27 CFR 479.71 - Proof of registration.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Proof of registration. 479.71 Section 479.71 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

27 CFR 479.71 - Proof of registration.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Proof of registration. 479.71 Section 479.71 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

27 CFR 479.118 - Proof of exportation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Proof of exportation. 479.118 Section 479.118 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

27 CFR 479.71 - Proof of registration.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Proof of registration. 479.71 Section 479.71 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

27 CFR 479.71 - Proof of registration.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Proof of registration. 479.71 Section 479.71 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

27 CFR 479.118 - Proof of exportation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Proof of exportation. 479.118 Section 479.118 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

27 CFR 479.118 - Proof of exportation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Proof of exportation. 479.118 Section 479.118 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

27 CFR 479.118 - Proof of exportation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Proof of exportation. 479.118 Section 479.118 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN...

30 CFR 18.62 - Tests to determine explosion-proof characteristics.

Code of Federal Regulations, 2010 CFR

2010-07-01

... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES... be varied. Motor armatures and/or rotors will be stationary in some tests and revolving in others... electrical components during some of the tests. Not less than 16 explosion tests shall be conducted; however...

Internal short circuit and accelerated rate calorimetry tests of lithium-ion cells: Considerations for methane-air intrinsic safety and explosion proof/flameproof protection methods.

PubMed

Dubaniewicz, Thomas H; DuCarme, Joseph P

2016-09-01

Researchers with the National Institute for Occupational Safety and Health (NIOSH) studied the potential for lithium-ion cell thermal runaway from an internal short circuit in equipment for use in underground coal mines. In this third phase of the study, researchers compared plastic wedge crush-induced internal short circuit tests of selected lithium-ion cells within methane (CH 4 )-air mixtures with accelerated rate calorimetry tests of similar cells. Plastic wedge crush test results with metal oxide lithium-ion cells extracted from intrinsically safe evaluated equipment were mixed, with one cell model igniting the chamber atmosphere while another cell model did not. The two cells models exhibited different internal short circuit behaviors. A lithium iron phosphate (LiFePO 4 ) cell model was tolerant to crush-induced internal short circuits within CH 4 -air, tested under manufacturer recommended charging conditions. Accelerating rate calorimetry tests with similar cells within a nitrogen purged 353-mL chamber produced ignitions that exceeded explosion proof and flameproof enclosure minimum internal pressure design criteria. Ignition pressures within a 20-L chamber with 6.5% CH 4 -air were relatively low, with much larger head space volume and less adiabatic test conditions. The literature indicates that sizeable lithium thionyl chloride (LiSOCl 2 ) primary (non rechargeable) cell ignitions can be especially violent and toxic. Because ignition of an explosive atmosphere is expected within explosion proof or flameproof enclosures, there is a need to consider the potential for an internal explosive atmosphere ignition in combination with a lithium or lithium-ion battery thermal runaway process, and the resulting effects on the enclosure.

Development of tube-packaged FBG strain sensor and application in the vibration experiment of submarine pipeline model

NASA Astrophysics Data System (ADS)

Ren, Liang; Li, Hong-Nan; Sun, Li; Li, Dong-Sheng

2005-05-01

Optical fiber sensors have received increasing attention in the fields of aeronautic and civil engineering for their superior ability of explosion proof, immunity to electromagnetic interference and high accuracy, especially fitting for measurement applications in harsh environment. In this paper, a novel FBG (fiber Bragg grating) strain sensor, which was packaged in a 1.2mm stainless steel tube by epoxy resin, was developed. Experiments were conducted on the universal material testing machine to calibrate its strain transferring characteristics. The sensor has the advantages of small size, high precision and flexible use, and demonstrates promising potentials. Ten of tube-packaged strain FBG sensors were applied in the vibration experiment of submarine pipeline model. The strain measured by FBG sensor agrees well with the electric resistance strain sensor.

Development of tube-packaged FBG strain sensor and application in the vibration experiment of submarine pipeline model

NASA Astrophysics Data System (ADS)

Ren, Liang; Li, Hong-Nan; Sun, Li; Li, Dong-Sheng

2005-02-01

Optical fiber sensors have received increasing attention in the fields of aeronautic and civil engineering for their superior ability of explosion proof, immunity to electromagnetic interference and high accuracy, especially fitting for measurement applications in harsh environment. In this paper, a novel FBG (fiber Bragg grating) strain sensor, which was packaged in a 1.2mm stainless steel tube by epoxy resin, was developed. Experiments were conducted on the universal material testing machine to calibrate its strain transferring characteristics. The sensor has the advantages of small size, high precision and flexible use, and demonstrates promising potentials. Ten of tube-packaged strain FBG sensors were applied in the vibration experiment of submarine pipeline model. The strain measured by FBG sensor agrees well with the electric resistance strain sensor.

30 CFR 20.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.2 Definitions. (a) Adequate... its lamp has been adjudged satisfactory under the requirements of this part. (c) Explosion-proof...

30 CFR 20.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.2 Definitions. (a) Adequate... its lamp has been adjudged satisfactory under the requirements of this part. (c) Explosion-proof...

30 CFR 20.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.2 Definitions. (a) Adequate... its lamp has been adjudged satisfactory under the requirements of this part. (c) Explosion-proof...

30 CFR 20.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... MINING PRODUCTS ELECTRIC MINE LAMPS OTHER THAN STANDARD CAP LAMPS § 20.2 Definitions. (a) Adequate... its lamp has been adjudged satisfactory under the requirements of this part. (c) Explosion-proof...

30 CFR 7.99 - Critical characteristics.

Code of Federal Regulations, 2010 CFR

2010-07-01

... proper adjustments. (h) Material and dimensions of gaskets that are essential in maintaining the explosion-proof integrity of the diesel power package. (i) Dimensions and assembly of flame arresters. (j...

30 CFR 7.99 - Critical characteristics.

Code of Federal Regulations, 2011 CFR

2011-07-01

... proper adjustments. (h) Material and dimensions of gaskets that are essential in maintaining the explosion-proof integrity of the diesel power package. (i) Dimensions and assembly of flame arresters. (j...

30 CFR 7.99 - Critical characteristics.

Code of Federal Regulations, 2013 CFR

2013-07-01

... proper adjustments. (h) Material and dimensions of gaskets that are essential in maintaining the explosion-proof integrity of the diesel power package. (i) Dimensions and assembly of flame arresters. (j...

30 CFR 18.38 - Leads through common walls.

Code of Federal Regulations, 2014 CFR

2014-07-01

... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design... from one explosion-proof enclosure to another through conduit, tubing, piping, or other solid-wall...

30 CFR 18.38 - Leads through common walls.

Code of Federal Regulations, 2013 CFR

2013-07-01

... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design... from one explosion-proof enclosure to another through conduit, tubing, piping, or other solid-wall...

30 CFR 18.38 - Leads through common walls.

Code of Federal Regulations, 2011 CFR

2011-07-01

... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design... from one explosion-proof enclosure to another through conduit, tubing, piping, or other solid-wall...

30 CFR 18.38 - Leads through common walls.

Code of Federal Regulations, 2012 CFR

2012-07-01

... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design... from one explosion-proof enclosure to another through conduit, tubing, piping, or other solid-wall...

Novel CE-MS technique for detection of high explosives using perfluorooctanoic acid as a MEKC and mass spectrometric complexation reagent.

PubMed

Brensinger, Karen; Rollman, Christopher; Copper, Christine; Genzman, Ashton; Rine, Jacqueline; Lurie, Ira; Moini, Mehdi

2016-01-01

To address the need for the forensic analysis of high explosives, a novel capillary electrophoresis mass spectrometry (CE-MS) technique has been developed for high resolution, sensitivity, and mass accuracy detection of these compounds. The technique uses perfluorooctanoic acid (PFOA) as both a micellar electrokinetic chromatography (MEKC) reagent for separation of neutral explosives and as the complexation reagent for mass spectrometric detection of PFOA-explosive complexes in the negative ion mode. High explosives that formed complexes with PFOA included RDX, HMX, tetryl, and PETN. Some nitroaromatics were detected as molecular ions. Detection limits in the high parts per billion range and linear calibration responses over two orders of magnitude were obtained. For proof of concept, the technique was applied to the quantitative analysis of high explosives in sand samples. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

46 CFR 194.05-7 - Explosives-Detail requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... shall be constructed of incombustible materials; awnings and tarpaulins shall be fire-resistant and/or flame proof fabric. (3) Items shall be properly secured by using existing vessel structures such as...

Development of an experimental system for characterization of high-temperature superconductors cooled by liquid hydrogen under the external magnetic field

NASA Astrophysics Data System (ADS)

Tatsumoto, H.; Shirai, Y.; Shiotsu, M.; Naruo, Y.; Kobayashi, H.; Inatani, Y.

2014-05-01

An experimental system has been developed to investigate electro-magnetic properties of high-Tc superconductors cooled by liquid hydrogen under the external magnetic field of up to 7 T. A LH2 cryostat is concentrically mounted on the inside of a LHe cryostat to cool a NbTi superconducting magnet. The experimental system is installed in an explosion-proof room. Explosion proof electrical devices are used and current leads are covered with an enclosure filled with nitrogen gas. A remote control system has been developed. Furthermore, the effects of stray magnetic field on the existing and the new devices are investigated and electro-magnetic shielding panels and enclosure made of iron were designed. It is confirmed through the cryogenic test that the experimental system meets the design requirements.

16 CFR 23.10 - Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust resistant...

Code of Federal Regulations, 2010 CFR

2010-01-01

... INDUSTRIES § 23.10 Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust...,” “rust proof,” or any other term of similar meaning to describe an industry product unless all parts of the product will be immune from rust and other forms of corrosion during the life expectancy of the...

16 CFR 23.10 - Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust resistant...

Code of Federal Regulations, 2011 CFR

2011-01-01

... INDUSTRIES § 23.10 Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust...,” “rust proof,” or any other term of similar meaning to describe an industry product unless all parts of the product will be immune from rust and other forms of corrosion during the life expectancy of the...

16 CFR 23.10 - Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust resistant...

Code of Federal Regulations, 2013 CFR

2013-01-01

... INDUSTRIES § 23.10 Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust...,” “rust proof,” or any other term of similar meaning to describe an industry product unless all parts of the product will be immune from rust and other forms of corrosion during the life expectancy of the...

16 CFR 23.10 - Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust resistant...

Code of Federal Regulations, 2014 CFR

2014-01-01

... INDUSTRIES § 23.10 Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust...,” “rust proof,” or any other term of similar meaning to describe an industry product unless all parts of the product will be immune from rust and other forms of corrosion during the life expectancy of the...

16 CFR 23.10 - Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust resistant...

Code of Federal Regulations, 2012 CFR

2012-01-01

... INDUSTRIES § 23.10 Misuse of “corrosion proof,” “noncorrosive,” “corrosion resistant,” “rust proof,” “rust...,” “rust proof,” or any other term of similar meaning to describe an industry product unless all parts of the product will be immune from rust and other forms of corrosion during the life expectancy of the...

46 CFR 153.214 - Personnel emergency and safety equipment.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-propelled ship must have the following: (a) Two stretchers or wire baskets complete with equipment for... Inspection or Certificate of Compliance. (3) A steel-cored lifeline with harness. (4) An explosion-proof lamp...

46 CFR 153.214 - Personnel emergency and safety equipment.

Code of Federal Regulations, 2011 CFR

2011-10-01

...-propelled ship must have the following: (a) Two stretchers or wire baskets complete with equipment for... Inspection or Certificate of Compliance. (3) A steel-cored lifeline with harness. (4) An explosion-proof lamp...

46 CFR 153.214 - Personnel emergency and safety equipment.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-propelled ship must have the following: (a) Two stretchers or wire baskets complete with equipment for... Inspection or Certificate of Compliance. (3) A steel-cored lifeline with harness. (4) An explosion-proof lamp...

46 CFR 153.214 - Personnel emergency and safety equipment.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-propelled ship must have the following: (a) Two stretchers or wire baskets complete with equipment for... Inspection or Certificate of Compliance. (3) A steel-cored lifeline with harness. (4) An explosion-proof lamp...

46 CFR 153.214 - Personnel emergency and safety equipment.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-propelled ship must have the following: (a) Two stretchers or wire baskets complete with equipment for... Inspection or Certificate of Compliance. (3) A steel-cored lifeline with harness. (4) An explosion-proof lamp...

On mechanism of explosive boiling in nanosecond regime

NASA Astrophysics Data System (ADS)

Çelen, Serap

2016-06-01

Today laser-based machining is used to manufacture vital parts for biomedical, aviation and aerospace industries. The aim of the paper is to report theoretical, numerical and experimental investigations of explosive boiling under nanosecond pulsed ytterbium fiber laser irradiation. Experiments were performed in an effective peak power density range between 1397 and 1450 MW/cm2 on pure titanium specimens. The threshold laser fluence for phase explosion, the pressure and temperature at the target surface and the velocity of the expulsed material were reported. A narrow transition zone was realized between the normal vaporization and phase explosion fields. The proof of heterogeneous boiling was given with detailed micrographs. A novel thermal model was proposed for laser-induced splashing at high fluences. Packaging factor and scattering arc radius terms were proposed to state the level of the melt ejection process. Results of the present investigation explain the explosive boiling during high-power laser interaction with metal.

POLLUTION DETECTION DOGS: PROOF OF CONCEPT

EPA Science Inventory

Dogs have been used extensively in law enforcement and military applications to detect narcotics and explosives for over thirty years. Dogs are regularly used in arson investigations to detect accelerants since they are much more accurate at discriminating between accelerants an...

New directions in the science and technology of advanced sheet explosive formulations and the key energetic materials used in the processing of sheet explosives: Emerging trends.

PubMed

Talawar, M B; Jangid, S K; Nath, T; Sinha, R K; Asthana, S N

2015-12-30

This review presents the work carried out by the international community in the area of sheet explosive formulations and its applications in various systems. The sheet explosive is also named as PBXs and is a composite material in which solid explosive particles like RDX, HMX or PETN are dispersed in a polymeric matrix, forms a flexible material that can be rolled/cut into sheet form which can be applied to any complex contour. The designed sheet explosive must possess characteristic properties such as flexible, cuttable, water proof, easily initiable, and safe handling. The sheet explosives are being used for protecting tanks (ERA), light combat vehicle and futuristic infantry carrier vehicle from different attacking war heads etc. Besides, sheet explosives find wide applications in demolition of bridges, ships, cutting and metal cladding. This review also covers the aspects such as risks and hazard analysis during the processing of sheet explosive formulations, effect of ageing on sheet explosives, detection and analysis of sheet explosive ingredients and the R&D efforts of Indian researchers in the development of sheet explosive formulations. To the best of our knowledge, there has been no review article published in the literature in the area of sheet explosives. Copyright © 2015 Elsevier B.V. All rights reserved.

Valve, explosive actuated, normally open, pyronetics model 1399

NASA Technical Reports Server (NTRS)

Avalos, E.

1971-01-01

Results of the tests to evaluate open valve, Model 1399 are reported for the the following tests: proof pressure leakage, actuation, disassembly, and burst pressure. It is concluded that the tests demonstrate the soundness of the structural integrity of the valve.

30 CFR 18.80 - Approval of machines assembled with certified or explosion-proof components.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Modifications of Approved Machines, and Permits To Use Experimental Equipment § 18.80 Approval of machines... approval. A design of the approval plate will accompany the notification of approval. (Refer to §§ 18.10...

30 CFR 18.80 - Approval of machines assembled with certified or explosion-proof components.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Modifications of Approved Machines, and Permits To Use Experimental Equipment § 18.80 Approval of machines... approval. A design of the approval plate will accompany the notification of approval. (Refer to §§ 18.10...

30 CFR 18.80 - Approval of machines assembled with certified or explosion-proof components.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Modifications of Approved Machines, and Permits To Use Experimental Equipment § 18.80 Approval of machines... approval. A design of the approval plate will accompany the notification of approval. (Refer to §§ 18.10...

30 CFR 18.80 - Approval of machines assembled with certified or explosion-proof components.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Modifications of Approved Machines, and Permits To Use Experimental Equipment § 18.80 Approval of machines... approval. A design of the approval plate will accompany the notification of approval. (Refer to §§ 18.10...

76 FR 30731 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... as systemic immune response. The method comprises administrating to the treated subject at least two... vaccination strategy assure both local (i.e. vaginal track) and systemic immunity. Development Status: Proof... technology can provide mucosal/local and systemic immunization simultaneously and thus it may prove to be...

30 CFR 18.80 - Approval of machines assembled with certified or explosion-proof components.

Code of Federal Regulations, 2014 CFR

2014-07-01

... approved machines will be accepted in lieu of certified components. (b) A single layout drawing (see Figure... approval. A design of the approval plate will accompany the notification of approval. (Refer to §§ 18.10...

Optical design and development of near-range compact lidar

NASA Astrophysics Data System (ADS)

Shiina, Tatsuo

2011-12-01

There are large demands to monitor the atmosphere in the closed space (hall, factory and so on), to check vegetation remotely and to detect hazardous gases such as explosive gas and bio terror from explosion-proof distance. On the contrary, traditional lidars have blind area, it is hard to monitor the atmosphere and the gas in the near range. In this study, optical designs and concrete developments for the atmosphere monitoring and the certain gas detection in near range were accomplished. Unique optical designs are introduced and their practical setups are explained.

46 CFR 35.30-30 - Portable electric equipment-TB/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., explosion-proof lamps approved by Underwriters Laboratories Inc., Factory Mutual Research Corporation, or... Underwriters Laboratories Inc., Factory Mutual Research Corporation, or other independent laboratory recognized...; (iv) Filled with Grade E liquid; or (v) Spaces where flammable gases are not expected to accumulate...

46 CFR 35.30-30 - Portable electric equipment-TB/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., explosion-proof lamps approved by Underwriters Laboratories Inc., Factory Mutual Research Corporation, or... Underwriters Laboratories Inc., Factory Mutual Research Corporation, or other independent laboratory recognized...; (iv) Filled with Grade E liquid; or (v) Spaces where flammable gases are not expected to accumulate...

46 CFR 35.30-30 - Portable electric equipment-TB/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., explosion-proof lamps approved by Underwriters Laboratories Inc., Factory Mutual Research Corporation, or... Underwriters Laboratories Inc., Factory Mutual Research Corporation, or other independent laboratory recognized...; (iv) Filled with Grade E liquid; or (v) Spaces where flammable gases are not expected to accumulate...

46 CFR 35.30-30 - Portable electric equipment-TB/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., explosion-proof lamps approved by Underwriters Laboratories Inc., Factory Mutual Research Corporation, or... Underwriters Laboratories Inc., Factory Mutual Research Corporation, or other independent laboratory recognized...; (iv) Filled with Grade E liquid; or (v) Spaces where flammable gases are not expected to accumulate...

46 CFR 35.30-30 - Portable electric equipment-TB/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., explosion-proof lamps approved by Underwriters Laboratories Inc., Factory Mutual Research Corporation, or... Underwriters Laboratories Inc., Factory Mutual Research Corporation, or other independent laboratory recognized...; (iv) Filled with Grade E liquid; or (v) Spaces where flammable gases are not expected to accumulate...

30 CFR 18.34 - Motors.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.34 Motors. Explosion-proof electric motor assemblies intended for use in approved equipment in underground... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Motors. 18.34 Section 18.34 Mineral Resources...

PINS Testing and Modification for Explosive Identification

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

E.H. Seabury; A.J. Caffrey

2011-09-01

The INL's Portable Isotopic Neutron Spectroscopy System (PINS)1 non-intrusively identifies the chemical fill of munitions and sealed containers. PINS is used routinely by the U.S. Army, the Defense Threat Reduction Agency, and foreign military units to determine the contents of munitions and other containers suspected to contain explosives, smoke-generating chemicals, and chemical warfare agents such as mustard and nerve gas. The objects assayed with PINS range from softball-sized M139 chemical bomblets to 200 gallon DOT 500X ton containers. INL had previously examined2 the feasibility of using a similar system for the identification of explosives, and based on this proof-of-principle test,more » the development of a dedicated system for the identification of explosives in an improvised nuclear device appears entirely feasible. INL has been tasked by NNSA NA-42 Render Safe Research and Development with the development of such a system.« less

30 CFR 7.302 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... conduit box when specified. A motor assembly is comprised of one or more explosion-proof enclosures. Plane.... A metallic enclosure used as a winding compartment, conduit box, or a combination of both that... portions. Stuffing box. An entrance with a recess filled with packing material for cables extending through...

30 CFR 7.302 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... conduit box when specified. A motor assembly is comprised of one or more explosion-proof enclosures. Plane.... A metallic enclosure used as a winding compartment, conduit box, or a combination of both that... portions. Stuffing box. An entrance with a recess filled with packing material for cables extending through...

30 CFR 7.302 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... conduit box when specified. A motor assembly is comprised of one or more explosion-proof enclosures. Plane.... A metallic enclosure used as a winding compartment, conduit box, or a combination of both that... portions. Stuffing box. An entrance with a recess filled with packing material for cables extending through...

30 CFR 7.301 - Purpose and effective date.

Code of Federal Regulations, 2010 CFR

2010-07-01

... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.301 Purpose... explosion-proof electric motor assemblies intended for use in approved equipment in underground mines... requirements of this part. Those motors that incorporate features not specifically addressed in this subpart...

Study on dynamic response measurement of the submarine pipeline by full-term FBG sensors.

PubMed

Zhou, Jinghai; Sun, Li; Li, Hongnan

2014-01-01

The field of structural health monitoring is concerned with accurately and reliably assessing the integrity of a given structure to reduce ownership costs, increase operational lifetime, and improve safety. In structural health monitoring systems, fiber Bragg grating (FBG) is a promising measurement technology for its superior ability of explosion proof, immunity to electromagnetic interference, and high accuracy. This paper is a study on the dynamic characteristics of fiber Bragg grating (FBG) sensors applied to a submarine pipeline, as well as an experimental investigation on a laboratory model of the pipeline. The dynamic response of a submarine pipeline under seismic excitation is a coupled vibration of liquid and solid interaction. FBG sensors and strain gauges are used to monitor the dynamic response of a submarine pipeline model under a variety of dynamic loading conditions and the maximum working frequency of an FBG strain sensor is calculated according to its dynamic strain responses. Based on the theoretical and experimental results, it can be concluded that FBG sensor is superior to strain gauge and satisfies the demand of dynamic strain measurement.

Study on Dynamic Response Measurement of the Submarine Pipeline by Full-Term FBG Sensors

PubMed Central

Zhou, Jinghai; Sun, Li; Li, Hongnan

2014-01-01

The field of structural health monitoring is concerned with accurately and reliably assessing the integrity of a given structure to reduce ownership costs, increase operational lifetime, and improve safety. In structural health monitoring systems, fiber Bragg grating (FBG) is a promising measurement technology for its superior ability of explosion proof, immunity to electromagnetic interference, and high accuracy. This paper is a study on the dynamic characteristics of fiber Bragg grating (FBG) sensors applied to a submarine pipeline, as well as an experimental investigation on a laboratory model of the pipeline. The dynamic response of a submarine pipeline under seismic excitation is a coupled vibration of liquid and solid interaction. FBG sensors and strain gauges are used to monitor the dynamic response of a submarine pipeline model under a variety of dynamic loading conditions and the maximum working frequency of an FBG strain sensor is calculated according to its dynamic strain responses. Based on the theoretical and experimental results, it can be concluded that FBG sensor is superior to strain gauge and satisfies the demand of dynamic strain measurement. PMID:24971391

30 CFR 18.53 - High-voltage longwall mining systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... and Design Requirements § 18.53 High-voltage longwall mining systems. (a) In each high-voltage motor...-interrupting devices must be designed and installed to prevent automatic reclosure. (d) Transformers with high... “open” position; (iv) When located in an explosion-proof enclosure, the device must be designed and...

30 CFR 18.53 - High-voltage longwall mining systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and Design Requirements § 18.53 High-voltage longwall mining systems. (a) In each high-voltage motor...-interrupting devices must be designed and installed to prevent automatic reclosure. (d) Transformers with high... “open” position; (iv) When located in an explosion-proof enclosure, the device must be designed and...

30 CFR 18.53 - High-voltage longwall mining systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... and Design Requirements § 18.53 High-voltage longwall mining systems. (a) In each high-voltage motor...-interrupting devices must be designed and installed to prevent automatic reclosure. (d) Transformers with high... “open” position; (iv) When located in an explosion-proof enclosure, the device must be designed and...

30 CFR 18.53 - High-voltage longwall mining systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... and Design Requirements § 18.53 High-voltage longwall mining systems. (a) In each high-voltage motor...-interrupting devices must be designed and installed to prevent automatic reclosure. (d) Transformers with high... “open” position; (iv) When located in an explosion-proof enclosure, the device must be designed and...

30 CFR 18.53 - High-voltage longwall mining systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and Design Requirements § 18.53 High-voltage longwall mining systems. (a) In each high-voltage motor...-interrupting devices must be designed and installed to prevent automatic reclosure. (d) Transformers with high... “open” position; (iv) When located in an explosion-proof enclosure, the device must be designed and...

30 CFR 18.62 - Tests to determine explosion-proof characteristics.

Code of Federal Regulations, 2013 CFR

2013-07-01

... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES... be varied. Motor armatures and/or rotors will be stationary in some tests and revolving in others... distortion of the enclosure exceeding 0.040 inch per linear foot. (c) When a pressure exceeding 125 pounds...

30 CFR 18.62 - Tests to determine explosion-proof characteristics.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES... be varied. Motor armatures and/or rotors will be stationary in some tests and revolving in others... distortion of the enclosure exceeding 0.040 inch per linear foot. (c) When a pressure exceeding 125 pounds...

30 CFR 18.62 - Tests to determine explosion-proof characteristics.

Code of Federal Regulations, 2012 CFR

2012-07-01

... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES... be varied. Motor armatures and/or rotors will be stationary in some tests and revolving in others... distortion of the enclosure exceeding 0.040 inch per linear foot. (c) When a pressure exceeding 125 pounds...

30 CFR 18.62 - Tests to determine explosion-proof characteristics.

Code of Federal Regulations, 2011 CFR

2011-07-01

... TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES... be varied. Motor armatures and/or rotors will be stationary in some tests and revolving in others... distortion of the enclosure exceeding 0.040 inch per linear foot. (c) When a pressure exceeding 125 pounds...

30 CFR 36.23 - Engine intake system.

Code of Federal Regulations, 2011 CFR

2011-07-01

... suitable means for secure assembly, or shall meet the requirements for flanged metal-to-metal flame-proof... deterioration in service. It shall be so mounted in the equipment assembly that it is protected from accidental... that will arrest the propagation of an explosion and shall be so designed that improper assembly is...

30 CFR 36.23 - Engine intake system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... suitable means for secure assembly, or shall meet the requirements for flanged metal-to-metal flame-proof... deterioration in service. It shall be so mounted in the equipment assembly that it is protected from accidental... that will arrest the propagation of an explosion and shall be so designed that improper assembly is...

30 CFR 75.815 - Disconnect devices.

Code of Federal Regulations, 2011 CFR

2011-07-01

... phase-to-phase voltage of the circuit in which they are installed, and for the full-load current of the... explosion-proof enclosures, must be capable of interrupting the full-load current of the circuit or designed and installed to cause the current to be interrupted automatically prior to the opening of the...

30 CFR 75.815 - Disconnect devices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... phase-to-phase voltage of the circuit in which they are installed, and for the full-load current of the... explosion-proof enclosures, must be capable of interrupting the full-load current of the circuit or designed and installed to cause the current to be interrupted automatically prior to the opening of the...

30 CFR 18.49 - Connection boxes on machines.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Connection boxes on machines. 18.49 Section 18... Design Requirements § 18.49 Connection boxes on machines. Connection boxes used to facilitate replacement of cables or machine components shall be explosion-proof. Portable-cable terminals on cable reels...

30 CFR 7.302 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... conduit box when specified. A motor assembly is comprised of one or more explosion-proof enclosures. Plane joint. A joint comprised of two adjoining surfaces in parallel planes. Step (rabbet) joint. A joint.... A step joint may be composed of a cylindrical portion and a plane portion or of two or more plane...

Proof Rules for Automated Compositional Verification through Learning

NASA Technical Reports Server (NTRS)

Barringer, Howard; Giannakopoulou, Dimitra; Pasareanu, Corina S.

2003-01-01

Compositional proof systems not only enable the stepwise development of concurrent processes but also provide a basis to alleviate the state explosion problem associated with model checking. An assume-guarantee style of specification and reasoning has long been advocated to achieve compositionality. However, this style of reasoning is often non-trivial, typically requiring human input to determine appropriate assumptions. In this paper, we present novel assume- guarantee rules in the setting of finite labelled transition systems with blocking communication. We show how these rules can be applied in an iterative and fully automated fashion within a framework based on learning.

Planned Destruction of Metal-Core Reactor: Simulation of Catastrophic Accidents and New Experimental Possibilities

NASA Astrophysics Data System (ADS)

Vorontsov, S. V.; Kuvshinov, M. I.; Narozhnyi, A. T.; Popov, V. A.; Solov'ev, V. P.; Yuferev, V. I.

2017-12-01

A reactor with a destructible core (RIR reactor) generating a pulse with an output of 1.5 × 1019 fissions and a full width at half maximum of 2.5 μs was developed and tested at VNIIEF. In the course of investigation, a computational-experimental method for laboratory calibration of the reactor was created and worked out. This method ensures a high accuracy of predicting the energy release in a real experiment with excess reactivity of 3βeff above prompt criticality. A transportable explosion-proof chamber was also developed, which ensures the safe localization of explosion products of the core of small-sized nuclear devices and charges of high explosives with equivalent mass of up to 100 kg of TNT.

Controlled human infection with RSV: The opportunities of experimental challenge.

PubMed

Habibi, Maximillian S; Chiu, Christopher

2017-01-11

Despite the recent explosion in RSV vaccine development, there remain substantial hurdles to overcome before licensing of effective vaccines will allow widespread use, particularly in high-risk populations. Incomplete understanding of mechanisms and correlates of protection against RSV mean that, for the time being, successful RSV vaccines must directly demonstrate efficacy, which necessitates large and costly clinical trials in naturally infected patients. To mitigate the risks inherent in progressing to these late-stage trials, experimental human RSV infection studies have recently been re-established, representing the interface between pre-clinical models and observational studies of patients. Not only can they be used for early proof-of-concept clinical trials to test vaccine efficacy, but human challenge studies also offer the potential to better understand protective immunity against RSV infection to improve vaccine design and delivery. In the past, controlled human infection studies with RSV have been instrumental in elucidating the influence of factors such as route of infection and type of inoculum on the course of disease. Recently, efficacy trials of novel RSV antiviral drugs have also been successfully undertaken. Now, with advances in technology, detailed investigations of human mucosal immunity in the RSV-infected airway are possible. These have indicated defects in RSV-induced humoral and CD8+ T cell immunity that may contribute to the recurrent symptomatic infection that occurs throughout life and should be circumvented by optimal vaccines. Here, we discuss the insights derived from RSV human challenge models; the major impediments to their more widespread uptake; and their potential benefit in accelerating vaccine development, including future directions to further enhance the relevance of these models to at-risk patient populations. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

30 CFR 18.29 - Access openings and covers, including unused lead-entrance holes.

Code of Federal Regulations, 2013 CFR

2013-07-01

... lead-entrance holes. 18.29 Section 18.29 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... unused lead-entrance holes. (a) Access openings in explosion-proof enclosures will be permitted only... Figure 1 in Appendix II.) (c) Holes in enclosures that are provided for lead entrances but which are not...

30 CFR 18.29 - Access openings and covers, including unused lead-entrance holes.

Code of Federal Regulations, 2011 CFR

2011-07-01

... lead-entrance holes. 18.29 Section 18.29 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... unused lead-entrance holes. (a) Access openings in explosion-proof enclosures will be permitted only... Figure 1 in Appendix II.) (c) Holes in enclosures that are provided for lead entrances but which are not...

30 CFR 18.29 - Access openings and covers, including unused lead-entrance holes.

Code of Federal Regulations, 2014 CFR

2014-07-01

... lead-entrance holes. 18.29 Section 18.29 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... unused lead-entrance holes. (a) Access openings in explosion-proof enclosures will be permitted only... Figure 1 in Appendix II.) (c) Holes in enclosures that are provided for lead entrances but which are not...

49 CFR 174.300 - Special handling requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Class 3 (flammable liquid) materials may not be loaded, transported, or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or... space is not equipped with any electrical apparatus that is not non-sparking or explosion-proof; (2...

49 CFR 174.300 - Special handling requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Class 3 (flammable liquid) materials may not be loaded, transported, or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or... space is not equipped with any electrical apparatus that is not non-sparking or explosion-proof; (2...

49 CFR 174.300 - Special handling requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Class 3 (flammable liquid) materials may not be loaded, transported, or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or... space is not equipped with any electrical apparatus that is not non-sparking or explosion-proof; (2...

43. BUILDING NO. 454, ORDNANCE FACILITY (BAG CHARGE FILLING PLANT), ...

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

43. BUILDING NO. 454, ORDNANCE FACILITY (BAG CHARGE FILLING PLANT), DETAIL OF EXPLOSION-PROOF ELECTRICAL SWITCH BOX (SWITCH GEAR INSIDE BOX SUBMERGED IN OIL TO QUENCH SPARKS), SWITCH EQUIPMENT MADE BY GENERAL ELECTRIC. - Picatinny Arsenal, 400 Area, Gun Bag Loading District, State Route 15 near I-80, Dover, Morris County, NJ

49 CFR 174.300 - Special handling requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Class 3 (flammable liquid) materials may not be loaded, transported, or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or... space is not equipped with any electrical apparatus that is not non-sparking or explosion-proof; (2...

49 CFR 174.300 - Special handling requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Class 3 (flammable liquid) materials may not be loaded, transported, or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or... space is not equipped with any electrical apparatus that is not non-sparking or explosion-proof; (2...

30 CFR 18.29 - Access openings and covers, including unused lead-entrance holes.

Code of Federal Regulations, 2012 CFR

2012-07-01

... lead-entrance holes. 18.29 Section 18.29 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... unused lead-entrance holes. (a) Access openings in explosion-proof enclosures will be permitted only... Figure 1 in Appendix II.) (c) Holes in enclosures that are provided for lead entrances but which are not...

Laser initiation of explosives

NASA Astrophysics Data System (ADS)

Singh, Manpreet; Sethi, V. S.

2002-09-01

Through laser initiation of explosives offers many advantages like controlled threshold energy over wide range, replacement of complicated safety arming mechanisms to simple and better system, immunity to RF/EMI environment etc, but there is greater difficulty to build detonator for all purpose applications and regular field trials. The challenges are to understand the interaction of laser radiation or its induced plasma with explosives, launching and transmission of high power laser beam, coupling and focussing to desired target area. This paper looks into the details of those facts.

30 CFR Appendix II to Subpart D of... - Appendix II to Subpart D of Part 18

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Approval 2G- Motor: (Manufacturing Company) Frame ___ Hp., ___ Volts, ___ Ph., ___ Cy., ___ R.P.M. X/P... wires shall not be used for grounding except in conjunction with diode(s) or equivalent. The operating voltage should match the voltage rating of the motor(s). 2. Servicing. Explosion-proof enclosures shall be...

30 CFR Appendix II to Subpart D of... - Appendix II to Subpart D of Part 18

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Approval 2G- Motor: (Manufacturing Company) Frame ___ Hp., ___ Volts, ___ Ph., ___ Cy., ___ R.P.M. X/P... wires shall not be used for grounding except in conjunction with diode(s) or equivalent. The operating voltage should match the voltage rating of the motor(s). 2. Servicing. Explosion-proof enclosures shall be...

30 CFR Appendix II to Subpart D of... - Appendix II to Subpart D of Part 18

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Approval 2G- Motor: (Manufacturing Company) Frame ___ Hp., ___ Volts, ___ Ph., ___ Cy., ___ R.P.M. X/P... wires shall not be used for grounding except in conjunction with diode(s) or equivalent. The operating voltage should match the voltage rating of the motor(s). 2. Servicing. Explosion-proof enclosures shall be...

30 CFR Appendix II to Subpart D of... - Appendix II to Subpart D of Part 18

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Approval 2G- Motor: (Manufacturing Company) Frame ___ Hp., ___ Volts, ___ Ph., ___ Cy., ___ R.P.M. X/P... wires shall not be used for grounding except in conjunction with diode(s) or equivalent. The operating voltage should match the voltage rating of the motor(s). 2. Servicing. Explosion-proof enclosures shall be...

30 CFR Appendix II to Subpart D of... - Appendix II to Subpart D of Part 18

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Approval 2G- Motor: (Manufacturing Company) Frame ___ Hp., ___ Volts, ___ Ph., ___ Cy., ___ R.P.M. X/P... wires shall not be used for grounding except in conjunction with diode(s) or equivalent. The operating voltage should match the voltage rating of the motor(s). 2. Servicing. Explosion-proof enclosures shall be...

Talking with Concerned Parents about Immunization

ERIC Educational Resources Information Center

Sturm, Lynne A.; Zimet, Gregory D.; Klausmeier, Thomas

2010-01-01

Clinical conversations between health professionals and parents can be frustrating for both parties when the topic is childhood immunization. Parents bring to the table personal models of decision making and experiences of risk that may differ from those of their health care providers. They may also feel confused by an explosion of information…

46 CFR 129.520 - Hazardous areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

... liquid with a flashpoint of below 140 °F (60 °C), or carries hazardous cargoes on deck or in integral...-storage spaces, or within 3 meters (10 feet) of a source of vapor on a weather deck unless the equipment... liquid unless the equipment is explosion-proof or intrinsically safe under § 111.105-9 or § 111.105-11 of...

46 CFR 129.520 - Hazardous areas.

Code of Federal Regulations, 2014 CFR

2014-10-01

... liquid with a flashpoint of below 140 °F (60 °C), or carries hazardous cargoes on deck or in integral...-storage spaces, or within 3 meters (10 feet) of a source of vapor on a weather deck unless the equipment... liquid unless the equipment is explosion-proof or intrinsically safe under § 111.105-9 or § 111.105-11 of...

46 CFR 129.520 - Hazardous areas.

Code of Federal Regulations, 2012 CFR

2012-10-01

... liquid with a flashpoint of below 140 °F (60 °C), or carries hazardous cargoes on deck or in integral...-storage spaces, or within 3 meters (10 feet) of a source of vapor on a weather deck unless the equipment... liquid unless the equipment is explosion-proof or intrinsically safe under § 111.105-9 or § 111.105-11 of...

29 CFR 1917.153 - Spray painting (See also § 1917.2, definition of Hazardous cargo, materials, substance, or...

Code of Federal Regulations, 2010 CFR

2010-07-01

... accumulate on electrical installations, wiring shall be in rigid conduit or in boxes containing no taps... pressure. (12) Wiring, motors and equipment in a spray booth shall be of approved explosion-proof type for..., Hazardous Locations. Wiring, motors and equipment within 20 feet (6.1m) of any interior spraying area and...

Detonation Diffraction in a Multi-Step Channel

DTIC Science & Technology

2010-12-01

openings. This allowed the detonation wave diffraction transmission limits to be determined for hydrogen/air mixtures and to better understand...imaging systems to provide shock wave detail and velocity information. The images were observed through a newly designed explosive proof optical section...stepped openings. This allowed the detonation wave diffraction transmission limits to be determined for hydrogen/air mixtures and to better

Solvent Recycling for Shipyards

DTIC Science & Technology

1993-05-01

Suvey results are included in Section 5) Survey manufacturers and compile information on available equipment and features . (Data is summarized in Section...should be placed on safety features . Important safety features include explosion-proof electricals and grounding protection, overpressure relief valves...solvent can dissolve a polymer plastic liner, or extract water from a clay liner, resulting in liner leakage. The threat is compounded by the ability

Sub-Nanogram Detection of RDX Explosive by Monoclonal Antibodies.

PubMed

Ulaeto, David O; Hutchinson, Alistair P; Nicklin, Stephen

2015-08-01

Polyclonal and monoclonal antibodies were raised to protein carrier molecules haptenized with RDX, a major component of many plastic explosives including Semtex. Sera from immunized mice detected RDX protein conjugates in standard ELISA. Clonally purified monoclonal antibodies had detection limits in the sub-ng/mL range for underivatized RDX in competition ELISA. The monoclonal antibodies are not dependent on the presence of taggants added during the manufacturing process, and are likely to have utility in the detection of any explosive containing RDX, or RDX contamination of environmental sites.

Sub-Nanogram Detection of RDX Explosive by Monoclonal Antibodies

PubMed Central

Hutchinson, Alistair P.; Nicklin, Stephen

2015-01-01

Polyclonal and monoclonal antibodies were raised to protein carrier molecules haptenized with RDX, a major component of many plastic explosives including Semtex. Sera from immunized mice detected RDX protein conjugates in standard ELISA. Clonally purified monoclonal antibodies had detection limits in the sub-ng/mL range for underivatized RDX in competition ELISA. The monoclonal antibodies are not dependent on the presence of taggants added during the manufacturing process, and are likely to have utility in the detection of any explosive containing RDX, or RDX contamination of environmental sites. PMID:26252765

Surgical Assisting

MedlinePlus

... CPR/BLS certification Acceptable health and immunization records Computer literacy Students also must be able to show proof of successful completion of basic science (college level) instruction, including: Microbiology Pathophysiology Pharmacology Anatomy ...

Chromium Elimination and Cannon Life Extension for Gun Tubes

DTIC Science & Technology

2012-08-30

the use of hexavalent chromium (VI) in the production of cannon barrels by developing a cost effective environmentally friendly Explosive Bonding...erosion- resistant chrome cobalt alloy matrix with 15% tungsten. Stellite is used as M60 machine gun barrel liner. Tantalum Cobalt Tungsten...Grounds (YPG) Preliminary proof of principle endurance testing at YPG shows promising results when conducted side by side to a chrome plated

Application and Prospects of High-strength Lightweight Materials used in Coal mine

NASA Astrophysics Data System (ADS)

He, Pan

2017-09-01

This paper describes some high-strength lightweight materials used in coal mine, and if their performance can meet the requirements of underground safety for explosion-proof, anti-static, friction sparks mine; and reviewed the species, characteristic, preparation process of high-strength lightweight materials for having inspired lightweight high-strength performance by modifying or changing the synthesis mode used in coal mine equipment.

Pulmonary arterial remodeling induced by a Th2 immune response

PubMed Central

Daley, Eleen; Emson, Claire; Guignabert, Christophe; de Waal Malefyt, Rene; Louten, Jennifer; Kurup, Viswanath P.; Hogaboam, Cory; Taraseviciene-Stewart, Laimute; Voelkel, Norbert F.; Rabinovitch, Marlene; Grunig, Ekkehard; Grunig, Gabriele

2008-01-01

Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4+ T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule α, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH. PMID:18227220

Proof of the Feasibility of Coherent and Incoherent Schemes for Pumping a Gamma-Ray Laser

DTIC Science & Technology

1991-12-31

Lasers - Donald Prosnitz 4.1.2 Millimeter and Submillimeter Lasers - Victor L Granatstein, Robert K. Parker, and Phillip A. Sprangle 4.2 X-Ray Lasers...Camacho SECTION 4: OTHER LASERS 4.1 Free-Electron Lasers .............................................. .. 515 William B. Colson and Donald Prosnitz 4.2...fluxes to pump the inversions, exceeding even those available from nuclear explosions , and to require neutron moderators having virtually infinite

Chapter 2: Innate Immunity

PubMed Central

Turvey, Stuart E.; Broide, David H.

2009-01-01

Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease. PMID:19932920

5. Credit BG. This interior view shows the weigh room, ...

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

5. Credit BG. This interior view shows the weigh room, looking west (240°): Electric lighting and scale read-outs (boxes with circular windows on the wall) are fitted with explosion-proof enclosures; these enclosures prevent malfunctioning electrical parts from sparking and starting fires or explosions. One marble table and scale have been removed at the extreme left of the view. Two remaining scales handle small and large quantities of propellants and additives. Marble tables do not absorb chemicals or conduct electricity; their mass also prevents vibration from upsetting the scales. The floor has an electrically conductive coating to dissipate static electric charges, thus preventing sparks which might ignite propellants. - Jet Propulsion Laboratory Edwards Facility, Weigh & Control Building, Edwards Air Force Base, Boron, Kern County, CA

[Three levels of stress reaction of the immune system in an acute infectious process in children (facts and a hypothesis)].

PubMed

Zheleznikova, G F

1997-01-01

Three variants of immune response (IR) in children with acute respiratory viral infections are determined and characterized in detail: the difference between these shows in the level of specific antibody production as well as in the non-specific immune suppression which is tested by lymphocyte blast transformation to phytogemagglutinin. According to our hypothesis, this phenomenon may by explained as a manifestation of three types of neuroendocrine IR regulation corresponding to three levels of immune system stress response. The proof of genetic and physiological factors involvement in the process of choosing any type of IR is adduced. The important role of ontogenetic development of cooperation between immune and nervous systems in IR variants formation is emphasized.

Amine-functionalized diatom frustules: a platform for specific and sensitive detection of nitroaromatic explosive derivative.

PubMed

Selvaraj, Viji; Thomas, Neethi; Anthuvan, Allen Joseph; Nagamony, Ponpandian; Chinnuswamy, Viswanathan

2017-12-14

In the present study, an attempt was made to develop a proof of concept for the detection of nitroaromatic explosive derivatives through the photoluminescence (PL) quenching process using functionalized diatom frustules as a sensing platform. The diatom frustules are composed of nanostructured, highly porous biogenic silica material and emit strong, visible blue PL upon UV excitation. PL-active biosilica was isolated from the marine diatom Nitzschia sp. and was amine-functionalized to develop a sensing platform. Functionalized diatom frustules were further characterized using field emission scanning electron microscope and a series of spectroscopic methods. When nitroaromatic compounds were bound to the functionalized diatom frustules biosilica, the PL intensity from the functionalized biosilica was partially quenched due to the electrophilic nature of the nitro (-NO) groups. The quenching process confirmed the Meisenheimer complex formation and was investigated by using Fourier transform infrared spectroscopy and time-resolved photoluminescence studies. The developed platform was further evaluated for its sensitivity and specificity, and the limit of detection (LOD) of the assay was determined as 1 μM for a series of nitroaromatic explosive compounds. In conclusion, the developed sensing platform will have great utility in the development of on-site detection platforms for sensitive detection of warfare explosive nitroaromatic compounds from the environment.

The Inglorious Death of Jumbo

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

Meade, Roger Allen

In the summer of 1944, J. Robert Oppenheimer and Los Alamos faced a crisis. An isotopic impurity in Plutonium rendered the metal unusable in a gun-assembled atomic bomb (i.e., Little Boy). Making this situation worse was a shortage of Uranium. The combination of these two problems threatened the entire wartime project. The answer to this dilemma, in part, was to develop a novel assembly method for Plutonium using the supersonic shock waves created by several tons of high explosives to compress a ball of Plutonium into a supercritical state. Since this method, implosion, was not much more than a theoreticalmore » construct, the Trinity test was devised to proof test the process. Given the speculative nature of implosion, Trinity was a gamble of sorts. If the test failed (i.e., little or no nuclear yield), the blast of the high explosives would scatter the scarce and expensive Plutonium over the surrounding desert. Since the probability of failure remained high into the early summer of 1945, some method of containing a failed nuclear explosion was needed. Jumbo was the answer.« less

Investigation of failure to separate an Inconel 718 frangible nut

NASA Technical Reports Server (NTRS)

Hoffman, William C., III; Hohmann, Carl

1994-01-01

The 2.5-inch frangible nut is used in two places to attach the Space Shuttle Orbiter to the External Tank. It must be capable of sustaining structural loads and must also separate into two pieces upon command. Structural load capability is verified by proof loading each flight nut, while ability to separate is verified on a sample of a production lot. Production lots of frangible nuts beginning in 1987 experienced an inability to reliably separate using one of two redundant explosive boosters. The problems were identified in lot acceptance tests, and the cause of failure has been attributed to differences in the response of the Inconel 718. Subsequent tests performed on the frangible nuts resulted in design modifications to the nuts along with redesign of the explosive booster to reliably separate the frangible nut. The problem history along with the design modifications to both the explosive booster and frangible nut are discussed in this paper. Implications of this failure experience impact any pyrotechnic separation system involving fracture of materials with respect to design margin control and lot acceptance testing.

Application of the modified transient plane source technique for early detection of liquid explosives

NASA Astrophysics Data System (ADS)

Bateman, Robert; Harris, Adam; Lee, Linda; Howle, Christopher R.; Ackermann, Sarah L. G.

2016-05-01

The paper will review the feasibility of adapting the Modified Transient Plane Source (MTPS) method as a screening tool for early-detection of explosives and hazardous materials. Materials can be distinguished from others based on their inherent thermal properties (e.g. thermal effusivity) in testing through different types of barrier materials. A complimentary advantage to this technique relative to other traditional detection technologies is that it can penetrate reflective barrier materials, such as aluminum, easily. A strong proof-of-principle is presented on application of the MTPS transient thermal property measuring in the early-screening of liquid explosives. The work demonstrates a significant sensitivity to distinguishing a wide range of fluids based on their thermal properties through a barrier material. The work covers various complicating factors to the longer-term adoption of such a method including the impact of carbonization and viscosity. While some technical challenges remain, the technique offers significant advantages in complimenting existing detection methods in being able to penetrate reflective metal containers (e.g. aluminum soft drinkscans) with ease.

Development of a Coded Aperture X-Ray Backscatter Imager for Explosive Device Detection

NASA Astrophysics Data System (ADS)

Faust, Anthony A.; Rothschild, Richard E.; Leblanc, Philippe; McFee, John Elton

2009-02-01

Defence R&D Canada has an active research and development program on detection of explosive devices using nuclear methods. One system under development is a coded aperture-based X-ray backscatter imaging detector designed to provide sufficient speed, contrast and spatial resolution to detect antipersonnel landmines and improvised explosive devices. The successful development of a hand-held imaging detector requires, among other things, a light-weight, ruggedized detector with low power requirements, supplying high spatial resolution. The University of California, San Diego-designed HEXIS detector provides a modern, large area, high-temperature CZT imaging surface, robustly packaged in a light-weight housing with sound mechanical properties. Based on the potential for the HEXIS detector to be incorporated as the detection element of a hand-held imaging detector, the authors initiated a collaborative effort to demonstrate the capability of a coded aperture-based X-ray backscatter imaging detector. This paper will discuss the landmine and IED detection problem and review the coded aperture technique. Results from initial proof-of-principle experiments will then be reported.

Optical Sensor of Thermal Gas Flow Based on Fiber Bragg Grating.

PubMed

Jiang, Xu; Wang, Keda; Li, Junqing; Zhan, Hui; Song, Zhenan; Che, Guohang; Lyu, Guohui

2017-02-15

This paper aims at solving the problem of explosion proof in measurement of thermal gas flow using electronic sensor by presenting a new type of flow sensor by optical fiber heating. A measuring unit based on fiber Bragg grating (FBG) for fluid temperature and a unit for heat dissipation are designed to replace the traditional electronic sensors. The light in C band from the amplified spontaneous emission (ASE) light source is split, with one part used to heat the absorbing coating and the other part used in the signal processing unit. In the heating unit, an absorbing coating is introduced to replace the traditional resistance heating module to minimize the risk of explosion. The measurement results demonstrate a fine consistency between the flow and temperature difference in simulation. The method to enhance the measurement resolution of flow is also discussed.

Isolated immune-related pancreatic exocrine insufficiency associated with pembrolizumab therapy.

PubMed

Prasanna, Thiru; McNeil, Catriona M; Nielsen, Theresa; Parkin, David

2018-03-01

We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis. Serum amylase and lipase were not elevated. There was no evidence of pancreatitis or pancreatic metastases on imaging. Significantly lower fecal elastase test on two occasions confirmed the diagnosis of pancreatic exocrine insufficiency. He was treated with pancreatic enzyme supplementation with complete resolution of diarrhea. This case reinforces the importance of awareness and anticipation of unusual immune-related adverse events related to checkpoint inhibitors.

Calculation of Containment Concentrations While Coating the Interior of a Bulk Storage Fuel Tank

DTIC Science & Technology

1990-05-01

connection plate Thief-hatch cutout-/ L7J * . Pipe -line connection 22’ B.C. Plan 28 1,15z holes(in top flange 20’ only) 234 1-20-diam dome Vent-line...inside tanks throughout course of work as required to maintain a vapor-free condition. Use exhaust fans, either explosion-proof electrically operated or...provide suction ductwork extending to areas of heaviest concentrations including lowest levels of tank. In no case shall exhaust fan capacity be less than

High-accurate optical fiber liquid level sensor

NASA Astrophysics Data System (ADS)

Sun, Dexing; Chen, Shouliu; Pan, Chao; Jin, Henghuan

1991-08-01

A highly accurate optical fiber liquid level sensor is presented. The single-chip microcomputer is used to process and control the signal. This kind of sensor is characterized by self-security and is explosion-proof, so it can be applied in any liquid level detecting areas, especially in the oil and chemical industries. The theories and experiments about how to improve the measurement accuracy are described. The relative error for detecting the measurement range 10 m is up to 0.01%.

40. BUILDING NO. 454, ORDNANCE FACILITY (BAG CHANGE FILLING PLANT), ...

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

40. BUILDING NO. 454, ORDNANCE FACILITY (BAG CHANGE FILLING PLANT), DETAIL SOUTHEAST SIDE OF EXTERIOR ELECTRICAL EQUIPMENT ROOM, SHOWING DOOR TO SEWING ROOM NO. 3, VENTILATOR FAN (OVER DOOR), STEAM LINE (PIPE), SEWING MACHINE MOTOR IN OVERHEAD, ALARM BELL, EXPLOSION-PROOF SWITCH BOXES, GROUNDS ON DOORS, PULL ALARM HANDLE (EXTREME RIGHT; PULLEY CABLE CONDUCTED IN CONDUIT TO SWITCH INSIDE BUILDING. PULLEYS INSIDE ALL ELBOW JOINTS.) - Picatinny Arsenal, 400 Area, Gun Bag Loading District, State Route 15 near I-80, Dover, Morris County, NJ

The National Shipbuilding Research Program. Update Handbook for Surface Preparation and Coatings in Tanks and Confined Areas

DTIC Science & Technology

2000-10-31

cleaning method are described in Naval Ships’ Technical Manual Chapter 631. 4.6.4 Citric Acid Cleaning The citric acid cleaning system is intended to...acquisition of necessary chemicals and tools, degreasing/cleaning, paint/stripping/removal, citric acid rust removal, passivation of bare steel, and drying...Figure 9-7 Hanging Explosion -Proof Light Box • Figure 9-8 Lighting in Tank • Figure 10-1 Hazardous Waste Storage Area • Figure 10-2 Solvent

Interacting supernovae and supernova impostors: Evidence of incoming supernova explosions?

NASA Astrophysics Data System (ADS)

Tartaglia, L.

2015-02-01

Violent eruptions, and consequently major mass loss, are a common feature of the so-called Luminous Blue Variable (LBV) stars. During major eruptive episodes LBVs mimic the behavior of real type IIn supernovae (SNe), showing comparable radiated energy and similar spectroscopic properties. For this reason these events are frequently labelled as SN impostors. Type IIn SN spectra are characterized by the presence of prominent narrow Balmer lines in emission. In most cases, SNe IIn arise from massive stars (M>8⊙) exploding in a dense H-rich circumstellar medium (CSM), produced by progenitor's mass loss prior to the SN explosion. Although the mechanisms triggering these eruptions are still unknown, recently we had direct proofs of the connection between very massive stars, their eruptions and ejecta-CSM interacting SNe. SNe 2006jc, 2010mc, 2011ht and the controversial SN 2009ip are famous cases in which we observed the explosion of the star months to years after major outbursts. In this context, the case of a recent transient event, LSQ13zm, is extremely interesting since we observed an outburst just ˜3 weeks before the terminal SN explosion. All of this may suggest that SN impostors occasionally herald true SN explosions. Nonetheless, there are several cases where major eruptions are followed by a quiescent phase in the LBV life. The impostor SN 2007sv is one of these cases, since it showed a single outburst event. Its photometric (a relatively faint absolute magnitude at the maximum) and spectroscopic properties (low velocity and temperature of the ejecta, and the absence of the typical elements produced in the explosive nucleosynthesis) strongly suggest that SN 2007sv was the giant eruption of an LBV, which has then returned in a quiescent stage.

Interacting supernovae and supernova impostors: Evidence of incoming supernova explosions?

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

Tartaglia, L.

2015-02-24

Violent eruptions, and consequently major mass loss, are a common feature of the so–called Luminous Blue Variable (LBV) stars. During major eruptive episodes LBVs mimic the behavior of real type IIn supernovae (SNe), showing comparable radiated energy and similar spectroscopic properties. For this reason these events are frequently labelled as SN impostors. Type IIn SN spectra are characterized by the presence of prominent narrow Balmer lines in emission. In most cases, SNe IIn arise from massive stars (M>8{sub ⊙}) exploding in a dense H–rich circumstellar medium (CSM), produced by progenitor’s mass loss prior to the SN explosion. Although the mechanismsmore » triggering these eruptions are still unknown, recently we had direct proofs of the connection between very massive stars, their eruptions and ejecta-CSM interacting SNe. SNe 2006jc, 2010mc, 2011ht and the controversial SN 2009ip are famous cases in which we observed the explosion of the star months to years after major outbursts. In this context, the case of a recent transient event, LSQ13zm, is extremely interesting since we observed an outburst just ∼3 weeks before the terminal SN explosion. All of this may suggest that SN impostors occasionally herald true SN explosions. Nonetheless, there are several cases where major eruptions are followed by a quiescent phase in the LBV life. The impostor SN 2007sv is one of these cases, since it showed a single outburst event. Its photometric (a relatively faint absolute magnitude at the maximum) and spectroscopic properties (low velocity and temperature of the ejecta, and the absence of the typical elements produced in the explosive nucleosynthesis) strongly suggest that SN 2007sv was the giant eruption of an LBV, which has then returned in a quiescent stage.« less

Immunology of BVDV vaccines

USDA-ARS?s Scientific Manuscript database

The use of vaccination to control bovine viral diarrhea virus (BVDV) infections presents exceptional challenges due to the nature of the virus, the unique interaction of the virus with the immune system, and its ability to establish persistent infections. The lack of proof reading function during th...

APSTNG: neutron interrogation for detection of explosives, drugs, and nuclear and chemical warfare materials

NASA Astrophysics Data System (ADS)

Rhodes, Edgar A.; Peters, Charles W.

1993-02-01

A recently developed neutron diagnostic probe system has the potential to satisfy a significant number of van-mobile and fixed-portal requirements for nondestructive detection, including monitoring of contraband explosives, drugs, and weapon materials, and treaty verification of sealed munitions. The probe is based on a unique associated-particle sealed-tube neutron generator (APSTNG) that interrogates the object of interest with a low-intensity beam of 14- MeV neutrons generated from the deuterium-tritium reaction and that detects the alpha-particle associated with each neutron. Gamma-ray spectra of resulting neutron reactions identify nuclides associated with all major chemicals in explosives, drugs, and chemical warfare agents, as well as many pollutants and fissile and fertile special nuclear material. Flight times determined from detection times of the gamma-rays and alpha-particles yield a separate coarse tomographic image of each identified nuclide. The APSTNG also forms the basis for a compact fast-neutron transmission imaging system that can be used along with or instead of the emission imaging system. Proof-of-concept experiments have been performed under laboratory conditions for simulated nuclear and chemical warfare munitions and for explosives and drugs. The small and relatively inexpensive APSTNG exhibits high reliability and can be quickly replaced. Surveillance systems based on APSTNG technology can avoid the large physical size, high capital and operating expenses, and reliability problems associated with complex accelerators.

Potential Mechanisms for Enhanced Zika Epidemic and Disease.

PubMed

Xia, Hongjie; Xie, Xuping; Shan, Chao; Shi, Pei-Yong

2018-05-11

A number of mechanisms have driven the explosive epidemics and severe diseases of Zika virus since 2007. Here, we comment on how herd immunity, heterologous flavivirus preimmunity, and viral mutations could enhance the epidemic potential and disease severity of Zika virus in humans.

Rape on Campus: Postsecondary Institutions as Third Party Defendants.

ERIC Educational Resources Information Center

Hauserman, Nancy; Lansing, Paul

1981-01-01

The implications and impact of immunity doctrines and the burden of proof upon the issues of postsecondary institutions' liability for sexual assaults occurring on campus are examined. The legal history of rape and rape cases, notably those civil cases involving third party defendants, are considered. (MLW)

A Novel Immunoreagent for the Specific and Sensitive Detection of the Explosive Triacetone Triperoxide (TATP).

PubMed

Walter, Maria Astrid; Panne, Ulrich; Weller, Michael G

2011-07-07

Triacetone triperoxide (TATP) is a primary explosive, which was used in various terrorist attacks in the past. For the development of biosensors, immunochemical µ-TAS, electronic noses, immunological test kits, or test strips, the availability of antibodies of high quality is crucial. Recently, we presented the successful immunization of mice, based on the design, synthesis, and conjugation of a novel TATP derivative. Here, the long-term immunization of rabbits is shown, which resulted in antibodies of extreme selectivity and more than 1,000 times better affinity in relation to the antibodies from mice. Detection limits below 10 ng L-1 (water) were achieved. The working range covers more than four decades, calculated from a precision profile. The cross-reactivity tests revealed an extraordinary selectivity of the antibodies-not a single compound could be identified as a relevant cross-reactant. The presented immunoreagent might be a major step for the development of highly sensitive and selective TATP detectors particularly for security applications.

A Novel Immunoreagent for the Specific and Sensitive Detection of the Explosive Triacetone Triperoxide (TATP)

PubMed Central

Walter, Maria Astrid; Panne, Ulrich; Weller, Michael G.

2011-01-01

Triacetone triperoxide (TATP) is a primary explosive, which was used in various terrorist attacks in the past. For the development of biosensors, immunochemical µ-TAS, electronic noses, immunological test kits, or test strips, the availability of antibodies of high quality is crucial. Recently, we presented the successful immunization of mice, based on the design, synthesis, and conjugation of a novel TATP derivative. Here, the long-term immunization of rabbits is shown, which resulted in antibodies of extreme selectivity and more than 1,000 times better affinity in relation to the antibodies from mice. Detection limits below 10 ng L−1 (water) were achieved. The working range covers more than four decades, calculated from a precision profile. The cross-reactivity tests revealed an extraordinary selectivity of the antibodies—not a single compound could be identified as a relevant cross-reactant. The presented immunoreagent might be a major step for the development of highly sensitive and selective TATP detectors particularly for security applications. PMID:25586922

Threshold for extinction and survival in stochastic tumor immune system

NASA Astrophysics Data System (ADS)

Li, Dongxi; Cheng, Fangjuan

2017-10-01

This paper mainly investigates the stochastic character of tumor growth and extinction in the presence of immune response of a host organism. Firstly, the mathematical model describing the interaction and competition between the tumor cells and immune system is established based on the Michaelis-Menten enzyme kinetics. Then, the threshold conditions for extinction, weak persistence and stochastic persistence of tumor cells are derived by the rigorous theoretical proofs. Finally, stochastic simulation are taken to substantiate and illustrate the conclusion we have derived. The modeling results will be beneficial to understand to concept of immunoediting, and develop the cancer immunotherapy. Besides, our simple theoretical model can help to obtain new insight into the complexity of tumor growth.

Travel Vaccines Enter the Digital Age: Creating a Virtual Immunization Record

PubMed Central

Wilson, Kumanan; Atkinson, Katherine M.; Bell, Cameron P.

2016-01-01

At present, proof of immunization against diseases such as yellow fever is required at some international borders in concordance with the International Health Regulations. The current standard, the International Certificate of Vaccination or Prophylaxis (ICVP), has limitations as a paper record including the possibility of being illegible, misplaced, or damaged. We believe that a complementary, digital record would offer advantages to public health and travelers alike. These include enhanced availability and reliability, potential to include lot specific information, and integration with immunization information systems. Challenges exist in implementation, particularly pertaining to verification at border crossings. We describe a potential course for the development and implementation of a digital ICVP record. PMID:26711516

The Making of a Generation.

ERIC Educational Resources Information Center

Levine, Arthur

1993-01-01

Group interviews with college undergraduates revealed five social and political events that they felt had most influenced their generation: the "Challenger" shuttle explosion; the end of the Cold War; the Persian Gulf War; the Acquired Immune Deficiency Syndrome (AIDS) epidemic; and the Rodney King beating and subsequent trials. (MSE)

FAILURE OF A NEUTRINO-DRIVEN EXPLOSION AFTER CORE-COLLAPSE MAY LEAD TO A THERMONUCLEAR SUPERNOVA

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

Kushnir, Doron; Katz, Boaz, E-mail: kushnir@ias.edu

We demonstrate that ∼10 s after the core-collapse of a massive star, a thermonuclear explosion of the outer shells is possible for some (tuned) initial density and composition profiles, assuming that the neutrinos failed to explode the star. The explosion may lead to a successful supernova, as first suggested by Burbidge et al. We perform a series of one-dimensional (1D) calculations of collapsing massive stars with simplified initial density profiles (similar to the results of stellar evolution calculations) and various compositions (not similar to 1D stellar evolution calculations). We assume that the neutrinos escaped with a negligible effect on themore » outer layers, which inevitably collapse. As the shells collapse, they compress and heat up adiabatically, enhancing the rate of thermonuclear burning. In some cases, where significant shells of mixed helium and oxygen are present with pre-collapsed burning times of ≲100 s (≈10 times the free-fall time), a thermonuclear detonation wave is ignited, which unbinds the outer layers of the star, leading to a supernova. The energy released is small, ≲10{sup 50} erg, and negligible amounts of synthesized material (including {sup 56}Ni) are ejected, implying that these 1D simulations are unlikely to represent typical core-collapse supernovae. However, they do serve as a proof of concept that the core-collapse-induced thermonuclear explosions are possible, and more realistic two-dimensional and three-dimensional simulations are within current computational capabilities.« less

The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.

PubMed

Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z

2013-11-01

We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

Medical Versus Nonmedical Immunization Exemptions for Child Care and School Attendance.

PubMed

2016-09-01

Routine childhood immunizations against infectious diseases are an integral part of our public health infrastructure. They provide direct protection to the immunized individual and indirect protection to children and adults unable to be immunized via the effect of community immunity. All 50 states, the District of Columbia, and Puerto Rico have regulations requiring proof of immunization for child care and school attendance as a public health strategy to protect children in these settings and to secondarily serve as a mechanism to promote timely immunization of children by their caregivers. Although all states and the District of Columbia have mechanisms to exempt school attendees from specific immunization requirements for medical reasons, the majority also have a heterogeneous collection of regulations and laws that allow nonmedical exemptions from childhood immunizations otherwise required for child care and school attendance. The American Academy of Pediatrics (AAP) supports regulations and laws requiring certification of immunization to attend child care and school as a sound means of providing a safe environment for attendees and employees of these settings. The AAP also supports medically indicated exemptions to specific immunizations as determined for each individual child. The AAP views nonmedical exemptions to school-required immunizations as inappropriate for individual, public health, and ethical reasons and advocates for their elimination. Copyright © 2016 by the American Academy of Pediatrics.

A small cysteine-rich protein from the Asian soybean rust fungus, Phakopsora pachyrhizi, suppresses plant immunity

USDA-ARS?s Scientific Manuscript database

The Asian soybean rust fungus, Phakopsora pachyrhizi, is an obligate pathogen capable of causing explosive disease epidemics that drastically reduce the yield of soybean (Glycine max). Currently, the molecular mechanisms by which P. pachyrhizi and other rust fungi cause disease are poorly understood...

Inborn Errors in Immunity

PubMed Central

Lionakis, M.S.; Hajishengallis, G.

2015-01-01

In recent years, the study of genetic defects arising from inborn errors in immunity has resulted in the discovery of new genes involved in the function of the immune system and in the elucidation of the roles of known genes whose importance was previously unappreciated. With the recent explosion in the field of genomics and the increasing number of genetic defects identified, the study of naturally occurring mutations has become a powerful tool for gaining mechanistic insight into the functions of the human immune system. In this concise perspective, we discuss emerging evidence that inborn errors in immunity constitute real-life models that are indispensable both for the in-depth understanding of human biology and for obtaining critical insights into common diseases, such as those affecting oral health. In the field of oral mucosal immunity, through the study of patients with select gene disruptions, the interleukin-17 (IL-17) pathway has emerged as a critical element in oral immune surveillance and susceptibility to inflammatory disease, with disruptions in the IL-17 axis now strongly linked to mucosal fungal susceptibility, whereas overactivation of the same pathways is linked to inflammatory periodontitis. PMID:25900229

Mechanism of action of mRNA-based vaccines.

PubMed

Iavarone, Carlo; O'hagan, Derek T; Yu, Dong; Delahaye, Nicolas F; Ulmer, Jeffrey B

2017-09-01

The present review summarizes the growing body of work defining the mechanisms of action of this exciting new vaccine technology that should allow rational approaches in the design of next generation mRNA vaccines. Areas covered: Bio-distribution of mRNA, localization of antigen production, role of the innate immunity, priming of the adaptive immune response, route of administration and effects of mRNA delivery systems. Expert commentary: In the last few years, the development of RNA vaccines had a fast growth, the rising number of proof will enable rational approaches to improving the effectiveness and safety of this modern class of medicine.

Innovative nuclear thermal propulsion technology evaluation - Results of the NASA/DOE task team study

NASA Technical Reports Server (NTRS)

Howe, Steven D.; Borowski, Stanley; Motloch, Chet; Helms, Ira; Diaz, Nils; Anghaie, Samim; Latham, Thomas

1991-01-01

In response to findings from two NASA/DOE nuclear propulsion workshops, six task teams were created to continue evaluation of various propulsion concepts, from which evolved an innovative concepts subpanel to evaluate thermal propulsion concepts which did not utilize solid fuel. This subpanel endeavored to evaluate each concept on a level technology basis, and to identify critical issues, technologies, and early proof-of-concept experiments. Results of the concept studies including the liquid core fission, the gas core fission, the fission foil reactors, explosively driven systems, fusion, and antimatter are presented.

The triple-ring nebula around SN 1987A: fingerprint of a binary merger.

PubMed

Morris, Thomas; Podsiadlowski, Philipp

2007-02-23

Supernova 1987A, the first naked-eye supernova observed since Kepler's supernova in 1604, defies a number of theoretical expectations. Its anomalies have long been attributed to a merger between two massive stars that occurred some 20,000 years before the explosion, but so far there has been no conclusive proof that this merger took place. Here, we present three-dimensional hydrodynamical simulations of the mass ejection associated with such a merger and the subsequent evolution of the ejecta, and we show that this accurately reproduces the properties of the triple-ring nebula surrounding the supernova.

U. S. Army Land Warfare Laboratory. Volume II Appendix B. Task Sheets

DTIC Science & Technology

1974-06-01

Free-Drop Water Container B-256 *06-S-64 Riot Shield 01-S-65 Cl Mob Control Equipment Studies 3-257 02-S-65 Compass - Fog and Fungus Proof B-258 03-S-65...Combustion Engine B-360 05-C-69 Mini-Grenade Munitions 3-36. 06-C-69 Explosive Detector - Plasma Chromatography -chnique B1-362 07-C-69 Grenade, Smoke...Mechanical Earth Waves B-406 05-P-63 Non-Electric Projector B-407 06-P-63 Communication by Earth Currents B-408 07-P-63 Ultrasonics B-409 08-P-63 Acoustic

Development of a novel low frequency GPR system for ultra-deep detection in Mine

NASA Astrophysics Data System (ADS)

Xu, Xianlei; Peng, Suping; Yang, Feng

2016-04-01

Mine disasters sources is the main source of the underground coal mine accidents in China. This paper describes the development of a novel explosion proof ground penetrating radar (GPR) for mine disasters sources detection, aiming to solve the current problems of the small detection range and low precision in the mine advanced detection in China. A high performance unipolar pulse transmitting unit is developed by using avalanche transistors, and an effective pulse excitation source network. And a new pluggable combined low-frequency antenna involving three frequencies with 12.5MHz, 25 MHz and 50MHz, is designed and developed. The plate-type structure is designed, aiming to enhance the directivity of the antenna, and the achievement of the antenna impedance matching is implemented in the feed point based on the extensions interface design, enhancing the antenna bandwidth and reducing the standing wave interference. Moreover, a high precision stepper delay circuit is designed by transforming the number of the operational amplifier step and using the differential compensation between the metal-oxide semiconductor field effect transistors, aiming to improve the accuracy of the signal acquisition system. In order to adapt to the mine environment, the explosion-proof design is implemented for the GPR system, including the host, transmitter, receiver, battery box, antenna, and other components.Mine detection experiments is carried out and the results show: the novel GPR system can effectively detect the location and depth of the geological disasters source with the depth greater than30 m and the diameter greater than 3m, the maximum detection depth can be up to 80m, which break the current detection depth limitations within 30m, providing an effective technical support for the ultra-deep mine disasters detection and the safety problems in coal mine production.

Necrotic enteritis: important role of intestinal immunity to Clostridium perfringens in pathogenesis and antibiotic alternative strategies to reduce the gut damage

USDA-ARS?s Scientific Manuscript database

The human population is projected to grow to 9-10 billion by the year 2050. As a consequence of the population explosion, food animal production must confront a new array of challenges including global food security, regulatory ban of antimicrobials, climate change, emerging infectious diseases, hi...

Herpesvirus microRNAs for use in gene therapy immune-evasion strategies.

PubMed

Bots, S T F; Hoeben, R C

2017-07-01

Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft may therefore require lifelong treatment with immunosuppressive drugs. An alternative approach to reduce graft rejection could involve the use of immune-evasion molecules. Expression of such molecules in cells of the graft may subvert recognition by the host's immune system. Viruses in particular are masters of exploitation and modulation of their hosts immune response. The Herpesviridae family provides a proof of concept for this as these viruses are capable to establish latency and a lifelong persistence in the infected hosts. While several viral proteins involved in immune evasion have been characterized, the Herpesviridae also encode a multitude of viral microRNA (miRNAs). Several of these miRNAs have been demonstrated to reduce the sensitivity of the infected cells to the destructive action of the host's immune cells. In this review, the miRNAs of some common herpesviruses that are associated with immune modulation will be discussed with a focus on their potential use in strategies aiming at generating non-immunogenic cells for transplantation.

Immune-Related Functions of the Hivep Gene Family in East African Cichlid Fishes

PubMed Central

Diepeveen, Eveline T.; Roth, Olivia; Salzburger, Walter

2013-01-01

Immune-related genes are often characterized by adaptive protein evolution. Selection on immune genes can be particularly strong when hosts encounter novel parasites, for instance, after the colonization of a new habitat or upon the exploitation of vacant ecological niches in an adaptive radiation. We examined a set of new candidate immune genes in East African cichlid fishes. More specifically, we studied the signatures of selection in five paralogs of the human immunodeficiency virus type I enhancer-binding protein (Hivep) gene family, tested their involvement in the immune defense, and related our results to explosive speciation and adaptive radiation events in cichlids. We found signatures of long-term positive selection in four Hivep paralogs and lineage-specific positive selection in Hivep3b in two radiating cichlid lineages. Exposure of the cichlid Astatotilapia burtoni to a vaccination with Vibrio anguillarum bacteria resulted in a positive correlation between immune response parameters and expression levels of three Hivep loci. This work provides the first evidence for a role of Hivep paralogs in teleost immune defense and links the signatures of positive selection to host–pathogen interactions within an adaptive radiation. PMID:24142922

Advances in quantum cascade lasers for security and crime-fighting

NASA Astrophysics Data System (ADS)

Normand, Erwan L.; Stokes, Robert J.; Hay, Kenneth; Foulger, Brian; Lewis, Colin

2010-10-01

Advances in the application of Quantum Cascade Lasers (QCL) to trace gas detection will be presented. The solution is real time (~1 μsec per scan), is insensitive to turbulence and vibration, and performs multiple measurements in one sweep. The QCL provides a large dynamic range, which is a linear response from ppt to % level. The concentration can be derived with excellent immunity from cross interference. Point sensing sensors developed by Cascade for home made and commercial explosives operate by monitoring key constituents in real time and matching this to a spatial event (i.e. sniffer device placed close to an object or person walking through portal (overt or covert). Programmable signature detection capability allows for detection of multiple chemical compounds along the most likely array of explosive chemical formulation. The advantages of configuration as "point sensing" or "stand off" will be discussed. In addition to explosives this method is highly applicable to the detection of mobile drugs labs through volatile chemical release.

A Systematic Methodology for Verifying Superscalar Microprocessors

NASA Technical Reports Server (NTRS)

Srivas, Mandayam; Hosabettu, Ravi; Gopalakrishnan, Ganesh

1999-01-01

We present a systematic approach to decompose and incrementally build the proof of correctness of pipelined microprocessors. The central idea is to construct the abstraction function by using completion functions, one per unfinished instruction, each of which specifies the effect (on the observables) of completing the instruction. In addition to avoiding the term size and case explosion problem that limits the pure flushing approach, our method helps localize errors, and also handles stages with interactive loops. The technique is illustrated on pipelined and superscalar pipelined implementations of a subset of the DLX architecture. It has also been applied to a processor with out-of-order execution.

Credit PSR. This view of the interior of the weighing ...

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

Credit PSR. This view of the interior of the weighing facility looks through the open double doors on the south side. A Toledo scale, rated at 3,000 pounds (1,363 Kg), is installed in the center of the floor; the smaller scale in the corner is rated for 200 pounds (91 Kg). The wall-mounted recording device records quantities weighed and serves as a record displaying that substances were in fact weighed. Note the explosion-proof fluorescent lighting above, and the 0.5 ton hoist - Jet Propulsion Laboratory Edwards Facility, Oxidizer Weigh & Storage Building, Edwards Air Force Base, Boron, Kern County, CA

[Alteration of textilfibres by explosion gases expelled distant from the muzzle (author's transl)].

PubMed

Bonte, W; Kijewski, H

1976-03-24

This paper presents the reconstruction of an unusual case of suicide. After raiding a branch-bank a robber fled shooting with his Sauer-Western revolver caliber .44 magnum at the pursuing policemen and succeeded in wrestling a pistol Walther caliber 7,65 mm from them. Under the fire of sub-machine guns he destroyed himself by a shot to the neck. Our investigations concerned a textile damage at the front of the sweater of the deceased surrounded by primer residue, showing characteristics of a close-up shot. The damage was identified as effect of explosion gases exhausting far-off the muzzle. The distance between this injury and the bullet hole corresponded with the length of the barrel of the Sauer-Western revolver and could be used for identification; it confirmed the diagnosis of a close-up shot at the neck, too. Collateral experiments with shots from distant ranges developed spadiceous melt figures of textile fibers around the bullet hole, the appearance of which is considered proof for a close-up shot commonly.

Cellular and Molecular Mechanisms of Anterior Chamber-Associated Immune Deviation (ACAID): What We Have Learned from Knockout Mice

PubMed Central

Vendomèle, Julie; Khebizi, Quentin; Fisson, Sylvain

2017-01-01

Anterior chamber-associated immune deviation (ACAID) is a well-known phenomenon that can occur after an antigen is introduced without any danger signal into the anterior chamber of a murine eye. It is reported to lead to an antigen-specific immune deviation throughout the body. Despite the relatively little evidence of this phenomenon in humans, it has been suggested as a potential prophylactic strategy in allograft rejections and in several autoimmune diseases. Cellular and molecular mechanisms of ACAID have been explored in different murine models mainly as proofs of concept, first by direct analyses of immune components in normal immunocompetent settings and by cell transfer experiments. Later, use of knockout (KO) mice has helped considerably to decipher ACAID mechanisms. However, several factors raise questions about the reliability and validity of studies using KO murine models. This mini-review summarizes results obtained with KO mice and discusses their advantages, their potential weaknesses, and their potential methods for further progress. PMID:29250068

Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation.

PubMed

Ueda, Masumi; Berger, Melvin; Gale, Robert Peter; Lazarus, Hillard M

2018-03-01

Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer. We review immunoglobulin formulations and discuss efficacy and potential adverse effects in the context of preventing infections and in graft-versus-host disease. We suggest an algorithm for evaluating acquired deficiencies of humoral immunity in persons with hematologic neoplasms and recommend appropriate use of immunoglobulin therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

HIV-1 vaccines

PubMed Central

Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H

2014-01-01

The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946

Peracetic Acid Treatment Generates Potent Inactivated Oral Vaccines from a Broad Range of Culturable Bacterial Species

PubMed Central

Moor, Kathrin; Wotzka, Sandra Y.; Toska, Albulena; Diard, Médéric; Hapfelmeier, Siegfried; Slack, Emma

2016-01-01

Our mucosal surfaces are the main sites of non-vector-borne pathogen entry, as well as the main interface with our commensal microbiota. We are still only beginning to understand how mucosal adaptive immunity interacts with commensal and pathogenic microbes to influence factors such as infectivity, phenotypic diversity, and within-host evolution. This is in part due to difficulties in generating specific mucosal adaptive immune responses without disrupting the mucosal microbial ecosystem itself. Here, we present a very simple tool to generate inactivated mucosal vaccines from a broad range of culturable bacteria. Oral gavage of 1010 peracetic acid-inactivated bacteria induces high-titer-specific intestinal IgA in the absence of any measurable inflammation or species invasion. As a proof of principle, we demonstrate that this technique is sufficient to provide fully protective immunity in the murine model of invasive non-typhoidal Salmonellosis, even in the face of severe innate immune deficiency. PMID:26904024

Dietary phytonutrients enhance gut innate immunity, modulate gut microbiota and improve disease resistance to coccidiosis and necrotic enteritis in broiler chickens

USDA-ARS?s Scientific Manuscript database

The human population is projected to grow to 9-10 billion by the year 2050. As a consequence of the population explosion, food animal production must confront a new array of challenges. Among these are global food security, climate change, emerging infectious diseases, regulatory ban of antimicrobi...

Proof-of-principle experiment of reference-frame-independent quantum key distribution with phase coding

PubMed Central

Liang, Wen-Ye; Wang, Shuang; Li, Hong-Wei; Yin, Zhen-Qiang; Chen, Wei; Yao, Yao; Huang, Jing-Zheng; Guo, Guang-Can; Han, Zheng-Fu

2014-01-01

We have demonstrated a proof-of-principle experiment of reference-frame-independent phase coding quantum key distribution (RFI-QKD) over an 80-km optical fiber. After considering the finite-key bound, we still achieve a distance of 50 km. In this scenario, the phases of the basis states are related by a slowly time-varying transformation. Furthermore, we developed and realized a new decoy state method for RFI-QKD systems with weak coherent sources to counteract the photon-number-splitting attack. With the help of a reference-frame-independent protocol and a Michelson interferometer with Faraday rotator mirrors, our system is rendered immune to the slow phase changes of the interferometer and the polarization disturbances of the channel, making the procedure very robust. PMID:24402550

New and emerging therapies for inflammatory bowel diseases.

PubMed

Grimm, Michael C

2009-10-01

The inflammatory bowel diseases have undergone an explosion of discovery in the last 10 years. The overwhelming focus of this has been in genetics and immune mechanisms of disease. While the former has provided critical information on predisposing factors, the latter has resulted in a panoply of novel immune-based therapies and technologies. These range from an improved approach to the use of conventional immunomodulators, such as azathioprine and 6-mercaptopurine, to commonplace availability of anti-tumor necrosis factor agents such as infliximab and adalimumab, through to small molecule inhibition of immune mediators. Unusual treatments, such as helminth infestation, stem cell transplantation, and leucocytapheresis, all derive from the burgeoning understanding of pathogenesis. Most important to our successful use of these therapies will be a fundamental understanding of the patient phenotypes and genotypes that will dictate particular treatment approaches in the future.

Successful Proof of Concept of Family Planning and Immunization Integration in Liberia

PubMed Central

Cooper, Chelsea M; Fields, Rebecca; Mazzeo, Corinne I; Taylor, Nyapu; Pfitzer, Anne; Momolu, Mary; Jabbeh-Howe, Cuallau

2015-01-01

ABSTRACT Globally, unmet need for postpartum family planning remains high, while immunization services are among the most wide-reaching and equitable interventions. Given overlapping time frames, integrating these services provides an opportunity to leverage existing health visits to offer women more comprehensive services. From March through November 2012, Liberia's government, with support from the Maternal and Child Health Integrated Program (MCHIP), piloted an integrated family planning and immunization model at 10 health facilities in Bong and Lofa counties. Vaccinators provided mothers bringing infants for routine immunization with targeted family planning and immunization messages and same-day referrals to co-located family planning services. In February 2013, we compared service statistics for family planning and immunization during the pilot against the previous year's statistics. We also conducted in-depth interviews with service providers and other personnel and focus group discussions with clients. Results showed that referral acceptance across the facilities varied from 10% to 45% per month, on average. Over 80% of referral acceptors completed the family planning visit that day, of whom over 90% accepted a contraceptive method that day. The total number of new contraceptive users at participating facilities increased by 73% in Bong and by 90% in Lofa. Women referred from immunization who accepted family planning that day accounted for 44% and 34% of total new contraceptive users in Bong and Lofa, respectively. In Lofa, pilot sites administered 35% more Penta 1 and 21% more Penta 3 doses during the pilot period compared with the same period of the previous year, while Penta 1 and Penta 3 administration decreased in non-pilot facilities. In Bong, there was little difference in the number of Penta 1 and Penta 3 doses administered between pilot and non-pilot facilities. In both counties, Penta 1 to Penta 3 dropout rates increased at pilot sites but not in non-pilot facilities, possibly due to higher than average background dropout rates at pilot sites prior to the intervention in Lofa and the disproportionate effect of data from 1 large facility in Bong. The project provided considerable basic support to assess this proof of concept. However, results suggest that introducing a simple model that is minimally disruptive to existing immunization service delivery can facilitate integration. The model is currently being scaled-up to other counties in Liberia, which could potentially contribute to increased postpartum contraceptive uptake, leading to longer birth intervals and improved health outcomes for children and mothers. PMID:25745121

[Endothelial dysfunction and nonspecific immune reactions in development and progression of osteoarthrosis in women engaged into manual work].

PubMed

Maliutina, N N; Nevzorova, M S

2015-01-01

The article considers mechanisms of development and progression of osteoarthrosis as an occupationally conditioned disease in women of manual work. Women working in physical overstrain conditions are under occupational risk with dysfunction of many body systems. The authors set a hypothesis on association of endothelial dysfunction markers dysbalance and structural remodelling of cartilage matrix as a proof of degenerative changes.

Potential of epigenetic therapies in non-cancerous conditions

PubMed Central

Mau, Theresa; Yung, Raymond

2014-01-01

There has been an explosion of knowledge in the epigenetics field in the past 20 years. The first epigenetic therapies have arrived in the clinic for cancer treatments. In contrast, much of the promise of epigenetic therapies for non-cancerous conditions remains in the laboratories. The current review will focus on the recent progress that has been made in understanding the pathogenic role of epigenetics in immune and inflammatory conditions, and how the knowledge may provide much needed new therapeutic targets for many autoimmune diseases. Dietary factors are increasingly recognized as potential modifiers of epigenetic marks that can influence health and diseases across generations. The current epigenomics revolution will almost certainly complement the explosion of personal genetics medicine to help guide treatment decisions and disease risk stratification. PMID:25566322

Catching Supernova Impostors

NASA Astrophysics Data System (ADS)

Elias-Rosa, Nancy

2015-08-01

Given the heterogeneity of the type IIn SNe (SN that show strong interaction with the circumstellar medium), sometimes sneak cases of powerful eruptions of luminous blue variables (LBV) copy the true appearance of a SN explosion. These cases are commonly known as ``SN impostors". Although the mechanisms triggering these eruptions are still unknown, recently we had direct proofs of the connection between very massive stars, their eruptions and type IIn SNe, such as the case of the controversial SN 2009ip. Even if these objects are quite rare, their number has increased in the last couple of years. In this poster I will summarise my work on this topic, showing the most recent object of study and the conclusions from their analysis.

An engineered vaccine of the Plasmodium vivax Duffy binding protein enhances induction of broadly neutralizing antibodies.

PubMed

Ntumngia, Francis B; Pires, Camilla V; Barnes, Samantha J; George, Miriam T; Thomson-Luque, Richard; Kano, Flora S; Alves, Jessica R S; Urusova, Darya; Pereira, Dhelio B; Tolia, Niraj H; King, Christopher L; Carvalho, Luzia H; Adams, John H

2017-10-23

Plasmodium vivax invasion into human reticulocytes is a complex process. The Duffy binding protein (DBP) dimerization with its cognate receptor is vital for junction formation in the invasion process. Due to its functional importance, DBP is considered a prime vaccine candidate, but variation in B-cell epitopes at the dimer interface of DBP leads to induction of strain-limited immunity. We believe that the polymorphic residues tend to divert immune responses away from functionally conserved epitopes important for receptor binding or DBP dimerization. As a proof of concept, we engineered the vaccine DEKnull to ablate the dominant Bc epitope to partially overcome strain-specific immune antibody responses. Additional surface engineering on the next generation immunogen, DEKnull-2, provides an immunogenicity breakthrough to conserved protective epitopes. DEKnull-2 elicits a stronger broadly neutralizing response and reactivity with long-term persistent antibody responses of acquired natural immunity. By using novel engineered DBP immunogens, we validate that the prime targets of protective immunity are conformational epitopes at the dimer interface. These successful results indicate a potential approach that can be used generally to improve efficacy of other malaria vaccine candidates.

Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato.

PubMed

Tacket, C O; Mason, H S; Losonsky, G; Clements, J D; Levine, M M; Arntzen, C J

1998-05-01

Compared with vaccine delivery by injection, oral vaccines offer the hope of more convenient immunization strategies and a more practical means of implementing universal vaccination programs throughout the world. Oral vaccines act by stimulating the immune system at effector sites (lymphoid tissue) located in the gut. Genetic engineering has been used with variable success to design living and non-living systems as a means to deliver antigens to these sites and to stimulate a desired immune response. More recently, plant biotechnology techniques have been used to create plants which contain a gene derived from a human pathogen; the resultant plant tissues will accumulate an antigenic protein encoded by the foreign DNA. In pre-clinical trials, we found that antigenic proteins produced in transgenic plants retained immunogenic properties when purified; if injected into mice the antigen caused production of protein-specific antibodies. Moreover, in some experiments, if the plant tissues were simply fed to mice, a mucosal immune response occurred. The present study was conducted as a proof of principle to determine if humans would also develop a serum and/or mucosal immune response to an antigen delivered in an uncooked foodstuff.

Mathematical modeling based on ordinary differential equations: A promising approach to vaccinology

PubMed Central

Bonin, Carla Rezende Barbosa; Fernandes, Guilherme Cortes; dos Santos, Rodrigo Weber; Lobosco, Marcelo

2017-01-01

ABSTRACT New contributions that aim to accelerate the development or to improve the efficacy and safety of vaccines arise from many different areas of research and technology. One of these areas is computational science, which traditionally participates in the initial steps, such as the pre-screening of active substances that have the potential to become a vaccine antigen. In this work, we present another promising way to use computational science in vaccinology: mathematical and computational models of important cell and protein dynamics of the immune system. A system of Ordinary Differential Equations represents different immune system populations, such as B cells and T cells, antigen presenting cells and antibodies. In this way, it is possible to simulate, in silico, the immune response to vaccines under development or under study. Distinct scenarios can be simulated by varying parameters of the mathematical model. As a proof of concept, we developed a model of the immune response to vaccination against the yellow fever. Our simulations have shown consistent results when compared with experimental data available in the literature. The model is generic enough to represent the action of other diseases or vaccines in the human immune system, such as dengue and Zika virus. PMID:28027002

Mathematical modeling based on ordinary differential equations: A promising approach to vaccinology.

PubMed

Bonin, Carla Rezende Barbosa; Fernandes, Guilherme Cortes; Dos Santos, Rodrigo Weber; Lobosco, Marcelo

2017-02-01

New contributions that aim to accelerate the development or to improve the efficacy and safety of vaccines arise from many different areas of research and technology. One of these areas is computational science, which traditionally participates in the initial steps, such as the pre-screening of active substances that have the potential to become a vaccine antigen. In this work, we present another promising way to use computational science in vaccinology: mathematical and computational models of important cell and protein dynamics of the immune system. A system of Ordinary Differential Equations represents different immune system populations, such as B cells and T cells, antigen presenting cells and antibodies. In this way, it is possible to simulate, in silico, the immune response to vaccines under development or under study. Distinct scenarios can be simulated by varying parameters of the mathematical model. As a proof of concept, we developed a model of the immune response to vaccination against the yellow fever. Our simulations have shown consistent results when compared with experimental data available in the literature. The model is generic enough to represent the action of other diseases or vaccines in the human immune system, such as dengue and Zika virus.

Active and passive immunization for cancer.

PubMed

Baxter, David

2014-01-01

Vaccination started around the 10th century AD as a means of preventing smallpox. By the end of the 19th century such therapeutic vaccines were well established with both active and passive preparations being used in clinical practice. Active immunization involved administering an immunogen that might be live/ attenuated, killed/ inactivated, toxoid or subunit in origin. Passive immunization involved giving pre-formed antibodies, usually to very recently exposed individuals. At about the same time such approaches were also tried to treat a variety of cancers - proof of principle for the protective role of the immune response against malignancy was established by the observation that tumors transplanted into syngeneic hosts were rejected by the host innate and adaptive responses. The impact of these therapeutic vaccination has taken a considerable time to become established - in part because target antigens against which an adaptive response can be directed do not appear to be uniquely expressed on malignant transformed cells; and also because tumor cells are able to manipulate their environment to downregulate the host immune response. Therapeutic cancer vaccines are also divided into active and passive types - the latter being subdivided into specific and non-specific vaccines. Active immunization utilizes an immunogen to generate a host response designed to eliminate the malignant cells, whereas in passive immunization preformed antibodies or cells are administered to directly eliminate the transformed cells - examples of each are considered in this review.

Active and passive immunization for cancer

PubMed Central

Baxter, David

2014-01-01

Vaccination started around the 10th century AD as a means of preventing smallpox. By the end of the 19th century such therapeutic vaccines were well established with both active and passive preparations being used in clinical practice. Active immunization involved administering an immunogen that might be live/ attenuated, killed/ inactivated, toxoid or subunit in origin. Passive immunization involved giving pre-formed antibodies, usually to very recently exposed individuals. At about the same time such approaches were also tried to treat a variety of cancers – proof of principle for the protective role of the immune response against malignancy was established by the observation that tumors transplanted into syngeneic hosts were rejected by the host innate and adaptive responses. The impact of these therapeutic vaccination has taken a considerable time to become established - in part because target antigens against which an adaptive response can be directed do not appear to be uniquely expressed on malignant transformed cells; and also because tumor cells are able to manipulate their environment to downregulate the host immune response. Therapeutic cancer vaccines are also divided into active and passive types – the latter being subdivided into specific and non-specific vaccines. Active immunization utilizes an immunogen to generate a host response designed to eliminate the malignant cells, whereas in passive immunization preformed antibodies or cells are administered to directly eliminate the transformed cells - examples of each are considered in this review. PMID:25424829

Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes

PubMed Central

Van Dyke, Marley C. Caballero; Chaturvedi, Ashok K.; Hardison, Sarah E.; Leopold Wager, Chrissy M.; Castro-Lopez, Natalia; Hole, Camaron R.; Wozniak, Karen L.; Wormley, Floyd L.

2017-01-01

Cryptococcosis is a fungal disease caused by multiple Cryptococcus serotypes; particularly C. neoformans (serotypes A and D) and C. gattii (serotypes B and C). To date, there is no clinically available vaccine to prevent cryptococcosis. Mice given an experimental pulmonary vaccination with a C. neoformans serotype A strain engineered to produce interferon-γ, denoted H99γ, are protected against a subsequent otherwise lethal experimental infection with C. neoformans serotype A. Thus, we determined the efficacy of immunization with C. neoformans strain H99γ to elicit broad-spectrum protection in BALB/c mice against multiple disparate Cryptococcus serotypes. We observed significantly increased survival rates and significantly decreased pulmonary fungal burden in H99γ immunized mice challenged with Cryptococcus serotypes A, B, or D compared to heat-killed H99γ (HKH99γ) immunized mice. Results indicated that prolonged protection against Cryptococcus serotypes B or D in H99γ immunized mice was CD4+ T cell dependent and associated with the induction of predominantly Th1-type cytokine responses. Interestingly, immunization with H99γ did not elicit greater protection against challenge with the Cryptococcus serotype C tested either due to low overall virulence of this strain or enhanced capacity of this strain to evade host immunity. Altogether, these studies provide “proof-of-concept” for the development of a cryptococcal vaccine that provides cross-protection against multiple disparate serotypes of Cryptococcus. PMID:29163469

Passive immunization of Pacific herring against viral hemorrhagic septicemia.

USGS Publications Warehouse

Hershberger, P.K.; Gregg, J.L.; Grady, C.A.; LaPatra, S.E.; Winton, J.R.

2011-01-01

The plasma of Pacific herring Clupea pallasii that survived laboratory-induced viral hemorrhagic septicemia (VHS) epizootics contained humoral substances that, when injected into naive animals, conferred passive immunity against the disease. Among groups exposed to viral hemorrhagic septicemia virus (VHSV), injection of donor plasma from VHS survivors resulted in significantly greater survival (50%) and significantly lower tissue titers (1.5 x 10(5) plaque-forming units [PFU]/g) than the injection of plasma from VHSV-naive donors (6% survival; 3.7 x 10(6) PFU/g). Additionally, the magnitude of the protective immune response increased during the postexposure period; plasma that was collected from survivors at 123 d postexposure (931 degree-days) provided greater protection than plasma collected from survivors at 60 d postexposure (409 degree-days). These results provide proof of concept that the VHSV exposure history of Pacific herring populations can be determined post hoc; furthermore, the results can be used as the foundation for developing additional high-throughput diagnostic techniques that may be effective at quantifying herd immunity and forecasting the potential for future VHS epizootics in populations of wild Pacific herring.

PD-1 immune checkpoint blockade promotes brain leukocyte infiltration and diminishes cyst burden in a mouse model of Toxoplasma infection.

PubMed

Xiao, Jianchun; Li, Ye; Yolken, Robert H; Viscidi, Raphael P

2018-06-15

Tissue cysts, the hallmark of chronic Toxoplasma gondii infection, are predominantly located in the brain making clearance of the parasite difficult. Currently available anti-T. gondii drugs are ineffective on cysts and fail to prevent reactivation of latent toxoplasmosis. We examined whether abrogation of inhibitory signaling pathways that maintain T cells in an exhausted state can be exploited for treating T. gondii tissue cysts. By using a mouse model of chronic toxoplasmosis, we showed immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway results in a significant reduction in brain cyst number (77% lower). We showed leukocyte infiltration (CD3+ T cells, CD8+ T cells, and CD11b + cells) in the leptomeninges, choroid plexus, and subependymal tissue, which are known routes of entry of immune cells into the brain, and in proximal brain parenchyma. Our study provides proof of concept for blockade of immune checkpoint inhibitors as a therapy for chronic toxoplasmosis and potentially for other brain pathogens. Copyright © 2018 Elsevier B.V. All rights reserved.

Nowhere to run, or hide. Current economic downturn may exacerbate hospitals' weakness with buildings, technology costs, reimbursements.

PubMed

Becker, Cinda

2008-04-21

As the economy moves through what many believe is a recession, healthcare won't be immune, experts say. "I don't know much in the economy that is recession-proof, and I don't think healthcare is either," says W. David Bradford, left, a Medical University of South Carolina economics professor. Because of the current economic conditions, some systems are rethinking where they put their money.

AIDS (Acquired Immune Deficiency Syndrome) and Employment Discrimination

DTIC Science & Technology

1987-09-30

factors include: presence of cytomegalovirus, Epstein - Barr virus , or other herpes viruses ; exposure to hepatitis; iatrogenic effect of steroids and other...to the virus . If a person carries the antibodies it is proof that they have been exposed to the virus because the antibodies do not develop without...these tests screen for the antibodies and not the virus itself, persons infected with HIV who do not develop the antibodies will test negative. It

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

Krieg, R.

For future pressurized-water reactors, which should be designed against core-meltdown accidents, missiles generated inside the containment present a severe problem for its integrity. The masses and geometries of the missiles, as well as their velocities, may vary to a great extent. Therefore a reliable proof of the containment integrity is very difficult. In this article the potential sources of missiles are discussed, and the conclusion was reached that the generation of heavy missiles must be prevented. Steam explosions must not damage the reactor vessel head. Thus fragments of the head cannot become missiles that endanger the containment shell. Furthermore, duringmore » a melt-through failure of the reactor vessel under high pressure, the resulting forces must not catapult the whole vessel against the containment shell. Only missiles caused by hydrogen explosions may be tolerable, but shielding structures that protect the containment shell may be required. Further investigations are necessary. Finally, measures are described showing that the generation of heavy missiles can indeed be prevented. Investigations are currently being carried out that will confirm the strength of the reactor vessel head. In addition, a device for retaining the fragments of a failing reactor vessel is discussed.« less

Protection of medical and paramedical university students in Lebanon against measles, mumps, rubella and varicella: active measures are needed.

PubMed

Chamat, Soulaima; Salameh, Pascale; Haddad, Nabil; Berry, Atika; Chedid, Philippe; Bouharoun-Tayoun, Hasnaa

2011-08-01

In many countries, universities require students to either show a physician-certified proof of immunity or to get vaccinated against measles, mumps, rubella and varicella, prior to their registration in medical and paramedical majors. The objective of this study was to evaluate the need to implement this policy in Lebanon. A cross-sectional study was performed on students of the Lebanese University (LU), faculties of Medicine, Dentistry, Pharmacy and Public Health. The serological immunity status was assessed by determining specific antibody titer and the disease and vaccination history of 502 students was collected. Based on percentages of susceptibility, a cost-effectiveness analysis was performed to compare systematic vaccination without prior serological testing with selective vaccination of seronegative students. Percentages of individuals with serologically confirmed immunity against varicella, measles, rubella and mumps were 93%, 86%, 88% and 75% respectively, and 42% of the students were susceptible to at least one of the pathogens covered by the MMR vaccine. Compilation of 186 vaccination records indicated that only 19 students (10%) had been adequately vaccinated. Moreover, among those, 7 students (37%) were still unprotected against at least one virus. Systematic vaccination against MMR was found to be 4-5 times less expensive than selective vaccination, while selective vaccination of seronegative individuals was more cost-efficient for varicella. Since, in this population, very few individuals were able to present a proof of adequate vaccination, it is recommended to systematically vaccinate healthcare students in Lebanon against MMR. For varicella, selective vaccination after serological testing should be performed. Copyright © 2011 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Highly Protective, Non-infectious Vaccine Against Ebola Virus Challenge

DTIC Science & Technology

2016-07-01

Single-Injection Trivalent Filovirus 428 Vaccine: Proof of Concept Study in Outbred Guinea Pigs . J Infect Dis. 429 29. Murin, C. D., M. L. Fusco, Z...Jahrling, and J. F. Smith. 2000. Recombinant RNA replicons derived from attenuated 442 Venezuelan equine encephalitis virus protect guinea pigs and...platform, 65 including ease of production and characterization, absence of virus replication concerns and the 66 robust immune stimulatory activity

A resonance based model of biological evolution

NASA Astrophysics Data System (ADS)

Damasco, Achille; Giuliani, Alessandro

2017-04-01

We propose a coarse grained physical model of evolution. The proposed model 'at least in principle' is amenable of an experimental verification even if this looks as a conundrum: evolution is a unique historical process and the tape cannot be reversed and played again. Nevertheless, we can imagine a phenomenological scenario tailored upon state transitions in physical chemistry in which different agents of evolution play the role of the elements of a state transition like thermal noise or resonance effects. The abstract model we propose can be of help for sketching hypotheses and getting rid of some well-known features of natural history like the so-called Cambrian explosion. The possibility of an experimental proof of the model is discussed as well.

Image-guided cancer surgery using near-infrared fluorescence

PubMed Central

Vahrmeijer, Alexander L.; Hutteman, Merlijn; van der Vorst, Joost R.; van de Velde, C.J.H.; Frangioni, John V.

2013-01-01

Paradigm shifts in surgery arise when surgeons are empowered to perform surgery faster, better, and/or less expensively. Optical imaging that exploits invisible near-infrared fluorescent light has the potential to improve cancer surgery outcomes while minimizing anesthesia time and lowering healthcare costs. Because of this, the last few years have witnessed an explosion of proof-of-concept clinical trials in the field. In this review, we introduce the concept of near-infrared fluorescence imaging for cancer surgery, review the clinical trial literature to date, outline the key issues pertaining to imaging system and contrast agent optimization, discuss limitations and leverage, and provide a framework for making the technology available for the routine care of cancer patients in the near future. PMID:23881033

Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific Diseases: Implications for Organ Allo- and Xeno-Transplantation

PubMed Central

Zhou, Ming; Hara, Hidetaka; Dai, Yifan; Mou, Lisha; Cooper, David K. C.; Wu, Changyou; Cai, Zhiming

2016-01-01

Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease. Furthermore, we summarize how circulating organ-specific miRNAs may have advantages over conventional methods for monitoring immune rejection in organ transplantation. Finally, we discuss the implications and challenges of applying miRNA to monitor organ survival and immune rejection in allo- or xeno-transplantation. PMID:27490531

Understanding Autoimmunity of Vitiligo and Alopecia Areata

PubMed Central

Rork, Jillian F.; Rashighi, Mehdi; Harris, John E.

2016-01-01

Purpose of review Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include non-targeted approaches such as corticosteroids, topical calcineurin inhibitors, narrow band UVB phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. Recent findings Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFN-γ, IFN-γ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. Summary The identification of IFN-γ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials. PMID:27191524

Correlative Gene Expression to Protective Seroconversion in Rift Valley Fever Vaccinates.

PubMed

Laughlin, Richard C; Drake, Kenneth L; Morrill, John C; Adams, L Garry

2016-01-01

Rift Valley fever Virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease, Rift Valley fever (RVF). In both humans and livestock, protective immunity can be achieved through vaccination. Earlier and more recent vaccine trials in cattle and sheep demonstrated a strong neutralizing antibody and total IgG response induced by the RVF vaccine, authentic recombinant MP-12 (arMP-12). From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with arMP-12. While the serology and protective response induced by arMP-12 has been studied, little attention has been paid to the underlying molecular and genetic events occurring prior to the serologic immune response. To address this, we isolated RNA from whole blood of vaccinated calves over a time course of 21 days before and after vaccination with arMP-12. The time course RNAs were sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to the vaccine induced immune response and its regulation. Additional bioinformatic analyses identified a correlative relationship between specific host immune response genes and protective immunity prior to the detection of protective serum neutralizing antibody responses. These results contribute an important proof of concept for identifying molecular and genetic components underlying the immune response to RVF vaccination and protection prior to serologic detection.

T cells for viral infections after allogeneic hematopoietic stem cell transplant

PubMed Central

Heslop, Helen E.

2016-01-01

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing “off the shelf” approaches. PMID:27207801

Overcoming immune tolerance in chronic hepatitis B by therapeutic vaccination.

PubMed

Dembek, Claudia; Protzer, Ulrike; Roggendorf, Michael

2018-05-08

The currently used nucleoside analogs (i.e. entecavir and tenofovir) with high barrier-to-resistance efficiently suppress viral replication, limit inflammation and reduce the sequelae of chronic hepatitis B, but cannot cure the disease and thus have to be applied long-term. Therapeutic vaccination as an approach to cure chronic hepatitis B has shown promising pre-clinical results, nevertheless the proof of its efficacy in clinical trials is still missing. This may be partially due to suboptimal vaccine design. A main obstacle in chronic hepatitis B, however, is the high load of viral antigens expressed and secreted, which has been proposed to cause antigen-specific immune tolerance. Reduction of the viral antigen load is therefore considered a key factor for success of immune-based therapies. Although nucleoside analogs do not reduce viral antigen expression, new antiviral strategies are becoming available. Targeting viral translation by siRNA or targeting release of HBsAg from infected hepatocytes by nucleic acid polymers both reduce the antigen load. They may be considered as pre-treatment for therapeutic vaccination to increase the potential to elicit an HBV-specific immune response able to control and cure chronic HBV infection. Copyright © 2018 Elsevier B.V. All rights reserved.

Neuroendocrine mechanisms for immune system regulation during stress in fish.

PubMed

Nardocci, Gino; Navarro, Cristina; Cortés, Paula P; Imarai, Mónica; Montoya, Margarita; Valenzuela, Beatriz; Jara, Pablo; Acuña-Castillo, Claudio; Fernández, Ricardo

2014-10-01

In the last years, the aquaculture crops have experienced an explosive and intensive growth, because of the high demand for protein. This growth has increased fish susceptibility to diseases and subsequent death. The constant biotic and abiotic changes experienced by fish species in culture are challenges that induce physiological, endocrine and immunological responses. These changes mitigate stress effects at the cellular level to maintain homeostasis. The effects of stress on the immune system have been studied for many years. While acute stress can have beneficial effects, chronic stress inhibits the immune response in mammals and teleost fish. In response to stress, a signaling cascade is triggered by the activation of neural circuits in the central nervous system because the hypothalamus is the central modulator of stress. This leads to the production of catecholamines, corticosteroid-releasing hormone, adrenocorticotropic hormone and glucocorticoids, which are the essential neuroendocrine mediators for this activation. Because stress situations are energetically demanding, the neuroendocrine signals are involved in metabolic support and will suppress the "less important" immune function. Understanding the cellular mechanisms of the neuroendocrine regulation of immunity in fish will allow the development of new pharmaceutical strategies and therapeutics for the prevention and treatment of diseases triggered by stress at all stages of fish cultures for commercial production. Copyright © 2014 Elsevier Ltd. All rights reserved.

A malaria vaccine for travelers and military personnel: Requirements and top candidates.

PubMed

Teneza-Mora, Nimfa; Lumsden, Joanne; Villasante, Eileen

2015-12-22

Malaria remains an important health threat to non-immune travelers with the explosive growth of global travel. Populations at high risk of acquiring malaria infections include once semi-immune travelers who visit friends and relatives, military forces, business travelers and international tourists with destinations to sub-Saharan Africa, where malaria transmission intensity is high. Most malaria cases have been associated with poor compliance with existing preventive measures, including chemoprophylaxis. High risk groups would benefit immensely from an efficacious vaccine to protect them against malaria infection and together make up a sizable market for such a vaccine. The attributes of an ideal malaria vaccine for non-immune travelers and military personnel include a protective efficacy of 80% or greater, durability for at least 6 months, an acceptable safety profile and compatibility with existing preventive measures. It is very likely that a malaria vaccine designed to effectively prevent infection and clinical disease in the non-immune traveler and military personnel will also protect semi-immune residents of malaria-endemic areas and contribute to malaria elimination by reducing or blocking malaria transmission. The RTS,S vaccine (GlaxoSmithKline) and the PfSPZ Vaccine (Sanaria Inc) are the leading products that would make excellent vaccine candidates for these vulnerable populations. Published by Elsevier Ltd.

[Auto-immune disorders as a possible cause of neuropsychiatric syndromes].

PubMed

Martinez-Martinez, P; Molenaar, P C; Losen, M; Hoffmann, C; Stevens, J; de Witte, L D; van Amelsvoort, T; van Os, J; Rutten, B P F

2015-01-01

Changes that occur in the behaviour of voltage-gated ion channels and ligand-gated receptor channels due to gene mutations or auto-immune attack are the cause of channelopathies in the central and peripheral nervous system. Although the relation between molecular channel defects and clinical symptoms has been explained in the case of many neuromuscular channelopathies, the pathophysiology of auto-immunity in neuropsychiatric syndromes is still unclear. To review recent findings regarding neuronal auto-immune reactions in severe neuropsychiatric syndromes. Using PubMed, we consulted the literature published between 1990 and August 2014 relating to the occurrence of auto-immune antibodies in severe and persistent neuropsychiatric syndromes. Auto-antibodies have only limited access to the central nervous system, but if they do enter the system they can, in some cases, cause disease. We discuss recent findings regarding the occurrence of auto-antibodies against ligand-activated receptor channels and potassium channels in neuropsychiatric and neurological syndromes, including schizophrenia and limbic encephalitis. Although the occurrence of several auto-antibodies in schizophrenia has been confirmed, there is still no proof of a causal relationship in the syndrome. We still have no evidence of the prevalence of auto-immunity in neuropsychiatric syndromes. The discovery that an antibody against an ion channel is associated with some neuropsychiatric disorders may mean that in future it will be possible to treat patients by means of immunosuppression, which could lead to an improvement in a patient's cognitive abilities.

Writing a review article - Are you making these mistakes?

PubMed

Daldrup-Link, Heike E

2018-01-01

An explosion of scientific publications over the last decades has increased the need for review articles: Carefully crafted scientific review articles can provide the novice reader with an overview of a new subject and provide the expert with a synthesis of scientific evidence, proof of reproducibility of published data and pooled estimates of common truth through meta-analyses. Unfortunately, while there are ample presentations and published guidelines for the preparation of scientific articles available, detailed information about how to properly prepare scientific review articles is relatively scarce. This perspective summarizes possible mistakes that can lead to misinformation in scientific review articles with the goal to help authors to improve the scientific contribution of their review article and thereby, increase the respective value of these articles for the scientific community.

Polyethylenimine-based micro/nanoparticles as vaccine adjuvants

PubMed Central

Shen, Chen; Li, Jun; Zhang, Yi; Li, Yuce; Shen, Guanxin; Zhu, Jintao; Tao, Juan

2017-01-01

Vaccines have shown great success in treating and preventing tumors and infections, while adjuvants are always demanded to ensure potent immune responses. Polyethylenimine (PEI), as one of the well-studied cationic polymers, has been used as a transfection reagent for decades. However, increasing evidence has shown that PEI-based particles are also capable of acting as adjuvants. In this paper, we briefly review the physicochemical properties and the broad applications of PEI in different fields, and elaborate on the intracellular processes of PEI-based vaccines. In addition, we sum up the proof of their in vivo and clinical applications. We also highlight some mechanisms proposed for the intrinsic immunoactivation function of PEI, followed by the challenges and future perspectives of the applications of PEI in the vaccines, as well as some strategies to elicit the desirable immune responses. PMID:28814862

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

PubMed Central

Tchakouté, Virginia L.; Graham, Simon P.; Jensen, Siv Aina; Makepeace, Benjamin L.; Nfon, Charles K.; Njongmeta, Leo M.; Lustigman, Sara; Enyong, Peter A.; Tanya, Vincent N.; Bianco, Albert E.; Trees, Alexander J.

2006-01-01

Onchocerciasis (river blindness) is a major parasitic disease of humans in sub-Saharan Africa caused by the microfilarial stage of the nematode Onchocerca volvulus. Using Onchocerca ochengi, a closely related species which infects cattle and is transmitted by the same black fly vector (Simulium damnosum sensu lato) as O. volvulus, we have conducted longitudinal studies after either natural field exposure or experimental infection to determine whether, and under what circumstances, protective immunity exists in onchocerciasis. On the basis of the adult worm burdens (nodules) observed, we determined that cattle reared in endemic areas without detectable parasites (putatively immune) were significantly less susceptible to heavy field challenge than age-matched, naïve controls (P = 0.002), whereas patently infected cattle, cured of infection by adulticide treatment with melarsomine, were fully susceptible. Cattle immunized with irradiated third-stage larvae were significantly protected against experimental challenge (100% reduction in median nodule load, P = 0.003), and vaccination also conferred resistance to severe and prolonged field challenge (64% reduction in median nodule load, P = 0.053; and a significant reduction in microfilarial positivity rates and density, P < 0.05). These results constitute evidence of protective immunity in a naturally evolved host–Onchocerca sp. relationship and provide proof-of-principle for immunoprophylaxis under experimental and field conditions. PMID:16585501

Personalized immune-interception of cancer and the battle of two adaptive systems--when is the time right?

PubMed

Dhodapkar, Madhav V

2013-03-01

A growing body of evidence points to a coevolutionary model of cancer, wherein the cross-talk between tumor cells (or their subclones) and the host determine the malignant potential of individual tumors. Most of this natural history is clinically invisible and includes preneoplastic states. The capacity of the immune system to recognize these incipient lesions provides the basis for targeting them immunologically to arrest the development of preneoplasia toward clinical cancer. Kimura and colleagues provide evidence of immunogenicity of a potential cancer vaccine in patients with a history of advanced colon adenomas. These studies provide proof-of-principle or feasibility of such an approach in the clinic. Here, we discuss emerging opportunities and challenges in harnessing the immune system to "intercept" the precursor or preneoplastic lesions. Both cancer cells as well as the immune system represent independent and complex systems with plasticity and adaptive potential. It is therefore likely that specific aspects of the cross-talk between tumor cells and host may differ between individual tumors and determine the evolution of both tumors and the host response. We try to make the case to consider individualized approaches based on the genetic make-up of tumor cells and properties of the host response. Such strategies may be needed to optimally position the immune system to prevent cancers. ©2013 AACR.

Immunotherapy targeting immune check-point(s) in brain metastases.

PubMed

Di Giacomo, Anna Maria; Valente, Monica; Covre, Alessia; Danielli, Riccardo; Maio, Michele

2017-08-01

Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype. These observations remain to be validated in larger clinical trials eventually designed also to address the efficacy of therapeutic mAb to immune check-point(s) within multimodality therapies for brain metastases. Noteworthy, the initial proofs of efficacy on immunotherapy in central nervous system metastases are already fostering clinical trials investigating its therapeutic potential also in primary brain tumors. We here review ongoing immunotherapeutic approaches to brain metastases and primary brain tumors, and the foreseeable strategies to overcome their main biologic hurdles and clinical challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physicochemical and immunological characterization of chitosan-coated bacteriophage nanoparticles for in vivo mycotoxin modeling.

PubMed

de Andrade, Carla Yoko Tanikawa; Yamanaka, Isabel; Schlichta, Laís S; Silva, Sabrina Karim; Picheth, Guilherme F; Caron, Luiz Felipe; de Moura, Juliana; de Freitas, Rilton Alves; Alvarenga, Larissa Magalhães

2018-04-01

To propose a novel modeling of aflatoxin immunization and surrogate toxin conjugate from AFB1 vaccines, an immunogen based on the mimotope, (i.e. a peptide-displayed phage that mimics aflatoxins epitope without toxin hazards) was designed. The recombinant phage 3P30 was identified by phage display technology and exhibited the ability to bind, dose dependent, specifically to its cognate target - anti-AFB1 antibody. In immunization assay, the phage-displayed mimotope and its peptide chemically synthesized were able to induce specific anti-AFB1 antibodies, indicating the proof of concept for aflatoxin mimicry. Furthermore, the phage 3P30 was homogeneously coated with chitosan, which also provided a tridimensional matrix network for mucosal delivery. After intranasal immunization, chitosan coated phages improved specific immunogenicity compared to the free antigen. It can be concluded that affinity-selected phage may contribute to the rational design of epitope-based vaccines in a prospectus for the control of aflatoxins and possibly other mycotoxins, and that chitosan coating improved the vectorization of the vaccine by the mucosal route. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inactivated coxsackievirus A10 experimental vaccines protect mice against lethal viral challenge.

PubMed

Shen, Chaoyun; Liu, Qingwei; Zhou, Yu; Ku, Zhiqiang; Wang, Lili; Lan, Ke; Ye, Xiaohua; Huang, Zhong

2016-09-22

Coxsackievirus A10 (CVA10) has become one of the major causative agents of hand, foot and mouth disease (HFMD). It is now recognized that CVA10 should be targeted for vaccine development. We report here that β-propiolactone inactivated whole-virus based CVA10 vaccines can elicit protective immunity in mice. We prepared two inactivated CVA10 experimental vaccines derived from the prototype strain CVA10/Kowalik and from a clinical isolate CVA10/S0148b, respectively. Immunization with the experimental vaccines elicited CVA10-specific serum antibodies in mice. The antisera from vaccinated mice could potently neutralize in vitro infection with either homologous or heterologous CVA10 strains. Importantly, passive transfer of the anti-CVA10 sera protected recipient mice against CVA10/Kowalik or CVA10/S0148b infections. Moreover, active immunization with the inactivated vaccines also conferred protection against homologous and heterologous infections in mice. Collectively, our results demonstrate the proof-of-concept for inactivated whole-virus based CVA10 vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants.

PubMed

Sellitto, Maria; Bai, Guoyun; Serena, Gloria; Fricke, W Florian; Sturgeon, Craig; Gajer, Pawel; White, James R; Koenig, Sara S K; Sakamoto, Joyce; Boothe, Dustin; Gicquelais, Rachel; Kryszak, Deborah; Puppa, Elaine; Catassi, Carlo; Ravel, Jacques; Fasano, Alessio

2012-01-01

Celiac disease (CD) is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8) and the environmental trigger (gluten) are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late) on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to deciphering the role of the gut microbiota on CD onset.

Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study.

PubMed

Cabel, L; Riva, F; Servois, V; Livartowski, A; Daniel, C; Rampanou, A; Lantz, O; Romano, E; Milder, M; Buecher, B; Piperno-Neumann, S; Bernard, V; Baulande, S; Bieche, I; Pierga, J Y; Proudhon, C; Bidard, F-C

2017-08-01

Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB. This prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria. ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5-41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5-94.9, P = 0.004). This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The evolution and regulation of the mucosal immune complexity in the basal chordate amphioxus.

PubMed

Huang, Shengfeng; Wang, Xin; Yan, Qingyu; Guo, Lei; Yuan, Shaochun; Huang, Guangrui; Huang, Huiqing; Li, Jun; Dong, Meiling; Chen, Shangwu; Xu, Anlong

2011-02-15

Both amphioxus and the sea urchin encode a complex innate immune gene repertoire in their genomes, but the composition and mechanisms of their innate immune systems, as well as the fundamental differences between two systems, remain largely unexplored. In this study, we dissect the mucosal immune complexity of amphioxus into different evolutionary-functional modes and regulatory patterns by integrating information from phylogenetic inferences, genome-wide digital expression profiles, time course expression dynamics, and functional analyses. With these rich data, we reconstruct several major immune subsystems in amphioxus and analyze their regulation during mucosal infection. These include the TNF/IL-1R network, TLR and NLR networks, complement system, apoptosis network, oxidative pathways, and other effector genes (e.g., peptidoglycan recognition proteins, Gram-negative binding proteins, and chitin-binding proteins). We show that beneath the superficial similarity to that of the sea urchin, the amphioxus innate system, despite preserving critical invertebrate components, is more similar to that of the vertebrates in terms of composition, expression regulation, and functional strategies. For example, major effectors in amphioxus gut mucous tissue are the well-developed complement and oxidative-burst systems, and the signaling network in amphioxus seems to emphasize signal transduction/modulation more than initiation. In conclusion, we suggest that the innate immune systems of amphioxus and the sea urchin are strategically different, possibly representing two successful cases among many expanded immune systems that arose at the age of the Cambrian explosion. We further suggest that the vertebrate innate immune system should be derived from one of these expanded systems, most likely from the same one that was shared by amphioxus.

Development and pre-clinical evaluation in the swine model of a mucosal vaccine tablet for human influenza viruses: A proof-of-concept study.

PubMed

Busignies, V; Simon, G; Mollereau, G; Bourry, O; Mazel, V; Rosa-Calatrava, M; Tchoreloff, P

2018-03-01

Liquid vaccine formulations present some disadvantages such as stability problems, cold chain requirement or administration by trained personnel. Vaccine formulated as tablets would present a wide range of progress such as an increase stability that would facilitate the administration, the distribution and the storage of vaccine formulations. This work investigates the possibility to develop a mucosal tablet vaccine for human influenza viruses. The tablets were tested in vitro for biological efficacy and stability and in vivo in swine as a model for influenza A virus immunity. First, the ability to produce by compaction a stable vaccine with a preserved antigen was demonstrated. In a second part, vaccine tablets were used to immunize pigs. After positioning the tablets on the buccal mucosa, the animals were challenged by inoculation of the A/H1N1 pandemic virus. The responses were compared to those observed in animals vaccinated intramuscularly with the commercial liquid vaccine. It was observed signs of priming of the pig's immune system with vaccine tablets, even if the immune response stayed lower than vaccination by intramuscular route. Thus, we present attractive results that indicate a promising potential for mucosal vaccine tablets. Copyright © 2018 Elsevier B.V. All rights reserved.

T cells for viral infections after allogeneic hematopoietic stem cell transplant.

PubMed

Bollard, Catherine M; Heslop, Helen E

2016-06-30

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches. © 2016 by The American Society of Hematology.

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation.

PubMed

Polak, Marta E; Ung, Chuin Ying; Masapust, Joanna; Freeman, Tom C; Ardern-Jones, Michael R

2017-04-06

Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis. Applying Boolean logic we assembled a Petri net-based model of the IRF-GRN which provides molecular pathway predictions for the induction of different transcriptional programmes in LCs. In silico simulations performed after model parameterisation with transcription factor expression values predicted that human LC activation of antigen-specific CD8 T cells would be differentially regulated by epidermal cytokine induction of specific IRF-controlled pathways. This was confirmed by in vitro measurement of IFN-γ production by activated T cells. As a proof of concept, this approach shows that stochastic modelling of a specific immune networks renders transcriptome data valuable for the prediction of functional outcomes of immune responses.

Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.

PubMed

Kulshreshtha, Parul; Tiwari, Ashutosh; Priyanka; Joon, Shikha; Sinha, Subrata; Bhatnagar, Rakesh

2015-12-01

Hybridomas were created using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor). Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immnized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H10 and H8) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). Single chain variable fragment (LETscFv) was derived from H10 hybridoma. H11 was found to have disease-enhancing property. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature. This in vitro abrogation of disease-enhancement provides the proof of concept that in polyclonal sera the disease enhancing character of a fraction of antibodies is overshadowed by the protective nature of the rest of the antibodies generated on active immunization. Copyright © 2015. Published by Elsevier Ltd.

Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8+ T-cell responses and immune memory

PubMed Central

Wu, Junjie; Waxman, David J

2015-01-01

Cancer chemotherapy using cytotoxic drugs can induce immunogenic tumor cell death; however, dosing regimens and schedules that enable single-agent chemotherapy to induce adaptive immune-dependent ablation of large, established tumors with activation of long-term immune memory have not been identified. Here, we investigate this issue in a syngeneic, implanted GL261 glioma model in immune-competent mice given cyclophosphamide on a 6-day repeating metronomic schedule. Two cycles of metronomic cyclophosphamide treatment induced sustained upregulation of tumor-associated CD8+ cytotoxic T lymphocyte (CTL) cells, natural killer (NK) cells, macrophages, and other immune cells. Expression of CTL- and NK–cell-shared effectors peaked on Day 6, and then declined by Day 9 after the second cyclophosphamide injection and correlated inversely with the expression of the regulatory T cell (Treg) marker Foxp3. Sustained tumor regression leading to tumor ablation was achieved after several cyclophosphamide treatment cycles. Tumor ablation required CD8+ T cells, as shown by immunodepletion studies, and was associated with immunity to re-challenge with GL261 glioma cells, but not B16-F10 melanoma or Lewis lung carcinoma cells. Rejection of GL261 tumor re-challenge was associated with elevated CTLs in blood and increased CTL infiltration in tumors, consistent with the induction of long-term, specific CD8+ T-cell anti-GL261 tumor memory. Co-depletion of CD8+ T cells and NK cells did not inhibit tumor regression beyond CD8+ T-cell depletion alone, suggesting that the metronomic cyclophosphamide-activated NK cells function via CD8a+ T cells. Taken together, these findings provide proof-of-concept that single-agent chemotherapy delivered on an optimized metronomic schedule can eradicate large, established tumors and induce long-term immune memory. PMID:26137402

HIV infection and specific mucosal immunity: workshop 4B.

PubMed

Challacombe, S J; Fidel, P L; Tugizov, S; Tao, L; Wahl, S M

2011-04-01

Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues-namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.

Rapid identification of genes controlling virulence and immunity in malaria parasites

PubMed Central

Xangsayarath, Phonepadith; Tang, Jianxia; Yahata, Kazuhide; Zoungrana, Augustin; Mitaka, Hayato; Acharjee, Arita; Datta, Partha P.; Hunt, Paul; Carter, Richard; Kaneko, Osamu; Mustonen, Ville; Pain, Arnab

2017-01-01

Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites. PMID:28704525

Combinatorial contextualization of peptidic epitopes for enhanced cellular immunity.

PubMed

Ito, Masaki; Hayashi, Kazumi; Adachi, Eru; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

2014-01-01

Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our "motif-programming" approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment.

Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders.

PubMed

Sun, Yu; Narayan, Vaibhav A; Wittenberg, Gayle M

2016-10-21

Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs. Here we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants. We found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants. These findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at the immune system may be helpful in relieving depressive symptoms, and suggest that it may be of value to test immune-modulators for antidepressant-like activity in future proof-of-concept studies.

Full pillar extraction at the Kathleen Mine with mobile roof supports

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

Grimm, E.S.

1994-12-31

The Voest Alpine Breaker Line Supports (ABLS) resemble self-propelled longwall shields. Each individual unit consists of four hydraulic legs extending from the base of the unit, pressing a solid flat canopy against the mine roof. Each support unit is capable of exerting 606 tons of force against the roof. A chain curtain on the sides and rear protects the interior of the support from falling rock. The internal scissoring lemniscate design allows for parallel movement of the canopy as it is raised or lowered. Each ABLS has 750 feet of 4 AWG trailing cable to supply 480 volts AC tomore » a permissible controller and a 40 hp explosion-proof electrical motor. The hydraulic pump and reservoir are self-contained and protected with an automatic fire suppression system.« less

Low-cost detection of RC-IED activation signals in VHF band

NASA Astrophysics Data System (ADS)

Camargo Suarez, Victor Hugo; Marulanda B., Jose Ignacio

2014-05-01

The proliferation of Radio Controlled Improvised Explosive Devices (RC-IED) is a growing threat around the world. The ease of construction and low cost of these devices are transforming common things in lethal tramps. The fight against this threats normally involves the use of sophisticated and expensive equipment of Electronic Warfare based on high speed DSP systems, just to detect the presence of detonation signals. In this work is showed how to find activation signals based on the characteristic of the power in a specific band and the previous knowledge about the detonation signals. As proof of concept we have taken the information about the RC-IEDs used in the Colombian conflict and develop an algorithm to find detonation signals based on the measured power in frequencies between 136 MHz and 174 MHz (2 meter civil band)

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

PubMed Central

Perez-Vilar, Silvia; Weibel, Daniel; Sturkenboom, Miriam; Black, Steven; Maure, Christine; Castro, Jose Luis; Bravo-Alcántara, Pamela; Dodd, Caitlin N.; Romio, Silvana A.; de Ridder, Maria; Nakato, Swabra; Molina-León, Helvert Felipe; Elango, Varalakshmi; Zuber, Patrick L.F.

2017-01-01

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders´Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs. PMID:28558983

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination.

PubMed

Perez-Vilar, Silvia; Weibel, Daniel; Sturkenboom, Miriam; Black, Steven; Maure, Christine; Castro, Jose Luis; Bravo-Alcántara, Pamela; Dodd, Caitlin N; Romio, Silvana A; de Ridder, Maria; Nakato, Swabra; Molina-León, Helvert Felipe; Elango, Varalakshmi; Zuber, Patrick L F

2018-01-08

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders'Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs. Copyright © 2017 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Re-evaluation of the immunological Big Bang.

PubMed

Flajnik, Martin F

2014-11-03

Classically the immunological 'Big Bang' of adaptive immunity was believed to have resulted from the insertion of a transposon into an immunoglobulin superfamily gene member, initiating antigen receptor gene rearrangement via the RAG recombinase in an ancestor of jawed vertebrates. However, the discovery of a second, convergent adaptive immune system in jawless fish, focused on the so-called variable lymphocyte receptors (VLRs), was arguably the most exciting finding of the past decade in immunology and has drastically changed the view of immune origins. The recent report of a new lymphocyte lineage in lampreys, defined by the antigen receptor VLRC, suggests that there were three lymphocyte lineages in the common ancestor of jawless and jawed vertebrates that co-opted different antigen receptor supertypes. The transcriptional control of these lineages during development is predicted to be remarkably similar in both the jawless (agnathan) and jawed (gnathostome) vertebrates, suggesting that an early 'division of labor' among lymphocytes was a driving force in the emergence of adaptive immunity. The recent cartilaginous fish genome project suggests that most effector cytokines and chemokines were also present in these fish, and further studies of the lamprey and hagfish genomes will determine just how explosive the Big Bang actually was. Copyright © 2014 Elsevier Ltd. All rights reserved.

Proof-of-principle contraband detection system for nonintrusive inspection

NASA Astrophysics Data System (ADS)

Sredniawski, Joseph J.; Debiak, T.; Kamykowski, E.; Rathke, John E.; Schmor, P.; Milton, Bill; Stanford, G.; Rogers, Joel; Boyd, J.; Brondo, J.

1997-02-01

A proof-of-principle (POP) contraband detection system (CDS), is under construction at Northrop Grumman's Advanced Technology and Development Center. We employ gamma resonance absorption to detect nitrogen or chlorine in explosives and certain forms of illegal drugs. Using tomography, 3D images of the total density and selected element density are generated. These characteristics together may be utilized with considerable confidence in determining if contraband is present in baggage or cargo. The CDS employs a high current DC electrostatic accelerator that provides a beam of proton sat either 1.75 or 1.89 MeV. These high energy particles impinge upon a target coated with 13C or 34S. The resultant resonant gamma rays are preferentially absorbed in either 14N or 35Cl. Because of the penetrating power of the gamma rays, this approach can be utilized for inspection of fully loaded aircraft containers such as the LD3. With proper design for handling baggage and with certain CDS design features not present in the POP, throughputs approaching 2000 bags/hour are estimated. Furthermore, the technology being developed for the CDS accelerator may have other applications such as for Boron Neutron Capture Therapy or Neutron Radiography. Our current program calls for testing of the POP CDS by late 1996. This paper presents the overall design, and characteristics of the CDS POP and the status of the program.

Recombinant proteins of Zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice.

PubMed

Lehrer, Axel T; Wong, Teri-Ann S; Lieberman, Michael M; Humphreys, Tom; Clements, David E; Bakken, Russell R; Hart, Mary Kate; Pratt, William D; Dye, John M

2018-05-24

Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death. Questions remain with regard to the few survivors of infection, who manage to mount an effective adaptive immune response. These questions concern the humoral and cellular components of this response, and whether such a response can be elicited by an appropriate prophylactic vaccine. The data reported herein describe the production and evaluation of a recombinant subunit Ebola virus vaccine candidate consisting of insect cell expressed Zaire ebolavirus (EBOV) surface glycoprotein (GP) and the matrix proteins VP24 and VP40. The recombinant subunit proteins are shown to be highly immunogenic in mice, yielding both humoral and cellular responses, as well as highly efficacious, providing up to 100% protection against a lethal challenge with live virus. These results demonstrate proof of concept for such a recombinant non-replicating vaccine candidate in the mouse model of EBOV which helps to elucidate immune correlates of protection and warrants further development. Copyright © 2017 Elsevier Ltd. All rights reserved.

[History of development of the live poliomyelitis vaccine from Sabin attenuated strains in 1959 and idea of poliomyelitis eradication].

PubMed

Lashkevich, V A

2013-01-01

In 1958 Poliomyelitis Institute in Moscow and Institute of Experimental Medicine in St. Petersburg received from A. Sabin the attenuated strains of poliomyelitis virus. The characteristics of the strains were thoroughly studied by A. A. Smorodintsev and coworkers. They found that the virulence of the strains fluctuated slightly in 10 consecutive passages through the intestine of the non-immune children. A part of the Sabin material was used by A. A. Smorodintsev and M. P. Chumakov in the beginning of 1959 for immunizing approximately 40000 children in Estonia, Lithuania, and Latvia. Epidemic poliomyelitis rate in these republics decreased from approximately 1000 cases yearly before vaccination to less than 20 in the third quarter of 1959. This was a convincing proof of the efficacy and safety of the vaccine from the attenuated Sabin strains. In 1959, according to A. Sabin's recommendation, a technology of live vaccine production was developed at the Poliomyelitis Institute, and several experimental lots of vaccine were prepared. In the second part of 1959, 13.5 million children in USSR were immunized. The epidemic poliomyelitis rate decreased 3-5 times in different regions without paralytic cases, which could be attributed to the vaccination. These results were the final proof of high efficiency and safety of live poliomyelitis vaccine from the attenuated Sabin strains. Based on these results, A. Sabin and M. P. Chumakov suggested in 1960 the idea of poliomyelitis eradication using mass immunization of children with live vaccine. 72 million persons up to 20 years old were vaccinated in USSR in 1960 with a 5 times drop in the paralytic rate. 50-year-long use of live vaccine results in poliomyelitis eradication in almost all countries worldwide. More than 10 million children were rescued from the death and palsy. Poliomyelitis eradication in a few countries where it still exists depends not on medical services but is defined by the attitude of their leaders to fight against poliomyelitis. In some developing countries the vaccination data are falsified, thereby threatening the polio epidemics reappearance and the virus spreading to other countries. Methods must be developed for detection and dealing with extremely rare persistent virus carriers. Because of all these constraints the outcome of poliomyelitis eradication at present is uncertain and vaccination must be continued. The world has become poliovaccine dependent.

Aerosol can puncture device operational test plan

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

Leist, K.J.

1994-05-03

Puncturing of aerosol cans is performed in the Waste Receiving and Processing Facility Module 1 (WRAP 1) process as a requirement of the waste disposal acceptance criteria for both transuranic (TRU) waste and low-level waste (LLW). These cans have contained such things as paints, lubricating oils, paint removers, insecticides, and cleaning supplies which were used in radioactive facilities. Due to Westinghouse Hanford Company (WHC) Fire Protection concerns of the baseline system`s fire/explosion proof characteristics, a study was undertaken to compare the baseline system`s design to commercially available puncturing devices. While the study found no areas which might indicate a riskmore » of fire or explosion, WHC Fire Protection determined that the puncturing system must have a demonstrated record of safe operation. This could be obtained either by testing the baseline design by an independent laboratory, or by substituting a commercially available device. As a result of these efforts, the commercially available Aerosolv can puncturing device was chosen to replace the baseline design. Two concerns were raised with the system. Premature blinding of the coalescing/carbon filter, due to its proximity to the puncture and draining operation; and overpressurization of the collection bottle due to its small volume and by blinding of the filter assembly. As a result of these concerns, testing was deemed necessary. The objective of this report is to outline test procedures for the Aerosolv.« less

Clinical Perspectives on Lupus Genetics: Advances and Opportunities

PubMed Central

James, Judith A.

2014-01-01

Synopsis In recent years, genome wide association studies have led to an explosion in the identification of regions containing confirmed genetic risk variants within complex human diseases, for example in systemic lupus erythematosus (SLE). Many of these strongest SLE genetic associations can be divided into groups based upon their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination (a process of marking proteins for degradation), DNA degradation, innate immunity, cellular immunity (B cell, T cell, neutrophil, monocytes), lymphocyte development, and antigen presentation. Recent advances have also demonstrated several genetic associations with SLE subphenotypes and subcriteria, such as autoantibody production, lupus nephritis, serositis, and arthritis. Despite the broad range of lupus genetic studies to date, many areas for further exploration remain to move lupus genetic studies toward clinically informative endpoints, such as identifying individuals at the greatest risk of end-organ damage, early mortality or poor response to a specific therapeutic regimen. PMID:25034154

Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation

PubMed Central

Almeida, Freya M Freyre; Blanco, Aracelys; Trujillo, Heidy; Hernández, Dunia; García, Daymir; Alba, José S; Abad, Matilde López; Merino, Nelson; Lobaina, Yadira

2016-01-01

ABSTRACT The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys. Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study. How to cite this article Freyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation. Euroasian J Hepato-Gastroenterol 2016;6(1):25-30. PMID:29201720

A novel DNA vaccine for reduction of PRRSV-induced negative immunomodulatory effects: A proof of concept.

PubMed

Suradhat, Sanipa; Wongyanin, Piya; Kesdangsakonwut, Sawang; Teankum, Komkrich; Lumyai, Mongkol; Triyarach, Sittikorn; Thanawongnuwech, Roongroje

2015-07-31

Viral-induced interleukin (IL)-10 and regulatory T lymphocytes (Tregs) are believed to play a major role in shaping the immunological and clinical outcomes following Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infection. Recently, it has been shown that PRRSV nucleocapsid (N) protein can induce IL-10 production which is essential for induction of PRRSV-specific Tregs. We hypothesized that immunity to N protein should reduce PRRSV-induced negative immunomodulatory effects which will be essential for establishing proper anti-PRRSV immunity in infected pigs. To investigate the immunomodulatory effects of DNA vaccine encoding a linearized, truncated form of PRRSV-N protein (pORF7t) which was designed to preferentially induce cell-mediated immunity against PRRSV N protein. Immunomodulatory effects of the novel DNA vaccine were investigated in an experimental vaccinated-challenged model. In addition, long-term immunomodulatory effects of the DNA vaccine were investigated in vaccinated pigs kept at the PRRSV-positive environment until the end of the fattening period. Pigs were vaccinated either prior to or following natural PRRSV infection. The results indicated that pORF7t could modulate the anti-PRRSV immune responses and promote the control of viral replication in the vaccinated-challenged pigs. Immunized pigs exhibited increased numbers of PRRSV-specific activated CD4(+)CD25(+) lymphocytes, reduced numbers of PRRSV-specific Tregs, and rapid viral clearance following infection. In a long-term study, regardless of the time of vaccination, DNA vaccine could modulate the host immune responses, resulted in enhanced PRRSV-specific IFN-γ producing cells, and reduced numbers of PRRSV-specific Tregs, without evidence of enhanced antibody responses. No vaccine adverse reaction was observed throughout the study. This study revealed the novel concept that PRRSV-specific immunity can be modulated by induction of cell-mediated immunity against the nucleocapsid protein. This concept could potentially benefit the development of PRRSV management and control strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

PubMed Central

Losen, Mario; Martinez-Martinez, Pilar; Molenaar, Peter C.; Lazaridis, Konstantinos; Tzartos, Socrates; Brenner, Talma; Duan, Rui-Sheng; Luo, Jie; Lindstrom, Jon; Kusner, Linda

2015-01-01

Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice. PMID:25796590

Targeting IL-2: an unexpected effect in treating immunological diseases.

PubMed

Ye, Congxiu; Brand, David; Zheng, Song G

2018-01-01

Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.

Novel immunotherapy vaccine development.

PubMed

Jutel, Marek; Akdis, Cezmi A

2014-12-01

Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept - as well as large, multicenter clinical studies. The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

Resistance to hepatitis C virus: potential genetic and immunological determinants.

PubMed

Mina, Michael M; Luciani, Fabio; Cameron, Barbara; Bull, Rowena A; Beard, Michael R; Booth, David; Lloyd, Andrew R

2015-04-01

Studies of individuals who were highly exposed but seronegative (HESN) for HIV infection led to the discovery that homozygosity for the Δ32 deletion mutation in the CCR5 gene prevents viral entry into target cells, and is associated with resistance to infection. Additionally, evidence for protective immunity has been noted in some HESN groups, such as sex workers in The Gambia. Population studies of individuals at high risk for hepatitis C virus infection suggest that an HESN phenotype exists. The body of evidence, which suggests that protective immunity allows clearance of hepatitis C virus without seroconversion is growing. Furthermore, proof-of-principle evidence from in-vitro studies shows that genetic polymorphisms can confer resistance to establishment of infection. This Review discusses the possibility that genetic mutations confer resistance against hepatitis C virus, and also explores evidence for protective immunity, including via genetically programmed variations in host responses. The data generally strengthens the notion that investigations of naturally arising polymorphisms within the hepatitis C virus interactome, and genetic association studies of well characterised HESN individuals, could identify potential targets for vaccine design and inform novel therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Balneotherapy in rheumatic diseases--an overview of novel and known aspects.

PubMed

Lange, U; Müller-Ladner, U; Schmidt, K L

2006-04-01

Balneotherapeutic applications to treat rheumatic diseases have a long-term tradition and are based on established scientific principles, and the majority of rheumatic diseases most frequently include balneotherapy. However, as other therapeutic strategies, balneological interventions require scientific proof of their effect and efficacy. Notably, recent studies providing evidence of the thermic and chemical effects on the immune system and cytokine milieu have enforced the revival of the traditional balneological interventions. This review provides an overview of the known as well as the novel aspects of balneotherapy and their clinical relevance in the treatment of rheumatic diseases.

Effect of traditional Chinese medicine for treating human immunodeficiency virus infections and acquired immune deficiency syndrome: Boosting immune and alleviating symptoms.

PubMed

Zou, Wen; Wang, Jian; Liu, Ying

2016-01-01

To respond to the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) epidemic in China, the integration of antiretroviral therapy (ART) and traditional Chinese medicine (TCM) has important implications in health outcomes, especially in China where the use of TCM is widespread. The National Free TCM Pilot Program for HIV Infected People began in 5 provinces (Henan, Hebei, Anhui, Hubei, and Guangdong) in 2004, and quickly scaled up to 19 provinces, autonomous regions, and municipalities in China including some places with high prevalence, 26,276 adults have been treated thus far. Usually, people with HIV infection seek TCM for four main reasons: to enhance immune function, to treat symptoms, to improve quality of life, and to reduce side effects related to medications. Evidences from randomized controlled clinical trials suggested some beneficial effects of use of traditional Chinese herbal medicine for HIV infections and AIDS. More proofs from large, well-designed, rigorous trials is needed to give firm support. Challenges include interaction between herbs and antiretroviral drugs, stigma and discrimination. The Free TCM Program has made considerable progress in providing the necessary alternative care and treatment for HIV-infected people in China, and has strong government support for continued improvement and expansion, establishing and improving a work mechanism integrating Chinese and Western medicines.

Functionalized Iron Oxide Nanoparticles for Controlling the Movement of Immune Cells

PubMed Central

White, Ethan E; Pai, Alex; Weng, Yiming; Suresh, Anil K.; Van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M.

2015-01-01

Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed “cell box” was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain. PMID:25848983

Functionalized iron oxide nanoparticles for controlling the movement of immune cells.

PubMed

White, Ethan E; Pai, Alex; Weng, Yiming; Suresh, Anil K; Van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M

2015-05-07

Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed "cell box" was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.

An autologous dendritic cell canine mammary tumor hybrid-cell fusion vaccine.

PubMed

Bird, R Curtis; Deinnocentes, Patricia; Church Bird, Allison E; van Ginkel, Frederik W; Lindquist, Joni; Smith, Bruce F

2011-01-01

Mammary cancer is among the most prevalent canine tumors and frequently resulting in death due to metastatic disease that is highly homologous to human breast cancer. Most canine tumors fail to raise effective immune reactions yet, some spontaneous remissions do occur. Hybrid canine dendritic cell-tumor cell fusion vaccines were designed to enhance antigen presentation and tumor immune recognition. Peripheral blood-derived autologous dendritic cell enriched populations were isolated from dogs based on CD11c(+) expression and fused with canine mammary tumor (CMT) cells for vaccination of laboratory Beagles. These hybrid cells were injected into popliteal lymph nodes of normal dogs, guided by ultrasound, and included CpG-oligonucleotide adjuvants. Three rounds of vaccination were delivered. Significant IgG responses were observed in all vaccinated dogs compared to vehicle-injected controls. Canine IgG antibodies recognized shared CMT antigens as was demonstrated by IgG-recognition of three unrelated/independently derived CMT cell lines, and recognition of freshly isolated, unrelated, primary biopsy-derived CMT cells. A bias toward an IgG2 isotype response was observed after two vaccinations in most dogs. Neither significant cytotoxic T cell responses were detected, nor adverse or side-effects due to vaccination or due to the induced immune responses noted. These data provide proof-of-principle for this cancer vaccine strategy and demonstrate the presence of shared CMT antigens that promote immune recognition of mammary cancer.

Recent progress in immune-based interventions to prevent HIV-1 transmission to children.

PubMed

Voronin, Yegor; Jani, Ilesh; Graham, Barney S; Cunningham, Coleen K; Mofenson, Lynne M; Musoke, Philippa M; Permar, Sallie R; Scarlatti, Gabriella

2017-12-01

Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV-1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV-1 infection. Thus, for the global community to achieve elimination of new paediatric HIV-1 infections, innovative approaches need to be explored. Immune-based approaches to prevention of mother-to-child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS-free generation. Immune-based interventions to prevent MTCT of HIV-1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof-of-concept has been established over the last two decades that passively administered HIV-1 Env-specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune-based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast-Track 2030 goals to eliminate new paediatric HIV infections. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Vitiligo: Focus on Clinical Aspects, Immunopathogenesis, and Therapy.

PubMed

Boniface, Katia; Seneschal, Julien; Picardo, Mauro; Taïeb, Alain

2018-02-01

Vitiligo is an acquired chronic depigmenting disorder of the skin, with an estimated prevalence of 0.5% of the general population, characterized by the development of white macules resulting from a loss of epidermal melanocytes. The nomenclature has been revised after an extensive international work within the vitiligo global issues consensus conference, and vitiligo (formerly non-segmental vitiligo) is now a consensus umbrella term for all forms of generalized vitiligo. Two other subsets of vitiligo are segmental vitiligo and unclassified/undetermined vitiligo, which corresponds to focal disease and rare variants. A series of hypopigmented disorders may masquerade as vitiligo, and some of them need to be ruled out by specific procedures including a skin biopsy. Multiple mechanisms are involved in melanocyte disappearance, namely genetic predisposition, environmental triggers, metabolic abnormalities, impaired renewal, and altered inflammatory and immune responses. The auto-immune/inflammatory theory is the leading hypothesis because (1) vitiligo is often associated with autoimmune diseases; (2) most vitiligo susceptibility loci identified through genome-wide association studies encode immunomodulatory proteins; and (3) prominent immune cell infiltrates are found in the perilesional margin of actively depigmenting skin. However, other studies support melanocyte intrinsic abnormalities with poor adaptation of melanocytes to stressors leading to melanocyte instability in the basal layer, and release of danger signals important for the activation of the immune system. Recent progress in the understanding of immune pathomechanisms opens interesting perspectives for innovative treatment strategies. The proof of concept in humans of targeting of the IFNγ /Th1 pathway is much awaited. The interplay between oxidative stress and altered immune responses suggests that additional strategies aiming at limiting type I interferon activation pathway as background stabilizing therapies could be an interesting approach in vitiligo. This review covers classification and clinical aspects, pathophysiology with emphasis on immunopathogenesis, and promising therapeutic approaches.

In vitro flow-through assay for rapid detection of endotoxin in human sera: A proof-of-concept.

PubMed

Kalita, Prasanta; Chaturvedula, Lakshmi M; Sritharan, Venkataraman; Gupta, Shalini

2017-05-01

An increase in endotoxin concentration in the bloodstream can trigger activation of innate immune response leading to septic shock. There is currently no method available for rapid endotoxin detection at a patient's bedside. We demonstrate a simple, portable and cost-effective strategy to measure endotoxin levels in human serum within 5min using a flow-through assay. A drop of serum containing LPS was spotted on an endotoxin-affinity membrane placed over high-wicking absorbent pads. Subsequent addition of polymyxin B sulfate drug-conjugated gold nanoparticles allowed concentration-dependent visualization of spots by the naked eye in the clinically-relevant range of 10pg/mL to 10ng/mL. The results were quantified using a concentration-calibrated color chart and the assay performance was tested with archival plasma samples of 18 known septicemia patients. The results showed a reasonably good correlation with the patients' hematological data. This proof-of-concept study puts forth an interesting alternative for early septicemia diagnosis in future. Copyright © 2017 Elsevier Inc. All rights reserved.

Functionalized iron oxide nanoparticles for controlling the movement of immune cells

NASA Astrophysics Data System (ADS)

White, Ethan E.; Pai, Alex; Weng, Yiming; Suresh, Anil K.; van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M.

2015-04-01

Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain. Electronic supplementary information (ESI) available: Transmission electron microscopy images of the particles, additional independent experiments for the NFκB activity and exocytosis assays, TEM images for the SPION untreated cells, bright field microscopy images of the cells alone in the presence and absence of magnet, images of the magnetic movement experiments at higher doses of SPION, full uncropped images of the post-migration LIVE/DEAD assay, and a video file of cell movement. See DOI: 10.1039/c3nr04421a

Composite overwrapped metallic tanks

NASA Technical Reports Server (NTRS)

Caudill, C. L.; Kirlin, R. L.

1972-01-01

Work is reported for fabricating and testing the fiberglass overwrapped titanium pressure vessel for cryogenic service. Difficulties encountered in the tank liner fabrication phase involved explosive forming, vacuum annealing, chemical milling and electron beam welding. While each of these processes and the nondestructive test methods employed are normally considered to be individually reliable, the combination of poor material together with fabrication and development reversals prevented the full achievement of the desired end results. Eight tanks plus a prototype and tool proofing article were produced. Six of the vessels failed during the hydrostatic sizing operation. One of the remaining tanks was hydrostatically pressurized to burst and the other was pressurized repeatedly at 75 F from 100 psi to the operating pressure until failure occurred. As a result, it is not possible to draw firm conclusions as to the true value of the design concept due to the problems encountered in the program.

Credit PSR. This view depicts the southwest and southeast facades ...

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

Credit PSR. This view depicts the southwest and southeast facades as seen when looking west southwest (260°). The building consists of a small lean-to control room and a two-story space containing a large casting pit. The pit, which can be seen through the open doors, was never used due to changes in JPL's mission. This steel frame structure is clad in "Transite" board (a fire resistant pressed asbestos composite material) and interior lighting consists of individual explosion proof lamps mounted around the walls. The building was rated for 10,000 pounds (4,545 Kg) of class 2 materials and four personnel. It was licensed 5 June 1989 for ammonium perchlorate (NH4C10,), ammonium nitrate (NH4NO3), and sodium nitrate (NaNO3) - Jet Propulsion Laboratory Edwards Facility, Casting & Curing Building, Edwards Air Force Base, Boron, Kern County, CA

Yakir Aharonov: From A to B

NASA Astrophysics Data System (ADS)

Pines, A.

Twenty years ago, I was accorded the privilege and pleasure of presenting the after banquet speech—reprinted below—at a conference celebrating the sixtieth year of my dear friend Yakir Aharonov. Does what I said then still hold today? You bet it does …the now adult Yakir has maintained the same burning curiosity, fiery enthusiasm and explosive genius for physics that characterized the life of the adolescent sixty year old. There may be no free lunch, but Yakir is living proof that there is free will, and he has exercised his free will to make ever more creative contributions to quantum physics, future and present. My admiration of Yakir as a scientist and mensch has only grown over the years. Sorry I can't be with you all at Chapman to participate in this marvelous eightieth year celebration. Dear Yakir, Ditsa and I wish you, Nilli and your family many more joyous years of health, science and friendship…' til 120.

Small scale thermal violence experiments for combined insensitive high explosive and booster materials

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

Rae, Philip J; Bauer, Clare L; Stennett, C

A small scale cook-off experiment has been designed to provide a violence metric for both booster and IHE materials, singly and in combination. The experiment has a simple, axisymmetric geometry provided by a 10 mm internal diameter cylindrical steel confinement up to 80 mm in length. Heating is applied from one end of the sample length creating pseudo 1-D heating profile and a thermal gradient across the sample(s). At the opposite end of the confinement to the heating block, a machined groove provides a point of rupture that generates a cylindrical fragment. The displacement of the external face of themore » fragment is detected by Heterodyne Velocimetry. Proof of concept experiments are reported focusing on HMX and TATB formulations, and are described in relation to confinement, ullage and heating profile. The development of a violence metric, based upon fragment velocity records is discussed.« less

Novel method to dynamically load cells in 3D-hydrogels culture for blast injury studies

NASA Astrophysics Data System (ADS)

Sory, David R.; Areias, Anabela C.; Overby, Darryl R.; Proud, William G.

2017-01-01

For at least a century explosive devices have been one of the most important causes of injuries in military conflicts as well as in terrorist attacks. Although significant experimental and modelling efforts have been focussed on blast injuries at the organ or tissue level, few studies have investigated the mechanisms of blast injuries at the cellular level. This paper introduces an in vitro method compatible with living cells to examine the effects of high stress and short-duration pulses relevant to blast loadings and blunt trauma. The experimental phase involves high strain-rate axial compression of cylindrical specimens within an hermetically sealed chamber made of biocompatible polymer. Numerical simulations were performed in order to verify the experimental loading conditions and to characterize the loading path within the sample. A proof of concept is presented so as to establish a new window to address fundamental questions regarding blast injury at the cellular level.

Pulmonary immunization of chickens using non-adjuvanted spray-freeze dried whole inactivated virus vaccine completely protects against highly pathogenic H5N1 avian influenza virus.

PubMed

Peeters, Ben; Tonnis, Wouter F; Murugappan, Senthil; Rottier, Peter; Koch, Guus; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J

2014-11-12

Highly pathogenic avian influenza (HPAI) H5N1 virus is a major threat to public health as well as to the global poultry industry. Most fatal human infections are caused by contact with infected poultry. Therefore, preventing the virus from entering the poultry population is a priority. This is, however, problematic in emergency situations, e.g. during outbreaks in poultry, as there are currently no mass application methods to effectively vaccinate large numbers of birds within a short period of time. To evaluate the suitability of needle-free pulmonary immunization for mass vaccination of poultry against HPAI H5N1, we performed a proof-of-concept study in which we investigated whether non-adjuvanted spray-freeze-dried (SFD) whole inactivated virus (WIV) can be used as a dry powder aerosol vaccine to immunize chickens. Our results show that chickens that received SFD-WIV vaccine as aerosolized powder directly at the syrinx (the site of the tracheal bifurcation), mounted a protective antibody response after two vaccinations and survived a lethal challenge with HPAI H5N1. Furthermore, both the number of animals that shed challenge virus, as well as the level of virus shedding, were significantly reduced. Based on antibody levels and reduction of virus shedding, pulmonary vaccination with non-adjuvanted vaccine was at least as efficient as intratracheal vaccination using live virus. Animals that received aerosolized SFD-WIV vaccine by temporary passive inhalation showed partial protection (22% survival) and a delay in time-to-death, thereby demonstrating the feasibility of the method, but indicating that the efficiency of vaccination by passive inhalation needs further improvement. Altogether our results provide a proof-of-concept that pulmonary vaccination using an SFD-WIV powder vaccine is able to protect chickens from lethal HPAI challenge. If the efficacy of pulmonary vaccination by passive inhalation can be improved, this method might be suitable for mass application. Copyright © 2014 Elsevier Ltd. All rights reserved.

ESD testing of the 8S actuator (u)

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

Mchugh, Douglas C

2010-12-03

The 8S actuator is a hot-wire initiated explosive component used to drive the W76-1 2X Acorn 1V valve. It is known to be safe from human electrostatic discharge (ESD) pin-to-pin and all pin-to-cup stimuli as well as 1 amp/1 watt safe. However low impedance (furniture) ESD stimuli applied pin-to-pin has not been evaluated. Components were tested and the results analyzed. The 8S actuator has been shown to be immune to human and severe furniture ESD, whether applied pin-to-pin or pin-to-cup.

Eat dirt and avoid atopy: the hygiene hypothesis revisited.

PubMed

Patki, Anil

2007-01-01

The explosive rise in the incidence of atopic diseases in the Western developed countries can be explained on the basis of the so-called "hygiene hypothesis". In short, it attributes the rising incidence of atopic dermatitis to reduced exposure to various childhood infections and bacterial endotoxins. Reduced exposure to dirt in the clean environment results in a skewed development of the immune system which results in an abnormal allergic response to various environmental allergens which are otherwise innocuous. This article reviews the historical aspects, epidemiological and immunological basis of the hygiene hypothesis and implications for Indian conditions.

Safety Profile of Good Manufacturing Practice Manufactured Interferon γ-Primed Mesenchymal Stem/Stromal Cells for Clinical Trials.

PubMed

Guess, Adam J; Daneault, Beth; Wang, Rongzhang; Bradbury, Hillary; La Perle, Krista M D; Fitch, James; Hedrick, Sheri L; Hamelberg, Elizabeth; Astbury, Caroline; White, Peter; Overolt, Kathleen; Rangarajan, Hemalatha; Abu-Arja, Rolla; Devine, Steven M; Otsuru, Satoru; Dominici, Massimo; O'Donnell, Lynn; Horwitz, Edwin M

2017-10-01

Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon γ (IFNγ) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule. This protocol eliminates the need to infuse cryopreserved, just thawed cells which may reduce the immune modulatory activity. Moreover, using (IFNγ) as a prototypic cytokine, we demonstrate the feasibility of priming the cells with any biologic agent. We then characterized MSCs and IFNγ primed MSCs prepared with our protocol, by karyotype, in vitro potential for malignant transformation, biodistribution, effect on engraftment of transplanted hematopoietic cells, and in vivo toxicity in immune deficient mice including a complete post-mortem examination. We found no evidence of toxicity attributable to the MSC or IFNγ primed MSCs. Our data suggest that the clinical risk of infusing MSCs or IFNγ primed MSCs produced by our two-step protocol is not greater than MSCs currently in practice. While actual proof of safety requires phase I clinical trials, our data support the use of either cell product in new clinical studies. Stem Cells Translational Medicine 2017;6:1868-1879. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Optical-fibre sensor system for monitoring the performance of the gas propellant centrifuge separator of a spacecraft

NASA Astrophysics Data System (ADS)

Romo-Medrano, Katya E.; Khotiaintsev, Sergei N.; García-Garduño, Victor

2004-08-01

An optical-fibre sensor system is presented for monitoring void fraction distribution in a spacecraft's gas and propellant centrifuge separator. The system could be used at the separator development stage or for monitoring, during ground tests, the elements of the spacecraft propulsion system. Our sensor system employs an array of point optical-fibre refractometric transducers installed in the form of several linear radial arrays on the separator rotating blades. We employed a small-size hemispherical optical detection element as the transducer and we optimized its parameters through numerical ray-tracing. The aim is to minimize the effect of the thin film of liquid that forms on the transducer's surface in this application. The features of this sensor system are: (1) an efficient matrix-type multiplexing scheme, (2) the installation of the main optoelectronic unit of the sensor in a hermetically sealed container inside the separator tank located on the rotating shaft and (3) the spark-proof and explosion-proof design of the sensor circuits and elements. The sensor is simple, reliable, low-cost and is capable of withstanding the factors involved during operation of the propulsion system such as cryogenic temperatures and chemically aggressive liquids. The novel elements and design concepts implemented in this sensor system can also find applications in other sensors for spacecraft propulsion systems and also in a variety of optical-fibre sensors used in scientific research and industry.

Varicella Immunization Requirements for US Colleges: 2014–2015 academic year

PubMed Central

Leung, Jessica; Marin, Mona; Leino, Victor; Even, Susan; Bialek, Stephanie R.

2017-01-01

Objective To obtain information on varicella pre-matriculation requirements in US colleges for undergraduate students during the 2014–2015 academic year. Participants Healthcare professionals and member-schools of the American College Health Association (ACHA). Methods An electronic survey was sent to ACHA members regarding school characteristics and whether schools had policies in place requiring that students show proof of 2-doses of varicella vaccination for school attendance. Results Only 27% (101/370) of schools had a varicella pre-matriculation requirement for undergraduate students. Only 68% of schools always enforced this requirement. Private schools, 4-year schools, Northeastern schools, those with <5,000 students, and schools located in a state with a 2-dose varicella vaccine mandate were significantly more likely to have a varicella pre-matriculation requirement. Conclusions A small proportion of US colleges have a varicella pre-matriculation requirement for varicella immunity. College vaccination requirements are an important tool for controlling varicella in these settings. PMID:26829449

Activation of the Mechanistic Target of Rapamycin in SLE: Explosion of Evidence in the Last Five Years.

PubMed

Oaks, Zachary; Winans, Thomas; Huang, Nick; Banki, Katalin; Perl, Andras

2016-12-01

The mechanistic target of rapamycin (mTOR) is a central regulator in cell growth, activation, proliferation, and survival. Activation of the mTOR pathway underlies the pathogenesis of systemic lupus erythematosus (SLE). While mTOR activation and its therapeutic reversal were originally discovered in T cells, recent investigations have also uncovered roles in other cell subsets including B cells, macrophages, and "non-immune" organs such as the liver and the kidney. Activation of mTOR complex 1 (mTORC1) precedes the onset of SLE and associated co-morbidities, such as anti-phospholipid syndrome (APS), and may act as an early marker of disease pathogenesis. Six case reports have now been published that document the development of SLE in patients with genetic activation of mTORC1. Targeting mTORC1 over-activation with N-acetylcysteine, rapamycin, and rapalogs provides an opportunity to supplant current therapies with severe side effect profiles such as prednisone or cyclophosphamide. In the present review, we will discuss the recent explosion of findings in support for a central role for mTOR activation in SLE.

Tracing explosives in soil with transcriptional regulators of Pseudomonas putida evolved for responding to nitrotoluenes

PubMed Central

Garmendia, Junkal; De Las Heras, Aitor; Galvão, Teca Calcagno; De Lorenzo, Víctor

2008-01-01

Summary Although different biological approaches for detection of anti‐personnel mines and other unexploded ordnance (UXO) have been entertained, none of them has been rigorously documented thus far in the scientific literature. The industrial 2,4,6 trinitrotoluene (TNT) habitually employed in the manufacturing of mines is at all times tainted with a small but significant proportion of the more volatile 2,4 dinitrotoluene (2,4 DNT) and other nitroaromatic compounds. By using mutation‐prone PCR and DNA sequence shuffling we have evolved in vitro and selected in vivo variants of the effector recognition domain of the toluene‐responsive XylR regulator of the soil bacterium Pseudomonas putida that responds to mono‐, bi‐ and trinitro substituted toluenes. Re‐introduction of such variants in P. putida settled the transcriptional activity of the cognate promoters (Po and Pu) as a function of the presence of nitrotoluenes in the medium. When strains bearing transcriptional fusions to reporters with an optical output (luxAB, GFP) were spread on soil spotted with nitrotoluenes, the signal triggered by promoter activation allowed localization of the target compounds on the soil surface. Our data provide a proof of concept that non‐natural transcription factors evolved to respond to nitroaromatics can be engineered in soil bacteria and inoculated on a target site to pinpoint the presence of explosives. This approach thus opens new ways to tackle this gigantic humanitarian problem. PMID:21261843

Study on the thermal ignition of gasoline-air mixture in underground oil depots based on experiment and numerical simulation

NASA Astrophysics Data System (ADS)

Ou, Yihong; Du, Yang; Jiang, Xingsheng; Wang, Dong; Liang, Jianjun

2010-04-01

The study on the special phenomenon, occurrence process and control mechanism of gasoline-air mixture thermal ignition in underground oil depots is of important academic and applied value for enriching scientific theories of explosion safety, developing protective technology against fire and decreasing the number of fire accidents. In this paper, the research on thermal ignition process of gasoline-air mixture in model underground oil depots tunnel has been carried out by using experiment and numerical simulation methods. The calculation result has been demonstrated by the experiment data. The five stages of thermal ignition course, which are slow oxidation stage, rapid oxidation stage, fire stage, flameout stage and quench stage, have been firstly defined and accurately descried. According to the magnitude order of concentration, the species have been divided into six categories, which lay the foundation for explosion-proof design based on the role of different species. The influence of space scale on thermal ignition in small-scale space has been found, and the mechanism for not easy to fire is that the wall reflection causes the reflux of fluids and changes the distribution of heat and mass, so that the progress of chemical reactions in the whole space are also changed. The novel mathematical model on the basis of unification chemical kinetics and thermodynamics established in this paper provides supplementary means for the analysis of process and mechanism of thermal ignition.

Quantum cascade laser-based screening portal for the detection of explosive precursors

NASA Astrophysics Data System (ADS)

Lindley, Ruth; Normand, Erwan; Howieson, Iain; McCulloch, Michael; Black, Paul; Lewis, Colin; Foulger, Brian

2007-10-01

In recent years, quantum cascade lasers (QCL) have been proven in robust, high-performance gas analyzers designed for continuous emission monitoring (CEM) in harsh environments. In 2006, Cascade Technologies reported progress towards adapting its patented technology for homeland security applications by publishing initial results on explosive compound detection. This paper presents the performance and results from a QCL-based people screening portal developed during the past year and aimed at the detection of precursors used in the make up of improvised explosive devices (IED). System tests have been carried out on a large number of potential interferents, together with target precursor materials, reinforcing original assumptions that compound fingerprinting can be effectively demonstrated using this technique. Results have shown that an extremely high degree of specificity can be achieved with a sub-second response time. Furthermore, it has been shown that unambiguous precursor signature recognition can be extended to compound mixtures associated with the intermediate stages in the make up of IEDs, whilst maintaining interferent immunity. The portal sensitivity was configured for parts per billion (ppb) detection level thresholds, but is currently being reconfigured for sub-ppb detection. In summary, the results obtained from the QCL based portal indicate that development of a low cost detection system, with enhanced features such as low false positive and high throughput screening of individuals or items, is possible. Development and testing was carried out with the support of the UK government.

Human Social Behavior and Demography Drive Patterns of Fine-Scale Dengue Transmission in Endemic Areas of Colombia

PubMed Central

Padmanabha, Harish; Correa, Fabio; Rubio, Camilo; Baeza, Andres; Osorio, Salua; Mendez, Jairo; Jones, James Holland; Diuk-Wasser, Maria A

2015-01-01

Dengue is known to transmit between humans and A. aegypti mosquitoes living in neighboring houses. Although transmission is thought to be highly heterogeneous in both space and time, little is known about the patterns and drivers of transmission in groups of houses in endemic settings. We carried out surveys of PCR positivity in children residing in 2-block patches of highly endemic cities of Colombia. We found high levels of heterogeneity in PCR positivity, varying from less than 30% in 8 of the 10 patches to 56 and 96%, with the latter patch containing 22 children simultaneously PCR positive (PCR22) for DEN2. We then used an agent-based model to assess the likely eco-epidemiological context of this observation. Our model, simulating daily dengue dynamics over a 20 year period in a single two block patch, suggests that the observed heterogeneity most likely derived from variation in the density of susceptible people. Two aspects of human adaptive behavior were critical to determining this density: external social relationships favoring viral introduction (by susceptible residents or infectious visitors) and immigration of households from non-endemic areas. External social relationships generating frequent viral introduction constituted a particularly strong constraint on susceptible densities, thereby limiting the potential for explosive outbreaks and dampening the impact of heightened vectorial capacity. Dengue transmission can be highly explosive locally, even in neighborhoods with significant immunity in the human population. Variation among neighborhoods in the density of local social networks and rural-to-urban migration is likely to produce significant fine-scale heterogeneity in dengue dynamics, constraining or amplifying the impacts of changes in mosquito populations and cross immunity between serotypes. PMID:26656072

Human Social Behavior and Demography Drive Patterns of Fine-Scale Dengue Transmission in Endemic Areas of Colombia.

PubMed

Padmanabha, Harish; Correa, Fabio; Rubio, Camilo; Baeza, Andres; Osorio, Salua; Mendez, Jairo; Jones, James Holland; Diuk-Wasser, Maria A

2015-01-01

Dengue is known to transmit between humans and A. aegypti mosquitoes living in neighboring houses. Although transmission is thought to be highly heterogeneous in both space and time, little is known about the patterns and drivers of transmission in groups of houses in endemic settings. We carried out surveys of PCR positivity in children residing in 2-block patches of highly endemic cities of Colombia. We found high levels of heterogeneity in PCR positivity, varying from less than 30% in 8 of the 10 patches to 56 and 96%, with the latter patch containing 22 children simultaneously PCR positive (PCR22) for DEN2. We then used an agent-based model to assess the likely eco-epidemiological context of this observation. Our model, simulating daily dengue dynamics over a 20 year period in a single two block patch, suggests that the observed heterogeneity most likely derived from variation in the density of susceptible people. Two aspects of human adaptive behavior were critical to determining this density: external social relationships favoring viral introduction (by susceptible residents or infectious visitors) and immigration of households from non-endemic areas. External social relationships generating frequent viral introduction constituted a particularly strong constraint on susceptible densities, thereby limiting the potential for explosive outbreaks and dampening the impact of heightened vectorial capacity. Dengue transmission can be highly explosive locally, even in neighborhoods with significant immunity in the human population. Variation among neighborhoods in the density of local social networks and rural-to-urban migration is likely to produce significant fine-scale heterogeneity in dengue dynamics, constraining or amplifying the impacts of changes in mosquito populations and cross immunity between serotypes.

Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity.

PubMed

De Martinis, Massimo; Franceschi, Claudio; Monti, Daniela; Ginaldi, Lia

2005-04-11

Immunosenescence is the consequence of the continuous attrition caused by chronic antigenic stress. The most important characteristics of immunosenescence (accumulation of memory and effector T cells, reduction of naive T cells, shrinkage of T cell repertoire, reduction of the immunological space) are compatible with this assumption. Immunosenescence can be taken as proof that the beneficial effects of the immune system, devoted to the neutralization of harmful agents early in life, become detrimental late in life, in a period not foreseen by evolution. This perspective could explain the mechanisms of the ageing process as well as the pathogenesis of age-related diseases.

A novel metaheuristic for continuous optimization problems: Virus optimization algorithm

NASA Astrophysics Data System (ADS)

Liang, Yun-Chia; Rodolfo Cuevas Juarez, Josue

2016-01-01

A novel metaheuristic for continuous optimization problems, named the virus optimization algorithm (VOA), is introduced and investigated. VOA is an iteratively population-based method that imitates the behaviour of viruses attacking a living cell. The number of viruses grows at each replication and is controlled by an immune system (a so-called 'antivirus') to prevent the explosive growth of the virus population. The viruses are divided into two classes (strong and common) to balance the exploitation and exploration effects. The performance of the VOA is validated through a set of eight benchmark functions, which are also subject to rotation and shifting effects to test its robustness. Extensive comparisons were conducted with over 40 well-known metaheuristic algorithms and their variations, such as artificial bee colony, artificial immune system, differential evolution, evolutionary programming, evolutionary strategy, genetic algorithm, harmony search, invasive weed optimization, memetic algorithm, particle swarm optimization and simulated annealing. The results showed that the VOA is a viable solution for continuous optimization.

Skin Barrier Disruption - A Requirement for Allergen Sensitization?

PubMed Central

De Benedetto, Anna; Kubo, Akiharu; Beck, Lisa A.

2011-01-01

For at least half a century, noninvasive techniques have been available to quantify skin barrier function, and these have shown that a number of human skin conditions and disorders are associated with defects in skin permeability. In the last decade, several genes responsible for skin barrier defects observed in both monogenetic and complex, polygenic disorders have been elucidated and functionally characterized. This has led to an explosion of work in the last six years that has identified pathways connecting epidermal barrier disruption and antigen uptake as well as the quality and/or magnitude of the antigen-specific adaptive immune response. This review will introduce the notion that diseases arise from the dynamic crosstalk that occurs between the skin barrier and immune system using atopic dermatitis or eczema as the disease prototype. Nevertheless, the concepts put forth are highly relevant to a number of antigen-driven disorders for which skin barrier is at least transiently compromised such as psoriasis, allergic contact dermatitis and blistering disorders. PMID:22217737

Current clinical trials testing combinations of immunotherapy and radiation.

PubMed

Crittenden, Marka; Kohrt, Holbrook; Levy, Ronald; Jones, Jennifer; Camphausen, Kevin; Dicker, Adam; Demaria, Sandra; Formenti, Silvia

2015-01-01

Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an abscopal effect. Granulocyte-macrophage colony-stimulating factor was administered during radiotherapy to a metastatic site in patients with metastatic solid tumors to translate evidence obtained in a murine model of syngeneic mammary carcinoma treated with cytokine FLT-3L and radiation. Subsequent clinical availability of vaccines and immune checkpoint inhibitors has triggered a wave of enthusiasm for testing them in combination with radiotherapy. Examples of ongoing clinical trials are described in this report. Importantly, most of these trials include careful immune monitoring of the patients enrolled and will generate important data about the proimmunogenic effects of radiation in combination with a variety of immune modulators, in different disease settings. Results of these studies are building a platform of evidence for radiotherapy as an adjuvant to immunotherapy and encourage the growth of this novel field of radiation oncology. Copyright © 2015 Elsevier Inc. All rights reserved.

HPV circulating tumor DNA to monitor the efficacy of anti-PD-1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report.

PubMed

Cabel, Luc; Bidard, François-Clément; Servois, Vincent; Cacheux, Wulfran; Mariani, Pascale; Romano, Emanuela; Minsat, Mathieu; Bieche, Ivan; Farkhondeh, Fereshteh; Jeannot, Emmanuelle; Buecher, Bruno

2017-10-15

Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV-associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD-1 immune checkpoint inhibitor, demonstrated significant efficacy as single-agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single-agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof-of-concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents. © 2017 UICC.

Immune Reconstitution After Autologous Hematopoietic Stem Cell Transplantation in Crohn’s Disease: Current Status and Future Directions. A Review on Behalf of the EBMT Autoimmune Diseases Working Party and the Autologous Stem Cell Transplantation In Refractory CD—Low Intensity Therapy Evaluation Study Investigators

PubMed Central

Pockley, Alan Graham; Lindsay, James O.; Foulds, Gemma A.; Rutella, Sergio; Gribben, John G.; Alexander, Tobias; Snowden, John A.

2018-01-01

Patients with treatment refractory Crohn’s disease (CD) suffer debilitating symptoms, poor quality of life, and reduced work productivity. Surgery to resect inflamed and fibrotic intestine may mandate creation of a stoma and is often declined by patients. Such patients continue to be exposed to medical therapy that is ineffective, often expensive and still associated with a burden of adverse effects. Over the last two decades, autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies have provided proof of concept that auto-HSCT can restore immunological tolerance in chronic autoimmunity via the eradication of pathological immune responses and a profound reconfiguration of the immune system. Herein, we review current experience of auto-HSCT for the treatment of CD as well as approaches that have been used to monitor immune reconstitution following auto-HSCT in patients with ADs, including CD. We also detail immune reconstitution studies that have been integrated into the randomized controlled Autologous Stem cell Transplantation In refractory CD—Low Intensity Therapy Evaluation trial, which is designed to test the hypothesis that auto-HSCT using reduced intensity mobilization and conditioning regimens will be a safe and effective means of inducing sustained control in refractory CD compared to standard of care. Immunological profiling will generate insight into the pathogenesis of the disease, restoration of responsiveness to anti-TNF therapy in patients with recurrence of endoscopic disease and immunological events that precede the onset of disease in patients that relapse after auto-HSCT. PMID:29670622

Pediatric Autoimmune Disorders Associated with Streptococcal Infections and Tourette's Syndrome in Preclinical Studies

PubMed Central

Spinello, Chiara; Laviola, Giovanni; Macrì, Simone

2016-01-01

Accumulating evidence suggests that Tourette's Syndrome (TS) – a multifactorial pediatric disorder characterized by the recurrent exhibition of motor tics and/or vocal utterances – can partly depend on immune dysregulation provoked by early repeated streptococcal infections. The natural and adaptive antibody-mediated reaction to streptococcus has been proposed to potentially turn into a pathological autoimmune response in vulnerable individuals. Specifically, in conditions of increased permeability of the blood brain barrier (BBB), streptococcus-induced antibodies have been proposed to: (i) reach neuronal targets located in brain areas responsible for motion control; and (ii) contribute to the exhibition of symptoms. This theoretical framework is supported by indirect evidence indicating that a subset of TS patients exhibit elevated streptococcal antibody titers upon tic relapses. A systematic evaluation of this hypothesis entails preclinical studies providing a proof of concept of the aforementioned pathological sequelae. These studies shall rest upon individuals characterized by a vulnerable immune system, repeatedly exposed to streptococcus, and carefully screened for phenotypes isomorphic to the pathological signs of TS observed in patients. Preclinical animal models may thus constitute an informative, useful tool upon which conducting targeted, hypothesis-driven experiments. In the present review we discuss the available evidence in preclinical models in support of the link between TS and pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS), and the existing gaps that future research shall bridge. Specifically, we report recent preclinical evidence indicating that the immune responses to repeated streptococcal immunizations relate to the occurrence of behavioral and neurological phenotypes reminiscent of TS. By the same token, we discuss the limitations of these studies: limited evidence of behavioral phenotypes isomorphic to tics and scarce knowledge about the immunological phenomena favoring the transition from natural adaptive immunity to pathological outcomes. PMID:27445678

A novel vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection.

PubMed

Lin, Hui-xing; Ma, Zhe; Yang, Xu-qiu; Fan, Hong-jie; Lu, Cheng-ping

2014-06-25

To develop a vaccine against Porcine circovirus type 2 (PCV2) and Streptococcus equi ssp. zooepidemicus (SEZ) co-infection, the genes of porcine IL-18, capsid protein (Cap) of PCV2 and M-like protein (SzP) of SEZ were inserted into the swinepox virus (SPV) genome by homologous recombination. The recombinant swinepox virus rSPV-ICS was verified by PCR and indirect immunofluorescence assays. To evaluate the immunogenicity of rSPV-ICS, 28 PCV2 and SEZ seronegative Bama minipigs were immunized with rSPV-ICS (n=8), commercial PCV2 vaccine and SEZ vaccine (n=8) or wild type SPV (n=8). The results showed that SzP-specific antibody and PCV2 neutralizing antibody of the rSPV-ICS immunized group increased significantly compared to the wild type SPV treated group after vaccination and increased continuously over time. The levels of IL-4 and IFN-γ in the rSPV-ICS immunized group were significantly higher than the other three groups, respectively. After been co-challenged with PCV2 and SEZ, 87.5% piglets in rSPV-ICS immunized group were survived. Significant reductions in gross lung lesion score, histopathological lung lesion score, and lymph node lesion score were noticed in the rSPV-ICS immunized group compared with the wtSPV treated group. The results suggested that the recombinant rSPV-ICS provided piglets with significant protection against PCV2-SEZ co-infection; thus, it offers proof-of-principle for the development of a vaccine for the prevention of these swine diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs) with important implication in immunity

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

Buoso, Erica; Galasso, Marilisa; Ronfani, Melania

We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p′DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p′DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response. In analogy to endogenous androgens, nandrolone induced a dose-related increase in RACK1 transcriptional activity andmore » protein expression, resulting in increased LPS-induced IL-8 and TNF-α production and proliferation in THP-1 cells. Conversely, p,p′DDT and p,p′DDE significantly decrease RACK1 expression, LPS-induced cytokine production and CD86 expression; with p,p′DDE exerting a stronger repressor effect than p,p′DDT, consistent with its stronger AR antagonistic effect. These results indicate that RACK1 could be a relevant target of EDCs, responding in opposite ways to agonist or antagonist of AR, representing a bridge between the endocrine system and the innate immune system. - Highlights: • RACK1 expression can be induced by AR agonists with a consequent enhancement of the response to LPS. • RACK1 can be negatively modulated by the AR antagonists DDT and its main metabolite p,p′DDE. • RACK1 can be a relevant target of EDCs, representing a bridge between the endocrine system and the immune system.« less

Assessment of immunogenic potential of Vero adapted formalin inactivated vaccine derived from novel ECSA genotype of Chikungunya virus.

PubMed

Tiwari, Mugdha; Parida, Manmohan; Santhosh, S R; Khan, Mohsin; Dash, Paban Kumar; Rao, P V Lakshmana

2009-04-21

The recent resurgence of Chikungunya virus (CHIKV) in India and Indian Ocean Islands with unusual clinical severity is a matter of great public health concern. Despite the fact that CHIKV resurgence is associated with epidemic of unprecedented magnitude, no approved licensed vaccine is currently available. In the present study, a Vero cell adapted purified formalin inactivated prototype vaccine candidate was prepared using a current Indian strain implicated with the explosive epidemic during 2006. The bulk preparation of the vaccine candidate was undertaken in microcarrier based spinner culture using cytodex-1 in virus production serum free medium. The inactivation of the virus was accomplished through standard formalin inactivation protocol. The mice were immunized subcutaneously with alhydrogel gel formulation of inactivated virus preparation. The assessment of both humoral and cell-mediated immune response was accomplished through ELISA, plaque reduction neutralization test (PRNT), microcytotoxicity assay and cytokine production assay. The results revealed that formalin inactivated vaccine candidate induced both high titered ELISA (1:51,200) and plaque reduction neutralizing antibodies (1:6400) with peak antibody titer being observed during 6 -- 8 weeks of post-vaccination. In the absence of suitable murine challenge model, the protective efficacy was established by both in vitro and in vivo neutralization tests. Further assessment of cellular immunity through in vitro stimulation of spleenocytes from immunized mice revealed augmentation of high levels of both pro- and anti-inflammatory cytokines, indicating a mixed balance of Th1 and Th2 response. These findings suggest that the formalin inactivated Chikungunya vaccine candidate reported in this study has very good immunogenic potential to neutralize the virus infectivity by augmenting both humoral and cell-mediated immune response.

Pharmacological Inhibition of PKCθ Counteracts Muscle Disease in a Mouse Model of Duchenne Muscular Dystrophy.

PubMed

Marrocco, V; Fiore, P; Benedetti, A; Pisu, S; Rizzuto, E; Musarò, A; Madaro, L; Lozanoska-Ochser, B; Bouché, M

2017-02-01

Inflammation plays a considerable role in the progression of Duchenne Muscular Dystrophy (DMD), a severe muscle disease caused by a mutation in the dystrophin gene. We previously showed that genetic ablation of Protein Kinase C θ (PKCθ) in mdx, the mouse model of DMD, improves muscle healing and regeneration, preventing massive inflammation. To establish whether pharmacological targeting of PKCθ in DMD can be proposed as a therapeutic option, in this study we treated young mdx mice with the PKCθ inhibitor Compound 20 (C20). We show that C20 treatment led to a significant reduction in muscle damage associated with reduced immune cells infiltration, reduced inflammatory pathways activation, and maintained muscle regeneration. Importantly, C20 treatment is efficient in recovering muscle performance in mdx mice, by preserving muscle integrity. Together, these results provide proof of principle that pharmacological inhibition of PKCθ in DMD can be considered an attractive strategy to modulate immune response and prevent the progression of the disease. Duchenne muscular dystrophy (DMD) is a severe muscle disease affecting 1:3500 male births. DMD is caused by a mutation in dystrophin gene, coding for a protein required for skeletal and cardiac muscle integrity. Lack of a functional dystrophin is primarily responsible for the muscle eccentric contraction-induced muscle damage, observed in dystrophic muscle. However, inflammation plays a considerable role in the progression of DMD. Glucocorticoids, which have anti-inflammatory properties, are being used to treat DMD with some success; however, long term treatment with these drugs induces muscle atrophy and wasting, outweighing their benefit. The identification of specific targets for anti-inflammatory therapies is one of the ongoing therapeutic options. Although blunting inflammation would not be a "cure" for the disease, the emerging clue is that multiple strategies, addressing different aspects of the pathology, which may eventually converge, may be successful. In this context, we previously showed that genetic ablation of Protein Kinase C θ (PKCθ), an enzyme known to be involved in immune response, in mdx, the mouse model of DMD, improves muscle healing and regeneration, preventing massive inflammation. To establish whether pharmacological targeting of PKCθ in DMD can be proposed as a therapeutic option, in this study we treated young mdx mice with the PKCθ inhibitor Compound 20 (C20). We show that C20 treatment led to a significant reduction in muscle damage associated with reduced immune cells infiltration, reduced inflammatory pathways activation, and maintained muscle regeneration. Importantly, C20 treatment is efficient in recovering muscle performance in mdx mice, by preserving muscle integrity. Together, these results provide proof of principle that pharmacological inhibition of PKCθ in DMD can be considered an attractive strategy to modulate immune response and prevent the progression of the disease. Copyright © 2017 3-V Biosciences. Published by Elsevier B.V. All rights reserved.

Immune cytokine response in combat casualties: blast or explosive trauma with or without secondary sepsis.

PubMed

Surbatovic, Maja; Filipovic, Nikola; Radakovic, Sonja; Stankovic, Nebojsa; Slavkovic, Zoran

2007-02-01

The aim of this study was to assess the prognostic value of tumor necrosis factor (TNF) alpha, interleukin (IL)-8, IL-4, and IL-10 in combat casualties. Fifty-six casualties with severe trauma (blast and explosive) who developed sepsis and 20 casualties with the same severity of trauma without sepsis were enrolled in this study. Fifty-five casualties developed multiple organ dysfunction syndrome; 36 died. Blood was drawn on the first day of trauma. Concentrations of IL-8, TNF-alpha, IL-4, and IL-10 were determined in plasma using enzyme-linked immunosorbent assays. Mean values of IL-8 were 230-fold, IL-10 were 42-fold, and TNF-alpha were 17-fold higher in trauma and sepsis group (p < 0.01). Mean values of IL-8 were 60-fold, TNF-alpha were 43.5-fold, and IL-10 were 70-fold higher in the multiple organ dysfunction syndrome group (p < 0.01). Mean values of IL-8 were 2.3-fold and IL-10 were 1.4-fold higher in nonsurvivors and TNF-alpha were 2.2-fold higher in survivors (p < 0.01). IL-4 had no significance as a predictor of severity and outcome.

GEODE 2: Manufacturing large area format cadmium-mercury-telluride crystals in a microgravity environment. Pressure sensor proof of concept

NASA Astrophysics Data System (ADS)

Gale, M. R.; Beattie, D. A.

In the GEODE 1 experiment, a semiconductor Cd-Hg telluride crystal was grown in the MASER1 sounding rocket. It was shown that bulk-quench Cd-Hg telluride crystallization in a microgravity environment results in a more homogeneous crystal structure than can be achieved terrestrially. In the GEODE 2 program, the wall thickness of the quartz ampoule containing the crystal will be reduced to improve the heat transfer characteristics during crystallization. Ampoule explosion must be prevented by active control of the pressure surrounding the weaker, thin-walled ampoule to match that inside the furnace. A prototype pressure sensor that uses the absorption of ultraviolet light by Hg vapor has been built and tested. Pressures from 4 to 40 atmospheres have been measured with a resolution better than 0.35 atmospheres over the entire range. The feasibility of the pressure measurement technique has been demonstrated, although some design improvements are required in order to make measurements more repeatable.

Mercuric iodide detector systems for identifying substances by x-ray energy dispersive diffraction

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

Iwanczyk, J.S.; Patt, B.E.; Wang, Y.J.

The use of mercuric iodide arrays for energy-dispersive x-ray diffraction (EDXRD) spectroscopy is now being investigated by the authors for inspection of specific crystalline powders in substances ranging from explosives to illicit drugs. Mercuric iodide has been identified as the leading candidate for replacing the Ge detectors previously employed in the development of this technique because HgI{sub 2} detectors: operate at or near room temperature; without the bulky apparatus associated with cryogenic cooling; and offer excellent spectroscopy performance with extremely high efficiency. Furthermore, they provide the practicality of constructing optimal array geometries necessary for these measurements. Proof of principle experimentsmore » have been performed using a single-HgI{sub 2} detector spectrometer. An energy resolution of 655 eV (FWHM) has been obtained for 60 keV gamma line from an {sup 241}Am source. The EDXRD signatures of various crystalline powdered compounds have been measured and the spectra obtained show the excellent potential of mercuric iodide for this application.« less

Mines Systems Safety Improvement Using an Integrated Event Tree and Fault Tree Analysis

NASA Astrophysics Data System (ADS)

Kumar, Ranjan; Ghosh, Achyuta Krishna

2017-04-01

Mines systems such as ventilation system, strata support system, flame proof safety equipment, are exposed to dynamic operational conditions such as stress, humidity, dust, temperature, etc., and safety improvement of such systems can be done preferably during planning and design stage. However, the existing safety analysis methods do not handle the accident initiation and progression of mine systems explicitly. To bridge this gap, this paper presents an integrated Event Tree (ET) and Fault Tree (FT) approach for safety analysis and improvement of mine systems design. This approach includes ET and FT modeling coupled with redundancy allocation technique. In this method, a concept of top hazard probability is introduced for identifying system failure probability and redundancy is allocated to the system either at component or system level. A case study on mine methane explosion safety with two initiating events is performed. The results demonstrate that the presented method can reveal the accident scenarios and improve the safety of complex mine systems simultaneously.

Tracing Titanium Escape

NASA Image and Video Library

2015-05-07

The plot of data from NASA's Nuclear Spectroscopic Telescope Array, or NuSTAR (right), amounts to a "smoking gun" of evidence in the mystery of how massive stars explode. The observations indicate that supernovae belonging to a class called Type II or core-collapse blast apart in a lopsided fashion, with the core of the star hurtling in one direction, and the ejected material mostly expanding the other way (see diagram in Figure 1). NuSTAR made the most precise measurements yet of a radioactive element, called titanium-44, in the supernova remnant called 1987A. NuSTAR sees high-energy X-rays, as shown here in the plot ranging from 60 to more than 80 kiloelectron volts. The spectral signature of titanium-44 is apparent as the two tall peaks. The white line shows where one would expect to see these spectral signatures if the titanium were not moving. The fact that the spectral peaks have shifted to lower energies indicates that the titanium has "redshifted," and is moving way from us. This is similar to what happens to a train's whistle as the train leaves the station. The whistle's sound shifts to lower frequencies. NuSTAR's detection of redshifted titanium reveals that the bulk of material ejected in the 1987A supernova is flying way from us at a velocity of 1.6 million miles per hour (2.6 million kilometers per hour). Had the explosion been spherical in nature, the titanium would have been seen flying uniformly in all directions. This is proof that this explosion occurred in an asymmetrical fashion. http://photojournal.jpl.nasa.gov/catalog/PIA19335

Modulation of GITR for cancer immunotherapy

PubMed Central

Schaer, David A; Murphy, Judith T; Wolchok, Jedd D

2012-01-01

Modulation of co-inhibitory and co-stimulatory receptors of the immune system has become a promising new approach for immunotherapy of cancer. With the recent FDA approval of CTLA-4 blockade serving as an important proof of principal, many new targets are now being translated into the clinic. Preclinical research has demonstrated that targeting glucocorticoid-induced tumor necrosis factor (TNF) receptor related gene (GITR), a member of TNF receptor superfamily, by agonist antibodies or natural ligand, can serve as an effective anti-tumor therapy. In this review, we will cover this research and the rationale that has led to initiation of two phase 1 clinical trials targeting GITR as a new immunotherapeutic approach for cancer. PMID:22245556

Security proof of counterfactual quantum cryptography against general intercept-resend attacks and its vulnerability

NASA Astrophysics Data System (ADS)

Zhang, Sheng; Wang, Jian; Tang, Chao-Jing

2012-06-01

Counterfactual quantum cryptography, recently proposed by Noh, is featured with no transmission of signal particles. This exhibits evident security advantages, such as its immunity to the well-known photon-number-splitting attack. In this paper, the theoretical security of counterfactual quantum cryptography protocol against the general intercept-resend attacks is proved by bounding the information of an eavesdropper Eve more tightly than in Yin's proposal [Phys. Rev. A 82 042335 (2010)]. It is also shown that practical counterfactual quantum cryptography implementations may be vulnerable when equipped with imperfect apparatuses, by proving that a negative key rate can be achieved when Eve launches a time-shift attack based on imperfect detector efficiency.

A new quantum sealed-bid auction protocol with secret order in post-confirmation

NASA Astrophysics Data System (ADS)

Wang, Jing-Tao; Chen, Xiu-Bo; Xu, Gang; Meng, Xiang-Hua; Yang, Yi-Xian

2015-10-01

A new security protocol for quantum sealed-bid auction is proposed to resist the collusion attack from some malicious bidders. The most significant feature of this protocol is that bidders prepare their particles with secret order in post-confirmation for encoding bids. In addition, a new theorem and its proof are given based on the theory of combinatorial mathematics, which can be used as evaluation criteria for the collusion attack. It is shown that the new protocol is immune to the collusion attack and meets the demand for a secure auction. Compared with those previous protocols, the security, efficiency and availability of the proposed protocol are largely improved.

RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

PubMed Central

Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

Emerging biological roles for erythropoietin in the nervous system.

PubMed

Brines, Michael; Cerami, Anthony

2005-06-01

Erythropoietin mediates an evolutionarily conserved, ancient immune response that limits damage to the heart, the nervous system and other tissues following injury. New evidence indicates that erythropoietin specifically prevents the destruction of viable tissue surrounding the site of an injury by signalling through a non-haematopoietic receptor. Engineered derivatives of erythropoietin that have a high affinity for this receptor have been developed, and these show robust tissue-protective effects in diverse preclinical models without stimulating erythropoiesis. A recent successful proof-of-concept clinical trial that used erythropoietin to treat human patients who had suffered a stroke encourages the evaluation of both this cytokine and non-erythropoietic derivatives as therapeutic agents to limit tissue injury.

Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-FVIII immunity

PubMed Central

Kuether, E. L.; Schroeder, J. A.; Fahs, S. A.; Cooley, B. C.; Chen, Y.; Montgomery, R. R.; Wilcox, D. A.; Shi, Q.

2012-01-01

Summary Background The development of inhibitory antibodies, referred to as inhibitors, against exogenous FVIII in a significant subset of patients with hemophilia A remains a persistent challenge to the efficacy of protein replacement therapy. Our previous studies using the transgenic approach provided proof-of-principle that platelet-specific expression could be successful for treating hemophilia A in the presence of inhibitory antibodies. Objective To investigate a clinically translatable approach for platelet gene therapy of hemophilia A with pre-existing inhibitors. Methods Platelet-FVIII expression in pre-immunized FVIIInull mice was introduced by transplantation of lentivirus-transduced bone marrow or enriched hematopoietic stem cells. FVIII expression was determined by a chromogenic assay. The transgene copy number per cell was quantitated by real time PCR. Inhibitor titer was measured by Bethesda assay. Phenotypic correction was assessed by the tail clipping assay and an electrolytic-induced venous injury model. Integration sites were analyzed by LAM-PCR. Results Therapeutic levels of platelet-FVIII expression were sustained long-term without evoking an anti-FVIII memory response in the transduced pre-immunized recipients. The tail clip survival test and the electrolytic injury model confirmed that hemostasis was improved in the treated animals. Sequential bone marrow transplants showed sustained platelet-FVIII expression resulting in phenotypic correction in pre-immunized secondary and tertiary recipients. Conclusions Lentivirus-mediated platelet-specific gene transfer improves hemostasis in hemophilic A mice with pre-existing inhibitors, indicating that this approach may be a promising strategy for gene therapy of hemophilia A even in the high-risk setting of pre-existing inhibitory antibodies. PMID:22632092

Vaccines against malaria-still a long way to go.

PubMed

Matuschewski, Kai

2017-08-01

Several species of Plasmodium cause a broad spectrum of human disease that range from nausea and fever to severe anemia, cerebral malaria, and multiorgan failure. In malaria-endemic countries, continuous exposure to Plasmodium sporozoite inoculations and subsequent blood infections elicit only partial and short-lived immunity, which gradually develops over many years of parasite exposure and multiple clinical episodes. The ambitious goal of malaria vaccinology over the past 70 years has been to develop an immunization strategy that mounts protection superior to naturally acquired immunity. Herein, three principal concepts in evidence-based malaria vaccine development are compared. Feasible leads are typically stand-alone subunit vaccine approaches that block Plasmodium parasite life cycle progression or parasite/host interactions, and they constitute the majority of candidates in preclinical research and early clinical testing. Integrated approaches incorporate malaria antigen(s) into licensed or emerging pediatric vaccine formulations. This strategy can complement the malaria control portfolio even if the antimalarial component is only partially effective and has led to the development of the only candidate vaccine to date, namely RTS,S-AS01. Experimental whole parasite vaccine approaches have been repeatedly shown to elicit sterile and lasting protection against identical parasite strains, but mass production, proof of broad protection against different parasite strains, and routes of vaccine delivery remain significant translational road blocks. Global access to an effective and affordable malaria vaccine will critically depend on innovative translational research that builds on a better molecular understanding of Plasmodium biology and host immunity. © 2017 Federation of European Biochemical Societies.

Current and Future Perspectives on Alginate Encapsulated Pancreatic Islet.

PubMed

Strand, Berit L; Coron, Abba E; Skjak-Braek, Gudmund

2017-04-01

Transplantation of pancreatic islets in immune protective capsules holds the promise as a functional cure for type 1 diabetes, also about 40 years after the first proof of principal study. The concept is simple in using semipermeable capsules that allow the ingress of oxygen and nutrients, but limit the access of the immune system. Encapsulated human islets have been evaluated in four small clinical trials where the procedure has been evaluated as safe, but lacking long-term efficacy. Host reactions toward the biomaterials used in the capsules may be one parameter limiting the long-term function of the graft in humans. The present article briefly discusses important capsule properties such as stability, permeability and biocompatibility, as well as possible strategies to overcome current challenges. Also, recent progress in capsule development as well as the production of insulin-producing cells from human stem cells that gives promising perspectives for the transplantation of encapsulated insulin-producing tissue is briefly discussed. Stem Cells Translational Medicine 2017;6:1053-1058. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein

PubMed Central

Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma; Heyndrickx, Leo; LaBranche, Celia; Applequist, Steven E.; Jansson, Marianne; De Silva, Thushan; Back, Jaap Willem; Achour, Adnane; Scarlatti, Gabriella; Fomsgaard, Anders; Montefiori, David; Stewart-Jones, Guillaume; Spetz, Anna-Lena

2014-01-01

Our knowledge of the binding sites for neutralizing antibodies (NAbs) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B-cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). Here we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and SIV Envs. Heterologous NAb titres, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of antibody binding reactivity revealed preferential recognition of the C1, C2, V2, V3 and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1. PMID:24829409

Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies.

PubMed

Xu, Chun; Goß, Annika Verena; Dorneburg, Carmen; Debatin, Klaus-Michael; Wei, Jiwu; Beltinger, Christian

2018-01-01

Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase clinical trials. However, pre-existing immunity against measles might be a hurdle for OMV therapy. OMV was inactivated with short-wavelength ultraviolet light (UV-C). Loss of replication and oncolytic activity of UV-inactivated OMV were confirmed by tissue culture infective dose 50 (TCID 50 ) assay using Vero cells and by flow cytometry using Jurkat cells. An enzyme-linked immunosorbent assay was performed to verify that UV-inactivated OMV remained antigenic. Different doses of UV-inactivated OMV were pre-cultured in media supplemented with measles immune serum. The mixture was transferred to Jurkat cells and active OMV was added. Active OMV-induced death of Jurkat cells was monitored by flow cytometry. UV-inactivation abrogates OMV replication while maintaining its antigenicity. UV-inactivated OMV sequesters pre-existing anti-MV antibodies in Jurkat cell culture, thereby protecting active OMV from neutralization and preserving oncolytic activity. We prove the principle that a non-replicating OMV can serve as a "decoy" for neutralizing anti-MV antibodies, thereby allowing antitumor activity of OMV.

Pan-Canadian assessment of pandemic immunization data collection: study methodology

PubMed Central

2010-01-01

Background The collection of individual-level pandemic (H1N1) 2009 influenza immunization data was considered important to facilitate optimal vaccine delivery and accurate assessment of vaccine coverage. These data are also critical for research aimed at evaluating the new vaccine's safety and effectiveness. Systems used to collect immunization data include manual approaches in which data are collected and retained on paper, electronic systems in which data are captured on computer at the point of vaccination and hybrid systems which are comprised of both computerized and manual data collection components. This study's objective was to compare the efficiencies and perceptions of data collection methods employed during Canada's pandemic (H1N1) 2009 influenza vaccination campaign. Methods/Design A pan-Canadian observational study was conducted in a convenience sample of public health clinics and healthcare institutions during the H1N1 vaccination campaign in the fall of 2009. The study design consisted of three stages: Stage 1 involved passive observation of the site's layout, processes and client flow; Stage 2 entailed timing site staff on 20 clients through five core immunization tasks: i) client registration, ii) medical history collection, iii) medical history review, iv) vaccine administration record keeping and v) preparation of proof of vaccine administration for the client; in Stage 3, site staff completed a questionnaire regarding perceived usability of the site's data collection approach. Before the national study began, a pilot study was conducted in three seasonal influenza vaccination sites in Ontario, to both test that the proposed methodology was logistically feasible and to determine inter-rater reliability in the measurements of the research staff. Comparative analyses will be conducted across the range of data collection methods with respect to time required to collect immunization data, number and type of individual-level data elements collected, and clinic staff perceptions of the usability of the method employed at their site, using analysis of variance (ANOVA). Discussion Various data collection methods were employed at immunization sites across Canada during the pandemic (H1N1) 2009 influenza vaccination campaign. Our comparison of methods can facilitate planning an efficient, coordinated approach for collecting immunization data in future influenza seasons. PMID:20624270

Pan-Canadian assessment of pandemic immunization data collection: study methodology.

PubMed

Pereira, Jennifer A; Quach, Susan; Heidebrecht, Christine; Foisy, Julie; Quan, Sherman; Finkelstein, Michael; Sikora, Christopher A; Bettinger, Julie A; Buckeridge, David L; McCarthy, Anne; Deeks, Shelley; Kwong, Jeffrey C

2010-06-08

The collection of individual-level pandemic (H1N1) 2009 influenza immunization data was considered important to facilitate optimal vaccine delivery and accurate assessment of vaccine coverage. These data are also critical for research aimed at evaluating the new vaccine's safety and effectiveness. Systems used to collect immunization data include manual approaches in which data are collected and retained on paper, electronic systems in which data are captured on computer at the point of vaccination and hybrid systems which are comprised of both computerized and manual data collection components. This study's objective was to compare the efficiencies and perceptions of data collection methods employed during Canada's pandemic (H1N1) 2009 influenza vaccination campaign. A pan-Canadian observational study was conducted in a convenience sample of public health clinics and healthcare institutions during the H1N1 vaccination campaign in the fall of 2009. The study design consisted of three stages: Stage 1 involved passive observation of the site's layout, processes and client flow; Stage 2 entailed timing site staff on 20 clients through five core immunization tasks: i) client registration, ii) medical history collection, iii) medical history review, iv) vaccine administration record keeping and v) preparation of proof of vaccine administration for the client; in Stage 3, site staff completed a questionnaire regarding perceived usability of the site's data collection approach. Before the national study began, a pilot study was conducted in three seasonal influenza vaccination sites in Ontario, to both test that the proposed methodology was logistically feasible and to determine inter-rater reliability in the measurements of the research staff. Comparative analyses will be conducted across the range of data collection methods with respect to time required to collect immunization data, number and type of individual-level data elements collected, and clinic staff perceptions of the usability of the method employed at their site, using analysis of variance (ANOVA). Various data collection methods were employed at immunization sites across Canada during the pandemic (H1N1) 2009 influenza vaccination campaign. Our comparison of methods can facilitate planning an efficient, coordinated approach for collecting immunization data in future influenza seasons.

Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses

PubMed Central

Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia; Swallow, Maxine; Bartel, Judith; Lycke, Nils Yngve; Barkan, Daniel; Martina, Mariana; Lujan, Hugo D.; Kalay, Hakan; van Kooyk, Yvette; Sparwasser, Tim D.; Berod, Luciana

2018-01-01

Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections. PMID:29662482

MYC2 Orchestrates a Hierarchical Transcriptional Cascade That Regulates Jasmonate-Mediated Plant Immunity in Tomato.

PubMed

Du, Minmin; Zhao, Jiuhai; Tzeng, David T W; Liu, Yuanyuan; Deng, Lei; Yang, Tianxia; Zhai, Qingzhe; Wu, Fangming; Huang, Zhuo; Zhou, Ming; Wang, Qiaomei; Chen, Qian; Zhong, Silin; Li, Chang-Bao; Li, Chuanyou

2017-08-01

The hormone jasmonate (JA), which functions in plant immunity, regulates resistance to pathogen infection and insect attack through triggering genome-wide transcriptional reprogramming in plants. We show that the basic helix-loop-helix transcription factor (TF) MYC2 in tomato ( Solanum lycopersicum ) acts downstream of the JA receptor to orchestrate JA-mediated activation of both the wounding and pathogen responses. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 655 MYC2-targeted JA-responsive genes. These genes are highly enriched in Gene Ontology categories related to TFs and the early response to JA, indicating that MYC2 functions at a high hierarchical level to regulate JA-mediated gene transcription. We also identified a group of MYC2-targeted TFs (MTFs) that may directly regulate the JA-induced transcription of late defense genes. Our findings suggest that MYC2 and its downstream MTFs form a hierarchical transcriptional cascade during JA-mediated plant immunity that initiates and amplifies transcriptional output. As proof of concept, we showed that during plant resistance to the necrotrophic pathogen Botrytis cinerea , MYC2 and the MTF JA2-Like form a transcription module that preferentially regulates wounding-responsive genes, whereas MYC2 and the MTF ETHYLENE RESPONSE FACTOR.C3 form a transcription module that preferentially regulates pathogen-responsive genes. © 2017 American Society of Plant Biologists. All rights reserved.

MYC2 Orchestrates a Hierarchical Transcriptional Cascade That Regulates Jasmonate-Mediated Plant Immunity in Tomato[OPEN

PubMed Central

Liu, Yuanyuan; Deng, Lei; Wu, Fangming; Huang, Zhuo; Zhou, Ming; Chen, Qian; Zhong, Silin

2017-01-01

The hormone jasmonate (JA), which functions in plant immunity, regulates resistance to pathogen infection and insect attack through triggering genome-wide transcriptional reprogramming in plants. We show that the basic helix-loop-helix transcription factor (TF) MYC2 in tomato (Solanum lycopersicum) acts downstream of the JA receptor to orchestrate JA-mediated activation of both the wounding and pathogen responses. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 655 MYC2-targeted JA-responsive genes. These genes are highly enriched in Gene Ontology categories related to TFs and the early response to JA, indicating that MYC2 functions at a high hierarchical level to regulate JA-mediated gene transcription. We also identified a group of MYC2-targeted TFs (MTFs) that may directly regulate the JA-induced transcription of late defense genes. Our findings suggest that MYC2 and its downstream MTFs form a hierarchical transcriptional cascade during JA-mediated plant immunity that initiates and amplifies transcriptional output. As proof of concept, we showed that during plant resistance to the necrotrophic pathogen Botrytis cinerea, MYC2 and the MTF JA2-Like form a transcription module that preferentially regulates wounding-responsive genes, whereas MYC2 and the MTF ETHYLENE RESPONSE FACTOR.C3 form a transcription module that preferentially regulates pathogen-responsive genes. PMID:28733419

[Non-specific immunosuppressive effect induced by A. actinomycetemcomitans].

PubMed

Ochiai, K; Kurita, T; Kamino, Y; Ikeda, T

1990-09-01

Previous studies have shown that immunosuppressive effects are related to the pathogenicity of periodontopathic bacteria and the development of periodontal disease. We reported soluble sonic extracts (SE) from A. actinomycetemcomitans and B. intermedius had a strong immunosuppressive effect on primary response of anti-SRBC plaque forming cells. SE from A. actinomycetemcomitans inhibited the IgM----IgG isotype switching. The purpose of this study was to investigate the effect of SE on secondary immunoresponse. As a control, mice (C3H/HeN) were immunized with intraperitoneal injection of SRBC and complete Freund's adjuvant, and additional SRBC after 30 days. In order to study the effect of SE from A. actinomycetemcomitans on secondary response, four groups were prepared in this study. One group of C3H/HeN mice were injected SE intravenously before the primary immunization of SRBC. The other three groups were given SE at different time on secondary injection of SRBC and designated the pre-, post-, or simultaneous injection, respectively. Hemolytic plaque assay was performed and estimated anti-SRBC plaque forming cells in each immunoglobulin class and IgG subclass, on the 5th day after the secondary injection. The immunosuppressive effect was found in all the groups which we examined. The present study strongly suggests that periodontopathic bacteria have strong adjuvant activity, and long-term Actinobacillus infection accompanied by periodontal fluctuation in bacterial flora may induce aberration in the immune system. The suppressed immune system explain the explosive growth of bacteria tested in our investigation, resulting in the mixed or opportunistic infection by bacteria harbored in the gingival crevice.

[The variola virus as a biological weapon].

PubMed

Mlinarić-Galinović, Gordana; Turković, Branko; Brudnjak, Zvonimir; Gjenero-Margan, Ira

2003-01-01

In view of the threat of use of the variola virus as a biological weapon, the interest of medical and other public in this causative agent that was eradicated in the wild at the end of the 1970s has increased. The paper gives an outline of the current knowledge on biological properties of the variola virus, and on the epidemiology, pathogenesis, clinical picture and prophylaxis of the disease caused by this virus. Descriptions of two sudden smallpox epidemics (Germany in 1970 and former Yugoslavia in 1972) could illustrate the potential of the smallpox virus as a biological weapon in bioterrorism and biological warfare. In fact, this virus can spread very readily through aerosol, which may lead to explosive epidemics. Not having been immunised, our population aged less than 25 years totally lacks the immunity. Older individuals are likely to have a low residual specific immunity to the agent. The only way to prevent a smallpox epidemic is by vaccination and patient isolation. A rapid smallpox diagnostics and prompt vaccination of all contacts is of utmost importance in stopping the outbreak.

Gene regulation by noncoding RNAs

PubMed Central

Patil, Veena S.; Zhou, Rui; Rana, Tariq M.

2015-01-01

The past two decades have seen an explosion in research on noncoding RNAs and their physiological and pathological functions. Several classes of small (20–30 nucleotides) and long (>200 nucleotides) noncoding RNAs have been firmly established as key regulators of gene expression in myriad processes ranging from embryonic development to innate immunity. In this review, we focus on our current understanding of the molecular mechanisms underlying the biogenesis and function of small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). In addition, we briefly review the relevance of small and long noncoding RNAs to human physiology and pathology and their potential to be exploited as therapeutic agents. PMID:24164576

Targeted therapy in lung cancer: IPASS and beyond, keeping abreast of the explosion of targeted therapies for lung cancer

PubMed Central

Savas, Peter; Hughes, Brett

2013-01-01

Advances in the treatment of non-small cell lung cancer (NSCLC) over the last decade have predominantly involved the development of therapies directed at molecular targets such as mutations in the epidermal growth factor receptor (EGFR) or rearrangements in the anaplastic lymphoma kinase (ALK) gene. Other targets have been discovered at low frequency, with multiple agents approved or in development for treatment of these rare molecular subtypes. The tumour microenvironment has also provided opportunities for therapies targeting angiogenesis and the host immune response. This review will provide an overview of current targeted therapies in NSCLC and promising treatment approaches on the horizon. PMID:24163750

Self-shielding flex-circuit drift tube, drift tube assembly and method of making

DOEpatents

Jones, David Alexander

2016-04-26

The present disclosure is directed to an ion mobility drift tube fabricated using flex-circuit technology in which every other drift electrode is on a different layer of the flex-circuit and each drift electrode partially overlaps the adjacent electrodes on the other layer. This results in a self-shielding effect where the drift electrodes themselves shield the interior of the drift tube from unwanted electro-magnetic noise. In addition, this drift tube can be manufactured with an integral flex-heater for temperature control. This design will significantly improve the noise immunity, size, weight, and power requirements of hand-held ion mobility systems such as those used for explosive detection.

Autosophy: an alternative vision for satellite communication, compression, and archiving

NASA Astrophysics Data System (ADS)

Holtz, Klaus; Holtz, Eric; Kalienky, Diana

2006-08-01

Satellite communication and archiving systems are now designed according to an outdated Shannon information theory where all data is transmitted in meaningless bit streams. Video bit rates, for example, are determined by screen size, color resolution, and scanning rates. The video "content" is irrelevant so that totally random images require the same bit rates as blank images. An alternative system design, based on the newer Autosophy information theory, is now evolving, which transmits data "contend" or "meaning" in a universally compatible 64bit format. This would allow mixing all multimedia transmissions in the Internet's packet stream. The new systems design uses self-assembling data structures, which grow like data crystals or data trees in electronic memories, for both communication and archiving. The advantages for satellite communication and archiving may include: very high lossless image and video compression, unbreakable encryption, resistance to transmission errors, universally compatible data formats, self-organizing error-proof mass memories, immunity to the Internet's Quality of Service problems, and error-proof secure communication protocols. Legacy data transmission formats can be converted by simple software patches or integrated chipsets to be forwarded through any media - satellites, radio, Internet, cable - without needing to be reformatted. This may result in orders of magnitude improvements for all communication and archiving systems.

49 CFR 172.522 - EXPLOSIVES 1.1, EXPLOSIVES 1.2 and EXPLOSIVES 1.3 placards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false EXPLOSIVES 1.1, EXPLOSIVES 1.2 and EXPLOSIVES 1.3... INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Placarding § 172.522 EXPLOSIVES 1.1, EXPLOSIVES 1.2 and EXPLOSIVES 1.3 placards. (a) Except for size and color, the EXPLOSIVES 1.1, EXPLOSIVES 1.2 and EXPLOSIVES 1.3...

49 CFR 172.522 - EXPLOSIVES 1.1, EXPLOSIVES 1.2 and EXPLOSIVES 1.3 placards.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false EXPLOSIVES 1.1, EXPLOSIVES 1.2 and EXPLOSIVES 1.3... INFORMATION, TRAINING REQUIREMENTS, AND SECURITY PLANS Placarding § 172.522 EXPLOSIVES 1.1, EXPLOSIVES 1.2 and EXPLOSIVES 1.3 placards. (a) Except for size and color, the EXPLOSIVES 1.1, EXPLOSIVES 1.2 and EXPLOSIVES 1.3...

Student Teachers’ Proof Schemes on Proof Tasks Involving Inequality: Deductive or Inductive?

NASA Astrophysics Data System (ADS)

Rosyidi, A. H.; Kohar, A. W.

2018-01-01

Exploring student teachers’ proof ability is crucial as it is important for improving the quality of their learning process and help their future students learn how to construct a proof. Hence, this study aims at exploring at the proof schemes of student teachers in the beginning of their studies. Data were collected from 130 proofs resulted by 65 Indonesian student teachers on two proof tasks involving algebraic inequality. To analyse, the proofs were classified into the refined proof schemes level proposed by Lee (2016) ranging from inductive, which only provides irrelevant inferences, to deductive proofs, which consider addressing formal representation. Findings present several examples of each of Lee’s level on the student teachers’ proofs spanning from irrelevant inferences, novice use of examples or logical reasoning, strategic use examples for reasoning, deductive inferences with major and minor logical coherence, and deductive proof with informal and formal representation. Besides, it was also found that more than half of the students’ proofs coded as inductive schemes, which does not meet the requirement for doing the proof for the proof tasks examined in this study. This study suggests teacher educators in teacher colleges to reform the curriculum regarding proof learning which can accommodate the improvement of student teachers’ proving ability from inductive to deductive proof as well from informal to formal proof.

Zonal wavefront sensing using a grating array printed on a polyester film

NASA Astrophysics Data System (ADS)

Pathak, Biswajit; Kumar, Suraj; Boruah, Bosanta R.

2015-12-01

In this paper, we describe the development of a zonal wavefront sensor that comprises an array of binary diffraction gratings realized on a transparent sheet (i.e., polyester film) followed by a focusing lens and a camera. The sensor works in a manner similar to that of a Shack-Hartmann wavefront sensor. The fabrication of the array of gratings is immune to certain issues associated with the fabrication of the lenslet array which is commonly used in zonal wavefront sensing. Besides the sensing method offers several important advantages such as flexible dynamic range, easy configurability, and option to enhance the sensing frame rate. Here, we have demonstrated the working of the proposed sensor using a proof-of-principle experimental arrangement.

Measurement-Device-Independent Quantum Key Distribution over 200 km

NASA Astrophysics Data System (ADS)

Tang, Yan-Lin; Yin, Hua-Lei; Chen, Si-Jing; Liu, Yang; Zhang, Wei-Jun; Jiang, Xiao; Zhang, Lu; Wang, Jian; You, Li-Xing; Guan, Jian-Yu; Yang, Dong-Xu; Wang, Zhen; Liang, Hao; Zhang, Zhen; Zhou, Nan; Ma, Xiongfeng; Chen, Teng-Yun; Zhang, Qiang; Pan, Jian-Wei

2014-11-01

Measurement-device-independent quantum key distribution (MDIQKD) protocol is immune to all attacks on detection and guarantees the information-theoretical security even with imperfect single-photon detectors. Recently, several proof-of-principle demonstrations of MDIQKD have been achieved. Those experiments, although novel, are implemented through limited distance with a key rate less than 0.1 bit /s . Here, by developing a 75 MHz clock rate fully automatic and highly stable system and superconducting nanowire single-photon detectors with detection efficiencies of more than 40%, we extend the secure transmission distance of MDIQKD to 200 km and achieve a secure key rate 3 orders of magnitude higher. These results pave the way towards a quantum network with measurement-device-independent security.

All-optical phase modulation for integrated interferometric biosensors.

PubMed

Dante, Stefania; Duval, Daphné; Sepúlveda, Borja; González-Guerrero, Ana Belen; Sendra, José Ramón; Lechuga, Laura M

2012-03-26

We present the theoretical and the experimental implementation of an all-optical phase modulation system in integrated Mach-Zehnder Interferometers to solve the drawbacks related to the periodic nature of the interferometric signal. Sensor phase is tuned by modulating the emission wavelength of low-cost commercial laser diodes by changing their output power. FFT deconvolution of the signal allows for direct phase readout, immune to sensitivity variations and to light intensity fluctuations. This simple phase modulation scheme increases the signal-to-noise ratio of the measurements in one order of magnitude, rendering in a sensor with a detection limit of 1.9·10⁻⁷ RIU. The viability of the all-optical modulation approach is demonstrated with an immunoassay detection as a biosensing proof of concept.

Proof-of-Principle for Immune Control of Global HIV-1 Reactivation In Vivo

PubMed Central

Smith, Nicola M. G.; Mlcochova, Petra; Watters, Sarah A.; Aasa-Chapman, Marlene M. I.; Rabin, Neil; Moore, Sally; Edwards, Simon G.; Garson, Jeremy A.; Grant, Paul R.; Ferns, R. Bridget; Kashuba, Angela; Mayor, Neema P.; Schellekens, Jennifer; Marsh, Steven G. E.; McMichael, Andrew J.; Perelson, Alan S.; Pillay, Deenan; Goonetilleke, Nilu; Gupta, Ravindra K.

2015-01-01

Background. Emerging data relating to human immunodeficiency virus type 1 (HIV-1) cure suggest that vaccination to stimulate the host immune response, particularly cytotoxic cells, may be critical to clearing of reactivated HIV-1–infected cells. However, evidence for this approach in humans is lacking, and parameters required for a vaccine are unknown because opportunities to study HIV-1 reactivation are rare. Methods. We present observations from a HIV-1 elite controller, not treated with combination antiretroviral therapy, who experienced viral reactivation following treatment for myeloma with melphalan and autologous stem cell transplantation. Mathematical modeling was performed using a standard viral dynamic model. Enzyme-linked immunospot, intracellular cytokine staining, and tetramer staining were performed on peripheral blood mononuclear cells; in vitro CD8 T-cell–mediated control of virion production by autologous CD4 T cells was quantified; and neutralizing antibody titers were measured. Results. Viral rebound was measured at 28 000 copies/mL on day 13 post-transplant before rapid decay to <50 copies/mL in 2 distinct phases with t1/2 of 0.71 days and 4.1 days. These kinetics were consistent with an expansion of cytotoxic effector cells and killing of productively infected CD4 T cells. Following transplantation, innate immune cells, including natural killer cells, recovered with virus rebound. However, most striking was the expansion of highly functional HIV-1–specific cytotoxic CD8 T cells, at numbers consistent with those applied in modeling, as virus control was regained. Conclusions. These observations provide evidence that the human immune response is capable of controlling coordinated global HIV-1 reactivation, remarkably with potency equivalent to combination antiretroviral therapy. These data will inform design of vaccines for use in HIV-1 curative interventions. PMID:25778749

Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody Gene Transfer Protects Nonhuman Primates from Mucosal Simian-Human Immunodeficiency Virus Infection

PubMed Central

Saunders, Kevin O.; Wang, Lingshu; Joyce, M. Gordon; Yang, Zhi-Yong; Balazs, Alejandro B.; Cheng, Cheng; Ko, Sung-Youl; Kong, Wing-Pui; Rudicell, Rebecca S.; Georgiev, Ivelin S.; Duan, Lijie; Foulds, Kathryn E.; Donaldson, Mitzi; Xu, Ling; Schmidt, Stephen D.; Todd, John-Paul; Baltimore, David; Roederer, Mario; Haase, Ashley T.; Kwong, Peter D.; Rao, Srinivas S.

2015-01-01

ABSTRACT Broadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, durable expression is essential for its broader use in humans. Gene-based expression of bnAbs provides a potential solution to this problem, although immune responses to the viral vector or to the antibody may limit its durability and efficacy. Here, we delivered an adeno-associated viral vector encoding a simianized form of a CD4bs bnAb, VRC07, and evaluated its immunogenicity and protective efficacy. The expressed antibody circulated in macaques for 16 weeks at levels up to 66 μg/ml, although immune suppression with cyclosporine (CsA) was needed to sustain expression. Gene-delivered simian VRC07 protected against simian-human immunodeficiency virus (SHIV) infection in monkeys 5.5 weeks after treatment. Gene transfer of an anti-HIV antibody can therefore protect against infection by viruses that cause AIDS in primates when the host immune responses are controlled. IMPORTANCE Sustained interventions that can prevent HIV-1 infection are needed to halt the spread of the HIV-1 pandemic. The protective capacity of anti-HIV antibody gene therapy has been established in mouse models of HIV-1 infection but has not been established for primates. We show here a proof-of-concept that gene transfer of anti-HIV antibody genes can protect against infection by viruses that cause AIDS in primates when host immune responses are controlled. PMID:26041300

Antigen presentation under the influence of 'immune evasion' proteins and its modulation by interferon-gamma: implications for immunotherapy of cytomegalovirus infection with antiviral CD8 T cells.

PubMed

Fink, Annette; Lemmermann, Niels A W; Gillert-Marien, Dorothea; Thomas, Doris; Freitag, Kirsten; Böhm, Verena; Wilhelmi, Vanessa; Reifenberg, Kurt; Reddehase, Matthias J; Holtappels, Rafaela

2012-11-01

Cytomegalovirus (CMV) disease with multiple organ manifestations is the most feared viral complication limiting the success of hematopoietic cell transplantation as a therapy of hematopoietic malignancies. A timely endogenous reconstitution of CD8 T cells controls CMV infection, and adoptive transfer of antiviral CD8 T cells is a therapeutic option to prevent CMV disease by bridging the gap between an early CMV reactivation and delayed endogenous reconstitution of protective immunity. Preclinical research in murine models has provided 'proof of concept' for CD8 T-cell therapy of CMV disease. Protection by CD8 T cells appears to be in conflict with the finding that CMVs encode proteins that inhibit antigen presentation to CD8 T cells by interfering with the constitutive trafficking of peptide-loaded MHC class I molecules (pMHC-I complexes) to the cell surface. Here, we have systematically explored antigen presentation in the presence of the three currently noted immune evasion proteins of murine CMV in all possible combinations and its modulation by pre-treatment of cells with interferon-gamma (IFN-γ). The data reveal improvement in antigen processing by pre-treatment with IFN-γ can almost overrule the inhibitory function of immune evasion molecules in terms of pMHC-I expression levels capable of triggering most of the specific CD8 T cells, though the intensity of stimulation did not retrieve their full functional capacity. Notably, an in vivo conditioning of host tissue cells with IFN-γ in adoptive cell transfer recipients constitutively overexpressing IFN-γ (B6-SAP-IFN-γ mice) enhanced the antiviral efficiency of CD8 T cells in this transgenic cytoimmunotherapy model.

Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study.

PubMed

Lankelma, Jacqueline M; Cranendonk, Duncan R; Belzer, Clara; de Vos, Alex F; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

2017-09-01

The gut microbiota is essential for the development of the intestinal immune system. Animal models have suggested that the gut microbiota also acts as a major modulator of systemic innate immunity during sepsis. Microbiota disruption by broad-spectrum antibiotics could thus have adverse effects on cellular responsiveness towards invading pathogens. As such, the use of antibiotics may attribute to immunosuppression as seen in sepsis. We aimed to test whether disruption of the gut microbiota affects systemic innate immune responses during endotoxemia in healthy subjects. In this proof-of-principle intervention trial, 16 healthy young men received either no treatment or broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days, after which all were administered lipopolysaccharide intravenously to induce a transient sepsis-like syndrome. At various time points, blood and faeces were sampled. Gut microbiota diversity was significantly lowered by the antibiotic treatment in all subjects. Clinical parameters, neutrophil influx, cytokine production, coagulation activation and endothelial activation during endotoxemia were not different between antibiotic-pretreated and control individuals. Antibiotic treatment had no impact on blood leucocyte responsiveness to various Toll-like receptor ligands and clinically relevant causative agents of sepsis ( Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli ) during endotoxemia. These findings suggest that gut microbiota disruption by broad-spectrum antibiotics does not affect systemic innate immune responses in healthy subjects during endotoxemia in humans, disproving our hypothesis. Further research is needed to test this hypothesis in critically ill patients. These data underline the importance of translating findings in mice to humans. ClinicalTrials.gov (NCT02127749; Pre-results). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Vaccine Efficacy against Malaria by the Combination of Porcine Parvovirus-Like Particles and Vaccinia Virus Vectors Expressing CS of Plasmodium

PubMed Central

Rodríguez, Dolores; González-Aseguinolaza, Gloria; Rodríguez, Juan R.; Vijayan, Aneesh; Gherardi, Magdalena; Rueda, Paloma; Casal, J. Ignacio; Esteban, Mariano

2012-01-01

With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8+ T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8+ T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria. PMID:22529915

Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium.

PubMed

Rodríguez, Dolores; González-Aseguinolaza, Gloria; Rodríguez, Juan R; Vijayan, Aneesh; Gherardi, Magdalena; Rueda, Paloma; Casal, J Ignacio; Esteban, Mariano

2012-01-01

With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8(+) T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+) T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.

Sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.

PubMed

Ramiro, Ricardo S; Alpedrinha, João; Carter, Lucy; Gardner, Andy; Reece, Sarah E

2011-03-01

Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction - that host immune responses have differential effects on the mating ability of males and females - have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely to be 'evolution-proof' than interventions directed at killing males or females. Given the drive to develop medical interventions that interfere with parasite mating, our data and theoretical models have important implications.

From research to phase III: preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccine.

PubMed

Guy, Bruno; Barrere, Beatrice; Malinowski, Claire; Saville, Melanie; Teyssou, Remy; Lang, Jean

2011-09-23

Dengue vaccine development has reached a major milestone with the initiation, in 2010, of the first phase III clinical trial to investigate the Sanofi Pasteur CYD tetravalent dengue vaccine (TDV). The CYD TDV candidate is composed of four recombinant, live, attenuated vaccines (CYD-1-4) based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the pre-membrane and envelope genes of one of the four dengue virus serotypes. The vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D, and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies showed that CYD TDV induces controlled stimulation of human dendritic cells, and significant immune responses in monkeys. Scale up and industrialization are being conducted in parallel with preclinical and clinical development to fulfill the needs of phase II/III trials, and to anticipate and facilitate supply and access to vaccine in the countries where the dengue disease burden makes it an urgent public health priority. The vaccine has now been administered to more than 6000 children and adults from dengue endemic and non-endemic areas and no safety concerns have arisen in any of the completed or ongoing trials. A three-dose vaccination regimen induces an immune response against all four serotypes in the large majority of vaccinees. Preexisting flavivirus immunity favors quicker and higher immune responses to CYD TDV, without adversely effecting clinical safety or increasing vaccine viremia. The observed level and nature of the cellular immune responses in humans are consistent with the good safety and immunogenicity profile of the vaccine. Preliminary results of an ongoing, proof-of-concept efficacy and large scale safety study in Thai children are expected by the end of 2012. Here we discuss the different steps and challenges of developing CYD TDV, from research to industrialization, and summarize some of the challenges to the successful introduction of a dengue vaccine into immunization programs. Copyright © 2011 Elsevier Ltd. All rights reserved.

Compliance with the vaccination schedule in children hospitalized with pneumonia and associated factors

PubMed Central

da Silva, Amanda Tabosa Pereira; Lima, Eduardo Jorge da Fonseca; Caminha, Maria de Fátima Costa; da Silva, Andresa Tabosa Pereira; Rodrigues, Edil de Albuquerque; dos Santos, Carmina Silva

2018-01-01

ABSTRACT OBJECTIVE: To verify the adequacy and factors associated with compliance with the immunization schedule (BCG, DTP-Hib, MMR, PCV-10) in children hospitalized with pneumonia at a pediatric referral hospital in Northeast Brazil. METHODS: This is a cross-sectional, descriptive study with an analytical component, with a sample of 452 children hospitalized with pneumonia at the Instituto de Medicina Integral Prof. Fernando Figueira, between 2010 and 2013. The inclusion criterion was children aged from one month to less than five years of age with proof in the immunization record. The exclusion criterion was the presence of hospital-acquired pneumonia or concomitant disease. We have evaluated the adequacy of the immunization schedule for the BCG, tetravalent, MMR, and 10-valent pneumococcal conjugate (PCV-10) vaccines. We used the chi-square test and Fisher's exact test followed by multivariate Poisson regression, estimating the crude and adjusted prevalence ratios and respective 95% confidence intervals. The variables with p < 0.20 in the univariate analysis were included in the multivariate analysis. RESULTS: There was good adequacy in the immunization schedule, except for PCV-10, which presented a percentage lower than 85%. We have observed an association between adequate compliance with the immunization schedule and education level of the mother (89.9% complete high school), sex of the child (87.2% female), age of the child (94.2% younger than six months), and breastfeeding (84.3% breastfed). CONCLUSIONS: Given the high rate of education level of the mother and the high percentage of breastfeeding, we can understand that there is a better understanding of the health of the child by the mothers studied in this study, showing the effectiveness of public policies for infant feeding. However, children did not have good adequacy of the immunization schedule of PCV-10, one of the main vaccines against pneumonia, which can be one of the main factors in the causes of hospitalization, with no influence on the classification of the severity of the disease. In this way, we emphasize that the causes of pneumonia morbidity are not associated with a single factor. PMID:29668816

Induction of Strain-Transcending Immunity against Plasmodium chabaudi adami Malaria with a Multiepitope DNA Vaccine

PubMed Central

Scorza, T.; Grubb, K.; Smooker, P.; Rainczuk, A.; Proll, D.; Spithill, T. W.

2005-01-01

A major goal of current malaria vaccine programs is to develop multivalent vaccines that will protect humans against the many heterologous malaria strains that circulate in endemic areas. We describe a multiepitope DNA vaccine, derived from a genomic Plasmodium chabaudi adami DS DNA expression library of 30,000 plasmids, which induces strain-transcending immunity in mice against challenge with P. c. adami DK. Segregation of this library and DNA sequence analysis identified vaccine subpools encoding open reading frames (ORFs)/peptides of >9 amino acids [aa] (the V9+ pool, 303 plasmids) and >50 aa (V50+ pool, 56 plasmids), respectively. The V9+ and V50+ plasmid vaccine subpools significantly cross-protected mice against heterologous P. c. adami DK challenge, and protection correlated with the induction of both specific gamma interferon production by splenic cells and opsonizing antibodies. Bioinformatic analysis showed that 22 of the V50+ ORFs were polypeptides conserved among three or more Plasmodium spp., 13 of which are predicted hypothetical proteins. Twenty-nine of these ORFs are orthologues of predicted Plasmodium falciparum sequences known to be expressed in the blood stage, suggesting that this vaccine pool encodes multiple blood-stage antigens. The results have implications for malaria vaccine design by providing proof-of-principle that significant strain-transcending immunity can be induced using multiepitope blood-stage DNA vaccines and suggest that both cellular responses and opsonizing antibodies are necessary for optimal protection against P. c. adami. PMID:15845504

Mass Measles Vaccination Campaign in Aila Cyclone-Affected Areas of West Bengal, India: An In-depth Analysis and Experiences.

PubMed

Mallik, Sarmila; Mandal, Pankaj Kumar; Ghosh, Pramit; Manna, Nirmalya; Chatterjee, Chitra; Chakrabarty, Debadatta; Bagchi, Saumendra Nath; Dasgupta, Samir

2011-12-01

Disaster-affected populations are highly vulnerable to outbreaks of measles. Therefore, a mass vaccination against measles was conducted in Aila cyclone-affected blocks of West Bengal, India in July 2009. The objectives of the present report were to conduct an in depth analysis of the campaign, and to discuss the major challenges. A block level micro-plan, which included mapping of the villages, health facilities, temporary settlements of disaster-affected population, communications available, formation of vaccination team, information education communication, vaccine storage, waste disposal, surveillance for adverse events following immunization, supervision and monitoring was developed. The rate of six months to five years old children, who were vaccinated by measles vaccine, was 70.7% and that of those who received one dose of vitamin A was 71.3%. Wastage factor for vaccine doses and auto-disable syringes were 1.09 and 1.07, respectively. Only 13 cases of adverse events following immunization were reported. An average of 0.91 puncture-proof containers per vaccination session was used. Despite the major challenges faced due to difficult to reach areas, inadequate infrastructure, manpower and communication, problems of vaccine storage and transport, the campaign achieved a remarkable success regarding measles vaccine coverage, improvements of cold chain infrastructure, formulating an efficient surveillance and reporting system for adverse events following immunization, building self-confidence of the stakeholders, and developing a biomedical waste disposal system.

Protection of calves by a prefusion-stabilized bovine RSV F vaccine.

PubMed

Zhang, Baoshan; Chen, Lei; Silacci, Chiara; Thom, Michelle; Boyington, Jeffrey C; Druz, Aliaksandr; Joyce, M Gordon; Guzman, Efrain; Kong, Wing-Pui; Lai, Yen-Ting; Stewart-Jones, Guillaume B E; Tsybovsky, Yaroslav; Yang, Yongping; Zhou, Tongqing; Baxa, Ulrich; Mascola, John R; Corti, Davide; Lanzavecchia, Antonio; Taylor, Geraldine; Kwong, Peter D

2017-03-08

Bovine respiratory syncytial virus, a major cause of respiratory disease in calves, is closely related to human RSV, a leading cause of respiratory disease in infants. Recently, promising human RSV-vaccine candidates have been engineered that stabilize the metastable fusion (F) glycoprotein in its prefusion state; however, the absence of a relevant animal model for human RSV has complicated assessment of these vaccine candidates. Here, we use a combination of structure-based design, antigenic characterization, and X-ray crystallography to translate human RSV F stabilization into the bovine context. A "DS2" version of bovine respiratory syncytial virus F with subunits covalently fused, fusion peptide removed, and pre-fusion conformation stabilized by cavity-filling mutations and intra- and inter-protomer disulfides was recognized by pre-fusion-specific antibodies, AM14, D25, and MPE8, and elicited bovine respiratory syncytial virus-neutralizing titers in calves >100-fold higher than those elicited by post-fusion F. When challenged with a heterologous bovine respiratory syncytial virus, virus was not detected in nasal secretions nor in respiratory tract samples of DS2-immunized calves; by contrast bovine respiratory syncytial virus was detected in all post-fusion- and placebo-immunized calves. Our results demonstrate proof-of-concept that DS2-stabilized RSV F immunogens can induce highly protective immunity from RSV in a native host with implications for the efficacy of prefusion-stabilized F vaccines in humans and for the prevention of bovine respiratory syncytial virus in calves.

A critical assessment of the association between postnatal toxoplasmosis and epilepsy in immune-competent patients.

PubMed

Uzorka, J W; Arend, S M

2017-07-01

While postnatal toxoplasmosis in immune-competent patients is generally considered a self-limiting and mild illness, it has been associated with a variety of more severe clinical manifestations. The causal relation with some manifestations, e.g. myocarditis, has been microbiologically proven, but this is not unequivocally so for other reported associations, such as with epilepsy. We aimed to systematically assess causality between postnatal toxoplasmosis and epilepsy in immune-competent patients. A literature search was performed. The Bradford Hill criteria for causality were used to score selected articles for each component of causality. Using an arbitrary but defined scoring system, the maximal score was 15 points (13 for case reports). Of 704 articles, five case reports or series and five case-control studies were selected. The strongest evidence for a causal relation was provided by two case reports and one case-control study, with a maximal causality score of, respectively, 9/13, 10/13 and 10/15. The remaining studies had a median causality score of 7 (range 5-9). No selection bias was identified, but 6/10 studies contained potential confounders (it was unsure whether the infection was pre- or postnatal acquired, or immunodeficiency was not specifically excluded). Based on the evaluation of the available literature, although scanty and of limited quality, a causal relationship between postnatal toxoplasmosis and epilepsy seems possible. More definite proof requires further research, e.g. by performing Toxoplasma serology in all de novo epilepsy cases.

Mass Measles Vaccination Campaign in Aila Cyclone-Affected Areas of West Bengal, India: An In-depth Analysis and Experiences

PubMed Central

Mallik, Sarmila; Mandal, Pankaj Kumar; Ghosh, Pramit; Manna, Nirmalya; Chatterjee, Chitra; Chakrabarty, Debadatta; Bagchi, Saumendra Nath; Dasgupta, Samir

2011-01-01

Disaster-affected populations are highly vulnerable to outbreaks of measles. Therefore, a mass vaccination against measles was conducted in Aila cyclone-affected blocks of West Bengal, India in July 2009. The objectives of the present report were to conduct an in depth analysis of the campaign, and to discuss the major challenges. A block level micro-plan, which included mapping of the villages, health facilities, temporary settlements of disaster-affected population, communications available, formation of vaccination team, information education communication, vaccine storage, waste disposal, surveillance for adverse events following immunization, supervision and monitoring was developed. The rate of six months to five years old children, who were vaccinated by measles vaccine, was 70.7% and that of those who received one dose of vitamin A was 71.3%. Wastage factor for vaccine doses and auto-disable syringes were 1.09 and 1.07, respectively. Only 13 cases of adverse events following immunization were reported. An average of 0.91 puncture-proof containers per vaccination session was used. Despite the major challenges faced due to difficult to reach areas, inadequate infrastructure, manpower and communication, problems of vaccine storage and transport, the campaign achieved a remarkable success regarding measles vaccine coverage, improvements of cold chain infrastructure, formulating an efficient surveillance and reporting system for adverse events following immunization, building self-confidence of the stakeholders, and developing a biomedical waste disposal system. PMID:23115416

A minimally invasive optical trapping system to understand cellular interactions at onset of an immune response

PubMed Central

Glass, David G.; McAlinden, Niall; Millington, Owain R.

2017-01-01

T-cells and antigen presenting cells are an essential part of the adaptive immune response system and how they interact is crucial in how the body effectively fights infection or responds to vaccines. Much of the experimental work studying interaction forces between cells has looked at the average properties of bulk samples of cells or applied microscopy to image the dynamic contact between these cells. In this paper we present a novel optical trapping technique for interrogating the force of this interaction and measuring relative interaction forces at the single-cell level. A triple-spot optical trap is used to directly manipulate the cells of interest without introducing foreign bodies such as beads to the system. The optical trap is used to directly control the initiation of cell-cell contact and, subsequently to terminate the interaction at a defined time point. The laser beam power required to separate immune cell pairs is determined and correlates with the force applied by the optical trap. As proof of concept, the antigen-specific increase in interaction force between a dendritic cell and a specific T-cell is demonstrated. Furthermore, it is demonstrated that this interaction force is completely abrogated when T-cell signalling is blocked. As a result the potential of using optical trapping to interrogate cellular interactions at the single cell level without the need to introduce foreign bodies such as beads is clearly demonstrated. PMID:29220398

27 CFR 555.182 - Exceptions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... testing of new or modified explosive materials; (2) Training in explosives detection or development or testing of explosives detection equipment; or (3) Forensic science purposes; or (b) Was plastic explosive... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.182...

27 CFR 555.182 - Exceptions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... testing of new or modified explosive materials; (2) Training in explosives detection or development or testing of explosives detection equipment; or (3) Forensic science purposes; or (b) Was plastic explosive... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.182...

Pancreatic cancer-specific cell death induced in vivo by cytoplasmic-delivered polyinosine-polycytidylic acid

PubMed Central

Bhoopathi, Praveen; Quinn, Bridget A.; Gui, Qin; Shen, Xue-Ning; Grossman, Steven R.; Das, Swadesh K.; Sarkar, Devanand; Fisher, Paul B.; Emdad, Luni

2014-01-01

Polyinosine-polycytidylic acid (pIC) is a synthetic dsRNA that acts as an immune agonist of TLR3 and RLR to activate dendritic and NK cells that can kill tumor cells. pIC can also trigger apoptosis in pancreatic ductal adenocarcinoma cells but its mechanism of action is obscure. In this study, we investigated the potential therapeutic activity of a formulation of pIC with polyethylenimine ([pIC]PEI) in PDAC and investigated its mechanism of action. [pIC]PEI stimulated apoptosis in PDAC cells without affecting normal pancreatic epithelial cells. Mechanistically, [pIC]PEI repressed XIAP and survivin expression and activated an immune response by inducing MDA-5, RIG-I and NOXA. Phosphorylation of AKT was inhibited by [pIC]PEI in PDAC and this event was critical for stimulating apoptosis through XIAP and survivin degradation. In vivo administration of [pIC]PEI inhibited tumor growth via AKT-mediated XIAP degradation in both subcutaneous and quasi-orthotopic-models of PDAC. Taken together, these results offer a preclinical proof-of-concept for the evaluation of [pIC]PEI as an immunochemotherapy to treat pancreatic cancer. PMID:25205107

Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein.

PubMed

Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma; Heyndrickx, Leo; LaBranche, Celia; Applequist, Steven E; Jansson, Marianne; De Silva, Thushan; Back, Jaap Willem; Achour, Adnane; Scarlatti, Gabriella; Fomsgaard, Anders; Montefiori, David; Stewart-Jones, Guillaume; Spetz, Anna-Lena

2014-06-15

Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1. Copyright © 2014 by The American Association of Immunologists, Inc.

Stress and food allergy: mechanistic considerations.

PubMed

Schreier, Hannah M C; Wright, Rosalind J

2014-04-01

Recent years have seen a marked increase in food allergy prevalence among children, particularly in Western countries, that cannot be explained by genetic factors alone. This has resulted in an increased effort to identify environmental risk factors underlying food allergies and to understand how these factors may be modified through interventions. Food allergy is an immune-mediated adverse reaction to food. Consequently, considerations of candidate risk factors have begun to focus on environmental influences that perturb the healthy development of the emerging immune system during critical periods of development (eg, prenatally and during early childhood), particularly in the gut. Given that psychosocial stress is known to play an important role in other allergic and inflammatory diseases, such as asthma, its potential role in food allergy is a growing area of research. However, research to date has largely focused on animal studies. This review synthesizes relevant animal research and epidemiological data, providing proof of concept for moderating influences of psychological stress on food allergy outcomes in humans. Pathways that may underlie associations between psychosocial stress and the expression of food allergy are discussed. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies

PubMed Central

Dorneburg, Carmen; Debatin, Klaus-Michael; Wei, Jiwu; Beltinger, Christian

2018-01-01

Background Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase clinical trials. However, pre-existing immunity against measles might be a hurdle for OMV therapy. Methods OMV was inactivated with short-wavelength ultraviolet light (UV-C). Loss of replication and oncolytic activity of UV-inactivated OMV were confirmed by tissue culture infective dose 50 (TCID50) assay using Vero cells and by flow cytometry using Jurkat cells. An enzyme-linked immunosorbent assay was performed to verify that UV-inactivated OMV remained antigenic. Different doses of UV-inactivated OMV were pre-cultured in media supplemented with measles immune serum. The mixture was transferred to Jurkat cells and active OMV was added. Active OMV-induced death of Jurkat cells was monitored by flow cytometry. Results UV-inactivation abrogates OMV replication while maintaining its antigenicity. UV-inactivated OMV sequesters pre-existing anti-MV antibodies in Jurkat cell culture, thereby protecting active OMV from neutralization and preserving oncolytic activity. Conclusion We prove the principle that a non-replicating OMV can serve as a “decoy” for neutralizing anti-MV antibodies, thereby allowing antitumor activity of OMV. PMID:29750140

Explosion of autoimmune diseases and the mosaic of old and novel factors

PubMed Central

Agmon-Levin, Nancy; Lian, Zhexiong; Shoenfeld, Yehuda

2011-01-01

In recent decades, an enormous effort has been made to elucidate the pathogenesis of autoimmune and autoinflammatory diseases. Autoimmunity is a multifactorial process in which genetic, immunological, environmental and hormonal factors play in concert, together representing what was termed years ago the ‘mosaic of autoimmunity'. To date, more than 80 systemic and organ-specific autoimmune diseases have been defined, and their cumulative burden is substantial, both medically and financially. Furthermore, the burden of autoimmune and autoinflammatory diseases is rising, making these diseases a ubiquitous global phenomenon that is predicted to further increase in the coming decades. In this issue of the journal, additional aspects of autoimmunity are detailed. Immune dysregulation and loss of self-tolerance are the cornerstones of autoimmunity. PMID:21358666

Cow’s Milk and Immune Function in the Respiratory Tract: Potential Mechanisms

PubMed Central

Perdijk, Olaf; van Splunter, Marloes; Savelkoul, Huub F. J.; Brugman, Sylvia; van Neerven, R. J. Joost

2018-01-01

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow’s milk. Indeed, recent studies show inverse associations between raw cow’s milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow’s milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow’s milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow’s milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow’s milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow’s milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms via which cow’s milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention. PMID:29483908

Cow's Milk and Immune Function in the Respiratory Tract: Potential Mechanisms.

PubMed

Perdijk, Olaf; van Splunter, Marloes; Savelkoul, Huub F J; Brugman, Sylvia; van Neerven, R J Joost

2018-01-01

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow's milk. Indeed, recent studies show inverse associations between raw cow's milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow's milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow's milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow's milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow's milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow's milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms via which cow's milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention.

Taple-top imaging of the non-adiabatically driven isomerization in the acetylene cation

NASA Astrophysics Data System (ADS)

Beaulieu, Samuel; Ibrahim, Heide; Wales, Benji; Schmidt, Bruno E.; Thiré, Nicolas; Bisson, Éric; Hebeisen, Christoph T.; Wanie, Vincent; Giguere, Mathieu; Kieffer, Jean-Claude; Sanderson, Joe; Schuurman, Michael S.; Légaré, François

2014-05-01

One of the primary goals of modern ultrafast science is to follow nuclear and electronic evolution of molecules as they undergo a photo-chemical reaction. Most of the interesting dynamics phenomena in molecules occur when an electronically excited state is populated. When the energy difference between electronic ground and excited states is large, Free Electron Laser (FEL) and HHG-based VUV sources were, up to date, the only light sources able to efficiently initiate those non-adiabatic dynamics. We have developed a simple table-top approach to initiate those rich dynamics via multiphoton absorption. As a proof of principle, we studied the ultrafast isomerization of the acetylene cation. We have chosen this model system for isomerization since the internal conversion mechanism which leads to proton migration is still under debate since decades. Using 266 nm multiphoton absorption as a pump and 800 nm induced Coulomb Explosion as a probe, we have shoot the first high-resolution molecular movie of the non-adiabatically driven proton migration in the acetylene cation. The experimental results are in excellent agreement with high level ab initio trajectory simulations.

Heat pump/refrigerator using liquid working fluid

DOEpatents

Wheatley, John C.; Paulson, Douglas N.; Allen, Paul C.; Knight, William R.; Warkentin, Paul A.

1982-01-01

A heat transfer device is described that can be operated as a heat pump or refrigerator, which utilizes a working fluid that is continuously in a liquid state and which has a high temperature-coefficient of expansion near room temperature, to provide a compact and high efficiency heat transfer device for relatively small temperature differences as are encountered in heating or cooling rooms or the like. The heat transfer device includes a pair of heat exchangers that may be coupled respectively to the outdoor and indoor environments, a regenerator connecting the two heat exchangers, a displacer that can move the liquid working fluid through the heat exchangers via the regenerator, and a means for alternately increasing and decreasing the pressure of the working fluid. The liquid working fluid enables efficient heat transfer in a compact unit, and leads to an explosion-proof smooth and quiet machine characteristic of hydraulics. The device enables efficient heat transfer as the indoor-outdoor temperature difference approaches zero, and enables simple conversion from heat pumping to refrigeration as by merely reversing the direction of a motor that powers the device.

Sports doping in the adolescent: the Faustian conundrum of Hors de Combat.

PubMed

Greydanus, Donald E; Patel, Dilip R

2010-06-01

The drive toward success in sports and the need for a cosmetically acceptable appearance have driven many adolescents to take a wide variety of so-called doping substances. The consumption of these chemicals in the hope and hype of improved sports performance, fueled by the easing of government restrictions on their proof of safety and efficacy, has resulted in an explosion of so-called ergogenic products available to our youth. Agents that have been used include anabolic steroids, anabolic-like agents, designer steroids, creatine, protein and amino acid supplements, minerals, antioxidants, stimulants, blood doping, erythropoietin, beta-blockers, and others. The use of these agents has considerable potential to cause physical and psychological damage. Use and misuse of drugs in this sports doping process should be discouraged. This discussion reviews some of the agents that are currently being used. Clinicians providing sports medicine care to youth, whether through anticipatory guidance or direct sports medicine management, should educate their young patients about the hype and hyperbole of these products that may keep them out instead of in the game at considerable financial cost to the unwary consumer.

Credit BG. This view looks northwest (290°) in the mixer ...

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

Credit BG. This view looks northwest (290°) in the mixer room at the 30-gallon Baker-Perkins model 121/2 PVM mixer and its associated equipment. The hopper in the left background feeds ingredients to the mixing pot when the hopper is mounted on the mixer frame; the hoist overhead is used to mount the hopper. The mixing pot is in its lowered position beneath the mixer blades. The pot is normally raised and secured to the upper half of the mixer, and a vacuum is applied during mixing operations to prevent the entrainment of air bubbles in the mix. A second mixing pot appears in the right background, and a pot vacuum lid appears in the extreme right foreground. The equipment on the palette in the left foreground is not related to the mixer. Note the explosion-proof fluorescent lighting fixtures suspended from the ceiling. The floor has an electrically conductive coating to dissipate static electrical charges - Jet Propulsion Laboratory Edwards Facility, Mixer & Casting Building, Edwards Air Force Base, Boron, Kern County, CA

Preservice Teacher Beliefs about Proofs.

ERIC Educational Resources Information Center

Mingus, Tabitha T. Y.; Grassl, Richard M.

1999-01-01

Describes the study of backgrounds, beliefs, and attitudes of teachers (n=51) about proofs. Explores four issues: (1) preservice teachers' experiences/exposure to proof; (2) their beliefs about what constitutes proof; (3) the role of proof in mathematics; and (4) their beliefs about when proof should be introduced in K-12 math classes. Discusses…

Integrating Algebra and Proof in High School: Students' Work with Multiple Variables and a Single Parameter in a Proof Context

ERIC Educational Resources Information Center

Martinez, Mara V.; Castro Superfine, Alison

2012-01-01

In the United States, researchers argue that proof is largely concentrated in the domain of high school geometry, thus providing students a distorted image of what proof entails, which is at odds with the central role that proof plays in mathematics. Despite the centrality of proof, there is a lack of studies addressing how to integrate proof into…

Evaluation of the concept of pressure proof testing fuselage structures

NASA Technical Reports Server (NTRS)

Harris, Charles E.; Orringer, Oscar

1991-01-01

The FAA and NASA have recently completed independent technical evaluations of the concept of pressure proof testing the fuselage of commercial transport airplanes. The results of these evaluations are summarized. The objectives of the evaluations were to establish the potential benefit of the pressure proof test, to quantify the most desirable proof test pressure, and to quantify the required proof test interval. The focus of the evaluations was on multiple-site cracks extending from adjacent rivet holes of a typical fuselage longitudinal lap splice joint. The FAA and NASA do not support pressure proof testing the fuselage of aging commercial transport aircraft. The argument against proof testing is as follows: (1) a single proof test does not insure an indefinite life; therefore, the proof test must be repeated at regular intervals; (2) for a proof factor of 1.33, the required proof test interval must be below 300 flights to account for uncertainties in the evaluation; (3) conducting the proof test at a proof factor of 1.5 would considerably exceed the fuselage design limit load; therefore, it is not consistent with accepted safe practices; and (4) better safety can be assured by implementing enhanced nondestructive inspection requirements, and adequate reliability can be achieved by an inspection interval several times longer than the proof test interval.

Dysregulated IL-1β Secretion in Autoinflammatory Diseases: A Matter of Stress?

PubMed Central

Carta, Sonia; Semino, Claudia; Sitia, Roberto; Rubartelli, Anna

2017-01-01

Infectious and sterile inflammation is induced by activation of innate immune cells. Triggering of toll-like receptors by pathogen-associated molecular pattern or damage-associated molecular pattern (PAMP or DAMP) molecules generates reactive oxygen species that in turn induce production and activation of pro-inflammatory cytokines such as IL-1β. Recent evidence indicates that cell stress due to common events, like starvation, enhanced metabolic demand, cold or heat, not only potentiates inflammation but may also directly trigger it in the absence of PAMPs or DAMPs. Stress-mediated inflammation is also a common feature of many hereditary disorders, due to the proteotoxic effects of mutant proteins. We propose that harmful mutant proteins can induce dysregulated IL-1β production and inflammation through different pathways depending on the cell type involved. When expressed in professional inflammatory cells, stress induced by the mutant protein activates in a cell-autonomous way the onset of inflammation and mediates its aberrant development, resulting in the explosive responses that hallmark autoinflammatory diseases. When expressed in non-immune cells, the mutant protein may cause the release of transcellular stress signals that trigger and propagate inflammation. PMID:28421072

"Fooling fido"--chemical and behavioral studies of pseudo-explosive canine training aids.

PubMed

Kranz, William D; Strange, Nicholas A; Goodpaster, John V

2014-12-01

Genuine explosive materials are traditionally employed in the training and testing of explosive-detecting canines so that they will respond reliably to these substances. However, challenges arising from the acquisition, storage, handling, and transportation of explosives have given rise to the development of "pseudo-explosive" training aids. These products attempt to emulate the odor of real explosives while remaining inert. Therefore, a canine trained on a pseudo-explosive should respond to its real-life analog. Similarly, a canine trained on an actual explosive should respond to the pseudo-explosive as if it was real. This research tested those assumptions with a focus on three explosives: single-base smokeless powder, 2,4,6-trinitrotoluene (TNT), and a RDX-based plastic explosive (Composition C-4). Using gas chromatography-mass spectrometry with solid phase microextraction as a pre-concentration technique, we determined that the volatile compounds given off by pseudo-explosive products consisted of various solvents, known additives from explosive formulations, and common impurities present in authentic explosives. For example, simulated smokeless powders emitted terpenes, 2,4-dinitrotoluene, diphenylamine, and ethyl centralite. Simulated TNT products emitted 2,4- and 2,6-dinitrotoluene. Simulated C-4 products emitted cyclohexanone, 2-ethyl-1-hexanol, and dimethyldinitrobutane. We also conducted tests to determine whether canines trained on pseudo-explosives are capable of alerting to genuine explosives and vice versa. The results show that canines trained on pseudo-explosives performed poorly at detecting all but the pseudo-explosives they are trained on. Similarly, canines trained on actual explosives performed poorly at detecting all but the actual explosives on which they were trained.

Photonic-assisted microwave signal multiplication and modulation using a silicon Mach–Zehnder modulator

PubMed Central

Long, Yun; Zhou, Linjie; Wang, Jian

2016-01-01

Photonic generation of microwave signal is obviously attractive for many prominent advantages, such as large bandwidth, low loss, and immunity to electromagnetic interference. Based on a single integrated silicon Mach–Zehnder modulator (MZM), we propose and experimentally demonstrate a simple and compact photonic scheme to enable frequency-multiplicated microwave signal. Using the fabricated integrated MZM, we also demonstrate the feasibility of microwave amplitude-shift keying (ASK) modulation based on integrated photonic approach. In proof-of-concept experiments, 2-GHz frequency-doubled microwave signal is generated using a 1-GHz driving signal. 750-MHz/1-GHz frequency-tripled/quadrupled microwave signals are obtained with a driving signal of 250 MHz. In addition, a 50-Mb/s binary amplitude coded 1-GHz microwave signal is also successfully generated. PMID:26832305

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

PubMed

Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

2015-01-01

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

Zonal wavefront sensing using a grating array printed on a polyester film

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

Pathak, Biswajit; Boruah, Bosanta R., E-mail: brboruah@iitg.ernet.in; Kumar, Suraj

2015-12-15

In this paper, we describe the development of a zonal wavefront sensor that comprises an array of binary diffraction gratings realized on a transparent sheet (i.e., polyester film) followed by a focusing lens and a camera. The sensor works in a manner similar to that of a Shack-Hartmann wavefront sensor. The fabrication of the array of gratings is immune to certain issues associated with the fabrication of the lenslet array which is commonly used in zonal wavefront sensing. Besides the sensing method offers several important advantages such as flexible dynamic range, easy configurability, and option to enhance the sensing framemore » rate. Here, we have demonstrated the working of the proposed sensor using a proof-of-principle experimental arrangement.« less

The effect of explosive percentage on underwater explosion energy release of hexanitrohexaazaisowurtzitane and octogen based aluminized explosives

NASA Astrophysics Data System (ADS)

Jiao, Qingjie; Wang, Qiushi; Nie, Jianxin; Guo, Xueyong; Zhang, Wei; Fan, Wenqi

2018-03-01

To control the explosion energy output by optimizing explosive components is a key requirement in a number of different application areas. The effect of different Al/O Ratio on underwater explosion of aluminized explosives has been studied detailedly. However, the effect of explosive percentage in the same Al/O Ratio is rarely researched, especially for Hexanitrohexaazaisowurtzitane (CL-20) based aluminized explosives. In this study, we performed the underwater explosion experiments with 1.2-kilogram explosives in order to investigate the explosion energy released from CL-20 and Octogen (HMX) based aluminized explosives. The percentage of the explosive varied from 5% to 30% and it is shown that: the shockwave peak pressure (pm) grows gradually; shock wave energy (Es) continues increasing, bubble energy (Eb) increases then decreases peaking at 15% for both formulas, and the total energy (E) and energy release rate (η) peak at 20% for CL-20 and 15% for HMX. This paper outlines the physical mechanism of Eb change under the influence of an aluminium initial reaction temperature and reaction active detonation product percentage coupling. The result shows that CL-20 is superior as a new high explosive and has promising application prospects in the regulation of explosive energy output for underwater explosives.

Atomic resolution elemental mapping using energy-filtered imaging scanning transmission electron microscopy with chromatic aberration correction.

PubMed

Krause, F F; Rosenauer, A; Barthel, J; Mayer, J; Urban, K; Dunin-Borkowski, R E; Brown, H G; Forbes, B D; Allen, L J

2017-10-01

This paper addresses a novel approach to atomic resolution elemental mapping, demonstrating a method that produces elemental maps with a similar resolution to the established method of electron energy-loss spectroscopy in scanning transmission electron microscopy. Dubbed energy-filtered imaging scanning transmission electron microscopy (EFISTEM) this mode of imaging is, by the quantum mechanical principle of reciprocity, equivalent to tilting the probe in energy-filtered transmission electron microscopy (EFTEM) through a cone and incoherently averaging the results. In this paper we present a proof-of-principle EFISTEM experimental study on strontium titanate. The present approach, made possible by chromatic aberration correction, has the advantage that it provides elemental maps which are immune to spatial incoherence in the electron source, coherent aberrations in the probe-forming lens and probe jitter. The veracity of the experiment is supported by quantum mechanical image simulations, which provide an insight into the image-forming process. Elemental maps obtained in EFTEM suffer from the effect known as preservation of elastic contrast, which, for example, can lead to a given atomic species appearing to be in atomic columns where it is not to be found. EFISTEM very substantially reduces the preservation of elastic contrast and yields images which show stability of contrast with changing thickness. The experimental application is demonstrated in a proof-of-principle study on strontium titanate. Copyright © 2017 Elsevier B.V. All rights reserved.

Computer simulation of explosion crater in dams with different buried depths of explosive

NASA Astrophysics Data System (ADS)

Zhang, Zhichao; Ye, Longzhen

2018-04-01

Based on multi-material ALE method, this paper conducted a computer simulation on the explosion crater in dams with different buried depths of explosive using LS-DYNA program. The results turn out that the crater size increases with the increase of buried depth of explosive at first, but closed explosion cavity rather than a visible crater is formed when the buried depth of explosive increases to some extent. The soil in the explosion cavity is taken away by the explosion products and the soil under the explosion cavity is compressed with its density increased. The research can provide some reference for the anti-explosion design of dams in the future.

A survey of noninteractive zero knowledge proof system and its applications.

PubMed

Wu, Huixin; Wang, Feng

2014-01-01

Zero knowledge proof system which has received extensive attention since it was proposed is an important branch of cryptography and computational complexity theory. Thereinto, noninteractive zero knowledge proof system contains only one message sent by the prover to the verifier. It is widely used in the construction of various types of cryptographic protocols and cryptographic algorithms because of its good privacy, authentication, and lower interactive complexity. This paper reviews and analyzes the basic principles of noninteractive zero knowledge proof system, and summarizes the research progress achieved by noninteractive zero knowledge proof system on the following aspects: the definition and related models of noninteractive zero knowledge proof system, noninteractive zero knowledge proof system of NP problems, noninteractive statistical and perfect zero knowledge, the connection between noninteractive zero knowledge proof system, interactive zero knowledge proof system, and zap, and the specific applications of noninteractive zero knowledge proof system. This paper also points out the future research directions.

Batch Proving and Proof Scripting in PVS

NASA Technical Reports Server (NTRS)

Munoz, Cesar A.

2007-01-01

The batch execution modes of PVS are powerful, but highly technical, features of the system that are mostly accessible to expert users. This paper presents a PVS tool, called ProofLite, that extends the theorem prover interface with a batch proving utility and a proof scripting notation. ProofLite enables a semi-literate proving style where specification and proof scripts reside in the same file. The goal of ProofLite is to provide batch proving and proof scripting capabilities to regular, non-expert, users of PVS.

27 CFR 555.183 - Importation of plastic explosives on or after April 24, 1997.

Code of Federal Regulations, 2014 CFR

2014-04-01

... explosives on or after April 24, 1997. 555.183 Section 555.183 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.183 Importation of plastic explosives on or after April 24...

27 CFR 555.183 - Importation of plastic explosives on or after April 24, 1997.

Code of Federal Regulations, 2012 CFR

2012-04-01

... explosives on or after April 24, 1997. 555.183 Section 555.183 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.183 Importation of plastic explosives on or after April 24...

27 CFR 555.183 - Importation of plastic explosives on or after April 24, 1997.

Code of Federal Regulations, 2011 CFR

2011-04-01

... explosives on or after April 24, 1997. 555.183 Section 555.183 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.183 Importation of plastic explosives on or after April 24...

27 CFR 555.183 - Importation of plastic explosives on or after April 24, 1997.

Code of Federal Regulations, 2013 CFR

2013-04-01

... explosives on or after April 24, 1997. 555.183 Section 555.183 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.183 Importation of plastic explosives on or after April 24...

Seismicity and infrasound associated with explosions at Mount St. Helens, 2004-2005: Chapter 6 in A volcano rekindled: the renewed eruption of Mount St. Helens, 2004-2006

USGS Publications Warehouse

Moran, Seth C.; McChesney, Patrick J.; Lockhart, Andrew B.; Sherrod, David R.; Scott, William E.; Stauffer, Peter H.

2008-01-01

Six explosions occurred during 2004-5 in association with renewed eruptive activity at Mount St. Helens, Washington. Of four explosions in October 2004, none had precursory seismicity and two had explosion-related seismic tremor that marked the end of the explosion. However, seismicity levels dropped following each of the October explosions, providing the primary instrumental means for explosion detection during the initial vent-clearing phase. In contrast, explosions on January 16 and March 8, 2005, produced noticeable seismicity in the form of explosion-related tremor, infrasonic signals, and, in the case of the March 8 explosion, an increase in event size ~2 hours before the explosion. In both 2005 cases seismic tremor appeared before any infrasonic signals and was best recorded on stations located within the crater. These explosions demonstrated that reliable explosion detection at volcanoes like Mount St. Helens requires seismic stations within 1-2 km of the vent and stations with multiple acoustic sensors.

A Novel Multilayered RFID Tagged Cargo Integrity Assurance Scheme

PubMed Central

Yang, Ming Hour; Luo, Jia Ning; Lu, Shao Yong

2015-01-01

To minimize cargo theft during transport, mobile radio frequency identification (RFID) grouping proof methods are generally employed to ensure the integrity of entire cargo loads. However, conventional grouping proofs cannot simultaneously generate grouping proofs for a specific group of RFID tags. The most serious problem of these methods is that nonexistent tags are included in the grouping proofs because of the considerable amount of time it takes to scan a high number of tags. Thus, applying grouping proof methods in the current logistics industry is difficult. To solve this problem, this paper proposes a method for generating multilayered offline grouping proofs. The proposed method provides tag anonymity; moreover, resolving disputes between recipients and transporters over the integrity of cargo deliveries can be expedited by generating grouping proofs and automatically authenticating the consistency between the receipt proof and pick proof. The proposed method can also protect against replay attacks, multi-session attacks, and concurrency attacks. Finally, experimental results verify that, compared with other methods for generating grouping proofs, the proposed method can efficiently generate offline grouping proofs involving several parties in a supply chain using mobile RFID. PMID:26512673

Significant issues in proof testing: A critical appraisal

NASA Technical Reports Server (NTRS)

Chell, G. G.; Mcclung, R. C.; Russell, D. A.; Chang, K. J.; Donnelly, B.

1994-01-01

Issues which impact on the interpretation and quantification of proof test benefits are reviewed. The importance of each issue in contributing to the extra quality assurance conferred by proof testing components is discussed, particularly with respect to the application of advanced fracture mechanics concepts to enhance the flaw screening capability of a proof test analysis. Items covered include the role in proof testing of elastic-plastic fracture mechanics, ductile instability analysis, deterministic versus probabilistic analysis, single versus multiple cycle proof testing, and non-destructive examination (NDE). The effects of proof testing on subsequent service life are reviewed, particularly with regard to stress redistribution and changes in fracture behavior resulting from the overload. The importance of proof test conditions are also addressed, covering aspects related to test temperature, simulation of service environments, test media and the application of real-time NDE. The role of each issue in a proof test methodology is assessed with respect to its ability to: promote proof test practice to a state-of-the-art; aid optimization of proof test design; and increase awareness and understanding of outstanding issues.

Chemical analysis kit for the presence of explosives

DOEpatents

Eckels, Joel Del [Livermore, CA; Nunes,; Peter, J [Danville, CA; Alcaraz, Armando [Livermore, CA; Whipple, Richard E [Livermore, CA

2011-05-10

A tester for testing for explosives associated with a test location comprising a first explosives detecting reagent; a first reagent holder, the first reagent holder containing the first explosives detecting reagent; a second explosives detecting reagent; a second reagent holder, the second reagent holder containing the second explosives detecting reagent; a sample collection unit for exposure to the test location, exposure to the first explosives detecting reagent, and exposure to the second explosives detecting reagent; and a body unit containing a heater for heating the sample collection unit for testing the test location for the explosives.

All-Optical Fibre Networks For Coal Mines

NASA Astrophysics Data System (ADS)

Zientkiewicz, Jacek K.

1987-09-01

A topic of the paper is fiber-optic integrated network (FOIN) suited to the most hostile environments existing in coal mines. The use of optical fibres for transmission of mine instrumentation data offers the prospects of improved safety and immunity to electromagnetic interference (EMI). The feasibility of optically powered sensors has opened up new opportunities for research into optical signal processing architectures. This article discusses a new fibre-optic sensor network involving a time domain multiplexing(TDM)scheme and optical signal processing techniques. The pros and cons of different FOIN topologies with respect to coal mine applications are considered. The emphasis has been placed on a recently developed all-optical fibre network using spread spectrum code division multiple access (COMA) techniques. The all-optical networks have applications in explosive environments where electrical isolation is required.

Coming-of-Age of Antibodies in Cancer Therapeutics.

PubMed

Ayyar, B Vijayalakshmi; Arora, Sushrut; O'Kennedy, Richard

2016-12-01

Antibody-based therapies have garnered considerable success in recent years. This is due to the availability of strategies to successfully engineer antibodies into humanized forms, better understanding of the biological processes involved in cancer development, the availability of novel recombinant antibody formats, better antibody selection platforms, and improved antibody conjugation methodologies. Such achievements have led to an explosion in the generation of antibodies and antibody-associated constructs for the treatment of cancer and other diseases. In this review, we critically assess recent trends in the development and applications of bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and immune checkpoint inhibitors (ICIs) as cancer therapeutics. We also highlight recent US FDA approvals and clinical trials of antibody-based cancer therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fiber-Optic Chemical Sensors and Fiber-Optic Bio-Sensors.

PubMed

Pospíšilová, Marie; Kuncová, Gabriela; Trögl, Josef

2015-09-30

This review summarizes principles and current stage of development of fiber-optic chemical sensors (FOCS) and biosensors (FOBS). Fiber optic sensor (FOS) systems use the ability of optical fibers (OF) to guide the light in the spectral range from ultraviolet (UV) (180 nm) up to middle infrared (IR) (10 μm) and modulation of guided light by the parameters of the surrounding environment of the OF core. The introduction of OF in the sensor systems has brought advantages such as measurement in flammable and explosive environments, immunity to electrical noises, miniaturization, geometrical flexibility, measurement of small sample volumes, remote sensing in inaccessible sites or harsh environments and multi-sensing. The review comprises briefly the theory of OF elaborated for sensors, techniques of fabrications and analytical results reached with fiber-optic chemical and biological sensors.

An historical overview of cavity-enhanced methods

NASA Astrophysics Data System (ADS)

Paldus, B. A.; Kachanov, A. A.

2005-10-01

An historical overview of laser-based, spectroscopic methods that employ high-finesse optical resonators is presented. The overview begins with the early work in atomic absorption (1962) and optical cavities (1974) that led to the first mirror reflectivity measurements in 1980. This paper concludes with very recent extensions of cavity-enhanced methods for the study of condensed-phase media and biological systems. Methods described here include cavity ring-down spectroscopy, integrated cavity output spectroscopy, and noise-immune cavity-enhanced optical heterodyne molecular spectroscopy. Given the explosive growth of the field over the past decade, this review does not attempt to present a comprehensive bibliography of all work published in cavity-enhanced spectroscopy, but rather strives to illustrate the rich history, creative diversity, and broad applications potential of these methods.

Systems Biology-Based Investigation of Host-Plasmodium Interactions.

PubMed

Smith, Maren L; Styczynski, Mark P

2018-05-18

Malaria is a serious, complex disease caused by parasites of the genus Plasmodium. Plasmodium parasites affect multiple tissues as they evade immune responses, replicate, sexually reproduce, and transmit between vertebrate and invertebrate hosts. The explosion of omics technologies has enabled large-scale collection of Plasmodium infection data, revealing systems-scale patterns, mechanisms of pathogenesis, and the ways that host and pathogen affect each other. Here, we provide an overview of recent efforts using systems biology approaches to study host-Plasmodium interactions and the biological themes that have emerged from these efforts. We discuss some of the challenges in using systems biology for this goal, key research efforts needed to address those issues, and promising future malaria applications of systems biology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Explosive simulants for testing explosive detection systems

DOEpatents

Kury, John W.; Anderson, Brian L.

1999-09-28

Explosives simulants that include non-explosive components are disclosed that facilitate testing of equipment designed to remotely detect explosives. The simulants are non-explosive, non-hazardous materials that can be safely handled without any significant precautions. The simulants imitate real explosives in terms of mass density, effective atomic number, x-ray transmission properties, and physical form, including moldable plastics and emulsions/gels.

Non-detonable and non-explosive explosive simulators

DOEpatents

Simpson, Randall L.; Pruneda, Cesar O.

1997-01-01

A simulator which is chemically equivalent to an explosive, but is not detonable or explodable. The simulator is a combination of an explosive material with an inert material, either in a matrix or as a coating, where the explosive has a high surface ratio but small volume ratio. The simulator has particular use in the training of explosives detecting dogs, calibrating analytical instruments which are sensitive to either vapor or elemental composition, or other applications where the hazards associated with explosives is undesirable but where chemical and/or elemental equivalence is required. The explosive simulants may be fabricated by different techniques. A first method involves the use of standard slurry coatings to produce a material with a very high binder to explosive ratio without masking the explosive vapor, and a second method involves coating inert substrates with thin layers of explosive.

The Expansion of Explosives Safety Education for the 21st Century

DTIC Science & Technology

2010-07-01

shape charges, explosive welding, thermite reaction – Sensitivity testing: drop hammer, electrospark discharge, friction – Physics of explosives, history... ATF ) • Phytoremediation workers use plants to remove explosives from soil and render the explosives harmless • Sales of explosives detection

A Survey of Noninteractive Zero Knowledge Proof System and Its Applications

PubMed Central

Wu, Huixin; Wang, Feng

2014-01-01

Zero knowledge proof system which has received extensive attention since it was proposed is an important branch of cryptography and computational complexity theory. Thereinto, noninteractive zero knowledge proof system contains only one message sent by the prover to the verifier. It is widely used in the construction of various types of cryptographic protocols and cryptographic algorithms because of its good privacy, authentication, and lower interactive complexity. This paper reviews and analyzes the basic principles of noninteractive zero knowledge proof system, and summarizes the research progress achieved by noninteractive zero knowledge proof system on the following aspects: the definition and related models of noninteractive zero knowledge proof system, noninteractive zero knowledge proof system of NP problems, noninteractive statistical and perfect zero knowledge, the connection between noninteractive zero knowledge proof system, interactive zero knowledge proof system, and zap, and the specific applications of noninteractive zero knowledge proof system. This paper also points out the future research directions. PMID:24883407

An Extended Proof-Carrying Code Framework for Security Enforcement

NASA Astrophysics Data System (ADS)

Pirzadeh, Heidar; Dubé, Danny; Hamou-Lhadj, Abdelwahab

The rapid growth of the Internet has resulted in increased attention to security to protect users from being victims of security threats. In this paper, we focus on security mechanisms that are based on Proof-Carrying Code (PCC) techniques. In a PCC system, a code producer sends a code along with its safety proof to the consumer. The consumer executes the code only if the proof is valid. Although PCC has been shown to be a useful security framework, it suffers from the sheer size of typical proofs -proofs of even small programs can be considerably large. In this paper, we propose an extended PCC framework (EPCC) in which, instead of the proof, a proof generator for the program in question is transmitted. This framework enables the execution of the proof generator and the recovery of the proof on the consumer's side in a secure manner using a newly created virtual machine called the VEP (Virtual Machine for Extended PCC).

Quantitative understanding of explosive stimulus transfer

NASA Technical Reports Server (NTRS)

Schimmel, M. L.

1973-01-01

The mechanisms of detonation transfer across hermetically sealed interfaces created by necessary interruptions in high explosive trains, such as at detonators to explosive columns, field joints in explosive columns, and components of munitions fuse trains are demostrated. Reliability of detonation transfer is limited by minimizing explosive quantities, the use of intensitive explosives for safety, and requirements to propagate across gaps and angles dictated by installation and production restraints. The major detonation transfer variables studied were: explosive quanity, sensitivity, and thickness, and the separation distances between donor and acceptor explosives.

The characterization and evaluation of accidental explosions

NASA Technical Reports Server (NTRS)

Strehlow, R. A.; Baker, W. E.

1975-01-01

Accidental explosions are discussed from a number of viewpoints. First, all accidental explosions, intentional explosions and natural explosions are characterized by type. Second, the nature of the blast wave produced by an ideal (point source or HE) explosion is discussed to form a basis for describing how other explosion processes yield deviations from ideal blast wave behavior. The current status blast damage mechanism evaluation is also discussed. Third, the current status of our understanding of each different category of accidental explosions is discussed in some detail.

What Is a Host? Incorporating the Microbiota into the Damage-Response Framework

PubMed Central

Pirofski, Liise-anne

2014-01-01

Since proof of the germ theory of disease in the late 19th century, a major focus of the fields of microbiology and infectious diseases has been to seek differences between pathogenic and nonpathogenic microbes and the role that the host plays in microbial pathogenesis. Remarkably, despite the increasing recognition that host immunity plays a role in microbial pathogenesis, there has been little discussion about what constitutes a host. Historically, hosts have been viewed in the context of their fitness or immunological status and characterized by adjectives such as immune, immunocompetent, immunosuppressed, immunocompromised, or immunologically impaired. However, in recent years it has become apparent that the microbiota has profound effects on host homeostasis and susceptibility to microbial diseases in addition to its effects on host immunity. This raises the question of how to incorporate the microbiota into defining a host. This definitional problem is further complicated because neither host nor microbial properties are adequate to predict the outcome of host-microbe interaction because this outcome exhibits emergent properties. In this essay, we revisit the damage-response framework (DRF) of microbial pathogenesis and demonstrate how it can incorporate the rapidly accumulating information being generated by the microbiome revolution. We use the tenets of the DRF to put forth the following definition of a host: a host is an entity that houses an associated microbiome/microbiota and interacts with microbes such that the outcome results in damage, benefit, or indifference, thus resulting in the states of symbiosis, colonization, commensalism, latency, and disease. PMID:25385796

Targeting B cells in immune-mediated inflammatory disease: a comprehensive review of mechanisms of action and identification of biomarkers.

PubMed

Dörner, Thomas; Kinnman, Nils; Tak, Paul P

2010-03-01

B cell-depletion therapy, particularly using anti-CD20 treatment, has provided proof of concept that targeting B cells and the humoral response may result in clinical improvements in immune-mediated inflammatory disease. In this review, the mechanisms of action of B cell-targeting drugs are investigated, and potential biomarkers associated with response to treatment in patients with autoimmune diseases are identified. Most available data relate to B cell depletion using anti-CD20 therapy (rituximab) in patients with rheumatoid arthritis (RA). Treatment leads to significant clinical benefit, but apparently fails to deplete long-lived plasma cells, and discontinuation is associated with relapse. Biomarkers commonly used in studies of B cell-targeted therapies include rheumatoid factor, anti-citrullinated peptide antibodies, and immunoglobulin (Ig) levels. More recently, there has been interest in markers such as B cell phenotype analysis, and B lymphocyte stimulator (BLyS)/a proliferation-inducing ligand (APRIL), the latter particularly in studies of the IgG Fc-transmembrane activator and CAML interactor (TACI) fusion protein (atacicept) and anti-BLyS therapy (belimumab). Data from clinical trials of B cell-depleting agents in RA suggest that specific autoantibodies, BLyS, APRIL, and circulating and synovial B lineage cell levels may have potential as biomarkers predictive of response to treatment. Further trials validating these markers against clinical outcomes in RA are required. In patients with systemic lupus erythematosus, Fc receptors and levels of circulating immune cells (including B cells and natural killer cells) may be relevant markers. 2010 Elsevier Inc. All rights reserved.

Non-detonable and non-explosive explosive simulators

DOEpatents

Simpson, R.L.; Pruneda, C.O.

1997-07-15

A simulator which is chemically equivalent to an explosive, but is not detonable or explodable is disclosed. The simulator is a combination of an explosive material with an inert material, either in a matrix or as a coating, where the explosive has a high surface ratio but small volume ratio. The simulator has particular use in the training of explosives detecting dogs, calibrating analytical instruments which are sensitive to either vapor or elemental composition, or other applications where the hazards associated with explosives is undesirable but where chemical and/or elemental equivalence is required. The explosive simulants may be fabricated by different techniques. A first method involves the use of standard slurry coatings to produce a material with a very high binder to explosive ratio without masking the explosive vapor, and a second method involves coating inert substrates with thin layers of explosive. 11 figs.

Thermal explosion violence of HMX-based explosives -- effect of composition, confinement and phase transition using the scaled thermal explosion experiment

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

Maienschein, J L; Wardell, J F; Reaugh, J E

We developed the Scaled Thermal Explosion Experiment (STEX) to provide a database of reaction violence from thermal explosion of explosives of interest. A cylinder of explosive, 1, 2 or 4 inches in diameter, is confined in a steel cylinder with heavy end caps, and heated under controlled conditions until it explodes. Reaction violence is quantified by micropower radar measurement of the cylinder wall velocity, and by strain gauge data at reaction onset. Here we describe the test concept and design, show that the conditions are well understood, and present initial data with HMX-based explosives. The HMX results show that anmore » explosive with high binder content yields less-violent reactions that an explosive with low binder content, and that the HMX phase at the time of explosion plays a key role in reaction violence.« less

Oriented Scintillation Spectrometer Experiment (OSSE). Revision A. Volume 1

DTIC Science & Technology

1988-05-19

SYSTEM-LEVEL ENVIRONMENTAL TESTS ................... 108 3.5.1 OPERATION REPORT, PROOF MODEL STRUCTURE TESTS.. .108 3.5.1.1 PROOF MODEL MODAL SURVEY...81 3-21 ALIGNMENT ERROR BUDGET, FOV, A4 ................ 82 3-22 ALIGNMENT ERROR BUDGET, ROTATION AXIS, A4 ...... 83 3-23 OSSE PROOF MODEL MODAL SURVEY...PROOF MODEL MODAL SURVEY .................. 112 3-27-1 OSSE PROOF MODEL STATIC LOAD TEST ............. 116 3-27-2 OSSE PROOF MODEL STATIC LOAD TEST

Steam explosion pretreatment of softwood: the effect of the explosive decompression on enzymatic digestibility.

PubMed

Pielhop, Thomas; Amgarten, Janick; von Rohr, Philipp Rudolf; Studer, Michael H

2016-01-01

Steam explosion pretreatment has been examined in many studies for enhancing the enzymatic digestibility of lignocellulosic biomass and is currently the most common pretreatment method in commercial biorefineries. The information available about the effect of the explosive decompression on the biochemical conversion is, however, very limited, and no studies prove that the latter is actually enhanced by the explosion. Hence, it is of great value to discern between the effect of the explosion on the one hand and the steaming on the other hand, to identify their particular influences on enzymatic digestibility. The effect of the explosive decompression in the steam explosion pretreatment of spruce wood chips on their enzymatic cellulose digestibility was studied systematically. The explosion had a high influence on digestibility, improving it by up to 90 % compared to a steam pretreatment without explosion. Two factors were identified to be essentially responsible for the effect of the explosion on enzymatic digestibility: pretreatment severity and pressure difference of the explosion. A higher pretreatment severity can soften up and weaken the lignocellulose structure more, so that the explosion can better break up the biomass and decrease its particle size, which enhances its digestibility. In particular, increasing the pressure difference of the explosion leads to more defibration, a smaller particle size and a better digestibility. Though differences were found in the micro- and nanostructure of exploded and non-exploded biomass, the only influence of the explosion on digestibility was found to be the macroscopic particle size reduction. Steam explosion treatments with a high severity and a high pressure difference of the explosion lead to a comparatively high cellulose digestibility of the-typically very recalcitrant-softwood biomass. This is the first study to show that explosion can enhance the enzymatic digestibility of lignocellulosic biomass. If the enhancing effect of the explosion is thoroughly exploited, even very recalcitrant biomass like softwood can be made enzymatically digestible.

Recombinant Swinepox Virus Expressing Glycoprotein E2 of Classical Swine Fever Virus Confers Complete Protection in Pigs upon Viral Challenge.

PubMed

Lin, Huixing; Ma, Zhe; Chen, Lei; Fan, Hongjie

2017-01-01

Classical swine fever (CSF) is a highly contagious and serious viral disease that affects the pig industry worldwide. The glycoprotein E2 of the classical swine fever virus (CSFV) can induce neutralizing antibodies, and it is widely used for novel vaccine development. To explore the development of a vaccine against CSFV infections, the gene of glycoprotein E2 was inserted into the swinepox virus (SPV) genome by homologous recombination. The culture titers of rSPV-E2 remained at about 4.3 × 10 6 TCID 50 for more than 60 passages in PK15 and swine testis cell lines. The rSPV-E2 could not be replicated in Vero, MDBK or other non-porcine cell lines. After two to three passages, the SPV specific gene of rSPV-E2 could not been detected in the non-porcine cell culture. To evaluate the immunogenicity of rSPV-E2, 20 CSFV seronegative minipigs were immunized with rSPV-E2, a commercial C-strain vaccine, wild-type SPV (wtSPV; negative control), or PBS (a no-challenge control). After challenge with CSFV, pigs in the rSPV-E2-immunized group showed significantly shorter fever duration compared with the wtSPV-treated group ( P  < 0.05). E2-specific antibodies in the rSPV-E2-immunized group increased dramatically after vaccination and increased continuously over time. CSFV genomic copies in the serum of rSPV-E2-immunized pigs were significantly less compared with the wtSPV-treated group at all time points after challenge ( P  < 0.01). Significant reduction in gross lung lesion scores, histopathological liver, spleen, lung, and kidney lesion scores were noted in the rSPV-E2-immunized group compared with the wtSPV-treated group ( P  < 0.01). The results suggested that the recombinant rSPV-E2 provided pigs with significant protection from CSFV infections; thus, rSPV-E2 offers proof of principle for the development of a vaccine for the prevention of CSFV infections in pigs.

Immunological and physical evaluation of the multistage tuberculosis subunit vaccine candidate H56/CAF01 formulated as a spray-dried powder.

PubMed

Thakur, Aneesh; Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Rose, Fabrice; Andersen, Peter; Christensen, Dennis; Foged, Camilla

2018-05-31

Liquid vaccine dosage forms have limited stability and require refrigeration during their manufacture, distribution and storage. In contrast, solid vaccine dosage forms, produced by for example spray drying, offer improved storage stability and reduced dependence on cold-chain facilities. This is advantageous for mass immunization campaigns for global public health threats, e.g., tuberculosis (TB), and offers cheaper vaccine distribution. The multistage subunit vaccine antigen H56, which is a fusion protein of the Mycobacterium tuberculosis (Mtb) antigens Ag85B, ESAT-6, and Rv2660, has been shown to confer protective efficacy against active TB before and after Mtb exposure in preclinical models, and it is currently undergoing clinical phase 2a testing. In several studies, including a recent study comparing multiple clinically relevant vaccine adjuvants, the T helper type 1 (Th1)/Th17-inducing adjuvant CAF01 was the most efficacious adjuvant for H56 to stimulate protective immunity against Mtb. With the long-term goal of designing a thermostable and self-administrable dry powder vaccine based on H56 and CAF01 for inhalation, we compared H56 spray-dried with CAF01 with the non-spray-dried H56/CAF01 vaccine with respect to their ability to induce systemic Th1, Th17 and humoral responses after subcutaneous immunization. Here we show that spray drying of the H56/CAF01 vaccine results in preserved antigenic epitope recognition and adjuvant activity of CAF01, and the spray-dried, reconstituted vaccine induces antigen-specific Th1, Th17 and humoral immune responses, which are comparable to those stimulated by the non-spray-dried H56/CAF01 vaccine. In addition, the spray-dried and reconstituted H56/CAF01 vaccine promotes similar polyfunctional CD4 + T-cell responses as the non-spray-dried vaccine. Thus, our study provides proof-of-concept that spray drying of the subunit vaccine H56/CAF01 preserves vaccine-induced humoral and cell-mediated immune responses. These results support our ongoing efforts to develop a thermostable, dry powder-based TB vaccine. Copyright © 2018 Elsevier Ltd. All rights reserved.

27 CFR 70.445 - Commerce in explosives.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Commerce in explosives. 70... Cartridges, and Explosives § 70.445 Commerce in explosives. Part 555 of title 27 CFR contains the regulations..., explosives, (b) Permits for users who buy or transport explosives in interstate or foreign commerce, (c...

27 CFR 70.445 - Commerce in explosives.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Commerce in explosives. 70... Cartridges, and Explosives § 70.445 Commerce in explosives. Part 555 of title 27 CFR contains the regulations..., explosives, (b) Permits for users who buy or transport explosives in interstate or foreign commerce, (c...

27 CFR 70.445 - Commerce in explosives.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Commerce in explosives. 70... Cartridges, and Explosives § 70.445 Commerce in explosives. Part 555 of title 27 CFR contains the regulations..., explosives, (b) Permits for users who buy or transport explosives in interstate or foreign commerce, (c...

27 CFR 70.445 - Commerce in explosives.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Commerce in explosives. 70... Cartridges, and Explosives § 70.445 Commerce in explosives. Part 555 of title 27 CFR contains the regulations..., explosives, (b) Permits for users who buy or transport explosives in interstate or foreign commerce, (c...

27 CFR 70.445 - Commerce in explosives.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Commerce in explosives. 70... Cartridges, and Explosives § 70.445 Commerce in explosives. Part 55 of title 27 CFR contains the regulations..., explosives, (b) Permits for users who buy or transport explosives in interstate or foreign commerce, (c...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2013 CFR

2013-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2014 CFR

2014-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2012 CFR

2012-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2011 CFR

2011-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2010 CFR

2010-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

Effect of type of explosives and physical-mechanical properties of explosive rock on formation of toxic gases in atmosphere of shafts

NASA Technical Reports Server (NTRS)

Mindeli, E. O.; Khudyakov, M. Y.

1981-01-01

The quality of toxic gases formed during explosive work in underground shafts depends upon the type of explosives and the conditions of explosion. Several types of explosives and rocks were examined. All remaining conditions were maintained the same (sandy-argillaceous stemming, electrical method of explosions, diameter of blast holes, and the direct triggering of charges).

Numerical Simulation on Smoke Spread and Temperature Distribution in a Corn Starch Explosion

NASA Astrophysics Data System (ADS)

Lin, CherngShing; Hsu, JuiPei

2018-01-01

It is discovered from dust explosion accidents in recent years that deep causes of the accidents lies in insufficient cognition of dust explosion danger, and no understanding on danger and information of the dust explosion. In the study, Fire Dynamics Simulator (FDS) evaluation tool is used aiming at Taiwan Formosa Fun Coast explosion accidents. The calculator is used for rebuilding the explosion situation. The factors affecting casualties under explosion are studied. The injured personnel participating in the party are evaluated according to smoke diffusion and temperature distribution for numerical simulation results. Some problems noted in the fire disaster after actual explosion are proposed, rational site analysis is given, thereby reducing dust explosion risk grade.

Investigating the Teaching and Learning of Proof: First Year Results.

ERIC Educational Resources Information Center

Martin, Tami S.; McCrone, Sharon Soucy

Although proof and reasoning are seen as fundamental components of learning mathematics, research shows that many students continue to struggle with geometric proofs. In order to relate pedagogical methods to students' understanding of geometric proof, this 3-year project focuses on 2 components of student understanding of proof, namely, students'…

Multimedia Resources Designed to Support Learning from Written Proofs: An Eye-Movement Study

ERIC Educational Resources Information Center

Roy, Somali; Inglis, Matthew; Alcock, Lara

2017-01-01

This paper presents two studies of an intervention designed to help undergraduates comprehend mathematical proofs. The intervention used multimedia resources that presented proofs with audio commentary and visual animations designed to focus attention on logical relationships. In study 1, students studied an e-Proof or a standard written proof and…

On the Analysis of Indirect Proofs: Contradiction and Contraposition

ERIC Educational Resources Information Center

Jourdan, Nicolas; Yevdokimov, Oleksiy

2016-01-01

The paper explores and clarifies the similarities and differences that exist between proof by contradiction and proof by contraposition. The paper also focuses on the concept of contradiction, and a general model for this method of proof is offered. The introduction of mathematical proof in the classroom remains a formidable challenge to students…

Proof Problems with Diagrams: An Opportunity for Experiencing Proofs and Refutations

ERIC Educational Resources Information Center

Komatsu, Kotaro; Tsujiyama, Yosuke; Sakamaki, Aruta; Koike, Norio

2014-01-01

It has become gradually accepted that proof and proving are essential at all grades of mathematical learning. Among the various aspects of proof and proving, this study addresses proofs and refutations described by Lakatos, in particular a part of increasing content by deductive guessing, to introduce an authentic process into mathematics…

Non-detonable explosive simulators

DOEpatents

Simpson, Randall L.; Pruneda, Cesar O.

1994-01-01

A simulator which is chemically equivalent to an explosive, but is not detonable. The simulator has particular use in the training of explosives detecting dogs and calibrating sensitive analytical instruments. The explosive simulants may be fabricated by different techniques, a first involves the use of standard slurry coatings to produce a material with a very high binder to explosive ratio without masking the explosive vapor, and the second involves coating inert beads with thin layers of explosive molecules.

32 CFR 644.531 - Warning to public of danger in handling explosive missiles.

Code of Federal Regulations, 2013 CFR

2013-07-01

... explosive missiles. 644.531 Section 644.531 National Defense Department of Defense (Continued) DEPARTMENT OF... handling explosive missiles. When any land which has been contaminated with explosive objects, or chemical..., in the event of the discovery of an explosive missile, or an object resembling an explosive missile...

32 CFR 644.531 - Warning to public of danger in handling explosive missiles.

Code of Federal Regulations, 2011 CFR

2011-07-01

... explosive missiles. 644.531 Section 644.531 National Defense Department of Defense (Continued) DEPARTMENT OF... handling explosive missiles. When any land which has been contaminated with explosive objects, or chemical..., in the event of the discovery of an explosive missile, or an object resembling an explosive missile...

29 CFR 1926.905 - Loading of explosives or blasting agents.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 8 2010-07-01 2010-07-01 false Loading of explosives or blasting agents. 1926.905 Section... Explosives § 1926.905 Loading of explosives or blasting agents. (a) Procedures that permit safe and efficient... have contained explosives or blasting agents. (g) No explosives or blasting agents shall be left...

Prediction of the explosion effect of aluminized explosives

NASA Astrophysics Data System (ADS)

Zhang, Qi; Xiang, Cong; Liang, HuiMin

2013-05-01

We present an approach to predict the explosion load for aluminized explosives using a numerical calculation. A code to calculate the species of detonation products of high energy ingredients and those of the secondary reaction of aluminum and the detonation products, velocity of detonation, pressure, temperature and JWL parameters of aluminized explosives has been developed in this study. Through numerical calculations carried out with this code, the predicted JWL parameters for aluminized explosives have been compared with those measured by the cylinder test. The predicted JWL parameters with this code agree with those measured by the cylinder test. Furthermore, the load of explosion for the aluminized explosive was calculated using the numerical simulation by using the JWL equation of state. The loads of explosion for the aluminized explosive obtained using the predicted JWL parameters have been compared with those using the measured JWL parameters. Both of them are almost the same. The numerical results using the predicted JWL parameters show that the explosion air shock wave is the strongest when the mass fraction of aluminum powder in the explosive mixtures is 30%. This result agrees with the empirical data.

Autoantigen-specific B-cell depletion overcomes failed immune tolerance in type 1 diabetes.

PubMed

Henry, Rachel A; Kendall, Peggy L; Thomas, James W

2012-08-01

Eliminating autoantigen-specific B cells is an attractive alternative to global B-cell depletion for autoimmune disease treatment. To identify the potential for targeting a key autoimmune B-cell specificity in type 1 diabetes, insulin-binding B cells were tracked within a polyclonal repertoire using heavy chain B-cell receptor (BCR) transgenic (VH125Tg) mice. Insulin-specific B cells are rare in the periphery of nonautoimmune VH125Tg/C57BL/6 mice and WT/NOD autoimmune mice, whereas they clearly populate 1% of mature B-cell subsets in VH125Tg/NOD mice. Autoantigen upregulates CD86 in anti-insulin B cells, suggesting they are competent to interact with T cells. Endogenous insulin occupies anti-insulin BCR beginning with antigen commitment in bone marrow parenchyma, as identified by a second anti-insulin monoclonal antibody. Administration of this monoclonal antibody selectively eliminates insulin-reactive B cells in vivo and prevents disease in WT/NOD mice. Unexpectedly, developing B cells are less amenable to depletion, despite increased BCR sensitivity. These findings exemplify how a critical type 1 diabetes B-cell specificity escapes immune tolerance checkpoints. Disease liability is corrected by eliminating this B-cell specificity, providing proof of concept for a novel therapeutic approach for autoimmune disease.

Identification of Compounds That Prolong Type I Interferon Signaling as Potential Vaccine Adjuvants.

PubMed

Shukla, Nikunj M; Arimoto, Kei-Ichiro; Yao, Shiyin; Fan, Jun-Bao; Zhang, Yue; Sato-Kaneko, Fumi; Lao, Fitzgerald S; Hosoya, Tadashi; Messer, Karen; Pu, Minya; Cottam, Howard B; Carson, Dennis A; Hayashi, Tomoko; Zhang, Dong-Er; Corr, Maripat

2018-05-01

Vaccines are reliant on adjuvants to enhance the immune stimulus, and type I interferons (IFNs) have been shown to be beneficial in augmenting this response. We were interested in identifying compounds that would sustain activation of an endogenous type I IFN response as a co-adjuvant. We began with generation of a human monocytic THP-1 cell line with an IFN-stimulated response element (ISRE)-β-lactamase reporter construct for high-throughput screening. Pilot studies were performed to optimize the parameters and conditions for this cell-based Förster resonance energy transfer (FRET) reporter assay for sustaining an IFN-α-induced ISRE activation signal. These conditions were confirmed in an initial pilot screen, followed by the main screen for evaluating prolongation of an IFN-α-induced ISRE activation signal at 16 h. Hit compounds were identified using a structure enrichment strategy based on chemoinformatic clustering and a naïve "Top X" approach. A select list of confirmed hits was then evaluated for toxicity and the ability to sustain IFN activity by gene and protein expression. Finally, for proof of concept, a panel of compounds was used to immunize mice as co-adjuvant with a model antigen and an IFN-inducing Toll-like receptor 4 agonist, lipopolysaccharide, as an adjuvant. Selected compounds significantly augmented antigen-specific immunoglobulin responses.

Liposomes loaded with bioactive lipids enhance antibacterial innate immunity irrespective of drug resistance.

PubMed

Poerio, Noemi; Bugli, Francesca; Taus, Francesco; Santucci, Marilina B; Rodolfo, Carlo; Cecconi, Francesco; Torelli, Riccardo; Varone, Francesco; Inchingolo, Riccardo; Majo, Fabio; Lucidi, Vincenzina; Mariotti, Sabrina; Nisini, Roberto; Sanguinetti, Maurizio; Fraziano, Maurizio

2017-03-27

Phagocytosis is a key mechanism of innate immunity, and promotion of phagosome maturation may represent a therapeutic target to enhance antibacterial host response. Phagosome maturation is favored by the timely and coordinated intervention of lipids and may be altered in infections. Here we used apoptotic body-like liposomes (ABL) to selectively deliver bioactive lipids to innate cells, and then tested their function in models of pathogen-inhibited and host-impaired phagosome maturation. Stimulation of macrophages with ABLs carrying phosphatidic acid (PA), phosphatidylinositol 3-phosphate (PI3P) or PI5P increased intracellular killing of BCG, by inducing phagosome acidification and ROS generation. Moreover, ABLs carrying PA or PI5P enhanced ROS-mediated intracellular killing of Pseudomonas aeruginosa, in macrophages expressing a pharmacologically-inhibited or a naturally-mutated cystic fibrosis transmembrane conductance regulator. Finally, we show that bronchoalveolar lavage cells from patients with drug-resistant pulmonary infections increased significantly their capacity to kill in vivo acquired bacterial pathogens when ex vivo stimulated with PA- or PI5P-loaded ABLs. Altogether, these results provide the proof of concept of the efficacy of bioactive lipids delivered by ABL to enhance phagosome maturation dependent antimicrobial response, as an additional host-directed strategy aimed at the control of chronic, recurrent or drug-resistant infections.

Glucose-6-Phosphatase Catalytic Subunit 3 (G6PC3) Deficiency Associated With Autoinflammatory Complications.

PubMed

Mistry, Anoop; Scambler, Thomas; Parry, David; Wood, Mark; Barcenas-Morales, Gabriela; Carter, Clive; Doffinger, Rainer; Savic, Sinisa

2017-01-01

G6PC3 deficiency typically causes severe congenital neutropenia, associated with susceptibility to infections, cardiac and urogenital abnormalities. However, here we describe two boys of Pakistani origin who were found to have G6PC3 deficiency due to c.130 C>T mutation, but who have clinical phenotypes that are typical for a systemic autoinflammatory syndrome. The index case presented with combination of unexplained fevers, severe mucosal ulcers, abdominal symptoms, and inflammatory arthritis. He eventually fully responded to anti-TNF therapy. In this study, we show that compared with healthy controls, neutrophils and monocytes from patients have reduced glycolytic reserve. Considering that healthy myeloid cells have been shown to switch their metabolic pathways to glycolysis in response to inflammatory cues, we studied what impact this might have on production of the inflammatory cytokines. We have demonstrated that patients' monocytes, in response to lipopolysaccharide, show significantly increased production of IL-1β and IL-18, which is NLRP3 inflammasome dependent. Furthermore, additional whole blood assays have also shown an enhanced production of IL-6 and TNF from the patients' cells. These cases provide further proof that autoinflammatory complications are also seen within the spectrum of primary immune deficiencies, and resulting from a wider dysregulation of the immune responses.

Glucose-6-Phosphatase Catalytic Subunit 3 (G6PC3) Deficiency Associated With Autoinflammatory Complications

PubMed Central

Mistry, Anoop; Scambler, Thomas; Parry, David; Wood, Mark; Barcenas-Morales, Gabriela; Carter, Clive; Doffinger, Rainer; Savic, Sinisa

2017-01-01

G6PC3 deficiency typically causes severe congenital neutropenia, associated with susceptibility to infections, cardiac and urogenital abnormalities. However, here we describe two boys of Pakistani origin who were found to have G6PC3 deficiency due to c.130 C>T mutation, but who have clinical phenotypes that are typical for a systemic autoinflammatory syndrome. The index case presented with combination of unexplained fevers, severe mucosal ulcers, abdominal symptoms, and inflammatory arthritis. He eventually fully responded to anti-TNF therapy. In this study, we show that compared with healthy controls, neutrophils and monocytes from patients have reduced glycolytic reserve. Considering that healthy myeloid cells have been shown to switch their metabolic pathways to glycolysis in response to inflammatory cues, we studied what impact this might have on production of the inflammatory cytokines. We have demonstrated that patients’ monocytes, in response to lipopolysaccharide, show significantly increased production of IL-1β and IL-18, which is NLRP3 inflammasome dependent. Furthermore, additional whole blood assays have also shown an enhanced production of IL-6 and TNF from the patients’ cells. These cases provide further proof that autoinflammatory complications are also seen within the spectrum of primary immune deficiencies, and resulting from a wider dysregulation of the immune responses. PMID:29163546

Accounting for Proof Test Data in a Reliability Based Design Optimization Framework

NASA Technical Reports Server (NTRS)

Ventor, Gerharad; Scotti, Stephen J.

2012-01-01

This paper investigates the use of proof (or acceptance) test data during the reliability based design optimization of structural components. It is assumed that every component will be proof tested and that the component will only enter into service if it passes the proof test. The goal is to reduce the component weight, while maintaining high reliability, by exploiting the proof test results during the design process. The proposed procedure results in the simultaneous design of the structural component and the proof test itself and provides the designer with direct control over the probability of failing the proof test. The procedure is illustrated using two analytical example problems and the results indicate that significant weight savings are possible when exploiting the proof test results during the design process.

Source spectral variation and yield estimation for small, near-source explosions

NASA Astrophysics Data System (ADS)

Yoo, S.; Mayeda, K. M.

2012-12-01

Significant S-wave generation is always observed from explosion sources which can lead to difficulty in discriminating explosions from natural earthquakes. While there are numerous S-wave generation mechanisms that are currently the topic of significant research, the mechanisms all remain controversial and appear to be dependent upon the near-source emplacement conditions of that particular explosion. To better understand the generation and partitioning of the P and S waves from explosion sources and to enhance the identification and discrimination capability of explosions, we investigate near-source explosion data sets from the 2008 New England Damage Experiment (NEDE), the Humble-Redwood (HR) series of explosions, and a Massachusetts quarry explosion experiment. We estimate source spectra and characteristic source parameters using moment tensor inversions, direct P and S waves multi-taper analysis, and improved coda spectral analysis using high quality waveform records from explosions from a variety of emplacement conditions (e.g., slow/fast burning explosive, fully tamped, partially tamped, single/ripple-fired, and below/above ground explosions). The results from direct and coda waves are compared to theoretical explosion source model predictions. These well-instrumented experiments provide us with excellent data from which to document the characteristic spectral shape, relative partitioning between P and S-waves, and amplitude/yield dependence as a function of HOB/DOB. The final goal of this study is to populate a comprehensive seismic source reference database for small yield explosions based on the results and to improve nuclear explosion monitoring capability.

Effectiveness of quality-control aids in verifying K-9-team explosive detection performance

NASA Astrophysics Data System (ADS)

Hallowell, Susan F.; Fischer, Douglas S.; Brasher, Jeffrey D.; Malone, Robert L.; Gresham, Garold L.; Rae, Cathy

1997-02-01

The Federal Aviation Administration (FAA) and supporting agencies conducted a developmental test and evaluation (DTE) to determine if quality control aids (QCAs) could be developed that would provide effective surrogates to actual explosives used for training and testing K-9 explosives detection teams. Non-detonable surrogates are required to alleviate logistics and contamination issues with explosives used sa training aids. Comparative K-9 team detection performance for explosives used as training aids and QCAs configurations of each explosive type were evaluated to determine the optimal configuration for the QCA configuration of each explosive type were evaluated to determine the optimal configuration for the QCAs. The configurations were a paper patch impregnated with a solution of the explosive, a cloth pouch filed with small amounts of solid explosive, and the non-hazardous explosive for security training and testing material. The DTE was conducted at Lackland Air Force Base in San Antonio, Texas, where the K-9 teams undergo initial training. Six FAA certified operational teams participated. All explosives and QCAs were presented to the K-9 teams using a 10 scent box protocol. The results show that K-9 team as are more sensitive to explosives than the candidate QCAs. More importantly, it was discovered that the explosives at Lackland AFB are cross-contaminated, meaning that explosives possessed volatile artifacts from other explosives. There are two potential hypotheses explaining why the dogs did not detect the QCAs. First, the cross-contamination of Lackland training explosives may mean that K-9 teams are only trained to detect the explosives with the most volatile chemical signatures. Alternatively, the QCA configurations may have been below the trained detection threshold of the K-9s. It is recommended that K-9 teams train on uncontaminated odors from properly designed QCAs to ensure that dogs respond to the appropriate explosive components, and not some other constituent or contaminant.

Tree-oriented interactive processing with an application to theorem-proving, appendix E

NASA Technical Reports Server (NTRS)

Hammerslag, David; Kamin, Samuel N.; Campbell, Roy H.

1985-01-01

The concept of unstructured structure editing and ted, an editor for unstructured trees, is described. Ted is used to manipulate hierarchies of information in an unrestricted manner. The tool was implemented and applied to the problem of organizing formal proofs. As a proof management tool, it maintains the validity of a proof and its constituent lemmas independently from the methods used to validate the proof. It includes an adaptable interface which may be used to invoke theorem provers and other aids to proof construction. Using ted, a user may construct, maintain, and verify formal proofs using a variety of theorem provers, proof checkers, and formatters.

Minimally invasive optical biopsy for oximetry

NASA Astrophysics Data System (ADS)

van der Putten, Marieke A.; Brewer, James M.; Harvey, Andrew R.

2017-02-01

The study of localised oxygen saturation in blood vessels can shed light on the etiology and progression of many diseases with which hypoxia is associated. For example, hypoxia in the tendon has been linked to early stages of rheumatoid arthritis, an auto-immune inflammatory disease. Vascular oximetry of deep tissue presents significant challenges as vessels are not optically accessible. In this paper, we present a novel multispectral imaging technique for vascular oximetry, and recent developments made towards its adaptation for minimally invasive imaging. We present proof-of-concept of the system and illumination scheme as well as the analysis technique. We present results of a validation study performed in vivo on mice with acutely inflamed tendons. Adaptation of the technique for minimally invasive microendoscopy is also presented, along with preliminary results of minimally invasive ex vivo vascular oximetry.

A cell culture-derived whole virus influenza A vaccine based on magnetic sulfated cellulose particles confers protection in mice against lethal influenza A virus infection.

PubMed

Pieler, Michael M; Frentzel, Sarah; Bruder, Dunja; Wolff, Michael W; Reichl, Udo

2016-12-07

Downstream processing and formulation of viral vaccines employs a large number of different unit operations to achieve the desired product qualities. The complexity of individual process steps involved, the need for time consuming studies towards the optimization of virus yields, and very high requirements regarding potency and safety of vaccines results typically in long lead times for the establishment of new processes. To overcome such obstacles, to enable fast screening of potential vaccine candidates, and to explore options for production of low cost veterinary vaccines a new platform for whole virus particle purification and formulation based on magnetic particles has been established. Proof of concept was carried out with influenza A virus particles produced in suspension Madin Darby canine kidney (MDCK) cells. The clarified, inactivated, concentrated, and diafiltered virus particles were bound to magnetic sulfated cellulose particles (MSCP), and directly injected into mice for immunization including positive and negative controls. We show here, that in contrast to the mock-immunized group, vaccination of mice with antigen-loaded MSCP (aMSCP) resulted in high anti-influenza A antibody responses and full protection against a lethal challenge with replication competent influenza A virus. Antiviral protection correlated with a 400-fold reduced number of influenza nucleoprotein gene copies in the lungs of aMSCP immunized mice compared to mock-treated animals, indicating the efficient induction of antiviral immunity by this novel approach. Thus, our data proved the use of MSCP for purification and formulation of the influenza vaccine to be fast and efficient, and to confer protection of mice against influenza A virus infection. Furthermore, the method proposed has the potential for fast purification of virus particles directly from bioreactor harvests with a minimum number of process steps towards formulation of low-cost veterinary vaccines, and for screening studies requiring fast purification protocols. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optically detonated explosive device

NASA Technical Reports Server (NTRS)

Yang, L. C.; Menichelli, V. J. (Inventor)

1974-01-01

A technique and apparatus for optically detonating insensitive high explosives, is disclosed. An explosive device is formed by containing high explosive material in a house having a transparent window. A thin metallic film is provided on the interior surface of the window and maintained in contact with the high explosive. A laser pulse provided by a Q-switched laser is focussed on the window to vaporize the metallic film and thereby create a shock wave which detonates the high explosive. Explosive devices may be concurrently or sequentially detonated by employing a fiber optic bundle to transmit the laser pulse to each of the several individual explosive devices.

Method for fabricating non-detonable explosive simulants

DOEpatents

Simpson, Randall L.; Pruneda, Cesar O.

1995-01-01

A simulator which is chemically equivalent to an explosive, but is not detonable. The simulator has particular use in the training of explosives detecting dogs and calibrating sensitive analytical instruments. The explosive simulants may be fabricated by different techniques, a first involves the use of standard slurry coatings to produce a material with a very high binder to explosive ratio without masking the explosive vapor, and the second involves coating inert beads with thin layers of explosive molecules.

Non-detonable explosive simulators

DOEpatents

Simpson, R.L.; Pruneda, C.O.

1994-11-01

A simulator which is chemically equivalent to an explosive, but is not detonable. The simulator has particular use in the training of explosives detecting dogs and calibrating sensitive analytical instruments. The explosive simulants may be fabricated by different techniques, a first involves the use of standard slurry coatings to produce a material with a very high binder to explosive ratio without masking the explosive vapor, and the second involves coating inert beads with thin layers of explosive molecules. 5 figs.

Ammonium nitrate explosive systems

DOEpatents

Stinecipher, Mary M.; Coburn, Michael D.

1981-01-01

Novel explosives which comprise mixtures of ammonium nitrate and an ammonium salt of a nitroazole in desired ratios are disclosed. A preferred nitroazole is 3,5-dinitro-1,2,4-triazole. The explosive and physical properties of these explosives may readily be varied by the addition of other explosives and oxidizers. Certain of these mixtures have been found to act as ideal explosives.

University Undergraduate Science Students' Validation and Comprehension of Written Proof in the Context of Infinite Series

ERIC Educational Resources Information Center

Moru, Eunice Kolitsoe; Nchejane, John; Ramollo, Motlatsi; Rammea, Lisema

2017-01-01

The reported study explored undergraduate science students' validation and comprehension of written proofs, reasons given either to accept or reject mathematical procedures employed in the proofs, and the difficulties students encountered in reading the proofs. The proofs were constructed using both the Comparison and the Integral tests in the…

A Physical Proof of the Pythagorean Theorem

ERIC Educational Resources Information Center

Treeby, David

2017-01-01

What proof of the Pythagorean theorem might appeal to a physics teacher? A proof that involved the notion of mass would surely be of interest. While various proofs of the Pythagorean theorem employ the circumcenter and incenter of a right-angled triangle, we are not aware of any proof that uses the triangle's center of mass. This note details one…

Examination of Secondary School Seventh Graders' Proof Skills and Proof Schemes

ERIC Educational Resources Information Center

Sen, Ceylan; Guler, Gursel

2015-01-01

The aim of this study is to examine current proof making skills of secondary school seventh graders using proof schemes. Data of the study were collected in two phases. Initially, Proof Schemes Test, which was developed by the researchers, was administrated to 250 seventh grade students from eight secondary schools, which were chosen randomly. The…

Proofs without Words: A Visual Application of Reasoning and Proof

ERIC Educational Resources Information Center

Bell, Carol J.

2011-01-01

Reasoning and Proof is one of the Process Standards set forth in National Council of Teachers of Mathematics' (NCTM) "Principles and Standards for School Mathematics." Thus, it is important to give students opportunities to build their reasoning skills and aid their understanding of the proof process. Teaching students how to do proofs is a…

Seismic Analysis of Three Bomb Explosions in Turkey

NASA Astrophysics Data System (ADS)

Necmioglu, O.; Semin, K. U.; Kocak, S.; Destici, C.; Teoman, U.; Ozel, N. M.

2016-12-01

Seismic analysis of three vehicle-installed bomb explosions occurred on 13 March 2016 in Ankara, 12 May 2016 in Diyarbakır and 9 July 2016 in Mardin have been conducted using data from the nearest stations (LOD, DYBB and MAZI) of the Boğaziçi University - Kandilli Observatory and Earthquake Research Institute's (KOERI) seismic network and compared with low-magnitude earthquakes in similar distance based on phase readings and frequency content. Amplitude spectra has been compared through Fourier transformation and earthquake-explosion frequency discrimination has been performed using various filter bands. Time-domain and spectral analysis have been performed using Geotool software provided by CTBTO. Local magnitude (ML) values have been calculated for each explosion by removing instrument-response and adding Wood-Anderson type instrument response. Approximate amount of explosives used in these explosions have been determined using empirical methods of Koper (2002). Preliminary results indicated that 16 tons TNT equivalent explosives have been used in 12 May 2016 Diyarbakır explosion, which is very much in accordance with the media reports claiming 15 tons of TNT. Our analysis for 9 July 2016 Mardin explosion matched the reported 5 tons of explosives. Results concerning 13 March 2016 Ankara explosion indicated that approximately 1,7 ton of TNT equivalent explosives were used in the attack whereas security and intelligence reports claimed 300 kg explosives as a combination of TNT, RDX and ammonium nitrate. The overestimated results obtained in our analysis for the Ankara explosion may be related due to i) high relative effectiveness factor of the RDX component of the explosive ii) inefficiency of Koper (2002) method in lower yields (since the method was developed using explosions with yields of 3-12 tons of TNT), iii) combination of both.

Velocity feedback control with a flywheel proof mass actuator

NASA Astrophysics Data System (ADS)

Kras, Aleksander; Gardonio, Paolo

2017-08-01

This paper presents four new proof mass actuators to be used in velocity feedback control systems for the control of vibrations of machines and flexible structures. A classical proof mass actuator is formed by a coil-magnet linear motor, with either the magnet or the armature-coil proof mass suspended on soft springs. This arrangement produces a net force effect at frequencies above the fundamental resonance frequency of the springs-proof mass system. Thus, it can be used to implement point velocity feedback loops, although the dynamic response and static deflection of the springs-proof mass system poses some stability and control performance limitations. The four proof mass actuators presented in this study include a flywheel element, which is used to augment the inertia effect of the suspended proof mass. The paper shows that the flywheel element modifies both the dynamic response and static deflection of the springs-proof mass system in such a way as the stability and control performance of velocity feedback loops using these actuators are significantly improved.

The stochastic dance of early HIV infection

NASA Astrophysics Data System (ADS)

Merrill, Stephen J.

2005-12-01

The stochastic nature of early HIV infection is described in a series of models, each of which captures aspects of the dance of HIV during the early stages of infection. It is to this highly variable target that the immune response must respond. The adaptability of the various components of the immune response is an important aspect of the system's operation, as the nature of the pathogens that the response will be required to respond to and the order in which those responses must be made cannot be known beforehand. As HIV infection has direct influence over cells responsible for the immune response, the dance predicts that the immune response will be also in a variable state of readiness and capability for this task of adaptation. The description of the stochastic dance of HIV here will use the tools of stochastic models, and for the most part, simulation. The justification for this approach is that the early stages and the development of HIV diversity require that the model to be able to describe both individual sample path and patient-to-patient variability. In addition, as early viral dynamics are best described using branching processes, the explosive growth of these models both predicts high variability and rapid response of HIV to changes in system parameters.In this paper, a basic viral growth model based on a time dependent continuous-time branching process is used to describe the growth of HIV infected cells in the macrophage and lymphocyte populations. Immigration from the reservoir population is added to the basic model to describe the incubation time distribution. This distribution is deduced directly from the modeling assumptions and the model of viral growth. A system of two branching processes, one in the infected macrophage population and one in the infected lymphocyte population is used to provide a description of the relationship between the development of HIV diversity as it relates to tropism (host cell preference). The role of the immune response to HIV and HIV infected cells is used to describe the movement of the infection from a few infected macrophages to a disease of infected CD4+ T lymphocytes.

49 CFR 172.411 - EXPLOSIVE 1.1, 1.2, 1.3, 1.4, 1.5 and 1.6 labels, and EXPLOSIVE Subsidiary label.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false EXPLOSIVE 1.1, 1.2, 1.3, 1.4, 1.5 and 1.6 labels..., 1.2, 1.3, 1.4, 1.5 and 1.6 labels, and EXPLOSIVE Subsidiary label. (a) Except for size and color....5 and EXPLOSIVE 1.6 labels must be as follows: EXPLOSIVE 1.4: EC02MR91.016 EXPLOSIVE 1.5: EC02MR91...

Insensitive fuze train for high explosives

DOEpatents

Cutting, Jack L.; Lee, Ronald S.; Von Holle, William G.

1994-01-01

A generic insensitive fuze train to initiate insensitive high explosives, such as PBXW-124. The insensitive fuze train uses a slapper foil to initiate sub-gram quantities of an explosive, such as HNS-IV or PETN. This small amount of explosive drives a larger metal slapper onto a booster charge of an insensitive explosive, such as UF-TATB. The booster charge initiates a larger charge of an explosive, such as LX-17, which in turn, initiates the insensitive high explosive, such as PBXW-124.

Method for fabricating non-detonable explosive simulants

DOEpatents

Simpson, R.L.; Pruneda, C.O.

1995-05-09

A simulator is disclosed which is chemically equivalent to an explosive, but is not detonable. The simulator has particular use in the training of explosives detecting dogs and calibrating sensitive analytical instruments. The explosive simulants may be fabricated by different techniques, a first involves the use of standard slurry coatings to produce a material with a very high binder to explosive ratio without masking the explosive vapor, and the second involves coating inert beads with thin layers of explosive molecules. 5 figs.

Insensitive fuze train for high explosives

DOEpatents

Cutting, J.L.; Lee, R.S.; Von Holle, W.G.

1994-01-04

A generic insensitive fuze train to initiate insensitive high explosives, such as PBXW-124 is described. The insensitive fuze train uses a slapper foil to initiate sub-gram quantities of an explosive, such as HNS-IV or PETN. This small amount of explosive drives a larger metal slapper onto a booster charge of an insensitive explosive, such as UF-TATB. The booster charge initiates a larger charge of an explosive, such as LX-17, which in turn, initiates the insensitive high explosive, such as PBXW-124. 3 figures.

Proof test and fatigue crack growth modeling on 2024-T3 aluminum alloy

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.; Poe, C. C., Jr.; Dawicke, D. S.

1990-01-01

Pressure proof testing of aircraft fuselage structures has been suggested as a means of screening critical crack sizes and of extending their useful life. The objective of this paper is to study the proof-test concept and to model the crack-growth process on a ductile material. Simulated proof and operational fatigue life tests have been conducted on cracked panels made of 2024-T3 aluminum alloy sheet material. A fatigue crack-closure model was modified to simulate the proof test and operational fatigue cycling. Using crack-growth rate and resistance-curve data, the model was able to predict crack growth during and after the proof load. These tests and analyses indicate that the proof test increases fatigue life; but the beneficial life, after a 1.33 or 1.5 proof, was less than a few hundred cycles.

Totally confined explosive welding. [apparatus to reduce noise level and protect personnel during explosive bonding

NASA Technical Reports Server (NTRS)

Bement, L. J. (Inventor)

1974-01-01

A method and associated apparatus for confining the undesirable by-products and limiting noise of explosive welding are discussed. The apparatus consists fo a simple enclosure into which the explosive is placed and within which the explosion occurs. The shape of the enclosure, the placement of the explosive, and the manner in which the enclosure is placed upon the material to be welded determine the force of the explosion transmitted to the proposed bond area. The explosion is totally confined within the enclosure thus reducing the noise level and preventing debris from being strewn about to contaminate the weld area or create personnel hazards.

The State of Proof in Finnish and Swedish Mathematics Textbooks--Capturing Differences in Approaches to Upper-Secondary Integral Calculus

ERIC Educational Resources Information Center

Bergwall, Andreas; Hemmi, Kirsti

2017-01-01

Students' difficulties with proof, scholars' calls for proof to be a consistent part of K-12 mathematics, and the extensive use of textbooks in mathematics classrooms motivate investigations on how proof-related items are addressed in mathematics textbooks. We contribute to textbook research by focusing on opportunities to learn proof-related…

Integrating Algebra and Proof in High School Mathematics: An Exploratory Study

ERIC Educational Resources Information Center

Martinez, Mara V.; Brizuela, Barbara M.; Superfine, Alison Castro

2011-01-01

Frequently, in the US students' work with proofs is largely concentrated to the domain of high school geometry, thus providing students with a distorted image of what proof entails, which is at odds with the central role that proof plays in mathematics. Despite the centrality of proof in mathematics, there is a lack of studies addressing how to…

On Mathematicians' Proof Skimming: A Reply to Inglis and Alcock

ERIC Educational Resources Information Center

Weber, Keith; Mejia-Ramos, Juan Pablo

2013-01-01

n a recent article, Inglis and Alcock (2012) contended that their data challenge the claim that when mathematicians validate proofs, they initially skim a proof to grasp its main idea before reading individual parts of the proof more carefully. This result is based on the fact that when mathematicians read proofs in their study, on average their…

Rethinking the Discovery Function of Proof within the Context of Proofs and Refutations

ERIC Educational Resources Information Center

Komatsu, Kotaro; Tsujiyama, Yosuke; Sakamaki, Aruta

2014-01-01

Proof and proving are important components of school mathematics and have multiple functions in mathematical practice. Among these functions of proof, this paper focuses on the discovery function that refers to invention of a new statement or conjecture by reflecting on or utilizing a constructed proof. Based on two cases in which eighth and ninth…

27 CFR 555.182 - Exceptions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... or modified explosive materials; (2) Training in explosives detection or development or testing of explosives detection equipment; or (3) Forensic science purposes; or (b) Was plastic explosive that, by April... 555.182 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES...

27 CFR 555.182 - Exceptions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... or modified explosive materials; (2) Training in explosives detection or development or testing of explosives detection equipment; or (3) Forensic science purposes; or (b) Was plastic explosive that, by April... 555.182 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES...

Proof test methodology for composites

NASA Technical Reports Server (NTRS)

Wu, Edward M.; Bell, David K.

1992-01-01

The special requirements for proof test of composites are identified based on the underlying failure process of composites. Two proof test methods are developed to eliminate the inevitable weak fiber sites without also causing flaw clustering which weakens the post-proof-test composite. Significant reliability enhancement by these proof test methods has been experimentally demonstrated for composite strength and composite life in tension. This basic proof test methodology is relevant to the certification and acceptance of critical composite structures. It can also be applied to the manufacturing process development to achieve zero-reject for very large composite structures.

The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis.

PubMed

Yeremenko, Nataliya; Paramarta, Jacqueline E; Baeten, Dominique

2014-07-01

Various novel therapies for spondyloarthritis (SpA) are currently under development. In this review, we discuss the scientific rational to target the interleukin (IL)-23/IL-17 axis in SpA and give an overview of the proof-of-concept trials with drugs directed towards this axis. Cumulative evidence from genetics (e.g. the strong genetic association with the IL-23 receptor gene), in-vitro models (e.g. the increased IL-23 production upon HLA-B27 misfolding), human expression studies (e.g. the expansion of IL-17 producing innate cells in SpA) and animal models (e.g. the increased IL-17 production in HLA-B27 transgenic rats) strongly supports the involvement of the IL-23/IL-17 axis in the pathogenesis of SpA. Ustekinumab (a monoclonal antibody directed against the common p40 subunit of IL-23 and IL-12), secukinumab, ixekizumab (both monoclonal antibodies directed against IL-17A), and brodalumab a monoclonal antibody against the IL-17RA receptor) have been recently used in proof-of-concept and randomized trials in the ankylosing spondylitis and/or psoriatic arthritis subforms of SpA, with overall very promising clinical efficacy. The first results for novel drugs blocking key cytokines in the IL-23/IL-17 axis are promising in SpA and more novel compounds are upcoming. This will teach us more on the role of the IL-23/IL-17 axis in the pathophysiology of SpA.

Yield Determination of Underground and Near Surface Explosions

NASA Astrophysics Data System (ADS)

Pasyanos, M.

2015-12-01

As seismic coverage of the earth's surface continues to improve, we are faced with signals from a wide variety of explosions from various sources ranging from oil train and ordnance explosions to military and terrorist attacks, as well as underground nuclear tests. We present on a method for determining the yield of underground and near surface explosions, which should be applicable for many of these. We first review the regional envelope method that was developed for underground explosions (Pasyanos et al., 2012) and more recently modified for near surface explosions (Pasyanos and Ford, 2015). The technique models the waveform envelope templates as a product of source, propagation (geometrical spreading and attenuation), and site terms, while near surface explosions include an additional surface effect. Yields and depths are determined by comparing the observed envelopes to the templates and minimizing the misfit. We then apply the method to nuclear and chemical explosions for a range of yields, depths, and distances. We will review some results from previous work, and show new examples from ordnance explosions in Scandinavia, nuclear explosions in Eurasia, and chemical explosions in Nevada associated with the Source Physics Experiments (SPE).

The Gut Microbiota in Immune-Mediated Inflammatory Diseases

PubMed Central

Forbes, Jessica D.; Van Domselaar, Gary; Bernstein, Charles N.

2016-01-01

The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

An evaluation of the pressure proof test concept for 2024-T3 aluminium alloy sheet

NASA Technical Reports Server (NTRS)

Dawicke, D. S.; Poe, C. C., Jr.; Newman, J. C.; Harris, C. E.

1991-01-01

The concept of pressure proof testing of fuselage structures with fatigue cracks to insure structural integrity was evaluated from a fracture mechanics viewpoint. A generic analytical and experimental investigation was conducted on uniaxially loaded flat panels with crack configurations and stress levels typical of longitudinal lap splice joints in commercial transport aircraft fuselages. The results revealed that the remaining fatigue life after a proof cycle was longer than that without the proof cycle because of crack growth retardation due to increased crack closure. However, based on a crack length that is slightly less than the critical value at the maximum proof stress, the minimum assured life or proof test interval must be no more than 550 pressure cycles for a 1.33 proof factor and 1530 pressure cycles for a 1.5 proof factor to prevent in-flight failures.

An evaluation of the pressure proof test concept for thin sheet 2024-T3

NASA Technical Reports Server (NTRS)

Dawicke, D. S.; Poe, C. C., Jr.; Newman, J. C., Jr.; Harris, C. E.

1990-01-01

The concept of pressure proof testing of fuselage structures with fatigue cracks to insure structural integrity was evaluated from a fracture mechanics viewpoint. A generic analytical and experimental investigation was conducted on uniaxially loaded flat panels with crack configurations and stress levels typical of longitudinal lap-splice joints in commercial transport aircraft fuselage. The results revealed that the remaining fatigue life after a proof test was longer than that without the proof test because of crack growth retardation due to increased crack closure. However, based on a crack length that is slightly less than the critical value at the maximum proof test stress, the minimum assured life or proof test interval must be no more than 550 pressure cycles for a 1.33 proof factor and 1530 pressure cycles for a 1.5 proof factor to prevent in-flight failures.

An evaluation of the pressure proof test concept for thin sheet 2024-T3

NASA Technical Reports Server (NTRS)

Dawicke, D. S.; Poe, C. C., Jr.; Newman, James C., Jr.; Harris, Charles E.

1990-01-01

The concept of pressure proof testing of fuselage structures with fatigue cracks to insure structural integrity was evaluated from a fracture mechanics viewpoint. A generic analytical and experimental investigation was conducted on uniaxially loaded flat panels with crack configurations and stress levels typical of longitudinal lap splice joints in commercial transport aircraft fuselages. The results revealed that the remaining fatigue life after a proof test was longer than that without the proof test because of crack growth retardation due to increased crack closure. However, based on a crack length that is slightly less than the critical value at the maximum proof test stress, the minimum assured life or proof test interval must be no more than 550 pressure cycles for a 1.33 proof factor and 1530 pressure cycles for a 1.5 proof factor to prevent in-flight failures.

[Understanding mistake-proofing].

PubMed

de Saint Maurice, G; Giraud, N; Ausset, S; Auroy, Y; Lenoir, B; Amalberti, R

2011-01-01

The mistake-proofing concept often refers to physical devices that prevent actors from making a wrong action. In anaesthesiology, one immediately thinks to specific design of outlets for medical gases. More generally, the principle of mistake-proofing is to avoid an error, by placing knowledge in the world rather than knowledge in the head. As it often happens in risk management, healthcare has received information transfers from the industry. Computer is changing the concept of mistake-proofing, initially based on physical design, such as aerospace and automotive industry. The mistake-proofing concept may be applied to prevention, detection, and mitigation of errors. The forcing functions are a specific part of mistake-proofing: they prevent a wrong action or they force a virtuous one. Grout proposes a little shortcut to identify mistake-proofing devices: "If it is not possible to picture it in action, it is probably not a mistake-proofing device". Copyright © 2010 Elsevier Masson SAS. All rights reserved.

A non-imaging polarized terahertz passive system for detecting and identifying concealed explosives

NASA Astrophysics Data System (ADS)

Karam, Mostafa A.; Meyer, Doug

2011-06-01

Existing terahertz THz systems for detecting concealed explosives are not capable of identifying explosive type which leads to higher false alarm rates. Moreover, some of those systems are imaging systems that invade personal privacy, and require more processing and computational resources. Other systems have no polarization preference which makes them incapable of capturing the geometric features of an explosive. In this study a non-imaging polarized THz passive system for detecting and identifying concealed explosives overcoming the forgoing shortcomings is developed. The system employs a polarized passive THz sensor in acquiring emitted data from a scene that may have concealed explosives. The acquired data are decomposed into their natural resonance frequencies, and the number of those frequencies is used as criteria in detecting the explosive presence. If the presence of an explosive is confirmed, a set of physically based retrieval algorithms is used in extracting the explosive dielectric constant/refractive index value from natural resonance frequencies and amplitudes of associated signals. Comparing the refractive index value against a database of refractive indexes of known explosives identifies the explosive type. As an application, a system having a dual polarized radiometer operating within the frequency band of 0.62- 0.82 THz is presented and used in detecting and identifying person borne C-4 explosive concealed under a cotton garment. The system showed higher efficiencies in detecting and identifying the explosive.

Characterization of fine volcanic ash from explosive eruption from Sakurajima volcano, South Japan

NASA Astrophysics Data System (ADS)

Nanayama, F.; Furukawa, R.; Ishizuka, Y.; Yamamoto, T.; Geshi, N.; Oishi, M.

2013-12-01

Explosive volcanic eruptions can affect infrastructure and ecosystem by their dispersion of the volcanic particle. Characterization of volcanic particle expelled by explosive eruption is crucial for evaluating for quantitative hazard assessment by future volcanic eruption. Especially for fine volcanic ash less than 64 micron in diameter, it can disperse vast area from the source volcano and be easily remobilized by surface wind and precipitation after the deposition. As fine volcanic ash is not preserved well at the earth surface and in strata except for enormously large scale volcanic eruption. In order to quantify quantitative characteristics of fine volcanic ash particle, we sampled volcanic ash directly falling from the eruption cloud from Showa crater, the most active vent of Sakurajima volcano, just before landing on ground. We newly adopted high precision digital microscope and particle grain size analyzer to develop hazard evaluation method of fine volcanic ash particle. Field survey was performed 5 sequential days in January, 2013 to take tamper-proof volcanic ash samples directly obtained from the eruption cloud of the Sakurajima volcano using disposable paper dishes and plastic pails. Samples were taken twice a day with time-stamp in 40 localities from 2.5 km to 43 km distant from the volcano. Japan Meteorological Agency reported 16 explosive eruptions of vulcanian style occurred during our survey and we took 140 samples of volcanic ash. Grain size distribution of volcanic ash was measured by particle grain size analyzer (Mophologi G3S) detecting each grain with parameters of particle diameter (0.3 micron - 1 mm), perimeter, length, area, circularity, convexity, solidity, and intensity. Component of volcanic ash was analyzed by CCD optical microscope (VHX-2000) which can take high resolution optical image with magnifying power of 100-2500. We discriminated each volcanic ash particle by color, texture of surface, and internal structure. Grain size distributions of volcanic ash from Sakurajima volcano have basically characteristics of unimodal and gaussian. Mode of distributions are 150 - 200 micron at 5 km and 70-80 micron at 20 km respectively from the Showa crater. Mode and deviation of the grain size distribution are function of distance from the source. Fine volcanic ash less than 1 micron in diameter is few and exists in every samples. Component of volcanic ash samples are dark-colored dense glass shard (ca. 50%), light-colored dense glass shard (10%), variously colored and vesiculated glass shard (10%), free crystal (20%), lithic fragment (10%), and altered fragment (less than 5%) which are mostly having similar ratio in every location suggesting single source process of the eruption. We also found fine volcanic ash samples less than 10 micron are frequently aggregated. The present study includes the result of "Research and Development of Margin Assessment Methodology of Decay Heat Removal Function against External Hazards" entrusted to Japan Atomic Energy Agency by the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).

Explosion risk evaluation during production of coating powder.

PubMed

Li, Gang; Yuan, Chunmiao; Chen, Baozhi

2007-10-22

Powder coating is widely used in industry to prevent equipment corrosion. More than 600 companies produce coating powder in China, but most do not understand the explosion hazard of such products. In the present investigation the explosibility parameters of a coating powder were determined. Results showed that the coating powder is explosible, though the ignition energy is higher than those of normal dusts such as coal powder and corn starch. Based on these experimental findings, a systematic explosion protection method is proposed, with explosion isolation and explosion venting being adopted as the main protective methods.

28 CFR 79.25 - Proof of onset of leukemia at least two years after first exposure, and proof of onset of a...

Code of Federal Regulations, 2010 CFR

2010-07-01

... years after first exposure, and proof of onset of a specified compensable disease more than five years... Specified Diseases Contracted After Exposure in an Affected Area (âDownwindersâ) § 79.25 Proof of onset of leukemia at least two years after first exposure, and proof of onset of a specified compensable disease...

28 CFR 79.25 - Proof of onset of leukemia at least two years after first exposure, and proof of onset of a...

Code of Federal Regulations, 2011 CFR

2011-07-01

... years after first exposure, and proof of onset of a specified compensable disease more than five years... Specified Diseases Contracted After Exposure in an Affected Area (âDownwindersâ) § 79.25 Proof of onset of leukemia at least two years after first exposure, and proof of onset of a specified compensable disease...

28 CFR 79.25 - Proof of onset of leukemia at least two years after first exposure, and proof of onset of a...

Code of Federal Regulations, 2012 CFR

2012-07-01

... years after first exposure, and proof of onset of a specified compensable disease more than five years... Specified Diseases Contracted After Exposure in an Affected Area (âDownwindersâ) § 79.25 Proof of onset of leukemia at least two years after first exposure, and proof of onset of a specified compensable disease...

28 CFR 79.25 - Proof of onset of leukemia at least two years after first exposure, and proof of onset of a...

Code of Federal Regulations, 2014 CFR

2014-07-01

... years after first exposure, and proof of onset of a specified compensable disease more than five years... Specified Diseases Contracted After Exposure in an Affected Area (âDownwindersâ) § 79.25 Proof of onset of leukemia at least two years after first exposure, and proof of onset of a specified compensable disease...

28 CFR 79.25 - Proof of onset of leukemia at least two years after first exposure, and proof of onset of a...

Code of Federal Regulations, 2013 CFR

2013-07-01

... years after first exposure, and proof of onset of a specified compensable disease more than five years... Specified Diseases Contracted After Exposure in an Affected Area (âDownwindersâ) § 79.25 Proof of onset of leukemia at least two years after first exposure, and proof of onset of a specified compensable disease...

Comparative Analysis on the Nature of Proof to Be Taught in Geometry: The Cases of French and Japanese Lower Secondary Schools

ERIC Educational Resources Information Center

Miyakawa, Takeshi

2017-01-01

This paper reports the results of an international comparative study on the nature of proof to be taught in geometry. Proofs in French and Japanese lower secondary schools were explored by analyzing curricular documents: mathematics textbooks and national curricula. Analyses on the three aspects of proof--statement, proof, and theory--suggested by…

Advancing Explosion Source Theory through Experimentation: Results from Seismic Experiments Since the Moratorium on Nuclear Testing

NASA Astrophysics Data System (ADS)

Bonner, J. L.; Stump, B. W.

2011-12-01

On 23 September 1992, the United States conducted the nuclear explosion DIVIDER at the Nevada Test Site (NTS). It would become the last US nuclear test when a moratorium ended testing the following month. Many of the theoretical explosion seismic models used today were developed from observations of hundreds of nuclear tests at NTS and around the world. Since the moratorium, researchers have turned to chemical explosions as a possible surrogate for continued nuclear explosion research. This talk reviews experiments since the moratorium that have used chemical explosions to advance explosion source models. The 1993 Non-Proliferation Experiment examined single-point, fully contained chemical-nuclear equivalence by detonating over a kiloton of chemical explosive at NTS in close proximity to previous nuclear explosion tests. When compared with data from these nearby nuclear explosions, the regional and near-source seismic data were found to be essentially identical after accounting for different yield scaling factors for chemical and nuclear explosions. The relationship between contained chemical explosions and large production mining shots was studied at the Black Thunder coal mine in Wyoming in 1995. The research led to an improved source model for delay-fired mining explosions and a better understanding of mining explosion detection by the International Monitoring System (IMS). The effect of depth was examined in a 1997 Kazakhstan Depth of Burial experiment. Researchers used local and regional seismic observations to conclude that the dominant mechanism for enhanced regional shear waves was local Rg scattering. Travel-time calibration for the IMS was the focus of the 1999 Dead Sea Experiment where a 10-ton shot was recorded as far away as 5000 km. The Arizona Source Phenomenology Experiments provided a comparison of fully- and partially-contained chemical shots with mining explosions, thus quantifying the reduction in seismic amplitudes associated with partial confinement. The Frozen Rock Experiment in 2006 found only minor differences in seismic coupling for explosions in frozen and unfrozen rock. The seismo-acoustic source function was the focus of the above- and below-ground Humble Redwood explosions (2007, 2009 ) in New Mexico and detonations of rocket motor explosions in Utah. Acoustic travel time calibration for the IMS was accomplished with the 2009 and 2011 100-ton surface explosions in southern Israel. The New England Damage Experiment in 2009 correlated increased shear wave generation with increased rock damage from explosions. Damage from explosions continues to be an important research topic at Nevada's National Center for Nuclear Security with the ongoing Source Physics Experiment. A number of exciting experiments are already planned for the future and thus continue the effort to improve global detection, location, and identification of nuclear explosions.

A new proof-of-principle contraband detection system

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

Sredniawski, J.J.; Debiak, T.; Kamykowski, E.

1995-12-01

A new concept for a CDS has been developed under a Phase I ARPA funded program; it uses gamma resonance absorption (GRA) to detect certain illegal drugs that may be transported in man-portable containers. A high detection probability for heroin and cocaine is possible with a device that is also searching for explosives. Elemental detection of both N and Cl is utilized, and with tomography, a 3D density image of the elements is generated. Total density image is also developed. These two together may be used with considerable confidence in determining if heroin or cocaine is present in the interrogatedmore » containers in a small quantity (1 kg). The CDS employs a high current ({ge}10 mA) DC accelerator that produces a beam of 1.75 or 1.89 MeV protons. These protons impact a target with coatings of {sup 13}C and {sup 34}S. Depending on the coating, the resultant resonant gamma rays are preferentially absorbed in either {sup 14}N or {sup 35}Cl. The resonant gammas come off the target in a conical fan at 80.7{degree} for N and 82{degree} for Cl; a common array of segmented BGO detectors is used over an arc of 53{degree} to provide input to an imaging subsystem. The tomography makes use of rotation and vertical translation of a baggage carousel holding typically 18 average sized bags for batch processing of the contents. The single proton accelerator and target can supply multiple detection stations with the appropriate gammas, a feature that may lead to very high throughput potential approaching 2000 bags/hr. Each detection station can operate somewhat independently from the others. This paper presents the overall requirements, design, operating principles, and characteristics of the CDS proof-of-principle device developed in the Phase I program.« less

System for fracturing an underground geologic formation

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

Mace, Jonathan L.; Tappan, Bryce C.; Seitz, Gerald J.

2017-03-14

An explosive system for fracturing an underground geologic formation adjacent to a wellbore can comprise a plurality of explosive units comprising an explosive material contained within the casing, and detonation control modules electrically coupled to the plurality of explosive units and configured to cause a power pulse to be transmitted to at least one detonator of at least one of the plurality of explosive units for detonation of the explosive material. The explosive units are configured to be positioned within a wellbore in spaced apart positions relative to one another along a string with the detonation control modules positioned adjacentmore » to the plurality of explosive units in the wellbore, such that the axial positions of the explosive units relative to the wellbore are at least partially based on geologic properties of the geologic formation adjacent the wellbore.« less

Explosion Generated Seismic Waves and P/S Methods of Discrimination from Earthquakes with Insights from the Nevada Source Physics Experiments

NASA Astrophysics Data System (ADS)

Walter, W. R.; Ford, S. R.; Pitarka, A.; Pyle, M. L.; Pasyanos, M.; Mellors, R. J.; Dodge, D. A.

2017-12-01

The relative amplitudes of seismic P-waves to S-waves are effective at identifying underground explosions among a background of natural earthquakes. These P/S methods appear to work best at frequencies above 2 Hz and at regional distances ( >200 km). We illustrate this with a variety of historic nuclear explosion data as well as with the recent DPRK nuclear tests. However, the physical basis for the generation of explosion S-waves, and therefore the predictability of this P/S technique as a function of path, frequency and event properties such as size, depth, and geology, remains incompletely understood. A goal of current research, such as the Source Physics Experiments (SPE), is to improve our physical understanding of the mechanisms of explosion S-wave generation and advance our ability to numerically model and predict them. The SPE conducted six chemical explosions between 2011 and 2016 in the same borehole in granite in southern Nevada. The explosions were at a variety of depths and sizes, ranging from 0.1 to 5 tons TNT equivalent yield. The largest were observed at near regional distances, with P/S ratios comparable to much larger historic nuclear tests. If we control for material property effects, the explosions have very similar P/S ratios independent of yield or magnitude. These results are consistent with explosion S-waves coming mainly from conversion of P- and surface waves, and are inconsistent with source-size based models. A dense sensor deployment for the largest SPE explosion allowed this conversion to be mapped in detail. This is good news for P/S explosion identification, which can work well for very small explosions and may be ultimately limited by S-wave detection thresholds. The SPE also showed explosion P-wave source models need to be updated for small and/or deeply buried cases. We are developing new P- and S-wave explosion models that better match all the empirical data. Historic nuclear explosion seismic data shows that the media in which the explosion takes place is quite important. These material property effects can surprisingly degrade the seismic waveform correlation of even closely spaced explosions in different media. The next phase of the SPE will contrast chemical explosions in dry alluvium with the prior SPE explosions in granite and historic nuclear tests in a variety of media.

DoD Contractors’ Safety Manual for Ammunition and Explosives.

DTIC Science & Technology

1997-09-01

grit, and other foreign material into operating buildings. 9. Windows and skylights . Non-shatterable glazing is preferred where an explosion...with the explosives being processed. Dull or damaged tools shall not be used for machining high explosives. k. The explosives products resulting from

30 CFR 57.6201 - Separation of transported explosive material.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Separation of transported explosive material... MINES Explosives Transportation-Surface and Underground § 57.6201 Separation of transported explosive material. Detonators shall not be transported on the same vehicle or conveyance with other explosives...

30 CFR 57.6201 - Separation of transported explosive material.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Separation of transported explosive material... MINES Explosives Transportation-Surface and Underground § 57.6201 Separation of transported explosive material. Detonators shall not be transported on the same vehicle or conveyance with other explosives...

Explosives tester

DOEpatents

Haas, Jeffrey S [San Ramon, CA; Howard, Douglas E [Livermore, CA; Eckels, Joel D [Livermore, CA; Nunes, Peter J [Danville, CA

2011-01-11

An explosives tester that can be used anywhere as a screening tool by non-technical personnel to determine whether a surface contains explosives. First and second explosives detecting reagent holders and dispensers are provided. A heater is provided for receiving the first and second explosives detecting reagent holders and dispensers.

An integrated experimental and computational approach to material selection for sound proof thermally insulted enclosure of a power generation system

NASA Astrophysics Data System (ADS)

Waheed, R.; Tarar, W.; Saeed, H. A.

2016-08-01

Sound proof canopies for diesel power generators are fabricated with a layer of sound absorbing material applied to all the inner walls. The physical properties of the majority of commercially available sound proofing materials reveal that a material with high sound absorption coefficient has very low thermal conductivity. Consequently a good sound absorbing material is also a good heat insulator. In this research it has been found through various experiments that ordinary sound proofing materials tend to rise the inside temperature of sound proof enclosure in certain turbo engines by capturing the heat produced by engine and not allowing it to be transferred to atmosphere. The same phenomenon is studied by creating a finite element model of the sound proof enclosure and performing a steady state and transient thermal analysis. The prospects of using aluminium foam as sound proofing material has been studied and it is found that inside temperature of sound proof enclosure can be cut down to safe working temperature of power generator engine without compromise on sound proofing.

Fourier Phase Domain Steganography: Phase Bin Encoding Via Interpolation

NASA Astrophysics Data System (ADS)

Rivas, Edward

2007-04-01

In recent years there has been an increased interest in audio steganography and watermarking. This is due primarily to two reasons. First, an acute need to improve our national security capabilities in light of terrorist and criminal activity has driven new ideas and experimentation. Secondly, the explosive proliferation of digital media has forced the music industry to rethink how they will protect their intellectual property. Various techniques have been implemented but the phase domain remains a fertile ground for improvement due to the relative robustness to many types of distortion and immunity to the Human Auditory System. A new method for embedding data in the phase domain of the Discrete Fourier Transform of an audio signal is proposed. Focus is given to robustness and low perceptibility, while maintaining a relatively high capacity rate of up to 172 bits/s.

Fiber-Optic Chemical Sensors and Fiber-Optic Bio-Sensors

PubMed Central

Pospíšilová, Marie; Kuncová, Gabriela; Trögl, Josef

2015-01-01

This review summarizes principles and current stage of development of fiber-optic chemical sensors (FOCS) and biosensors (FOBS). Fiber optic sensor (FOS) systems use the ability of optical fibers (OF) to guide the light in the spectral range from ultraviolet (UV) (180 nm) up to middle infrared (IR) (10 µm) and modulation of guided light by the parameters of the surrounding environment of the OF core. The introduction of OF in the sensor systems has brought advantages such as measurement in flammable and explosive environments, immunity to electrical noises, miniaturization, geometrical flexibility, measurement of small sample volumes, remote sensing in inaccessible sites or harsh environments and multi-sensing. The review comprises briefly the theory of OF elaborated for sensors, techniques of fabrications and analytical results reached with fiber-optic chemical and biological sensors. PMID:26437407

Unconventional High-Performance Laser Protection System Based on Dichroic Dye-Doped Cholesteric Liquid Crystals

NASA Astrophysics Data System (ADS)

Zhang, Wanshu; Zhang, Lanying; Liang, Xiao; Le Zhou; Xiao, Jiumei; Yu, Li; Li, Fasheng; Cao, Hui; Li, Kexuan; Yang, Zhou; Yang, Huai

2017-02-01

High-performance and cost-effective laser protection system is of crucial importance for the rapid advance of lasers in military and civilian fields leading to severe damages of human eyes and sensitive optical devices. However, it is crucially hindered by the angle-dependent protective effect and the complex preparation process. Here we demonstrate that angle-independence, good processibility, wavelength tunability, high optical density and good visibility can be effectuated simultaneously, by embedding dichroic anthraquinone dyes in a cholesteric liquid crystal matrix. More significantly, unconventional two-dimensional parabolic protection behavior is reported for the first time that in stark contrast to the existing protection systems, the overall parabolic protection behavior enables protective effect to increase with incident angles, hence providing omnibearing high-performance protection. The protective effect is controllable by dye concentration, LC cell thickness and CLC reflection efficiency, and the system can be made flexible enabling applications in flexible and even wearable protection devices. This research creates a promising avenue for the high-performance and cost-effective laser protection, and may foster the development of optical applications such as solar concentrators, car explosion-proof membrane, smart windows and polarizers.

Honeycomb-like porous gel polymer electrolyte membrane for lithium ion batteries with enhanced safety.

PubMed

Zhang, Jinqiang; Sun, Bing; Huang, Xiaodan; Chen, Shuangqiang; Wang, Guoxiu

2014-08-29

Lithium ion batteries have shown great potential in applications as power sources for electric vehicles and large-scale energy storage. However, the direct uses of flammable organic liquid electrolyte with commercial separator induce serious safety problems including the risk of fire and explosion. Herein, we report the development of poly(vinylidene difluoride-co-hexafluoropropylene) polymer membranes with multi-sized honeycomb-like porous architectures. The as-prepared polymer electrolyte membranes contain porosity as high as 78%, which leads to the high electrolyte uptake of 86.2 wt%. The PVDF-HFP gel polymer electrolyte membranes exhibited a high ionic conductivity of 1.03 mS cm(-1) at room temperature, which is much higher than that of commercial polymer membranes. Moreover, the as-obtained gel polymer membranes are also thermally stable up to 350 °C and non-combustible in fire (fire-proof). When applied in lithium ion batteries with LiFePO4 as cathode materials, the gel polymer electrolyte demonstrated excellent electrochemical performances. This investigation indicates that PVDF-HFP gel polymer membranes could be potentially applicable for high power lithium ion batteries with the features of high safety, low cost and good performance.

Honeycomb-like porous gel polymer electrolyte membrane for lithium ion batteries with enhanced safety

NASA Astrophysics Data System (ADS)

Zhang, Jinqiang; Sun, Bing; Huang, Xiaodan; Chen, Shuangqiang; Wang, Guoxiu

2014-08-01

Lithium ion batteries have shown great potential in applications as power sources for electric vehicles and large-scale energy storage. However, the direct uses of flammable organic liquid electrolyte with commercial separator induce serious safety problems including the risk of fire and explosion. Herein, we report the development of poly(vinylidene difluoride-co-hexafluoropropylene) polymer membranes with multi-sized honeycomb-like porous architectures. The as-prepared polymer electrolyte membranes contain porosity as high as 78%, which leads to the high electrolyte uptake of 86.2 wt%. The PVDF-HFP gel polymer electrolyte membranes exhibited a high ionic conductivity of 1.03 mS cm-1 at room temperature, which is much higher than that of commercial polymer membranes. Moreover, the as-obtained gel polymer membranes are also thermally stable up to 350°C and non-combustible in fire (fire-proof). When applied in lithium ion batteries with LiFePO4 as cathode materials, the gel polymer electrolyte demonstrated excellent electrochemical performances. This investigation indicates that PVDF-HFP gel polymer membranes could be potentially applicable for high power lithium ion batteries with the features of high safety, low cost and good performance.

Honeycomb-like porous gel polymer electrolyte membrane for lithium ion batteries with enhanced safety

PubMed Central

Zhang, Jinqiang; Sun, Bing; Huang, Xiaodan; Chen, Shuangqiang; Wang, Guoxiu

2014-01-01

Lithium ion batteries have shown great potential in applications as power sources for electric vehicles and large-scale energy storage. However, the direct uses of flammable organic liquid electrolyte with commercial separator induce serious safety problems including the risk of fire and explosion. Herein, we report the development of poly(vinylidene difluoride-co-hexafluoropropylene) polymer membranes with multi-sized honeycomb-like porous architectures. The as-prepared polymer electrolyte membranes contain porosity as high as 78%, which leads to the high electrolyte uptake of 86.2 wt%. The PVDF-HFP gel polymer electrolyte membranes exhibited a high ionic conductivity of 1.03 mS cm−1 at room temperature, which is much higher than that of commercial polymer membranes. Moreover, the as-obtained gel polymer membranes are also thermally stable up to 350°C and non-combustible in fire (fire-proof). When applied in lithium ion batteries with LiFePO4 as cathode materials, the gel polymer electrolyte demonstrated excellent electrochemical performances. This investigation indicates that PVDF-HFP gel polymer membranes could be potentially applicable for high power lithium ion batteries with the features of high safety, low cost and good performance. PMID:25168687

Neutrino Astrophysics in Slowly Rotating Spacetimes Permeated by Nonlinear Electrodynamics Fields

NASA Astrophysics Data System (ADS)

Mosquera Cuesta, Herman J.

2017-02-01

Many theoretical and astrophysical arguments involve consideration of the effects of super strong electromagnetic fields and the rotation during the late stages of core-collapse supernovae. In what follows, we solve Einstein field equations that are minimally coupled to an arbitrary (current-free) Born-Infeld nonlinear Lagrangian L(F,G) of electrodynamics (NLED) in the slow rotation regime a ≪ r+ (outer horizon size), up to first order in a/r. We cross-check the physical properties of such NLED spacetime w.r.t. against the Maxwell one. A study case on both neutrino flavor ({ν }e\\to {ν }μ ,{ν }τ ) oscillations and flavor+helicity (spin) flip ({ν }e\\to {\\overline{ν }}μ ,τ ) gyroscopic precession proves that in the spacetime of a slowly rotating nonlinear charged black hole (RNCBH), the neutrino dynamics translates into a positive enhancement of the r-process (reduction of the electron fraction Ye < 0.5). Consequently, it guarantees successful hyperluminous core-collapse supernova explosions due to the enlargement of the number and amount of decaying nuclide species. This posits that, as far as the whole luminosity is concerned, hypernovae will be a proof of the formation of astrophysical RNCBH.

DESIGNING AN OPPORTUNITY FUEL WITH BIOMASS AND TIRE-DERIVED FUEL FOR COFIRING AT WILLOW ISLAND GENERATING STATION AND COFIRING SAWDUST WITH COAL AT ALBRIGHT GENERATING STATION

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

K. Payette; D. Tillman

During the period October 1, 2001--December 31, 2001, Allegheny Energy Supply Co., LLC (Allegheny) completed construction of the Willow Island cofiring project. This included completion of the explosion proof electrical wiring, the control system, and the control software. Procedures for system checkout, shakedown, and initial operation were initiated during this period. During this time period the 100-hour test of the Albright Generating Station cofiring facility was completed. The testing demonstrated that cofiring at the Albright Generating Station could reliably contribute to a ''4P Strategy''--reduction of SO{sub 2}, NO{sub x}, mercury, and greenhouse gas emissions over a significant load range. Duringmore » this period of time Allegheny Energy conducted facility tours of both Albright and Willow Island for the Biomass Interest Group of the Electric Power Research Institute. This report summarizes the activities associated with the Designer Opportunity Fuel program, and demonstrations at Willow Island and Albright Generating Stations. It details the completion of construction activities at the Willow Island site along with the 100-hr test at the Albright site.« less

Real time in-situ sensing of damage evolution in nanocomposite bonded surrogate energetic materials

NASA Astrophysics Data System (ADS)

Sengezer, Engin C.; Seidel, Gary D.

2016-04-01

The current work aims to explore the potential for in-situ structural health monitoring in polymer bonded energetic materials through the introduction of carbon nanotubes (CNTs) into the binder phase as a means to establish a significant piezoresistive response through the resulting nanocomposite binder. The experimental effort herein is focused towards electro-mechanical characterization of surrogate materials in place of actual energetic (explosive) materials in order to provide proof of concept for the strain and damage sensing. The electrical conductivity and the piezoresistive behavior of samples containing randomly oriented MWCNTs introduced into the epoxy (EPON 862) binder of 70 wt% ammonium perchlorate-epoxy hybrid composites are quantitatively and qualitatively evaluated. Brittle failure going through linear elastic behavior, formation of microcracks leading to reduction in composite load carrying capacity and finally macrocracks resulting in eventual failure are observed in the mechanical response of MWNT-ammonium perchlorateepoxy hybrid composites. Incorporating MWNTs into local polymer binder improves the effective stiffness about 40% compared to neat ammonium perchlorate-polymer samples. The real time in-situ relative change in resistance for MWNT hybrid composites was detected with the applied strains through piezoresistive response.

Can Asteroid Airbursts Cause Dangerous Tsunami?.

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

Boslough, Mark B.

I have performed a series of high-resolution hydrocode simulations to generate “source functions” for tsunami simulations as part of a proof-of-principle effort to determine whether or not the downward momentum from an asteroid airburst can couple energy into a dangerous tsunami in deep water. My new CTH simulations show enhanced momentum multiplication relative to a nuclear explosion of the same yield. Extensive sensitivity and convergence analyses demonstrate that results are robust and repeatable for simulations with sufficiently high resolution using adaptive mesh refinement. I have provided surface overpressure and wind velocity fields to tsunami modelers to use as time-dependent boundarymore » conditions and to test the hypothesis that this mechanism can enhance the strength of the resulting shallow-water wave. The enhanced momentum result suggests that coupling from an over-water plume-forming airburst could be a more efficient tsunami source mechanism than a collapsing impact cavity or direct air blast alone, but not necessarily due to the originally-proposed mechanism. This result has significant implications for asteroid impact risk assessment and airburst-generated tsunami will be the focus of a NASA-sponsored workshop at the Ames Research Center next summer, with follow-on funding expected.« less

27 CFR 555.26 - Prohibited shipment, transportation, receipt, possession, or distribution of explosive materials.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., transportation, receipt, possession, or distribution of explosive materials. 555.26 Section 555.26 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Administrative and Miscellaneous Provisions § 555.26 Prohibited shipment...

27 CFR 555.26 - Prohibited shipment, transportation, receipt, possession, or distribution of explosive materials.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., transportation, receipt, possession, or distribution of explosive materials. 555.26 Section 555.26 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Administrative and Miscellaneous Provisions § 555.26 Prohibited shipment...

27 CFR 555.26 - Prohibited shipment, transportation, receipt, possession, or distribution of explosive materials.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., transportation, receipt, possession, or distribution of explosive materials. 555.26 Section 555.26 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Administrative and Miscellaneous Provisions § 555.26 Prohibited shipment...

27 CFR 555.26 - Prohibited shipment, transportation, receipt, possession, or distribution of explosive materials.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., transportation, receipt, possession, or distribution of explosive materials. 555.26 Section 555.26 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Administrative and Miscellaneous Provisions § 555.26 Prohibited shipment...

27 CFR 555.26 - Prohibited shipment, transportation, receipt, possession, or distribution of explosive materials.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., transportation, receipt, possession, or distribution of explosive materials. 555.26 Section 555.26 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Administrative and Miscellaneous Provisions § 555.26 Prohibited shipment...

40 CFR 265.382 - Open burning; waste explosives.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Open burning; waste explosives. 265... DISPOSAL FACILITIES Thermal Treatment § 265.382 Open burning; waste explosives. Open burning of hazardous waste is prohibited except for the open burning and detonation of waste explosives. Waste explosives...

40 CFR 265.382 - Open burning; waste explosives.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Open burning; waste explosives. 265... DISPOSAL FACILITIES Thermal Treatment § 265.382 Open burning; waste explosives. Open burning of hazardous waste is prohibited except for the open burning and detonation of waste explosives. Waste explosives...

40 CFR 265.382 - Open burning; waste explosives.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Open burning; waste explosives. 265... DISPOSAL FACILITIES Thermal Treatment § 265.382 Open burning; waste explosives. Open burning of hazardous waste is prohibited except for the open burning and detonation of waste explosives. Waste explosives...

40 CFR 265.382 - Open burning; waste explosives.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Open burning; waste explosives. 265... DISPOSAL FACILITIES Thermal Treatment § 265.382 Open burning; waste explosives. Open burning of hazardous waste is prohibited except for the open burning and detonation of waste explosives. Waste explosives...

40 CFR 265.382 - Open burning; waste explosives.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Open burning; waste explosives. 265... DISPOSAL FACILITIES Thermal Treatment § 265.382 Open burning; waste explosives. Open burning of hazardous waste is prohibited except for the open burning and detonation of waste explosives. Waste explosives...

30 CFR 56.6201 - Separation of transported explosive material.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Separation of transported explosive material... Explosives Transportation § 56.6201 Separation of transported explosive material. Detonators shall not be transported on the same vehicle or conveyance with other explosives except as follows: (a) Detonators in...

30 CFR 56.6201 - Separation of transported explosive material.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Separation of transported explosive material... Explosives Transportation § 56.6201 Separation of transported explosive material. Detonators shall not be transported on the same vehicle or conveyance with other explosives except as follows: (a) Detonators in...

The Wording of a Proof: Hardy's Second "Elegant" Proof--The Pythagorean School's Irrationality of Square Root of 2

ERIC Educational Resources Information Center

Padula, Janice

2006-01-01

One of the most interesting and important proofs in the history of mathematics is the Pythagorean school's proof of the "irrationality" of the square root of 2. After a brief look at G. H. Hardy (1941) thoughts regarding it, two versions of the classic Pythagorean proof are examined and discussed in this article, one written by an American…

30 CFR 7.306 - Explosion tests.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Explosion tests. 7.306 Section 7.306 Mineral... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.306 Explosion tests. (a) The following shall be used for conducting an explosion test: (1) An explosion test chamber designed...

30 CFR 7.306 - Explosion tests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Explosion tests. 7.306 Section 7.306 Mineral... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.306 Explosion tests. (a) The following shall be used for conducting an explosion test: (1) An explosion test chamber designed...

30 CFR 7.306 - Explosion tests.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Explosion tests. 7.306 Section 7.306 Mineral... MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.306 Explosion tests. (a) The following shall be used for conducting an explosion test: (1) An explosion test chamber designed...

29 CFR 1926.902 - Surface transportation of explosives.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 8 2014-07-01 2014-07-01 false Surface transportation of explosives. 1926.902 Section 1926... Explosives § 1926.902 Surface transportation of explosives. (a) Transportation of explosives shall meet the provisions of Department of Transportation regulations contained in 46 CFR parts 146-149, Water Carriers; 49...

29 CFR 1926.902 - Surface transportation of explosives.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 8 2012-07-01 2012-07-01 false Surface transportation of explosives. 1926.902 Section 1926... Explosives § 1926.902 Surface transportation of explosives. (a) Transportation of explosives shall meet the provisions of Department of Transportation regulations contained in 46 CFR parts 146-149, Water Carriers; 49...

29 CFR 1926.902 - Surface transportation of explosives.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 8 2011-07-01 2011-07-01 false Surface transportation of explosives. 1926.902 Section 1926... Explosives § 1926.902 Surface transportation of explosives. (a) Transportation of explosives shall meet the provisions of Department of Transportation regulations contained in 46 CFR parts 146-149, Water Carriers; 49...

29 CFR 1926.902 - Surface transportation of explosives.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 8 2013-07-01 2013-07-01 false Surface transportation of explosives. 1926.902 Section 1926... Explosives § 1926.902 Surface transportation of explosives. (a) Transportation of explosives shall meet the provisions of Department of Transportation regulations contained in 46 CFR parts 146-149, Water Carriers; 49...

27 CFR 555.180 - Prohibitions relating to unmarked plastic explosives.

Code of Federal Regulations, 2014 CFR

2014-04-01

... person shall manufacture any plastic explosive that does not contain a detection agent. (b) No person..., receive, or possess any plastic explosive that does not contain a detection agent. This paragraph does not... Plastic Explosives means the Convention on the Marking of Plastic Explosives for the Purposes of Detection...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2011 CFR

2011-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2012 CFR

2012-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...

27 CFR 555.180 - Prohibitions relating to unmarked plastic explosives.

Code of Federal Regulations, 2012 CFR

2012-04-01

... person shall manufacture any plastic explosive that does not contain a detection agent. (b) No person..., receive, or possess any plastic explosive that does not contain a detection agent. This paragraph does not... Plastic Explosives means the Convention on the Marking of Plastic Explosives for the Purposes of Detection...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2013 CFR

2013-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2014 CFR

2014-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...