76 FR 14417 - Prospective Grant of Exclusive License

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... acids, vectors, TDP producing host cells, antibodies and methods of use'' (HHS Ref. No. E-281-1999/0... prospective exclusive license territory may be worldwide and the field of use may be for the use of the... license in the field of use filed in response to this notice will be treated as objections to the grant of...

75 FR 29785 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

... Guide, DG-1248, ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License..., ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License Examinations, and... or acceptance of a nuclear power plant simulation facility for use in operator and senior operator...

Virus-Vectored Influenza Virus Vaccines

PubMed Central

Tripp, Ralph A.; Tompkins, S. Mark

2014-01-01

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

Intravenous Therapy Instruction for Licensed Practical Nurses. Instructor's Guide.

ERIC Educational Resources Information Center

Springer, Pam; Carey, Jean

This Idaho instructor's guide lists tasks and enabling objectives, outlines instruction, and provides handout masters, overhead masters, and tests for intravenous therapy (IV) instruction for licensed practical nurses. Following an introduction and a list of criteria for successful completion of IV therapy courses, the document lists tasks and…

9 CFR 107.2 - Products under State license.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., contaminated, dangerous, or harmful viruses, serums, toxins, or analogous products. (c) Each product to be... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTIONS FROM PREPARATION...: (1) The State has the authority to license viruses, serums, toxins, and analogous products and...

Intravenous Fluid Therapy Course for the Licensed Practical Nurse. Instructor Guide.

ERIC Educational Resources Information Center

Missouri Univ., Columbia. Instructional Materials Lab.

This curriculum guide provides materials for a 10-unit intravenous (IV) therapy course for licensed practical nurses. Units contain from one to nine lessons. The first unit provides an introduction and orientation to the course. Subsequent units concern documentation, anatomy and physiology as applied to IV therapy, fundamental aspects of fluid…

Interpreting and Negotiating Licensing Agreements: A Guidebook for the Library, Research, and Teaching Professions.

ERIC Educational Resources Information Center

Bielefield, Arlene; Cheeseman, Lawrence

This guide is designed to help librarians, researchers, and teachers understand and negotiate licensing agreements for electronic resources. Chapter 1 is an introduction to contract law. Chapter 2 describes the various types of licensing agreements, including shrink-wrap, Webwrap, and custom licenses that are negotiated clause-by-clause; examples…

9 CFR 102.4 - U.S. Veterinary Biologics Establishment License.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false U.S. Veterinary Biologics Establishment License. 102.4 Section 102.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

9 CFR 102.4 - U.S. Veterinary Biologics Establishment License.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false U.S. Veterinary Biologics Establishment License. 102.4 Section 102.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

Lessons from HIV-1 vaccine efficacy trials.

PubMed

Excler, Jean-Louis; Michael, Nelson L

2016-11-01

Only four HIV-1 vaccine concepts have been tested in six efficacy trials with no product licensed to date. Several scientific and programmatic lessons can be learned from these studies generating new hypotheses and guiding future steps. RV144 [ALVAC-HIV (canarypox vector) and AIDSVAX B/E (bivalent gp120 HIV-1 subtype B and CRF01_AE)] remains the only efficacy trial that demonstrated a modest vaccine efficacy, which led to the identification of immune correlates of risk. Progress on subtype-specific, ALVAC (canarypox vector) and gp120 vaccine prime-boost approaches has been slow, but we are finally close to the launch of an efficacy study in Africa in 2016. The quest of a globally effective HIV-1 vaccine has led to the development of new approaches. Efficacy studies of combinations of Adenovirus type 26 (Ad26)/Modified Vaccinia Ankara (MVA)/gp140 vaccines with mosaic designs will enter efficacy studies mid-2017 and cytomegalovirus (CMV)-vectored vaccines begin Phase I studies at the same time. Future HIV-1 vaccine efficacy trials face practical challenges as effective nonvaccine prevention programs are projected to decrease HIV-1 incidence. An HIV-1 vaccine is urgently needed. Increased industry involvement, mobilization of resources, expansion of a robust pipeline of new concepts, and robust preclinical challenge studies will be essential to accelerate efficacy testing of next generation HIV-1 vaccine candidates.

76 FR 65544 - Standard Format and Content of License Applications for Mixed Oxide Fuel Fabrication Facilities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-21

...The U.S. Nuclear Regulatory Commission (NRC or Commission) is issuing a revision to regulatory guide (RG) 3.39, ``Standard Format and Content of License Applications for Mixed Oxide Fuel Fabrication Facilities.'' This guide endorses the standard format and content for license applications and integrated safety analysis (ISA) summaries described in the current version of NUREG-1718, ``Standard Review Plan for the Review of an Application for a Mixed Oxide (MOX) Fuel Fabrication Facility,'' as a method that the NRC staff finds acceptable for meeting the regulatory requirements of Title 10 of the Code of Federal Regulations (10 CFR) part 70, ``Domestic Licensing of Special Nuclear Material'' for mixed oxide fuel fabrication facilities.

Development of a domain-specific genetic language to design Chlamydomonas reinhardtii expression vectors.

PubMed

Wilson, Mandy L; Okumoto, Sakiko; Adam, Laura; Peccoud, Jean

2014-01-15

Expression vectors used in different biotechnology applications are designed with domain-specific rules. For instance, promoters, origins of replication or homologous recombination sites are host-specific. Similarly, chromosomal integration or viral delivery of an expression cassette imposes specific structural constraints. As de novo gene synthesis and synthetic biology methods permeate many biotechnology specialties, the design of application-specific expression vectors becomes the new norm. In this context, it is desirable to formalize vector design strategies applicable in different domains. Using the design of constructs to express genes in the chloroplast of Chlamydomonas reinhardtii as an example, we show that a vector design strategy can be formalized as a domain-specific language. We have developed a graphical editor of context-free grammars usable by biologists without prior exposure to language theory. This environment makes it possible for biologists to iteratively improve their design strategies throughout the course of a project. It is also possible to ensure that vectors designed with early iterations of the language are consistent with the latest iteration of the language. The context-free grammar editor is part of the GenoCAD application. A public instance of GenoCAD is available at http://www.genocad.org. GenoCAD source code is available from SourceForge and licensed under the Apache v2.0 open source license.

Hydropower: A Regulatory Guide to Permitting and Licensing in Idaho, Montana, Oregon, and Washington.

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

McCoy, Gilbert A.

1992-12-01

The design, construction and operation of a hydropower project can result in many potential impacts. These potential impacts are of concern to a host of federal, state, and local authorities. Early consultation with land and water management, fish and wildlife resource protection, and health and human safety-oriented agencies should occur to determine specific concerns and study requirements for each proposed project. This Guide to Permitting and Licensing outlines the characteristic features of attractive hydropower sites; summarizes an array of developmental constraints; illustrates potential environmental impacts and concerns; and summarizes all federal, state, and local permitting and licensing requirements.

Hydropower : A Regulatory Guide to Permitting and Licensing in Idaho, Montana, Oregon, and Washington.

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

McCoy, Gilbert A.

1992-12-01

The design, construction and operation of a hydropower project can result in many potential impacts. These potential impacts are of concern to a host of federal, state, and local authorities. Early consultation with land and water management, fish and wildlife resource protection, and health and human safety-oriented agencies should occur to determine specific concerns and study requirements for each proposed project. This Guide to Permitting and Licensing outlines the characteristic features of attractive hydropower sites; summarizes an array of developmental constraints; illustrates potential environmental impacts and concerns; and summarizes all federal, state, and local permitting and licensing requirements.

75 FR 1830 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

... review of applications for permits and licenses. RG 5.71, ``Cyber Security Programs for Nuclear... NUCLEAR REGULATORY COMMISSION [NRC-2010-0009] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

Licensing: pros and cons for biotech.

PubMed

Villiger, Ralph; Bogdan, Boris

2009-03-01

This article guides the reader through strategic considerations when facing the option to license a drug development project. It is crucial to understand these licensing events in their full complexity in order to achieve maximum value for the company and the shareholders, while minimizing risk. First, the nature of various license agreements and the needs of licensor and licensee are discussed. Second, the main strategic issues for the licensor are explained and a guideline, how to come to a decision whether to license and to what terms, is given. Third, the authors explain how to overcome different assumptions when negotiating a license contract.

Supermodes in Coupled Multi-Core Waveguide Structures

DTIC Science & Technology

2016-04-01

and therefore can be treated as linear polarization (LP) modes. In essence, the LP modes are scalar approximations of the vector mode fields and contain...field, including the discovery of optical discrete solitons , Bragg and vector solitons in fibers, nonlinear surface waves, and the discovery of self...increased for an isolated core, it can guide high-order modes. For optical fibers with low re- fractive index contrast, the vector modes are weakly guided

Comparison of astigmatic correction after femtosecond lenticule extraction and wavefront-guided LASIK for myopic astigmatism.

PubMed

Ali, Mohamed A; Kobashi, Hidenaga; Kamiya, Kazutaka; Igarashi, Akihito; Miyake, Toshiyuki; Elewa, Mohamed Ehab M; Komatsu, Mari; Shimizu, Kimiya

2014-12-01

To compare postoperative astigmatic correction between femtosecond lenticule extraction (FLEx) and wavefront-guided LASIK in eyes with myopic astigmatism. Fifty-eight eyes of 41 patients undergoing FLEx and 49 eyes of 29 patients undergoing wavefront-guided LASIK to correct myopic astigmatism were examined. Visual acuity, cylindrical refraction, predictability of the astigmatic correction, and astigmatic vector components were compared between groups 6 months after surgery. There was no statistically significant difference in manifest cylindrical refraction (P = .08) or percentage of eyes within ± 0.50 diopter (D) of its refraction (P = .11) between the surgical procedures. The index of success in FLEx was statistically significantly better than that of wavefront-guided LASIK (P = .02), although there was no significant difference between the groups in other indices (eg, surgically induced astigmatism, target-induced astigmatism, astigmatic correction index, angle of error, difference vector, and flattening index). Subgroup analysis showed that FLEx had a better index of success (P = .02) and difference vector (P = .04) than wavefront-guided LASIK in the low cylinder subgroup; the angle of error in FLEx was significantly smaller than that of wavefront-guided LASIK in the moderate cylinder subgroup (P = .03). Both FLEx and wavefront-guided LASIK worked well for the correction of myopic astigmatism by the 6-month follow-up visit. Although FLEx had a better index of success than wavefront-guided LASIK when using vector analysis, it appears equivalent to wavefront-guided LASIK in terms of visual acuity and the correction of astigmatism. Copyright 2014, SLACK Incorporated.

Improving Exam Performance in Introductory Biology through the Use of Preclass Reading Guides.

PubMed

Lieu, Rebekah; Wong, Ashley; Asefirad, Anahita; Shaffer, Justin F

2017-01-01

High-structure courses or flipped courses require students to obtain course content before class so that class time can be used for active-learning exercises. While textbooks are used ubiquitously in college biology courses for content dissemination, studies have shown that students frequently do not read their textbooks. To address this issue, we created preclass reading guides that provided students with a way to actively engage with the required reading for each day of class. To determine whether reading guide completion before class is associated with increased performance, we surveyed students about their use of reading guides in two sections of a large-enrollment (400+ students) introductory biology course and used multiple linear regression models to identify significant correlations. The results indicated that greater than 80% of students completed the reading guides before class and that full completion of the reading guides before class was significantly positively correlated with exam performance. Reading guides in most cases were used similarly between different student groups (based on gender, ethnicity, and aptitude). These results suggest that optional preclass reading guides may help students stay on track to acquire course content in introductory biology and thus result in improved exam performance. © 2017 R. Lieu, A. Wong, A. Asefirad, and J. F. Shaffer. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Medicine Handbook.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Office of the Professions.

A reference guide to laws, rules, and regulations that govern medical practice in New York State is presented. After an overview of professional regulation in the state, licensing requirements/procedures for medicine are described including education and postgraduate training requirements, state licensing examinations, and application…

75 FR 48382 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0275] Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-1228, ``Standard Format and Content of License Termination Plans for Nuclear Power Reactors.'' FOR FURTHER INFORMATION CONTACT: James C....

75 FR 55808 - Prospective Grant of Exclusive License: Development of AAV5 Based Therapeutics To Treat Human...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-14

.... Patent 6, 855, 314 entitled ``AAV5 Vector for Transducing Brain Cells and Lung Cells'' [HHS Ref. No. E... sale of AAV5 based therapeutic products to be delivered to the brain, eyes and liver for treatment of... vectors and particles. The specific brain cells that are targeted by AAV5 belong to both non-neuronal...

Inhibition of HBV replication in vivo using helper-dependent adenovirus vectors to deliver antiviral RNA interference expression cassettes.

PubMed

Crowther, Carol; Mowa, Mohube B; Ely, Abdullah; Arbuthnot, Patrick B

2014-01-01

HBV is hyperendemic to southern Africa and parts of Asia, but licensed antivirals have little effect on limiting life-threatening complications of the infection. Although RNA interference (RNAi)-based gene silencing has shown therapeutic potential, difficulties with delivery of anti-HBV RNAi effectors remain an obstacle to their clinical use. To address concerns about the transient nature of transgene expression and toxicity resulting from immunostimulation by recombinant adenovirus vectors (Ads), utility of RNAi-activating anti-HBV helper-dependent (HD) Ads were assessed in this study. Following intravenous administration of 5×10(9) unmodified or pegylated HD Ad infectious particles to HBV transgenic mice, HBV viral loads and serum HBV surface antigen levels were monitored for 12 weeks. Immunostimulation of HD Ads was assessed by measuring inflammatory cytokines, hepatic function and immune response to the co-delivered LacZ reporter gene. Unmodified and pegylated HD Ads transduced 80-90% of hepatocytes and expressed short hairpin RNAs (shRNAs) were processed to generate intended HBV-targeting guides. Markers of HBV replication were decreased by approximately 95% and silencing was sustained for 8 weeks. Unmodified HD Ads induced release of proinflammatory cytokines and there was evidence of an adaptive immune response to β-galactosidase. However the HD Ad-induced innate immune response was minimal in preparations that were enriched with infectious particles. HD Ads have potential utility for delivery of therapeutic HBV-silencing sequences and alterations of these vectors to attenuate their immune responses may further improve their efficacy.

Intravenous Therapy.

ERIC Educational Resources Information Center

Galliart, Barbara

Intended for teaching licensed practical nurses, this curriculum guide provides information related to the equipment and skills required for nursing care of patients needing intravenous (IV) therapy. It also explains the roles and responsibilities of the licensed practical nurse with regard to intravenous therapy. Each of the 15 instructional…

Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

PubMed Central

Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. PMID:25446819

Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

PubMed

Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. Copyright © 2014. Published by Elsevier Ltd.

36 CFR 7.13 - Yellowstone National Park.

Code of Federal Regulations, 2014 CFR

2014-07-01

... license. Non-commercially guided group means a group of no more than five snowmobiles, including a non... traveling together in Yellowstone National Park on any given day or a non-commercially guided group, which... ascertain which snowmobiles in the park are part of a non-commercially guided group. (vi) Non-commercial...

Irrigation Systems. Instructor's Guide.

ERIC Educational Resources Information Center

Amarillo Coll., TX.

This guide is intended for use by licensed irrigators who wish to teach others how to design and install residential and commercial irrigation systems. The materials included in the guide have been developed under the assumption that the instructors who use it have little or no formal training as teachers. The first section presents detailed…

75 FR 33361 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

... staff needs in its review of applications for permits and licenses. Revision 4 of Regulatory Guide 1.28... (Design and Construction).'' Proposed RG 1.28, Revision 4, extends the scope of the NRC's endorsement to...: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.28...

Security management techniques and evaluative checklists for security force effectiveness. Technical report (final) Sep 80-Jul 81

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

Schurman, D.L.; Datesman, G.H. Jr; Truitt, J.O.

The report presents a system for evaluating and correcting deficiencies in security-force effectiveness in licensed nuclear facilities. There are four checklists which security managers can copy directly, or can use as guidelines for developing their own checklists. The checklists are keyed to corrective-action guides found in the body of the report. In addition to the corrective-action guides, the report gives background information on the nature of security systems and discussions of various special problems of the licensed nuclear industry.

Nutrition and Meal Planning in Child-Care Programs: A Practical Guide.

ERIC Educational Resources Information Center

Edelstein, Sari

Designed to assist child care center managers in planning nutritious meals for children in centers or licensed home day care programs, this guide presents information on the nutritional requirements of infants and children, sample menus for child care centers, and resources for further information. The first part of the guide details the…

PGA/MOEAD: a preference-guided evolutionary algorithm for multi-objective decision-making problems with interval-valued fuzzy preferences

NASA Astrophysics Data System (ADS)

Luo, Bin; Lin, Lin; Zhong, ShiSheng

2018-02-01

In this research, we propose a preference-guided optimisation algorithm for multi-criteria decision-making (MCDM) problems with interval-valued fuzzy preferences. The interval-valued fuzzy preferences are decomposed into a series of precise and evenly distributed preference-vectors (reference directions) regarding the objectives to be optimised on the basis of uniform design strategy firstly. Then the preference information is further incorporated into the preference-vectors based on the boundary intersection approach, meanwhile, the MCDM problem with interval-valued fuzzy preferences is reformulated into a series of single-objective optimisation sub-problems (each sub-problem corresponds to a decomposed preference-vector). Finally, a preference-guided optimisation algorithm based on MOEA/D (multi-objective evolutionary algorithm based on decomposition) is proposed to solve the sub-problems in a single run. The proposed algorithm incorporates the preference-vectors within the optimisation process for guiding the search procedure towards a more promising subset of the efficient solutions matching the interval-valued fuzzy preferences. In particular, lots of test instances and an engineering application are employed to validate the performance of the proposed algorithm, and the results demonstrate the effectiveness and feasibility of the algorithm.

Prediction task guided representation learning of medical codes in EHR.

PubMed

Cui, Liwen; Xie, Xiaolei; Shen, Zuojun

2018-06-18

There have been rapidly growing applications using machine learning models for predictive analytics in Electronic Health Records (EHR) to improve the quality of hospital services and the efficiency of healthcare resource utilization. A fundamental and crucial step in developing such models is to convert medical codes in EHR to feature vectors. These medical codes are used to represent diagnoses or procedures. Their vector representations have a tremendous impact on the performance of machine learning models. Recently, some researchers have utilized representation learning methods from Natural Language Processing (NLP) to learn vector representations of medical codes. However, most previous approaches are unsupervised, i.e. the generation of medical code vectors is independent from prediction tasks. Thus, the obtained feature vectors may be inappropriate for a specific prediction task. Moreover, unsupervised methods often require a lot of samples to obtain reliable results, but most practical problems have very limited patient samples. In this paper, we develop a new method called Prediction Task Guided Health Record Aggregation (PTGHRA), which aggregates health records guided by prediction tasks, to construct training corpus for various representation learning models. Compared with unsupervised approaches, representation learning models integrated with PTGHRA yield a significant improvement in predictive capability of generated medical code vectors, especially for limited training samples. Copyright © 2018. Published by Elsevier Inc.

Guide for Determining Compliance With the Clean Air Act Standards for Radionuclide Emissions From NRC-Licensed and Non-DOE Federal Facilities: Revision 2

EPA Pesticide Factsheets

The requirements described apply to certain facilities licensed by the Nuclear Regulatory Commission (NRC) or its Agreement States to handle radioactive materials. Federal facilities not part of the Department of Energy (DOE) are also covered.

78 FR 37325 - License Renewal of Nuclear Power Plants; Generic Environmental Impact Statement and Standard...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

... Nuclear Power Plants; Generic Environmental Impact Statement and Standard Review Plans for Environmental... for Nuclear Power Plants, Supplement 1: Operating License Renewal'' (ESRP). The ESRP serves as a guide... published a final rule, ``Revisions to Environmental Review for Renewal of Nuclear Power Plant Operating...

47 CFR 101.1007 - Geographic service areas and number of licenses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Geographic service areas and number of licenses. 101.1007 Section 101.1007 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... in the Rand McNally 1992 Commercial Atlas & Marketing Guide, 123rd Edition, at pages 38-39, that...

75 FR 5630 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-03

... specific parts of the NRC's regulations, techniques that the staff uses in evaluating specific problems or postulated accidents, and data that the staff needs in its review of applications for permits and licenses... in license applications and for monitoring and reporting effluent data by licensees. The guidance is...

77 FR 63343 - Biweekly Notice: Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... PWR [Pressurized-Water Reactor] Steam Generator Tubes'' (Reference 32) and [Nuclear Energy Institute... maintains the required structural margins of the SG tubes for both normal and accident conditions. Nuclear Energy Institute 97-06, ``Steam Generator Program Guidelines'' (Reference 8), and NRC Regulatory Guide 1...

Recommended practices for DSRC licensing and spectrum management : a guide for management, regulation, deployment, and administration for a connected vehicle environment.

DOT National Transportation Integrated Search

2015-12-01

The goal of this document is to make licensing requirements transparent and best practices accessible to any organization, public or private, seeking to deploy Connected Vehicle Dedicated Short Range Communications (DSRC) Roadside Units (RSU) a...

Comparison of Moderate- to High-Astigmatism Corrections Using WaveFront-Guided Laser In Situ Keratomileusis and Small-Incision Lenticule Extraction.

PubMed

Zhang, Jiamei; Wang, Yan; Chen, Xiaoqin

2016-04-01

To evaluate and compare refractive outcomes of moderate- and high-astigmatism correction after wavefront-guided laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). This comparative study enrolled a total of 64 eyes that had undergone SMILE (42 eyes) and wavefront-guided LASIK (22 eyes). Preoperative cylindrical diopters were ≤-2.25 D in moderate- and >-2.25 D in high-astigmatism subgroups. The refractive results were analyzed based on the Alpins vector method that included target-induced astigmatism, surgically induced astigmatism, difference vector, correction index, index of success, magnitude of error, angle of error, and flattening index. All subjects completed the 3-month follow-up. No significant differences were found in the target-induced astigmatism, surgically induced astigmatism, and difference vector between SMILE and wavefront-guided LASIK. However, the average angle of error value was -1.00 ± 3.16 after wavefront-guided LASIK and 1.22 ± 3.85 after SMILE with statistical significance (P < 0.05). The absolute angle of error value was statistically correlated with difference vector and index of success after both procedures. In the moderate-astigmatism group, correction index was 1.04 ± 0.15 after wavefront-guided LASIK and 0.88 ± 0.15 after SMILE (P < 0.05). However, in the high-astigmatism group, correction index was 0.87 ± 0.13 after wavefront-guided LASIK and 0.88 ± 0.12 after SMILE (P = 0.889). Both procedures showed preferable outcomes in the correction of moderate and high astigmatism. However, high astigmatism was undercorrected after both procedures. Axial error of astigmatic correction may be one of the potential factors for the undercorrection.

76 FR 35922 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... CONTACT: Harriet Karagiannis, Regulatory Guide Development Branch, Division of Engineering, Office of... direct the use of individual monitoring devices. In addition, 10 CFR part 34, ``Licenses for Industrial Radiography and Radiation Safety Requirements for Industrial Radiographic Operations,'' includes a specific...

Parent-Teen Training Aide = Guia de Instruccion para Padres y Jovenes.

ERIC Educational Resources Information Center

California State Dept. of Motor Vehicles, Sacramento.

This handbook is designed to guide California parents in helping their teenagers practice the driving skills required to obtain a driver license. The first section includes information on the following topics: meeting California driver training and licensing requirements, understanding the parent's role as the driving instructor's aide, using the…

Graduated Driver Licensing in the United States: Evaluation Results from the Early Programs.

ERIC Educational Resources Information Center

Shope, Jean T.; Molnar, Lisa J.

2003-01-01

Review of graduated driver-licensing (GDL) programs in six states. Concludes that GDL programs are effective in reducing the crash risk of teenage drivers and that the impact of these studies and others to come will guide future research, practice, and policy. (Contains 2 tables and 19 references.) (AUTHOR/WFA)

78 FR 663 - Decommissioning Planning During Operations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-04

...] Decommissioning Planning During Operations AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide..., ``Decommissioning Planning During Operations.'' The guide describes a method that the NRC staff considers acceptable for use by holders of licenses in complying with the NRC's Decommissioning Planning Rule (DPR) (76 FR...

Practical automatic Arabic license plate recognition system

NASA Astrophysics Data System (ADS)

Mohammad, Khader; Agaian, Sos; Saleh, Hani

2011-02-01

Since 1970's, the need of an automatic license plate recognition system, sometimes referred as Automatic License Plate Recognition system, has been increasing. A license plate recognition system is an automatic system that is able to recognize a license plate number, extracted from image sensors. In specific, Automatic License Plate Recognition systems are being used in conjunction with various transportation systems in application areas such as law enforcement (e.g. speed limit enforcement) and commercial usages such as parking enforcement and automatic toll payment private and public entrances, border control, theft and vandalism control. Vehicle license plate recognition has been intensively studied in many countries. Due to the different types of license plates being used, the requirement of an automatic license plate recognition system is different for each country. [License plate detection using cluster run length smoothing algorithm ].Generally, an automatic license plate localization and recognition system is made up of three modules; license plate localization, character segmentation and optical character recognition modules. This paper presents an Arabic license plate recognition system that is insensitive to character size, font, shape and orientation with extremely high accuracy rate. The proposed system is based on a combination of enhancement, license plate localization, morphological processing, and feature vector extraction using the Haar transform. The performance of the system is fast due to classification of alphabet and numerals based on the license plate organization. Experimental results for license plates of two different Arab countries show an average of 99 % successful license plate localization and recognition in a total of more than 20 different images captured from a complex outdoor environment. The results run times takes less time compared to conventional and many states of art methods.

End-to-end system of license plate localization and recognition

NASA Astrophysics Data System (ADS)

Zhu, Siyu; Dianat, Sohail; Mestha, Lalit K.

2015-03-01

An end-to-end license plate recognition system is proposed. It is composed of preprocessing, detection, segmentation, and character recognition to find and recognize plates from camera-based still images. The system utilizes connected component (CC) properties to quickly extract the license plate region. A two-stage CC filtering is utilized to address both shape and spatial relationship information to produce high precision and to recall values for detection. Floating peak and valleys of projection profiles are used to cut the license plates into individual characters. A turning function-based method is proposed to quickly and accurately recognize each character. It is further accelerated using curvature histogram-based support vector machine. The INFTY dataset is used to train the recognition system, and MediaLab license plate dataset is used for testing. The proposed system achieved 89.45% F-measure for detection and 87.33% accuracy for overall recognition rate which is comparable to current state-of-the-art systems.

75 FR 79049 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

... (RG) 5.80, ``Pressure-Sensitive and Tamper-Indicating Device Seals for Material Control and Accounting... and licenses. Regulatory Guide 5.80, ``Pressure-Sensitive and Tamper-Indicating Device Seals for... and Use of Pressure-Sensitive Seals on Containers for Onsite Storage of Special Nuclear Material...

77 FR 18871 - Administrative Guide for Verifying Compliance With Packaging Requirements for Shipment and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... Packaging Requirements for Shipment and Receipt of Radioactive Material AGENCY: Nuclear Regulatory... with Packaging Requirements for Shipment and Receipt of Radioactive Material.'' This regulatory guide... for transporting licensed material under 10 CFR part 71, ``Packaging and Transportation of Radioactive...

Full-field drift Hamiltonian particle orbits in 3D geometry

NASA Astrophysics Data System (ADS)

Cooper, W. A.; Graves, J. P.; Brunner, S.; Isaev, M. Yu

2011-02-01

A Hamiltonian/Lagrangian theory to describe guiding centre orbit drift motion which is canonical in the Boozer coordinate frame has been extended to include full electromagnetic perturbed fields in anisotropic pressure 3D equilibria with nested magnetic flux surfaces. A redefinition of the guiding centre velocity to eliminate the motion due to finite equilibrium radial magnetic fields and the choice of a gauge condition that sets the radial component of the electromagnetic vector potential to zero are invoked to guarantee that the Boozer angular coordinates retain the canonical structure. The canonical momenta are identified and the guiding centre particle radial drift motion and parallel gyroradius evolution are derived. The particle coordinate position is linearly modified by wave-particle interactions. All the nonlinear wave-wave interactions appear explicitly only in the evolution of the parallel gyroradius. The radial variation of the electrostatic potential is related to the binormal component of the displacement vector for MHD-type perturbations. The electromagnetic vector potential projections can then be determined from the electrostatic potential and the radial component of the MHD displacement vector.

Visualization of the energy flow for guided forward and backward waves in and around a fluid-loaded elastic cylindrical shell via the Poynting vector field

NASA Astrophysics Data System (ADS)

Dean, Cleon E.; Braselton, James P.

2004-05-01

Color-coded and vector-arrow grid representations of the Poynting vector field are used to show the energy flow in and around a fluid-loaded elastic cylindrical shell for both forward- and backward-propagating waves. The present work uses a method adapted from a simpler technique due to Kaduchak and Marston [G. Kaduchak and P. L. Marston, ``Traveling-wave decomposition of surface displacements associated with scattering by a cylindrical shell: Numerical evaluation displaying guided forward and backward wave properties,'' J. Acoust. Soc. Am. 98, 3501-3507 (1995)] to isolate unidirectional energy flows.

Inservice Training Seminar for the Driver Licensing Administrative Hearing Officer. Participant's Manual.

ERIC Educational Resources Information Center

National Highway Traffic Safety Administration (DOT), Washington, DC.

For use by trainees, this guide is the third of three designed for a two-day inservice training seminar for driver licensing administrative hearing officers. Participant's schedule information and materials are presented in three sections. The first includes the seminar agenda. Day 1 encompasses six units: (1) introduction, (2) the highway safety…

77 FR 31655 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-29

... controverted. In addition, the requestor/petitioner shall provide a brief explanation of the bases for the... against burst, as discussed in Regulatory Guide (RG) 1.121, ``Bases for Plugging Degraded PWR [Pressurized... Institute] 97-06, Revision 3, ``Steam Generator Program Guidelines'' (Reference 1) and RG 1.121, ``Bases for...

Compulsory licensing in Canada and Thailand: comparing regimes to ensure legitimate use of the WTO rules.

PubMed

Lybecker, Kristina M; Fowler, Elisabeth

2009-01-01

This paper examines two recent examples of compulsory licensing legislation: one globally embraced regime and one internationally controversial regime operating under the same WTO rules. In particular, we consider Canadian legislation and the use of compulsory licensing for HIV/AIDS drugs destined for a developing country. This is then contrasted with the conditions under which Thai authorities are pursuing compulsory licenses, the outcomes of their compulsory licenses, as well as the likely impact of the Thai policy. Finally, we construct a rubric to evaluate characteristics of a successful regime. This is used to analyze the Canadian and Thai regimes and frame the expected implications of each national policy. It is hoped that the assessment will guide changes to compulsory licensing design to ensure that legitimate regimes are embraced while illegitimate ones are disallowed.

BioCore Guide: A Tool for Interpreting the Core Concepts of Vision and Change for Biology Majors.

PubMed

Brownell, Sara E; Freeman, Scott; Wenderoth, Mary Pat; Crowe, Alison J

2014-01-01

Vision and Change in Undergraduate Biology Education outlined five core concepts intended to guide undergraduate biology education: 1) evolution; 2) structure and function; 3) information flow, exchange, and storage; 4) pathways and transformations of energy and matter; and 5) systems. We have taken these general recommendations and created a Vision and Change BioCore Guide-a set of general principles and specific statements that expand upon the core concepts, creating a framework that biology departments can use to align with the goals of Vision and Change. We used a grassroots approach to generate the BioCore Guide, beginning with faculty ideas as the basis for an iterative process that incorporated feedback from more than 240 biologists and biology educators at a diverse range of academic institutions throughout the United States. The final validation step in this process demonstrated strong national consensus, with more than 90% of respondents agreeing with the importance and scientific accuracy of the statements. It is our hope that the BioCore Guide will serve as an agent of change for biology departments as we move toward transforming undergraduate biology education. © 2014 S. E. Brownell et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

36 CFR 25.3 - Supervision; suspensions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Supervision; suspensions. 25.3 Section 25.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL MILITARY PARKS; LICENSED GUIDE SERVICE REGULATIONS § 25.3 Supervision; suspensions. (a) The guide...

36 CFR 25.3 - Supervision; suspensions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Supervision; suspensions. 25.3 Section 25.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL MILITARY PARKS; LICENSED GUIDE SERVICE REGULATIONS § 25.3 Supervision; suspensions. (a) The guide...

36 CFR 25.3 - Supervision; suspensions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Supervision; suspensions. 25.3 Section 25.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL MILITARY PARKS; LICENSED GUIDE SERVICE REGULATIONS § 25.3 Supervision; suspensions. (a) The guide...

36 CFR 25.3 - Supervision; suspensions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Supervision; suspensions. 25.3 Section 25.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL MILITARY PARKS; LICENSED GUIDE SERVICE REGULATIONS § 25.3 Supervision; suspensions. (a) The guide...

36 CFR 25.3 - Supervision; suspensions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Supervision; suspensions. 25.3 Section 25.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL MILITARY PARKS; LICENSED GUIDE SERVICE REGULATIONS § 25.3 Supervision; suspensions. (a) The guide...

The Case for a Smoker's License

PubMed Central

Chapman, Simon

2012-01-01

Background to the debate Tobacco continues to kill millions of people around the world each year and its use is increasing in some countries, which makes the need for new, creative, and radical efforts to achieve the tobacco control endgame vitally important. One such effort is discussed in this PLOS Medicine Debate, where Simon Chapman presents his proposal for a “smoker's license” and Jeff Collin argues against. Chapman sets out a case for introducing a smart card license for smokers designed to limit access to tobacco products and encourage cessation. Key elements of the smoker's license include smokers setting daily limits, financial incentives for permanent license surrender, and a test of health risk knowledge for commencing smokers. Collin argues against the proposal, saying that it would shift focus away from the real vector of the epidemic—the tobacco industry—and that by focusing on individuals it would censure victims, increase stigmatization of smokers, and marginalize the poor. PMID:23152726

Dengue and Chikungunya Vector Control Pocket Guide

USDA-ARS?s Scientific Manuscript database

This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

Cell-Penetrating Peptide-Mediated Delivery of Cas9 Protein and Guide RNA for Genome Editing.

PubMed

Suresh, Bharathi; Ramakrishna, Suresh; Kim, Hyongbum

2017-01-01

The clustered, regularly interspaced, short palindromic repeat (CRISPR)-associated (Cas) system represents an efficient tool for genome editing. It consists of two components: the Cas9 protein and a guide RNA. To date, delivery of these two components has been achieved using either plasmid or viral vectors or direct delivery of protein and RNA. Plasmid- and virus-free direct delivery of Cas9 protein and guide RNA has several advantages over the conventional plasmid-mediated approach. Direct delivery results in shorter exposure time at the cellular level, which in turn leads to lower toxicity and fewer off-target mutations with reduced host immune responses, whereas plasmid- or viral vector-mediated delivery can result in uncontrolled integration of the vector sequence into the host genome and unwanted immune responses. Cell-penetrating peptide (CPP), a peptide that has an intrinsic ability to translocate across cell membranes, has been adopted as a means of achieving efficient Cas9 protein and guide RNA delivery. We developed a method for treating human cell lines with CPP-conjugated recombinant Cas9 protein and CPP-complexed guide RNAs that leads to endogenous gene disruption. Here we describe a protocol for preparing an efficient CPP-conjugated recombinant Cas9 protein and CPP-complexed guide RNAs, as well as treatment methods to achieve safe genome editing in human cell lines.

INDUSTRIAL RADIOGRAPHY COURSE, INSTRUCTOR'S GUIDE, VOLUME 1.

ERIC Educational Resources Information Center

Texas A and M Univ., College Station. Engineering Extension Service.

THE PURPOSE OF THE GUIDE IS TO GIVE MAXIMUM ASSISTANCE TO INSTRUCTORS IN PLANNING THE TRAINING OF LICENSED INDUSTRIAL RADIOGRAPHERS. IT WAS DEVELOPED BY THE ENGINEERING EXTENSION SERVICE, TEXAS AGRICULTURAL AND MECHANICAL UNIVERSITY, COLLEGE STATION, TEXAS. THE 21 UNITS INCLUDE (1) INDUSTRIAL APPLICATIONS, (2) NONDESTRUCTIVE TESTING METHODS, (3)…

50 CFR 300.61 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the time period between the first deployment of fishing gear into the water from a vessel after any... who holds an annual sport guide license issued by the Alaska Department of Fish and Game, or a person who provides sport fishing guide services. Charter vessel operator, for purposes of § 300.65(d), means...

Magnetically enhanced adeno-associated viral vector delivery for human neural stem cell infection.

PubMed

Kim, Eunmi; Oh, Ji-Seon; Ahn, Ik-Sung; Park, Kook In; Jang, Jae-Hyung

2011-11-01

Gene therapy technology is a powerful tool to elucidate the molecular cues that precisely regulate stem cell fates, but developing safe vehicles or mechanisms that are capable of delivering genes to stem cells with high efficiency remains a challenge. In this study, we developed a magnetically guided adeno-associated virus (AAV) delivery system for gene delivery to human neural stem cells (hNSCs). Magnetically guided AAV delivery resulted in rapid accumulation of vectors on target cells followed by forced penetration of the vectors across the plasma membrane, ultimately leading to fast and efficient cellular transduction. To combine AAV vectors with the magnetically guided delivery, AAV was genetically modified to display hexa-histidine (6xHis) on the physically exposed loop of the AAV2 capsid (6xHis AAV), which interacted with nickel ions chelated on NTA-biotin conjugated to streptavidin-coated superparamagnetic iron oxide nanoparticles (NiStNPs). NiStNP-mediated 6xHis AAV delivery under magnetic fields led to significantly enhanced cellular transduction in a non-permissive cell type (i.e., hNSCs). In addition, this delivery method reduced the viral exposure times required to induce a high level of transduction by as much as to 2-10 min of hNSC infection, thus demonstrating the great potential of magnetically guided AAV delivery for numerous gene therapy and stem cell applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural damage detection using deep learning of ultrasonic guided waves

NASA Astrophysics Data System (ADS)

Melville, Joseph; Alguri, K. Supreet; Deemer, Chris; Harley, Joel B.

2018-04-01

Structural health monitoring using ultrasonic guided waves relies on accurate interpretation of guided wave propagation to distinguish damage state indicators. However, traditional physics based models do not provide an accurate representation, and classic data driven techniques, such as a support vector machine, are too simplistic to capture the complex nature of ultrasonic guide waves. To address this challenge, this paper uses a deep learning interpretation of ultrasonic guided waves to achieve fast, accurate, and automated structural damaged detection. To achieve this, full wavefield scans of thin metal plates are used, half from the undamaged state and half from the damaged state. This data is used to train our deep network to predict the damage state of a plate with 99.98% accuracy given signals from just 10 spatial locations on the plate, as compared to that of a support vector machine (SVM), which achieved a 62% accuracy.

Practical method for targeted disruption of cilia-related genes by using CRISPR/Cas9-mediated, homology-independent knock-in system.

PubMed

Katoh, Yohei; Michisaka, Saki; Nozaki, Shohei; Funabashi, Teruki; Hirano, Tomoaki; Takei, Ryota; Nakayama, Kazuhisa

2017-04-01

The CRISPR/Cas9 system has revolutionized genome editing in virtually all organisms. Although the CRISPR/Cas9 system enables the targeted cleavage of genomic DNA, its use for gene knock-in remains challenging because levels of homologous recombination activity vary among various cells. In contrast, the efficiency of homology-independent DNA repair is relatively high in most cell types. Therefore the use of a homology-independent repair mechanism is a possible alternative for efficient genome editing. Here we constructed a donor knock-in vector optimized for the CRISPR/Cas9 system and developed a practical system that enables efficient disruption of target genes by exploiting homology-independent repair. Using this practical knock-in system, we successfully disrupted genes encoding proteins involved in ciliary protein trafficking, including IFT88 and IFT20, in hTERT-RPE1 cells, which have low homologous recombination activity. The most critical concern using the CRISPR/Cas9 system is off-target cleavage. To reduce the off-target cleavage frequency and increase the versatility of our knock-in system, we constructed a universal donor vector and an expression vector containing Cas9 with enhanced specificity and tandem sgRNA expression cassettes. We demonstrated that the second version of our system has improved usability. © 2017 Katoh et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Guided Radiation Beams in Free Electron Lasers.

DTIC Science & Technology

1988-05-19

the electron beam in an FEL that the radiation beam will remain guided. 0 20 II. Refractive Index Associated with FELs In our model, the vector ...eIAw/ymOc(exp(ikwz) + c.c.) ex/2 , is the wiggle velocity, y is the Lorentz factor, Aw is the vector potential amplitude of the planar wiggler...Balboa Avenue Palo Alto, CA 94303 San Diego, CA 92123 38 Dr. S. Krinsky Nat. Synchrotron Light Source Dr. Michael Lavan Brookhaven National Laboratory U.S

9 CFR 117.5 - Segregation of animals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Segregation of animals. 117.5 Section 117.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.5 - Segregation of animals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Segregation of animals. 117.5 Section 117.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.3 - Admittance of animals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Admittance of animals. 117.3 Section 117.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.5 - Segregation of animals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Segregation of animals. 117.5 Section 117.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.3 - Admittance of animals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Admittance of animals. 117.3 Section 117.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.3 - Admittance of animals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Admittance of animals. 117.3 Section 117.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.5 - Segregation of animals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Segregation of animals. 117.5 Section 117.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.5 - Segregation of animals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Segregation of animals. 117.5 Section 117.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.3 - Admittance of animals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Admittance of animals. 117.3 Section 117.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

9 CFR 117.3 - Admittance of animals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Admittance of animals. 117.3 Section 117.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED...

From bench to almost bedside: the long road to a licensed Ebola virus vaccine.

PubMed

Wong, Gary; Mendoza, Emelissa J; Plummer, Francis A; Gao, George F; Kobinger, Gary P; Qiu, Xiangguo

2018-02-01

The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered: This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans. Expert opinion: Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics.

From bench to almost bedside: The long road to a licensed Ebola virus vaccine

PubMed Central

Wong, Gary; Mendoza, Emelissa J.; Plummer, Francis A.; Gao, George F.; Kobinger, Gary P.; Qiu, Xiangguo

2018-01-01

Introduction The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans. Expert opinion Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics. PMID:29148858

The Here, Now and Tomorrow of Cable Television in Education; A Planning Guide.

ERIC Educational Resources Information Center

Massachusetts Advisory Council on Education, Boston.

In order for the potential of cable television to be applied for educational benefit, educators must effectively communicate their priorities and needs to both licensing authorities and cable companies. This guide familiarizes educators and school committees with their options and prepares them to take part in local franchise negotiations. It…

What Is a Day's Work? A Personnel Practices Guide for Household Employees and Employers.

ERIC Educational Resources Information Center

Bowen, Uvelia S. A.

The guide presents the policies of the Household Employment Association for Reevaluation and Training (HEART) for upgrading the status of household employment. An overview is given of the association's methods of recruitment, training (in its licensed, private trade school), community education, job development, and post-placement counseling. The…

First Steps to Success. A Guide to Preparing Students for the Job Market.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY.

This guide, based on a survey of more than 100 New York City employers, lists the qualifications needed for 20 entry-level positions. The occupations profiled are as follows: bookkeeper, carpenter, child care worker, computer data entry/programmer, food service aide, home attendant, janitor/cleaner, legal assistant/paralegal, licensed practical…

Automation of the guiding center expansion

NASA Astrophysics Data System (ADS)

Burby, J. W.; Squire, J.; Qin, H.

2013-07-01

We report on the use of the recently developed Mathematica package VEST (Vector Einstein Summation Tools) to automatically derive the guiding center transformation. Our Mathematica code employs a recursive procedure to derive the transformation order-by-order. This procedure has several novel features. (1) It is designed to allow the user to easily explore the guiding center transformation's numerous non-unique forms or representations. (2) The procedure proceeds entirely in cartesian position and velocity coordinates, thereby producing manifestly gyrogauge invariant results; the commonly used perpendicular unit vector fields e1,e2 are never even introduced. (3) It is easy to apply in the derivation of higher-order contributions to the guiding center transformation without fear of human error. Our code therefore stands as a useful tool for exploring subtle issues related to the physics of toroidal momentum conservation in tokamaks.

Automation of The Guiding Center Expansion

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

J. W. Burby, J. Squire and H. Qin

2013-03-19

We report on the use of the recently-developed Mathematica package VEST (Vector Einstein Summation Tools) to automatically derive the guiding center transformation. Our Mathematica code employs a recursive procedure to derive the transformation order-by-order. This procedure has several novel features. (1) It is designed to allow the user to easily explore the guiding center transformation's numerous nonunique forms or representations. (2) The procedure proceeds entirely in cartesian position and velocity coordinates, thereby producing manifestly gyrogauge invariant results; the commonly-used perpendicular unit vector fields e1, e2 are never even introduced. (3) It is easy to apply in the derivation of higher-ordermore » contributions to the guiding center transformation without fear of human error. Our code therefore stands as a useful tool for exploring subtle issues related to the physics of toroidal momentum conservation in tokamaks« less

9 CFR 117.2 - Animal facilities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Animal facilities. 117.2 Section 117.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.2...

9 CFR 117.6 - Removal of animals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Removal of animals. 117.6 Section 117.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS...

9 CFR 117.4 - Test animals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Test animals. 117.4 Section 117.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.4...

9 CFR 117.2 - Animal facilities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Animal facilities. 117.2 Section 117.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.2...

9 CFR 117.2 - Animal facilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Animal facilities. 117.2 Section 117.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.2...

9 CFR 117.4 - Test animals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Test animals. 117.4 Section 117.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.4...

9 CFR 117.2 - Animal facilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Animal facilities. 117.2 Section 117.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.2...

9 CFR 117.6 - Removal of animals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Removal of animals. 117.6 Section 117.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS...

9 CFR 117.4 - Test animals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Test animals. 117.4 Section 117.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.4...

9 CFR 117.2 - Animal facilities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Animal facilities. 117.2 Section 117.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.2...

9 CFR 117.6 - Removal of animals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Removal of animals. 117.6 Section 117.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS...

9 CFR 117.6 - Removal of animals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Removal of animals. 117.6 Section 117.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS...

9 CFR 117.6 - Removal of animals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Removal of animals. 117.6 Section 117.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS...

76 FR 63309 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-12

.... Infectious Hepatitis E Virus Genotype 3 Recombinants--Prospective Vaccine Candidates and Vector System Description of Technology: Infection by Hepatitis E virus (HEV) is a relevant health issue in a number of... Platform-- Desired exogenous sequences can be inserted into the viral genome without inactivating the virus...

76 FR 59173 - Standard Format and Content of License Applications for Conventional Uranium Mills

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

...On May 30, 2008 (73 FR 31152), the U.S. Nuclear Regulatory Commission (NRC) published for public comment a notice of issuance and availability of Draft Regulatory Guide (DG)-3024, ``Standard Format and Content of License Applications for Conventional Uranium Mills.'' DG- 3024 was a proposed Revision 2 of Regulatory Guide (RG) 3.5. However, upon further consideration the NRC has decided not to revise RG 3.5 at this time. For this reason, DG-3024 will be withdrawn. The comment period closed on August 4, 2008, and 6 comments were received. The comments received will be considered and incorporated as appropriate if the NRC decides to revise RG 3.5 in the future.

Nuclear routing networks span between nuclear pore complexes and genomic DNA to guide nucleoplasmic trafficking of biomolecules

PubMed Central

Malecki, Marek; Malecki, Bianca

2012-01-01

In health and disease, biomolecules, which are involved in gene expression, recombination, or reprogramming have to traffic through the nucleoplasm, between nuclear pore complexes (NPCs) and genomic DNA (gDNA). This trafficking is guided by the recently revealed nuclear routing networks (NRNs). In this study, we aimed to investigate, if the NRNs have established associations with the genomic DNA in situ and if the NRNs have capabilities to bind the DNA de novo. Moreover, we aimed to study further, if nucleoplasmic trafficking of the histones, rRNA, and transgenes’ vectors, between the NPCs and gDNA, is guided by the NRNs. We used Xenopus laevis oocytes as the model system. We engineered the transgenes’ DNA vectors equipped with the SV40 LTA nuclear localization signals (NLS) and/or HIV Rev nuclear export signals (NES). We purified histones, 5S rRNA, and gDNA. We rendered all these molecules superparamagnetic and fluorescent for detection with nuclear magnetic resonance (NMR), total reflection x-ray fluorescence (TXRF), energy dispersive x-ray spectroscopy (EDXS), and electron energy loss spectroscopy (EELS). The NRNs span between the NPCs and genomic DNA. They form firm bonds with the gDNA in situ. After complete digestion of the nucleic acids with the RNases and DNases, the newly added DNA - modified with the dNTP analogs, bonds firmly to the NRNs. Moreover, the NRNs guide the trafficking of the DNA transgenes’ vectors - modified with the SV40 LTA NLS, following their import into the nuclei through the NPCs. The pathway is identical to that of histones. The NRNs also guide the trafficking of the DNA transgenes’ vectors, modified with the HIV Rev NES, to the NPCs, followed by their export out of the nuclei. Ribosomal RNAs follow the same pathway. To summarize, the NRNs are the structures connecting the NPCs and the gDNA. They guide the trafficking of the biomolecules between the NPCs and the gDNA. PMID:23275893

77 FR 69866 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-21

... for Diabetes and Obesity Description of Technology: This invention is directed to adeno- associated virus (AAV) vector delivery of exendin-4 (Ex-4) to salivary glands as treatment for diabetes and obesity... and weight profile in two rat models of obesity and type 2 diabetes. Further, AAV-mediated delivery of...

The use of NUREGs 1199 and 1200 in the Illinois LLW licensing program

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

Klinger, J.G.; Harmon, D.F.

1991-12-31

This paper will describe how the LLW licensing staff of the Illinois Department of Nuclear Safety used NRC`s NUREG 1199, NUREG 1200, NUREG 1300 and Regulatory Guide 4.18 in its licensing program for reviewing and evaluating a LLW disposal facility license application. The paper will discuss how Illinois guidance documents were prepared based on modifications made to these NRC documents which were necessary to take into account site and facility specific considerations, as well as changes required by Illinois statutes and regulatory codes. The paper will review the recent revisions (January 1991) to NUREG 1199 and 1200 and the importancemore » of these revisions. The paper will also discuss recommended modifications to these NRC documents and provide an update on the status of the Department`s review and evaluation of an application for a license to site, construct and operate a LLW disposal facility in Illinois.« less

Automation of the guiding center expansion

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

Burby, J. W.; Squire, J.; Qin, H.

2013-07-15

We report on the use of the recently developed Mathematica package VEST (Vector Einstein Summation Tools) to automatically derive the guiding center transformation. Our Mathematica code employs a recursive procedure to derive the transformation order-by-order. This procedure has several novel features. (1) It is designed to allow the user to easily explore the guiding center transformation's numerous non-unique forms or representations. (2) The procedure proceeds entirely in cartesian position and velocity coordinates, thereby producing manifestly gyrogauge invariant results; the commonly used perpendicular unit vector fields e{sub 1},e{sub 2} are never even introduced. (3) It is easy to apply in themore » derivation of higher-order contributions to the guiding center transformation without fear of human error. Our code therefore stands as a useful tool for exploring subtle issues related to the physics of toroidal momentum conservation in tokamaks.« less

A novel double fine guide sensor design on space telescope

NASA Astrophysics Data System (ADS)

Zhang, Xu-xu; Yin, Da-yi

2018-02-01

To get high precision attitude for space telescope, a double marginal FOV (field of view) FGS (Fine Guide Sensor) is proposed. It is composed of two large area APS CMOS sensors and both share the same lens in main light of sight. More star vectors can be get by two FGS and be used for high precision attitude determination. To improve star identification speed, the vector cross product in inter-star angles for small marginal FOV different from traditional way is elaborated and parallel processing method is applied to pyramid algorithm. The star vectors from two sensors are then used to attitude fusion with traditional QUEST algorithm. The simulation results show that the system can get high accuracy three axis attitudes and the scheme is feasibility.

36 CFR 25.1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and published for the regulation and maintenance of licensed guide service at all national military... Secretary of the Interior upon the recommendation of the Director of the National Park Service. ...

COL Application Content Guide for HTGRs: Revision to RG 1.206, Part 1 - Status Report

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

Wayne Moe

2012-08-01

A combined license (COL) application is required by the Nuclear Regulatory Commission (NRC) for all proposed nuclear plants. The information requirements for a COL application are set forth in 10 CFR 52.79, “Contents of Applications; Technical Information in Final Safety Analysis Report.” An applicant for a modular high temperature gas-cooled reactor (HTGR) must develop and submit for NRC review and approval a COL application which conforms to these requirements. The technical information necessary to allow NRC staff to evaluate a COL application and resolve all safety issues related to a proposed nuclear plant is detailed and comprehensive. To this, Regulatorymore » Guide (RG) 1.206, “Combined License Applications for Nuclear Power Plants” (LWR Edition), was developed to assist light water reactor (LWR) applicants in incorporating and effectively formatting required information for COL application review (Ref. 1). However, the guidance prescribed in RG 1.206 presumes a LWR design proposal consistent with the systems and functions associated with large LWR power plants currently operating under NRC license.« less

Reverse chemical ecology approach for the identification of a mosquito oviposition attractant

USDA-ARS?s Scientific Manuscript database

Pheromones and other semiochemicals play a crucial role in today’s integrated pest and vector management strategies for controlling populations of insects causing loses to agriculture and vectoring diseases to humans. These semiochemicals are typically discovered by bioassay-guided approaches. Here,...

Practical Nursing Curriculum Guide. Including the Expanded Functions of I.V. Therapy and LPN Management. Invest in Success.

ERIC Educational Resources Information Center

Idaho State Dept. of Education, Boise. Div. of Vocational Education.

Under the Idaho state system for curriculum development in vocational education, Technical Committees made up solely of industry personnel are responsible for drawing up task lists for each program. The first part of this guide contains a curriculum for instruction of practical nurses who are eligible to sit for the license examination upon…

10 CFR Appendix C to Part 50 - A Guide for the Financial Data and Related Information Required To Establish Financial...

Code of Federal Regulations, 2012 CFR

2012-01-01

... Required To Establish Financial Qualifications for Construction Permits and Combined Licenses C Appendix C... FACILITIES Pt. 50, App. C Appendix C to Part 50—A Guide for the Financial Data and Related Information... production plant costs $ (b) Transmission, distribution, and general plant costs $ (c) Nuclear fuel inventory...

Dark-bright soliton pairs in nonlocal nonlinear media.

PubMed

Lin, Yuan Yao; Lee, Ray-Kuang

2007-07-09

We study the formation of dark-bright vector soliton pairs in nonlocal Kerr-type nonlinear medium. We show, by analytical analysis and direct numerical calculation, that in addition to stabilize of vector soliton pairs nonlocal nonlinearity also helps to reduce the threshold power for forming a guided bright soliton. With help of the nonlocality, it is expected that the observation of dark-bright vector soliton pairs in experiments becomes more workable.

Insecticide Resistance Management

DTIC Science & Technology

2013-01-01

been a side effect of insect vector control programs since 1914, and insect disease vectors in over 45 countries are resistant to at least one...the CDC and WHO bioassays can be performed on various insects , the remainder of the guide will focus specifically on how to detect resistance in...mosquito vector populations. For a description of how to develop a bioassay for resistance testing in other groups of insects , refer to the following

AAV viral vector delivery to the brain by shape-conforming MR-guided infusions.

PubMed

Bankiewicz, Krystof S; Sudhakar, Vivek; Samaranch, Lluis; San Sebastian, Waldy; Bringas, John; Forsayeth, John

2016-10-28

Gene transfer technology offers great promise as a potential therapeutic approach to the brain but has to be viewed as a very complex technology. Success of ongoing clinical gene therapy trials depends on many factors such as selection of the correct genetic and anatomical target in the brain. In addition, selection of the viral vector capable of transfer of therapeutic gene into target cells, along with long-term expression that avoids immunotoxicity has to be established. As with any drug development strategy, delivery of gene therapy has to be consistent and predictable in each study subject. Failed drug and vector delivery will lead to failed clinical trials. In this article, we describe our experience with AAV viral vector delivery system, that allows us to optimize and monitor in real time viral vector administration into affected regions of the brain. In addition to discussing MRI-guided technology for administration of AAV vectors we have developed and now employ in current clinical trials, we also describe ways in which infusion cannula design and stereotactic trajectory may be used to maximize the anatomical coverage by using fluid backflow. This innovative approach enables more precise coverage by fitting the shape of the infusion to the shape of the anatomical target. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of an acid-resistant Salmonella Typhi Ty21a attenuated vector for improved oral vaccine delivery

USDA-ARS?s Scientific Manuscript database

The licensed oral, live-attenuated bacterial vaccine for typhoid fever, Salmonella Typhi strain Ty21a, has also been utilized as a vaccine delivery platform for expression of diverse foreign antigens that stimulate protection against shigellosis, anthrax, plague, or human papilloma virus. However, T...

Gene Therapy Vector for the Treatment of Glycogen Storage Disease Type Ia (GSD-Ia) | NCI Technology Transfer Center | TTC

Cancer.gov

GSD-Ia is an inherited disorder of metabolism associated with life-threatening hypoglycemia, hepatic malignancy, and renal failure caused by the deficiency of glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC). NICHD seeks parties to license this invention towards commercialization.

A Neurocomputational Model of Goal-Directed Navigation in Insect-Inspired Artificial Agents

PubMed Central

Goldschmidt, Dennis; Manoonpong, Poramate; Dasgupta, Sakyasingha

2017-01-01

Despite their small size, insect brains are able to produce robust and efficient navigation in complex environments. Specifically in social insects, such as ants and bees, these navigational capabilities are guided by orientation directing vectors generated by a process called path integration. During this process, they integrate compass and odometric cues to estimate their current location as a vector, called the home vector for guiding them back home on a straight path. They further acquire and retrieve path integration-based vector memories globally to the nest or based on visual landmarks. Although existing computational models reproduced similar behaviors, a neurocomputational model of vector navigation including the acquisition of vector representations has not been described before. Here we present a model of neural mechanisms in a modular closed-loop control—enabling vector navigation in artificial agents. The model consists of a path integration mechanism, reward-modulated global learning, random search, and action selection. The path integration mechanism integrates compass and odometric cues to compute a vectorial representation of the agent's current location as neural activity patterns in circular arrays. A reward-modulated learning rule enables the acquisition of vector memories by associating the local food reward with the path integration state. A motor output is computed based on the combination of vector memories and random exploration. In simulation, we show that the neural mechanisms enable robust homing and localization, even in the presence of external sensory noise. The proposed learning rules lead to goal-directed navigation and route formation performed under realistic conditions. Consequently, we provide a novel approach for vector learning and navigation in a simulated, situated agent linking behavioral observations to their possible underlying neural substrates. PMID:28446872

A Neurocomputational Model of Goal-Directed Navigation in Insect-Inspired Artificial Agents.

PubMed

Goldschmidt, Dennis; Manoonpong, Poramate; Dasgupta, Sakyasingha

2017-01-01

Despite their small size, insect brains are able to produce robust and efficient navigation in complex environments. Specifically in social insects, such as ants and bees, these navigational capabilities are guided by orientation directing vectors generated by a process called path integration. During this process, they integrate compass and odometric cues to estimate their current location as a vector, called the home vector for guiding them back home on a straight path. They further acquire and retrieve path integration-based vector memories globally to the nest or based on visual landmarks. Although existing computational models reproduced similar behaviors, a neurocomputational model of vector navigation including the acquisition of vector representations has not been described before. Here we present a model of neural mechanisms in a modular closed-loop control-enabling vector navigation in artificial agents. The model consists of a path integration mechanism, reward-modulated global learning, random search, and action selection. The path integration mechanism integrates compass and odometric cues to compute a vectorial representation of the agent's current location as neural activity patterns in circular arrays. A reward-modulated learning rule enables the acquisition of vector memories by associating the local food reward with the path integration state. A motor output is computed based on the combination of vector memories and random exploration. In simulation, we show that the neural mechanisms enable robust homing and localization, even in the presence of external sensory noise. The proposed learning rules lead to goal-directed navigation and route formation performed under realistic conditions. Consequently, we provide a novel approach for vector learning and navigation in a simulated, situated agent linking behavioral observations to their possible underlying neural substrates.

Experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses

PubMed Central

Mooney, Alaina J; Tompkins, S Mark

2013-01-01

Influenza A viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. While the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. Thus, there is need of improved influenza vaccines and vaccination strategies. This review discusses advances in alternative influenza vaccines, touching briefly on licensed vaccines and vaccine antigens; then reviewing recombinant subunit vaccines, virus-like particle vaccines and DNA vaccines, with the main focus on virus-vectored vaccine approaches. PMID:23440999

14 CFR 171.11 - Maintenance and operations requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Communications Commission's licensing requirements and show that he has the special knowledge and skills needed... maintenance procedures and servicing guides stating the frequency of servicing. (8) Air-ground communications...

14 CFR 171.11 - Maintenance and operations requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Communications Commission's licensing requirements and show that he has the special knowledge and skills needed... maintenance procedures and servicing guides stating the frequency of servicing. (8) Air-ground communications...

14 CFR 171.11 - Maintenance and operations requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Communications Commission's licensing requirements and show that he has the special knowledge and skills needed... maintenance procedures and servicing guides stating the frequency of servicing. (8) Air-ground communications...

Evaluation of the Efficacy, Potential for Vector Transmission, and Duration of Immunity of MP-12, an Attenuated Rift Valley Fever Virus Vaccine Candidate, in Sheep

PubMed Central

Bennett, Kristine E.; Drolet, Barbara S.; Lindsay, Robbin; Mecham, James O.; Reeves, Will K.; Weingartl, Hana M.; Wilson, William C.

2015-01-01

Rift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. In North America, there are susceptible ruminant hosts and competent mosquito vectors, yet there are no fully licensed animal vaccines for this arthropod-borne virus, should it be introduced. Studies in sheep and cattle have found the attenuated strain of RVFV, MP-12, to be both safe and efficacious based on early testing, and a 2-year conditional license for use in U.S. livestock has been issued. The purpose of this study was to further determine the vaccine's potential to infect mosquitoes, the duration of humoral immunity to 24 months postvaccination, and the ability to prevent disease and viremia from a virulent challenge. Vaccination experiments conducted in sheep found no evidence of a potential for vector transmission to 4 North American mosquito species. Neutralizing antibodies were elicited, with titers of >1:40 still present at 24 months postvaccination. Vaccinates were protected from clinical signs and detectable viremia after challenge with virulent virus, while control sheep had fever and high-titered viremia extending for 5 days. Antibodies to three viral proteins (nucleocapsid N, the N-terminal half of glycoprotein GN, and the nonstructural protein from the short segment NSs) were also detected to 24 months using competitive enzyme-linked immunosorbent assays. This study demonstrates that the MP-12 vaccine given as a single dose in sheep generates protective immunity to a virulent challenge with antibody duration of at least 2 years, with no evidence of a risk for vector transmission. PMID:26041042

United States Air Force Guide to Operational Surveillance of Medically Important Vectors and Pests Operational Entomology

DTIC Science & Technology

2006-08-15

Programs Section 3. Sampling Equipment Sampling Equipment Solid-State Army Miniature (SSAM) trap ABC style trap Encephalitis Vector Survey Trap CDC...Baseline Survey - these are conducted to determine the types of vectors and pests occurring in the area of operations, their respective breeding sites...or source habitat, and seasonal activity patterns. Operational Survey - data collected in an operational survey are used specifically to aid pest

Targeted genome editing in a quail cell line using a customized CRISPR/Cas9 system.

PubMed

Ahn, Jinsoo; Lee, Joonbum; Park, Ju Yeon; Oh, Keon Bong; Hwang, Seongsoo; Lee, Chang-Won; Lee, Kichoon

2017-05-01

Soon after RNA-guided Cas9 (CRISPR-associated protein 9) endonuclease opened a new era of targeted genome editing, the CRISPR/Cas9 platform began to be extensively used to modify genes in various types of cells and organisms. However, successful CRISPR/Cas9-mediated insertion/deletion (indel) mutation remains to be demonstrated in avian cell lines. The objective of this study was to design a poultry-specific CRISPR/Cas9 system to efficiently introduce targeted deletion mutation in chromosomes of the quail muscle clone 7 (QM7) cell line using a customized quail CRISPR vector. In this study, two avian-specific promoters, quail 7SK (q7SK) promoter and CBh promoter, the hybrid form of cytomegalovirus and chicken β-actin promoters, were cloned into a CRISPR vector for the expression of guide RNA and Cas9 protein, respectively. Then, guide RNA, which was designed to target 20-base pair (bp) nucleotides in the quail melanophilin (MLPH) locus, was ligated to the modified CRISPR vector and transfected to QM7 cells. Our results showed multiple indel mutations in the quail MLPH locus in nearly half of the alleles being tested, suggesting the high efficiency of the system for targeted gene modification. The new CRISPR vector developed from this study has the potential application to generate knockout avian cell lines and knockout poultry. © 2016 Poultry Science Association Inc.

Spin wave filtering and guiding in Permalloy/iron nanowires

NASA Astrophysics Data System (ADS)

Silvani, R.; Kostylev, M.; Adeyeye, A. O.; Gubbiotti, G.

2018-03-01

We have investigated the spin wave filtering and guiding properties of periodic array of single (Permalloy and Fe) and bi-layer (Py/Fe) nanowires (NWs) by means of Brillouin light scattering measurements and micromagnetic simulations. For all the nanowire arrays, the thickness of the layers is 10 nm while all NWs have the same width of 340 nm and edge-to-edge separation of 100 nm. Spin wave dispersion has been measured in the Damon-Eshbach configuration for wave vector either parallel or perpendicular to the nanowire length. This study reveals the filtering property of the spin waves when the wave vector is perpendicular to the NW length, with frequency ranges where the spin wave propagation is permitted separated by frequency band gaps, and the guiding property of NW when the wave vector is oriented parallel to the NW, with spin wave modes propagating in parallel channels in the central and edge regions of the NW. The measured dispersions were well reproduced by micromagnetic simulations, which also deliver the spatial profiles for the modes at zero wave vector. To reproduce the dispersion of the modes localized close to the NW edges, uniaxial anisotropy has been introduced. In the case of Permalloy/iron NWs, the obtained results have been compared with those for a 20 nm thick effective NW having average magnetic properties of the two materials.

HAL/S programmer's guide. [space shuttle flight software language

NASA Technical Reports Server (NTRS)

Newbold, P. M.; Hotz, R. L.

1974-01-01

HAL/S is a programming language developed to satisfy the flight software requirements for the space shuttle program. The user's guide explains pertinent language operating procedures and described the various HAL/S facilities for manipulating integer, scalar, vector, and matrix data types.

The Environmental Assessment and Management (TEAM) Guide: Mississippi Supplement

DTIC Science & Technology

2010-03-01

4 The Environmental Assessment and Management (TEAM) Guide: Mississippi Supplement C on st ru ct io n E n gi...resins manufacturing 10. pulp and paper industry 11. rubber and miscellaneous paper products 12. stone, glass, clay, and concrete products 13...contaminant risk assessment of the material. 4 . The registrant of the by-product must have the certification of a professional engineer licensed in

75 FR 22674 - U.S. Department of State Advisory Committee on Private International Law Study Group Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... Intellectual Property (IP) The Department of State, Office of the Legal Adviser, Private International Law and... rights in intellectual property, as well as possible future work in UNCITRAL on an IP licensing guide.../689), as well as the draft text of the IP supplement to the Guide (A/CN.9/700 and Add. 1-7) that will...

75 FR 28663 - Government-Owned Inventions, Available for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... Crack Arresting Barrier. NASA Case No. MFS-32605-1-CIP: Neutron Guides and Methods of Fabrication. NASA...-32697-1: Friction Modifier Using Adherent Metallic Multilayered or Mixed Element Layer Conversion...

A review of the vector management methods to prevent and control outbreaks of West Nile virus infection and the challenge for Europe

PubMed Central

2014-01-01

West Nile virus infection is a growing concern in Europe. Vector management is often the primary option to prevent and control outbreaks of the disease. Its implementation is, however, complex and needs to be supported by integrated multidisciplinary surveillance systems and to be organized within the framework of predefined response plans. The impact of the vector control measures depends on multiple factors and the identification of the best combination of vector control methods is therefore not always straightforward. Therefore, this contribution aims at critically reviewing the existing vector control methods to prevent and control outbreaks of West Nile virus infection and to present the challenges for Europe. Most West Nile virus vector control experiences have been recently developed in the US, where ecological conditions are different from the EU and vector control is organized under a different regulatory frame. The extrapolation of information produced in North America to Europe might be limited because of the seemingly different epidemiology in the European region. Therefore, there is an urgent need to analyse the European experiences of the prevention and control of outbreaks of West Nile virus infection and to perform robust cost-benefit analysis that can guide the implementation of the appropriate control measures. Furthermore, to be effective, vector control programs require a strong organisational backbone relying on a previously defined plan, skilled technicians and operators, appropriate equipment, and sufficient financial resources. A decision making guide scheme is proposed which may assist in the process of implementation of vector control measures tailored on specific areas and considering the available information and possible scenarios. PMID:25015004

Driver fitness medical guidelines.

DOT National Transportation Integrated Search

2009-09-01

This guide provides guidance to assist licensing agencies in making decisions about an individuals fitness for driving. This is the first attempt to produce a consolidated document covering medical conditions included in the task agreement between...

Geothermal : A Regulatory Guide to Leasing, Permitting, and Licensing in Idaho, Montana, Oregon, and Washington.

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

Bloomquist, R.Gordon

1991-10-01

The actual geothermal exploration and development may appear to be a simple and straightforward process in comparison to the legal and institutional maze which the developer must navigate in order to obtain all of the federal, state, and local leases, permits, licenses, and approvals necessary at each step in the process. Finally, and often most difficult, is obtaining a contract for the sale of thermal energy, brine, steam, or electricity. This guide is designed to help developers interested in developing geothermal resource sites in the Bonneville Power Administration Service Territory in the state of Idaho, Montana, Oregon, and Washington bettermore » understand the federal, state, and local institutional process, the roles and responsibilities of each agency, and how and when to make contact in order to obtain the necessary documents.« less

A recombinant Rift Valley fever virus glycoprotein subunit vaccine confers full protection against Rift Valley fever challenge in sheep

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suita...

Dengue and Chikungunya Vector Control Pocket Guide

DTIC Science & Technology

2012-01-27

Aedes aegypti readily bites people indoors and will rest on wall surfaces after taking a...countries are areas where dengue risk is well known. Aedes aegypti , Ae. albopictus and Ae. polynesiensis are three mosquito species that are...vectors of dengue. Aedes aegypti accounts for >95% of all cases worldwide. During deployments, all three species must be

The influence of learning on host plant preference in a significant phytopathogen vector, Diaphorina citri

USDA-ARS?s Scientific Manuscript database

Although specialist herbivorous insects are guided by innate responses to host plant cues, host plant preference may be influenced by experience and is not dictated by instinct alone. The effect of learning on host plant preference was examined in the Asian citrus psyllid, Diaphorina citri, vector ...

76 FR 66090 - Facility Operating License Amendment From Virginia Electric and Power Company, Surry Power...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... operating pressures, leakage from primary water stress corrosion cracking below the proposed limited... discussed in Regulatory Guide (RG) 1.121, ``Bases for Plugging Degraded PWR [Pressurized-Water Reactor...

SapTrap, a Toolkit for High-Throughput CRISPR/Cas9 Gene Modification in Caenorhabditis elegans.

PubMed

Schwartz, Matthew L; Jorgensen, Erik M

2016-04-01

In principle, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 allows genetic tags to be inserted at any locus. However, throughput is limited by the laborious construction of repair templates and guide RNA constructs and by the identification of modified strains. We have developed a reagent toolkit and plasmid assembly pipeline, called "SapTrap," that streamlines the production of targeting vectors for tag insertion, as well as the selection of modified Caenorhabditis elegans strains. SapTrap is a high-efficiency modular plasmid assembly pipeline that produces single plasmid targeting vectors, each of which encodes both a guide RNA transcript and a repair template for a particular tagging event. The plasmid is generated in a single tube by cutting modular components with the restriction enzyme SapI, which are then "trapped" in a fixed order by ligation to generate the targeting vector. A library of donor plasmids supplies a variety of protein tags, a selectable marker, and regulatory sequences that allow cell-specific tagging at either the N or the C termini. All site-specific sequences, such as guide RNA targeting sequences and homology arms, are supplied as annealed synthetic oligonucleotides, eliminating the need for PCR or molecular cloning during plasmid assembly. Each tag includes an embedded Cbr-unc-119 selectable marker that is positioned to allow concurrent expression of both the tag and the marker. We demonstrate that SapTrap targeting vectors direct insertion of 3- to 4-kb tags at six different loci in 10-37% of injected animals. Thus SapTrap vectors introduce the possibility for high-throughput generation of CRISPR/Cas9 genome modifications. Copyright © 2016 by the Genetics Society of America.

Interim Terrain Data (ITD) and Vector Product Interim Terrain Data (VITD) user's guide

DOT National Transportation Integrated Search

1996-09-01

This guide is intended to be a convenient reference for users of these types of terrain analysis data. ITD is a digitized version of the standard 1:50,000-scale tactical terrain analysis data base (TTADB) product produced by the Defense Mapping Agenc...

Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS): Phase 1 Test and Evaluation Development Guide

DTIC Science & Technology

2014-11-01

Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS): Phase 1 Test and Evaluation Development Guide Craig...Self-initiated sensemaking ........................................................................................... 19 Feature Vector Format: Tasks...The Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS) Program aimed to build computational cognitive

Chiropractic Handbook.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Office of the Professions.

This reference guide contains laws, regulations, and licensing requirements and procedures governing chiropractic practice in New York State. Following a general introduction to professional regulation in New York State, licensure requirements are spelled out in detail, including general requirements, education requirements, examination…

What Is Technology Transfer? | Poster

Cancer.gov

The NCI Technology Transfer Center (TTC) facilitates partnerships between NIH research laboratories and external partners. With a team of technology transfer specialists, NCI TTC guides interactions from discovery to patenting, as well as from collaboration and invention development to licensing.

75 FR 32834 - U.S. Department of State Advisory Committee on Private International Law Study Group Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-09

... Intellectual Property (IP) The Department of State, Office of the Legal Adviser, Private International Law and... IP licensing guide. The meeting will take place on Thursday, June 17, 2010 from 2:30 p.m. to 4 p.m... in New York (A/CN.9/689), as well as the draft text of the IP supplement to the Guide (A/CN.9/700 and...

Guided imagery and distraction therapy in paediatric hospice care.

PubMed

Russell, Carol; Smart, Susan

2007-03-01

Available evidence indicates deficits in the pain management of children with analgesic drugs used outside licensed boundaries, in situations where their pharmacokinetics are untested. A case series is used to demonstrate the effectiveness of more holistic techniques such as guided imagery and distraction therapy in reducing the pain experienced by children in the hospice setting. Using these techniques it may be possible to reduce the amount of analgesia or the frequency of administration.

On sufficient statistics of least-squares superposition of vector sets.

PubMed

Konagurthu, Arun S; Kasarapu, Parthan; Allison, Lloyd; Collier, James H; Lesk, Arthur M

2015-06-01

The problem of superposition of two corresponding vector sets by minimizing their sum-of-squares error under orthogonal transformation is a fundamental task in many areas of science, notably structural molecular biology. This problem can be solved exactly using an algorithm whose time complexity grows linearly with the number of correspondences. This efficient solution has facilitated the widespread use of the superposition task, particularly in studies involving macromolecular structures. This article formally derives a set of sufficient statistics for the least-squares superposition problem. These statistics are additive. This permits a highly efficient (constant time) computation of superpositions (and sufficient statistics) of vector sets that are composed from its constituent vector sets under addition or deletion operation, where the sufficient statistics of the constituent sets are already known (that is, the constituent vector sets have been previously superposed). This results in a drastic improvement in the run time of the methods that commonly superpose vector sets under addition or deletion operations, where previously these operations were carried out ab initio (ignoring the sufficient statistics). We experimentally demonstrate the improvement our work offers in the context of protein structural alignment programs that assemble a reliable structural alignment from well-fitting (substructural) fragment pairs. A C++ library for this task is available online under an open-source license.

Current status, challenges and perspectives in the development of vaccines against yellow fever, dengue, Zika and chikungunya viruses.

PubMed

Silva, José V J; Lopes, Thaísa R R; Oliveira-Filho, Edmilson F de; Oliveira, Renato A S; Durães-Carvalho, Ricardo; Gil, Laura H V G

2018-06-01

Emerging and re-emerging viral infections transmitted by insect vectors (arthopode-borne viruses, arbovirus) are a serious threat to global public health. Among them, yellow fever (YFV), dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses are particularly important in tropical and subtropical regions. Although vector control is one of the most used prophylactic measures against arboviruses, it often faces obstacles, such as vector diversity, uncontrolled urbanization and increasing resistance to insecticides. In this context, vaccines may be the best control strategy for arboviral diseases. Here, we provide a general overview about licensed vaccines and the most advanced vaccine candidates against YFV, DENV, CHIKV and ZIKV. In particular, we highlight vaccine difficulties, the current status of the most advanced strategies and discuss how the molecular characteristics of each virus can influence the choice of the different vaccine formulations. Copyright © 2018 Elsevier B.V. All rights reserved.

Topography-Guided Transepithelial Surface Ablation in the Treatment of Moderate to High Astigmatism.

PubMed

Chen, Xiangjun; Stojanovic, Aleksandar; Simonsen, David; Wang, Xiaorui; Liu, Yanhua; Utheim, Tor Paaske

2016-06-01

To analyze the outcomes of treatment of astigmatism of 2.00 diopters (D) or greater with topography-guided transepithelial surface ablation. Retrospective analysis of a series of 206 eyes divided into two groups: myopic astigmatism (153 eyes) and mixed astigmatism (53 eyes). All cases were treated with topography-guided transepithelial surface ablation. Efficacy, safety, and predictability were evaluated, and vector analysis of cylindrical correction was performed. The median preoperative spherical equivalent was -2.63 and -0.63 D for the myopic and mixed astigmatism groups, respectively, with median cylinder of -2.50 D. Postoperative uncorrected distance visual acuity was 20/20 or better in 92% and 83% of eyes in the myopic and mixed astigmatism groups, respectively; the corresponding efficacy indices were 1.00 and 0.96 and residual astigmatism of 0.50 D or less was present in 82.4% and 56.7% of eyes in the myopic and mixed astigmatism groups, respectively. The arithmetic mean magnitude of the difference vector was 0.38 (myopic) and 0.65 (mixed) D. Difference vector magnitude was positively correlated with the magnitude of target induced astigmatism in both groups. The geometric mean coefficient of adjustment index was 1.04 and 1.19, representing undercorrection of 4% and 19% in the myopic and mixed astigmatism groups, respectively. Topography-guided transepithelial ablation is a safe, effective, and predictable treatment for moderate to high astigmatism. [J Refract Surg. 2016;32(6):418-425.]. Copyright 2016, SLACK Incorporated.

Design of single-polarization wavelength splitter based on photonic crystal fiber.

PubMed

Zhang, Shanshan; Zhang, Weigang; Geng, Pengcheng; Li, Xiaolan; Ruan, Juan

2011-12-20

A new single-polarization wavelength splitter based on the photonic crystal fiber (PCF) has been proposed. The full-vector finite-element method (FEM) is applied to analyze the single-polarization single-mode guiding properties. Splitting of two different wavelengths is realized by adjusting the structural parameters. The semi-vector three-dimensional beam propagation method is employed to confirm the wavelength splitting characteristics of the PCF. Numerical simulations show that the wavelengths of 1.3 μm and 1.55 μm are split for a fiber length of 10.7 mm with single-polarization guiding in each core. The crosstalk between the two cores is low over appreciable optical bandwidths.

Guiding automated left ventricular chamber segmentation in cardiac imaging using the concept of conserved myocardial volume.

PubMed

Garson, Christopher D; Li, Bing; Acton, Scott T; Hossack, John A

2008-06-01

The active surface technique using gradient vector flow allows semi-automated segmentation of ventricular borders. The accuracy of the algorithm depends on the optimal selection of several key parameters. We investigated the use of conservation of myocardial volume for quantitative assessment of each of these parameters using synthetic and in vivo data. We predicted that for a given set of model parameters, strong conservation of volume would correlate with accurate segmentation. The metric was most useful when applied to the gradient vector field weighting and temporal step-size parameters, but less effective in guiding an optimal choice of the active surface tension and rigidity parameters.

A method of vehicle license plate recognition based on PCANet and compressive sensing

NASA Astrophysics Data System (ADS)

Ye, Xianyi; Min, Feng

2018-03-01

The manual feature extraction of the traditional method for vehicle license plates has no good robustness to change in diversity. And the high feature dimension that is extracted with Principal Component Analysis Network (PCANet) leads to low classification efficiency. For solving these problems, a method of vehicle license plate recognition based on PCANet and compressive sensing is proposed. First, PCANet is used to extract the feature from the images of characters. And then, the sparse measurement matrix which is a very sparse matrix and consistent with Restricted Isometry Property (RIP) condition of the compressed sensing is used to reduce the dimensions of extracted features. Finally, the Support Vector Machine (SVM) is used to train and recognize the features whose dimension has been reduced. Experimental results demonstrate that the proposed method has better performance than Convolutional Neural Network (CNN) in the recognition and time. Compared with no compression sensing, the proposed method has lower feature dimension for the increase of efficiency.

Improved Prefusion Stability, Optimized Codon Usage, and Augmented Virion Packaging Enhance the Immunogenicity of Respiratory Syncytial Virus Fusion Protein in a Vectored-Vaccine Candidate

PubMed Central

Liang, Bo; Ngwuta, Joan O.; Surman, Sonja; Kabatova, Barbora; Liu, Xiang; Lingemann, Matthias; Liu, Xueqiao; Yang, Lijuan; Herbert, Richard; Swerczek, Joanna; Chen, Man; Moin, Syed M.; Kumar, Azad; McLellan, Jason S.; Kwong, Peter D.; Graham, Barney S.; Collins, Peter L.

2017-01-01

ABSTRACT Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but it lacks a licensed vaccine or suitable antiviral drug. A live attenuated chimeric bovine/human parainfluenza virus type 3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naive children, rB/HPIV3 was well tolerated but the immunogenicity of wild-type RSV F was unsatisfactory. We previously modified RSV F with a designed disulfide bond (DS) to increase stability in the prefusion (pre-F) conformation and to be efficiently packaged in the vector virion. Here, we further stabilized pre-F by adding both disulfide and cavity-filling mutations (DS-Cav1), and we also modified RSV F codon usage to have a lower CpG content and a higher level of expression. This RSV F open reading frame was evaluated in rB/HPIV3 in three forms: (i) pre-F without vector-packaging signal, (ii) pre-F with vector-packaging signal, and (iii) secreted pre-F ectodomain trimer. Despite being efficiently expressed, the secreted pre-F was poorly immunogenic. DS-Cav1 stabilized pre-F, with or without packaging, induced higher titers of pre-F specific antibodies in hamsters, and improved the quality of RSV-neutralizing serum antibodies. Codon-optimized RSV F containing fewer CpG dinucleotides had higher F expression, replicated more efficiently in vivo, and was more immunogenic. The combination of DS-Cav1 pre-F stabilization, optimized codon usage, reduced CpG content, and vector packaging significantly improved vector immunogenicity and protective efficacy against RSV. This provides an improved vectored RSV vaccine candidate suitable for pediatric clinical evaluation. IMPORTANCE RSV and HPIV3 are the first and second leading viral causes of severe pediatric respiratory disease worldwide. Licensed vaccines or suitable antiviral drugs are not available. We are developing a chimeric rB/HPIV3 vector expressing RSV F as a bivalent RSV/HPIV3 vaccine and have been evaluating means to increase RSV F immunogenicity. In this study, we evaluated the effects of improved stabilization of F in the pre-F conformation and of codon optimization resulting in reduced CpG content and greater pre-F expression. Reduced CpG content dampened the interferon response to infection, promoting higher replication and increased F expression. We demonstrate that improved pre-F stabilization and strategic manipulation of codon usage, together with efficient pre-F packaging into vector virions, significantly increased F immunogenicity in the bivalent RSV/HPIV3 vaccine. The improved immunogenicity included induction of increased titers of high-quality complement-independent antibodies with greater pre-F site Ø binding and greater protection against RSV challenge. PMID:28539444

A Novel Immunogenic Spore Coat-Associated Protein in Bacillus Anthracis: Characterization via Proteomics Approaches and a Vector-Based Vaccine System

PubMed Central

Liu, Yu-Tsueng; Lin, Shwu-Bin; Huang, Cheng-Po; Huang, Chun-Ming

2007-01-01

New generation anthrax vaccines have been actively explored with the aim of enhancing efficacies and decreasing undesirable side effects that could be caused by licensed vaccines. Targeting novel antigens and/or eliminating the requirements for multiple needle injections and adjuvants are major objectives in the development of new anthrax vaccines. Using proteomics approaches, we identified a spore coat-associated protein (SCAP) in Bacillus anthracis. An E. coli vector-based vaccine system was used to determine the immunogenicity of SCAP. Mice generated detectable SCAP antibodies three weeks after intranasal immunization with an intact particle of ultraviolet (UV)-irradiated E. coli vector overproducing SCAP. The production of SCAP antibodies was detected via western blotting and SCAP-spotted antigen-arrays. The adjuvant effect of a UV-irradiated E. coli vector eliminates the necessity of boosting and the use of other immunomodulators which will foster the screening and manufacturing of new generation anthrax vaccines. More importantly, the immunogenic SCAP may potentially be a new candidate for the development of anthrax vaccines. PMID:18029197

The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

PubMed Central

Smith, Ryan C; Vega-Rodríguez, Joel; Jacobs-Lorena, Marcelo

2014-01-01

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission. PMID:25185005

76 FR 50274 - Terrestrial Environmental Studies for Nuclear Power Stations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0182] Terrestrial Environmental Studies for Nuclear Power... draft regulatory guide (DG), DG-4016, ``Terrestrial Environmental Studies for Nuclear Power Stations... environmental studies and analyses supporting licensing decisions for nuclear power reactors. DATES: Submit...

A Deterministic Model to Quantify Risk and Guide Mitigation Strategies to Reduce Bluetongue Virus Transmission in California Dairy Cattle

PubMed Central

Mayo, Christie; Shelley, Courtney; MacLachlan, N. James; Gardner, Ian; Hartley, David; Barker, Christopher

2016-01-01

The global distribution of bluetongue virus (BTV) has been changing recently, perhaps as a result of climate change. To evaluate the risk of BTV infection and transmission in a BTV-endemic region of California, sentinel dairy cows were evaluated for BTV infection, and populations of Culicoides vectors were collected at different sites using carbon dioxide. A deterministic model was developed to quantify risk and guide future mitigation strategies to reduce BTV infection in California dairy cattle. The greatest risk of BTV transmission was predicted within the warm Central Valley of California that contains the highest density of dairy cattle in the United States. Temperature and parameters associated with Culicoides vectors (transmission probabilities, carrying capacity, and survivorship) had the greatest effect on BTV’s basic reproduction number, R0. Based on these analyses, optimal control strategies for reducing BTV infection risk in dairy cattle will be highly reliant upon early efforts to reduce vector abundance during the months prior to peak transmission. PMID:27812161

75 FR 22868 - Withdrawal of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Characterization of Seismic Sources and Determination of Safe Shutdown Earthquake Ground Motion.'' FOR FURTHER.... Nuclear Regulatory Commission (NRC) is withdrawing RG 1.165, ``Identification and Characterization of... alter the licensing basis of any currently operating reactor or any of the currently issued early site...

Public Accountancy Handbook.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Office of the Professions.

A reference guide to laws, rules, and regulations that govern public accountancy practice in New York State is presented. In addition to identifying licensing requirements/procedures for certified public accountants, general provisions of Title VIII of the Education Law are covered, along with state management, professional misconduct, and…

The Generalization of Visuomotor Learning to Untrained Movements and Movement Sequences Based on Movement Vector and Goal Location Remapping

PubMed Central

Wu, Howard G.

2013-01-01

The planning of goal-directed movements is highly adaptable; however, the basic mechanisms underlying this adaptability are not well understood. Even the features of movement that drive adaptation are hotly debated, with some studies suggesting remapping of goal locations and others suggesting remapping of the movement vectors leading to goal locations. However, several previous motor learning studies and the multiplicity of the neural coding underlying visually guided reaching movements stand in contrast to this either/or debate on the modes of motor planning and adaptation. Here we hypothesize that, during visuomotor learning, the target location and movement vector of trained movements are separately remapped, and we propose a novel computational model for how motor plans based on these remappings are combined during the control of visually guided reaching in humans. To test this hypothesis, we designed a set of experimental manipulations that effectively dissociated the effects of remapping goal location and movement vector by examining the transfer of visuomotor adaptation to untrained movements and movement sequences throughout the workspace. The results reveal that (1) motor adaptation differentially remaps goal locations and movement vectors, and (2) separate motor plans based on these features are effectively averaged during motor execution. We then show that, without any free parameters, the computational model we developed for combining movement-vector-based and goal-location-based planning predicts nearly 90% of the variance in novel movement sequences, even when multiple attributes are simultaneously adapted, demonstrating for the first time the ability to predict how motor adaptation affects movement sequence planning. PMID:23804099

International guide to prescribing psychotropic medication for the management of problem behaviours in adults with intellectual disabilities

PubMed Central

DEB, SHOUMITRO; KWOK, HENRY; BERTELLI, MARCO; SALVADOR-CARULLA, LUIS; BRADLEY, ELSPETH; TORR, JENNIFER; BARNHILL, JARRET

2009-01-01

Psychotropic medications are used regularly to manage problem behaviours among people with intellectual disabilities. This causes concern because often these medications are used out of their licensed indications in this context. The WPA Section on Psychiatry of Intellectual Disability has recently developed an evidence and consensus-based international guide for practitioners for the use of psychotropic medications for problem behaviours among adults with intellectual disabilities. This guide advises on assessment of behaviours, producing a formulation, initiation of treatment, assessment of out-come and adverse effects, follow-up arrangements, and possibility of discontinuation of treatment. PMID:19812757

Evaluation of efficacy, potential for vector transmission and duration of immunity testing of MP-12, an attenuated Rift Valley fever virus vaccine candidate, in sheep

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. There are currently no fully licensed vaccines for this arthropod-borne virus in the US. Studies in sheep and cattle have found an attenuated strain of RVFV, MP-12, to be both safe and efficacious, and a conditi...

Clustering, climate and dengue transmission.

PubMed

Junxiong, Pang; Yee-Sin, Leo

2015-06-01

Dengue is currently the most rapidly spreading vector-borne disease, with an increasing burden over recent decades. Currently, neither a licensed vaccine nor an effective anti-viral therapy is available, and treatment largely remains supportive. Current vector control strategies to prevent and reduce dengue transmission are neither efficient nor sustainable as long-term interventions. Increased globalization and climate change have been reported to influence dengue transmission. In this article, we reviewed the non-climatic and climatic risk factors which facilitate dengue transmission. Sustainable and effective interventions to reduce the increasing threat from dengue would require the integration of these risk factors into current and future prevention strategies, including dengue vaccination, as well as the continuous support and commitment from the political and environmental stakeholders.

The natural history and incidence of Yersinia pestis and prospects for vaccination.

PubMed

Williamson, E D; Oyston, P C F

2012-07-01

Plague is an ancient, serious, infectious disease which is still endemic in regions of the modern world and is a potential biothreat agent. This paper discusses the natural history of the bacterium and its evolution into a flea-vectored bacterium able to transmit bubonic plague. It reviews the incidence of plague in the modern world and charts the history of vaccines which have been used to protect against the flea-vectored disease, which erupts as bubonic plague. Current approaches to vaccine development to protect against pneumonic, as well as bubonic, plague are also reviewed. The considerable challenges in achieving a vaccine which is licensed for human use and which will comprehensively protect against this serious human pathogen are assessed.

Impact of vectorborne parasitic neglected tropical diseases on child health.

PubMed

Barry, Meagan A; Murray, Kristy O; Hotez, Peter J; Jones, Kathryn M

2016-07-01

Chagas disease, leishmaniasis, onchocerciasis and lymphatic filariasis are all vectorborne neglected tropical diseases (NTDs) that are responsible for significant disease burden in impoverished children and adults worldwide. As vectorborne parasitic diseases, they can all be targeted for elimination through vector control strategies. Examples of successful vector control programmes for these diseases over the past two decades have included the Southern Cone Initiative against Chagas disease, the Kala-azar Control Scheme against leishmaniasis, the Onchocerciasis Control Programme and the lymphatic filariasis control programme in The Gambia. A common vector control component in all of these programmes is the use of adulticides including dichlorodiphenyltrichloroethane and newer synthetic pyrethroid insecticides against the insect vectors of disease. Household spraying has been used against Chagas disease and leishmaniasis, and insecticide-treated bed nets have helped prevent leishmaniasis and lymphatic filariasis. Recent trends in vector control focus on collaborations between programmes and sectors to achieve integrated vector management that addresses the holistic vector control needs of a community rather than approaching it on a disease-by-disease basis, with the goals of increased efficacy, sustainability and cost-effectiveness. As evidence of vector resistance to currently used insecticide regimens emerges, research to develop new and improved insecticides and novel control strategies will be critical in reducing disease burden. In the quest to eliminate these vectorborne NTDs, efforts need to be made to continue existing control programmes, further implement integrated vector control strategies and stimulate research into new insecticides and control methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Hearing Aid Buying Guide: Sound Advice

MedlinePlus

... to have at least two years of supervised training to earn a license to practice. Working With a Hearing Healthcare Provider • The provider or the office should have convenient business hours, offer walk-in repair service, and make it easy to schedule an appointment. • ...

Medicine Handbook.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Office of the Professions.

A reference guide to laws, rules, and regulations that govern medical practice in the State of New York is presented. In addition to identifying licensing requirements/procedures for physicians, general provisions of Title VIII of the Education Law are covered along with state management, professional misconduct, and authorized acts. Regulations…

Professional Counselors Licensure Preparation Study Session Booklet.

ERIC Educational Resources Information Center

Richardson, Julia K.

This study guide, designed to help counselors prepare for the Virginia Professional Counselor License Application, provides a review of counseling techniques and procedures, evaluation and appraisal procedures, and group theories and techniques. Other topics reviewed in the materials include professional identity, function and ethics, and abnormal…

Interaction of Flavivirus with their mosquito vectors and their impact on the human health in the Americas.

PubMed

Valderrama, Anayansi; Díaz, Yamilka; López-Vergès, Sandra

2017-10-28

Some of the major arboviruses with public health importance, such as dengue, yellow fever, Zika and West Nile virus are mosquito-borne or mosquito-transmitted Flavivirus. Their principal vectors are from the family Culicidae, Aedes aegypti and Aedes albopictus being responsible of the urban cycles of dengue, Zika and yellow fever virus. These vectors are highly competent for transmission of many arboviruses. The genetic variability of the vectors, the environment and the viral diversity modulate the vector competence, in this context, it is important to determine which vector species is responsible of an outbreak in areas where many vectors coexist. As some vectors can transmit several flaviviruses and some flaviviruses can be transmitted by different species of vectors, through this review we expose importance of yellow fever, dengue and Zika virus in the world and the Americas, as well as the updated knowledge about these flaviviruses in their interaction with their mosquito vectors, guiding us on what is probably the beginning of a new stage in which the simultaneity of outbreaks will occur more frequently. Copyright © 2017 Elsevier Inc. All rights reserved.

VEST: Abstract Vector Calculus Simplification in Mathematica

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

J. Squire, J. Burby and H. Qin

2013-03-12

We present a new package, VEST (Vector Einstein Summation Tools), that performs abstract vector calculus computations in Mathematica. Through the use of index notation, VEST is able to reduce scalar and vector expressions of a very general type using a systematic canonicalization procedure. In addition, utilizing properties of the Levi-Civita symbol, the program can derive types of multi-term vector identities that are not recognized by canonicalization, subsequently applying these to simplify large expressions. In a companion paper [1], we employ VEST in the automation of the calculation of Lagrangians for the single particle guiding center system in plasma physics, amore » computation which illustrates its ability to handle very large expressions. VEST has been designed to be simple and intuitive to use, both for basic checking of work and more involved computations. __________________________________________________« less

VEST: Abstract vector calculus simplification in Mathematica

NASA Astrophysics Data System (ADS)

Squire, J.; Burby, J.; Qin, H.

2014-01-01

We present a new package, VEST (Vector Einstein Summation Tools), that performs abstract vector calculus computations in Mathematica. Through the use of index notation, VEST is able to reduce three-dimensional scalar and vector expressions of a very general type to a well defined standard form. In addition, utilizing properties of the Levi-Civita symbol, the program can derive types of multi-term vector identities that are not recognized by reduction, subsequently applying these to simplify large expressions. In a companion paper Burby et al. (2013) [12], we employ VEST in the automation of the calculation of high-order Lagrangians for the single particle guiding center system in plasma physics, a computation which illustrates its ability to handle very large expressions. VEST has been designed to be simple and intuitive to use, both for basic checking of work and more involved computations.

Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors

PubMed Central

Chorny, Michael; Fishbein, Ilia; Tengood, Jillian E.; Adamo, Richard F.; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

Gene therapeutic strategies have shown promise in treating vascular disease. However, their translation into clinical use requires pharmaceutical carriers enabling effective, site-specific delivery as well as providing sustained transgene expression in blood vessels. While replication-deficient adenovirus (Ad) offers several important advantages as a vector for vascular gene therapy, its clinical applicability is limited by rapid inactivation, suboptimal transduction efficiency in vascular cells, and serious systemic adverse effects. We hypothesized that novel zinc oleate-based magnetic nanoparticles (MNPs) loaded with Ad would enable effective arterial cell transduction by shifting vector processing to an alternative pathway, protect Ad from inactivation by neutralizing factors, and allow site-specific gene transfer to arteries treated with stent angioplasty using a 2-source magnetic guidance strategy. Ad-loaded MNPs effectively transduced cultured endothelial and smooth muscle cells under magnetic conditions compared to controls and retained capacity for gene transfer after exposure to neutralizing antibodies and lithium iodide, a lytic agent causing disruption of free Ad. Localized arterial gene expression significantly stronger than in control animal groups was demonstrated after magnetically guided MNP delivery in a rat stenting model 2 and 9 d post-treatment, confirming feasibility of using Ad-loaded MNPs to achieve site-specific transduction in stented blood vessels. In conclusion, Ad-loaded MNPs formed by controlled precipitation of zinc oleate represent a novel delivery system, well-suited for efficient, magnetically targeted vascular gene transfer.—Chorny, M., Fishbein, I., Tengood, J. E., Adamo, R. F., Alferiev, I. S., Levy, R. J. Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors. PMID:23407712

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys.

PubMed

Fleuriet, Jérome; Walton, Mark M G; Ono, Seiji; Mustari, Michael J

2016-06-01

Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract.

Commercial Drivers License Workplace Literacy Project. Computer Training.

ERIC Educational Resources Information Center

Minnesota Teamsters Service Bureau, Minneapolis.

These course outlines and instructor's guides were developed for a workplace literacy project conducted cooperatively through the Minnesota Teamsters Service Bureau and Northeast Metro Technical College. They are part of the job-specific curriculum for commercial truck drivers developed during the project. The beginning computer course introduces…

10 CFR 36.35 - Source rack protection.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Source rack protection. 36.35 Section 36.35 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR IRRADIATORS Design and Performance... guides to prevent products and product carriers from hitting or touching the rack or mechanism. ...

Sparse kernel methods for high-dimensional survival data.

PubMed

Evers, Ludger; Messow, Claudia-Martina

2008-07-15

Sparse kernel methods like support vector machines (SVM) have been applied with great success to classification and (standard) regression settings. Existing support vector classification and regression techniques however are not suitable for partly censored survival data, which are typically analysed using Cox's proportional hazards model. As the partial likelihood of the proportional hazards model only depends on the covariates through inner products, it can be 'kernelized'. The kernelized proportional hazards model however yields a solution that is dense, i.e. the solution depends on all observations. One of the key features of an SVM is that it yields a sparse solution, depending only on a small fraction of the training data. We propose two methods. One is based on a geometric idea, where-akin to support vector classification-the margin between the failed observation and the observations currently at risk is maximised. The other approach is based on obtaining a sparse model by adding observations one after another akin to the Import Vector Machine (IVM). Data examples studied suggest that both methods can outperform competing approaches. Software is available under the GNU Public License as an R package and can be obtained from the first author's website http://www.maths.bris.ac.uk/~maxle/software.html.

User's guide to PANCOR: A panel method program for interference assessment in slotted-wall wind tunnels

NASA Technical Reports Server (NTRS)

Kemp, William B., Jr.

1990-01-01

Guidelines are presented for use of the computer program PANCOR to assess the interference due to tunnel walls and model support in a slotted wind tunnel test section at subsonic speeds. Input data requirements are described in detail and program output and general program usage are described. The program is written for effective automatic vectorization on a CDC CYBER 200 class vector processing system.

Chiropractic. New York State.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Office of the Professions.

A reference guide to laws, rules, and regulations that govern the chiropractic practice in New York State is presented. After an overview of professional regulation in the state, licensing requirements/procedures for chiropractors are described. Provisions of Title VIII, Articles 130 and 132, of the Education Law are also covered, along with…

CEC Standards for Professional Practice in Special Education.

ERIC Educational Resources Information Center

Council for Exceptional Children, Reston, VA.

This document brings together professional standards of the special education profession adopted by the Council for Exceptional Children (CEC). The standards represent the efforts of special educators to govern their own practice, guide agencies that certify or license special educators, and improve programs that prepare special educators. The…

78 FR 24438 - Evaluations of Explosions Postulated To Occur at Nearby Facilities and on Transportation Routes...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... Nearby Facilities and on Transportation Routes Near Nuclear Power Plants AGENCY: Nuclear Regulatory... Nearby Facilities and on Transportation Routes Near Nuclear Power Plants.'' This regulatory guide describes for applicants seeking nuclear power reactor licenses and licensees of nuclear power reactors...

Library and Classroom Use of Copyrighted Videotapes and Computer Software.

ERIC Educational Resources Information Center

Reed, Mary Hutchings; Stanek, Debra

1986-01-01

This pullout guide addresses issues regarding library use of copyrighted videotapes and computer software. Guidelines for videotapes cover in-classroom use, in-library use in public library, loan, and duplication. Guidelines for computer software cover purchase conditions, avoiding license restrictions, loaning, archival copies, and in-library and…

Commercial Drivers License Workplace Literacy Project. Preparatory Course.

ERIC Educational Resources Information Center

Minnesota Teamsters Service Bureau, Minneapolis.

This course syllabus was developed for a workplace literacy project conducted cooperatively through the Minnesota Teamsters Service Bureau and Northeast Metro Technical College. It is part of the job-specific curriculum for commercial truck drivers developed during the project. This guide lists the courses necessary to complete a 24-credit diploma…

Broadening Research on Communication and School Public Relations

ERIC Educational Resources Information Center

Kowalski, Theodore J.

2005-01-01

Effective communication and public relations are recognized as core competencies for school administration as evidenced by national standards guiding preparation and licensing in most states. Even so, surprisingly little research has been conducted by doctoral students and professors on these two subjects. This article presents a case for…

Career Development Course: Instructor's Handbook and Curriculum Guide.

ERIC Educational Resources Information Center

Hunsaker, Alan

A ten-week course in career development for unemployed, low-income, dropout-prone teenagers is described. Topics covered include job applications, resumes, interviewing, ancillary needs (e.g., driver's licenses and social security numbers), the want ads, and employment agencies. Goals, objectives, and discussion items are provided for each topic.…

Computational Study of Fluidic Thrust Vectoring using Separation Control in a Nozzle

NASA Technical Reports Server (NTRS)

Deere, Karen; Berrier, Bobby L.; Flamm, Jeffrey D.; Johnson, Stuart K.

2003-01-01

A computational investigation of a two- dimensional nozzle was completed to assess the use of fluidic injection to manipulate flow separation and cause thrust vectoring of the primary jet thrust. The nozzle was designed with a recessed cavity to enhance the throat shifting method of fluidic thrust vectoring. The structured-grid, computational fluid dynamics code PAB3D was used to guide the design and analyze over 60 configurations. Nozzle design variables included cavity convergence angle, cavity length, fluidic injection angle, upstream minimum height, aft deck angle, and aft deck shape. All simulations were computed with a static freestream Mach number of 0.05. a nozzle pressure ratio of 3.858, and a fluidic injection flow rate equal to 6 percent of the primary flow rate. Results indicate that the recessed cavity enhances the throat shifting method of fluidic thrust vectoring and allows for greater thrust-vector angles without compromising thrust efficiency.

Improving Vector Evaluated Particle Swarm Optimisation by Incorporating Nondominated Solutions

PubMed Central

Lim, Kian Sheng; Ibrahim, Zuwairie; Buyamin, Salinda; Ahmad, Anita; Naim, Faradila; Ghazali, Kamarul Hawari; Mokhtar, Norrima

2013-01-01

The Vector Evaluated Particle Swarm Optimisation algorithm is widely used to solve multiobjective optimisation problems. This algorithm optimises one objective using a swarm of particles where their movements are guided by the best solution found by another swarm. However, the best solution of a swarm is only updated when a newly generated solution has better fitness than the best solution at the objective function optimised by that swarm, yielding poor solutions for the multiobjective optimisation problems. Thus, an improved Vector Evaluated Particle Swarm Optimisation algorithm is introduced by incorporating the nondominated solutions as the guidance for a swarm rather than using the best solution from another swarm. In this paper, the performance of improved Vector Evaluated Particle Swarm Optimisation algorithm is investigated using performance measures such as the number of nondominated solutions found, the generational distance, the spread, and the hypervolume. The results suggest that the improved Vector Evaluated Particle Swarm Optimisation algorithm has impressive performance compared with the conventional Vector Evaluated Particle Swarm Optimisation algorithm. PMID:23737718

Improving Vector Evaluated Particle Swarm Optimisation by incorporating nondominated solutions.

PubMed

Lim, Kian Sheng; Ibrahim, Zuwairie; Buyamin, Salinda; Ahmad, Anita; Naim, Faradila; Ghazali, Kamarul Hawari; Mokhtar, Norrima

2013-01-01

The Vector Evaluated Particle Swarm Optimisation algorithm is widely used to solve multiobjective optimisation problems. This algorithm optimises one objective using a swarm of particles where their movements are guided by the best solution found by another swarm. However, the best solution of a swarm is only updated when a newly generated solution has better fitness than the best solution at the objective function optimised by that swarm, yielding poor solutions for the multiobjective optimisation problems. Thus, an improved Vector Evaluated Particle Swarm Optimisation algorithm is introduced by incorporating the nondominated solutions as the guidance for a swarm rather than using the best solution from another swarm. In this paper, the performance of improved Vector Evaluated Particle Swarm Optimisation algorithm is investigated using performance measures such as the number of nondominated solutions found, the generational distance, the spread, and the hypervolume. The results suggest that the improved Vector Evaluated Particle Swarm Optimisation algorithm has impressive performance compared with the conventional Vector Evaluated Particle Swarm Optimisation algorithm.

VizieR Online Data Catalog: FARGO_THORIN 1.0 hydrodynamic code (Chrenko+, 2017)

NASA Astrophysics Data System (ADS)

Chrenko, O.; Broz, M.; Lambrechts, M.

2017-07-01

This archive contains the source files, documentation and example simulation setups of the FARGO_THORIN 1.0 hydrodynamic code. The program was introduced, described and used for simulations in the paper. It is built on top of the FARGO code (Masset, 2000A&AS..141..165M, Baruteau & Masset, 2008ApJ...672.1054B) and it is also interfaced with the REBOUND integrator package (Rein & Liu, 2012A&A...537A.128R). THORIN stands for Two-fluid HydrOdynamics, the Rebound integrator Interface and Non-isothermal gas physics. The program is designed for self-consistent investigations of protoplanetary systems consisting of a gas disk, a disk of small solid particles (pebbles) and embedded protoplanets. Code features: I) Non-isothermal gas disk with implicit numerical solution of the energy equation. The implemented energy source terms are: Compressional heating, viscous heating, stellar irradiation, vertical escape of radiation, radiative diffusion in the midplane and radiative feedback to accretion heating of protoplanets. II) Planets evolved in 3D, with close encounters allowed. The orbits are integrated using the IAS15 integrator (Rein & Spiegel, 2015MNRAS.446.1424R). The code detects the collisions among planets and resolve them as mergers. III) Refined treatment of the planet-disk gravitational interaction. The code uses a vertical averaging of the gravitational potential, as outlined in Muller & Kley (2012A&A...539A..18M). IV) Pebble disk represented by an Eulerian, presureless and inviscid fluid. The pebble dynamics is affected by the Epstein gas drag and optionally by the diffusive effects. We also implemented the drag back-reaction term into the Navier-Stokes equation for the gas. Archive summary: ------------------------------------------------------------------------- directory/file Explanation ------------------------------------------------------------------------- /in_relax Contains setup of the first example simulation /in_wplanet Contains setup of the second example simulation /srcmain Contains the source files of FARGOTHORIN /src_reb Contains the source files of the REBOUND integrator package to be linked with THORIN GUNGPL3 GNU General Public License, version 3 LICENSE License agreement README Simple user's guide UserGuide.pdf Extended user's guide refman.pdf Programer's guide ----------------------------------------------------------------------------- (1 data file).

The path from student to mentor and from chromosomes to replication to genomics.

PubMed

Gerbi, Susan A

2016-11-01

The American Society for Cell Biology Women in Cell Biology Sandra Masur Senior Award recognizes leadership in scientific accomplishments and in mentoring, which are intertwined. My development as a scientist reflects important mentors in my life, including my father and Joe Gall, who is my "Doktor Vater." In turn, as an established investigator, my scientific successes in researching 1) chromosomes, their replication and genomics, and 2) ribosomes, their structure, evolution, and biogenesis, reflects the hard work of my students and postdocs, for whom I act as a mentor, guiding them in their research and along their career paths. © 2016 Gerbi. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

PubMed Central

Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

2016-01-01

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

Vector vortex beam generation with dolphin-shaped cell meta-surface.

PubMed

Yang, Zhuo; Kuang, Deng-Feng; Cheng, Fang

2017-09-18

We present a dolphin-shaped cell meta-surface, which is a combination of dolphin-shaped metallic cells and dielectric substrate, for vector vortex beam generation with the illumination of linearly polarized light. Surface plasmon polaritons are excited at the boundary of the metallic cells, then guided by the metallic structures, and finally squeezed to the tips to form highly localized strong electromagnetic fields, which generate the intensity of vector vortex beams at z component. Synchronously, the abrupt phase change produced by the meta-surface is utilized to explain the vortex phase generated by elements. The new kind of structure can be utilized for communication, bioscience, and materiality.

MO-DE-202-03: Image-Guided Surgery and Interventions in the Advanced Multimodality Image-Guided Operating (AMIGO) Suite

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

Kapur, T.

At least three major trends in surgical intervention have emerged over the last decade: a move toward more minimally invasive (or non-invasive) approach to the surgical target; the development of high-precision treatment delivery techniques; and the increasing role of multi-modality intraoperative imaging in support of such procedures. This symposium includes invited presentations on recent advances in each of these areas and the emerging role for medical physics research in the development and translation of high-precision interventional techniques. The four speakers are: Keyvan Farahani, “Image-guided focused ultrasound surgery and therapy” Jeffrey H. Siewerdsen, “Advances in image registration and reconstruction for image-guidedmore » neurosurgery” Tina Kapur, “Image-guided surgery and interventions in the advanced multimodality image-guided operating (AMIGO) suite” Raj Shekhar, “Multimodality image-guided interventions: Multimodality for the rest of us” Learning Objectives: Understand the principles and applications of HIFU in surgical ablation. Learn about recent advances in 3D–2D and 3D deformable image registration in support of surgical safety and precision. Learn about recent advances in model-based 3D image reconstruction in application to intraoperative 3D imaging. Understand the multi-modality imaging technologies and clinical applications investigated in the AMIGO suite. Understand the emerging need and techniques to implement multi-modality image guidance in surgical applications such as neurosurgery, orthopaedic surgery, vascular surgery, and interventional radiology. Research supported by the NIH and Siemens Healthcare.; J. Siewerdsen; Grant Support - National Institutes of Health; Grant Support - Siemens Healthcare; Grant Support - Carestream Health; Advisory Board - Carestream Health; Licensing Agreement - Carestream Health; Licensing Agreement - Elekta Oncology.; T. Kapur, P41EB015898; R. Shekhar, Funding: R42CA137886 and R41CA192504 Disclosure and CoI: IGI Technologies, small-business partner on the grants.« less

Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer.

PubMed

Jin, Chuan; Fotaki, Grammatiki; Ramachandran, Mohanraj; Nilsson, Berith; Essand, Magnus; Yu, Di

2016-07-01

Chimeric antigen receptor (CAR) T-cell therapy is a new successful treatment for refractory B-cell leukemia. Successful therapeutic outcome depends on long-term expression of CAR transgene in T cells, which is achieved by delivering transgene using integrating gamma retrovirus (RV) or lentivirus (LV). However, uncontrolled RV/LV integration in host cell genomes has the potential risk of causing insertional mutagenesis. Herein, we describe a novel episomal long-term cell engineering method using non-integrating lentiviral (NILV) vector containing a scaffold/matrix attachment region (S/MAR) element, for either expression of transgenes or silencing of target genes. The insertional events of this vector into the genome of host cells are below detection level. CD19 CAR T cells engineered with a NILV-S/MAR vector have similar levels of CAR expression as T cells engineered with an integrating LV vector, even after numerous rounds of cell division. NILV-S/MAR-engineered CD19 CAR T cells exhibited similar cytotoxic capacity upon CD19(+) target cell recognition as LV-engineered T cells and are as effective in controlling tumor growth in vivo We propose that NILV-S/MAR vectors are superior to current options as they enable long-term transgene expression without the risk of insertional mutagenesis and genotoxicity. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Real-time solar magnetograph operation system software design and user's guide

NASA Technical Reports Server (NTRS)

Wang, C.

1984-01-01

The Real Time Solar Magnetograph (RTSM) Operation system software design on PDP11/23+ is presented along with the User's Guide. The RTSM operation software is for real time instrumentation control, data collection and data management. The data is used for vector analysis, plotting or graphics display. The processed data is then easily compared with solar data from other sources, such as the Solar Maximum Mission (SMM).

User's guide for vectorized code EQUIL for calculating equilibrium chemistry on Control Data STAR-100 computer

NASA Technical Reports Server (NTRS)

Kumar, A.; Graves, R. A., Jr.; Weilmuenster, K. J.

1980-01-01

A vectorized code, EQUIL, was developed for calculating the equilibrium chemistry of a reacting gas mixture on the Control Data STAR-100 computer. The code provides species mole fractions, mass fractions, and thermodynamic and transport properties of the mixture for given temperature, pressure, and elemental mass fractions. The code is set up for the electrons H, He, C, O, N system of elements. In all, 24 chemical species are included.

Precision targeting in guided munition using IR sensor and MmW radar

NASA Astrophysics Data System (ADS)

Sreeja, S.; Hablani, H. B.; Arya, H.

2015-10-01

Conventional munitions are not guided with sensors and therefore miss the target, particularly if the target is mobile. The miss distance of these munitions can be decreased by incorporating sensors to detect the target and guide the munition during flight. This paper is concerned with a Precision Guided Munition(PGM) equipped with an infrared sensor and a millimeter wave radar [IR and MmW, for short]. Three-dimensional flight of the munition and its pitch and yaw motion models are developed and simulated. The forward and lateral motion of a target tank on the ground is modeled as two independent second-order Gauss-Markov process. To estimate the target location on the ground and the line-of-sight rate to intercept it an Extended Kalman Filter is composed whose state vector consists of cascaded state vectors of missile dynamics and target dynamics. The line-of-sight angle measurement from the infrared seeker is by centroiding the target image in 40 Hz. The centroid estimation of the images in the focal plane is at a frequency of 10 Hz. Every 10 Hz, centroids of four consecutive images are averaged, yielding a time-averaged centroid, implying some measurement delay. The miss distance achieved by including by image processing delays is 1:45m.

Precision targeting in guided munition using infrared sensor and millimeter wave radar

NASA Astrophysics Data System (ADS)

Sulochana, Sreeja; Hablani, Hari B.; Arya, Hemendra

2016-07-01

Conventional munitions are not guided with sensors and therefore miss the target, particularly if the target is mobile. The miss distance of these munitions can be decreased by incorporating sensors to detect the target and guide the munition during flight. This paper is concerned with a precision guided munition equipped with an infrared (IR) sensor and a millimeter wave radar (MmW). Three-dimensional flight of the munition and its pitch and yaw motion models are developed and simulated. The forward and lateral motion of a target tank on the ground is modeled as two independent second-order Gauss-Markov processes. To estimate the target location on the ground and the line-of-sight (LOS) rate to intercept it, an extended Kalman filter is composed whose state vector consists of cascaded state vectors of missile dynamics and target dynamics. The LOS angle measurement from the IR seeker is by centroiding the target image in 40 Hz. The centroid estimation of the images in the focal plane is at a frequency of 10 Hz. Every 10 Hz, centroids of four consecutive images are averaged, yielding a time-averaged centroid, implying some measurement delay. The miss distance achieved by including image processing delays is 1.45 m.

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys

PubMed Central

Fleuriet, Jérome; Walton, Mark M. G.; Ono, Seiji; Mustari, Michael J.

2016-01-01

Purpose Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. Methods We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. Results We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Conclusions Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract PMID:27309621

75 FR 61321 - Domestic Licensing of Production and Utilization Facilities; Updates to Incorporation by...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

... electronic reading room at http://www.nrc.gov/reading-rm/adams.html . From this page, the public can gain... Regulatory Guides dated April 2009. The NRC's electronic reading room contains later versions of these Draft... in the training provided to examiners. Computer-based training, through the use of animations...

78 FR 31614 - Implementation of Regulatory Guide 1.221 on Design-Basis Hurricane and Hurricane Missiles

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-24

... for Nuclear Power Plants,'' in support of NRC reviews of early site permit (ESP), standard design... NUREG-0800, ``Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants... License Applications for Nuclear Power Plants, (LWR Edition)'' (ML070630003) In addition, this ISG...

Nurse Assistant Instructor Guide.

ERIC Educational Resources Information Center

Connecticut State Dept. of Education, Hartford. Div. of Vocational, Technical, and Adult Education.

This document is designed to assist the teacher in a nurse assistant certification program. The program is intended to prepare students for entry-level employment in a long-term care facility or with a licensed home health care agency. The 135-hour course teaches basic skills in patient care that will qualify the student to assist the licensed…

Training Manual: Driver Education. Vocational Strategies for Special Needs Students.

ERIC Educational Resources Information Center

Blanc, Doreen V.

Lessons presented in this manual, developed as part of the vocational strategies project, are designed to provide driver education for mildly handicapped special needs students placed in jobs that require a driver's license. The guide is intended for use in conjunction with a vocational program in automotive mechanics, or integrated into a…

Orientation to Health Occupations: Curriculum Guide for Health Occupations, Phase 3.

ERIC Educational Resources Information Center

Benedict, Mary; And Others

The document outlines a curriculum designed to prepare students for advanced health occupations. It is divided into four sections which offer basic information for: registered nurse and licensed practical nurse (32 units); dental assistant (19 units); medical assistant (26 units); and ward clerk (10 units). Each unit is divided into several topics…

A Conceptual Framework for Graduate Teaching Assistant Professional Development Evaluation and Research.

PubMed

Reeves, Todd D; Marbach-Ad, Gili; Miller, Kristen R; Ridgway, Judith; Gardner, Grant E; Schussler, Elisabeth E; Wischusen, E William

2016-01-01

Biology graduate teaching assistants (GTAs) are significant contributors to the educational mission of universities, particularly in introductory courses, yet there is a lack of empirical data on how to best prepare them for their teaching roles. This essay proposes a conceptual framework for biology GTA teaching professional development (TPD) program evaluation and research with three overarching variable categories for consideration: outcome variables, contextual variables, and moderating variables. The framework's outcome variables go beyond GTA satisfaction and instead position GTA cognition, GTA teaching practice, and undergraduate learning outcomes as the foci of GTA TPD evaluation and research. For each GTA TPD outcome variable, key evaluation questions and example assessment instruments are introduced to demonstrate how the framework can be used to guide GTA TPD evaluation and research plans. A common conceptual framework is also essential to coordinating the collection and synthesis of empirical data on GTA TPD nationally. Thus, the proposed conceptual framework serves as both a guide for conducting GTA TPD evaluation at single institutions and as a means to coordinate research across institutions at a national level. © 2016 T. D. Reeves et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Automotive applications of superconductors

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

Ginsberg, M.

1987-01-01

These proceedings compile papers on supercomputers in the automobile industry. Titles include: An automotive engineer's guide to the effective use of scalar, vector, and parallel computers; fluid mechanics, finite elements, and supercomputers; and Automotive crashworthiness performance on a supercomputer.

Phase 1 environmental report for the Advanced Neutron Source at Oak Ridge National Laboratory

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

Blasing, T.J.; Brown, R.A.; Cada, G.F.

1992-02-01

The US Department of Energy (DOE) has proposed the construction and operation of the Advanced Neutron Source (ANS), a 330-MW(f) reactor, at Oak Ridge National Laboratory (ORNL) to support neutron scattering and nuclear physics experiments. ANS would provide a steady-state source of neutrons that are thermalized to produce sources of hot, cold, and very coal neutrons. The use of these neutrons in ANS experiment facilities would be an essential component of national research efforts in basic materials science. Additionally, ANS capabilities would include production of transplutonium isotopes, irradiation of potential fusion and fission reactor materials, activation analysis, and production ofmore » medical and industrial isotopes such as {sup 252}Cf. Although ANS would not require licensing by the US Nuclear Regulatory Commission (NRC), DOE regards the design, construction, and operation of ANS as activities that would produce a licensable facility; that is, DOE is following the regulatory guidelines that NRC would apply if NRC were licensing the facility. Those guidelines include instructions for the preparation of an environmental report (ER), a compilation of available data and preliminary analyses regarding the environmental impacts of nuclear facility construction and operation. The ER, described and outlined in NRC Regulatory Guide 4.2, serves as a background document to facilitate the preparation of environmental impact statements (EISs). Using Regulatory Guide 4.2 as a model, this ANS ER provides analyses and information specific to the ANS site and area that can be adopted (and modified, if necessary) for the ANS EIS. The ER is being prepared in two phases. Phase 1 ER includes many of the data and analyses needed to prepare the EIS but does not include data or analyses of alternate sites or alternate technologies. Phase 2 ER will include the additional data and analyses stipulated by Regulatory Guide 4.2.« less

Evaluation of Commercial and Field-Expedient Baited Traps for House Flies, Musca domestica L. (Diptera: Muscidae)

DTIC Science & Technology

2009-01-09

Vector Ecology 34 (1): 99-103. 2009. Keyword Index : House fly, Musca domestica, trapping. INTRODUCTION Traps have been a mainstay of house fly (Musca...attract synanthropic flies. Proc. Pap. 46th Ann. Conf. Calif. Mosq. Vector Contr. Assoc. pp. 70-73. Pickens, L. G. and R. W. Miller. 1987. Techniques...1139: 279- 284. SAS Institute. 1992. SAS users guide: statistics. SAS Institute, Cary, NC. Warner, W. B. 1991. Attractant composition for synanthropic

Walking Drosophila align with the e-vector of linearly polarized light through directed modulation of angular acceleration

PubMed Central

Velez, Mariel M.; Wernet, Mathias F.; Clark, Damon A.

2014-01-01

Understanding the mechanisms that link sensory stimuli to animal behavior is a central challenge in neuroscience. The quantitative description of behavioral responses to defined stimuli has led to a rich understanding of different behavioral strategies in many species. One important navigational cue perceived by many vertebrates and insects is the e-vector orientation of linearly polarized light. Drosophila manifests an innate orientation response to this cue (‘polarotaxis’), aligning its body axis with the e-vector field. We have established a population-based behavioral paradigm for the genetic dissection of neural circuits guiding polarotaxis to both celestial as well as reflected polarized stimuli. However, the behavioral mechanisms by which flies align with a linearly polarized stimulus remain unknown. Here, we present a detailed quantitative description of Drosophila polarotaxis, systematically measuring behavioral parameters that are modulated by the stimulus. We show that angular acceleration is modulated during alignment, and this single parameter may be sufficient for alignment. Furthermore, using monocular deprivation, we show that each eye is necessary for modulating turns in the ipsilateral direction. This analysis lays the foundation for understanding how neural circuits guide these important visual behaviors. PMID:24810784

Implementation of 10 CFR 20.1406 Through Life Cycle Planning for Decommissioning

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

O'Donnell, E.; Ott, W.R.

2008-01-15

The focus of this paper is on a regulatory guide (draft guide DG-4012) being developed by the Office of Nuclear Regulatory Research for the implementation of 10 CFR 20.1406. The draft guide was published in the Federal Register on July 31, 2007 for a 90 day public comment period. Besides being available in the Federal Register, it is also available electronically in NRC's agency data management system (ADAMS). The accession number is ML0712100110. 10 CFR 20.1406 requires license applicants, other than renewals, after August 20, 1997, '..to describe in the application how facility design and procedures for operation will minimize,more » to the extent practicable, contamination of the facility and the environment, facilitate eventual decommissioning, and minimize to the extent practicable, the generation of radioactive waste'. The intent of the regulation is to diminish the occurrence and severity of 'legacy sites' by taking measures that will reduce and control contamination and facilitate eventual decommissioning. 10 CFR 20.1406 is significant because it applies to all new facilities and in the very near future (perhaps as soon as the fall of 2007), the U.S. Nuclear Regulatory Commission (NRC) anticipates receiving one or more license applications for new nuclear power plants. The regulatory guide is intended to facilitate that licensing by providing suggestions of things an applicant can do to minimize contamination of the facility and the environment, minimize generation of waste, and to facilitate decommissioning. Over 100 different kinds of activities are covered by license applications submitted to the NRC. They do not all reflect the same potential for contamination of a facility and the environment, or for the generation of radioactive waste. Therefore, an applicant should use sound judgment to evaluate the potential for contamination and the consequences of such contamination in deciding on the extent to which this guide applies to any given facility or activity. Factors which may enter into this decision include form (e.g., dry solids, liquids, gases), inventory, and environmental mobility of unintended releases. The bulk of the guidance presented in the guide will consist of specific design considerations drawn from nuclear industry experience and lessons learned from decommissioning. These design suggestions provide examples of measures which can be combined to support a contaminant management philosophy for a new facility. The principles embodied in this philosophy are threefold: (1) prevention of unintended release, (2) early detection if there is unintended release of radioactive contamination, and (3) prompt and aggressive clean-up should there be an unintended release of radioactive contamination. If the guiding principles are followed through the use of 'good' engineering and science, as well as careful attention to operational practices, it should result in meeting the requirements of 10 CFR 20.1406. All this should be considered in the context of the life cycle of the facility from the early planning stages through the final plans for decommissioning and waste disposal. Some of the mechanisms which can be employed for life cycle planning are described further in the Discussion section. In summary: The principles of the guide are threefold: prevention, early detection, and prompt response. If these guiding principles are followed through the use of 'good' engineering and science, as well as careful attention to operational practices, it should result in meeting the requirements of 10 CFR 20 In summary, the thrust of this guide is for an applicant to use technically sound engineering judgment and a practical risk-informed approach to achieve the objectives of 10 CFR 20.1406. This approach should consider the materials and processes involved (e.g., solids, liquids, gases) and focus on: (1) the relative significance of potential contamination; (2) areas most susceptible to leaks; and (3) the appropriate level of consideration to prevention and control of contamination that should be incorporated in facility design. Since the applicability of the guidance is a facility-by-facility decision, early consultation with the NRC is strongly suggested.« less

Open-Source GIS

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

Vatsavai, Raju; Burk, Thomas E; Lime, Steve

2012-01-01

The components making up an Open Source GIS are explained in this chapter. A map server (Sect. 30.1) can broadly be defined as a software platform for dynamically generating spatially referenced digital map products. The University of Minnesota MapServer (UMN Map Server) is one such system. Its basic features are visualization, overlay, and query. Section 30.2 names and explains many of the geospatial open source libraries, such as GDAL and OGR. The other libraries are FDO, JTS, GEOS, JCS, MetaCRS, and GPSBabel. The application examples include derived GIS-software and data format conversions. Quantum GIS, its origin and its applications explainedmore » in detail in Sect. 30.3. The features include a rich GUI, attribute tables, vector symbols, labeling, editing functions, projections, georeferencing, GPS support, analysis, and Web Map Server functionality. Future developments will address mobile applications, 3-D, and multithreading. The origins of PostgreSQL are outlined and PostGIS discussed in detail in Sect. 30.4. It extends PostgreSQL by implementing the Simple Feature standard. Section 30.5 details the most important open source licenses such as the GPL, the LGPL, the MIT License, and the BSD License, as well as the role of the Creative Commons.« less

Conserved Elements Vaccine for HIV | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) developed a DNA vaccine using conserved elements of HIV-1 Gag, administered in a prime-boost vaccination protocol. Two of the HIV Gag CE DNA vectors have been tested in a rhesus macaque model. Priming with the Gag CE vaccine and boosting with full length Gag DNA showed increased immune responses when compared to vaccination with Gag alone. Researchers seek licensing and/or co-development research collaborations for development this DNA vaccine.

MRI Guided Brain Stimulation without the Use of a Neuronavigation System

PubMed Central

Vaghefi, Ehsan; Byblow, Winston D.; Stinear, Cathy M.; Thompson, Benjamin

2015-01-01

A key issue in the field of noninvasive brain stimulation (NIBS) is the accurate localization of scalp positions that correspond to targeted cortical areas. The current gold standard is to combine structural and functional brain imaging with a commercially available “neuronavigation” system. However, neuronavigation systems are not commonplace outside of specialized research environments. Here we describe a technique that allows for the use of participant-specific functional and structural MRI data to guide NIBS without a neuronavigation system. Surface mesh representations of the head were generated using Brain Voyager and vectors linking key anatomical landmarks were drawn on the mesh. Our technique was then used to calculate the precise distances on the scalp corresponding to these vectors. These calculations were verified using actual measurements of the head and the technique was used to identify a scalp position corresponding to a brain area localized using functional MRI. PMID:26413537

Magnetofection™ of NMDA Receptor Subunits GluN1 and GluN2A Expression Vectors in Non-Neuronal Host Cells.

PubMed

Bruneau, Nadine; Szepetowski, Pierre

2017-01-01

The functional study of reconstituted NMDA receptors (NMDARs) in host cells requires that the corresponding vectors for the expression of the NMDAR subunits are co-transfected with high efficiency. Magnetofection™ is a technology used to deliver nucleic acids to cells. It is driven and site-specifically guided by the attractive forces of magnetic fields acting on magnetic nanoparticles that are associated with nucleic acid vectors. In magnetofection™, cationic lipids form self-assembled complexes with the nucleic acid vectors of interest. Those complexes are then associated with magnetic nanoparticles that are concentrated at the surface of cultured cells by applying a permanent magnetic field. Magnetofection™ is a simple method to transfect cultured cells with high transfection rates. Satisfactory expression levels are obtained with very low amounts of nucleic acid vector. Moreover, incubation time with host cells is less than 1 h, as compared with the several hours needed with standard transfection assays.

Energy-exchange collisions of dark-bright-bright vector solitons.

PubMed

Radhakrishnan, R; Manikandan, N; Aravinthan, K

2015-12-01

We find a dark component guiding the practically interesting bright-bright vector one-soliton to two different parametric domains giving rise to different physical situations by constructing a more general form of three-component dark-bright-bright mixed vector one-soliton solution of the generalized Manakov model with nine free real parameters. Moreover our main investigation of the collision dynamics of such mixed vector solitons by constructing the multisoliton solution of the generalized Manakov model with the help of Hirota technique reveals that the dark-bright-bright vector two-soliton supports energy-exchange collision dynamics. In particular the dark component preserves its initial form and the energy-exchange collision property of the bright-bright vector two-soliton solution of the Manakov model during collision. In addition the interactions between bound state dark-bright-bright vector solitons reveal oscillations in their amplitudes. A similar kind of breathing effect was also experimentally observed in the Bose-Einstein condensates. Some possible ways are theoretically suggested not only to control this breathing effect but also to manage the beating, bouncing, jumping, and attraction effects in the collision dynamics of dark-bright-bright vector solitons. The role of multiple free parameters in our solution is examined to define polarization vector, envelope speed, envelope width, envelope amplitude, grayness, and complex modulation of our solution. It is interesting to note that the polarization vector of our mixed vector one-soliton evolves in sphere or hyperboloid depending upon the initial parametric choices.

[Radiation protection in medical research : Licensing requirement for the use of radiation and advice for the application procedure].

PubMed

Minkov, V; Klammer, H; Brix, G

2017-07-01

In Germany, persons who are to be exposed to radiation for medical research purposes are protected by a licensing requirement. However, there are considerable uncertainties on the part of the applicants as to whether licensing by the competent Federal Office for Radiation Protection is necessary, and regarding the choice of application procedure. The article provides explanatory notes and practical assistance for applicants and an outlook on the forthcoming new regulations concerning the law on radiation protection of persons in the field of medical research. Questions and typical mistakes in the application process were identified and evaluated. The qualified physicians involved in a study are responsible for deciding whether a license is required for the intended application of radiation. The decision can be guided by answering the key question whether the study participants would undergo the same exposures regarding type and extent if they had not taken part in the study. When physicians are still unsure about their decision, they can seek the advisory service provided by the professional medical societies. Certain groups of people are particularly protected through the prohibition or restriction of radiation exposure. A simplified licensing procedure is used for a proportion of diagnostic procedures involving radiation when all related requirements are met; otherwise, the regular licensing procedure should be used. The new radiation protection law, which will enter into force on the 31st of december 2018, provides a notification procedure in addition to deadlines for both the notification and the licensing procedures. In the article, the authors consider how eligible studies involving applications of radiation that are legally not admissible at present may be feasible in the future, while still ensuring a high protection level for study participants.

Interpreting linear support vector machine models with heat map molecule coloring

PubMed Central

2011-01-01

Background Model-based virtual screening plays an important role in the early drug discovery stage. The outcomes of high-throughput screenings are a valuable source for machine learning algorithms to infer such models. Besides a strong performance, the interpretability of a machine learning model is a desired property to guide the optimization of a compound in later drug discovery stages. Linear support vector machines showed to have a convincing performance on large-scale data sets. The goal of this study is to present a heat map molecule coloring technique to interpret linear support vector machine models. Based on the weights of a linear model, the visualization approach colors each atom and bond of a compound according to its importance for activity. Results We evaluated our approach on a toxicity data set, a chromosome aberration data set, and the maximum unbiased validation data sets. The experiments show that our method sensibly visualizes structure-property and structure-activity relationships of a linear support vector machine model. The coloring of ligands in the binding pocket of several crystal structures of a maximum unbiased validation data set target indicates that our approach assists to determine the correct ligand orientation in the binding pocket. Additionally, the heat map coloring enables the identification of substructures important for the binding of an inhibitor. Conclusions In combination with heat map coloring, linear support vector machine models can help to guide the modification of a compound in later stages of drug discovery. Particularly substructures identified as important by our method might be a starting point for optimization of a lead compound. The heat map coloring should be considered as complementary to structure based modeling approaches. As such, it helps to get a better understanding of the binding mode of an inhibitor. PMID:21439031

Vector species richness increases haemorrhagic disease prevalence through functional diversity modulating the duration of seasonal transmission.

PubMed

Park, Andrew W; Cleveland, Christopher A; Dallas, Tad A; Corn, Joseph L

2016-06-01

Although many parasites are transmitted between hosts by a suite of arthropod vectors, the impact of vector biodiversity on parasite transmission is poorly understood. Positive relationships between host infection prevalence and vector species richness (SR) may operate through multiple mechanisms, including (i) increased vector abundance, (ii) a sampling effect in which species of high vectorial capacity are more likely to occur in species-rich communities, and (iii) functional diversity whereby communities comprised species with distinct phenologies may extend the duration of seasonal transmission. Teasing such mechanisms apart is impeded by a lack of appropriate data, yet could highlight a neglected role for functional diversity in parasite transmission. We used statistical modelling of extensive host, vector and microparasite data to test the hypothesis that functional diversity leading to longer seasonal transmission explained variable levels of disease in a wildlife population. We additionally developed a simple transmission model to guide our expectation of how an increased transmission season translates to infection prevalence. Our study demonstrates that vector SR is associated with increased levels of disease reporting, but not via increases in vector abundance or via a sampling effect. Rather, the relationship operates by extending the length of seasonal transmission, in line with theoretical predictions.

Comparative Study of Vocational Nursing Curriculum and Employer Requirements. Update. Napa Valley College, October 1991-June 1992.

ERIC Educational Resources Information Center

Zylinski, Doris; And Others

In 1991-92, a project was undertaken at Napa Valley College to update the college's 1990 Comparative Study of Vocational Nursing Curriculum and Employer Requirements, to develop a model articulation program for licensed nurses pursuing associate degrees, and to produce a guide for recruiting and retaining underrepresented groups in vocational…

Obstacle-avoiding navigation system

DOEpatents

Borenstein, Johann; Koren, Yoram; Levine, Simon P.

1991-01-01

A system for guiding an autonomous or semi-autonomous vehicle through a field of operation having obstacles thereon to be avoided employs a memory for containing data which defines an array of grid cells which correspond to respective subfields in the field of operation of the vehicle. Each grid cell in the memory contains a value which is indicative of the likelihood, or probability, that an obstacle is present in the respectively associated subfield. The values in the grid cells are incremented individually in response to each scan of the subfields, and precomputation and use of a look-up table avoids complex trigonometric functions. A further array of grid cells is fixed with respect to the vehicle form a conceptual active window which overlies the incremented grid cells. Thus, when the cells in the active window overly grid cell having values which are indicative of the presence of obstacles, the value therein is used as a multiplier of the precomputed vectorial values. The resulting plurality of vectorial values are summed vectorially in one embodiment of the invention to produce a virtual composite repulsive vector which is then summed vectorially with a target-directed vector for producing a resultant vector for guiding the vehicle. In an alternative embodiment, a plurality of vectors surrounding the vehicle are computed, each having a value corresponding to obstacle density. In such an embodiment, target location information is used to select between alternative directions of travel having low associated obstacle densities.

Bioactivity and laundering resistance of five commercially available, factory-treated permethrin-impregnated fabrics for the prevention of mosquito-borne diseases: the need for a standardized testing and licensing procedure.

PubMed

Faulde, Michael K; Pages, Frederic; Uedelhoven, Waltraud

2016-04-01

Personal protective measures against hematophagous vectors constitute the first line of defense against arthropod-borne diseases. In this regard, a major advance has been the development of residual insecticides that can be impregnated into clothing. Currently, however, information on specific treatment procedures, initial insecticide concentrations, arthropod toxicity, residual activity, and laundering resistance is either fragmentary or non-existent, and no World Health Organization Pesticides Evaluation Scheme or other guidelines exist for the standardized testing and licensing of insecticide-treated clothing. The aim of this study was to analyze the insecticide content, contact toxicity, laundering resistance, and residual activity of five commercially available and commonly used permethrin-treated fabrics-Insect Shield, ExOfficio, Sol's Monarch T-shirts, battle dress uniforms (BDUs), and Labonal socks-against vector-competent Aedes aegypti, Anopheles stephensi, and Culex pipiens mosquitoes under laboratory conditions. Prior to laundering, permethrin concentrations ranged from 4300 to 870 mg/m(2) whereas, after 100 defined machine launderings, the remaining permethrin content fell to between 1800 and 20 mg/m(2), a percentage permethrin loss of 58.1 to 98.5 %. The highest 99 % knockdown (KD99) efficacy of permethrin was detected in Ae. aegypti, followed by An. stephensi and Cx. pipiens demonstrating that Ae. aegypti is the most sensitive species and Cx. pipiens the least sensitive. After 100 launderings, the remaining biocidal efficacy differed markedly among the five brands, with KD99 times varying from 38.8 ± 2.9 to >360 min for Ae. aegypti, from 44 ± 3.5 to >360 min for An. stephensi, and from 98 ± 10.6 to >360 min for Cx. pipiens. Overall, the ranking of the residual biocidal efficacies within the five brands tested was as follows: BDU ≈ Labonal > Sol's Monarch > ExOfficio > Insect Shield. When applying German Armed Forces licensing conditions, none of the four products available in the civilian market would completely meet all the necessary efficacy and safety requirements fulfilled by BDUs. Therefore, we strongly recommend standardized testing and licensing procedures for insecticide-treated clothing, with defined cutoff values for initial maximum and post-laundering minimum concentrations of permethrin as well as figures for permethrin migration rates, arthropod toxicity, homogeneity on fabrics, residual activity, and laundering resistance.

Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

PubMed

Warimwe, George M; Lorenzo, Gema; Lopez-Gil, Elena; Reyes-Sandoval, Arturo; Cottingham, Matthew G; Spencer, Alexandra J; Collins, Katharine A; Dicks, Matthew D J; Milicic, Anita; Lall, Amar; Furze, Julie; Turner, Alison V; Hill, Adrian V S; Brun, Alejandro; Gilbert, Sarah C

2013-12-05

Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

Awareness of the 2010 guidelines implemented by the New York State Education Department for respiratory therapists in their role as clinical preceptors.

PubMed

Smith, Stephen G; Brittelli, John; Scott, Lisa Benz

2014-12-01

In 1993, the New York State (NYS) legislature and governor signed into law the Respiratory Therapy Guide to Practice Education Law to guide and regulate the profession of respiratory care under the auspices of the New York State Education Department. New guidelines were implemented by the New York State Education Department for respiratory therapists (RTs) in 2010 to provide the opportunity for RTs to receive continuing education units (CEUs) when participating as clinical preceptors. This study was conducted in June 2012 to determine the extent to which the NYS RTs are aware of the new licensing guidelines and amendments. In June 2012, a web-based survey was e-mailed to 2,503 NYS members of the New York State Society for Respiratory Care, 14% of which (n= 360) completed the survey. The survey included 21 items to assess RTs' awareness of the licensing guidelines that were implemented in 2010, and these respondents were analyzed using basic descriptive statistics. The study showed that 50% of the respondents were not aware of eligibility to earn CEUs as a clinical preceptor in NYS. Twenty-eight percent responded correctly that licensed RTs were eligible to earn CEUs as a clinical preceptor in NYS. In addition, 67% of those who responded were unaware of how many CEUs could be earned for each renewal period for clinical precepting. Finally, 70% of the respondents indicated that they would be inclined to seek employment at a facility that has a clinical affiliation with a university or college respiratory care program. The findings indicate that more education is needed in NYS to make licensed RTs aware of the 2010 guidelines. Practitioners may require incentives to become actively involved in the clinical education of respiratory care students as their clinical preceptors. Copyright © 2014 by Daedalus Enterprises.

DEVELOPMENT OF HFE SECTIONS OF DG-1145.

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

HIGGINS,J.C.; OHARA, J.M.; BONGARRA, J.

2007-03-26

For the licensing of the current fleet of commercial nuclear power plants (NPPs), the Nuclear Regulatory Commission (NRC) used two key documents, NUREG-0800 and Regulatory Guide (RG) 1.70. RG 1.70 provided guidance to applicants on the contents needed in their Safety Analysis Reports (SARs) submitted as part of their application to construct or operate an NPP. NUREG-0800, the NRC Standard Review Plan (SRP), provides guidance to the NRR staff reviewers on performing their safety reviews of these applications. As part of the preparation for a new wave of improved NPP designs the NRC is in the process of updating themore » SRP and is also developing a new RG designated as draft RG or DG-1145, ''Combined License Applications for Nuclear Power Plants (LWR Edition).'' This will eventually become RG 1.206 and will take the place of RG 1.70. This will provide guidance for combined license (COL) applicants, as well as for other 10CFR Part 52 variations that are permitted.« less

Comparative assessment of fluorescent transgene methods for quantitative imaging in human cells.

PubMed

Mahen, Robert; Koch, Birgit; Wachsmuth, Malte; Politi, Antonio Z; Perez-Gonzalez, Alexis; Mergenthaler, Julia; Cai, Yin; Ellenberg, Jan

2014-11-05

Fluorescence tagging of proteins is a widely used tool to study protein function and dynamics in live cells. However, the extent to which different mammalian transgene methods faithfully report on the properties of endogenous proteins has not been studied comparatively. Here we use quantitative live-cell imaging and single-molecule spectroscopy to analyze how different transgene systems affect imaging of the functional properties of the mitotic kinase Aurora B. We show that the transgene method fundamentally influences level and variability of expression and can severely compromise the ability to report on endogenous binding and localization parameters, providing a guide for quantitative imaging studies in mammalian cells. © 2014 Mahen et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

User's Guide for Monthly Vector Wind Profile Model

NASA Technical Reports Server (NTRS)

Adelfang, S. I.

1999-01-01

The background, theoretical concepts, and methodology for construction of vector wind profiles based on a statistical model are presented. The derived monthly vector wind profiles are to be applied by the launch vehicle design community for establishing realistic estimates of critical vehicle design parameter dispersions related to wind profile dispersions. During initial studies a number of months are used to establish the model profiles that produce the largest monthly dispersions of ascent vehicle aerodynamic load indicators. The largest monthly dispersions for wind, which occur during the winter high-wind months, are used for establishing the design reference dispersions for the aerodynamic load indicators. This document includes a description of the computational process for the vector wind model including specification of input data, parameter settings, and output data formats. Sample output data listings are provided to aid the user in the verification of test output.

Rule-Based Design of Plant Expression Vectors Using GenoCAD.

PubMed

Coll, Anna; Wilson, Mandy L; Gruden, Kristina; Peccoud, Jean

2015-01-01

Plant synthetic biology requires software tools to assist on the design of complex multi-genic expression plasmids. Here a vector design strategy to express genes in plants is formalized and implemented as a grammar in GenoCAD, a Computer-Aided Design software for synthetic biology. It includes a library of plant biological parts organized in structural categories and a set of rules describing how to assemble these parts into large constructs. Rules developed here are organized and divided into three main subsections according to the aim of the final construct: protein localization studies, promoter analysis and protein-protein interaction experiments. The GenoCAD plant grammar guides the user through the design while allowing users to customize vectors according to their needs. Therefore the plant grammar implemented in GenoCAD will help plant biologists take advantage of methods from synthetic biology to design expression vectors supporting their research projects.

MO-DE-202-00: Image-Guided Interventions: Advances in Intraoperative Imaging, Guidance, and An Emerging Role for Medical Physics in Surgery

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

NONE

At least three major trends in surgical intervention have emerged over the last decade: a move toward more minimally invasive (or non-invasive) approach to the surgical target; the development of high-precision treatment delivery techniques; and the increasing role of multi-modality intraoperative imaging in support of such procedures. This symposium includes invited presentations on recent advances in each of these areas and the emerging role for medical physics research in the development and translation of high-precision interventional techniques. The four speakers are: Keyvan Farahani, “Image-guided focused ultrasound surgery and therapy” Jeffrey H. Siewerdsen, “Advances in image registration and reconstruction for image-guidedmore » neurosurgery” Tina Kapur, “Image-guided surgery and interventions in the advanced multimodality image-guided operating (AMIGO) suite” Raj Shekhar, “Multimodality image-guided interventions: Multimodality for the rest of us” Learning Objectives: Understand the principles and applications of HIFU in surgical ablation. Learn about recent advances in 3D–2D and 3D deformable image registration in support of surgical safety and precision. Learn about recent advances in model-based 3D image reconstruction in application to intraoperative 3D imaging. Understand the multi-modality imaging technologies and clinical applications investigated in the AMIGO suite. Understand the emerging need and techniques to implement multi-modality image guidance in surgical applications such as neurosurgery, orthopaedic surgery, vascular surgery, and interventional radiology. Research supported by the NIH and Siemens Healthcare.; J. Siewerdsen; Grant Support - National Institutes of Health; Grant Support - Siemens Healthcare; Grant Support - Carestream Health; Advisory Board - Carestream Health; Licensing Agreement - Carestream Health; Licensing Agreement - Elekta Oncology.; T. Kapur, P41EB015898; R. Shekhar, Funding: R42CA137886 and R41CA192504 Disclosure and CoI: IGI Technologies, small-business partner on the grants.« less

MO-DE-202-01: Image-Guided Focused Ultrasound Surgery and Therapy

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

Farahani, K.

At least three major trends in surgical intervention have emerged over the last decade: a move toward more minimally invasive (or non-invasive) approach to the surgical target; the development of high-precision treatment delivery techniques; and the increasing role of multi-modality intraoperative imaging in support of such procedures. This symposium includes invited presentations on recent advances in each of these areas and the emerging role for medical physics research in the development and translation of high-precision interventional techniques. The four speakers are: Keyvan Farahani, “Image-guided focused ultrasound surgery and therapy” Jeffrey H. Siewerdsen, “Advances in image registration and reconstruction for image-guidedmore » neurosurgery” Tina Kapur, “Image-guided surgery and interventions in the advanced multimodality image-guided operating (AMIGO) suite” Raj Shekhar, “Multimodality image-guided interventions: Multimodality for the rest of us” Learning Objectives: Understand the principles and applications of HIFU in surgical ablation. Learn about recent advances in 3D–2D and 3D deformable image registration in support of surgical safety and precision. Learn about recent advances in model-based 3D image reconstruction in application to intraoperative 3D imaging. Understand the multi-modality imaging technologies and clinical applications investigated in the AMIGO suite. Understand the emerging need and techniques to implement multi-modality image guidance in surgical applications such as neurosurgery, orthopaedic surgery, vascular surgery, and interventional radiology. Research supported by the NIH and Siemens Healthcare.; J. Siewerdsen; Grant Support - National Institutes of Health; Grant Support - Siemens Healthcare; Grant Support - Carestream Health; Advisory Board - Carestream Health; Licensing Agreement - Carestream Health; Licensing Agreement - Elekta Oncology.; T. Kapur, P41EB015898; R. Shekhar, Funding: R42CA137886 and R41CA192504 Disclosure and CoI: IGI Technologies, small-business partner on the grants.« less

MO-DE-202-04: Multimodality Image-Guided Surgery and Intervention: For the Rest of Us

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

Shekhar, R.

At least three major trends in surgical intervention have emerged over the last decade: a move toward more minimally invasive (or non-invasive) approach to the surgical target; the development of high-precision treatment delivery techniques; and the increasing role of multi-modality intraoperative imaging in support of such procedures. This symposium includes invited presentations on recent advances in each of these areas and the emerging role for medical physics research in the development and translation of high-precision interventional techniques. The four speakers are: Keyvan Farahani, “Image-guided focused ultrasound surgery and therapy” Jeffrey H. Siewerdsen, “Advances in image registration and reconstruction for image-guidedmore » neurosurgery” Tina Kapur, “Image-guided surgery and interventions in the advanced multimodality image-guided operating (AMIGO) suite” Raj Shekhar, “Multimodality image-guided interventions: Multimodality for the rest of us” Learning Objectives: Understand the principles and applications of HIFU in surgical ablation. Learn about recent advances in 3D–2D and 3D deformable image registration in support of surgical safety and precision. Learn about recent advances in model-based 3D image reconstruction in application to intraoperative 3D imaging. Understand the multi-modality imaging technologies and clinical applications investigated in the AMIGO suite. Understand the emerging need and techniques to implement multi-modality image guidance in surgical applications such as neurosurgery, orthopaedic surgery, vascular surgery, and interventional radiology. Research supported by the NIH and Siemens Healthcare.; J. Siewerdsen; Grant Support - National Institutes of Health; Grant Support - Siemens Healthcare; Grant Support - Carestream Health; Advisory Board - Carestream Health; Licensing Agreement - Carestream Health; Licensing Agreement - Elekta Oncology.; T. Kapur, P41EB015898; R. Shekhar, Funding: R42CA137886 and R41CA192504 Disclosure and CoI: IGI Technologies, small-business partner on the grants.« less

MO-DE-202-02: Advances in Image Registration and Reconstruction for Image-Guided Neurosurgery

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

Siewerdsen, J.

At least three major trends in surgical intervention have emerged over the last decade: a move toward more minimally invasive (or non-invasive) approach to the surgical target; the development of high-precision treatment delivery techniques; and the increasing role of multi-modality intraoperative imaging in support of such procedures. This symposium includes invited presentations on recent advances in each of these areas and the emerging role for medical physics research in the development and translation of high-precision interventional techniques. The four speakers are: Keyvan Farahani, “Image-guided focused ultrasound surgery and therapy” Jeffrey H. Siewerdsen, “Advances in image registration and reconstruction for image-guidedmore » neurosurgery” Tina Kapur, “Image-guided surgery and interventions in the advanced multimodality image-guided operating (AMIGO) suite” Raj Shekhar, “Multimodality image-guided interventions: Multimodality for the rest of us” Learning Objectives: Understand the principles and applications of HIFU in surgical ablation. Learn about recent advances in 3D–2D and 3D deformable image registration in support of surgical safety and precision. Learn about recent advances in model-based 3D image reconstruction in application to intraoperative 3D imaging. Understand the multi-modality imaging technologies and clinical applications investigated in the AMIGO suite. Understand the emerging need and techniques to implement multi-modality image guidance in surgical applications such as neurosurgery, orthopaedic surgery, vascular surgery, and interventional radiology. Research supported by the NIH and Siemens Healthcare.; J. Siewerdsen; Grant Support - National Institutes of Health; Grant Support - Siemens Healthcare; Grant Support - Carestream Health; Advisory Board - Carestream Health; Licensing Agreement - Carestream Health; Licensing Agreement - Elekta Oncology.; T. Kapur, P41EB015898; R. Shekhar, Funding: R42CA137886 and R41CA192504 Disclosure and CoI: IGI Technologies, small-business partner on the grants.« less

Wide-angle full-vector beam propagation method based on an alternating direction implicit preconditioner

NASA Astrophysics Data System (ADS)

Chui, Siu Lit; Lu, Ya Yan

2004-03-01

Wide-angle full-vector beam propagation methods (BPMs) for three-dimensional wave-guiding structures can be derived on the basis of rational approximants of a square root operator or its exponential (i.e., the one-way propagator). While the less accurate BPM based on the slowly varying envelope approximation can be efficiently solved by the alternating direction implicit (ADI) method, the wide-angle variants involve linear systems that are more difficult to handle. We present an efficient solver for these linear systems that is based on a Krylov subspace method with an ADI preconditioner. The resulting wide-angle full-vector BPM is used to simulate the propagation of wave fields in a Y branch and a taper.

Wide-angle full-vector beam propagation method based on an alternating direction implicit preconditioner.

PubMed

Chui, Siu Lit; Lu, Ya Yan

2004-03-01

Wide-angle full-vector beam propagation methods (BPMs) for three-dimensional wave-guiding structures can be derived on the basis of rational approximants of a square root operator or its exponential (i.e., the one-way propagator). While the less accurate BPM based on the slowly varying envelope approximation can be efficiently solved by the alternating direction implicit (ADI) method, the wide-angle variants involve linear systems that are more difficult to handle. We present an efficient solver for these linear systems that is based on a Krylov subspace method with an ADI preconditioner. The resulting wide-angle full-vector BPM is used to simulate the propagation of wave fields in a Y branch and a taper.

Conceptual Elements: A Detailed Framework to Support and Assess Student Learning of Biology Core Concepts.

PubMed

Cary, Tawnya; Branchaw, Janet

2017-01-01

The Vision and Change in Undergraduate Biology Education: Call to Action report has inspired and supported a nationwide movement to restructure undergraduate biology curricula to address overarching disciplinary concepts and competencies. The report outlines the concepts and competencies generally but does not provide a detailed framework to guide the development of the learning outcomes, instructional materials, and assessment instruments needed to create a reformed biology curriculum. In this essay, we present a detailed Vision and Change core concept framework that articulates key components that transcend subdisciplines and scales for each overarching biological concept, the Conceptual Elements (CE) Framework. The CE Framework was developed using a grassroots approach of iterative revision and incorporates feedback from more than 60 biologists and undergraduate biology educators from across the United States. The final validation step resulted in strong national consensus, with greater than 92% of responders agreeing that each core concept list was ready for use by the biological sciences community, as determined by scientific accuracy and completeness. In addition, we describe in detail how educators and departments can use the CE Framework to guide and document reformation of individual courses as well as entire curricula. © 2017 T. Cary and J. Branchaw. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Urban residents' response to and evaluation of low-carbon travel policies: Evidence from a survey of five eastern cities in China.

PubMed

Geng, Jichao; Long, Ruyin; Chen, Hong; Li, Qianwen

2018-07-01

To address the problems of excessive energy consumption and global climate change, the Chinese government has issued numerous policies to guide urban residents' low-carbon travel behavior. To evaluate the validity of these policies from the perspective of public opinion, this study summarizes 22 policies from the four vantage points of economics, administration, technology, and public information and then measures residents' response to and evaluation of policies based on survey data on 1977 urban residents using stratified random sampling in five cities in eastern China. The results indicate that from the viewpoint of policy response, administrative policies for promoting public transport show the highest degree of response, followed by public information, technological, and economic policies. Specifically, the responses to parking and congestion fee policies are relatively stronger than those to vehicle purchase tax, vehicle and vessel tax, and fuel surcharge policies. Moreover, the responses to fuel surcharge policy are even weaker than car-restriction policies, including license-plate number restriction, license-plate lottery, and license-plate auction policies. From the viewpoint of policy evaluation, administrative policies for promoting public transport obtain the highest evaluations, followed by economic and technological policies. Residents' evaluations of car-restriction and public information policies are the lowest. In addition, a four-paradigm model is introduced to illustrate residents' reactions to each policy in terms of response and evaluation. Finally, several implementation strategies, including the anterior, concurrent, optional, core, supporting, and assisting policy options are proposed to guide urban residents' low-carbon travel behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

A model of how different biology experts explain molecular and cellular mechanisms.

PubMed

Trujillo, Caleb M; Anderson, Trevor R; Pelaez, Nancy J

2015-01-01

Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations. © 2015 C. M. Trujillo et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Clinical development of Ebola vaccines

PubMed Central

Sridhar, Saranya

2015-01-01

The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

PubMed Central

Nakayama, Yoshikazu; Aruga, Atsushi

2015-01-01

Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region. PMID:26344953

Ultrafast Optics: Vector Cavity Fiber Lasers - Physics and Technology

DTIC Science & Technology

2016-06-14

with a quasi- vector cavity both numerically and experimentally. It is expected that through the study a deep and comprehensive understanding on the...799-801, Jun. 1997. 31. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like pulse in a gain-guided soliton fiber laser," Opt...solitons in a ring fiber laser," Optics Communications 281 (22), 5614 (2008). 110. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like

Ultrafast Optics: Vector Cavity Laser - Physics and Technology

DTIC Science & Technology

2016-06-14

with a quasi- vector cavity both numerically and experimentally. It is expected that through the study a deep and comprehensive understanding on the...799-801, Jun. 1997. 31. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like pulse in a gain-guided soliton fiber laser," Opt...solitons in a ring fiber laser," Optics Communications 281 (22), 5614 (2008). 110. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like

Ultrafast Optics - Vector Cavity Lasers: Physics and Technology

DTIC Science & Technology

2016-06-14

with a quasi- vector cavity both numerically and experimentally. It is expected that through the study a deep and comprehensive understanding on the...799-801, Jun. 1997. 31. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like pulse in a gain-guided soliton fiber laser," Opt...solitons in a ring fiber laser," Optics Communications 281 (22), 5614 (2008). 110. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like

Monte Carlo simulation of a dynamical fermion problem: The light q sup 2 q sup 2 system

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

Grondin, G.

1991-01-01

We present results from a Guided Random Walk Monte Carlo simulation of the light q{sup 2}{bar q}{sup 2} system in a Coulomb-plus-linear quark potential model using an Intel iPSC/860 hypercube. A solvable model problem is first considered, after which we study the full q{sup 2}{bar q}{sup 2} system in (J,I) = (2,2) and (2,0) sectors. We find evidence for no bound states below the vector-vector threshold in these systems. 17 refs., 6 figs.

Recognizing the enemy within: licensing RNA-guided genome defense

PubMed Central

Dumesic, Phillip A.; Madhani, Hiten D.

2014-01-01

How do cells distinguish normal genes from transposons? Although much has been learned about RNAi-related RNA silencing pathways responsible for genome defense, this fundamental question remains. The literature points to several classes of mechanisms. In some cases, double-stranded RNA structures produced by transposon inverted repeats or antisense integration trigger endo-siRNA biogenesis. In other instances, DNA features associated with transposons—such as their unusual copy number, chromosomal arrangement, and/or chromatin environment—license RNA silencing. Finally, recent studies have identified improper transcript processing events, such as stalled pre-mRNA splicing, as signals for siRNA production. Thus, the suboptimal gene expression properties of selfish elements can enable their identification by RNA silencing pathways. PMID:24280023

Summary of Regional Conferences: Increasing Minority Access to the Licensed Professions through Two-Year College Programs.

ERIC Educational Resources Information Center

State Univ. of New York, Albany. Two Year Coll. Development Center.

In 1984-85, a cooperative project was undertaken in New York to address the issue of minority access to those professions that can be entered through two-year college programs (e.g., animal health technology, certified shorthand reporting, dental hygienist, land surveying, and physical therapist assistant). Project activities were guided by a…

Peterson's Guide to Nursing Programs. Baccalaureate and Graduate Nursing Education in the U.S. and Canada. Second Edition.

ERIC Educational Resources Information Center

American Association of Colleges of Nursing, Washington, DC.

This revised and updated directory of nursing programs in the United States, U.S. Territories, and Canada includes details on over 2,000 undergraduate and graduate programs at over 625 colleges. Information is also listed for continuing education programs, fast-track options for Registered Nurses and Licensed Practical Nurses, clinical nurse…

77 FR 70484 - Preoperational Testing of Onsite Electric Power Systems To Verify Proper Load Group Assignments...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... publicly available documents online in the NRC Library at http://www.nrc.gov/reading-rm/adams.html . To... reproduce them. NRC's PDR: You may examine and purchase copies of public documents at the NRC's PDR, Room O1... that the staff needs in its review of applications for permits and licenses. The draft regulatory guide...

Barroom Aggression in Hoboken, New Jersey: Don't Blame the Bouncers!

ERIC Educational Resources Information Center

Roberts, James C.

2007-01-01

Relying on a structured observation guide listing a large number of variables shown to be good predictors of aggression in bars by past researchers, trained observers spent a total of 444 hours collecting data in 25 licensed drinking establishments in Hoboken, New Jersey. Observations took place at two separate time periods, 7:30pm-10:30pm and…

75 FR 5632 - Office of New Reactors; Interim Staff Guidance on the Review of Nuclear Power Plant Designs Using...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-03

....8 and Regulatory Guide 1.206, ``Combined License Applications for Nuclear Power Plants (LWR Edition... Management System (ADAMS) Accession No. ML092640035). This ISG provides new guidance information for... (SRP), Section 8.3.1 and Sections 9.5.4 through 9.5.8. The NRC staff issues DC/COL-ISGs to facilitate...

Advancing climate justice and the right to health through procedural rights.

PubMed

Hall, Margaux J

2014-06-14

Scholars have increasingly recognized the ways in which climate change threatens the human rights of people around the world, with a disproportionate burden on the rights of already vulnerable persons. At particular risk to these populations is the right to health, as well as to interconnected human rights. Yet, scholars have generally not provided a thorough assessment of precisely how human rights law can catalyze a response to climate change to effectively avert health harms. This article suggests that human rights law is better suited to guide procedural responses to climate change and its health harms than it is to guide substantive decision-making. This article describes the ways in which climate change implicates the right to health and then analyzes human rights law's response. While acknowledging the intrinsic value of human rights in prompting climate change action, the article focuses its analysis on human rights' instrumental value in this arena. Copyright © 2014 Hall. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Development by Design in Colombia: Making Mitigation Decisions Consistent with Conservation Outcomes

PubMed Central

Saenz, Shirley; Walschburger, Tomas; González, Juan Carlos; León, Jorge; McKenney, Bruce; Kiesecker, Joseph

2013-01-01

Mitigation policy and regulatory frameworks are consistent in their strong support for the mitigation hierarchy of: (1) avoiding impacts, (2) minimizing impacts, and then (3) offsetting/compensating for residual impacts. While mitigation frameworks require developers to avoid, minimize and restore biodiversity on-site before considering an offset for residual impacts, there is a lack of quantitative guidance for this decision-making process. What are the criteria for requiring impacts be avoided altogether? Here we examine how conservation planning can guide the application of the mitigation hierarchy to address this issue. In support of the Colombian government's aim to improve siting and mitigation practices for planned development, we examined five pilot projects in landscapes expected to experience significant increases in mining, petroleum and/or infrastructure development. By blending landscape-level conservation planning with application of the mitigation hierarchy, we can proactively identify where proposed development and conservation priorities would be in conflict and where impacts should be avoided. The approach we outline here has been adopted by the Colombian Ministry of Environment and Sustainable Development to guide licensing decisions, avoid piecemeal licensing, and promote mitigation decisions that maintain landscape condition. PMID:24339972

Development by design in Colombia: making mitigation decisions consistent with conservation outcomes.

PubMed

Saenz, Shirley; Walschburger, Tomas; González, Juan Carlos; León, Jorge; McKenney, Bruce; Kiesecker, Joseph

2013-01-01

Mitigation policy and regulatory frameworks are consistent in their strong support for the mitigation hierarchy of: (1) avoiding impacts, (2) minimizing impacts, and then (3) offsetting/compensating for residual impacts. While mitigation frameworks require developers to avoid, minimize and restore biodiversity on-site before considering an offset for residual impacts, there is a lack of quantitative guidance for this decision-making process. What are the criteria for requiring impacts be avoided altogether? Here we examine how conservation planning can guide the application of the mitigation hierarchy to address this issue. In support of the Colombian government's aim to improve siting and mitigation practices for planned development, we examined five pilot projects in landscapes expected to experience significant increases in mining, petroleum and/or infrastructure development. By blending landscape-level conservation planning with application of the mitigation hierarchy, we can proactively identify where proposed development and conservation priorities would be in conflict and where impacts should be avoided. The approach we outline here has been adopted by the Colombian Ministry of Environment and Sustainable Development to guide licensing decisions, avoid piecemeal licensing, and promote mitigation decisions that maintain landscape condition.

Good medical ethics, from the inside out--and back again.

PubMed

Oakley, Justin

2015-01-01

I argue here that good medical ethics requires an empirically-informed moral psychology of medical virtue along with sound action-guiding prescriptions for virtuous medical practice. After distinguishing between three levels of justification, I indicate how medical virtue ethics can draw constructively on relevant empirical research in developing feasible and realistic aspirational standards for doctors, and in evaluating how policymakers can support doctors in acting on the virtues that doctors agreed to be guided by when they joined the profession. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Computational Study of an Axisymmetric Dual Throat Fluidic Thrust Vectoring Nozzle for a Supersonic Aircraft Application

NASA Technical Reports Server (NTRS)

Deere, Karen A.; Flamm, Jeffrey D.; Berrier, Bobby L.; Johnson, Stuart K.

2007-01-01

A computational investigation of an axisymmetric Dual Throat Nozzle concept has been conducted. This fluidic thrust-vectoring nozzle was designed with a recessed cavity to enhance the throat shifting technique for improved thrust vectoring. The structured-grid, unsteady Reynolds- Averaged Navier-Stokes flow solver PAB3D was used to guide the nozzle design and analyze performance. Nozzle design variables included extent of circumferential injection, cavity divergence angle, cavity length, and cavity convergence angle. Internal nozzle performance (wind-off conditions) and thrust vector angles were computed for several configurations over a range of nozzle pressure ratios from 1.89 to 10, with the fluidic injection flow rate equal to zero and up to 4 percent of the primary flow rate. The effect of a variable expansion ratio on nozzle performance over a range of freestream Mach numbers up to 2 was investigated. Results indicated that a 60 circumferential injection was a good compromise between large thrust vector angles and efficient internal nozzle performance. A cavity divergence angle greater than 10 was detrimental to thrust vector angle. Shortening the cavity length improved internal nozzle performance with a small penalty to thrust vector angle. Contrary to expectations, a variable expansion ratio did not improve thrust efficiency at the flight conditions investigated.

Intracellular trafficking of hybrid gene delivery vectors.

PubMed

Keswani, Rahul K; Lazebnik, Mihael; Pack, Daniel W

2015-06-10

Viral and non-viral gene delivery vectors are in development for human gene therapy, but both exhibit disadvantages such as inadequate efficiency, lack of cell-specific targeting or safety concerns. We have recently reported the design of hybrid delivery vectors combining retrovirus-like particles with synthetic polymers or lipids that are efficient, provide sustained gene expression and are more stable compared to native retroviruses. To guide further development of this promising class of gene delivery vectors, we have investigated their mechanisms of intracellular trafficking. Moloney murine leukemia virus-like particles (M-VLPs) were complexed with chitosan (Chi) or liposomes (Lip) comprising DOTAP, DOPE and cholesterol to form the hybrid vectors (Chi/M-VLPs and Lip/M-VLPs, respectively). Transfection efficiency and cellular internalization of the vectors were quantified in the presence of a panel of inhibitors of various endocytic pathways. Intracellular transport and trafficking kinetics of the hybrid vectors were dependent on the synthetic component and used a combination of clathrin- and caveolar-dependent endocytosis and macropinocytosis. Chi/M-VLPs were slower to transfect compared to Lip/M-VLPs due to the delayed detachment of the synthetic component. The synthetic component of hybrid gene delivery vectors plays a significant role in their cellular interactions and processing and is a key parameter for the design of more efficient gene delivery vehicles. Copyright © 2015 Elsevier B.V. All rights reserved.

Magnetic nanoparticles for efficient cell transduction with Semliki Forest virus.

PubMed

Kurena, Baiba; Vežāne, Aleksandra; Skrastiņa, Dace; Trofimova, Olga; Zajakina, Anna

2017-07-01

Semliki Forest virus (SFV) is a potential cancer gene therapy vector capable of providing high and transient expression of heterologous proteins in mammalian cells. However, SFV has shown suboptimal transduction levels in several cancer cell types as well as wide biodistribution of SFV has been observed after in vivo applications. Magnetic nanoparticles (MNPs) have been shown to increase cell transduction with several viral vectors in vitro under an external magnetic field and enhance magnetically guided viral vector delivery. Here, we examined a panel of MNPs for enhanced cancer cell transduction with SFV vector. Magneto-transduction using positively charged MNPs increased Semliki Forest virus transduction in TS/A mouse mammary carcinoma cells in vitro in the presence of fetal bovine serum. Positively charged MNPs efficiently captured SFV particles independently of capturing medium, and MNPs-SFV complexes were successfully separated from suspension by magnetic precipitation. These results reveal the potential application of MNPs for enhanced gene delivery by SFV vector as well as proposes magnetic precipitation for efficient concentration of SFV particles from different media. Copyright © 2017 Elsevier B.V. All rights reserved.

Zoonotic aspects of vector-borne infections.

PubMed

Failloux, A-B; Moutailler, S

2015-04-01

Vector-borne diseases are principally zoonotic diseases transmitted to humans by animals. Pathogens such as bacteria, parasites and viruses are primarily maintained within an enzootic cycle between populations of non-human primates or other mammals and largely non-anthropophilic vectors. This 'wild' cycle sometimes spills over in the form of occasional infections of humans and domestic animals. Lifestyle changes, incursions by humans into natural habitats and changes in agropastoral practices create opportunities that make the borders between wildlife and humans more permeable. Some vector-borne diseases have dispensed with the need for amplification in wild or domestic animals and they can now be directly transmitted to humans. This applies to some viruses (dengue and chikungunya) that have caused major epidemics. Bacteria of the genus Bartonella have reduced their transmission cycle to the minimum, with humans acting as reservoir, amplifier and disseminator. The design of control strategies for vector-borne diseases should be guided by research into emergence mechanisms in order to understand how a wild cycle can produce a pathogen that goes on to cause devastating urban epidemics.

Kablammo: an interactive, web-based BLAST results visualizer.

PubMed

Wintersinger, Jeff A; Wasmuth, James D

2015-04-15

Kablammo is a web-based application that produces interactive, vector-based visualizations of sequence alignments generated by BLAST. These visualizations can illustrate many features, including shared protein domains, chromosome structural modifications and genome misassembly. Kablammo can be used at http://kablammo.wasmuthlab.org. For a local installation, the source code and instructions are available under the MIT license at http://github.com/jwintersinger/kablammo. jeff@wintersinger.org. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Accurate shade image matching by using a smartphone camera.

PubMed

Tam, Weng-Kong; Lee, Hsi-Jian

2017-04-01

Dental shade matching by using digital images may be feasible when suitable color features are properly manipulated. Separating the color features into feature spaces facilitates favorable matching. We propose using support vector machines (SVM), which are outstanding classifiers, in shade classification. A total of 1300 shade tab images were captured using a smartphone camera with auto-mode settings and no flash. The images were shot at angled distances of 14-20cm from a shade guide at a clinic equipped with light tubes that produced a 4000K color temperature. The Group 1 samples comprised 1040 tab images, for which the shade guide was randomly positioned in the clinic, and the Group 2 samples comprised 260 tab images, for which the shade guide had a fixed position in the clinic. Rectangular content was cropped manually on each shade tab image and further divided into 10×2 blocks. The color features extracted from the blocks were described using a feature vector. The feature vectors in each group underwent SVM training and classification by using the "leave-one-out" strategy. The top one and three accuracies of Group 1 were 0.86 and 0.98, respectively, and those of Group 2 were 0.97 and 1.00, respectively. This study provides a feasible technique for dental shade classification that uses the camera of a mobile device. The findings reveal that the proposed SVM classification might outperform the shade-matching results of previous studies that have performed similarity measurements of ΔE levels or used an S, a*, b* feature set. Copyright © 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Self-focusing therapeutic gene delivery with intelligent gene vector swarms: intra-swarm signalling through receptor transgene expression in targeted cells.

PubMed

Tolmachov, Oleg E

2015-01-01

Gene delivery in vivo that is tightly focused on the intended target cells is essential to maximize the benefits of gene therapy and to reduce unwanted side-effects. Cell surface markers are immediately available for probing by therapeutic gene vectors and are often used to direct gene transfer with these vectors to specific target cell populations. However, it is not unusual for the choice of available extra-cellular markers to be too scarce to provide a reliable definition of the desired therapeutically relevant set of target cells. Therefore, interrogation of intra-cellular determinants of cell-specificity, such as tissue-specific transcription factors, can be vital in order to provide detailed cell-guiding information to gene vector particles. An important improvement in cell-specific gene delivery can be achieved through auto-buildup in vector homing efficiency using intelligent 'self-focusing' of swarms of vector particles on target cells. Vector self-focusing was previously suggested to rely on the release of diffusible chemo-attractants after a successful target-specific hit by 'scout' vector particles. I hypothesize that intelligent self-focusing behaviour of swarms of cell-targeted therapeutic gene vectors can be accomplished without the employment of difficult-to-use diffusible chemo-attractants, instead relying on the intra-swarm signalling through cells expressing a non-diffusible extra-cellular receptor for the gene vectors. In the proposed model, cell-guiding information is gathered by the 'scout' gene vector particles, which: (1) attach to a variety of cells via a weakly binding (low affinity) receptor; (2) successfully facilitate gene transfer into these cells; (3) query intra-cellular determinants of cell-specificity with their transgene expression control elements and (4) direct the cell-specific biosynthesis of a vector-encoded strongly binding (high affinity) cell-surface receptor. Free members of the vector swarm loaded with therapeutic cargo are then attracted to and internalized into the intended target cells via the expressed cognate strongly binding extra-cellular receptor, causing escalation of gene transfer into these cells and increasing the copy number of the therapeutic gene expression modules. Such self-focusing swarms of gene vectors can be either homogeneous, with 'scout' and 'therapeutic' members of the swarm being structurally identical, or, alternatively, heterogeneous (split), with 'scout' and 'therapeutic' members of the swarm being structurally specialized. It is hoped that the proposed self-focusing cell-targeted gene vector swarms with receptor-mediated intra-swarm signalling could be particularly effective in 'top-up' gene delivery scenarios, achieving high-level and sustained expression of therapeutic transgenes that are prone to shut-down through degradation and silencing. Crucially, in contrast to low-precision 'general location' vector guidance by diffusible chemo-attractants, ear-marking non-diffusible receptors can provide high-accuracy targeting of therapeutic vector particles to the specific cell, which has undergone a 'successful cell-specific hit' by a 'scout' vector particle. Opportunities for cell targeting could be expanded, since in the proposed model of self-focusing it could be possible to probe a broad selection of intra-cellular determinants of cell-specificity and not just to rely exclusively on extra-cellular markers of cell-specificity. By employing such self-focusing gene vectors for the improvement of cell-targeted delivery of therapeutic genes, e.g., in cancer therapy or gene addition therapy of recessive genetic diseases, it could be possible to broaden a leeway for the reduction of the vector load and, consequently, to minimize undesired vector cytotoxicity, immune reactions, and the risk of inadvertent genetic modification of germline cells in genetic treatment in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

Pathogenic effects of Rift Valley fever virus NSs gene are alleviated in cultured cells by expressed antiviral short hairpin RNAs.

PubMed

Scott, Tristan; Paweska, Janusz T; Arbuthnot, Patrick; Weinberg, Marc S

2012-01-01

Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, may cause severe hepatitis, encephalitis and haemorrhagic fever in humans. There are currently no available licensed vaccines or therapies to treat the viral infection in humans. RNA interference (RNAi)-based viral gene silencing offers a promising approach to inhibiting replication of this highly pathogenic virus. The small (S) segment of the RVFV tripartite genome carries the genetic determinates for pathogenicity during infection. This segment encodes the non-structural S (NSs) and essential nucleocapsid (N) genes. To advance RNAi-based inhibition of RVFV replication, we designed several Pol III short hairpin RNA (shRNA) expression cassettes against the NSs and N genes, including a multimerized plasmid vector that included four shRNA expression cassettes. Effective target silencing was demonstrated using full- and partial-length target reporter assays, and confirmed by western blot analysis of exogenous N and NSs expression. Small RNA northern blots showed detectable RNAi guide strand formation from single and multimerized shRNA constructs. Using a cell culture model of RVFV replication, shRNAs targeting the N gene decreased intracellular nucleocapsid protein concentration and viral replication. The shRNAs directed against the NSs gene reduced NSs protein concentrations and alleviated NSs-mediated cytotoxicity, which may be caused by host transcription suppression. These data are the first demonstration that RNAi activators have a potential therapeutic benefit for countering RVFV infection.

Advanced Computational Framework for Environmental Management ZEM, Version 1.x

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

Vesselinov, Velimir V.; O'Malley, Daniel; Pandey, Sachin

2016-11-04

Typically environmental management problems require analysis of large and complex data sets originating from concurrent data streams with different data collection frequencies and pedigree. These big data sets require on-the-fly integration into a series of models with different complexity for various types of model analyses where the data are applied as soft and hard model constraints. This is needed to provide fast iterative model analyses based on the latest available data to guide decision-making. Furthermore, the data and model are associated with uncertainties. The uncertainties are probabilistic (e.g. measurement errors) and non-probabilistic (unknowns, e.g. alternative conceptual models characterizing site conditions).more » To address all of these issues, we have developed an integrated framework for real-time data and model analyses for environmental decision-making called ZEM. The framework allows for seamless and on-the-fly integration of data and modeling results for robust and scientifically-defensible decision-making applying advanced decision analyses tools such as Bayesian- Information-Gap Decision Theory (BIG-DT). The framework also includes advanced methods for optimization that are capable of dealing with a large number of unknown model parameters, and surrogate (reduced order) modeling capabilities based on support vector regression techniques. The framework is coded in Julia, a state-of-the-art high-performance programing language (http://julialang.org). The ZEM framework is open-source and can be applied to any environmental management site. The framework will be open-source and released under GPL V3 license.« less

Recommended Immunization Schedules for Persons Aged 0 through 18 Years--United States, 2010. Morbidity and Mortality Weekly Report QuickGuide. Volume 58, Number 51 & 52

ERIC Educational Resources Information Center

Centers for Disease Control and Prevention, 2010

2010-01-01

The Advisory Committee on Immunization Practices (ACIP) annually publishes an immunization schedule for persons aged 0 through 18 years that summarizes recommendations for currently licensed vaccines for children aged 18 years and younger and includes recommendations in effect as of December 15, 2009. The changes to the previous schedule are…

Role of Community and Technical Colleges in Producing Nursing Graduates: Rethinking the Pipeline for Guided Pathways. Research Report 17-1

ERIC Educational Resources Information Center

Washington State Board for Community and Technical Colleges, 2017

2017-01-01

Though it is still possible to enter the nursing profession with a Licensed Practical Nursing Certificate (LPN) or an Associate's Degree in Nursing (ADN), it is becoming increasingly necessary to get a Bachelor of Science in Nursing (BSN) in order to be assured of continued employment. The Associate in Applied Science-T Nursing Degree prepares…

NCI Technology Transfer Center | TTC

Cancer.gov

The National Cancer Institute’s Technology Transfer Center (TTC) facilitates partnerships between the NIH research laboratories and external partners. With specialized teams, TTC guides the interactions of our partners from the point of discovery to patenting, from invention development to licensing. We play a key role in helping to accelerate development of cutting-edge research by connecting our partners to NIH’s world-class researchers, facilities, and knowledge.

10 CFR Appendix I to Part 50 - Numerical Guides for Design Objectives and Limiting Conditions for Operation To Meet the...

Code of Federal Regulations, 2013 CFR

2013-01-01

... in Light-Water-Cooled Nuclear Power Reactor Effluents I Appendix I to Part 50 Energy NUCLEAR... Criterion “As Low as is Reasonably Achievable” for Radioactive Material in Light-Water-Cooled Nuclear Power... light-water-cooled nuclear power reactors licensed under 10 CFR part 50 or part 52 of this chapter. The...

10 CFR Appendix I to Part 50 - Numerical Guides for Design Objectives and Limiting Conditions for Operation To Meet the...

Code of Federal Regulations, 2012 CFR

2012-01-01

... in Light-Water-Cooled Nuclear Power Reactor Effluents I Appendix I to Part 50 Energy NUCLEAR... Criterion “As Low as is Reasonably Achievable” for Radioactive Material in Light-Water-Cooled Nuclear Power... light-water-cooled nuclear power reactors licensed under 10 CFR part 50 or part 52 of this chapter. The...

10 CFR Appendix I to Part 50 - Numerical Guides for Design Objectives and Limiting Conditions for Operation To Meet the...

Code of Federal Regulations, 2014 CFR

2014-01-01

... in Light-Water-Cooled Nuclear Power Reactor Effluents I Appendix I to Part 50 Energy NUCLEAR... Criterion “As Low as is Reasonably Achievable” for Radioactive Material in Light-Water-Cooled Nuclear Power... light-water-cooled nuclear power reactors licensed under 10 CFR part 50 or part 52 of this chapter. The...

NRC safety research in support of regulation - FY 1994. Volume 9

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

NONE

This report, the tenth in a series of annual reports, was prepared in response to congressional inquiries concerning how nuclear regulatory research is used. It summarizes the accomplishments of the Office of Nuclear Regulatory Research during FY 1994. The goal of the Office of Nuclear Regulatory Research (RES) is to ensure the availability of sound technical bases for timely rulemaking and related decisions in support of NRC regulatory/licensing/inspection activities. RES also has responsibilities related to the resolution of generic safety issues and to the review of licensee submittals regarding individual plant examinations. It is the responsibility of RES to conductmore » the NRC`s rulemaking process, including the issuance of regulatory guides and rules that govern NRC licensed activities.« less

State-vector formalism and the Legendre polynomial solution for modelling guided waves in anisotropic plates

NASA Astrophysics Data System (ADS)

Zheng, Mingfang; He, Cunfu; Lu, Yan; Wu, Bin

2018-01-01

We presented a numerical method to solve phase dispersion curve in general anisotropic plates. This approach involves an exact solution to the problem in the form of the Legendre polynomial of multiple integrals, which we substituted into the state-vector formalism. In order to improve the efficiency of the proposed method, we made a special effort to demonstrate the analytical methodology. Furthermore, we analyzed the algebraic symmetries of the matrices in the state-vector formalism for anisotropic plates. The basic feature of the proposed method was the expansion of field quantities by Legendre polynomials. The Legendre polynomial method avoid to solve the transcendental dispersion equation, which can only be solved numerically. This state-vector formalism combined with Legendre polynomial expansion distinguished the adjacent dispersion mode clearly, even when the modes were very close. We then illustrated the theoretical solutions of the dispersion curves by this method for isotropic and anisotropic plates. Finally, we compared the proposed method with the global matrix method (GMM), which shows excellent agreement.

Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy

PubMed Central

Bengtsson, Niclas E.; Hall, John K.; Odom, Guy L.; Phelps, Michael P.; Andrus, Colin R.; Hawkins, R. David; Hauschka, Stephen D.; Chamberlain, Joel R.; Chamberlain, Jeffrey S.

2017-01-01

Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx4cv mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. Muscle-restricted Cas9 expression enables direct editing of the mutation, multi-exon deletion or complete gene correction via homologous recombination in myogenic cells. Treated muscles express dystrophin in up to 70% of the myogenic area and increased force generation following intramuscular delivery. Furthermore, systemic administration of the vectors results in widespread expression of dystrophin in both skeletal and cardiac muscles. Our results demonstrate that AAV-mediated muscle-specific gene editing has significant potential for therapy of neuromuscular disorders. PMID:28195574

Generating an Open Reading Frame (ORF) Entry Clone and Destination Clone.

PubMed

Reece-Hoyes, John S; Walhout, Albertha J M

2018-01-02

This protocol describes using the Gateway recombinatorial cloning system to create an Entry clone carrying an open reading frame (ORF) and then to transfer the ORF into a Destination vector. In this example, BP recombination is used to clone an ORF from a cDNA source into the Donor vector pDONR 221. The ORF from the resulting Entry clone is then transferred into the Destination vector pDEST-15; the product (the Destination clone) will express the ORF as an amino-terminal GST-fusion. The technique can be used as a guide for cloning any other DNA fragment of interest-a promoter sequence or 3' untranslated region (UTR), for example-with substitutions of different genetic material such as genomic DNA, att sites, and vectors as required. The series of constructions and transformations requires 9-15 d, not including time that may be required for sequence confirmation, if desired/necessary. © 2018 Cold Spring Harbor Laboratory Press.

Considerations for the use of human participants in vector biology research: a tool for investigators and regulators.

PubMed

Achee, Nicole L; Youngblood, Laura; Bangs, Michael J; Lavery, James V; James, Stephanie

2015-02-01

A thorough search of the existing literature has revealed that there are currently no published recommendations or guidelines for the interpretation of US regulations on the use of human participants in vector biology research (VBR). An informal survey of vector biologists has indicated that issues related to human participation in vector research have been largely debated by academic, national, and local Institutional Review Boards (IRBs) in the countries where the research is being conducted, and that interpretations and subsequent requirements made by these IRBs have varied widely. This document is intended to provide investigators and corresponding scientific and ethical review committee members an introduction to VBR methods involving human participation and the legal and ethical framework in which such studies are conducted with a focus on US Federal Regulations. It is also intended to provide a common perspective for guiding researchers, IRB members, and other interested parties (i.e., public health officials conducting routine entomological surveillance) in the interpretation of human subjects regulations pertaining to VBR.

A Guided Tour of Mathematical Methods

NASA Astrophysics Data System (ADS)

Snieder, Roel

2009-04-01

1. Introduction; 2. Dimensional analysis; 3. Power series; 4. Spherical and cylindrical co-ordinates; 5. The gradient; 6. The divergence of a vector field; 7. The curl of a vector field; 8. The theorem of Gauss; 9. The theorem of Stokes; 10. The Laplacian; 11. Conservation laws; 12. Scale analysis; 13. Linear algebra; 14. The Dirac delta function; 15. Fourier analysis; 16. Analytic functions; 17. Complex integration; 18. Green's functions: principles; 19. Green's functions: examples; 20. Normal modes; 21. Potential theory; 22. Cartesian tensors; 23. Perturbation theory; 24. Asymptotic evaluation of integrals; 25. Variational calculus; 26. Epilogue, on power and knowledge; References.

Unfolding the chaperone story.

PubMed

Hartl, F Ulrich

2017-11-01

Protein folding in the cell was originally assumed to be a spontaneous process, based on Anfinsen's discovery that purified proteins can fold on their own after removal from denaturant. Consequently cell biologists showed little interest in the protein folding process. This changed only in the mid and late 1980s, when the chaperone story began to unfold. As a result, we now know that in vivo, protein folding requires assistance by a complex machinery of molecular chaperones. To ensure efficient folding, members of different chaperone classes receive the nascent protein chain emerging from the ribosome and guide it along an ordered pathway toward the native state. I was fortunate to contribute to these developments early on. In this short essay, I will describe some of the critical steps leading to the current concept of protein folding as a highly organized cellular process. © 2017 Hartl. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A Primer for Developing Measures of Science Content Knowledge for Small-Scale Research and Instructional Use.

PubMed

Bass, Kristin M; Drits-Esser, Dina; Stark, Louisa A

2016-01-01

The credibility of conclusions made about the effectiveness of educational interventions depends greatly on the quality of the assessments used to measure learning gains. This essay, intended for faculty involved in small-scale projects, courses, or educational research, provides a step-by-step guide to the process of developing, scoring, and validating high-quality content knowledge assessments. We illustrate our discussion with examples from our assessments of high school students' understanding of concepts in cell biology and epigenetics. Throughout, we emphasize the iterative nature of the development process, the importance of creating instruments aligned to the learning goals of an intervention or curricula, and the importance of collaborating with other content and measurement specialists along the way. © 2016 K. M. Bass et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging

PubMed Central

Sato, M; Figueiredo, ML; Burton, JB; Johnson, M; Chen, M; Powell, R; Gambhir, SS; Carey, M; Wu, L

2009-01-01

Effective treatment for recurrent, disseminated prostate cancer is notably limited. We have developed adenoviral vectors with a prostate-specific two-step transcriptional amplification (TSTA) system that would express therapeutic genes at a robust level to target metastatic disease. The TSTA system employs the prostate-specific antigen (PSA) promoter/enhancer to drive a potent synthetic activator, which in turn activates the expression of the therapeutic gene. In this study, we explored different configurations of this bipartite system and discovered that physical separation of the two TSTA components into E1 and E3 regions of adenovirus was able to enhance androgen regulation and cell-discriminatory expression. The TSTA vectors that express imaging reporter genes were assessed by noninvasive imaging technologies in animal models. The improved selectivity of the E1E3 configured vector was reflected in silenced ectopic expression in the lung. Significantly, the enhanced specificity of the E1E3 vector enabled the detection of lung metastasis of prostate cancer. An E1E3 TSTA vector that expresses the herpes simplex virus thymidine kinase gene can effectively direct positron emission tomography (PET) imaging of the tumor. The prostate-targeted gene delivery vectors with robust and cell-specific expression capability will advance the development of safe and effective imaging guided therapy for recurrent metastatic stages of prostate cancer. PMID:18305574

Modeling Malaria Vector Distribution under Climate Change Scenarios in Kenya

NASA Astrophysics Data System (ADS)

Ngaina, J. N.

2017-12-01

Projecting the distribution of malaria vectors under climate change is essential for planning integrated vector control strategies for sustaining elimination and preventing reintroduction of malaria. However, in Kenya, little knowledge exists on the possible effects of climate change on malaria vectors. Here we assess the potential impact of future climate change on locally dominant Anopheles vectors including Anopheles gambiae, Anopheles arabiensis, Anopheles merus, Anopheles funestus, Anopheles pharoensis and Anopheles nili. Environmental data (Climate, Land cover and elevation) and primary empirical geo-located species-presence data were identified. The principle of maximum entropy (Maxent) was used to model the species' potential distribution area under paleoclimate, current and future climates. The Maxent model was highly accurate with a statistically significant AUC value. Simulation-based estimates suggest that the environmentally suitable area (ESA) for Anopheles gambiae, An. arabiensis, An. funestus and An. pharoensis would increase under all two scenarios for mid-century (2016-2045), but decrease for end century (2071-2100). An increase in ESA of An. Funestus was estimated under medium stabilizing (RCP4.5) and very heavy (RCP8.5) emission scenarios for mid-century. Our findings can be applied in various ways such as the identification of additional localities where Anopheles malaria vectors may already exist, but has not yet been detected and the recognition of localities where it is likely to spread to. Moreover, it will help guide future sampling location decisions, help with the planning of vector control suites nationally and encourage broader research inquiry into vector species niche modeling

Verification and Validation Strategy for LWRS Tools

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

Carl M. Stoots; Richard R. Schultz; Hans D. Gougar

2012-09-01

One intension of the Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program is to create advanced computational tools for safety assessment that enable more accurate representation of a nuclear power plant safety margin. These tools are to be used to study the unique issues posed by lifetime extension and relicensing of the existing operating fleet of nuclear power plants well beyond their first license extension period. The extent to which new computational models / codes such as RELAP-7 can be used for reactor licensing / relicensing activities depends mainly upon the thoroughness with which they have been verifiedmore » and validated (V&V). This document outlines the LWRS program strategy by which RELAP-7 code V&V planning is to be accomplished. From the perspective of developing and applying thermal-hydraulic and reactivity-specific models to reactor systems, the US Nuclear Regulatory Commission (NRC) Regulatory Guide 1.203 gives key guidance to numeric model developers and those tasked with the validation of numeric models. By creating Regulatory Guide 1.203 the NRC defined a framework for development, assessment, and approval of transient and accident analysis methods. As a result, this methodology is very relevant and is recommended as the path forward for RELAP-7 V&V. However, the unique issues posed by lifetime extension will require considerations in addition to those addressed in Regulatory Guide 1.203. Some of these include prioritization of which plants / designs should be studied first, coupling modern supporting experiments to the stringent needs of new high fidelity models / codes, and scaling of aging effects.« less

Analysis of Genetic Algorithm for Rule-Set Production (GARP) modeling approach for predicting distributions of fleas implicated as vectors of plague, Yersinia pestis, in California.

PubMed

Adjemian, Jennifer C Z; Girvetz, Evan H; Beckett, Laurel; Foley, Janet E

2006-01-01

More than 20 species of fleas in California are implicated as potential vectors of Yersinia pestis. Extremely limited spatial data exist for plague vectors-a key component to understanding where the greatest risks for human, domestic animal, and wildlife health exist. This study increases the spatial data available for 13 potential plague vectors by using the ecological niche modeling system Genetic Algorithm for Rule-Set Production (GARP) to predict their respective distributions. Because the available sample sizes in our data set varied greatly from one species to another, we also performed an analysis of the robustness of GARP by using the data available for flea Oropsylla montana (Baker) to quantify the effects that sample size and the chosen explanatory variables have on the final species distribution map. GARP effectively modeled the distributions of 13 vector species. Furthermore, our analyses show that all of these modeled ranges are robust, with a sample size of six fleas or greater not significantly impacting the percentage of the in-state area where the flea was predicted to be found, or the testing accuracy of the model. The results of this study will help guide the sampling efforts of future studies focusing on plague vectors.

A Parallel Vector Machine for the PM Programming Language

NASA Astrophysics Data System (ADS)

Bellerby, Tim

2016-04-01

PM is a new programming language which aims to make the writing of computational geoscience models on parallel hardware accessible to scientists who are not themselves expert parallel programmers. It is based around the concept of communicating operators: language constructs that enable variables local to a single invocation of a parallelised loop to be viewed as if they were arrays spanning the entire loop domain. This mechanism enables different loop invocations (which may or may not be executing on different processors) to exchange information in a manner that extends the successful Communicating Sequential Processes idiom from single messages to collective communication. Communicating operators avoid the additional synchronisation mechanisms, such as atomic variables, required when programming using the Partitioned Global Address Space (PGAS) paradigm. Using a single loop invocation as the fundamental unit of concurrency enables PM to uniformly represent different levels of parallelism from vector operations through shared memory systems to distributed grids. This paper describes an implementation of PM based on a vectorised virtual machine. On a single processor node, concurrent operations are implemented using masked vector operations. Virtual machine instructions operate on vectors of values and may be unmasked, masked using a Boolean field, or masked using an array of active vector cell locations. Conditional structures (such as if-then-else or while statement implementations) calculate and apply masks to the operations they control. A shift in mask representation from Boolean to location-list occurs when active locations become sufficiently sparse. Parallel loops unfold data structures (or vectors of data structures for nested loops) into vectors of values that may additionally be distributed over multiple computational nodes and then split into micro-threads compatible with the size of the local cache. Inter-node communication is accomplished using standard OpenMP and MPI. Performance analyses of the PM vector machine, demonstrating its scaling properties with respect to domain size and the number of processor nodes will be presented for a range of hardware configurations. The PM software and language definition are being made available under unrestrictive MIT and Creative Commons Attribution licenses respectively: www.pm-lang.org.

Targeted gene knock-in by homology-directed genome editing using Cas9 ribonucleoprotein and AAV donor delivery.

PubMed

Gaj, Thomas; Staahl, Brett T; Rodrigues, Gonçalo M C; Limsirichai, Prajit; Ekman, Freja K; Doudna, Jennifer A; Schaffer, David V

2017-06-20

Realizing the full potential of genome editing requires the development of efficient and broadly applicable methods for delivering programmable nucleases and donor templates for homology-directed repair (HDR). The RNA-guided Cas9 endonuclease can be introduced into cells as a purified protein in complex with a single guide RNA (sgRNA). Such ribonucleoproteins (RNPs) can facilitate the high-fidelity introduction of single-base substitutions via HDR following co-delivery with a single-stranded DNA oligonucleotide. However, combining RNPs with transgene-containing donor templates for targeted gene addition has proven challenging, which in turn has limited the capabilities of the RNP-mediated genome editing toolbox. Here, we demonstrate that combining RNP delivery with naturally recombinogenic adeno-associated virus (AAV) donor vectors enables site-specific gene insertion by homology-directed genome editing. Compared to conventional plasmid-based expression vectors and donor templates, we show that combining RNP and AAV donor delivery increases the efficiency of gene addition by up to 12-fold, enabling the creation of lineage reporters that can be used to track the conversion of striatal neurons from human fibroblasts in real time. These results thus illustrate the potential for unifying nuclease protein delivery with AAV donor vectors for homology-directed genome editing. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness

PubMed Central

Doroudchi, M Mehdi; Greenberg, Kenneth P; Liu, Jianwen; Silka, Kimberly A; Boyden, Edward S; Lockridge, Jennifer A; Arman, A Cyrus; Janani, Ramesh; Boye, Shannon E; Boye, Sanford L; Gordon, Gabriel M; Matteo, Benjamin C; Sampath, Alapakkam P; Hauswirth, William W; Horsager, Alan

2011-01-01

Previous work established retinal expression of channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, a viable ChR2-based human therapy must meet several key criteria: (i) ChR2 expression must be targeted, robust, and long-term, (ii) ChR2 must provide long-term and continuous therapeutic efficacy, and (iii) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2. We achieved specific and stable expression of ChR2 in ON bipolar cells using a recombinant adeno-associated viral vector (rAAV) packaged in a tyrosine-mutated capsid. Targeted expression led to ChR2-driven electrophysiological ON responses in postsynaptic retinal ganglion cells and significant improvement in visually guided behavior for multiple models of blindness up to 10 months postinjection. Light levels to elicit visually guided behavioral responses were within the physiological range of cone photoreceptors. Finally, chronic ChR2 expression was nontoxic, with transgene biodistribution limited to the eye. No measurable immune or inflammatory response was observed following intraocular vector administration. Together, these data indicate that virally delivered ChR2 can provide a viable and efficacious clinical therapy for photoreceptor disease-related blindness. PMID:21505421

Cylindrical Vector Beams for Rapid Polarization-Dependent Measurements in Atomic Systems

DTIC Science & Technology

2011-12-05

www.opticsinfobase.org/abstract.cfm?URI=oe-18-24-25035. 16. S. Tripathi and K. C. Toussaint, Jr., “Rapid Mueller matrix polarimetry based on parallelized...optical trapping [11], atom guiding [12], laser machining [13], charged particle acceleration [14,15], and polarimetry [16]. Yet despite numerous

The maxillary palp of aedes aegypti, a model of multisensory integration

USDA-ARS?s Scientific Manuscript database

Female yellow-fever mosquitoes, Aedes aegypti, are obligate blood-feeders and vectors of the pathogens that cause dengue fever, yellow fever and Chikungunya. This feeding behavior concludes a series of multisensory events guiding the mosquito to its host from a distance. The antennae and maxillary...

A hitchhiker's guide to the Maritimes: anthropogenic transport facilitates long-distance dispersal of an invasive marine crab to Newfoundland

EPA Science Inventory

We analyzed mitochondrial and microsatellite genetic data from European and Northwest Atlantic populations sampled during 1999-2002 to determine probable source locations and vectors for the Placentia Bay introduction discovered in 2007. We also analyzed Placentia Bay demographi...

AE9/AP9/SPM Radiation Environment Model: User’s Guide

DTIC Science & Technology

2014-02-18

5776 DTIC COPY NOTICE AND SIGNATURE PAGE Using Government drawings, specifications, or other data included in this document for any purpose other...specifications, or other data does not license the holder or any other person or corporation; or convey any rights or permission to manufacture, use...collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources

Stepping Stones To Using "Caring for Our Children": National Health and Safety Performance Standards for Out-of-Home Child Care Programs. Protecting Children from Harm.

ERIC Educational Resources Information Center

Colorado Univ. Health Sciences Center, Denver.

Developed in support of state licensing and regulatory agencies as well as state child care, health, and resource and referral agencies, and a variety of other public and private organizations, parents, and advocacy groups, this guide identifies those standards most needed for the prevention of injury, morbidity, and mortality in child care…

[Licensing of Pharmaceuticals and Medical Devices in Germany: Weaknesses and Opportunities].

PubMed

Reinhardt, D; Wildner, M

2016-12-01

The purpose of this study is to describe and compare the licensing of pharmaceuticals and medical devices in Germany. Weaknesses and opportunities of the respective processes are identified. Methods: To describe and compare the two approaches, a systematic literature review was conducted, followed by an archival analysis, guided by experts. Unstructured interviews were conducted with experts (users, financers, surveillants and producers) personally or by telephone to identify weaknesses and opportunities. The data were evaluated by content analysis according to Mayring and MAXQDA 11. The results were critically assessed by comparing them with the current academic literature. Results: A central market authorization for medical devices was mentioned often, but seems politically not viable. However, quality, methodology and depth of the analyses necessary for the licensing of medical devices, especially for high-risk devices, can and should strive for higher standards, comparable to those of pharmaceuticals. With regard to post-market surveillance, the systems for both pharmaceuticals and medical devices should be improved. Innovativeness and competitiveness of European medical device manufacturers should not be promoted by reduced evidence standards and patient safety. Subsidies or easier licensing procedures for small product lines with particular importance for public health, similar to orphan drug regulations, are more desirable. Conclusion: This study helps to identify areas of improvement for licensing of pharmaceuticals and medical devices. Concrete recommendations were developed. Higher evidence standards should be mandatory especially for high-risk devices, comparable to those of pharmaceuticals. Post-marketing surveillance should be improved for pharmaceuticals and medical devices. © Georg Thieme Verlag KG Stuttgart · New York.

Mapping of courses on vector biology and vector-borne diseases systems: time for a worldwide effort.

PubMed

Casas, Jérôme; Lazzari, Claudio; Insausti, Teresita; Launois, Pascal; Fouque, Florence

2016-11-01

Major emergency efforts are being mounted for each vector-borne disease epidemiological crisis anew, while knowledge about the biology of arthropods vectors is dwindling slowly but continuously, as is the number of field entomologists. The discrepancy between the rates of production of knowledge and its use and need for solving crises is widening, in particular due to the highly differing time spans of the two concurrent processes. A worldwide web based search using multiple key words and search engines of onsite and online courses in English, Spanish, Portuguese, French, Italian and German concerned with the biology of vectors identified over 140 courses. They are geographically and thematically scattered, the vast majority of them are on-site, with very few courses using the latest massive open online course (MOOC) powerfulness. Over two third of them is given in English and Western Africa is particularity poorly represented. The taxonomic groups covered are highly unbalanced towards mosquitoes. A worldwide unique portal to guide students of all grades and levels of expertise, in particular those in remote locations, is badly needed. This is the objective a new activity supported by the Special Programme for Research and Training in Tropical Diseases (TDR).

Reanalyzing the "far medial" (transcondylar-transtubercular) approach based on three anatomical vectors: the ventral posterolateral corridor.

PubMed

Chakravarthi, Srikant; Monroy-Sosa, Alejandro; Gonen, Lior; Fukui, Melanie; Rovin, Richard; Kojis, Nathaniel; Lindsay, Mark; Khalili, Sammy; Celix, Juanita; Corsten, Martin; Kassam, Amin B

2018-06-01

Endoscopic endonasal access to the jugular foramen and occipital condyle - the transcondylar-transtubercular approach - is anatomically complex and requires detailed knowledge of the relative position of critical neurovascular structures, in order to avoid inadvertent injury and resultant complications. However, access to this region can be confusing as the orientation and relationships of osseous, vascular, and neural structures are very much different from traditional dorsal approaches. This review aims at providing an organizational construct for a more understandable framework in accessing the transcondylar-transtubercular window. The region can be conceptualized using a three-vector coordinate system: vector 1 represents a dorsal or ventral corridor, vector 2 represents the outer and inner circumferential anatomical limits; in an "onion-skin" fashion, key osseous, vascular, and neural landmarks are organized based on a 360-degree skull base model, and vector 3 represents the final core or target of the surgical corridor. The creation of an organized "global-positioning system" may better guide the surgeon in accessing the far-medial transcondylar-transtubercular region, and related pathologies, and help understand the surgical limits to the occipital condyle and jugular foramen - the ventral posterolateral corridor - via the endoscopic endonasal approach.

Mapping of courses on vector biology and vector-borne diseases systems: time for a worldwide effort

PubMed Central

Casas, Jérôme; Lazzari, Claudio; Insausti, Teresita; Launois, Pascal; Fouque, Florence

2016-01-01

Major emergency efforts are being mounted for each vector-borne disease epidemiological crisis anew, while knowledge about the biology of arthropods vectors is dwindling slowly but continuously, as is the number of field entomologists. The discrepancy between the rates of production of knowledge and its use and need for solving crises is widening, in particular due to the highly differing time spans of the two concurrent processes. A worldwide web based search using multiple key words and search engines of onsite and online courses in English, Spanish, Portuguese, French, Italian and German concerned with the biology of vectors identified over 140 courses. They are geographically and thematically scattered, the vast majority of them are on-site, with very few courses using the latest massive open online course (MOOC) powerfulness. Over two third of them is given in English and Western Africa is particularity poorly represented. The taxonomic groups covered are highly unbalanced towards mosquitoes. A worldwide unique portal to guide students of all grades and levels of expertise, in particular those in remote locations, is badly needed. This is the objective a new activity supported by the Special Programme for Research and Training in Tropical Diseases (TDR). PMID:27759770

PLUS: open-source toolkit for ultrasound-guided intervention systems.

PubMed

Lasso, Andras; Heffter, Tamas; Rankin, Adam; Pinter, Csaba; Ungi, Tamas; Fichtinger, Gabor

2014-10-01

A variety of advanced image analysis methods have been under the development for ultrasound-guided interventions. Unfortunately, the transition from an image analysis algorithm to clinical feasibility trials as part of an intervention system requires integration of many components, such as imaging and tracking devices, data processing algorithms, and visualization software. The objective of our paper is to provide a freely available open-source software platform-PLUS: Public software Library for Ultrasound-to facilitate rapid prototyping of ultrasound-guided intervention systems for translational clinical research. PLUS provides a variety of methods for interventional tool pose and ultrasound image acquisition from a wide range of tracking and imaging devices, spatial and temporal calibration, volume reconstruction, simulated image generation, and recording and live streaming of the acquired data. This paper introduces PLUS, explains its functionality and architecture, and presents typical uses and performance in ultrasound-guided intervention systems. PLUS fulfills the essential requirements for the development of ultrasound-guided intervention systems and it aspires to become a widely used translational research prototyping platform. PLUS is freely available as open source software under BSD license and can be downloaded from http://www.plustoolkit.org.

A Guided Tour of Mathematical Methods for the Physical Sciences

NASA Astrophysics Data System (ADS)

Snieder, Roel; van Wijk, Kasper

2015-05-01

1. Introduction; 2. Dimensional analysis; 3. Power series; 4. Spherical and cylindrical coordinates; 5. Gradient; 6. Divergence of a vector field; 7. Curl of a vector field; 8. Theorem of Gauss; 9. Theorem of Stokes; 10. The Laplacian; 11. Scale analysis; 12. Linear algebra; 13. Dirac delta function; 14. Fourier analysis; 15. Analytic functions; 16. Complex integration; 17. Green's functions: principles; 18. Green's functions: examples; 19. Normal modes; 20. Potential-field theory; 21. Probability and statistics; 22. Inverse problems; 23. Perturbation theory; 24. Asymptotic evaluation of integrals; 25. Conservation laws; 26. Cartesian tensors; 27. Variational calculus; 28. Epilogue on power and knowledge.

A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5)

PubMed Central

Phan, Shannon I.; Chen, Zhenhai; Xu, Pei; Li, Zhuo; Gao, Xiudan; Foster, Stephanie L.; Teng, Michael N.; Tripp, Ralph A.; Sakamoto, Kaori; He, Biao

2014-01-01

Human respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. It also causes significant morbidity and mortality in elderly and immune compromised individuals. No licensed vaccine currently exists. Parainfluenza virus 5 (PIV5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. To evaluate the efficacy of PIV5 as a RSV vaccine vector, we generated two recombinant PIV5 viruses - one expressing the fusion (F) protein and the other expressing the attachment glycoprotein (G) of RSV strain A2 (RSV A2). The vaccine strains were used separately for single-dose vaccinations in BALB/c mice. The results showed that both vaccines induced RSV antigen-specific antibody responses, with IgG2a/IgG1 ratios similar to those seen in wild-type RSV A2 infection. After challenging the vaccinated mice with RSV A2, histopathology of lung sections showed that the vaccines did not exacerbate lung lesions relative to RSV A2-immunized mice. Importantly, both F and G vaccines induced protective immunity. Therefore, PIV5 presents an attractive platform for vector-based vaccines against RSV infection. PMID:24717150

Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates.

PubMed

Bolton, Diane L; Santra, Sampa; Swett-Tapia, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Mach, Linh; Naim, Hussein; Kozlowski, Pamela A; Lifton, Michelle; Goudsmit, Jaap; Letvin, Norman; Roederer, Mario; Radošević, Katarina

2012-09-07

Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag immunization alone elicited robust measles-specific humoral and cellular responses, but failed to elicit transgene (Gag)-specific immune responses, following aerosol or intratracheal/intramuscular delivery. However, when administered as a priming vaccine to a heterologous boost with recombinant adenovirus serotype 5 expressing the same transgene, rMV-Gag significantly enhanced Gag-specific T lymphocyte responses following rAd5 immunization. Gag-specific humoral responses were not enhanced, however, which may be due to either the transgene or the vector. Cellular response priming by rMV against the transgene was highly effective even when using a suboptimal dose of rAd5 for the boost. These data demonstrate feasibility of using rMV as a priming component of heterologous prime-boost vaccine regimens for pathogens requiring strong cellular responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Diversity of breeding habitats of anophelines (Diptera: Culicidae) in Ramgarh district, Jharkhand, India.

PubMed

Pandey, Siddharth; Das, M K; Dhiman, Ramesh C

2016-01-01

The Ramgarh district of Jharkhand state, India is highly malarious owing to abundance of different malaria vector species, namely Anopheles culicifacies, An. fluviatilis and An. annularis. In spite of high prevalence of malaria vectors in Ramgarh, their larval ecology and climatic conditions affecting malaria dynamics have never been studied. Therefore, the objective of this study was to identify the diversity of potential breeding habitats and breeding preferences of anopheline vectors in the Ramgarh district. Anopheles immature collection was carried out at potential aquatic habitats in Ramgarh and Gola sites using the standard dipper on fortnightly basis from August 2012 to July 2013. The immatures were reared till adult emergence and further identified using standard keys. Temperature of outdoor and water bodies was recorded through temperature data loggers, and rainfall through standard rain gauges installed at each site. A total of 6495 immature specimens representing 17 Anopheles species including three malaria vectors, viz. An. culicifacies, An. fluviatilis and An. annularis were collected from 11 types of breeding habitats. The highly preferred breeding habitats of vector anophelines were river bed pools, rivulets, wells, ponds, river margins, ditches and irrigation channels. Larval abundance of vector species showed site-specific variation with temperature and rainfall patterns throughout the year. The Shannon-Weiner diversity index ranged from 0.19 to 1.94 at Ramgarh site and 0.16 to 1.76 at Gola site. The study revealed that malaria vector species have been adapted to breed in a wide range of water bodies. The regular monitoring of such specific vector breeding sites under changing ecological and environmental conditions will be useful in guiding larval control operations selectively for effective vector/ malaria control.

75 FR 554 - Pacific Halibut Fisheries; Limited Access for Guided Sport Charter Vessels in Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

...NMFS issues regulations creating a limited access system for charter vessels in the guided sport fishery for Pacific halibut in waters of International Pacific Halibut Commission Regulatory Areas 2C (Southeast Alaska) and 3A (Central Gulf of Alaska). This limited access system limits the number of charter vessels that may participate in the guided sport fishery for halibut in these areas. NMFS will issue a charter halibut permit to a licensed charter fishing business owner based on his or her past participation in the charter halibut fishery and to a Community Quota Entity representing specific rural communities. All charter halibut permit holders are subject to limits on the number of permits they may hold and on the number of charter vessel anglers who may catch and retain halibut on permitted charter vessels. This action is necessary to achieve the approved halibut fishery management goals of the North Pacific Fishery Management Council. The intended effect is to curtail growth of fishing capacity in the guided sport fishery for halibut.

Impact damage imaging in a curved composite panel with wavenumber index via Riesz transform

NASA Astrophysics Data System (ADS)

Chang, Huan-Yu; Yuan, Fuh-Gwo

2018-03-01

The barely visible impact damages reduce the strength of composite structures significantly; however, they are difficult to be detected during regular visual inspection. A guided wave based damage imaging condition method is developed and applied on a curved composite panel, which is a part of an aileron from a retired Boeing C-17 Globemaster III. Ultrasonic guided waves are excited by a piezoelectric transducer (PZT) and then captured by a laser Doppler vibrometer (LDV). The wavefield images are constructed by measuring the out-of-plane velocity point by point within interrogation region, and the anomalies at the damage area can be observed with naked eye. The discontinuities of material properties leads to the change of wavenumber while the wave propagating through the damaged area. These differences in wavenumber can be observed by deriving instantaneous wave vector via Riesz transform (RT), and then be shown and highlighted with the proposed imaging condition named wavenumber index (WI). RT can be introduced as a two-dimensional (2-D) generalization of Hilbert transform (HT) to derive instantaneous phases, amplitudes, orientations of a guided-wave field. WI employs the instantaneous wave vector and weighted instantaneous wave energy computed from the instantaneous amplitudes, yielding high sensitivity and sharp damage image with computational efficiency. The BVID of the composite structure becomes therefore "visible" with the developed technique.

Safety and tolerability of MRI-guided infusion of AAV2-hAADC into the mid-brain of nonhuman primate

PubMed Central

Sebastian, Waldy San; Kells, Adrian P; Bringas, John; Samaranch, Lluis; Hadaczek, Piotr; Ciesielska, Agnieszka; Macayan, Michael J; Pivirotto, Phillip J; Forsayeth, John; Osborne, Sheryl; Wright, J Fraser; Green, Foad; Heller, Gregory; Bankiewicz, Krystof S

2014-01-01

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal-recessive neurological disorder caused by mutations in the DDC gene that leads to an inability to synthesize catecholamines and serotonin. As a result, patients suffer compromised development, particularly in motor function. A recent gene replacement clinical trial explored putaminal delivery of recombinant adeno-associated virus serotype 2 vector encoding human AADC (AAV2-hAADC) in AADC-deficient children. Unfortunately, patients presented only modest amelioration of motor symptoms, which authors acknowledged could be due to insufficient transduction of putamen. We hypothesize that, with the development of a highly accurate MRI-guided cannula placement technology, a more effective approach might be to target the affected mid-brain neurons directly. Transduction of AADC-deficient dopaminergic neurons in the substantia nigra and ventral tegmental area with locally infused AAV2-hAADC would be expected to lead to restoration of normal dopamine levels in affected children. The objective of this study was to assess the long-term safety and tolerability of bilateral AAV2-hAADC MRI-guided pressurized infusion into the mid-brain of nonhuman primates. Animals received either vehicle, low or high AAV2-hAADC vector dose and were euthanized 1, 3, or 9 months after surgery. Our data indicate that effective mid-brain transduction was achieved without untoward effects. PMID:25541617

Justice foundations for the Comprehensive Law Movement.

PubMed

Dewhurst, Dale

2010-01-01

Authors examining the developing dispute resolution alternatives to the adversarial system have identified nine converging "vectors" or alternatives in what has been termed the Comprehensive Law Movement. These authors have sought to understand how the developing vectors can remain separate and vibrant movements while sharing common ground. Some analyze these developments as being within law and legal practice, others see them as alternative approaches to law, and still others take a combined approach. It will be impossible to understand how these vectors have meaningful differences from law and legal practice if the search is limited to looking within law and legal practice. It will be impossible to understand how these vectors have meaningful commonalities with law and legal practice if the search is limited to looking external to law and legal practice. Instead of comparing the vectors with the adversarial system, higher order criteria are required. What is needed is a comprehensive and internally consistent super-system of norms; one that can be used to evaluate the adversarial system and the evolving vectors on an equal footing. An Aristotelian natural law virtue theory of justice can: (a) provide a functional guiding definition of justice; (b) serve as a comprehensive and internally consistent super-system of norms; and (c) provide the theoretical and evaluative foundation required to clarify the relationships among the adversarial system and the developing vectors. Finally, it will become clear why the Comprehensive Law Movement might be more appropriately conceptualized as the Comprehensive Justice Movement. Copyright © 2010 Elsevier Ltd. All rights reserved.

Transcriptomics-guided development of RNA interference strategies to manage whiteflies: a globally distributed vector of crop viruses

USDA-ARS?s Scientific Manuscript database

Over 300 viruses are transmitted by the whitefly, Bemisia tabaci, with 90% of them belonging to the genus, Begomovirus. Begomoviruses are exclusively transmitted by whiteflies to a range of agriculture crops, resulting in billions of dollars lost annually, while jeopardizing food security worldwide....

Gravity related features of plant growth behavior studied with rotating machines

NASA Technical Reports Server (NTRS)

Brown, A. H.

1996-01-01

Research in plant physiology consists mostly of studies on plant growth because almost everything a plant does is done by growing. Most aspects of plant growth are strongly influenced by the earth's gravity vector. Research on those phenomena address scientific questions specifically about how plants use gravity to guide their growth processes.

Environmental and social-demographic predictors of the southern house mosquito Culex quinquefasciatus in New Orleans, Louisiana

USDA-ARS?s Scientific Manuscript database

Flooding events have become common throughout the world yet our understanding of how these events affect the spatial and temporal distribution of disease vectors such as mosquitoes is limited. This knowledge can guide development of effective and timely strategies for mitigating mosquito-borne disea...

Investigation of Performance Improvements Including Application of Inlet Guide Vanes to a Cross-flow Fan

DTIC Science & Technology

2009-09-01

25 Figure 17. IGV Cut Out from Fluid Domain...Figure 22. Installed IGVS as Viewed from the CFF Inlet.................................................30 Figure 23. Schematic of Turbine Test Rig (TTR...44 Figure 28. Close In View of Velocity Vector Plot Near IGVS for 6IGV Model..............45 Figure 29

Industrial Prep, Volume Four, Junior Year--Contents: Mathematics and Guidance.

ERIC Educational Resources Information Center

Hackensack Public Schools, NJ.

As part of a 3-year comprehensive interdisciplinary program in industrial preparation for vocational students, this 11th Grade teaching guide consists of units on technical mathematics and guidance. Designed as supportive material for related physics and English curriculums, the first four sections of Volume 4 on algebra, vectors, simple machines,…

Teacher's Handbook for English for Living: A Set of Materials Designed to Teach Coping Skills and Language Skills to Adolescents for Whom English Is a Second Language.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Bilingual Education.

This guide provides directions for teaching a series of units on survival skills in English as a second language (ESL). A brief general background of second language instruction and a short bibliography are included. The modules cover: (1) "Getting a Driver's License and Buying a Car"; (2) "Want Ads and Employment Agencies";…

Experimental Characterization of Guided Waves by Their Surface Displacement Vector Field

NASA Astrophysics Data System (ADS)

Barth, M.; Köhler, B.; Schubert, L.

2009-03-01

The development new nondestructive evaluation (NDE) and structural health monitoring (SHM) methods utilizing guided elastic waves needs a good understanding of wave propagation properties and the interaction of the waves with structures and defects. If the geometrical and stiffness properties of the components are well known, these effects can be studied very efficiently by numerical modeling. But very often there is a lack of precise knowledge of all necessary elastic properties; accurate and non-disturbing measurements are without alternative in these cases. The mapping of wave fields can be done by scanning laser vibrometers as demonstrated in a number of cases. Originally, a laser vibrometer provides only information from one displacement component. To get all three displacement components, the simultaneous measurement with three vibrometers is offered commercially. This is a very expensive approach. The paper describes a method which uses only one vibrometer sequentially for getting all three vector components. It allows determining additional parameters for characterizing wave modes as e.g. the ellipticity. The capability of this approach is demonstrated for the characterization of Lamb waves.

ML 3.1 developer's guide.

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

Sala, Marzio; Hu, Jonathan Joseph; Tuminaro, Raymond Stephen

2004-05-01

ML development was started in 1997 by Ray Tuminaro and Charles Tong. Currently, there are several full- and part-time developers. The kernel of ML is written in ANSI C, and there is a rich C++ interface for Trilinos users and developers. ML can be customized to run geometric and algebraic multigrid; it can solve a scalar or a vector equation (with constant number of equations per grid node), and it can solve a form of Maxwell's equations. For a general introduction to ML and its applications, we refer to the Users Guide [SHT04], and to the ML web site, http://software.sandia.gov/ml.

Vector radiative transfer code SORD: Performance analysis and quick start guide

NASA Astrophysics Data System (ADS)

Korkin, Sergey; Lyapustin, Alexei; Sinyuk, Alexander; Holben, Brent; Kokhanovsky, Alexander

2017-10-01

We present a new open source polarized radiative transfer code SORD written in Fortran 90/95. SORD numerically simulates propagation of monochromatic solar radiation in a plane-parallel atmosphere over a reflecting surface using the method of successive orders of scattering (hence the name). Thermal emission is ignored. We did not improve the method in any way, but report the accuracy and runtime in 52 benchmark scenarios. This paper also serves as a quick start user's guide for the code available from ftp://maiac.gsfc.nasa.gov/pub/skorkin, from the JQSRT website, or from the corresponding (first) author.

User's guide for NASCRIN: A vectorized code for calculating two-dimensional supersonic internal flow fields

NASA Technical Reports Server (NTRS)

Kumar, A.

1984-01-01

A computer program NASCRIN has been developed for analyzing two-dimensional flow fields in high-speed inlets. It solves the two-dimensional Euler or Navier-Stokes equations in conservation form by an explicit, two-step finite-difference method. An explicit-implicit method can also be used at the user's discretion for viscous flow calculations. For turbulent flow, an algebraic, two-layer eddy-viscosity model is used. The code is operational on the CDC CYBER 203 computer system and is highly vectorized to take full advantage of the vector-processing capability of the system. It is highly user oriented and is structured in such a way that for most supersonic flow problems, the user has to make only a few changes. Although the code is primarily written for supersonic internal flow, it can be used with suitable changes in the boundary conditions for a variety of other problems.

B-physics anomalies: a guide to combined explanations

NASA Astrophysics Data System (ADS)

Buttazzo, Dario; Greljo, Admir; Isidori, Gino; Marzocca, David

2017-11-01

Motivated by additional experimental hints of Lepton Flavour Universality violation in B decays, both in charged- and in neutral-current processes, we analyse the ingredients necessary to provide a combined description of these phenomena. By means of an Effective Field Theory (EFT) approach, based on the hypothesis of New Physics coupled predominantly to the third generation of left-handed quarks and leptons, we show how this is possible. We demonstrate, in particular, how to solve the problems posed by electroweak precision tests and direct searches with a rather natural choice of model parameters, within the context of a U(2) q ×U(2)ℓ flavour symmetry. We further exemplify the general EFT findings by means of simplified models with explicit mediators in the TeV range: coloured scalar or vector leptoquarks and colour-less vectors. Among these, the case of an SU(2) L -singlet vector leptoquark emerges as a particularly simple and successful framework.

A Computational Study of a New Dual Throat Fluidic Thrust Vectoring Nozzle Concept

NASA Technical Reports Server (NTRS)

Deere, Karen A.; Berrier, Bobby L.; Flamm, Jeffrey D.; Johnson, Stuart K.

2005-01-01

A computational investigation of a two-dimensional nozzle was completed to assess the use of fluidic injection to manipulate flow separation and cause thrust vectoring of the primary jet thrust. The nozzle was designed with a recessed cavity to enhance the throat shifting method of fluidic thrust vectoring. Several design cycles with the structured-grid, computational fluid dynamics code PAB3D and with experiments in the NASA Langley Research Center Jet Exit Test Facility have been completed to guide the nozzle design and analyze performance. This paper presents computational results on potential design improvements for best experimental configuration tested to date. Nozzle design variables included cavity divergence angle, cavity convergence angle and upstream throat height. Pulsed fluidic injection was also investigated for its ability to decrease mass flow requirements. Internal nozzle performance (wind-off conditions) and thrust vector angles were computed for several configurations over a range of nozzle pressure ratios from 2 to 7, with the fluidic injection flow rate equal to 3 percent of the primary flow rate. Computational results indicate that increasing cavity divergence angle beyond 10 is detrimental to thrust vectoring efficiency, while increasing cavity convergence angle from 20 to 30 improves thrust vectoring efficiency at nozzle pressure ratios greater than 2, albeit at the expense of discharge coefficient. Pulsed injection was no more efficient than steady injection for the Dual Throat Nozzle concept.

Considerations for the Use of Human Participants in Vector Biology Research: A Tool for Investigators and Regulators

PubMed Central

Youngblood, Laura; Bangs, Michael J.; Lavery, James V.; James, Stephanie

2015-01-01

Abstract A thorough search of the existing literature has revealed that there are currently no published recommendations or guidelines for the interpretation of US regulations on the use of human participants in vector biology research (VBR). An informal survey of vector biologists has indicated that issues related to human participation in vector research have been largely debated by academic, national, and local Institutional Review Boards (IRBs) in the countries where the research is being conducted, and that interpretations and subsequent requirements made by these IRBs have varied widely. This document is intended to provide investigators and corresponding scientific and ethical review committee members an introduction to VBR methods involving human participation and the legal and ethical framework in which such studies are conducted with a focus on US Federal Regulations. It is also intended to provide a common perspective for guiding researchers, IRB members, and other interested parties (i.e., public health officials conducting routine entomological surveillance) in the interpretation of human subjects regulations pertaining to VBR. PMID:25700039

SVGenes: a library for rendering genomic features in scalable vector graphic format.

PubMed

Etherington, Graham J; MacLean, Daniel

2013-08-01

Drawing genomic features in attractive and informative ways is a key task in visualization of genomics data. Scalable Vector Graphics (SVG) format is a modern and flexible open standard that provides advanced features including modular graphic design, advanced web interactivity and animation within a suitable client. SVGs do not suffer from loss of image quality on re-scaling and provide the ability to edit individual elements of a graphic on the whole object level independent of the whole image. These features make SVG a potentially useful format for the preparation of publication quality figures including genomic objects such as genes or sequencing coverage and for web applications that require rich user-interaction with the graphical elements. SVGenes is a Ruby-language library that uses SVG primitives to render typical genomic glyphs through a simple and flexible Ruby interface. The library implements a simple Page object that spaces and contains horizontal Track objects that in turn style, colour and positions features within them. Tracks are the level at which visual information is supplied providing the full styling capability of the SVG standard. Genomic entities like genes, transcripts and histograms are modelled in Glyph objects that are attached to a track and take advantage of SVG primitives to render the genomic features in a track as any of a selection of defined glyphs. The feature model within SVGenes is simple but flexible and not dependent on particular existing gene feature formats meaning graphics for any existing datasets can easily be created without need for conversion. The library is provided as a Ruby Gem from https://rubygems.org/gems/bio-svgenes under the MIT license, and open source code is available at https://github.com/danmaclean/bioruby-svgenes also under the MIT License. dan.maclean@tsl.ac.uk.

Parallel implementation of an adaptive and parameter-free N-body integrator

NASA Astrophysics Data System (ADS)

Pruett, C. David; Ingham, William H.; Herman, Ralph D.

2011-05-01

Previously, Pruett et al. (2003) [3] described an N-body integrator of arbitrarily high order M with an asymptotic operation count of O(MN). The algorithm's structure lends itself readily to data parallelization, which we document and demonstrate here in the integration of point-mass systems subject to Newtonian gravitation. High order is shown to benefit parallel efficiency. The resulting N-body integrator is robust, parameter-free, highly accurate, and adaptive in both time-step and order. Moreover, it exhibits linear speedup on distributed parallel processors, provided that each processor is assigned at least a handful of bodies. Program summaryProgram title: PNB.f90 Catalogue identifier: AEIK_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEIK_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC license, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 3052 No. of bytes in distributed program, including test data, etc.: 68 600 Distribution format: tar.gz Programming language: Fortran 90 and OpenMPI Computer: All shared or distributed memory parallel processors Operating system: Unix/Linux Has the code been vectorized or parallelized?: The code has been parallelized but has not been explicitly vectorized. RAM: Dependent upon N Classification: 4.3, 4.12, 6.5 Nature of problem: High accuracy numerical evaluation of trajectories of N point masses each subject to Newtonian gravitation. Solution method: Parallel and adaptive extrapolation in time via power series of arbitrary degree. Running time: 5.1 s for the demo program supplied with the package.

A Guide for Graduate Students Interested in Postdoctoral Positions in Biology Education Research.

PubMed

Aikens, Melissa L; Corwin, Lisa A; Andrews, Tessa C; Couch, Brian A; Eddy, Sarah L; McDonnell, Lisa; Trujillo, Gloriana

Postdoctoral positions in biology education research (BER) are becoming increasingly common as the field grows. However, many life science graduate students are unaware of these positions or do not understand what these positions entail or the careers with which they align. In this essay, we use a backward-design approach to inform life science graduate students of postdoctoral opportunities in BER. Beginning with the end in mind, we first discuss the types of careers to which BER postdoctoral positions lead. We then discuss the different types of BER postdoctoral positions, drawing on our own experiences and those of faculty mentors. Finally, we discuss activities in which life science graduate students can engage that will help them gauge whether BER aligns with their research interests and develop skills to be competitive for BER postdoctoral positions. © 2016 M. L. Aikens, L. A. Corwin, et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Regulating the sale of tobacco in New Zealand: A qualitative analysis of retailers' views and implications for advocacy.

PubMed

Robertson, Lindsay; Marsh, Louise; Hoek, Janet; McGee, Rob; Egan, Richard

2015-12-01

In contrast to the sale of alcohol and other psychoactive substances, the retail availability of tobacco in New Zealand (NZ) is relatively unregulated. Tobacco is almost universally available, and the absence of a licensing scheme for tobacco retailers makes enforcement of retail-level legislation challenging. As a key stakeholder group, the views of tobacco retailers are likely to influence the tobacco retail policies that gain political support. We explored NZ tobacco retailers' views towards mandatory licensing of tobacco retailers, and how they perceived policies that would reduce tobacco availability. We conducted face-to-face interviews with tobacco retail store owners and managers throughout NZ (n=21). A semi-structured interview guide was used, and interviews explored participants' views of existing tobacco retail policies, the NZ government's goal of becoming a smokefree country by 2025, possible future policies, such as licensing of tobacco retailers, and perceptions of selling tobacco. Qualitative content analysis was conducted using the interview transcripts as the data source. The tobacco retailers interviewed expressed varying views on how tobacco sales should be regulated. Around half of the study participants were positive or indifferent about mandatory retailer licensing, and several believed licensing would not have a large impact on them. The idea of restricting the sale of tobacco within 500m of a school was generally well received by participants, and had more support than policies that would prohibit certain outlet types from selling tobacco. In contrast to claims made by industry-related organisations, a proposed licensing policy is unlikely to be met with blanket opposition from tobacco retailers. Advocacy efforts may garner more support for tobacco retail policies if the purpose of policies was framed in terms of protecting young people from smoking. Copyright © 2015 Elsevier B.V. All rights reserved.

Formation mechanism of guided resonances and bound states in the continuum in photonic crystal slabs

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

Gao, Xingwei; Hsu, Chia Wei; Zhen, Bo

2016-08-25

We develop a formalism, based on the mode expansion method, to describe the guided resonances and bound states in the continuum (BICs) in photonic crystal slabs with one-dimensional periodicity. This approach provides analytic insights to the formation mechanisms of these states: the guided resonances arise from the transverse Fabry–Pérot condition, and the divergence of the resonance lifetimes at the BICs is explained by a destructive interference of radiation from different propagating components inside the slab. As a result, we show BICs at the center and on the edge of the Brillouin zone protected by symmetry, BICs at generic wave vectorsmore » not protected by symmetry, and the annihilation of BICs at low-symmetry wave vectors.« less

Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery.

PubMed

Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

2015-04-10

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.

Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery

PubMed Central

Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

2015-01-01

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release. PMID:25867479

CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection

PubMed Central

Liu, Jingjing; Zhang, Di; Kimata, Jason T.; Zhou, Paul

2014-01-01

CCR5, a coreceptor for HIV-1 entry, is a major target for drug and genetic intervention against HIV-1. Genetic intervention strategies have knocked down CCR5 expression levels by shRNA or disrupted the CCR5 gene using zinc finger nucleases (ZFN) or Transcription activator-like effector nuclease (TALEN). In the present study, we silenced CCR5 via CRISPR associated protein 9 (Cas9) and single guided RNAs (sgRNAs). We constructed lentiviral vectors expressing Cas9 and CCR5 sgRNAs. We show that a single round transduction of lentiviral vectors expressing Cas9 and CCR5 sgRNAs into HIV-1 susceptible human CD4+ cells yields high frequencies of CCR5 gene disruption. CCR5 gene-disrupted cells are not only resistant to R5-tropic HIV-1, including transmitted/founder (T/F) HIV-1 isolates, but also have selective advantage over CCR5 gene-undisrupted cells during R5-tropic HIV-1 infection. Importantly, using T7 endonuclease I assay we did not detect genome mutations at potential off-target sites that are highly homologous to these CCR5 sgRNAs in stably transduced cells even at 84 days post transduction. Thus we conclude that silencing of CCR5 via Cas9 and CCR5-specific sgRNAs could be a viable alternative strategy for engineering resistance against HIV-1. PMID:25541967

Normal mode-guided transition pathway generation in proteins

PubMed Central

Lee, Byung Ho; Seo, Sangjae; Kim, Min Hyeok; Kim, Youngjin; Jo, Soojin; Choi, Moon-ki; Lee, Hoomin; Choi, Jae Boong

2017-01-01

The biological function of proteins is closely related to its structural motion. For instance, structurally misfolded proteins do not function properly. Although we are able to experimentally obtain structural information on proteins, it is still challenging to capture their dynamics, such as transition processes. Therefore, we need a simulation method to predict the transition pathways of a protein in order to understand and study large functional deformations. Here, we present a new simulation method called normal mode-guided elastic network interpolation (NGENI) that performs normal modes analysis iteratively to predict transition pathways of proteins. To be more specific, NGENI obtains displacement vectors that determine intermediate structures by interpolating the distance between two end-point conformations, similar to a morphing method called elastic network interpolation. However, the displacement vector is regarded as a linear combination of the normal mode vectors of each intermediate structure, in order to enhance the physical sense of the proposed pathways. As a result, we can generate more reasonable transition pathways geometrically and thermodynamically. By using not only all normal modes, but also in part using only the lowest normal modes, NGENI can still generate reasonable pathways for large deformations in proteins. This study shows that global protein transitions are dominated by collective motion, which means that a few lowest normal modes play an important role in this process. NGENI has considerable merit in terms of computational cost because it is possible to generate transition pathways by partial degrees of freedom, while conventional methods are not capable of this. PMID:29020017

NLSEmagic: Nonlinear Schrödinger equation multi-dimensional Matlab-based GPU-accelerated integrators using compact high-order schemes

NASA Astrophysics Data System (ADS)

Caplan, R. M.

2013-04-01

We present a simple to use, yet powerful code package called NLSEmagic to numerically integrate the nonlinear Schrödinger equation in one, two, and three dimensions. NLSEmagic is a high-order finite-difference code package which utilizes graphic processing unit (GPU) parallel architectures. The codes running on the GPU are many times faster than their serial counterparts, and are much cheaper to run than on standard parallel clusters. The codes are developed with usability and portability in mind, and therefore are written to interface with MATLAB utilizing custom GPU-enabled C codes with the MEX-compiler interface. The packages are freely distributed, including user manuals and set-up files. Catalogue identifier: AEOJ_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEOJ_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 124453 No. of bytes in distributed program, including test data, etc.: 4728604 Distribution format: tar.gz Programming language: C, CUDA, MATLAB. Computer: PC, MAC. Operating system: Windows, MacOS, Linux. Has the code been vectorized or parallelized?: Yes. Number of processors used: Single CPU, number of GPU processors dependent on chosen GPU card (max is currently 3072 cores on GeForce GTX 690). Supplementary material: Setup guide, Installation guide. RAM: Highly dependent on dimensionality and grid size. For typical medium-large problem size in three dimensions, 4GB is sufficient. Keywords: Nonlinear Schröodinger Equation, GPU, high-order finite difference, Bose-Einstien condensates. Classification: 4.3, 7.7. Nature of problem: Integrate solutions of the time-dependent one-, two-, and three-dimensional cubic nonlinear Schrödinger equation. Solution method: The integrators utilize a fully-explicit fourth-order Runge-Kutta scheme in time and both second- and fourth-order differencing in space. The integrators are written to run on NVIDIA GPUs and are interfaced with MATLAB including built-in visualization and analysis tools. Restrictions: The main restriction for the GPU integrators is the amount of RAM on the GPU as the code is currently only designed for running on a single GPU. Unusual features: Ability to visualize real-time simulations through the interaction of MATLAB and the compiled GPU integrators. Additional comments: Setup guide and Installation guide provided. Program has a dedicated web site at www.nlsemagic.com. Running time: A three-dimensional run with a grid dimension of 87×87×203 for 3360 time steps (100 non-dimensional time units) takes about one and a half minutes on a GeForce GTX 580 GPU card.

Clinical Outcomes of SMILE With a Triple Centration Technique and Corneal Wavefront-Guided Transepithelial PRK in High Astigmatism.

PubMed

Jun, Ikhyun; Kang, David Sung Yong; Reinstein, Dan Z; Arba-Mosquera, Samuel; Archer, Timothy J; Seo, Kyoung Yul; Kim, Tae-Im

2018-03-01

To comparatively investigate the clinical outcomes, vector parameters, and corneal aberrations of small incision lenticule extraction (SMILE) with a triple centration technique and corneal wavefront-guided transepithelial photorefractive keratectomy (PRK) for the correction of high astigmatism. This retrospective, comparative case series study included 89 eyes (89 patients) that received treatment for myopia with high astigmatism (≥ 2.50 diopters) using SMILE with a triple centration technique (SMILE group; 45 eyes) and corneal wavefront-guided transepithelial PRK (transepithelial PRK group; 44 eyes). Visual acuity measurement, manifest refraction, slit-lamp examination, autokeratometry, corneal topography, and evaluation of corneal wavefront aberration were performed preoperatively and at 1, 3, and 6 months after surgery. The safety, efficacy, vector parameters, and corneal aberrations at 6 months after surgery were compared between the two groups. At 6 months after surgery, the transepithelial PRK and SMILE groups exhibited comparable mean uncorrected distance visual acuities (-0.06 ± 0.07 and -0.05 ± 0.07 logMAR, respectively), safety, efficacy, and predictability of refractive and visual outcomes. There was a slight but statistically significant difference in the correction index between the transepithelial PRK and SMILE groups (0.96 ± 0.11 and 0.91 ± 0.10, respectively). Whereas the transepithelial PRK group exhibited increased corneal spherical aberration and significantly reduced corneal coma and trefoil, no changes in aberrometric values were noted in the SMILE group. Both SMILE with a triple centration technique and corneal wavefront-guided transepithelial PRK are effective and provide predictable outcomes for the correction of high myopic astigmatism, although slight undercorrection was observed in the SMILE group. The triple centration technique was helpful in astigmatism correction by SMILE. [J Refract Surg. 2018;34(3):156-163.]. Copyright 2018, SLACK Incorporated.

Gyro-gauge-independent formulation of the guiding-center reduction to arbitrary order in the Larmor radius

NASA Astrophysics Data System (ADS)

de Guillebon, L.; Vittot, M.

2013-10-01

Guiding-center reduction is studied using gyro-gauge-independent coordinates. The Lagrangian 1-form of charged particle dynamics is Lie transformed without introducing a gyro-gauge, but using directly the unit vector of the component of the velocity perpendicular to the magnetic field as the coordinate corresponding to Larmor gyration. The reduction is shown to provide a maximal reduction for the Lagrangian and to work for all orders in the Larmor radius, following exactly the same procedure as when working with the standard gauge-dependent coordinate. The gauge-dependence is removed from the coordinate system by using a constrained variable for the gyro-angle. The closed 1-form dθ is replaced by a more general non-closed 1-form, which is equal to dθ in the gauge-dependent case. The gauge vector is replaced by a more general connection in the definition of the gradient, which behaves as a covariant derivative, in perfect agreement with the circle-bundle picture. This explains some results of previous works, whose gauge-independent expressions did not correspond to gauge fixing but did indeed correspond to connection fixing. In addition, some general results are obtained for the guiding-center reduction. The expansion is polynomial in the cotangent of the pitch-angle as an effect of the structure of the Lagrangian, preserved by Lie derivatives. The induction for the reduction is shown to rely on the inversion of a matrix, which is the same for all orders higher than three. It is inverted and explicit induction relations are obtained to go to an arbitrary order in the perturbation expansion. The Hamiltonian and symplectic representations of the guiding-center reduction are recovered, but conditions for the symplectic representation at each order are emphasized.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies.

PubMed

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A

2017-08-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy.

Modeling of Mean-VaR portfolio optimization by risk tolerance when the utility function is quadratic

NASA Astrophysics Data System (ADS)

Sukono, Sidi, Pramono; Bon, Abdul Talib bin; Supian, Sudradjat

2017-03-01

The problems of investing in financial assets are to choose a combination of weighting a portfolio can be maximized return expectations and minimizing the risk. This paper discusses the modeling of Mean-VaR portfolio optimization by risk tolerance, when square-shaped utility functions. It is assumed that the asset return has a certain distribution, and the risk of the portfolio is measured using the Value-at-Risk (VaR). So, the process of optimization of the portfolio is done based on the model of Mean-VaR portfolio optimization model for the Mean-VaR done using matrix algebra approach, and the Lagrange multiplier method, as well as Khun-Tucker. The results of the modeling portfolio optimization is in the form of a weighting vector equations depends on the vector mean return vector assets, identities, and matrix covariance between return of assets, as well as a factor in risk tolerance. As an illustration of numeric, analyzed five shares traded on the stock market in Indonesia. Based on analysis of five stocks return data gained the vector of weight composition and graphics of efficient surface of portfolio. Vector composition weighting weights and efficient surface charts can be used as a guide for investors in decisions to invest.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies

PubMed Central

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A.

2017-01-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy. PMID:28817344

Safety and licensing of a small modular gas-cooled reactor system

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

Brown, N.W.; Kelley, A.P. Jr.

A modular side-by-side high-temperature gas-cooled reactor (SBS-HTGR) is being developed by Interatom/Kraftwerk Union (KWU). The General Electric Company and Interatom/KWU entered into a proprietary working agreement to continue develop jointly of the SBS-HTGR. A study on adapting the SBS-HTGR for application in the US has been completed. The study investigated the safety characteristics and the use of this type of design in an innovative approach to licensing. The safety objective guiding the design of the modular SBS-HTGR is to control radionuclide release by the retention of fission products within the fuel particles with minimal reliance on active design features. Themore » philosophy on which this objective is predicated is that by providing a simple safety case, the safety criteria can be demonstrated as being met with high confidence through conduct of a full-scale module safety test.« less

Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

PubMed

Volz, A; Sutter, G

2017-01-01

Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

Ethical and Human Rights Foundations of Health Policy: Lessons from Comprehensive Reform in Mexico.

PubMed

Frenk, Julio; Gómez-Dantés, Octavio

2015-12-10

This paper discusses the use of an explicit ethical and human rights framework to guide a reform intended to provide universal and comprehensive social protection in health for all Mexicans, independently of their socio-economic status or labor market condition. This reform was designed, implemented, and evaluated by making use of what Michael Reich has identified as the three pillars of public policy: technical, political, and ethical. The use of evidence and political strategies in the design and negotiation of the Mexican health reform is briefly discussed in the first part of this paper. The second part examines the ethical component of the reform, including the guiding concept and values, as well as the specific entitlements that gave operational meaning to the right to health care that was enshrined in Mexico's 1983 Constitution. The impact of this rights-based health reform, measured through an external evaluation, is discussed in the final section. The main message of this paper is that a clear ethical framework, combined with technical excellence and political skill, can deliver major policy results. Copyright © 2015 Frenk and Gómez-Dantés. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Insights in luteovirid structural biology guided by chemical cross-linking and high resolution mass spectrometry

USDA-ARS?s Scientific Manuscript database

Interactions among plant pathogenic viruses in the family /react-text Luteoviridae react-text: 233 and their plant hosts and insect vectors are governed by the topology of the viral capsid, which is the sole vehicle for long distance movement of the viral genome. Previous application of a mass spect...

Toward Automating Web Protocol Configuration for a Programmable Logic Controller Emulator

DTIC Science & Technology

2014-06-19

Security Risks for Industrial Control Systems ,” VDE 2004 Congress, Berlin, Germany, October 2004, pp. 1-7. [Cis12] Cisco, NetFlow Configuration Guide...Date 29 May 2014 Date AFIT-ENG-T-14-J-4 Abstract Industrial Control Systems (ICS) remain vulnerable through attack vectors that exist within programmable...5 2.2 Industrial Control Systems

A Padawan Programmer's Guide to Developing Software Libraries.

PubMed

Yurkovich, James T; Yurkovich, Benjamin J; Dräger, Andreas; Palsson, Bernhard O; King, Zachary A

2017-11-22

With the rapid adoption of computational tools in the life sciences, scientists are taking on the challenge of developing their own software libraries and releasing them for public use. This trend is being accelerated by popular technologies and platforms, such as GitHub, Jupyter, R/Shiny, that make it easier to develop scientific software and by open-source licenses that make it easier to release software. But how do you build a software library that people will use? And what characteristics do the best libraries have that make them enduringly popular? Here, we provide a reference guide, based on our own experiences, for developing software libraries along with real-world examples to help provide context for scientists who are learning about these concepts for the first time. While we can only scratch the surface of these topics, we hope that this article will act as a guide for scientists who want to write great software that is built to last. Copyright © 2017 Elsevier Inc. All rights reserved.

Study on the precision of the guide control system of independent wheel

NASA Astrophysics Data System (ADS)

ji, Y.; Ren, L.; Li, R.; Sun, W.

2016-09-01

The torque ripple of permanent magnet synchronous motor vector with active control is studied in this paper. The ripple appears because of the impact of position detection and current detection, the error generated in inverter and the influence of motor ontology (magnetic chain harmonic and the cogging effect and so on). Then, the simulation dynamic model of bogie with permanent magnet synchronous motor vector control system is established with MATLAB/Simulink. The stability of bogie with steering control is studied. The relationship between the error of the motor and the precision of the control system is studied. The result shows that the existing motor does not meet the requirements of the control system.

Improving Vector Evaluated Particle Swarm Optimisation Using Multiple Nondominated Leaders

PubMed Central

Lim, Kian Sheng; Buyamin, Salinda; Ahmad, Anita; Shapiai, Mohd Ibrahim; Naim, Faradila; Mubin, Marizan; Kim, Dong Hwa

2014-01-01

The vector evaluated particle swarm optimisation (VEPSO) algorithm was previously improved by incorporating nondominated solutions for solving multiobjective optimisation problems. However, the obtained solutions did not converge close to the Pareto front and also did not distribute evenly over the Pareto front. Therefore, in this study, the concept of multiple nondominated leaders is incorporated to further improve the VEPSO algorithm. Hence, multiple nondominated solutions that are best at a respective objective function are used to guide particles in finding optimal solutions. The improved VEPSO is measured by the number of nondominated solutions found, generational distance, spread, and hypervolume. The results from the conducted experiments show that the proposed VEPSO significantly improved the existing VEPSO algorithms. PMID:24883386

The inference of vector magnetic fields from polarization measurements with limited spectral resolution

NASA Technical Reports Server (NTRS)

Lites, B. W.; Skumanich, A.

1985-01-01

A method is presented for recovery of the vector magnetic field and thermodynamic parameters from polarization measurement of photospheric line profiles measured with filtergraphs. The method includes magneto-optic effects and may be utilized on data sampled at arbitrary wavelengths within the line profile. The accuracy of this method is explored through inversion of synthetic Stokes profiles subjected to varying levels of random noise, instrumental wave-length resolution, and line profile sampling. The level of error introduced by the systematic effect of profile sampling over a finite fraction of the 5 minute oscillation cycle is also investigated. The results presented here are intended to guide instrumental design and observational procedure.

Amplitude and dynamics of polarization-plane signaling in the central complex of the locust brain

PubMed Central

Bockhorst, Tobias

2015-01-01

The polarization pattern of skylight provides a compass cue that various insect species use for allocentric orientation. In the desert locust, Schistocerca gregaria, a network of neurons tuned to the electric field vector (E-vector) angle of polarized light is present in the central complex of the brain. Preferred E-vector angles vary along slices of neuropils in a compasslike fashion (polarotopy). We studied how the activity in this polarotopic population is modulated in ways suited to control compass-guided locomotion. To this end, we analyzed tuning profiles using measures of correlation between spike rate and E-vector angle and, furthermore, tested for adaptation to stationary angles. The results suggest that the polarotopy is stabilized by antagonistic integration across neurons with opponent tuning. Downstream to the input stage of the network, responses to stationary E-vector angles adapted quickly, which may correlate with a tendency to steer a steady course previously observed in tethered flying locusts. By contrast, rotating E-vectors corresponding to changes in heading direction under a natural sky elicited nonadapting responses. However, response amplitudes were particularly variable at the output stage, covarying with the level of ongoing activity. Moreover, the responses to rotating E-vector angles depended on the direction of rotation in an anticipatory manner. Our observations support a view of the central complex as a substrate of higher-stage processing that could assign contextual meaning to sensory input for motor control in goal-driven behaviors. Parallels to higher-stage processing of sensory information in vertebrates are discussed. PMID:25609107

Fiber-guided modes conversion using superposed helical gratings

NASA Astrophysics Data System (ADS)

Ma, Yancheng; Fang, Liang; Wu, Guoan

2017-03-01

Optical fibers can support various modal forms, including vector modes, linear polarization (LP) modes, and orbital angular momentum (OAM) modes, etc. The modal correlation among these modes is investigated via Jones matrix, associated with polarization and helical phase corresponding to spin angular momentum (SAM) and OAM of light, respectively. We can generate different modal forms by adopting superposed helical gratings (SHGs) with opposite helix orientations. Detailed analysis and discussion on mode conversion is given as for mode coupling in optical fibers with both low and high contrast index, respectively. Our study may deepen the understanding for various fiber-guided modes and mode conversion among them via fiber gratings.

Inhibition of HIV-1 gene expression by retroviral vector-mediated small-guide RNAs that direct specific RNA cleavage by tRNase ZL

PubMed Central

Habu, Yuichiro; Miyano-Kurosaki, Naoko; Kitano, Michiko; Endo, Yumihiko; Yukita, Masakazu; Ohira, Shigeru; Takaku, Hiroaki; Nashimoto, Masayuki; Takaku, Hiroshi

2005-01-01

The tRNA 3′-processing endoribonuclease (tRNase Z or 3′ tRNase; EC 3.1.26.11) is an essential enzyme that removes the 3′ trailer from pre-tRNA. The long form (tRNase ZL) can cleave a target RNA in vitro at the site directed by an appropriate small-guide RNA (sgRNA). Here, we investigated whether this sgRNA/tRNase ZL strategy could be applied to gene therapy for AIDS. We tested the ability of four sgRNA-expression plasmids to inhibit HIV-1 gene expression in COS cells, using a transient-expression assay. The three sgRNAs guide inhibition of HIV-1 gene expression in cultured COS cells. Analysis of the HIV-1 mRNA levels suggested that sgRNA directed the tRNase ZL to mediate the degradation of target RNA. The observation that sgRNA was localized primarily in nuclei suggests that tRNase ZL cleaves the HIV-1 mRNA when complexed with sgRNA in this location. We also examined the ability of two retroviral vectors expressing sgRNA to suppress HIV-1 expression in HIV-1-infected Jurkat T cells. sgRNA-SL4 suppressed HIV-1 expression almost completely in infected cells for up to 18 days. These results suggest that the sgRNA/tRNase ZL approach is effective in downregulating HIV-1 gene expression. PMID:15647506

Construction of CRISPR Libraries for Functional Screening.

PubMed

Carstens, Carsten P; Felts, Katherine A; Johns, Sarah E

2018-01-01

Identification of gene function has been aided by the ability to generate targeted gene knockouts or transcriptional repression using the CRISPR/CAS9 system. Using pooled libraries of guide RNA expression vectors that direct CAS9 to a specific genomic site allows identification of genes that are either enriched or depleted in response to a selection scheme, thus linking the affected gene to the chosen phenotype. The quality of the data generated by the screening is dependent on the quality of the guide RNA delivery library with regards to error rates and especially evenness of distribution of the guides. Here, we describe a method for constructing complex plasmid libraries based on pooled designed oligomers with high representation and tight distributions. The procedure allows construction of plasmid libraries of >60,000 members with a 95th/5th percentile ratio of less than 3.5.

Production of adenovirus vectors and their use as a delivery system for influenza vaccines

PubMed Central

Vemula, Sai V.; Mittal, Suresh K.

2010-01-01

IMPORTANCE OF THE FIELD With the emergence of highly pathogenic avian influenza H5N1 viruses that have crossed species barriers and are responsible for lethal infections in humans in many countries, there is an urgent need for the development of effective vaccines which can be produced in large quantities at a short notice and confer broad protection against these H5N1 variants. In order to meet the potential global vaccine demand in a pandemic scenario, new vaccine-production strategies must be explored in addition to the currently used egg-based technology for seasonal influenza. AREAS COVERED IN THIS REVIEW Adenovirus (Ad) based influenza vaccines represent an attractive alternative/supplement to the currently licensed egg-based influenza vaccines. Ad-based vaccines are relatively inexpensive to manufacture, and their production process does not require either chicken eggs or labor intensive and time-consuming processes necessitating enhanced biosafety facilities. Most importantly, in a pandemic situation, this vaccine strategy could offer a stockpiling option to reduce the response time before a strain-matched vaccine could be developed. WHAT THE READER WILL GAIN This review discusses Ad-vector technology and the current progress in the development of Ad-based influenza vaccines. TAKE HOME MESSAGE Ad vector-based influenza vaccines for pandemic preparedness are under development to meet the global vaccine demand. PMID:20822477

Innovative Techniques for Estimating Illegal Activities in a Human-Wildlife-Management Conflict

PubMed Central

Cross, Paul; St. John, Freya A. V.; Khan, Saira; Petroczi, Andrea

2013-01-01

Effective management of biological resources is contingent upon stakeholder compliance with rules. With respect to disease management, partial compliance can undermine attempts to control diseases within human and wildlife populations. Estimating non-compliance is notoriously problematic as rule-breakers may be disinclined to admit to transgressions. However, reliable estimates of rule-breaking are critical to policy design. The European badger (Meles meles) is considered an important vector in the transmission and maintenance of bovine tuberculosis (bTB) in cattle herds. Land managers in high bTB prevalence areas of the UK can cull badgers under license. However, badgers are also known to be killed illegally. The extent of illegal badger killing is currently unknown. Herein we report on the application of three innovative techniques (Randomized Response Technique (RRT); projective questioning (PQ); brief implicit association test (BIAT)) for investigating illegal badger killing by livestock farmers across Wales. RRT estimated that 10.4% of farmers killed badgers in the 12 months preceding the study. Projective questioning responses and implicit associations relate to farmers' badger killing behavior reported via RRT. Studies evaluating the efficacy of mammal vector culling and vaccination programs should incorporate estimates of non-compliance. Mitigating the conflict concerning badgers as a vector of bTB requires cross-disciplinary scientific research, departure from deep-rooted positions, and the political will to implement evidence-based management. PMID:23341973

Innovative techniques for estimating illegal activities in a human-wildlife-management conflict.

PubMed

Cross, Paul; St John, Freya A V; Khan, Saira; Petroczi, Andrea

2013-01-01

Effective management of biological resources is contingent upon stakeholder compliance with rules. With respect to disease management, partial compliance can undermine attempts to control diseases within human and wildlife populations. Estimating non-compliance is notoriously problematic as rule-breakers may be disinclined to admit to transgressions. However, reliable estimates of rule-breaking are critical to policy design. The European badger (Meles meles) is considered an important vector in the transmission and maintenance of bovine tuberculosis (bTB) in cattle herds. Land managers in high bTB prevalence areas of the UK can cull badgers under license. However, badgers are also known to be killed illegally. The extent of illegal badger killing is currently unknown. Herein we report on the application of three innovative techniques (Randomized Response Technique (RRT); projective questioning (PQ); brief implicit association test (BIAT)) for investigating illegal badger killing by livestock farmers across Wales. RRT estimated that 10.4% of farmers killed badgers in the 12 months preceding the study. Projective questioning responses and implicit associations relate to farmers' badger killing behavior reported via RRT. Studies evaluating the efficacy of mammal vector culling and vaccination programs should incorporate estimates of non-compliance. Mitigating the conflict concerning badgers as a vector of bTB requires cross-disciplinary scientific research, departure from deep-rooted positions, and the political will to implement evidence-based management.

Vaccines and immunization strategies for dengue prevention

PubMed Central

Liu, Yang; Liu, Jianying; Cheng, Gong

2016-01-01

Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future. PMID:27436365

Strengthening tactical planning and operational frameworks for vector control: the roadmap for malaria elimination in Namibia.

PubMed

Chanda, Emmanuel; Ameneshewa, Birkinesh; Angula, Hans A; Iitula, Iitula; Uusiku, Pentrina; Trune, Desta; Islam, Quazi M; Govere, John M

2015-08-05

Namibia has made tremendous gains in malaria control and the epidemiological trend of the disease has changed significantly over the past years. In 2010, the country reoriented from the objective of reducing disease morbidity and mortality to the goal of achieving malaria elimination by 2020. This manuscript outlines the processes undertaken in strengthening tactical planning and operational frameworks for vector control to facilitate expeditious malaria elimination in Namibia. The information sources for this study included all available data and accessible archived documentary records on malaria vector control in Namibia. A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases, Google Scholar, PubMed and WHO, using a combination of search terms. To attain the goal of elimination in Namibia, systems are being strengthened to identify and clear all infections, and significantly reduce human-mosquito contact. Particularly, consolidating vector control for reducing transmission at the identified malaria foci will be critical for accelerated malaria elimination. Thus, guarding against potential challenges and the need for evidence-based and sustainable vector control instigated the strengthening of strategic frameworks by: adopting the integrated vector management (IVM) strategy; initiating implementation of the global plan for insecticide resistance management (GPIRM); intensifying malaria vector surveillance; improving data collection and reporting systems on DDT; updating the indoor residual spraying (IRS) data collection and reporting tool; and, improving geographical reconnaissance using geographical information system-based satellite imagery. Universal coverage with IRS and long-lasting insecticidal nets, supplemented by larval source management in the context of IVM and guided by vector surveillance coupled with rational operationalization of the GPIRM, will enable expeditious attainment of elimination in Namibia. However, national capacity to plan, implement, monitor and evaluate interventions will require adequate and sustained support for technical, physical infrastructure, and human and financial resources for entomology and vector control operations.

Heading-vector navigation based on head-direction cells and path integration.

PubMed

Kubie, John L; Fenton, André A

2009-05-01

Insect navigation is guided by heading vectors that are computed by path integration. Mammalian navigation models, on the other hand, are typically based on map-like place representations provided by hippocampal place cells. Such models compute optimal routes as a continuous series of locations that connect the current location to a goal. We propose a "heading-vector" model in which head-direction cells or their derivatives serve both as key elements in constructing the optimal route and as the straight-line guidance during route execution. The model is based on a memory structure termed the "shortcut matrix," which is constructed during the initial exploration of an environment when a set of shortcut vectors between sequential pairs of visited waypoint locations is stored. A mechanism is proposed for calculating and storing these vectors that relies on a hypothesized cell type termed an "accumulating head-direction cell." Following exploration, shortcut vectors connecting all pairs of waypoint locations are computed by vector arithmetic and stored in the shortcut matrix. On re-entry, when local view or place representations query the shortcut matrix with a current waypoint and goal, a shortcut trajectory is retrieved. Since the trajectory direction is in head-direction compass coordinates, navigation is accomplished by tracking the firing of head-direction cells that are tuned to the heading angle. Section 1 of the manuscript describes the properties of accumulating head-direction cells. It then shows how accumulating head-direction cells can store local vectors and perform vector arithmetic to perform path-integration-based homing. Section 2 describes the construction and use of the shortcut matrix for computing direct paths between any pair of locations that have been registered in the shortcut matrix. In the discussion, we analyze the advantages of heading-based navigation over map-based navigation. Finally, we survey behavioral evidence that nonhippocampal, heading-based navigation is used in small mammals and humans. Copyright 2008 Wiley-Liss, Inc.

MRI-Guided Delivery of Viral Vectors.

PubMed

Salegio, Ernesto A; Bringas, John; Bankiewicz, Krystof S

2016-01-01

Gene therapy has emerged as a potential avenue of treatment for many neurological disorders. Technological advances in imaging techniques allow for the monitoring of real-time infusions into the brain of rodents, nonhuman primates, and humans. Here, we discuss the use of magnetic resonance imaging (MRI) as a tool in the delivery of adeno-associated viral (AAV) particles into brain of nonhuman primates.

Experimental Study of an Axisymmetric Dual Throat Fluidic Thrust Vectoring Nozzle for Supersonic Aircraft Application

NASA Technical Reports Server (NTRS)

Flamm, Jeffrey D.; Deere, Karen A.; Mason, Mary L.; Berrier, Bobby L.; Johnson, Stuart K.

2007-01-01

An axisymmetric version of the Dual Throat Nozzle concept with a variable expansion ratio has been studied to determine the impacts on thrust vectoring and nozzle performance. The nozzle design, applicable to a supersonic aircraft, was guided using the unsteady Reynolds-averaged Navier-Stokes computational fluid dynamics code, PAB3D. The axisymmetric Dual Throat Nozzle concept was tested statically in the Jet Exit Test Facility at the NASA Langley Research Center. The nozzle geometric design variables included circumferential span of injection, cavity length, cavity convergence angle, and nozzle expansion ratio for conditions corresponding to take-off and landing, mid climb and cruise. Internal nozzle performance and thrust vectoring performance was determined for nozzle pressure ratios up to 10 with secondary injection rates up to 10 percent of the primary flow rate. The 60 degree span of injection generally performed better than the 90 degree span of injection using an equivalent injection area and number of holes, in agreement with computational results. For injection rates less than 7 percent, thrust vector angle for the 60 degree span of injection was 1.5 to 2 degrees higher than the 90 degree span of injection. Decreasing cavity length improved thrust ratio and discharge coefficient, but decreased thrust vector angle and thrust vectoring efficiency. Increasing cavity convergence angle from 20 to 30 degrees increased thrust vector angle by 1 degree over the range of injection rates tested, but adversely affected system thrust ratio and discharge coefficient. The dual throat nozzle concept generated the best thrust vectoring performance with an expansion ratio of 1.0 (a cavity in between two equal minimum areas). The variable expansion ratio geometry did not provide the expected improvements in discharge coefficient and system thrust ratio throughout the flight envelope of typical a supersonic aircraft. At mid-climb and cruise conditions, the variable geometry design compromised thrust vector angle achieved, but some thrust vector control would be available, potentially for aircraft trim. The fixed area, expansion ratio of 1.0, Dual Throat Nozzle provided the best overall compromise for thrust vectoring and nozzle internal performance over the range of NPR tested compared to the variable geometry Dual Throat Nozzle.

O Electromagnetic Power Waves and Power Density Components.

NASA Astrophysics Data System (ADS)

Petzold, Donald Wayne

1980-12-01

On January 10, 1884 Lord Rayleigh presented a paper entitled "On the Transfer of Energy in the Electromagnetic Field" to the Royal Society of London. This paper had been authored by the late Fellow of Trinity College, Cambridge, Professor J. H. Poynting and in it he claimed that there was a general law for the transfer of electromagnetic energy. He argued that associated with each point in space is a quantity, that has since been called the Poynting vector, that is a measure of the rate of energy flow per unit area. His analysis was concerned with the integration of this power density vector at all points over an enclosing surface of a specific volume. The interpretation of this Poynting vector as a true measure of the local power density was viewed with great skepticism unless the vector was integrated over a closed surface, as the development of the concept required. However, within the last decade or so Shadowitz indicates that a number of prominent authors have argued that the criticism of the interpretation of Poynting's vector as a local power density vector is unjustified. The present paper is not concerned with these arguments but instead is concerned with a decomposition of Poynting's power density vector into two and only two components: one vector which has the same direction as Poynting's vector and which is called the forward power density vector, and another vector, directed opposite to the Poynting vector and called the reverse power density vector. These new local forward and reverse power density vectors will be shown to be dependent upon forward and reverse power wave vectors and these vectors in turn will be related to newly defined forward and reverse components of the electric and magnetic fields. The sum of these forward and reverse power density vectors, which is simply the original Poynting vector, is associated with the total electromagnetic energy traveling past the local point. Another vector which is the difference between the forward and reverse power density vectors and which will be shown to be associated with the total electric and magnetic field energy densities existing at a local point will also be introduced. These local forward and reverse power density vectors may be integrated over a surface to determine the forward and reverse powers and from these results problems related to maximum power transfer or efficiency of electromagnetic energy transmission in space may be studied in a manner similar to that presently being done with transmission lines, wave guides, and more recently with two port multiport lumped parameter systems. These new forward and reverse power density vectors at a point in space are analogous to the forward and revoltages or currents and power waves as used with the transmission line, waveguide, or port. These power wave vectors in space are a generalization of the power waves as developed by Penfield, Youla, and Kurokawa and used with the scattering parameters associated with transmission lines, waveguides and ports.

Potential Distribution of Chagas Disease Vectors (Hemiptera, Reduviidae, Triatominae) in Colombia, Based on Ecological Niche Modeling

PubMed Central

Suárez-Escudero, Laura C.; González-Caro, Sebastián

2016-01-01

Ecological niche modeling of Triatominae bugs allow us to establish the local risk of transmission of the parasite Trypanosoma cruzi, which causes Chagas disease. This information could help to guide health authority recommendations on infection monitoring, prevention, and control. In this study, we estimated the geographic distribution of triatomine species in Colombia and identified the relationship between landscape structure and climatic factors influencing their occurrence. A total of 2451 records of 4 triatomine species (Panstrongylus geniculatus, Rhodnius pallescens, R. prolixus, and Triatoma maculata) were analyzed. The variables that provided more information to explain the ecologic niche of these vectors were related to precipitation, altitude, and temperature. We found that the species with the broadest potential geographic distribution were P. geniculatus, R. pallescens, and R. prolixus. In general, the models predicted the highest occurrence probability of these vectors in the eastern slope of the Eastern Cordillera, the southern region of the Magdalena valley, and the Sierra Nevada of Santa Marta. PMID:28115946

The Gene Therapy Resource Program: A Decade of Dedication to Translational Research by the National Heart, Lung, and Blood Institute.

PubMed

Flotte, Terence R; Daniels, Eric; Benson, Janet; Bevett-Rose, Jeneé M; Cornetta, Kenneth; Diggins, Margaret; Johnston, Julie; Sepelak, Susan; van der Loo, Johannes C M; Wilson, James M; McDonald, Cheryl L

2017-12-01

Over a 10-year period, the Gene Therapy Resource Program (GTRP) of the National Heart Lung and Blood Institute has provided a set of core services to investigators to facilitate the clinical translation of gene therapy. These services have included a preclinical (research-grade) vector production core; current Good Manufacturing Practice clinical-grade vector cores for recombinant adeno-associated virus and lentivirus vectors; a pharmacology and toxicology core; and a coordinating center to manage program logistics and to provide regulatory and financial support to early-phase clinical trials. In addition, the GTRP has utilized a Steering Committee and a Scientific Review Board to guide overall progress and effectiveness and to evaluate individual proposals. These resources have been deployed to assist 82 investigators with 172 approved service proposals. These efforts have assisted in clinical trial implementation across a wide range of genetic, cardiac, pulmonary, and blood diseases. Program outcomes and potential future directions of the program are discussed.

All-in-One CRISPR-Cas9/FokI-dCas9 Vector-Mediated Multiplex Genome Engineering in Cultured Cells.

PubMed

Sakuma, Tetsushi; Sakamoto, Takuya; Yamamoto, Takashi

2017-01-01

CRISPR-Cas9 enables highly convenient multiplex genome engineering in cultured cells, because it utilizes generic Cas9 nuclease and an easily customizable single-guide RNA (sgRNA) for site-specific DNA double-strand break induction. We previously established a multiplex CRISPR-Cas9 assembly system for constructing an all-in-one vector simultaneously expressing multiple sgRNAs and Cas9 nuclease or other Cas9 variants including FokI-dCas9, which supersedes the wild-type Cas9 with regard to high specificity. In this chapter, we describe a streamlined protocol to design and construct multiplex CRISPR-Cas9 or FokI-dCas9 vectors, to introduce them into cultured cells by lipofection or electroporation, to enrich the genomically edited cells with a transient puromycin selection, to validate the mutation efficiency by Surveyor nuclease assay, and to perform off-target analyses. We show that our protocol enables highly efficient multiplex genome engineering even in hard-to-transfect HepG2 cells.

Potential Distribution of Chagas Disease Vectors (Hemiptera, Reduviidae, Triatominae) in Colombia, Based on Ecological Niche Modeling.

PubMed

Parra-Henao, Gabriel; Suárez-Escudero, Laura C; González-Caro, Sebastián

2016-01-01

Ecological niche modeling of Triatominae bugs allow us to establish the local risk of transmission of the parasite Trypanosoma cruzi, which causes Chagas disease. This information could help to guide health authority recommendations on infection monitoring, prevention, and control. In this study, we estimated the geographic distribution of triatomine species in Colombia and identified the relationship between landscape structure and climatic factors influencing their occurrence. A total of 2451 records of 4 triatomine species ( Panstrongylus geniculatus , Rhodnius pallescens , R. prolixus , and Triatoma maculata ) were analyzed. The variables that provided more information to explain the ecologic niche of these vectors were related to precipitation, altitude, and temperature. We found that the species with the broadest potential geographic distribution were P. geniculatus , R. pallescens , and R. prolixus . In general, the models predicted the highest occurrence probability of these vectors in the eastern slope of the Eastern Cordillera, the southern region of the Magdalena valley, and the Sierra Nevada of Santa Marta.

Sparse Solutions for Single Class SVMs: A Bi-Criterion Approach

NASA Technical Reports Server (NTRS)

Das, Santanu; Oza, Nikunj C.

2011-01-01

In this paper we propose an innovative learning algorithm - a variation of One-class nu Support Vector Machines (SVMs) learning algorithm to produce sparser solutions with much reduced computational complexities. The proposed technique returns an approximate solution, nearly as good as the solution set obtained by the classical approach, by minimizing the original risk function along with a regularization term. We introduce a bi-criterion optimization that helps guide the search towards the optimal set in much reduced time. The outcome of the proposed learning technique was compared with the benchmark one-class Support Vector machines algorithm which more often leads to solutions with redundant support vectors. Through out the analysis, the problem size for both optimization routines was kept consistent. We have tested the proposed algorithm on a variety of data sources under different conditions to demonstrate the effectiveness. In all cases the proposed algorithm closely preserves the accuracy of standard one-class nu SVMs while reducing both training time and test time by several factors.

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination

PubMed Central

Brady, Oliver J.; Godfray, H. Charles J.; Tatem, Andrew J.; Gething, Peter W.; Cohen, Justin M.; McKenzie, F. Ellis; Perkins, T. Alex; Reiner, Robert C.; Tusting, Lucy S.; Sinka, Marianne E.; Moyes, Catherine L.; Eckhoff, Philip A.; Scott, Thomas W.; Lindsay, Steven W.; Hay, Simon I.; Smith, David L.

2016-01-01

Background Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. Methods and Results Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. Conclusions Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. PMID:26822603

Milestone Completion Report WBS 1.3.5.05 ECP/VTK-m FY17Q3 [MS-17/02] Faceted Surface Normals STDA05-3.

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

Moreland, Kenneth D.

2017-07-01

The FY17Q3 milestone of the ECP/VTK-m project includes the completion of a VTK-m filter that computes normal vectors for surfaces. Normal vectors are those that point perpendicular to the surface and are an important direction when rendering the surface. The implementation includes the parallel algorithm itself, a filter module to simplify integrating it into other software, and documentation in the VTK-m Users’ Guide. With the completion of this milestone, we are able to necessary information to rendering systems to provide appropriate shading of surfaces. This milestone also feeds into subsequent milestones that progressively improve the approximation of surface direction.

Generic accelerated sequence alignment in SeqAn using vectorization and multi-threading.

PubMed

Rahn, René; Budach, Stefan; Costanza, Pascal; Ehrhardt, Marcel; Hancox, Jonny; Reinert, Knut

2018-05-03

Pairwise sequence alignment is undoubtedly a central tool in many bioinformatics analyses. In this paper, we present a generically accelerated module for pairwise sequence alignments applicable for a broad range of applications. In our module, we unified the standard dynamic programming kernel used for pairwise sequence alignments and extended it with a generalized inter-sequence vectorization layout, such that many alignments can be computed simultaneously by exploiting SIMD (Single Instruction Multiple Data) instructions of modern processors. We then extended the module by adding two layers of thread-level parallelization, where we a) distribute many independent alignments on multiple threads and b) inherently parallelize a single alignment computation using a work stealing approach producing a dynamic wavefront progressing along the minor diagonal. We evaluated our alignment vectorization and parallelization on different processors, including the newest Intel® Xeon® (Skylake) and Intel® Xeon Phi™ (KNL) processors, and use cases. The instruction set AVX512-BW (Byte and Word), available on Skylake processors, can genuinely improve the performance of vectorized alignments. We could run single alignments 1600 times faster on the Xeon Phi™ and 1400 times faster on the Xeon® than executing them with our previous sequential alignment module. The module is programmed in C++ using the SeqAn (Reinert et al., 2017) library and distributed with version 2.4. under the BSD license. We support SSE4, AVX2, AVX512 instructions and included UME::SIMD, a SIMD-instruction wrapper library, to extend our module for further instruction sets. We thoroughly test all alignment components with all major C++ compilers on various platforms. rene.rahn@fu-berlin.de.

Distinct Immunogenicity and Efficacy of Poxvirus-Based Vaccine Candidates against Ebola Virus Expressing GP and VP40 Proteins.

PubMed

Lázaro-Frías, Adrián; Gómez-Medina, Sergio; Sánchez-Sampedro, Lucas; Ljungberg, Karl; Ustav, Mart; Liljeström, Peter; Muñoz-Fontela, César; Esteban, Mariano; García-Arriaza, Juan

2018-06-01

Zaire and Sudan ebolavirus species cause a severe disease in humans and nonhuman primates (NHPs) characterized by a high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013 to 2016 outbreak in West Africa highlighted the need for EVD-specific medical countermeasures. Here, we generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing either the virus glycoprotein (GP) or GP together with the virus protein 40 (VP40) forming virus-like particles (VLPs). In a human monocytic cell line, the different MVA vectors (termed MVA-EBOVs and MVA-SUDVs) triggered robust innate immune responses, with production of beta interferon (IFN-β), proinflammatory cytokines, and chemokines. Additionally, several innate immune cells, such as dendritic cells, neutrophils, and natural killer cells, were differentially recruited in the peritoneal cavity of mice inoculated with MVA-EBOVs. After immunization of mice with a homologous prime/boost protocol (MVA/MVA), total IgG antibodies against GP or VP40 from Zaire and Sudan ebolavirus were differentially induced by these vectors, which were mainly of the IgG1 and IgG3 isotypes. Remarkably, an MVA-EBOV construct coexpressing GP and VP40 protected chimeric mice challenged with EBOV to a greater extent than a vector expressing GP alone. These results support the consideration of MVA-EBOVs and MVA-SUDVs expressing GP and VP40 and producing VLPs as best-in-class potential vaccine candidates against EBOV and SUDV. IMPORTANCE EBOV and SUDV cause a severe hemorrhagic fever affecting humans and NHPs. Since their discovery in 1976, they have caused several sporadic epidemics, with the recent outbreak in West Africa from 2013 to 2016 being the largest and most severe, with more than 11,000 deaths being reported. Although some vaccines are in advanced clinical phases, less expensive, safer, and more effective licensed vaccines are desirable. We generated and characterized head-to-head the immunogenicity and efficacy of five novel vaccines against EBOV and SUDV based on the poxvirus MVA expressing GP or GP and VP40. The expression of GP and VP40 leads to the formation of VLPs. These MVA-EBOV and MVA-SUDV recombinants triggered robust innate and humoral immune responses in mice. Furthermore, MVA-EBOV recombinants expressing GP and VP40 induced high protection against EBOV in a mouse challenge model. Thus, MVA expressing GP and VP40 and producing VLPs is a promising vaccine candidate against EBOV and SUDV. Copyright © 2018 American Society for Microbiology.

Coupled-mode theory and Fano resonances in guided-mode resonant gratings: the conical diffraction mounting.

PubMed

Bykov, Dmitry A; Doskolovich, Leonid L; Soifer, Victor A

2017-01-23

We study resonances of guided-mode resonant gratings in conical mounting. By developing 2D time-dependent coupled-mode theory we obtain simple approximations of the transmission and reflection coefficients. Being functions of the incident light's frequency and in-plane wave vector components, the obtained approximations can be considered as multi-variable generalizations of the Fano line shape. We show that the approximations are in good agreement with the rigorously calculated transmission and reflection spectra. We use the developed theory to investigate angular tolerances of the considered structures and to obtain mode excitation conditions. In particular, we obtain the cross-polarization mode excitation conditions in the case of conical mounting.

The Newick utilities: high-throughput phylogenetic tree processing in the UNIX shell.

PubMed

Junier, Thomas; Zdobnov, Evgeny M

2010-07-01

We present a suite of Unix shell programs for processing any number of phylogenetic trees of any size. They perform frequently-used tree operations without requiring user interaction. They also allow tree drawing as scalable vector graphics (SVG), suitable for high-quality presentations and further editing, and as ASCII graphics for command-line inspection. As an example we include an implementation of bootscanning, a procedure for finding recombination breakpoints in viral genomes. C source code, Python bindings and executables for various platforms are available from http://cegg.unige.ch/newick_utils. The distribution includes a manual and example data. The package is distributed under the BSD License. thomas.junier@unige.ch

Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain

PubMed Central

Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A.; Song, Juan

2016-01-01

Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4–/– mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4–/– mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design. PMID:27699236

Chikungunya, climate change, and human rights.

PubMed

Meason, Braden; Paterson, Ryan

2014-06-14

Chikungunya is a re-emerging arbovirus that causes significant morbidity and some mortality. Global climate change leading to warmer temperatures and changes in rainfall patterns allow mosquito vectors to thrive at altitudes and at locations where they previously have not, ultimately leading to a spread of mosquito-borne diseases. While mutations to the chikungunya virus are responsible for some portion of the re-emergence, chikungunya epidemiology is closely tied with weather patterns in Southeast Asia. Extrapolation of this regional pattern, combined with known climate factors impacting the spread of malaria and dengue, summate to a dark picture of climate change and the spread of this disease from south Asia and Africa into Europe and North America. This review describes chikungunya and collates current data regarding its spread in which climate change plays an important part. We also examine human rights obligations of States and others to protect against this disease. Copyright © 2014 Meason, Paterson. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

User's guide to STIPPAN: A panel method program for slotted tunnel interference prediction

NASA Technical Reports Server (NTRS)

Kemp, W. B., Jr.

1985-01-01

Guidelines are presented for use of the computer program STIPPAN to simulate the subsonic flow in a slotted wind tunnel test section with a known model disturbance. Input data requirements are defined in detail and other aspects of the program usage are discussed in more general terms. The program is written for use in a CDC CYBER 200 class vector processing system.

Study Guide for a Beginning Course in Ground-Water Hydrology: Part 1 -- Course Participants

DTIC Science & Technology

1990-01-01

and Lonnquist, 1971 , fig. 7.) . . . . . . . . . . . . . . . . . . . . . . 99 Vector areas associated with branches in a square-mesh finite...water reservoir. (From Bennett and Giusti, 1971 .). 112 Location and general geographic features of Long Island, New York. (From Franke and...Techniques of Water- Resources Investigations of the U.S. Geological Survey, Book 2, Chapter Fl, 97 p. Stallman, R. W., 1971 , Aquifer-test design

Simplified CRISPR tools for efficient genome editing and streamlined protocols for their delivery into mammalian cells and mouse zygotes.

PubMed

Jacobi, Ashley M; Rettig, Garrett R; Turk, Rolf; Collingwood, Michael A; Zeiner, Sarah A; Quadros, Rolen M; Harms, Donald W; Bonthuis, Paul J; Gregg, Christopher; Ohtsuka, Masato; Gurumurthy, Channabasavaiah B; Behlke, Mark A

2017-05-15

Genome editing using the CRISPR/Cas9 system requires the presence of guide RNAs bound to the Cas9 endonuclease as a ribonucleoprotein (RNP) complex in cells, which cleaves the host cell genome at sites specified by the guide RNAs. New genetic material may be introduced during repair of the double-stranded break via homology dependent repair (HDR) if suitable DNA templates are delivered with the CRISPR components. Early methods used plasmid or viral vectors to make these components in the host cell, however newer approaches using recombinant Cas9 protein with synthetic guide RNAs introduced directly as an RNP complex into cells shows faster onset of action with fewer off-target effects. This approach also enables use of chemically modified synthetic guide RNAs that have improved nuclease stability and reduces the risk of triggering an innate immune response in the host cell. This article provides detailed methods for genome editing using the RNP approach with synthetic guide RNAs using lipofection or electroporation in mammalian cells or using microinjection in murine zygotes, with or without addition of a single-stranded HDR template DNA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Directional nonlinear guided wave mixing: Case study of counter-propagating shear horizontal waves

NASA Astrophysics Data System (ADS)

Hasanian, Mostafa; Lissenden, Cliff J.

2018-04-01

While much nonlinear ultrasonics research has been conducted on higher harmonic generation, wave mixing provides the potential for sensitive measurements of incipient damage unencumbered by instrumentation nonlinearity. Studies of nonlinear ultrasonic wave mixing, both collinear and noncollinear, for bulk waves have shown the robust capability of wave mixing for early damage detection. One merit of bulk wave mixing lies in their non-dispersive nature, but guided waves enable inspection of otherwise inaccessible material and a variety of mixing options. Co-directional guided wave mixing was studied previously, but arbitrary direction guided wave mixing has not been addressed until recently. Wave vector analysis is applied to study variable mixing angles to find wave mode triplets (two primary waves and a secondary wave) resulting in the phase matching condition. As a case study, counter-propagating Shear Horizontal (SH) guided wave mixing is analyzed. SH wave interactions generate a secondary Lamb wave mode that is readily receivable. Reception of the secondary Lamb wave mode is compared for an angle beam transducer, an air coupled transducer, and a laser Doppler vibrometer (LDV). Results from the angle beam and air coupled transducers are quite consistent, while the LDV measurement is plagued by variability issues.

A Biomechanical Modeling Guided CBCT Estimation Technique

PubMed Central

Zhang, You; Tehrani, Joubin Nasehi; Wang, Jing

2017-01-01

Two-dimensional-to-three-dimensional (2D-3D) deformation has emerged as a new technique to estimate cone-beam computed tomography (CBCT) images. The technique is based on deforming a prior high-quality 3D CT/CBCT image to form a new CBCT image, guided by limited-view 2D projections. The accuracy of this intensity-based technique, however, is often limited in low-contrast image regions with subtle intensity differences. The solved deformation vector fields (DVFs) can also be biomechanically unrealistic. To address these problems, we have developed a biomechanical modeling guided CBCT estimation technique (Bio-CBCT-est) by combining 2D-3D deformation with finite element analysis (FEA)-based biomechanical modeling of anatomical structures. Specifically, Bio-CBCT-est first extracts the 2D-3D deformation-generated displacement vectors at the high-contrast anatomical structure boundaries. The extracted surface deformation fields are subsequently used as the boundary conditions to drive structure-based FEA to correct and fine-tune the overall deformation fields, especially those at low-contrast regions within the structure. The resulting FEA-corrected deformation fields are then fed back into 2D-3D deformation to form an iterative loop, combining the benefits of intensity-based deformation and biomechanical modeling for CBCT estimation. Using eleven lung cancer patient cases, the accuracy of the Bio-CBCT-est technique has been compared to that of the 2D-3D deformation technique and the traditional CBCT reconstruction techniques. The accuracy was evaluated in the image domain, and also in the DVF domain through clinician-tracked lung landmarks. PMID:27831866

Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

PubMed Central

Mavroudi, Maria; Zarogoulidis, Paul; Porpodis, Konstantinos; Kioumis, Ioannis; Lampaki, Sofia; Yarmus, Lonny; Malecki, Raf; Zarogoulidis, Konstantinos; Malecki, Marek

2014-01-01

Introduction Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The statistics speak for themselves with the grim reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem cells’ guided gene therapy. Review of therapeutic strategies in preclinical and clinical trials Stem cells have the unique potential for self renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells only. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for therapeutic use of stem cells is their cancerous transformation. Therefore, we discuss various strategies to safeguard stem cell guided gene therapy against iatrogenic cancerogenesis. Perspectives Defining cancer biomarkers to facilitate early diagnosis, elucidating cancer genomics and proteomics with modern tools of next generation sequencing, and analyzing patients’ gene expression profiles provide essential data to elucidate molecular dynamics of cancer and to consider them for crafting pharmacogenomics-based personalized therapies. Streamlining of these data into genetic engineering of stem cells facilitates their use as the vectors delivering therapeutic genes into specific cancer cells. In this realm, stem cells guided gene therapy becomes a promising new frontier in personalized and targeted therapy of cancer. PMID:24860662

Databases post-processing in Tensoral

NASA Technical Reports Server (NTRS)

Dresselhaus, Eliot

1994-01-01

The Center for Turbulent Research (CTR) post-processing effort aims to make turbulence simulations and data more readily and usefully available to the research and industrial communities. The Tensoral language, introduced in this document and currently existing in prototype form, is the foundation of this effort. Tensoral provides a convenient and powerful protocol to connect users who wish to analyze fluids databases with the authors who generate them. In this document we introduce Tensoral and its prototype implementation in the form of a user's guide. This guide focuses on use of Tensoral for post-processing turbulence databases. The corresponding document - the Tensoral 'author's guide' - which focuses on how authors can make databases available to users via the Tensoral system - is currently unwritten. Section 1 of this user's guide defines Tensoral's basic notions: we explain the class of problems at hand and how Tensoral abstracts them. Section 2 defines Tensoral syntax for mathematical expressions. Section 3 shows how these expressions make up Tensoral statements. Section 4 shows how Tensoral statements and expressions are embedded into other computer languages (such as C or Vectoral) to make Tensoral programs. We conclude with a complete example program.

American Medical Society for Sports Medicine (AMSSM) position statement: interventional musculoskeletal ultrasound in sports medicine.

PubMed

Finnoff, Jonathan T; Hall, Mederic M; Adams, Erik; Berkoff, David; Concoff, Andrew L; Dexter, William; Smith, Jay

2015-02-01

The use of diagnostic and interventional ultrasound has significantly increased over the past decade. A majority of the increased utilisation is by non-radiologists. In sports medicine, ultrasound is often used to guide interventions such as aspirations, diagnostic or therapeutic injections, tenotomies, releases and hydrodissections. Critically review the literature related to the accuracy, efficacy and cost-effectiveness of ultrasound-guided injections (USGIs) in major, intermediate and small joints; and soft tissues. Systematic review of the literature. USGIs are more accurate than landmark-guided injections (LMGIs; strength of recommendation taxonomy (SORT) Evidence Rating=A). USGIs are more efficacious than LMGIs (SORT Evidence Rating=B). USGIs are more cost-effective than LMGIs (SORT Evidence Rating=B). Ultrasound guidance is required to perform many new procedures (SORT Evidence Rating=C). The findings of this position statement indicate there is strong evidence that USGIs are more accurate than LMGI, moderate evidence that they are more efficacious and preliminary evidence that they are more cost-effective. Furthermore, ultrasound-guided (USG) is required to perform many new, advanced procedures and will likely enable the development of innovative USG surgical techniques in the future. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Vector with a Single Promoter for In Vitro Transcription and Mammalian Cell Expression of CRISPR gRNAs.

PubMed

Romanienko, Peter J; Giacalone, Joseph; Ingenito, Joanne; Wang, Yijie; Isaka, Mayumi; Johnson, Thomas; You, Yun; Mark, Willie H

2016-01-01

The genomes of more than 50 organisms have now been manipulated due to rapid advancement of gene editing technology. One way to perform gene editing in the mouse using the CRISPR/CAS system, guide RNA (gRNA) and CAS9 mRNA transcribed in vitro are microinjected into fertilized eggs that are then allowed to develop to term. As a rule, gRNAs are tested first in tissue culture cells and the one with the highest locus-specific cleavage activity is chosen for microinjection. For cell transfections, gRNAs are typically expressed using the human U6 promoter (hU6). However, gRNAs for microinjection into zygotes are obtained by in vitro transcription from a T7 bacteriophage promoter in a separate plasmid vector. Here, we describe the design and construction of a combined U6T7 hybrid promoter from which the same gRNA sequence can be expressed. An expression vector containing such a hybrid promoter can now be used to generate gRNA for testing in mammalian cells as well as for microinjection purposes. The gRNAs expressed and transcribed from this vector are found to be functional in cells as well as in mice.

Triatomine Infestation in Guatemala: Spatial Assessment after Two Rounds of Vector Control

PubMed Central

Manne, Jennifer; Nakagawa, Jun; Yamagata, Yoichi; Goehler, Alexander; Brownstein, John S.; Castro, Marcia C.

2012-01-01

In 2000, the Guatemalan Ministry of Health initiated a Chagas disease program to control Rhodnius prolixus and Triatoma dimidiata by periodic house spraying with pyrethroid insecticides to characterize infestation patterns and analyze the contribution of programmatic practices to these patterns. Spatial infestation patterns at three time points were identified using the Getis-Ord Gi*(d) test. Logistic regression was used to assess predictors of reinfestation after pyrethroid insecticide administration. Spatial analysis showed high and low clusters of infestation at three time points. After two rounds of spray, 178 communities persistently fell in high infestation clusters. A time lapse between rounds of vector control greater than 6 months was associated with 1.54 (95% confidence interval = 1.07–2.23) times increased odds of reinfestation after first spray, whereas a time lapse of greater than 1 year was associated with 2.66 (95% confidence interval = 1.85–3.83) times increased odds of reinfestation after first spray compared with localities where the time lapse was less than 180 days. The time lapse between rounds of vector control should remain under 1 year. Spatial analysis can guide targeted vector control efforts by enabling tracking of reinfestation hotspots and improved targeting of resources. PMID:22403315

Sleeping in fits and starts: a practical guide to distinguishing nocturnal epilepsy from sleep disorders.

PubMed

Derry, Christopher P

2014-12-01

Accurately diagnosing sleep-related events, and particularly distinguishing nocturnal frontal lobe seizures from other sleep disorders such as parasomnias, can be challenging. This article reviews the differential diagnosis of paroxysmal events from sleep, epileptic and non-epileptic, considers important diagnostic points in the history, and evaluates the role of investigations in this setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Consolidating tactical planning and implementation frameworks for integrated vector management in Uganda.

PubMed

Okia, Michael; Okui, Peter; Lugemwa, Myers; Govere, John M; Katamba, Vincent; Rwakimari, John B; Mpeka, Betty; Chanda, Emmanuel

2016-04-14

Integrated vector management (IVM) is the recommended approach for controlling some vector-borne diseases (VBD). In the face of current challenges to disease vector control, IVM is vital to achieve national targets set for VBD control. Though global efforts, especially for combating malaria, now focus on elimination and eradication, IVM remains useful for Uganda which is principally still in the control phase of the malaria continuum. This paper outlines the processes undertaken to consolidate tactical planning and implementation frameworks for IVM in Uganda. The Uganda National Malaria Control Programme with its efforts to implement an IVM approach to vector control was the 'case' for this study. Integrated management of malaria vectors in Uganda remained an underdeveloped component of malaria control policy. In 2012, knowledge and perceptions of malaria vector control policy and IVM were assessed, and recommendations for a specific IVM policy were made. In 2014, a thorough vector control needs assessment (VCNA) was conducted according to WHO recommendations. The findings of the VCNA informed the development of the national IVM strategic guidelines. Information sources for this study included all available data and accessible archived documentary records on VBD control in Uganda. The literature was reviewed and adapted to the local context and translated into the consolidated tactical framework. WHO recommends implementation of IVM as the main strategy to vector control and has encouraged member states to adopt the approach. However, many VBD-endemic countries lack IVM policy frameworks to guide implementation of the approach. In Uganda most VBD coexists and could be managed more effectively if done in tandem. In order to successfully control malaria and other VBD and move towards their elimination, the country needs to scale up proven and effective vector control interventions and also learn from the experience of other countries. The IVM strategy is important in consolidating inter-sectoral collaboration and coordination and providing the tactical direction for effective deployment of vector control interventions along the five key elements of the approach and to align them with contemporary epidemiology of VBD in the country. Uganda has successfully established an evidence-based IVM approach and consolidated strategic planning and operational frameworks for VBD control. However, operating implementation arrangements as outlined in the national strategic guidelines for IVM and managing insecticide resistance, as well as improving vector surveillance, are imperative. In addition, strengthened information, education and communication/behaviour change and communication, collaboration and coordination will be crucial in scaling up and using vector control interventions.

MicroRNA-Regulated Non-Viral Vectors with Improved Tumor Specificity in an Orthotopic Rat Model of Hepatocellular Carcinoma

PubMed Central

Ronald, John A.; Katzenberg, Regina; Nielsen, Carsten H.; Jae, Hwan Jun; Hofmann, Lawrence V.; Gambhir, Sanjiv S.

2013-01-01

In hepatocellular carcinoma, tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs are powerful negative regulators of gene expression and many are down-regulated in human HCC. We identified seven miRNAs that are also down-regulated in tumors in a rat hepatoma model (p<0.05) and attempted to improve tumor specificity by constructing a panel of luciferase-expressing vectors containing binding sites for these microRNAs. Attenuation of luciferase expression by the corresponding microRNAs was confirmed across various cell lines and in mouse liver. We then tested our vectors in tumor-bearing rats and identified two microRNAs, miR-26a and miR-122, that significantly decreased expression in liver compared to control vector (6.40% and 0.26%, respectively; p<0.05). In tumor, miR-122 had a non-significant trend towards decreased (~50%) expression , while miR-26 had no significant effect on tumor expression. To our knowledge this is the first work using differentially expressed microRNAs to de-target transgene expression in an orthotopic hepatoma model and identification of miR-26a in addition to miR-122 for de-targeting liver. Considering the heterogeneity of microRNA expression in human HCC, this information will be important in guiding development of more personalized vectors for the treatment of this devastating disease. PMID:23719066

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination.

PubMed

Brady, Oliver J; Godfray, H Charles J; Tatem, Andrew J; Gething, Peter W; Cohen, Justin M; McKenzie, F Ellis; Perkins, T Alex; Reiner, Robert C; Tusting, Lucy S; Sinka, Marianne E; Moyes, Catherine L; Eckhoff, Philip A; Scott, Thomas W; Lindsay, Steven W; Hay, Simon I; Smith, David L

2016-02-01

Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Dengue and Chikungunya Vector Control Pocket Guide

DTIC Science & Technology

2014-05-01

mosquito eggs, larvae, or pupae. Examples of such items are tarps, discarded bottles, flower pot saucers, and rain gauges. In areas where there...coconut husks, (4) tires, (5) barrels, (6) water storage tanks, (7) bromeliads and axils of banana trees, (8) obstructed roof gutters, (9) plant pot...regularly Store under roof Fill with sand Throw Away/ Recycle Buckets X X X Flower Pot Saucers X X Roof Gutters X Discarded

Study Modules for Calculus-Based General Physics. [Includes Modules 3-5: Planar Motion; Newton's Laws; and Vector Multiplication].

ERIC Educational Resources Information Center

Fuller, Robert G., Ed.; And Others

This is part of a series of 42 Calculus Based Physics (CBP) modules totaling about 1,000 pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized course in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

Image quality guided approach for adaptive modelling of biometric intra-class variations

NASA Astrophysics Data System (ADS)

Abboud, Ali J.; Jassim, Sabah A.

2010-04-01

The high intra-class variability of acquired biometric data can be attributed to several factors such as quality of acquisition sensor (e.g. thermal), environmental (e.g. lighting), behavioural (e.g. change face pose). Such large fuzziness of biometric data can cause a big difference between an acquired and stored biometric data that will eventually lead to reduced performance. Many systems store multiple templates in order to account for such variations in the biometric data during enrolment stage. The number and typicality of these templates are the most important factors that affect system performance than other factors. In this paper, a novel offline approach is proposed for systematic modelling of intra-class variability and typicality in biometric data by regularly selecting new templates from a set of available biometric images. Our proposed technique is a two stage algorithm whereby in the first stage image samples are clustered in terms of their image quality profile vectors, rather than their biometric feature vectors, and in the second stage a per cluster template is selected from a small number of samples in each clusters to create an ultimate template sets. These experiments have been conducted on five face image databases and their results will demonstrate the effectiveness of proposed quality guided approach.

Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector

PubMed Central

Kabadi, Ami M.; Ousterout, David G.; Hilton, Isaac B.; Gersbach, Charles A.

2014-01-01

Engineered DNA-binding proteins that manipulate the human genome and transcriptome have enabled rapid advances in biomedical research. In particular, the RNA-guided CRISPR/Cas9 system has recently been engineered to create site-specific double-strand breaks for genome editing or to direct targeted transcriptional regulation. A unique capability of the CRISPR/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide RNAs (sgRNAs) targeted to distinct genomic sites. This approach can be used to simultaneously create multiple DNA breaks or to target multiple transcriptional activators to a single promoter for synergistic enhancement of gene induction. To address the need for uniform and sustained delivery of multiplex CRISPR/Cas9-based genome engineering tools, we developed a single lentiviral system to express a Cas9 variant, a reporter gene and up to four sgRNAs from independent RNA polymerase III promoters that are incorporated into the vector by a convenient Golden Gate cloning method. Each sgRNA is efficiently expressed and can mediate multiplex gene editing and sustained transcriptional activation in immortalized and primary human cells. This delivery system will be significant to enabling the potential of CRISPR/Cas9-based multiplex genome engineering in diverse cell types. PMID:25122746

National Advisory Committee on Immunization (NACI). Supplementary statement MMR vaccine and anaphylactic hypersensitivity to egg or egg-related antigens.

PubMed

1996-07-15

The fourth edition of the Canadian Immunization Guide (1993) recommends that "persons who have a history of anaphylactic hypersensitivity to hens' eggs (urticaria, swelling of the mouth and throat, difficulty in breathing or hypotension) should not be given measles vaccine except under special precautions." The precautions outlined include skin testing with diluted vaccine and graded challenge vaccination if the skin test is positive. Results of several recent studies have questioned such a cautious approach. NACI has reviewed all available data and revised its guidelines accordingly. The following revised guidelines are a major departure from the previously published recommendations. They will appear in the next edition of the Canadian Immunization Guide. A measles-rubella combination vaccine (Mo-Ru Viraten Berna TM) recently licensed in Canada contains no avian proteins and therefore can be used without regard to egg allergy.

Rational Improvement of Molar Absorptivity Guided by Oscillator Strength: A Case Study with Furoindolizine-Based Core Skeleton.

PubMed

Lee, Youngjun; Jo, Ala; Park, Seung Bum

2015-12-21

The rational improvement of photophysical properties can be highly valuable for the discovery of novel organic fluorophores. Using our new design strategy guided by the oscillator strength, we developed a series of full-color-tunable furoindolizine analogs with improved molar absorptivity through the fusion of a furan ring into the indolizine-based Seoul fluorophore. The excellent correlation between the computable values (oscillator strength and theoretical S0 -S1 energy gap) and photophysical properties (molar absorptivity and emission wavelength) confirmed the effectualness of our design strategy. © 2015 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.

Crossing the Threshold: Bringing Biological Variation to the Foreground.

PubMed

Batzli, Janet M; Knight, Jennifer K; Hartley, Laurel M; Maskiewicz, April Cordero; Desy, Elizabeth A

2016-01-01

Threshold concepts have been referred to as "jewels in the curriculum": concepts that are key to competency in a discipline but not taught explicitly. In biology, researchers have proposed the idea of threshold concepts that include such topics as variation, randomness, uncertainty, and scale. In this essay, we explore how the notion of threshold concepts can be used alongside other frameworks meant to guide instructional and curricular decisions, and we examine the proposed threshold concept of variation and how it might influence students' understanding of core concepts in biology focused on genetics and evolution. Using dimensions of scientific inquiry, we outline a schema that may allow students to experience and apply the idea of variation in such a way that it transforms their future understanding and learning of genetics and evolution. We encourage others to consider the idea of threshold concepts alongside the Vision and Change core concepts to provide a lens for targeted instruction and as an integrative bridge between concepts and competencies. © 2016 J. M. Batzli et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

View_SPECPR: Software for Plotting Spectra (Installation Manual and User's Guide, Version 1.2)

USGS Publications Warehouse

Kokaly, Raymond F.

2008-01-01

This document describes procedures for installing and using the 'View_SPECPR' software system to plot spectra stored in SPECPR (SPECtrum Processing Routines) files. The View_SPECPR software is comprised of programs written in IDL (Interactive Data Language) that run within the ENVI (ENvironment for Visualizing Images) image processing system. SPECPR files are used by earth-remote-sensing scientists and planetary scientists for storing spectra collected by laboratory, field, and remote sensing instruments. A widely distributed SPECPR file is the U.S. Geological Survey (USGS) spectral library that contains thousands of spectra of minerals, vegetation, and man-made materials (Clark and others, 2007). SPECPR files contain reflectance data and associated wavelength and spectral resolution data, as well as meta-data on the time and date of collection and spectrometer settings. Furthermore, the SPECPR file automatically tracks changes to data records through its 'history' fields. For more details on the format and content of SPECPR files, see Clark (1993). For more details on ENVI, see ITT (2008). This program has been updated using an ENVI 4.5/IDL7.0 full license operating on a Windows XP operating system and requires the installation of the iTools components of IDL7.0; however, this program should work with full licenses on UNIX/LINUX systems. This software has not been tested with ENVI licenses on Windows Vista or Apple Operating Systems.

Be(ing) prepared: Guide and Scout participation, childhood social position and mental health at age 50-a prospective birth cohort study.

PubMed

Dibben, Chris; Playford, Chris; Mitchell, Richard

2017-03-01

Mental health is a major concern in many countries. We explore whether youth participation in the Scouts and Guides could protect mental health in later life and in particular whether it might reduce inequalities in mental health associated with early life socioeconomic position. Using the 1958 birth cohort National Child Development Study, we tested whether Scouts-Guide attendance was associated with mental health (SF-36, Mental Health Index (MHI-5)) controlling for childhood risk factors and interacted with social class. Of the 9603 cohort members, 28% had participated in the Scouts-Guides. The average MHI-5 score was 74.8 (SD 18.2) at age 50. After adjustment, for potential childhood confounders, participation in Scouts-Guides was associated with a better MHI-5 score of 2.22 (CI 1.32 to 3.08). Among those who had not been a Scout-Guide, there was a gradient in mental health at age 50 by childhood social position, adjusting for other childhood risk factors. This gradient was absent among those who had been a Scout-Guide. Scout-Guides had an 18% lower odds of an MHI-5 score indicative of mood or anxiety disorder. The findings appeared robust to various tests for residual confounding. Participation in Guides or Scouts was associated with better mental health and narrower mental health inequalities, at age 50. This suggests that youth programmes that support resilience and social mobility through developing the potential for continued progressive self-education, 'soft' non-cognitive skills, self-reliance, collaboration and activities in natural environments may be protective of mental health in adulthood. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Targeting vector construction through recombineering.

PubMed

Malureanu, Liviu A

2011-01-01

Gene targeting in mouse embryonic stem cells is an essential, yet still very expensive and highly time-consuming, tool and method to study gene function at the organismal level or to create mouse models of human diseases. Conventional cloning-based methods have been largely used for generating targeting vectors, but are hampered by a number of limiting factors, including the variety and location of restriction enzymes in the gene locus of interest, the specific PCR amplification of repetitive DNA sequences, and cloning of large DNA fragments. Recombineering is a technique that exploits the highly efficient homologous recombination function encoded by λ phage in Escherichia coli. Bacteriophage-based recombination can recombine homologous sequences as short as 30-50 bases, allowing manipulations such as insertion, deletion, or mutation of virtually any genomic region. The large availability of mouse genomic bacterial artificial chromosome (BAC) libraries covering most of the genome facilitates the retrieval of genomic DNA sequences from the bacterial chromosomes through recombineering. This chapter describes a successfully applied protocol and aims to be a detailed guide through the steps of generation of targeting vectors through recombineering.

Comparison of Aedes aegypti (Diptera: Culicidae) resting behavior on two fabric types under consideration for insecticide treatment in a push-pull strategy.

PubMed

Tainchum, Krajana; Polsomboon, Suppaluck; Grieco, John P; Suwonkerd, Wannapa; Prabaripai, Atchariya; Sungvornyothin, Sungsit; Chareonviriyaphap, Theeraphap; Achee, Nicole L

2013-01-01

Aedes aegypti (L.), the primary vector of dengue and dengue hemorrhagic fever, breeds and rests predominately inside human dwellings. With no current vaccine available, vector control remains the mainstay for dengue management and novel approaches continue to be needed to reduce virus transmission. This requires a full understanding of Ae. aegypti ecology to design effective strategies. One novel approach is the use of contact irritants at target resting sites inside homes to make the surface unacceptable and cause vectors to escape before biting. The objective of the current study was to observe indoor resting behavior patterns of female Ae. aegypti within experimental huts in response to two fabrics under consideration for insecticide treatment: cotton and polyester. Results indicate that fabric type, coverage ratio of dark to light fabric and placement configuration (vertical vs. horizontal) all influenced the resting pattern of mosquito cohorts. Findings from this study will guide evaluations of a push-pull strategy designed to exploit contact irritant behaviors and drive Ae. aegypti out of homes prefeeding.

On the Improvement of Convergence Performance for Integrated Design of Wind Turbine Blade Using a Vector Dominating Multi-objective Evolution Algorithm

NASA Astrophysics Data System (ADS)

Wang, L.; Wang, T. G.; Wu, J. H.; Cheng, G. P.

2016-09-01

A novel multi-objective optimization algorithm incorporating evolution strategies and vector mechanisms, referred as VD-MOEA, is proposed and applied in aerodynamic- structural integrated design of wind turbine blade. In the algorithm, a set of uniformly distributed vectors is constructed to guide population in moving forward to the Pareto front rapidly and maintain population diversity with high efficiency. For example, two- and three- objective designs of 1.5MW wind turbine blade are subsequently carried out for the optimization objectives of maximum annual energy production, minimum blade mass, and minimum extreme root thrust. The results show that the Pareto optimal solutions can be obtained in one single simulation run and uniformly distributed in the objective space, maximally maintaining the population diversity. In comparison to conventional evolution algorithms, VD-MOEA displays dramatic improvement of algorithm performance in both convergence and diversity preservation for handling complex problems of multi-variables, multi-objectives and multi-constraints. This provides a reliable high-performance optimization approach for the aerodynamic-structural integrated design of wind turbine blade.

Studies of machinable ceramics for dental applications. 1. Color analysis.

PubMed

Taira, M; Wakasa, K; Yamaki, M; Tanaka, N; Shintani, H

1989-12-01

Machinable ceramics that can be cut and even lathed have recently been developed in industry. As a first step in evaluating the feasibility of such ceramics in dentistry, eight machinable ceramics were examined for color using the Vita shade guide and a chroma-meter reflectance instrument. We discovered that the studied machinable ceramics varied significantly from the Vita shade guide by the color difference vector, delta E. These machinable ceramics appeared very white and strongly opaque due to their high brightness (L*) values. For intra-oral applications, we expect that L* values of machinable ceramics will be reduced by modification of their microstructures, including their matrix and dispersed phases, while their excellent machinability due to the cleavage of dispersed crystals should be retained.

Small But Increasingly Mighty: Latest Advances in AAV Vector Research, Design, and Evolution.

PubMed

Grimm, Dirk; Büning, Hildegard

2017-11-01

Recombinant gene delivery vectors derived from naturally occurring or genetically engineered adeno-associated viruses (AAV) have taken center stage in human gene therapy, fueled by rapidly accumulating and highly encouraging clinical data. Nonetheless, it has also become evident that the current generation of AAV vectors will require improvements in transduction potency, antibody evasion, and cell specificity in order to realize their full potential and to widen applicability in larger patient cohorts. Fortunately, in the recent past, the field has seen a flurry of exciting new developments that enhance our understanding of AAV vector biology, including virus-host interactions, and/or that expand our arsenal of technologies for AAV capsid design and evolution. This review highlights a collection of latest advances in these areas, which, in the authors' opinion, hold particular promise to propel the AAV vector field forward in the near future, especially when applied in combination. These include fundamental novel insights into the AAV life cycle, from an unexpected role of autophagy and interactions with other viruses to the (re-)discovery of a universal AAV receptor and the function of AAV-AAP for capsid assembly. Concurrently, recent successes in the rational design of next-generation synthetic AAV capsids are pointed out, exemplified by the structure-guided derivation of AAV mutants displaying robust in vivo immune evasion. Finally, a variety of new and innovative strategies for high-throughput generation and screening of AAV capsid libraries are briefly reviewed, including Cre recombinase-based selection, ancestral AAV capsid reconstruction, and DNA barcoding of AAV genomes. All of these examples showcase the present momentum in the AAV field and, together with work by many other academic or industrial entities, raise substantial optimism that the remaining hurdles for human gene therapy with AAV vectors will (soon) be overcome.

Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro.

PubMed

von Rhein, Christine; Weidner, Tatjana; Henß, Lisa; Martin, Judith; Weber, Christopher; Sliva, Katja; Schnierle, Barbara S

2016-01-01

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever, and severe arthritis that can persist for years. CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions including Europe and the United States of America. CHIKV has recently caused large outbreaks in Latin America. No treatment or licensed CHIKV vaccine exists. Traditional medicines are known to have anti-viral effects; therefore, we examined whether curcumin or Boswellia serrata gum resin extract have antiviral activity against CHIKV. Both compounds blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV infection in vitro. In addition, vesicular stomatitis virus vector particles and viral infections were also inhibited to the same extent, indicating a broad antiviral activity. Although the bioavailability of these compounds is rather poor, they might be used as a lead structure to develop more effective antiviral drugs or might be used topically to prevent CHIKV spread in the skin after mosquito bites. Copyright © 2015 Elsevier B.V. All rights reserved.

Lyme disease: why the controversy?

PubMed

Beaman, M H

2016-12-01

Some Australians have become convinced of the existence of locally acquired Lyme disease (LD). The history of LD, since its recognition in the early 1970s, is reviewed as a model for investigative approaches to unknown syndromes. Australian Management Guidelines for LD include the requirement for diagnostic testing by National Association of Testing Authorities-accredited laboratories using Therapeutic Goods Administration-licensed tests, which result in the efficient diagnosis of LD in overseas travellers. Despite this, patients who have not left Australia pay many thousands of dollars for non-specialist consultations and testing at overseas laboratories. Unproven long-term therapy with multiple antibiotics has resulted in serious complications, including allergies, line sepsis, pancreatitis and pseudomembranous colitis. Studies have shown that LD vectors are not found in Australia, and Lyme Borrelia has not been found in Australian vectors, animals or patients with autochthonous illnesses. I propose that (i) A non-controversial name for the chronic syndrome should be adopted, 'Australian Multisystem Disorder'. (ii) Research funding should enable the development of a consensus case definition and studies of the epidemiology of this syndrome with laboratory investigations to identify an aetiology and surrogate markers of disease. Prospective, randomised treatment studies could then be undertaken using ethical protocols. © 2016 Royal Australasian College of Physicians.

A recombinant virus vaccine that protects against both Chikungunya and Zika virus infections.

PubMed

Chattopadhyay, Anasuya; Aguilar, Patricia V; Bopp, Nathen E; Yarovinsky, Timur O; Weaver, Scott C; Rose, John K

2018-06-22

Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently expanded their range in the world and caused serious and widespread outbreaks of near pandemic proportions. There are no licensed vaccines that protect against these co-circulating viruses that are transmitted by invasive mosquito vectors. We report here on the development of a single-dose, bivalent experimental vaccine for CHIKV and ZIKV. This vaccine is based on a chimeric vesicular stomatitis virus (VSV) that expresses the CHIKV envelope polyprotein (E3-E2-6K-E1) in place of the VSV glycoprotein (G) and also expresses the membrane-envelope (ME) glycoproteins of ZIKV. This vaccine induced neutralizing antibody responses to both CHIKV and ZIKV in wild-type mice and in interferon receptor-deficient A129 mice, animal models for CHIKV and ZIKV infection. A single vaccination of A129 mice with the vector protected these mice against infection with both CHIKV and ZIKV. Our single-dose vaccine could provide durable, low-cost protection against both CHIKV and ZIKV for people traveling to or living in areas where both viruses are circulating, which include most tropical regions in the world. Copyright © 2018. Published by Elsevier Ltd.

Immunogenicity and protective efficacy of a replication-defective infectious bronchitis virus vaccine using an adenovirus vector and administered in ovo.

PubMed

Zeshan, Basit; Zhang, Lili; Bai, Juan; Wang, Xinglong; Xu, Jiarong; Jiang, Ping

2010-06-01

In ovo vaccination remains an attractive option for a cost effective, uniform and mass application of vaccines for commercial poultry. However, the vaccines which can be delivered safely by this method are limited and there is no currently licensed embryo-safe vaccine against infectious bronchitis virus (IBV). In this study, a recombinant adenovirus expressing the S1 gene of nephropathogenic IBV (rAd-S1) was constructed and the immune responses and protective efficacy against homologous challenge were evaluated after in ovo vaccination. The results showed that the rAd-S1 led to dramatic augmentation of humoral and cellular responses in birds vaccinated in ovo followed by an intramuscular inoculation. Both IFN-gamma and IL-4 in chicken's lymphocytes were produced by this strategy. Following challenge with IBV, the chickens vaccinated with recombinant adenovirus showed fewer nephropathic lesions and less severe clinical signs as compared to those receiving wild-type adenovirus or PBS. The construction of non-replicating human adenovirus vector encoding S1 gene of IBV and its in ovo delivery demonstrated the potential of an alternative vaccination strategy against IBV. Copyright 2010 Elsevier B.V. All rights reserved.

A recombinant pseudorabies virus expressing rabies virus glycoprotein: safety and immunogenicity in dogs.

PubMed

Yuan, Ziguo; Zhang, Shoufeng; Liu, Ye; Zhang, Fei; Fooks, Anthony R; Li, Qianxue; Hu, Rongliang

2008-03-04

Several recombinant vaccines expressing the rabies virus glycoprotein have been developed, particularly for the oral vaccination of wildlife. While these vaccines induce protective immunity in some animal species such as foxes, they are less effective in others. Pseudorabies virus (PRV) has been licensed for use as a live vaccine in pigs and possesses an excellent safety and efficacy record. We have used it to construct a recombinant virus, rPRV/eGFP/rgp, expressing the rabies virus glycoprotein. This recombinant virus has been shown to be safe for dogs by oral and intramuscular routes of inoculation and was demonstrated to induce immune responses against both pseudorabies and rabies in dogs after a single oral dose of 2 x 10(7.0) plaque forming units (PFU). Neutralizing antibody titers against rabies reached > 0.5 IU/ml and 1:64-1:128 against pseudorabies by 5 weeks post-vaccination in all dogs, indicating that the pseudorabies virus vector infected dogs and replicated in vivo, and that the rabies virus glycoprotein had been expressed and an effective immune response elicited. Antibody titers were maintained for over 6 months. This suggests that pseudorabies virus could be an effective live vector for recombinant rabies oral vaccination.

Research on gesture recognition of augmented reality maintenance guiding system based on improved SVM

NASA Astrophysics Data System (ADS)

Zhao, Shouwei; Zhang, Yong; Zhou, Bin; Ma, Dongxi

2014-09-01

Interaction is one of the key techniques of augmented reality (AR) maintenance guiding system. Because of the complexity of the maintenance guiding system's image background and the high dimensionality of gesture characteristics, the whole process of gesture recognition can be divided into three stages which are gesture segmentation, gesture characteristic feature modeling and trick recognition. In segmentation stage, for solving the misrecognition of skin-like region, a segmentation algorithm combing background mode and skin color to preclude some skin-like regions is adopted. In gesture characteristic feature modeling of image attributes stage, plenty of characteristic features are analyzed and acquired, such as structure characteristics, Hu invariant moments features and Fourier descriptor. In trick recognition stage, a classifier based on Support Vector Machine (SVM) is introduced into the augmented reality maintenance guiding process. SVM is a novel learning method based on statistical learning theory, processing academic foundation and excellent learning ability, having a lot of issues in machine learning area and special advantages in dealing with small samples, non-linear pattern recognition at high dimension. The gesture recognition of augmented reality maintenance guiding system is realized by SVM after the granulation of all the characteristic features. The experimental results of the simulation of number gesture recognition and its application in augmented reality maintenance guiding system show that the real-time performance and robustness of gesture recognition of AR maintenance guiding system can be greatly enhanced by improved SVM.

The effects of business practices, licensing, and intellectual property on development and dissemination of the polymerase chain reaction: case study

PubMed Central

Fore, Joe; Wiechers, Ilse R; Cook-Deegan, Robert

2006-01-01

Introduction Polymerase chain reaction (PCR) was a seminal genomic technology discovered, developed, and patented in an industry setting. Since the first of its core patents expired in March, 2005, we are in a position to view the entire lifespan of the patent, examining how the intellectual property rights have impacted its use in the biomedical community. Given its essential role in the world of molecular biology and its commercial success, the technology can serve as a case study for evaluating the effects of patenting biological research tools on biomedical research. Case description Following its discovery, the technique was subjected to two years of in-house development, during which issues of inventorship and publishing/patenting strategies caused friction between members of the development team. Some have feared that this delay impeded subsequent research and may have been due to trade secrecy or the desire for obtaining lucrative intellectual property rights. However, our analysis of the history indicates that the main reasons for the delay were benign and were primarily due to difficulties in perfecting the PCR technique. Following this initial development period, the technology was made widely available, but was subject to strict licensing terms and patent protection, leading to an extensive litigation history. Discussion and evaluation PCR has earned approximately $2 billion in royalties for the various rights-holders while also becoming an essential research tool. However, using citation trend analysis, we are able to see that PCR's patented status did not preclude it from being adopted in a similar manner as other non-patented genomic research tools (specifically, pBR322 cloning vector and Maxam-Gilbert sequencing). Conclusion Despite the heavy patent protection and rigid licensing schemes, PCR seems to have disseminated so widely because of the practices of the corporate entities which have controlled these patents, namely through the use of business partnerships and broad corporate licensing, adaptive licensing strategies, and a "rational forbearance" from suing researchers for patent infringement. While far from definitive, our analysis seems to suggest that, at least in the case of PCR, patenting of genomic research tools need not impede their dissemination, if the technology is made available through appropriate business practices. PMID:16817955

SPV: a JavaScript Signaling Pathway Visualizer.

PubMed

Calderone, Alberto; Cesareni, Gianni

2018-03-24

The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, different entities, cellular compartments and interaction types are hardly distinguishable. SPV (Signaling Pathway Visualizer) is a free open source JavaScript library which offers a series of pre-defined elements, compartments and interaction types meant to facilitate the representation of signaling pathways consisting of causal interactions without neglecting simple protein-protein interaction networks. freely available under Apache version 2 license; Source code: https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js. sinnefa@gmail.com.

Advances in the development of next-generation anthrax vaccines.

PubMed

Friedlander, Arthur M; Little, Stephen F

2009-11-05

Anthrax, a disease of herbivores, only rarely infects humans. However, the threat of using Bacillus anthracis, the causative agent, to intentionally produce disease has been the impetus for development of next-generation vaccines. Two licensed vaccines have been available for human use for several decades. These are composed of acellular culture supernatants containing the protective antigen (PA) component of the anthrax toxins. In this review we summarize the various approaches used to develop improved vaccines. These efforts have included the use of PA with newer adjuvants and delivery systems, including bacterial and viral vectors and DNA vaccines. Attempts to broaden the protection afforded by PA-based vaccines have focused on adding other B. anthracis components, including spore and capsule antigens.

Respiratory syncytial virus vaccines: an update on those in the immediate pipeline.

PubMed

Esposito, Susanna; Pietro, Giada Di

2016-10-01

Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infection among infants and the elderly worldwide. Despite its long history, no licensed vaccine is available. Recently, advances in the knowledge of RSV biology and pathology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines. The aim of this review is to analyze RSV characteristics, to consider the history of RSV vaccines and to discuss RSV vaccines currently in development. Among the candidates in clinical trials, nanoparticle and subunit vaccines seem to be the most promising for pregnant women and the elderly, whereas live-attenuated or vector-based vaccines appear to be optimal for the pediatric population.

The Newick utilities: high-throughput phylogenetic tree processing in the Unix shell

PubMed Central

Junier, Thomas; Zdobnov, Evgeny M.

2010-01-01

Summary: We present a suite of Unix shell programs for processing any number of phylogenetic trees of any size. They perform frequently-used tree operations without requiring user interaction. They also allow tree drawing as scalable vector graphics (SVG), suitable for high-quality presentations and further editing, and as ASCII graphics for command-line inspection. As an example we include an implementation of bootscanning, a procedure for finding recombination breakpoints in viral genomes. Availability: C source code, Python bindings and executables for various platforms are available from http://cegg.unige.ch/newick_utils. The distribution includes a manual and example data. The package is distributed under the BSD License. Contact: thomas.junier@unige.ch PMID:20472542

Development of Zika Virus Vaccines

PubMed Central

Makhluf, Huda; Shresta, Sujan

2018-01-01

Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain–Barré syndrome, an autoimmune disease characterized by neurological deficits. Although there are currently licensed vaccines for other flaviviruses, there remains an urgent need for preventative vaccines against ZIKV infection. Herein we describe the current efforts to accelerate the development of ZIKV vaccines using various platforms, including live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in silico-predicted immunogenic viral epitopes. Many of these approaches have leveraged lessons learned from past experience with Dengue and other flavivirus vaccines. PMID:29346287

Second order harmonic guided wave mutual interactions in plate: Vector analysis, numerical simulation, and experimental results

NASA Astrophysics Data System (ADS)

Hasanian, Mostafa; Lissenden, Cliff J.

2017-08-01

The extraordinary sensitivity of nonlinear ultrasonic waves to the early stages of material degradation makes them excellent candidates for nondestructive material characterization. However, distinguishing weak material nonlinearity from instrumentation nonlinearity remains problematic for second harmonic generation approaches. A solution to this problem is to mix waves having different frequencies and to let their mutual interaction generate sum and difference harmonics at frequencies far from those of the instrumentation. Mixing of bulk waves and surface waves has been researched for some time, but mixing of guided waves has not yet been investigated in depth. A unique aspect of guided waves is their dispersive nature, which means we need to assure that a wave can propagate at the sum or difference frequency. A wave vector analysis is conducted that enables selection of primary waves traveling in any direction that generate phase matched secondary waves. We have tabulated many sets of primary waves and phase matched sum and difference harmonics. An example wave mode triplet of two counter-propagating collinear shear horizontal waves that interact to generate a symmetric Lamb wave at the sum frequency is simulated using finite element analysis and then laboratory experiments are conducted. The finite element simulation eliminates issues associated with instrumentation nonlinearities and signal-to-noise ratio. A straightforward subtraction method is used in the experiments to identify the material nonlinearity induced mutual interaction and show that the generated Lamb wave propagates on its own and is large enough to measure. Since the Lamb wave has different polarity than the shear horizontal waves the material nonlinearity is clearly identifiable. Thus, the mutual interactions of shear horizontal waves in plates could enable volumetric characterization of material in remote regions from transducers mounted on just one side of the plate.

The AAV-mediated and RNA-guided CRISPR/Cas9 system for gene therapy of DMD and BMD.

PubMed

Wang, Jing-Zhang; Wu, Peng; Shi, Zhi-Min; Xu, Yan-Li; Liu, Zhi-Jun

2017-08-01

Mutations in the dystrophin gene (Dmd) result in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), which afflict many newborn boys. In 2016, Brain and Development published several interesting articles on DMD treatment with antisense oligonucleotide, kinase inhibitor, and prednisolone. Even more strikingly, three articles in the issue 6271 of Science in 2016 provide new insights into gene therapy of DMD and BMD via the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). In brief, adeno-associated virus (AAV) vectors transport guided RNAs (gRNAs) and Cas9 into mdx mouse model, gRNAs recognize the mutated Dmd exon 23 (having a stop codon), and Cas9 cut the mutated exon 23 off the Dmd gene. These manipulations restored expression of truncated but partially functional dystrophin, improved skeletal and cardiac muscle function, and increased survival of mdx mice significantly. This review concisely summarized the related advancements and discussed their primary implications in the future gene therapy of DMD, including AAV-vector selection, gRNA designing, Cas9 optimization, dystrophin-restoration efficiency, administration routes, and systemic and long-term therapeutic efficacy. Future orientations, including off-target effects, safety concerns, immune responses, precision medicine, and Dmd-editing in the brain (potentially blocked by the blood-brain barrier) were also elucidated briefly. Collectively, the AAV-mediated and RNA-guided CRISPR/Cas9 system has major superiorities compared with traditional gene therapy, and might contribute to the treatment of DMD and BMD substantially in the near future. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Technology platforms: opportunities and development perspectives

NASA Astrophysics Data System (ADS)

Belyakov, G. P.; Avramchikova, N. T.; Belyakova, G. Y.; Chuvashova, M. N.

2016-11-01

The term “technology platform” is used to define thematic scopes in terms of which technological priorities are formed concerning state, business, science and education cooperation that are aimed to solve the problem of state technological independence. The authors have examined the implementation of this tool so that to concentrate essential resources in priority-driven vectors of science and technological advancement of a guiding cluster of innovative technologies in the field of space applications.

Study Modules for Calculus-Based General Physics. [Includes Modules 1 and 2: Dimensions and Vector Addition; Rectilinear Motion; plus a Trigonometry and Calculus Review].

ERIC Educational Resources Information Center

Fuller, Robert G., Ed.; And Others

This is part of a series of 42 Calculus Based Physics (CBP) modules totaling about 1,000 pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized course in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge.

PubMed

Wang, Dai; Phan, Shannon; DiStefano, Daniel J; Citron, Michael P; Callahan, Cheryl L; Indrawati, Lani; Dubey, Sheri A; Heidecker, Gwendolyn J; Govindarajan, Dhanasekaran; Liang, Xiaoping; He, Biao; Espeseth, Amy S

2017-06-01

Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 10 3 PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 10 6 PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate. IMPORTANCE A safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys that had been infected previously. Our data suggest that PIV5-vectored vaccines could potentially protect both the pediatric and elderly populations and support continued development of the vector platform. Copyright © 2017 American Society for Microbiology.

High Efficiency CRISPR/Cas9-mediated Gene Editing in Primary Human T-cells Using Mutant Adenoviral E4orf6/E1b55k "Helper" Proteins.

PubMed

Gwiazda, Kamila S; Grier, Alexandra E; Sahni, Jaya; Burleigh, Stephen M; Martin, Unja; Yang, Julia G; Popp, Nicholas A; Krutein, Michelle C; Khan, Iram F; Jacoby, Kyle; Jensen, Michael C; Rawlings, David J; Scharenberg, Andrew M

2016-09-29

Many future therapeutic applications of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 and related RNA-guided nucleases are likely to require their use to promote gene targeting, thus necessitating development of methods that provide for delivery of three components-Cas9, guide RNAs and recombination templates-to primary cells rendered proficient for homology-directed repair. Here, we demonstrate an electroporation/transduction codelivery method that utilizes mRNA to express both Cas9 and mutant adenoviral E4orf6 and E1b55k helper proteins in association with adeno-associated virus (AAV) vectors expressing guide RNAs and recombination templates. By transiently enhancing target cell permissiveness to AAV transduction and gene editing efficiency, this novel approach promotes efficient gene disruption and/or gene targeting at multiple loci in primary human T-cells, illustrating its broad potential for application in translational gene editing.

Genome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening

PubMed Central

Joung, Julia; Konermann, Silvana; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Platt, Randall J.; Brigham, Mark D.; Sanjana, Neville E.; Zhang, Feng

2017-01-01

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified from the screen, we further describe strategies for confirming the screening phenotype as well as genetic perturbation through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9–15 weeks followed by 4–5 weeks of validation. PMID:28333914

Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening.

PubMed

Joung, Julia; Konermann, Silvana; Gootenberg, Jonathan S; Abudayyeh, Omar O; Platt, Randall J; Brigham, Mark D; Sanjana, Neville E; Zhang, Feng

2017-04-01

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified by the screen, we further describe strategies for confirming the screening phenotype, as well as genetic perturbation, through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9-15 weeks, followed by 4-5 weeks of validation.

Mission Accomplished? We Need a Guide to the 'Post Release' World of Wolbachia for Aedes-borne Disease Control.

PubMed

Ritchie, Scott A; van den Hurk, Andrew F; Smout, Michael J; Staunton, Kyran M; Hoffmann, Ary A

2018-03-01

Historically, sustained control of Aedes aegypti, the vector of dengue, chikungunya, yellow fever, and Zika viruses, has been largely ineffective. Subsequently, two novel 'rear and release' control strategies utilizing mosquitoes infected with Wolbachia are currently being developed and deployed widely. In the incompatible insect technique, male Aedes mosquitoes, infected with Wolbachia, suppress populations through unproductive mating. In the transinfection strategy, both male and female Wolbachia-infected Ae. aegypti mosquitoes rapidly infect the wild population with Wolbachia, blocking virus transmission. It is critical to monitor the long-term stability of Wolbachia in host populations, and also the ability of this bacterium to continually inhibit virus transmission. Ongoing release and monitoring programs must be future-proofed should political support weaken when these vectors are successfully controlled. Copyright © 2017 Elsevier Ltd. All rights reserved.

GenoCAD Plant Grammar to Design Plant Expression Vectors for Promoter Analysis.

PubMed

Coll, Anna; Wilson, Mandy L; Gruden, Kristina; Peccoud, Jean

2016-01-01

With the rapid advances in prediction tools for discovery of new promoters and their cis-elements, there is a need to improve plant expression methodologies in order to facilitate a high-throughput functional validation of these promoters in planta. The promoter-reporter analysis is an indispensible approach for characterization of plant promoters. It requires the design of complex plant expression vectors, which can be challenging. Here, we describe the use of a plant grammar implemented in GenoCAD that will allow the users to quickly design constructs for promoter analysis experiments but also for other in planta functional studies. The GenoCAD plant grammar includes a library of plant biological parts organized in structural categories to facilitate their use and management and a set of rules that guides the process of assembling these biological parts into large constructs.

Optimizing fusion PIC code performance at scale on Cori Phase 2

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

Koskela, T. S.; Deslippe, J.

In this paper we present the results of optimizing the performance of the gyrokinetic full-f fusion PIC code XGC1 on the Cori Phase Two Knights Landing system. The code has undergone substantial development to enable the use of vector instructions in its most expensive kernels within the NERSC Exascale Science Applications Program. We study the single-node performance of the code on an absolute scale using the roofline methodology to guide optimization efforts. We have obtained 2x speedups in single node performance due to enabling vectorization and performing memory layout optimizations. On multiple nodes, the code is shown to scale wellmore » up to 4000 nodes, near half the size of the machine. We discuss some communication bottlenecks that were identified and resolved during the work.« less

IMOJEV(®): a Yellow fever virus-based novel Japanese encephalitis vaccine.

PubMed

Appaiahgari, Mohan Babu; Vrati, Sudhanshu

2010-12-01

Japanese encephalitis (JE) is a disease of the CNS caused by Japanese encephalitis virus (JEV). The disease appears in the form of frequent outbreaks in most south- and southeast Asian countries and the virus has become endemic in several areas. There is no licensed therapy available and disease control by vaccination is considered to be most effective. Mouse brain-derived inactivated JE vaccines, although immunogenic, have several limitations in terms of safety, availability and requirement for multiple doses. Owing to these drawbacks, the WHO called for the development of novel, safe and more efficacious JE vaccines. Several candidate vaccines have been developed and at least three of them that demonstrated strong immunogenicity after one or two doses of the vaccine in animal models were subsequently tested in various clinical trials. One of these vaccines, IMOJEV(®) (JE-CV and previously known as ChimeriVax™-JE), is a novel recombinant chimeric virus vaccine, developed using the Yellow fever virus (YFV) vaccine vector YFV17D, by replacing the cDNA encoding the envelope proteins of YFV with that of an attenuated JEV strain SA14-14-2. IMOJEV was found to be safe, highly immunogenic and capable of inducing long-lasting immunity in both preclinical and clinical trials. Moreover, a single dose of IMOJEV was sufficient to induce protective immunity, which was similar to that induced in adults by three doses of JE-VAX(®), a mouse brain-derived inactivated JE vaccine. Recently, Phase III trials evaluating the immunogenicity and safety of the chimeric virus vaccine have been successfully completed in some JE-endemic countries and the vaccine manufacturers have filed an application for vaccine registration. IMOJEV may thus be licensed for use in humans as an improved alternative to the currently licensed JE vaccines.

Plant-made vaccines against West Nile virus are potent, safe, and economically feasible

PubMed Central

Chen, Qiang

2015-01-01

The threat of West Nile virus (WNV) epidemics with increasingly severe neuroinvasive infections demands the development and licensing of effective vaccines. To date, vaccine candidates based on inactivated, live-attenuated, or chimeric virus, and viral DNA and WNV protein subunits have been developed. Some have been approved for veterinary use or are under clinical investigation, yet no vaccine has been licensed for human use. Reaching the milestone of a commercialized human vaccine, however, may largely depend on the economics of vaccine production. Analysis suggests that currently only novel low-cost production technologies would allow vaccination to outcompete the cost of surveillance and clinical treatment. Here, we review progress using plants to address the economic challenges of WNV vaccine production. The advantages of plants as hosts for vaccine production in cost, speed and scalability, especially those of viral vector-based transient expression systems, are discussed. The progress in developing WNV subunit vaccines in plants is reviewed within the context of their expression, characterization, downstream processing, and immunogenicity in animal models. The development of vaccines based on enveloped and non-enveloped virus-like particles is also discussed. These advancements suggest that plants may provide a production platform that offers potent, safe and affordable human vaccines against WNV. PMID:25676782

Plant-made vaccines against West Nile virus are potent, safe, and economically feasible.

PubMed

Chen, Qiang

2015-05-01

The threat of West Nile virus (WNV) epidemics with increasingly severe neuroinvasive infections demands the development and licensing of effective vaccines. To date, vaccine candidates based on inactivated, live-attenuated, or chimeric virus, and viral DNA and WNV protein subunits have been developed. Some have been approved for veterinary use or are under clinical investigation, yet no vaccine has been licensed for human use. Reaching the milestone of a commercialized human vaccine, however, may largely depend on the economics of vaccine production. Analysis suggests that currently only novel low-cost production technologies would allow vaccination to outcompete the cost of surveillance and clinical treatment. Here, we review progress using plants to address the economic challenges of WNV vaccine production. The advantages of plants as hosts for vaccine production in cost, speed and scalability, especially those of viral vector-based transient expression systems, are discussed. The progress in developing WNV subunit vaccines in plants is reviewed within the context of their expression, characterization, downstream processing, and immunogenicity in animal models. The development of vaccines based on enveloped and non-enveloped virus-like particles is also discussed. These advancements suggest that plants may provide a production platform that offers potent, safe and affordable human vaccines against WNV. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction.

PubMed

Tsafa, Effrosyni; Al-Bahrani, Mariam; Bentayebi, Kaoutar; Przystal, Justyna; Suwan, Keittisak; Hajitou, Amin

2016-08-09

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP.

A Field Trial of Alternative Targeted Screening Strategies for Chagas Disease in Arequipa, Peru

PubMed Central

Hunter, Gabrielle C.; Borrini-Mayorí, Katty; Ancca Juárez, Jenny; Castillo Neyra, Ricardo; Verastegui, Manuela R.; Malaga Chavez, Fernando S.; Cornejo del Carpio, Juan Geny; Córdova Benzaquen, Eleazar; Náquira, César; Gilman, Robert H.; Bern, Caryn; Levy, Michael Z.

2012-01-01

Background Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa, population ∼860,000. It is unclear how to implement cost-effective screening programs across a large urban and periurban environment. Methods We compared four alternative screening strategies in 18 periurban communities, testing individuals in houses with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Vector data were obtained from routine Ministry of Health insecticide application campaigns. We performed ring case detection (radius of 15 m) around seropositive individuals, and collected data on costs of implementation for each strategy. Results Infection was detected in 21 of 923 (2.28%) participants. Cases had lived more time on average in rural places than non-cases (7.20 years versus 3.31 years, respectively). Significant risk factors on univariate logistic regression for infection were age (OR 1.02; p = 0.041), time lived in a rural location (OR 1.04; p = 0.022), and time lived in an infested area (OR 1.04; p = 0.008). No multivariate model with these variables fit the data better than a simple model including only the time lived in an area with triatomine bugs. There was no significant difference in prevalence across the screening strategies; however a self-assessment of disease risk may have biased participation, inflating prevalence among residents of houses where no infestation was detected. Testing houses with infected-vectors was least expensive. Ring case detection yielded four secondary cases in only one community, possibly due to vector-borne transmission in this community, apparently absent in the others. Conclusions Targeted screening for urban Chagas disease is promising in areas with ongoing vector-borne transmission; however, these pockets of epidemic transmission remain difficult to detect a priori. The flexibility to adapt to the epidemiology that emerges during screening is key to an efficient case detection intervention. In heterogeneous urban environments, self-assessments of risk and simple residence history questionnaires may be useful to identify those at highest risk for Chagas disease to guide diagnostic efforts. PMID:22253939

A field trial of alternative targeted screening strategies for Chagas disease in Arequipa, Peru.

PubMed

Hunter, Gabrielle C; Borrini-Mayorí, Katty; Ancca Juárez, Jenny; Castillo Neyra, Ricardo; Verastegui, Manuela R; Malaga Chavez, Fernando S; Cornejo del Carpio, Juan Geny; Córdova Benzaquen, Eleazar; Náquira, César; Gilman, Robert H; Bern, Caryn; Levy, Michael Z

2012-01-01

Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa, population ∼860,000. It is unclear how to implement cost-effective screening programs across a large urban and periurban environment. We compared four alternative screening strategies in 18 periurban communities, testing individuals in houses with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Vector data were obtained from routine Ministry of Health insecticide application campaigns. We performed ring case detection (radius of 15 m) around seropositive individuals, and collected data on costs of implementation for each strategy. Infection was detected in 21 of 923 (2.28%) participants. Cases had lived more time on average in rural places than non-cases (7.20 years versus 3.31 years, respectively). Significant risk factors on univariate logistic regression for infection were age (OR 1.02; p = 0.041), time lived in a rural location (OR 1.04; p = 0.022), and time lived in an infested area (OR 1.04; p = 0.008). No multivariate model with these variables fit the data better than a simple model including only the time lived in an area with triatomine bugs. There was no significant difference in prevalence across the screening strategies; however a self-assessment of disease risk may have biased participation, inflating prevalence among residents of houses where no infestation was detected. Testing houses with infected-vectors was least expensive. Ring case detection yielded four secondary cases in only one community, possibly due to vector-borne transmission in this community, apparently absent in the others. Targeted screening for urban Chagas disease is promising in areas with ongoing vector-borne transmission; however, these pockets of epidemic transmission remain difficult to detect a priori. The flexibility to adapt to the epidemiology that emerges during screening is key to an efficient case detection intervention. In heterogeneous urban environments, self-assessments of risk and simple residence history questionnaires may be useful to identify those at highest risk for Chagas disease to guide diagnostic efforts.

CRISPR/Cas9-Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development.

PubMed

Okoli, Arinze; Okeke, Malachy I; Tryland, Morten; Moens, Ugo

2018-01-22

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them.

Reviewing molecular adaptations of Lyme borreliosis spirochetes in the context of reproductive fitness in natural transmission cycles.

PubMed

Tsao, Jean I

2009-01-01

Lyme borreliosis (LB) is caused by a group of pathogenic spirochetes - most often Borrelia burgdorferi, B. afzelii, and B. garinii - that are vectored by hard ticks in the Ixodes ricinus-persulcatus complex, which feed on a variety of mammals, birds, and lizards. Although LB is one of the best-studied vector-borne zoonoses, the annual incidence in North America and Europe leads other vector-borne diseases and continues to increase. What factors make the LB system so successful, and how can researchers hope to reduce disease risk - either through vaccinating humans or reducing the risk of contacting infected ticks in nature? Discoveries of molecular interactions involved in the transmission of LB spirochetes have accelerated recently, revealing complex interactions among the spirochete-tick-vertebrate triad. These interactions involve multiple, and often redundant, pathways that reflect the evolution of general and specific mechanisms by which the spirochetes survive and reproduce. Previous reviews have focused on the molecular interactions or population biology of the system. Here molecular interactions among the LB spirochete, its vector, and vertebrate hosts are reviewed in the context of natural maintenance cycles, which represent the ecological and evolutionary contexts that shape these interactions. This holistic system approach may help researchers develop additional testable hypotheses about transmission processes, interpret laboratory results, and guide development of future LB control measures and management.

Optical coherence tomography guided microinjections in live mouse embryos: high-resolution targeted manipulation for mouse embryonic research.

PubMed

Syed, Saba H; Coughlin, Andrew J; Garcia, Monica D; Wang, Shang; West, Jennifer L; Larin, Kirill V; Larina, Irina V

2015-05-01

The ability to conduct highly localized delivery of contrast agents, viral vectors, therapeutic or pharmacological agents, and signaling molecules or dyes to live mammalian embryos is greatly desired to enable a variety of studies in the field of developmental biology, such as investigating the molecular regulation of cardiovascular morphogenesis. To meet such a demand, we introduce, for the first time, the concept of employing optical coherence tomography (OCT)-guide microinjections in live mouse embryos, which provides precisely targeted manipulation with spatial resolution at the micrometer scale. The feasibility demonstration is performed with experimental studies on cultured live mouse embryos at E8.5 and E9.5. Additionally, we investigate the OCT-guided microinjection of gold–silica nanoshells to the yolk sac vasculature of live cultured mouse embryos at the stage when the heart just starts to beat, as a potential approach for dynamic assessment of cardiovascular form and function before the onset of blood cell circulation. Also, the capability of OCT to quantitatively monitor and measure injection volume is presented. Our results indicate that OCT-guided microinjection could be a useful tool for mouse embryonic research.

Optical coherence tomography guided microinjections in live mouse embryos: high-resolution targeted manipulation for mouse embryonic research

PubMed Central

Syed, Saba H.; Coughlin, Andrew J.; Garcia, Monica D.; Wang, Shang; West, Jennifer L.; Larin, Kirill V.; Larina, Irina V.

2015-01-01

Abstract. The ability to conduct highly localized delivery of contrast agents, viral vectors, therapeutic or pharmacological agents, and signaling molecules or dyes to live mammalian embryos is greatly desired to enable a variety of studies in the field of developmental biology, such as investigating the molecular regulation of cardiovascular morphogenesis. To meet such a demand, we introduce, for the first time, the concept of employing optical coherence tomography (OCT)-guide microinjections in live mouse embryos, which provides precisely targeted manipulation with spatial resolution at the micrometer scale. The feasibility demonstration is performed with experimental studies on cultured live mouse embryos at E8.5 and E9.5. Additionally, we investigate the OCT-guided microinjection of gold–silica nanoshells to the yolk sac vasculature of live cultured mouse embryos at the stage when the heart just starts to beat, as a potential approach for dynamic assessment of cardiovascular form and function before the onset of blood cell circulation. Also, the capability of OCT to quantitatively monitor and measure injection volume is presented. Our results indicate that OCT-guided microinjection could be a useful tool for mouse embryonic research. PMID:25581495

A simple and novel grading method for retraction and overshoot in Duane retraction syndrome.

PubMed

Kekunnaya, Ramesh; Moharana, Ruby; Tibrewal, Shailja; Chhablani, Preeti-Patil; Sachdeva, Virender

2016-11-01

Strabismus in Duane retraction syndrome is frequently associated with significant globe retraction and overshoots. However, there is no method to objectively grade retraction and overshoot. Our purpose is to describe a novel objective grading method. This novel and simple grading method has excellent agreement. It will help standardise measurements and guide the clinician in taking the decision for surgery and predicting its outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Building organizational capacity for a healthy work environment through role-based professional practice.

PubMed

Cornett, Patricia A; O'Rourke, Maria W

2009-01-01

The professional practice of registered nurses (RNs) and their professional role competence are key variables that have an impact on quality and patient safety. Organizations in which RNs practice must have the capacity to fully support the professional role of those RNs in exercising their legitimate power derived through nurse licensing laws and professional standards and ethics. The interplay of individual RN practice and organizational practice, and measurement thereof, are the essence of organizational capacity. Two models are discussed that tie together the attributes of healthy workplace environments and provide the structure to guide and sustain organizational capacity.

Nature, Mind, and Medicine: A Model for Mind-Body Healing.

PubMed

Kaufman, Jason A

2018-04-27

The human mind-body possesses a remarkable innate ability to heal. Grounded in the evolutionarily conserved systems of the brain and body, nature appears to function as the fundamental source of wellness along the two vectors of attention and relaxation. Yet, our species is moving away from nature at a time when humanity is just beginning to rediscover its benefits. Exposure to natural environments may provide a "window" of healing that can be extended through a continuum of intervention through the use of guided meditation and ultimately hypnotic suggestion. The result may be an improved ability to promote greater executive functioning and more robust immune regulation. The time has come for a more holistic medicine guided by the hand of nature. Copyright © 2018 Elsevier Inc. All rights reserved.

Cogeneration : A Regulatory Guide to Leasing, Permitting, and Licensing in Idaho, Montana, Oregon, and Washington.

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

Deshaye, Joyce; Bloomquist, R.Gordon

1992-12-01

This guidebook focuses on cogeneration development. It is one of a series of four guidebooks recently prepared to introduce the energy developer to the federal, state and local agencies that regulate energy facilities in Idaho, Montana, Oregon, and Washington (the Bonneville Power Administration Service Territory). It was prepared specifically to help cogeneration developers obtain the permits, licenses and approvals necessary to construct and operate a cogeneration facility. The regulations, agencies and policies described herein are subject to change. Changes are likely to occur whenever energy or a project becomes a political issue, a state legislature meets, a preexisting popular ormore » valuable land use is thought threatened, elected and appointed officials change, and new directions are imposed on states and local governments by the federal government. Accordingly, cogeneration developers should verify and continuously monitor the status of laws and rules that might affect their plans. Developers are cautioned that the regulations described herein may only be a starting point on the road to obtaining all the necessary permits.« less

Vector analysis of astigmatic correction after small-incision lenticule extraction and femtosecond-assisted LASIK for low to moderate myopic astigmatism.

PubMed

Chan, Tommy C Y; Ng, Alex L K; Cheng, George P M; Wang, Zheng; Ye, Cong; Woo, Victor C P; Tham, Clement C Y; Jhanji, Vishal

2016-04-01

To compare astigmatic correction between femtosecond-assisted laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). A total of 111 patients were included in this prospective study. Fifty-seven eyes were treated with LASIK and 54 eyes were treated with SMILE for myopia with low to moderate (-0.25 to -4.0 D) astigmatism. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity and manifest refraction were measured preoperatively and at 1 and 3 months postoperatively. Visual and refractive outcomes were reported. Changes in refractive astigmatism were evaluated using vector analysis. Preoperative characteristics were similar between both groups. The UDVA at 1 and 3 months was better in the LASIK group compared with the SMILE group (p<0.009). Postoperative cylinder was higher in the SMILE group (p<0.001). Fewer eyes attained the attempted cylindrical correction in the SMILE group (p<0.029). Vector analysis showed no significant difference in target-induced astigmatism (p=0.091) and angle of error (p>0.596) between the two groups. Surgically induced astigmatism was significantly lower in the SMILE group (p<0.023), while the difference vector (p<0.001) and absolute angle of error (p<0.016) were significantly higher in the SMILE group. No significant difference was found in these parameters between 1 and 3 months in both groups (p>0.122). Our results showed that SMILE offered a less favourable astigmatic correction comparable to femtosecond-assisted LASIK in eyes with low to moderate myopic astigmatism. The alignment of treatment was more variable in SMILE, leading to a lower efficacy compared with LASIK by 3 months postoperatively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Recombinant low-seroprevalent adenoviral vectors Ad26 and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV infection in cotton rats.

PubMed

Widjojoatmodjo, Myra N; Bogaert, Lies; Meek, Bob; Zahn, Roland; Vellinga, Jort; Custers, Jerome; Serroyen, Jan; Radošević, Katarina; Schuitemaker, Hanneke

2015-10-05

RSV is an important cause of lower respiratory tract infections in children, the elderly and in those with underlying medical conditions. Although the high disease burden indicates an urgent need for a vaccine against RSV, no licensed RSV vaccine is currently available. We developed an RSV vaccine candidate based on the low-seroprevalent human adenovirus serotypes 26 and 35 (Ad26 and Ad35) encoding the RSV fusion (F) gene. Single immunization of mice with either one of these vectors induced high titers of RSV neutralizing antibodies and high levels of F specific interferon-gamma-producing T cells. A Th1-type immune response was indicated by a high IgG2a/IgG1 ratio of RSV-specific antibodies, strong induction of RSV-specific interferon-gamma and tumor necrosis factor-alpha cytokine producing CD8 Tcells, and low RSV-specific CD4 T-cell induction. Both humoral and cellular responses were increased upon a boost with RSV-F expressing heterologous adenovirus vector (Ad35 boost after Ad26 prime or vice versa). Both single immunization and prime-boost immunization of cotton rats induced high and long-lasting RSV neutralizing antibody titers and protective immunity against lung and nasal RSV A2 virus load up to at least 30 weeks after immunization. Cotton rats were also completely protected against challenge with a RSV B strain (B15/97) after heterologous prime-boost immunization. Lungs from vaccinated animals showed minimal damage or inflammatory infiltrates post-challenge, in contrast to animals vaccinated with formalin-inactivated virus. Our results suggest that recombinant human adenoviral Ad26 and Ad35 vectors encoding the RSV F gene have the potential to provide broad and durable protection against RSV in humans, and appear safe to be investigated in infants. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.

PubMed

Mire, Chad E; Geisbert, Joan B; Marzi, Andrea; Agans, Krystle N; Feldmann, Heinz; Geisbert, Thomas W

2013-01-01

Ebola virus (EBOV) causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs). Currently, there are no licensed vaccines or therapeutics for human use. Recombinant vesicular stomatitis virus (rVSV)-based vaccine vectors, which encode an EBOV glycoprotein in place of the VSV glycoprotein, have shown 100% efficacy against homologous Sudan ebolavirus (SEBOV) or Zaire ebolavirus (ZEBOV) challenge in NHPs. In addition, a single injection of a blend of three rVSV vectors completely protected NHPs against challenge with SEBOV, ZEBOV, the former Côte d'Ivoire ebolavirus, and Marburg virus. However, recent studies suggest that complete protection against the newly discovered Bundibugyo ebolavirus (BEBOV) using several different heterologous filovirus vaccines is more difficult and presents a new challenge. As BEBOV caused nearly 50% mortality in a recent outbreak any filovirus vaccine advanced for human use must be able to protect against this new species. Here, we evaluated several different strategies against BEBOV using rVSV-based vaccines. Groups of cynomolgus macaques were vaccinated with a single injection of a homologous BEBOV vaccine, a single injection of a blended heterologous vaccine (SEBOV/ZEBOV), or a prime-boost using heterologous SEBOV and ZEBOV vectors. Animals were challenged with BEBOV 29-36 days after initial vaccination. Macaques vaccinated with the homologous BEBOV vaccine or the prime-boost showed no overt signs of illness and survived challenge. In contrast, animals vaccinated with the heterologous blended vaccine and unvaccinated control animals developed severe clinical symptoms consistent with BEBOV infection with 2 of 3 animals in each group succumbing. These data show that complete protection against BEBOV will likely require incorporation of BEBOV glycoprotein into the vaccine or employment of a prime-boost regimen. Fortunately, our results demonstrate that heterologous rVSV-based filovirus vaccine vectors employed in the prime-boost approach can provide protection against BEBOV using an abbreviated regimen, which may have utility in outbreak settings.

Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

PubMed

Meseda, Clement A; Atukorale, Vajini; Kuhn, Jordan; Schmeisser, Falko; Weir, Jerry P

2016-01-01

The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.

The Causal Mediation Formula - A Guide to the Assessment of Pathways and Mechanisms

DTIC Science & Technology

2011-10-01

for estimating CDE(z) in observational studies (in the presence of unobserved confounders) can be derived using do- calculus (Pearl, 2009, pp. 85–88...2011; Albert and Nelson , 2011). 7In the presence of measured and unmeasured confounders, the general conditions under which NDE is estimable from...achieve this independence (see footnote 7), that Z may represent a vector of variables, and that integrals should replace summations when dealing with

Patient-specific targeting guides compared with traditional instrumentation for glenoid component placement in shoulder arthroplasty: a multi-surgeon study in 70 arthritic cadaver specimens.

PubMed

Throckmorton, Thomas W; Gulotta, Lawrence V; Bonnarens, Frank O; Wright, Stephen A; Hartzell, Jeffrey L; Rozzi, William B; Hurst, Jason M; Frostick, Simon P; Sperling, John W

2015-06-01

The purpose of this study was to compare the accuracy of patient-specific guides for total shoulder arthroplasty (TSA) with traditional instrumentation in arthritic cadaver shoulders. We hypothesized that the patient-specific guides would place components more accurately than standard instrumentation. Seventy cadaver shoulders with radiographically confirmed arthritis were randomized in equal groups to 5 surgeons of varying experience levels who were not involved in development of the patient-specific guidance system. Specimens were then randomized to patient-specific guides based off of computed tomography scanning, standard instrumentation, and anatomic TSA or reverse TSA. Variances in version or inclination of more than 10° and more than 4 mm in starting point were considered indications of significant component malposition. TSA glenoid components placed with patient-specific guides averaged 5° of deviation from the intended position in version and 3° in inclination; those with standard instrumentation averaged 8° of deviation in version and 7° in inclination. These differences were significant for version (P = .04) and inclination (P = .01). Multivariate analysis of variance to compare the overall accuracy for the entire cohort (TSA and reverse TSA) revealed patient-specific guides to be significantly more accurate (P = .01) for the combined vectors of version and inclination. Patient-specific guides also had fewer instances of significant component malposition than standard instrumentation did. Patient-specific targeting guides were more accurate than traditional instrumentation and had fewer instances of component malposition for glenoid component placement in this multi-surgeon cadaver study of arthritic shoulders. Long-term clinical studies are needed to determine if these improvements produce improved functional outcomes. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Treatment of Parkinson's disease in rats by Nrf2 transfection using MRI-guided focused ultrasound delivery of nanomicrobubbles

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

Long, Ling; Cai, Xiaodong; Guo, Ruomi

Parkinson's disease (PD) is a very common neurological disorder. However, effective therapy is lacking. Although the blood-brain-barrier (BBB) protects the brain, it prevents the delivery of about 90% of drugs and nucleotides into the brain, thereby hindering the development of gene therapy for PD. Magnetic resonance imaging (MRI)-guided focused ultrasound delivery of microbubbles enhances the delivery of gene therapy vectors across the BBB and improves transfection efficiency. In the present study, we delivered nuclear factor E2-related factor 2 (Nrf2, NFE2L2) contained in nanomicrobubbles into the substantia nigra of PD rats by MRI-guided focused ultrasound, and we examined the effect ofmore » Nrf2 over-expression in this animal model of PD. The rat model of PD was established by injecting 6-OHDA in the right substantia nigra stereotactically. Plasmids (pDC315 or pDC315/Nrf2) were loaded onto nanomicrobubbles, and then injected through the tail vein with the assistance of MRI-guided focused ultrasound. MRI-guided focused ultrasound delivery of nanomicrobubbles increased gene transfection efficiency. Furthermore, Nrf2 gene transfection reduced reactive oxygen species levels, thereby protecting neurons in the target region. - Highlights: • MRI-guided focused ultrasound enhances gene transfection into the brain of rats. • Increased Nrf2 expression protects neurons in the rat model of PD. • Nrf2 protects neurons in PD by inhibiting ROS production.« less

Control-group feature normalization for multivariate pattern analysis of structural MRI data using the support vector machine.

PubMed

Linn, Kristin A; Gaonkar, Bilwaj; Satterthwaite, Theodore D; Doshi, Jimit; Davatzikos, Christos; Shinohara, Russell T

2016-05-15

Normalization of feature vector values is a common practice in machine learning. Generally, each feature value is standardized to the unit hypercube or by normalizing to zero mean and unit variance. Classification decisions based on support vector machines (SVMs) or by other methods are sensitive to the specific normalization used on the features. In the context of multivariate pattern analysis using neuroimaging data, standardization effectively up- and down-weights features based on their individual variability. Since the standard approach uses the entire data set to guide the normalization, it utilizes the total variability of these features. This total variation is inevitably dependent on the amount of marginal separation between groups. Thus, such a normalization may attenuate the separability of the data in high dimensional space. In this work we propose an alternate approach that uses an estimate of the control-group standard deviation to normalize features before training. We study our proposed approach in the context of group classification using structural MRI data. We show that control-based normalization leads to better reproducibility of estimated multivariate disease patterns and improves the classifier performance in many cases. Copyright © 2016 Elsevier Inc. All rights reserved.

Precision of computer-assisted core decompression drilling of the knee.

PubMed

Beckmann, J; Goetz, J; Bäthis, H; Kalteis, T; Grifka, J; Perlick, L

2006-06-01

Core decompression by exact drilling into the ischemic areas is the treatment of choice in early stages of osteonecrosis of the femoral condyle. Computer-aided surgery might enhance the precision of the drilling and lower the radiation exposure time of both staff and patients. The aim of this study was to evaluate the precision of the fluoroscopically based VectorVision-navigation system in an in vitro model. Thirty sawbones were prepared with a defect filled up with a radiopaque gypsum sphere mimicking the osteonecrosis. 20 sawbones were drilled by guidance of an intraoperative navigation system VectorVision (BrainLAB, Munich, Germany). Ten sawbones were drilled by fluoroscopic control only. A statistically significant difference with a mean distance of 0.58 mm in the navigated group and 0.98 mm in the control group regarding the distance to the desired mid-point of the lesion could be stated. Significant difference was further found in the number of drilling corrections as well as radiation time needed. The fluoroscopic-based VectorVision-navigation system shows a high feasibility and precision of computer-guided drilling with simultaneously reduction of radiation time and therefore could be integrated into clinical routine.

Taiwan's Travel and Border Health Measures in Response to Zika.

PubMed

Ho, Li-Li; Tsai, Yu-Hui; Lee, Wang-Ping; Liao, Szu-Tsai; Wu, Li-Gin; Wu, Yi-Chun

Zika virus has recently emerged as a worldwide public health concern. Travel and border health measures stand as one of the main strategies and frontline defenses in responding to international epidemics. As of October 31, 2016, Taiwan has reported 13 imported cases, 5 of which were detected through routine entry screening and active monitoring at international airports. This article shares Taiwan's disease surveillance activities at designated points of entry and travel and border health measures in response to Zika. The Taiwan government collaborates with its tourism industry to disseminate information about precautionary measures and encourages tour guides to report suspected individuals or events to activate early response measures. Taiwan also engages in vector control activities at points of entry, including targeting aircraft from countries where vector-borne diseases are endemic, implementing mosquito sweep measures, and collecting vector surveillance data. In future emerging and reemerging disease events, entry surveillance at designated points of entry may enable early detection of diseases of international origin and more rapid activation of public health preparedness activities and international collaboration. Taiwan will continue to maximize border and travel health measures in compliance with IHR (2005) requirements, which rely on continued risk assessment, practical implementation activities, and engagement with all stakeholders.

GenomeDiagram: a python package for the visualization of large-scale genomic data.

PubMed

Pritchard, Leighton; White, Jennifer A; Birch, Paul R J; Toth, Ian K

2006-03-01

We present GenomeDiagram, a flexible, open-source Python module for the visualization of large-scale genomic, comparative genomic and other data with reference to a single chromosome or other biological sequence. GenomeDiagram may be used to generate publication-quality vector graphics, rastered images and in-line streamed graphics for webpages. The package integrates with datatypes from the BioPython project, and is available for Windows, Linux and Mac OS X systems. GenomeDiagram is freely available as source code (under GNU Public License) at http://bioinf.scri.ac.uk/lp/programs.html, and requires Python 2.3 or higher, and recent versions of the ReportLab and BioPython packages. A user manual, example code and images are available at http://bioinf.scri.ac.uk/lp/programs.html.

Design and efficacy of an Ecohealth competency-based course on the prevention and control of vector diseases in Latin America.

PubMed

Magaña-Valladares, Laura; Rodríguez, Mario Henry; Betanzos-Reyes, Ángel Francisco; Riojas-Rodríguez, Horacio; Quezada-Jiménez, María Laura; Suárez-Conejero, Juana Elvira; Lamadrid-Figueroa, Héctor

2018-01-01

To design and analyze the efficacy of an Ecohealth competency-based course on the prevention and control of vector-borne-diseases for specific stakeholders. Multiple stakeholders and sectors of the region were consulted to identify Ecohealth group-specific competencies using an adjusted analysis matrix. Eight courses based on the competencies were implemented to train EA tutors. The effectiveness of the course was evaluated through the use of paired- t-tests by intervention group. Strategic, tactical, academia and community stakeholder groups and their competencies were identified. An overall gain of 43 percentage points (p<0.001) was observed in terms of competencies score in trained tutors, which further trained 1 033 people. The identification of the stakeholders and their competencies proved to be useful to guide training courses to significantly improve the initial competencies and create a critical mass to further advance the EA in the region.

Lipid nanoparticle vectorization of indocyanine green improves fluorescence imaging for tumor diagnosis and lymph node resection.

PubMed

Navarro, Fabrice P; Berger, Michel; Guillermet, Stéphanie; Josserand, Véronique; Guyon, Laurent; Neumann, Emmanuelle; Vinet, Françoise; Texier, Isabelle

2012-10-01

Fluorescence imaging is opening a new era in image-guided surgery and other medical applications. The only FDA approved contrast agent in the near infrared is IndoCyanine Green (ICG), which despites its low toxicity, displays poor chemical and optical properties for long-term and sensitive imaging applications in human. Lipid nanoparticles are investigated for improving ICG optical properties and in vivo fluorescence imaging sensitivity. 30 nm diameter lipid nanoparticles (LNP) are loaded with ICG. Their characterization and use for tumor and lymph node imaging are described. Nano-formulation benefits dye optical properties (6 times improved brightness) and chemical stability (>6 months at 4 degrees C in aqueous buffer). More importantly, LNP vectorization allows never reported sensitive and prolonged (>1 day) labeling of tumors and lymph nodes. Composed of human-use approved ingredients, this novel ICG nanometric formulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.

TALEN- and CRISPR/Cas9-Mediated Gene Editing in Human Pluripotent Stem Cells Using Lipid-Based Transfection.

PubMed

Hendriks, William T; Jiang, Xin; Daheron, Laurence; Cowan, Chad A

2015-08-03

Using custom-engineered nuclease-mediated genome editing, such as Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) RNA-guided Cas9 nucleases, human pluripotent stem cell (hPSC) lines with knockout or mutant alleles can be generated and differentiated into various cell types. This strategy of genome engineering in hPSCs will prove invaluable for studying human biology and disease. Here, we provide a detailed protocol for design and construction of TALEN and CRISPR vectors, testing of their nuclease activity, and delivery of TALEN or CRISPR vectors into hPSCs. In addition, we describe the use of single-stranded oligodeoxynucleotides (ssODNs) to introduce or repair point mutations. Next, we describe the identification of edited hPSC clones without antibiotic selection, including their clonal selection, genotyping, and expansion for downstream applications. Copyright © 2015 John Wiley & Sons, Inc.

Top partner-resonance interplay in a composite Higgs framework

NASA Astrophysics Data System (ADS)

Yepes, Juan; Zerwekh, Alfonso

2018-04-01

Guided us by the scenario of weak scale naturalness and the possible existence of exotic resonances, we have explored in a SO(5) Composite Higgs setup the interplay among three matter sectors: elementary, top partners and vector resonances. We parametrize it through explicit interactions of spin-1 SO(4)-resonances, coupled to the SO(5)-invariant fermionic currents and tensors presented in this work. Such invariants are built upon the Standard Model fermion sector as well as top partners sourced by the unbroken SO(4). The mass scales entailed by the top partner and vector resonance sectors will control the low energy effects emerging from our interplaying model. Its phenomenological impact and parameter spaces have been considered via flavor-dijet processes and electric dipole moments bounds. Finally, the strength of the Nambu-Goldstone symmetry breaking and the extra couplings implied by the top partner mass scales are measured in accordance with expected estimations.

Effective 2D-3D medical image registration using Support Vector Machine.

PubMed

Qi, Wenyuan; Gu, Lixu; Zhao, Qiang

2008-01-01

Registration of pre-operative 3D volume dataset and intra-operative 2D images gradually becomes an important technique to assist radiologists in diagnosing complicated diseases easily and quickly. In this paper, we proposed a novel 2D/3D registration framework based on Support Vector Machine (SVM) to compensate the disadvantages of generating large number of DRR images in the stage of intra-operation. Estimated similarity metric distribution could be built up from the relationship between parameters of transform and prior sparse target metric values by means of SVR method. Based on which, global optimal parameters of transform are finally searched out by an optimizer in order to guide 3D volume dataset to match intra-operative 2D image. Experiments reveal that our proposed registration method improved performance compared to conventional registration method and also provided a precise registration result efficiently.

Tensoral for post-processing users and simulation authors

NASA Technical Reports Server (NTRS)

Dresselhaus, Eliot

1993-01-01

The CTR post-processing effort aims to make turbulence simulations and data more readily and usefully available to the research and industrial communities. The Tensoral language, which provides the foundation for this effort, is introduced here in the form of a user's guide. The Tensoral user's guide is presented in two main sections. Section one acts as a general introduction and guides database users who wish to post-process simulation databases. Section two gives a brief description of how database authors and other advanced users can make simulation codes and/or the databases they generate available to the user community via Tensoral database back ends. The two-part structure of this document conforms to the two-level design structure of the Tensoral language. Tensoral has been designed to be a general computer language for performing tensor calculus and statistics on numerical data. Tensoral's generality allows it to be used for stand-alone native coding of high-level post-processing tasks (as described in section one of this guide). At the same time, Tensoral's specialization to a minute task (namely, to numerical tensor calculus and statistics) allows it to be easily embedded into applications written partly in Tensoral and partly in other computer languages (here, C and Vectoral). Embedded Tensoral, aimed at advanced users for more general coding (e.g. of efficient simulations, for interfacing with pre-existing software, for visualization, etc.), is described in section two of this guide.

Arenavirus reverse genetics for vaccine development

PubMed Central

Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin; Carlos de la Torre, Juan

2013-01-01

Arenaviruses are important human pathogens with no Food and Drug Administration (FDA)-licensed vaccines available and current antiviral therapy being limited to an off-label use of the nucleoside analogue ribavirin of limited prophylactic efficacy. The development of reverse genetics systems represented a major breakthrough in arenavirus research. However, rescue of recombinant arenaviruses using current reverse genetics systems has been restricted to rodent cells. In this study, we describe the rescue of recombinant arenaviruses from human 293T cells and Vero cells, an FDA-approved line for vaccine development. We also describe the generation of novel vectors that mediate synthesis of both negative-sense genome RNA and positive-sense mRNA species of lymphocytic choriomeningitis virus (LCMV) directed by the human RNA polymerases I and II, respectively, within the same plasmid. This approach reduces by half the number of vectors required for arenavirus rescue, which could facilitate virus rescue in cell lines approved for human vaccine production but that cannot be transfected at high efficiencies. We have shown the feasibility of this approach by rescuing both the Old World prototypic arenavirus LCMV and the live-attenuated vaccine Candid#1 strain of the New World arenavirus Junín. Moreover, we show the feasibility of using these novel strategies for efficient rescue of recombinant tri-segmented both LCMV and Candid#1. PMID:23364194

The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction

PubMed Central

Tsafa, Effrosyni; Al-Bahrani, Mariam; Bentayebi, Kaoutar; Przystal, Justyna; Suwan, Keittisak; Hajitou, Amin

2016-01-01

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP. PMID:27437775

Bioinspired Star-Shaped Poly(l-lysine) Polypeptides: Efficient Polymeric Nanocarriers for the Delivery of DNA to Mesenchymal Stem Cells.

PubMed

Walsh, David P; Murphy, Robert D; Panarella, Angela; Raftery, Rosanne M; Cavanagh, Brenton; Simpson, Jeremy C; O'Brien, Fergal J; Heise, Andreas; Cryan, Sally-Ann

2018-05-07

The field of tissue engineering is increasingly recognizing that gene therapy can be employed for modulating in vivo cellular response thereby guiding tissue regeneration. However, the field lacks a versatile and biocompatible gene delivery platform capable of efficiently delivering transgenes to mesenchymal stem cells (MSCs), a cell type often refractory to transfection. Herein, we describe the extensive and systematic exploration of three architectural variations of star-shaped poly(l-lysine) polypeptide (star-PLL) with varying number and length of poly(l-lysine) arms as potential nonviral gene delivery vectors for MSCs. We demonstrate that star-PLL vectors are capable of self-assembling with pDNA to form stable, cationic nanomedicines. Utilizing high content screening, live cell imaging, and mechanistic uptake studies we confirm the intracellular delivery of pDNA by star-PLLs to MSCs is a rapid process, which likely proceeds via a clathrin-independent mechanism. We identify a star-PLL composition with 64 poly(l-lysine) arms and five l-lysine subunits per arm as a particularly efficient vector that is capable of delivering both reporter genes and the therapeutic transgenes bone morphogenetic protein-2 and vascular endothelial growth factor to MSCs. This composition facilitated a 1000-fold increase in transgene expression in MSCs compared to its linear analogue, linear poly(l-lysine). Furthermore, it demonstrated comparable transgene expression to the widely used vector polyethylenimine using a lower pDNA dose with significantly less cytotoxicity. Overall, this study illustrates the ability of the star-PLL vectors to facilitate efficient, nontoxic nucleic acid delivery to MSCs thereby functioning as an innovative nanomedicine platform for tissue engineering applications.

Addressing vulnerability, building resilience: community-based adaptation to vector-borne diseases in the context of global change.

PubMed

Bardosh, Kevin Louis; Ryan, Sadie J; Ebi, Kris; Welburn, Susan; Singer, Burton

2017-12-11

The threat of a rapidly changing planet - of coupled social, environmental and climatic change - pose new conceptual and practical challenges in responding to vector-borne diseases. These include non-linear and uncertain spatial-temporal change dynamics associated with climate, animals, land, water, food, settlement, conflict, ecology and human socio-cultural, economic and political-institutional systems. To date, research efforts have been dominated by disease modeling, which has provided limited practical advice to policymakers and practitioners in developing policies and programmes on the ground. In this paper, we provide an alternative biosocial perspective grounded in social science insights, drawing upon concepts of vulnerability, resilience, participation and community-based adaptation. Our analysis was informed by a realist review (provided in the Additional file 2) focused on seven major climate-sensitive vector-borne diseases: malaria, schistosomiasis, dengue, leishmaniasis, sleeping sickness, chagas disease, and rift valley fever. Here, we situate our analysis of existing community-based interventions within the context of global change processes and the wider social science literature. We identify and discuss best practices and conceptual principles that should guide future community-based efforts to mitigate human vulnerability to vector-borne diseases. We argue that more focused attention and investments are needed in meaningful public participation, appropriate technologies, the strengthening of health systems, sustainable development, wider institutional changes and attention to the social determinants of health, including the drivers of co-infection. In order to respond effectively to uncertain future scenarios for vector-borne disease in a changing world, more attention needs to be given to building resilient and equitable systems in the present.

Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T-cells

PubMed Central

Scholler, John; Brady, Troy L.; Binder-Scholl, Gwendolyn; Hwang, Wei-Ting; Plesa, Gabriela; Hege, Kristen M.; Vogel, Ashley N.; Kalos, Michael; Riley, James L.; Deeks, Steven G.; Mitsuyasu, Ronald T.; Bernstein, Wendy B.; Aronson, Naomi E.; Levine, Bruce L.; Bushman, Frederic D.; June, Carl H.

2015-01-01

The success of adoptive T cell gene transfer for treatment of cancer and HIV is predicated on generating a response that is both durable and safe. Here we report long term results from three clinical trials to evaluate gammaretroviral vector engineered T-cells for HIV. The vector encoded a chimeric antigen receptor (CAR) comprised of CD4 linked to the CD3-ζ signaling chain (CD4ζ). CAR T-cells were detected in 98% of samples tested for at least 11 years post-infusion at frequencies that exceed average T cell levels after most vaccine approaches. The CD4ζ transgene retained expression and function. There was no evidence of vector-induced immortalization of cells as integration site distributions showed no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in growth control or transformation. The CD4ζ T cells have stable levels of engraftment, with decay half-lives that exceed 16 years, in marked contrast to previous trials testing engineered T cells. These findings indicate that host immunosuppression prior to T cell transfer is not required in order to achieve long term persistence of gene-modified T cells. Further, our results emphasize the safety of T cells modified by retroviral gene transfer in clinical application, as measured in >500 patient years of follow up. Thus, previous safety issues with integrating viral vectors are hematopoietic stem cell or transgene intrinsic, and not a general feature of retroviral vectors. Engineered T cells are a promising form of synthetic biology for long term delivery of protein based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases. PMID:22553251

Quantitative evaluation of first, second, and third generation hairpin systems reveals the limit of mammalian vector-based RNAi

PubMed Central

Watanabe, Colin; Cuellar, Trinna L.; Haley, Benjamin

2016-01-01

ABSTRACT Incorporating miRNA-like features into vector-based hairpin scaffolds has been shown to augment small RNA processing and RNAi efficiency. Therefore, defining an optimal, native hairpin context may obviate a need for hairpin-specific targeting design schemes, which confound the movement of functional siRNAs into shRNA/artificial miRNA backbones, or large-scale screens to identify efficacious sequences. Thus, we used quantitative cell-based assays to compare separate third generation artificial miRNA systems, miR-E (based on miR-30a) and miR-3G (based on miR-16-2 and first described in this study) to widely-adopted, first and second generation formats in both Pol-II and Pol-III expression vector contexts. Despite their unique structures and strandedness, and in contrast to first and second-generation RNAi triggers, the third generation formats operated with remarkable similarity to one another, and strong silencing was observed with a significant fraction of the evaluated target sequences within either promoter context. By pairing an established siRNA design algorithm with the third generation vectors we could readily identify targeting sequences that matched or exceeded the potency of those discovered through large-scale sensor-based assays. We find that third generation hairpin systems enable the maximal level of siRNA function, likely through enhanced processing and accumulation of precisely-defined guide RNAs. Therefore, we predict future gains in RNAi potency will come from improved hairpin expression and identification of optimal siRNA-intrinsic silencing properties rather than further modification of these scaffolds. Consequently, third generation systems should be the primary format for vector-based RNAi studies; miR-3G is advantageous due to its small expression cassette and simplified, cost-efficient cloning scheme. PMID:26786363

Potential for Mosquitoes (Diptera: Culicidae) From Florida to Transmit Rift Valley Fever Virus

DTIC Science & Technology

2013-09-01

Guide for the Care and Use of Laboratory Animals, NationalResearchCouncil, 2011. Theuse of any speciÞcproduct does not constitute endorsement of that...from North America are competent vectors and might be involved in the natural transmission cycle so that the appropriate control measures can be used if...collected in sufÞ- cient numbers for evaluation (Table 1). Viruses and Virus Assay.We used the ZH501 strain of RVFV, isolated in 1977 from the blood of a 10

SU-E-J-45: The Correlation Between CBCT Flat Panel Misalignment and 3D Image Guidance Accuracy

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

Kenton, O; Valdes, G; Yin, L

Purpose To simulate the impact of CBCT flat panel misalignment on the image quality, the calculated correction vectors in 3D image guided proton therapy and to determine if these calibration errors can be caught in our QA process. Methods The X-ray source and detector geometrical calibration (flexmap) file of the CBCT system in the AdaPTinsight software (IBA proton therapy) was edited to induce known changes in the rotational and translational calibrations of the imaging panel. Translations of up to ±10 mm in the x, y and z directions (see supplemental) and rotational errors of up to ±3° were induced. Themore » calibration files were then used to reconstruct the CBCT image of a pancreatic patient and CatPhan phantom. Correction vectors were calculated for the patient using the software’s auto match system and compared to baseline values. The CatPhan CBCT images were used for quantitative evaluation of image quality for each type of induced error. Results Translations of 1 to 3 mm in the x and y calibration resulted in corresponding correction vector errors of equal magnitude. Similar 10mm shifts were seen in the y-direction; however, in the x-direction, the image quality was too degraded for a match. These translational errors can be identified through differences in isocenter from orthogonal kV images taken during routine QA. Errors in the z-direction had no effect on the correction vector and image quality.Rotations of the imaging panel calibration resulted in corresponding correction vector rotations of the patient images. These rotations also resulted in degraded image quality which can be identified through quantitative image quality metrics. Conclusion Misalignment of CBCT geometry can lead to incorrect translational and rotational patient correction vectors. These errors can be identified through QA of the imaging isocenter as compared to orthogonal images combined with monitoring of CBCT image quality.« less

CRISPR/Cas9 mediates efficient conditional mutagenesis in Drosophila.

PubMed

Xue, Zhaoyu; Wu, Menghua; Wen, Kejia; Ren, Menda; Long, Li; Zhang, Xuedi; Gao, Guanjun

2014-09-05

Existing transgenic RNA interference (RNAi) methods greatly facilitate functional genome studies via controlled silencing of targeted mRNA in Drosophila. Although the RNAi approach is extremely powerful, concerns still linger about its low efficiency. Here, we developed a CRISPR/Cas9-mediated conditional mutagenesis system by combining tissue-specific expression of Cas9 driven by the Gal4/upstream activating site system with various ubiquitously expressed guide RNA transgenes to effectively inactivate gene expression in a temporally and spatially controlled manner. Furthermore, by including multiple guide RNAs in a transgenic vector to target a single gene, we achieved a high degree of gene mutagenesis in specific tissues. The CRISPR/Cas9-mediated conditional mutagenesis system provides a simple and effective tool for gene function analysis, and complements the existing RNAi approach. Copyright © 2014 Xue et al.

Climate Influence on Emerging Risk Areas for Rift Valley Fever Epidemics in Tanzania.

PubMed

Mweya, Clement N; Mboera, Leonard E G; Kimera, Sharadhuli I

2017-07-01

Rift Valley Fever (RVF) is a climate-related arboviral infection of animals and humans. Climate is thought to represent a threat toward emerging risk areas for RVF epidemics globally. The objective of this study was to evaluate influence of climate on distribution of suitable breeding habitats for Culex pipiens complex, potential mosquito vector responsible for transmission and distribution of disease epidemics risk areas in Tanzania. We used ecological niche models to estimate potential distribution of disease risk areas based on vectors and disease co-occurrence data approach. Climatic variables for the current and future scenarios were used as model inputs. Changes in mosquito vectors' habitat suitability in relation to disease risk areas were estimated. We used partial receiver operating characteristic and the area under the curves approach to evaluate model predictive performance and significance. Habitat suitability for Cx. pipiens complex indicated broad-scale potential for change and shift in the distribution of the vectors and disease for both 2020 and 2050 climatic scenarios. Risk areas indicated more intensification in the areas surrounding Lake Victoria and northeastern part of the country through 2050 climate scenario. Models show higher probability of emerging risk areas spreading toward the western parts of Tanzania from northeastern areas and decrease in the southern part of the country. Results presented here identified sites for consideration to guide surveillance and control interventions to reduce risk of RVF disease epidemics in Tanzania. A collaborative approach is recommended to develop and adapt climate-related disease control and prevention strategies.

CRISPR/Cas9—Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development

PubMed Central

Okoli, Arinze; Okeke, Malachy I.; Tryland, Morten; Moens, Ugo

2018-01-01

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them. PMID:29361752

Associated patterns of insecticide resistance in field populations of malaria vectors across Africa.

PubMed

Hancock, Penelope A; Wiebe, Antoinette; Gleave, Katherine A; Bhatt, Samir; Cameron, Ewan; Trett, Anna; Weetman, David; Smith, David L; Hemingway, Janet; Coleman, Michael; Gething, Peter W; Moyes, Catherine L

2018-06-05

The development of insecticide resistance in African malaria vectors threatens the continued efficacy of important vector control methods that rely on a limited set of insecticides. To understand the operational significance of resistance we require quantitative information about levels of resistance in field populations to the suite of vector control insecticides. Estimation of resistance is complicated by the sparsity of observations in field populations, variation in resistance over time and space at local and regional scales, and cross-resistance between different insecticide types. Using observations of the prevalence of resistance in mosquito species from the Anopheles gambiae complex sampled from 1,183 locations throughout Africa, we applied Bayesian geostatistical models to quantify patterns of covariation in resistance phenotypes across different insecticides. For resistance to the three pyrethroids tested, deltamethrin, permethrin, and λ-cyhalothrin, we found consistent forms of covariation across sub-Saharan Africa and covariation between resistance to these pyrethroids and resistance to DDT. We found no evidence of resistance interactions between carbamate and organophosphate insecticides or between these insecticides and those from other classes. For pyrethroids and DDT we found significant associations between predicted mean resistance and the observed frequency of kdr mutations in the Vgsc gene in field mosquito samples, with DDT showing the strongest association. These results improve our capacity to understand and predict resistance patterns throughout Africa and can guide the development of monitoring strategies. Copyright © 2018 the Author(s). Published by PNAS.

Lack of Trypanosoma cruzi Infection in Urban Roof Rats (Rattus rattus) at a Texas Facility Housing Naturally Infected Nonhuman Primates

PubMed Central

Hodo, Carolyn L; Bertolini, Nicole R; Bernal, John C; VandeBerg, John L; Hamer, Sarah A

2017-01-01

The protozoan parasite Trypanosoma cruzi causes Chagas disease, uses kissing bugs as a vector, and is maintained in nature by a variety of wildlife reservoirs. Many natural cases of Chagas disease have been reported in NHP at facilities across the southern United States, where infected vectors and wildlife occur. Infection of NHP with T. cruzi can diminish their value as research models and lead to health problems and death. Identifying the modes of transmission and role of wildlife reservoirs in these facilities is therefore critical to guide interventions to reduce transmission. Here we investigated the role of roof rats (Rattus rattus), the most abundant nuisance species at a primate facility in San Antonio, in the maintenance and transmission of T. cruzi. The hearts and blood from the carcasses of the 145 rats collected underwent 2 independent PCR assays for detection of T. cruzi and other trypanosomes. The 145 hearts and 61 blood samples were all negative for T. cruzi. This population sample of 145 subjects would allow the detection of disease prevalence of 0.020 with a confidence level of 95%. The limited active vector surveillance efforts by our team combined with passive surveillance by facility personnel yielded no kissing bugs during the study period. Our results suggest that roof rats are unlikely to be important local reservoirs of T. cruzi at this facility. Further investigation of transmission dynamics across multiple years and more comprehensive vector surveillance is warranted. PMID:28905716

Lack of Trypanosoma cruzi Infection in Urban Roof Rats (Rattus rattus) at a Texas Facility Housing Naturally Infected Nonhuman Primates.

PubMed

Hodo, Carolyn L; Bertolini, Nicole R; Bernal, John C; VandeBerg, John L; Hamer, Sarah A

2017-01-01

The protozoan parasite Trypanosoma cruzi causes Chagas disease, uses kissing bugs as a vector, and is maintained in nature by a variety of wildlife reservoirs. Many natural cases of Chagas disease have been reported in NHP at facilities across the southern United States, where infected vectors and wildlife occur. Infection of NHP with T. cruzi can diminish their value as research models and lead to health problems and death. Identifying the modes of transmission and role of wildlife reservoirs in these facilities is therefore critical to guide interventions to reduce transmission. Here we investigated the role of roof rats (Rattus rattus), the most abundant nuisance species at a primate facility in San Antonio, in the maintenance and transmission of T. cruzi. The hearts and blood from the carcasses of the 145 rats collected underwent 2 independent PCR assays for detection of T. cruzi and other trypanosomes. The 145 hearts and 61 blood samples were all negative for T. cruzi. This population sample of 145 subjects would allow the detection of disease prevalence of 0.020 with a confidence level of 95%. The limited active vector surveillance efforts by our team combined with passive surveillance by facility personnel yielded no kissing bugs during the study period. Our results suggest that roof rats are unlikely to be important local reservoirs of T. cruzi at this facility. Further investigation of transmission dynamics across multiple years and more comprehensive vector surveillance is warranted.

Fuzzy inference enhanced information recovery from digital PIV using cross-correlation combined with particle tracking

NASA Technical Reports Server (NTRS)

Wernet, Mark P.

1995-01-01

Particle Image Velocimetry provides a means of measuring the instantaneous 2-component velocity field across a planar region of a seeded flowfield. In this work only two camera, single exposure images are considered where both cameras have the same view of the illumination plane. Two competing techniques which yield unambiguous velocity vector direction information have been widely used for reducing the single exposure, multiple image data: cross-correlation and particle tracking. Correlation techniques yield averaged velocity estimates over subregions of the flow, whereas particle tracking techniques give individual particle velocity estimates. The correlation technique requires identification of the correlation peak on the correlation plane corresponding to the average displacement of particles across the subregion. Noise on the images and particle dropout contribute to spurious peaks on the correlation plane, leading to misidentification of the true correlation peak. The subsequent velocity vector maps contain spurious vectors where the displacement peaks have been improperly identified. Typically these spurious vectors are replaced by a weighted average of the neighboring vectors, thereby decreasing the independence of the measurements. In this work fuzzy logic techniques are used to determine the true correlation displacement peak even when it is not the maximum peak on the correlation plane, hence maximizing the information recovery from the correlation operation, maintaining the number of independent measurements and minimizing the number of spurious velocity vectors. Correlation peaks are correctly identified in both high and low seed density cases. The correlation velocity vector map can then be used as a guide for the particle tracking operation. Again fuzzy logic techniques are used, this time to identify the correct particle image pairings between exposures to determine particle displacements, and thus velocity. The advantage of this technique is the improved spatial resolution which is available from the particle tracking operation. Particle tracking alone may not be possible in the high seed density images typically required for achieving good results from the correlation technique. This two staged approach offers a velocimetric technique capable of measuring particle velocities with high spatial resolution over a broad range of seeding densities.

Microsimulation Modeling for Health Decision Sciences Using R: A Tutorial.

PubMed

Krijkamp, Eline M; Alarid-Escudero, Fernando; Enns, Eva A; Jalal, Hawre J; Hunink, M G Myriam; Pechlivanoglou, Petros

2018-04-01

Microsimulation models are becoming increasingly common in the field of decision modeling for health. Because microsimulation models are computationally more demanding than traditional Markov cohort models, the use of computer programming languages in their development has become more common. R is a programming language that has gained recognition within the field of decision modeling. It has the capacity to perform microsimulation models more efficiently than software commonly used for decision modeling, incorporate statistical analyses within decision models, and produce more transparent models and reproducible results. However, no clear guidance for the implementation of microsimulation models in R exists. In this tutorial, we provide a step-by-step guide to build microsimulation models in R and illustrate the use of this guide on a simple, but transferable, hypothetical decision problem. We guide the reader through the necessary steps and provide generic R code that is flexible and can be adapted for other models. We also show how this code can be extended to address more complex model structures and provide an efficient microsimulation approach that relies on vectorization solutions.

An efficient and portable SIMD algorithm for charge/current deposition in Particle-In-Cell codes

DOE PAGES

Vincenti, H.; Lobet, M.; Lehe, R.; ...

2016-09-19

In current computer architectures, data movement (from die to network) is by far the most energy consuming part of an algorithm (≈20pJ/word on-die to ≈10,000 pJ/word on the network). To increase memory locality at the hardware level and reduce energy consumption related to data movement, future exascale computers tend to use many-core processors on each compute nodes that will have a reduced clock speed to allow for efficient cooling. To compensate for frequency decrease, machine vendors are making use of long SIMD instruction registers that are able to process multiple data with one arithmetic operator in one clock cycle. SIMD registermore » length is expected to double every four years. As a consequence, Particle-In-Cell (PIC) codes will have to achieve good vectorization to fully take advantage of these upcoming architectures. In this paper, we present a new algorithm that allows for efficient and portable SIMD vectorization of current/charge deposition routines that are, along with the field gathering routines, among the most time consuming parts of the PIC algorithm. Our new algorithm uses a particular data structure that takes into account memory alignment constraints and avoids gather/scat;ter instructions that can significantly affect vectorization performances on current CPUs. The new algorithm was successfully implemented in the 3D skeleton PIC code PICSAR and tested on Haswell Xeon processors (AVX2-256 bits wide data registers). Results show a factor of ×2 to ×2.5 speed-up in double precision for particle shape factor of orders 1–3. The new algorithm can be applied as is on future KNL (Knights Landing) architectures that will include AVX-512 instruction sets with 512 bits register lengths (8 doubles/16 singles). Program summary Program Title: vec_deposition Program Files doi:http://dx.doi.org/10.17632/nh77fv9k8c.1 Licensing provisions: BSD 3-Clause Programming language: Fortran 90 External routines/libraries:  OpenMP > 4.0 Nature of problem: Exascale architectures will have many-core processors per node with long vector data registers capable of performing one single instruction on multiple data during one clock cycle. Data register lengths are expected to double every four years and this pushes for new portable solutions for efficiently vectorizing Particle-In-Cell codes on these future many-core architectures. One of the main hotspot routines of the PIC algorithm is the current/charge deposition for which there is no efficient and portable vector algorithm. Solution method: Here we provide an efficient and portable vector algorithm of current/charge deposition routines that uses a new data structure, which significantly reduces gather/scatter operations. Vectorization is controlled using OpenMP 4.0 compiler directives for vectorization which ensures portability across different architectures. Restrictions: Here we do not provide the full PIC algorithm with an executable but only vector routines for current/charge deposition. These scalar/vector routines can be used as library routines in your 3D Particle-In-Cell code. However, to get the best performances out of vector routines you have to satisfy the two following requirements: (1) Your code should implement particle tiling (as explained in the manuscript) to allow for maximized cache reuse and reduce memory accesses that can hinder vector performances. The routines can be used directly on each particle tile. (2) You should compile your code with a Fortran 90 compiler (e.g Intel, gnu or cray) and provide proper alignment flags and compiler alignment directives (more details in README file).« less

An efficient and portable SIMD algorithm for charge/current deposition in Particle-In-Cell codes

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

Vincenti, H.; Lobet, M.; Lehe, R.

In current computer architectures, data movement (from die to network) is by far the most energy consuming part of an algorithm (≈20pJ/word on-die to ≈10,000 pJ/word on the network). To increase memory locality at the hardware level and reduce energy consumption related to data movement, future exascale computers tend to use many-core processors on each compute nodes that will have a reduced clock speed to allow for efficient cooling. To compensate for frequency decrease, machine vendors are making use of long SIMD instruction registers that are able to process multiple data with one arithmetic operator in one clock cycle. SIMD registermore » length is expected to double every four years. As a consequence, Particle-In-Cell (PIC) codes will have to achieve good vectorization to fully take advantage of these upcoming architectures. In this paper, we present a new algorithm that allows for efficient and portable SIMD vectorization of current/charge deposition routines that are, along with the field gathering routines, among the most time consuming parts of the PIC algorithm. Our new algorithm uses a particular data structure that takes into account memory alignment constraints and avoids gather/scat;ter instructions that can significantly affect vectorization performances on current CPUs. The new algorithm was successfully implemented in the 3D skeleton PIC code PICSAR and tested on Haswell Xeon processors (AVX2-256 bits wide data registers). Results show a factor of ×2 to ×2.5 speed-up in double precision for particle shape factor of orders 1–3. The new algorithm can be applied as is on future KNL (Knights Landing) architectures that will include AVX-512 instruction sets with 512 bits register lengths (8 doubles/16 singles). Program summary Program Title: vec_deposition Program Files doi:http://dx.doi.org/10.17632/nh77fv9k8c.1 Licensing provisions: BSD 3-Clause Programming language: Fortran 90 External routines/libraries:  OpenMP > 4.0 Nature of problem: Exascale architectures will have many-core processors per node with long vector data registers capable of performing one single instruction on multiple data during one clock cycle. Data register lengths are expected to double every four years and this pushes for new portable solutions for efficiently vectorizing Particle-In-Cell codes on these future many-core architectures. One of the main hotspot routines of the PIC algorithm is the current/charge deposition for which there is no efficient and portable vector algorithm. Solution method: Here we provide an efficient and portable vector algorithm of current/charge deposition routines that uses a new data structure, which significantly reduces gather/scatter operations. Vectorization is controlled using OpenMP 4.0 compiler directives for vectorization which ensures portability across different architectures. Restrictions: Here we do not provide the full PIC algorithm with an executable but only vector routines for current/charge deposition. These scalar/vector routines can be used as library routines in your 3D Particle-In-Cell code. However, to get the best performances out of vector routines you have to satisfy the two following requirements: (1) Your code should implement particle tiling (as explained in the manuscript) to allow for maximized cache reuse and reduce memory accesses that can hinder vector performances. The routines can be used directly on each particle tile. (2) You should compile your code with a Fortran 90 compiler (e.g Intel, gnu or cray) and provide proper alignment flags and compiler alignment directives (more details in README file).« less

Protective immunity against tularemia provided by an adenovirus-vectored vaccine expressing Tul4 of Francisella tularensis.

PubMed

Kaur, Ravinder; Chen, Shan; Arévalo, Maria T; Xu, Qingfu; Chen, Yanping; Zeng, Mingtao

2012-03-01

Francisella tularensis, a category A bioterrorism agent, is a highly infectious organism that is passed on via skin contact and inhalation routes. A live attenuated vaccine strain (LVS) has been developed, but it has not been licensed for public use by the FDA due to safety concerns. Thus, there exists a need for a safer and improved vaccine. In this study, we have constructed a replication-incompetent adenovirus, Ad/opt-Tul4, carrying a codon-optimized gene for expression of a membrane protein, Tul4, of F. tularensis LVS. Its ability to protect against lethal challenge and its immunogenicity were evaluated in a murine model. An intramuscular injection of a single dose (1 × 10(7) PFU) of Ad/opt-Tul4 elicited a robust Tul4-specific antibody response. Assays suggest a Th1-driven response. A single dose elicited 20% protection against challenge with 100 × 50% lethal dose (LD(50)) F. tularensis LVS; two additional booster shots resulted in 60% protection. In comparison, three doses of 5 μg recombinant Tul4 protein did not elicit significant protection against challenge. Therefore, the Ad/opt-Tul4 vaccine was more effective than the protein vaccine, and protection was dose dependent. Compared to LVS, the protection rate is lower, but an adenovirus-vectored vaccine may be more attractive due to its enhanced safety profile and mucosal route of delivery. Furthermore, simple genetic modification of the vaccine may potentially produce antibodies protective against a fully virulent strain of F. tularensis. Our data support the development and further research of an adenovirus-vectored vaccine against Tul4 of F. tularensis LVS.

Methods for multiple-telescope beam imaging and guiding in the near-infrared

NASA Astrophysics Data System (ADS)

Anugu, N.; Amorim, A.; Gordo, P.; Eisenhauer, F.; Pfuhl, O.; Haug, M.; Wieprecht, E.; Wiezorrek, E.; Lima, J.; Perrin, G.; Brandner, W.; Straubmeier, C.; Le Bouquin, J.-B.; Garcia, P. J. V.

2018-05-01

Atmospheric turbulence and precise measurement of the astrometric baseline vector between any two telescopes are two major challenges in implementing phase-referenced interferometric astrometry and imaging. They limit the performance of a fibre-fed interferometer by degrading the instrument sensitivity and the precision of astrometric measurements and by introducing image reconstruction errors due to inaccurate phases. A multiple-beam acquisition and guiding camera was built to meet these challenges for a recently commissioned four-beam combiner instrument, GRAVITY, at the European Southern Observatory Very Large Telescope Interferometer. For each telescope beam, it measures (a) field tip-tilts by imaging stars in the sky, (b) telescope pupil shifts by imaging pupil reference laser beacons installed on each telescope using a 2 × 2 lenslet and (c) higher-order aberrations using a 9 × 9 Shack-Hartmann. The telescope pupils are imaged to provide visual monitoring while observing. These measurements enable active field and pupil guiding by actuating a train of tip-tilt mirrors placed in the pupil and field planes, respectively. The Shack-Hartmann measured quasi-static aberrations are used to focus the auxiliary telescopes and allow the possibility of correcting the non-common path errors between the adaptive optics systems of the unit telescopes and GRAVITY. The guiding stabilizes the light injection into single-mode fibres, increasing sensitivity and reducing the astrometric and image reconstruction errors. The beam guiding enables us to achieve an astrometric error of less than 50 μas. Here, we report on the data reduction methods and laboratory tests of the multiple-beam acquisition and guiding camera and its performance on-sky.

Magnetic guide-wire navigation in pulmonary and systemic arterial catheterization: initial experience in pigs.

PubMed

Grosse-Wortmann, Lars; Grabitz, Ralf; Seghaye, Marie-Christine

2007-04-01

Cardiovascular catheterization can be challenging whenever a stenosis or an abnormal vascular course interferes with probing the target vessel. This study addresses the feasibility of navigating a guide wire with a magnetic tip by an external magnetic field through pulmonary and systemic arteries in an experimental porcine model. We investigated six piglets using magnetic guide-wire navigation. Two pulmonary arteriograms were taken from different angles in order to reconstruct the three-dimensional vessel anatomy. A computer interface then calculated three-dimensional coordinates for the vessel in space. Using these coordinates, two external magnets were positioned to create magnetic vectors along the expected vessel course. Magnetically enabled guide wires were then navigated into the vessels using the magnetic field to orient the guide-wire tips. Aortic and renal branches were addressed in a similar fashion. Difficulty in reaching the target vessel was reflected by the number of attempts that were necessary. After 10 failed attempts, the maneuver was recorded to have failed. Thirty-five of 37 (94.6%) arteries with branches at acute angles were reached successfully using magnetic navigation. In two pigs, the left upper lobe artery could not be probed. Peripheral arteries of small diameter were easier to reach than large central arteries, requiring less attempts. Magnetic guide-wire navigation is feasible in the arteries of the lungs, the head and neck, and the kidneys. It is particularly useful in entering small arterial branches at acute angles and may facilitate interventional therapy in a variety of vascular diseases in children and adults.

Inhibition of CRISPR/Cas9-Mediated Genome Engineering by a Type I Interferon-Induced Reduction in Guide RNA Expression.

PubMed

Machitani, Mitsuhiro; Sakurai, Fuminori; Wakabayashi, Keisaku; Nakatani, Kosuke; Takayama, Kazuo; Tachibana, Masashi; Mizuguchi, Hiroyuki

2017-01-01

Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome engineering technology is a powerful tool for generation of cells and animals with engineered mutations in their genomes. In order to introduce the CRISPR/Cas9 system into target cells, nonviral and viral vectors are often used; however, such vectors trigger innate immune responses associated with production of type I interferons (IFNs). We have recently demonstrated that type I IFNs inhibit short-hairpin RNA-mediated gene silencing, which led us to hypothesize that type I IFNs may also inhibit CRISPR/Cas9-mediated genome mutagenesis. Here we investigated this hypothesis. A single-strand annealing assay using a reporter plasmid demonstrated that CRISPR/Cas9-mediated cleavage efficiencies of the target double-stranded DNA were significantly reduced by IFNα. A mismatch recognition nuclease-dependent genotyping assay also demonstrated that IFNα reduced insertion or deletion (indel) mutation levels by approximately half. Treatment with IFNα did not alter Cas9 protein expression levels, whereas the copy numbers of guide RNA (gRNA) were significantly reduced by IFNα stimulation. These results indicate that type I IFNs significantly reduce gRNA expression levels following introduction of the CRISPR/Cas9 system in the cells, leading to a reduction in the efficiencies of CRISPR/Cas9-mediated genome mutagenesis. Our findings provide important clues for the achievement of efficient genome engineering using the CRISPR/Cas9 system.

Building national capacity for research mentor training: an evidence-based approach to training the trainers.

PubMed

Pfund, Christine; Spencer, Kimberly C; Asquith, Pamela; House, Stephanie C; Miller, Sarah; Sorkness, Christine A

2015-01-01

Research mentor training (RMT), based on the published Entering Mentoring curricula series, has been shown to improve the knowledge and skills of research mentors across career stages, as self-reported by both the mentors engaged in training and their mentees. To promote widespread dissemination and empower others to implement this evidence-based training at their home institutions, we developed an extensive, interactive, multifaceted train-the-trainer workshop. The specific goals of these workshops are to 1) increase facilitator knowledge of an RMT curriculum, 2) increase facilitator confidence in implementing the curriculum, 3) provide a safe environment to practice facilitation of curricular activities, and 4) review implementation strategies and evaluation tools. Data indicate that our approach results in high satisfaction and significant confidence gains among attendees. Of the 195 diverse attendees trained in our workshops since Fall 2010, 44% report implementation at 39 different institutions, collectively training more than 500 mentors. Further, mentors who participated in the RMT sessions led by our trained facilitators report high facilitator effectiveness in guiding discussion. Implications and challenges to building the national capacity needed for improved research mentoring relationships are discussed. © 2015 C. Pfund, K. C. Spencer, et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

How Four Scientists Integrate Thermodynamic and Kinetic Theory, Context, Analogies, and Methods in Protein-Folding and Dynamics Research: Implications for Biochemistry Instruction.

PubMed

Jeffery, Kathleen A; Pelaez, Nancy; Anderson, Trevor R

2018-01-01

To keep biochemistry instruction current and relevant, it is crucial to expose students to cutting-edge scientific research and how experts reason about processes governed by thermodynamics and kinetics such as protein folding and dynamics. This study focuses on how experts explain their research into this topic with the intention of informing instruction. Previous research has modeled how expert biologists incorporate research methods, social or biological context, and analogies when they talk about their research on mechanisms. We used this model as a guiding framework to collect and analyze interview data from four experts. The similarities and differences that emerged from analysis indicate that all experts integrated theoretical knowledge with their research context, methods, and analogies when they explained how phenomena operate, in particular by mapping phenomena to mathematical models; they explored different processes depending on their explanatory aims, but readily transitioned between different perspectives and explanatory models; and they explained thermodynamic and kinetic concepts of relevance to protein folding in different ways that aligned with their particular research methods. We discuss how these findings have important implications for teaching and future educational research. © 2018 K. A. Jeffery et al. CBE—Life Sciences Education © 2018 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Development and Validation of a Rubric for Diagnosing Students' Experimental Design Knowledge and Difficulties.

PubMed

Dasgupta, Annwesa P; Anderson, Trevor R; Pelaez, Nancy

2014-01-01

It is essential to teach students about experimental design, as this facilitates their deeper understanding of how most biological knowledge was generated and gives them tools to perform their own investigations. Despite the importance of this area, surprisingly little is known about what students actually learn from designing biological experiments. In this paper, we describe a rubric for experimental design (RED) that can be used to measure knowledge of and diagnose difficulties with experimental design. The development and validation of the RED was informed by a literature review and empirical analysis of undergraduate biology students' responses to three published assessments. Five areas of difficulty with experimental design were identified: the variable properties of an experimental subject; the manipulated variables; measurement of outcomes; accounting for variability; and the scope of inference appropriate for experimental findings. Our findings revealed that some difficulties, documented some 50 yr ago, still exist among our undergraduate students, while others remain poorly investigated. The RED shows great promise for diagnosing students' experimental design knowledge in lecture settings, laboratory courses, research internships, and course-based undergraduate research experiences. It also shows potential for guiding the development and selection of assessment and instructional activities that foster experimental design. © 2014 A. P. Dasgupta et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A "Scientific Diversity" Intervention to Reduce Gender Bias in a Sample of Life Scientists.

PubMed

Moss-Racusin, Corinne A; van der Toorn, Jojanneke; Dovidio, John F; Brescoll, Victoria L; Graham, Mark J; Handelsman, Jo

2016-01-01

Mounting experimental evidence suggests that subtle gender biases favoring men contribute to the underrepresentation of women in science, technology, engineering, and mathematics (STEM), including many subfields of the life sciences. However, there are relatively few evaluations of diversity interventions designed to reduce gender biases within the STEM community. Because gender biases distort the meritocratic evaluation and advancement of students, interventions targeting instructors' biases are particularly needed. We evaluated one such intervention, a workshop called "Scientific Diversity" that was consistent with an established framework guiding the development of diversity interventions designed to reduce biases and was administered to a sample of life science instructors (N = 126) at several sessions of the National Academies Summer Institute for Undergraduate Education held nationwide. Evidence emerged indicating the efficacy of the "Scientific Diversity" workshop, such that participants were more aware of gender bias, expressed less gender bias, and were more willing to engage in actions to reduce gender bias 2 weeks after participating in the intervention compared with 2 weeks before the intervention. Implications for diversity interventions aimed at reducing gender bias and broadening the participation of women in the life sciences are discussed. © 2016 C. A. Moss-Racusin et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Scientific teaching: defining a taxonomy of observable practices.

PubMed

Couch, Brian A; Brown, Tanya L; Schelpat, Tyler J; Graham, Mark J; Knight, Jennifer K

2015-03-02

Over the past several decades, numerous reports have been published advocating for changes to undergraduate science education. These national calls inspired the formation of the National Academies Summer Institutes on Undergraduate Education in Biology (SI), a group of regional workshops to help faculty members learn and implement interactive teaching methods. The SI curriculum promotes a pedagogical framework called Scientific Teaching (ST), which aims to bring the vitality of modern research into the classroom by engaging students in the scientific discovery process and using student data to inform the ongoing development of teaching methods. With the spread of ST, the need emerges to systematically define its components in order to establish a common description for education researchers and practitioners. We describe the development of a taxonomy detailing ST's core elements and provide data from classroom observations and faculty surveys in support of its applicability within undergraduate science courses. The final taxonomy consists of 15 pedagogical goals and 37 supporting practices, specifying observable behaviors, artifacts, and features associated with ST. This taxonomy will support future educational efforts by providing a framework for researchers studying the processes and outcomes of ST-based course transformations as well as a concise guide for faculty members developing classes. © 2015 B. A. Couch et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Investigating the Role of an Inquiry-Based Biology Lab Course on Student Attitudes and Views toward Science.

PubMed

Jeffery, Erica; Nomme, Kathy; Deane, Thomas; Pollock, Carol; Birol, Gülnur

2016-01-01

Students' academic experiences can influence their conceptualization of science. In contrast experts hold particular beliefs, perceptions, opinions, and attitudes about science that are often absent in first-year undergraduate students. Shifts toward more expert-like attitudes and views have been linked to improved student engagement, critical-thinking ability, conceptual understanding, and academic performance. In this study, we investigate shifts in attitudes and views toward science by students in four biology classes with differences in student enrollment, academic support, and instruction. We observe significant, positive effects of enrollment in a guided-inquiry lab course and academic performance on the percentage of expert-like student attitudes and views at the end of term. We also identify variation in two aspects of student attitudes and views: 1) confidence and interest and 2) understanding and acceptance. In particular, enrollment in the lab course boosts student confidence and interest in scientific inquiry in the short term, even for students with low academic performance or little English-language experience. Our results suggest that low-performing students in particular may require additional opportunities for experiential learning or greater academic support to develop expert-like perceptions of biology as a science. © 2016 E. Jeffery et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Promoting inquiry-based teaching in laboratory courses: are we meeting the grade?

PubMed

Beck, Christopher; Butler, Amy; da Silva, Karen Burke

2014-01-01

Over the past decade, repeated calls have been made to incorporate more active teaching and learning in undergraduate biology courses. The emphasis on inquiry-based teaching is especially important in laboratory courses, as these are the courses in which students are applying the process of science. To determine the current state of research on inquiry-based teaching in undergraduate biology laboratory courses, we reviewed the recent published literature on inquiry-based exercises. The majority of studies in our data set were in the subdisciplines of biochemistry, cell biology, developmental biology, genetics, and molecular biology. In addition, most exercises were guided inquiry, rather than open ended or research based. Almost 75% of the studies included assessment data, with two-thirds of these studies including multiple types of assessment data. However, few exercises were assessed in multiple courses or at multiple institutions. Furthermore, assessments were rarely based on published instruments. Although the results of the studies in our data set show a positive effect of inquiry-based teaching in biology laboratory courses on student learning gains, research that uses the same instrument across a range of courses and institutions is needed to determine whether these results can be generalized. © 2014 C. Beck et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Differences in metacognitive regulation in introductory biology students: when prompts are not enough.

PubMed

Stanton, Julie Dangremond; Neider, Xyanthe N; Gallegos, Isaura J; Clark, Nicole C

2015-01-01

Strong metacognition skills are associated with learning outcomes and student performance. Metacognition includes metacognitive knowledge-our awareness of our thinking-and metacognitive regulation-how we control our thinking to facilitate learning. In this study, we targeted metacognitive regulation by guiding students through self-evaluation assignments following the first and second exams in a large introductory biology course (n = 245). We coded these assignments for evidence of three key metacognitive-regulation skills: monitoring, evaluating, and planning. We found that nearly all students were willing to take a different approach to studying but showed varying abilities to monitor, evaluate, and plan their learning strategies. Although many students were able to outline a study plan for the second exam that could effectively address issues they identified in preparing for the first exam, only half reported that they followed their plans. Our data suggest that prompting students to use metacognitive-regulation skills is effective for some students, but others need help with metacognitive knowledge to execute the learning strategies they select. Using these results, we propose a continuum of metacognitive regulation in introductory biology students. By refining this model through further study, we aim to more effectively target metacognitive development in undergraduate biology students. © 2015 J. D. Stanton et al. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Inherited Susceptibility to Cancer: Comparing Breast and Ovarian Cancers to Colon Cancers

PubMed Central

Cook-Deegan, Robert; DeRienzo, Christopher; Carbone, Julia; Chandrasekharan, Subhashini; Heaney, Christopher; Conover, Christopher

2011-01-01

Genetic testing for inherited susceptibility to breast and ovarian cancer can be compared to similar testing for colorectal cancer as a “natural experiment.” Inherited susceptibility accounts for a similar fraction of both cancers and genetic testing results guide decisions about options for prophylactic surgery in both sets of conditions. One major difference is that in the United States, Myriad Genetics is the sole provider of genetic testing, because it has sole control of relevant patents for BRCA1 and BRCA2 genes whereas genetic testing for familial colorectal cancer is available from multiple laboratories. Colorectal cancer-associated genes are also patented, but they have been nonexclusively licensed. Prices for BRCA1 and 2 testing do not reflect an obvious price premium attributable to exclusive patent rights compared to colorectal cancer testing, and indeed Myriad’s per unit costs are somewhat lower for BRCA1/2 testing than testing for colorectal cancer susceptibility. Myriad has not enforced patents against basic research, and negotiated a Memorandum of Understanding with the National Cancer Institute in 1999 for institutional BRCA testing in clinical research. The main impact of patenting and licensing in BRCA compared to colorectal cancer is the business model of genetic testing, with a sole provider for BRCA and multiple laboratories for colorectal cancer genetic testing. Myriad’s sole provider model has not worked in jurisdictions outside the United States, largely because of differences in breadth of patent protection, responses of government health services, and difficulty in patent enforcement. PMID:20393305

Comparison of five-axis milling and rapid prototyping for implant surgical templates.

PubMed

Park, Ji-Man; Yi, Tae-Kyoung; Koak, Jai-Young; Kim, Seong-Kyoon; Park, Eun-Jin; Heo, Seong-Joo

2014-01-01

This study aims to compare and evaluate the accuracy of surgical templates fabricated using coordinate synchronization processing with five-axis milling and design-related processing with rapid prototyping (RP). Master phantoms with 10 embedded gutta-percha cylinders hidden under artificial gingiva were fabricated and imaged using cone beam computed tomography. Vectors of the hidden cylinders were extracted and transferred to those of the planned implants through reverse engineering using virtual planning software. An RP-produced template was fabricated by stereolithography in photopolymer at the RP center according to planned data. Metal sleeves were bonded after holes were bored (group RP). For the milled template, milling coordinates were synchronized using the conversion process for the coordinate synchronization platform located on the model's bottom. Metal bushings were set on holes milled on the five-axis milling machine, on which the model was fixed through the coordinate synchronization plate, and the framework was constructed on the model using orthodontic resin (group CS). A computed tomography image was taken with templates firmly fixed on models using anchor pins (RP) or anchor screws (CS). The accuracy was analyzed via reverse engineering. Differences between the two groups were compared by repeated measures two-factor analysis. From the reverse-engineered image of the template on the experimental model, RP-produced templates showed significantly larger deviations than did milled surgical guides. Maximum deviations of the group RP were 1.58 mm (horizontal), 1.68 mm (vertical), and 8.51 degrees (angular); those of the group CS were 0.68 mm (horizontal), 0.41 mm (vertical), and 3.23 degrees (angular). A comparison of milling and RP template production methods showed that a vector-milled surgical guide had significantly smaller deviations than did an RP-produced template. The accuracy of computer-guided milled surgical templates was within the safety margin of previous studies.

Ebola virus vaccines: an overview of current approaches

PubMed Central

Marzi, Andrea; Feldmann, Heinz

2016-01-01

Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible. PMID:24575870

Genetically Engineered Poxviruses for Recombinant Gene Expression, Vaccination, and Safety

NASA Astrophysics Data System (ADS)

Moss, Bernard

1996-10-01

Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure--function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients.

Advances in the understanding, management, and prevention of dengue.

PubMed

Hermann, Laura L; Gupta, Swati B; Manoff, Susan B; Kalayanarooj, Siripen; Gibbons, Robert V; Coller, Beth-Ann G

2015-03-01

Dengue causes more human morbidity globally than any other vector-borne viral disease. Recent research has led to improved epidemiological methods that predict disease burden and factors involved in transmission, a better understanding of immune responses in infection, and enhanced animal models. In addition, a number of control measures, including preventative vaccines, are in clinical trials. However, significant gaps remain, including the need for better surveillance in large parts of the world, methods to predict which individuals will develop severe disease, and immunologic correlates of protection against dengue illness. During the next decade, dengue will likely expand its geographic reach and become an increasing burden on health resources in affected areas. Licensed vaccines and antiviral agents are needed in order to effectively control dengue and limit disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Topical herpes simplex virus 2 (HSV-2) vaccination with human papillomavirus vectors expressing gB/gD ectodomains induces genital-tissue-resident memory CD8+ T cells and reduces genital disease and viral shedding after HSV-2 challenge.

PubMed

Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N; Pang, Yuk Ying; Thompson, Cynthia D; Lowy, Douglas R; Cohen, Jeffrey I; Schiller, John T

2015-01-01

No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8(+) T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8(+) T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. Genital herpes is a highly prevalent chronic disease caused by HSV infection. To date, there is no licensed vaccine against HSV infection. This study describes intravaginal vaccination with a nonreplicating HPV-based vector expressing HSV glycoprotein antigens. The data presented in this study underscore the potential of HPV-based vectors as a platform for the induction of genital-tissue-resident memory T cell responses and the control of local manifestations of primary HSV infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Topical Herpes Simplex Virus 2 (HSV-2) Vaccination with Human Papillomavirus Vectors Expressing gB/gD Ectodomains Induces Genital-Tissue-Resident Memory CD8+ T Cells and Reduces Genital Disease and Viral Shedding after HSV-2 Challenge

PubMed Central

Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N.; Pang, Yuk Ying; Thompson, Cynthia D.; Lowy, Douglas R.; Cohen, Jeffrey I.

2014-01-01

ABSTRACT No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8+ T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8+ T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. IMPORTANCE Genital herpes is a highly prevalent chronic disease caused by HSV infection. To date, there is no licensed vaccine against HSV infection. This study describes intravaginal vaccination with a nonreplicating HPV-based vector expressing HSV glycoprotein antigens. The data presented in this study underscore the potential of HPV-based vectors as a platform for the induction of genital-tissue-resident memory T cell responses and the control of local manifestations of primary HSV infection. PMID:25320297

Figures of Merit Software: Description, User's Guide, Installation Notes, Versions Description, and License Agreement

NASA Technical Reports Server (NTRS)

hoelzer, H. D.; Fourroux, K. A.; Rickman, D. L.; Schrader, C. M.

2011-01-01

Figures of Merit (FoMs) and the FoM software provide a method for quantitatively evaluating the quality of a regolith simulant by comparing the simulant to a reference material. FoMs may be used for comparing a simulant to actual regolith material, specification by stating the value a simulant s FoMs must attain to be suitable for a given application and comparing simulants from different vendors or production runs. FoMs may even be used to compare different simulants to each other. A single FoM is conceptually an algorithm that computes a single number for quantifying the similarity or difference of a single characteristic of a simulant material and a reference material and provides a clear measure of how well a simulant and reference material match or compare. FoMs have been constructed to lie between zero and 1, with zero indicating a poor or no match and 1 indicating a perfect match. FoMs are defined for modal composition, particle size distribution, particle shape distribution, (aspect ratio and angularity), and density. This TM covers the mathematics, use, installation, and licensing for the existing FoM code in detail.

Don't Discount Societal Value in Cost-Effectiveness Comment on "Priority Setting for Universal Health Coverage: We Need Evidence-Informed Deliberative Processes, Not Just More Evidence on Cost-Effectiveness".

PubMed

Hall, William

2017-01-14

As healthcare resources become increasingly scarce due to growing demand and stagnating budgets, the need for effective priority setting and resource allocation will become ever more critical to providing sustainable care to patients. While societal values should certainly play a part in guiding these processes, the methodology used to capture these values need not necessarily be limited to multi-criterion decision analysis (MCDA)-based processes including 'evidence-informed deliberative processes.' However, if decision-makers intend to not only incorporates the values of the public they serve into decisions but have the decisions enacted as well, consideration should be given to more direct involvement of stakeholders. Based on the examples provided by Baltussen et al, MCDA-based processes like 'evidence-informed deliberative processes' could be one way of achieving this laudable goal. © 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.