Sample records for warfare nrdc knocks

  1. Nardilysin controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation.

    PubMed

    Kanda, Keitaro; Sakamoto, Jiro; Matsumoto, Yoshihide; Ikuta, Kozo; Goto, Norihiro; Morita, Yusuke; Ohno, Mikiko; Nishi, Kiyoto; Eto, Koji; Kimura, Yuto; Nakanishi, Yuki; Ikegami, Kanako; Yoshikawa, Takaaki; Fukuda, Akihisa; Kawada, Kenji; Sakai, Yoshiharu; Ito, Akihiro; Yoshida, Minoru; Kimura, Takeshi; Chiba, Tsutomu; Nishi, Eiichiro; Seno, Hiroshi

    2018-04-19

    Colon cancer is a complex disease affected by a combination of genetic and epigenetic factors. Here we demonstrate that nardilysin (N-arginine dibasic convertase; NRDC), a metalloendopeptidase of the M16 family, regulates intestinal tumorigenesis via its nuclear functions. NRDC is highly expressed in human colorectal cancers. Deletion of the Nrdc gene in ApcMin mice crucially suppressed intestinal tumor development. In ApcMin mice, epithelial cell-specific deletion of Nrdc recapitulated the tumor suppression observed in Nrdc-null mice. Moreover, epithelial cell-specific overexpression of Nrdc significantly enhanced tumor formation in ApcMin mice. Notably, epithelial NRDC controlled cell apoptosis in a gene dosage-dependent manner. In human colon cancer cells, nuclear NRDC directly associated with HDAC1, and controlled both acetylation and stabilization of p53, with alterations of p53 target apoptotic factors. These findings demonstrate that NRDC is critically involved in intestinal tumorigenesis through its epigenetic regulatory function, and targeting NRDC may lead to a novel prevention or therapeutic strategy against colon cancer.

  2. Nardilysin promotes hepatocellular carcinoma through activation of signal transducer and activator of transcription 3.

    PubMed

    Kasai, Yosuke; Toriguchi, Kan; Hatano, Etsuro; Nishi, Kiyoto; Ohno, Mikiko; Yoh, Tomoaki; Fukuyama, Keita; Nishio, Takahiro; Okuno, Masayuki; Iwaisako, Keiko; Seo, Satoru; Taura, Kojiro; Kurokawa, Masato; Kunichika, Makoto; Uemoto, Shinji; Nishi, Eiichiro

    2017-05-01

    Nardilysin (NRDC) is a metalloendopeptidase of the M16 family. We previously showed that NRDC activates inflammatory cytokine signaling, including interleukin-6-signal transducer and activator of transcription 3 (STAT3) signaling. NRDC has been implicated in the promotion of breast, gastric and esophageal cancer, as well as the development of liver fibrosis. In this study, we investigated the role of NRDC in the promotion of hepatocellular carcinoma (HCC), both clinically and experimentally. We found that NRDC expression was upregulated threefold in HCC tissue compared to the adjacent non-tumor liver tissue, which was confirmed by immunohistochemistry and western blotting. We also found that high serum NRDC was associated with large tumor size (>3 cm, P = 0.016) and poor prognosis after hepatectomy (median survival time 32.0 vs 73.9 months, P = 0.003) in patients with hepatitis C (n = 120). Diethylnitrosamine-induced hepatocarcinogenesis was suppressed in heterozygous NRDC-deficient mice compared to their wild-type littermates. Gene silencing of NRDC with miRNA diminished the growth of Huh-7 and Hep3B spheroids in vitro. Notably, phosphorylation of STAT3 was decreased in NRDC-depleted Huh-7 spheroids compared to control spheroids. The effect of a STAT3 inhibitor (S3I-201) on the growth of Huh-7 spheroids was reduced in NRDC-depleted cells relative to controls. Our results show that NRDC is a promising prognostic marker for HCC in patients with hepatitis C, and that NRDC promotes tumor growth through activation of STAT3. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. Nardilysin is involved in autoimmune arthritis via the regulation of tumour necrosis factor alpha secretion

    PubMed Central

    Fujii, Takayuki; Nishi, Eiichiro; Ito, Hiromu; Yoshitomi, Hiroyuki; Furu, Moritoshi; Okabe, Namiko; Ohno, Mikiko; Nishi, Kiyoto; Morita, Yusuke; Morita, Yugo; Azukizawa, Masayuki; Okahata, Akinori; Tomizawa, Takuya; Kimura, Takeshi; Matsuda, Shuichi

    2017-01-01

    Objective Tumour necrosis factor alpha (TNF-α) plays an important role in rheumatoid arthritis (RA). TNF-α is synthesised as a membrane-anchored precursor and is fully activated by a disintegrin and metalloproteinase 17 (ADAM17)-mediated ectodomain shedding. Nardilysin (NRDC) facilitates ectodomain shedding via activation of ADAM17. This study was undertaken to elucidate the role of NRDC in RA. Methods NRDC-deficient (Nrdc–/–) mice and macrophage-specific NRDC-deficient (NrdcdelM) mice were examined in murine RA models, collagen antibody-induced arthritis (CAIA) and K/BxN serum transfer arthritis (K/BxN STA). We evaluated the effect of gene deletion or silencing of Nrdc on ectodomain shedding of TNF-α in macrophages or monocytes. NRDC concentration in synovial fluid from patients with RA and osteoarthritis (OA) were measured. We also examined whether local gene silencing of Nrdc ameliorated CAIA. Results CAIA and K/BxN STA were significantly attenuated in Nrdc–/– mice and NrdcdelM mice. Gene deletion or silencing of Nrdc in macrophages or THP-1 cells resulted in the reduction of TNF-α shedding. The level of NRDC is higher in synovial fluid from RA patients compared with that from OA patients. Intra-articular injection of anti-Nrdcsmall interfering RNA ameliorated CAIA. Conclusion These data indicate that NRDC plays crucial roles in the pathogenesis of autoimmune arthritis and could be a new therapeutic target for RA treatment. PMID:28955486

  4. Critical roles of nardilysin in the maintenance of body temperature homoeostasis.

    PubMed

    Hiraoka, Yoshinori; Matsuoka, Tatsuhiko; Ohno, Mikiko; Nakamura, Kazuhiro; Saijo, Sayaka; Matsumura, Shigenobu; Nishi, Kiyoto; Sakamoto, Jiro; Chen, Po-Min; Inoue, Kazuo; Fushiki, Tohru; Kita, Toru; Kimura, Takeshi; Nishi, Eiichiro

    2014-01-01

    Body temperature homoeostasis in mammals is governed centrally through the regulation of shivering and non-shivering thermogenesis and cutaneous vasomotion. Non-shivering thermogenesis in brown adipose tissue (BAT) is mediated by sympathetic activation, followed by PGC-1α induction, which drives UCP1. Here we identify nardilysin (Nrd1 and NRDc) as a critical regulator of body temperature homoeostasis. Nrd1(-/-) mice show increased energy expenditure owing to enhanced BAT thermogenesis and hyperactivity. Despite these findings, Nrd1(-/-) mice show hypothermia and cold intolerance that are attributed to the lowered set point of body temperature, poor insulation and impaired cold-induced thermogenesis. Induction of β3-adrenergic receptor, PGC-1α and UCP1 in response to cold is severely impaired in the absence of NRDc. At the molecular level, NRDc and PGC-1α interact and co-localize at the UCP1 enhancer, where NRDc represses PGC-1α activity. These findings reveal a novel nuclear function of NRDc and provide important insights into the mechanism of thermoregulation.

  5. Nardilysin regulates inflammation, metaplasia, and tumors in murine stomach.

    PubMed

    Kimura, Yuto; Ikuta, Kozo; Kimura, Takeshi; Chiba, Tsutomu; Oshima, Hiroko; Oshima, Masanobu; Nishi, Eiichiro; Seno, Hiroshi

    2017-02-23

    Chronic inflammation contributes to a wide variety of human disorders. In the stomach, longstanding gastritis often results in structural alterations in the gastric mucosa, including metaplastic changes and gastric cancers. Therefore, it is important to elucidate factors that are involved in gastric inflammation. Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins. Here, we have demonstrated that Nrdc crucially regulates gastric inflammation caused by Helicobacter felis infection or forced expression of prostaglandin E 2 in K19-C2mE mice. Metaplastic changes following gastric inflammation were suppressed by the deletion of Nrdc. Furthremore, the deletion of Nrdc significantly suppressed N-methyl-N-nitrosourea (MNU)-induced gastric tumorigenesis in the murine stomach. These data may lead to a global therapeutic approach against various gastric disorders by targeting Nrdc.

  6. Critical roles of nardilysin in the maintenance of body temperature homoeostasis

    PubMed Central

    Hiraoka, Yoshinori; Matsuoka, Tatsuhiko; Ohno, Mikiko; Nakamura, Kazuhiro; Saijo, Sayaka; Matsumura, Shigenobu; Nishi, Kiyoto; Sakamoto, Jiro; Chen, Po-Min; Inoue, Kazuo; Fushiki, Tohru; Kita, Toru; Kimura, Takeshi; Nishi, Eiichiro

    2014-01-01

    Body temperature homoeostasis in mammals is governed centrally through the regulation of shivering and non-shivering thermogenesis and cutaneous vasomotion. Non-shivering thermogenesis in brown adipose tissue (BAT) is mediated by sympathetic activation, followed by PGC-1α induction, which drives UCP1. Here we identify nardilysin (Nrd1 and NRDc) as a critical regulator of body temperature homoeostasis. Nrd1−/− mice show increased energy expenditure owing to enhanced BAT thermogenesis and hyperactivity. Despite these findings, Nrd1−/− mice show hypothermia and cold intolerance that are attributed to the lowered set point of body temperature, poor insulation and impaired cold-induced thermogenesis. Induction of β3-adrenergic receptor, PGC-1α and UCP1 in response to cold is severely impaired in the absence of NRDc. At the molecular level, NRDc and PGC-1α interact and co-localize at the UCP1 enhancer, where NRDc represses PGC-1α activity. These findings reveal a novel nuclear function of NRDc and provide important insights into the mechanism of thermoregulation. PMID:24492630

  7. EPA's Response to NRDC's Public Statement

    EPA Pesticide Factsheets

    Natural Resource Defense Council made comments about EPA's pesticide program and protection of bees, following a FOIA request regarding clothianidin. NRDC misrepresented EPA efforts to mitigate Colony Collapse Disorder (CCD) and general pollinator decline.

  8. Towards a More Complete and Accurate Experimental Nuclear Reaction Data Library (EXFOR): International Collaboration Between Nuclear Reaction Data Centres (NRDC)

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

    Otuka, N., E-mail: n.otsuka@iaea.org; Dupont, E.; Semkova, V.

    The International Network of Nuclear Reaction Data Centres (NRDC) coordinated by the IAEA Nuclear Data Section (NDS) successfully collaborates in the maintenance and development of the EXFOR library. As the scope of published data expands (e.g. to higher energy, to heavier projectile) to meet the needs of research and applications, it has become a challenging task to maintain both the completeness and accuracy of the EXFOR library. Evolution of the library highlighting recent developments is described.

  9. CSEWG

    Science.gov Websites

    Nuclear Data Evaluation Co-operation (WPEC) Nuclear Reaction Data Centers, NRDC (IAEA Vienna) EMPIRE , Nuclear Reaction Model Code Atlas of Neutron Resonances The Cross Section Evaluation Working Group (CSEWG

  10. INDUSTRIAL WASTEWATER

    EPA Science Inventory

    This document contains: federal legislation, NRDC consent degree, regulations, the research program, and the different treatments used for petrochemistry, pesticides, inorganic chemicals, batteries, metal finishing, iron and steel, electric power, textiles and leather industries.

  11. EPA Responds to NRDC's 2008 Freedom of Information Act Complaint on Clothianidin

    EPA Pesticide Factsheets

    The Natural Resources Defense Council had made a FOIA request for information on the pesticide clothianidin in relation to pollinator protection and Colony Collapse Disorder (CCD), and inaccurately represented EPA's efforts to protect bees.

  12. Federal Register: Proposed Revisions to the Consolidated Permit Regulations in Accordance with the Settlement Agreement

    EPA Pesticide Factsheets

    On November 16, 1981, EPA entered into a settlement agreement with numerous industry petitioners In the consolidated permit regulations litigation (NRDC v. EPA and consolidated cases, No. 80-1607 (D.C. Cir., filed June 2, 1980)).

  13. On June 7, 1982, EPA entered into a settlement agreement on ...

    EPA Pesticide Factsheets

    On June 7, 1982, EPA entered into a settlement agreement on Clean Water Act issues with numerous industry petitioners in the consolidated permit regulations litigation (NRDC v. EPA and consolidated cases, No. 80-1607 (D.C. Cir. filed June 2, 1980)).

  14. 75 FR 81126 - Revisions to Lead Ambient Air Monitoring Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-27

    ... Council (NRDC), the Missouri Coalition for the Environment Foundation, Physicians for Social... estimates from the 2002 and 2005 NEI (Table 2) and estimated design values (i.e., 3-month rolling average Pb... year of lead to protect public health with an adequate margin of safety. The available evidence...

  15. 77 FR 54402 - Dichlorvos (DDVP); Order Denying NRDC's Objections on Remand

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... may be calculated separately for different age-based population groups (e.g., non-nursing infants) or... in conjunction with experimental toxicity data in assessing risk to humans from exposure to chemical substances. (Ref. 4). These numerical factors are designed to provide an additional margin of safety so that...

  16. 77 FR 23135 - 2,4-D; Order Denying NRDC's Petition To Revoke Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

    ... cannot be determined (``non-threshold effects''). Because EPA identified only threshold effect risks for... uncertainty or safety factors \\1\\ in conjunction with experimental toxicity data in assessing risk to humans... difference in sensitivity between humans and experimental animals (i.e., inter-species sensitivity) and...

  17. 75 FR 55997 - Carbaryl; Order Denying NRDC's Objections and Requests for Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... Agency's application of the BMD approach as a scientifically supportable method for deriving PODs in... application methods -- all pet uses (dusts and liquids) except collars, aerosol products for various uses... registrants that these uses and application methods must be deleted from their carbaryl product labels. EPA...

  18. 75 FR 71145 - San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ... DEPARTMENT OF THE INTERIOR Bureau of Reclamation San Joaquin River Restoration Program: Reach 4B...: Bureau of Reclamation, Interior. ACTION: Revised notice of intent to prepare an Environmental Impact...., the NRDC, Friant Water Users Authority, and the Departments of the Interior and Commerce (Settling...

  19. 75 FR 47465 - Pymetrozine; Regulation Denying NRDC's Objections on Remand

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... adverse effects are caused by either short-term (e.g., acute) or longer-term (e.g., chronic) pesticide... correspondingly levels of concern, for both short and long exposure periods as well as for the different routes of..., short-term, chronic, and cancer risks and EPA quantitatively assessed these risks in making its safety...

  20. 75 FR 316 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition to List the Insular Population...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration 50 CFR Parts 223 and 224...), Department of Commerce. ACTION: 90-day petition finding; request for information. SUMMARY: We, NMFS, announce...: Background On October 1, 2009, we received a petition from the Natural Resources Defense Council (NRDC...

  1. 77 FR 43222 - Endangered and Threatened Wildlife and Plants; Designation of Critical Habitat for the Tidewater...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-24

    ... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service 50 CFR Part 17 [Docket No. FWS-R8-ES-2011... Federal Actions On April 15, 2009, Natural Resources Defense Council (NRDC) filed a lawsuit in the U.S... consultation history for natural resource management projects suggests that these projects are generally...

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

    Semkova, Valentina; Otuka, Naohiko; Mikhailiukova, Marina

    Members of the International Network of Nuclear Reaction Data Centres (NRDC) have collaborated since the 1960s on the worldwide collection, compilation and dissemination of experimental nuclear reaction data. New publications are systematically complied, and all agreed data assembled and incorporated within the EXFOR database. Here, recent upgrades to achieve greater completeness of the contents are described, along with reviews and adjustments of the compilation rules for specific types of data.

  3. U.S. Strategic Nuclear Forces: Background, Developments, and Issues

    DTIC Science & Technology

    2013-10-22

    32 Safety, Security, and Management ...by Amy F. Woolf. 2 Natural Resources Defense Council. Table of U.S. Strategic Offensive Force Loadings. Archive of Nuclear Data. http://www.nrdc.org...12000 14000 16000 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 Year N um be r Launchers Warheads Source: Natural Resources Defense Council

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

    Otuka, N.; Pritychenko, B.; Otuka, N.

    The International Network of Nuclear Reaction Data Centres (NRDC) coordinated by the IAEA Nuclear Data Section (NDS) successfully collaborates in the maintenance and development of the EXFOR library. Likewise, as the scope of published data expands (e.g. to higher energy, to heavier projectile) to meet the needs of research and applications, it has become a challenging task to maintain both the completeness and accuracy of the EXFOR library. Evolution of the library highlighting recent developments is described.

  5. EXFOR – a global experimental nuclear reaction data repository: Status and new developments

    DOE PAGES

    Semkova, Valentina; Otuka, Naohiko; Mikhailiukova, Marina; ...

    2017-09-13

    Members of the International Network of Nuclear Reaction Data Centres (NRDC) have collaborated since the 1960s on the worldwide collection, compilation and dissemination of experimental nuclear reaction data. New publications are systematically complied, and all agreed data assembled and incorporated within the EXFOR database. Here, recent upgrades to achieve greater completeness of the contents are described, along with reviews and adjustments of the compilation rules for specific types of data.

  6. Beyond-the-Box Thinking on Future War: The Art and Science of Unrestricted Warfare

    DTIC Science & Technology

    2009-04-01

    Studies Institute, US Army War College, 2008. Mattis , James N., and Frank Hoffman. “Future Warfare: The Rise of Hybrid Warfare.” Proceedings...nanotechnologies will augment the current bio -chemical capabilities, moving the battlefield into a microscopic arena. As seen before, the traditional American way...Military Trans-military Non-military Atomic Warfare Diplomatic Warfare Financial Warfare Conventional Warfare Network Warfare Trade Warfare Bio

  7. Cyber Warfare/Cyber Terrorism

    DTIC Science & Technology

    2004-03-19

    Section 1 of this paper provides an overview of cyber warfare as an element of information warfare, starting with the general background of the...alternative form of conflict, reviews the traditional principles of warfare and why they may or may not apply to cyber warfare , and proposes new principles of...warfare that may be needed to conduct cyber warfare . Section 1 concludes with a review of offensive and defensive cyber warfare concepts. Section 2

  8. Cyber Warfare: China’s Strategy to Dominate in Cyber Space

    DTIC Science & Technology

    2011-06-10

    CYBER WARFARE : CHINA‘S STRATEGY TO DOMINATE IN CYBER SPACE A thesis presented to the Faculty of the U.S. Army Command and...warfare supports the use of cyber warfare in future conflict. The IW militia unit organization provides each Chinese military region commander with...China, Strategy, Cyber Warfare , Cyber Space, Information Warfare, Electronic Warfare 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18

  9. Cyber Warfare: An Evolution in Warfare not Just War Theory

    DTIC Science & Technology

    2013-04-05

    cyber warfare is greatly debated. While some argue that Just War Theory is irrelevant to cyber warfare , a careful analysis demonstrates that it is a...useful tool for considering the morality of cyber warfare . This paper examines the application of Just War Theory to cyber warfare and contends that...Just War Theory is a useful tool for considering the morality of cyber warfare .

  10. Adapting Unconventional Warfare Doctrine to Cyberspace Operations: An Examination of Hacktivist Based Insurgencies

    DTIC Science & Technology

    2015-06-12

    Unconventional Warfare, Cyberspace Operations, Cyber Warfare , Hacktivism, China, Russia, Georgia, Estonia, Umbrella Revolution, UW, Cyber, Guerilla, Hacktivist...6 Cyber Warfare ............................................................................................................. 7...Internet, and cyber warfare , the nature of the human element in cyberspace exhibits only a scientific advancement in the evolution of warfare, not a

  11. 78 FR 58524 - Takes of Marine Mammals Incidental to Specified Activities; U.S. Navy Training and Testing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-24

    ... and testing activities: anti-surface warfare; anti- submarine warfare; mine warfare; naval special warfare; major training activities; Naval Air Systems Command (NAVAIR) testing; anti-surface warfare testing; anti-submarine warfare testing; Naval Sea Systems Command (NAVSEA) testing; and Office of Naval...

  12. On Cyber Warfare Command and Control Systems

    DTIC Science & Technology

    2004-06-01

    longer adequate to rely solely on the now traditional defense-in-depth strategy. We must recognize that we are engaged in a form of warfare, cyber warfare , and... warfare . This causes security devices to be used ineffectively and responses to be untimely. Cyber warfare then becomes a one-sided battle where the... cyber warfare strategy and tactics requires a cyber warfare command and control system. Responses to cyber attacks do not require offensive measures

  13. Does the Economy or Surface Warfare Officer Career Pay Affect Surface Warfare Officer Retention?

    DTIC Science & Technology

    2014-12-01

    be a career SWO (Surface Warfare Enterprise, 2013). 6 Military pay was more important to men than women ...OR SURFACE WARFARE OFFICER CAREER PAY AFFECT SURFACE WARFARE OFFICER RETENTION? by Meagan B. Makarenko December 2014 Thesis Advisor...2014 3. REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE DOES THE ECONOMY OR SURFACE WARFARE OFFICER CAREER PAY AFFECT

  14. Strategic Impact of Cyber Warfare Rules for the United States

    DTIC Science & Technology

    2010-03-01

    Despite the growing complexities of cyberspace and the significant strategic challenge cyber warfare poses on the United States’ vital interests few...specific rules for cyber warfare exist. The United States should seek to develop and maintain cyber warfare rules in order to establish...exemplify the need for multilaterally prepared cyber warfare rules that will reduce the negative influence cyber warfare presently has on the United States’ national interests.

  15. Initial Report of the Deans Cyber Warfare Ad Hoc Committee

    DTIC Science & Technology

    2011-12-22

    in a cyber warfare environment. Among the more notable recent developments have been the establishment of a new Cyber Warfare Command (USCYBERCOM) at...information-warfare-centric organization. Clearly, future Naval Academy graduates will be expected to know more about cyber warfare than those we have...graduated in the past. The Academic Dean and Provost tasked an ad hoc committeethe Cyber Warfare ad hoc Committeeto examine how USNA can best ensure that

  16. Sources of Occupational Stress and Prevalence of Burnout and Clinical Distress Among U.S. Air Force Cyber Warfare Operators

    DTIC Science & Technology

    2013-01-01

    distress within the cyber warfare community. This study involved cyber warfare operators including active duty (n = 376) and civilian contractor and...revealed that when compared to civilian cyber warfare operators, active duty cyber warfare operators are more likely to suffer from the facets of...8217 write-in responses revealed cyber warfare operators attributed shift work, shift changes, and hours worked as the primary sources of high occupational

  17. Cyber warfare and electronic warfare integration in the operational environment of the future: cyber electronic warfare

    NASA Astrophysics Data System (ADS)

    Askin, Osman; Irmak, Riza; Avsever, Mustafa

    2015-05-01

    For the states with advanced technology, effective use of electronic warfare and cyber warfare will be the main determining factor of winning a war in the future's operational environment. The developed states will be able to finalize the struggles they have entered with a minimum of human casualties and minimum cost thanks to high-tech. Considering the increasing number of world economic problems, the development of human rights and humanitarian law it is easy to understand the importance of minimum cost and minimum loss of human. In this paper, cyber warfare and electronic warfare concepts are examined in conjunction with the historical development and the relationship between them is explained. Finally, assessments were carried out about the use of cyber electronic warfare in the coming years.

  18. Department of Defenses Enhanced Requirement for Offensive Cyber Warfare Operations

    DTIC Science & Technology

    2010-04-01

    The Department of Defense (DoD) needs to further develop its offensive cyber warfare capabilities at all levels. In an asymmetric environment...battlefields. If the DoD does not prosecute offensive cyber warfare tactics then the DoD has effectively allowed a significant advantage to be given...offensive cyber warfare operations, These states utilize their cyber warfare capabilities to support their national, operational and strategic

  19. Beyond Mission Command: Maneuver Warfare for Cyber Command and Control

    DTIC Science & Technology

    2015-05-18

    operation in an A2AD environment. 15. SUBJECT TERMS command and control; maneuver warfare; cyberspace; cyberspace operations; cyber warfare , mission...Some Principles of Cyber Warfare (NWC 2160) (U.S. Naval War College, Joint Military Operations Department, Newport, RI: U.S. Naval War College...research/ innovationleadership.pdf. Crowell, Richard M. Some Principles of Cyber Warfare (NWC 2160). U.S. Naval War College, Joint Military Operations

  20. Anxiety, depression, and posttraumatic stress in Iranian survivors of chemical warfare.

    PubMed

    Hashemian, Farnoosh; Khoshnood, Kaveh; Desai, Mayur M; Falahati, Farahnaz; Kasl, Stanislav; Southwick, Steven

    2006-08-02

    In the 1980-1988 Iran-Iraq War, extensive use of chemical weapons resulted in high rates of morbidity and mortality. While much is known about the physical consequences of chemical warfare, there is a paucity of information about the long-term effects of chemical attacks on mental health. To assess the long-term psychological impact of chemical warfare on a civilian population. Cross-sectional randomized survey conducted in July 2004 of 153 civilians in 3 towns exposed to warfare in northwestern Iran: Oshnaviyeh (low-intensity conventional warfare), Rabat (high-intensity conventional warfare), and Sardasht (both high-intensity conventional warfare and chemical weapons). Full or partial posttraumatic stress disorder (PTSD) diagnosis, anxiety symptoms, and depressive symptoms were assessed using Farsi versions of the Clinician-Administered PTSD Scale, Hamilton Scale for Anxiety, and Beck Depression Inventory, respectively. Overall participation rate was 93%. Respondents had a mean age of 45 years and were all of Kurdish ethnicity. Among individuals exposed to both high-intensity warfare and chemical weapons, prevalence rates for lifetime PTSD, current PTSD, major anxiety symptoms, and severe depressive symptoms were 59%, 33%, 65%, and 41%, respectively. Among the low-intensity warfare group, the corresponding rates were 8%, 2%, 18%, and 6%, respectively, while intermediate rates were found among those exposed to high-intensity warfare but not to chemical weapons (31%, 8%, 26%, and 12%, respectively). Compared with individuals exposed to low-intensity warfare, those exposed to both high-intensity warfare and chemical weapons were at higher risk for lifetime PTSD (odds ratio [OR], 18.6; 95% confidence interval [CI], 5.8-59.4), current PTSD (OR, 27.4; 95% CI, 3.4-218.2), increased anxiety symptoms (OR, 14.6; 95% CI, 6.0-35.6), and increased depressive symptoms (OR, 7.2; 95% CI, 3.3-15.9). Exposure to high-intensity warfare but not to chemical weapons was also significantly associated with lifetime PTSD (OR, 5.4; 95% CI, 1.7-17.6), compared with those in the low-intensity warfare group. Further, compared with individuals exposed to high-intensity warfare alone, those exposed to both high-intensity warfare and chemical weapons were at higher risk for lifetime PTSD (OR, 3.4; 95% CI, 1.5-7.4), current PTSD (OR, 6.2; 95% CI, 2.0-20.1), increased anxiety symptoms (OR, 5.6; 95% CI, 2.5-12.6), and increased depressive symptoms (OR, 3.7; 95% CI, 1.8-7.2). Exposure to chemical warfare is an extreme traumatic event that has long-lasting adverse consequences on mental health.

  1. The Theory of Unconventional Warfare: Win, Lose, and Draw

    DTIC Science & Technology

    2008-12-01

    UNCONVENTIONAL WARFARE MODEL ...................................12 1. Planning Phase...Superiority over Time........................................................................11  Figure 3.  Unconventional Warfare Model ...superiority through the six principles of UW illustrated below in the UW model . . B. THE UNCONVENTIONAL WARFARE MODEL Figure 3. Unconventional

  2. Cyber warfare: Armageddon in a Teacup?

    DTIC Science & Technology

    2009-12-11

    Security concerns over the growing capability of Cyber Warfare are in the forefront of national policy and security discussions. In order to enable a...realistic discussion of the topic this thesis seeks to analyze demonstrated Cyber Warfare capability and its ability to achieve strategic political...objectives. This study examines Cyber Warfare conducted against Estonia in 2007, Georgia in 2008, and Israel in 2008. In all three cases Cyber Warfare did

  3. At the Crossroads of Cyber Warfare: Signposts for the Royal Australian Air Force

    DTIC Science & Technology

    2011-06-01

    At the Crossroads of Cyber Warfare : Signposts for the Royal Australian Air Force by Craig Stallard, Squadron leader, Royal...in the conduct of cyber warfare . The 2009 Defence White Paper provided some clarity by indentifying cyber warfare as critical to the maintenance...of national security, but left open the most important issue: should cyber warfare be a joint engagement or a service oriented fight? The RAAF

  4. Cyber Warfare: New Character with Strategic Results

    DTIC Science & Technology

    2013-03-01

    The advent of cyber warfare has sparked a debate amongst theorists as to whether timeless Clausewitzian principles remain true in the 21st century...Violence, uncertainty, and rationality still accurately depict the nature of cyber warfare , however, its many defining attributes and means by which...this style of warfare is conducted has definitively changed the character of war. Although cyber warfare is contested in the cyber domain, it often

  5. Cyber Security: A Road Map for Turkey

    DTIC Science & Technology

    2012-03-19

    Cyber warfare is a form of information warfare, sometimes seen as analogous to conventional warfare, among a range of potential actors, including...nation states, non-state groups, and a complex hybrid of conflict involving both state and non-state actors. Cyber warfare is a tool of national power...An entire nation s ability to operate and fight in the information age is vital toward survival. Nowadays, cyber warfare is mostly focused on

  6. A Better State of War: Surmounting the Ethical Cliff in Cyber Warfare

    DTIC Science & Technology

    2014-06-01

    This study analyzes the emergent field of cyber warfare through the lens of commonly-accepted tenets of ethical warfare. By comparing the...foundational understanding of concepts that determine the justice of wars (jus ad bellum) and justice in war (jus en bello) with the capabilities cyber warfare offers...analyzing how cyber warfare affects each of the core concepts introduced above. The fourth chapter presents a case study that tests the theoretical

  7. Cyber-Warfare: Jus Post Bellum

    DTIC Science & Technology

    2015-03-01

    used to design a cyber - warfare jus post bellum framework. It also analyzes analogies to traditional warfare in the damage assessment and aid provided...and the ability to contain and reverse cyberattacks. This thesis proposes a cyber - warfare jus post bellum framework, with emphasis on prevention and

  8. 75 FR 6642 - Notice of Proposed Information Collection; Naval Special Warfare Recruiting Directorate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-10

    ... Information Collection; Naval Special Warfare Recruiting Directorate AGENCY: Department of the Navy, DoD. ACTION: Notice. SUMMARY: The Naval Special Warfare (NSW) Recruiting Directorate announces the submission... the proposal and associated collection instruments, write to the Director, Naval Special Warfare...

  9. The role of rewards in motivating participation in simple warfare.

    PubMed

    Glowacki, Luke; Wrangham, Richard W

    2013-12-01

    In the absence of explicit punitive sanctions, why do individuals voluntarily participate in intergroup warfare when doing so incurs a mortality risk? Here we consider the motivation of individuals for participating in warfare. We hypothesize that in addition to other considerations, individuals are incentivized by the possibility of rewards. We test a prediction of this "cultural rewards war-risk hypothesis" with ethnographic literature on warfare in small-scale societies. We find that a greater number of benefits from warfare is associated with a higher rate of death from conflict. This provides preliminary support for the relationship between rewards and participation in warfare.

  10. Employing U.S. Information Operations Against Hybrid Warfare Threats

    DTIC Science & Technology

    2013-03-01

    Article 51.24 Cyber warfare is unique in that vulnerabilities that a network target may have could be discovered by software developers who then... cyber warfare rather than physical combat, a future subject to air strikes or ground-forces raids would likely be a powerful deterrent. Some in the U.S...Manwaring, The Complexity of Modern Asymmetric Warfare, (Norman, OK: Univ. of Oklahoma Press, 2012), 126-129. 23 Arie J. Schaap, “ Cyber Warfare Operations

  11. Developing a Hybrid Virtualization Platform Design for Cyber Warfare Training and Education

    DTIC Science & Technology

    2010-06-01

    CYBER WARFARE TRAINING AND EDUCATION THESIS Kyle E. Stewart 2nd...Government. AFIT/GCE/ENG/10-06 DEVELOPING A HYBRID VIRTUALIZATION PLATFORM DESIGN FOR CYBER WARFARE TRAINING...APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED. AFIT/GCE/ENG/10-06 DEVELOPING A HYBRID VIRTUALIZATION PLATFORM DESIGN FOR CYBER WARFARE

  12. Chinese National Strategy of Total War

    DTIC Science & Technology

    2008-06-01

    Cyber Warfare Michael J. Good, BA Major, USA June 2008 APPROVED FOR PUBLIC RELEASE; DISTRIBUTION IS...who allowed me into the Cyber Warfare , my fellow students in the Cyber Warfare IDE program who have been great friends and mentors, and my fellow...Hackers and Other Cyber Criminals .............................................................................41 PLA Cyber Warfare

  13. 77 FR 60678 - Takes of Marine Mammals Incidental to Specified Activities; U.S. Navy Training and Testing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-04

    ...-submarine warfare; mine warfare; naval special warfare; Naval Air Systems Command (NAVAIR) testing; Naval Sea Systems Command (NAVSEA) testing; Space and Naval Warfare Systems Command (SPAWAR) testing; and Office of Naval Research (ONR) and Naval Research Laboratory (NRL) testing. Detailed descriptions of...

  14. Hybrid Warfare: the 21st Century Russian Way of Warfare

    DTIC Science & Technology

    2017-05-25

    in Ukraine, can be best understood by examining it in relation to the ideas and theories of such preeminent theorists as Sun Tzu and Carl von...theories of warfare, of which Russia’s hybrid warfare is one of the most recent. Writing over two thousand years ago, Sun Tzu stated, “The art of...warfare is deceit.”17 Sun Tzu continued, stating that the “highest excellence” in war was not in winning every battle, but in subduing the enemy’s

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

    Pamminger, Michael; Sevik, James; Scarcelli, Riccardo

    The compression ratio is a strong lever to increase the efficiency of an internal combustion engine. However, among others, it is limited by the knock resistance of the fuel used. Natural gas shows a higher knock resistance compared to gasoline, which makes it very attractive for use in internal combustion engines. The current paper describes the knock behavior of two gasoline fuels, and specific incylinder blend ratios with one of the gasoline fuels and natural gas. The engine used for these investigations is a single cylinder research engine for light duty application which is equipped with two separate fuel systems.more » Both fuels can be used simultaneously which allows for gasoline to be injected into the intake port and natural gas to be injected directly into the cylinder to overcome the power density loss usually connected with port fuel injection of natural gas. Adding natural gas at wide open throttle helps to reduce knock mitigating measures and increases the efficiency and power density compared to the other gasoline type fuels with lower knock resistance. The used methods, knock intensity and number of pressure waves, do not show significant differences in knock behavior for the natural gas - gasoline blends compared to the gasoline type fuels. A knock integral was used to describe the knock onset location of the fuels tested. Two different approaches were used to determine the experimental knock onset and were compared to the knock onset delivered by the knock integral (chemical knock onset). The gasoline type fuels show good agreement between chemical and experimental knock onset. However, the natural gas -gasoline blends show higher discrepancies comparing chemical and experimental knock onset.« less

  16. 78 FR 53109 - Security Zones; Naval Base Point Loma; Naval Mine Anti-Submarine Warfare Command; San Diego Bay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ...-AA87 Security Zones; Naval Base Point Loma; Naval Mine Anti-Submarine Warfare Command; San Diego Bay... Anti-Submarine Warfare Command to protect the relocated marine mammal program. These security zone... Warfare Command, the Commander of Naval Region Southwest, or a designated representative of those...

  17. Deactivating Chemical Agents Using Enzyme-Coated Nanofibers Formed by Electrospinning

    DTIC Science & Technology

    2016-01-01

    7.3mM/mg). Key words Coaxial electrospinning, DFPase, Enzyme, chemical warfare , nanofiber, decontamination . Introduction Chemical warfare ...Krile, R.; Nishioka, M.; Taylor, M.; Riggs, K.; Stone, H. Decontamination of Toxic Industrial Chemicals and Chemical Warfare Agents On Building...298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 MATS COATINGS ELECTROSPINNING CHEMICAL WARFARE

  18. Toxic Warfare

    DTIC Science & Technology

    2002-02-01

    Prepared for the United States Air Force Approved for public release; distribution unlimited Theodore Karasik Project AIR FORCE R TOXIC WARFARE...Report Documentation Page Report Date 000002002 Report Type N/A Dates Covered (from... to) - Title and Subtitle Toxic Warfare Contract Number Grant...310) 451-6915; Email: order@rand.org Library of Congress Cataloging-in-Publication Data Karasik, Theodore William. Toxic warfare / Theodore Karasik

  19. Small Ships Revival: From Cold War Anti-Invasion and Guerrilla Warfare Tactics to Highly Capable Force Multiplier in Littoral and Expeditionary Warfare

    DTIC Science & Technology

    2010-05-03

    this gap might be filled. It will focus on the surface warfare aspect of sea control, though it touches on antiair warfare, mine warfare and...Sea As the flotilla acquired battle power […] the vital, most difficult, and most absorbing problem has become not how to increase the power of a...proving that their performance is absolutely necessary to these operations. Com Fr Amphib TG of the NATO Reaction Force-8 after Exercise Brilliant Midas

  20. 78 FR 72025 - Security Zones; Naval Base Point Loma; Naval Mine Anti Submarine Warfare Command; San Diego Bay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-02

    ...-AA87 Security Zones; Naval Base Point Loma; Naval Mine Anti Submarine Warfare Command; San Diego Bay... establishing a new security zone at the Naval Mine and Anti-Submarine Warfare Command to protect the relocated... Commander of Naval Base Point Loma, the Commander of the Naval Mine Anti Submarine Warfare Command, and the...

  1. Intrafamily and intragenomic conflicts in human warfare

    PubMed Central

    2017-01-01

    Recent years have seen an explosion of multidisciplinary interest in ancient human warfare. Theory has emphasized a key role for kin-selected cooperation, modulated by sex-specific demography, in explaining intergroup violence. However, conflicts of interest remain a relatively underexplored factor in the evolutionary-ecological study of warfare, with little consideration given to which parties influence the decision to go to war and how their motivations may differ. We develop a mathematical model to investigate the interplay between sex-specific demography and human warfare, showing that: the ecology of warfare drives the evolution of sex-biased dispersal; sex-biased dispersal modulates intrafamily and intragenomic conflicts in relation to warfare; intragenomic conflict drives parent-of-origin-specific patterns of gene expression—i.e. ‘genomic imprinting’—in relation to warfare phenotypes; and an ecological perspective of conflicts at the levels of the gene, individual, and social group yields novel predictions as to pathologies associated with mutations and epimutations at loci underpinning human violence. PMID:28228515

  2. Intrafamily and intragenomic conflicts in human warfare.

    PubMed

    Micheletti, Alberto J C; Ruxton, Graeme D; Gardner, Andy

    2017-02-22

    Recent years have seen an explosion of multidisciplinary interest in ancient human warfare. Theory has emphasized a key role for kin-selected cooperation, modulated by sex-specific demography, in explaining intergroup violence. However, conflicts of interest remain a relatively underexplored factor in the evolutionary-ecological study of warfare, with little consideration given to which parties influence the decision to go to war and how their motivations may differ. We develop a mathematical model to investigate the interplay between sex-specific demography and human warfare, showing that: the ecology of warfare drives the evolution of sex-biased dispersal; sex-biased dispersal modulates intrafamily and intragenomic conflicts in relation to warfare; intragenomic conflict drives parent-of-origin-specific patterns of gene expression-i.e. 'genomic imprinting'-in relation to warfare phenotypes; and an ecological perspective of conflicts at the levels of the gene, individual, and social group yields novel predictions as to pathologies associated with mutations and epimutations at loci underpinning human violence. © 2017 The Authors.

  3. Replication Does Survive Information Warfare Attacks

    DTIC Science & Technology

    1997-01-01

    warfare, storage jamming, unauthorized modification, Trojan horse 1 INTRODUCTION Ammann, Jajodia, McCollum, and Blaustein define information warfare as the...information warfare, and we adopt the latter term. To provide context, Amman et al. specifically do not consider Trojan horses within the database system...called internal jammers (McDermott and Goldschalg, 1996b)), but instead consider a wide range of attacks other than Trojan horses . Both groups agree that

  4. 14th Annual Expeditionary Warfare Conference

    DTIC Science & Technology

    2009-11-19

    Untitled Document 2009expedition.html[5/12/2016 8:33:22 AM] 14th ANNUAL EXPEDITIONARY WARFARE CONFERENCE “Expeditionary Warfare in a Complex Joint...WWW.NDIA.ORG/MEETINGS/0700 “Expeditionary Warfare in a Complex Joint Operating Environment” BAY POINT MARRIOTT HOTEL, PANAMA CITY, FL...Focus: The purpose of the Quadrennial Defense Review (QDR) is to determine the nation’s defense strategy and establish a defense program for

  5. Creating Paths of Change: Under What Conditions Can Special Operations be the Supported Command

    DTIC Science & Technology

    2018-03-01

    goals.” Daft, Essentials of Organization Theory and Design , 48); I. V. Gordon et al., Comparing US Army Systems with Foreign Counterparts: Identifying...CODE A 13. ABSTRACT (maximum 200 words) This thesis focuses on command and control for irregular warfare operations and the organizational design ...compound warfare, unconventional warfare, special action force, village stability operations, organizational design , conventional warfare

  6. Electronic Warfare for Cyber Warriors

    DTIC Science & Technology

    2008-06-01

    This research paper provides complete course content for the AFIT EENG 509, Electronic Warfare class. It is intended as a replacement for the existing course and designed for Intermediate Developmental Education (IDE) students in the Cyber Warfare degree program. This course provides relevant academic courseware and study material to give cyber warriors an academic and operational perspective on electronic warfare and its integration in the cyber domain.

  7. U.S. Command Relationships in the Conduct of Cyber Warfare: Establishment, Exercise, and Institutionalization of Cyber Coordinating Authority

    DTIC Science & Technology

    2010-05-03

    FINAL 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE U.S. Command Relationships in the Conduct of Cyber Warfare : Establishment...U.S. Command Relationships in the Conduct of Cyber Warfare : Establishment, Exercise, and Institutionalization of Cyber Coordinating Authority...Relationships in the Conduct of Cyber Warfare : Establishment, Exercise, and Institutionalization of Cyber Coordinating Authority The character of

  8. Remote sensing of chemical warfare agent by CO2 -lidar

    NASA Astrophysics Data System (ADS)

    Geiko, Pavel P.; Smirnov, Sergey S.

    2014-11-01

    The possibilities of remote sensing of chemical warfare agent by differential absorption method were analyzed. The CO2 - laser emission lines suitable for sounding of chemical warfare agent with provision for disturbing absorptions by water vapor were choose. The detection range of chemical warfare agents was estimated for a lidar based on CO2 - laser The other factors influencing upon echolocation range were analyzed.

  9. 33 CFR 165.1103 - Security Zone; Naval Mine Anti Submarine Warfare Command; San Diego Bay, San Diego, CA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Submarine Warfare Command; San Diego Bay, San Diego, CA. 165.1103 Section 165.1103 Navigation and Navigable... Eleventh Coast Guard District § 165.1103 Security Zone; Naval Mine Anti Submarine Warfare Command; San... the Naval Mine Anti Submarine Warfare Command, bound by the following coordinates: 32°43′40.9″ N, 117...

  10. Electronic Warfare Closed Loop Laboratory (EWCLL) Antenna Motor Software and Hardware Development

    DTIC Science & Technology

    2016-09-01

    ARL-TN-0779 ● SEP 2016 US Army Research Laboratory Electronic Warfare Closed Loop Laboratory (EWCLL) Antenna Motor Software and...Electronic Warfare Closed Loop Laboratory (EWCLL) Antenna Motor Software and Hardware Development by Neal Tesny Sensors and Electron Devices Directorate...TITLE AND SUBTITLE Electronic Warfare Closed Loop Laboratory (EWCLL) Antenna Motor Software and Hardware Development 5a. CONTRACT NUMBER 5b

  11. Mammalian Toxicology Testing: Problem Definition Study, Global Army Toxicology Requirements.

    DTIC Science & Technology

    1981-03-01

    Electronic Warfare Equipment (D251) Tactical ECK System (64750A) Protective Electronic Warfare Equipment (D540) High Energy Electromagnetic Radiation...Fighting Portable Weapon (for IFV) Smoke Grenade Launcher Staff Smart, Target-Activated Fire-and-Forget Tactical ECK System (63755A) Protective Electronic...Warfare Equipment (D251) Tactical ECK System (64750A) Protective Electronic Warfare Equipment (D540) High Energy Electromagnetic Radiation Weapons (e.g

  12. The Characterization and Measurement of Cyber Warfare, Spring 2008 - Project 08-01

    DTIC Science & Technology

    2008-05-01

    Global Innovation and Strategy Center The Characterization and Measurement of Cyber Warfare Spring 2008 – Project 08-01 May 2008...and Measurement of Cyber Warfare N/A N/A N/A 08-01Dobitz, Kyle Haas, Brad Holtje, Michael Jokerst, Amanda Ochsner, Geoff Silva, Stephanie...research team as critical for purposes of cyber act characterization: Motivation, Intent, Target, Effects, and Actors. cyberspace, cyber warfare , targets

  13. Refocusing Cyber Warfare Thought

    DTIC Science & Technology

    2013-02-01

    January–February 2013 Air & Space Power Journal | 44 FeatureCyber Focus Refocusing Cyber Warfare Thought Maj Sean C. Butler, USAF In September 2007...1. REPORT DATE FEB 2013 2. REPORT TYPE 3. DATES COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE Refocusing Cyber Warfare Thought 5a...2013 Air & Space Power Journal | 45 Butler Refocusing Cyber Warfare Thought FeatureCyber Focus characterized by the use of electronics and the

  14. Nodes and Codes: The Reality of Cyber Warfare

    DTIC Science & Technology

    2012-05-17

    Nodes and Codes explores the reality of cyber warfare through the story of Stuxnet, a string of weaponized code that reached through a domain...nodes. Stuxnet served as a proof-of-concept for cyber weapons and provided a comparative laboratory to study the reality of cyber warfare from the...military powers most often associated with advanced, offensive cyber attack capabilities. The reality of cyber warfare holds significant operational

  15. Cyberspace as a Complex Adaptive System and the Policy and Operational Implications for Cyber Warfare

    DTIC Science & Technology

    2014-05-22

    CYBERSPACE AS A COMPLEX ADAPTIVE SYSTEM AND THE POLICY AND OPERTIONAL IMPLICATIONS FOR CYBER WARFARE A Monograph by Major Albert O. Olagbemiro...serves the US, especially in regards to the protect ion o f the 1S. SUBJECT TERMS omplex Adaptive System, Cyberspace, lnfosphere, Cyber Warfare ber...System and the Policy and Operational Implications for Cyber Warfare Approved by: __________________________________, Monograph Director Jeffrey

  16. Warfighting in Cyberspace

    DTIC Science & Technology

    2007-01-01

    warfare ). Although the defensive elements of IO and cyber warfare are important, to narrow the scope of our thesis, the remainder of the argu- ment...adversary decisions away from taking action against our will. Now, let us contrast IO doctrine with what we propose for cyber warfare . The focus of... cyber warfare is on using cyberspace (by operating within or through it) to attack personnel, facilities, or equipment with the intent of degrading

  17. Defending Our Satellites: The Need for Electronic Warfare Education and Training

    DTIC Science & Technology

    2015-12-01

    intercept Allied bombers attacking at night.9 As a result of the electronic warfare advantage that systems like Window and Airborne Cigar be- stowed...74 | Air & Space Power Journal Defending Our Satellites The Need for Electronic Warfare Education and Training Lt Col E. Lincoln Bonner, USAF...expanding education and training in the use of electronic warfare to defend US satellites and improve their survivability. The following discussion

  18. Highlights of the Department of the Navy FY 2013 Budget

    DTIC Science & Technology

    2012-02-01

    ability to perform undersea warfare to include high altitude launched torpedo capability, surface warfare and ISR missions make it a critical force...60B and SH-60F helicopters, whose primary mission areas are undersea warfare and surface warfare. This platform will have numerous capability...sensors to detect, localize, classify and identify undersea threats at a safe distance from friendly ships. The Remote Multi-Mission Vehicle provides

  19. Remaining Relevant: Historical Contributions, Civil-Military Challenges, and Anti-Submarine Warfare Capabilities on Coast Guard Cutters

    DTIC Science & Technology

    2018-03-01

    HISTORICAL CONTRIBUTIONS, CIVIL-MILITARY CHALLENGES, AND ANTI-SUBMARINE WARFARE CAPABILITIES ON COAST GUARD CUTTERS by Brian A. Smicklas...CONTRIBUTIONS, CIVIL- MILITARY CHALLENGES, AND ANTI-SUBMARINE WARFARE CAPABILITIES ON COAST GUARD CUTTERS 5. FUNDING NUMBERS 6. AUTHOR(S) Brian A...MILITARY CHALLENGES, AND ANTI-SUBMARINE WARFARE CAPABILITIES ON COAST GUARD CUTTERS Brian A. Smicklas Commander, U.S. Coast Guard B.S., Coast

  20. The intensity of knock in an internal combustion engine: An experimental and modeling study

    NASA Astrophysics Data System (ADS)

    Cowart, J. S.; Haghooie, M.; Newman, C. E.; Davis, G. C.; Pitz, W. J.; Westbrook, C. K.

    1992-09-01

    Experimental data have been obtained that characterize knock occurrence times and knock intensities in a spark ignition engine operating on indolene and 91 primary reference fuel, as spark timing and inlet temperature were varied. Individual, in-cylinder pressure histories measured under knocking conditions were conditioned and averaged to obtain representative pressure traces. These averaged pressure histories were used as input to a reduced and detailed chemical kinetic model. The time derivative of CO concentration and temperature were correlated with the measured knock intensity and percent cycles knocking. The goal was to evaluate the potential of using homogeneous, chemical kinetic models as predictive tools for knock intensity.

  1. The Art of Aerial Warfare

    DTIC Science & Technology

    2005-03-01

    14 3 THE POLITICAL DIMENSIONS OF AERIAL WARFARE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 How Political Effects in...Aerial Warfare . . . . . . Outweigh Military Effects . . . . . . . . . . . . . . . 19 Political Targets Versus Military Targets . . . . . 22...34 4 MILITARY AND POLITICAL EFFECTS OF STRATEGIC ATTACK . . . . . . . . . . . . . . . . . . 35 The Premise of

  2. Knock down of the myostatin gene by RNA interference increased body weight in chicken.

    PubMed

    Bhattacharya, T K; Shukla, R; Chatterjee, R N; Dushyanth, K

    2017-01-10

    Myostatin is a negative regulator of muscular growth in poultry and other animals. Of several approaches, knocking down the negative regulator is an important aspect to augment muscular growth in chicken. Knock down of myostatin gene has been performed by shRNA acting against the expression of gene in animals. Two methods of knock down of gene in chicken such as embryo manipulation and sperm mediated method have been performed. The hatching percentage in embryo manipulation and sperm mediated method of knock down was 58.0 and 41.5%, respectively. The shRNA in knock down chicken enhanced body weight at 6 weeks by 26.9%. The dressing percentage and serum biochemical parameters such as SGPT and alkaline phosphatase differed significantly (P<0.05) between knock down and control birds. It is concluded that knocking down the myostatin gene successfully augmented growth in chicken. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Development of JSDF Cyber Warfare Defense Critical Capability

    DTIC Science & Technology

    2010-03-01

    attack identification capability is essential for a nation to defend her vital infrastructures against offensive cyber warfare . Although the necessity of...cyber-attack identification capability is quite clear, the Japans preparation against cyber warfare is quite limited.

  4. 15th Annual Expeditionary Warfare Conference - Expeditionary Operations - What’s Next

    DTIC Science & Technology

    2010-10-07

    00 PM - 5:00 PM Mine Warfare Capabilities Essential for Expeditionary Warfare Salon 1 (limited to first 120 registrants) Session Focus...have priority – Requires additional conceptual development, gaming & exercises Questions? 23

  5. CYBER WARFARE GOVERNANCE: EVALUATION OF CURRENT INTERNATIONAL AGREEMENTS ON THE OFFENSIVE USE OF CYBER

    DTIC Science & Technology

    2015-10-01

    AIR COMMAND AND STAFF COLLEGE DISTANCE LEARNING AIR UNIVERSITY CYBER WARFARE GOVERNANCE: EVALUATION OF CURRENT INTERNATIONAL AGREEMENTS ON THE...order to prevent catastrophic second and third order effects. Rule 43 “prohibits means or methods of cyber warfare that indiscriminate by nature...Means and methods of cyber warfare are indiscriminate by nature if they cannot be: directed at a specific military objective, or limited in their

  6. Cyber Warfare: A Need for Beyond Goldwater-Nichols

    DTIC Science & Technology

    2011-05-13

    of Military Studies Research Paper September 2010- May 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Cyber Warfare : "A Need for Beyond Goldwater...22134-5068 MASTER OF MlLIT AR Y STUDJES Cyber Warfare : "A Need for Beyond Goldwater Nichols" SlffiMITTED IN PARTIAL FULFitLMENT OF THE...DOCUMENT IS PERMITTED PROVIDED PROPER ACKNOWLEDGEMENT IS MADE.· l . ii EXECUTIVE SUMMARY Title: Cyber Warfare : "A Need for Beyond Goldwater Nichols

  7. Civil Affairs in Unconventional Warfare

    DTIC Science & Technology

    2013-05-23

    goals as Mao Tse -tung states, “Military action is a method used to attain a political goal. While military affairs and political affairs are not...OSS to Green Beret: The Birth at Special Forces (Novato, CA: Presidio Press, 1986), 149-51. 25Mao Tse -tung, On Guerrilla Warfare (New York: Classic...House Books, 2009), 39. 26David Galula, Counterinsurgency Warfare, 4; and Mao Tse -tung, On Guerrilla Warfare, 3-4. 27Ibid., 12-13. 28Ibid

  8. Piezocomposites for Active Surface Control

    DTIC Science & Technology

    1999-01-19

    and the Underwater Sound Reference Detachment (USRD) in Orlando, FL. During the period of the program, USRD became part of the Naval Undersea Warfare...Appendix B DEPARTMENT OF THE NAVY NAVAL UNDERSEA WARFARE CENTER 1176 HOWELL STREET NEWPORT Rl 02«41-170i NAVAL UNDERSEA WARFARE CENTER...dissemination only as directed by Commanding Officer, Naval Undersea Warfare Center (18 AUG i99o ) or higher DoD authority. Page 1 of 1 USRD CALIBRATION

  9. Chemical warfare and the Gulf War: a review of the impact on Gulf veterans' health.

    PubMed

    Riddle, James R; Brown, Mark; Smith, Tyler; Ritchie, Elspeth Cameron; Brix, Kelley Ann; Romano, James

    2003-08-01

    It is unlikely that Gulf War veterans are suffering chronic effects from illnesses caused by chemical warfare nerve agent exposure. Extensive investigation and review by several expert panels have determined that no evidence exists that chemical warfare nerve agents were used during the Gulf War. At no time before, during, or after the war was there confirmation of symptoms among anyone, military or civilian, caused by chemical warfare nerve agent exposure. However, studies of Gulf War veterans have found belief that chemical weapons were used, significantly associated with both severe and mild-moderate illnesses. The psychological impact of a chemical warfare attack, either actual or perceived, can result in immediate and long-term health consequences. The deployment or war-related health impact from life-threatening experiences of the Gulf War, including the perceived exposure to chemical warfare agents, should be considered as an important cause of morbidity among Gulf War veterans.

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

    Sileghem, L.; Wallner, T.; Verhelst, S.

    As knock is one of the main factors limiting the efficiency of spark-ignition engines, the introduction of alcohol blends could help to mitigate knock concerns due to the elevated knock resistance of these blends. A model that can accurately predict their autoignition behavior would be of great value to engine designers. The current work aims to develop such a model for alcohol–gasoline blends. First, a mixing rule for the autoignition delay time of alcohol–gasoline blends is proposed. Subsequently, this mixing rule is used together with an autoignition delay time correlation of gasoline and an autoignition delay time cor-relation of methanolmore » in a knock integral model that is implemented in a two-zone engine code. The pre-dictive performance of the resulting model is validated through comparison against experimental measurements on a CFR engine for a range of gasoline–methanol blends. The knock limited spark advance, the knock intensity, the knock onset crank angle and the value of the knock integral at the experimental knock onset have been simulated and compared to the experimental values derived from in-cylinder pressure measurements.« less

  11. Maneuver Warfare in Cyberspace

    DTIC Science & Technology

    1997-01-01

    government departments and agencies; (2) National security and military strategies must outline a response to the threats and opportunities of cyber ... warfare ; and (3) the Department of Defense’s offensive and defensive responsibilities, parameters, and capabilities for strategic information warfare need

  12. Cyber Power in the 21st Century

    DTIC Science & Technology

    2008-12-01

    Cyber Warfare .................................................................86 V. Conclusions and Recommendations...40 2 – Asymmetric Effects of Cyber Warfare ........................................................................41 1 CYBER POWER... cyber warfare capabilities with other elements of national power, as evidenced by the concept of “informationization” (xinxihua) put forward in

  13. Difficult Decisions: Chemical Warfare.

    ERIC Educational Resources Information Center

    Slesnick, Irwin L.; Miller, John A.

    1988-01-01

    Gives the background history and chemistry of modern day chemical warfare from World War I to the present. Provides discussion questions to stimulate deeper thinking on the issue. Contains a discussion activity called "Can New Chemical Weapons Lead to Humane Warfare?" (CW)

  14. Technological advancements for the detection of and protection against biological and chemical warfare agents.

    PubMed

    Eubanks, Lisa M; Dickerson, Tobin J; Janda, Kim D

    2007-03-01

    There is a growing need for technological advancements to combat agents of chemical and biological warfare, particularly in the context of the deliberate use of a chemical and/or biological warfare agent by a terrorist organization. In this tutorial review, we describe methods that have been developed both for the specific detection of biological and chemical warfare agents in a field setting, as well as potential therapeutic approaches for treating exposure to these toxic species. In particular, nerve agents are described as a typical chemical warfare agent, and the two potent biothreat agents, anthrax and botulinum neurotoxin, are used as illustrative examples of potent weapons for which countermeasures are urgently needed.

  15. Chemical and biological warfare: General studies. (Latest citations from the NTIS bibliographic database). NewSearch

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

    Not Available

    1994-10-01

    The bibliography contains citations concerning federally sponsored and conducted studies into chemical and biological warfare operations and planning. These studies cover areas not addressed in other parts of this series. The topics include production and storage of agents, delivery techniques, training, military and civil defense, general planning studies, psychological reactions to chemical warfare, evaluations of materials exposed to chemical agents, and studies on banning or limiting chemical warfare. Other published searches in this series on chemical warfare cover detection and warning, defoliants, protection, and biological studies, including chemistry and toxicology. (Contains 250 citations and includes a subject term index andmore » title list.)« less

  16. Chemical and biological warfare: General studies. (Latest citations from the NTIS bibliographic database). Published Search

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

    NONE

    1997-11-01

    The bibliography contains citations concerning federally sponsored and conducted studies into chemical and biological warfare operations and planning. These studies cover areas not addressed in other parts of this series. The topics include production and storage of agents, delivery techniques, training, military and civil defense, general planning studies, psychological reactions to chemical warfare, evaluations of materials exposed to chemical agents, and studies on banning or limiting chemical warfare. Other published searches in this series on chemical warfare cover detection and warning, defoliants, protection, and biological studies, including chemistry and toxicology.(Contains 50-250 citations and includes a subject term index and titlemore » list.) (Copyright NERAC, Inc. 1995)« less

  17. Chemical and biological warfare: General studies. (Latest citations from the NTIS bibliographic database). Published Search

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

    NONE

    1996-10-01

    The bibliography contains citations concerning federally sponsored and conducted studies into chemical and biological warfare operations and planning. These studies cover areas not addressed in other parts of this series. The topics include production and storage of agents, delivery techniques, training, military and civil defense, general planning studies, psychological reactions to chemical warfare, evaluations of materials exposed to chemical agents, and studies on banning or limiting chemical warfare. Other published searches in this series on chemical warfare cover detection and warning, defoliants, protection, and biological studies, including chemistry and toxicology. (Contains 50-250 citations and includes a subject term index andmore » title list.) (Copyright NERAC, Inc. 1995)« less

  18. Chemical and biological warfare: General studies. (Latest citations from the NTIS bibliographic database). Published Search

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

    NONE

    1995-09-01

    The bibliography contains citations concerning federally sponsored and conducted studies into chemical and biological warfare operations and planning. These studies cover areas not addressed in other parts of this series. The topics include production and storage of agents, delivery techniques, training, military and civil defense, general planning studies, psychological reactions to chemical warfare, evaluations of materials exposed to chemical agents, and studies on banning or limiting chemical warfare. Other published searches in this series on chemical warfare cover detection and warning, defoliants, protection, and biological studies, including chemistry and toxicology.(Contains 50-250 citations and includes a subject term index and titlemore » list.) (Copyright NERAC, Inc. 1995)« less

  19. Air & Space Power Journal. Volume 22, Number 3, Fall 2008

    DTIC Science & Technology

    2008-09-01

    PHd, UsaF, retired* Red Flag exercises, well known as training components of air warfare, will also become a staple of cyber warfare . —Former...it wishes to meet former secretary Wynne’s vision of a significantly enhanced cyber - warfare environ­ ment. This change is so monumental that full...this reviewer’s judgment, only one area does not receive adequate examination: cyber warfare . Although Drew and Snow make note of it in several

  20. RFID as a Tool in Cyber Warfare

    DTIC Science & Technology

    2010-11-01

    RTO-MP-IST-091 P4 - 1 RFID as a Tool in Cyber Warfare Mikko Kiviharju P.O.Box 10 FIN-11311 Riihimaki FINLAND mikko.kiviharju@mil.fi...auditing existing systems and planning new establishments. 1 INTRODUCTION Cyber warfare , especially computer network operations (CNO) have a deep...SUBTITLE RFID as a Tool in Cyber Warfare 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK

  1. Cyber Warfare as an Operational Fire

    DTIC Science & Technology

    2010-04-03

    This paper explores cyber warfare as an option for creating operational fires effects. Initially, cyberspace is defined and explained from the...fires are defined and the advantages of their use are explained. From there, discussion focuses on how cyber warfare fulfills the purposes of...operational fires. Finally, the paper draws conclusions about the viability of cyber warfare as an operational fire and makes recommendations about how to prioritize the activities of the newly approved U.S. Cyber Command.

  2. Emerging Roles of Combat Communication Squadrons in Cyber Warfare as Related to Computer Network Attack, Defense and Exploitation

    DTIC Science & Technology

    2011-06-01

    EMERGING ROLES OF COMBAT COMMUNICATION SQUADRONS IN CYBER WARFARE AS RELATED TO COMPUTER NETWORK ATTACK, DEFENSE AND EXPLOITATION GRADUATE RESEARCH...Communication Squadrons in Cyber Warfare as Related to Computer Network Attack, Defense and Exploitation GRADUATE RESEARCH PROJECT Presented to the Faculty...Education and Training Command In Partial Fulfillment of the Requirements for the Degree of Master of Cyber Warfare Michael J. Myers Major, USAF June 2011

  3. Counter-Unmanned Aerial Vehicle Warfare: Kill Authorizations for the Carrier Strike Group

    DTIC Science & Technology

    2016-06-10

    COUNTER-UNMANNED AERIAL VEHICLE WARFARE: KILL AUTHORIZATIONS FOR THE CARRIER STRIKE GROUP A thesis presented to the Faculty...the Carrier Strike Group 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) LCDR Joshua C. Mattingly, U.S...including armed UAVs in an offensive role, but counter- UAV warfare is a new warfare area within the larger realm of air defense. Small Group 1 and 2

  4. Warfare or partnership: which way for health care?

    PubMed

    MacStravic, R S

    1990-01-01

    There are many voices urging health care organizations to adopt aggressive competitive warfare, but a careful look at the dynamics affecting health care suggests that partnership may be at least as promising a strategy as warfare to promote mission and survival.

  5. Cyber Warfare: Protecting Military Systems

    DTIC Science & Technology

    2000-01-01

    Software is a key component in nearly every critical system used by the Department of Defense. Attacking the software in a system- cyber warfare - is a...revolutionary method of pursuing war. This article describes various cyber warfare approaches and suggests methods to counter them.

  6. Biological warfare agents

    PubMed Central

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

  7. The Impacts of Modern Warfare on Freshwater Ecosystems

    NASA Astrophysics Data System (ADS)

    Francis, Robert A.

    2011-11-01

    There is increasing recognition and concern regarding the impacts of modern industrial warfare on the environment. Freshwater ecosystems are perhaps the most vulnerable to warfare-related impacts, which is of concern given that they provide so many essential environmental resources and services to society. Despite this, there has been little work to establish and quantify the types of impacts (both negative and positive) that warfare may have on such systems. This paper firstly highlights why rivers and lakes may be susceptible to warfare-related impacts, before synthesizing the available literature to explore the following main themes: intensification of wartime resource acquisition, use of water as an offensive or defensive weapon, direct and indirect effects of explosive ordnance, increased pollution, introduction of invasive alien species, and positive ecological impacts. This is then followed by a discussion of the implications of such impacts in relation to future warfare, including a consideration of the efficacy of existing legal instruments to protect the environment during conflict, and the trend for war to become more localized and `informal', and therefore less regulated. Finally, the paper identifies key research foci for understanding and mitigating the effects of warfare on freshwater ecosystems.

  8. Coalition FORCEnet Implementation Analysis

    DTIC Science & Technology

    2006-09-01

    C2 grid, and Engagement grid. As a result, enabled Network- Centric warfare for Coalition Forces shows a significant increase in capabilities. Joint...209 14. SUBJECT TERMS FORCEnet, Coalition Forces, AUSCANNZUKUS, Network- Centric Warfare (NCW), Data Mining, EXTEND Modeling, Expeditionary...NETWORK- CENTRIC WARFARE AND FORCENET .....................................................................................................1 B

  9. Summary of Research 1998, Interdisciplinary Academic Groups

    DTIC Science & Technology

    1999-08-01

    Seismic Sonar, Biosonar SEISMO ACOUSTIC DETECTION OF MINES BURIED IN THE SURF ZONE Thomas Muir, Chair of Mine Warfare Undersea Warfare Academic Group...Mine Warfare KEYWORDS: Mining, Mine Countermeasures, Surf Zone, Seismic Sonar, Biosonar PHYSICS OF SEISMIC INTERFACE WAVES IN THE SURF ZONE

  10. History of the Chemical Warfare Service in World War II. Biological Warfare Research in the United States, Volume 2

    DTIC Science & Technology

    1947-11-01

    of proteins and other substances of high molecular weight derived from bacteria, or from natural products with antibacterial activity Proteins and...WARFARE RESEARCH IS THE UNITED r STATES, is one of a series of historical monographs on the research and development activities of the Chemical...TSC Committee 16 War Research Service 13 A5C Committee •• 21 CWS Activities Under TSRS 22 Transfer of Biological Warfare Program to TTar

  11. Bridging the Gap in the Realm of Information Dominance: A Concept of Operations for the Naval Postgraduate School Center for Cyber Warfare

    DTIC Science & Technology

    2010-09-01

    THE REALM OF INFORMATION DOMINANCE : A CONCEPT OF OPERATIONS FOR THE NAVAL POSTGRADUATE SCHOOL CENTER FOR CYBER WARFARE by Cynthia R. Duke...Bridging the Gap in the Realm of Information Dominance : A Concept of Operations for the Naval Postgraduate School Center for Cyber Warfare 6...of importance to the U.S. Military service and its allies. 15. NUMBER OF PAGES 102 14. SUBJECT TERMS Cyber Warfare, Information Dominance 16

  12. USAF Cyber Capability Development: A Vision for Future Cyber Warfare & a Concept for Education of Cyberspace Leaders

    DTIC Science & Technology

    2009-04-01

    Significant and interrelated problems are hindering the Air Force’s development of cyber warfare capabilities. The first is a lack of awareness about...why the AF has chosen to take cyber warfare on as a core capability on par with air and space. The second stems from the lack of a commonly...the cyber capabilities needed in the future? The contributions of this research include a strategic vision for future cyber warfare capabilities that

  13. Capability of the People’s Republic of China to Conduct Cyber Warfare and Computer Network Exploitation

    DTIC Science & Technology

    2009-10-09

    Capability of the People’s Republic of China to Conduct Cyber Warfare and Computer Network Exploitation Prepared for The US-China Economic and...the People?s Republic of China to Conduct Cyber Warfare and Computer Network Exploitation 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...Capability of the People’s Republic of China to Conduct Cyber Warfare and Computer Network Exploitation 2 US-China Economic and Security Review

  14. Knock detection system to improve petrol engine performance, using microphone sensor

    NASA Astrophysics Data System (ADS)

    Sujono, Agus; Santoso, Budi; Juwana, Wibawa Endra

    2017-01-01

    An increase of power and efficiency of spark ignition engines (petrol engines) are always faced with the problem of knock. Even the characteristics of the engine itself are always determined from the occurrence of knock. Until today, this knocking problem has not been solved completely. Knock is caused by principal factors that are influenced by the engine rotation, the load or opening the throttle and spark advance (ignition timing). In this research, the engine is mounted on the engine test bed (ETB) which is equipped with the necessary sensors. Knock detection using a new method, which is based on pattern recognition, which through the knock sound detection by using a microphone sensor, active filter, the regression of the normalized envelope function, and the calculation of the Euclidean distance is used for identifying knock. This system is implemented with a microcontroller which uses fuzzy logic controller ignition (FLIC), which aims to set proper spark advance, in accordance with operating conditions. This system can improve the engine performance for approximately 15%.

  15. Application of Solid Phase Microextraction Coupled with Gas Chromatography/Mass Spectrometry as a Rapid Method for Field Sampling and Analysis of Chemical Warfare Agents and Toxic Industrial Chemicals

    DTIC Science & Technology

    2003-01-01

    PHASE MICROEXTRACTION COUPLED WITH GAS CHROMATOGRAPHY/MASS SPECTROMETRY AS A RAPID METHOD FOR FIELD SAMPLING AND ANALYSIS OF CHEMICAL WARFARE AGENTS...SAMPLING AND ANALYSIS OF CHEMICAL WARFARE AGENTS AND TOXIC INDUSTRIAL CHEMICALS 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...GAS CHROMATOGRAPHY/MASS SPECTROMETRY AS A RAPID METHOD FOR FIELD SAMPLING AND ANALYSIS OF CHEMICAL WARFARE AGENTS AND TOXIC INDUSTRIAL CHEMICALS

  16. Status of dental health in chemical warfare victims: the case of Isfahan, Iran.

    PubMed

    Mottaghi, Ahmad; Hoseinzade, Abolfath; Zamani, Elham; Araghizade, Habib Allah

    2012-01-01

    Little evidence is available regarding the dental health of victims of chemical warfare in Iran. Therefore, in this study, we examined the decayed, missing, and filled teeth index (DMFT), community periodontal index of treatment needs (CPITN), and saliva secretion rate of chemical warfare victims living in the province of Isfahan in Iran. This case-control study was conducted with 300 chemical warfare victims as the treatment group and 300 age-matched individuals without exposure to chemical warfare as the control group. DMFT and CPITN indices and saliva secretion rate were measured and compared between the two groups. Chemical warfare victims had significantly higher scores than the control group for decayed teeth (4.25 ± 3.88 vs 3.52 ± 2.81; P=0.009), missing teeth (8.79 ± 9.3 vs 6.15 ± 8.43; P<0.001), total DMFT index (17.00 ± 6.72 vs 13.20 ± 6.89; P<0.001), and CPTIN (2.81 ± 0.81 vs 1.71 ± 1.04; P<0.001). However, no significant difference was observed between the two groups in filled teeth (4.00 ± 4.2 vs 3.59 ± 2.48; P=0.148). The level of saliva secretion in warfare victims was significantly lower than that in the control group (1.71 ± 0.05 vs 3.85 ± 1.95 cc/5 min; P<0.001). Chemical warfare victims have relatively poor dental/oral health. Chemical injury might cause a dysfunction in saliva secretion, with decrease in saliva secretion increasing the risk for tooth decay and periodontal disorders. Further research is required to find out the exact underlying mechanisms and the factors associated with poor dental/oral health in chemical warfare victims.

  17. Relation Between Spark-Ignition Engine Knock, Detonation Waves, and Autoignition as Shown by High-Speed Photography

    NASA Technical Reports Server (NTRS)

    Miller, Cearcy D

    1946-01-01

    A critical review of literature bearing on the autoignition and detonation-wave theories of spark-ignition engine knock and on the nature of gas vibrations associated with combustion and knock results in the conclusion that neither the autoignition theory nor the detonation-wave theory is an adequate explanation of spark-ignition engine knock. A knock theory is proposed, combining the autoignition and detonation-wave theories, which introduces the idea that the detonation wave develops in autoignited or after-burning gases, and ascribes comparatively low-pitched heavy knocks to autoignition but high-pitched pinging knocks to detonation waves with the possibility of combinations of the two types of knocks. Analysis of five shots of knocking combustion, taken with the NACA high-speed motion-picture camera at the rate of 40,000 photographs per second reveals propagation speeds ranging from 3250 to more than 5500 feet per second. The range of propagation speeds from 3250 to more than 5500 feet per second is held to be considered with the proposed combined theory but not with either the simple autoignition theory or the simple detonation-wave theory.

  18. "No practical capabilities": American biological and chemical warfare programs during the Korean war.

    PubMed

    Crane, Conrad C

    2002-01-01

    Much controversy still surrounds accusations that American forces in the Far East during the Korean War used biological warfare against North Korea and China. An analysis of recently declassified documents reveals that, although the United States attempted to accelerate its development and acquisition of such weapons during that period, its efforts to create a viable biological warfare capability were unsuccessful. Plans to similarly expand chemical warfare stocks and capabilities were also frustrated. Technological difficulties, personnel shortages, bureaucratic battles between the armed services, and policy limitations combined to hold back advances in American chemical and biological warfare. In light of the recent fears of terrorist attacks with such weapons, this analysis highlights the great difficulties involved in developing, acquiring, and delivering such capabilities.

  19. Development and evaluation of an efficient heterologous gene knock-in reporter system in Lactococcus lactis.

    PubMed

    Lu, Yifei; Yan, Hongxiang; Deng, Jiezhong; Huang, Zhigang; Jin, Xurui; Yu, Yanlan; Hu, Qiwen; Hu, Fuquan; Wang, Jing

    2017-09-18

    Lactococcus lactis is a food grade probiotics and widely used to express heterologous proteins. Generally, target genes are knocked into the L. lactis genome through double-crossover recombination to express heterologous proteins stably. However, creating marker-less heterologous genes knocked-in clones is laborious. In this study, an efficient heterologous gene knock-in reporter system was developed in L. lactis NZ9000. Our knock-in reporter system consists of a temperature-sensitive plasmid pJW and a recombinant L. lactis strain named NZB. The pJW contains homologous arms, and was constructed to knock-in heterologous genes at a fixed locus of NZ9000 genome. lacZ (β-galactosidase) gene was knocked into the chromosome of NZ9000 as a counter-selective marker through the plasmid pJW to generate NZB. The engineered NZB strain formed blue colonies on X-Gal plate. The desired double-crossover mutants formed white colonies distinctive from the predominantly blue colonies (parental and plasmid-integrated clones) when the embedded lacZ was replaced with the target heterologous genes carried by pJW in NZB. By using the system, the heterologous gene knocked-in clones are screened by colony phenotype change rather than by checking colonies individually. Our new knock-in reporter system provides an efficient method to create heterologous genes knocked-in clones.

  20. Establishing a Cyber Warrior Force

    DTIC Science & Technology

    2004-09-01

    Cyber Warfare is widely touted to be the next generation of warfare. As America’s reliance on automated systems and information technology increases...so too does the potential vulnerability to cyber attack. Nation and non-nation states are developing the capability to wage cyber warfare . Historically

  1. Detecting Biological Warfare Agents

    PubMed Central

    Song, Linan; Ahn, Soohyoun

    2005-01-01

    We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array. PMID:16318712

  2. Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.

    PubMed

    Aida, Tomomi; Nakade, Shota; Sakuma, Tetsushi; Izu, Yayoi; Oishi, Ayu; Mochida, Keiji; Ishikubo, Harumi; Usami, Takako; Aizawa, Hidenori; Yamamoto, Takashi; Tanaka, Kohichi

    2016-11-28

    Although CRISPR/Cas enables one-step gene cassette knock-in, assembling targeting vectors containing long homology arms is a laborious process for high-throughput knock-in. We recently developed the CRISPR/Cas-based precise integration into the target chromosome (PITCh) system for a gene cassette knock-in without long homology arms mediated by microhomology-mediated end-joining. Here, we identified exonuclease 1 (Exo1) as an enhancer for PITCh in human cells. By combining the Exo1 and PITCh-directed donor vectors, we achieved convenient one-step knock-in of gene cassettes and floxed allele both in human cells and mouse zygotes. Our results provide a technical platform for high-throughput knock-in.

  3. Surface Warfare Officers Initial Training For Future Success

    DTIC Science & Technology

    2018-03-01

    updating and creating learning modules and Surface Warfare Officer School (SWOS) staffing as well as weaknesses in the methodologies used for...and Surface Warfare Officer School (SWOS) staffing as well as weaknesses in the methodologies used for training. We conclude that the Basic Division... METHODOLOGY ....................................................................................9 1. Staff Interviews

  4. A Deeper Level of Network Intelligence: Combating Cyber Warfare

    DTIC Science & Technology

    2010-04-01

    A Deeper Level of Network Intelligence: Combating Cyber Warfare This information is provided for your review only and is not for any distribution...A Deeper Level of Network Intelligence: Combating Cyber Warfare 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  5. LESSONS FROM THE FRONT: A CASE STUDY OF RUSSIAN CYBER WARFARE

    DTIC Science & Technology

    2015-12-01

    Lessons From The Front: A Case Study Of Russian Cyber Warfare looks to capitalize on the lessons learned from the alleged Russian cyber-offensive on...through the careful analysis and comparison of two disparate conflicts related by their collision with Russian cyber - warfare . Following case study

  6. The Implications of Preemptive and Preventive War Doctrines: A Reconsideration

    DTIC Science & Technology

    2007-07-01

    geopolitics, ideology , and personality as combining to produce the fatal brew which resulted in 42 years of nuclear shadowed global menace.26 But...preventive war. 49 1. Preventive war is war, and preventive warfare is warfare. It is not a distinctive genus of war and warfare. The distinguishing

  7. 15 CFR 742.2 - Proliferation of chemical and biological weapons.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... in ECCN 1C350 (precursor and intermediate chemicals used in the production of chemical warfare agents... on the CCL, chemical detection systems controlled by 1A004.c for detecting chemical warfare agents... used in the production of chemical weapons precursors or chemical warfare agents. (vii) Equipment and...

  8. J. F. C. Fuller: His Methods, Insights, and Vision

    DTIC Science & Technology

    1999-04-01

    contributed immensely to the body of knowledge concerning warfare. As a military scientist, MG Fuller attempted to do for warfare what Copernicus did for... astronomy , Newton for physics, and Darwin for natural history: establish a higher order for the study warfare based on scientific analysis and methods

  9. Biodegradation of Organophosphate Chemical Warfare Agents by Activated Sludge

    DTIC Science & Technology

    2012-03-01

    Holmstedt, B. (1963). Structure- activity relationships of the organophosphorus anticholinesterase agents. In: Koelle, G.B. (ed.), Handbuch...BIODEGRADATION OF ORGANOPHOSPHATE CHEMICAL WARFARE AGENTS BY ACTIVATED SLUDGE Steven J. Schuldt...AFIT/GES/ENV/12-M04 BIODEGRADATION OF ORGANOPHOSPHATE CHEMICAL WARFARE AGENTS BY ACTIVATED SLUDGE THESIS Presented to the

  10. Examining U.S. Irregular Warfare Doctrine

    DTIC Science & Technology

    2008-06-01

    48 Future Theories ...Questions, and Hypotheses The classic warfare theories (i.e. Sun Tzu, Clausewitz, and so forth) directly apply to this research since they form the...Tzu, their theories on the conduct of warfare, and its close tie to politics, form the basis for examining the content of the manuals. The Marine

  11. Technical Support Services for the Office of Naval Research Littoral Warfare Advanced Development Project

    DTIC Science & Technology

    2005-09-30

    Technical Support Services for the Office of Naval Research Littoral Warfare Advanced Development Project William R. Metzger Marine...Support Services for the Office of Naval Research Littoral Warfare Advanced Development Project 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

  12. The Future of Warfare and Impact of Space Operations

    DTIC Science & Technology

    2011-01-01

    cyber warfare is occurring as a preferred method of conflict between large players on the global stage. Smaller players also have reasons to avoid conventional warfare and remain hidden. In Iraq and Afghanistan, those who fight against us attempt to remain hidden. The individual who places an improvised explosive device (IED) attempts to engage us without exposure or identification. Those who aid the individual emplacing an IED do so with hidden networks of support. The IED is an anonymous weapon. Both cyber warfare and insurgent use of IEDs depend

  13. Software Acquisition in the Age of Cyber Warfare

    DTIC Science & Technology

    2011-05-01

    s c h o o l o f S Y S T E M S a n d L O G I S T I C S education service research Software Acquisition in the Age of Cyber Warfare Maj...DATE MAY 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE Software Acquisition in the Age of Cyber Warfare 5a...AFIT Cyber 200/300 Courses Cyber Warfare IDE Program 34 Special Emphasis On… Enterprise Integration (Active Directory, PKI) Security

  14. The Fate of Chemical Warfare Agents in the Environment

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

    Talmage, Sylvia Smith; Munro, Nancy B; Watson, Annetta Paule

    2007-01-01

    Chemical Warfare Agents, Second Edition has been totally revised since the successful first edition and expanded to about three times the length, with many new chapters and much more in-depth consideration of all the topics. The chapters have been written by distinguished international experts in various aspects of chemical warfare agents and edited by an experienced team to produce a clear review of the field. The book now contains a wealth of material on the mechanisms of action of the major chemical warfare agents, including the nerve agent cyclosarin, formally considered to be of secondary importance, as well as ricinmore » and abrin. Chemical Warfare Agents, Second Edition discusses the physico-chemical properties of chemical warfare agents, their dispersion and fate in the environment, their toxicology and management of their effects on humans, decontamination and protective equipment. New chapters cover the experience gained after the use of sarin to attack travelers on the Tokyo subway and how to deal with the outcome of the deployment of riot control agents such as CS gas. This book provides a comprehensive review of chemical warfare agents, assessing all available evidence regarding the medical, technical and legal aspects of their use. It is an invaluable reference work for physicians, public health planners, regulators and any other professionals involved in this field.« less

  15. A method of estimating the knock rating of hydrocarbon fuel blend

    NASA Technical Reports Server (NTRS)

    Sanders, Newell D

    1943-01-01

    The usefulness of the knock ratings of pure hydrocarbon compounds would be increased if some reliable method of calculating the knock ratings of fuel blends was known. The purpose of this study was to investigate the possibility of developing a method of predicting the knock ratings of fuel blends.

  16. A Method of Estimating the Knock Rating of Hydrocarbon Fuel Blends

    NASA Technical Reports Server (NTRS)

    Sanders, Newell D.

    1943-01-01

    The usefulness of the knock ratings of pure hydrocarbon compounds would be increased if some reliable method of calculating the knock ratings of fuel blends was known. The purpose of this study was to investigate the possibility of developing a method of predicting the knock ratings of fuel blends.

  17. Porcine Knock-in Fibroblasts Expressing hDAF on α-1,3-Galactosyltransferase (GGTA1) Gene Locus.

    PubMed

    Kim, Ji Woo; Kim, Hye-Min; Lee, Sang Mi; Kang, Man-Jong

    2012-10-01

    The Galactose-α1,3-galactose (α1,3Gal) epitope is responsible for hyperacute rejection in pig-to-human xenotransplantation. Human decay-accelerating factor (hDAF) is a cell surface regulatory protein that serves as a complement inhibitor to protect self cells from complement attack. The generation of α1,3-galactosyltransferase (GGTA1) knock-out pigs expressing DAF is a necessary step for their use as organ donors for humans. In this study, we established GGTA1 knock-out cell lines expressing DAF from pig ear fibroblasts for somatic cell nuclear transfer. hDAF expression was detected in hDAF knock-in heterozygous cells, but not in normal pig cells. Expression of the GGTA1 gene was lower in the knock-in heterozygous cell line compared to the normal pig cell. Knock-in heterozygous cells afforded more effective protection against cytotoxicity with human serum than with GGTA1 knock-out heterozygous and control cells. These cell lines may be used in the production of GGTA1 knock-out and DAF expression pigs for xenotransplantation.

  18. Simulation research on the effect of cooled EGR, supercharging and compression ratio on downsized SI engine knock

    NASA Astrophysics Data System (ADS)

    Shu, Gequn; Pan, Jiaying; Wei, Haiqiao; Shi, Ning

    2013-03-01

    Knock in spark-ignition(SI) engines severely limits engine performance and thermal efficiency. The researches on knock of downsized SI engine have mainly focused on structural design, performance optimization and advanced combustion modes, however there is little for simulation study on the effect of cooled exhaust gas recirculation(EGR) combined with downsizing technologies on SI engine performance. On the basis of mean pressure and oscillating pressure during combustion process, the effect of different levels of cooled EGR ratio, supercharging and compression ratio on engine dynamic and knock characteristic is researched with three-dimensional KIVA-3V program coupled with pressure wave equation. The cylinder pressure, combustion temperature, ignition delay timing, combustion duration, maximum mean pressure, and maximum oscillating pressure at different initial conditions are discussed and analyzed to investigate potential approaches to inhibiting engine knock while improving power output. The calculation results of the effect of just cooled EGR on knock characteristic show that appropriate levels of cooled EGR ratio can effectively suppress cylinder high-frequency pressure oscillations without obvious decrease in mean pressure. Analysis of the synergistic effect of cooled EGR, supercharging and compression ratio on knock characteristic indicates that under the condition of high supercharging and compression ratio, several times more cooled EGR ratio than that under the original condition is necessarily utilized to suppress knock occurrence effectively. The proposed method of synergistic effect of cooled EGR and downsizing technologies on knock characteristic, analyzed from the aspects of mean pressure and oscillating pressure, is an effective way to study downsized SI engine knock and provides knock inhibition approaches in practical engineering.

  19. Influence of Compression Ratio on High Load Performance and Knock Behavior for Gasoline Port-Fuel Injection, Natural Gas Direct Injection and Blended Operation in a Spark Ignition Engine

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

    Pamminger, Michael; Sevik, James; Scarcelli, Riccardo

    Natural Gas (NG) is an alternative fuel which has attracted a lot of attention recently, in particular in the US due to shale gas availability. The higher hydrogen-to-carbon (H/C) ratio, compared to gasoline, allows for decreasing carbon dioxide emissions throughout the entire engine map. Furthermore, the high knock resistance of NG allows increasing the efficiency at high engine loads compared to fuels with lower knock resistance. NG direct injection (DI) allows for fuel to be added after intake valve closing (IVC) resulting in an increase in power density compared to an injection before IVC. Steady-state engine tests were performed onmore » a single-cylinder research engine equipped with gasoline (E10) port-fuel injection (PFI) and NG DI to allow for in-cylinder blending of both fuels. Knock investigations were performed at two discrete compression ratios (CR), 10.5 and 12.5. Operating conditions span mid-load, wide-open-throttle and boosted conditions, depending on the knock response of the fuel blend. Blended operation was performed using E10 gasoline and NG. An additional gasoline type fuel (E85) with higher knock resistance than E10 was used as a high-octane reference fuel, since the octane rating of E10-NG fuel blends is unknown. Spark timing was varied at different loads under stoichiometric conditions in order to study the knock response as well as the effects on performance and efficiency. As anticipated, results suggest that the knock resistance can be increased significantly by increasing the NG amount. Comparing the engine operation with the least knock resistant fuel, E10 PFI, and the fuel blend with the highest knock resistance, 75% NG DI, shows an increase in indicated mean effective pressure of about 9 bar at CR 12.5. The usage of reference fuels with known knock characteristics allowed an assessment of knock characteristic of intermediate E10-NG blend levels. Mathematical correlations were developed allowing characterizing the occurrence of knocking combustion by using the Livengood-Wu knock integral. For most of the fueling strategies and operating conditions, the mathematical correlations show good agreement when compared to experimental data.« less

  20. Metal organic frameworks for the catalytic detoxification of chemical warfare nerve agents

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

    Hupp, Joseph T.; Farha, Omar K.; Katz, Michael J.

    A method of using a metal organic framework (MOF) comprising a metal ion and an at least bidendate organic ligand to catalytically detoxify chemical warfare nerve agents including exposing the metal-organic-framework (MOF) to the chemical warfare nerve agent and catalytically decomposing the nerve agent with the MOF.

  1. Impact of Alleged Russian Cyber Attacks

    DTIC Science & Technology

    2009-05-01

    security. 15. SUBJECT TERMS Cyber Security, Cyber Warfare , Estonia, Georgia, Russian Federation Cyber Strategy, Convention on Cybercrime, NATO Center...Federation ......................................................................................... 33  X.  The Future of Russian Cyber Warfare ................................................................... 39...Issue 15.09); Binoy Kampmark, Cyber Warfare Between Estonia And Russia, (Contemporary Review: Autumn, 2003), p 288-293; Jaak Aaviksoo, Address by the

  2. United States Coast Guard Antisubmarine Warfare (ASW) in the Maritime Defense Zone (MDZ) - A Strategic Approach

    DTIC Science & Technology

    1989-03-01

    RIC ILE COPY AIR WAR COLLGE REEAC R~pCR UNITED STATES COAST GUARD ANTISUBMARINE WARFARE (ASW) IN THE MARITIME DEFENSE ZONE (MDZ) -A STRATEGIC...going to perform in these MDZs. Those tasks identified so far include: port and coastal physical security & preventive safety, mine warfare

  3. Countering Gray-Zone Hybrid Threats: An Analysis of Russias New Generation Warfare and Implications for the US Army

    DTIC Science & Technology

    2016-10-18

    education ...Publication (JP) 1, Doctrine for the Armed Forces of the United States, there are two forms of warfare, traditional and irregular, and...combat mission in 2010. Looking at OIF, the US Army participated in both traditional and irregular warfare and the characterization of

  4. Maneuver Warfare revisited: a plea for balance

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

    Hamilton, M,R.

    1986-04-01

    This paper is a plea for balance in the current pursuit of understanding of the concept and the teaching of Maneuver Warfare. It specifically addresses the need for a more-complete analysis of some of the more-common historical examples commonly offered as examples of the supremecy of Maneuver Warfare. The paper in no way disagrees with the desirability of conducting the kinds of operations associated with the ill-defined concepts offered by advocates of Maneuver Warfare but suggests that the desirable results of historical battles may be too readily ascribed to the dynamic, offensive actions of the victorious side. Secondly, the papermore » points out the lack of utility and applicability of some common buzzwords being used in today's Army. Specifically assailed is the concept of turning within a decision cycle. The paper describes the reasons that this commonly used phrase has little applicability to ground warfare. Finally, the paper mentions the tendency for the Maneuver Warfare camp to cloud discussion of doctrine in a kind of intellectualism and elitism that has no use in forming the necessary consensus demanded by doctrine.« less

  5. The evolution of human warfare.

    PubMed

    Pitman, George R

    2011-01-01

    Here we propose a new theory for the origins and evolution of human warfare as a complex social phenomenon involving several behavioral traits, including aggression, risk taking, male bonding, ingroup altruism, outgroup xenophobia, dominance and subordination, and territoriality, all of which are encoded in the human genome. Among the family of great apes only chimpanzees and humans engage in war; consequently, warfare emerged in their immediate common ancestor that lived in patrilocal groups who fought one another for females. The reasons for warfare changed when the common ancestor females began to immigrate into the groups of their choice, and again, during the agricultural revolution.

  6. Optimized knock-in of point mutations in zebrafish using CRISPR/Cas9.

    PubMed

    Prykhozhij, Sergey V; Fuller, Charlotte; Steele, Shelby L; Veinotte, Chansey J; Razaghi, Babak; Robitaille, Johane M; McMaster, Christopher R; Shlien, Adam; Malkin, David; Berman, Jason N

    2018-06-14

    We have optimized point mutation knock-ins into zebrafish genomic sites using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 reagents and single-stranded oligodeoxynucleotides. The efficiency of knock-ins was assessed by a novel application of allele-specific polymerase chain reaction and confirmed by high-throughput sequencing. Anti-sense asymmetric oligo design was found to be the most successful optimization strategy. However, cut site proximity to the mutation and phosphorothioate oligo modifications also greatly improved knock-in efficiency. A previously unrecognized risk of off-target trans knock-ins was identified that we obviated through the development of a workflow for correct knock-in detection. Together these strategies greatly facilitate the study of human genetic diseases in zebrafish, with additional applicability to enhance CRISPR-based approaches in other animal model systems.

  7. A Photographic Study of Combustion and Knock in a Spark-Ignition Engine

    NASA Technical Reports Server (NTRS)

    Rothrock, A M; Spencer, R C

    1938-01-01

    Report presents the results of a photographic study of the combustion in a spark-ignition engine using both Schlieren and flame photographs taken at high rates of speed. Although shock waves are present after knock occurs, there was no evidence of any type of sonic or supersonic compression waves existing in the combustion gases prior to the occurrence of knock. Artificially induced shock waves in the engine did not in themselves cause knock. The photographs also indicate that, although auto-ignition ahead of the flame front may occur in conjunction with knock, it is not necessary for the occurrence of knock. There is also evidence that the reaction is not completed in the flame front but continues for some time after the flame front has passed through the charge.

  8. Computer-Assisted Performance Evaluation for Navy Anti-Air Warfare Training: Concepts, Methods, and Constraints.

    ERIC Educational Resources Information Center

    Chesler, David J.

    An improved general methodological approach for the development of computer-assisted evaluation of trainee performance in the computer-based simulation environment is formulated in this report. The report focuses on the Tactical Advanced Combat Direction and Electronic Warfare system (TACDEW) at the Fleet Anti-Air Warfare Training Center at San…

  9. Smart Climatology Applications for Undersea Warfare

    DTIC Science & Technology

    2008-09-01

    Comparisons of these climatologies with existing Navy climatologies based on the Generalized Digital Environmental Model ( GDEM ) reveal differences in sonic...undersea warfare. 15. NUMBER OF PAGES 117 14. SUBJECT TERMS antisubmarine warfare, climate variations, climatology, GDEM , ocean, re...climatologies based on the Generalized Digital Environmental Model ( GDEM ) to our smart ocean climatologies reveal a number of differences. The

  10. DETERMINING ELECTRONIC AND CYBER ATTACK RISK LEVEL FOR UNMANNED AIRCRAFT IN A CONTESTED ENVIRONMENT

    DTIC Science & Technology

    2016-08-01

    AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY DETERMINING ELECTRONIC AND CYBER ATTACK RISK LEVEL FOR UNMANNED AIRCRAFT IN A CONTESTED ENVIRONMENT...iii ABSTRACT During operations in a contested air environment, adversary electronic warfare (EW) and cyber-attack capability will pose a high...10 Russian Federation Electronic Warfare Systems ...................................................12 Chinese Cyber Warfare Program

  11. Manufacturing Technology and Industrial Modernization Incentive Programs

    DTIC Science & Technology

    1991-07-01

    report are those of the contractors and should not be Interpreted as representing the official policies, either expressed or Impli.d, of tte Naval Ocean...Countaermeaue * Undersea countermeasures. special warfare, amphibious warfare. tamc mine countermeasures, and diving Dkected energy . Naval Surface Warfare...Insensitie highly energetic materials -Command control, commiunications, ocean surveillance, surface- and air-launched undersea weapons, and submarine arctic

  12. The Handicap Principle, Strategic Information Warfare and the Paradox of Asymmetry

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

    Ma, Zhanshan; Sheldon, Frederick T; Krings, Axel

    2010-01-01

    The term asymmetric threat (or warfare) often refers to tactics utilized by countries, terrorist groups, or individuals to carry out attacks on a superior opponent while trying to avoid direct confrontation. Information warfare is sometimes also referred to as a type of asymmetric warfare perhaps due to its asymmetry in terms of cost and efficacy. Obviously, there are differences and commonalities between two types of asymmetric warfare. One major difference lies in the goal to avoid confrontation and one commonality is the asymmetry. Regardless, the unique properties surrounding asymmetric warfare warrant a strategic-level study. Despite enormous studies conducted in themore » last decade, a consensus on the strategy a nation state should take to deal with asymmetric threat seems still intriguing. In this article, we try to shed some light on the issue from the handicap principle in the context of information warfare. The Handicap principle was first proposed by Zahavi (1975) to explain the honesty or reliability of animal communication signals. He argued that in a signaling system such as one used in mate selection, a superior male is able to signal with a highly developed "handicap" to demonstrate its quality, and the handicap serves "as a kind of (quality) test imposed on the individual" (Zahavi 1975, Searcy and Nowicki 2005). The underlying thread that inspires us for the attempt to establish a connection between the two apparently unrelated areas is the observation that competition, communication and cooperation (3C), which are three fundamental processes in nature and against which natural selection optimize living things, may also make sense in human society. Furthermore, any communication networks, whether it is biological networks (such as animal communication networks) or computer networks (such as the Internet) must be reasonably reliable (honest in the case of animal signaling) to fulfill its missions for transmitting and receiving messages. The strategic goal of information warfare is then to destroy or defend the reliability (honesty) of communication networks. The handicap principle that governs the reliability (honesty) of animal communication networks can be considered as the nature s version of information warfare strategy because it is a product of natural selection. What is particularly interesting is to transfer the evolutionary game theory models [e.g., Sir Philip Sydney (SPS) game] for the handicap principle to the study of information warfare. In a broad perspective, we realize that the handicap principle may actually contradict the principle of asymmetry in asymmetric warfare. Anyway, not every species of animals has evolved expensive signaling equipments like male peacocks (whose exaggerated train is an example of handicap). Furthermore, the handicap principle is not only about communication, and it also embodies the spirits of cooperation and competition. In human societies, communication modulates cooperation and competition; so does in animal communication networks. Therefore, to evolve or maintain a sustainable communication network, the proper strategy should be to balance (modulate) the cooperation and competition with communication tools (information warfare tools), which is perhaps in contradiction with the asymmetric strategy. There might be a paradox in the strategy of asymmetric warfare, and whether or not information warfare can be used as an asymmetric tool is still an open question.« less

  13. Establishment of expanded and streamlined pipeline of PITCh knock-in – a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO

    PubMed Central

    Nakamae, Kazuki; Nishimura, Yuki; Takenaga, Mitsumasa; Sakamoto, Naoaki; Ide, Hiroshi; Sakuma, Tetsushi; Yamamoto, Takashi

    2017-01-01

    ABSTRACT The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in. Here, we established a streamlined pipeline to design and perform PITCh knock-in to further expand the availability of this method by creating web-based design software, PITCh designer (http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html), as well as presenting an experimental example of versatile gene cassette knock-in. PITCh designer can automatically design not only the appropriate microhomologies but also the primers to construct locus-specific donor vectors for PITCh knock-in. By using our newly established pipeline, a reporter cell line for monitoring endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO) cell line can be produced systematically. Using these new variations of PITCh, an exogenous promoter-driven gene cassette expressing fluorescent protein gene and drug resistance gene can be integrated into a safe harbor or a specific gene locus to create transgenic reporter cells (PITCh-TG) or knockout cells with reporter knock-in (PITCh-KIKO), respectively. PMID:28453368

  14. Establishment of expanded and streamlined pipeline of PITCh knock-in - a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO.

    PubMed

    Nakamae, Kazuki; Nishimura, Yuki; Takenaga, Mitsumasa; Nakade, Shota; Sakamoto, Naoaki; Ide, Hiroshi; Sakuma, Tetsushi; Yamamoto, Takashi

    2017-05-04

    The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in. Here, we established a streamlined pipeline to design and perform PITCh knock-in to further expand the availability of this method by creating web-based design software, PITCh designer ( http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html ), as well as presenting an experimental example of versatile gene cassette knock-in. PITCh designer can automatically design not only the appropriate microhomologies but also the primers to construct locus-specific donor vectors for PITCh knock-in. By using our newly established pipeline, a reporter cell line for monitoring endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO) cell line can be produced systematically. Using these new variations of PITCh, an exogenous promoter-driven gene cassette expressing fluorescent protein gene and drug resistance gene can be integrated into a safe harbor or a specific gene locus to create transgenic reporter cells (PITCh-TG) or knockout cells with reporter knock-in (PITCh-KIKO), respectively.

  15. Bowlegs and Knock-Knees

    MedlinePlus

    ... Español Text Size Email Print Share Bowlegs and Knock-Knees Page Content Article Body Toddlers’ legs often ... about two years old, then they’ll look knock-kneed until they are about six years of ...

  16. Objective evaluation of the knocking sound of a diesel engine considering the temporal and frequency masking effect simultaneously

    NASA Astrophysics Data System (ADS)

    Yun, Dong-Un; Lee, Sang-Kwon

    2017-06-01

    In this paper, we present a novel method for an objective evaluation of knocking noise emitted by diesel engines based on the temporal and frequency masking theory. The knocking sound of a diesel engine is a vibro-acoustic sound correlated with the high-frequency resonances of the engine structure and a periodic impulsive sound with amplitude modulation. Its period is related to the engine speed and includes specific frequency bands related to the resonances of the engine structure. A knocking sound with the characteristics of a high-frequency impulsive wave can be masked by low-frequency sounds correlated with the harmonics of the firing frequency and broadband noise. The degree of modulation of the knocking sound signal was used for such objective evaluations in previous studies, without considering the masking effect. However, the frequency masking effect must be considered for the objective evaluation of the knocking sound. In addition to the frequency masking effect, the temporal masking effect occurs because the period of the knocking sound changes according to the engine speed. Therefore, an evaluation method considering the temporal and frequency masking effect is required to analyze the knocking sound objectively. In this study, an objective evaluation method considering the masking effect was developed based on the masking theory of sound and signal processing techniques. The method was applied successfully for the objective evaluation of the knocking sound of a diesel engine.

  17. RPA Field Simulations:Dilemma Training for Legal and Ethical Decision Making

    DTIC Science & Technology

    2015-11-07

    Simulation  Two phases in RPA Field Simulation – classroom phase and field phase  Purpose: link theoretical understanding/ moral reasoning with...rapid, informed decision-making/ moral behavior IRREGULAR WARFARE  U.S. dominates conventional warfare, but irregular warfare falls under Things...aspects: Mental simulation of action Modify Implement Will it work? MORAL REASONING/BEHAVIOR Military-Leader Responsibility requires

  18. Antidotes and treatments for chemical warfare/terrorism agents: an evidence-based review.

    PubMed

    Rodgers, G C; Condurache, C T

    2010-09-01

    This article reviews the evidence supporting the efficacy of antidotes used or recommended for the potential chemical warfare agents of most concern. Chemical warfare agents considered include cyanide, vesicants, pulmonary irritants such as chlorine and phosgene, and nerve agents. The strength of evidence for most antidotes is weak, highlighting the need for additional research in this area.

  19. Navy Operational Planner: Anti-Submarine Warfare with Time-Dependent Performance

    DTIC Science & Technology

    2017-09-01

    PLANNER: ANTI-SUBMARINE WARFARE WITH TIME -DEPENDENT PERFORMANCE by Anthony M. Baldessari September 2017 Thesis Advisor: W. Matthew...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instruction, searching...REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE NAVY OPERATIONAL PLANNER: ANTI-SUBMARINE WARFARE WITH TIME -DEPENDENT

  20. Pacific Missile Range Facility Intercept Test Support. Environmental Assessment/Overseas Environmental Assessment

    DTIC Science & Technology

    2010-04-01

    frequency monitoring, target control, and electronic warfare and networked operations. Kokee supports tracking radars, telemetry, communications, and...owned island of Niihau provide support and sites for a remotely operated PMRF surveillance radar, a Test Vehicle Recovery Site, an electronic warfare...site, multiple electronic warfare portable simulator sites, a marker for aircraft mining exercise programs, and a helicopter terrain-following

  1. Chemical Weapons Disposal: Improvements Needed in Program Accountability and Financial Management

    DTIC Science & Technology

    2000-05-01

    United States General Accounting Office PAQ Report to Congressional Committees May 2000 CHEMICAL WEAPONS DISPOSAL Improvements Needed in Program...warfare materiel, and former production facilities and identify and locate buried chemical warfare materiel. Alternative Technologies and Approaches...production facilities, and buried chemical warfare materiel. These items are described in table 1. Table 1: Nonstockpile Chemical Materiel Category

  2. Homeland Biological Warfare Consequence Management: Capabilities and Needs Assessment

    DTIC Science & Technology

    2001-04-01

    AU/ACSC/105/2001-04 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY HOMELAND BIOLOGICAL WARFARE CONSEQUENCE MANAGEMENT: CAPABILITIES AND NEEDS...Dates Covered (from... to) - Title and Subtitle Homeland biological Warfare Consequence Management: Capabilities and Needs Assessment Contract...FEMA, DoJ, DoD, HHS, etc.) make a comprehensive, organized solution to the problem difficult. Focusing on the consequence management functions

  3. Chemical warfare agents.

    PubMed

    Kuca, Kamil; Pohanka, Miroslav

    2010-01-01

    Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

  4. Ketone Body Metabolic Enzyme OXCT1 Regulates Prostate Cancer Chemoresistance

    DTIC Science & Technology

    2015-12-01

    increased ADP/ATP, NAD +/NADH and oxygen consumption in docetaxel treated cells compared to control knock down cells, therefore induced metabolic...substrate for mitochondrial oxidative phosphorylation and ATP biosynthesis. Next, we examined NAD +/NADH levels in OXC1 knock down prostate cancer cells...The results showed that after docetaxel treatment, NAD + level was significantly increased in OXCT1 knock down cells compared to control knock down

  5. Knock probability estimation through an in-cylinder temperature model with exogenous noise

    NASA Astrophysics Data System (ADS)

    Bares, P.; Selmanaj, D.; Guardiola, C.; Onder, C.

    2018-01-01

    This paper presents a new knock model which combines a deterministic knock model based on the in-cylinder temperature and an exogenous noise disturbing this temperature. The autoignition of the end-gas is modelled by an Arrhenius-like function and the knock probability is estimated by propagating a virtual error probability distribution. Results show that the random nature of knock can be explained by uncertainties at the in-cylinder temperature estimation. The model only has one parameter for calibration and thus can be easily adapted online. In order to reduce the measurement uncertainties associated with the air mass flow sensor, the trapped mass is derived from the in-cylinder pressure resonance, which improves the knock probability estimation and reduces the number of sensors needed for the model. A four stroke SI engine was used for model validation. By varying the intake temperature, the engine speed, the injected fuel mass, and the spark advance, specific tests were conducted, which furnished data with various knock intensities and probabilities. The new model is able to predict the knock probability within a sufficient range at various operating conditions. The trapped mass obtained by the acoustical model was compared in steady conditions by using a fuel balance and a lambda sensor and differences below 1 % were found.

  6. Development of versatile non-homologous end joining-based knock-in module for genome editing.

    PubMed

    Sawatsubashi, Shun; Joko, Yudai; Fukumoto, Seiji; Matsumoto, Toshio; Sugano, Shigeo S

    2018-01-12

    CRISPR/Cas9-based genome editing has dramatically accelerated genome engineering. An important aspect of genome engineering is efficient knock-in technology. For improved knock-in efficiency, the non-homologous end joining (NHEJ) repair pathway has been used over the homology-dependent repair pathway, but there remains a need to reduce the complexity of the preparation of donor vectors. We developed the versatile NHEJ-based knock-in module for genome editing (VIKING). Using the consensus sequence of the time-honored pUC vector to cut donor vectors, any vector with a pUC backbone could be used as the donor vector without customization. Conditions required to minimize random integration rates of the donor vector were also investigated. We attempted to isolate null lines of the VDR gene in human HaCaT keratinocytes using knock-in/knock-out with a selection marker cassette, and found 75% of clones isolated were successfully knocked-in. Although HaCaT cells have hypotetraploid genome composition, the results suggest multiple clones have VDR null phenotypes. VIKING modules enabled highly efficient knock-in of any vectors harboring pUC vectors. Users now can insert various existing vectors into an arbitrary locus in the genome. VIKING will contribute to low-cost genome engineering.

  7. Tracking of Pacific walruses in the Chukchi Sea using a single hydrophone.

    PubMed

    Mouy, Xavier; Hannay, David; Zykov, Mikhail; Martin, Bruce

    2012-02-01

    The vocal repertoire of Pacific walruses includes underwater sound pulses referred to as knocks and bell-like calls. An extended acoustic monitoring program was performed in summer 2007 over a large region of the eastern Chukchi Sea using autonomous seabed-mounted acoustic recorders. Walrus knocks were identified in many of the recordings and most of these sounds included multiple bottom and surface reflected signals. This paper investigates the use of a localization technique based on relative multipath arrival times (RMATs) for potential behavior studies. First, knocks are detected using a semi-automated kurtosis-based algorithm. Then RMATs are matched to values predicted by a ray-tracing model. Walrus tracks with vertical and horizontal movements were obtained. The tracks included repeated dives between 4.0 m and 15.5 m depth and a deep dive to the sea bottom (53 m). Depths at which bell-like sounds are produced, average knock production rate and source levels estimates of the knocks were determined. Bell sounds were produced at all depths throughout the dives. Average knock production rates varied from 59 to 75 knocks/min. Average source level of the knocks was estimated to 177.6 ± 7.5 dB re 1 μPa peak @ 1 m. © 2012 Acoustical Society of America

  8. Forms of war.

    PubMed

    Vogel, H; Bartelt, D

    2007-08-01

    Under war conditions, employed weapons can be identified on radiographs obtained in X-ray diagnostic. The analysis of such X-ray films allows concluding that there are additional information about the conditions of transport and treatment; it shall be shown that there are X-ray findings which are typical and characteristic for certain forms of warfare. The radiograms have been collected during thirty years; they come from hospitals, where war casualties had been treated, and personal collections. The material is selected, because in war X-ray diagnostic will be limited and the interest of the opposing parties influence the access to the material; furthermore the possibilities to publish or to communicate facts and thoughts are different. Citizens of the USA, GB, France, or Israel will have easier access to journals than those of Vietnam, Chad, and Zimbabwe. Under war conditions, poor countries, like North Vietnam may develop own concepts of medical care. There are X-ray findings which are typical or even characteristic for air warfare, guerrilla warfare, gas war, desert warfare, conventional warfare, and annihilation warfare, and city guerrilla warfare/civil war. The examples demonstrate that weapons and the conditions of transport and treatment can be recognized by X-ray findings. The radiogram can be read like a document. In War, there are differences between a treatment and imaging diagnostic in countries, which control the air space and in those who do not. Medical care of the poor, i.e. in countries (in general those opposing the western nations) will hardly be published, and poverty has no advocate.

  9. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency.

    PubMed

    Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y Eugene; Zhang, Jifeng

    2016-01-28

    Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.

  10. Sink or Swim: The Marine Corps Capacity to Conduct a Marine Expeditionary Brigade Amphibious Assault using Expeditionary Maneuver Warfare

    DTIC Science & Technology

    2010-03-01

    Expeditionary Maneuver Warfare? This study addresses the equipment issues surrounding the Marine expeditionary brigade ’s’ ability to conduct an amphibious...addresses the equipment issues surrounding the expeditionary brigade’s ability to conduct an amphibious assault under expeditionary maneuver warfare in...1 Issues and Elements of the Modern-Day MEB Assault .................................................................. 2 The Marine Corps

  11. User Guide for Unmanned Aerial System (UAS) Operations on the National Ranges

    DTIC Science & Technology

    2007-11-01

    WARFARE CENTER WEAPONS DIVISION, PT. MUGU NAVAL AIR WARFARE CENTER WEAPONS DIVISION, CHINA LAKE NAVAL AIR WARFARE CENTER AIRCRAFT DIVISION, PATUXENT...with IFR Instrument Flight Rules MRTFB Major Range and Test Facility Base NAS National Airspace System NM nautical mile NTIA National...sectional charts, Instrument Flight Rules ( IFR ) enroute charts, and terminal area charts. The floor and ceiling, operating hours, and controlling

  12. Coast Guard SOF

    DTIC Science & Technology

    2006-02-01

    Forces units into known Viet Cong (VC) strongholds, participating in direct action raids on VC junk bases, conducting psychological operations, and...and General McClure established the Army’s Psychological Warfare Cen- ter and 10th Special Forces Group in 1952.62 President Kennedy’s interest in...counterinsurgency warfare paved the way for the “Green Beret,” for which Army Special Forces renamed the Psychological Warfare Center the JFK Special

  13. Marine recreation and public health microbiology: Quest for the ideal indicator

    USGS Publications Warehouse

    Griffin, Dale W.; Lipp, Erin K.; McLaughlin, Molly R.; Rose, Joan B.

    2001-01-01

    Four-fifths of the population of the United States live in close proximity to the oceans or Great Lakes, and approximately 100 million Americans use the marine environment for recreation each year (Thurman 1994). Consequently, contamination of lakes, rivers, and coastal waters raises significant public health issues. Among the leading sources of chemical and biological contamination of these waters and associated beaches are sewer systems, septic tanks, stormwater runoff, industrial wastes, wastewater injection wells, cesspits, animal wastes, commercial and private boat wastes, and human recreation. In 1997, 649 beach closings or advisories were caused by sewage spills and overflows (NRDC 1998). In Florida alone, approximately 500 million gallons of sewage were released along the coast each year during the late 1980s (Neshyba 1987). Thus one of the primary concerns in public health is the risk that humans using the marine environment for recreational activities will encounter microbial pathogens.

  14. Marine recreation and public health microbiology: quest for the ideal indicator

    USGS Publications Warehouse

    Griffin, Dale W.; Lipp, Erin K.; McLaughlin, Molly R.; Rose, Joan B.

    2001-01-01

    Four-fifths of the population of the United States live in close proximity to the oceans or Great Lakes, and approximately 100 million Americans use the marine environment for recreation each year (Thurman 1994). Consequently, contamination of lakes, rivers, and coastal waters raises significant public health issues. Among the leading sources of chemical and biological contamination of these waters and associated beaches are sewer systems, septic tanks, stormwater runoff, industrial wastes, wastewater injection wells, cesspits, animal wastes, commercial and private boat wastes, and human recreation. In 1997, 649 beach closings or advisories were caused by sewage spills and overflows (NRDC 1998). In Florida alone, approximately 500 million gallons of sewage were released along the coast each year during the late 1980s (Neshyba 1987). Thus one of the primary concerns in public health is the risk that humans using the marine environment for recreational activities will encounter microbial pathogens.

  15. Military medicine and the ethics of war: British colonial warfare during the Seven Years War (1756-63).

    PubMed

    Charters, Erica

    2010-01-01

    This article examines 18th-century European warfare, tracing the first formal codifications of conventions of war, frequently introduced by military physicians and initially regarding the treatment of the sick and wounded. It outlines to what extent these conventions were followed in practice, particularly in the challenging environment of American irregular warfare, with a focus on the most well-known incident of "biological warfare" in the period: the deliberate spread of smallpox by British officers among Amerindians in 1763. More broadly, it demonstrates that the history of military medicine provides a fruitful method with which to uncover assumptions about the ethics of war.

  16. Simulated experiment for elimination of chemical and biological warfare agents by making use of microwave plasma torch

    NASA Astrophysics Data System (ADS)

    Hong, Yong C.; Kim, Jeong H.; Uhm, Han S.

    2004-02-01

    The threat of chemical and biological warfare agents in a domestic terrorist attack and in military conflict is increasing worldwide. Elimination and decontamination of chemical and biological warfare (CBW) agents are immediately required after such an attack. Simulated experiment for elimination of CBW agents by making use of atmospheric-pressure microwave plasma torches is carried out. Elimination of biological warfare agents indicated by the vitrification or burnout of sewage sludge powders and decomposition of toluene gas as a chemical agent stimulant are presented. A detailed characterization for the elimination of the simulant chemicals using Fourier transform infrared and gas chromatography is also presented.

  17. About the bears and the bees: Adaptive responses to asymmetric warfare

    NASA Astrophysics Data System (ADS)

    Ryan, Alex

    Conventional military forces are organised to generate large scale effects against similarly structured adversaries. Asymmetric warfare is a 'game' between a conventional military force and a weaker adversary that is unable to match the scale of effects of the conventional force. In asymmetric warfare, an insurgents' strategy can be understood using a multi-scale perspective: by generating and exploiting fine scale complexity, insurgents prevent the conventional force from acting at the scale they are designed for. This paper presents a complex systems approach to the problem of asymmetric warfare, which shows how future force structures can be designed to adapt to environmental complexity at multiple scales and achieve full spectrum dominance.

  18. About the bears and the bees: Adaptive responses to asymmetric warfare

    NASA Astrophysics Data System (ADS)

    Ryan, Alex

    Conventional military forces are organised to generate large scale effects against similarly structured adversaries. Asymmetric warfare is a `game' between a conventional military force and a weaker adversary that is unable to match the scale of effects of the conventional force. In asymmetric warfare, an insurgents' strategy can be understood using a multi-scale perspective: by generating and exploiting fine scale complexity, insurgents prevent the conventional force from acting at the scale they are designed for. This paper presents a complex systems approach to the problem of asymmetric warfare, which shows how future force structures can be designed to adapt to environmental complexity at multiple scales and achieve full spectrum dominance.

  19. 'Knock, and it shall be opened': knocking out and knocking in to reveal mechanisms of disease and novel therapies.

    PubMed

    Hacking, Douglas F

    2008-12-01

    Recent significant advances in molecular biology have generated genetically modified bacteria, yeast, nematodes, fruit flies, and fish. However, it is the genetic modification of mammalian model organisms, particularly the mouse, that has the greatest potential to shed light on human development, physiology and pathology in ways that have significant implications for neonatal and paediatric clinical practice. Here, we review some of the techniques for knocking out (inactivating), mutating and knocking in (inserting) selected genes that are important to neonatology and show how this research will lead both to a better understanding of disease and to novel therapies for infants and children.

  20. Hige Compression Ratio Turbo Gasoline Engine Operation Using Alcohol Enhancement

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

    Heywood, John; Jo, Young Suk; Lewis, Raymond

    The overall objective of this project was to quantify the potential for improving the performance and efficiency of gasoline engine technology by use of alcohols to suppress knock. Knock-free operation is obtained by direct injection of a second “anti-knock” fuel such as ethanol, which suppresses knock when, with gasoline fuel, knock would occur. Suppressing knock enables increased turbocharging, engine downsizing, and use of higher compression ratios throughout the engine’s operating map. This project combined engine testing and simulation to define knock onset conditions, with different mixtures of gasoline and alcohol, and with this information quantify the potential for improving themore » efficiency of turbocharged gasoline spark-ignition engines, and the on-vehicle fuel consumption reductions that could then be realized. The more focused objectives of this project were therefore to: Determine engine efficiency with aggressive turbocharging and downsizing and high compression ratio (up to a compression ratio of 13.5:1) over the engine’s operating range; Determine the knock limits of a turbocharged and downsized engine as a function of engine speed and load; Determine the amount of the knock-suppressing alcohol fuel consumed, through the use of various alcohol-gasoline and alcohol-water gasoline blends, for different driving cycles, relative to the gasoline consumed; Determine implications of using alcohol-boosted engines, with their higher efficiency operation, in both light-duty and medium-duty vehicle sectors.« less

  1. Design and implementation of intelligent electronic warfare decision making algorithm

    NASA Astrophysics Data System (ADS)

    Peng, Hsin-Hsien; Chen, Chang-Kuo; Hsueh, Chi-Shun

    2017-05-01

    Electromagnetic signals and the requirements of timely response have been a rapid growth in modern electronic warfare. Although jammers are limited resources, it is possible to achieve the best electronic warfare efficiency by tactical decisions. This paper proposes the intelligent electronic warfare decision support system. In this work, we develop a novel hybrid algorithm, Digital Pheromone Particle Swarm Optimization, based on Particle Swarm Optimization (PSO), Ant Colony Optimization (ACO) and Shuffled Frog Leaping Algorithm (SFLA). We use PSO to solve the problem and combine the concept of pheromones in ACO to accumulate more useful information in spatial solving process and speed up finding the optimal solution. The proposed algorithm finds the optimal solution in reasonable computation time by using the method of matrix conversion in SFLA. The results indicated that jammer allocation was more effective. The system based on the hybrid algorithm provides electronic warfare commanders with critical information to assist commanders in effectively managing the complex electromagnetic battlefield.

  2. Chemical warfare, past and future. Study project

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

    Tzihor, A.

    1992-05-15

    World War I was arena for the first use of chemical warfare. The enormous tactical success brought about by this first time use of chemical weapons caused the continued development of more sophisticated tactics and weapons in this category of unconventional warfare. This phenomenon has carried through to today. However, at present, because of technological developments, the global economic situation, and political factors, coupled with the inability of the western world to control the proliferation of chemical weapons, a situation weapon of mass destruction. Recent use by Iraq against Kurdish civilian indicates that chemical warfare is no longer limited tomore » the battlefield. The western nations have a need to understand the risk. This paper conducts an analysis of past lessons and the factors which will affect the use of chemical warfare in the future. From this analysis, the paper reaches conclusions concerning the significant threat chemical weapons pose for the entire world in the not too distant future.« less

  3. Efficacy Evaluation of Current and Future Naval Mine Warfare Neutralization Method

    DTIC Science & Technology

    2016-12-01

    Distribution is unlimited. EFFICACY EVALUATION OF CURRENT AND FUTURE NAVAL MINE WARFARE NEUTRALIZATION METHOD by Team MIW Cohort SE311-152O...EFFICACY EVALUATION OF CURRENT AND FUTURE NAVAL MINE WARFARE NEUTRALIZATION METHOD 5. FUNDING NUMBERS 6. AUTHOR (S) Team MIW, Systems Engineering...NEUTRALIZATION METHOD Team MIW, Systems Engineering Cohort SE311-152O Submitted in partial fulfillment of the requirements for the degrees of

  4. Computer Network Attack: An Operational Tool?

    DTIC Science & Technology

    2003-01-17

    Spectrum of Conflict, Cyber Warfare , Preemptive Strike, Effects Based Targeting. 15. Abstract: Computer Network Attack (CNA) is defined as...great deal of attention as the world’s capabilities in cyber - warfare grow. 11 Although addressing the wide ranging legal aspects of CNA is beyond the...the notion of cyber - warfare has not yet developed to the point that international norms have been established.15 These norms will be developed in

  5. The U.S. Needs International Cyber Treaties

    DTIC Science & Technology

    2010-03-01

    formed to deal with issues surrounding cyber warfare . However, no major treaties between nations exist regarding this form of combat. Examining...the history of cyber warfare , the inadequate international response, the obstacles to international agreement, and poor U.S. readiness demonstrates...the current need for the U.S. to lead the effort to codify treaties. First, a brief history of cyber warfare helps to shed light on the international

  6. Cyber Capabilities for Global Strike in 2035

    DTIC Science & Technology

    2012-02-15

    operations force, by treating cyber warfare capabilities in the same manner as it treats its other weapon systems. It argues that despite preconceptions of...As such, while automation is required, cyber warfare will be much more manpower intensive than is currently understood, and will require a force that...constantly keeping cyber warfare capabilities in pace with the technologies of the environment.This paper reaches these conclusions by first providing a

  7. Cyber Capabilities for Global Strike in 2035

    DTIC Science & Technology

    2012-02-15

    operations force, by treating cyber warfare capabilities in the same manner as it treats its other weapon systems. It argues that despite preconceptions of...As such, while automation is required, cyber warfare will be much more manpower intensive than is currently understood, and will require a force...constantly keeping cyber warfare capabilities in pace with the technologies of the environment. This paper reaches these conclusions by first providing a

  8. Integrating Defense, Diplomacy, and Development (3 D) in the Naval Special Warfare Operator

    DTIC Science & Technology

    2010-12-01

    DIPLOMACY, AND DEVELOPMENT (3 D) IN THE NAVAL SPECIAL WARFARE OPERATOR by William Fiack William Roberts Tim Sulick December 2010...Development (3 D) in the Naval Special Warfare Operator 6. AUTHOR(S) William Fiack, William Roberts, Timothy Sulick 5. FUNDING NUMBERS 7. PERFORMING...MONITORING AGENCY NAME(S) AND ADDRESS(ES) N/A 10. SPONSORING/MONITORING AGENCY REPORT NUMBER 11. SUPPLEMENTARY NOTES The views expressed in

  9. Chemical Warfare: Many Unanswered Questions.

    DTIC Science & Technology

    1983-04-29

    of Defense DSB Defense Science Board GAO U.S. General Accounting Office IDA Institute for Defense Analyses JCS Joint Chiefs of Staff SIPRI Stockholm...Defense Science Board in 1980, DOD specifically asked it to review intelligence data on chemical warfare, and DSB’s 1981 report accordingly presents its...Defense Science Board report suggests, however, that its com- - ments are based on a composite of intelligence information on Soviet chemical warfare

  10. The Airpower Advantage in Future Warfare: The Need for Strategy

    DTIC Science & Technology

    2007-12-01

    political situation which gener- ates war and therefore warfare, foreign and domestic; the social- cultural ideologies , attitudes, habits of mind, and...the ideological rivalries that contributed so powerfully to interstate rivalry, ambition, and anxiety are all but defunct, save only in two respects...instead to fit that still improving competence into a truly holistic approach to warfare. That approach, in its turn, needs to fit into a genu - inely

  11. Calming the Churn: Resolving the Dilemma of Rotational Warfare in Counterinsurgency

    DTIC Science & Technology

    2013-12-01

    warfare in counterinsurgency Publisher Monterey, California: Naval Postgraduate School Issue Date 2013-12 URL http://hdl.handle.net/10945/38873... TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE CALMING THE CHURN: RESOLVING THE DILEMMA OF ROTATIONAL WARFARE IN COUNTERINSURGENCY...operations, however, would not last and, after only a year, MacArthur was sent to other duties thanks to personality conflicts with Taft. His replacement

  12. A Game Theoretic Model Of Strategic Conflict In Cyberspace

    DTIC Science & Technology

    2012-01-01

    EXECUTIVE SUMMARY Conflict in cyberspace is difficult to analyze; methods developed for other dimensions of conflict, such as land warfare , war at sea...and missile warfare , do not adequately address cyber conflict. A characteristic that distinguishes cyber conflict is that actors do not know the...strategic and policy guidance. To analyze the strategic decisions involved in cyber conflict, we use a game theoretic framework—we view cyber warfare as a

  13. US Army Special Warfare. Its Origins: Psychological and Unconventional Warfare, 1941-1952

    DTIC Science & Technology

    1982-01-01

    remained a fundamental military organization. Simultaneously, however, a few thinkers began to consider the possibility of forces capable of operating at...guerrilla warfare. He had been impressed as well by the British system of intelligence and counter- intelligence, as conducted by their Secret Intelligence...highly respected Columbia Broadcasting System reporter like Elmer Davis as its first director. Although most existing information services were trans

  14. Technology Strategy Integration

    DTIC Science & Technology

    2012-06-01

    History of Weaponry and Warfare from Prehistory to the Present (New York: Free Press : Distributed by Simon & Schuster, 2002), 191. 57 Robert L... Prehistory to the Present, 182. 60 O’Connell and Batchelor, Soul of the Sword: An Illustrated History of Weaponry and Warfare from Prehistory to the...Illustrated History of Weaponry and Warfare from Prehistory to the Present, 390. 62 O’Connell and Batchelor, Soul of the Sword: An Illustrated

  15. Sub state Unconventional Warfare: Expanding United States Military Political Options

    DTIC Science & Technology

    2016-05-26

    phases due to competing incumbent efforts. Giap was influenced in his understanding of revolutionary war phasing by Sun Tzu who Giap called one of his...Challenge of Unconventional Warfare. London: Routledge, 2012. Ames, Roger T. Sun - Tzu The Art of Warfare. New York: Ballantine Books, 1993. Amin, Samir...Guerrilla: Insurgents, Patriots, and Terrorists from Sun Tzu to Bin Laden. London: Brassey’s Inc., 2004. Rosenau, William, Subversion and Insurgency

  16. The role of the sand in chemical warfare agent exposure among Persian Gulf War veterans: Al Eskan disease and "dirty dust".

    PubMed

    Korényi-Both, A L; Svéd, L; Korényi-Both, G E; Juncer, D J; Korényi-Both, A L; Székely, A

    2000-05-01

    The purpose of this paper is to inquire into the relationship between Al Eskan disease and the probable exposure to chemical warfare agents by Persian Gulf War veterans. Al Eskan disease, first reported in 1991, compromises the body's immunological defense and is a result of the pathogenic properties of the extremely fine, dusty sand located in the central and eastern region of the Arabian peninsula. The disease manifests with localized expression of multisystem disorder. Signs and symptoms of Al Eskan disease have been termed by the news media "Persian Gulf syndrome." The dust becomes a warfare agent when toxic chemicals are microimpregnated into inert particles. The "dirty dust" concept, that the toxicity of an agent could be enhanced by absorption into inactive particles, dates from World War I. A growing body of evidence shows that coalition forces have encountered Iraqi chemical warfare in the theater of operation/Persian Gulf War to a much greater extent than early U.S. Department of Defense information had indicated. Veterans of that war were exposed to chemical warfare agents in the form of direct (deliberate) attacks by chemical weapons, such as missiles and mines, and indirect (accidental) contamination from demolished munition production plants and storage areas, or otherwise. We conclude that the microimpregnated sand particles in the theater of operation/Persian Gulf War depleted the immune system and simultaneously acted as vehicles for low-intensity exposure to chemical warfare agents and had a modifying-intensifying effect on the toxicity of exposed individuals. We recommend recognition of a new term, "dirty sand," as a subcategory of dirty dust/dusty chemical warfare agents. Our ongoing research efforts to investigate the health impact of chemical warfare agent exposure among Persian Gulf War veterans suggest that Al Eskan disease is a plausible and preeminent explanation for the preponderance of Persian Gulf War illnesses.

  17. Determination of knock characteristics in spark ignition engines: an approach based on ensemble empirical mode decomposition

    NASA Astrophysics Data System (ADS)

    Li, Ning; Yang, Jianguo; Zhou, Rui; Liang, Caiping

    2016-04-01

    Knock is one of the major constraints to improve the performance and thermal efficiency of spark ignition (SI) engines. It can also result in severe permanent engine damage under certain operating conditions. Based on the ensemble empirical mode decomposition (EEMD), this paper proposes a new approach to determine the knock characteristics in SI engines. By adding a uniformly distributed and finite white Gaussian noise, the EEMD can preserve signal continuity in different scales and therefore alleviates the mode-mixing problem occurring in the classic empirical mode decomposition (EMD). The feasibilities of applying the EEMD to detect the knock signatures of a test SI engine via the pressure signal measured from combustion chamber and the vibration signal measured from cylinder head are investigated. Experimental results show that the EEMD-based method is able to detect the knock signatures from both the pressure signal and vibration signal, even in initial stage of knock. Finally, by comparing the application results with those obtained by short-time Fourier transform (STFT), Wigner-Ville distribution (WVD) and discrete wavelet transform (DWT), the superiority of the EEMD method in determining knock characteristics is demonstrated.

  18. Relation between Spark-Ignition Engine Knock, Detonation Waves, and Autoignition as Shown by High-Speed Photography

    DTIC Science & Technology

    1946-01-01

    unfortunate” fiat this work has not, in the past few years , received more carcf~ll considera- tion. Th~ photographs of %kolik and Voinov wcro taken through a...with the propo8ed combined theory but not with either the simple autoignition theory or the simple detonation- wace theory. INTRODUCTION Knock is one of...countries for about 25 yeara. The past researches on knock have uncovered an immense amount of information, not only concerning the basic nature of knock but

  19. System and method for controlling engine knock using electro-hydraulic valve actuation

    DOEpatents

    Brennan, Daniel G

    2013-12-10

    A control system for an engine includes a knock control module and a valve control module. The knock control module adjusts a period that one or more of an intake valve and an exhaust valve of a cylinder are open based on engine knock corresponding to the cylinder. The valve control module, based on the adjusted period, controls the one or more of the intake valve and the exhaust valve using one or more hydraulic actuators.

  20. Understanding fuel anti-knock performances in modern SI engines using fundamental HCCI experiments

    DOE PAGES

    Yang, Yi; Dec, John E.; Sjoberg, Magnus; ...

    2015-08-19

    Modern spark-ignition (SI) engine technologies have considerably changed in-cylinder conditions under which fuel autoignition and engine knock take place. In this paper, fundamental HCCI engine experiments are proposed as a means for characterizing the impact of these technologies on the knock propensity of different fuels. In particular, the impacts of turbocharging, direct injection (DI), and downspeeding on operation with ethanol and gasoline are investigated to demonstrate this approach. Results reported earlier for ethanol and gasoline on HCCI combustion are revisited with the new perspective of how their autoignition characteristics fit into the anti-knock requirement in modern SI engines. For example,more » the weak sensitivity to pressure boost demonstrated by ethanol in HCCI autoignition can be used to explain the strong knock resistance of ethanol fuels for turbocharged SI engines. Further, ethanol's high sensitivity to charge temperature makes charge cooling, which can be produced by fuel vaporization via direct injection or by piston expansion via spark-timing retard, very effective for inhibiting knock. On the other hand, gasoline autoignition shows a higher sensitivity to pressure, so only very low pressure boost can be applied before knock occurs. Gasoline also demonstrates low temperature sensitivity, so it is unable to make as effective use of the charge cooling produced by fuel vaporization or spark retard. These arguments comprehensively explain literature results on ethanol's substantially better anti-knock performance over gasoline in modern turbocharged DISI engines. Fundamental HCCI experiments such as these can thus be used as a diagnostic and predictive tool for knock-limited SI engine performance for various fuels. As a result, examples are presented where HCCI experiments are used to identify biofuel compounds with good potential for modern SI-engine applications.« less

  1. Deficiency in the manganese efflux transporter SLC30A10 induces severe hypothyroidism in mice.

    PubMed

    Hutchens, Steven; Liu, Chunyi; Jursa, Thomas; Shawlot, William; Chaffee, Beth K; Yin, Weiling; Gore, Andrea C; Aschner, Michael; Smith, Donald R; Mukhopadhyay, Somshuvra

    2017-06-09

    Manganese is an essential metal that becomes toxic at elevated levels. Loss-of-function mutations in SLC30A10, a cell-surface-localized manganese efflux transporter, cause a heritable manganese metabolism disorder resulting in elevated manganese levels and parkinsonian-like movement deficits. The underlying disease mechanisms are unclear; therefore, treatment is challenging. To understand the consequences of loss of SLC30A10 function at the organism level, we generated Slc30a10 knock-out mice. During early development, knock-outs were indistinguishable from controls. Surprisingly, however, after weaning and compared with controls, knock-out mice failed to gain weight, were smaller, and died prematurely (by ∼6-8 weeks of age). At 6 weeks, manganese levels in the brain, blood, and liver of the knock-outs were ∼20-60-fold higher than controls. Unexpectedly, histological analyses revealed that the brain and liver of the knock-outs were largely unaffected, but their thyroid exhibited extensive alterations. Because hypothyroidism leads to growth defects and premature death in mice, we assayed for changes in thyroid and pituitary hormones. At 6 weeks and compared with controls, the knock-outs had markedly reduced thyroxine levels (∼50-80%) and profoundly increased thyroid-stimulating hormone levels (∼800-1000-fold), indicating that Slc30a10 knock-out mice develop hypothyroidism. Importantly, a low-manganese diet produced lower tissue manganese levels in the knock-outs and rescued the phenotype, suggesting that manganese toxicity was the underlying cause. Our unanticipated discovery highlights the importance of determining the role of thyroid dysfunction in the onset and progression of manganese-induced disease and identifies Slc30a10 knock-out mice as a new model for studying thyroid biology. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

    PubMed

    McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

    2015-01-01

    The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

  3. Estimated Chemical Warfare Agent Surface Clearance Goals for Remediation Pre-Planning

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

    Dolislager, Frederick; Bansleben, Dr. Donald; Watson, Annetta Paule

    2010-01-01

    Health-based surface clearance goals, in units of mg/cm2, have been developed for the persistent chemical warfare agents sulfur mustard (HD) and nerve agent VX as well as their principal degradation products. Selection of model parameters and critical receptor (toddler child) allow calculation of surface residue estimates protective for the toddler child, the general population and adult employees of a facilty that has undergone chemical warfare agent attack.

  4. COIN in Cyberspace: Focusing Air Force Doctrine Development

    DTIC Science & Technology

    2007-01-01

    cyberspace and began codifying its cyber warfare doctrine. This effort is hampered, however, by a limited understanding of cyberspace by rank and file Air...Force members. Many believe cyberspace and cyber warfare are the responsibility of the communications community. If this new doctrine is to be...doctrine to build upon, the Air Force can create unity of effort among Airmen at all levels, ensure unity of purpose in the prosecution of cyber warfare , and

  5. In Pursuit of an Aptitude Test for Potential Cyberspace Warriors

    DTIC Science & Technology

    2007-03-01

    may well be training their soldiers in the art of cyber warfare to attack our infrastructure and defend their own. It seems like a no-brainer that...communications. Certainly this is an area that could be exploited in cyber warfare . Another subject with little reference was regarding linguistic...Journal, 40(3), 769-780. Parks, R. C., & duggan, D. P. (2001). Principles of cyber - warfare . Proceeding of the 2001 IEEE Workshop on Information

  6. Self-Development for Cyber Warriors

    DTIC Science & Technology

    2011-11-10

    Aggressive self-development is a critical task for the cyber warfare professional. No matter the quality, formal training and education programs age...Books and Science Fiction); Technology and Cyber-Related Magazines and Blogs; Specific Cyber Warfare Journal and Magazine Articles; Key Documents on...the strengths and weaknesses of the major donor career fields to the cyber workforce, and a Self-Assessment of Cyber Domain Expertise for readers who wish to assess their own cyber warfare expertise.

  7. Finding the Balance to Combat a Hybrid Threat

    DTIC Science & Technology

    2013-05-23

    supporting operation to conventional warfare. Mao Tse -tung stated that guerrilla warfare is one aspect of total war, because it cannot win a war by itself.15...of Military and Associated Terms, 147. 15Mao Tse -tung, On Guerrilla Warfare, trans. Samuel B. Griffith II (Champaign, IL: University of Illinois...to deny the Vietcong or the North Vietnamese sanctuary in neither Laos nor Cambodia. Summary In Afghanistan, insurgency has become more a

  8. The Combat Vehicle Command and Control System: Combat Performance of Armor Battalions Using Interactive Simulation

    DTIC Science & Technology

    1994-05-01

    Command and Control display. Using Ml tank simulators in the Mounted Warfare Test Bed at Fort Knox, Kentucky, the researchers evaluated tank battalion... Warfare Test Bed (MWTB) at Fort Knox, Kentucky, eight MOS-qualified armor crews (battalion commander, battalion opera- tions officer, three company...concerned with identifying ways that the CVCC system might best benefit the battlefield commander, and potential modifications to mounted warfare TTPs

  9. Modeling Anti-Air Warfare With Discrete Event Simulation and Analyzing Naval Convoy Operations

    DTIC Science & Technology

    2016-06-01

    WARFARE WITH DISCRETE EVENT SIMULATION AND ANALYZING NAVAL CONVOY OPERATIONS by Ali E. Opcin June 2016 Thesis Advisor: Arnold H. Buss Co...REPORT DATE June 2016 3. REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE MODELING ANTI-AIR WARFARE WITH DISCRETE EVENT...In this study, a discrete event simulation (DES) was built by modeling ships, and their sensors and weapons, to simulate convoy operations under

  10. Fractal Effects in Lanchester Models of Combat

    DTIC Science & Technology

    2009-08-01

    Lanchester models. 8. References 1 Aircraft in Warfare : The Dawn of the Fourth Arm, F W Lanchester , Constable & Co., London, 1916. 2 The Calculus of...Intermediate Asymptotics, G I Barenblatt, CUP, 1996. 14 Lanchester Models of Warfare Volumes 1 and 2, J G Taylor, Operations Research Society of America...Nagabhushana, Computers and Operations Research, 21, 615-628, 1994. 20 DSTO-TR-2331 18 Lanchester Type Models of Warfare , H K Weiss, Proc.First

  11. A Heuristic Decision Making Model to Mitigate Adverse Consequences in a Network Centric Warfare/Sense and Respond System

    DTIC Science & Technology

    2005-05-01

    made. 4. Do military decision makers identify / analyze adverse consequences presently? Few do based on this research and most don’t do it effectively ...A HEURISTIC DECISION MAKING MODEL TO MITIGATE ADVERSE CONSEQUENCES IN A NETWORK CENTRIC WARFARE / SENSE AND RESPOND SYSTEM...ENS/05-01 A HEURISTIC DECISION MAKING MODEL TO MITIGATE ADVERSE CONSEQUENCES IN A NETWORK CENTRIC WARFARE / SENSE AND RESPOND SYSTEM

  12. The Strategic and Political Impacts of Collateral Damage from Strike Warfare

    DTIC Science & Technology

    2015-03-01

    damage from strike warfare focuses on legal, humanitarian, and moral issues . To oversimplify, killing non-combatants is bad, but it happens, and not...humanitarian, and moral issues . To oversimplify, killing non- combatants is bad, but it happens, and not always by accident. Therefore, it is instructive...method of bombing. A significant amount of research on the effects of collateral damage from strike warfare focuses on humanitarian and moral issues

  13. Network Centric Warfare Case Study: U.S. V Corps and 3rd Infantry Division (Mechanized) During Operation Iraqi Freedom Combat Operations (Mar-Apr 2003). Volume 3. Network Centric Warfare Insights

    DTIC Science & Technology

    2003-01-01

    OPSEC), military deception, psychological operations (PSYOPS), special information operations (IO), information assurance, physical security...nonlethal effects, such as operational 8 Network Centric Warfare Case Study security (OPSEC), military deception, psychological operations (PSYOP...Support Operations Group ASR Alternate Supply Route; or, Ammunition Supply Rate ATACMS Army Tactical Missile System ATARS Advanced

  14. Biomaterials for mediation of chemical and biological warfare agents.

    PubMed

    Russell, Alan J; Berberich, Jason A; Drevon, Geraldine F; Koepsel, Richard R

    2003-01-01

    Recent events have emphasized the threat from chemical and biological warfare agents. Within the efforts to counter this threat, the biocatalytic destruction and sensing of chemical and biological weapons has become an important area of focus. The specificity and high catalytic rates of biological catalysts make them appropriate for decommissioning nerve agent stockpiles, counteracting nerve agent attacks, and remediation of organophosphate spills. A number of materials have been prepared containing enzymes for the destruction of and protection against organophosphate nerve agents and biological warfare agents. This review discusses the major chemical and biological warfare agents, decontamination methods, and biomaterials that have potential for the preparation of decontamination wipes, gas filters, column packings, protective wear, and self-decontaminating paints and coatings.

  15. Generation of an allelic series of knock-in mice using recombinase-mediated cassette exchange (RMCE).

    PubMed

    Roebroek, Anton J M; Van Gool, Bart

    2014-01-01

    Molecular genetic strategies applying embryonic stem cell (ES cell) technologies to study the function of a gene in mice or to generate a mouse model for a human disease are continuously under development. Next to (conditional) inactivation of genes the application and importance of approaches to generate knock-in mutations are increasing. In this chapter the principle and application of recombinase-mediated cassette exchange (RMCE) are discussed as being a new emerging knock-in strategy, which enables easy generation of a series of different knock-in mutations within one gene. An RMCE protocol, which was used to generate a series of different knock-in mutations in the Lrp1 gene of ES cells, is described in detail as an example of how RMCE can be used to generate highly efficiently an allelic series of differently modified ES cell clones from a parental modified ES cell clone. Subsequently the differently modified ES cell clones can be used to generate an allelic series of mutant knock-in mice.

  16. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency

    PubMed Central

    Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y. Eugene; Zhang, Jifeng

    2016-01-01

    Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells. PMID:26817820

  17. Role of blood ribosomal protein S19 in coagulum resorption: a study using Gln137Glu-ribosomal protein S19 gene knock-in mouse.

    PubMed

    Chen, Jun; Fujino, Rika; Zhao, Rui; Semba, Umeko; Araki, Kimi; Yamamoto, Tetsuro

    2014-11-01

    Sera of human, guinea pig or mouse contain a strong monocyte chemoattractant capacity that is attributed to the ribosomal protein S19 (RP S19) oligomers generated during blood coagulation. In contrast, sera prepared from Gln137Glu-RP S19 gene knock-in mice contained negligible chemoattractant capacity. When coagula that had been pre-formed from the blood of both the wild type and knock-in mice were intraperitoneally inserted into host mice, after 3 days of recovery, the knock-in mouse coagula remained larger than the wild type mouse coagula. The wild type mouse coagula were covered by multiple macrophage layers at the surface and were infiltrated inside by macrophages. Knock-in mouse coagula exhibited less macrophage involvement. When coagula of knock-in mice and coagula of knock-in mice containing C5a/RP S19, an artificial substitute of the RP S19 oligomers, were intraperitoneally inserted as pairs, the C5a/RP S19 containing coagulum was more rapidly absorbed, concomitant with increased macrophage involvement. Finally, when the knock-in mouse and wild type mouse coagula pairs were inserted into mice in which macrophages had been depleted using clodronate liposome, the size difference of recovered coagula was reversed. These results indicate the importance of the RP S19 oligomer-induced macrophage recruitment in coagulum resorption. © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  18. Military Engineers and Chemical Warfare Troops (Inzhenernye Voiska Khimicheskie Voiska),

    DTIC Science & Technology

    MILITARY FORCES(FOREIGN), *MILITARY ORGANIZATIONS, MILITARY ENGINEERING , INFANTRY, AMPHIBIOUS OPERATIONS, MINELAYING, ARMORED VEHICLES, NUCLEAR...RADIATION, DOSIMETERS, CHEMICAL WARFARE, PROTECTIVE CLOTHING, DECONTAMINATION, HEALTH PHYSICS.

  19. Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

    PubMed

    Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

    2016-11-16

    The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Coalition Logistics: A Case Study in Operation Restore Hope

    DTIC Science & Technology

    1994-06-03

    coalition operations."° In Seland’s interview with Colonel Wolfgang Kopp, chief of staff, German/Franco Brigade, Colonel Kopp stated that key members...February 1994. 21William G. Pagonis and Michael D. Krause , "Operational Logistics and the Gulf War," The Institute of Land Warfare: The Land Warfare...Headquarters, 1989. Pagonis, William G. and Michael D. Krause . "Operational Logistics and the Gulf War." The Land Warfare Paper No. 13. Arlington, Virginia

  1. Mission Accomplished! Or Not? A Study about Success in Information Operations

    DTIC Science & Technology

    2012-09-01

    sensors and presented on a man-machine interface, e.g., a computer screen or on a radar plan position indicator. In modern warfare, staff and...has to be achievable; otherwise, it can be viewed simply as dreaming. Compared to sea, land and even air warfare, information warfare is a young...shares some of its characteristics with the air and sea domains. All of them exist without borders. In addition, they cannot be fortified or

  2. Pirates of the Nuclear Age: The Role of U.S. Submarines in Modern Trade Warfare

    DTIC Science & Technology

    2016-07-14

    have sought to influence the outcome of the conflict by targeting enemy commerce . This influence historically called for the use of privateers...submarines took the position of privateers as the ideal force for conducting commerce warfare. Throughout World War Two (WWII) commerce warfare using... commerce ) remains. From the time of Greek city-states, to the privateers of the age of sail, to the submarines of WWI and WWII, targeting the

  3. The Combat Vehicle Command and Control System. Combat Performance of Armor Battalions Using Interactive Simulation

    DTIC Science & Technology

    1994-01-31

    ncluded the Commander’s Independent Thermal Viewer and a Command and Control display. Using 1 tank simulators in the Mounted Warfare Test Bed at Fort...CCD), the Commander’s Independent Thermal Viewer (CITV), and digital TOC workstations. Using autoloading tank simulators in the Mounted Warfare Test...identifying ways that the CVCC system might best benefit the battlefield commander, and potential modifications to mounted warfare TTPs. Another area of

  4. The Combat Vehicle Command and Control System. Combat Performance of Armor Battalions Using Distributed Interactive Simulation

    DTIC Science & Technology

    1993-12-15

    and Control disqlay. Using M1 tank simulators in the Mounted Warfare Test Bed at Fort Knox, KY, the evaluation focused on tank battalion oierations...and digital TOC workstations. Using autoloading tank simulators in the Mounted Warfare Test Bed (MWTB) at Fort Knox, Kentucky, eight MOS-qualified...might best benefit the battlefield commander, and potential modifications to mounted warfare TTPs. Another area of interest is the implication for

  5. Gray Zone Warfare: German and Russian Political Warfare, 1935-1939, and 2001

    DTIC Science & Technology

    2017-06-09

    Stretching and Exploiting Thresholds for High -Order War: How Russia, China, and Iran are Eroding American Influence Using Time-Tested Measures...PSYOP Terminology,” in American Institutes for Research, Department of the Army Pamphlet 525-7-1-2, The Art and Science of Psychological Operations...efforts to attack the enemies’ “ power , influence, and will.”88 In the United States, Irregular Warfare was not a part of doctrine until 2007, when the

  6. Winning the Counterinsurgency Fight in Iraq: The Role of Political Culture in Counterinsurgency Warfare 2003-2006 in Iraq

    DTIC Science & Technology

    2006-05-26

    Winning the Counterinsurgency Fight in Iraq: The Role of Political Culture in Counterinsurgency Warfare 2003-2006 in Iraq A Monograph by Major...Counterinsurgency Fight in Iraq: The Role of Political Culture in Counterinsurgency Warfare 2003-2006 in Iraq 5c. PROGRAM ELEMENT NUMBER 5d. PROJECT NUMBER 5e...14. ABSTRACT This monograph provides insight into the importance of political culture in relation to developing a counterinsurgency strategy. This

  7. Linear Goal Programming as a Military Decision Aid.

    DTIC Science & Technology

    1988-04-01

    JAMES F. MAJOR9 USAF 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year, Month, Day) 15. PAGE COUNT IFROM____ TO 1988 APRIL 64 16...air warfare, advanced armour warfare, the potential f or space warfare, and many other advances have expanded the breadth of weapons employed to the...written by A. Charnes and W. W. Cooper, Management Models and Industrial Applications of Linear Programming In 1961.(3:5) Since this time linear

  8. Submarine Warfare in the 20th & 21st Centuries: A Bibliography

    DTIC Science & Technology

    2003-12-01

    International studies series ser. no. 02-019). 49 p. Bailey, Thomas Andrew and Paul B. Ryan. The Lusitania disaster: an episode in modern warfare and...verlagshandlung, 1939. 212 p. Ellis, Frederick D. The tragedy of the Lusitania : embracing authentic stories by the survivors and eye-witnesses of the disaster...warfare; a study of its methods and spirit, including the crime of the " Lusitania ," a record of observations and evidence. New York, London, D. Appleton

  9. The Human Domain and the Future of Army Warfare: Present as Prelude to 2050

    DTIC Science & Technology

    2017-07-01

    ERDC/CERL MP-17-2 ii Abstract Studies on the future of warfare tend to focus on technology and place but largely overlook the actors. Warfare in 2050...will be predominantly urban, utilizing robotics and other advanced technologies , but at the core will re- main an inherently human and political...collaboration for success. Despite the ap- peal of advanced technology , the U.S. Army could greatly benefit by looking beyond strictly technological

  10. Feasibility Study for the Use of Green, Bio-Based, Efficient Reactive Sorbent Material to Neutralize Chemical Warfare Agents

    DTIC Science & Technology

    2012-08-02

    REPORT Feasibility study for the use of green, bio-based, efficient reactive sorbent material to neutralize chemical warfare agents 14. ABSTRACT 16...way cellulose, lignin and hemicelluloses interact as well as whole wood dissolution occurs in ILs. The present project was conducted to 1. REPORT...Feasibility study for the use of green, bio-based, efficient reactive sorbent material to neutralize chemical warfare agents Report Title ABSTRACT Over the

  11. Personal protection during resuscitation of casualties contaminated with chemical or biological warfare agents--a survey of medical first responders.

    PubMed

    Brinker, Andrea; Prior, Kate; Schumacher, Jan

    2009-01-01

    The threat of mass casualties caused by an unconventional terrorist attack is a challenge for the public health system, with special implications for emergency medicine, anesthesia, and intensive care. Advanced life support of patients injured by chemical or biological warfare agents requires an adequate level of personal protection. The aim of this study was to evaluate the personal protection knowledge of emergency physicians and anesthetists who would be at the frontline of the initial health response to a chemical/biological warfare agent incident. After institutional review board approval, knowledge of personal protection measures among emergency medicine (n = 28) and anesthetics (n = 47) specialty registrars in the South Thames Region of the United Kingdom was surveyed using a standardized questionnaire. Participants were asked for the recommended level of personal protection if a chemical/biological warfare agent(s) casualty required advanced life support in the designated hospital resuscitation area. The best awareness within both groups was regarding severe acute respiratory syndrome, and fair knowledge was found regarding anthrax, plague, Ebola, and smallpox. In both groups, knowledge about personal protection requirements against chemical warfare agents was limited. Knowledge about personal protection measures for biological agents was acceptable, but was limited for chemical warfare agents. The results highlight the need to improve training and education regarding personal protection measures for medical first receivers.

  12. Human thrombomodulin knock-in mice reveal differential effects of human thrombomodulin on thrombosis and atherosclerosis.

    PubMed

    Raife, Thomas J; Dwyre, Denis M; Stevens, Jeff W; Erger, Rochelle A; Leo, Lorie; Wilson, Katina M; Fernández, Jose A; Wilder, Jennifer; Kim, Hyung-Suk; Griffin, John H; Maeda, Nobuyo; Lentz, Steven R

    2011-11-01

    We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta (P<0.01) and lung (P<0.001). Activation of endogenous protein C following infusion of thrombin was decreased by 90% in knock-in mice compared with wild-type mice (P<0.05). Carotid artery thrombosis induced by photochemical injury occurred more rapidly in knock-in mice (12±3 minutes) than in wild-type mice (31±6 minutes; P<0.05). No differences in serum cytokine levels were detected between knock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E-deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo.

  13. [Medecine, Law, and Knowledge Production about the "Civilized" War in the Long 19th Century].

    PubMed

    Goltermann, Svenja

    2015-01-01

    The aim to 'civilize' warfare accompanied Medicine and International Law ever since the mid-19th century. However, the entanglement of Medicine and Law, crucial for such an endeavour, has not been taken into consideration so far; likewise, the huge importance of medical knowledge for the perception of wars and their ramifications did not garner much attention in historical research. Hence, by focusing on the 'long' 19th century, this paper shows, firstly, that the production of surgical knowledge during warfare aimed at measuring the effects of combat on human bodies in order to develop prognostic medical knowledge for future wars, as well as maintaining the combat strength of soldiers. Moreover, this knowledge production during warfare strived for the enhancement of medical competence in the diagnosis and treatment of wounds in general. Secondly, I show that this medical knowledge was not only relevant for warfare, but also crucial for the design of International Law: it served to nourish the debates among the so called 'civilized' nations about legitimate and illegitimate weaponry and warfare.

  14. 48 CFR 205.301 - General.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... not available, in accordance with 225.7002-2(b); or (B) The acquisition is for chemical warfare... determined that this acquisition of chemical warfare protective clothing furthers an agreement with a...

  15. 48 CFR 205.301 - General.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... not available, in accordance with 225.7002-2(b); or (B) The acquisition is for chemical warfare... determined that this acquisition of chemical warfare protective clothing furthers an agreement with a...

  16. 48 CFR 205.301 - General.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... not available, in accordance with 225.7002-2(b); or (B) The acquisition is for chemical warfare... determined that this acquisition of chemical warfare protective clothing furthers an agreement with a...

  17. [RS-1 enhanced the efficiency of CRISPR-Cas9 mediated knock-in of human lactoferrin].

    PubMed

    Zhou, Wenjun; Guo, Rihong; Deng, Mingtian; Wang, Feng; Zhang, Yanli

    2017-08-25

    This study aims to knock out the goat β-lactoglobulin (BLG) gene using CRISPR-Cas9 system and knock in human lactoferrin (hLF) at the BLG locus, and further study the effect of RAD51 stimulatory compound (RS-1) on homologous recombination efficiency. First, we designed an sgRNA targeting the first exon of goat BLG gene and constructed a co-expression vector pCas9-sgBLG. This sgRNA vector was then transfected into goat ear fibroblasts (GEFs), and the target region was examined by T7EN1 assay and sequencing. Second, we constructed a targeting vector pBHA-hLF-NIE including NEO and EGFP genes based on BLG gene locus. This targeting vector together with pCas9-sgBLG expression vector was co-transfected into GEFs. Transfected cells were then treated with 0, 5, 10 and 20 μmol/L RS-1 for 72 h to analyse the EGFP expression efficiency. Next, we used 800 μg/mL G418 to screen G418-resistent cell clones, and studied hLF site-specific knock-in cell clones by PCR and sequencing. The editing efficiency of sgBLG was between 25% and 31%. The EGFP expression efficiency indicated that the gene knock-in efficiency was improved by RS-1 in a dose-dependent manner, which could reach 3.5-fold compared to the control group. The percentage of positive cells with hLF knock-in was increased to 32.61% when 10 μmol/L RS-1 was used. However, when the concentration of RS-1 increased to 20 μmol/L, the percentage of positive cells decreased to 22.22% and resulted in an increase of senescent cell clone number. These results suggested that hLF knock-in and BLG knock-out in GEFs were achieved by using CRISPR/Cas9 system, and optimum concentration of RS-1 could improve knock-in efficiency, which provides a reference for efficiently obtaining gene knock-in cells using CRISPR/Cas9 in the future.

  18. Effects of Heat of Vaporization and Octane Sensitivity on Knock-Limited Spark Ignition Engine Performance

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

    Ratcliff, Matthew A; Burton, Jonathan L; Sindler, Petr

    Knock-limited loads for a set of surrogate gasolines all having nominal 100 research octane number (RON), approximately 11 octane sensitivity (S), and a heat of vaporization (HOV) range of 390 to 595 kJ/kg at 25 degrees C were investigated. A single-cylinder spark-ignition engine derived from a General Motors Ecotec direct injection (DI) engine was used to perform load sweeps at a fixed intake air temperature (IAT) of 50 degrees C, as well as knock-limited load measurements across a range of IATs up to 90 degrees C. Both DI and pre-vaporized fuel (supplied by a fuel injector mounted far upstream ofmore » the intake valves and heated intake runner walls) experiments were performed to separate the chemical and thermal effects of the fuels' knock resistance. The DI load sweeps at 50 degrees C intake air temperature showed no effect of HOV on the knock-limited performance. The data suggest that HOV acts as a thermal contributor to S under the conditions studied. Measurement of knock-limited loads from the IAT sweeps for DI at late combustion phasing showed that a 40 vol% ethanol (E40) blend provided additional knock resistance at the highest temperatures, compared to a 20 vol% ethanol blend and hydrocarbon fuel with similar RON and S. Using the pre-vaporized fuel system, all the high S fuels produced nearly identical knock-limited loads at each temperature across the range of IATs studied. For these fuels RON ranged from 99.2 to 101.1 and S ranged from 9.4 to 12.2, with E40 having the lowest RON and highest S. The higher knock-limited loads for E40 at the highest IATs examined were consistent with the slightly higher S for this fuel, and the lower engine operating condition K values arising from use of this fuel. The study highlights how fuel HOV can affect the temperature at intake valve closing, and consequently the pressure-temperature history of the end gas leading to more negative values of K, thereby enhancing the effect of S on knock resistance.« less

  19. North Korean Protective Mine Warfare: An Analysis of the Naval Minefields at Wonsan, Chinnampo and Hungnam during the Korean War

    DTIC Science & Technology

    2010-04-01

    the United States Navy and the general military history community as well. As a result, studies involving mine warfare have been neglected. In...that particular campaign. The Navy, lulled into a sense of complacency, has neglected mine warfare studies . Naval Intelligence has made little attempt...Farragut famously ignored the mineline there to destroy the Confederate fleet nearby. While extensive mining also occurred during World War One , the United

  20. Cyber ACTS/SAASS: A Second Year of Command and Staff College for the Future Leaders of Our Cyber Forces

    DTIC Science & Technology

    2009-01-01

    objectives. The Air Force is struggling to determine the best way of developing offensive and defensive capabilities for cyber warfare . Our warfighting...education (IDE) cyber warfare program at the Air Force Institute of Technology (AFIT), located at Wright-Patterson AFB, Ohio. I propose that the Air...Force create a two-year professional military education (PME) path consisting of ACSC followed by AFIT’s cyber warfare program, paralleling the current path of ACSC followed by SAASS.

  1. Application of Solid Phase Microextraction with Gas Chromatography-Mass Spectrometry as a Rapid, Reliable, and Safe Method for Field Sampling and Analysis of Chemical Warfare Agent Precursors

    DTIC Science & Technology

    2005-03-01

    in hair samples with analysis by GC-MS [41,42]. The research discussed here examined a polydimethylsiloxane polymer with 10% activated charcoal (PDMS...Field Sampling and Analysis of Chemical Warfare Agent Precursors” Name of Candidate: LT Douglas Parrish Doctor of Philosophy, Environmental...Microextraction with Gas Chromatography-Mass Spectrometry as a Rapid, Reliable, and Safe Method for Field Sampling and Analysis of Chemical Warfare

  2. Liquid Chromatography Electrospray Ionization Mass Spectrometric (LC-ESI-MS) and Desorption Electrospray Ionization Mass Spectrometric (DESI-MS) Identification of Chemical Warfare Agents in Consumer Products

    DTIC Science & Technology

    2007-06-01

    T ACanadaY Approved for PublicR Distribution Uln& Liquid Chromatography Electrospray Ionization Mass Spectrometric ( LC -ESI- MS) and Desorption...consumer products with chemical warfare agents or other toxic chemicals. Liquid chromatography electrospray ionization mass spectrometry ( LC -ESI-MS) and...house LC -ESI-MS and LC -ESI-MS/MS methods were evaluated for the determination of chemical warfare agents in spiked bottled water samples. The

  3. Continuous Acoustic Sensing With an Unmanned Aerial Vehicle System for Anti-Submarine Warfare in a High-Threat Area

    DTIC Science & Technology

    2015-12-01

    strive in multiple warfare areas. This research benefits not only the Navy, through enhancement of offensive warfighting by testing the next...multiple warfare areas. This research benefits not only the Navy, through enhancement of offensive warfighting by testing the next generation of...produce and definitely worth the research and testing to be a positive asset for the Navy. It not only can stay on station for an exponential amount of

  4. Chemical warfare agents

    PubMed Central

    Ganesan, K.; Raza, S. K.; Vijayaraghavan, R.

    2010-01-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided. PMID:21829312

  5. Set Up for Failure: The Use of US Security Force Assistance to Prepare Foreign Security Forces for Traditional Combat Operations

    DTIC Science & Technology

    2017-05-17

    Do the SFA lessons drawn from the unconventional warfare focus of the post-9-11 paradigm hold true across the spectrum of conflict, or are there...relevance. Do the SFA lessons drawn from the unconventional warfare focus of the post-9-11 paradigm hold true across the spectrum of conflict, or...traditional warfare is fought changes from epoch to epoch as technology, armament, and other factors change, but certain immutable principles hold true

  6. Defining Islamic Way of Warfare and Its Comparison with Al Qaeda Doctrine

    DTIC Science & Technology

    2012-06-08

    DEFINING ISLAMIC WAY OF WARFARE AND ITS COMPARISON WITH AL QAEDA DOCTRINE A thesis presented to the Faculty of the U.S. Army...subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO...Islamic way of warfare. It is important to understand that anything, to be qualified as Islamic, has to have a reference from the core sources of Islam

  7. What Good Are Warfare Models?

    DTIC Science & Technology

    1981-05-01

    PROFESSIONAL PAPER 306 / May 1981 WHAT GOOD ARE WARFARE MODELS? Thomas E. Anger DTICS E LECTE ,JUN 2198 1 j CENTER FOR NAVAL ANALYSES 81 6 19 025 V...WHAT GOOD ARE WARFARE MODELS? Thomas E. /Anger J Accession For !ETIS GRA&I DTIC TAB thonnounceldŕ 5 By-C Availability Codes iAva il aand/or Di1st...least flows from a life-or-death incenLive to make good guesses when choosing weapons, forces, or strategies. It is not surprising, however, that

  8. Unmanned Warfare: Second and Third Order Effects Stemming from the Afghan Operational Environment between 2001 and 2010

    DTIC Science & Technology

    2011-06-10

    the very nature of warfare took a dramatic step into the future. With new assets capable of remaining airborne for nearly 24 hours and live video ...warfare took a dramatic step into the future. With new assets capable of remaining airborne for nearly 24 hours and live video feeds streaming to...shape the battlefield during protracted combat operations. From the real time video feeds, to the 24 hour coverage of an area of interest, tangible

  9. Space and Naval Warfare Systems Command and Overall Navy Needs to Improve Management of Waiver and Deferral Requests

    DTIC Science & Technology

    2015-10-08

    Management of Waiver and Deferral Requests Visit us at www.dodig.mil Objective Our objective for this audit was to evaluate the Space and Naval Warfare...We conducted this audit in accordance with generally accepted government auditing standards. We considered management comments on a draft of...OFFICIAL USE ON Y Introduction DODIG-2016-003 │ 1 Introduction Objective Our objective for this audit was to evaluate the Space and Naval Warfare

  10. Opportunity Knocks: A Connecticut School-Community Partnership Closes the Door on Preschool Expulsion

    ERIC Educational Resources Information Center

    Fahey, Christine; Ihle, Pat; Macary, Susan; O'Callahan, Cliff

    2007-01-01

    Several years ago, the people of Middletown made young children a priority by forming a coalition called Opportunity Knocks. A school-community partnership, Opportunity Knocks includes representatives from local health and social service agencies, early childhood educators, and families, all committed to improving the health and well-being of…

  11. The Effect of Compression Ratio on Knock Limits of High-Performance Fuels in a CFR Engine II : Blends of 2,2,3-Trimethylpentane with 28-R

    NASA Technical Reports Server (NTRS)

    Tower, Leonard K

    1945-01-01

    The knock-limited performance of blends of 0,50; and 100 percent by volume of 2,2,3-trimethylpentane in 28-R fuel determined with a modified F-4 engine at three sets of conditions varying from severe to mild at each of three compression ratios (6.0, 8.0, and 10.0). A comparison of the knock-limited performance of 2,2,3-trimethylpentane with that of triptane (2,2,3-trimethylbutane) is included. The knock-Limited performance of 2,2,3-trimethylpontane was usually more sensitive to either compression ratio or inlet-air temperature than 28-R fuel, but the ratio of the knock-limited indicated mean effective pressure of a given blend containing 2,2,3-trimethypentane and 28-R to the indicated mean effective pressure of 28-R alone was not greatly affected by compression ratio if the engine operating conditions were mild. Although 2,2,3-trimethylpentane in general had a lower knock-limited performance than triptane, the characteristics of the two fuels were somewhat similar.

  12. MMEJ-assisted gene knock-in using TALENs and CRISPR-Cas9 with the PITCh systems.

    PubMed

    Sakuma, Tetsushi; Nakade, Shota; Sakane, Yuto; Suzuki, Ken-Ichi T; Yamamoto, Takashi

    2016-01-01

    Programmable nucleases enable engineering of the genome by utilizing endogenous DNA double-strand break (DSB) repair pathways. Although homologous recombination (HR)-mediated gene knock-in is well established, it cannot necessarily be applied in every cell type and organism because of variable HR frequencies. We recently reported an alternative method of gene knock-in, named the PITCh (Precise Integration into Target Chromosome) system, assisted by microhomology-mediated end-joining (MMEJ). MMEJ harnesses independent machinery from HR, and it requires an extremely short homologous sequence (5-25 bp) for DSB repair, resulting in precise gene knock-in with a more easily constructed donor vector. Here we describe a streamlined protocol for PITCh knock-in, including the design and construction of the PITCh vectors, and their delivery to either human cell lines by transfection or to frog embryos by microinjection. The construction of the PITCh vectors requires only a few days, and the entire process takes ∼ 1.5 months to establish knocked-in cells or ∼ 1 week from injection to early genotyping in frog embryos.

  13. Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.

    PubMed

    den Hartog, Carolina R; Beckley, Jacob T; Smothers, Thetford C; Lench, Daniel H; Holseberg, Zack L; Fedarovich, Hleb; Gilstrap, Meghin J; Homanics, Gregg E; Woodward, John J

    2013-01-01

    Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p.) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.

  14. Alterations in Ethanol-Induced Behaviors and Consumption in Knock-In Mice Expressing Ethanol-Resistant NMDA Receptors

    PubMed Central

    den Hartog, Carolina R.; Beckley, Jacob T.; Smothers, Thetford C.; Lench, Daniel H.; Holseberg, Zack L.; Fedarovich, Hleb; Gilstrap, Meghin J.; Homanics, Gregg E.; Woodward, John J.

    2013-01-01

    Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75–2.0 g/kg; IP) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol. PMID:24244696

  15. Culture time of vitrified/warmed zygotes before microinjection affects the production efficiency of CRISPR-Cas9-mediated knock-in mice.

    PubMed

    Nakagawa, Yoshiko; Sakuma, Tetsushi; Nishimichi, Norihisa; Yokosaki, Yasuyuki; Takeo, Toru; Nakagata, Naomi; Yamamoto, Takashi

    2017-05-15

    Robust reproductive engineering techniques are required for the efficient and rapid production of genetically modified mice. We have reported the efficient production of genome-edited mice using reproductive engineering techniques, such as ultra-superovulation, in vitro fertilization (IVF) and vitrification/warming of zygotes. We usually use vitrified/warmed fertilized oocytes created by IVF for microinjection because of work efficiency and flexible scheduling. Here, we investigated whether the culture time of zygotes before microinjection influences the efficiency of producing knock-in mice. Knock-in mice were generated using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system and single-stranded oligodeoxynucleotide (ssODN) or PITCh (Precise Integration into Target Chromosome) system, a method of integrating a donor vector assisted by microhomology-mediated end-joining. The cryopreserved fertilized oocytes were warmed, cultured for several hours and microinjected at different timings. Microinjection was performed with Cas9 protein, guide RNA(s), and an ssODN or PITCh donor plasmid for the ssODN knock-in and the PITCh knock-in, respectively. Different production efficiencies of knock-in mice were observed by changing the timing of microinjection. Our study provides useful information for the CRISPR-Cas9-based generation of knock-in mice. © 2017. Published by The Company of Biologists Ltd.

  16. Highly efficient CRISPR/HDR-mediated knock-in for mouse embryonic stem cells and zygotes.

    PubMed

    Wang, Bangmei; Li, Kunyu; Wang, Amy; Reiser, Michelle; Saunders, Thom; Lockey, Richard F; Wang, Jia-Wang

    2015-10-01

    The clustered regularly interspaced short palindromic repeat (CRISPR) gene editing technique, based on the non-homologous end-joining (NHEJ) repair pathway, has been used to generate gene knock-outs with variable sizes of small insertion/deletions with high efficiency. More precise genome editing, either the insertion or deletion of a desired fragment, can be done by combining the homology-directed-repair (HDR) pathway with CRISPR cleavage. However, HDR-mediated gene knock-in experiments are typically inefficient, and there have been no reports of successful gene knock-in with DNA fragments larger than 4 kb. Here, we describe the targeted insertion of large DNA fragments (7.4 and 5.8 kb) into the genomes of mouse embryonic stem (ES) cells and zygotes, respectively, using the CRISPR/HDR technique without NHEJ inhibitors. Our data show that CRISPR/HDR without NHEJ inhibitors can result in highly efficient gene knock-in, equivalent to CRISPR/HDR with NHEJ inhibitors. Although NHEJ is the dominant repair pathway associated with CRISPR-mediated double-strand breaks (DSBs), and biallelic gene knock-ins are common, NHEJ and biallelic gene knock-ins were not detected. Our results demonstrate that efficient targeted insertion of large DNA fragments without NHEJ inhibitors is possible, a result that should stimulate interest in understanding the mechanisms of high efficiency CRISPR targeting in general.

  17. Motor Deficits and Cerebellar Atrophy in Elovl5 Knock Out Mice.

    PubMed

    Hoxha, Eriola; Gabriele, Rebecca M C; Balbo, Ilaria; Ravera, Francesco; Masante, Linda; Zambelli, Vanessa; Albergo, Cristian; Mitro, Nico; Caruso, Donatella; Di Gregorio, Eleonora; Brusco, Alfredo; Borroni, Barbara; Tempia, Filippo

    2017-01-01

    Spino-Cerebellar-Ataxia type 38 (SCA38) is caused by missense mutations in the very long chain fatty acid elongase 5 gene, ELOVL5 . The main clinical findings in this disease are ataxia, hyposmia and cerebellar atrophy. Mice in which Elovl5 has been knocked out represent a model of the loss of function hypothesis of SCA38. In agreement with this hypothesis, Elovl5 knock out mice reproduced the main symptoms of patients, motor deficits at the beam balance test and hyposmia. The cerebellar cortex of Elovl5 knock out mice showed a reduction of thickness of the molecular layer, already detectable at 6 months of age, confirmed at 12 and 18 months. The total perimeter length of the Purkinje cell (PC) layer was also reduced in Elovl5 knock out mice. Since Elovl5 transcripts are expressed by PCs, whose dendrites are a major component of the molecular layer, we hypothesized that an alteration of their dendrites might be responsible for the reduced thickness of this layer. Reconstruction of the dendritic tree of biocytin-filled PCs, followed by Sholl analysis, showed that the distribution of distal dendrites was significantly reduced in Elovl5 knock out mice. Dendritic spine density was conserved. These results suggest that Elovl5 knock out mice recapitulate SCA38 symptoms and that their cerebellar atrophy is due, at least in part, to a reduced extension of PC dendritic arborization.

  18. Strong morphological defects in conditional Arabidopsis abp1 knock-down mutants generated in absence of functional ABP1 protein.

    PubMed

    Michalko, Jaroslav; Glanc, Matouš; Perrot-Rechenmann, Catherine; Friml, Jiří

    2016-01-01

    The Auxin Binding Protein 1 (ABP1) is one of the most studied proteins in plants. Since decades ago, it has been the prime receptor candidate for the plant hormone auxin with a plethora of described functions in auxin signaling and development. The developmental importance of ABP1 has recently been questioned by identification of Arabidopsis thaliana abp1 knock-out alleles that show no obvious phenotypes under normal growth conditions. In this study, we examined the contradiction between the normal growth and development of the abp1 knock-outs and the strong morphological defects observed in three different ethanol-inducible abp1 knock-down mutants ( abp1-AS, SS12K, SS12S). By analyzing segregating populations of abp1 knock-out vs. abp1 knock-down crosses we show that the strong morphological defects that were believed to be the result of conditional down-regulation of ABP1 can be reproduced also in the absence of the functional ABP1 protein. This data suggests that the phenotypes in  abp1 knock-down lines are due to the off-target effects and asks for further reflections on the biological function of ABP1 or alternative explanations for the missing phenotypic defects in the abp1 loss-of-function alleles.

  19. [Establishment of L-periaxin gene knock-out RSC96 cell line].

    PubMed

    Liang, Min; Peng, Tingting; Shi, Yawei

    2016-12-25

    Periaxin, a protein of noncompact myelin, is specifically expressed in the peripheral nervous system (PNS). There are two protein isoform L-periaxin and S-Periaxin by alternative splicing of periaxin gene, playing an important role in the initiation of myelin formation. So far, 18 different mutation sites in L-periaxin gene have been found to induce the peripheral demyelinating neurological charcot-marie-tooth diseases subtype 4F (CMT4F). The technique of activation of transcription activator-like effector nucleases (TALENS) was used to knock out the L-periaxin gene in RSC 96 cell line of Rattus. According to the design principle, the knock-out site of L-periaxin was assured to NLS domain of L-periaxin, which is target sequence of left and right arms of TALEN. The knock-out vectors of TALEN-L and TALEN-R were established and transfected into RSC96 cell. After puromycin screening, L-periaxin was knocked out successfully in RSC96 cell, which is confirmed by DNA sequence. The mutation efficiency is 21.6%. S-periaxin, not L-periaxin can be detected by Western blotting in L-periaxin gene knock-out RSC96 cell. The cell growth rate was decreased and the number of cells in G1 increased and decreased in S phase in L-periaxin gene knock-out RSC96 cell by flow cytometry and MTT assay.

  20. Femoral vessel injuries in modern warfare since Vietnam.

    PubMed

    Pearl, Jonathan P; McNally, Michael P; Perdue, Philip W

    2003-09-01

    The incidence of lower extremity injuries is high in modern warfare; however the mortality rate from these injuries is low. Despite the overall low mortality of lower extremity injuries, many deaths in modern conflicts are due to femoral vessel injury. The modern warfare literature was reviewed. In Somalia, 1 of the 14 reported deaths was due to a laceration of the superficial femoral artery. In the Persian Gulf, three deaths were reported in an Army field hospital, one resulted from uncontrolled hemorrhage from a profunda femoris artery wound and two others resulted from traumatic amputations with consequent major arterial injury. Despite the advances in modern body armor, the groin is left unprotected. A strategy to help minimize U.S. casualties in modern warfare may be a method of field hemostasis specifically designed for femoral vessel injury.

  1. Detection of biological warfare agents using ultra violet-laser induced fluorescence LIDAR

    NASA Astrophysics Data System (ADS)

    Joshi, Deepti; Kumar, Deepak; Maini, Anil K.; Sharma, Ramesh C.

    This review has been written to highlight the threat of biological warfare agents, their types and detection. Bacterial biological agent Bacillus anthracis (bacteria causing the disease anthrax) which is most likely to be employed in biological warfare is being discussed in detail. Standoff detection of biological warfare agents in aerosol form using Ultra violet-Laser Induced Fluorescence (UV-LIF) spectroscopy method has been studied. Range-resolved detection and identification of biological aerosols by both nano-second and non-linear femto-second LIDAR is also discussed. Calculated received fluorescence signal for a cloud of typical biological agent Bacillus globigii (Simulants of B. anthracis) at a location of ˜5.0 km at different concentrations in presence of solar background radiation has been described. Overview of current research efforts in internationally available working UV-LIF LIDAR systems are also mentioned briefly.

  2. Gender differences in the impact of warfare exposure on self-rated health.

    PubMed

    Wang, Joyce M; Lee, Lewina O; Spiro, Avron

    2015-01-01

    This study examined gender differences in the impact of warfare exposure on self-reported physical health. Data are from the 2010 National Survey of Veterans, a nationally representative survey of veterans from multiple eras of service. Regression analyses assessed gender differences in the association between warfare exposure (deployment to a war zone, exposure to casualties) and health status and functional impairment, adjusting for sociodemographics. Women reported better health status but greater functional impairment than men. Among men, those who experienced casualties only or both casualties and deployment to a war zone had worse health compared with those who experienced neither stressor or deployment to a war zone only. Among women, those who experienced casualties only or both stressors reported worse health than those who experienced war zone only, who did not differ from the unexposed. No association was found between warfare exposure and functional impairment in women; in men, however, those who experienced exposure to casualties or both stressors had greater odds of functional impairment compared with those who experienced war zone only or neither stressor. Exposure to casualties may be more predictive of health than deployment to a war zone, especially for men. We did not find a stronger association between warfare exposure and health for women than men. Given that the expansion of women's military roles has allowed them to serve in direct combat, their degree and scope of warfare exposure is likely to increase in the future. Copyright © 2015 Jacobs Institute of Women's Health. All rights reserved.

  3. Gender Differences in the Impact of Warfare Exposure on Self-Rated Health

    PubMed Central

    Wang, Joyce M.; Lee, Lewina O.; Spiro, Avron

    2014-01-01

    BACKGROUND This study examined gender differences in the impact of warfare exposure on self-reported physical health. METHODS Data are from the 2010 National Survey of Veterans, a nationally representative survey of veterans from multiple eras of service. Regression analyses assessed gender differences in the association between warfare exposure (deployment to a war zone, exposure to casualties) and health status and functional impairment, adjusting for sociodemographics. FINDINGS Women reported better health status but greater functional impairment than men. In men, those who experienced casualties only or both casualties and deployment to a war zone had worse health compared to those who experienced neither stressor or deployment to a war zone only. In women, those who experienced casualties only or both stressors reported worse health than those who experienced war zone only, who did not differ from the unexposed. No association was found between warfare exposure and functional impairment in women, but in men, those who experienced exposure to casualties or both stressors had greater odds of functional impairment compared to those who experienced war zone only or neither stressor. CONCLUSIONS Exposure to casualties may be more predictive of health than deployment to a war zone, especially for men. We did not find a stronger association between warfare exposure and health for women than men. Given that the expansion of women's military roles has allowed them to serve in direct combat, their degree and scope of warfare exposure is likely to increase in the future. PMID:25442366

  4. Measurement of Knock Characteristics in Spark-ignition Engines

    NASA Technical Reports Server (NTRS)

    Schutz, R

    1940-01-01

    This paper presents a discussion of three potential sources of error in recording engine knocking which are: the natural oscillation of the membrane, the shock process between test contacts, and the danger of burned contacts. Following this discussion, the paper calls attention to various results which make the bouncing-pin indicator appear fundamentally unsuitable for recording knock phenomena.

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

    Yang, Yi; Dec, John E.; Sjoberg, Magnus

    Modern spark-ignition (SI) engine technologies have considerably changed in-cylinder conditions under which fuel autoignition and engine knock take place. In this paper, fundamental HCCI engine experiments are proposed as a means for characterizing the impact of these technologies on the knock propensity of different fuels. In particular, the impacts of turbocharging, direct injection (DI), and downspeeding on operation with ethanol and gasoline are investigated to demonstrate this approach. Results reported earlier for ethanol and gasoline on HCCI combustion are revisited with the new perspective of how their autoignition characteristics fit into the anti-knock requirement in modern SI engines. For example,more » the weak sensitivity to pressure boost demonstrated by ethanol in HCCI autoignition can be used to explain the strong knock resistance of ethanol fuels for turbocharged SI engines. Further, ethanol's high sensitivity to charge temperature makes charge cooling, which can be produced by fuel vaporization via direct injection or by piston expansion via spark-timing retard, very effective for inhibiting knock. On the other hand, gasoline autoignition shows a higher sensitivity to pressure, so only very low pressure boost can be applied before knock occurs. Gasoline also demonstrates low temperature sensitivity, so it is unable to make as effective use of the charge cooling produced by fuel vaporization or spark retard. These arguments comprehensively explain literature results on ethanol's substantially better anti-knock performance over gasoline in modern turbocharged DISI engines. Fundamental HCCI experiments such as these can thus be used as a diagnostic and predictive tool for knock-limited SI engine performance for various fuels. As a result, examples are presented where HCCI experiments are used to identify biofuel compounds with good potential for modern SI-engine applications.« less

  6. Electromyographic evidence in support of a knock-in mouse model of DYT1 Dystonia.

    PubMed

    DeAndrade, Mark P; Trongnetrpunya, Amy; Yokoi, Fumiaki; Cheetham, Chad C; Peng, Ning; Wyss, J Michael; Ding, Mingzhou; Li, Yuqing

    2016-11-01

    DYT1 dystonia is an autosomal-dominant movement disorder characterized by abnormal, often repetitive, movements and postures. Its hallmark feature is sustained or intermittent contractions of muscles involving co-contractions of antagonist muscle pairs. The symptoms are relieved with the anticholinergic drug trihexyphenidyl. The primary mutation is a trinucleotide deletion (ΔGAG) in DYT1/TOR1A, which codes for torsinA. Previous studies showed that (1) heterozygous Dyt1 ΔGAG knock-in mice, which have an analogous mutation in the endogenous gene, exhibit motor deficits and altered corticostriatal synaptic plasticity in the brain and (2) these deficits can be rescued by trihexyphenidyl. However, brain imaging studies suggest that the Dyt1 knock-in mouse models nonmanifesting mutation carriers of DYT1 dystonia. The aim of this work was to examine the hallmark features of DYT1 dystonia in the Dyt1 knock-in mice by analyzing muscular activities. Wireless telemetry devices with biopotential channels were implanted to the bicep and the rectus femori muscles in Dyt1 knock-in mice, and muscular activities were recorded before and after trihexyphenidyl administration. (1) Consistent with DYT1 dystonia patients, Dyt1 knock-in mice showed sustained contractions and co-contractions of the antagonistic bicep femoris and rectus femoris. (2) The abnormal muscle contractions were normalized by trihexyphenidyl. The results suggest that the motor deficits in Dyt1 knock-in mice are likely produced by abnormal muscle contractions, and Dyt1 knock-in mice can potentially be used as a manifesting disease model to study pathophysiology and develop novel therapeutics. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  7. Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma.

    PubMed

    Arzt, Lisa; Halbwedl, Iris; Gogg-Kamerer, Margit; Popper, Helmut H

    2017-07-01

    Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail. A miRNA profiling was performed on 52 MPM tissue samples. Upregulated miRNAs (targeting SOCS1/3) were knocked-down using miRNA inhibitors. mRNA expression levels of STAT1/3, SOCS1/3 were detected in MPM cell lines. STAT1 has been knocked-down using siRNA and qPCR was used to detect mRNA expression levels of all JAK/STAT family members and genes that regulate them. An immunohistochemical staining was performed to detect the expression of caspases. STAT1 was upregulated and STAT3 was downregulated, SOCS1/3 protein was not detected but it was possible to detect SOCS1/3 mRNA in MPM cell lines. The upregulated miRNAs were successfully knocked-down, however the expected effect on SOCS1 expression was not detected. STAT1 knock-down had different effects on STAT3/5 expression. Caspase 3a and 8 expression was found to be increased after STAT1 knock-down. The physiologic regulation of STAT1 via SOCS1 is completely lost in MPM and it does not seem that the miRNAs identified by now, do inhibit the expression of SOCS1. MPM cell lines compensate STAT1 knock-down by increasing the expression of STAT3 or STAT5a, two genes which are generally considered to be oncogenes. And much more important, STAT1 knock-down induces apoptosis in MPM cell lines and STAT1 might therefore be a target for therapeutic intervention.

  8. Knock-in fibroblasts and transgenic blastocysts for expression of human FGF2 in the bovine β-casein gene locus using CRISPR/Cas9 nuclease-mediated homologous recombination.

    PubMed

    Jeong, Young-Hee; Kim, Yeong Ji; Kim, Eun Young; Kim, Se Eun; Kim, Jiwoo; Park, Min Jee; Lee, Hong-Gu; Park, Se Pill; Kang, Man-Jong

    2016-06-01

    Many transgenic domestic animals have been developed to produce therapeutic proteins in the mammary gland, and this approach is one of the most important methods for agricultural and biomedical applications. However, expression and secretion of a protein varies because transgenes are integrated at random sites in the genome. In addition, distal enhancers are very important for transcriptional gene regulation and tissue-specific gene expression. Development of a vector system regulated accurately in the genome is needed to improve production of therapeutic proteins. The objective of this study was to develop a knock-in system for expression of human fibroblast growth factor 2 (FGF2) in the bovine β-casein gene locus. The F2A sequence was fused to the human FGF2 gene and inserted into exon 3 of the β-casein gene. We detected expression of human FGF2 mRNA in the HC11 mouse mammary epithelial cells by RT-PCR and human FGF2 protein in the culture media using western blot analysis when the knock-in vector was introduced. We transfected the knock-in vector into bovine ear fibroblasts and produced knock-in fibroblasts using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Moreover, the CRISPR/Cas9 system was more efficient than conventional methods. In addition, we produced knock-in blastocysts by somatic cell nuclear transfer using the knock-in fibroblasts. Our knock-in fibroblasts may help to create cloned embryos for development of transgenic dairy cattle expressing human FGF2 protein in the mammary gland via the expression system of the bovine β-casein gene.

  9. [Application of atomic absorption spectrometry in the engine knock detection].

    PubMed

    Chen, Li-Dan

    2013-02-01

    Because existing human experience diagnosis method and apparatus for auxiliary diagnosis method are difficult to diagnose quickly engine knock. Atomic absorption spectrometry was used to detect the automobile engine knock in in innovative way. After having determined Fe, Al, Cu, Cr and Pb content in the 35 groups of Audi A6 engine oil whose travel course is 2 000 -70 000 kilometers and whose sampling interval is 2 000 kilometers by atomic absorption spectrometry, the database of primary metal content in the same automobile engine at different mileage was established. The research shows that the main metal content fluctuates within a certain range. In practical engineering applications, after the determination of engine oil main metal content and comparison with its database value, it can not only help to diagnose the type and location of engine knock without the disintegration and reduce vehicle maintenance costs and improve the accuracy of engine knock fault diagnosis.

  10. Fascin-1 knock-down of human glioma cells reduces their microvilli/filopodia while improving their susceptibility to lymphocyte-mediated cytotoxicity

    PubMed Central

    Hoa, Neil T; Ge, Lisheng; Erickson, Kate L; Kruse, Carol A; Cornforth, Andrew N; Kuznetsov, Yurii; McPherson, Alex; Martini, Filippo; Jadus, Martin R

    2015-01-01

    Cancer cells derived from Glioblastoma multiforme possess membranous protrusions allowing these cells to infiltrate surrounding tissue, while resisting lymphocyte cytotoxicity. Microvilli and filopodia are supported by actin filaments cross-linked by fascin. Fascin-1 was genetically silenced within human U251 glioma cells; these knock-down glioma cells lost their microvilli/filopodia. The doubling time of these fascin-1 knock-down cells was doubled that of shRNA control U251 cells. Fascin-1 knock-down cells lost their transmigratory ability responding to interleukin-6 or insulin-like growth factor-1. Fascin-1 silenced U251 cells were more easily killed by cytolytic lymphocytes. Fascin-1 knock-down provides unique opportunities to augment glioma immunotherapy by simultaneously targeting several key glioma functions: like cell transmigration, cell division and resisting immune responses. PMID:25901196

  11. Why people believe they were exposed to biological or chemical warfare: a survey of Gulf War veterans.

    PubMed

    Brewer, Noel T; Lillie, Sarah E; Hallman, William K

    2006-04-01

    The study sought to understand better how people come to believe they have been exposed to biological and chemical warfare. We conducted telephone interviews with 1,009 American veterans (65% response rate) deployed and not deployed to the Gulf War, a conflict during which there were credible threats that such warfare could be used. Only 6% of non-Gulf War veterans reported exposure to biological or chemical warfare, but most of Gulf War veterans reported exposure (64%). The majority of these were unsure whether the exposure was chemical or biological in nature. The most commonly reported exposure indicators were receiving an alert from the military and having physical symptoms. Veterans who were certain of the type of exposure (biological or chemical) were more likely to recall having been told by the military and to recall physical symptoms. Future communications with soldiers and the general public about biological and chemical warfare may need to emphasize the uncertain nature of such risk information. Evaluations of exposure diagnostic technologies should take into account the problem of people initially believing, but not later discounting, false positive results.

  12. Oxidative decontamination of chemical and biological warfare agents using L-Gel.

    PubMed

    Raber, Ellen; McGuire, Raymond

    2002-08-05

    A decontamination method has been developed using a single reagent that is effective both against chemical warfare (CW) and biological warfare (BW) agents. The new reagent, "L-Gel", consists of an aqueous solution of a mild commercial oxidizer, Oxone, together with a commercial fumed silica gelling agent, Cab-O-Sil EH-5. L-Gel is non-toxic, environmentally friendly, relatively non-corrosive, maximizes contact time because of its thixotropic nature, clings to walls and ceilings, and does not harm carpets or painted surfaces. The new reagent also addresses the most demanding requirements for decontamination in the civilian sector, including availability, low maintenance, ease of application and deployment by a variety of dispersal mechanisms, minimal training and acceptable expense. Experiments to test the effectiveness of L-Gel were conducted at Lawrence Livermore National Laboratory and independently at four other locations. L-Gel was tested against all classes of chemical warfare agents and against various biological warfare agent surrogates, including spore-forming bacteria and non-virulent strains of real biological agents. Testing showed that L-Gel is as effective against chemical agents and biological materials, including spores, as the best military decontaminants.

  13. The Cyber Warfare Professional: Realizations for Developing the Next Generation

    DTIC Science & Technology

    2011-01-01

    consequences for the others. However, just as airpower soon emerged as a revolution in military affairs during the early twentieth century, so may cyber warfare become the next revolution for the new millennium.

  14. Textbook of Military Medicine. Part 1. Warfare, Weaponry, and the Casualty. Part 5. Conventional Warfare. Ballistic, Blast, and Burn Injuries

    DTIC Science & Technology

    1991-01-01

    United States. Because the vast majority of our patients are not active -duty military personnel, it may seem that our day-to-day ac- tivities are far... activated . A designated time-delay fuse uses an Source: Reference 8 15 Conventional Warfare: Ballistic, Blast, and Burn Injuries explosion and the...be found embedded and unexploded in tissue. The fuse is located at the tip of the warhead, and is activated and will deionate on contact only after

  15. Encyclopedia of Explosives and Related Items. Volume 10

    DTIC Science & Technology

    1983-01-01

    trinitroethyl stearate 6 E330 Ethyiphosphorodimethylamidycyanadate se Ethyl-substituted acid amides, N-trinitro derivs GA chemical warfare agent 2.C 167; 6...6 GI Galex 6 G8-G9 GA (chemical warfare agent ) 6 G 1 Galil rifle 6 G9 GA see Dimethylaminocyanophosphoric acid Galil rifle 6 G9 5 D1308-D1309 Gabeaud...G45 Gas volumes produced on expln or detonation Gelatina explosiva de guerra 6 G45 of expls 6 G36-G41 Gelatina gomma 6 G45 Gas warfare agents 2 C165

  16. SIGINT, EW, and EIW in the Korean People’s Army: An Overview of Development and Organization

    DTIC Science & Technology

    2005-08-01

    Joseph S. Bermudez Jr. "The basic key to victory in modern warfare is to do well in electronic warfare …" Kim Jong Il96 For many years now the...96 “ Kim Jong Il Stresses Electronic Warfare Capabilities,” Radio P’yongyang, 24 September 1999, as cited in FBIS. Bytes and Bullets... Kim Jong Il98 Details concerning how the MPAF developed this understanding, and how it has organized and planned to conduct SIGINT, EW and EIW

  17. Information Warfare and the Principles of War.

    DTIC Science & Technology

    1997-02-07

    information dominance , control of ’cyberspace’ or the ’Infosphere’ and Information Warfare. Some argue that Information Warfare (IW) is just a repackaging of old concepts and current practices, while others contend it is the next Revolution in Military Affairs (RMA). The question that needs to be addressed is; can IW achieve strategic and operational military objectives on its on merit? A way to answer this questions is to analyze IW against our current doctrine. Using the principles of war as a framework, does IW fit (or can it be employed) in the

  18. Air Force Cyber Warfare: Now and the Future

    DTIC Science & Technology

    2013-10-01

    cyber warfare in popular culture. Most of them focus on the individual s uncanny grasp of technology the ability to exploit any system with a dizzying flurry of keystrokes or to fend off adversaries with a smartphone, a paper clip, and an ingenious plan. These socially awkward heroes and heroines fill the silver screen with visions of a new kind of warfare. Contradicting these stereotypes, Air Force cyber operations are carefully planned and controlled by disciplined, rigorously trained operators. Rather than acting alone, these professionals produce effects in support of

  19. U.S. Army Chemical Corps Historical Studies, Gas Warfare in World War I: The 5th Division Captures Frapelle, August 1918

    DTIC Science & Technology

    1958-03-01

    U. S . ARMY CHEMICAL CORPS HISTORICAL STUDIES GAS WARFARE IN WORLD WAR I THE 5t1h DIVISION CAPTURES FRAPELLF, 00 August 1918 CTD Offce t e Chef Ch mal...j JNSPECrrr / D~iJ f ; t t] GA o WARFARE IN WORLD WAR I By - --------- St ixdy Number 7 t:a . • ’ I : : . .. s U.S. ARMY CHEIICAL CORPS [ist...Analysi s Concerning the Weight of Shell . . . . . . . ... . 38 The Cost of Frapelle . . . . . . . . . . . .. 41 Medical Department Comments

  20. Science, Technology, and Warfare. Proceedings of the Military History Symposium (3rd) Held at the United States Air Force Academy (Colorado Springs, Colorado) on 8-9 May 1969

    DTIC Science & Technology

    1970-09-01

    between science-technology and warfare. The stereotyped theory of a linear relationship between science, technology, and warfare satisfies the facts...therefore discarded piecemeal. Only with Mahan’s theory did this condition change. Morison then considers the opposite problem today: one in which the...1938), 1:531. = A s is now very well known, the impetus theory expounded with variations by all the most important writers on philosophy of motion

  1. Using RNA interference to knock down the adhesion protein TES.

    PubMed

    Griffith, Elen

    2007-01-01

    RNA interference (RNAi) is a specific and efficient method to knock down protein levels using small interfering RNAs (siRNAs), which target mRNA degradation. RNAi can be used in mammalian cell culture systems to target any protein of interest, and several studies have used this method to knock down adhesion proteins. We used siRNAs to knock down the levels of TES, a focal adhesion protein, in HeLa cells. We demonstrated knockdown of both TES mRNA and TES protein. Although total knockdown of TES was not achieved, the observed reduction in TES protein was sufficient to result in a cellular phenotype of reduced actin stress fibers.

  2. The Knock-Limited Performance of Fuel Blends Containing Spiropentane, Methylenecyclobutane, Di-Tert-Butyl Ether, Methyl Tert-Butyl Ether, and Triptane

    NASA Technical Reports Server (NTRS)

    Meyer, Carl L.

    1946-01-01

    Tests show that at inlet-air temperatures of 250 deg F and 100 deg F the knock-limited performance of the base fuel of blends, leaded with 4 ml TEL per gallon and containing 20 percent spiropentane, was reduced at fuel/air ratios below 0.085. The 20 percent methylenecyclobutane reduced the knock-limited power of the base fuel at fuel/air ratios below 0.112. Di-tert-butyl ether, methyl-tert-butyl ether, and triptane increased the knock-limited power of the base fuel at all fuel/air ratios and at both temperatures.

  3. Analysis of Spark-Ignition Engine Knock as Seen in Photographs Taken at 200,000 Frames Per Second

    NASA Technical Reports Server (NTRS)

    Miller, Cearcy D; Olsen, H Lowell; Logan, Walter O , Jr; Osterstrom, Gordon E

    1946-01-01

    A motion picture of the development of knock in a spark-ignition engine is presented, which consists of 20 photographs taken at intervals of 5 microseconds, or at a rate of 200,000 photographs per second, with an equivalent wide-open exposure time of 6.4 microseconds for each photograph. A motion picture of a complete combustion process, including the development of knock, taken at the rate of 40,000 photographs per second is also presented to assist the reader in orienting the photographs of the knock development taken at 200,000 frames per second.

  4. Efficient generation of knock-in transgenic zebrafish carrying reporter/driver genes by CRISPR/Cas9-mediated genome engineering.

    PubMed

    Kimura, Yukiko; Hisano, Yu; Kawahara, Atsuo; Higashijima, Shin-ichi

    2014-10-08

    The type II bacterial CRISPR/Cas9 system is rapidly becoming popular for genome-engineering due to its simplicity, flexibility, and high efficiency. Recently, targeted knock-in of a long DNA fragment via homology-independent DNA repair has been achieved in zebrafish using CRISPR/Cas9 system. This raised the possibility that knock-in transgenic zebrafish could be efficiently generated using CRISPR/Cas9. However, how widely this method can be applied for the targeting integration of foreign genes into endogenous genomic loci is unclear. Here, we report efficient generation of knock-in transgenic zebrafish that have cell-type specific Gal4 or reporter gene expression. A donor plasmid containing a heat-shock promoter was co-injected with a short guide RNA (sgRNA) targeted for genome digestion, a sgRNA targeted for donor plasmid digestion, and Cas9 mRNA. We have succeeded in establishing stable knock-in transgenic fish with several different constructs for 4 genetic loci at a frequency being exceeding 25%. Due to its simplicity, design flexibility, and high efficiency, we propose that CRISPR/Cas9-mediated knock-in will become a standard method for the generation transgenic zebrafish.

  5. Closed loop statistical performance analysis of N-K knock controllers

    NASA Astrophysics Data System (ADS)

    Peyton Jones, James C.; Shayestehmanesh, Saeed; Frey, Jesse

    2017-09-01

    The closed loop performance of engine knock controllers cannot be rigorously assessed from single experiments or simulations because knock behaves as a random process and therefore the response belongs to a random distribution also. In this work a new method is proposed for computing the distributions and expected values of the closed loop response, both in steady state and in response to disturbances. The method takes as its input the control law, and the knock propensity characteristic of the engine which is mapped from open loop steady state tests. The method is applicable to the 'n-k' class of knock controllers in which the control action is a function only of the number of cycles n since the last control move, and the number k of knock events that have occurred in this time. A Cumulative Summation (CumSum) based controller falls within this category, and the method is used to investigate the performance of the controller in a deeper and more rigorous way than has previously been possible. The results are validated using onerous Monte Carlo simulations, which confirm both the validity of the method and its high computational efficiency.

  6. Optimization of the production of knock-in alleles by CRISPR/Cas9 microinjection into the mouse zygote.

    PubMed

    Raveux, Aurélien; Vandormael-Pournin, Sandrine; Cohen-Tannoudji, Michel

    2017-02-17

    Microinjection of the CRISPR/Cas9 system in zygotes is an efficient and comparatively fast method to generate genetically modified mice. So far, only few knock-in mice have been generated using this approach, and because no systematic study has been performed, parameters controlling the efficacy of CRISPR/Cas9-mediated targeted insertion are not fully established. Here, we evaluated the effect of several parameters on knock-in efficiency changing only one variable at a time. We found that knock-in efficiency was dependent on injected Cas9 mRNA and single-guide RNA concentrations and that cytoplasmic injection resulted in more genotypic complexity compared to pronuclear injection. Our results also indicated that injection into the pronucleus compared to the cytoplasm is preferable to generate knock-in alleles with an oligonucleotide or a circular plasmid. Finally, we showed that Cas9D10A nickase variant was less efficient than wild-type Cas9 for generating knock-in alleles and caused a higher rate of mosaicism. Thus, our study provides valuable information that will help to improve the future production of precise genetic modifications in mice.

  7. Enhanced serotonin response in the hippocampus of Galphaz protein knock-out mice.

    PubMed

    Oleskevich, Sharon; Leck, Kwong-Joo; Matthaei, Klaus; Hendry, Ian A

    2005-06-21

    The serotonin-1A [5-hydroxytryptamine 1A (5HT1A)] receptor is important for emotional and homeostatic processes in the central nervous system. In the hippocampus, the 5HT1A receptor couples to inhibitory Gi/o proteins to decrease pyramidal cell excitability. Here we investigate the 5HT1A receptor in a mouse deficient in the alpha-subunit of Gz protein (Galphaz knock-out). Behavioural tests showed heightened anxiety and depression-like behaviour in the Galphaz knock-out mice. Whole-cell recording in CA1 pyramidal neurons showed a significantly greater 5HT1A receptor-mediated potassium current in Galphaz knock-out mice. The effect was independent of 5HT4 receptors as the slow after-hyperpolarization was unaffected and a slow depolarization was absent in the Galphaz knock-out mice. Other receptors linked to Gi/o proteins [gamma-aminobutyric acid type B receptor (GABAB), adenosine A1 and muscarinic acetylcholine receptors] were not affected in Galphaz knock-out mice. These results suggest that the 5HT1A receptor may be linked to Galphaz protein, as reported previously in cell culture but shown here in an intact neural network.

  8. Analysis of Knock Phenomenon Induced in a Constant Volume Chamber by Local Gas Temperature Measurement and Visualization

    NASA Astrophysics Data System (ADS)

    Moriyoshi, Yasuo; Kobayashi, Shigemi; Enomoto, Yoshiteru

    Knock phenomenon in SI engines is regarded as an auto-ignition of unburned end-gas, and it has been widely examined by using rapid compression machines (RCM), shock-tubes or test engines. Recent researches point out the importance of the low temperature chemical reaction and the negative temperature coefficient (NTC). To investigate the effects, analyses of instantaneous local gas temperature, flow visualization and gaseous pressure were conducted in this study. As measurements using real engines are too difficult to analyze, the authors aimed to make measurements using a constant volume vessel under knock conditions where propagating flame exists during the induction time of auto-ignition. Adopting the two-wire thermocouple method enabled us to measure the instantaneous local gas temperature until the moment when the flame front passes by. High-speed images inside the unburned region were also recorded simultaneously using an endoscope. As a result, it was found that when knock occurs, the auto-ignition initiation time seems slightly early compared to the results without knock. This causes a higher volume ratio of unburned mixture and existence of many hot spots and stochastically leads to an initiation of knock.

  9. Interagency Cooperation for Irregular Warfare at the Combatant Command

    DTIC Science & Technology

    2009-01-01

    Directorate, and the USSOCOM Interagency Task Force ( IATF ) offer examples of JIACGs coping with the issues of IW. Each organization possesses strengths...46 USSOCOM IATF History...Force for Irregular Warfare ( IATF IW).33 EUCOM conducts interagency

  10. A history of biological and chemical warfare and terrorism.

    PubMed

    Malloy, C D

    2000-07-01

    This article provides a brief history of biological warfare and terrorism. It contends that examining disease in history provides public health specialists with the knowledge necessary to improve our surveillance system for potential acts of bioterrorism.

  11. Fluorescent sensors for the detection of chemical warfare agents.

    PubMed

    Burnworth, Mark; Rowan, Stuart J; Weder, Christoph

    2007-01-01

    Along with biological and nuclear threats, chemical warfare agents are some of the most feared weapons of mass destruction. Compared to nuclear weapons they are relatively easy to access and deploy, which makes them in some aspects a greater threat to national and global security. A particularly hazardous class of chemical warfare agents are the nerve agents. Their rapid and severe effects on human health originate in their ability to block the function of acetylcholinesterase, an enzyme that is vital to the central nervous system. This article outlines recent activities regarding the development of molecular sensors that can visualize the presence of nerve agents (and related pesticides) through changes of their fluorescence properties. Three different sensing principles are discussed: enzyme-based sensors, chemically reactive sensors, and supramolecular sensors. Typical examples are presented for each class and different fluorescent sensors for the detection of chemical warfare agents are summarized and compared.

  12. An evolutionary theory of large-scale human warfare: Group-structured cultural selection.

    PubMed

    Zefferman, Matthew R; Mathew, Sarah

    2015-01-01

    When humans wage war, it is not unusual for battlefields to be strewn with dead warriors. These warriors typically were men in their reproductive prime who, had they not died in battle, might have gone on to father more children. Typically, they are also genetically unrelated to one another. We know of no other animal species in which reproductively capable, genetically unrelated individuals risk their lives in this manner. Because the immense private costs borne by individual warriors create benefits that are shared widely by others in their group, warfare is a stark evolutionary puzzle that is difficult to explain. Although several scholars have posited models of the evolution of human warfare, these models do not adequately explain how humans solve the problem of collective action in warfare at the evolutionarily novel scale of hundreds of genetically unrelated individuals. We propose that group-structured cultural selection explains this phenomenon. © 2015 Wiley Periodicals, Inc.

  13. Changing the Scale and Efficiency of Chemical Warfare Countermeasure Discovery Using the Zebrafish

    PubMed Central

    Peterson, Randall T.; MacRae, Calum A.

    2013-01-01

    As the scope of potential chemical warfare agents grows rapidly and as the diversity of potential threat scenarios expands with non-state actors, so a need for innovative approaches to countermeasure development has emerged. In the last few years, the utility of the zebrafish as a model organism that is amenable to high-throughput screening has become apparent and this system has been applied to the unbiased discovery of chemical warfare countermeasures. This review summarizes the in vivo screening approach that has been pioneered in the countermeasure discovery arena, and highlights the successes to date as well as the potential challenges in moving the field forward. Importantly, the establishment of a zebrafish platform for countermeasure discovery would offer a rapid response system for the development of antidotes to the continuous stream of new potential chemical warfare agents. PMID:24273586

  14. Detection of biological warfare agents using ultra violet-laser induced fluorescence LIDAR.

    PubMed

    Joshi, Deepti; Kumar, Deepak; Maini, Anil K; Sharma, Ramesh C

    2013-08-01

    This review has been written to highlight the threat of biological warfare agents, their types and detection. Bacterial biological agent Bacillus anthracis (bacteria causing the disease anthrax) which is most likely to be employed in biological warfare is being discussed in detail. Standoff detection of biological warfare agents in aerosol form using Ultra violet-Laser Induced Fluorescence (UV-LIF) spectroscopy method has been studied. Range-resolved detection and identification of biological aerosols by both nano-second and non-linear femto-second LIDAR is also discussed. Calculated received fluorescence signal for a cloud of typical biological agent Bacillus globigii (Simulants of B. anthracis) at a location of ~5.0 km at different concentrations in presence of solar background radiation has been described. Overview of current research efforts in internationally available working UV-LIF LIDAR systems are also mentioned briefly. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Efficient Knock-in of a Point Mutation in Porcine Fibroblasts Using the CRISPR/Cas9-GMNN Fusion Gene.

    PubMed

    Gerlach, Max; Kraft, Theresia; Brenner, Bernhard; Petersen, Björn; Niemann, Heiner; Montag, Judith

    2018-06-13

    During CRISPR/Cas9 mediated genome editing, site-specific double strand breaks are introduced and repaired either unspecific by non-homologous end joining (NHEJ) or sequence dependent by homology directed repair (HDR). Whereas NHEJ-based generation of gene knock-out is widely performed, the HDR-based knock-in of specific mutations remains a bottleneck. Especially in primary cell lines that are essential for the generation of cell culture and animal models of inherited human diseases, knock-in efficacy is insufficient and needs significant improvement. Here, we tested two different approaches to increase the knock-in frequency of a specific point mutation into the MYH7 -gene in porcine fetal fibroblasts. We added a small molecule inhibitor of NHEJ, SCR7 (5,6-bis((E)-benzylideneamino)-2-mercaptopyrimidin-4-ol), during genome editing and screened cell cultures for the point mutation. However, this approach did not yield increased knock-in rates. In an alternative approach, we fused humanized Cas9 (hCas9) to the N-terminal peptide of the Geminin gene ( GMNN ). The fusion protein is degraded in NHEJ-dominated cell cycle phases, which should increase HDR-rates. Using hCas9- GMNN and point mutation-specific real time PCR screening, we found a two-fold increase in genome edited cell cultures. This increase of HDR by hCas9- GMNN provides a promising way to enrich specific knock-in in porcine fibroblast cultures for somatic cloning approaches.

  16. Knock-in of Enhanced Green Fluorescent Protein or/and Human Fibroblast Growth Factor 2 Gene into β-Casein Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein.

    PubMed

    Lee, Sang Mi; Kim, Ji Woo; Jeong, Young-Hee; Kim, Se Eun; Kim, Yeong Ji; Moon, Seung Ju; Lee, Ji-Hye; Kim, Keun-Jung; Kim, Min-Kyu; Kang, Man-Jong

    2014-11-01

    Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo) as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5' arm and 3' arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP) was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands.

  17. Knock-in of Enhanced Green Fluorescent Protein or/and Human Fibroblast Growth Factor 2 Gene into β-Casein Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein

    PubMed Central

    Lee, Sang Mi; Kim, Ji Woo; Jeong, Young-Hee; Kim, Se Eun; Kim, Yeong Ji; Moon, Seung Ju; Lee, Ji-Hye; Kim, Keun-Jung; Kim, Min-Kyu; Kang, Man-Jong

    2014-01-01

    Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo) as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5′ arm and 3′ arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP) was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands. PMID:25358326

  18. Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

    PubMed

    Ono, Motoharu; Yamada, Kayo; Avolio, Fabio; Afzal, Vackar; Bensaddek, Dalila; Lamond, Angus I

    2015-01-01

    We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

  19. CRISPR/Cas9 Allows Efficient and Complete Knock-In of a Destabilization Domain-Tagged Essential Protein in a Human Cell Line, Allowing Rapid Knockdown of Protein Function

    PubMed Central

    Park, Arnold; Won, Sohui T.; Pentecost, Mickey; Bartkowski, Wojciech; Lee, Benhur

    2014-01-01

    Although modulation of protein levels is an important tool for study of protein function, it is difficult or impossible to knockdown or knockout genes that are critical for cell growth or viability. For such genes, a conditional knockdown approach would be valuable. The FKBP protein-based destabilization domain (DD)-tagging approach, which confers instability to the tagged protein in the absence of the compound Shield-1, has been shown to provide rapid control of protein levels determined by Shield-1 concentration. Although a strategy to knock-in DD-tagged protein at the endogenous loci has been employed in certain parasite studies, partly due to the relative ease of knock-in as a result of their mostly haploid lifecycles, this strategy has not been demonstrated in diploid or hyperploid mammalian cells due to the relative difficulty of achieving complete knock-in in all alleles. The recent advent of CRISPR/Cas9 homing endonuclease-mediated targeted genome cleavage has been shown to allow highly efficient homologous recombination at the targeted locus. We therefore assessed the feasibility of using CRISPR/Cas9 to achieve complete knock-in to DD-tag the essential gene Treacher Collins-Franceschetti syndrome 1 (TCOF1) in human 293T cells. Using a double antibiotic selection strategy to select clones with at least two knock-in alleles, we obtained numerous complete knock-in clones within three weeks of initial transfection. DD-TCOF1 expression in the knock-in cells was Shield-1 concentration-dependent, and removal of Shield-1 resulted in destabilization of DD-TCOF1 over the course of hours. We further confirmed that the tagged TCOF1 retained the nucleolar localization of the wild-type untagged protein, and that destabilization of DD-TCOF1 resulted in impaired cell growth, as expected for a gene implicated in ribosome biogenesis. CRISPR/Cas9-mediated homologous recombination to completely knock-in a DD tag likely represents a generalizable and efficient strategy to achieve rapid modulation of protein levels in mammalian cells. PMID:24743236

  20. CRISPR/Cas9 allows efficient and complete knock-in of a destabilization domain-tagged essential protein in a human cell line, allowing rapid knockdown of protein function.

    PubMed

    Park, Arnold; Won, Sohui T; Pentecost, Mickey; Bartkowski, Wojciech; Lee, Benhur

    2014-01-01

    Although modulation of protein levels is an important tool for study of protein function, it is difficult or impossible to knockdown or knockout genes that are critical for cell growth or viability. For such genes, a conditional knockdown approach would be valuable. The FKBP protein-based destabilization domain (DD)-tagging approach, which confers instability to the tagged protein in the absence of the compound Shield-1, has been shown to provide rapid control of protein levels determined by Shield-1 concentration. Although a strategy to knock-in DD-tagged protein at the endogenous loci has been employed in certain parasite studies, partly due to the relative ease of knock-in as a result of their mostly haploid lifecycles, this strategy has not been demonstrated in diploid or hyperploid mammalian cells due to the relative difficulty of achieving complete knock-in in all alleles. The recent advent of CRISPR/Cas9 homing endonuclease-mediated targeted genome cleavage has been shown to allow highly efficient homologous recombination at the targeted locus. We therefore assessed the feasibility of using CRISPR/Cas9 to achieve complete knock-in to DD-tag the essential gene Treacher Collins-Franceschetti syndrome 1 (TCOF1) in human 293T cells. Using a double antibiotic selection strategy to select clones with at least two knock-in alleles, we obtained numerous complete knock-in clones within three weeks of initial transfection. DD-TCOF1 expression in the knock-in cells was Shield-1 concentration-dependent, and removal of Shield-1 resulted in destabilization of DD-TCOF1 over the course of hours. We further confirmed that the tagged TCOF1 retained the nucleolar localization of the wild-type untagged protein, and that destabilization of DD-TCOF1 resulted in impaired cell growth, as expected for a gene implicated in ribosome biogenesis. CRISPR/Cas9-mediated homologous recombination to completely knock-in a DD tag likely represents a generalizable and efficient strategy to achieve rapid modulation of protein levels in mammalian cells.

  1. A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.

    PubMed

    Bouhy, Delphine; Juneja, Manisha; Katona, Istvan; Holmgren, Anne; Asselbergh, Bob; De Winter, Vicky; Hochepied, Tino; Goossens, Steven; Haigh, Jody J; Libert, Claude; Ceuterick-de Groote, Chantal; Irobi, Joy; Weis, Joachim; Timmerman, Vincent

    2018-01-01

    Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces impairments in autophagy that may aggravate the phenotype.

  2. 77 FR 60679 - Takes of Marine Mammals Incidental to Specified Activities; U.S. Navy Training and Testing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-04

    ...; the Undersea Warfare Training Range; the Key West Range Complex; the Naval Surface Warfare Center... of Protected Resources, National Marine Fisheries Service, 1315 East-West Highway, Silver Spring, MD...

  3. Simulating cyber warfare and cyber defenses: information value considerations

    NASA Astrophysics Data System (ADS)

    Stytz, Martin R.; Banks, Sheila B.

    2011-06-01

    Simulating cyber warfare is critical to the preparation of decision-makers for the challenges posed by cyber attacks. Simulation is the only means we have to prepare decision-makers for the inevitable cyber attacks upon the information they will need for decision-making and to develop cyber warfare strategies and tactics. Currently, there is no theory regarding the strategies that should be used to achieve objectives in offensive or defensive cyber warfare, and cyber warfare occurs too rarely to use real-world experience to develop effective strategies. To simulate cyber warfare by affecting the information used for decision-making, we modify the information content of the rings that are compromised during in a decision-making context. The number of rings affected and value of the information that is altered (i.e., the closeness of the ring to the center) is determined by the expertise of the decision-maker and the learning outcome(s) for the simulation exercise. We determine which information rings are compromised using the probability that the simulated cyber defenses that protect each ring can be compromised. These probabilities are based upon prior cyber attack activity in the simulation exercise as well as similar real-world cyber attacks. To determine which information in a compromised "ring" to alter, the simulation environment maintains a record of the cyber attacks that have succeeded in the simulation environment as well as the decision-making context. These two pieces of information are used to compute an estimate of the likelihood that the cyber attack can alter, destroy, or falsify each piece of information in a compromised ring. The unpredictability of information alteration in our approach adds greater realism to the cyber event. This paper suggests a new technique that can be used for cyber warfare simulation, the ring approach for modeling context-dependent information value, and our means for considering information value when assigning cyber resources to information protection tasks. The first section of the paper introduces the cyber warfare simulation challenge and the reasons for its importance. The second section contains background information related to our research. The third section contains a discussion of the information ring technique and its use for simulating cyber attacks. The fourth section contains a summary and suggestions for research.

  4. Intelligence, Information Technology, and Information Warfare.

    ERIC Educational Resources Information Center

    Davies, Philip H. J.

    2002-01-01

    Addresses the use of information technology for intelligence and information warfare in the context of national security and reviews the status of clandestine collection. Discusses hacking, human agent collection, signal interception, covert action, counterintelligence and security, and communications between intelligence producers and consumers…

  5. 78 FR 22529 - Notice of Intent To Grant Partially Exclusive Patent License; Max-Viz, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-16

    ... Technology Applications, Space and Naval Warfare Systems Center Pacific, Code 72120, 53560 Hull St, Bldg A33... Technology Applications, Space and Naval Warfare Systems Center Pacific, Code 72120, 53560 Hull St, Bldg A33...

  6. Offensive Cyber Capability: Can it Reduce Cyberterrorism

    DTIC Science & Technology

    2010-12-02

    33 Lech J. Janczewski, and Andrew M. Colarik, eds., Cyber Warfare and Cyber Terrorism (New York: Information Science Reference, 2008...Science and Business Media, 2008. Janczewski, Lech , J. and Andrew M. Colarik, eds., Cyber Warfare and Cyber Terrorism. New York: Information Science

  7. Electronic Warfare and Radar Systems Engineering Handbook

    DTIC Science & Technology

    1999-04-01

    EWRL Electronic Warfare Reprogrammable ELNOT Emitter Library Notation Library (USN) EM Electromagnetic EWSI EW Systems Integration E-Mail Electronic...ram air turbine (RAT) propellers used to power aircraft pods, helicopter rotor blades, and protruding surfaces of automobile hubcaps will all provide

  8. Tissue-based water quality biosensors for detecting chemical warfare agents

    DOEpatents

    Greenbaum, Elias [Oak Ridge, TN; Sanders, Charlene A [Knoxville, TN

    2003-05-27

    A water quality sensor for detecting the presence of at least one chemical or biological warfare agent includes: a cell; apparatus for introducing water into the cell and discharging water from the cell adapted for analyzing photosynthetic activity of naturally occurring, free-living, indigenous photosynthetic organisms in water; a fluorometer for measuring photosynthetic activity of naturally occurring, free-living, indigenous photosynthetic organisms drawn into the cell; and an electronics package that analyzes raw data from the fluorometer and emits a signal indicating the presence of at least one chemical or biological warfare agent in the water.

  9. Exploring the Human Fabric through an Analyst's Eyes

    NASA Astrophysics Data System (ADS)

    Belov, Nadya; Patti, Jeff; Wilcox, Saki; Almanzar, Rafael; Kim, Janet; Kellogg, Jennifer; Dang, Steven

    The nature and type of conflicts drastically changed in the last half of the twentieth century. Wars are no longer limited to the field; they are supplemented with guerrilla warfare and other asymmetric warfare tactics including domestic terrorism. Domestic terrorism has demonstrated a need for improved homeland security capabilities. Establishing and maintaining the understanding of the key players and the underlying social networks is essential to combating asynchronous warfare tactics. Herein, we identify the key challenges addressed by our Collection/Exploitation Decision System (CEDS) that assist analysts in maintaining an up-to-date understanding of dynamic human networks.

  10. The effect of SIRT1 protein knock down on PGC-1α acetylation during skeletal muscle contraction.

    PubMed

    Park, Dae Ryoung; Kim, Jeong Seok; Kim, Chang Keun

    2014-03-01

    The purpose of this study was to investigate the effect of Sirtuin 1 (SIRT1) and General control nonderepressible 5 (GCN5) knock down on peroxisome proliferator- activated receptor gamma coactivator 1-alpha (PGC-1α) deacetylation during electrical stimulated skeletal muscle contraction. Skeletal muscle primary cell were isolated from C57BL/6 mice gastrocnemius and transfected lentiviral SIRT1 and GCN5 shRNA. Knock downed muscle cell were stimulated by electrical stimulation (1Hz, 3min) and collected for PGC-1α deceatylation assays. Immunoprecipitation performed for PGC-1α deacetylation, acetyl-lysine level was measured. Our resulted showed SIRT1 knock down not influenced to PGC-1α deacetylation during electrical stimulation induced muscle contraction while GCN5 knock down decreased PGC-1α deacetylation significantly (p<0.05). This study can be concluded that GCN5 is a critical factor for muscle contraction induced PGC-1α deacetylation.

  11. The Reduced Effectiveness of EGR to Mitigate Knock at High Loads in Boosted SI Engines

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

    Szybist, James P.; Wagnon, Scott W.; Splitter, Derek A.

    Numerous studies have demonstrated that exhaust gas recirculation (EGR) can attenuate knock propensity in spark ignition (SI) engines at naturally aspirated or lightly boosted conditions. In this paper, we investigate the role of cooled EGR under higher load conditions with multiple fuel compositions, where highly retarded combustion phasing typical of modern SI engines was used. It was found that under these conditions, EGR attenuation of knock is greatly reduced, where EGR doesn’t allow significant combustion phasing advance as it does under lighter load conditions. Detailed combustion analysis shows that when EGR is added, the polytropic coefficient increases causing the compressivemore » pressure and temperature to increase. At sufficiently highly boosted conditions, the increase in polytropic coefficient and additional trapped mass from EGR can sufficiently reduce fuel ignition delay to overcome knock attenuation effects. Kinetic modeling demonstrates that the effectiveness of EGR to mitigate knock is highly dependent on the pressure-temperature condition. Experiments at 2000 rpm have confirmed reduced fuel ignition delay under highly boosted conditions relevant to modern downsized boosted SI engines, where in-cylinder pressure is higher and the temperature is cooler. Finally, at these conditions, charge reactivity increases compared to naturally aspirated conditions, and attenuation of knock by EGR is reduced.« less

  12. The Reduced Effectiveness of EGR to Mitigate Knock at High Loads in Boosted SI Engines

    DOE PAGES

    Szybist, James P.; Wagnon, Scott W.; Splitter, Derek A.; ...

    2017-09-04

    Numerous studies have demonstrated that exhaust gas recirculation (EGR) can attenuate knock propensity in spark ignition (SI) engines at naturally aspirated or lightly boosted conditions. In this paper, we investigate the role of cooled EGR under higher load conditions with multiple fuel compositions, where highly retarded combustion phasing typical of modern SI engines was used. It was found that under these conditions, EGR attenuation of knock is greatly reduced, where EGR doesn’t allow significant combustion phasing advance as it does under lighter load conditions. Detailed combustion analysis shows that when EGR is added, the polytropic coefficient increases causing the compressivemore » pressure and temperature to increase. At sufficiently highly boosted conditions, the increase in polytropic coefficient and additional trapped mass from EGR can sufficiently reduce fuel ignition delay to overcome knock attenuation effects. Kinetic modeling demonstrates that the effectiveness of EGR to mitigate knock is highly dependent on the pressure-temperature condition. Experiments at 2000 rpm have confirmed reduced fuel ignition delay under highly boosted conditions relevant to modern downsized boosted SI engines, where in-cylinder pressure is higher and the temperature is cooler. Finally, at these conditions, charge reactivity increases compared to naturally aspirated conditions, and attenuation of knock by EGR is reduced.« less

  13. Paired immunoglobulin-like receptor B knockout does not enhance axonal regeneration or locomotor recovery after spinal cord injury.

    PubMed

    Nakamura, Yuka; Fujita, Yuki; Ueno, Masaki; Takai, Toshiyuki; Yamashita, Toshihide

    2011-01-21

    Myelin components that inhibit axonal regeneration are believed to contribute significantly to the lack of axonal regeneration noted in the adult central nervous system. Three proteins found in myelin, Nogo, myelin-associated glycoprotein, and oligodendrocyte-myelin glycoprotein, inhibit neurite outgrowth in vitro. All of these proteins interact with the same receptors, namely, the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PIR-B). As per previous reports, corticospinal tract (CST) regeneration is not enhanced in NgR-knock-out mice after spinal cord injury. Therefore, we assessed CST regeneration in PIR-B-knock-out mice. We found that hindlimb motor function, as assessed using the Basso mouse scale, footprint test, inclined plane test, and beam walking test, did not differ between the PIR-B-knock-out and wild-type mice after dorsal hemisection of the spinal cord. Further, tracing of the CST fibers after injury did not reveal enhanced axonal regeneration or sprouting in the CST of the PIR-B-knock-out mice. Systemic administration of NEP1-40, a NgR antagonist, to PIR-B knock-out mice did not enhance the regenerative response. These results indicate that PIR-B knock-out is not sufficient to induce extensive axonal regeneration after spinal cord injury.

  14. Analysis of Spark-Ignition Engine Knock as Seen in Photographs Taken at 200,000 Frames Per Second

    NASA Technical Reports Server (NTRS)

    Miller, Cearcy D.; Olsen, H. Lowell; Logan, Walter O., Jr.; Osterstrom, Gordon E

    1946-01-01

    A motion picture of the development of knock in a spark-ignition engine, is presented, which consists of 20 photographs taken at intervals of 5 microseconds, or at a rate of 200,000 photographs a second, with an equivalent wide-open exposure time of 6.4 microseconds for each photograph. A motion picture of a complete combustion process, including the development of knock, taken at the rate of 40,000 photographs a second is also presented to assist the reader in orienting the photographs of the knock development taken at 200,000 frames per second. The photographs taken at 200,000 frames per second are analyzed and the conclusion is made that the type of knock in the spark-ignition engine involving violent gas vibration originates as self-propagating disturbance starting at a point in the.burn1ig or autoigniting gases and spreading out from that point through the incompletely burned gases at a rate as high as 6800 feet per second, or about twice the speed of sound in the burned gases. Apparent formation of free carbon particles in both the burning and the burned gas is observed within 10 microseconds after passage of the knock disturbance through the gases.

  15. Novel In Vivo Model for Combinatorial Fluorescence Labeling in Mouse Prostate

    PubMed Central

    Fang, Xiaolan; Gyabaah, Kenneth; Nickkholgh, Bita; Cline, J. Mark; Balaji, K.C.

    2015-01-01

    BACKGROUND The epithelial layer of prostate glands contains several types of cells, including luminal and basal cells. Yet there is paucity of animal models to study the cellular origin of normal or neoplastic development in the prostate to facilitate the treatment of heterogenous prostate diseases by targeting individual cell lineages. METHODS We developed a mouse model that expresses different types of fluorescent proteins (XFPs) specifically in prostatic cells. Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock-out, K-RasG12D knock-in, and Phosphatase and tensin homolog (PTEN) and PKD1 double knock-out mice under the control of PB-Cre promoter. RESULTS In vivo XFP signals were observed in prostate of PKD1 knock-out, K-RasG12D knock-in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic, and neoplastic prostate, respectively. The patchy expression pattern of XFPs in neoplasia tissue indicated the clonal origin of cancer cells in the prostate. CONCLUSIONS The transgenic mouse models demonstrate combinatorial fluorescent protein expression in normal and cancerous prostatic tissues. This novel prostate-specific fluorescent labeled mouse model, which we named Prorainbow, could be useful in studying benign and malignant pathology of prostate. PMID:25753731

  16. Novel In Vivo model for combinatorial fluorescence labeling in mouse prostate.

    PubMed

    Fang, Xiaolan; Gyabaah, Kenneth; Nickkholgh, Bita; Cline, J Mark; Balaji, K C

    2015-06-15

    The epithelial layer of prostate glands contains several types of cells, including luminal and basal cells. Yet there is paucity of animal models to study the cellular origin of normal or neoplastic development in the prostate to facilitate the treatment of heterogenous prostate diseases by targeting individual cell lineages. We developed a mouse model that expresses different types of fluorescent proteins (XFPs) specifically in prostatic cells. Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock-out, K-Ras(G) (12) (D) knock-in, and Phosphatase and tensin homolog (PTEN) and PKD1 double knock-out mice under the control of PB-Cre promoter. In vivo XFP signals were observed in prostate of PKD1 knock-out, K-Ras(G) (12) (D) knock-in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic, and neoplastic prostate, respectively. The patchy expression pattern of XFPs in neoplasia tissue indicated the clonal origin of cancer cells in the prostate. The transgenic mouse models demonstrate combinatorial fluorescent protein expression in normal and cancerous prostatic tissues. This novel prostate-specific fluorescent labeled mouse model, which we named Prorainbow, could be useful in studying benign and malignant pathology of prostate. © 2015 Wiley Periodicals, Inc.

  17. Exploring the Relationship Between Octane Sensitivity and Heat-of-Vaporization

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

    Sluder, C. Scott; Szybist, James P.; McCormick, Robert L.

    2016-04-05

    The latent heat-of-vaporization (HoV) of blends of biofuel and hydrocarbon components into gasolines has recently experienced expanded interest because of the potential for increased HoV to increase fuel knock resistance in direct-injection (DI) engines. Several studies have been conducted, with some studies identifying an additional anti-knock benefit from HoV and others failing to arrive at the same conclusion. Consideration of these studies holistically shows that they can be grouped according to the level of fuel octane sensitivity variation within their fuel matrices. When comparing fuels of different octane sensitivity significant additional anti-knock benefits associated with HoV are sometimes observed. Studiesmore » that fix the octane sensitivity find that HoV does not produce additional anti-knock benefit. New studies were performed at ORNL and NREL to further investigate the relationship between HoV and octane sensitivity. Three fuels were formulated for the ORNL study with matched RON and octane sensitivity, but with differing HoV. Experiments with these fuels in a 1.6-liter GTDI engine showed that the fuels exhibited very similar combustion phasing under knock-limited spark advance (KLSA) conditions. Fuels having a range of RON, octane sensitivity, and HoV were tested at NREL in a single-cylinder GDI engine under conditions where octane sensitivity has little effect on knock resistance. KLSA was found to be well correlated with RON. These results reinforce the concept that HoV anti-knock effects can be viewed as a contributor to octane sensitivity. From this viewpoint, HoV effects manifest themselves as increases in octane sensitivity.« less

  18. The knock-down of the expression of MdMLO19 reduces susceptibility to powdery mildew (Podosphaera leucotricha) in apple (Malus domestica).

    PubMed

    Pessina, Stefano; Angeli, Dario; Martens, Stefan; Visser, Richard G F; Bai, Yuling; Salamini, Francesco; Velasco, Riccardo; Schouten, Henk J; Malnoy, Mickael

    2016-10-01

    Varieties resistant to powdery mildew (PM; caused by Podosphaera leucotricha) are a major component of sustainable apple production. Resistance can be achieved by knocking-out susceptibility S-genes to be singled out among members of the MLO (Mildew Locus O) gene family. Candidates are MLO S-genes of phylogenetic clade V up-regulated upon PM inoculation, such as MdMLO11 and 19 (clade V) and MdMLO18 (clade VII). We report the knock-down through RNA interference of MdMLO11 and 19, as well as the complementation of resistance with MdMLO18 in the Arabidopsis thaliana triple mlo mutant Atmlo2/6/12. The knock-down of MdMLO19 reduced PM disease severity by 75%, whereas the knock-down of MdMLO11, alone or in combination with MdMLO19, did not result in any reduction or additional reduction of susceptibility compared with MdMLO19 alone. The test in A. thaliana excluded a role for MdMLO18 in PM susceptibility. Cell wall appositions (papillae) were present in both PM-resistant and PM-susceptible plants, but were larger in resistant lines. No obvious negative phenotype was observed in plants with mlo genes knocked down. Apparently, MdMLO19 plays the pivotal role in apple PM susceptibility and its knock-down induces a very significant level of resistance. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  19. Knock knee and the gait of six-year-old children.

    PubMed

    Pretkiewicz-Abacjew, E

    2003-06-01

    Knock knee (genu valgum) interferes with the locomotive and supporting function of the lower limb. In static conditions the load-bearing axis of the valgus limb is displaced laterally in relation to the middle of the joint, causing the knee joint, the ankle joint, and the foot as a whole to be weighted in the wrong way. The purpose of this work is to examine the influence of knock knee on gait kinematics. The gait of twenty-two 6-year-old children of both sexes in whom knock knee had been medically diagnosed was compared with the gait of 33 children of the same age whose knee joints conformed to the norm in formation and position. Gait was recorded separately for the sagittal and the frontal planes, using a video-computer system. The results of the examination indicated statistically significant differences in the gait of the two groups of children. These differences related mainly to the time features of gait and to data on the angles in the knee and ankle joints. Although the results obtained for other features of gait did not reveal statistical differences, these did indicate that the children with knock knee walked more slowly and with a lower cadence. The results indicate that knock knee in 6-year-old children has an adverse impact on the mechanics of the lower limb joints in gait and causes a deterioration in gait quality. Thus knock knee in children should not be treated merely as a superficial defect but should be subject to therapy and, more importantly, taken into account when introducing children to early sports training.

  20. Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine-dependent epilepsy using CRISPR-Cas9 technology

    PubMed Central

    Zabinyakov, Nikita; Bullivant, Garrett; Cao, Feng; Fernandez Ojeda, Matilde; Jia, Zheng Ping; Wen, Xiao-Yan; Dowling, James J.; Salomons, Gajja S.

    2017-01-01

    Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features. Treatment with pyridoxine, arginine and lysine-restricted diet does not normalize neurodevelopmental outcome or accumulation of neurotoxic metabolites. There is no animal model for high throughput drug screening. For this reason, we developed and characterized the first knock-out aldh7a1 zebrafish model using CRISPR-Cas9 technology. Zebrafish aldh7a1 mutants were generated by using a vector free method of CRISPR-Cas9 mutagenesis. Genotype analysis of aldh7a1 knock-out zebrafish was performed by high resolution melt analysis, direct sequencing and QIAxcel system. Electroencephalogram was performed. Alpha-AASA, piperideine 6-carboxylate and pipecolic acid, were measured by liquid chromatography-tandem mass spectrometry. Our knock-out aldh7a1 zebrafish has homozygous 5 base pair (bp) mutation in ALDH7A1. Knock-out aldh7a1 embryos have spontaneous rapid increase in locomotion and a rapid circling swim behavior earliest 8-day post fertilization (dpf). Electroencephalogram revealed large amplitude spike discharges compared to wild type. Knock-out aldh7a1 embryos have elevated alpha-AASA, piperideine 6-carboxylate and pipecolic acid compared to wild type embryos at 3 dpf. Knock-out aldh7a1 embryos showed no aldh7a1 protein by western blot compared to wild type. Our knock-out aldh7a1 zebrafish is a well characterized model for large-scale drug screening using behavioral and biochemical features and accurately recapitulates the human PDE-ALDH7A1 disease. PMID:29053735

  1. Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine-dependent epilepsy using CRISPR-Cas9 technology.

    PubMed

    Zabinyakov, Nikita; Bullivant, Garrett; Cao, Feng; Fernandez Ojeda, Matilde; Jia, Zheng Ping; Wen, Xiao-Yan; Dowling, James J; Salomons, Gajja S; Mercimek-Andrews, Saadet

    2017-01-01

    Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features. Treatment with pyridoxine, arginine and lysine-restricted diet does not normalize neurodevelopmental outcome or accumulation of neurotoxic metabolites. There is no animal model for high throughput drug screening. For this reason, we developed and characterized the first knock-out aldh7a1 zebrafish model using CRISPR-Cas9 technology. Zebrafish aldh7a1 mutants were generated by using a vector free method of CRISPR-Cas9 mutagenesis. Genotype analysis of aldh7a1 knock-out zebrafish was performed by high resolution melt analysis, direct sequencing and QIAxcel system. Electroencephalogram was performed. Alpha-AASA, piperideine 6-carboxylate and pipecolic acid, were measured by liquid chromatography-tandem mass spectrometry. Our knock-out aldh7a1 zebrafish has homozygous 5 base pair (bp) mutation in ALDH7A1. Knock-out aldh7a1 embryos have spontaneous rapid increase in locomotion and a rapid circling swim behavior earliest 8-day post fertilization (dpf). Electroencephalogram revealed large amplitude spike discharges compared to wild type. Knock-out aldh7a1 embryos have elevated alpha-AASA, piperideine 6-carboxylate and pipecolic acid compared to wild type embryos at 3 dpf. Knock-out aldh7a1 embryos showed no aldh7a1 protein by western blot compared to wild type. Our knock-out aldh7a1 zebrafish is a well characterized model for large-scale drug screening using behavioral and biochemical features and accurately recapitulates the human PDE-ALDH7A1 disease.

  2. Coercive Air Strategy in Post-Cold War Peace Operations

    DTIC Science & Technology

    1999-06-01

    Fariborz L. Mokhtari , ed., Peacemaking, Peacekeeping and Coalition Warfare: The Future Role of the United Nations (Washington, D.C: National Defense...Technical Information Center, 1993. Mokhtari , Fariborz L. ed. “Peacemaking, Peacekeeping and Coalition Warfare: The Future Role of the United Nations

  3. Adaptive Army: Embracing the Concept of Operational Manoeuvre from the Sea

    DTIC Science & Technology

    2010-05-05

    PEACE Source: Headquarters Training Command- Army. Land Warfare Doctrine LWD 3-01: Formation Tactics. Australian Army, November 27, 2003. 27...Amphibious Capability Implementation Team, June 15, 2009. Headquarters Training Comrriand- Army. Land Warfare Doctrine LWD 3-0: Operations. Australian Army

  4. Health-related quality of life of chemical warfare victims: an assessment with the use of a specific tool.

    PubMed

    Biat Saeed, Khaled; Parandeh, Akram; Alhani, Fatemeh; Salaree, Mohammad Mehdi

    2014-02-01

    Exposure to chemical warfare gases significantly changes the quality of life (QoL) of victims and has significant chronic adverse effects. This study sought to assess the health-related QoL (HRQoL) of chemical victims by means of a tool specifically designed for this purpose. The correlation of their QoL with several demographic factors was evaluated as well. In this descriptive cross-sectional study, 120 chemical warfare victims were selected from subjects presenting to selected medical centers in Tehran in 2012 using convenience sampling. Two questionnaires of demographic information and HRQoL of chemical warfare victims (specific tool) were used for data collection. The data were analyzed using SPSS version 20 software (IBM, Armonk, NY, USA). The mean and standard deviation (mean ± SD) of scores obtained by chemical warfare victims in physical, psychosocial and spiritual domains was 39.6 ± 16.5, 42.1 ± 15.2 and 82.4 ± 15.4, respectively. Different age groups showed a significant difference in the psychosocial domain score (P < 0.01). Also, the physical and spiritual domain scores had significant differences with respect to the level of education (P < 0.001). The occupational status showed significant differences in the psychosocial and spiritual domains scores of QoL (P < 0.001). The physical and psychosocial domain scores also accounted for a significant difference with respect to the duration and severity of pulmonary symptoms (P < 0.05). Considering the importance and high value of spirituality in chemical warfare victims, it can be used as strategically for these patients to help them cope with their injury and improve their physical and psychosocial health and QoL.

  5. Intraosseous vascular access in the treatment of chemical warfare casualties assessed by advanced simulation: proposed alteration of treatment protocol.

    PubMed

    Vardi, Amir; Berkenstadt, Haim; Levin, Inbal; Bentencur, Ariel; Ziv, Amitai

    2004-06-01

    Current treatment protocols for chemical warfare casualties assume no IV access during the early treatment stages. Time constraints in mass casualty scenarios, impaired manual dexterity of medical personnel wearing protective gear, and victims' complex clinical presentations render standard IV access techniques impractical. A newly developed spring-driven, trigger-operated intraosseous infusion device may offer an effective solution. Sophisticated simulators were developed and used to mimic scenarios of chemical warfare casualties for assessing the feasibility of intraosseous infusion delivery. We evaluated the clinical performance of medical teams in full protective gear. The success rate in intraosseous insertion, time to completion of treatment goals, and outcome were measured in a simulated setting. Medical teams from major hospitals in Israel, designated for emergency response in a real chemical warfare mass casualty scenario, were trained in a simulated setting. All 94 participating physicians were supplied with conventional treatment modalities: only the 64 study group physicians received intraosseous devices. The simulated survival rate was 73.4% for the study group and 3.3% for the controls (P < 0.001). Treatment goals were achieved within 3.5 min (range, 1-9 min) in the study group and within >10 min for controls (P < 0.001), and the complication rate for intraosseous use was 13.8%. Personnel satisfaction with the intraosseous device was unanimous and high. New-generation intraosseous infusions have great potential value in the early treatment stages of chemical warfare casualties. In a chemical warfare mass casualty scenario, the protective gear worn by medical personnel, the time constraints, and the casualties' medical condition impose limitations on the establishment of IV access during early treatment of the victims. A spring-driven, trigger-operated intraosseous infusion delivery system may offer an effective solution.

  6. Health-Related Quality of Life of Chemical Warfare Victims: An Assessment with the Use of a Specific Tool

    PubMed Central

    Biat Saeed, Khaled; Parandeh, Akram; Alhani, Fatemeh; Salaree, Mohammad Mehdi

    2014-01-01

    Background: Exposure to chemical warfare gases significantly changes the quality of life (QoL) of victims and has significant chronic adverse effects. Objective: This study sought to assess the health-related QoL (HRQoL) of chemical victims by means of a tool specifically designed for this purpose. The correlation of their QoL with several demographic factors was evaluated as well. Patients and Methods: In this descriptive cross-sectional study, 120 chemical warfare victims were selected from subjects presenting to selected medical centers in Tehran in 2012 using convenience sampling. Two questionnaires of demographic information and HRQoL of chemical warfare victims (specific tool) were used for data collection. The data were analyzed using SPSS version 20 software (IBM, Armonk, NY, USA). Results: The mean and standard deviation (mean ± SD) of scores obtained by chemical warfare victims in physical, psychosocial and spiritual domains was 39.6 ± 16.5, 42.1 ± 15.2 and 82.4 ± 15.4, respectively. Different age groups showed a significant difference in the psychosocial domain score (P < 0.01). Also, the physical and spiritual domain scores had significant differences with respect to the level of education (P < 0.001). The occupational status showed significant differences in the psychosocial and spiritual domains scores of QoL (P < 0.001). The physical and psychosocial domain scores also accounted for a significant difference with respect to the duration and severity of pulmonary symptoms (P < 0.05). Conclusions: Considering the importance and high value of spirituality in chemical warfare victims, it can be used as strategically for these patients to help them cope with their injury and improve their physical and psychosocial health and QoL. PMID:24719824

  7. 16 CFR 309.17 - Labels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... height) knocked out of a 1″ (2.54 cm) deep band. The type for the words “MINIMUM” and the principal... should be set as “normal.” The type for the fuel name is 50 point (1/2″ 1.27 cm) cap height) knocked out... point (1/2″ 1.27 cm) cap height) knocked out of a 1″ (2.54 cm) deep band. All other type is 24 pt. (1/4...

  8. 16 CFR 309.17 - Labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... height) knocked out of a 1″ (2.54 cm) deep band. The type for the words “MINIMUM” and the principal... should be set as “normal.” The type for the fuel name is 50 point (1/2″ 1.27 cm) cap height) knocked out... point (1/2″ 1.27 cm) cap height) knocked out of a 1″ (2.54 cm) deep band. All other type is 24 pt. (1/4...

  9. Targeting Transcription Elongation Machinery for Breast Cancer Therapy

    DTIC Science & Technology

    2017-05-01

    be performed to evaluate the pausing index for RNA Pol II. The potential role of a Super Enhancer will also be tested by knocking down the mediator...generation of all the cell lines stably knocking out the components of various P-TEFb complexes and performed some of the biochemical experiments...assessing the changes in P-TEFb complex formation upon knocking down or overexpression of various components. Funding Support: NIH Has there been a

  10. Targeting the Prometastatic Microenvironment of the Involuting mammary gland

    DTIC Science & Technology

    2016-09-01

    metastatic variants and by lentiviral knock down. 15. SUBJECT TERMS Cell Adhesion, Involution, Metastasis, Latent TGFbeta Binding Protein, Pregnancy...metastatic parental cell line (Report year 2 Fig. 4). We generated a lentiviral knock down system that effectively reduced LTBP1 expression within this cell...this pilot set of animals and will be infecting and following a larger cohort by IVIS to track the effect of knocking down Ltbp1 on metastasis in

  11. Efficient gene knock-out and knock-in with transgenic Cas9 in Drosophila.

    PubMed

    Xue, Zhaoyu; Ren, Mengda; Wu, Menghua; Dai, Junbiao; Rong, Yikang S; Gao, Guanjun

    2014-03-21

    Bacterial Cas9 nuclease induces site-specific DNA breaks using small gRNA as guides. Cas9 has been successfully introduced into Drosophila for genome editing. Here, we improve the versatility of this method by developing a transgenic system that expresses Cas9 in the Drosophila germline. Using this system, we induced inheritable knock-out mutations by injecting only the gRNA into embryos, achieved highly efficient mutagenesis by expressing gRNA from the promoter of a novel non-coding RNA gene, and recovered homologous recombination-based knock-in of a fluorescent marker at a rate of 4.5% by co-injecting gRNA with a circular DNA donor. Copyright © 2014 Xue et al.

  12. The Aircraft Infrared Measurements Guide

    DTIC Science & Technology

    1983-03-01

    the infrared portion of the electromagnetic spectrum, but should include measure- ments across that portion of the spectrum using optical /electro... optical tech- nology. Comments should be addressed to: Commander/Director Office of Missile Electronic Warfare US Army Electronic Warfare Laboratory ATTN...58 Spatial Radiometer ................................................ 58 Seekers ( Nonimaging

  13. 13. Photocopy of drawing (original in possession of Naval Surface ...

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

    13. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) WIND TUNNEL BUILDING, ELEVATIONS, 1941 - Naval Surface Warfare Center, Subsonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  14. 50 CFR 216.274 - Mitigation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... safe speed. Release of ordnance through cloud cover is prohibited: aircraft must be able to actually... would be used. These aircraft would be capable of flying at the slow safe speeds necessary to enable... patrol aircraft aircrews, and Anti-submarine Warfare (ASW)/Mine Warfare (MIW) helicopter crews shall...

  15. 50 CFR 216.274 - Mitigation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... safe speed. Release of ordnance through cloud cover is prohibited: aircraft must be able to actually... would be used. These aircraft would be capable of flying at the slow safe speeds necessary to enable... patrol aircraft aircrews, and Anti-submarine Warfare (ASW)/Mine Warfare (MIW) helicopter crews shall...

  16. 50 CFR 216.274 - Mitigation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... safe speed. Release of ordnance through cloud cover is prohibited: aircraft must be able to actually... would be used. These aircraft would be capable of flying at the slow safe speeds necessary to enable... patrol aircraft aircrews, and Anti-submarine Warfare (ASW)/Mine Warfare (MIW) helicopter crews shall...

  17. Environmental Warfare

    ERIC Educational Resources Information Center

    Barnaby, Frank

    1976-01-01

    Recent discussions at the Conference of the Committee on Disarmament have focused on the use of artificial changes in the environment as a method of warfare. A far more urgent task is development of a specific ban on already available techniques of environmental damage and a general and complete disarmament. (BT)

  18. Contamination source review for Building E5974, Edgewood Area, Aberdeen Proving Ground, Maryland

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

    Billmark, K.A.; Emken, M.E.; O`Reilly, D.P.

    1995-09-01

    This report documents the results of a contamination source review of Building E5974 at the Aberdeen Proving Ground (APG) in Maryland. The primary mission at APG has been the testing and evaluation of US Army warfare materials. Since its beginning in 1917, the Edgewood Area of APG has been the principal location for chemical warfare agent research, development, and testing in the US. APG was also used for producing chemical warfare agents during both world wars, and it has been a center for the storage of chemical warfare material. An attempt was made to identify and define areas of toxicmore » or hazardous contaminants and to assess the physical condition and accessibility of APG buildings. The information obtained from this review may be used to assist the US Army in planning for the future use or disposition of the buildings. The contamination source review consisted of the following tasks: historical records search, physical inspection, photographic documentation, geophysical investigation, and collection of air samples.« less

  19. The United States and biological warfare: secrets from the early cold war and Korea.

    PubMed

    Bruwer, A

    2001-01-01

    The United States and Biological Warfare is about accusations that the United States resorted to bacteriological warfare at a time of great military stress during the Korean War. In December 1951, the then US Secretary of Defense ordered early readiness for offensive use of biological weapons. Soon afterwards, the North Korean and Chinese armies accused the United States of starting a large-scale biological warfare experiment in Korea. The US State Department denied the accusation. Both parties to the dispute maintain their positions today. The authors spent 20 years researching the accusations in North America, Europe and Japan. They were the first foreigners to be given access to Chinese classified documents. The reader is also introduced to the concept of 'plausible denial', an official US policy which allowed responsible governmental representatives to deny knowledge of certain events. The authors hope that their work will contribute to the understanding of a time when modern war expanded into a new type of violence.

  20. Violence in the prehistoric period of Japan: the spatio-temporal pattern of skeletal evidence for violence in the Jomon period.

    PubMed

    Nakao, Hisashi; Tamura, Kohei; Arimatsu, Yui; Nakagawa, Tomomi; Matsumoto, Naoko; Matsugi, Takehiko

    2016-03-01

    Whether man is predisposed to lethal violence, ranging from homicide to warfare, and how that may have impacted human evolution, are among the most controversial topics of debate on human evolution. Although recent studies on the evolution of warfare have been based on various archaeological and ethnographic data, they have reported mixed results: it is unclear whether or not warfare among prehistoric hunter-gatherers was common enough to be a component of human nature and a selective pressure for the evolution of human behaviour. This paper reports the mortality attributable to violence, and the spatio-temporal pattern of violence thus shown among ancient hunter-gatherers using skeletal evidence in prehistoric Japan (the Jomon period: 13 000 cal BC-800 cal BC). Our results suggest that the mortality due to violence was low and spatio-temporally highly restricted in the Jomon period, which implies that violence including warfare in prehistoric Japan was not common. © 2016 The Author(s).

  1. Violence in the prehistoric period of Japan: the spatio-temporal pattern of skeletal evidence for violence in the Jomon period

    PubMed Central

    Nakao, Hisashi; Tamura, Kohei; Arimatsu, Yui; Nakagawa, Tomomi; Matsumoto, Naoko; Matsugi, Takehiko

    2016-01-01

    Whether man is predisposed to lethal violence, ranging from homicide to warfare, and how that may have impacted human evolution, are among the most controversial topics of debate on human evolution. Although recent studies on the evolution of warfare have been based on various archaeological and ethnographic data, they have reported mixed results: it is unclear whether or not warfare among prehistoric hunter–gatherers was common enough to be a component of human nature and a selective pressure for the evolution of human behaviour. This paper reports the mortality attributable to violence, and the spatio-temporal pattern of violence thus shown among ancient hunter–gatherers using skeletal evidence in prehistoric Japan (the Jomon period: 13 000 cal BC–800 cal BC). Our results suggest that the mortality due to violence was low and spatio-temporally highly restricted in the Jomon period, which implies that violence including warfare in prehistoric Japan was not common. PMID:27029838

  2. Chemical warfare agents. Classes and targets.

    PubMed

    Schwenk, Michael

    2018-09-01

    Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation. The present work briefly surveys classes and toxicologically relevant features of chemical warfare agents and describes mechanisms of toxic action. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. IMS software developments for the detection of chemical warfare agent

    NASA Technical Reports Server (NTRS)

    Klepel, ST.; Graefenhain, U.; Lippe, R.; Stach, J.; Starrock, V.

    1995-01-01

    Interference compounds like gasoline, diesel, burning wood or fuel, etc. are presented in common battlefield situations. These compounds can cause detectors to respond as a false positive or interfere with the detector's ability to respond to target compounds such as chemical warfare agents. To ensure proper response of the ion mobility spectrometer to chemical warfare agents, two special software packages were developed and incorporated into the Bruker RAID-1. The programs suppress interferring signals caused by car exhaust or smoke gases resulting from burning materials and correct the influence of variable sample gas humidity which is important for detection and quantification of blister agents like mustard gas or lewisite.

  4. Development of practical methods for removal of radiological, biological, and chemical contaminants from water supplies. Final report

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

    Woodward, R.L.; Robeck, G.G.

    1958-06-01

    Laboratory and engineering studies were conducted to determine the design criteria and cost estimated of providing and operating devices to protect against radiological, biological and chemical warfare agents that may contaminate shore based Naval water supplies. Small disposable columns of mixed cation-anion exchange resins will remove the soluble radionuclides enough to suffice for immediate drinking and culinary purposes. Chemical warfare agents are so numerous and varied that it is not feasible to provide a single protective device to cope with them. Chlorination with free available chlorine residuals of 1 mg liter will handle most biological warfare agents.

  5. Glutaminyl Cyclase Knock-out Mice Exhibit Slight Hypothyroidism but No Hypogonadism

    PubMed Central

    Schilling, Stephan; Kohlmann, Stephanie; Bäuscher, Christoph; Sedlmeier, Reinhard; Koch, Birgit; Eichentopf, Rico; Becker, Andreas; Cynis, Holger; Hoffmann, Torsten; Berg, Sabine; Freyse, Ernst-Joachim; von Hörsten, Stephan; Rossner, Steffen; Graubner, Sigrid; Demuth, Hans-Ulrich

    2011-01-01

    Glutaminyl cyclases (QCs) catalyze the formation of pyroglutamate (pGlu) residues at the N terminus of peptides and proteins. Hypothalamic pGlu hormones, such as thyrotropin-releasing hormone and gonadotropin-releasing hormone are essential for regulation of metabolism and fertility in the hypothalamic pituitary thyroid and gonadal axes, respectively. Here, we analyzed the consequences of constitutive genetic QC ablation on endocrine functions and on the behavior of adult mice. Adult homozygous QC knock-out mice are fertile and behave indistinguishably from wild type mice in tests of motor function, cognition, general activity, and ingestion behavior. The QC knock-out results in a dramatic drop of enzyme activity in the brain, especially in hypothalamus and in plasma. Other peripheral organs like liver and spleen still contain QC activity, which is most likely caused by its homolog isoQC. The serum gonadotropin-releasing hormone, TSH, and testosterone concentrations were not changed by QC depletion. The serum thyroxine was decreased by 24% in homozygous QC knock-out animals, suggesting a mild hypothyroidism. QC knock-out mice were indistinguishable from wild type with regard to blood glucose and glucose tolerance, thus differing from reports of thyrotropin-releasing hormone knock-out mice significantly. The results suggest a significant formation of the hypothalamic pGlu hormones by alternative mechanisms, like spontaneous cyclization or conversion by isoQC. The different effects of QC depletion on the hypothalamic pituitary thyroid and gonadal axes might indicate slightly different modes of substrate conversion of both enzymes. The absence of significant abnormalities in QC knock-out mice suggests the presence of a therapeutic window for suppression of QC activity in current drug development. PMID:21330373

  6. Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive.

    PubMed

    Williams, Michael R; DeSpenza, Tyrone; Li, Meijie; Gulledge, Allan T; Luikart, Bryan W

    2015-01-21

    Developing neurons must regulate morphology, intrinsic excitability, and synaptogenesis to form neural circuits. When these processes go awry, disorders, including autism spectrum disorder (ASD) or epilepsy, may result. The phosphatase Pten is mutated in some patients having ASD and seizures, suggesting that its mutation disrupts neurological function in part through increasing neuronal activity. Supporting this idea, neuronal knock-out of Pten in mice can cause macrocephaly, behavioral changes similar to ASD, and seizures. However, the mechanisms through which excitability is enhanced following Pten depletion are unclear. Previous studies have separately shown that Pten-depleted neurons can drive seizures, receive elevated excitatory synaptic input, and have abnormal dendrites. We therefore tested the hypothesis that developing Pten-depleted neurons are hyperactive due to increased excitatory synaptogenesis using electrophysiology, calcium imaging, morphological analyses, and modeling. This was accomplished by coinjecting retroviruses to either "birthdate" or birthdate and knock-out Pten in granule neurons of the murine neonatal dentate gyrus. We found that Pten knock-out neurons, despite a rapid onset of hypertrophy, were more active in vivo. Pten knock-out neurons fired at more hyperpolarized membrane potentials, displayed greater peak spike rates, and were more sensitive to depolarizing synaptic input. The increased sensitivity of Pten knock-out neurons was due, in part, to a higher density of synapses located more proximal to the soma. We determined that increased synaptic drive was sufficient to drive hypertrophic Pten knock-out neurons beyond their altered action potential threshold. Thus, our work contributes a developmental mechanism for the increased activity of Pten-depleted neurons. Copyright © 2015 the authors 0270-6474/15/350943-17$15.00/0.

  7. The Expression of TALEN before Fertilization Provides a Rapid Knock-Out Phenotype in Xenopus laevis Founder Embryos.

    PubMed

    Miyamoto, Kei; Suzuki, Ken-Ichi T; Suzuki, Miyuki; Sakane, Yuto; Sakuma, Tetsushi; Herberg, Sarah; Simeone, Angela; Simpson, David; Jullien, Jerome; Yamamoto, Takashi; Gurdon, J B

    2015-01-01

    Recent advances in genome editing using programmable nucleases have revolutionized gene targeting in various organisms. Successful gene knock-out has been shown in Xenopus, a widely used model organism, although a system enabling less mosaic knock-out in founder embryos (F0) needs to be explored in order to judge phenotypes in the F0 generation. Here, we injected modified highly active transcription activator-like effector nuclease (TALEN) mRNA to oocytes at the germinal vesicle (GV) stage, followed by in vitro maturation and intracytoplasmic sperm injection, to achieve a full knock-out in F0 embryos. Unlike conventional injection methods to fertilized embryos, the injection of TALEN mRNA into GV oocytes allows expression of nucleases before fertilization, enabling them to work from an earlier stage. Using this procedure, most of developed embryos showed full knock-out phenotypes of the pigmentation gene tyrosinase and/or embryonic lethal gene pax6 in the founder generation. In addition, our method permitted a large 1 kb deletion. Thus, we describe nearly complete gene knock-out phenotypes in Xenopus laevis F0 embryos. The presented method will help to accelerate the production of knock-out frogs since we can bypass an extra generation of about 1 year in Xenopus laevis. Meantime, our method provides a unique opportunity to rapidly test the developmental effects of disrupting those genes that do not permit growth to an adult able to reproduce. In addition, the protocol shown here is considerably less invasive than the previously used host transfer since our protocol does not require surgery. The experimental scheme presented is potentially applicable to other organisms such as mammals and fish to resolve common issues of mosaicism in founders.

  8. Protective Garments for Public Officials

    DTIC Science & Technology

    1973-08-01

    Approved for public release; distribution urlimited. U. S. ARMY IAND WARFARE LABORATORY Aberdeen Proving Ground , Maryland 21005 ABSTRACT TThis task has...unlimited. - U. S. ARMY LAND WARFARE LABORATORY .&1 A~ereemProinaGroun~d. Morviarnd 21005 Aberden Pov\\J TECHNICAL REPORT NO. LW j<B0B73 PROTECTIVE

  9. 10. Photocopy of drawing (original in possession of Naval Surface ...

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

    10. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) SUPERSONIC WIND TUNNEL BUILDING, GROUND FLOOR PLAN, 1947 - Naval Surface Warfare Center, Supersonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  10. PERMANENCE OF BIOLOGICAL AND CHEMICAL WARFARE AGENTS IN MUNICIPAL SOLID WASTE LANDFILL LEACHATES

    EPA Science Inventory

    The objective of this work is to permit EPA/ORD's National Homeland Security Research Center (NHSRC) and Edgewood Chemical Biological Center to collaborate together to test the permanence of biological and chemical warfare agents in municipal solid waste landfills. Research into ...

  11. Anti-Submarine Warfare (ASW) Capability Transformation: Strategy of Response to Effects Based Warfare

    DTIC Science & Technology

    2011-06-01

    the ROK Cheonan destroyer by a probable PRK submarine. Despite the authoritative findings of an International team that forensically examined the...evidence of the sinking implicating PRK , North Korea continues to maintain its innocence and deny any involvement, especially since there is

  12. Strategic Analysis of Irregular Warfare

    DTIC Science & Technology

    2010-03-01

    the same mathematical equations used by Lanchester .10 Irregular Warfare Theory and Doctrine It is time to develop new analytical methods and models...basis on which to build, similar to what Lanchester provided almost 100 years ago. Figure 9 portrays both Lanchester’s approach and an irregular 17

  13. 14. Photocopy of drawing (original in possession of Naval Surface ...

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

    14. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) WIND TUNNEL, FRAMING PLAN, TOP AND BOTTOM, 1941 - Naval Surface Warfare Center, Subsonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  14. WASTE MINIZATION OPPORTUNITY ASSESSMENT: NAVAL UNDERSEA WARFARE ENGINEERING STATION - KEYPORT, WA

    EPA Science Inventory

    This report describes the application of EPA's waste minimization assessment procedures to a torpedo maintenance facility at the Naval Undersea Warfare Engineering Station, Keyport, WA. he assessment focused on the Mark 48 shop and the Mark 46 shop. hese shops service the Mark 48...

  15. The Venus "Shell-over-Star" hieroglyph and Maya warfare: An examination of the interpretation of a Mayan symbol

    NASA Astrophysics Data System (ADS)

    Voit, Claudia Ann

    For decades, Maya scholars have associated the Mayan "Shell-Star" (also referred to as "Star-War") hieroglyph with Maya warfare. Put forward by scholars such as Floyd Lounsbury and David Kelley, and later advanced by Linda Schele, David Freidel, Ian Graham, Peter Matthews, Anthony Aveni and others, there are now dozens of published articles and chapters relating the hieroglyph to Venus and warfare. Venus is one of the most notable celestial objects outside of the Sun and Moon and was highly visible to the inhabitants of the Maya world. The Dresden Codex (an astronomical almanac) contains important information about the planet Venus, and the calendar section was deciphered by the librarian and mathematician, Ernst Förstemann in the late 1800s. In his decipherment, he deduced that the numbers contained in the tables must be connected to the orbital period of the planet. There is no other planet with the same orbital period 3 as Venus. Förstemann suggested that the decoded astronomy tables were used by the Maya to determine when to wage war. This interpretation, along with others, like Floyd Lounsbury`s study of Venus and the Long Count date at Bonampak were the seeds that have led to methodological errors that first began to take root in Maya research. The idea of the Venus association with warfare took hold and continues to propagate. Many scholars continue to assert that the "shell-star" glyph is related to warfare events. Others, like Gerardo Aldana, and Stanley Guenter, have recently come forward to reexamine and question the hieroglyph and its relationship, if any, to Maya warfare. I suggest, further, that methodological errors may have occurred along the way. I propose that these errors include data lost in translation, and inaccurate translations. In addition, the statistical analysis of Venus cycles has weak points. If this identification of the errors is correct, we need to re-evaluate the weakened foundation on which we are building our assertions about the role of Venus in Maya warfare. In this work, I examine the initial and subsequent interpretations of the Mayan "shell-star" hieroglyph, a symbol that has begun to generate an increasing amount of discussion among Mayan scholars over the last several years. In addition, I discuss new arguments (like that of Gerardo Aldana) regarding the role of Venus in Maya warfare. Finally, I would like to provide some suggestions for future research regarding this subject.

  16. Generation of Knock-in Mouse by Genome Editing.

    PubMed

    Fujii, Wataru

    2017-01-01

    Knock-in mice are useful for evaluating endogenous gene expressions and functions in vivo. Instead of the conventional gene-targeting method using embryonic stem cells, an exogenous DNA sequence can be inserted into the target locus in the zygote using genome editing technology. In this chapter, I describe the generation of epitope-tagged mice using engineered endonuclease and single-stranded oligodeoxynucleotide through the mouse zygote as an example of how to generate a knock-in mouse by genome editing.

  17. Identification of rat Rosa26 locus enables generation of knock-in rat lines ubiquitously expressing tdTomato.

    PubMed

    Kobayashi, Toshihiro; Kato-Itoh, Megumi; Yamaguchi, Tomoyuki; Tamura, Chihiro; Sanbo, Makoto; Hirabayashi, Masumi; Nakauchi, Hiromitsu

    2012-11-01

    Recent discovery of a method for derivation and culture of germline-competent rat pluripotent stem cells (PSCs) enables generation of transgenic rats or knock-out rats via genetic modification of such PSCs. This opens the way to use rats, as is routine in mice, for analyses of gene functions or physiological features. In mouse or human, one widely used technique to express a gene of interest stably and ubiquitously is to insert that gene into the Rosa26 locus via gene targeting of PSCs. Rosa26 knock-in mice conditionally expressing a reporter or a toxin gene have contributed to tracing or ablation of specific cell lineages. We successfully identified a rat orthologue of the mouse Rosa26 locus. Insertion of tdTomato, a variant of red fluorescent protein, into the Rosa26 locus of PSCs of various rat strains allows ubiquitous expression of tdTomato. Through germline transmission of one Rosa26-tdTomato knock-in embryonic stem cell line, we also obtained tdTomato knock-in rats. These expressed tdTomato ubiquitously throughout their bodies, which indicates that the rat Rosa26 locus conserves functions of its orthologues in mouse and human. The new tools described here (targeting vectors, knock-in PSCs, and rats) should be useful for a variety of research using rats.

  18. [Perspectives in the treatments of poisonings by organophosphorus insecticides and warfare nerve agents].

    PubMed

    Sogorb-Sánchez, M A; Vilanova-Gisbert, E; Carrera-González, V

    Organophosphorus compounds are worldwide employed as insecticides and are yearly responsible of several millions of poisonings. The chemical structure of most of the warfare nerve agents also corresponds with an organophosphorus compound. Organophosphorus insecticides and warfare nerve agents exert their main toxicological effects through inhibition of acetylcholinesterase. Current treatments of patients poisoned with organophosphorus compounds include atropine (in order to protect muscarinic receptors), oximes (in order to accelerate the reactivation of the inhibited acetylcholinesterase) and benzodiazepines (in order to avoid convulsions). The administration of phosphotriesterases (enzymes involved in the detoxication of organophosphorus compounds through hydrolysis) is a very effective treatment against poisonings by organophosphorus insecticides and warfare nerve agents. There are experimental preventive treatments based on the simultaneous administration of carbamates and certain antimuscarinic drugs, different from atropine, which notably improve the efficacy of the classical treatments applied after poisonings by warfare nerve agents. The treatments based in the administration of phosphotriesterases might be the response to the call of the World Health Organization for searching new treatments with capability to reduce the high mortality recorded in the cases of poisonings by organophosphorus compounds. These treatments can be applied in a preventive way without the intrinsic neurotoxicity associated to the preventive treatments based on carbamates and antimuscarinic drugs. Therefore, these treatments are specially interesting for people susceptible to suffer severe exposures, i.e. sprayers in the farms.

  19. Efficient generation of Rosa26 knock-in mice using CRISPR/Cas9 in C57BL/6 zygotes.

    PubMed

    Chu, Van Trung; Weber, Timm; Graf, Robin; Sommermann, Thomas; Petsch, Kerstin; Sack, Ulrike; Volchkov, Pavel; Rajewsky, Klaus; Kühn, Ralf

    2016-01-16

    The CRISPR/Cas9 system is increasingly used for gene inactivation in mouse zygotes, but homology-directed mutagenesis and use of inbred embryos are less established. In particular, Rosa26 knock-in alleles for the insertion of transgenes in a genomic 'safe harbor' site, have not been produced. Here we applied CRISPR/Cas9 for the knock-in of 8-11 kb inserts into Rosa26 of C57BL/6 zygotes. We found that 10-20 % of live pups derived from microinjected zygotes were founder mutants, without apparent off-target effects, and up to 50 % knock-in embryos were recovered upon coinjection of Cas9 mRNA and protein. Using this approach, we established a new mouse line for the Cre/loxP-dependent expression of Cas9. Altogether, our protocols and resources support the fast and direct generation of new Rosa26 knock-in alleles and of Cas9-mediated in vivo gene editing in the widely used C57BL/6 inbred strain.

  20. Targeted knock-in of an scFv-Fc antibody gene into the hprt locus of Chinese hamster ovary cells using CRISPR/Cas9 and CRIS-PITCh systems.

    PubMed

    Kawabe, Yoshinori; Komatsu, Shinya; Komatsu, Shodai; Murakami, Mai; Ito, Akira; Sakuma, Tetsushi; Nakamura, Takahiro; Yamamoto, Takashi; Kamihira, Masamichi

    2018-05-01

    Chinese hamster ovary (CHO) cells have been used as host cells for the production of pharmaceutical proteins. For the high and stable production of target proteins, the transgene should be integrated into a suitable genomic locus of host cells. Here, we generated knock-in CHO cells, in which transgene cassettes without a vector backbone sequence were integrated into the hprt locus of the CHO genome using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and CRISPR-mediated precise integration into target chromosome (CRIS-PITCh) systems. We investigated the efficiency of targeted knock-in of transgenes using these systems. As a practical example, we generated knock-in CHO cells producing an scFv-Fc antibody using the CRIS-PITCh system mediated by microhomology sequences for targeting. We found that the CRIS-PITCh system can facilitate targeted knock-in for CHO cell engineering. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. The Age of Irregular Warfare: So What?

    DTIC Science & Technology

    2010-01-01

    Lynne Rienner, 2002), and Michael Vlahos , Fighting Identity: Sacred War and World Change (Westport, CT: Praeger Security Interna- tional, 2009). 7...the forms that warfare will take.” 8 I agree with Michael Vlahos that we poten- tially make matters worse by using the image of a triangle to depict

  2. IW Cyberlaw. The Legal Issues of Information Warfare

    DTIC Science & Technology

    1999-01-01

    actions. The Information Warfare Center at Kelly AFB, Texas, casts a wide net in its definition of information war- fare. Its view is that... Maura T. McGowan, in an unpublished study en- titled “Law of Armed Conflict” (Colorado Springs, Colo.: United States Air Force Academy, Department of

  3. Defining Deterrence in Cyberspace Working Toward a Framework to Integrate Cyber Deterrence

    DTIC Science & Technology

    2011-04-01

    The goal of deterrence is not to deter the use of a particular weapon. Rather, a nation deters undesirable behavior. Cyber warfare can produce three...associated limitations will not produce a strategically decisive result. Cyber warfare must be used in conjunction with other instruments of power to

  4. Defense Standardization Program Journal, April/Jun 2007

    DTIC Science & Technology

    2007-06-01

    Delivers Far-Reaching Standardization 9 Air Force Cyber Warfare Training 14 DMSMS Working Group Reaches Out to Programs 18 An Effects-Based Metrics...defend- ers their first 10 cyber warfare combat "sorties" and prepared them for net- work crew positions. Four MAJCOMs participated in BD 2002.The Air

  5. Models, Analysis, and Recommendations Pertaining to the Retention of Naval Special Warfare s Mid-Level Officers

    DTIC Science & Technology

    2013-12-01

    The Analytic Hierarch/Network Process,” in Rev. R. Acad. Cien. Serie A. Mat (RACSAM), submitted by Francisco Javier Giron (Real Academia de Ciencias ...Academia de Ciencias : Spain. Scott, Nathan. Naval Special Warfare Officer Retention Survey. Monterey, CA: NPS Press, September 2013. Whittenberger

  6. 12. Photocopy of drawing (original in possession of Naval Surface ...

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

    12. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) SUPERSONIC WIND TUNNEL, STEEL VACUUM SPHERE, FOUNDATION PLAN, ELEVATION AND DETAILS, 1947 - Naval Surface Warfare Center, Supersonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  7. 23. Photocopy of drawing (original in possession of Naval Surface ...

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

    23. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) 7 X 10 FOOT SONIC WIND TUNNEL, FAN HOUSING ASSEMBLY, 1952 - Naval Surface Warfare Center, Transonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  8. 9. Photocopy of photograph (original photograph in the collection of ...

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

    9. Photocopy of photograph (original photograph in the collection of Naval Surface Warfare Center Carderock Division, Bethesda, MD) VIEW SOUTH, SUPERSONIC WIND TUNNEL TEST SECTION, ca 1950 - Naval Surface Warfare Center, Supersonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  9. 10. Photocopy of photograph (original photograph in the collection of ...

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

    10. Photocopy of photograph (original photograph in the collection of Naval Surface Warfare Center Carderock Division, Bethesda, MD) VIEW SOUTHWEST, SUBSONIC WIND TUNNEL BUILDING, 1943 - Naval Surface Warfare Center, Subsonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  10. 19. Photocopy of drawing (original In possession of Naval Surface ...

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

    19. Photocopy of drawing (original In possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) 7 X 10 FOOT SONIC WIND TUNNEL PLOT AND GRADING PLAN, 1952 - Naval Surface Warfare Center, Transonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  11. 21. Photocopy of drawing (original in possession of Naval Surface ...

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

    21. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) 7 X 10 FOOT SONIC WIND TUNNEL, LABORATORY AND OFFICE BUILDING, 1950 - Naval Surface Warfare Center, Transonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  12. 12. Photocopy of drawing (original in possession of Naval Surface ...

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

    12. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) WIND TUNNEL BUILDING, FIRST FLOOR PLAN, NOTE OPEN SHOP, 1941 - Naval Surface Warfare Center, Subsonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  13. 11. Photocopy of drawing (original in possession of Naval Surface ...

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

    11. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) SUPERSONIC WIND TUNNEL BUILDING, SECTIONS AND DETAILS, MECHANICAL, 1947 - Naval Surface Warfare Center, Supersonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  14. 11. Photocopy of photograph (original photograph In the collection of ...

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

    11. Photocopy of photograph (original photograph In the collection of Naval Surface Warfare Center Carderock Division, Bethesda, MD) VIEW NORTHEAST, INTERIOR, SUBSONIC WIND TUNNEL FAN ASSEMBLY, 1943 - Naval Surface Warfare Center, Subsonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  15. New Developments in Chinese Strategic Psychological Warfare

    DTIC Science & Technology

    2005-01-01

    Taoism , which coupled hardness with softness in warfare, was not the only influence on the theory of psychological operations in ancient China. Other...portraying Islamic martyrs who appear to speak to soldiers from the clouds.38 In contemporary wars, such as the Gulf War, the first targets attacked have

  16. Conquest from Within: A Comparative Analysis between Soviet Active Measures and United States Unconventional Warfare Doctrine

    DTIC Science & Technology

    2015-05-27

    irregular threats. Unconventional Warfare (UW), traditionally a Special Operations Forces core activity, has served U.S. strategic interests in a variety...Special Operations Forces core activity, has served U.S. strategic interests in a variety of operational environments. Throughout the Cold War, the

  17. Binding of chemical warfare agent simulants as guests in a coordination cage: contributions to binding and a fluorescence-based response.

    PubMed

    Taylor, Christopher G P; Piper, Jerico R; Ward, Michael D

    2016-05-07

    Cubic coordination cages act as competent hosts for several alkyl phosphonates used as chemical warfare agent simulants; a range of cage/guest structures have been determined, contributions to guest binding analysed, and a fluorescent response to guest binding demonstrated.

  18. Al Qaeda and Fourth Generation Warfare as its Strategy

    DTIC Science & Technology

    2008-01-01

    and materia ~ as well as money, from one point ofthe non- linear battlefield to another, thereby giving more flexibility to obtain the right materials...translated by Griffith, Samuel B., On Guerilla Warfare, (1937),21-22. 14 Bodansky, Yossef, Bin Laden The Man Who Declared War on America (Rocklin: Prima

  19. Portable Sensor for Chemical Nerve Agents and Organophosphorus Compounds

    DTIC Science & Technology

    2015-08-18

    as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of the high toxicity and the...agents have been exploited for use as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of

  20. Prognostication: Do the Services See the Same Future of Warfare?

    DTIC Science & Technology

    2008-05-01

    conduct of war, warfare. 24 Dana Johnson, Scott Pace, C. Bryan Gabbard , Space: Emerging Options for National Power, (RAND, 1998), 10. 25 Creveld, 145...Bryan Gabbard . Space: Emerging Options for National Power, RAND http://www.rand.org/pubs/monograph_reports/MR517/, 1998. (Accessed 5 January 2008

  1. Integrated Biological Warfare Technology Platform (IBWTP). Intelligent Software Supporting Situation Awareness, Response, and Operations

    DTIC Science & Technology

    2007-01-01

    15 4.2.3. Users of Systems for Combating Biological Warfare ................................ 16 4.2.4...21 4.3.1. Existing Biosurveillance Systems .............................................................. 22 4.3.2. Automatic Integration...74 6.4.4. Multi-Agent System Management System (MMS).................................... 75 6.4.5. Agent Glossary

  2. The Role of the National Guard in Homeland Security

    DTIC Science & Technology

    2007-05-01

    Fulcrum Publishing, 1996), 19. 22Ibid., 20. 23Thomas Andrew Bailey and Paul B. Ryan, The Lusitania Disaster: An Episode in Modern Warfare and...Bailey, Thomas Andrew, and Paul B. Ryan. The Lusitania Disaster: An Episode in Modern Warfare and Diplomacy. New York, NY: Free Press, 1975. Ball

  3. Role of Reconnaissance in the Counterattack.

    DTIC Science & Technology

    2016-05-26

    Bejing: Foreign Language Press, 1967), 107. Sun - Tzu , The Art of Warfare, translated by Robert Ames (New York: Ballantine Books, 1993), 113. 14 B.H...dhat: qissat hayati. Cairo, Egypt: al-Maktab al-Misri al-Hadith, 1985. Sun - Tzu . The Art of Warfare. Translated by Robert Ames. New York: Ballantine...39 Bibliography

  4. The Decline of Air Assault Operations

    DTIC Science & Technology

    2016-05-26

    Anthology (Carlisle Barracks: US Army War College, 2000), 6-7. 94 Clausewitz, 198; Sun Tzu , The Art of Warfare, trans. Robert Ames (New York...Encyclopedia of World War II. Santa Barbara: ABC-CLIO, 2004. Tzu , Sun . The Art of Warfare. Trans. Robert Ames. New York: Ballentine Books, 1993. 55... Bibliography ...................................................................................................................................51 iv

  5. 15. Photocopy of drawing (original in possession of Naval Surface ...

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

    15. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) WIND TUNNEL, ELEVATIONS E-E TO H-H AND SECTIONS, 1941 - Naval Surface Warfare Center, Subsonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  6. A Genome-Wide Knockout Screen to Identify Genes Involved in Acquired Carboplatin Resistance

    DTIC Science & Technology

    2016-07-01

    library screen to identify genes that when knocked out render human ovarian cells > 2.5-fold resistant to CBDCA; 2) Validate the ability of...a GeCKOv2 library screen to identify genes that when knocked out render human ovarian cells > 2.5-fold resistant to CBDCA; 2) validate the ability of...resistance in either cell lines or clinical samples. The CRIPSR-cas9 technology now provides us with a major new tool to introduce knock out mutations

  7. Genetics Home Reference: mucopolysaccharidosis type IV

    MedlinePlus

    ... individuals develop various skeletal abnormalities, including short stature, knock knees, and abnormalities of the ribs, chest, spine, ... links) Encyclopedia: Cloudy cornea Encyclopedia: Hypermobile joints Encyclopedia: Knock ... Morquio syndrome Encyclopedia: Mucopolysaccharides Health Topic: ...

  8. Lack of huntingtin promotes neural stem cells differentiation into glial cells while neurons expressing huntingtin with expanded polyglutamine tracts undergo cell death.

    PubMed

    Conforti, Paola; Camnasio, Stefano; Mutti, Cesare; Valenza, Marta; Thompson, Morgan; Fossale, Elisa; Zeitlin, Scott; MacDonald, Marcy E; Zuccato, Chiara; Cattaneo, Elena

    2013-02-01

    Huntington's disease (HD) is a neurodegenerative disorder that affects muscle coordination and diminishes cognitive abilities. The genetic basis of the disease is an expansion of CAG repeats in the Huntingtin (Htt) gene. Here we aimed to generate a series of mouse neural stem (NS) cell lines that carried varying numbers of CAG repeats in the mouse Htt gene (Hdh CAG knock-in NS cells) or that had Hdh null alleles (Hdh knock-out NS cells). Towards this end, Hdh CAG knock-in mouse ES cell lines that carried an Htt gene with 20, 50, 111, or 140 CAG repeats or that were Htt null were neuralized and converted into self-renewing NS cells. The resulting NS cell lines were immunopositive for the neural stem cell markers NESTIN, SOX2, and BLBP and had similar proliferative rates and cell cycle distributions. After 14 days in vitro, wild-type NS cells gave rise to cultures composed of 70% MAP2(+) neurons and 30% GFAP(+) astrocytes. In contrast, NS cells with expanded CAG repeats underwent neuronal cell death, with only 38%±15% of the MAP2(+) cells remaining at the end of the differentiation period. Cell death was verified by increased caspase 3/7 activity on day 14 of the neuronal differentiation protocol. Interestingly, Hdh knock-out NS cells treated using the same neuronal differentiation protocol showed a dramatic increase in the number of GFAP(+) cells on day 14 (61%±20% versus 24%±10% in controls), and a massive decrease of MAP2(+) neurons (30%±11% versus 64%±17% in controls). Both Hdh CAG knock-in NS cells and Hdh knock-out NS cells showed reduced levels of Bdnf mRNA during neuronal differentiation, in agreement with data obtained previously in HD mouse models and in post-mortem brain samples from HD patients. We concluded that Hdh CAG knock-in and Hdh knock-out NS cells have potential as tools for investigating the roles of normal and mutant HTT in differentiated neurons and glial cells of the brain. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Tissue-based standoff biosensors for detecting chemical warfare agents

    DOEpatents

    Greenbaum, Elias; Sanders, Charlene A.

    2003-11-18

    A tissue-based, deployable, standoff air quality sensor for detecting the presence of at least one chemical or biological warfare agent, includes: a cell containing entrapped photosynthetic tissue, the cell adapted for analyzing photosynthetic activity of the entrapped photosynthetic tissue; means for introducing an air sample into the cell and contacting the air sample with the entrapped photosynthetic tissue; a fluorometer in operable relationship with the cell for measuring photosynthetic activity of the entrapped photosynthetic tissue; and transmitting means for transmitting analytical data generated by the fluorometer relating to the presence of at least one chemical or biological warfare agent in the air sample, the sensor adapted for deployment into a selected area.

  10. Chemical-warfare techniques for insect control: insect 'pests' in Germany before and after World War I.

    PubMed

    Jansen, S

    2000-01-01

    During World War I, chemical-warfare practices were introduced into economic entomology in Germany. Fritz Haber, 'the father of chemical warfare', realized that Germany could not win the war and thus looked for 'civilian' uses for his chemical arsenal. Before the war, there was a rhetoric of dangerous 'masses' of insects but the large-scale techniques needed to deal with them had not been developed. The gap between rhetoric and practices enabled entomology to integrate chemical weapons into its working methods. This article traces transformations in the ways of seeing insects and their control from the mid-nineteenth century to after World War I.

  11. The Entomological Institute of the Waffen-SS: evidence for offensive biological warfare research in the third Reich.

    PubMed

    Reinhardt, Klaus

    2013-12-01

    In January 1942, Heinrich Himmler, head of the Schutzstaffel (SS) and police in Nazi Germany, ordered the creation of an entomological institute to study the physiology and control of insects that inflict harm to humans. Founded in the grounds of the concentration camp at Dachau, it has been the focus of previous research, notably into the question of whether it was involved in biological warfare research. This article examines research protocols by the appointed leader Eduard May, presented here for the first time, which confirm the existence of an offensive biological warfare research programme in Nazi Germany. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Genetics Home Reference: hereditary hypophosphatemic rickets

    MedlinePlus

    ... noticeable of these abnormalities are bowed legs or knock knees (a condition in which the lower legs ... Information & Resources MedlinePlus (4 links) Encyclopedia: Bowlegs Encyclopedia: Knock Knees Encyclopedia: Rickets Health Topic: Rickets Genetic and ...

  13. Flight Investigation of the Knock-Limited Performance of a Triptane Blend, a Toluene Blend, and 28-R Fuel in an R-1830-75 Engine

    NASA Technical Reports Server (NTRS)

    Blackman, Calvin C.

    1946-01-01

    Knock-limited performance data were obtained for three fuels on an R-1830-75 engine in a B-24D airplane at engine speeds of 1800, 2250, and 2600 rpm, a spark advance of 25 degrees B.T.C., and carburetor-air temperatures of 85 F for 1800 and 2250 rpm and 100 F for 2600 rpm. The test fuels were a blend of 80 percent 28-R plus 20 percent triptane (leaded to 4.5 ml TEL/gal), a blend of 80 percent 28-R plus 15 percent toluene (leaded to 4.5 ml TEL / gal), and 28-R fuel. The knock-limited manifold pressure of the toluene blend depreciated more in the lean region than the triptane blend or 28-R fuel. The knock-limited brake horsepower for the triptane blend varied from 16 to 25 percent higher than 28-R in the lean region and 18 to 30 percent higher in the rich region. The knock-limited brake horsepower of the toluene blend was approximately 15 percent higher than that of 28-R in the rich region and varied from 2 to 10 percent higher in the lean region. Knock limits of the triptane blend and 28-R fuel tested in the R-1830-75 engine agreed with limits for the same fuels determined with the R-1830-94 engine for engine speeds of 1800 and 2250 rpm.

  14. CRISPR/Cas9-mediated knock-in of an optimized TetO repeat for live cell imaging of endogenous loci.

    PubMed

    Tasan, Ipek; Sustackova, Gabriela; Zhang, Liguo; Kim, Jiah; Sivaguru, Mayandi; HamediRad, Mohammad; Wang, Yuchuan; Genova, Justin; Ma, Jian; Belmont, Andrew S; Zhao, Huimin

    2018-06-15

    Nuclear organization has an important role in determining genome function; however, it is not clear how spatiotemporal organization of the genome relates to functionality. To elucidate this relationship, a method for tracking any locus of interest is desirable. Recently clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) or transcription activator-like effectors were adapted for imaging endogenous loci; however, they are mostly limited to visualization of repetitive regions. Here, we report an efficient and scalable method named SHACKTeR (Short Homology and CRISPR/Cas9-mediated Knock-in of a TetO Repeat) for live cell imaging of specific chromosomal regions without the need for a pre-existing repetitive sequence. SHACKTeR requires only two modifications to the genome: CRISPR/Cas9-mediated knock-in of an optimized TetO repeat and its visualization by TetR-EGFP expression. Our simplified knock-in protocol, utilizing short homology arms integrated by polymerase chain reaction, was successful at labeling 10 different loci in HCT116 cells. We also showed the feasibility of knock-in into lamina-associated, heterochromatin regions, demonstrating that these regions prefer non-homologous end joining for knock-in. Using SHACKTeR, we were able to observe DNA replication at a specific locus by long-term live cell imaging. We anticipate the general applicability and scalability of our method will enhance causative analyses between gene function and compartmentalization in a high-throughput manner.

  15. Characterization of a knock-in mouse model of the homozygous p.V37I variant in Gjb2.

    PubMed

    Chen, Ying; Hu, Lingxiang; Wang, Xueling; Sun, Changling; Lin, Xin; Li, Lei; Mei, Ling; Huang, Zhiwu; Yang, Tao; Wu, Hao

    2016-09-13

    The homozygous p.V37I variant in GJB2 is prevalent in East and Southeast Asians and may lead to mild-to-moderate hearing loss with reduced penetrance. To investigate the pathogenic mechanism underlying this variant, we generated a knock-in mouse model of homozygous p.V37I by an embryonic stem cell gene targeting method. Auditory brainstem response test showed that the knock-in mice developed progressive, mild-to-moderate hearing loss over the first 4-9 months. Overall no significant developmental and morphological abnormality was observed in the knock-in mouse cochlea, while confocal immunostaining and electron microscopic scanning revealed minor loss of the outer hair cells. Gene expression microarray analysis identified 105 up-regulated and 43 down-regulated genes in P5 knock-in mouse cochleae (P < 0.05 adjusted by the Benjamini &Hochberg method), among which four top candidate genes with the highest fold-changes or implication to deafness Fcer1g, Nnmt and Lars2 and Cuedc1 were verified by quantitative real-time PCR. Our study demonstrated that the homozygous p.V37I knock-in mouse modeled the hearing phenotype of the human patients and can serve as a useful animal model for further studies. The differentially expressed genes identified in this study may shed new insights into the understanding of the pathogenic mechanism and the phenotypic modification of homozygous p.V37I.

  16. Immobilization of Enzymes in Nanoporous Host Materials: A Nanobiotechnological Approach to Decontamination and Demilitarization of Chemical and Biological Warfare Agents

    DTIC Science & Technology

    2002-05-06

    Organophosphorus compounds (OPs) are highly toxic and found extensive use as pesticides , insecticides and potential chemical warfare (CW) agents . Recently...commonly used substrate, the serine protease inhibitor diisopropyl fluorophosphates (DFP), and different fluoride-containing G-type nerve agents such as...

  17. Joint Command and Control of Cyber Operations: The Joint Force Cyber Component Command (JFCCC)

    DTIC Science & Technology

    2012-05-04

    relies so heavily on complex command and control systems and interconnectivity in general, cyber warfare has become a serious topic of interest at the...defensive cyber warfare into current and future operations and plans. In particular, Joint Task Force (JTF) Commanders must develop an optimum method to

  18. 21st Century Cyber Security: Legal Authorities and Requirements

    DTIC Science & Technology

    2012-03-22

    Cyber warfare has risen to the level of strategic effect. Exigent threats in cyberspace are a critical U.S. strategic vulnerability for which U.S...operations cross many sections of United States Code. But, they have not yielded a genuine whole-of-government approach. This SRP argues that cyber warfare has

  19. Defending a New Domain: The Pentagon’s Cyberstrategy

    DTIC Science & Technology

    2010-01-01

    mentali.tT will not work. The United States cannot retreat behind a Maginot Line offire- wttlls or it will risk being overrun. Cyber - warfare is like...provides a dear and accountable way to marshal cyber - warfare resources from across tl~e military. A single chain of command runs f’rom the U.S

  20. Rethinking Cultural Influences on Warfare

    DTIC Science & Technology

    2012-05-17

    36 Jarole B. Manheim, Richard C. Lars Willnat, and Craig Brians , Empirical Political...Willnat, and Craig Brians , Empirical Political Analysis: Quantitative and Qualitative Research Methods (New York: Pearson Education Inc, 2008... Boxer Rebellions. In 1950, China was emerging from 13 years of protracted warfare with Japan and a civil war between the Chinese Communist Party (CCP

  1. 20. Photocopy of drawing (original in possession of Naval Surface ...

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

    20. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) 7 X 10 FOOT SONIC WIND TUNNEL FIRST FLOOR PLANS AND DETAILS, 1948 - Naval Surface Warfare Center, Transonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  2. 22. Photocopy of drawing (original in possession of Naval Surface ...

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

    22. Photocopy of drawing (original in possession of Naval Surface Warfare Center Carderock Division, Bethesda, MD) 7 X 10 FOOT SONIC WIND TUNNEL, INSTALLATION OF POWER EQUIPMENT AND ACCESSORIES, 1950 - Naval Surface Warfare Center, Transonic Wind Tunnel Building, Bounded by Clara Barton Parkway & McArthur Boulevard, Silver Spring, Montgomery County, MD

  3. Canada’s Army and the Concept of Maneuver Warfare: The Legacy of the Twentieth Century (1899-1998)

    DTIC Science & Technology

    2002-01-01

    comprehensiveness and authenticity. Canadian operational experience in peace and war over the last century has been characterized by: static warfare; attrition; lack...2 THE BOER WAR (1899 - 1901) .............................................................................................5...PRELUDE TO WORLD WAR I (1902 - 1913) ........................................................................8 WORLD WAR ONE (1914 - 1918

  4. Above the Influence: The Strategic Effects of Airpower in Irregular Warfare

    DTIC Science & Technology

    2010-06-01

    INDOCHINA. . . . . . . . . . . . . . . . . . . . . 105 APPENDIX B: MAP OF LAOS . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 APPENDIX...perspectives. These perspectives involve the use of airpower in North Vietnam, South Vietnam, and Laos . The overarching political endstate or...Nagl, ―Principles, Imperatives, and Paradoxes of Counterinsurgency,‖ 50; Mao Tse -Tung, Problems of Strategy in Guerrilla Warfare, 215-216; Gray

  5. 75 FR 20828 - Availability for Non-Exclusive, Exclusive, or Partially Exclusive Licensing of U.S. Patent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... all types of harmful chemicals, specifically chemical warfare agents (CWAs). The topical skin protectant offers a barrier property and an active moiety that serves to neutralize chemical warfare agents...: Department of the Army, DoD. ACTION: Notice. SUMMARY: Announcement is made of the availability for licensing...

  6. 78 FR 63971 - Notice of Availability of Record of Decision for Outdoor Research, Development, Test and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... Outdoor Research, Development, Test and Evaluation Activities at Naval Surface Warfare Center, Dahlgren Division, Dahlgren, VA AGENCY: Department of the Navy, DoD. ACTION: Notice. SUMMARY: The Department of the... proposed action, announces its decision to expand the Naval Surface Warfare Center, Dahlgren Division's...

  7. 78 FR 55326 - Determinations Regarding Use of Chemical Weapons in Syria Under the Chemical and Biological...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-10

    ... DEPARTMENT OF STATE [Public Notice 8460] Determinations Regarding Use of Chemical Weapons in Syria Under the Chemical and Biological Weapons Control and Warfare Elimination Act of 1991 AGENCY: Bureau of...(d) of the Chemical and Biological Weapons Control and Warfare Elimination Act of 1991, as amended...

  8. 75 FR 58373 - Notice of Intent To Grant Exclusive Patent License; DQE, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... objections are to be filed with Naval Surface Warfare Center, Crane Division, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001. FOR FURTHER INFORMATION CONTACT: Mr. Christopher Monsey, Naval Surface Warfare Center, Crane Division, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001, telephone 812-854...

  9. 77 FR 14508 - Notice of Availability of Government-Owned Inventions; Available for Licensing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... launching device). ADDRESSES: Written objections are to be filed with Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001. FOR FURTHER INFORMATION CONTACT: Mr. Christopher Monsey, Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN...

  10. 77 FR 5242 - Notice of Availability of Government-Owned Invention; Available for Licensing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... weapon mount). ADDRESSES: Written objections are to be filed with Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001. FOR FURTHER INFORMATION CONTACT: Mr. Christopher Monsey, Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN...

  11. Public Discussion of Nuclear Warfare: A Time for Hope.

    ERIC Educational Resources Information Center

    Cooper, Martha

    Anti-nuclear discourse, which peaked in 1981-82, signaled an emergence of public discourse on the nuclear warfare issue. During the development of the original atomic bomb, public discussion of the issue was severely restricted, but immediately after the bombing of Hiroshima and Nagasaki, discourse on the subject increased. During the Cold War…

  12. Defending the Borderland: Ukrainian Military Experiences with IO, Cyber, and EW

    DTIC Science & Technology

    2017-12-01

    31 Tactical Information Operations...seeks to understand the current state of hybrid warfare in Ukraine with a particular emphasis on the use of Information Operations (IO), Electronic...understanding of the conditions that enabled this style of warfare and how Russia has exploited those conditions in Ukraine will serve to inform

  13. An Empirical Examination of the Warfare Metaphor with Respect to Pre-Service Elementary Teachers

    ERIC Educational Resources Information Center

    Cobern, William W.; Loving, Cathleen C.; Davis, Edward B.; Terpstra, Jeff

    2013-01-01

    Since its origination in the late nineteenth century, the warfare metaphor has been used to characterize the relationship between science and religion, especially orthodox Christianity. Though thoroughly discredited by historians of science, the ideological descendants of Thomas Huxley, who spoke of science in quasi-religious terms, have kept the…

  14. Nuclear Arms and National Security. 1983 National Issues Forum.

    ERIC Educational Resources Information Center

    Melville, Keith, Ed.

    Appropriate for secondary school social studies, this booklet outlines approaches for dealing with the threat of nuclear warfare in six sections. The first section, "Learning to Live with Nuclear Weapons," introduces the topic and considers what can be done to decrease the risk of nuclear warfare without jeopardizing the nation's security. "Arms…

  15. Unmanned Systems In Integrating Cross domain Naval Fires

    DTIC Science & Technology

    2016-06-01

    requirement for the battery . Lithium - Ion batteries have the remarkable characteristic of high energy density. A Lithium -Sulphur-Dioxide battery can...163 xi LIST OF FIGURES Figure 1. NPS Warfare Innovation Continuum...during the Warfare Innovation Workshop during Enrichment Week, September 2015. This four-day forum brought together students and faculty, defense

  16. Joint Operations

    DTIC Science & Technology

    2006-09-17

    the GCC must evaluate the need for force protection support following the guidelines of DOD Instruction 3020.41, Contractor Personnel Authorized to...EA electronic attack EM electromagnetic EP emergency preparedness EW electronic warfare FCC functional combatant commander FDO flexible deterrent...their primary destructive mechanism (lasers, radio frequency weapons, particle beams). b. electronic protection. That division of electronic warfare

  17. Waste minimization opportunity assessment: Naval Undersea Warfare Engineering Station, Keyport, Washington. Project summary

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

    NONE

    The Environmental Protection Agency (EPA) has developed a systematic approach to identify, select and implement options to reduce or eliminate hazardous waste. The report describes the application of the waste minimization assessment procedures to a torpedo maintenance facility at the Naval Undersea Warfare Engineering Station in Keyport, WA (NUWES Keyport).

  18. The Future of Amphibious Operations: Shaping the Expeditionary Strike Group to Fight in the Joint Task Force

    DTIC Science & Technology

    2010-02-01

    1 Charles E. Wilhelm, Expeditionary Warfare.marine corps gazette, 79(6), 28-30. Retrieved October 15, 2009, from Career and Technical Education . (Document...Expeditionary warfare.marine corps gazette, 79(6), 28- 30. Retrieved October 15, 2009, from Career and Technical Education . (Document ID: 4455650

  19. Conventional Warfare and United States Military Involvement in Latin America: Early Adolescents' Views.

    ERIC Educational Resources Information Center

    Roscoe, Bruce; And Others

    1988-01-01

    Assessed adolescents' views concerning conventional war and compared views to those of adolescents 15 years ago. Surveyed 362 seventh graders regarding conventional warfare and United States military involvement in Latin America. Compared to adolescents in 1971, adolescents in 1986 were somewhat more accepting of war. Many were skeptical of…

  20. Surface Warfare. Mainstreaming, Mine Warfare. May/June 1998, Vol. 23, No. 3

    DTIC Science & Technology

    1998-06-01

    grappling with a paper tiger. Nor is it a fleeting thought process — some- thing heard in briefings and filed away in the warrior’s subconscious ...tecting device designed to work with the Quickstrike series of bottom mines. This new TDD can be reprogrammed to enable the Quickstrike mines to

  1. A SAFE AND RAPID METHOD FOR BIOLOGICAL AND CHEMICAL DECONTAMINATION OF BUILDINGS AND EQUIPMENT USING THE TERRACAP™ CB DECON SYSTEM - PHASE I

    EPA Science Inventory

    Today’s world and political climate lends itself to potential attacks by hostile forces and terrorists where both exterior and interior surfaces of vehicles, buildings, or equipment could become contaminated with biological warfare (BW) or chemical warfare (CW) agents. R...

  2. Multifunctional ultra-high vacuum apparatus for studies of the interactions of chemical warfare agents on complex surfaces

    NASA Astrophysics Data System (ADS)

    Wilmsmeyer, Amanda R.; Gordon, Wesley O.; Davis, Erin Durke; Mantooth, Brent A.; Lalain, Teri A.; Morris, John R.

    2014-01-01

    A fundamental understanding of the surface chemistry of chemical warfare agents is needed to fully predict the interaction of these toxic molecules with militarily relevant materials, catalysts, and environmental surfaces. For example, rules for predicting the surface chemistry of agents can be applied to the creation of next generation decontaminants, reactive coatings, and protective materials for the warfighter. Here, we describe a multifunctional ultra-high vacuum instrument for conducting comprehensive studies of the adsorption, desorption, and surface chemistry of chemical warfare agents on model and militarily relevant surfaces. The system applies reflection-absorption infrared spectroscopy, x-ray photoelectron spectroscopy, and mass spectrometry to study adsorption and surface reactions of chemical warfare agents. Several novel components have been developed to address the unique safety and sample exposure challenges that accompany the research of these toxic, often very low vapor pressure, compounds. While results of vacuum-based surface science techniques may not necessarily translate directly to environmental processes, learning about the fundamental chemistry will begin to inform scientists about the critical aspects that impact real-world applications.

  3. Contamination source review for Building E5978, Edgewood Area, Aberdeen Proving Ground, Maryland

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

    Mosqueda, G.; Dougherty, J.; Draugelis, A.K.

    1995-09-01

    This report documents the results of a contamination source review of Building E5978 at the Aberdeen Proving Group (APG) in Maryland. The primary mission at APG has been the testing and evaluation of US Army warfare materials. Since its beginning in 1917, the Edgewood Area of APG has been the principal location for chemical warfare agent research, development, and testing in the US. APG was also used for producing chemical warfare agents during both world wars, and it has been a center for the storage of chemical warfare material. An attempt was made to identify and define areas of toxicmore » or hazardous contaminants and to assess the physical condition and accessibility of APG buildings. The information obtained from this review may be used to assist the US Army in planning for the future use or disposition of the buildings. The contamination source review consisted of the following tasks: historical records search, physical inspection, photographic documentation, geophysical investigation, and collection of air samples for the presence of volatile organic compounds.« less

  4. Contamination source review for Building E3641, Edgewood Area, Aberdeen Proving Ground, Maryland

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

    Zellmer, S.D.; Draugelis, A.K.; Rueda, J.

    1995-09-01

    This report documents the results of a contamination source review of Building E3641 at the Aberdeen Proving Ground (APG) in Maryland. The primary mission at APG has been the testing and evaluation of US Army warfare materials. Since its beginning in 1917, the Edgewood Area of APG has been the principal location for chemical warfare agent research, development, and testing in the US. APG was also used for producing chemical warfare agents during both world wars, and it has been a center for the storage of chemical warfare material. An attempt was made to identify and define areas of toxicmore » or hazardous contaminants and to assess the physical condition and accessibility of APG buildings. The information obtained from this review may be used to assist the US Army in planning for the future use or disposition of the buildings. The contamination source review consisted of the following tasks: historical records search, physical inspection, photographic documentation, geophysical investigation, and review of available records regarding underground storage tanks associated with each building.« less

  5. Multifunctional ultra-high vacuum apparatus for studies of the interactions of chemical warfare agents on complex surfaces.

    PubMed

    Wilmsmeyer, Amanda R; Gordon, Wesley O; Davis, Erin Durke; Mantooth, Brent A; Lalain, Teri A; Morris, John R

    2014-01-01

    A fundamental understanding of the surface chemistry of chemical warfare agents is needed to fully predict the interaction of these toxic molecules with militarily relevant materials, catalysts, and environmental surfaces. For example, rules for predicting the surface chemistry of agents can be applied to the creation of next generation decontaminants, reactive coatings, and protective materials for the warfighter. Here, we describe a multifunctional ultra-high vacuum instrument for conducting comprehensive studies of the adsorption, desorption, and surface chemistry of chemical warfare agents on model and militarily relevant surfaces. The system applies reflection-absorption infrared spectroscopy, x-ray photoelectron spectroscopy, and mass spectrometry to study adsorption and surface reactions of chemical warfare agents. Several novel components have been developed to address the unique safety and sample exposure challenges that accompany the research of these toxic, often very low vapor pressure, compounds. While results of vacuum-based surface science techniques may not necessarily translate directly to environmental processes, learning about the fundamental chemistry will begin to inform scientists about the critical aspects that impact real-world applications.

  6. Airborne exposure limits for chemical and biological warfare agents: is everything set and clear?

    PubMed

    Sabelnikov, Alex; Zhukov, Vladimir; Kempf, C Ruth

    2006-08-01

    Emergency response strategies (guidelines) for biological, chemical, nuclear, or radiological terrorist events should be based on scientifically established exposure limits for all the agents or materials involved. In the case of a radiological terrorist event, emergency response guidelines (ERG) have been worked out. In the case of a terrorist event with the use of chemical warfare (CW) agents the situation is not that clear, though the new guidelines and clean-up values are being generated based on re-evaluation of toxicological and risk data. For biological warfare (BW) agents, such guidelines do not yet exist. In this paper the current status of airborne exposure limits (AELs) for chemical and biological warfare (CBW) agents are reviewed. Particular emphasis is put on BW agents that lack such data. An efficient, temporary solution to bridge the gap in experimental infectious data and to set provisional AELs for BW agents is suggested. It is based on mathematically generated risks of infection for BW agents grouped by their alleged ID50 values in three categories: with low, intermediate and high ID50 values.

  7. Modeling the transport of chemical warfare agents and simulants in polymeric substrates for reactive decontamination

    NASA Astrophysics Data System (ADS)

    Pearl, Thomas; Mantooth, Brent; Varady, Mark; Willis, Matthew

    2014-03-01

    Chemical warfare agent simulants are often used for environmental testing in place of highly toxic agents. This work sets the foundation for modeling decontamination of absorbing polymeric materials with the focus on determining relationships between agents and simulants. The correlations of agents to simulants must consider the three way interactions in the chemical-material-decontaminant system where transport and reaction occur in polymer materials. To this end, diffusion modeling of the subsurface transport of simulants and live chemical warfare agents was conducted for various polymer systems (e.g., paint coatings) with and without reaction pathways with applied decontamination. The models utilized 1D and 2D finite difference diffusion and reaction models to simulate absorption and reaction in the polymers, and subsequent flux of the chemicals out of the polymers. Experimental data including vapor flux measurements and dynamic contact angle measurements were used to determine model input parameters. Through modeling, an understanding of the relationship of simulant to live chemical warfare agent was established, focusing on vapor emission of agents and simulants from materials.

  8. Multifunctional ultra-high vacuum apparatus for studies of the interactions of chemical warfare agents on complex surfaces

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

    Wilmsmeyer, Amanda R.; Morris, John R.; Gordon, Wesley O.

    2014-01-15

    A fundamental understanding of the surface chemistry of chemical warfare agents is needed to fully predict the interaction of these toxic molecules with militarily relevant materials, catalysts, and environmental surfaces. For example, rules for predicting the surface chemistry of agents can be applied to the creation of next generation decontaminants, reactive coatings, and protective materials for the warfighter. Here, we describe a multifunctional ultra-high vacuum instrument for conducting comprehensive studies of the adsorption, desorption, and surface chemistry of chemical warfare agents on model and militarily relevant surfaces. The system applies reflection-absorption infrared spectroscopy, x-ray photoelectron spectroscopy, and mass spectrometry tomore » study adsorption and surface reactions of chemical warfare agents. Several novel components have been developed to address the unique safety and sample exposure challenges that accompany the research of these toxic, often very low vapor pressure, compounds. While results of vacuum-based surface science techniques may not necessarily translate directly to environmental processes, learning about the fundamental chemistry will begin to inform scientists about the critical aspects that impact real-world applications.« less

  9. Development of a one-step gene knock-out and knock-in method for metabolic engineering of Aureobasidium pullulans.

    PubMed

    Guo, Jian; Wang, Yuanhua; Li, Baozhong; Huang, Siyao; Chen, Yefu; Guo, Xuewu; Xiao, Dongguang

    2017-06-10

    Aureobasidium pullulans is an increasingly attractive host for bio-production of pullulan, heavy oil, polymalic acid, and a large spectrum of extracellular enzymes. To date, genetic manipulation of A. pullulans mainly relies on time-consuming conventional restriction enzyme digestion and ligation methods. In this study, we present a one-step homologous recombination-based method for rapid genetic manipulation in A. pullulans. Overlaps measuring >40bp length and 10μg DNA segments for homologous recombination provided maximum benefits to transformation of A. pullulans. This optimized method was successfully applied to PKSIII gene (encodes polyketide synthase) knock-out and gltP gene (encodes glycolipid transfer protein) knock-in. After disruption of PKSIII gene, secretion of melanin decreased slightly. The melanin purified from disruptant showed lower reducing capacity compared with that of the parent strain, leading to a decrease in exopolysaccharide production. Knock-in of gltP gene resulted in at least 4.68-fold increase in heavy oil production depending on the carbon source used, indicating that gltP can regulate heavy oil synthesis in A. pullulans. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation.

    PubMed

    Chen, Ding; Xu, Tao; Tu, Mengjun; Xu, Jinlin; Zhou, Chenchen; Cheng, Lulu; Yang, Ruqing; Yang, Tanchu; Zheng, Weiwei; He, Xiubin; Deng, Ruzhi; Ge, Xianglian; Li, Jin; Song, Zongming; Zhao, Junzhao; Gu, Feng

    2017-01-01

    X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation ( RS1 , p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1 -KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1 -KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice ( RS1 -KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.

  11. 40 CFR 91.6 - Reference materials.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Appendix A to Subpart D. ASTM D2699-92: Standard Test Method for Knock Characteristics of Motor Fuels by the Research Method Appendix A to Subpart D. ASTM D2700-92: Standard Test Method for Knock...

  12. 29 CFR 1926.350 - Gas welding and cutting.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... from being knocked over while in use. (8) When work is finished, when cylinders are empty, or when..., or gangways. Assigned storage places shall be located where cylinders will not be knocked over or...

  13. 40 CFR 91.6 - Reference materials.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Appendix A to Subpart D. ASTM D2699-92: Standard Test Method for Knock Characteristics of Motor Fuels by the Research Method Appendix A to Subpart D. ASTM D2700-92: Standard Test Method for Knock...

  14. 40 CFR 90.7 - Reference materials.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Appendix A to subpart D, Table 3. ASTM D2699-92: Standard Test Method for Knock Characteristics of Motor... Knock Characteristics of Motor and Aviation Fuels by the Motor Method Appendix A to subpart D, Table 3...

  15. 40 CFR 90.7 - Reference materials.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Appendix A to subpart D, Table 3. ASTM D2699-92: Standard Test Method for Knock Characteristics of Motor... Knock Characteristics of Motor and Aviation Fuels by the Motor Method Appendix A to subpart D, Table 3...

  16. Do Structural Missense Variants in the ATM Gene Found in Women With Breast Cancer Cause Breast Cancer in Knock-in Mouse Strains?

    DTIC Science & Technology

    2006-04-01

    W81XWH-05-1-0282 TITLE: Do Structural Missense Variants in the ATM Gene Found in Women with Breast Cancer Cause Breast Cancer in "Knock-in...5a. CONTRACT NUMBER Do Structural Missense Variants in the ATM Gene Found in Women with Breast Cancer Cause Breast Cancer in "Knock-in" Mouse...human cohort-specific missense mutations will develop breast cancer with dominant inheritance in a subset of animals. It also is hypothesized that

  17. Proton Knock-Out in Hall A

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

    Kees de Jager

    Proton knock-out is studied in a broad program in Hall A at Jefferson Lab. The first experiment performed in Hall A studied the {sup 16}O(e,e'p) reaction. Since then proton knock-out experiments have studied a variety of aspects of that reaction, from single-nucleon properties to its mechanism, such as final-state interactions and two-body currents, in nuclei from {sup 2}H to {sup 16}O. In this review the results of this program will be summarized and an outlook given of future accomplishments.

  18. Knocking in the Otto-cycle Engine

    NASA Technical Reports Server (NTRS)

    Weinhart, H

    1939-01-01

    Engine knock is, as is known, preceded by normal burning of the first part of the charge, and only the part burned last (residual charge), knocks. The aim of the present measurements was, first, to reexamine the combustion form in this residual charge, because of the absence of uniform and frequently contradictory results in the very extensive literature on the subject. On top of that, an attempt was to be made to gain a deeper insight into the mechanism accompanying the combustion process, by means of the electrical test equipment perfected in recent years.

  19. Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice.

    PubMed

    Brütsch, Simone Hanna; Wang, Chi Chiu; Li, Lu; Stender, Hannelore; Neziroglu, Nilgün; Richter, Constanze; Kuhn, Hartmut; Borchert, Astrid

    2015-02-01

    Glutathione peroxidases (Gpx) and lipoxygenases (Alox) are functional counterplayers in the metabolism of hydroperoxy lipids that regulate cellular redox homeostasis. Gpx4 is a moonlighting protein that has been implicated not only as an enzyme in anti-oxidative defense, gene expression regulation, and programmed cell death, but also as a structural protein in spermatogenesis. Homozygous Gpx4 knock-out mice are not viable, but molecular reasons for intrauterine lethality are not completely understood. This study was aimed at investigating whether the lack of catalytic activity or the impaired function as structural protein is the dominant reason for embryonic lethality. We further explored whether the pro-oxidative enzyme mouse 12/15 lipoxygenase (Alox15) plays a major role in embryonic lethality of Gpx4-deficient mice. To achieve these goals, we first created knock-in mice, which express a catalytically inactive Gpx4 mutant (Sec46Ala). As homozygous Gpx4-knock-out mice Sec46Ala-Gpx4(+/+) knock-in animals are not viable but undergo intrauterine resorption between embryonic day 6 and 7 (E6-7). In contrast, heterozygous knock-in mice (Sec46Ala-Gpx4(-/+)) are viable, fertile and do not show major phenotypic alterations. Interestingly, homozygous Alox15 deficiency did not rescue the U46A-Gpx4(+/+) mice from embryonic lethality. In fact, when heterozygous U46A-Gpx4(-/+) mice were stepwise crossed into an Alox15-deficent background, no viable U46A-Gpx4(+/+)+Alox15(-/-) individuals were obtained. However, we were able to identify U46A-Gpx4(+/+)+Alox15(-/-) embryos in the state of resorption around E7. These data suggest that the lack of catalytic activity is the major reason for the embryonic lethality of Gpx4(-/-) mice and that systemic inactivation of the Alox15 gene does not rescue homozygous knock-in mice expressing catalytically silent Gpx4.

  20. Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.

    PubMed

    Beccano-Kelly, Dayne A; Kuhlmann, Naila; Tatarnikov, Igor; Volta, Mattia; Munsie, Lise N; Chou, Patrick; Cao, Li-Ping; Han, Heather; Tapia, Lucia; Farrer, Matthew J; Milnerwood, Austen J

    2014-01-01

    Mutations in Leucine-Rich Repeat Kinase-2 (LRRK2) result in familial Parkinson's disease and the G2019S mutation alone accounts for up to 30% in some ethnicities. Despite this, the function of LRRK2 is largely undetermined although evidence suggests roles in phosphorylation, protein interactions, autophagy and endocytosis. Emerging reports link loss of LRRK2 to altered synaptic transmission, but the effects of the G2019S mutation upon synaptic release in mammalian neurons are unknown. To assess wild type and mutant LRRK2 in established neuronal networks, we conducted immunocytochemical, electrophysiological and biochemical characterization of >3 week old cortical cultures of LRRK2 knock-out, wild-type overexpressing and G2019S knock-in mice. Synaptic release and synapse numbers were grossly normal in LRRK2 knock-out cells, but discretely reduced glutamatergic activity and reduced synaptic protein levels were observed. Conversely, synapse density was modestly but significantly increased in wild-type LRRK2 overexpressing cultures although event frequency was not. In knock-in cultures, glutamate release was markedly elevated, in the absence of any change to synapse density, indicating that physiological levels of G2019S LRRK2 elevate probability of release. Several pre-synaptic regulatory proteins shown by others to interact with LRRK2 were expressed at normal levels in knock-in cultures; however, synapsin 1 phosphorylation was significantly reduced. Thus, perturbations to the pre-synaptic release machinery and elevated synaptic transmission are early neuronal effects of LRRK2 G2019S. Furthermore, the comparison of knock-in and overexpressing cultures suggests that one copy of the G2019S mutation has a more pronounced effect than an ~3-fold increase in LRRK2 protein. Mutant-induced increases in transmission may convey additional stressors to neuronal physiology that may eventually contribute to the pathogenesis of Parkinson's disease.

  1. Elevated progranulin contributes to synaptic and learning deficit due to loss of fragile X mental retardation protein.

    PubMed

    Zhang, Kun; Li, Yu-Jiao; Guo, Yanyan; Zheng, Kai-Yin; Yang, Qi; Yang, Le; Wang, Xin-Shang; Song, Qian; Chen, Tao; Zhuo, Min; Zhao, Ming-Gao

    2017-12-01

    Fragile X syndrome is an inheritable form of intellectual disability caused by loss of fragile X mental retardation protein (FMRP, encoded by the FMR1 gene). Absence of FMRP caused overexpression of progranulin (PGRN, encoded by GRN), a putative tumour necrosis factor receptor ligand. In the present study, we found that progranulin mRNA and protein were upregulated in the medial prefrontal cortex of Fmr1 knock-out mice. In Fmr1 knock-out mice, elevated progranulin caused insufficient dendritic spine pruning and late-phase long-term potentiation in the medial prefrontal cortex of Fmr1 knock-out mice. Partial progranulin knock-down restored spine morphology and reversed behavioural deficits, including impaired fear memory, hyperactivity, and motor inflexibility in Fmr1 knock-out mice. Progranulin increased levels of phosphorylated glutamate ionotropic receptor GluA1 and nuclear factor kappa B in cultured wild-type neurons. Tumour necrosis factor receptor 2 antibody perfusion blocked the effects of progranulin on GluA1 phosphorylation; this result indicates that tumour necrosis factor receptor 2 is required for progranulin-mediated GluA1 phosphorylation and late-phase long-term potentiation expression. However, high basal level of progranulin in Fmr1 knock-out mice prevented further facilitation of synaptic plasticity by exogenous progranulin. Partial downregulation of progranulin or tumour necrosis factor receptor 2/nuclear factor kappa B signalling restored synaptic plasticity and memory deficits in Fmr1 knock-out mice. These findings suggest that elevated PGRN is linked to cognitive deficits of fragile X syndrome, and the progranulin/tumour necrosis factor receptor 2 signalling pathway may be a putative therapeutic target for improving cognitive deficits in fragile X syndrome. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Knock-Outs, Stick-Outs, Cut-Outs: Clipping Paths Separate Objects from Background.

    ERIC Educational Resources Information Center

    Wilson, Bradley

    1998-01-01

    Outlines a six-step process that allows computer operators, using Photoshop software, to create "knock-outs" to precisely define the path that will serve to separate the object from the background. (SR)

  3. Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment.

    PubMed

    Wu, Kaiming; Zhao, Zhenxian; Liu, Kuanzhi; Zhang, Jian; Li, Guanghua; Wang, Liang

    2017-07-03

    Long non-coding RNAs (LncRNAs) have been recently regarded as systemic regulators in multiple biologic processes including tumorigenesis. In this study, we observed the expression of lncRNA lnc-sox5 was significantly increased in colorectal cancer (CRC). Despite the CRC cell growth, cell cycle and cell apoptosis was not affected by lnc-sox5 knock-down, lnc-sox5 knock-down suppressed CRC cell migration and invasion. In addition, xenograft animal model suggested that lnc-sox5 knock-down significantly suppressed the CRC tumorigenesis. Our results also showed that the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was significantly reduced by lnc-sox5 knock-down and therefore modulated the infiltration and cytotoxicity of CD3 + CD8 + T cells. Taken together, these results suggested that lnc-sox5 unbalances tumor microenvironment to regulate colorectal cancer progression.

  4. A High-Speed Motion-Picture Study of Normal Combustion, Knock and Preignition in a Spark-Ignition Engines

    NASA Technical Reports Server (NTRS)

    Rothrock, A M; Spencer, R C; Miller, Cearcy D

    1941-01-01

    Combustion in a spark-ignition engine was investigated by means of the NACA high-speed motion-picture cameras. This camera is operated at a speed of 40,000 photographs a second and therefore makes possible the study of changes that take place in the intervals as short as 0.000025 second. When the motion pictures are projected at the normal speed of 16 frames a second, any rate of movement shown is slowed down 2500 times. Photographs are presented of normal combustion, of combustion from preignitions, and of knock both with and without preignition. The photographs of combustion show that knock may be preceded by a period of exothermic reaction in the end zone that persists for a time interval of as much as 0.0006 second. The knock takes place in 0.00005 second or less.

  5. Situation Awareness Information Dominance & Information Warfare.

    DTIC Science & Technology

    1997-02-01

    Information warfare and its primary objective of achieving information dominance over enemy forces have arisen as a major area of emphasis for future...military actions. The concept of information dominance and the issues involved in attaining it are explored through a model of situation awareness...directions for the development of systems to support the goal of information dominance can be established.

  6. An Ecological Examination of Rural Mozambican Women's Attainment of Postwar Wellbeing

    ERIC Educational Resources Information Center

    Deacon, Zermarie; Sullivan, Cris

    2010-01-01

    Women's experiences of warfare and postwar recovery are qualitatively different from those of men. However, to date, the processes whereby women recover from the gendered impacts of war have not been sufficiently explored. In order to address this gap in the literature and to inform policies and services aimed at women recovering from warfare, a…

  7. FY04 NDCEE Annual Technologies Publications

    DTIC Science & Technology

    2006-03-14

    Crane Division, Indiana Naval Surface Warfare Center, Indian Head Division (IHDiv), Maryland Navy Ammunition Program Office New Jersey Institute of...full-scale field demonstrations • Coordinated literature reviews, data requests, and telephone interviews with Naval Surface Warfare Center, Crane ...Armored Recon ABN Assault Vehicle, Bridge Launcher Armored Vehicle, Carrier Ammunition, Crane Shovel 20-ton, Hammer Pile Drivers, and Howitzers. Points of

  8. FY04 NDCEE Annual Technologies Publication

    DTIC Science & Technology

    2006-03-14

    Crane Division, Indiana Naval Surface Warfare Center, Indian Head Division (IHDiv), Maryland Navy Ammunition Program Office New Jersey Institute of...full-scale field demonstrations • Coordinated literature reviews, data requests, and telephone interviews with Naval Surface Warfare Center, Crane ...Armored Recon ABN Assault Vehicle, Bridge Launcher Armored Vehicle, Carrier Ammunition, Crane Shovel 20-ton, Hammer Pile Drivers, and Howitzers. Points of

  9. An outbreak of chickenpox in a military field hospital--the implications for biological warfare.

    PubMed Central

    Hepburn, N C; Brooks, T J

    1991-01-01

    An outbreak of chickenpox with spread to patients and staff on the isolation ward of a British field hospital during the Gulf war is described. The implications for the design and operation of field hospital isolation units should transmissible biological warfare agents be encountered in any future conflict are discussed. PMID:1774746

  10. Coalition Warfare: the Leadership Challenges

    DTIC Science & Technology

    2011-05-19

    Approved for Public Release; Distribution is Unlimited Coalition Warfare: The leadership challenges A Monograph by Colonel Mark J Thornhill...The leadership challenges . 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Colonel Mark J. Thornhill...multinational operations, leadership challenges , leadership attributes, unity of command. 16. SECURITY CLASSIFICATION OF: UNCLASSIFIED 17. LIMITATION OF

  11. 78 FR 55687 - Notice of Intent To Grant Partially Exclusive Patent License; Silvanus, LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-11

    ... with Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001. FOR FURTHER INFORMATION CONTACT: Mr. Christopher Monsey, Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001, telephone 812-854-4100. Authority: 35 U.S.C. 207...

  12. 76 FR 23314 - Notice of Intent To Grant Partially Exclusive Patent License; Sean Linehan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-26

    ... are to be filed with Naval Surface Warfare Center, Crane Division, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001. FOR FURTHER INFORMATION CONTACT: Mr. Christopher Monsey, Naval Surface Warfare Center, Crane Division, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001, telephone 812-854-4100...

  13. 77 FR 5242 - Notice of Intent To Grant Exclusive Patent License; Daniel Defense, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001. FOR FURTHER INFORMATION CONTACT: Mr. Christopher Monsey, Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001, telephone (812) 854-4100. Authority: 35 U.S.C. 207, 37...

  14. 77 FR 23673 - Notice of Intent To Grant Exclusive Patent License; Aurora Technologies, LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-20

    ... objections are to be filed with the Naval Surface Warfare Center, Crane Div, Code OOL, Bldg. 2, 300 Highway 361, Crane, IN 47522-5001. FOR FURTHER INFORMATION CONTACT: Mr. Christopher Monsey, Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001, telephone 812-854-4100...

  15. Delivering Savings with Open Architecture and Product Lines

    DTIC Science & Technology

    2011-04-30

    p.m. Chair: Christopher Deegan , Executive Director, Program Executive Office for Integrated Warfare Systems Delivering Savings with Open...Architectures Walt Scacchi and Thomas Alspaugh, Institute for Software Research Christopher Deegan —Executive Director, Program Executive Officer...Integrated Warfare Systems (PEO IWS). Mr. Deegan directs the development, acquisition, and fleet support of 150 combat weapon system programs managed by 350

  16. Anti-Submarine Warfare: Still an Essential Warfare Art

    DTIC Science & Technology

    1993-02-19

    34 U.S. Naval Institute ProceedinQs, June 1992, 52. 11. Ibid., 53. 21. Ibid., 53. "D. Holland, 33. 2. Robert 0. Crawshaw , "What Is a Maritime Action...June 1992, 52-54. 4. Byron, John L. "A New Target for the Submarine Force." U.S. Naval Institute Proceedings, January 1990, 38-39. 5. Crawshaw

  17. The Physics of Warfare

    ERIC Educational Resources Information Center

    Giordano, Gerardo

    2015-01-01

    Recently, I was tasked with the creation and execution of a new themed general education physics class called The Physics of Warfare. In the past, I had used the theme of a class, such as the physics of sports medicine, as a way to create homework and in-class activities, generate discussions, and provide an application to demonstrate that physics…

  18. Technology Transfer Summary Report (FY92), Naval Surface Warfare Center Dahlgren Division

    DTIC Science & Technology

    1994-04-20

    communications; no formal records are kept of these. Community Technical Outreach NSWCDD participates in the "Science and Engineering Apprentice" and the " Bay ...ADMINISTRATOR’S OFFICE NAVAL UNDERSEA WARFARE CENTER PO BOX 545 DIVISION NEWPORT SEQUIM WA 98382 NEWPORI’ RI 02841-5047 ATTN GIFT AND EXCHANGE DIV 4 ATTN CODE 00

  19. Technology Transition for Hybrid Warfare

    DTIC Science & Technology

    2010-02-16

    and Iraq. At the same time, the science and technology base must provide the disruptive technologies to defeat future conventional enemies. This... disruptive technologies will be needed to retain long-term technological superiority in conventional warfare. Incremental improvement is the most...technology to be missed. Disruptive technologies are the second type of technological change and involve revolutionary concepts involving large technological

  20. Military Air Power: The CADRE Digest of Air Power Opinions and Thoughts

    DTIC Science & Technology

    1990-10-01

    SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS Air warfare; Air power; Military art and science 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...bibliographical references. 1. Air warfare. 2. Air power. 3. Military art and science . 1. Air University (US). Center for Aerospace Doctrine, Research, and...on Policy and War........................................ ........................................57 War as Art and Science

  1. Control of Supercavitating Vehicles using Transverse Jets

    DTIC Science & Technology

    2016-03-15

    Experimental Technique All experiments reported here were conducted at the Naval Undersea Warfare Center (NUWC) closed loop research water tunnel in Newport...mass of moving parts of the assembly. The second element considered was tte loss term associated with flow restriction across the orifice which was...W. Henoch, Hydrodynamics Branch, Naval Undersea Warfare Center, Newport, RI. 49

  2. Ultrasensitive detection of explosives and chemical warfare agents by low-pressure photoionization mass spectrometry.

    PubMed

    Sun, Wanqi; Liang, Miao; Li, Zhen; Shu, Jinian; Yang, Bo; Xu, Ce; Zou, Yao

    2016-08-15

    On-spot monitoring of threat agents needs high sensitive instrument. In this study, a low-pressure photoionization mass spectrometer (LPPI-MS) was employed to detect trace amounts of vapor-phase explosives and chemical warfare agent mimetics under ambient conditions. Under 10-s detection time, the limits of detection of 2,4-dinitrotoluene, nitrotoluene, nitrobenzene, and dimethyl methyl phosphonate were 30, 0.5, 4, and 1 parts per trillion by volume, respectively. As compared to those obtained previously with PI mass spectrometric techniques, an improvement of 3-4 orders of magnitude was achieved. This study indicates that LPPI-MS will open new opportunities for the sensitive detection of explosives and chemical warfare agents. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. MOFwich: Sandwiched Metal-Organic Framework-Containing Mixed Matrix Composites for Chemical Warfare Agent Removal.

    PubMed

    Peterson, Gregory W; Lu, Annie X; Hall, Morgan G; Browe, Matthew A; Tovar, Trenton; Epps, Thomas H

    2018-02-28

    This work describes a new strategy for fabricating mixed matrix composites containing layered metal-organic framework (MOF)/polymer films as functional barriers for chemical warfare agent protection. Through the use of mechanically robust polymers as the top and bottom encasing layers, a high-MOF-loading, high-performance-core layer can be sandwiched within. We term this multifunctional composite "MOFwich". We found that the use of elastomeric encasing layers enabled core layer reformation after breakage, an important feature for composites and membranes alike. The incorporation of MOFs into the core layer led to enhanced removal of chemical warfare agents while simultaneously promoting moisture vapor transport through the composite, showcasing the promise of these composites for protection applications.

  4. A Comparison of Neutron-Based Non-Destructive Assessment Methods for Chemical Warfare Materiel and High Explosives

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

    E.H. Seabury; D.L. Chichester; C.J. Wharton

    2008-08-01

    Prompt Gamma Neutron Activation Analysis (PGNAA) systems employ neutrons as a probe to interrogate items, e.g. chemical warfare materiel-filled munitions. The choice of a neutron source in field-portable systems is determined by its ability to excite nuclei of interest, operational concerns such as radiological safety and ease-of-use, and cost. Idaho National Laboratory’s PINS Chemical Assay System has traditionally used a Cf-252 isotopic neutron source, but recently a Deuterium-Tritium (DT) Electronic Neutron Generator (ENG) has been tested as an alternate neutron source. This paper presents the results of using both of these neutron sources to interrogate chemical warfare materiel (CWM) andmore » high explosive (HE) filled munitions.« less

  5. A Comparison of Neutron-Based Non-Destructive Assessment Methods for Chemical Warfare Material and High Explosives

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

    Seabury, E. H.; Chichester, D. L.; Wharton, C. J.

    2009-03-10

    Prompt Gamma Neutron Activation Analysis (PGNAA) systems employ neutrons as a probe to interrogate items, e.g. chemical warfare materiel-filled munitions. The choice of a neutron source in field-portable systems is determined by its ability to excite nuclei of interest, operational concerns such as radiological safety and ease-of-use, and cost. Idaho National Laboratory's PINS Chemical Assay System has traditionally used a {sup 252}Cf isotopic neutron source, but recently a deuterium-tritium (DT) electronic neutron generator (ENG) has been tested as an alternate neutron source. This paper presents the results of using both of these neutron sources to interrogate chemical warfare materiel (CWM)more » and high explosive (HE) filled munitions.« less

  6. Particle Swarm Social Adaptive Model for Multi-Agent Based Insurgency Warfare Simulation

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

    Cui, Xiaohui; Potok, Thomas E

    2009-12-01

    To better understand insurgent activities and asymmetric warfare, a social adaptive model for modeling multiple insurgent groups attacking multiple military and civilian targets is proposed and investigated. This report presents a pilot study using the particle swarm modeling, a widely used non-linear optimal tool to model the emergence of insurgency campaign. The objective of this research is to apply the particle swarm metaphor as a model of insurgent social adaptation for the dynamically changing environment and to provide insight and understanding of insurgency warfare. Our results show that unified leadership, strategic planning, and effective communication between insurgent groups are notmore » the necessary requirements for insurgents to efficiently attain their objective.« less

  7. Age- and region-specific imbalances of basal amino acids and monoamine metabolism in limbic regions of female Fmr1 knock-out mice.

    PubMed

    Gruss, Michael; Braun, Katharina

    2004-07-01

    The Fragile X syndrome, a common form of mental retardation in humans, originates from the loss of expression of the Fragile X mental retardation gene leading to the absence of the encoded Fragile X mental retardation protein 1 (FMRP). A broad pattern of morphological and behavioral abnormalities is well described for affected humans as well as Fmr1 knock-out mice, a transgenic animal model for the human Fragile X syndrome. In the present study, we examined neurochemical differences between female Fmr1 knock-out and wildtype mice with particular focus on neurotransmission. Significant age- and region-specific differences of basal tissue neurotransmitter and metabolite levels measured by high performance liquid chromatography were found. Those differences were more numerous in juvenile animals (postnatal day (PND) 28-31) compared to adults (postnatal day 209-221). In juvenile female knock-out mice, especially aspartate and taurine were increased in cortical regions, striatum, cerebellum, and brainstem. Furthermore, compared to the wildtype animals, the juvenile knock-out mice displayed an increased level of neuronal inhibition in the hippocampus and brainstem reflected by decreased ratios of (aspartate + glutamate)/(taurine + GABA), as well as an increased dopamine (DA) turnover in cortical regions, striatum, and hippocampus. These results provide the first evidence that the lack of FMRP expression in female Fmr1 knock-out mice is accompanied by age-dependent, region-specific alterations in brain amino acids, and monoamine turnover, which might be related to the reported synaptical and behavioural alterations in these animals.

  8. Starch Binding Domain-containing Protein 1 Plays a Dominant Role in Glycogen Transport to Lysosomes in Liver*

    PubMed Central

    Sun, Tao; Yi, Haiqing; Yang, Chunyu; Kishnani, Priya S.; Sun, Baodong

    2016-01-01

    A small portion of cellular glycogen is transported to and degraded in lysosomes by acid α-glucosidase (GAA) in mammals, but it is unclear why and how glycogen is transported to the lysosomes. Stbd1 has recently been proposed to participate in glycogen trafficking to lysosomes. However, our previous study demonstrated that knockdown of Stbd1 in GAA knock-out mice did not alter lysosomal glycogen storage in skeletal muscles. To further determine whether Stbd1 participates in glycogen transport to lysosomes, we generated GAA/Stbd1 double knock-out mice. In fasted double knock-out mice, glycogen accumulation in skeletal and cardiac muscles was not affected, but glycogen content in liver was reduced by nearly 73% at 3 months of age and by 60% at 13 months as compared with GAA knock-out mice, indicating that the transport of glycogen to lysosomes was suppressed in liver by the loss of Stbd1. Exogenous expression of human Stbd1 in double knock-out mice restored the liver lysosomal glycogen content to the level of GAA knock-out mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another mutant that contains only the N-terminal 24 hydrophobic segment and the C-terminal starch binding domain (CBM20) interlinked by an HA tag. Our results demonstrate that Stbd1 plays a dominant role in glycogen transport to lysosomes in liver and that the N-terminal transmembrane region and the C-terminal CBM20 domain are critical for this function. PMID:27358407

  9. 40 CFR 745.65 - Lead-based paint hazards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... caused by impact from a related building component (such as a door knob that knocks into a wall or a door that knocks against its door frame. (3) Any chewable lead-based painted surface on which there is...

  10. 40 CFR 745.65 - Lead-based paint hazards.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... caused by impact from a related building component (such as a door knob that knocks into a wall or a door that knocks against its door frame. (3) Any chewable lead-based painted surface on which there is...

  11. Functional characterization of three MicroRNAs of the Asian Tiger Mosquito, Aedes albopictus

    PubMed Central

    2013-01-01

    Background Temporal and stage specific expression of microRNAs (miRNAs) in embryos, larvae, pupae and adults of Aedes albopictus showed differential expression levels across the four developmental stages, indicating their potential regulatory roles in mosquito development. The functional characterization of these miRNAs was not known. Accordingly our study evaluated the functional characterization of three miRNAs, which are temporally up-regulated in the various developmental stages of Ae. albopictus mosquitoes. Methods miRNA mimics, inhibitors and negative controls were designed and their knock-in and knock-down efficiency were analyzed by qRT-PCR after transfecting the mosquito cell lines C6/36, and also by injecting in their specific developmental stages. The functional role of each individual miRNA was analyzed with various parameters of development such as, hatching rate and hatching time in embryos, eclosion rate in larvae, longevity and fecundity in the adult mosquitoes. Results The knock-in with the specifically designed miRNA mimics showed increased levels of expression of miRNA compared with their normal controls. We confirmed these findings using qRT-PCR, both by in vitro expression in C6/36 mosquito cell lines after transfection as well as in in vivo expression in developmental stages of mosquitoes by microinjection. The knock-down of expression with the corresponding inhibitors showed a considerable decrease in the expression levels of these miRNAs and obvious functional effects in Ae. albopictus development, detected by a decrease in the hatching rate of embryos and eclosion rate in larvae and a marked reduction in longevity and fecundity in adults. Conclusion This study carried out by knock-in and knock-down of specifically and temporally expressed miRNAs in Ae. albopictus by microinjection is a novel study to delineate the importance of the miRNA expression in regulating mosquito development. The knock-down and loss of function of endogenously expressed miRNAs by the miRNA inhibitors in specific developmental stages had considerable effects on development, but enhancement of their gain of function was not observed on knock-in of these specific miRNAs. Hence, our study indicates that an optimal level of endogenous expression of miRNA is indispensable for the normal development and maintenance of the vectorial population density and pathogen transmissibility of this mosquito vector. PMID:23924583

  12. Nuclear, biological and chemical warfare. Part I: Medical aspects of nuclear warfare.

    PubMed

    Kasthuri, A S; Pradhan, A B; Dham, S K; Bhalla, I P; Paul, J S

    1990-04-01

    Casualties in earlier wars were due much more to diseases than to weapons. Mention has been made in history of the use of biological agents in warfare, to deny the enemy food and water and to cause disease. In the first world war chemical agents were used to cause mass casualties. Nuclear weapons were introduced in the second world war. Several countries are now involved in developing nuclear, biological and chemical weapon systems, for the mass annihilation of human beings, animals and plants, and to destroy the economy of their enemies. Recently, natural calamities and accidents in nuclear, chemical and biological laboratories and industries have caused mass instantaneous deaths in civilian population. The effects of future wars will not be restricted to uniformed persons. It is time that physicians become aware of the destructive potential of these weapons. Awareness, immediate protective measures and first aid will save a large number of persons. This series of articles will outline the medical aspects of nuclear, biological and chemical weapon systems in three parts. Part I will deal with the biological effects of a nuclear explosion. The short and long term effects due to blast, heat and associated radiation are highlighted. In Part II, the role of biological agents which cause commoner or new disease patterns is mentioned. Some of the accidents from biological warfare laboratories are a testimony to its potential deleterious effects. Part III deals with medical aspects of chemical warfare agents, which in view of their mass effects can overwhelm the existing medical resources, both civilian and military.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Hard Religious Questions in "Knee-Knock Rise" and "Tuck Everlasting."

    ERIC Educational Resources Information Center

    Milner, Joseph O.

    1995-01-01

    Discusses the way Natalie Babbitt brings up issues of religious conflict and questions about religious certainty and skepticism in her young adult novels. Pays particular attention to two of her novels: "Knee-Knock Rise" and "Tuck Everlasting." (HB)

  14. When Your Back Hurts: Don't Let Back Pain Knock You Flat

    MedlinePlus

    ... Your Back Hurts Don’t Let Back Pain Knock You Flat En español Send us your comments ... Complementary Health Approaches Halt the Hurt! References The SPORT Value Compass: Do the Extra Costs of Undergoing ...

  15. Legitimacy as an Operational Factor: An Alternative Analysis

    DTIC Science & Technology

    2006-10-23

    Napoleon I9 In his book, Operational Warfare, Dr. Milan Vego notes, “All great military leaders had an uncommon ability to...elements of one, or perhaps both, of the remaining factors. 9 Milan Vego, Operational Warfare...44 Ibid., 161. 45 Richard Schultz , In the Aftermath of War (Newport RI: U.S. Naval War College, 2006; reprint, Montgomery, AL: Air University

  16. 75 FR 52518 - Meeting of the Chief of Naval Operations (CNO) Executive Panel

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ...The Chief of Naval Operations (CNO) Executive Panel will report on the findings and recommendations of the Cyber Warfare Subcommittee to the CNO. The meeting will consist of discussions of current and future Navy strategy, plans, and policies in support of the organizing, manning, training, and equipping of Cyber Warfare forces for current and future operations.

  17. Just War and Postmodern Warfare: A German Case Study

    DTIC Science & Technology

    2015-04-01

    warfare construct, Germany is shaping a military concept based on recent conflicts and unfettered by biases of conventional strategies, organizations...remain sovereign while subconsciously evolving toward liberal democratic ideas. In respecting each country’s political sensitivities, Germany’s...before exhausting all diplomatic, economic and information instruments. Whereas the term AU/ACSC/PINSON/AY15 13 “interests” may bias the United

  18. Oceanography and Mine Warfare

    DTIC Science & Technology

    2000-03-13

    of breaking waves , the position and strength of surface currents, and the propagation of the tide into very shallow waters. In the surf zone...6) sediment properties determine shock wave propagation , a method for mine neutralization in the surf zone. 48 OCEANOGRAPHY AND MINE WARFARE...mines will be buried in the sediments, sedimentary explosive shock wave propagation is critical for determining operational performance. Presently, we

  19. The United States Army 1996 Modernization Plan.

    DTIC Science & Technology

    1996-03-08

    and a cadre of operations, intelligence, fire support, air defense, and nuclear, biological, and chemical warfare personnel. As required, ARSPACE will...aerial and stand-off chemical and biological detection systems. " Decontamination improvements include Modular Decontamination System fielding in the near... Chemical . As many as 25 nations are producing and stockpiling chemical weapons. Weapons systems from mortars to missiles can deliver chemical warfare (CW

  20. 78 FR 55687 - Notice of Availability of Government-Owned Invention; Available for Licensing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-11

    ... Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001. FOR FURTHER INFORMATION CONTACT: Mr. Christopher Monsey, Naval Surface Warfare Center, Crane Div, Code OOL, Bldg 2, 300 Highway 361, Crane, IN 47522-5001, telephone 812-854-4100. (Authority: 35 U.S.C. 207, 37 CFR Part 404) N.A...

  1. FOA Information from the Research Institute of Swedish National Defence on Electronic Warfare (FOA Orientar om Electronic Warfare),

    DTIC Science & Technology

    1967-01-01

    probablity ot penetring to target in the preaence of atr do- fance . Curve P, =probebility of destro),ing target in the presence of air defence. Weapon...so rendering the lions. At high frequencies ( gen - quency range and sector of ter- traffic less sensitive to jamming. erally those tsed on radio links

  2. Naval Warfare

    DTIC Science & Technology

    2010-03-01

    Naval Doctrine Publication 1 Naval Warfare March 2010 Doctrine The only satisfactory method of ensuring unity of effort lies in due...LCDR Dudley W. Knox, USN “The Role of Doctrine in Naval Warfare” U.S. Naval Institute Proceedings, 1915 01 March 2010 FOREWORD United States (US...naval doctrine is the foundation upon which our tactics, techniques, and procedures are built. It articulates operational concepts that govern the

  3. Network Centric Warfare in the U.S. Navy’s Fifth Fleet. Network-Supported Operational Level Command and Control in Operation Enduring Freedom

    DTIC Science & Technology

    2004-06-01

    Mark Adkins Director of Research Ph.D Human Communication adkins@arizona.edu Dr. John Kruse Director of Programming Ph.D Management Information Systems...Theory • Network Centric Warfare • Technology Adoption – Technology Adoption Model – Technology Transition Model • Human Communication – Social Context

  4. Naval Surface Warfare Center Carderock Division, Technical Digest

    DTIC Science & Technology

    2001-12-01

    Survivability Systems: An Overview Fred J. Fisch 139 Modeling and Simulation of Weapons Effects on Ships Robert R. Wunderlick 143 Intelligent Networks ...communications capability of forces afloat to support emerging network -centric warfare doc- trines. Stealth, for our next generation of warships...fully-inte- grated, fully- networked electronic countermeasures system, developed in parallel and in close coordination with sister systems. An

  5. Military Reengineering Between the World Wars

    DTIC Science & Technology

    2005-01-01

    University. I am also grateful to Tamera Dorland for her much-needed perspectives. Any inaccura- cies remain mine alone. xxiii Abbreviations FFRDC...or shape any motorization opportunities that under- mined their branch’s immediate interests. Infantry chiefs such as Robert Allen, Stephen Fuqua...Warfare, An- napolis, Md.: Naval Institute Press, 1983, p. 187. 85 Kenneth J. Clifford, Amphibious Warfare Development in Britannia and America from

  6. Containing Revolutionary Islam: Reassessing the Problem and the Approach

    DTIC Science & Technology

    2017-03-01

    2011), xx. 83 Russ Rodgers, Fundamentals of Islamic Asymmetric Warfare: A Documentary Analysis of the Principles of Muhammad (Lewiston, NY: Edwin...have not yet effectively coalesced or managed to spark the greater revolution they seek. They remain fragmented, choosing divergent activities in...Libertarian Rebuttal. Auburn, AL: Ludwig von Mises Institute, 2015. Rodgers, Russ. Fundamentals of Islamic Asymmetric Warfare: A Documentary Analysis

  7. Command Post Program Study. Volume 1 - Main Report

    DTIC Science & Technology

    1973-03-01

    Field Manual 30-9, Military Intelligence Battalion - Field Am. Washington: March 1968. _ Field Manual 32-20, Electronic Warfare. Washington: 14...Mechanized). A-18 TOE 30-88T, Military Intelligence Support Detachment, Military Intelligence Battalion, Field Army. TOE 30-206T, Headquarters and... Field Manual 30-9, Military Intelligence Battalion - Field Army. Washington: March 1968. _ Field Manual 32-20, Electronic Warfare. Washington: 14

  8. Rapid Analysis of Chemical Warfare Agents and Their Hydrolysis Products by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS)

    DTIC Science & Technology

    2009-10-01

    of chemical warfare agents in natural water samples by solid-phase microextraction. Anal. Chem., 69, 1866-72. [36] Sng , M.T. and Ng ,W.F. (1999). In...liquid phase microextraction of alkylphosphonic acids from water. J. Chromatogr. A., 1141, 151-157. [43] Lee, H.S.N., Sng , M.T., Basheer, C., and Lee

  9. The Sea of Simulation: Improving Naval Shiphandling Training and Readiness through Game-Based Learning

    DTIC Science & Technology

    2012-03-01

    Officer SWOI Surface Warfare Officer Introduction SWOS Surface Warfare Officers School xvii TFT Thin Film Transistor ULTRA Unit Level Training...designed the experiment , including participants, procedures, facilities selection, and materials. Chapter IV: Results and Discussion. This chapter...contains the results of experimentation and an interpretation of those results . Chapter V: Conclusions. This chapter provides an overall assessment

  10. Factors Affecting the Retention Decisions of Female Surface Warfare Officers

    DTIC Science & Technology

    2003-03-01

    NAVAL POSTGRADUATE SCHOOL Monterey, California THESIS Approved for public release; distribution is unlimited. FACTORS AFFECTING THE RETENTION...Warfare Officers 6. AUTHOR(S) Clifton, Elizabeth A. 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School ...for the degree of MASTER OF SCIENCE IN LEADERSHIP AND HUMAN RESOURCE DEVELOPMENT from the NAVAL POSTGRADUATE SCHOOL March 2003

  11. Maritime In Situ Sensing Inter-Operable Networks (MISSION)

    DTIC Science & Technology

    2013-09-30

    creating acoustic communications (acomms) technologies enabling underwater sensor networks and distributed systems. Figure 1. Project MISSION...Marn, S. Ramp, F. Bahr, “Implementation of an Underwater Wireless Sensor Network in San Francisco Bay,” Proc. 10th International Mine Warfare...NILUS – An Underwater Acoustic Sensor Network Demonstrator System,” Proc. 10th International Mine Warfare Technology Symposium, Monterey, CA, May 7

  12. [Synapse maturation and autism: learning from neuroligin model mice].

    PubMed

    Tabuchi, Katsuhiko; Chang, WenHsin; Hang, WenHsin; Asgar, Nur Farehan; Asgar, Nur Farehan Mohamed; Pramanik, Gopal

    2014-02-01

    Autism is a neurodevelopmental disorder characterized by impairments in social interaction, communication, and restricted and repetitive behavior. Synaptic defects have been implicated in autism; nevertheless, the cause is still largely unknown. A mutation that substitutes cysteine for arginine at residue 451 of Neuroligin-3 (R451C) is the first monogenic mutation identified in idiopathic autism patients. To study the relationship between this mutation and autism, we generated knock-in mice that recapitulated this mutation. The knock-in mice were born and grew up normally without showing any major physical phenotypes, but showed a deficit in social interaction. We studied synaptic function in the layer II/III pyramidal neurons in the somatosensory cortex and found inhibitory synaptic transmission was enhanced in the knock-in mice. The administration of GABA blocker rescued social interaction, suggesting that this caused autistic behavior in these mice. We also found, by Morris water maze test, that spatial learning and memory were significantly enhanced in the knock-in mice. Electrophysiology in the CA1 region of the hippocampus revealed that LTP, the NMDA/AMPA ratio, and NR2B function were enhanced, indicating that synaptic maturation was impaired in the knock-in mice. This may cause the deficit in social behavior and extraordinary memory ability occasionally seen in autistic patients.

  13. True-breeding targeted gene knock-out in barley using designer TALE-nuclease in haploid cells.

    PubMed

    Gurushidze, Maia; Hensel, Goetz; Hiekel, Stefan; Schedel, Sindy; Valkov, Vladimir; Kumlehn, Jochen

    2014-01-01

    Transcription activator-like effector nucleases (TALENs) are customizable fusion proteins able to cleave virtually any genomic DNA sequence of choice, and thereby to generate site-directed genetic modifications in a wide range of cells and organisms. In the present study, we expressed TALENs in pollen-derived, regenerable cells to establish the generation of instantly true-breeding mutant plants. A gfp-specific TALEN pair was expressed via Agrobacterium-mediated transformation in embryogenic pollen of transgenic barley harboring a functional copy of gfp. Thanks to the haploid nature of the target cells, knock-out mutations were readily detected, and homozygous primary mutant plants obtained following genome duplication. In all, 22% of the TALEN transgenics proved knocked out with respect to gfp, and the loss of function could be ascribed to the deletions of between four and 36 nucleotides in length. The altered gfp alleles were transmitted normally through meiosis, and the knock-out phenotype was consistently shown by the offspring of two independent mutants. Thus, here we describe the efficient production of TALEN-mediated gene knock-outs in barley that are instantaneously homozygous and non-chimeric in regard to the site-directed mutations induced. This TALEN approach has broad applicability for both elucidating gene function and tailoring the phenotype of barley and other crop species.

  14. Fluorescent protein tagging of endogenous protein in brain neurons using CRISPR/Cas9-mediated knock-in and in utero electroporation techniques

    PubMed Central

    Uemura, Takeshi; Mori, Takuma; Kurihara, Taiga; Kawase, Shiori; Koike, Rie; Satoga, Michiru; Cao, Xueshan; Li, Xue; Yanagawa, Toru; Sakurai, Takayuki; Shindo, Takayuki; Tabuchi, Katsuhiko

    2016-01-01

    Genome editing is a powerful technique for studying gene functions. CRISPR/Cas9-mediated gene knock-in has recently been applied to various cells and organisms. Here, we successfully knocked in an EGFP coding sequence at the site immediately after the first ATG codon of the β-actin gene in neurons in the brain by the combined use of the CRISPR/Cas9 system and in utero electroporation technique, resulting in the expression of the EGFP-tagged β-actin protein in cortical layer 2/3 pyramidal neurons. We detected EGFP fluorescence signals in the soma and neurites of EGFP knock-in neurons. These signals were particularly abundant in the head of dendritic spines, corresponding to the localization of the endogenous β-actin protein. EGFP knock-in neurons showed no detectable changes in spine density and basic electrophysiological properties. In contrast, exogenously overexpressed EGFP-β-actin showed increased spine density and EPSC frequency, and changed resting membrane potential. Thus, our technique provides a potential tool to elucidate the localization of various endogenous proteins in neurons by epitope tagging without altering neuronal and synaptic functions. This technique can be also useful for introducing a specific mutation into genes to study the function of proteins and genomic elements in brain neurons. PMID:27782168

  15. Intracellular generation of single-strand template increases the knock-in efficiency by combining CRISPR/Cas9 with AAV.

    PubMed

    Xiao, Qing; Min, Taishan; Ma, Shuangping; Hu, Lingna; Chen, Hongyan; Lu, Daru

    2018-04-18

    Targeted integration of transgenes facilitates functional genomic research and holds prospect for gene therapy. The established microhomology-mediated end-joining (MMEJ)-based strategy leads to the precise gene knock-in with easily constructed donor, yet the limited efficiency remains to be further improved. Here, we show that single-strand DNA (ssDNA) donor contributes to efficient increase of knock-in efficiency and establishes a method to achieve the intracellular linearization of long ssDNA donor. We identified that the CRISPR/Cas9 system is responsible for breaking double-strand DNA (dsDNA) of palindromic structure in inverted terminal repeats (ITRs) region of recombinant adeno-associated virus (AAV), leading to the inhibition of viral second-strand DNA synthesis. Combing Cas9 plasmids targeting genome and ITR with AAV donor delivery, the precise knock-in of gene cassette was achieved, with 13-14% of the donor insertion events being mediated by MMEJ in HEK 293T cells. This study describes a novel method to integrate large single-strand transgene cassettes into the genomes, increasing knock-in efficiency by 13.6-19.5-fold relative to conventional AAV-mediated method. It also provides a comprehensive solution to the challenges of complicated production and difficult delivery with large exogenous fragments.

  16. Fluorescent protein tagging of endogenous protein in brain neurons using CRISPR/Cas9-mediated knock-in and in utero electroporation techniques.

    PubMed

    Uemura, Takeshi; Mori, Takuma; Kurihara, Taiga; Kawase, Shiori; Koike, Rie; Satoga, Michiru; Cao, Xueshan; Li, Xue; Yanagawa, Toru; Sakurai, Takayuki; Shindo, Takayuki; Tabuchi, Katsuhiko

    2016-10-26

    Genome editing is a powerful technique for studying gene functions. CRISPR/Cas9-mediated gene knock-in has recently been applied to various cells and organisms. Here, we successfully knocked in an EGFP coding sequence at the site immediately after the first ATG codon of the β-actin gene in neurons in the brain by the combined use of the CRISPR/Cas9 system and in utero electroporation technique, resulting in the expression of the EGFP-tagged β-actin protein in cortical layer 2/3 pyramidal neurons. We detected EGFP fluorescence signals in the soma and neurites of EGFP knock-in neurons. These signals were particularly abundant in the head of dendritic spines, corresponding to the localization of the endogenous β-actin protein. EGFP knock-in neurons showed no detectable changes in spine density and basic electrophysiological properties. In contrast, exogenously overexpressed EGFP-β-actin showed increased spine density and EPSC frequency, and changed resting membrane potential. Thus, our technique provides a potential tool to elucidate the localization of various endogenous proteins in neurons by epitope tagging without altering neuronal and synaptic functions. This technique can be also useful for introducing a specific mutation into genes to study the function of proteins and genomic elements in brain neurons.

  17. Optimization of a CRISPR/Cas9-mediated Knock-in Strategy at the Porcine Rosa26 Locus in Porcine Foetal Fibroblasts.

    PubMed

    Xie, Zicong; Pang, Daxin; Wang, Kankan; Li, Mengjing; Guo, Nannan; Yuan, Hongming; Li, Jianing; Zou, Xiaodong; Jiao, Huping; Ouyang, Hongsheng; Li, Zhanjun; Tang, Xiaochun

    2017-06-08

    Genetically modified pigs have important roles in agriculture and biomedicine. However, genome-specific knock-in techniques in pigs are still in their infancy and optimal strategies have not been extensively investigated. In this study, we performed electroporation to introduce a targeting donor vector (a non-linearized vector that did not contain a promoter or selectable marker) into Porcine Foetal Fibroblasts (PFFs) along with a CRISPR/Cas9 vector. After optimization, the efficiency of the EGFP site-specific knock-in could reach up to 29.6% at the pRosa26 locus in PFFs. Next, we used the EGFP reporter PFFs to address two key conditions in the process of achieving transgenic pigs, the limiting dilution method and the strategy to evaluate the safety and feasibility of the knock-in locus. This study demonstrates that we establish an efficient procedures for the exogenous gene knock-in technique and creates a platform to efficiently generate promoter-less and selectable marker-free transgenic PFFs through the CRISPR/Cas9 system. This study should contribute to the generation of promoter-less and selectable marker-free transgenic pigs and it may provide insights into sophisticated site-specific genome engineering techniques for additional species.

  18. Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids

    PubMed Central

    Sakuma, Tetsushi; Takenaga, Mitsumasa; Kawabe, Yoshinori; Nakamura, Takahiro; Kamihira, Masamichi; Yamamoto, Takashi

    2015-01-01

    Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized targeting vectors, named PITCh (Precise Integration into Target Chromosome) vectors. Here we describe TALEN and PITCh vector-mediated integration of long gene cassettes, including a single-chain Fv-Fc (scFv-Fc) gene, in Chinese hamster ovary (CHO) cells, with comparison of targeting and cloning efficiency among several donor design and culture conditions. We achieved 9.6-kb whole plasmid integration and 7.6-kb backbone-free integration into a defined genomic locus in CHO cells. Furthermore, we confirmed the reasonable productivity of recombinant scFv-Fc protein of the knock-in cells. Using our protocol, the knock-in cell clones could be obtained by a single transfection and a single limiting dilution using a 96-well plate, without constructing targeting vectors containing long homology arms. Thus, the study described herein provides a highly practical strategy for gene knock-in of large DNA in CHO cells, which accelerates high-throughput generation of cell lines stably producing any desired biopharmaceuticals, including huge antibody proteins. PMID:26473830

  19. Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids.

    PubMed

    Sakuma, Tetsushi; Takenaga, Mitsumasa; Kawabe, Yoshinori; Nakamura, Takahiro; Kamihira, Masamichi; Yamamoto, Takashi

    2015-10-09

    Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized targeting vectors, named PITCh (Precise Integration into Target Chromosome) vectors. Here we describe TALEN and PITCh vector-mediated integration of long gene cassettes, including a single-chain Fv-Fc (scFv-Fc) gene, in Chinese hamster ovary (CHO) cells, with comparison of targeting and cloning efficiency among several donor design and culture conditions. We achieved 9.6-kb whole plasmid integration and 7.6-kb backbone-free integration into a defined genomic locus in CHO cells. Furthermore, we confirmed the reasonable productivity of recombinant scFv-Fc protein of the knock-in cells. Using our protocol, the knock-in cell clones could be obtained by a single transfection and a single limiting dilution using a 96-well plate, without constructing targeting vectors containing long homology arms. Thus, the study described herein provides a highly practical strategy for gene knock-in of large DNA in CHO cells, which accelerates high-throughput generation of cell lines stably producing any desired biopharmaceuticals, including huge antibody proteins.

  20. Miniaturized low-cost ion mobility spectrometer for fast detection of chemical warfare agents.

    PubMed

    Zimmermann, Stefan; Barth, Sebastian; Baether, Wolfgang K M; Ringer, Joachim

    2008-09-01

    Ion mobility spectrometry (IMS) is a well-known method for detecting hazardous compounds in air. Typical applications are the detection of chemical warfare agents, highly toxic industrial compounds, explosives, and drugs of abuse. Detection limits in the low part per billion range, fast response times, and simple instrumentation make this technique more and more popular. In particular, there is an increasing demand for miniaturized low-cost IMS for hand-held devices and air monitoring of public areas by sensor networks. In this paper, we present a miniaturized aspiration condenser type ion mobility spectrometer for fast detection of chemical warfare agents. The device is easy to manufacture and allows single substance identification down to low part per billion-level concentrations within seconds. The improved separation power results from ion focusing by means of geometric constraints and fluid dynamics. A simple pattern recognition algorithm is used for the identification of trained substances in air. The device was tested at the German Armed Forces Scientific Institute for Protection Technologies-NBC-Protection. Different chemical warfare agents, such as sarin, tabun, soman, US-VX, sulfur mustard, nitrogen mustard, and lewisite were tested. The results are presented here.

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