing: 1990-91 thru 2005-06

ERIC Educational Resources Information Center

US Department of Education, 2006

2006-01-01

The nationwide Teacher Shortage Area (TSA) lists for the 2004-05 and 2005-06 school years have been completed and are listed by state in this document. A state that desires to propose teacher shortage areas for designation must submit the information required under the program regulations for the following programs: (1) Targeted teacher deferment…

43 CFR 420.21 - Procedure for designating areas for off-road vehicle use.

Code of Federal Regulations, 2010 CFR

2010-10-01

... affected Federal, State, and county agencies' opinions for opening or closing an area or trail in a manner... restrict areas and trails is necessary to attain the objectives of the regulations of this part. (a) Regional Directors shall designate and publicize those areas and trails which are open to off-road vehicle...

The Co-Metabolism within the Gut-Brain Metabolic Interaction: Potential Targets for Drug Treatment and Design.

PubMed

Obrenovich, Mark; Flückiger, Rudolf; Sykes, Lorraine; Donskey, Curtis

2016-01-01

We know that within the complex mammalian gut is any number of metabolic biomes. The gut has been sometimes called the "second brain" within the "gut-brain axis". A more informative term would be the gut-brain metabolic interactome, which is coined here to underscore the relationship between the digestive system and cognitive function or dysfunction as the case may be. Co-metabolism between the host and the intestinal microbiota is essential for life's processes. How diet, lifestyle, antibiotics and other factors shape the gut microbiome constitutes a rapidly growing area of research. Conversely, the gut microbiome also affects mammalian systems. Metabolites of the gut-brain axis are potential targets for treatment and drug design since the interaction or biochemical interplay results in net metabolite production or end-products with either positive or negative effects on human health. This review explores the gut-brain metabolic interactome, with particular emphasis on drug design and treatment strategies and how commensal bacteria or their disruption lead to dysbiosis and the effect this has on neurochemistry. Increasing data indicate that the intestinal microbiome can affect neurobiology, from mental and even behavioral health to memory, depression, mood, anxiety, obesity, cravings and even the creation and maintenance of the blood brain barrier.

Inhibitor designing, virtual screening, and docking studies for methyltransferase: A potential target against dengue virus

PubMed Central

Singh, Jagbir; Kumar, Mahesh; Mansuri, Rani; Sahoo, Ganesh Chandra; Deep, Aakash

2016-01-01

Aim: Aim of this work was to design and identify some S-adenosyl-L-homocysteine (SAH) analogs as inhibitors of S-adenosyl-L-methionine-dependent methyltransferase (MTase) protein using computational approaches. Introduction: According to the current scenario the dengue has been a global burden. The people are being killed by dengue virus in an abundant number. Despite of lot of research being going on dengue worldwide, there is no single drug which can kill its virus. This creates an urge for new drug target identification and designing. MTase has been reported as an effective target against dengue virus as it catalyzes an essential step in methylation and capping of viral RNA for viral replication. Materials and Methods: The crystal structure of MTase in complex with SAH was used for designing new analogs of SAH. SAH analogs designed were analyzed on the basis of docking, ADMET, and toxicity analysis done using Discovery Studio 3.5. Results: Seventeen analogs found noncarcinogenic, nonmutagenic, as well as good ADMET properties and good drug-like profile. Conclusion: These SAH analogs, inhibitors of MTase may act as drugs against dengue virus. Further synthesis and biological testing against dengue virus is under observation. PMID:27413346

The Roots of Alzheimer's Disease: Are High-Expanding Cortical Areas Preferentially Targeted?†.

PubMed

Fjell, Anders M; Amlien, Inge K; Sneve, Markus H; Grydeland, Håkon; Tamnes, Christian K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

2015-09-01

Alzheimer's disease (AD) is regarded a human-specific condition, and it has been suggested that brain regions highly expanded in humans compared with other primates are selectively targeted. We calculated shared and unique variance in the distribution of AD atrophy accounted for by cortical expansion between macaque and human, affiliation to the default mode network (DMN), ontogenetic development and normal aging. Cortical expansion was moderately related to atrophy, but a critical discrepancy was seen in the medial temporo-parietal episodic memory network. Identification of "hotspots" and "coldspots" of expansion across several primate species did not yield compelling evidence for the hypothesis that highly expanded regions are specifically targeted. Controlling for distribution of atrophy in aging substantially attenuated the expansion-AD relationship. A path model showed that all variables explained unique variance in AD atrophy but were generally mediated through aging. This supports a systems-vulnerability model, where critical networks are subject to various negative impacts, aging in particular, rather than being selectively targeted in AD. An alternative approach is suggested, focused on the interplay of the phylogenetically old and preserved medial temporal lobe areas with more highly expanded association cortices governed by different principles of plasticity and stability. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy.

PubMed

Raman, Marine C C; Rizkallah, Pierre J; Simmons, Ruth; Donnellan, Zoe; Dukes, Joseph; Bossi, Giovanna; Le Provost, Gabrielle S; Todorov, Penio; Baston, Emma; Hickman, Emma; Mahon, Tara; Hassan, Namir; Vuidepot, Annelise; Sami, Malkit; Cole, David K; Jakobsen, Bent K

2016-01-13

Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity T-cell receptors (TCRs) provide an ideal approach to target cancer cells, with emerging clinical data showing significant promise. Nevertheless, the risk of off target reactivity remains a key concern, as exemplified in a recent clinical report describing fatal cardiac toxicity, following administration of MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity with an unrelated epitope from the Titin protein presented on cardiac tissue. Here, we investigated the structural mechanism enabling TCR cross-recognition of MAGE-A3 and Titin, and applied the resulting data to rationally design mutants with improved antigen discrimination, providing a proof-of-concept strategy for altering the fine specificity of a TCR towards an intended target antigen. This study represents the first example of direct molecular mimicry leading to clinically relevant fatal toxicity, mediated by a modified enhanced affinity TCR designed for cancer immunotherapy. Furthermore, these data demonstrate that self-antigens that are expressed at high levels on healthy tissue should be treated with extreme caution when designing immuno-therapeutics.

Constraints in distortion-invariant target recognition system simulation

NASA Astrophysics Data System (ADS)

Iftekharuddin, Khan M.; Razzaque, Md A.

2000-11-01

Automatic target recognition (ATR) is a mature but active research area. In an earlier paper, we proposed a novel ATR approach for recognition of targets varying in fine details, rotation, and translation using a Learning Vector Quantization (LVQ) Neural Network (NN). The proposed approach performed segmentation of multiple objects and the identification of the objects using LVQNN. In this current paper, we extend the previous approach for recognition of targets varying in rotation, translation, scale, and combination of all three distortions. We obtain the analytical results of the system level design to show that the approach performs well with some constraints. The first constraint determines the size of the input images and input filters. The second constraint shows the limits on amount of rotation, translation, and scale of input objects. We present the simulation verification of the constraints using DARPA's Moving and Stationary Target Recognition (MSTAR) images with different depression and pose angles. The simulation results using MSTAR images verify the analytical constraints of the system level design.

Deep Extragalactic VIsible Legacy Survey (DEVILS): Motivation, Design and Target Catalogue

NASA Astrophysics Data System (ADS)

Davies, L. J. M.; Robotham, A. S. G.; Driver, S. P.; Lagos, C. P.; Cortese, L.; Mannering, E.; Foster, C.; Lidman, C.; Hashemizadeh, A.; Koushan, S.; O'Toole, S.; Baldry, I. K.; Bilicki, M.; Bland-Hawthorn, J.; Bremer, M. N.; Brown, M. J. I.; Bryant, J. J.; Catinella, B.; Croom, S. M.; Grootes, M. W.; Holwerda, B. W.; Jarvis, M. J.; Maddox, N.; Meyer, M.; Moffett, A. J.; Phillipps, S.; Taylor, E. N.; Windhorst, R. A.; Wolf, C.

2018-06-01

The Deep Extragalactic VIsible Legacy Survey (DEVILS) is a large spectroscopic campaign at the Anglo-Australian Telescope (AAT) aimed at bridging the near and distant Universe by producing the highest completeness survey of galaxies and groups at intermediate redshifts (0.3 < z < 1.0). Our sample consists of ˜60,000 galaxies to Y<21.2 mag, over ˜6 deg2 in three well-studied deep extragalactic fields (Cosmic Origins Survey field, COSMOS, Extended Chandra Deep Field South, ECDFS and the X-ray Multi-Mirror Mission Large-Scale Structure region, XMM-LSS - all Large Synoptic Survey Telescope deep-drill fields). This paper presents the broad experimental design of DEVILS. Our target sample has been selected from deep Visible and Infrared Survey Telescope for Astronomy (VISTA) Y-band imaging (VISTA Deep Extragalactic Observations, VIDEO and UltraVISTA), with photometry measured by PROFOUND. Photometric star/galaxy separation is done on the basis of NIR colours, and has been validated by visual inspection. To maximise our observing efficiency for faint targets we employ a redshift feedback strategy, which continually updates our target lists, feeding back the results from the previous night's observations. We also present an overview of the initial spectroscopic observations undertaken in late 2017 and early 2018.

45 CFR 1321.29 - Designation of planning and service areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Designation of planning and service areas. 1321.29 Section 1321.29 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON AGING, OLDER AMERICANS...

A numerically optimized active shield for improved TMS targeting

PubMed Central

Hernandez-Garcia, Luis; Hall, Timothy; Gomez, Luis; Michielssen, Eric

2010-01-01

Transcranial magnetic stimulation (TMS) devices suffer of poor targeting and penetration depth. A new approach to designing TMS coils is introduced in order to improve the focus of the stimulation region through the use of actively shielded probes. Iterative optimization techniques were used to design different active shielding coils for TMS probes. The new approach aims to increase the amount of energy deposited in a thin cylindrical region below the probe relative to the energy deposited elsewhere in the region (“sharpness”), while simultaneously increase the induced electric field deep in the target region relative to the surface (“penetration”). After convergence, the resulting designs showed that there is a clear tradeoff between sharpness and penetration that can be controlled by the choice of a tuning parameter. The resulting designs were tested on a realistic human head conductivity model, taking the contribution from surface charges into account. The design of choice reduced penetration depths by 16.7%. The activated surface area was reduced by 24.1 % and the volume of the activation was reduced from 42.6% by the shield. Restoring the lost penetration could be achieved by increasing the total power to the coil by 16.3%, but in that case, the stimulated volume reduction was only 13.1% and there was a slight increase in the stimulated surface area (2.9 %) PMID:20965451

Raytracing and Direct-Drive Targets

NASA Astrophysics Data System (ADS)

Schmitt, Andrew J.; Bates, Jason; Fyfe, David; Eimerl, David

2013-10-01

Accurate simulation of the effects of laser imprinting and drive asymmetries in directly driven targets requires the ability to distinguish between raytrace noise and the intensity structure produced by the spatial and temporal incoherence of optical smoothing. We have developed and implemented a smoother raytrace algorithm for our mpi-parallel radiation hydrodynamics code, FAST3D. The underlying approach is to connect the rays into either sheets (in 2D) or volume-enclosing chunks (in 3D) so that the absorbed energy distribution continuously covers the propagation area illuminated by the laser. We will describe the status and show the different scalings encountered in 2D and 3D problems as the computational size, parallelization strategy, and number of rays is varied. Finally, we show results using the method in current NIKE experimental target simulations and in proposed symmetric and polar direct-drive target designs. Supported by US DoE/NNSA.

A new vertical axis wind turbine design for urban areas

NASA Astrophysics Data System (ADS)

Frunzulica, Florin; Cismilianu, Alexandru; Boros, Alexandru; Dumitrache, Alexandru; Suatean, Bogdan

2016-06-01

In this paper we aim at developing the model of a Vertical Axis Wind Turbine (VAWT) with the short-term goal of physically realising this turbine to operate at a maximmum power of 5 kW. The turbine is designed for household users in the urban or rural areas and remote or isolated residential areas (hardly accsessible). The proposed model has a biplane configuration on each arm of the VAWT (3 × 2 = 6 blades), allowing for increased performance of the turbine at TSR between 2 and 2.5 (urban area operation) compared to the classic vertical axis turbines. Results that validate the proposed configuration as well as passive control methods to increase the performance of the classic VAWTs are presented.

Designing a Mobile Training System in Rural Areas with Bayesian Factor Models

ERIC Educational Resources Information Center

Omidi Najafabadi, Maryam; Mirdamadi, Seyed Mehdi; Payandeh Najafabadi, Amir Teimour

2014-01-01

The facts that the wireless technologies (1) are more convenient; and (2) need less skill than desktop computers, play a crucial role to decrease digital gap in rural areas. This study employed the Bayesian Confirmatory Factor Analysis (CFA) to design a mobile training system in rural areas of Iran. It categorized challenges, potential, and…

Double-shell target fabrication workshop-2016 report

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

Wang, Y. Morris; Oertel, John; Farrell, Michael

On June 30, 2016, over 40 representatives from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), General Atomics (GA), Laboratory for Laser Energetics (LLE), Schafer Corporation, and NNSA headquarter attended a double-shell (DS) target fabrication workshop at Livermore, California. Pushered-single-shell (PSS) and DS metalgas platforms potentially have a large impact on programmatic applications. The goal of this focused workshop is to bring together target fabrication scientists, physicists, and designers to brainstorm future PSS and DS target fabrication needs and strategies. This one-day workshop intends to give an overall view of historical information, recent approaches, and future research activitiesmore » at each participating organization. Five topical areas have been discussed that are vital to the success of future DS target fabrications, including inner metal shells, foam spheres, outer ablators, fill tube assembly, and metrology.« less

Target validation: linking target and chemical properties to desired product profile.

PubMed

Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

2011-01-01

The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

Recovering actives in multi-antitarget and target design of analogs of the myosin II inhibitor blebbistatin

NASA Astrophysics Data System (ADS)

Roman, Bart I.; Guedes, Rita C.; Stevens, Christian V.; García-Sosa, Alfonso T.

2018-05-01

In multitarget drug design, it is critical to identify active and inactive compounds against a variety of targets and antitargets. Multitarget strategies thus test the limits of available technology, be that in screening large databases of compounds versus a large number of targets, or in using in silico methods for understanding and reliably predicting these pharmacological outcomes. In this paper, we have evaluated the potential of several in silico approaches to predict the target, antitarget and physicochemical profile of (S)-blebbistatin, the best-known myosin II ATPase inhibitor, and a series of analogs thereof. Standard and augmented structure-based design techniques could not recover the observed activity profiles. A ligand-based method using molecular fingerprints was, however, able to select actives for myosin II inhibition. Using further ligand- and structure-based methods, we also evaluated toxicity through androgen receptor binding, affinity for an array of antitargets and the ADME profile (including assay-interfering compounds) of the series. In conclusion, in the search for (S)-blebbistatin analogs, the dissimilarity distance of molecular fingerprints to known actives and the computed antitarget and physicochemical profile of the molecules can be used for compound design for molecules with potential as tools for modulating myosin II and motility-related diseases.

Interactive Inverse Design Optimization of Fuselage Shape for Low-Boom Supersonic Concepts

NASA Technical Reports Server (NTRS)

Li, Wu; Shields, Elwood; Le, Daniel

2008-01-01

This paper introduces a tool called BOSS (Boom Optimization using Smoothest Shape modifications). BOSS utilizes interactive inverse design optimization to develop a fuselage shape that yields a low-boom aircraft configuration. A fundamental reason for developing BOSS is the need to generate feasible low-boom conceptual designs that are appropriate for further refinement using computational fluid dynamics (CFD) based preliminary design methods. BOSS was not developed to provide a numerical solution to the inverse design problem. Instead, BOSS was intended to help designers find the right configuration among an infinite number of possible configurations that are equally good using any numerical figure of merit. BOSS uses the smoothest shape modification strategy for modifying the fuselage radius distribution at 100 or more longitudinal locations to find a smooth fuselage shape that reduces the discrepancies between the design and target equivalent area distributions over any specified range of effective distance. For any given supersonic concept (with wing, fuselage, nacelles, tails, and/or canards), a designer can examine the differences between the design and target equivalent areas, decide which part of the design equivalent area curve needs to be modified, choose a desirable rate for the reduction of the discrepancies over the specified range, and select a parameter for smoothness control of the fuselage shape. BOSS will then generate a fuselage shape based on the designer's inputs in a matter of seconds. Using BOSS, within a few hours, a designer can either generate a realistic fuselage shape that yields a supersonic configuration with a low-boom ground signature or quickly eliminate any configuration that cannot achieve low-boom characteristics with fuselage shaping alone. A conceptual design case study is documented to demonstrate how BOSS can be used to develop a low-boom supersonic concept from a low-drag supersonic concept. The paper also contains a study

Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes

PubMed Central

2015-01-01

We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of 68/67Ga3+ and Gd3+, respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM–1 s–1 at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with 67Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection. PMID:25615011

Designing Targeted Educational Voucher Schemes for the Poor in Developing Countries

NASA Astrophysics Data System (ADS)

Shafiq, M. Najeeb

2010-02-01

A targeted educational voucher scheme (TEVS) is often proposed for the poor in developing countries. Essentially, TEVS involves issuing vouchers to poor households, thus enabling them to pay tuition and fees for their children's schooling at participating non-public schools. However, little is known about TEVS' design in developing countries. This article provides the foundation for constructing a TEVS and conducting subsequent scientific evaluations to support, modify or oppose such a system. Specifically, this article uses three policy instruments to design a TEVS: regulation, support services and finance. Regulation here refers to the rules that must be adhered to by participating households, children and schools. Support services refer to services facilitating the participation of children, households, schools, and financial and political supporters. Finance refers to the value of each voucher, total TEVS costs and sources of finance.

78 FR 44459 - Designation of Health Professional(s) Shortage Areas

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service 42 CFR Part 5 Designation of Health Professional(s) Shortage Areas CFR Correction 0 In Title 42 of the Code of Federal Regulations, Parts 1 to 399... the phrase ``as having a mental health professional(s)'', insert the word ``shortage'' before the...

36 CFR 212.51 - Designation of roads, trails, and areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... administrative use by the Forest Service; (5) Use of any fire, military, emergency, or law enforcement vehicle... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Designation of roads, trails, and areas. 212.51 Section 212.51 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF...

42 CFR Appendix E to Part 5 - Criteria for Designation of Areas Having Shortages of Podiatric Professional(s)

Code of Federal Regulations, 2011 CFR

2011-10-01

... barriers (such as economic or cultural barriers). C. Determination of Degree of Shortage. Designated areas... 42 Public Health 1 2011-10-01 2011-10-01 false Criteria for Designation of Areas Having Shortages... OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS DESIGNATION OF HEALTH PROFESSIONAL(S) SHORTAGE AREAS...

The Advanced Linked Extended Reconnaissance & Targeting Technology Demonstration project

NASA Astrophysics Data System (ADS)

Edwards, Mark

2008-04-01

The Advanced Linked Extended Reconnaissance & Targeting (ALERT) Technology Demonstration (TD) project is addressing many operational needs of the future Canadian Army's Surveillance and Reconnaissance forces. Using the surveillance system of the Coyote reconnaissance vehicle as an experimental platform, the ALERT TD project aims to significantly enhance situational awareness by fusing multi-sensor and tactical data, developing automated processes, and integrating beyond line-of-sight sensing. The project is exploiting important advances made in computer processing capability, displays technology, digital communications, and sensor technology since the design of the original surveillance system. As the major research area within the project, concepts are discussed for displaying and fusing multi-sensor and tactical data within an Enhanced Operator Control Station (EOCS). The sensor data can originate from the Coyote's own visible-band and IR cameras, laser rangefinder, and ground-surveillance radar, as well as from beyond line-of-sight systems such as mini-UAVs and unattended ground sensors. Video-rate image processing has been developed to assist the operator to detect poorly visible targets. As a second major area of research, automatic target cueing capabilities have been added to the system. These include scene change detection, automatic target detection and aided target recognition algorithms processing both IR and visible-band images to draw the operator's attention to possible targets. The merits of incorporating scene change detection algorithms are also discussed. In the area of multi-sensor data fusion, up to Joint Defence Labs level 2 has been demonstrated. The human factors engineering aspects of the user interface in this complex environment are presented, drawing upon multiple user group sessions with military surveillance system operators. The paper concludes with Lessons Learned from the project. The ALERT system has been used in a number of C4ISR

Comparison of a fully mapped plot design to three alternative designs for volume and area estimates using Maine inventory data

Treesearch

Stanford L. Arner

1998-01-01

A fully mapped plot design is compared to three alternative designs using data collected for the recent inventory of Maine's forest resources. Like the fully mapped design, one alternative eliminates the bias of previous procedures, and should be less costly and more consistent. There was little difference in volume and area estimates or in sampling errors among...

Mixed-Fidelity Approach for Design of Low-Boom Supersonic Aircraft

NASA Technical Reports Server (NTRS)

Li, Wu; Shields, Elwood; Geiselhart, Karl

2011-01-01

This paper documents a mixed-fidelity approach for the design of low-boom supersonic aircraft with a focus on fuselage shaping.A low-boom configuration that is based on low-fidelity analysis is used as the baseline. The fuselage shape is modified iteratively to obtain a configuration with an equivalent-area distribution derived from computational fluid dynamics analysis that attempts to match a predetermined low-boom target area distribution and also yields a low-boom ground signature. The ground signature of the final configuration is calculated by using a state-of-the-art computational-fluid-dynamics-based boom analysis method that generates accurate midfield pressure distributions for propagation to the ground with ray tracing. The ground signature that is propagated from a midfield pressure distribution has a shaped ramp front, which is similar to the ground signature that is propagated from the computational fluid dynamics equivalent-area distribution. This result supports the validity of low-boom supersonic configuration design by matching a low-boom equivalent-area target, which is easier to accomplish than matching a low-boom midfield pressure target.

Large Area Solid Radiochemistry (LASR) collector at the National Ignition Facility

NASA Astrophysics Data System (ADS)

Waltz, Cory; Gharibyan, Narek; Hardy, Mike; Shaughnessy, Dawn; Jedlovec, Don; Smith, Cal

2017-08-01

The flux of neutrons and charged particles produced from inertial confinement fusion experiments at the National Ignition Facility (NIF) induces measurable concentrations of nuclear reaction products in various target materials. The collection and radiochemical analysis of the post-shot debris can be utilized as an implosion diagnostic to obtain information regarding fuel areal density and ablator-fuel mixing. Furthermore, assessment of the debris from specially designed targets, material doped in capsules or mounted on the external surface of the target assembly, can support experiments relevant to nuclear forensic research. To collect the shot debris, we have deployed the Large Area Solid Radiochemistry Collector (LASR) at NIF. LASR uses a main collector plate that contains a large collection foil with an exposed 20 cm diameter surface located ˜50 cm from the NIF target. This covers ˜0.12 steradians, or about 1% of the total solid angle. We will describe the design, analysis, and operation of this experimental platform as well as the initial results. To speed up the design process 3-dimensional printing was utilized. Design analysis includes the dynamic loading of the NIF target vaporized mass, which was modeled using LS-DYNA.

Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy

PubMed Central

Raman, Marine C C; Rizkallah, Pierre J; Simmons, Ruth; Donnellan, Zoe; Dukes, Joseph; Bossi, Giovanna; Le Provost, Gabrielle S; Todorov, Penio; Baston, Emma; Hickman, Emma; Mahon, Tara; Hassan, Namir; Vuidepot, Annelise; Sami, Malkit; Cole, David K; Jakobsen, Bent K.

2016-01-01

Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity T-cell receptors (TCRs) provide an ideal approach to target cancer cells, with emerging clinical data showing significant promise. Nevertheless, the risk of off target reactivity remains a key concern, as exemplified in a recent clinical report describing fatal cardiac toxicity, following administration of MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity with an unrelated epitope from the Titin protein presented on cardiac tissue. Here, we investigated the structural mechanism enabling TCR cross-recognition of MAGE-A3 and Titin, and applied the resulting data to rationally design mutants with improved antigen discrimination, providing a proof-of-concept strategy for altering the fine specificity of a TCR towards an intended target antigen. This study represents the first example of direct molecular mimicry leading to clinically relevant fatal toxicity, mediated by a modified enhanced affinity TCR designed for cancer immunotherapy. Furthermore, these data demonstrate that self-antigens that are expressed at high levels on healthy tissue should be treated with extreme caution when designing immuno-therapeutics. PMID:26758806

LH2 Target Design & Position Survey Techniques for the MUSE experiment for Precise Proton Radius Measurement

NASA Astrophysics Data System (ADS)

Le Pottier, Luc; Roy, Pryiashee; Lorenzon, Wolfgang; Raymond, Richard; Steinberg, Noah; Rossi de La Fuente, Erick; MUSE (MUon proton Scattering Experiment) Collaboration

2017-09-01

The proton radius puzzle is a currently unresolved problem which has intrigued the scientific community, dealing with a 7 σ discrepancy between the proton radii determined from muonic hydrogen spectroscopy and electron scattering measurements. The MUon Scattering Experiment (MUSE) aims to resolve this puzzle by performing the first simultaneous elastic scattering measurements of both electrons and muons on the proton, which will allow the comparison of the radii from the two interactions with reduced systematic uncertainties. The data from this experiment is expected to provide the best test of lepton universality to date. The experiment will take place at the Paul Scherrer Institute in Switzerland in 2018. An essential component of the experiment is a liquid hydrogen (LH2) cryotarget system. Our group at the University of Michigan is responsible for the design, fabrication and installation of this system. Here we present our LH2 target cell design and fabrication techniques for successful operation at 20 K and 1 atm, and our computer vision-based target position survey system which will determine the position of the target, installed inside a vacuum chamber, with 0.01 mm or better precision at the height of the liquid hydrogen target and along the beam direction during the experiment.

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

PubMed Central

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

2014-01-01

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

Design of Secure ECG-Based Biometric Authentication in Body Area Sensor Networks

PubMed Central

Peter, Steffen; Pratap Reddy, Bhanu; Momtaz, Farshad; Givargis, Tony

2016-01-01

Body area sensor networks (BANs) utilize wireless communicating sensor nodes attached to a human body for convenience, safety, and health applications. Physiological characteristics of the body, such as the heart rate or Electrocardiogram (ECG) signals, are promising means to simplify the setup process and to improve security of BANs. This paper describes the design and implementation steps required to realize an ECG-based authentication protocol to identify sensor nodes attached to the same human body. Therefore, the first part of the paper addresses the design of a body-area sensor system, including the hardware setup, analogue and digital signal processing, and required ECG feature detection techniques. A model-based design flow is applied, and strengths and limitations of each design step are discussed. Real-world measured data originating from the implemented sensor system are then used to set up and parametrize a novel physiological authentication protocol for BANs. The authentication protocol utilizes statistical properties of expected and detected deviations to limit the number of false positive and false negative authentication attempts. The result of the described holistic design effort is the first practical implementation of biometric authentication in BANs that reflects timing and data uncertainties in the physical and cyber parts of the system. PMID:27110785

Design of Secure ECG-Based Biometric Authentication in Body Area Sensor Networks.

PubMed

Peter, Steffen; Reddy, Bhanu Pratap; Momtaz, Farshad; Givargis, Tony

2016-04-22

Body area sensor networks (BANs) utilize wireless communicating sensor nodes attached to a human body for convenience, safety, and health applications. Physiological characteristics of the body, such as the heart rate or Electrocardiogram (ECG) signals, are promising means to simplify the setup process and to improve security of BANs. This paper describes the design and implementation steps required to realize an ECG-based authentication protocol to identify sensor nodes attached to the same human body. Therefore, the first part of the paper addresses the design of a body-area sensor system, including the hardware setup, analogue and digital signal processing, and required ECG feature detection techniques. A model-based design flow is applied, and strengths and limitations of each design step are discussed. Real-world measured data originating from the implemented sensor system are then used to set up and parametrize a novel physiological authentication protocol for BANs. The authentication protocol utilizes statistical properties of expected and detected deviations to limit the number of false positive and false negative authentication attempts. The result of the described holistic design effort is the first practical implementation of biometric authentication in BANs that reflects timing and data uncertainties in the physical and cyber parts of the system.

Small School Design in Practice. Central Ideas -- Focus on The Catskill Area Project.

ERIC Educational Resources Information Center

Tremlett, Willard L.; And Others

Describing major features of the New York Catskill Area Project in Small School Design (CAPSSD) begun in 1957, this pamphlet addresses: (1) Basic Concepts in Small School Design (flexible scheduling, multiple classes, organizational interdependency, teacher versatility, student planning, technological communications, and interagency cooperation);…

76 FR 44613 - Designation of Eight Counties as High Intensity Drug Trafficking Areas

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... OFFICE OF NATIONAL DRUG CONTROL POLICY Designation of Eight Counties as High Intensity Drug Trafficking Areas AGENCY: Office of National Drug Control Policy. ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy has designated eight additional counties as High Intensity Drug...

Opto-mechanical system design of test system for near-infrared and visible target

NASA Astrophysics Data System (ADS)

Wang, Chunyan; Zhu, Guodong; Wang, Yuchao

2014-12-01

Guidance precision is the key indexes of the guided weapon shooting. The factors of guidance precision including: information processing precision, control system accuracy, laser irradiation accuracy and so on. The laser irradiation precision is an important factor. This paper aimed at the demand of the precision test of laser irradiator，and developed the laser precision test system. The system consists of modified cassegrain system, the wide range CCD camera, tracking turntable and industrial PC, and makes visible light and near infrared target imaging at the same time with a Near IR camera. Through the analysis of the design results, when it exposures the target of 1000 meters that the system measurement precision is43mm, fully meet the needs of the laser precision test.

10 CFR 60.132 - Additional design criteria for surface facilities in the geologic repository operations area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... geologic repository operations area. 60.132 Section 60.132 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES Technical Criteria Design Criteria for the Geologic Repository Operations Area § 60.132 Additional design criteria for surface facilities in...

Targeting therapeutics to the glomerulus with nanoparticles.

PubMed

Zuckerman, Jonathan E; Davis, Mark E

2013-11-01

Nanoparticles are an enabling technology for the creation of tissue-/cell-specific therapeutics that have been investigated extensively as targeted therapeutics for cancer. The kidney, specifically the glomerulus, is another accessible site for nanoparticle delivery that has been relatively overlooked as a target organ. Given the medical need for the development of more potent, kidney-targeted therapies, the use of nanoparticle-based therapeutics may be one such solution to this problem. Here, we review the literature on nanoparticle targeting of the glomerulus. Specifically, we provide a broad overview of nanoparticle-based therapeutics and how the unique structural characteristics of the glomerulus allow for selective, nanoparticle targeting of this area of the kidney. We then summarize literature examples of nanoparticle delivery to the glomerulus and elaborate on the appropriate nanoparticle design criteria for glomerular targeting. Finally, we discuss the behavior of nanoparticles in animal models of diseased glomeruli and review examples of nanoparticle therapeutic approaches that have shown promise in animal models of glomerulonephritic disease. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Engineering synthetic TAL effectors with orthogonal target sites

PubMed Central

Garg, Abhishek; Lohmueller, Jason J.; Silver, Pamela A.; Armel, Thomas Z.

2012-01-01

The ability to engineer biological circuits that process and respond to complex cellular signals has the potential to impact many areas of biology and medicine. Transcriptional activator-like effectors (TALEs) have emerged as an attractive component for engineering these circuits, as TALEs can be designed de novo to target a given DNA sequence. Currently, however, the use of TALEs is limited by degeneracy in the site-specific manner by which they recognize DNA. Here, we propose an algorithm to computationally address this problem. We apply our algorithm to design 180 TALEs targeting 20 bp cognate binding sites that are at least 3 nt mismatches away from all 20 bp sequences in putative 2 kb human promoter regions. We generated eight of these synthetic TALE activators and showed that each is able to activate transcription from a targeted reporter. Importantly, we show that these proteins do not activate synthetic reporters containing mismatches similar to those present in the genome nor a set of endogenous genes predicted to be the most likely targets in vivo. Finally, we generated and characterized TALE repressors comprised of our orthogonal DNA binding domains and further combined them with shRNAs to accomplish near complete repression of target gene expression. PMID:22581776

10 CFR 60.131 - General design criteria for the geologic repository operations area.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., systems, and components important to safety shall be designed to withstand dynamic effects such as missile... radioactivity areas; and (6) A radiation alarm system to warn of significant increases in radiation levels... system shall be designed with provisions for calibration and for testing its operability. (b) Protection...

Antarctica’s Protected Areas Are Inadequate, Unrepresentative, and at Risk

PubMed Central

Shaw, Justine D.; Terauds, Aleks; Riddle, Martin J.; Possingham, Hugh P.; Chown, Steven L.

2014-01-01

Antarctica is widely regarded as one of the planet's last true wildernesses, insulated from threat by its remoteness and declaration as a natural reserve dedicated to peace and science. However, rapidly growing human activity is accelerating threats to biodiversity. We determined how well the existing protected-area system represents terrestrial biodiversity and assessed the risk to protected areas from biological invasions, the region's most significant conservation threat. We found that Antarctica is one of the planet's least protected regions, with only 1.5% of its ice-free area formally designated as specially protected areas. Five of the distinct ice-free ecoregions have no specially designated areas for the protection of biodiversity. Every one of the 55 designated areas that protect Antarctica's biodiversity lies closer to sites of high human activity than expected by chance, and seven lie in high-risk areas for biological invasions. By any measure, including Aichi Target 11 under the Convention on Biological Diversity, Antarctic biodiversity is poorly protected by reserves, and those reserves are threatened. PMID:24936869

75 FR 57481 - Statutorily Mandated Designation of Difficult Development Areas and Qualified Census Tracts for 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... makes new DDA designations annually for purposes of the Low-Income Housing Tax Credit (LIHTC) under... questions on how areas are designated and on geographic definitions, contact Michael K. Hollar, Senior... Budget (OMB) first published new metropolitan area definitions incorporating 2000 Census data in OMB...

Re-Entry Point Targeting for LEO Spacecraft using Aerodynamic Drag

NASA Technical Reports Server (NTRS)

Omar, Sanny; Bevilacqua, Riccardo; Fineberg, Laurence; Treptow, Justin; Johnson, Yusef; Clark, Scott

2016-01-01

Most Low Earth Orbit (LEO) spacecraft do not have thrusters and re-enter atmosphere in random locations at uncertain times. Objects pose a risk to persons, property, or other satellites. Has become a larger concern with the recent increase in small satellites. Working on a NASA funded project to design a retractable drag device to expedite de-orbit and target a re-entry location through modulation of the drag area. Will be discussing the re-entry point targeting algorithm here.

44 CFR 206.40 - Designation of affected areas and eligible assistance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Designation of affected areas and eligible assistance. 206.40 Section 206.40 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The...

44 CFR 206.40 - Designation of affected areas and eligible assistance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Designation of affected areas and eligible assistance. 206.40 Section 206.40 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The...

44 CFR 206.40 - Designation of affected areas and eligible assistance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Designation of affected areas and eligible assistance. 206.40 Section 206.40 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The...

44 CFR 206.40 - Designation of affected areas and eligible assistance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Designation of affected areas and eligible assistance. 206.40 Section 206.40 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The...

44 CFR 206.40 - Designation of affected areas and eligible assistance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Designation of affected areas and eligible assistance. 206.40 Section 206.40 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE The...

The design and application of large area intensive lens array focal spots measurement system

NASA Astrophysics Data System (ADS)

Chen, Bingzhen; Yao, Shun; Yang, Guanghui; Dai, Mingchong; Wang, Zhiyong

2014-12-01

Concentrating Photovoltaic (CPV) modules are getting thinner and using smaller cells now days. Correspondingly, large area intensive lens arrays with smaller unit dimension and shorter focal length are wanted. However, the size and power center of lens array focal spots usually differ from the design value and are hard to measure, especially under large area situation. It is because the machining error and deformation of material of the lens array are hard to simulate in the optical design process. Thus the alignment error between solar cells and focal spots in the module assembly process will be hard to control. Under this kind of situation, the efficiency of CPV module with thinner body and smaller cells is much lower than expected. In this paper, a design of large area lens array focal spots automatic measurement system is presented, as well as its prototype application results. In this system, a four-channel parallel light path and its corresponding image capture and process modules are designed. These modules can simulate focal spots under sunlight and have the spots image captured and processed using charge coupled devices and certain gray level algorithm. Thus the important information of focal spots such as spot size and location will be exported. Motion control module based on grating scale signal and interval measurement method are also employed in this system in order to get test results with high speed and high precision on large area lens array no less than 1m×0.8m. The repeatability of the system prototype measurement is +/-10μm with a velocity of 90 spot/min. Compared to the original module assembled using coordinates from optical design, modules assembled using data exported from the prototype is 18% higher in output power, reaching a conversion efficiency of over 31%. This system and its design can be used in the focal spot measurement of planoconvex lens array and Fresnel lens array, as well as other kinds of large area lens array application

Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

PubMed

Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

2015-07-01

Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

Optical system design of solar-blind UV target receiver with large FOV