Minimum compliance topology optimization of shell–infill composites for additive manufacturing

NARCIS (Netherlands)

Wu, J.; Clausen, Anders; Sigmund, Ole

2017-01-01

Additively manufactured parts are often composed of two sub-structures, a solid shell forming their exterior and a porous infill occupying the interior. To account for this feature this paper presents a novel method for generating simultaneously optimized shell and infill in the context of

Infilling Littleton Street Mine, Wallsall, with colliery spoil rock paste

Energy Technology Data Exchange (ETDEWEB)

Jarvis, S.T.; Braithwaite, P.A. [Ove Arup and Partners, Birmingham (United Kingdom)

1993-12-31

Describes the filling of an abandoned underground mine with low strength (12-20 kPa) paste made of coal mining waste. With a volume of 550,000 m{sup 3}, it was the largest mine to be filled with rock paste to date. The abandoned mine, flooded with underground water, consists of room and pillar workings at shallow depth of 35 to 60 m. Height of the underground mine cavity varies between 4 and 8 m. The process of infilling and tests and systems for monitoring infilling completeness and strength are described. Benefits of rock paste over other forms of infilling are discussed. Land reclamation work at the source sites is also described. Mineral waste source sites and specifications of the materials are given. After work completion, about 18 ha of derelict urban land were released for redevelopment. 6 refs.

Experimental investigation of the seismic performance of the R/C frames with reinforced masonry infills

Science.gov (United States)

Tanjung, Jafril; Maidiawati, Nugroho, Fajar

2017-10-01

Intensive studies regarding the investigation of seismic performance of reinforced concrete (R/C) frames which are infilled with brick masonry walls have been carried out by several researchers within the last three-decades. According to authors' field and experimentally experiences conclude that the unreinforced brick masonry infills significantly contributes to increase the seismic performance of the R/C frame structure. Unfortunately, the presence of brick masonry infill walls causes several undesirable effects such as short column, soft-storey, torsion and out of plane collapse. In this study, a strengthening technique for the brick masonry infills were experimentally investigated to improve the seismic performance of the R/C frame structures. For this purpose, four experimental specimens have been prepared, i.e. one of bare R/C frame (BF), one of R/C frame infilled with unreinforced brick-masonry wall (IFUM) and two of R/C frames were infilled with reinforced brick-masonry wall (IFRM-1 and IFRM-2). The bare frame and R/C frame infilled with unreinforced brick-masonry wall represents the typical R/C buildings' construction in Indonesia assuming the brick-masonry wall as the non-structural elements. The brick-masonry wall infills in specimens IFRM-1 and IFRM-2 were strengthened by using embedded ϕ4 plain steel bar on their diagonal and center of brick-masonry wall, respectively. All specimens were laterally pushed-over. The lateral loading and its lateral displacement, failure mechanism and their crack pattern were recorded during experimental works. Comparison of the experimental results of these four specimens conclude that the strengthening of the brick-masonry infills wall gave the significantly increasing of the seismic performance of the R/C frame. The seismic performance was evaluated based on the lateral strength of the R/C specimen. The embedded plain steel bar on brick-masonry also reduces the diagonal crack on the brick-masonry wall. It seems that

Racking shear resistance of steel frames with corner connected precast concrete infill panels

NARCIS (Netherlands)

Hoenderkamp, J.C.D.; Snijder, H.H.; Hofmeyer, H.

2015-01-01

When precast concrete infill panels are connected to steel frames at discrete locations, interaction at the structural interface is neither complete nor absent. The contribution of precast concrete infill panels to the lateral stiffness and strength of steel frames can be significant depending on

121 115 Infilling Direction and Fluid Commu

African Journals Online (AJOL)

2008-12-02

Dec 2, 2008 ... Keywords: Kolo Creek, reservoir geochemistry, reservoir continuity, Niger Delta, petroleum migration ... The infilling of petroleum reservoirs is a ..... Association of Petroleum Geologists Bulletin. 81: 222–248. Hunt, J.M. (1996). Petroleum Geochemistry and. Geology. Freeman and Company, New York.

Serviceability limit state related to excessive lateral deformations to account for infill walls in the structural model

Directory of Open Access Journals (Sweden)

G. M. S. ALVA

Full Text Available Brazilian Codes NBR 6118 and NBR 15575 provide practical values for interstory drift limits applied to conventional modeling in order to prevent negative effects in masonry infill walls caused by excessive lateral deformability, however these codes do not account for infill walls in the structural model. The inclusion of infill walls in the proposed model allows for a quantitative evaluation of structural stresses in these walls and an assessment of cracking in these elements (sliding shear diagonal tension and diagonal compression cracking. This paper presents the results of simulations of single-story one-bay infilled R/C frames. The main objective is to show how to check the serviceability limit states under lateral loads when the infill walls are included in the modeling. The results of numerical simulations allowed for an evaluation of stresses and the probable cracking pattern in infill walls. The results also allowed an identification of some advantages and limitations of the NBR 6118 practical procedure based on interstory drift limits.

Stormwater Infrastructure at Risk: Predicting the Impacts of Increased Imperviousness due to Infill Development in a Semi-arid Urban Neighborhood

Science.gov (United States)

Hogue, T. S.; Panos, C.; McCray, J. E.; Gilliom, R.

2017-12-01

This research investigates the impacts of infill development (or "redevelopment") on urban stormwater runoff and explores avenues for re-inventing stormwater management strategies for the City of Denver, Colorado. As a rapidly developing city, Denver is facing a cycle of increasing population and redevelopment in the form of infill (where under-utilized parcels within the City are redeveloped into high-density residential land uses). Infill development increases stormwater runoff by introducing more impervious surfaces, including roofs and driveways, which produce more runoff (additional stormwater). However, there is debate on the impact of infill patterns on runoff behavior, peak flows, and flood frequency events. We used a calibrated, high-resolution PCSWMM model to simulate three redevelopment scenarios within the 1000-acre Berkeley neighborhood of northwest Denver. The scenarios utilized future predictions of redevelopment to simulate increases in imperviousness by 1.1, 4.5, and 8.7 percent by 2024, 2034, and 2044, respectively, for a range of design storms. Results predict that, on average, for each 1% increase in impervious area due to infill development, surface runoff volume will increase by 1.28% in the Berkeley neighborhood. Results demonstrate the limitations of the existing storm sewer network as pipes throughout the catchment reach capacity for events larger than the 2-yr storm for all three scenarios. Spatial maps of the catchment pinpoint subcatchments and sewer nodes of concern, namely surrounding a rapidly growing business corridor and the local Interstate. Overall, results indicate the infrastructure of the Berkeley neighborhood may be at risk, and that current stormwater capture policies may need to be revisited to accommodate both future infill development and climate change. This research provides a quantitative basis for implementing potential changes as well as examining the possibility of using the additional stormwater from redevelopment

Robust, functional nanocrystal solids by infilling with atomic layer deposition

Energy Technology Data Exchange (ETDEWEB)

Liu, Yao; Gibbs, Markelle; Perkins, Craig L.; Tolentino, Jason; Zarghami, Mohammad H.; Bustamante, Jr., J.; Law, Matt

2011-12-14

Thin films of colloidal semiconductor nanocrystals (NCs) are inherently metatstable materials prone to oxidative and photothermal degradation driven by their large surface-to-volume ratios and high surface energies. The fabrication of practical electronic devices based on NC solids hinges on preventing oxidation, surface diffusion, ripening, sintering, and other unwanted physicochemical changes that can plague these materials. Here we use low-temperature atomic layer deposition (ALD) to infill conductive PbSe NC solids with metal oxides to produce inorganic nanocomposites in which the NCs are locked in place and protected against oxidative and photothermal damage. Infilling NC field-effect transistors and solar cells with amorphous alumina yields devices that operate with enhanced and stable performance for at least months in air. Furthermore, ALD infilling with ZnO lowers the height of the inter-NC tunnel barrier for electron transport, yielding PbSe NC films with electron mobilities of 1 cm² V^-1 s^-1. Our ALD technique is a versatile means to fabricate robust NC solids for optoelectronic devices.

Infill architecture: Design approaches for in-between buildings and 'bond' as integrative element

Directory of Open Access Journals (Sweden)

Alfirević Đorđe

2015-01-01

Full Text Available The aim of the paper is to draw attention to the view that the two key elements in achieving good quality of architecture infill in immediate, current surroundings, are the selection of optimal creative method of infill architecture and adequate application of 'the bond' as integrative element, The success of achievement and the quality of architectural infill mainly depend on the assessment of various circumstances, but also on the professionalism, creativity, sensibility, and finally innovativeness of the architect, In order for the infill procedure to be carried out adequately, it is necessary to carry out the assessment of quality of the current surroundings that the object will be integrated into, and then to choose the creative approach that will allow the object to establish an optimal dialogue with its surroundings, On a wider scale, both theory and the practice differentiate thee main creative approaches to infill objects: amimetic approach (mimesis, bassociative approach and ccontrasting approach, Which of the stated approaches will be chosen depends primarily on the fact whether the existing physical structure into which the object is being infilled is 'distinct', 'specific' or 'indistinct', but it also depends on the inclination of the designer, 'The bond' is a term which in architecture denotes an element or zone of one object, but in some instances it can refer to the whole object which has been articulated in a specific way, with an aim of reaching the solution for the visual conflict as is often the case in situations when there is a clash between the existing objects and the newly designed or reconstructed object, This paper provides in-depth analysis of different types of bonds, such as 'direction as bond', 'cornice as bond', 'structure as bond', 'texture as bond' and 'material as bond', which indicate complexity and multiple layers of the designing process of object interpolation.

Numerical Study on the In-Plane and Out-of-Plane Resistance of Brick Masonry Infill Panels in Steel Frames

Directory of Open Access Journals (Sweden)

Vahid Bahreini

2017-01-01

Full Text Available Masonry infill walls are one of the main forms of interior partitions and exterior walls in many parts of the world. Nevertheless, serious damage and loss of stability of many masonry infill walls had been reported during recent earthquakes. To improve their performance, the interaction between these infill walls and the bounding frames needs to be properly investigated. Such interaction can dramatically increase the stiffness of the frame in the in-plane direction. To avoid the negative aspects of inappropriate interactions between the frame and infill wall, some kind of isolation needs to be introduced. In this paper, three different configurations have been evaluated by using the general finite element software, ABAQUS. Nonlinear pushover and time history analyses have been conducted for each of the three configurations. Results showed that isolation of the infill from the frame has a significant effect on the in-plane response of infilled frames. Furthermore, adequate out-of-plane stability of the infill wall has been achieved. The results show that masonry infill walls that have full contact at the top of the wall but isolated from columns have shown acceptable performance.

Prediction of the Fundamental Period of Infilled RC Frame Structures Using Artificial Neural Networks

Directory of Open Access Journals (Sweden)

Panagiotis G. Asteris

2016-01-01

Full Text Available The fundamental period is one of the most critical parameters for the seismic design of structures. There are several literature approaches for its estimation which often conflict with each other, making their use questionable. Furthermore, the majority of these approaches do not take into account the presence of infill walls into the structure despite the fact that infill walls increase the stiffness and mass of structure leading to significant changes in the fundamental period. In the present paper, artificial neural networks (ANNs are used to predict the fundamental period of infilled reinforced concrete (RC structures. For the training and the validation of the ANN, a large data set is used based on a detailed investigation of the parameters that affect the fundamental period of RC structures. The comparison of the predicted values with analytical ones indicates the potential of using ANNs for the prediction of the fundamental period of infilled RC frame structures taking into account the crucial parameters that influence its value.

Exploiting Additive Manufacturing Infill in Topology Optimization for Improved Buckling Load

DEFF Research Database (Denmark)

Clausen, Anders; Aage, Niels; Sigmund, Ole

2016-01-01

Additive manufacturing (AM) permits the fabrication of functionally optimized components with high geometrical complexity. The opportunity of using porous infill as an integrated part of the manufacturing process is an example of a unique AM feature. Automated design methods are still incapable...... the standard and coating approaches to topology optimization for the MBB beam benchmark case. The optimized structures are additively manufactured using a filamentary technique. This experimental study validates the numerical model used in the coating approach. Depending on the properties of the infill...

Mechanical model for steel frames with discretely connected precast concrete infill panels with window openings

NARCIS (Netherlands)

Teeuwen, P.A.; Kleinman, C.S.; Snijder, H.H.

2012-01-01

This paper presents a mechanical model for a structure comprising of steel frames with discretely connected precast concrete infill panels having window openings, termed semi-integral infilled frames. The discrete panel-to-frame connections are realized by structural bolts acting under compression.

Spatial and temporal variability in sedimentation rates associated with cutoff channel infill deposits: Ain River, France

Science.gov (United States)

Piégay, H.; Hupp, C.R.; Citterio, A.; Dufour, S.; Moulin, B.; Walling, D.E.

2008-01-01

Floodplain development is associated with lateral accretion along stable channel geometry. Along shifting rivers, the floodplain sedimentation is more complex because of changes in channel position but also cutoff channel presence, which exhibit specific overflow patterns. In this contribution, the spatial and temporal variability of sedimentation rates in cutoff channel infill deposits is related to channel changes of a shifting gravel bed river (Ain River, France). The sedimentation rates estimated from dendrogeomorphic analysis are compared between and within 14 cutoff channel infills. Detailed analyses along a single channel infill are performed to assess changes in the sedimentation rates through time by analyzing activity profiles of the fallout radionuclides 137Cs and unsupported 210Pb. Sedimentation rates are also compared within the channel infills with rates in other plots located in the adjacent floodplain. Sedimentation rates range between 0.65 and 2.4 cm a−1 over a period of 10 to 40 years. The data provide additional information on the role of distance from the bank, overbank flow frequency, and channel geometry in controlling the sedimentation rate. Channel infills, lower than adjacent floodplains, exhibit higher sedimentation rates and convey overbank sediment farther away within the floodplain. Additionally, channel degradation, aggradation, and bank erosion, which reduce or increase the distance between the main channel and the cutoff channel aquatic zone, affect local overbank flow magnitude and frequency and therefore sedimentation rates, thereby creating a complex mosaic of sedimentation zones within the floodplain and along the cutoff channel infills. Last, the dendrogeomorphic and 137Cs approaches are cross validated for estimating the sedimentation rate within a channel infill.

Buckling Resistance of Basalt Fiber Reinforced Polymer Infill Panel Subjected to Elevated Temperatures

OpenAIRE

Viriyavudh Sim; Woo Young Jung

2017-01-01

Performance of Basalt Fiber Reinforced Polymer (BFRP) sandwich infill panel system under diagonal compression was studied by means of numerical analysis. Furthermore, the variation of temperature was considered to affect the mechanical properties of BFRP, since their composition was based on polymeric material. Moreover, commercial finite element analysis platform ABAQUS was used to model and analyze this infill panel system. Consequently, results of the analyses show that the overall perform...

Self-supporting rhombic infill structures for additive manufacturing

DEFF Research Database (Denmark)

Wu, Jun; Wang, Charlie C.L.; Zhang, Xiaoting

2016-01-01

Recent work has demonstrated that the interior material layout of a 3D model can be designed to make a fabricated replica satisfy application-specific demands on its physical properties, such as resistance to external loads. A widely used practice to fabricate such models is by layer-based additive...... manufacturing (AM), which however suffers from the problem of adding and removing interior supporting structures. In this paper, we present a novel method for generating application-specific infill structures on rhombic cells so that the resultant structures can automatically satisfy manufacturing requirements...... on overhang-angle and wall-thickness. Additional supporting structures can be avoided entirely in our framework. To achieve this, we introduce the usage of an adaptive rhombic grid, which is built from an input surface model. Starting from the initial sparse set of rhombic cells, via numerical optimization...

Experimental Tests on Bending Behavior of Profiled Steel Sheeting Dry Board Composite Floor with Geopolymer Concrete Infill

Directory of Open Access Journals (Sweden)

Mohd Isa Jaffar

Full Text Available Abstract Profiled Steel Sheet Dry Board (PSSDB system is a lightweight composite structure comprises Profiled Steel Sheeting and Dry Board connected by self-drilling and self-tapping screws. This study introduced geopolymer concrete, an eco-friendly material without cement content as an infill material in the PSSDB floor system to highlight its effect onto the PSSDB (with full and half-size dry boards floor system's stiffness and strength. Experimental tests on various full scale PSSDB floor specimens were conducted under uniformly distributed transverse loads. Results illustrate that the rigidity of the panel with geopolymer concrete infill with half-size dry board (HBGPC increases by 43% relative to that of the panel with normal concrete infill with full-size dry board (FBNC. The developed finite-element modeling (FEM successfully predicts the behavior of FBGPC model with 94.8% accuracy. Geopolymer concrete infill and dry board size influence the strength panel, infill contact stiffness, and mid-span deflection of the profiled steel sheeting/dry board (PSSDB flooring system.

Masonry Infilling Effect On Seismic Vulnerability and Performance Level of High Ductility RC Frames

International Nuclear Information System (INIS)

Ghalehnovi, M.; Shahraki, H.

2008-01-01

In last years researchers preferred behavior-based design of structure to force-based one for designing and construction of the earthquake-resistance structures, this method is named performance based designing. The main goal of this method is designing of structure members for a certain performance or behavior. On the other hand in most of buildings, load bearing frames are infilled with masonry materials which leads to considerable changes in mechanical properties of frames. But usually infilling wall's effect has been ignored in nonlinear analysis of structures because of complication of the problem and lack of simple logical solution. As a result lateral stiffness, strength, ductility and performance of the structure will be computed with less accuracy. In this paper by use of Smooth hysteretic model for masonry infillings, some high ductile RC frames (4, 8 stories including 1, 2 and 3 spans) designed according to Iranian code are considered. They have been analyzed by nonlinear dynamic method in two states, with and without infilling. Then their performance has been determined with criteria of ATC 40 and compared with recommended performance in Iranian seismic code (standard No. 2800)

Experimental investigations into in-plane stiffness and strength of steel frames with precast concrete infill panels

NARCIS (Netherlands)

Hoenderkamp, J.C.D.; Hofmeyer, H.; Snijder, H.H.; Richard Liew, J.; Choo, Y.S.

2007-01-01

At Eindhoven University of Technology a research program on composite construction is underway aiming at the development of design rules for steel frames with precast concrete infill panels subject to horizontal loading. In two projects, 3 by 3 m steel frames are infilled with concrete: solid

Infill Walls Contribution on the Progressive Collapse Resistance of a Typical Mid-rise RC Framed Building

Science.gov (United States)

Besoiu, Teodora; Popa, Anca

2017-10-01

This study investigates the effect of the autoclaved aerated concrete infill walls on the progressive collapse resistance of a typical RC framed structure. The 13-storey building located in Brăila (a zone with high seismic risk in Romania) was designed according to the former Romanian seismic code P13-70 (1970). Two models of the structure are generated in the Extreme Loading® for Structures computer software: a model with infill walls and a model without infill walls. Following GSA (2003) Guidelines, a nonlinear dynamic procedure is used to determine the progressive collapse risk of the building when a first-storey corner column is suddenly removed. It was found that, the structure is not expected to fail under the standard GSA loading: DL+0.25LL. Moreover, if the infill walls are introduced in the model, the maximum vertical displacement of the node above the removed column is reduced by about 48%.

Modelling of masonry infill walls participation in the seismic behaviour of RC buildings using OpenSees

Science.gov (United States)

Furtado, André; Rodrigues, Hugo; Arêde, António

2015-06-01

Recent earthquakes show that masonry infill walls should be taken into account during the design and assessment process of structures, since this type of non-structural elements increase the in-plane stiffness of the structure and consequently the natural period. An overview of the past researches conducted on the modelling of masonry infilled frame issues has been done, with discussion of past analytical investigations and different modelling approaches that many authors have proposed, including micro- and macro-modelling strategies. After this, the present work presents an improved numerical model, based on the Rodrigues et al. (J Earthq Eng 14:390-416, 2010) approach, for simulating the masonry infill walls behaviour in the computer program OpenSees. The main results of the in-plane calibration analyses obtained with one experimental test are presented and discussed. For last, two reinforced concrete regular buildings were studied and subjected to several ground motions, with and without infills' walls.

Measuring the Air Quality and Transportation Impacts of Infill Development

Science.gov (United States)

This report summarizes three case studies. The analysis shows how standard forecasting tools can be modified to capture at least some of the transportation and air quality benefits of brownfield and infill development.

Investigating the influence of infill percentage on the mechanical properties of fused deposition modelled ABS parts

Directory of Open Access Journals (Sweden)

Kenny Álvarez

2016-09-01

Full Text Available 3D printing is a manufacturing process that is usually used for modeling and prototyping. One of the most popular printing techniques is fused deposition modeling (FDM, which is based on adding melted material layer by layer. Although FDM has several advantages with respect to other manufacturing materials, there are several problems that have to be faced. When setting the printing options, several parameters have to be taken into account, such as temperature, speed, infill percentage, etc. Selecting these parameters is often a great challenge for the user, and is generally solved by experience without considering the influence of variations in the parameters on the mechanical properties of the printed parts.This article analyzes the influence of the infill percentage on the mechanical properties of ABS (Acrylonitrile Butadiene Styrene printed parts. In order to characterize this influence, test specimens for tensile strength and Charpy tests were printed with a Makerbot Replicator 2X printer, in which the infill percentage was varied but the rest of the printing parameters were kept constant. Three different results were analyzed for these tests: tensile strength, impact resistance, and effective printing time. Results showed that the maximum tensile force (1438N and tensile stress (34,57MPa were obtained by using 100% infill. The maximum impact resistance, 1,55J, was also obtained with 100% infill. In terms of effective printing time, results showed that printing with an infill range between 50% and 98% is not recommended, since the effective printing time is higher than with a 100% infill and the tensile strength and impact resistance are smaller. In addition, in comparing the results of our analysis with results from other authors, it can be concluded that the printer type and plastic roll significantly influence the mechanical properties of ABS parts.

Infill Panels and the tube connection in timber frames

NARCIS (Netherlands)

Leijten, A.J.M.; Jorissen, A.J.M.; Hoenderkamp, J.C.D.

2012-01-01

In recent years timber infill panels have been proposed for multi-story column-beam frame structures with the aim to substitute the stabilizing function of column-beam moment connections. The preliminary study reported in this paper considers a column-beam timber frame where stability is assured by

Lateral Stiffness of Timber Frames with CLT Infill Panels

NARCIS (Netherlands)

Leijten, A.J.M.; Jorissen, A.J.M.; Hoenderkamp, J.C.D.; Haddad, Y.M.

2011-01-01

In recent years timber infill panels have been proposed for multi-story column-beam frame structures with the aim to substitute the stabilizing function of column-beam moment connections. The preliminary study reported in this paper considers a column-beam timber frame where stability is assured by

Analysis of steel frames with precast concrete infill panels

NARCIS (Netherlands)

Teeuwen, P.A; Kleinman, C.S.; Snijder, H.H.; Hofmeyer, H.; IABSE-AIPPC-IVBH, xx

2008-01-01

This paper presents experimental and numerical analyses of a new type of hybrid lateral load resisting structure. This structure consists of a steel frame with a discretely connected precast concrete infill panel with a window opening. The discrete connections are formed by structural bolts on the

Composite action of steel frames and precast concrete infill panels with corner connections – Part 1 : experiments

NARCIS (Netherlands)

Hoenderkamp, J.C.D.; Snijder, H.H.; Hofmeyer, H.; Liew, J.Y.R.; Lee, S.C.

2012-01-01

When precast concrete infill panels are connected to steel frames at discrete locations, interaction at the structural interface is neither complete nor absent. The contribution of precast concrete infill panels to the lateral stiffness and strength of steel frames can be significant depending on

Sedimentary infilling of bedrock-controlled palaeo-embayments off Cape Trafalgar, Strait of Gibraltar (Gulf of Cadiz)

Science.gov (United States)

de Castro, Sandra; Lobo, Francisco J.

2018-02-01

This study investigates two bedrock-controlled palaeo-coastal embayments on the Barbate Platform off Cape Trafalgar near the Strait of Gibraltar (Gulf of Cadiz shelf, SW Iberian Peninsula), aiming to reveal their infilling dynamics and the influence of rocky outcrops on shallow-water hydrodynamics and sediment transport. The approach relies on detailed multibeam bathymetric data, high-resolution seismic profiles and tidal current simulations. Elongated rocky outcrops formed a palaeo-coast when sea level was approximately 35 to 20 m below that of the present day, and bound a relatively flat area. However, the seismic profiles enabled to distinguish two main troughs (A and B) that were infilled following a distinctive evolution during the last transgression. Five seismic units were identified (I to V, from base to top). Deposit A is composed of seismic units II to V and is interpreted as a marine embayment infill, here termed the Barbate palaeo-embayment (BPE). Deposit B is composed of seismic units I to IV and is interpreted as a palaeo-valley infill, here termed the Barbate palaeo-valley (BPV). The complex internal stratigraphic architecture depicts an overall evolution from tidal/fluvial deposits to shallow-water marine deposits. Most significant is the occurrence of coupled tidal flats/estuarine sand bars constituting the infilling of the BPE; this suggests the persistence of a high-energy current in a shallow, confined embayment, which was amplified by the rocky outcrop constrictions and possibly facilitated by the episodic movement of a normal fault. In contrast to this active setting, the nearby straight and narrow BPV was subjected to lower-energy infilling dynamics during its initial flooding phases. There, tidal activity was possibly reduced by the straight morphology of the valley and the occurrence of a topographic constriction (i.e. the Barbate Passage) at the mouth of the valley.

Crater relaxation on Titan aided by low thermal conductivity sand infill

Science.gov (United States)

Schurmeier, Lauren R.; Dombard, Andrew J.

2018-05-01

Titan's few impact craters are currently many hundreds of meters shallower than the depths expected. Assuming these craters initially had depths equal to that of similar-size fresh craters on Ganymede and Callisto (moons of similar size, composition, and target lithology), then some process has shallowed them over time. Since nearly all of Titan's recognized craters are located within the arid equatorial sand seas of organic-rich dunes, where rain is infrequent, and atmospheric sedimentation is expected to be low, it has been suggested that aeolian infill plays a major role in shallowing the craters. Topographic relaxation at Titan's current heat flow was previously assumed to be an unimportant process on Titan due to its low surface temperature (94 K). However, our estimate of the thermal conductivity of Titan's organic-rich sand is remarkably low (0.025 W m-1 K-1), and when in thick deposits, will result in a thermal blanketing effect that can aid relaxation. Here, we simulate the relaxation of Titan's craters Afekan, Soi, and Sinlap including thermal effects of various amounts of sand inside and around Titan's craters. We find that the combination of aeolian infill and subsequent relaxation can produce the current crater depths in a geologically reasonable period of time using Titan's current heat flow. Instead of needing to fill completely the missing volume with 100% sand, only ∼62%, ∼71%, and ∼97%, of the volume need be sand at the current basal heat flux for Afekan, Soi, and Sinlap, respectively. We conclude that both processes are likely at work shallowing these craters, and this finding contributes to why Titan overall lacks impact craters in the arid equatorial regions.

Time-transgressive tunnel valley formation indicated by infill sediment structure, North Sea - the role of glaciohydraulic supercooling

DEFF Research Database (Denmark)

Kristensen, Thomas Bojer; Piotrowski, Jan; Huuse, Mads

2008-01-01

Structure and lithology of the infill sediments from 16 subglacial buried tunnel valleys of Pleistocene age in the North Sea were analyzed using 3D seismic data and geophysical log data from five hydrocarbon exploration wells. The infill sediments are characterized by three seismic facies: Facies...

Engineered cementitious composites for strengthening masonry infilled reinforced concrete frames

DEFF Research Database (Denmark)

Dehghani, Ayoub; Nateghi-Alahi, Fariborz; Fischer, Gregor

2015-01-01

The results of the second part of a comprehensive experimental program, aimed at investigating the behavior of masonry infilled reinforced concrete (RC) frames strengthened with fiber reinforced engineered cementitious composites (ECC) used as an overlay on the masonry wall, are presented...

Infill Optimization for Additive Manufacturing - Approaching Bone-like Porous Structures

DEFF Research Database (Denmark)

Wu, Jun; Aage, Niels; Westermann, Ruediger

2018-01-01

Porous structures such as trabecular bone are widely seen in nature. These structures exhibit superior mechanical properties whilst being lightweight. In this paper, we present a method to generate bone-like porous structures asl ightweight infill for additive manufacturing. Our method builds upon...

An effective simplified model of composite compression struts for partially-restrained steel frame with reinforced concrete infill walls

Science.gov (United States)

Sun, Guohua; Chuang-Sheng, Walter Yang; Gu, Qiang; DesRoches, Reginald

2018-04-01

To resolve the issue regarding inaccurate prediction of the hysteretic behavior by micro-based numerical analysis for partially-restrained (PR) steel frames with solid reinforced concrete (RC) infill walls, an innovative simplified model of composite compression struts is proposed on the basis of experimental observation on the cracking distribution, load transferring mechanism, and failure modes of RC infill walls filled in PR steel frame. The proposed composite compression struts model for the solid RC infill walls is composed of α inclined struts and main diagonal struts. The α inclined struts are used to reflect the part of the lateral force resisted by shear connectors along the frame-wall interface, while the main diagonal struts are introduced to take into account the rest of the lateral force transferred along the diagonal direction due to the complicated interaction between the steel frame and RC infill walls. This study derives appropriate formulas for the effective widths of the α inclined strut and main diagonal strut, respectively. An example of PR steel frame with RC infill walls simulating simulated by the composite inclined compression struts model is illustrated. The maximum lateral strength and the hysteresis curve shape obtained from the proposed composite strut model are in good agreement with those from the test results, and the backbone curve of a PR steel frame with RC infill walls can be predicted precisely when the inter-story drift is within 1%. This simplified model can also predict the structural stiffness and the equivalent viscous damping ratio well when the inter-story drift ratio exceeds 0.5%.

Composite Behaviour of Steel Frames with Precast Concrete Infill Panels

NARCIS (Netherlands)

Hoenderkamp, J.C.D.; Hofmeyer, H.; Snijder, H.H.; B. Hoffmeister, xx; O. Hechler, xx

2005-01-01

This paper presents preliminary experimental and numerical results of an investigation into the composite behaviour of a steel frame with a precast concrete infill panel (S-PCP) subject to a lateral load. The steel-concrete connections consist of two plates connected with two bolts which are loaded

Behavior of masonry strengthened infilled reinforced concrete frames under in-plane load

Directory of Open Access Journals (Sweden)

Lila M. Abdel-Hafez

2015-08-01

The ductility of infilled frame strengthened with ferrocement was the best of all strengthened frames, while strengthening with GFRP increases its ultimate load carrying capacity but reduces its ductility.

Analytical modeling of masonry infilled steel frames

International Nuclear Information System (INIS)

Flanagan, R.D.; Jones, W.D.; Bennett, R.M.

1991-01-01

A comprehensive program is underway at the Oak Ridge Y-12 Plant to evaluate the seismic capacity of unreinforced hollow clay tile infilled steel frames. This program has three major parts. First, preliminary numerical analyses are conducted to predict behavior, initial cracking loads, ultimate capacity loads, and to identify important parameters. Second, in-situ and laboratory tests are performed to obtain constitutive parameters and confirm predicted behavior. Finally, the analytical techniques are refined based on experimental results. This paper summarizes the findings of the preliminary numerical analyses. A review of current analytical methods was conducted and a subset of these methods was applied to known experimental results. Parametric studies were used to find the sensitivity of the behavior to various parameters. Both in-plane and out-of-plane loads were examined. Two types of out-of-plane behavior were examined, the inertial forces resulting from the mass of the infill panel and the out-of-plane forces resulting from interstory drift. Cracking loads were estimated using linear elastic analysis and an elliptical failure criterion. Calculated natural frequencies were correlated with low amplitude vibration testing. Ultimate behavior under inertial loads was estimated using a modified yield line procedure accounting for membrane stresses. The initial stiffness and ultimate capacity under in-plane loadings were predicted using finite element analyses. Results were compared to experimental data and to failure loads obtained using plastic collapse theory

The flow properties of colliery spoil rockpaste as used in the infilling of abandoned mine workings

Energy Technology Data Exchange (ETDEWEB)

Ghataora, G.S.; Jarvis, S.T. [University of Birmingham, Birmingham (United Kingdom)

1998-07-01

Colliery spoil is the major constituent of colliery spoil 'rockpaste' which has been used to infill abandoned limestone mines in the West Midlands of England since the early 1980s. The other constituents of rockpaste are pulverised fuel ash, lime and water. A key property of the rockpaste is its ability to flow within the mine workings over considerable distances before setting. This paper describes the work carried out to identify suitable sites as sources of colliery spoil for making rockpaste and goes on to consider the flow properties of the material and the monitoring methods used on-site. A full-scale trial comprising infilling a 6600 m{sup 3} section of an abandoned mine was conducted prior to the infilling of the Littleton Street Mine which had a volume of about 500 000 m{sup 3}. As well as describing the methods used for monitoring the movement of rockpaste material, a description is also given of a dip-meter developed specifically for the purpose of measuring the level of paste in the mine. The monitoring systems developed for use in the two case studies presented in this paper are now being used extensively for infilling other abandoned mine workings. 5 refs., 16 figs., 1 tab., 1 plate.

Mechanical characterization and force-displacement hysteretic curves from in-plane cyclic tests on strong masonry infills.

Science.gov (United States)

Morandi, Paolo; Hak, Sanja; Magenes, Guido

2018-02-01

This article contains information related to a recent study "Performance-based interpretation of in-plane cyclic tests on RC frames with strong masonry infills" (Morandi et al., 2017 [1]). Motivated by the necessity to improve the knowledge of the in-plane seismic response of rigid strong masonry infills, a wide experimental campaign based on in-plane cyclic tests on full-scale RC infilled frame specimens, supplemented with a complete characterization of the materials, has been conducted at the laboratory of the Department of Civil Engineering and Architecture of the University of Pavia. The masonry is constituted by vertically perforated 35 cm thick clay units with tongue and groove and dry head-joints and general-purpose mortar bed-joints. The paper reports the results of the mechanical characterization and of the force-displacement hysteretic curves from the in-plane cyclic tests.

Composite action of steel frames and precast concrete infill panels with corner connections – Part 2 : finite element analysis

NARCIS (Netherlands)

Hoenderkamp, J.C.D.; Hofmeyer, H.; Snijder, H.H.; Liew, J.Y.R.; Lee, S.C.

2012-01-01

When precast concrete infill panels are connected to steel frames at discrete locations, interaction at the structural interface is neither complete nor absent. The contribution of precast concrete infill panels to the lateral stiffness and strength of steel frames can be significant depending on

The shear resistance of steel frames infilled with CASIEL wall panels

NARCIS (Netherlands)

Ng'Andu, B.M.; Vermeltfoort, A.T.

2007-01-01

In Europe, calcium silicate element (CASIEL) walls are increasingly employed as partitions and intemal claddings in buildings. When surrounded by frames, the interaction between the CASIEL infills and the frames has a significant influence on the load transmission paths of building structures. In

Leaching of zinc from rubber infill on artificial turf (football pitches)

NARCIS (Netherlands)

Verschoor AJ; LER

2007-01-01

Many artificial football pitches are treated with a rubber infill made of recycled tyres. From this material zinc leaches to the soil, groundwater and surface water. [This can present significant environmental risks, particularly for aquatic life.] Human health risks posed by leaching of zinc are

Experimental evaluation of the prevention methods for the interface between masonry infill walls and concrete columns

Directory of Open Access Journals (Sweden)

A. P. Tramontin

Full Text Available Cracks that form at the interfaces between masonry structures are common uncontrolled occurrences in buildings. Numerous methods have been proposed by the construction industry to address this problem. Cracks continuously form in the joints between concrete columns and masonry infill walls. In this study, the most common methods for preventing these types of cracks were evaluated in laboratory experiments. Column masonry models were constructed using different types of joints between concrete columns and masonry infill walls, such as steel bars and steel mesh. The efficiency of each type of joint method was evaluated by performing direct tensile tests (pullout tests on the models and monitoring the evolution of the crack opening in the joint between the column and wall, as a function of load applied to the model. The results from this study indicate that the model composed of "electrowelded wire mesh without steel angles" is the best model for controlling cracking in the joints between concrete columns and masonry infill walls.

Infill Optimization for Additive Manufacturing-Approaching Bone-Like Porous Structures.

Science.gov (United States)

Wu, Jun; Aage, Niels; Westermann, Rudiger; Sigmund, Ole

2018-02-01

Porous structures such as trabecular bone are widely seen in nature. These structures are lightweight and exhibit strong mechanical properties. In this paper, we present a method to generate bone-like porous structures as lightweight infill for additive manufacturing. Our method builds upon and extends voxel-wise topology optimization. In particular, for the purpose of generating sparse yet stable structures distributed in the interior of a given shape, we propose upper bounds on the localized material volume in the proximity of each voxel in the design domain. We then aggregate the local per-voxel constraints by their p-norm into an equivalent global constraint, in order to facilitate an efficient optimization process. Implemented on a high-resolution topology optimization framework, our results demonstrate mechanically optimized, detailed porous structures which mimic those found in nature. We further show variants of the optimized structures subject to different design specifications, and we analyze the optimality and robustness of the obtained structures.

Push-Pull interface connections in steel frames with precast concrete infill panels

NARCIS (Netherlands)

Hoenderkamp, J.C.D.; Snijder, H.H.; Hofmeyer, H.

2012-01-01

This paper presents experimental and finite element results of investigations into the stiffness and strength of three discrete interface connections between simple steel frames and precast concrete infill panels serving as lateral bracing. The ability of the connections to resist compression and

Performance of Reinforced Concrete Beam with Differently Positioned Replacement Zones of Block Infill under Low Impact Loads

Directory of Open Access Journals (Sweden)

Mokhatar Shahrul Niza

2017-01-01

Full Text Available This paper reveals a study performed on reinforced concrete with artificial aggregate concrete block infill composite beams to innovate a lightweight reinforced concrete utilizing polyethylene (PE waste materials, such as waste plastic bags. Six beam specimens of normal reinforced concrete (NRC and different block infill replacement zone positions RCAI (RZ1 beams containing 100% MAPEA with 50, 95, and 1,000 mm width, height, and length, respectively, were provided for the block infill, whereas RCAI (RZ2 with different block infill positions containing a 100% MAPEA with 50, 115, and 1000 mm width, height, and length were provided and tested under low impact load. The steel impactor with blunt nose dropped at 0.6 m height which equivalent to 3.5 m/s. The behaviors of the beams were studied relative to the impact force-time and displacement-time histories, the flexural/ bending cracks, and the impact failure. Results show that the overall failure modes of all the beam specimens were successfully recorded. In addition, the residual displacements of the RZ2 was almost same than those of the RZ1 and the significantly lower than those of the NRC. In the reinforced concrete beams, less stressed concrete near the neutral axis can be replaced by certain light weight material like waste plastic bags as modified artificial polyethylene aggregates to serve as an artificial aggregate.

Sustainable Construction for Urban Infill Development Using Engineered Massive Wood Panel Systems

Directory of Open Access Journals (Sweden)

Steffen Lehmann

2012-10-01

Full Text Available Prefabricated engineered solid wood panel construction systems can sequester and store CO2. Modular cross-laminated timber (CLT, also called cross-lam panels form the basis of low-carbon, engineered construction systems using solid wood panels that can be used to build residential infill developments of 10 storeys or higher. Multi-apartment buildings of 4 to 10 storeys constructed entirely in timber, such as recently in Europe, are innovative, but their social and cultural acceptance in Australia and North America is at this stage still uncertain. Future commercial utilisation is only possible if there is a user acceptance. The author is part of a research team that aims to study two problems: first models of urban infill; then focus on how the use of the CLT systems can play an important role in facilitating a more livable city with better models of infill housing. Wood is an important contemporary building resource due to its low embodied energy and unique attributes. The potential of prefabricated engineered solid wood panel systems, such as CLT, as a sustainable building material and system is only just being realised around the globe. Since timber is one of the few materials that has the capacity to store carbon in large quantities over a long period of time, solid wood panel construction offers the opportunity of carbon engineering, to turn buildings into ‘carbon sinks’. Thus some of the historically negative environmental impact of urban development and construction can be turned around with CLT construction on brownfield sites.

Thermal tuning of a silicon photonic crystal cavity infilled with an elastomer

NARCIS (Netherlands)

Erdamar, A.K.; Van Leest, M.M.; Picken, S.J.; Caro, J.

2011-01-01

Thermal tuning of the transmission of an elastomer infilled photonic crystal cavity is studied. An elastomer has a thermal expansion-induced negative thermo-optic coefficient that leads to a strong decrease of the refractive index upon heating. This property makes elastomer highly suitable for

Influence of masonry infill walls on longitudinal forces in columns of ...

African Journals Online (AJOL)

In this paper the result of conducted numerical studies based on space calculation models are presented. It presents the results of a conducted numerical assessment of the influence of masonry infill walls on variation and redistribution of efforts arising in columns of a cast-in-situ framed building. The quantitative data of the ...

The FP4026 Research Database on the fundamental period of RC infilled frame structures.

Science.gov (United States)

Asteris, Panagiotis G

2016-12-01

The fundamental period of vibration appears to be one of the most critical parameters for the seismic design of buildings because it strongly affects the destructive impact of the seismic forces. In this article, important research data (entitled FP4026 Research Database (Fundamental Period-4026 cases of infilled frames) based on a detailed and in-depth analytical research on the fundamental period of reinforced concrete structures is presented. In particular, the values of the fundamental period which have been analytically determined are presented, taking into account the majority of the involved parameters. This database can be extremely valuable for the development of new code proposals for the estimation of the fundamental period of reinforced concrete structures fully or partially infilled with masonry walls.

The FP4026 Research Database on the fundamental period of RC infilled frame structures

Directory of Open Access Journals (Sweden)

Panagiotis G. Asteris

2016-12-01

Full Text Available The fundamental period of vibration appears to be one of the most critical parameters for the seismic design of buildings because it strongly affects the destructive impact of the seismic forces. In this article, important research data (entitled FP4026 Research Database (Fundamental Period-4026 cases of infilled frames based on a detailed and in-depth analytical research on the fundamental period of reinforced concrete structures is presented. In particular, the values of the fundamental period which have been analytically determined are presented, taking into account the majority of the involved parameters. This database can be extremely valuable for the development of new code proposals for the estimation of the fundamental period of reinforced concrete structures fully or partially infilled with masonry walls.

Cooling joint width and secondary mineral infilling characteristics in four Grande Ronde Basalt flows at the Hanford Site, Washington

International Nuclear Information System (INIS)

Lindberg, J.W.

1988-09-01

Widths were measured and percentages of secondary mineral infilling types were estimated 3194 cooling joints in basalt core of the Rocky Coulee, Cohassett, McCoy Canyon, and Umtanum basalt flows. The core was from core holes RRL-2, RRL-6, RRL-14, and DC-16 on the Hanford Site in Washington State. Joint width was characterized by determining the frequency distribution in each of 16 flow/core hole combination samples (4 flows by 4 core holes = 16 samples) and comparing the distributions between intraflow structures, between basalt flows, and between core holes. Joint infilling was characterized by determining the percentage of joints with each secondary mineral type present and then comparing flows and comparing intraflow instructures. Basalt flows, intraflow structures, and core holes cannot be differentiated consistently on the basis of joint width. There is only one population of widths that can be characterized by a log-normal distribution, an arithmetic mean of 0. 23 mm(9.0E-04in.), and a standard deviation of 0.49 mm (1.9E-03in.). Clay is the predominant infilling type followed by silica and zeolite. For example, 98.1% of the randomly selected joints from the Cohassett flow are filled predominately with clay, 6.5% have zeolite predominating, and 4.0% have silica predominating. Only 19(0.6%) of the 3194 joints measured have observable void space. Basalt flows and intraflow structures cannot be differentiated on the basis joint infilling types, except for the Umtanum entablature. Joint width and infilling types are correlated, and secondary minerals fill basalt cooling joints in a particular sequence

The contribution of CASIEL infill walls to the shear resistance of steel frames

NARCIS (Netherlands)

Ng'Andu, B.M.; Martens, D.R.W; Vermeltfoort, A.T.

2006-01-01

In Europe, calcium silicate element (CASIEL) walls are increasingly employed as partitions and external claddings in buildings. The CASIEL infills and the frames mutually interact through frame-wall interfaces. This interaction has a significant influence on the load transmission paths of building

Structural behavior of lightweight bamboo reinforced concrete slab with EPS infill panel

Science.gov (United States)

Wibowo, Ari; Wijatmiko, Indradi; Nainggolan, Christin Remayanti

2017-09-01

Eco-friendly, green, and natural materials have become increasingly important issues in supporting sustainable development, for the substitution of nonrenewable materials such as steel. Bamboo has been considered in many studies to replace steel in reinforced concrete elements. Further investigation has been carried out to obtain lightweight and eco-friendly reinforced concrete slabs by using bamboo bars as reinforcement and recycled materials such as EPS (expanded polystyrene) as infill panel. The flexural loading test on full scale one-way slabs test has been conducted. The results showed that the flexural strength of specimens decreased marginally of about 6% but with the weight advantage of 27% less compared with those of steel rebar reinforced concrete slab with the same dimension. Two type shear-connectors comprising of concrete and bamboo studs were also investigated which showed that the bamboo stud provided better ductility compared to that of slab with concrete as shear connector. Overall, the reinforced concrete slab with bamboo reinforcement and EPS infill panel showed reasonably good performance compared to slabs with steel rebar.

No-infill 3D Printing

Science.gov (United States)

Wei, Xiao-Ran; Zhang, Yu-He; Geng, Guo-Hua

2016-09-01

In this paper, we examined how printing the hollow objects without infill via fused deposition modeling, one of the most widely used 3D-printing technologies, by partitioning the objects to shell parts. More specifically, we linked the partition to the exact cover problem. Given an input watertight mesh shape S, we developed region growing schemes to derive a set of surfaces that had inside surfaces that were printable without support on the mesh for the candidate parts. We then employed Monte Carlo tree search over the candidate parts to obtain the optimal set cover. All possible candidate subsets of exact cover from the optimal set cover were then obtained and the bounded tree was used to search the optimal exact cover. We oriented each shell part to the optimal position to guarantee the inside surface was printed without support, while the outside surface was printed with minimum support. Our solution can be applied to a variety of models, closed-hollowed or semi-closed, with or without holes, as evidenced by experiments and performance evaluation on our proposed algorithm.

Experimental Investigation of the Shear Resistance of Steel Frames with Precast Concrete Infill Panels

NARCIS (Netherlands)

Hoenderkamp, J.C.D.; Hofmeyer, H.; Snijder, H.H.

2010-01-01

At the Technische Universiteit Eindhoven a research program on composite construction is underway aiming at the development of design rules for steel frames with discretely connected precast concrete infill panels subject to in-plane horizontal loading. This paper presents experimental and finite

An experimental investigation on the ultimate strength of epoxy repaired braced partial infilled RC frames

Science.gov (United States)

Dubey, Shailendra Kumar Damodar; Kute, Sunil

2014-09-01

Due to earthquake, buildings are damaged partially or completely. Particularly structures with soft storey are mostly affected. In general, such damaged structures are repaired and reused. In this regard, an experimental investigation was planned and conducted on models of single-bay, single-storey of partial concrete infilled reinforced concrete (RC) frames up to collapse with corner, central and diagonal steel bracings. Such collapsed frames were repaired with epoxy resin and retested. The initiative was to identify the behaviour, extent of restored ultimate strength and deflection of epoxy-retrofitted frames in comparison to the braced RC frames. The performance of such frames has been considered only for lateral loads. In comparison to bare RC frames, epoxy repaired partial infilled frames have significant increase in the lateral load capacity. Central bracing is more effective than corner and diagonal bracing. For the same load, epoxy repaired frames have comparable deflection than similar braced frames.

Influence of system controls on the Late Quaternary geomorphic evolution of a rapidly-infilled incised-valley system: The lower Manawatu valley, North Island New Zealand

Science.gov (United States)

Clement, Alastair J. H.; Fuller, Ian C.

2018-02-01

The Manawatu incised-valley estuary was rapidly infilled between 12,000-4700 cal. yr BP. A combination of empirical measurements of sedimentation rates, a reconstruction of relative sea-level (RSL) change, and digital elevation models of key surfaces within the Holocene sedimentary fill of the valley were integrated to produce a numerical model to investigate the influence of the system controls of sea-level change, sediment flux, and accommodation space on the rapid infilling history of the palaeo-estuary. The numerical model indicates that sediment flux into the palaeo-estuary was greatest during the Holocene marine transgression between 12,000-8000 years BP. The average rate of sediment deposition in the estuary during this period was 1.0 M m3 yr- 1. This rapid rate of sedimentation was controlled by the rate of accommodation space creation, as regulated by the rate of sea-level rise and the antecedent configuration of the valley. By the time sea levels stabilised c. 7500 cal. yr BP, the palaeo-estuary had been substantively infilled. Limited accommodation space resulted in rapid infilling of the central basin, though sediment flux into the estuary between 7100 and 4500 cal. yr BP was at a lower rate of 234,000 m3 yr- 1. The limited accommodation space also influenced hydrodynamic conditions in the estuarine central basin, driving export of fine-grained sediment from the estuary. Once the accommodation space of the estuarine basin was infilled sediment bypassed the system, with a consequent reduction in the sedimentation rate in the valley. More accurate partitioning of the sources of sediment driving the infilling is necessary to quantify sediment bypassing. Post-depositional lowering of RSL index points from the valley is driven by neotectonics and sediment compaction.

Concrete Infill Monitoring in Concrete-Filled FRP Tubes Using a PZT-Based Ultrasonic Time-of-Flight Method.

Science.gov (United States)

Luo, Mingzhang; Li, Weijie; Hei, Chuang; Song, Gangbing

2016-12-07

Concrete-filled fiber-reinforced polymer tubes (CFFTs) have attracted interest for their structural applications in corrosive environments. However, a weak interfacial strength between the fiber-reinforced polymer (FRP) tube and the concrete infill may develop due to concrete shrinkage and inadequate concrete compaction during concrete casting, which will destroy the confinement effect and thereby reduce the load bearing capacity of a CFFT. In this paper, the lead zirconate titanate (PZT)-based ultrasonic time-of-flight (TOF) method was adopted to assess the concrete infill condition of CFFTs. The basic idea of this method is that the velocity of the ultrasonic wave propagation in the FRP material is about half of that in concrete material. Any voids or debonding created along the interface between the FRP tube and the concrete will delay the arrival time between the pairs of PZT transducers. A comparison of the arrival times of the PZT pairs between the intact and the defected CFFT was made to assess the severity of the voids or the debonding. The feasibility of the methodology was analyzed using a finite-difference time-domain-based numerical simulation. Experiments were setup to validate the numerical results, which showed good agreement with the numerical findings. The results showed that the ultrasonic time-of-flight method is able to detect the concrete infill condition of CFFTs.

Concrete Infill Monitoring in Concrete-Filled FRP Tubes Using a PZT-Based Ultrasonic Time-of-Flight Method

Science.gov (United States)

Luo, Mingzhang; Li, Weijie; Hei, Chuang; Song, Gangbing

2016-01-01

Concrete-filled fiber-reinforced polymer tubes (CFFTs) have attracted interest for their structural applications in corrosive environments. However, a weak interfacial strength between the fiber-reinforced polymer (FRP) tube and the concrete infill may develop due to concrete shrinkage and inadequate concrete compaction during concrete casting, which will destroy the confinement effect and thereby reduce the load bearing capacity of a CFFT. In this paper, the lead zirconate titanate (PZT)-based ultrasonic time-of-flight (TOF) method was adopted to assess the concrete infill condition of CFFTs. The basic idea of this method is that the velocity of the ultrasonic wave propagation in the FRP material is about half of that in concrete material. Any voids or debonding created along the interface between the FRP tube and the concrete will delay the arrival time between the pairs of PZT transducers. A comparison of the arrival times of the PZT pairs between the intact and the defected CFFT was made to assess the severity of the voids or the debonding. The feasibility of the methodology was analyzed using a finite-difference time-domain-based numerical simulation. Experiments were setup to validate the numerical results, which showed good agreement with the numerical findings. The results showed that the ultrasonic time-of-flight method is able to detect the concrete infill condition of CFFTs. PMID:27941617

Out-of-plane behavior of hollow clay tile walls infilled between steel frames

International Nuclear Information System (INIS)

Butala, M.B.; Jones, W.D.; Beavers, J.E.

1991-01-01

Several Buildings at the Department of Energy (DOE) Oak Ridge Y-1 2 Plant rely on unreinforced hollow clay tile walls (HCTW) infilled between unbraced, non-moment resisting steel frames to resist natural phenomena forces, seismic and wind. One critical building relies on moment resisting steel frames in one direction while relying on unreinforced HCTWs infilled between the columns in the orthogonal direction to resist these forces. The HCTWs must act as shear walls while maintaining out-of-plane lateral stability. In assessing the safety of these buildings to seismic forces, several models to study the in- and out-of-plane effects were made and analyzed. The study of the moment resisting steel framed building indicated that bending stresses in the walls were induced by building drift and not by inertial forces per se. The discovery of this phenomenon was some what of a surprise in that the analysis performed is not typically used in design of these structures. The study indicated that the walls began to crack at their interface with the foundation at a low open-quotes gclose quotes level and that horizontal cracking at different elevations continued until the walls exhibited little bending resistance

Effect of Various Interface Thicknesses on the Behaviour of Infilled frame Subjected to Lateral Load

Science.gov (United States)

Senthil, K.; Muthukumar, S.; Rupali, S.; Satyanarayanan, K. S.

2018-03-01

Two dimensional numerical investigations were carried out to study the influence of interface thickness on the behaviour of reinforced concrete frames subjected to in-plane lateral loads using commercial finite element tool SAP 2000. The cement mortar, cork and foam was used as interface material and their effect was studied by varying thicknesses as 6, 8, 10, 14 and 20 mm. The effect of lateral loads on infill masonry wall was also studied by varying arbitrary loads as 10, 20, 40 and 60 kN. The resistance of the frame with cement mortar was found maximum with the interface thickness 10 mm therefore, it is concluded that the maximum influence of interface thickness of 10 mm was found effective. The resistance of integral infill frame with cork and foam interface was found maximum with the interface thickness 6 mm and it is concluded that 6 mm thick interface among the chosen thickness was found effective.

Experiments and FE-model for a connection between steel frames and precast concrete infill panels (Stuttgart)

NARCIS (Netherlands)

Teeuwen, P.A; Kleinman, C.S.; Snijder, H.H.; Hofmeyer, H.; Eligehausen, R.; Fuchs, W.; Genesio, G.; Grosser, P.

2007-01-01

The paper presents experimental and FE results of investigations into the structural behaviour of a connection between steel frames and precast concrete infill panels, forming a recently developed lateral load resisting system. The discrete connections, being structural bolts on the column and beam

Mechanical characterization and force-displacement hysteretic curves from in-plane cyclic tests on strong masonry infills

Directory of Open Access Journals (Sweden)

Paolo Morandi

2018-02-01

Full Text Available This article contains information related to a recent study “Performance-based interpretation of in-plane cyclic tests on RC frames with strong masonry infills” (Morandi et al., 2017 [1]. Motivated by the necessity to improve the knowledge of the in-plane seismic response of rigid strong masonry infills, a wide experimental campaign based on in-plane cyclic tests on full-scale RC infilled frame specimens, supplemented with a complete characterization of the materials, has been conducted at the laboratory of the Department of Civil Engineering and Architecture of the University of Pavia. The masonry is constituted by vertically perforated 35 cm thick clay units with tongue and groove and dry head-joints and general-purpose mortar bed-joints. The paper reports the results of the mechanical characterization and of the force-displacement hysteretic curves from the in-plane cyclic tests.

Full-scale testing of infilled steel frames with precast concrete panels provided with a window opening

NARCIS (Netherlands)

Teeuwen, P.A; Kleinman, C.S.; Snijder, H.H.; Hofmeyer, H.

2008-01-01

As an alternative to conventional structures for tall buildings, a hybrid lateral load resisting building system has been designed, enabling the assembly of tall buildings directly from truck. It consists of steel frames with discretely connected precast concrete infill panels provided with a window

Assessing metal contamination from construction and demolition (C&D) waste used to infill wetlands: using Deroceras reticulatum (Mollusca: Gastropoda).

Science.gov (United States)

Staunton, John A; Mc Donnell, Rory J; Gormally, Michael J; Williams, Chris D; Henry, Tiernan; Morrison, Liam

2014-11-01

Large quantities of construction and demolition waste (C&D) are produced globally every year, with little known about potential environmental impacts. In the present study, the slug, Deroceras reticulatum (Mollusca: Gastropoda) was used as the first biomonitor of metals (Ag, As, Ba, Cd, Co, Cr, Cu, Mn, Mo, Ni, Pb, Sb, Se, Ti, Tl, V and Zn) on wetlands post infilling with construction and demolition (C&D) waste. The bioaccumulation of As, Ba, Cd, Co, Sb, Se and Tl were found to be significantly elevated in slugs collected on C&D waste when compared to unimproved pastures (control sites), while Mo, Se and Sr had significantly higher concentrations in slugs collected on C&D waste when compared to known contaminated sites (mining locations), indicating the potential hazardous nature of C&D waste to biota. Identifying exact sources for these metals within the waste can be problematic, due to its heterogenic nature. Biomonitors are a useful tool for future monitoring and impact studies, facilitating policy makers and regulations in other countries regarding C&D waste infill. In addition, improving separation of C&D waste to allow increased reuse and recycling is likely to be effective in reducing the volume of waste being used as infill, subsequently decreasing potential metal contamination.

Characterization of Exposure Potential during Activities on Synthetic Turf Fields with Recycled Tire Crumb Rubber Infill

Science.gov (United States)

The Federal Research Action Plan on Recycled Tire Crumb Used on Playing Fields and Playgrounds (FRAP), released in February 2016, is a multi-agency research plan in response to concerns over the use of tire crumb rubber as infill on synthetic turf fields. The FRAP outlines specif...

Neogene basin infilling from cosmogenic nuclides (10Be and 21Ne) in Atacama, Chile

Science.gov (United States)

Sanchez, Caroline; Regard, Vincent; Carretier, Sébastien; Riquelme, Rodrigo; Blard, Pierre-Henri; Campos, Eduardo; Brichau, Stéphanie; Lupker, Marteen; Hérail, Gérard

2017-04-01

In the hyperarid Atacama Desert, northern Chile, Neogene sediments host copper rich layers (exotic supergene mineralization). Current mines are excavated into relatively thin (production (quickly decreasing with depth) and disintegration (not for 21Ne). Sampling depths are at ˜100 m and at ˜50 m below the desert surface. First, 21Ne gives lower boundaries for upstream erosion rates or local sedimentation rate. These bounds are between 2 and 10 m/Ma, which is quite important for the area. The ratio between the two cosmogenic nuclides indicate a maximum burial age of 12 Ma (minimal erosion rate of 15 m/Ma) and is surprisingly similar from bottom to top, indicating a probable rapid infilling. We finally processed a Monte-Carlo inversion. This inversion helps taking into account the post-deposition muonic production of cosmogenic nuclides. Inversion results is dependent on the muonic production scheme. Interestingly, the similarity in concentrations from bottom to top pleads for quite low production at depth. Our data finally indicates a quick infilling between 12.5 and 10 Ma BP accounting for ˜100 m of deposition (minimum sedimentation rate of 40 m/Ma).

Sediment-infill volcanic breccia from the Neoarchean Shimoga greenstone terrane, western Dharwar Craton: Implications on pyroclastic volcanism and sedimentation in an active continental margin

Science.gov (United States)

Manikyamba, C.; Saha, Abhishek; Ganguly, Sohini; Santosh, M.; Lingadevaru, M.; Rajanikanta Singh, M.; Subba Rao, D. V.

2014-12-01

We report sediment-infill volcanic breccia from the Neoarchean Shimoga greenstone belt of western Dharwar Craton which is associated with rhyolites, chlorite schists and pyroclastic rocks. The pyroclastic rocks of Yalavadahalli area of Shimoga greenstone belt host volcanogenic Pb-Cu-Zn mineralization. The sediment-infill volcanic breccia is clast-supported and comprises angular to sub-angular felsic volcanic clasts embedded in a dolomitic matrix that infilled the spaces in between the framework of volcanic clasts. The volcanic clasts are essentially composed of alkali feldspar and quartz with accessory biotite and opaques. These clasts have geochemical characteristics consistent with that of the associated potassic rhyolites from Daginkatte Formation. The rare earth elements (REE) and high field strength element (HFSE) compositions of the sediment-infill volcanic breccia and associated mafic and felsic volcanic rocks suggest an active continental margin setting for their generation. Origin, transport and deposition of these rhyolitic clasts and their aggregation with infiltrated carbonate sediments may be attributed to pyroclastic volcanism, short distance transportation of felsic volcanic clasts and their deposition in a shallow marine shelf in an active continental margin tectonic setting where the rhyolitic clasts were cemented by carbonate material. This unique rock type, marked by close association of pyroclastic volcanic rocks and shallow marine shelf sediments, suggest shorter distance between the ridge and shelf in the Neoarchean plate tectonic scenario.

Topology optimization of structures and infill for additive manufacturing

DEFF Research Database (Denmark)

Sigmund, Ole; Clausen, Anders; Groen, Jeroen Peter

Topology optimization (TO) [1] is a widely used tool for generating optimal structures for subsequent realization by additive manufacturing (AM) methods. TO is a numerical method that, based on iterated finite element analyses, gradient-based optimization algorithms and design parameterizations...... described by point clouds, delivers optimal but often rather complex topologies. As such, TO is a design method that takes full advantage of the large design freedom offered by AM technologies. Much recent effortin the TO community has been devoted to the development of algorithms that take manufacturing...... as a design gimmick to illustrate the capabilities of AM to mimic natural creations like honeycombs and bonestructure. Partly for manufacturing reasons, infill microstructure is often built as open-walled foam structures. However, as maybe unknown by many, open-walled microstructures are not optimal...

INFIL1D: a quasi-analytical model for simulating one-dimensional, constant flux infiltration

International Nuclear Information System (INIS)

Simmons, C.S.; McKeon, T.J.

1984-04-01

The program INFIL1D is designed to calculate approximate wetting-front advance into an unsaturated, uniformly moist, homogeneous soil profile, under constant surface-flux conditions. The code is based on a quasi-analytical method, which utilizes an assumed invariant functional relationship between reduced (normalized) flux and water content. The code uses general hydraulic property data in tabular form to simulate constant surface-flux infiltration. 10 references, 4 figures

Development of infill drilling recovery models for carbonates reservoirs using neural networks and multivariate statistical as a novel method

International Nuclear Information System (INIS)

Soto, R; Wu, Ch. H; Bubela, A M

1999-01-01

This work introduces a novel methodology to improve reservoir characterization models. In this methodology we integrated multivariate statistical analyses, and neural network models for forecasting the infill drilling ultimate oil recovery from reservoirs in San Andres and Clearfork carbonate formations in west Texas. Development of the oil recovery forecast models help us to understand the relative importance of dominant reservoir characteristics and operational variables, reproduce recoveries for units included in the database, forecast recoveries for possible new units in similar geological setting, and make operational (infill drilling) decisions. The variety of applications demands the creation of multiple recovery forecast models. We have developed intelligent software (Soto, 1998), oilfield intelligence (01), as an engineering tool to improve the characterization of oil and gas reservoirs. 01 integrates neural networks and multivariate statistical analysis. It is composed of five main subsystems: data input, preprocessing, architecture design, graphic design, and inference engine modules. One of the challenges in this research was to identify the dominant and the optimum number of independent variables. The variables include porosity, permeability, water saturation, depth, area, net thickness, gross thickness, formation volume factor, pressure, viscosity, API gravity, number of wells in initial water flooding, number of wells for primary recovery, number of infill wells over the initial water flooding, PRUR, IWUR, and IDUR. Multivariate principal component analysis is used to identify the dominant and the optimum number of independent variables. We compared the results from neural network models with the non-parametric approach. The advantage of the non-parametric regression is that it is easy to use. The disadvantage is that it retains a large variance of forecast results for a particular data set. We also used neural network concepts to develop recovery

Application of the local-to-global approach to the study of infilled frame structures under seismic loading

International Nuclear Information System (INIS)

Combescure, D.

2000-01-01

The seismic performance of civil engineering structures may be estimated by using two levels of modelling. At the local level, each constituent has its own constitutive law and geometric finite element support. The main phenomena such as the cracking and the crushing of concrete and masonry could be reproduced by using the continuous damage or plasticity theories. However the cost of the computations does not allow extensive or dynamic studies and thus the global level - where the constitutive laws based on empirical rules reproduce the behaviour of the structural elements - represents the unique strategy for the analysis of complete civil engineering structures under seismic loading. The present paper aims at presenting the application of these two modelling levels in order to assess the seismic performance of masonry infilled R/C frame structures. The one-bay masonry infilled frames tested at Lisbon under cyclic loading and the four-storey building tested at ELSA have been used for the validation of the modelling approach. (orig.)

Widespread infilling of tidal channels and navigable waterways in human-modified tidal deltaplain of southwest Bangladesh

Directory of Open Access Journals (Sweden)

Carol Wilson

2017-12-01

Full Text Available Since the 1960s, ~5000 km2 of tidal deltaplain in southwest Bangladesh has been embanked and converted to densely inhabited, agricultural islands (i.e., polders. This landscape is juxtaposed to the adjacent Sundarbans, a pristine mangrove forest, both well connected by a dense network of tidal channels that effectively convey water and sediment throughout the region. The extensive embanking in poldered areas, however, has greatly reduced the tidal prism (i.e., volume of water transported through local channels. We reveal that >600 km of these major waterways have infilled in recent decades, converting to land through enhanced sedimentation and the direct blocking of waterways by embankments and sluice gates. Nearly all of the observed closures (~98% have occurred along the embanked polder systems, with no comparable changes occurring in channels of the Sundarbans (<2% change. We attribute most of the channel infilling to the local reduction of tidal prism in poldered areas and the associated decline in current velocities. The infilled channels account for ~90 km2 of new land in the last 40–50 years, the rate of which, ~2 km2/yr, offsets the 4 km2/yr that is eroded at the coast, and is equivalent to ~20% of the new land produced naturally at the Ganges-Brahmaputra tidal rivermouth. Most of this new land, called ‘khas’ in Bengali, has been reclaimed for agriculture or aquaculture, contributing to the local economy. However, benefits are tempered by the loss of navigable waterways for commerce, transportation, and fishing, as well as the forced rerouting of tidal waters and sediments necessary to sustain this low-lying landscape against rising sea level. A more sustainable delta will require detailed knowledge of the consequences of these hydrodynamic changes to support more scientifically-grounded management of water, sediment, and tidal energy distribution.

The Advanced Linked Extended Reconnaissance & Targeting Technology Demonstration project

Science.gov (United States)

Edwards, Mark

2008-04-01

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

Modeling the Sedimentary Infill of Lakes in the East African Rift: A Case Study of Multiple versus Single Rift Basin Segments

Science.gov (United States)

Zhang, C.; Scholz, C. A.

2016-12-01

The sedimentary basins in the East African Rift are considered excellent modern examples for investigating sedimentary infilling and evolution of extensional systems. Some lakes in the western branch of the rift have formed within single-segment systems, and include Lake Albert and Lake Edward. The largest and oldest lakes developed within multi-segment systems, and these include Lake Tanganyika and Lake Malawi. This research aims to explore processes of erosion and sedimentary infilling of the catchment area in single-segment rift (SSR) and multi-segment rift (MSR) systems. We consider different conditions of regional precipitation and evaporation, and assess the resulting facies architecture through forward modeling, using state-of-the-art commercial basin modeling software. Dionisos is a three-dimensional numerical stratigraphic forward modeling software program, which simulates basin-scale sediment transport based on empirical water- and gravity-driven diffusion equations. It was classically used to quantify the sedimentary architecture and basin infilling of both marine siliciclastic and carbonate environments. However, we apply this approach to continental rift basin environments. In this research, two scenarios are developed, one for a MSR and the other for a SSR. The modeled systems simulate the ratio of drainage area and lake surface area observed in modern Lake Tanganyika and Lake Albert, which are examples of MSRs and SSRs, respectively. The main parameters, such as maximum subsidence rate, water- and gravity-driven diffusion coefficients, rainfall, and evaporation, are approximated using these real-world examples. The results of 5 million year model runs with 50,000 year time steps show that MSRs are characterized by a deep water lake with relatively modest sediment accumulation, while the SSRs are characterized by a nearly overfilled lake with shallow water depths and thick sediment accumulation. The preliminary modeling results conform to the features

Assessing artificial neural networks and statistical methods for infilling missing soil moisture records

Science.gov (United States)

Dumedah, Gift; Walker, Jeffrey P.; Chik, Li

2014-07-01

Soil moisture information is critically important for water management operations including flood forecasting, drought monitoring, and groundwater recharge estimation. While an accurate and continuous record of soil moisture is required for these applications, the available soil moisture data, in practice, is typically fraught with missing values. There are a wide range of methods available to infilling hydrologic variables, but a thorough inter-comparison between statistical methods and artificial neural networks has not been made. This study examines 5 statistical methods including monthly averages, weighted Pearson correlation coefficient, a method based on temporal stability of soil moisture, and a weighted merging of the three methods, together with a method based on the concept of rough sets. Additionally, 9 artificial neural networks are examined, broadly categorized into feedforward, dynamic, and radial basis networks. These 14 infilling methods were used to estimate missing soil moisture records and subsequently validated against known values for 13 soil moisture monitoring stations for three different soil layer depths in the Yanco region in southeast Australia. The evaluation results show that the top three highest performing methods are the nonlinear autoregressive neural network, rough sets method, and monthly replacement. A high estimation accuracy (root mean square error (RMSE) of about 0.03 m/m) was found in the nonlinear autoregressive network, due to its regression based dynamic network which allows feedback connections through discrete-time estimation. An equally high accuracy (0.05 m/m RMSE) in the rough sets procedure illustrates the important role of temporal persistence of soil moisture, with the capability to account for different soil moisture conditions.

Durability of Geopolymer Lightweight Concrete Infilled LECA in Seawater Exposure

Science.gov (United States)

Razak, R. A.; Abdullah, M. M. A. B.; Yahya, Z.; Hamid, M. S. A.

2017-11-01

This paper describes a development of lightweight concrete using lightweight expanded clay aggregate (LECA) in fly ash (FA) based geopolymer immersed in seawater. The objective of this research is to compare the performance of geopolymer concrete (GPC) with ordinary Portland cement (OPC) concrete infilled lightweight expanded clay aggregate (LECA) in seawater exposure. Geopolymer concrete is produced by using alkaline activator to activate the raw material, FA. The highest compressive strength of this study is 42.0 MPa at 28 days and 49.8 MPa at 60 days. The density for this concrete is in the range of 1580 kg/m3 to 1660 kg/m3. The result for water absorption is in the range of 6.82% to 14.72%. However, the test results of weight loss is in the range between 0.30% to 0.43%.

Socioeconomic Impact of Infill Drilling Recovery from Carbonate Reservoirs in the Permian Basin, West Texas

Science.gov (United States)

1994-05-01

called corporate income tax . The aforementioned taxes are computed from the infill drilling recovery revenue calculated using an oil price ranging...production is not used in these computations. However, oil and gas production is used to compute the federal corporate income tax . 6.2 Advalorem Tax Revenue...billion of the corporate income tax collected in 1992. This is a humbling fact because one can see how much effort it takes to generate 0.17% of the

Holocene evolution of the Tonle Sap Lake: valley network infill and rates of sedimentation in Cambodia's Great Lake

Science.gov (United States)

Best, J.; Darby, S. E.; Langdon, P. G.; Hackney, C. R.; Leyland, J.; Parsons, D. R.; Aalto, R. E.; Marti, M.

2017-12-01

Tonle Sap Lake, the largest freshwater lake in SE Asia (c. 120km long and 35 km wide), is a vital ecosystem that provides 40-60% of the protein for the population of Cambodia. The lake is fed by flow from the Mekong River that causes the lake rise in level by c. 8m during monsoonal and cyclone-related floods, with drainage of the lake following the monsoon. Hydropower dam construction on the Mekong River has raised concerns as to the fragility of the Tonle Sap habitat due to any changing water levels and sedimentation rates within the lake. This paper details results of sub-bottom profiling surveys of Tonle Sap Lake in October 2014 that detailed the stratigraphy of the lake and assessed rates of infill. An Innomar Parametric Echo Sounder (PES) was used to obtain c. 250 km of sub-bottom profiles, with penetration up to 15m below the lake bed at a vertical resolution of c. 0.20m. These PES profiles were linked to cores from the north of the lake and previous literature. The PES profiles reveal a network of valleys, likely LGM, with relief up to c. 15-20m, that have been infilled by a suite of Holocene sediments. The valley surface is picked out as a strong reflector throughout the lake, and displays a series of valleys that are up to c. 15m deep and commonly 50-200m wide, although some of the largest valleys are 1.2km in width. Modelling of channel network incision during LGM conditions generates landscapes consistent with our field observations. The Tonle Sap valley network is infilled by sediments that show firstly fluvial and/or subaerial slope sedimentation, and then by extensive, parallel-bedded, lacustrine sedimentation. Lastly, the top c. 1m of sedimentation is marked by a distinct basal erosional surface that can be traced over much of the Tonle Sap Lake, and that is overlain by a series of parallel PES reflections. This upper sediment layer is interpreted to represent sedimentation in the Tonle Sap lake due to sediment suspension settling but after a period

Repeated catastrophic valley infill following medieval earthquakes in the Nepal Himalaya

Science.gov (United States)

Schwanghart, Wolfgang; Bernhardt, Anne; Stolle, Amelie; Hoelzmann, Philipp; Adhikari, Basanta R.; Andermann, Christoff; Tofelde, Stefanie; Merchel, Silke; Rugel, Georg; Fort, Monique; Korup, Oliver

2016-01-01

Geomorphic footprints of past large Himalayan earthquakes are elusive, although they are urgently needed for gauging and predicting recovery times of seismically perturbed mountain landscapes. We present evidence of catastrophic valley infill following at least three medieval earthquakes in the Nepal Himalaya. Radiocarbon dates from peat beds, plant macrofossils, and humic silts in fine-grained tributary sediments near Pokhara, Nepal’s second-largest city, match the timing of nearby M > 8 earthquakes in ~1100, 1255, and 1344 C.E. The upstream dip of tributary valley fills and x-ray fluorescence spectrometry of their provenance rule out local sources. Instead, geomorphic and sedimentary evidence is consistent with catastrophic fluvial aggradation and debris flows that had plugged several tributaries with tens of meters of calcareous sediment from a Higher Himalayan source >60 kilometers away.

Repeated catastrophic valley infill following medieval earthquakes in the Nepal Himalaya.

Science.gov (United States)

Schwanghart, Wolfgang; Bernhardt, Anne; Stolle, Amelie; Hoelzmann, Philipp; Adhikari, Basanta R; Andermann, Christoff; Tofelde, Stefanie; Merchel, Silke; Rugel, Georg; Fort, Monique; Korup, Oliver

2016-01-08

Geomorphic footprints of past large Himalayan earthquakes are elusive, although they are urgently needed for gauging and predicting recovery times of seismically perturbed mountain landscapes. We present evidence of catastrophic valley infill following at least three medieval earthquakes in the Nepal Himalaya. Radiocarbon dates from peat beds, plant macrofossils, and humic silts in fine-grained tributary sediments near Pokhara, Nepal's second-largest city, match the timing of nearby M > 8 earthquakes in ~1100, 1255, and 1344 C.E. The upstream dip of tributary valley fills and x-ray fluorescence spectrometry of their provenance rule out local sources. Instead, geomorphic and sedimentary evidence is consistent with catastrophic fluvial aggradation and debris flows that had plugged several tributaries with tens of meters of calcareous sediment from a Higher Himalayan source >60 kilometers away. Copyright © 2016, American Association for the Advancement of Science.

The advanced linked extended reconnaissance and targeting technology demonstration project

Science.gov (United States)

Cruickshank, James; de Villers, Yves; Maheux, Jean; Edwards, Mark; Gains, David; Rea, Terry; Banbury, Simon; Gauthier, Michelle

2007-06-01

The Advanced Linked Extended Reconnaissance & Targeting (ALERT) Technology Demonstration (TD) project is addressing key operational needs of the future Canadian Army's Surveillance and Reconnaissance forces by fusing multi-sensor and tactical data, developing automated processes, and integrating beyond line-of-sight sensing. We discuss concepts for displaying and fusing multi-sensor and tactical data within an Enhanced Operator Control Station (EOCS). The sensor data can originate from the Coyote's own visible-band and IR cameras, laser rangefinder, and ground-surveillance radar, as well as beyond line-of-sight systems such as a mini-UAV and unattended ground sensors. The authors address technical issues associated with the use of fully digital IR and day video cameras and discuss video-rate image processing developed to assist the operator to recognize poorly visible targets. Automatic target detection and recognition algorithms processing both IR and visible-band images have been investigated to draw the operator's attention to possible targets. The machine generated information display requirements are presented with the human factors engineering aspects of the user interface in this complex environment, with a view to establishing user trust in the automation. The paper concludes with a summary of achievements to date and steps to project completion.

Sediment yield model implementation based on check dam infill stratigraphy in a semiarid Mediterranean catchment

Directory of Open Access Journals (Sweden)

G. Bussi

2013-08-01

Full Text Available Soil loss and sediment transport in Mediterranean areas are driven by complex non-linear processes which have been only partially understood. Distributed models can be very helpful tools for understanding the catchment-scale phenomena which lead to soil erosion and sediment transport. In this study, a modelling approach is proposed to reproduce and evaluate erosion and sediment yield processes in a Mediterranean catchment (Rambla del Poyo, Valencia, Spain. Due to the lack of sediment transport records for model calibration and validation, a detailed description of the alluvial stratigraphy infilling a check dam that drains a 12.9 km2 sub-catchment was used as indirect information of sediment yield data. These dam infill sediments showed evidences of at least 15 depositional events (floods over the time period 1990–2009. The TETIS model, a distributed conceptual hydrological and sediment model, was coupled to the Sediment Trap Efficiency for Small Ponds (STEP model for reproducing reservoir retention, and it was calibrated and validated using the sedimentation volume estimated for the depositional units associated with discrete runoff events. The results show relatively low net erosion rates compared to other Mediterranean catchments (0.136 Mg ha−1 yr−1, probably due to the extensive outcrops of limestone bedrock, thin soils and rather homogeneous vegetation cover. The simulated sediment production and transport rates offer model satisfactory results, further supported by in-site palaeohydrological evidences and spatial validation using additional check dams, showing the great potential of the presented data assimilation methodology for the quantitative analysis of sediment dynamics in ungauged Mediterranean basins.

Anthropogenic infilling of a Bermudian sinkhole and its impact on sedimentation and benthic foraminifera in the adjacent anchialine cave environment

Directory of Open Access Journals (Sweden)

Jacquelyn N. Cresswell

2017-09-01

Full Text Available In the mid-20th century, an inland brackish pond from Bermuda, known as Eve’s Pond, was filled with marine sediment from an adjacent coastal lagoon. At this time, an eyewitness reported “…sediment billowing out of the Green Bay Cave for days…”, which is a marine-dominated anchialine cave located proximal to the former location of Eve’s Pond (~200 m. The purpose of this study was to evaluate the potential impact of this infilling event on cave sedimentation and benthic meiofaunal communities, as proxied by the unicellular protists foraminifera that remain preserved in the sediment record. Eight sediment cores were collected from an underwater passage in Green Bay Cave in a transect towards the location where Eve’s Pond was surveyed in 1901 CE. The sediment cores were analyzed for visual and density changes (photography, X-radiography, textural variability, benthic foraminifera fauna and diversity, and radiocarbon dating. The recovered sediment cores mostly sampled a late Holocene carbonate mud facies that had been described during previous research in the cave, with benthic foraminiferal assemblages post-dating the onset of seawater circulating between the saline groundwater flooding the cave and the adjacent Harrington Sound ~1,900 years ago. However, two cores located further into the cave (cores 13 and 17 contain a carbonate sand layer with lagoon foraminifera that is anomalous with respect to the Holocene depositional history of the cave and is most likely related to the mid-20th century infilling of Eve’s Pond. Examination of these two cores showed that after the infilling event, the community of benthic foraminifera rapidly reverted to pre-impact assemblages with foraminiferal stygophiles (e.g., Spirophthalmidium emaciatum, Sigmoilina tenuis, which were not displaced by new colonizers introduced into the cave by the dredge spoils. We caution that the results cannot be extrapolated to the pelagic crustacean community, but the

An environmental reconstruction of the sediment infill of the Bogota basin (Columbia) during the last 3 million years from abiotic and biotic proxies

NARCIS (Netherlands)

Torres, V.; Vandenberghe, J.; Hooghiemstra, H.

2005-01-01

The lacustrine sediments of the intramontane basin of Bogotá (4°N, 2550 m altitude) were collected in a 586-m deep core Funza-2. Absolute datings show sediment infill started c. 3.2 Ma and continued almost without interruptions as a result of the balance between tectonic subsidence and sediment

Towards sustainable settlement growth: A new multi-criteria assessment for implementing environmental targets into strategic urban planning

Energy Technology Data Exchange (ETDEWEB)

Schetke, Sophie, E-mail: schetke@uni-bonn.de [Institute of Geodesy and Geoinformation, Dept. of Urban Planning and Real Estate Management, University of Bonn, Nussallee 1, 53115 Bonn (Germany); Haase, Dagmar, E-mail: dagmar.haase@ufz.de [Humboldt University of Berlin, Department of Geography, Rudower Chaussee 16, 10099 Berlin, Germany, Helmholtz Centre for Environmental Research - UFZ, Department of Computational Landscape Ecology, Permoserstr. 15, 04318 Leipzig (Germany); Koetter, Theo, E-mail: koetter@uni-bonn.de [Institute of Geodesy and Geoinformation, Dept. of Urban Planning and Real Estate Management, University of Bonn, Nussallee 1, 53115 Bonn (Germany)

2012-01-15

For nearly one decade, the German political and research-agenda has been to a large extent determined by the ongoing question of how to limit the expansion of settlement areas around cities in order to preserve natural resources, make settlement growth more sustainable and to strengthen the re-use of existing inner-urban areas (see a.o. Koetter et al. 2009a, 2010; Schetke et al. 2009, 2010b). What is already under discussion within the international literature are the recommendations of the German Council for Sustainability to quantitatively reduce the daily greenfield consumption from the current rate of over 100 ha per day to a rate of 30 ha per day in 2020 and to bring urban infill development up to a ratio of 3:1 with greenfield development (German Council for Sustainability, 2004).). This paper addresses the added value beyond those abstract political targets and presents an innovative, multi-criteria assessment (MCA) of greenfield and infill sites to evaluate their sustainability and resource efficiency. MCA development and its incorporation into a Decision Support System (DSS) were accomplished by utilising a stakeholder-driven approach. The resulting tool can be applied in preparing and revising land-use plans. The paper presents the concept and the development process of the MCA-DSS. Test runs with planners prove that the evaluation of potential housing sites using individually weighted environmental indicators helps to identify those strategies of housing development that accord most closely with sustainability goals. The tests further show that the development of greenfield sites generally exhibits less sustainability than that of infill sites. - Highlights: Black-Right-Pointing-Pointer This paper presents an innovative, multi-criteria assessment (MCA) of greenfield and infill sites. Black-Right-Pointing-Pointer The MCA evaluates sustainability and resource efficiency of potential housing sites in a stakeholder-driven approach. Black

Towards sustainable settlement growth: A new multi-criteria assessment for implementing environmental targets into strategic urban planning

International Nuclear Information System (INIS)

Schetke, Sophie; Haase, Dagmar; Kötter, Theo

2012-01-01

For nearly one decade, the German political and research-agenda has been to a large extent determined by the ongoing question of how to limit the expansion of settlement areas around cities in order to preserve natural resources, make settlement growth more sustainable and to strengthen the re-use of existing inner-urban areas (see a.o. Kötter et al. 2009a, 2010; Schetke et al. 2009, 2010b). What is already under discussion within the international literature are the recommendations of the German Council for Sustainability to quantitatively reduce the daily greenfield consumption from the current rate of over 100 ha per day to a rate of 30 ha per day in 2020 and to bring urban infill development up to a ratio of 3:1 with greenfield development (German Council for Sustainability, 2004).). This paper addresses the added value beyond those abstract political targets and presents an innovative, multi-criteria assessment (MCA) of greenfield and infill sites to evaluate their sustainability and resource efficiency. MCA development and its incorporation into a Decision Support System (DSS) were accomplished by utilising a stakeholder-driven approach. The resulting tool can be applied in preparing and revising land-use plans. The paper presents the concept and the development process of the MCA-DSS. Test runs with planners prove that the evaluation of potential housing sites using individually weighted environmental indicators helps to identify those strategies of housing development that accord most closely with sustainability goals. The tests further show that the development of greenfield sites generally exhibits less sustainability than that of infill sites. - Highlights: ► This paper presents an innovative, multi-criteria assessment (MCA) of greenfield and infill sites. ► The MCA evaluates sustainability and resource efficiency of potential housing sites in a stakeholder-driven approach. ► Test runs with planners identified prominent environmental indicators

Fractures and fracture infillings of the Eye-Dashwa Lakes pluton, Atikokan, Ontario

International Nuclear Information System (INIS)

Stone, Denver; Kamineni, D.C.

1982-01-01

Fractures in the Eye-Dashwa pluton near Atikokan, Ontario can be subdivided on the basis of their filling materials. These materials include aplite, epidote, chlorite, and gypsum-carbonate-clay, listed in order of decreasing age established from crosscutting relations. Textues indicate that infilling occurred during fracture growth. Continuous cooling of the pluton during fracturing is inferred from the expected crystallization temperatures of fillings. Fracturing began before the pluton was completely solidified (650-600 0 C) and continued to temperatures below 100 0 C. Many fractures appear to have been sealed by the filling materials after initiation but were subsequently sheared and filled by lower temperatue materials. Apparently the majority of fractures formed during or immediately after pluton solidification and new fractures became smaller and more restricted in location as cooling progressed. Fractures and filling materials are seen as important features in assessing the possibility of movement of radionuclides in aqueous solutions away from a nuclear fuel waste repository

Analysis of an infill scenario for Rotterdam. Traffic noise, air pollution, and public health in relation to urban density and traffic of cars and bicycles

NARCIS (Netherlands)

Schaminée, S.; Rietveld, E.; Salomons, E.; Kluizenaar, Y. de; Borsboom, J.; Borst, H.; Guit, M.

2012-01-01

An analysis is presented of various elements of an infill scenario for the center of Rotterdam in the year 2030, corresponding to a population increase from about 30,000 to 60,000 inhabitants. We have implemented detailed future building designs in our software instrument Urban Strategy, and

Estimating environmental value losses from earth materials excavation and infilling for large-scale airport construction: a case of Dalian Offshore Airport, Dalian, China.

Science.gov (United States)

Yan, Hua-Kun; Wang, Nuo; Wu, Nuan; Song, Nan-Qi; Zhu, Dao-Li

2017-09-01

Large-scale airport construction removes large quantities of earth materials, resulting in serious environmental pollution and ecosystem damage. However, studies of environmental concerns caused by the materials used in airport construction are still preliminary, and those case studies on the impacts of large-scale offshore airport development are very limited. China's Dalian Offshore Airport is considered here to study the environmental value loss from 240 million m 3 of materials excavations and 21 km 2 of artificial island infillings. The findings show that the calculated annual environmental value loss for the development of the Dalian Offshore Airport is approximately US$7.75 million, including US$1.81 million and US$1.47 million of direct economic loss of timber resources and marine biology resources, respectively, and US$1.53 million and US$2.79 million value losses of forest and marine ecosystem services damaged caused by materials excavation and infilling, respectively. The conclusions of this study provide an important foundation to quantitatively analyse the environmental impact of the Dalian Offshore Airport's development and can be used as a reference for similar engineering and environment impact assessment programs.

Quantifying Sediment Characteristics and Infilling Rate within a Ship Shoal Dredge Borrow Area, Offshore Louisiana

Science.gov (United States)

Xue, Z.; Wilson, C.; Bentley, S. J.; Xu, K.; Liu, H.; Li, C.; Miner, M. D.

2017-12-01

Barrier islands provide protection to interior wetlands and maintain estuarine gradients. Mississippi River delta plain barrier islands are undergoing rapid disintegration due to high rates of subsidence and a deficit in the coastal sand supply. To mitigate for barrier island land loss, Louisiana has implemented a restoration program that intends to supplement coastal sand deficits by introducing sand from outside of the active coastal system. Inner-shelf shoals offshore Louisiana are one of the only sand resource options containing large volumes of restoration quality sand. Ship Shoal is one of these inner-shelf shoals that was produced by marine reworking of former Mississippi River Delta barrier island sediments during late Holocene time. Though indirect effects to protected areas or infrastructure adjacent to excavations have been considered, there is a paucity of observational data on their evolution. Caminada borrow area, dredged in 2013-2016 for the Caminada Headland Restoration Project, provides a valuable opportunity to validate and improve predictive models for how borrow areas evolve. In July 2017, a subbottom and bathymetric geophysical survey was conducted and sediment cores were collected to test the hypothesis that sedimentation within the excavation is affected by lateral bedload transport after initial rapid infill as slopes equilibrate. Preliminary results show the sediment within the excavation is predominantly very fine sand with isolated mud drapes. These sediments overlay older delta complex muddy strata. This contrasts strongly with other dredge pits outside of shoal areas and closer to shore, which have been infilled largely by advection of fine suspended sediments of fluvial origin. Laboratory work on cores will include laser grain size, x-ray analyses of sedimentary structures, and radiochemistry analyses for rates and age of deposition. With the knowledge of stratigraphy and sediment dynamics surrounding the dredge pit, we can quantify

Fast Formation of Conductive Material by Simultaneous Chemical Process for Infilling Through-Silicon Via

Science.gov (United States)

Kawakita, Jin; Chikyow, Toyohiro

2012-06-01

It is necessary to develop a fast and inexpensive fabrication process of vertical electric wiring by through-silicon via (TSV) technology for advanced three-dimensional semiconductor devices. In this research, a fast-forming conductive composite was successfully developed by simultaneous deposition of conductive organic polymer (polypyrrole) and metal (silver) from the liquid phase, accelerated by photoirradiation. The growth rate of the composite was 38 nm·s-1, which is more than 10 times higher than that of copper by conventional plating. The electric conductivity of the composite was 2.1×104 Ω-1·cm-1, which is on the same level as general metal conductors. In addition, the effects of reaction conditions on the growth rate and the conductivity of the composites were revealed. From these results, the infilling time of the TSV was expected to shorten from the present 2-10 h to 5-10 m.

Recording of the Holocene sediment infilling in a confined tide-dominated estuary: the bay of Brest (Britanny, France)

Science.gov (United States)

Gregoire, Gwendoline; Le Roy, Pascal; Ehrhold, Axel; Jouet, Gwenael; Garlan, Thierry

2016-04-01

Modern estuaries constitute key areas for the preservation of sedimentary deposits related to the Holocene period. Several previous studies using stratigraphic reconstructions in such environments allowed to characterise the major parameters controlling the Holocene transgressive sequence and to decipher their respective role in the sedimentary infill: (1) the evolution of main hydrologic factors (wave or tide-dominated environment), (2) the sea level fluctuation and (3) the morphologies of the bedrock and the coastline. Nevertheless, the timing of the transgressive deposits and the detailed facies need to be precise in regard to the stratigraphic schemes. The Bay of Brest (Western Brittany, France) offers the opportunity to examine these points and to compare with previous studies. It constitutes an original tide-dominated estuary that communicates to the open sea (Iroise Sea) by a narrow strait. Two main rivers (Aulne and Elorn) are connected to a submerged paleovalleys network that was incised in the Paleozoic basement during lowstands and still preserved in the present morphology. It delineates the central basin surrounded by tidal flat located in sheltered area. The analysis of high and very-high resolution seismic lines recorded through the whole bay combined with sediment cores (up to 4.5 m long) and radiocarbon dating allow to precise the architecture and the timing of the thick Holocene coastal wedge. It is preserved from the valley network to the shore and presents a longitudinal variability (downstream-upstream evolution). The infill is divided into two successive stages (corresponding to the transgressive and highstand system tracts) which laterally evolve from the paleo-valley to the coast. Two units constitute the transgressive system tract. The oldest, dated from 8200 to 7000 cal B.P. is composed of fine-grained, organic-rich tidal flat deposits located in the sheltered area and organised in levees on the terrace bordering the paleo-valley. A tidal

Targeted Adenoviral Vector Demonstrates Enhanced Efficacy for In Vivo Gene Therapy of Uterine Leiomyoma.

Science.gov (United States)

Abdelaziz, Mohamed; Sherif, Lotfy; ElKhiary, Mostafa; Nair, Sanjeeta; Shalaby, Shahinaz; Mohamed, Sara; Eziba, Noura; El-Lakany, Mohamed; Curiel, David; Ismail, Nahed; Diamond, Michael P; Al-Hendy, Ayman

2016-04-01

Gene therapy is a potentially effective non-surgical approach for the treatment of uterine leiomyoma. We demonstrated that targeted adenovirus vector, Ad-SSTR-RGD-TK/GCV, was highly effective in selectively inducing apoptosis and inhibiting proliferation of human leiomyoma cells in vitro while sparing normal myometrial cells. An in-vivo study, to compare efficacy and safety of modified adenovirus vector Ad-SSTR-RGD-TK/GCV versus untargeted vector for treatment of leiomyoma. Female nude mice were implanted with rat leiomyoma cells subcutaneously. Then mice were randomized into three groups. Group 1 received Ad-LacZ (marker gene), Group 2 received untargeted Ad-TK, and Group 3 received the targeted Ad-SSTR-RGD-TK. Tumors were measured weekly for 4 weeks. Then mice were sacrificed and tissue samples were collected. Evaluation of markers of apoptosis, proliferation, extracellular matrix, and angiogenesis was performed using Western Blot & Immunohistochemistry. Statistical analysis was done using ANOVA. Dissemination of adenovirus was assessed by PCR. In comparison with the untargeted vector, the targeted adenoviral vector significantly shrank leiomyoma size (P leiomyoma lesions with both targeted and untargeted adenovirus. Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial. © The Author(s) 2016.

Fracture calcites at Olkiluoto. Evidence from quaternary infills for palaeohydrogeology

International Nuclear Information System (INIS)

Gehoer, S.; Kaerki, A.; Taikina-aho, O.; Karhu, J.; Loefman, J.; Pitkaenen, P.; Ruotsalainen, P.

2002-02-01

Recently formed secondary minerals, predominantly calcite, occur in varying amounts as fracture infills, and the calcite types, their chemical compositions and isotope ratios reflect the compositions and physicochemical factors of the groundwater system in which they were formed. Fluid inclusions trapped in calcites give direct evidence of trapping temperatures and past salinities and of the chemical compositions of the palaeo fluids. A wide range of mineralogical and geochemical examinations were carried out within the EQUIP project to examine features of this kind. The fracture calcites at the Olkiluoto site are of various origins and represent several textural types. The exact number of calcite-producing events is unknown, but the duration of the period that was appropriate for the precipitation of low temperature calcite is estimated to have exceeded 1000 Ma. Thus the number of genetically related calcite units is assumed to be considerable. This study was focused on the petrogenesis of calcites crystallized in fractures of high water conductivity during the latest stages of geological evolution. The majority of these late stage calcites form physically homogeneous, scaly layers, and in a few cases thin layers composed of idiomorphic crystals. Chemically these are almost stoichiometric calcites (CaCO 3 ). The MnO content may exceed 1%, while the amounts of other elements present are minor, although the trace element concentrations, particularly those of large ionic trace elements, can be used as distinguishing features for the recognition of individual precipitates representing different calcite generations. Evidence from fluid inclusions, or more correctly from the absence of these in the late stage calcites, can be interpreted as an indication of slow rates of crystallization under cool conditions. Many chemical variables, e.g. oxygen isotope ratios, demonstrate an equilibrium between the latest calcites and water similar to the present groundwater. Older

Fracture calcites at Olkiluoto. Evidence from quaternary infills for palaeohydrogeology

Energy Technology Data Exchange (ETDEWEB)

Gehoer, S.; Kaerki, A.; Taikina-aho, O. [Kivitieto Oy (Finland); Karhu, J. [Helsinki Univ. (Finland); Loefman, J. [VTT Processes, Espoo (Finland); Pitkaenen, P. [VTT Building and Transport, Espoo (Finland); Ruotsalainen, P. [TUKES, Helsinki (Finland)

2002-02-01

Recently formed secondary minerals, predominantly calcite, occur in varying amounts as fracture infills, and the calcite types, their chemical compositions and isotope ratios reflect the compositions and physicochemical factors of the groundwater system in which they were formed. Fluid inclusions trapped in calcites give direct evidence of trapping temperatures and past salinities and of the chemical compositions of the palaeo fluids. A wide range of mineralogical and geochemical examinations were carried out within the EQUIP project to examine features of this kind. The fracture calcites at the Olkiluoto site are of various origins and represent several textural types. The exact number of calcite-producing events is unknown, but the duration of the period that was appropriate for the precipitation of low temperature calcite is estimated to have exceeded 1000 Ma. Thus the number of genetically related calcite units is assumed to be considerable. This study was focused on the petrogenesis of calcites crystallized in fractures of high water conductivity during the latest stages of geological evolution. The majority of these late stage calcites form physically homogeneous, scaly layers, and in a few cases thin layers composed of idiomorphic crystals. Chemically these are almost stoichiometric calcites (CaCO{sub 3}). The MnO content may exceed 1%, while the amounts of other elements present are minor, although the trace element concentrations, particularly those of large ionic trace elements, can be used as distinguishing features for the recognition of individual precipitates representing different calcite generations. Evidence from fluid inclusions, or more correctly from the absence of these in the late stage calcites, can be interpreted as an indication of slow rates of crystallization under cool conditions. Many chemical variables, e.g. oxygen isotope ratios, demonstrate an equilibrium between the latest calcites and water similar to the present groundwater. Older

Physics-Based Simulation and Experiment on Blast Protection of Infill Walls and Sandwich Composites Using New Generation of Nano Particle Reinforced Materials

Science.gov (United States)

Irshidat, Mohammad

A critical issue for the development of nanotechnology is our ability to understand, model, and simulate the behavior of small structures and to make the connection between nano structure properties and their macroscopic functions. Material modeling and simulation helps to understand the process, to set the objectives that could guide laboratory efforts, and to control material structures, properties, and processes at physical implementation. These capabilities are vital to engineering design at the component and systems level. In this research, experimental-computational-analytical program was employed to investigate the performance of the new generation of polymeric nano-composite materials, like nano-particle reinforced elastomeric materials (NPREM), for the protection of masonry structures against blast loads. New design tools for using these kinds of materials to protect Infill Walls (e.g. masonry walls) against blast loading were established. These tools were also extended to cover other type of panels like sandwich composites. This investigation revealed that polymeric nano composite materials are strain rate sensitive and have large amount of voids distributed randomly inside the materials. Results from blast experiments showed increase in ultimate flexural resistance achieved by both unreinforced and nano reinforced polyurea retrofit systems applied to infill masonry walls. It was also observed that a thin elastomeric coating on the interior face of the walls could be effective at minimizing the fragmentation resulting from blast. More conclusions are provided with recommended future research.

Scale-up of high specific activity {sup 186g}Re production using graphite-encased thick {sup 186}W targets and demonstration of an efficient target recycling process

Energy Technology Data Exchange (ETDEWEB)

Balkin, Ethan R.; Gagnon, Katherine; Dorman, Eric [Washington Univ., Seattle, WA (United States). Dept. of Radiation Oncology; and others

2017-07-01

Production of high specific activity {sup 186g}Re is of interest for development of theranostic radiopharmaceuticals. Previous studies have shown that high specific activity {sup 186g}Re can be obtained by cyclotron irradiation of enriched {sup 186}W via the {sup 186}W(d,2n){sup 186g}Re reaction, but most irradiations were conducted at low beam currents and for short durations. In this investigation, enriched {sup 186}W metal targets were irradiated at high incident deuteron beam currents to demonstrate production rates and contaminants produced when using thick targets. Full-stopping thick targets, as determined using SRIM, were prepared by uniaxial pressing of powdered natural abundance W metal or 96.86% enriched {sup 186}W metal encased between two layers of graphite flakes for target material stabilization. An assessment of structural integrity was made on each target preparation. To assess the performance of graphite-encased thick {sup 186}W metal targets, along with the impact of encasing on the separation chemistry, targets were first irradiated using a 22 MeV deuteron beam for 10 min at 10, 20, and 27 μA, with an estimated nominal deuteron energy of 18.7 MeV on the {sup 186}W target material (after energy degradation correction from top graphite layer). Gamma-ray spectrometry was performed post EOB on all targets to assess production yields and radionuclidic byproducts. The investigation also evaluated a method to recover and recycle enriched target material from a column isolation procedure. Material composition analyses of target materials, pass-through/wash solutions and recycling process isolates were conducted with SEM, FTIR, XRD, EDS and ICP-MS spectrometry. To demonstrate scaled-up production, a graphite-encased {sup 186}W target made from recycled {sup 186}W was irradiated for ∝2 h with 18.7 MeV deuterons at a beam current of 27 μA to provide 0.90 GBq (24.3 mCi) of {sup 186g}Re, decay-corrected to the end of bombardment. ICP-MS analysis of the

Demonstration of a neonlike argon soft-x-ray laser with a picosecond-laser-irradiated gas puff target.

Science.gov (United States)

Fiedorowicz, H; Bartnik, A; Dunn, J; Smith, R F; Hunter, J; Nilsen, J; Osterheld, A L; Shlyaptsev, V N

2001-09-15

We demonstrate a neonlike argon-ion x-ray laser, using a short-pulse laser-irradiated gas puff target. The gas puff target was formed by pulsed injection of gas from a high-pressure solenoid valve through a nozzle in the form of a narrow slit and irradiated with a combination of long, 600-ps and short, 6-ps high-power laser pulses with a total of 10 J of energy in a traveling-wave excitation scheme. Lasing was observed on the 3p (1)S(0)?3s (1)P(1) transition at 46.9 nm and the 3d (1)P(1)?3p (1)P(1) transition at 45.1 nm. A gain of 11 cm(-1) was measured on these transitions for targets up to 0.9 cm long.

Neotendon infilling of a full thickness rotator cuff foot print tear following ultrasound guided liquid platelet rich plasma injection and percutaneous tenotomy: favourable outcome up to one year [v1; ref status: indexed, http://f1000r.es/xz

Directory of Open Access Journals (Sweden)

Arockia Doss

2013-01-01

Full Text Available This is a case report on excellent clinical outcome and neotendon infilling at one year follow up in a degenerative rotator cuff full thickness tear following percutaneous tenotomy and platelet rich plasma injection.

Demonstrator for Automatic Target Classification in SAR Imagery

NARCIS (Netherlands)

Wit, J.J.M. de; Broek, A.C. van den; Dekker, R.J.

2006-01-01

Due to the increasing use of unmanned aerial vehicles (UAV) for reconnaissance, surveillance, and target acquisition applications, the interest in synthetic aperture radar (SAR) systems is growing. In order to facilitate the processing of the enormous amount of SAR data on the ground, automatic

Search-Lidar Demonstrator for Detection of Small Sea-Surface Targets

NARCIS (Netherlands)

Heuvel, J.C. van den; Bekman, H.H.P.T.; Putten, F.J.M. van; Cohen, L.H.; Schleijpen, H.M.A.

2008-01-01

Coastal surveillance and naval operations in the littoral both have to deal with the threat of small sea-surface targets. These targets have a low radar cross-section and a low velocity that makes them hard to detect by radar. Typical threats include jet skis, FIAC’s, and speedboats. Lidar

Use of targeted medication reviews to deliver preconception care: A demonstration project.

Science.gov (United States)

DiPietro Mager, Natalie A; Bright, David R; Markus, Dani; Weis, Lindsey; Hartzell, David M; Gartner, James

To demonstrate the ability of a statewide network of community pharmacists to provide preconception care services with the use of targeted medication reviews (TMRs). Community pharmacists are well qualified and well positioned to assist in this public health priority; however, there are no documented case studies of pharmacists providing preconception care with the use of TMRs. Through the demonstration project, pharmacists provided educational TMRs focused on 3 elements of preconception care to women aged 15 to 45 years enrolled in a nonprofit managed care plan: (1) medications that may cause fetal harm (category D/X); (2) folic acid use; and (3) immunizations. TMRs were generated and released to the individual pharmacy where that patient had prescriptions filled. Any practicing pharmacist in Ohio participating in the medication therapy management platform with a patient in the sample received a TMR notification. The pharmacists documented and billed for the service through this commercially available platform. Nineteen weeks after implementation of the TMRs, 1149 individual pharmacists from 818 different pharmacies had completed at least 1 TMR. Pharmacists completed 33% of all TMR opportunities with a 65% success rate. Establishing new services that were focused on preconception care resulted in rapid integration into existing medication therapy management processes in hundreds of pharmacies across Ohio. These results may help to provide justification for additional payers to reimburse for similar services. Through demonstrating the impact on preconception care, the role of the community pharmacist may continue to expand to include provision of additional preventive care services following the model developed in this initiative. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Rubber bearing and bitumen infill support system for seismic protection of nuclear power plant structures

International Nuclear Information System (INIS)

Ahmed, K.M.

1981-01-01

The prestressed concrete pressure vessel (PCPV) for the AGR is of cylindrical type. The whole of the reactor primary circuit is contained within the PCPV vault and includes the reactor core and support structures, boilers and gas circulators. The PCPV is essentially free standing on its foundation raft. In order to transmit gravitational and seismic loads between the PCPV and the foundation raft, a support system is used which consists of concentric rings of neoprene pads and a thin annulus of bitumen infill. In order to assess the importance of both stiffness and damping of the PCPV support system on the overall AGR response, detailed parametric studies were carried out using time-history dynamic analysis in conjunction with the modal superposition technique. The effects of both stiffness and damping are compared in terms of the maximum dynamic response (maximum accelerations and maximum relative displacements) and also floor response spectra at various locations on the nuclear island. It is clearly apparent from these investigations that for an appropriate range of structures on the nuclear island (such as the PCPV and its internals), greater reduction in seismic loading can be achieved by proper selection of stiffnesses and damping of the PCPV support system without resorting to strengthening techniques. (orig./HP)

Immobilisation of shredded waste in a cement matrix

International Nuclear Information System (INIS)

James, J.M.; Smith, D.L.

1987-10-01

The work covered in the period of this report was aimed at proving the infilling capabilities of waste packages containing shredded paper and plastic simulant waste material held in a basket. The programme required the production of 200 and 500 litre packages and a demonstration that infilling could be attained to give a minimum of voidage in the completed cemented product. The procurement, testing and fitting of level detectors was an important part of this work to demonstrate a means of controlling the process to prevent overfilling of the packages. Evaluation of full-scale cemented products was required to confirm previously reported properties of density and homogeneity in packages produced by the reference encapsulation process and to demonstrate package integrity under sea-disposal conditions. A standard feedstock for the continuity of a long-term programme was required. Such a product, based on an analysis of arisings from plutonium gloveboxes, was produced in bulk and characterised. The previously observed movement of waste during infilling, due to its low density compared with that of the infill grout, required further assessment. During the period, 200, 400 and 500 litre drums required for future active infilling trials were modified and despatched to AERE Harwell for waste loading. These drums were fitted with level detectors and with grout spreader troughs which had been identified during the development programme. A prototype automated Grout Infill Test Rig designed by BNF plc was delivered to Winfrith towards the end of the period for practical assessment trials. (author)

Surface-geophysical techniques used to detect existing and infilled scour holes near bridge piers

Science.gov (United States)

Placzek, Gary; Haeni, F.P.

1995-01-01

Surface-geophysical techniques were used with a position-recording system to study riverbed scour near bridge piers. From May 1989 to May 1993. Fathometers, fixed- and swept-frequency con- tinuous seismic-reflection profiling (CSP) systems, and a ground-penetrating radar (GPR) system were used with a laser-positioning system to measure the depth and extent of existing and infilled scour holes near bridge piers. Equipment was purchased commercially and modified when necessary to interface the components and (or) to improve their performance. Three 200-kHz black-and-white chart- recording Fathometers produced profiles of the riverbed that included existing scour holes and exposed pier footings. The Fathometers were used in conjunction with other geophysical techniques to help interpret the geophysical data. A 20-kHz color Fathometer delineated scour-hole geometry and, in some cases, the thickness of fill material in the hole. The signal provided subbottom information as deep as 10 ft in fine-grained materials and resolved layers of fill material as thin as 1 foot thick. Fixed-frequency and swept-frequency CSP systems were evaluated. The fixed-frequency system used a 3.5-, 7.0-, or 14-kHz signal. The 3.5-kHz signal pene- trated up to 50 ft of fine-grained material and resolved layers as thin as 2.5-ft thick. The 14-kHz signal penetrated up to 20 ft of fine-grained material and resolved layers as thin as 1-ft thick. The swept-frequency systems used a signal that swept from 2- to 16-kHz. With this system, up to 50 ft of penetration was achieved, and fill material as thin as 1 ft was resolved. Scour-hole geometry, exposed pier footings, and fill thickness in scour holes were detected with both CSP systems. The GPR system used an 80-, 100-, or 300-megahertz signal. The technique produced records in water up to 15 ft deep that had a specific conductance less than 200x11ms/cm. The 100-MHz signal penetrated up to 40 ft of resistive granular material and resolved layers as

The Bruton Tyrosine Kinase (BTK) Inhibitor Acalabrutinib Demonstrates Potent On-Target Effects and Efficacy in Two Mouse Models of Chronic Lymphocytic Leukemia

DEFF Research Database (Denmark)

Herman, Sarah E M; Montraveta, Arnau; Niemann, Carsten U

2017-01-01

into the drinking water.Results: Utilizing biochemical assays, we demonstrate that acalabrutinib is a highly selective BTK inhibitor as compared with ibrutinib. In the human CLL NSG xenograft model, treatment with acalabrutinib demonstrated on-target effects, including decreased phosphorylation of PLCγ2, ERK......). In two complementary mouse models of CLL, acalabrutinib significantly reduced tumor burden and increased survival compared with vehicle treatment. Overall, acalabrutinib showed increased BTK selectivity compared with ibrutinib while demonstrating significant antitumor efficacy in vivo on par...... with ibrutinib. Clin Cancer Res; 23(11); 2831-41. ©2016 AACR....

Modeling the influence of the BRDF characteristics of vegetation on the retrieval of solar-induced chlorophyll fluorescence under different illumination conditions

Science.gov (United States)

Liu, Xinjie; Liu, Liangyun

2017-04-01

The Fraunhofer Line Discrimination (FLD) principle is the main approach used for the retrieval of solar-induced chlorophyll fluorescence (SIF). The basic assumption of the FLD principle is that the apparent reflectance spectra without SIF in-filling are smooth in the region of the absorption bands. However, in fact, this assumption is not valid due to the so-called "direct radiation in-filling" effect caused by the non-linear contribution of direct and diffuse radiation at the oxygen absorption bands, which are widely used for ground-based SIF retrieval. In this study, we first analyzed the physical mechanism of the direct radiation in-filling effect on the oxygen absorption bands and found that the bias in the SIF retrieval caused by the direct radiation in-filling effect at the O2-A band was less than 20% based on the use of a simulated dataset. Secondly, we established a simple correction model of the direct radiation in-filling effect. We found that the direct radiation in-filling effect at the O2-A band was directly proportional to the difference between the reflectance of the direct and diffuse radiation, and that the coefficient of proportionality was well correlated with the diffuse-to-global radiation ratio in the form of a quadratic function. The coefficient of determination (R-squared) for this correlation was 0.97. Finally, the model was validated using both simulated and field datasets. The validation results show that the bias in the SIF retrieval caused by the direct radiation in-filling effect can be efficiently corrected using the model proposed in this paper. This study thus provides a possible approach to estimating and correcting for the direct radiation-infilling effect using prior knowledge of the BRDF characteristics of direct and diffuse radiation for specific targets.

Target detection and localization in shallow water: an experimental demonstration of the acoustic barrier problem at the laboratory scale.

Science.gov (United States)

Marandet, Christian; Roux, Philippe; Nicolas, Barbara; Mars, Jérôme

2011-01-01

This study demonstrates experimentally at the laboratory scale the detection and localization of a wavelength-sized target in a shallow ultrasonic waveguide between two source-receiver arrays at 3 MHz. In the framework of the acoustic barrier problem, at the 1/1000 scale, the waveguide represents a 1.1-km-long, 52-m-deep ocean acoustic channel in the kilohertz frequency range. The two coplanar arrays record in the time-domain the transfer matrix of the waveguide between each pair of source-receiver transducers. Invoking the reciprocity principle, a time-domain double-beamforming algorithm is simultaneously performed on the source and receiver arrays. This array processing projects the multireverberated acoustic echoes into an equivalent set of eigenrays, which are defined by their launch and arrival angles. Comparison is made between the intensity of each eigenray without and with a target for detection in the waveguide. Localization is performed through tomography inversion of the acoustic impedance of the target, using all of the eigenrays extracted from double beamforming. The use of the diffraction-based sensitivity kernel for each eigenray provides both the localization and the signature of the target. Experimental results are shown in the presence of surface waves, and methodological issues are discussed for detection and localization.

Demonstration of a high-intensity neutron source based on a liquid-lithium target for Accelerator based Boron Neutron Capture Therapy.

Science.gov (United States)

Halfon, S; Arenshtam, A; Kijel, D; Paul, M; Weissman, L; Berkovits, D; Eliyahu, I; Feinberg, G; Kreisel, A; Mardor, I; Shimel, G; Shor, A; Silverman, I; Tessler, M

2015-12-01

A free surface liquid-lithium jet target is operating routinely at Soreq Applied Research Accelerator Facility (SARAF), bombarded with a ~1.91 MeV, ~1.2 mA continuous-wave narrow proton beam. The experiments demonstrate the liquid lithium target (LiLiT) capability to constitute an intense source of epithermal neutrons, for Accelerator based Boron Neutron Capture Therapy (BNCT). The target dissipates extremely high ion beam power densities (>3 kW/cm(2), >0.5 MW/cm(3)) for long periods of time, while maintaining stable conditions and localized residual activity. LiLiT generates ~3×10(10) n/s, which is more than one order of magnitude larger than conventional (7)Li(p,n)-based near threshold neutron sources. A shield and moderator assembly for BNCT, with LiLiT irradiated with protons at 1.91 MeV, was designed based on Monte Carlo (MCNP) simulations of BNCT-doses produced in a phantom. According to these simulations it was found that a ~15 mA near threshold proton current will apply the therapeutic doses in ~1h treatment duration. According to our present results, such high current beams can be dissipated in a liquid-lithium target, hence the target design is readily applicable for accelerator-based BNCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

First Demonstration of Combined kV/MV Image-Guided Real-Time Dynamic Multileaf-Collimator Target Tracking

International Nuclear Information System (INIS)

Cho, Byungchul; Poulsen, Per R.; Sloutsky, Alex; Sawant, Amit; Keall, Paul J.

2009-01-01

Purpose: For intrafraction motion management, a real-time tracking system was developed by combining fiducial marker-based tracking via simultaneous kilovoltage (kV) and megavoltage (MV) imaging and a dynamic multileaf collimator (DMLC) beam-tracking system. Methods and Materials: The integrated tracking system employed a Varian Trilogy system equipped with kV/MV imaging systems and a Millennium 120-leaf MLC. A gold marker in elliptical motion (2-cm superior-inferior, 1-cm left-right, 10 cycles/min) was simultaneously imaged by the kV and MV imagers at 6.7 Hz and segmented in real time. With these two-dimensional projections, the tracking software triangulated the three-dimensional marker position and repositioned the MLC leaves to follow the motion. Phantom studies were performed to evaluate time delay from image acquisition to MLC adjustment, tracking error, and dosimetric impact of target motion with and without tracking. Results: The time delay of the integrated tracking system was ∼450 ms. The tracking error using a prediction algorithm was 0.9 ± 0.5 mm for the elliptical motion. The dose distribution with tracking showed better target coverage and less dose to surrounding region over no tracking. The failure rate of the gamma test (3%/3-mm criteria) was 22.5% without tracking but was reduced to 0.2% with tracking. Conclusion: For the first time, a complete tracking system combining kV/MV image-guided target tracking and DMLC beam tracking was demonstrated. The average geometric error was less than 1 mm, and the dosimetric error was negligible. This system is a promising method for intrafraction motion management.

Accelerated reliability demonstration under competing failure modes

International Nuclear Information System (INIS)

Luo, Wei; Zhang, Chun-hua; Chen, Xun; Tan, Yuan-yuan

2015-01-01

The conventional reliability demonstration tests are difficult to apply to products with competing failure modes due to the complexity of the lifetime models. This paper develops a testing methodology based on the reliability target allocation for reliability demonstration under competing failure modes at accelerated conditions. The specified reliability at mission time and the risk caused by sampling of the reliability target for products are allocated for each failure mode. The risk caused by degradation measurement fitting of the target for a product involving performance degradation is equally allocated to each degradation failure mode. According to the allocated targets, the accelerated life reliability demonstration test (ALRDT) plans for the failure modes are designed. The accelerated degradation reliability demonstration test plans and the associated ALRDT plans for the degradation failure modes are also designed. Next, the test plan and the decision rules for the products are designed. Additionally, the effects of the discreteness of sample size and accepted number of failures for failure modes on the actual risks caused by sampling for the products are investigated. - Highlights: • Accelerated reliability demonstration under competing failure modes is studied. • The method is based on the reliability target allocation involving the risks. • The test plan for the products is based on the plans for all the failure modes. • Both failure mode and degradation failure modes are considered. • The error of actual risks caused by sampling for the products is small enough

Aragonite infill in overgrown conceptacles of coralline Lithothamnion spp. (Hapalidiaceae, Hapalidiales, Rhodophyta): new insights in biomineralization and phylomineralogy.

Science.gov (United States)

Krayesky-Self, Sherry; Richards, Joseph L; Rahmatian, Mansour; Fredericq, Suzanne

2016-04-01

New empirical and quantitative data in the study of calcium carbonate biomineralization and an expanded coralline psbA framework for phylomineralogy are provided for crustose coralline red algae. Scanning electron microscopy (SEM) and energy dispersive spectrometry (SEM-EDS) pinpointed the exact location of calcium carbonate crystals within overgrown reproductive conceptacles in rhodolith-forming Lithothamnion species from the Gulf of Mexico and Pacific Panama. SEM-EDS and X-ray diffraction (XRD) analysis confirmed the elemental composition of these calcium carbonate crystals to be aragonite. After spore release, reproductive conceptacles apparently became overgrown by new vegetative growth, a strategy that may aid in sealing the empty conceptacle chamber, hence influencing the chemistry of the microenvironment and in turn promoting aragonite crystal growth. The possible relevance of various types of calcium carbonate polymorphs present in the complex internal structure and skeleton of crustose corallines is discussed. This is the first study to link SEM, SEM-EDS, XRD, Microtomography and X-ray microscopy data of aragonite infill in coralline algae with phylomineralogy. The study contributes to the growing body of literature characterizing and speculating about how the relative abundances of carbonate biominerals in corallines may vary in response to changes in atmospheric pCO2 , ocean acidification, and global warming. © 2016 Phycological Society of America.

Infilling and flooding of the Mekong River incised valley during deglacial sea-level rise

Science.gov (United States)

Tjallingii, Rik; Stattegger, Karl; Wetzel, Andreas; Van Phach, Phung

2010-06-01

The abrupt transition from fluvial to marine deposition of incised-valley-fill sediments retrieved from the southeast Vietnamese shelf, accurately records the postglacial transgression after 14 ka before present (BP). Valley-filling sediments consist of fluvial mud, whereas sedimentation after the transgression is characterized by shallow-marine carbonate sands. This change in sediment composition is accurately marked in high-resolution X-ray fluorescence (XRF) core scanning records. Rapid aggradation of fluvial sediments at the river mouth nearly completely filled the Mekong incised valley prior to flooding. However, accumulation rates strongly reduced in the valley after the river-mouth system flooded and stepped back. This also affected the sediment supply to deeper parts of the southeast Vietnamese shelf. Comparison of the Mekong valley-filling with the East Asian sea-level history of sub- and inter-tidal sediment records shows that the transgressive surface preserved in the incised-valley-fill records is a robust sea-level indicator. The valley was nearly completely filled with fluvial sediments between 13.0 and 9.5 ka BP when sea-level rose rather constantly with approximately 10 mm/yr, as indicated by the East Asian sea-level record. At shallower parts of the shelf, significant sediment reworking and the establishment of estuarine conditions at the final stage of infilling complicates accurate dating of the transgressive surface. Nevertheless, incised-valley-fill records and land-based drill sites indicate a vast and rapid flooding of the shelf from the location of the modern Vietnamese coastline to the Cambodian lowlands between 9.5 ka and 8.5 ka BP. Fast flooding of this part of the shelf is related with the low shelf gradient and a strong acceleration of the East Asian sea-level rise from 34 to 9 meter below modern sea level (mbsl) corresponding to the sea-level jump of melt water pulse (MWP) 1C.

High Density Infill in Cracks and Protrusions from the Articular Calcified Cartilage in Osteoarthritis in Standardbred Horse Carpal Bones

Directory of Open Access Journals (Sweden)

Sheila Laverty

2015-04-01

Full Text Available We studied changes in articular calcified cartilage (ACC and subchondral bone (SCB in the third carpal bones (C3 of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA. Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT image sets for the presence of high-density mineral infill (HDMI in ACC cracks and possible high-density mineralized protrusions (HDMP from the ACC mineralizing (tidemark front (MF into hyaline articular cartilage (HAC. We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA.

Strand Invasion Based Amplification (SIBA®): a novel isothermal DNA amplification technology demonstrating high specificity and sensitivity for a single molecule of target analyte.

Science.gov (United States)

Hoser, Mark J; Mansukoski, Hannu K; Morrical, Scott W; Eboigbodin, Kevin E

2014-01-01

Isothermal nucleic acid amplification technologies offer significant advantages over polymerase chain reaction (PCR) in that they do not require thermal cycling or sophisticated laboratory equipment. However, non-target-dependent amplification has limited the sensitivity of isothermal technologies and complex probes are usually required to distinguish between non-specific and target-dependent amplification. Here, we report a novel isothermal nucleic acid amplification technology, Strand Invasion Based Amplification (SIBA). SIBA technology is resistant to non-specific amplification, is able to detect a single molecule of target analyte, and does not require target-specific probes. The technology relies on the recombinase-dependent insertion of an invasion oligonucleotide (IO) into the double-stranded target nucleic acid. The duplex regions peripheral to the IO insertion site dissociate, thereby enabling target-specific primers to bind. A polymerase then extends the primers onto the target nucleic acid leading to exponential amplification of the target. The primers are not substrates for the recombinase and are, therefore unable to extend the target template in the absence of the IO. The inclusion of 2'-O-methyl RNA to the IO ensures that it is not extendible and that it does not take part in the extension of the target template. These characteristics ensure that the technology is resistant to non-specific amplification since primer dimers or mis-priming are unable to exponentially amplify. Consequently, SIBA is highly specific and able to distinguish closely-related species with single molecule sensitivity in the absence of complex probes or sophisticated laboratory equipment. Here, we describe this technology in detail and demonstrate its use for the detection of Salmonella.

Strand Invasion Based Amplification (SIBA®: a novel isothermal DNA amplification technology demonstrating high specificity and sensitivity for a single molecule of target analyte.

Directory of Open Access Journals (Sweden)

Mark J Hoser

Full Text Available Isothermal nucleic acid amplification technologies offer significant advantages over polymerase chain reaction (PCR in that they do not require thermal cycling or sophisticated laboratory equipment. However, non-target-dependent amplification has limited the sensitivity of isothermal technologies and complex probes are usually required to distinguish between non-specific and target-dependent amplification. Here, we report a novel isothermal nucleic acid amplification technology, Strand Invasion Based Amplification (SIBA. SIBA technology is resistant to non-specific amplification, is able to detect a single molecule of target analyte, and does not require target-specific probes. The technology relies on the recombinase-dependent insertion of an invasion oligonucleotide (IO into the double-stranded target nucleic acid. The duplex regions peripheral to the IO insertion site dissociate, thereby enabling target-specific primers to bind. A polymerase then extends the primers onto the target nucleic acid leading to exponential amplification of the target. The primers are not substrates for the recombinase and are, therefore unable to extend the target template in the absence of the IO. The inclusion of 2'-O-methyl RNA to the IO ensures that it is not extendible and that it does not take part in the extension of the target template. These characteristics ensure that the technology is resistant to non-specific amplification since primer dimers or mis-priming are unable to exponentially amplify. Consequently, SIBA is highly specific and able to distinguish closely-related species with single molecule sensitivity in the absence of complex probes or sophisticated laboratory equipment. Here, we describe this technology in detail and demonstrate its use for the detection of Salmonella.

APPLICATION OF INTEGRATED RESERVOIR MANAGEMENT AND RESERVOIR CHARACTERIZATION

Energy Technology Data Exchange (ETDEWEB)

Jack Bergeron; Tom Blasingame; Louis Doublet; Mohan Kelkar; George Freeman; Jeff Callard; David Moore; David Davies; Richard Vessell; Brian Pregger; Bill Dixon; Bryce Bezant

2000-03-01

Reservoir performance and characterization are vital parameters during the development phase of a project. Infill drilling of wells on a uniform spacing, without regard to characterization does not optimize development because it fails to account for the complex nature of reservoir heterogeneities present in many low permeability reservoirs, especially carbonate reservoirs. These reservoirs are typically characterized by: (1) large, discontinuous pay intervals; (2) vertical and lateral changes in reservoir properties; (3) low reservoir energy; (4) high residual oil saturation; and (5) low recovery efficiency. The operational problems they encounter in these types of reservoirs include: (1) poor or inadequate completions and stimulations; (2) early water breakthrough; (3) poor reservoir sweep efficiency in contacting oil throughout the reservoir as well as in the nearby well regions; (4) channeling of injected fluids due to preferential fracturing caused by excessive injection rates; and (5) limited data availability and poor data quality. Infill drilling operations only need target areas of the reservoir which will be economically successful. If the most productive areas of a reservoir can be accurately identified by combining the results of geological, petrophysical, reservoir performance, and pressure transient analyses, then this ''integrated'' approach can be used to optimize reservoir performance during secondary and tertiary recovery operations without resorting to ''blanket'' infill drilling methods. New and emerging technologies such as geostatistical modeling, rock typing, and rigorous decline type curve analysis can be used to quantify reservoir quality and the degree of interwell communication. These results can then be used to develop a 3-D simulation model for prediction of infill locations. The application of reservoir surveillance techniques to identify additional reservoir ''pay'' zones

Influences of Shear History and Infilling on the Mechanical Characteristics and Acoustic Emissions of Joints

Science.gov (United States)

Meng, Fanzhen; Zhou, Hui; Wang, Zaiquan; Zhang, Liming; Kong, Liang; Li, Shaojun; Zhang, Chuanqing

2017-08-01

Filled joints, which are characterized by high deformability and low shear strength, are among the most critical discontinuities in rock mass and may be sheared repeatedly when subject to cyclic loading. Shear tests were carried out on tension splitting joints, with soil and granular cement mortar particles used as infillings, and the effects of the shear history on the mechanical behavior and acoustic emission (AE) of clean and filled joints were studied. The maximum strength in the subsequent shears was approximately 60% of the peak strength of the first shear for a clean joint, and the friction angle degraded from 63° to 45° after the first shear. The maximum shear strength of the filled joints was lower than 35% of the peak strength of the clean joint under the same normal stress. The change in the shear strength of filled joints with the number of shearing cycles was closely related to the transformation of the shear medium. Rolling friction occurred and the shear strength was low for the granular particle-filled joint, but the strength was elevated when the particles were crushed and sliding friction occurred. The AEs were significantly reduced during the second shear for the clean joint, and the peak AEs were mainly obtained at or near the turning point of the shear stress curve for the filled joint. The AEs were the highest for the cement particle-filled joint and lowest for the dry soil-filled joint; when subjected to repeated shears, the AEs were more complex because of the continuous changes to the shear medium. The evolution of the AEs with the shear displacement can accurately reflect the shear failure mechanism during a single shear process.

Effect of grain size on the sorption and desorption of SeO42- and SeO32- in columns of crushed granite and fracture infill from granitic water under dynamic conditions

International Nuclear Information System (INIS)

Videnska, K.; Institute of Chemical Technology, Prague; Palagyi, S.; Czech Technical University, Prague; Stamberg, K.; Vodickova, H.; Havlova, V.

2013-01-01

The sorption of 2 x 10 -5 mol/dm 3 Na 2 SeO 4 and Na 2 SeO 3 dissolved in synthetic granitic water (SGW) were investigated in columns of crushed granite and fracture infill (clay minerals) of various grain sizes. Desorption was studied using pure SGW. The goal of study was the quantification of the effect of grain size on the retardation and distribution coefficients of SeO 4 2- and SeO 3 2- , as well as on the other transport parameters (Peclet number and hydrodynamic dispersion coefficient). A model based on the erfc-function, assuming a non-linear reversible equilibrium sorption/desorption isotherm, was used for evaluation of sorption/desorption and transport parameters. The determination of selenium was performed using an ICP-MS technique. The experimental breakthrough curves were fitted using non-linear regression procedure, in the course of which the parameters mentioned were sought. Summing up, no sorption was recorded in the case of SeO 4 2- under these conditions. The values of retardation coefficients were practically one for all studied grain sizes. On the other hand, significant sorption was found for SeO 3 2- : depending on the grain size, the retardation coefficients varied between 1.6-8.7 in pure granite and 1.8-37.2 in infill materials. These values correspond to distribution coefficients of 0.2-2.5 and 0.2-12.7 cm 3 /g, respectively. The both parameters have similar values in a case of desorption which reflects the reversible character of sorption process. It was found that retardation and distribution coefficients and sorption capacity for SeO 3 2- also increase with decreasing grain size. (author)

Results from the search-lidar demonstrator project for detection of small Sea-Surface targets

NARCIS (Netherlands)

Heuvel, J.C. van den; Putten, F.J.M. van; Cohen, L.H.; Kemp, R.A.W.; Franssen, G.C.

2009-01-01

Coastal surveillance and naval operations in the littoral both have to deal with the threat of small sea-surface targets. These targets have a low radar cross-section and a low velocity that makes them hard to detect by radar. Typical threats include jet skis, FIAC's, and speedboats. Previous lidar

The Role of Conjoining (Tie) Channels in Lowland Floodplain Development and Lake Infilling

Science.gov (United States)

Rowland, J. C.; Dietrich, W. E.; Day, G.; Lepper, K.; Wilson, C. J.

2003-12-01

In simple models of lowland river systems, water and sediment enter the main stem via tributary and secondary channels and are only redistributed to the floodplain during overbank and crevasse splay events. Along numerous river systems across the globe, however, water and sediment are regularly exchanged between the river and off river water bodies via stable, narrow channels. These channels, known as tie channels on the Fly River in Papua New Guinea and batture channels along the lower Mississippi, are largely overlooked but important components of floodplain sediment dispersal where they exist. These channels become pathways of sediment dispersal to the floodplain system when elevated river stages force sediment-laden flows into the off-river water bodies. On the Fly River, it is estimated that about 50% of the sediment delivery to the floodplain is via these channels, and along low gradient tributary channels during flood driven flow reversals. During low flow, tie channels serve to drain the floodplain. With the outgoing flows, large amounts sediment can be carried and lost to the floodplain; floodplain lakes progressively infill with sediment as the mouth of these channels steadily prograde lakeward. These lake deposits not only become significant stratigraphic components of floodplains (traditionally referred to as clay plugs), but are important local sinks recording hundreds to thousands of years of river history. As with all sinks, the proper interpretation of these stratigraphic records requires understanding the processes by which sediment is delivered to the sink and how these processes alter the paleohydraulic and climatic signals of interest. We have conducted field investigations of conjoining channels in Papua New Guinea (the Fly and Strickland Rivers), Louisiana (Raccourci Old River ~ 65 km upriver of Baton Rouge) and Alaska (Birch Creek). These field investigations include extensive surveys of both cross and along channel morphological trends

MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

Energy Technology Data Exchange (ETDEWEB)

Walsh, Edward G., E-mail: edward_walsh@brown.edu [Brown University, Department of Neuroscience (United States); Mills, David R. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Lim, Sierin; Sana, Barindra [Nanyang Technological University, Division of Bioengineering (Singapore); Brilliant, Kate E. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Park, William K. C. [Rhode Island Hospital, Department of Diagnostic Imaging (United States)

2013-01-15

A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r{sub 1} and r{sub 2}. The r{sub 1} and r{sub 2} values of the uniformly distributed modified ferritin were significantly higher (r{sub 1} = 1,290 mM{sup -1} s{sup -1} and r{sub 2} = 5,740 mM{sup -1} s{sup -1}) than values observed for wild-type ferritin (e.g., horse spleen, r{sub 1} = 0.674 mM{sup -1} s{sup -1}, r{sub 2} = 95.54 mM{sup -1} s{sup -1}). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T{sub 2} contrast with negligible T{sub 1} effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.

Determining the concentration of individual eruptive events of the CAMP: Distinguishing interflow hiatuses from subterranean alteration and void infilling.

Science.gov (United States)

Olsen, P. E.; Kent, D. V.; Et-Touhami, M.

2012-04-01

More important than the total volume of eruptives in a LIP is the concentration in time of individual eruptions with timescales relevant for environmental change. In CAMP lavas, interflow sedimentary and reddened levels are interpreted as evidence of significant time between flows of hundreds to thousands of years allowing soil development and sediment deposition. Additionally, cross-cutting or enclosed sediment bodies, and basalt and sediment mixtures are interpreted as clastic intrusions and phreatic mixing (peperites). Here we show that most such occurrences are more consistent with post-emplacement alteration and void infill by sediment. Criteria for recognizing void fillings in cross-cutting, enclosed or mixed basalt include: 1) paleo-horizontal sediment stratification independent of basalt clasts or void walls - i.e., geopedal; 2) presence of clasts alien to underlying units such as lithic clasts or bones, the latter analogous to karst occurrences; 3) presence of current structures such as ripples; 4) lack of basalt chill margins; and 5) preserved stratigraphy related to overlying units. Criteria for recognizing flow-contact-parallel sediment bodies and reddened and altered contacts as post-emplacement alteration and void infill include: 1) reddening and alteration of both the upper surface of the older flow AND the lower surface of the overlying flow (caused by post-emplacement ground-water-flow); 2) presence of clasts derived from the bottom of the overlying flow; 3) location of tabular sediment bodies within blisters and paleosurface-parallel crack-sheets of the older flow, rather than at the contact between flows; and 4) physical connection between paleosurface-parallel sediment bodies and sediment bodies that cross-cutting the younger flow exhibiting post-emplacement features described above. Features that might be indicative of deposition at the land surface but are not include: 1) roots, which can penetrate for tens of meters through sediment

Commercial incineration demonstration

International Nuclear Information System (INIS)

Borduin, L.C.; Neuls, A.S.

1981-01-01

Low-level radioactive wastes (LLW) generated by nuclear utilities presently are shipped to commercial burial grounds for disposal. Substantially increasing shipping and disposal charges have sparked renewed industry interest in incineration and other advanced volume reduction techniques as potential cost-saving measures. Repeated inquiries from industry sources regarding LLW applicability of the Los Alamos controlled-air incineration (CAI) design led DOE to initiate this commercial demonstration program in FY-1980. The selected program approach to achieving CAI demonstration at a utility site is a DOE sponsored joint effort involving Los Alamos, a nuclear utility, and a liaison subcontractor. Required development tasks and responsibilities of the particpants are described. Target date for project completion is the end of FY-1985

High or Low Target Prevalence Increases the Dual-Target Cost in Visual Search

Science.gov (United States)

Menneer, Tamaryn; Donnelly, Nick; Godwin, Hayward J.; Cave, Kyle R.

2010-01-01

Previous studies have demonstrated a dual-target cost in visual search. In the current study, the relationship between search for one and search for two targets was investigated to examine the effects of target prevalence and practice. Color-shape conjunction stimuli were used with response time, accuracy and signal detection measures. Performance…

First demonstration of multi-MeV proton acceleration from a cryogenic hydrogen ribbon target

Science.gov (United States)

Kraft, Stephan D.; Obst, Lieselotte; Metzkes-Ng, Josefine; Schlenvoigt, Hans-Peter; Zeil, Karl; Michaux, Sylvain; Chatain, Denis; Perin, Jean-Paul; Chen, Sophia N.; Fuchs, Julien; Gauthier, Maxence; Cowan, Thomas E.; Schramm, Ulrich

2018-04-01

We show efficient laser driven proton acceleration up to 14 MeV from a 62 μm thick cryogenic hydrogen ribbon. Pulses of the short pulse laser ELFIE at LULI with a pulse length of ≈350 fs at an energy of 8 J per pulse are directed onto the target. The results are compared to proton spectra from metal and plastic foils with different thicknesses and show a similarly good performance both in maximum energy as well as in proton number. Thus, this target type is a promising candidate for experiments with high repetition rate laser systems.

LIFE Target Fabrication Research Plan Sept 2008

Energy Technology Data Exchange (ETDEWEB)

Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

2008-11-10

The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

Demonstrator for objective driven SON operation

NARCIS (Netherlands)

Schmelz, L.C.; Eisenblätter, A.; Hahn, S.; Kürner, T.; Litjens, R.; Lobinger, A.; Lohmüller, S.; Sas, B.; Türke, U.

2014-01-01

The demonstrator shows a self-management system for heterogeneous mobile wireless networks that uses context-specific and weighted Key Performance Indicator (KPI) target values defined by the operator to automatically and autonomously configure and control the operation of Self-Organising Network

Pecan Street Grid Demonstration Program. Final technology performance report

Energy Technology Data Exchange (ETDEWEB)

None, None

2015-02-10

This document represents the final Regional Demonstration Project Technical Performance Report (TPR) for Pecan Street Inc.’s (Pecan Street) Smart Grid Demonstration Program, DE-OE-0000219. Pecan Street is a 501(c)(3) smart grid/clean energy research and development organization headquartered at The University of Texas at Austin (UT). Pecan Street worked in collaboration with Austin Energy, UT, Environmental Defense Fund (EDF), the City of Austin, the Austin Chamber of Commerce and selected consultants, contractors, and vendors to take a more detailed look at the energy load of residential and small commercial properties while the power industry is undergoing modernization. The Pecan Street Smart Grid Demonstration Program signed-up over 1,000 participants who are sharing their home or businesses’s electricity consumption data with the project via green button protocols, smart meters, and/or a home energy monitoring system (HEMS). Pecan Street completed the installation of HEMS in 750 homes and 25 commercial properties. The program provided incentives to increase the installed base of roof-top solar photovoltaic (PV) systems, plug-in electric vehicles with Level 2 charging, and smart appliances. Over 200 participants within a one square mile area took advantage of Austin Energy and Pecan Street’s joint PV incentive program and installed roof-top PV as part of this project. Of these homes, 69 purchased or leased an electric vehicle through Pecan Street’s PV rebate program and received a Level 2 charger from Pecan Street. Pecan Street studied the impacts of these technologies along with a variety of consumer behavior interventions, including pricing models, real-time feedback on energy use, incentive programs, and messaging, as well as the corresponding impacts on Austin Energy’s distribution assets.The primary demonstration site was the Mueller community in Austin, Texas. The Mueller development, located less than three miles from the Texas State Capitol

Pilots' Attention Distributions Between Chasing a Moving Target and a Stationary Target.

Science.gov (United States)

Li, Wen-Chin; Yu, Chung-San; Braithwaite, Graham; Greaves, Matthew

2016-12-01

Attention plays a central role in cognitive processing; ineffective attention may induce accidents in flight operations. The objective of the current research was to examine military pilots' attention distributions between chasing a moving target and a stationary target. In the current research, 37 mission-ready F-16 pilots participated. Subjects' eye movements were collected by a portable head-mounted eye-tracker during tactical training in a flight simulator. The scenarios of chasing a moving target (air-to-air) and a stationary target (air-to-surface) consist of three operational phases: searching, aiming, and lock-on to the targets. The findings demonstrated significant differences in pilots' percentage of fixation during the searching phase between air-to-air (M = 37.57, SD = 5.72) and air-to-surface (M = 33.54, SD = 4.68). Fixation duration can indicate pilots' sustained attention to the trajectory of a dynamic target during air combat maneuvers. Aiming at the stationary target resulted in larger pupil size (M = 27,105, SD = 6565), reflecting higher cognitive loading than aiming at the dynamic target (M = 23,864, SD = 8762). Pilots' visual behavior is not only closely related to attention distribution, but also significantly associated with task characteristics. Military pilots demonstrated various visual scan patterns for searching and aiming at different types of targets based on the research settings of a flight simulator. The findings will facilitate system designers' understanding of military pilots' cognitive processes during tactical operations. They will assist human-centered interface design to improve pilots' situational awareness. The application of an eye-tracking device integrated with a flight simulator is a feasible and cost-effective intervention to improve the efficiency and safety of tactical training.Li W-C, Yu C-S, Braithwaite G, Greaves M. Pilots' attention distributions between chasing a moving target and a stationary target. Aerosp Med

G-quadruplex aptamer targeting Protein A and its capability to detect Staphylococcus aureus demonstrated by ELONA.

Science.gov (United States)

Stoltenburg, Regina; Krafčiková, Petra; Víglaský, Viktor; Strehlitz, Beate

2016-09-21

Aptamers for whole cell detection are selected mostly by the Cell-SELEX procedure. Alternatively, the use of specific cell surface epitopes as target during aptamer selections allows the development of aptamers with ability to bind whole cells. In this study, we integrated a formerly selected Protein A-binding aptamer PA#2/8 in an assay format called ELONA (Enzyme-Linked OligoNucleotide Assay) and evaluated the ability of the aptamer to recognise and bind to Staphylococcus aureus presenting Protein A on the cell surface. The full-length aptamer and one of its truncated variants could be demonstrated to specifically bind to Protein A-expressing intact cells of S. aureus, and thus have the potential to expand the portfolio of aptamers that can act as an analytical agent for the specific recognition and rapid detection of the bacterial pathogen. The functionality of the aptamer was found to be based on a very complex, but also highly variable structure. Two structural key elements were identified. The aptamer sequence contains several G-clusters allowing folding into a G-quadruplex structure with the potential of dimeric and multimeric assembly. An inverted repeat able to form an imperfect stem-loop at the 5'-end also contributes essentially to the aptameric function.

Hybrid reactors: recent progress of a demonstration pilot

International Nuclear Information System (INIS)

Billebaud, Annick

2006-12-01

Accelerator driven sub-critical reactors are subject of many research programmes since more than ten years, with the aim of testing the feasibility of the concept as well as their efficiency as a transmutation tool. Several key points like the accelerator, the spallation target, or neutronics in a subcritical medium were investigated extensively these last years, allowing for technological choices and the design of a low power European demonstration ADS (a few tens of MWth). Programmes dedicated to subcritical reactor piloting proposed a monitoring procedure to be validated in forthcoming experiments. Accelerator R and D provided the design of a LINAC for an ADS and research work on accelerator reliability is going on. A spallation target was operated at PSI and the design of a windowless target is in progress. All this research work converges to the design of a European demonstration ADS, the ETD/XT-ADS, which could be the Belgian MYRRHA project. (author)

Target-to-Target Repetition Cost and Location Negative Priming Are Dissociable: Evidence for Different Mechanisms

Science.gov (United States)

Chao, Hsuan-Fu

2011-01-01

In a location-selection task, the repetition of a prior distractor location as the target location would slow down the response. This effect is termed the location negative priming (NP) effect. Recently, it has been demonstrated that repetition of a prior target location as the current target location would also slow down response. Because such…

Experimental study on the influence of the opening in brick-masonry wall to seismic performance of reinforced concrete frame structures

Science.gov (United States)

Maidiawati, Tanjung, Jafril; Medriosa, Hamdeni

2017-10-01

Reinforced concrete (RC) frame structures with brick-masonry infills are commonly used in developing countries and high-risk seismic area, such as Indonesia. Significant researches have been carried out for studying the seismic performance of RC frame structures with brick-masonry infills. Only few of them focused on effects of the opening in the brick-masonry infill to the seismic performance of the RC frame structures. The presence of opening in brick-masonry infill is often used for placing doors and windows as well, however, it may reduce the seismic performance of the RC frame structure. In the current study, they influence of the opening in brick-masonry infills to the seismic performance RC frame structure will experimentally evaluated. Five of 1/4-scaled single story and single bay RC frame specimens were prepared, i.e. an RC bare frame, a clay brick-masonry infilled RC frame and three of clay brick-masonry infilled RC frame with openings in the brick-masonry infills. The last three specimens were clay brick infilled RC frame with a center opening, clay brick infilled RC frame with two openings used for placing the windows and clay brick infilled RC frame with opening for placing the door. The specimens pushed over by applying the static monotonic lateral load to the upper beam of the RC frame structures. The incremental of the lateral load and the lateral displacement of RC frame's column was recorded during test. The crack propagation and the major cracks were also observed to identify the mechanism failure of specimens. As the results, the opening in the brick-masonry wall controls the failure mechanism, the lateral strength and the stiffness of the overall of infilled RC frame structure. The diagonal shear crack pattern was found on brick-masonry wall without opening, on other hand the different crack patterns were observed on brick-masonry wall with openings. Although the opening in the brick masonry infill reduced the lateral strength and stiffness of

JAERI/KEK target material program overview

International Nuclear Information System (INIS)

Kikuchi, Kenji; Kogawa, Hiroyuki; Sasa, Toshinobu

2001-01-01

Mercury target was designed for megawatt neutron scattering facility in JAERI/KEK spallation neutron source. The incident proton energy and current are 3 GeV and 333 μA, respectively: the total proton energy is 1 MW in short pulses at a frequency of 25 Hz. Under the guide rule the mercury target was designed: the maximum temperature of target window is 170degC and induced stresses for the type 316 stainless steel are within limits of design guide. In order to demonstrate ADS (Accelerator Driven Systems) transmutation critical and engineering facilities have been designed conceptually. In engineering facility lead-bismuth spallation target station is to be planned. Objective to build the facility is to demonstrate material irradiation. According to neutronics calculation irradiation damage of the target vessel window will be 5 dpa per year. (author)

A method for comparing impacts with real targets to impacts onto the IAEA unyielding target

International Nuclear Information System (INIS)

Ammerman, D.J.

1991-01-01

The severity of the IAEA accident conditions test requirement (IAEA 1990) of an impact onto an essentially unyielding target from a drop height of 9 meters encompasses a large fraction of all real world impacts. This is true, in part, because of the unyielding nature of the impact target. Impacts onto the unyielding target have severities equivalent to higher velocity impacts onto real targets which are not unyielding. The severity of impacts with yielding targets is decreased by the amount of the impact energy absorbed in damaging the target. In demonstrating the severity of the regulatory impact event it is advantageous to be able to relate this impact onto an essentially unyielding target to impacts with yielding targets

Demonstration of the CDMA-mode CAOS smart camera.

Science.gov (United States)

Riza, Nabeel A; Mazhar, Mohsin A

2017-12-11

Demonstrated is the code division multiple access (CDMA)-mode coded access optical sensor (CAOS) smart camera suited for bright target scenarios. Deploying a silicon CMOS sensor and a silicon point detector within a digital micro-mirror device (DMD)-based spatially isolating hybrid camera design, this smart imager first engages the DMD starring mode with a controlled factor of 200 high optical attenuation of the scene irradiance to provide a classic unsaturated CMOS sensor-based image for target intelligence gathering. Next, this CMOS sensor provided image data is used to acquire a focused zone more robust un-attenuated true target image using the time-modulated CDMA-mode of the CAOS camera. Using four different bright light test target scenes, successfully demonstrated is a proof-of-concept visible band CAOS smart camera operating in the CDMA-mode using up-to 4096 bits length Walsh design CAOS pixel codes with a maximum 10 KHz code bit rate giving a 0.4096 seconds CAOS frame acquisition time. A 16-bit analog-to-digital converter (ADC) with time domain correlation digital signal processing (DSP) generates the CDMA-mode images with a 3600 CAOS pixel count and a best spatial resolution of one micro-mirror square pixel size of 13.68 μm side. The CDMA-mode of the CAOS smart camera is suited for applications where robust high dynamic range (DR) imaging is needed for un-attenuated un-spoiled bright light spectrally diverse targets.

Demonstration of Autonomous Rendezvous Technology (DART) Project Summary

Science.gov (United States)

Rumford, TImothy E.

2003-01-01

Since the 1960's, NASA has performed numerous rendezvous and docking missions. The common element of all US rendezvous and docking is that the spacecraft has always been piloted by astronauts. Only the Russian Space Program has developed and demonstrated an autonomous capability. The Demonstration of Autonomous Rendezvous Technology (DART) project currently funded under NASA's Space Launch Initiative (SLI) Cycle I, provides a key step in establishing an autonomous rendezvous capability for the United States. DART's objective is to demonstrate, in space, the hardware and software necessary for autonomous rendezvous. Orbital Sciences Corporation intends to integrate an Advanced Video Guidance Sensor and Autonomous Rendezvous and Proximity Operations algorithms into a Pegasus upper stage in order to demonstrate the capability to autonomously rendezvous with a target currently in orbit. The DART mission will occur in April 2004. The launch site will be Vandenburg AFB and the launch vehicle will be a Pegasus XL equipped with a Hydrazine Auxiliary Propulsion System 4th stage. All mission objectives will be completed within a 24 hour period. The paper provides a summary of mission objectives, mission overview and a discussion on the design features of the chase and target vehicles.

TargetSpy: a supervised machine learning approach for microRNA target prediction.

Science.gov (United States)

Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

2010-05-28

Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila

TargetSpy: a supervised machine learning approach for microRNA target prediction

Directory of Open Access Journals (Sweden)

Langenberger David

2010-05-01

Full Text Available Abstract Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I no seed match requirement, II seed match requirement, and III conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on

Design of the FMIT lithium target

International Nuclear Information System (INIS)

Hassberger, J.A.; Annese, C.E.; Greenwell, R.K.; Ingham, J.G.; Miles, R.R.; Miller, W.C.

1981-01-01

Development of the liquid lithium target for the Fusion Materials Irradiation Test (FMIT) Facility is described. The target concept, major design goals and design requirements are presented. Progress made in the research and development areas leading to detailed design of the target is discussed. This progress, including experimental and analytic results, demonstrates that the FMIT target design is capable of meeting its major design goals and requirements

Customized three-dimensional printed optical phantoms with user defined absorption and scattering

Science.gov (United States)

Pannem, Sanjana; Sweer, Jordan; Diep, Phuong; Lo, Justine; Snyder, Michael; Stueber, Gabriella; Zhao, Yanyu; Tabassum, Syeda; Istfan, Raeef; Wu, Junjie; Erramilli, Shyamsunder; Roblyer, Darren M.

2016-03-01

The use of reliable tissue-simulating phantoms spans multiple applications in spectroscopic imaging including device calibration and testing of new imaging procedures. Three-dimensional (3D) printing allows for the possibility of optical phantoms with arbitrary geometries and spatially varying optical properties. We recently demonstrated the ability to 3D print tissue-simulating phantoms with customized absorption (μa) and reduced scattering (μs`) by incorporating nigrosin, an absorbing dye, and titanium dioxide (TiO2), a scattering agent, to acrylonitrile butadiene styrene (ABS) during filament extrusion. A physiologically relevant range of μa and μs` was demonstrated with high repeatability. We expand our prior work here by evaluating the effect of two important 3D-printing parameters, percent infill and layer height, on both μa and μs`. 2 cm3 cubes were printed with percent infill ranging from 10% to 100% and layer height ranging from 0.15 to 0.40 mm. The range in μa and μs` was 27.3% and 19.5% respectively for different percent infills at 471 nm. For varying layer height, the range in μa and μs` was 27.8% and 15.4% respectively at 471 nm. These results indicate that percent infill and layer height substantially alter optical properties and should be carefully controlled during phantom fabrication. Through the use of inexpensive hobby-level printers, the fabrication of optical phantoms may advance the complexity and availability of fully customizable phantoms over multiple spatial scales. This technique exhibits a wider range of adaptability than other common methods of fabricating optical phantoms and may lead to improved instrument characterization and calibration.

Full-Carpet Design of a Low-Boom Demonstrator Concept

Science.gov (United States)

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

2015-01-01

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

Infill and mire evolution of a typical kettle hole: young ages at great depths (Jackenmoos, Austria)

Science.gov (United States)

Götz, Joachim; Salcher, Bernhard

2015-04-01

Kettle holes are very common features in proglacial environments. Myriads of small, often circular shaped lakes are indicative of dead ice slowly melting out after the collapse of glaciers and subsequent burial of glaciofluvial sediments. Many of these lakes transformed into mires during the Postglacial and the Holocene. Still, little is known about the mechanisms leading to mire formation in such environments. We aim to analyse the shape and the postglacial history of infilling and peat accumulation of a typical dead ice kettle using 2D resistivity surveying, core-drilling, 14C dating and palynologic analyses. The kettle hole mire is located within a small kame delta deposit just south of the LGM extend of the Salzach Piedmont glacier (Austria/Germany). Today, the mire is a spot of exceptional high biodiversity and under protection. Sediment core samples extracted in the deepest (c. 10-14 m) and central part of the kettle directly overly lacustrine fine sediments and yielded young ages covering the subatlantic period only. Young ages are in agreement with palynologic results comprising e.g. pollen of secale (rye) and juglans (walnut). However, these deposits are situated beneath a massive water body (10 m), only covered by a thin floating mat. A second, more distally situated drill core indicates the thinning of this water body at the expense of peat deposits covering the Late Glacial to Middle Holocene. Multiple 2D resistivity data support drilling information and enabled us to reconstruct the shape of the basin. The transition from lacustrine sediments to the water body above is characterised by a sharp increase in resistivity. Furthermore, the resistivity pattern within the entire kettle indicates an increase towards the centre, most probably as a result of the changing nutrient content. The postglacial evolution of the mire is in agreement with the concept of "floating mat terrestrialisation", representing a horizontal growth of the floating mat from the edges

The drug target genes show higher evolutionary conservation than non-target genes.

Science.gov (United States)

Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

2016-01-26

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

Solar Europe industry initiative: research technology development and demonstration in support of 2020 and long-term targets

NARCIS (Netherlands)

Sinke, W.C.; Fraile Montoro, D.; Despotou, E.; Nowak, S.; Perezagua, E.

2010-01-01

The European Union has set an ambitious target for the implementation of renewable energy technologies by 2020, i.e. a share of 20% of the total energy consumption. In support of these targets the Strategic Energy Technology (SET) Plan has been initiated by the European Commission. One of the key

TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

Directory of Open Access Journals (Sweden)

Yi-An Chen

Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.

Targeted Therapies for Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E

Targeted therapies have become standard therapies for patients with non-small cell lung cancer (NSCLC). A phase III trial of carboplatin and paclitaxel with and without bevacizumab in patients with advanced NSCLC with non-squamous histology demonstrated a statistically significant improvement in efficacy. In patients with NSCLC with an activating epidermal growth factor receptor (EGFR) mutation (defined as exon 19 deletion and exon 21 L858R point mutation), phase III trials of EGFR tyrosine kinase inhibitors (TKI) compared to platinum-based chemotherapy have demonstrated superior efficacy in the first-line setting. In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting. A second-generation ALK inhibitor, ceritinib, is available for patients who have progressed after or were intolerant of crizotinib. Crizotinib has also demonstrated activity on patients with ROS1 rearrangements, and BRAF inhibitors (dabrafenib, vemurafenib) have demonstrated activity in patients with NSCLC with BRAF V600E mutation. The oncogenic mutations that are susceptible to targeted therapy are mainly found in non-squamous NSCLC. The development of targeted therapy in patients with squamous NSCLC has been more challenging due to the genomic complexity observed in the squamous histology and the low prevalence of EGFR, ALK, and ROS1 molecular alterations. A phase III trial of cisplatin and gemcitabine with and without necitumumab in patients with advanced NSCLC with squamous histology demonstrated a statistically significant improvement in progression-free and overall survival.

A 20 kw beam-on-target test of a high-power liquid lithium target for RIA

International Nuclear Information System (INIS)

Reed, Claude B.; Nolen, Jerry A.; Specht, James R.; Novick, Vincent J.; Plotkin, Perry

2004-01-01

The high-power heavy-ion beams produced by the Rare Isotope Accelerator (RIA) driver linac have large energy deposition density in solids and in many cases no solid materials would survive the full beam power. Liquid lithium technology has been proposed to solve this problem in RIA. Specifically, a windowless target for the production of radioactive ions via fragmentation, consisting of a jet of about 3 cm thickness of flowing liquid lithium, exposed to the beamline vacuum [1,2] is being developed. To demonstrate that power densities equivalent to a 200-kW RIA uranium beam, deposited in the first 4 mm of a flowing lithium jet, can be handled by the windowless target design, a high power 1 MeV Dynamitron was leased and a test stand prepared to demonstrate the target's capability of absorbing and carrying away a 20kW heat load without disrupting either the 5 mm x 10 mm flowing lithium jet target or the beam line vacuum

Fabrication of cryogenic inertial-confinement-fusion targets using target free-fall technique. Report No. 2-82

International Nuclear Information System (INIS)

Kim, K.; Murphy, M.J.

1982-04-01

Techniques for fabricating cryogenic inertial confinement fusion targets (i.e., spherical shells containing a uniform layer of DT ice) are investigated using target free-fall concept. Detection and characterization of the moving targets are effected by optoelectronic means, of which the principal is an RF ac-interferometer. This interferometer system demonstrates, for the first time, the speed capabilities of the phase-modulation ac-interferometry. New techiques developed for handling, holding, launching, and transporting targets are also described. Results obtained at both room and cryogenic temperatures are presented

Demonstrator study for micro-ranging-laser device

Science.gov (United States)

Henkel, Hartmut; Bernhardt, Bodo; Pereira do Carmo, J.

2017-11-01

Within ESA's Innovation Triangle Initiative (ITI) a demonstrator breadboard for a micro-ranging-laser device "MYLRAD" has been developed. Its working principle is the measurement of the round-trip delay time of a laser beam as a phase shift. The demonstrator consists of the laser diode (30 mW, square wave AM), optics, APD detector, narrowband preamplifier, limiter, and a phase digitiser based on a novel noise-shaping synchroniser (NSS) circuit; this works without ADCs and can be built from rad-hard components for space. The system timing and the digitiser algorithm are performed by an FPGA. The demonstrator has been tested at ranges from 1 m to 30 m. With a static non-cooperative target an RMS noise of 1 mm at a result rate of 60 Hz was reached. The demonstrator needs less than 2.5 W power.

The mechanism of gene targeting in human somatic cells.

Directory of Open Access Journals (Sweden)

Yinan Kan

2014-04-01

Full Text Available Gene targeting in human somatic cells is of importance because it can be used to either delineate the loss-of-function phenotype of a gene or correct a mutated gene back to wild-type. Both of these outcomes require a form of DNA double-strand break (DSB repair known as homologous recombination (HR. The mechanism of HR leading to gene targeting, however, is not well understood in human cells. Here, we demonstrate that a two-end, ends-out HR intermediate is valid for human gene targeting. Furthermore, the resolution step of this intermediate occurs via the classic DSB repair model of HR while synthesis-dependent strand annealing and Holliday Junction dissolution are, at best, minor pathways. Moreover, and in contrast to other systems, the positions of Holliday Junction resolution are evenly distributed along the homology arms of the targeting vector. Most unexpectedly, we demonstrate that when a meganuclease is used to introduce a chromosomal DSB to augment gene targeting, the mechanism of gene targeting is inverted to an ends-in process. Finally, we demonstrate that the anti-recombination activity of mismatch repair is a significant impediment to gene targeting. These observations significantly advance our understanding of HR and gene targeting in human cells.

Independent review of Oak Ridge HCTW test program and development of seismic evaluation criteria

International Nuclear Information System (INIS)

1995-05-01

Many of the existing buildings at the Oak Ridge Y-12 Plant are steel frame construction with unreinforced hollow clay tile infill walls (HCTW). The HCTW infill provides some lateral seismic resistance to the design/evaluation basis earthquake; however acceptance criteria for this construction must be developed. The basis for the development of seismic criteria is the Oak Ridge HCTW testing and analysis program and the target performance goals of DOE 5480.28 and DOE-STD-1020-94. This report documents and independent review of the testing and analysis program and development of recommended acceptance criteria for Oak Ridge HCTW construction. The HCTW test program included ''macro'' wall in-plane and out-of-plane tests, full-scale wall in-plane and out-of-plane tests, in-situ out-of-plane test, shake table tests, and masonry component tests

Internal targets for LEAR

International Nuclear Information System (INIS)

Kilian, K.; Gspann, J.; Mohl, D.; Poth, H.

1984-01-01

This chapter considers the use of thin internal targets in conjunction with phase-space cooling at the Low-Energy Antiproton Ring (LEAR). Topics considered include the merits of internal target operation; the most efficient use of antiprotons and of proton synchrotron (PS) protons, highest center-of-mass (c.m.) energy resolution; highest angular resolution and access to extreme angles; the transparent environment for all reaction products; a windowless source and pure targets; highest luminosity and count rates; access to lowest energies with increasing resolution; internal target thickness and vacuum requirements; required cooling performance; and modes of operation. It is demonstrated that an internal target in conjunction with phase-space cooling has the potential of better performance in terms of the economic use of antiprotons and consequently of PS protons; energy resolution; angular resolution; maximum reaction rate capability (statistical precision); efficient parasitic operation; transparency of the target for reaction products; access to low energies; and the ease of polarized target experiments. It is concluded that all p - experiments which need high statistics and high p - flux, such as studies of rare channels or broad, weak resonance structures, would profit from internal targets

Molecular Targets for Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Mather, S.J.

2009-01-01

radiolabelled regulatory peptides and their metabolically stabilised analogues. Antigen epitopes: Antibodies, as unlabelled biological drugs, are becoming of increasing interest. They exert an antibody-dependent cellular cytotoxicity which leads to lysis of tumour cells. Radiolabelled versions of these (and other) antibodies are being developed worldwide. The disadvantage of the long circulating time of antibodies can be solved by engineering fragments such as diabodies, bivalent single chain variable fragments (scFv), minibodies or by pretargeting approaches. Transmembrane transporters: Other interesting targets are transporters for radiolabelled amino acids and nutrients. Cancer cells require an increased supply of many such nutrients and obtain these by increased expression of some types of amino-acid transporter. A more detailed analysis of the relationship between amino-acid uptake and transporter expression in normal and malignant cells would be very valuable in identifying the clinical therapeutic potential of this class of tracer. Tumour blood supply: Tumours require an efficient blood supply to grow and metastatise and active angiogenesis of new blood vessels is a feature of many tumours. Specific receptors expressed during this process represent a novel class of targets for TRT. Extra-cellular matrix: Recently, another relevant class of target antigens has raised interest. Lectins, or carbohydrate binding proteins, recognize specific oligosaccharide structures on glycoproteins and glycolipids. It is well known that protein and lipid glycosylation are consistently altered in cancer cells for the aberrant activity of specific glycosyltransferase and glycosydases. Experimental evidence demonstrated that tumor growth and progression may depend, at least in part, on the presence of altered glycoproteins on the cell surface, which can mediate aberrant receptor-ligand interactions. (author)

High-efficiency target-ion sources for RIB generation

International Nuclear Information System (INIS)

Alton, G.D.

1993-01-01

A brief review is given of high-efficiency ion sources which have been developed or are under development at ISOL facilities which show particular promise for use at existing, future, or radioactive ion beam (RIB) facilities now under construction. Emphasis will be placed on those sources which have demonstrated high ionization efficiency, species versatility, and operational reliability and which have been carefully designed for safe handling in the high level radioactivity radiation fields incumbent at such facilities. Brief discussions will also be made of the fundamental processes which affect the realizable beam intensities in target-ion sources. Among the sources which will be reviewed will be selected examples of state-of-the-art electron-beam plasma-type ion sources, thermal-ionization, surface-ionization, ECR, and selectively chosen ion source concepts which show promise for radioactive ion beam generation. A few advanced, chemically selective target-ion sources will be described, such as sources based on the use of laser-resonance ionization, which, in principle, offer a more satisfactory solution to isobaric contamination problems than conventional electromagnetic techniques. Particular attention will be given to the sources which have been selected for initial or future use at the Holifield Radioactive Ion Beam Facility now under construction at the Oak Ridge National Laboratory

HIRFL–CSR internal cluster target

International Nuclear Information System (INIS)

Shao, Caojie; Lu, Rongchun; Cai, Xiaohong; Yu, Deyang; Ruan, Fangfang; Xue, Yingli; Zhang, Jianming; Torpokov, D.K.; Nikolenko, D.

2013-01-01

Highlights: • An internal cluster target was built and installed at HIRFL–CSR. • The target thickness for H 2 amounts up to 6.6 × 10 12 atoms/cm 2 . • The feasibility and stability of the internal cluster target were verified by on-line experiments. -- Abstract: Since HIRFL–CSR internal cluster target was built, it has played a key role in in-ring experiments at HIRFL–CSR. So far it have been operated with five gas species as targets for scattering experiments, i.e. hydrogen, nitrogen, argon, neon, and krypton. The obtained highest thickness for hydrogen target amounts up to 10 12 atoms/cm 2 , and those of other targets are larger than 10 13 atoms/cm 2 with the background pressure of 10 −11 mbar in CSR. The target thickness can be varied by regulating the nozzle temperature and pressure of the inlet gas. The first online internal target experiment dedicated to investigate radioactive electron capture (REC) process with Xe 54+ ions colliding with the nitrogen target demonstrated the stability and reliability of the internal target system. In addition, hydrogen and krypton were also tested online in recent experiments, which indicate the target system can meet experimental requirements for the thickness of target, pressure in scattering chamber, and long-term stability

Improving Global Multi-target Tracking with Local Updates

DEFF Research Database (Denmark)

Milan, Anton; Gade, Rikke; Dick, Anthony

2014-01-01

-target tracker, if they result in a reduction in the global cost function. Since tracking failures typically arise when targets become occluded, we propose a local data association scheme to maintain the target identities in these situations. We demonstrate a reduction of up to 50% in the global cost function...

Moderator Demonstration Facility Design and Optimization

Energy Technology Data Exchange (ETDEWEB)

McClanahan, Tucker C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gallmeier, Franz X. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Iverson, Erik B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-02-01

The Spallation Neutron Source (SNS) facility at Oak Ridge National Laboratory (ORNL) is implementing a Moderator Demonstration Facility (MDF) to demonstrate the performance characteristics of advanced moderators central to the Second Target Station (STS) for SNS. The MDF will use the "spare" front-end installation within the SNS accelerator support complex – an ion source, radio-frequency quadrupole (RFQ) accelerator, and medium-energy beam transport (MEBT) chopper - to provide a 2.5 MeV proton beam of peak current 50 mA and maximum pulse length of less than 10 s at a repetition rate of no more than 60 Hz to a suitable neutron-producing target to demonstrate those aspects of moderator performance necessary to meet the goals of the STS design e ort. The accelerator beam parameters are not open to variation beyond that described above - they are fixed by the nature of the spare front-end installation (the Integrated Test Stand Facility; ITSF). Accordingly, there are some neutronic challenges in developing prototypic moderator illumination from a very non-prototypic primary neutron source; the spallation source we are attempting to mimic has an extended neutron source volume approximately 40 cm long (in the direction of the proton beam), approximately 10 cm wide (horizontally transverse to the proton beam) and approximately 5 cm high (vertically transverse to the proton beam), and an isotropic evaporation energy spectrum with mean energy above 1 MeV. In contrast, the primary neutron source available from the 7Li(p,n) reaction (the most prolific at 2.5 MeV proton energy by more than an order of magnitude) is strongly anisotropic, with an energy spectrum that is both strongly dependent on emission angle and kinematically limited to less than 700 keV, and the interaction zone between the incident protons and any target material (neutron-producing or not) is intrinsically limited to a few tens of microns. The MDF will be unique and innovative amongst the world�

Low-enriched uranium high-density target project. Compendium report

Energy Technology Data Exchange (ETDEWEB)

Vandegrift, George; Brown, M. Alex; Jerden, James L.; Gelis, Artem V.; Stepinski, Dominique C.; Wiedmeyer, Stanley; Youker, Amanda; Hebden, Andrew; Solbrekken, G; Allen, C; Robertson., D; El-Gizawy, Sherif; Govindarajan, Srisharan; Hoyer, Annemarie; Makarewicz, Philip; Harris, Jacob; Graybill, Brian; Gunn, Andy; Berlin, James; Bryan, Chris; Sherman, Steven; Hobbs, Randy; Griffin, F. P.; Chandler, David; Hurt, C. J.; Williams, Paul; Creasy, John; Tjader, Barak; McFall, Danielle; Longmire, Hollie

2016-09-01

At present, most ⁹⁹Mo is produced in research, test, or isotope production reactors by irradiation of highly enriched uranium targets. To achieve the denser form of uranium needed for switching from high to low enriched uranium (LEU), targets in the form of a metal foil (~125-150 µm thick) are being developed. The LEU High Density Target Project successfully demonstrated several iterations of an LEU-fission-based Mo-99 technology that has the potential to provide the world’s supply of Mo-99, should major producers choose to utilize the technology. Over 50 annular high density targets have been successfully tested, and the assembly and disassembly of targets have been improved and optimized. Two target front-end processes (acidic and electrochemical) have been scaled up and demonstrated to allow for the high-density target technology to mate up to the existing producer technology for target processing. In the event that a new target processing line is started, the chemical processing of the targets is greatly simplified. Extensive modeling and safety analysis has been conducted, and the target has been qualified to be inserted into the High Flux Isotope Reactor, which is considered above and beyond the requirements for the typical use of this target due to high fluence and irradiation duration.

Gene silencing in Tribolium castaneum as a tool for the targeted identification of candidate RNAi targets in crop pests.

Science.gov (United States)

Knorr, Eileen; Fishilevich, Elane; Tenbusch, Linda; Frey, Meghan L F; Rangasamy, Murugesan; Billion, Andre; Worden, Sarah E; Gandra, Premchand; Arora, Kanika; Lo, Wendy; Schulenberg, Greg; Valverde-Garcia, Pablo; Vilcinskas, Andreas; Narva, Kenneth E

2018-02-01

RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T 0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.

Long-Lifetime Low-Scatter Neutron Polarization Target

International Nuclear Information System (INIS)

Richardson, Jonathan M.

2004-01-01

Polarized neutrons scattering is an important technology for characterizing magnetic and other materials. Polarized helium three (P-3He) is a novel technology for creating polarized beams and, perhaps more importantly, for the analysis of polarization in highly divergent scattered beams. Analysis of scattered beams requires specialized targets with complex geometries to ensure accurate results. Special materials and handling procedures are required to give the targets a long useful lifetime. In most cases, the targets must be shielded from stray magnetic fields from nearby equipment. SRL has developed and demonstrated hybrid targets made from glass and aluminum. We have also developed and calibrated a low-field NMR system for measuring polarization lifetimes. We have demonstrated that our low-field system is able to measure NMR signals in the presence of conducting (metallic) cell elements. We have also demonstrated a non-magnetic valve that can be used to seal the cells. We feel that these accomplishments in Phase I are sufficient to ensure a successful Phase II program. The commercial market for this technology is solid. There are over nine neutron scattering centers in the US and Canada and over 22 abroad. Currently, the US plans to build a new $1.4B scattering facility called the Spallation Neutron Source (SNS). The technology developed in this project will allow SRL to supply targets to both existing and future facilities. SRL is also involved with the application of P-3He to medical imaging

Autonomous Target Ranging Techniques

DEFF Research Database (Denmark)

Jørgensen, Peter Siegbjørn; Jørgensen, John Leif; Denver, Troelz

2003-01-01

of this telescope, a fast determination of the range to and the motion of the detected targets are important. This is needed in order to prepare the future observation strategy for each target, i.e. when is the closest approach where imaging will be optimal. In order to quickly obtain such a determination two...... ranging strategies are presented. One is an improved laser ranger with an effective range with non-cooperative targets of at least 10,000 km, demonstrated in ground tests. The accuracy of the laser ranging will be approximately 1 m. The laser ranger may furthermore be used for trajectory determination...... of nano-gravity probes, which will perform direct mass measurements of selected targets. The other is triangulation from two spacecraft. For this method it is important to distinguish between detection and tracking range, which will be different for Bering since different instruments are used...

Impact of Target Distance, Target Size, and Visual Acuity on the Video Head Impulse Test.

Science.gov (United States)

Judge, Paul D; Rodriguez, Amanda I; Barin, Kamran; Janky, Kristen L

2018-05-01

The video head impulse test (vHIT) assesses the vestibulo-ocular reflex. Few have evaluated whether environmental factors or visual acuity influence the vHIT. The purpose of this study was to evaluate the influence of target distance, target size, and visual acuity on vHIT outcomes. Thirty-eight normal controls and 8 subjects with vestibular loss (VL) participated. vHIT was completed at 3 distances and with 3 target sizes. Normal controls were subdivided on the basis of visual acuity. Corrective saccade frequency, corrective saccade amplitude, and gain were tabulated. In the normal control group, there were no significant effects of target size or visual acuity for any vHIT outcome parameters; however, gain increased as target distance decreased. The VL group demonstrated higher corrective saccade frequency and amplitude and lower gain as compared with controls. In conclusion, decreasing target distance increases gain for normal controls but not subjects with VL. Preliminarily, visual acuity does not affect vHIT outcomes.

Design of a covert RFID tag network for target discovery and target information routing.

Science.gov (United States)

Pan, Qihe; Narayanan, Ram M

2011-01-01

Radio frequency identification (RFID) tags are small electronic devices working in the radio frequency range. They use wireless radio communications to automatically identify objects or people without the need for line-of-sight or contact, and are widely used in inventory tracking, object location, environmental monitoring. This paper presents a design of a covert RFID tag network for target discovery and target information routing. In the design, a static or very slowly moving target in the field of RFID tags transmits a distinct pseudo-noise signal, and the RFID tags in the network collect the target information and route it to the command center. A map of each RFID tag's location is saved at command center, which can determine where a RFID tag is located based on each RFID tag's ID. We propose the target information collection method with target association and clustering, and we also propose the information routing algorithm within the RFID tag network. The design and operation of the proposed algorithms are illustrated through examples. Simulation results demonstrate the effectiveness of the design.

Kalman filter data assimilation: targeting observations and parameter estimation.

Science.gov (United States)

Bellsky, Thomas; Kostelich, Eric J; Mahalov, Alex

2014-06-01

This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly located observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.

Kalman filter data assimilation: Targeting observations and parameter estimation

International Nuclear Information System (INIS)

Bellsky, Thomas; Kostelich, Eric J.; Mahalov, Alex

2014-01-01

This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly located observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation

The effect of target and non-target similarity on neural classification performance: A boost from confidence

Directory of Open Access Journals (Sweden)

Amar R Marathe

2015-08-01

Full Text Available Brain computer interaction (BCI technologies have proven effective in utilizing single-trial classification algorithms to detect target images in rapid serial visualization presentation tasks. While many factors contribute to the accuracy of these algorithms, a critical aspect that is often overlooked concerns the feature similarity between target and non-target images. In most real-world environments there are likely to be many shared features between targets and non-targets resulting in similar neural activity between the two classes. It is unknown how current neural-based target classification algorithms perform when qualitatively similar target and non-target images are presented. This study address this question by comparing behavioral and neural classification performance across two conditions: first, when targets were the only infrequent stimulus presented amongst frequent background distracters; and second when targets were presented together with infrequent non-targets containing similar visual features to the targets. The resulting findings show that behavior is slower and less accurate when targets are presented together with similar non-targets; moreover, single-trial classification yielded high levels of misclassification when infrequent non-targets are included. Furthermore, we present an approach to mitigate the image misclassification. We use confidence measures to assess the quality of single-trial classification, and demonstrate that a system in which low confidence trials are reclassified through a secondary process can result in improved performance.

Target Capture during Mos1 Transposition*

Science.gov (United States)

Pflieger, Aude; Jaillet, Jerôme; Petit, Agnès; Augé-Gouillou, Corinne; Renault, Sylvaine

2014-01-01

DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide. PMID:24269942

Should Low Molecular Weight PSMA Targeted Ligands Get Bigger and Use Albumin Ligands for PSMA Targeting?

OpenAIRE

Huang, Steve S.; Heston, Warren D.W.

2017-01-01

Prostate Specific Membrane Antigen (PSMA) is strongly expressed in prostate cancer. Recently a number of low-molecular-weight inhibitors have demonstrated excellent PSMA targeting activity for both imaging as well as Lutecium-177 radiotherapy in human trials. The paper by Choy et al raises the question of whether we can further increase the effectiveness of PSMA targeted therapy by adding an albumin-binding entity to low-molecular-weight agents

Poison pills: A defensive measure against a hostile takeover or a demonstration of power of the target company

Directory of Open Access Journals (Sweden)

Jovanović-Zattila Milena

2014-01-01

Full Text Available The balance of power is particularly at stake in hostile takeovers, which makes the issue of establishing the balance of power one of the most controversial issues in the contemporary company law. In the circumstances of direct market competition and the need to have a dominant market position, companies are necessarily forced to constantly upgrade and advance their offensive and defensive methods, techniques and strategies. In order to prevent a hostile takeover, the target company may resort to an array of defence mechanisms, the most prominent of which are 'poison pills'. In spite of being perceived as the most powerful tool for obstructing hostile takeovers (and commonly designated as the 'Holy Grail' among the defensive mechanisms, there are many pros and cons underlying their application. One of the positive effects of using the poison pills is that the fear of takeovers makes the target company management more disciplined and efficient in business operations. The negative consequences are reflected in the relationship between the company board of directors and the shareholders. The target company management makes a unilateral decision on using a poison pill and this decision does not have to be approved by the shareholders in the General Meeting; however, this is highly inconsistent with the basic principles of corporate governance. The asymmetry of information, where the management (an agent has disproportionately more relevant information at its disposal than the shareholders (principals, generates a conflict between the management and the shareholders. In company law, this agency problem is generally known as the principal-agent problem, which is most prominent in a takeover. Poison pills are often associated with the discrimination of the target company shareholders, but not necessarily. The controversial nature of this defensive measure which can be applied by the target company has given rise to numerous debates on the need to

Discovery of the mineral brucite (magnesium hydroxide) in the tropical calcifying alga Polystrata dura (Peyssonneliales, Rhodophyta).

Science.gov (United States)

Nash, Merinda C; Russell, Bayden D; Dixon, Kyatt R; Liu, Minglu; Xu, Huifang

2015-06-01

Red algae of the family Peyssonneliaceae typically form thin crusts impregnated with aragonite. Here, we report the first discovery of brucite in a thick red algal crust (~1 cm) formed by the peyssonnelioid species Polystrata dura from Papua New Guinea. Cells of P. dura were found to be infilled by the magnesium-rich mineral brucite [Mg(OH)2 ]; minor amounts of magnesite and calcite were also detected. We propose that cell infill may be associated with the development of thick (> ~5 mm) calcified red algal crusts, integral components of tropical biotic reefs. If brucite infill within the P. dura crust enhances resistance to dissolution similarly to crustose coralline algae that infill with dolomite, then these crusts would be more resilient to future ocean acidification than crusts without infill. © 2015 Phycological Society of America.

Targeted association mapping demonstrating the complex molecular genetics of fatty acid formation in soybean.

Science.gov (United States)

Li, Ying-hui; Reif, Jochen C; Ma, Yan-song; Hong, Hui-long; Liu, Zhang-xiong; Chang, Ru-zhen; Qiu, Li-juan

2015-10-23

The relative abundance of five dominant fatty acids (FAs) (palmitic, stearic, oleic, linoleic and linolenic acids) is a major factor determining seed quality in soybean. To clarify the currently poorly understood genetic architecture of FAs in soybean, targeted association analysis was conducted in 421 diverse accessions phenotyped in three environments and genotyped using 1536 pre-selected SNPs. The population of 421 soybean accessions displayed significant genetic variation for each FA. Analysis of the molecular data revealed three subpopulations, which reflected a trend depending on latitude of cultivation. A total of 37 significant (p seed quality of soybean with benefits for human health and for food processing.

Characterization of third-harmonic target plan irradiance on the National Ignition Facility Beamlet demonstration project

International Nuclear Information System (INIS)

Wegner, P.J.; Van Wonterghem, B.M.; Dixit, S.N.; Henesian, M.A.; Barker, C.E.; Thompson, C.E.; Seppala, L.G.; Caird, J.A.

1997-01-01

The Beamlet laser is a single-aperture prototype for the National Ignition Facility (NIF). We have recently installed and activated a 55 m 3 vacuum vessel and associated diagnostic package at the output of the Beamlet that we are using to characterize target plane irradiance at high power. Measurements obtained both with and without a kinoform diffractive optic are reported. Dependences on critical laser parameters including output power, spatial filtering, and wavefront correction are discussed and compared with simulations

TU-H-CAMPUS-IeP2-05: Breast and Soft Tissue-Equivalent 3D Printed Phantoms for Imaging and Dosimetry

International Nuclear Information System (INIS)

Hintenlang, D; Terracino, B

2016-01-01

Purpose: The study has the goal to demonstrate that breast and soft tissue-equivalent phantoms for dosimetry applications in the diagnostic energy range can be fabricated using common 3D printing methods. Methods: 3D printing provides the opportunity to rapidly prototype uniquely designed objects from a variety of materials. Common 3D printers are usually limited to printing objects based on thermoplastic materials such as PLA, or ABS. The most commonly available plastic is PLA, which has a density significantly greater than soft tissue. We utilized a popular 3D printer to demonstrate that tissue specific phantom materials can be generated through the careful selection of 3D printing parameters. A series of stepwedges were designed and printed using a Makerbot Replicator2 3D printing system. The print file provides custom adjustment of the infill density, orientation and position of the object on the printer stage, selection of infill patterns, and other control parameters. The x-ray attenuation and uniformity of fabricated phantoms were evaluated and compared to common tissue-equivalent phantom materials, acrylic and BR12. X-ray exposure measurements were made using narrow beam geometry on a clinical mammography unit at 28 kVp on the series of phantoms. The 3D printed phantoms were imaged at 28 kVp to visualize the internal structure and uniformity in different planes of the phantoms. Results: By utilizing specific in-fill density and patterns we are able to produce a phantom closely matching the attenuation characteristics of BR12 at 28 kVp. The in-fill patterns used are heterogeneous, so a judicious selection of fill pattern and the orientation of the fill pattern must be made in order to obtain homogenous attenuation along the intended direction of beam propagation. Conclusions: By careful manipulation of the printing parameters, breast and soft tissue-equivalent phantoms appropriate for use at imaging energies can be fabricated using 3D printing techniques.

TU-H-CAMPUS-IeP2-05: Breast and Soft Tissue-Equivalent 3D Printed Phantoms for Imaging and Dosimetry

Energy Technology Data Exchange (ETDEWEB)

Hintenlang, D; Terracino, B [University Florida, Gainesville, FL (United States)

2016-06-15

Purpose: The study has the goal to demonstrate that breast and soft tissue-equivalent phantoms for dosimetry applications in the diagnostic energy range can be fabricated using common 3D printing methods. Methods: 3D printing provides the opportunity to rapidly prototype uniquely designed objects from a variety of materials. Common 3D printers are usually limited to printing objects based on thermoplastic materials such as PLA, or ABS. The most commonly available plastic is PLA, which has a density significantly greater than soft tissue. We utilized a popular 3D printer to demonstrate that tissue specific phantom materials can be generated through the careful selection of 3D printing parameters. A series of stepwedges were designed and printed using a Makerbot Replicator2 3D printing system. The print file provides custom adjustment of the infill density, orientation and position of the object on the printer stage, selection of infill patterns, and other control parameters. The x-ray attenuation and uniformity of fabricated phantoms were evaluated and compared to common tissue-equivalent phantom materials, acrylic and BR12. X-ray exposure measurements were made using narrow beam geometry on a clinical mammography unit at 28 kVp on the series of phantoms. The 3D printed phantoms were imaged at 28 kVp to visualize the internal structure and uniformity in different planes of the phantoms. Results: By utilizing specific in-fill density and patterns we are able to produce a phantom closely matching the attenuation characteristics of BR12 at 28 kVp. The in-fill patterns used are heterogeneous, so a judicious selection of fill pattern and the orientation of the fill pattern must be made in order to obtain homogenous attenuation along the intended direction of beam propagation. Conclusions: By careful manipulation of the printing parameters, breast and soft tissue-equivalent phantoms appropriate for use at imaging energies can be fabricated using 3D printing techniques.

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

Science.gov (United States)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

Science.gov (United States)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

A new transfer system for solid targets

Science.gov (United States)

Klug, J.; Buckley, K. R.; Zeisler, S. K.; Dodd, M.; Tsao, P.; Hoehr, C.; Economou, C.; Corsaut, J.; Appiah, J. P.; Kovacs, M. S.; Valliant, J. F.; Benard, F.; Ruth, T. J.; Schaffer, P.

2012-12-01

As part of a collaborative research project funded by Natural Resources Canada, TRIUMF has designed and manufactured solid target and solid target processing systems for the production of technetium-99m using small medical cyclotrons. The system described herein is capable of transporting the target from a hotcell, where the target is loaded and processed, to the cyclotron and back again. The versatility of the transfer system was demonstrated through the successful installation and operation on the ACSI TR 19 at the BC Cancer Agency, the GE PETtrace cyclotrons at Lawson Health Research (LHRI) and the Centre for Probe Development and Commercialization (CDPC).

Nuclear physics with internal targets in electron storage rings

International Nuclear Information System (INIS)

Holt, R.J.

1986-01-01

Two key experiments in nuclear physics will be discussed in order to illustrate the advantages of the internal target method and demonstrate the power of polarization techniques in electron scattering studies. The progress of internal target experiments will be discussed and the technology of internal polarized target development will be reviewed. 43 refs., 11 figs

Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging.

Science.gov (United States)

Su, Weiping; Xing, Rubing; Guha, Abhijit; Gutmann, David H; Sherman, Larry S

2007-05-01

Neurofibromatosis 1 (NF1) is a common genetic disease that predisposes patients to peripheral nerve tumors and central nervous system (CNS) abnormalities including low-grade astrocytomas and cognitive disabilities. Using mice with glial fibrillary acidic protein (GFAP)-targeted Nf1 loss (Nf1(GFAP)CKO mice), we found that Nf1(-/-) astrocytes proliferate faster and are more invasive than wild-type astrocytes. In light of our previous finding that aberrant expression of the MET receptor tyrosine kinase contributes to the invasiveness of human NF1-associated malignant peripheral nerve sheath tumors, we sought to determine whether MET expression is aberrant in the brains of Nf1 mutant mice. We found that Nf1(-/-) astrocytes express slightly more MET than wild-type cells in vitro, but do not express elevated MET in situ. However, fiber tracts containing myelinated axons in the hippocampus, midbrain, cerebral cortex, and cerebellum express higher than normal levels of MET in older (> or =6 months) Nf1(GFAP)CKO mice. Both Nf1(GFAP)CKO and wild-type astrocytes induced MET expression in neurites of wild-type hippocampal neurons in vitro, suggesting that astrocyte-derived signals may induce MET in Nf1 mutant mice. Because the Nf1 gene product functions as a RAS GTPase, we examined MET expression in the brains of mice with GFAP-targeted constitutively active forms of RAS. MET was elevated in axonal fiber tracts in mice with active K-RAS but not H-RAS. Collectively, these data suggest that loss of Nf1 in either astrocytes or GFAP(+) neural progenitor cells results in increased axonal MET expression, which may contribute to the CNS abnormalities in children and adults with NF1. (c) 2007 Wiley-Liss, Inc.

Quantum Illumination-Based Target Detection and Discrimination

Science.gov (United States)

2014-06-30

photodiode with an estimated quantum efficiency of 85% and an ultralow-noise transimpedance amplifier . Compared with to our initial QI measurements...demonstrated high signal-to-noise ratio (SNR) quantum-illumination target detection in a lossy, noisy environment using an optical parametric amplifier ...Research Triangle Park, NC 27709-2211 quantum communication, target detection, entanglement, parametric downconversion, optical parametric amplifiers

Reconstruction of deglacial sea surface temperature in the tropical Pacific from selective analysis of a fossil coral

Energy Technology Data Exchange (ETDEWEB)

Allison, N.; Finch, A.A.; Tudhope, A.W.; Newville, M.; Sutton, S.R.; Ellam, R.M. (St Andrews); (Edinburgh); (Scottish); (UC); (St Andrews)

2010-07-13

The Sr/Ca of coral skeletons demonstrates potential as an indicator of sea surface temperatures (SSTs). However, the glacial-interglacial SST ranges predicted from Sr/Ca of fossil corals are usually higher than from other marine proxies. We observed infilling of secondary aragonite, characterized by high Sr/Ca ratios, along intraskeletal pores of a fossil coral from Papua New Guinea that grew during the penultimate deglaciation (130 {+-} 2 ka). Selective microanalysis of unaltered areas of the fossil coral indicates that SSTs at {approx}130 ka were {le} 1 C cooler than at present in contrast with bulk measurements (combining infilled and unaltered areas) which indicate a difference of 6-7 C. The analysis of unaltered areas of fossil skeletons by microprobe techniques may offer a route to more accurate reconstruction of past SSTs.

Increasing vaccine potency through exosome antigen targeting.

Science.gov (United States)

Hartman, Zachary C; Wei, Junping; Glass, Oliver K; Guo, Hongtao; Lei, Gangjun; Yang, Xiao-Yi; Osada, Takuya; Hobeika, Amy; Delcayre, Alain; Le Pecq, Jean-Bernard; Morse, Michael A; Clay, Timothy M; Lyerly, Herbert K

2011-11-21

While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to exosomes has been established which takes advantage of the ability of the factor V like C1C2 domain of lactadherin to specifically address proteins to exosomes. Using this approach, we hypothesized that TAAs could be targeted to exosomes to potentially increase their immunogenicity, as exosomes have been demonstrated to traffic to antigen presenting cells (APC). To investigate this possibility, we created adenoviral vectors expressing the extracellular domain (ECD) of two non-mutated TAAs often found in tumors of cancer patients, carcinoembryonic antigen (CEA) and HER2, and coupled them to the C1C2 domain of lactadherin. We found that these C1C2 fusion proteins had enhanced expression in exosomes in vitro. We saw significant improvement in antigen specific immune responses to each of these antigens in naïve and tolerant transgenic animal models and could further demonstrate significantly enhanced therapeutic anti-tumor effects in a human HER2+ transgenic animal model. These findings demonstrate that the mode of secretion and trafficking can influence the immunogenicity of different human TAAs, and may explain the lack of immunogenicity of non-mutated TAAs found in cancer patients. They suggest that exosomal targeting could enhance future anti-tumor vaccination protocols. This targeting exosome process could also be adapted for the development of more potent vaccines in some viral and parasitic diseases where the classical vaccine approach has demonstrated limitations. Copyright © 2011 Elsevier Ltd. All rights reserved.

Biomineral repair of abalone shell apertures.

Science.gov (United States)

Cusack, Maggie; Guo, Dujiao; Chung, Peter; Kamenos, Nicholas A

2013-08-01

The shell of the gastropod mollusc, abalone, is comprised of nacre with an outer prismatic layer that is composed of either calcite or aragonite or both, depending on the species. A striking characteristic of the abalone shell is the row of apertures along the dorsal margin. As the organism and shell grow, new apertures are formed and the preceding ones are filled in. Detailed investigations, using electron backscatter diffraction, of the infill in three species of abalone: Haliotis asinina, Haliotis gigantea and Haliotis rufescens reveals that, like the shell, the infill is composed mainly of nacre with an outer prismatic layer. The infill prismatic layer has identical mineralogy as the original shell prismatic layer. In H. asinina and H. gigantea, the prismatic layer of the shell and infill are made of aragonite while in H. rufescens both are composed of calcite. Abalone builds the infill material with the same high level of biological control, replicating the structure, mineralogy and crystallographic orientation as for the shell. The infill of abalone apertures presents us with insight into what is, effectively, shell repair. Copyright © 2013 Elsevier Inc. All rights reserved.

Contextual remapping in visual search after predictable target-location changes.

Science.gov (United States)

Conci, Markus; Sun, Luning; Müller, Hermann J

2011-07-01

Invariant spatial context can facilitate visual search. For instance, detection of a target is faster if it is presented within a repeatedly encountered, as compared to a novel, layout of nontargets, demonstrating a role of contextual learning for attentional guidance ('contextual cueing'). Here, we investigated how context-based learning adapts to target location (and identity) changes. Three experiments were performed in which, in an initial learning phase, observers learned to associate a given context with a given target location. A subsequent test phase then introduced identity and/or location changes to the target. The results showed that contextual cueing could not compensate for target changes that were not 'predictable' (i.e. learnable). However, for predictable changes, contextual cueing remained effective even immediately after the change. These findings demonstrate that contextual cueing is adaptive to predictable target location changes. Under these conditions, learned contextual associations can be effectively 'remapped' to accommodate new task requirements.

Multi-Robot, Multi-Target Particle Swarm Optimization Search in Noisy Wireless Environments

Energy Technology Data Exchange (ETDEWEB)

Kurt Derr; Milos Manic

2009-05-01

Multiple small robots (swarms) can work together using Particle Swarm Optimization (PSO) to perform tasks that are difficult or impossible for a single robot to accomplish. The problem considered in this paper is exploration of an unknown environment with the goal of finding a target(s) at an unknown location(s) using multiple small mobile robots. This work demonstrates the use of a distributed PSO algorithm with a novel adaptive RSS weighting factor to guide robots for locating target(s) in high risk environments. The approach was developed and analyzed on multiple robot single and multiple target search. The approach was further enhanced by the multi-robot-multi-target search in noisy environments. The experimental results demonstrated how the availability of radio frequency signal can significantly affect robot search time to reach a target.

Identification of synaptic targets of Drosophila pumilio.

Directory of Open Access Journals (Sweden)

Gengxin Chen

2008-02-01

Full Text Available Drosophila Pumilio (Pum protein is a translational regulator involved in embryonic patterning and germline development. Recent findings demonstrate that Pum also plays an important role in the nervous system, both at the neuromuscular junction (NMJ and in long-term memory formation. In neurons, Pum appears to play a role in homeostatic control of excitability via down regulation of para, a voltage gated sodium channel, and may more generally modulate local protein synthesis in neurons via translational repression of eIF-4E. Aside from these, the biologically relevant targets of Pum in the nervous system remain largely unknown. We hypothesized that Pum might play a role in regulating the local translation underlying synapse-specific modifications during memory formation. To identify relevant translational targets, we used an informatics approach to predict Pum targets among mRNAs whose products have synaptic localization. We then used both in vitro binding and two in vivo assays to functionally confirm the fidelity of this informatics screening method. We find that Pum strongly and specifically binds to RNA sequences in the 3'UTR of four of the predicted target genes, demonstrating the validity of our method. We then demonstrate that one of these predicted target sequences, in the 3'UTR of discs large (dlg1, the Drosophila PSD95 ortholog, can functionally substitute for a canonical NRE (Nanos response element in vivo in a heterologous functional assay. Finally, we show that the endogenous dlg1 mRNA can be regulated by Pumilio in a neuronal context, the adult mushroom bodies (MB, which is an anatomical site of memory storage.

Design and Demonstration of a Material-Plasma Exposure Target Station for Neutron Irradiated Samples

International Nuclear Information System (INIS)

Rapp, Juergen; Aaron, A. M.; Bell, Gary L.; Burgess, Thomas W.; Ellis, Ronald James; Giuliano, D.; Howard, R.; Kiggans, James O.; Lessard, Timothy L.; Ohriner, Evan Keith; Perkins, Dale E.; Varma, Venugopal Koikal

2015-01-01

Fusion energy is the most promising energy source for the future, and one of the most important problems to be solved progressing to a commercial fusion reactor is the identification of plasma-facing materials compatible with the extreme conditions in the fusion reactor environment. The development of plasma-material interaction (PMI) science and the technology of plasma-facing components are key elements in the development of the next step fusion device in the United States, the so-called Fusion Nuclear Science Facility (FNSF). All of these PMI issues and the uncertain impact of the 14-MeV neutron irradiation have been identified in numerous expert panel reports to the fusion community. The 2007 Greenwald report classifies reactor plasma-facing materials (PFCs) and materials as the only Tier 1 issues, requiring a ''. . . major extrapolation from the current state of knowledge, need for qualitative improvements and substantial development for both the short and long term.'' The Greenwald report goes on to list 19 gaps in understanding and performance related to the plasma-material interface for the technology facilities needed for DEMO-oriented R&D and DEMO itself. Of the 15 major gaps, six (G7, G9, G10, G12, G13) can possibly be addressed with ORNL's proposal of an advanced Material Plasma Exposure eXperiment. Establishing this mid-scale plasma materials test facility at ORNL is a key element in ORNL's strategy to secure a leadership role for decades of fusion R&D. That is to say, our end goal is to bring the ''signature facility'' FNSF home to ORNL. This project is related to the pre-conceptual design of an innovative target station for a future Material-Plasma Exposure eXperiment (MPEX). The target station will be designed to expose candidate fusion reactor plasma-facing materials and components (PFMs and PFCs) to conditions anticipated in fusion reactors, where PFCs will be exposed to dense high-temperature hydrogen plasmas providing steady-state heat fluxes of

Testing of the prototype FMIT target with liquid lithium

International Nuclear Information System (INIS)

Miller, W.C.; Annese, C.E.; Berg, J.D.; Miles, R.R.

1984-01-01

Testing of a molten lithium target was performed to evaluate hydraulic stability, determine surface evaporation rates, and map the detailed contour of the high speed, free surface wall jet. The results confirmed predictions by demonstrating acceptable performance of a prototype target

Remote handling for an ISIS target change

International Nuclear Information System (INIS)

Broome, T.A.; Holding, M.

1989-01-01

During 1987 two ISIS targets were changed. This document describes the main features of the remote handling aspects of the work. All the work has to be carried out using remote handling techniques. The radiation level measured on the surface of the reflector when the second target had been removed was about 800 mGy/h demonstrating that hands on operations on any part of the target reflector moderator assembly is not practical. The target changes were the first large scale operations in the Target Station Remote Handling Cell and a great deal was learned about both equipment and working practices. Some general principles emerged which are applicable to other active handling tasks on facilities like ISIS and these are discussed below. 8 figs

Spallation source neutron target systems

International Nuclear Information System (INIS)

Russell, G.; Brown, R.; Collier, M.; Donahue, J.

1996-01-01

This is the final report for a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The project sought to design a next-generation spallation source neutron target system for the Manuel Lujan, Jr., Neutron Scattering Center (LANSCE) at Los Alamos. It has been recognized for some time that new advanced neutron sources are needed in the US if the country is to maintain a competitive position in several important scientific and technological areas. A recent DOE panel concluded that the proposed Advanced Neutron Source (a nuclear reactor at Oak Ridge National Laboratory) and a high-power pulsed spallation source are both needed in the near future. One of the most technically challenging designs for a spallation source is the target station itself and, more specifically, the target-moderator-reflector arrangement. Los Alamos has demonstrated capabilities in designing, building, and operating high-power spallation-neutron-source target stations. Most of the new design ideas proposed worldwide for target system design for the next generation pulsed spallation source have either been conceived and implemented at LANSCE or proposed by LANSCE target system designers. These concepts include split targets, flux-trap moderators, back scattering and composite moderators, and composite reflectors

Studi Eksperimental tentang Pengaruh Dinding Bata Merah Terhadap Ketahanan Lateral Struktur Beton Bertulang

Directory of Open Access Journals (Sweden)

Jafril Tanjung

2016-08-01

Full Text Available Reinforced-Concrete (R/C frame structures with unreinforced clay brick masonry (URM infill walls are commonly used in developing countries with regions of high seismicity. The walls are usually treated as non-structural components, and their interaction with the bounding frames is often ignored in designing process. Field evidences after West Sumatera earthquake have shown that URM infill walls can help reduce the vulnerability of the R/C frame structures against lateral load. In the present paper, it is an attempt to highlight the series laboratory experimental results of the R/C frame structures with URM infill walls. Results of the experimental studies which have indicated URM infill walls can have a significant influence on the lateral resistance of the R/C frame structures. Increasing the lateral resistance is also observed on the R/C frame structures uses larger size of the clay brick masonry and uses mortar on the infill walls’ surfaces.

On the Chinese Carbon Reduction Target

Directory of Open Access Journals (Sweden)

Michinori Uwasu

2010-06-01

Full Text Available In November 2009, China pledged a 40–45% decrease in CO2 emissions per GDP by 2020, as compared with the 2005 level. Although carbon intensity (emission targets by nature are ambiguous, this study demonstrates that China’s pledge is consistent with the current Chinese domestic agenda that simultaneously pursues economic growth and energy security. The target numbers in the pledge seem reasonable, given the technological feasibility and measures, considered along with the assumption that moderate economic growth will occur. However, the study also argues that financial and institutional constraints exist as potential obstacles to achieving the target if the trend of the current economic tendencies continues.

Design and Demonstration of a Material-Plasma Exposure Target Station for Neutron Irradiated Samples

Energy Technology Data Exchange (ETDEWEB)

Rapp, Juergen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Aaron, A. M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bell, Gary L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Burgess, Thomas W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ellis, Ronald James [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Giuliano, D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howard, R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kiggans, James O. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lessard, Timothy L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ohriner, Evan Keith [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Perkins, Dale E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Varma, Venugopal Koikal [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2015-10-20

Fusion energy is the most promising energy source for the future, and one of the most important problems to be solved progressing to a commercial fusion reactor is the identification of plasma-facing materials compatible with the extreme conditions in the fusion reactor environment. The development of plasma–material interaction (PMI) science and the technology of plasma-facing components are key elements in the development of the next step fusion device in the United States, the so-called Fusion Nuclear Science Facility (FNSF). All of these PMI issues and the uncertain impact of the 14-MeV neutron irradiation have been identified in numerous expert panel reports to the fusion community. The 2007 Greenwald report classifies reactor plasma-facing materials (PFCs) and materials as the only Tier 1 issues, requiring a “. . . major extrapolation from the current state of knowledge, need for qualitative improvements and substantial development for both the short and long term.” The Greenwald report goes on to list 19 gaps in understanding and performance related to the plasma–material interface for the technology facilities needed for DEMO-oriented R&D and DEMO itself. Of the 15 major gaps, six (G7, G9, G10, G12, G13) can possibly be addressed with ORNL’s proposal of an advanced Material Plasma Exposure eXperiment. Establishing this mid-scale plasma materials test facility at ORNL is a key element in ORNL’s strategy to secure a leadership role for decades of fusion R&D. That is to say, our end goal is to bring the “signature facility” FNSF home to ORNL. This project is related to the pre-conceptual design of an innovative target station for a future Material–Plasma Exposure eXperiment (MPEX). The target station will be designed to expose candidate fusion reactor plasma-facing materials and components (PFMs and PFCs) to conditions anticipated in fusion reactors, where PFCs will be exposed to dense high-temperature hydrogen plasmas providing steady

Enhanced target normal sheath acceleration of protons from intense laser interaction with a cone-tube target

Directory of Open Access Journals (Sweden)

K. D. Xiao

2016-01-01

Full Text Available Laser driven proton acceleration is proposed to be greatly enhanced by using a cone-tube target, which can be easily manufactured by current 3D-print technology. It is observed that energetic electron bunches are generated along the tube and accelerated to a much higher temperature by the combination of ponderomotive force and longitudinal electric field which is induced by the optical confinement of the laser field. As a result, a localized and enhanced sheath field is produced at the rear of the target and the maximum proton energy is about three-fold increased based on the two-dimentional particle-in-cell simulation results. It is demonstrated that by employing this advanced target scheme, the scaling of the proton energy versus the laser intensity is much beyond the normal target normal sheath acceleration (TNSA case.

A small scale accelerator driven subcritical assembly development and demonstration experiment at LAMPF

International Nuclear Information System (INIS)

Wender, S.A.; Venneri, F.; Bowman, C.D.; Arthur, E.D.; Heighway, E.A.; Beard, C.A.; Bracht, R.R.; Buksa, J.J.; Chavez, W.; DeVolder, B.G.

1994-01-01

A small scale experiment is described that will demonstrate many of the aspects of accelerator-driven transmutation technology. This experiment uses the high-power proton beam from the Los Alamos Meson Physics Facility accelerator and will be located in the Area-A experimental hall. Beam currents of up to 1 mA will be used to produce neutrons with a molten lead target. The target is surrounded by a molten salt and graphite moderator blanket. Fissionable material can be added to the molten salt to demonstrate plutonium burning or transmutation of commercial spent fuel or energy production from thorium. The experiment will be operated at power levels up to 5 MW t

Object-based target templates guide attention during visual search.

Science.gov (United States)

Berggren, Nick; Eimer, Martin

2018-05-03

During visual search, attention is believed to be controlled in a strictly feature-based fashion, without any guidance by object-based target representations. To challenge this received view, we measured electrophysiological markers of attentional selection (N2pc component) and working memory (sustained posterior contralateral negativity; SPCN) in search tasks where two possible targets were defined by feature conjunctions (e.g., blue circles and green squares). Critically, some search displays also contained nontargets with two target features (incorrect conjunction objects, e.g., blue squares). Because feature-based guidance cannot distinguish these objects from targets, any selective bias for targets will reflect object-based attentional control. In Experiment 1, where search displays always contained only one object with target-matching features, targets and incorrect conjunction objects elicited identical N2pc and SPCN components, demonstrating that attentional guidance was entirely feature-based. In Experiment 2, where targets and incorrect conjunction objects could appear in the same display, clear evidence for object-based attentional control was found. The target N2pc became larger than the N2pc to incorrect conjunction objects from 250 ms poststimulus, and only targets elicited SPCN components. This demonstrates that after an initial feature-based guidance phase, object-based templates are activated when they are required to distinguish target and nontarget objects. These templates modulate visual processing and control access to working memory, and their activation may coincide with the start of feature integration processes. Results also suggest that while multiple feature templates can be activated concurrently, only a single object-based target template can guide attention at any given time. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Flash trajectory imaging of target 3D motion

Science.gov (United States)

Wang, Xinwei; Zhou, Yan; Fan, Songtao; He, Jun; Liu, Yuliang

2011-03-01

We present a flash trajectory imaging technique which can directly obtain target trajectory and realize non-contact measurement of motion parameters by range-gated imaging and time delay integration. Range-gated imaging gives the range of targets and realizes silhouette detection which can directly extract targets from complex background and decrease the complexity of moving target image processing. Time delay integration increases information of one single frame of image so that one can directly gain the moving trajectory. In this paper, we have studied the algorithm about flash trajectory imaging and performed initial experiments which successfully obtained the trajectory of a falling badminton. Our research demonstrates that flash trajectory imaging is an effective approach to imaging target trajectory and can give motion parameters of moving targets.

Sodium modulates opioid receptors through a membrane component different from G-proteins. Demonstration by target size analysis

International Nuclear Information System (INIS)

Ott, S.; Costa, T.; Herz, A.

1988-01-01

The target size for opioid receptor binding was studied after manipulations known to affect the interactions between receptor and GTP-binding regulatory proteins (G-proteins). Addition of GTP or its analogs to the binding reaction, exposure of intact cells to pertussis toxin prior to irradiation, or treatment of irradiated membranes with N-ethylmaleimide did not change the target size (approximately equal to 100 kDa) for opioid receptors in NG 108-15 cells and rat brain. These data suggest that the 100-kDa species does not include an active subunit of a G-protein or alternatively that GTP does not promote the dissociation of the receptor-G-protein complex. The presence of Na+ (100 mM) in the radioligand binding assay induced a biphasic decay curve for agonist binding and a flattening of the monoexponential decay curve for a partial agonist. In both cases the effect was explained by an irradiation-induced loss of the low affinity state of the opioid receptor produced by the addition of Na+. This suggests that an allosteric inhibitor that mediates the effect of sodium on the receptor is destroyed at low doses of irradiation, leaving receptors which are no longer regulated by sodium. The effect of Na+ on target size was slightly increased by the simultaneous addition of GTP but was not altered by pertussis toxin treatment. Thus, the sodium unit is distinct from G-proteins and may represent a new component of the opioid receptor complex. Assuming a simple bimolecular model of one Na+ unit/receptor, the size of this inhibitor can be measured as 168 kDa

Progress in transmutation targets from Efttra

International Nuclear Information System (INIS)

Haas, D.; Fernandez, A.; Warin, D.; Bonnerot, J.M.; Garzenne, C.; Scaffidi-Argentina, F.; Maschek, W.; Schram, R.; Klaassen, F.

2007-01-01

Since 15 years, the EFTTRA partners have organised programmes to demonstrate the feasibility of the transmutation of americium in uranium-free targets. In the related transmutation scenario, the targets are introduced in a thermal neutron zone of a fast reactor, to maximize the efficiency of transmutation. Amongst these programmes, those carried out in the HFR reactor in Petten have led to important conclusions and are still at the core of the research in that field. The analysis of the EFTTRA T4 and T4bis irradiation experiments, carried out with targets of MgAl 2 O 4 +11 wt% 241 Am, showed that the release/trapping of helium is the key issue for target design, and also demonstrated a lack of technical benefits of this material, due to a unsatisfactory in-pile behaviour in terms of irradiation damage and chemical stability. A new irradiation experiment called HELIOS is currently under fabrication and will be carried out in HFR. The in-pile behaviour of U-free fuels and targets such as (Am,Zr)O 2 , (Pu,Am,Zr)O 2 , CERCER (MgO) or CERMET (Mo) will be examined. The irradiation temperature will be high enough in some of the pins to be able to tune the release of a significant fraction of helium produced so that the material swelling can be minimized as much as reasonably possible. The HELIOS irradiation experiment is planned to be carried out in the HFR core and shall last 300 full power days starting in 2007. (authors)

Type I-E CRISPR-Cas Systems Discriminate Target from Non-Target DNA through Base Pairing-Independent PAM Recognition

Science.gov (United States)

Datsenko, Kirill A.; Jackson, Ryan N.; Wiedenheft, Blake; Severinov, Konstantin; Brouns, Stan J. J.

2013-01-01

Discriminating self and non-self is a universal requirement of immune systems. Adaptive immune systems in prokaryotes are centered around repetitive loci called CRISPRs (clustered regularly interspaced short palindromic repeat), into which invader DNA fragments are incorporated. CRISPR transcripts are processed into small RNAs that guide CRISPR-associated (Cas) proteins to invading nucleic acids by complementary base pairing. However, to avoid autoimmunity it is essential that these RNA-guides exclusively target invading DNA and not complementary DNA sequences (i.e., self-sequences) located in the host's own CRISPR locus. Previous work on the Type III-A CRISPR system from Staphylococcus epidermidis has demonstrated that a portion of the CRISPR RNA-guide sequence is involved in self versus non-self discrimination. This self-avoidance mechanism relies on sensing base pairing between the RNA-guide and sequences flanking the target DNA. To determine if the RNA-guide participates in self versus non-self discrimination in the Type I-E system from Escherichia coli we altered base pairing potential between the RNA-guide and the flanks of DNA targets. Here we demonstrate that Type I-E systems discriminate self from non-self through a base pairing-independent mechanism that strictly relies on the recognition of four unchangeable PAM sequences. In addition, this work reveals that the first base pair between the guide RNA and the PAM nucleotide immediately flanking the target sequence can be disrupted without affecting the interference phenotype. Remarkably, this indicates that base pairing at this position is not involved in foreign DNA recognition. Results in this paper reveal that the Type I-E mechanism of avoiding self sequences and preventing autoimmunity is fundamentally different from that employed by Type III-A systems. We propose the exclusive targeting of PAM-flanked sequences to be termed a target versus non-target discrimination mechanism. PMID:24039596

The influences of the AMO and NAO on the sedimentary infill in an Azores Archipelago lake since ca. 1350 CE

Science.gov (United States)

Hernández, Armand; Sáez, Alberto; Bao, Roberto; Raposeiro, Pedro M.; Trigo, Ricardo M.; Doolittle, Sara; Masqué, Pere; Rull, Valentí; Gonçalves, Vítor; Vázquez-Loureiro, David; Rubio-Inglés, María J.; Sánchez-López, Guiomar; Giralt, Santiago

2017-07-01

The location of the Azores Archipelago in the North Atlantic makes this group of islands an excellent setting to study the long-term behavior of large oceanic and atmospheric climate dynamic patterns, such as the Atlantic Multidecadal Oscillation (AMO) and the North Atlantic Oscillation (NAO). Here, we present the impacts of these patterns on Lake Empadadas (Azores Archipelago) from the Medieval Climate Anomaly (MCA) - Little Ice Age (LIA) transition to the present based on sedimentological, geochemical and biological characterizations of the sedimentary record. Multivariate analyses of a number of proxies including X-ray fluorescence (XRF), X-ray diffraction (XRD), total organic and inorganic carbon (TOC and TIC) and diatom life forms abundance reveal that the sedimentary infill evolution has been controlled by (i) fluctuations in the lake level and (ii) variations in organic matter accumulation. Both processes are governed by climate variability and modulated by anthropogenic activities associated with changes on the lake catchment. Changes in these two sedimentary processes have been used to infer five stages: (i) the MCA-LIA transition (ca. 1350-1450 CE) was characterized by a predominantly positive AMO phase, which led to intermediate lake levels and high organic matter concentration; (ii) the first half of the LIA (ca. 1450-1600 CE) was characterized by predominant lowstand conditions and intermediate organic matter deposition mainly related to negative AMO phases; (iii) the second half of the LIA (ca. 1600-1850 CE) was characterized by negative AMO and NAO phases, implying intermediate lake levels and high organic matter deposition; (iv) the Industrial era (ca. 1850-1980 CE) was characterized by the lowest lake level and organic matter accumulation associated with negative AMO phases; and (v) the period spanning between 1980 CE and the present reveals the highest lake levels and low organic matter deposition, being associated with very positive AMO

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

Science.gov (United States)

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

2017-05-01

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

G-quadruplex aptamer targeting Protein A and its capability to detect Staphylococcus aureus demonstrated by ELONA

OpenAIRE

Stoltenburg, Regina; Kraf?ikov?, Petra; V?glask?, Viktor; Strehlitz, Beate

2016-01-01

Aptamers for whole cell detection are selected mostly by the Cell-SELEX procedure. Alternatively, the use of specific cell surface epitopes as target during aptamer selections allows the development of aptamers with ability to bind whole cells. In this study, we integrated a formerly selected Protein A-binding aptamer PA#2/8 in an assay format called ELONA (Enzyme-Linked OligoNucleotide Assay) and evaluated the ability of the aptamer to recognise and bind to Staphylococcus aureus presenting P...

Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling.

Science.gov (United States)

Vlot, Anna H C; de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; van Westen, Gerard J P; de Lange, Elizabeth C M

2017-12-04

Selectivity is an important attribute of effective and safe drugs, and prediction of in vivo target and tissue selectivity would likely improve drug development success rates. However, a lack of understanding of the underlying (pharmacological) mechanisms and availability of directly applicable predictive methods complicates the prediction of selectivity. We explore the value of combining physiologically based pharmacokinetic (PBPK) modeling with quantitative structure-activity relationship (QSAR) modeling to predict the influence of the target dissociation constant (K D ) and the target dissociation rate constant on target and tissue selectivity. The K D values of CB1 ligands in the ChEMBL database are predicted by QSAR random forest (RF) modeling for the CB1 receptor and known off-targets (TRPV1, mGlu5, 5-HT1a). Of these CB1 ligands, rimonabant, CP-55940, and Δ 8 -tetrahydrocanabinol, one of the active ingredients of cannabis, were selected for simulations of target occupancy for CB1, TRPV1, mGlu5, and 5-HT1a in three brain regions, to illustrate the principles of the combined PBPK-QSAR modeling. Our combined PBPK and target binding modeling demonstrated that the optimal values of the K D and k off for target and tissue selectivity were dependent on target concentration and tissue distribution kinetics. Interestingly, if the target concentration is high and the perfusion of the target site is low, the optimal K D value is often not the lowest K D value, suggesting that optimization towards high drug-target affinity can decrease the benefit-risk ratio. The presented integrative structure-pharmacokinetic-pharmacodynamic modeling provides an improved understanding of tissue and target selectivity.

Ultrasonic backscatter imaging by shear-wave-induced echo phase encoding of target locations.

Science.gov (United States)

McAleavey, Stephen

2011-01-01

We present a novel method for ultrasound backscatter image formation wherein lateral resolution of the target is obtained by using traveling shear waves to encode the lateral position of targets in the phase of the received echo. We demonstrate that the phase modulation as a function of shear wavenumber can be expressed in terms of a Fourier transform of the lateral component of the target echogenicity. The inverse transform, obtained by measurements of the phase modulation over a range of shear wave spatial frequencies, yields the lateral scatterer distribution. Range data are recovered from time of flight as in conventional ultrasound, yielding a B-mode-like image. In contrast to conventional ultrasound imaging, where mechanical or electronic focusing is used and lateral resolution is determined by aperture size and wavelength, we demonstrate that lateral resolution using the proposed method is independent of the properties of the aperture. Lateral resolution of the target is achieved using a stationary, unfocused, single-element transducer. We present simulated images of targets of uniform and non-uniform shear modulus. Compounding for speckle reduction is demonstrated. Finally, we demonstrate image formation with an unfocused transducer in gelatin phantoms of uniform shear modulus.

Water testing of the FMIT lithium target

International Nuclear Information System (INIS)

Hassberger, J.A.; Ingham, J.G.

1981-11-01

Results of water tests of the lithium target design for the Fusion Materials Irradiation Test (FMIT) Facility demonstrate hydraulic features essential for acceptable target operation and confirm predictions of the target performance. This high speed, free surface, curved-wall jet has been shown to generate a stable surface shape and to provide the high velocities and pressures within the fluid needed to remove the 3.5 MW of power generated within the jet during FMIT operation. Measurements of the jet performance are found to fall within limits bounded by one- and two-dimensional potential flow predictions. This agreement between measured and predicted performance provides for a significant level of confidence in the ability of the FMIT lithium target to meet its design and functional objectives

An ergonomics action research demonstration: integrating human factors into assembly design processes.

Science.gov (United States)

Village, J; Greig, M; Salustri, F; Zolfaghari, S; Neumann, W P

2014-01-01

In action research (AR), the researcher participates 'in' the actions in an organisation, while simultaneously reflecting 'on' the actions to promote learning for both the organisation and the researchers. This paper demonstrates a longitudinal AR collaboration with an electronics manufacturing firm where the goal was to improve the organisation's ability to integrate human factors (HF) proactively into their design processes. During the three-year collaboration, all meetings, workshops, interviews and reflections were digitally recorded and qualitatively analysed to inform new 'actions'. By the end of the collaboration, HF tools with targets and sign-off by the HF specialist were integrated into several stages of the design process, and engineers were held accountable for meeting the HF targets. We conclude that the AR approach combined with targeting multiple initiatives at different stages of the design process helped the organisation find ways to integrate HF into their processes in a sustainable way. Researchers acted as a catalyst to help integrate HF into the engineering design process in a sustainable way. This paper demonstrates how an AR approach can help achieve HF integration, the benefits of using a reflective stance and one method for reporting an AR study.

Output optics for Aurora: Beam separation, pulse stacking, and target focusing

International Nuclear Information System (INIS)

McLeod, J.

1987-01-01

An end-to-end technology demonstration prototype for large-scale ultraviolet laser systems of interest for short wavelength, inertial confinement fusion (ICF) investigations. The system is designed to employ optical angular multiplexing and serial amplification by electron-beam-driven KrF laser amplifiers to deliver to ICF targets a stack of pulses with a duration of 5 ns containing several kilojoules at a wavelength of 248 nm. The optical system has been designed in two phases. The first phase carries only through the amplifier train and does not include a target chamber or any demultiplexing. During first-phase design, the system was conceived of as only an amplifier demonstration and not as an end-to-end system demonstration. The design concept for second-phase optics that provides demultiplexing and carries the laser light to target is presented

Demonstrating ignition hydrodynamic equivalence in direct-drive cryogenic implosions on OMEGA

International Nuclear Information System (INIS)

Goncharov, V N; Regan, S P; Sangster, T C; Betti, R; Boehly, T R; Campbell, E M; Delettrez, J A; Edgell, D H; Epstein, R; Forrest, C J; Froula, D H; Glebov, V Yu; Harding, D R; Hu, S X; Igumenshchev, I V; Marshall, F J; McCrory, R L; Michel, D T; Myatt, J F; Radha, P B

2016-01-01

Achieving ignition in a direct-drive cryogenic implosion at the National Ignition Facility (NIF) requires reaching central stagnation pressures in excess of 100 Gbar, which is a factor of 3 to 4 less than what is required for indirect-drive designs. The OMEGA Laser System is used to study the physics of cryogenic implosions that are hydrodynamically equivalent to the spherical ignition designs of the NIF. Current cryogenic implosions on OMEGA have reached 56 Gbar, and implosions with shell convergence CR< 17 and fuel adiabat α > 3.5 proceed close to 1-D predictions. Demonstrating hydrodynamic equivalence on OMEGA will require reducing coupling losses caused by cross-beam energy transfer (CBET), minimizing long- wavelength nonuniformity seeded by power imbalance and target offset, and removing target debris occumulated during cryogenic target production. (paper)

MEGAPIE spallation target: Design, manufacturing and preliminary tests of the first pro-typical spallation target for future ADS

International Nuclear Information System (INIS)

Latge, Ch.; Laffont, G.; Groeschel, F.; Thomsen, K.; Wagner, W.; Agostini, P.; Dierckx, M.; Fazio, C.; Kirchner, T.; Kurata, Y.; Song, T.; Woloshun, K.

2006-01-01

Partitioning and Transmutation (P and T) techniques could contribute to reduce the radioactive inventory and its associated radiotoxicity. Sub-critical Accelerator Driven Systems (ADS) are potential candidates as dedicated transmutation systems, and thus their development is a relevant R and D topic in Europe. Following a first phase focused on the understanding of the basic principles of ADS (e.g. the programme MUSE), the R and D has been streamlined and focused on practical demonstration key issues. These demonstrations cover high intensity proton accelerators (beam current in the range 1 to 20 mA), spallation targets of high power and their effective coupling with a subcritical core. Presently there is general consensus that up to 1 MW of beam power solid targets are feasible from a heat removal point of view. For higher power levels liquid metal targets are the option of choice because of their higher heat removal capability, higher spallation material density in the volume and lower specific radioactivity, Therefore, a key experiment in the ADS road map, the Megawatt Pilot Experiment (MEGAPIE) (1 MW) was initiated in 1999 in order to design and build a liquid lead-bismuth spallation target, then to operate it into the Swiss spallation neutron facility SINQ at Paul Scherrer Institute (PSI). It has to be equipped to provide the largest possible amount of scientific and technical information without jeopardizing its safe operation. The minimum design service life has been fixed at 1 year (6000 mAh). Whereas the interest of the partner institutes is driven by the development needs of ADS, PSI interest lies also in the potential use of a LM target as a SINQ standard target providing a higher neutron flux than the current solid targets. Calculations of the radial distribution of the undisturbed thermal neutron flux for the LBE target in comparison to the former Zircaloy and current steel-clad solid lead target were done with different nuclear codes; nevertheless

Clean Coal Diesel Demonstration Project

Energy Technology Data Exchange (ETDEWEB)

Robert Wilson

2006-10-31

A Clean Coal Diesel project was undertaken to demonstrate a new Clean Coal Technology that offers technical, economic and environmental advantages over conventional power generating methods. This innovative technology (developed to the prototype stage in an earlier DOE project completed in 1992) enables utilization of pre-processed clean coal fuel in large-bore, medium-speed, diesel engines. The diesel engines are conventional modern engines in many respects, except they are specially fitted with hardened parts to be compatible with the traces of abrasive ash in the coal-slurry fuel. Industrial and Municipal power generating applications in the 10 to 100 megawatt size range are the target applications. There are hundreds of such reciprocating engine power-plants operating throughout the world today on natural gas and/or heavy fuel oil.

SNS Target Test Facility for remote handling design and verification

International Nuclear Information System (INIS)

Spampinato, P.T.; Graves, V.B.; Schrock, S.L.

1998-01-01

The Target Test Facility will be a full-scale prototype of the Spallation Neutron Source Target Station. It will be used to demonstrate remote handling operations on various components of the mercury flow loop and for thermal/hydraulic testing. This paper describes the remote handling aspects of the Target Test Facility. Since the facility will contain approximately 1 cubic meter of mercury for the thermal/hydraulic tests, an enclosure will also be constructed that matches the actual Target Test Cell

SU-F-T-181: Proton Therapy Tissue-Equivalence of 3D Printed Materials

International Nuclear Information System (INIS)

Taylor, P; Craft, D; Followill, D; Howell, R

2016-01-01

Purpose: This work investigated the proton tissue-equivalence of various 3D printed materials. Methods: Three 3D printers were used to create 5 cm cubic phantoms made of different plastics with varying percentages of infill. White resin, polylactic acid (PLA), and NinjaFlex plastics were used. The infills ranged from 15% to 100%. Each phantom was scanned with a CT scanner to obtain the HU value. The relative linear stopping power (RLSP) was then determined using a multi-layer ion chamber in a 200 MeV proton beam. The RLSP was measured both parallel and perpendicular to the print direction for each material. Results: The HU values of the materials ranged from lung-equivalent (−820 HU σ160) when using a low infill, to soft-tissue-equivalent 159 (σ12). The RLSP of the materials depended on the orientation of the beam relative to the print direction. When the proton beam was parallel to the print direction, the RLSP was generally higher than the RLSP in the perpendicular orientation, by up to 45%. This difference was smaller (less than 6%) for the materials with 100% infill. For low infill cubes irradiated parallel to the print direction, the SOBP curve showed extreme degradation of the beam in the distal region. The materials with 15–25% infill had wide-ranging agreement with a clinical HU-RLSP conversion curve, with some measurements falling within 1% of the curve and others deviating up to 45%. The materials with 100% infill all fell within 7% of the curve. Conclusion: While some materials tested fall within 1% of a clinical HU-RLSP curve, caution should be taken when using 3D printed materials with proton therapy, as the orientation of the beam relative to the print direction can result in a large change in RLSP. Further investigation is needed to measure how the infill pattern affects the material RLSP. This work was supported by PHS grant CA180803.

SU-F-T-181: Proton Therapy Tissue-Equivalence of 3D Printed Materials

Energy Technology Data Exchange (ETDEWEB)

Taylor, P; Craft, D; Followill, D; Howell, R [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: This work investigated the proton tissue-equivalence of various 3D printed materials. Methods: Three 3D printers were used to create 5 cm cubic phantoms made of different plastics with varying percentages of infill. White resin, polylactic acid (PLA), and NinjaFlex plastics were used. The infills ranged from 15% to 100%. Each phantom was scanned with a CT scanner to obtain the HU value. The relative linear stopping power (RLSP) was then determined using a multi-layer ion chamber in a 200 MeV proton beam. The RLSP was measured both parallel and perpendicular to the print direction for each material. Results: The HU values of the materials ranged from lung-equivalent (−820 HU σ160) when using a low infill, to soft-tissue-equivalent 159 (σ12). The RLSP of the materials depended on the orientation of the beam relative to the print direction. When the proton beam was parallel to the print direction, the RLSP was generally higher than the RLSP in the perpendicular orientation, by up to 45%. This difference was smaller (less than 6%) for the materials with 100% infill. For low infill cubes irradiated parallel to the print direction, the SOBP curve showed extreme degradation of the beam in the distal region. The materials with 15–25% infill had wide-ranging agreement with a clinical HU-RLSP conversion curve, with some measurements falling within 1% of the curve and others deviating up to 45%. The materials with 100% infill all fell within 7% of the curve. Conclusion: While some materials tested fall within 1% of a clinical HU-RLSP curve, caution should be taken when using 3D printed materials with proton therapy, as the orientation of the beam relative to the print direction can result in a large change in RLSP. Further investigation is needed to measure how the infill pattern affects the material RLSP. This work was supported by PHS grant CA180803.

Histone lysine demethylases as targets for anticancer therapy

DEFF Research Database (Denmark)

Højfeldt, Jonas W; Agger, Karl; Helin, Kristian

2013-01-01

It has recently been demonstrated that the genes controlling the epigenetic programmes that are required for maintaining chromatin structure and cell identity include genes that drive human cancer. This observation has led to an increased awareness of chromatin-associated proteins as potentially...... interesting drug targets. The successful introduction of DNA methylation and histone deacetylase (HDAC) inhibitors for the treatment of specific subtypes of cancer has paved the way for the use of epigenetic therapy. Here, we highlight key biological findings demonstrating the roles of members of the histone...... lysine demethylase class of enzymes in the development of cancers, discuss the potential and challenges of therapeutically targeting them, and highlight emerging small-molecule inhibitors of these enzymes....

Drug-Target Interaction Prediction through Label Propagation with Linear Neighborhood Information.

Science.gov (United States)

Zhang, Wen; Chen, Yanlin; Li, Dingfang

2017-11-25

Interactions between drugs and target proteins provide important information for the drug discovery. Currently, experiments identified only a small number of drug-target interactions. Therefore, the development of computational methods for drug-target interaction prediction is an urgent task of theoretical interest and practical significance. In this paper, we propose a label propagation method with linear neighborhood information (LPLNI) for predicting unobserved drug-target interactions. Firstly, we calculate drug-drug linear neighborhood similarity in the feature spaces, by considering how to reconstruct data points from neighbors. Then, we take similarities as the manifold of drugs, and assume the manifold unchanged in the interaction space. At last, we predict unobserved interactions between known drugs and targets by using drug-drug linear neighborhood similarity and known drug-target interactions. The experiments show that LPLNI can utilize only known drug-target interactions to make high-accuracy predictions on four benchmark datasets. Furthermore, we consider incorporating chemical structures into LPLNI models. Experimental results demonstrate that the model with integrated information (LPLNI-II) can produce improved performances, better than other state-of-the-art methods. The known drug-target interactions are an important information source for computational predictions. The usefulness of the proposed method is demonstrated by cross validation and the case study.

50 kW laser weapon demonstrator of Rheinmetall Waffe munition

Science.gov (United States)

Ludewigt, K.; Riesbeck, Th.; Graf, A.; Jung, M.

2013-10-01

We will present the setup of a 50 kW Laser Weapon Demonstrator (LWD) and results achieved with this system. The LWD is a ground based Air Defence system consisting of a Skyguard sensor unit for target acquisition and two laser equipped weapon turrets. The weapon turrets used are standard air defence turrets of Rheinmetall Air Defence which were equipped with several 10 kW Laser Weapon Modules (LWM). Each LWM consists of one 10 kW fiber laser and a beam forming unit (BFU). Commercial of the shelf fiber laser were modified for our defence applications. The BFU providing diffraction limited beam focusing, target imaging and fine tracking of the target was developed. The LWD was tested in a firing campaign at Rheinmetall test ground in Switzerland. All laser beams of both weapon turrets were superimposed on stationary and dynamic targets. Test results of the LWD for the scenarios Air Defence and C-RAMM (counter rockets, artillery, mortar and missiles) will be presented. An outlook for the next development stage towards a 100 kW class laser weapon on RWM will be given.

Target injection and engagement for neutron generation at 1 Hz

International Nuclear Information System (INIS)

Komeda, Osamu; Mori, Yoshitaka; Nishimura, Yasuhiko

2013-01-01

Target injection is a key technology to realizing inertial fusion energy. Here we present the first demonstration of target injection and neutron generation. We injected more than 600 spherical deuterated polystyrene (C 8 D 8 ) bead targets during 10 minutes at 1 Hz. After the targets fell for a distance of 18 cm, we applied the synchronized laser-diode-pumped ultra-intense laser HAMA and successfully generated neutrons repeatedly. The result is a step toward fusion power and also suggests possible industrial neutron sources. (author)

Autoradiographic demonstration of target cells for the mineralocorticoid aldosterone in the rat pineal gland

International Nuclear Information System (INIS)

Ruehle, H.J.; Ermisch, A.

1987-01-01

Male rats received [ 3 H]aldosterone 30 min before sacrifice. Autoradiograms were prepared from brain and pineal gland by a thaw-mount technique. Grain counting revealed that the pineal retained 4 times as much radioactivity as brain regions with tight capillaries. Using an appropriate method of quantitative autoradiogram evaluation, it was shown that in adrenalectomized animals, but not after shamoperiation, 28% of the pinealocytes concentrated the steroid in their nuclei. This is the first demonstration of saturable mineralocorticoid binding in the pineal gland. (author)

3D seismic surveys for shallow targets

Energy Technology Data Exchange (ETDEWEB)

Lawton, D.C.; Stewart, R.R.; Bertram, M.B. [Calgary Univ., AB (Canada). Dept. of Geoscience, Consortium for Research in Elastic Wave Exploration Seismology

2008-07-01

Although 3D seismic surveys are generally used to map deep hydrocarbon plays, this study demonstrated that they can be useful for characterizing shallow targets, such as oilsands deposits. A high-resolution 3D seismic survey was undertaken to map shallow stratigraphy near Calgary, Alberta. The project demonstrated the efficacy of reflection seismic surveys for shallow targets ranging from 100 to 500 metres. The purpose of the program was to map shallow stratigraphy and structure to depths of up to 500m, and to investigate shallow aquifers in the study area. The results of the survey illustrated the opportunity that 3D seismic surveys provide for mapping shallow reflectors and the acquisition geometry needed to image them. Applications include mapping the distribution of shallow aquifers, delineating shallow coals and investigating oilsands deposits. 2 refs., 5 figs.

Acoustic Parametric Array for Identifying Standoff Targets

Science.gov (United States)

Hinders, M. K.; Rudd, K. E.

2010-02-01

An integrated simulation method for investigating nonlinear sound beams and 3D acoustic scattering from any combination of complicated objects is presented. A standard finite-difference simulation method is used to model pulsed nonlinear sound propagation from a source to a scattering target via the KZK equation. Then, a parallel 3D acoustic simulation method based on the finite integration technique is used to model the acoustic wave interaction with the target. Any combination of objects and material layers can be placed into the 3D simulation space to study the resulting interaction. Several example simulations are presented to demonstrate the simulation method and 3D visualization techniques. The combined simulation method is validated by comparing experimental and simulation data and a demonstration of how this combined simulation method assisted in the development of a nonlinear acoustic concealed weapons detector is also presented.

Fibers as solid, internal targets for storage rings

International Nuclear Information System (INIS)

Przewoski, B.v.

1994-01-01

It has been demonstrated that fibers or micro ribbons provide the possibility to expose solid targets to a stored ion beam. Compared to gas targets or micro particle targets fiber targets require a relatively small technical effort, since differential pumping systems are not necessary to maintain the ring vacuum. Since stationary fibers are often too thick to allow for long enough lifetimes of the stored beam to be useful for experiments, a methods has been developed to move the fiber periodically through the beam. That way, the time averaged target thickness is small compared to the thickness the same fiber would have, if it were stationary in the path of the beam. In addition, the time averaged thickness can be adjusted if the amplitude of the fiber motion is increased or decreased to obtain a thinner or thicker target respectively. Measurements that compare the lifetime of the stored beam in the presence of a fiber target with the lifetime of a stored beam in the presence of a gas target show that a fiber target of a certain time averaged target thickness is equivalent to a homogeneous target of the same thickness. The data are in good agreement with Monte Carlo calculations

DESAIN BANGUNAN BARU PADA KAWASAN PELESTARIAN DI SURABAYA

Directory of Open Access Journals (Sweden)

Timoticin Kwanda

2004-01-01

Full Text Available After a period of property crash in 1997, later in 2001 the increase of economic growth has produced new infill building development or infill design in the heritage areas of Surabaya. According to some internationally known charters and recommendations, principles of new infill design in the heritage areas have been developed, such as the Recommendation concerning the Safeguarding and Contemporary Role of Historic Areas (UNESCO, 1976, the Washington Charter (1987, and the World Heritage Cities Management Guide (UNESCO, 1991. In general, the principles state that new infill design should be undertaken in an architectural style which is compatible with the surrounding character of buildings and the context. Unfortunately in Surabaya, some cases of new infill designs have damaged the character of the heritage areas. Therefore, in the future the city of Surabaya should ensuring that new infill design is appropriate by preparing design guidelines, conservation plan and conservation areas. Abstract in Bahasa Indonesia : Setelah kehancuran usaha propeti yang terjadi pada tahun 1997, pada tahun 2001 pertumbuhan ekonomi telah menghasilkan pembangunan bangunan baru atau infill design pada kawasan pelestarian di Surabaya. Berdasarkan beberapa piagam yang dikenal didunia, prinsip-prinsip desain bangunan baru pada kawasan pelestarian telah dikenal seperti The Recommendation concerning the Safeguarding and Contemporary Role of Historic Areas (UNESCO, 1976, The Washington Charter (1987, and The World Heritage Cities Management Guide (UNESCO, 1991. Secara umum, prinsip-prinsip ini menyatakan bahwa desain bangunan baru harus dilaksanakan dengan memperhatikan langgam arsitektur yang serasi dengan karakter dan konteks bangunan-bangunan disekitarnya. Namun sangat disayangkan bahwa di Surabaya beberapa kasus desain bangunan baru telah merusak karakter kawasan pelestarian. Oleh karena itu, pada masa yang akan datang kota Surabaya harus memastikan bahwa desain

The Effects of Temperature and CO2-induced Acidification on Skeletal Morphology of the Tropical Reef-building Coral Siderastrea siderea

Science.gov (United States)

Cobleigh, K.

2016-02-01

Coral reefs are threatened by increasing sea surface temperatures and decreasing surface seawater pH. Although numerous experimental studies have examined the effects of these global scale stressors on corals, few have quantified the effects of temperature and acidification on coral skeletal morphology. We conducted controlled laboratory experiments to investigate the effects of temperature (25, 28, 32°C) and CO2-induced ocean acidification (pCO2 = 324, 477, 604, 2553 µatm) on skeletal morphology of the highly resilient Caribbean reef-building coral Siderastrea siderea over a 95-day interval. Post-treatment S. siderea corallites from nearshore, backreef, and forereef colonies were imaged via stereo microscopy to evaluate impact of warming and acidification on corallite height and infilling. Both an increase and decrease in temperature relative to the control (i.e., near-present-day temperatures) resulted in increased corallite height but decreased skeletal infilling. In contrast, corals reared under the lowest (i.e., pre-industrial) and highest pCO2 treatments (i.e., extreme pCO2) exhibited both decreased corallite height and skeletal infilling relative to the control. We observed no difference in corallite height or infilling across reef zones, either within or across treatments. Interestingly, the warming projected for the end of the 21st century (32°C) resulted in increased corallite height and reduced corallite infilling. Acidification projected for the same interval (pCO2 = 604 µatm) also resulted in increased corallite height and decreased infilling. Collectively, our results suggest that these two global stressors will result in S. siderea corallites that are taller yet less infilled by the end of the 21st century. Changes in S. siderea arising from warming and acificiation may exacerbate observed declines in coral health across Caribbean reef systems.

Extended Target Recognition in Cognitive Radar Networks

Directory of Open Access Journals (Sweden)

Xiqin Wang

2010-11-01

Full Text Available We address the problem of adaptive waveform design for extended target recognition in cognitive radar networks. A closed-loop active target recognition radar system is extended to the case of a centralized cognitive radar network, in which a generalized likelihood ratio (GLR based sequential hypothesis testing (SHT framework is employed. Using Doppler velocities measured by multiple radars, the target aspect angle for each radar is calculated. The joint probability of each target hypothesis is then updated using observations from different radar line of sights (LOS. Based on these probabilities, a minimum correlation algorithm is proposed to adaptively design the transmit waveform for each radar in an amplitude fluctuation situation. Simulation results demonstrate performance improvements due to the cognitive radar network and adaptive waveform design. Our minimum correlation algorithm outperforms the eigen-waveform solution and other non-cognitive waveform design approaches.

Hybrid reactors: recent progress of a demonstration pilot; Reacteurs hybrides: avancees recentes pour un demonstrateur

Energy Technology Data Exchange (ETDEWEB)

Billebaud, Annick [Laboratoire de Physique Subatomique et de Cosmologie IN2P3-CNRS/UJF/INPG, 53 av. des Martyrs, 38026 Grenoble Cedex (France)

2006-12-15

Accelerator driven sub-critical reactors are subject of many research programmes since more than ten years, with the aim of testing the feasibility of the concept as well as their efficiency as a transmutation tool. Several key points like the accelerator, the spallation target, or neutronics in a subcritical medium were investigated extensively these last years, allowing for technological choices and the design of a low power European demonstration ADS (a few tens of MWth). Programmes dedicated to subcritical reactor piloting proposed a monitoring procedure to be validated in forthcoming experiments. Accelerator R and D provided the design of a LINAC for an ADS and research work on accelerator reliability is going on. A spallation target was operated at PSI and the design of a windowless target is in progress. All this research work converges to the design of a European demonstration ADS, the ETD/XT-ADS, which could be the Belgian MYRRHA project. (author)

Improved OAM-Based Radar Targets Detection Using Uniform Concentric Circular Arrays

Directory of Open Access Journals (Sweden)

Mingtuan Lin

2016-01-01

Full Text Available Without any relative moves or beam scanning, the novel Orbital-Angular-Momentum- (OAM- based radar targets detection technique using uniform concentric circular arrays (UCCAs shows the azimuthal estimation ability, which provides new perspective for radar system design. However, the main estimation method, that is, Fast Fourier Transform (FFT, under this scheme suffers from low resolution. As a solution, this paper rebuilds the OAM-based radar targets detection model and introduces the multiple signal classification (MUSIC algorithm to improve the resolution for detecting targets within the main lobes. The spatial smoothing technique is proposed to tackle the coherent problem brought by the proposed model. Analytical study and simulation demonstrate the superresolution estimation capacity the MUSIC algorithm can achieve for detecting targets within the main lobes. The performance of the MUSIC algorithm to detect targets not illuminated by the main lobes is further evaluated. Despite the fact that MUSIC algorithm loses the resolution advantage under this case, its estimation is more robust than that of the FFT method. Overall, the proposed MUSIC algorithm for the OAM-based radar system demonstrates the superresolution ability for detecting targets within the main lobes and good robustness for targets out of the main lobes.

Exploiting target amplitude information to improve multi-target tracking

Science.gov (United States)

Ehrman, Lisa M.; Blair, W. Dale

2006-05-01

Closely-spaced (but resolved) targets pose a challenge for measurement-to-track data association algorithms. Since the Mahalanobis distances between measurements collected on closely-spaced targets and tracks are similar, several elements of the corresponding kinematic measurement-to-track cost matrix are also similar. Lacking any other information on which to base assignments, it is not surprising that data association algorithms make mistakes. One ad hoc approach for mitigating this problem is to multiply the kinematic measurement-to-track likelihoods by amplitude likelihoods. However, this can actually be detrimental to the measurement-to-track association process. With that in mind, this paper pursues a rigorous treatment of the hypothesis probabilities for kinematic measurements and features. Three simple scenarios are used to demonstrate the impact of basing data association decisions on these hypothesis probabilities for Rayleigh, fixed-amplitude, and Rician targets. The first scenario assumes that the tracker carries two tracks but only one measurement is collected. This provides insight into more complex scenarios in which there are fewer measurements than tracks. The second scenario includes two measurements and one track. This extends naturally to the case with more measurements than tracks. Two measurements and two tracks are present in the third scenario, which provides insight into the performance of this method when the number of measurements equals the number of tracks. In all cases, basing data association decisions on the hypothesis probabilities leads to good results.

Hierarchical effects on target detection and conflict monitoring

Science.gov (United States)

Cao, Bihua; Gao, Feng; Ren, Maofang; Li, Fuhong

2016-01-01

Previous neuroimaging studies have demonstrated a hierarchical functional structure of the frontal cortices of the human brain, but the temporal course and the electrophysiological signature of the hierarchical representation remains unaddressed. In the present study, twenty-one volunteers were asked to perform a nested cue-target task, while their scalp potentials were recorded. The results showed that: (1) in comparison with the lower-level hierarchical targets, the higher-level targets elicited a larger N2 component (220–350 ms) at the frontal sites, and a smaller P3 component (350–500 ms) across the frontal and parietal sites; (2) conflict-related negativity (non-target minus target) was greater for the lower-level hierarchy than the higher-level, reflecting a more intensive process of conflict monitoring at the final step of target detection. These results imply that decision making, context updating, and conflict monitoring differ among different hierarchical levels of abstraction. PMID:27561989

Integrated Targeting and Guidance for Powered Planetary Descent

Science.gov (United States)

Azimov, Dilmurat M.; Bishop, Robert H.

2018-02-01

This paper presents an on-board guidance and targeting design that enables explicit state and thrust vector control and on-board targeting for planetary descent and landing. These capabilities are developed utilizing a new closed-form solution for the constant thrust arc of the braking phase of the powered descent trajectory. The key elements of proven targeting and guidance architectures, including braking and approach phase quartics, are employed. It is demonstrated that implementation of the proposed solution avoids numerical simulation iterations, thereby facilitating on-board execution of targeting procedures during the descent. It is shown that the shape of the braking phase constant thrust arc is highly dependent on initial mass and propulsion system parameters. The analytic solution process is explicit in terms of targeting and guidance parameters, while remaining generic with respect to planetary body and descent trajectory design. These features increase the feasibility of extending the proposed integrated targeting and guidance design to future cargo and robotic landing missions.

The Automatic Measurement of Targets

DEFF Research Database (Denmark)

Höhle, Joachim

1997-01-01

The automatic measurement of targets is demonstrated by means of a theoretical example and by an interactive measuring program for real imagery from a réseau camera. The used strategy is a combination of two methods: the maximum correlation coefficient and the correlation in the subpixel range...... interactive software is also part of a computer-assisted learning program on digital photogrammetry....

Targeted drugs in radiation therapy

International Nuclear Information System (INIS)

Favaudon, V.; Hennequin, C.; Hennequin, C.

2004-01-01

New drugs aiming at the development of targeted therapies have been assayed in combination with ionizing radiation over the past few years. The rationale of this concept comes from the fact that the cytotoxic potential of targeted drugs is limited, thus requiring concomitant association with a cytotoxic agent for the eradication of tumor cells. Conversely a low level of cumulative toxicity is expected from targeted drugs. Most targeted drugs act through inhibition of post-translational modifications of proteins, such as dimerization of growth factor receptors, prenylation reactions, or phosphorylation of tyrosine or serine-threonine residues. Many systems involving the proteasome, neo-angiogenesis promoters, TGF-β, cyclooxygenase or the transcription factor NF-κB, are currently under investigation in hopes they will allow a control of cell proliferation, apoptosis, cell cycle progression, tumor angiogenesis and inflammation. A few drugs have demonstrated an antitumor potential in particular phenotypes. In most instances, however, radiation-drug interactions proved to be strictly additive in terms of cell growth inhibition or induced cell death. Strong potentiation of the response to radiotherapy is expected to require interaction with DNA repair mechanisms. (authors)

The Use of Biotin to Demonstrate Immunohistochemistry, Western Blotting, and Dot Blots in University Practical Classes

Science.gov (United States)

Millar, Thomas James; Knighton, Ronald; Chuck, Jo-Anne

2012-01-01

Immunological detection of proteins is an essential method to demonstrate to undergraduate biology students, however, is often difficult in resource and time poor student laboratory sessions. This method describes a failsafe method to rapidly and economically demonstrate this technique using biotinylated proteins or biotin itself as targets for…

Targeted gene therapy and cell reprogramming in Fanconi anemia

Science.gov (United States)

Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A

2014-01-01

Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. PMID:24859981

Targeted Therapy for Melanoma

International Nuclear Information System (INIS)

Quinn, Thomas; Moore, Herbert

2016-01-01

The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of "2"1"2Pb labeled DOTA-Re(Arg"1"1)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter "2"1"2Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

Targeted Therapy for Melanoma

Energy Technology Data Exchange (ETDEWEB)

Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

2016-12-05

The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the ^212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg¹¹)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of ²¹²Pb labeled DOTA-Re(Arg¹¹)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter ²¹²Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

Category-based attentional guidance can operate in parallel for multiple target objects.

Science.gov (United States)

Jenkins, Michael; Grubert, Anna; Eimer, Martin

2018-04-30

The question whether the control of attention during visual search is always feature-based or can also be based on the category of objects remains unresolved. Here, we employed the N2pc component as an on-line marker for target selection processes to compare the efficiency of feature-based and category-based attentional guidance. Two successive displays containing pairs of real-world objects (line drawings of kitchen or clothing items) were separated by a 10 ms SOA. In Experiment 1, target objects were defined by their category. In Experiment 2, one specific visual object served as target (exemplar-based search). On different trials, targets appeared either in one or in both displays, and participants had to report the number of targets (one or two). Target N2pc components were larger and emerged earlier during exemplar-based search than during category-based search, demonstrating the superior efficiency of feature-based attentional guidance. On trials where target objects appeared in both displays, both targets elicited N2pc components that overlapped in time, suggesting that attention was allocated in parallel to these target objects. Critically, this was the case not only in the exemplar-based task, but also when targets were defined by their category. These results demonstrate that attention can be guided by object categories, and that this type of category-based attentional control can operate concurrently for multiple target objects. Copyright © 2018 Elsevier B.V. All rights reserved.

Advanced Simulation Capability for Environmental Management: Development and Demonstrations - 12532

Energy Technology Data Exchange (ETDEWEB)

Freshley, Mark D.; Freedman, Vicky; Gorton, Ian [Pacific Northwest National Laboratory, MSIN K9-33, P.O. Box 999, Richland, WA 99352 (United States); Hubbard, Susan S. [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 50B-4230, Berkeley, CA 94720 (United States); Moulton, J. David; Dixon, Paul [Los Alamos National Laboratory, MS B284, P.O. Box 1663, Los Alamos, NM 87544 (United States)

2012-07-01

The U.S. Department of Energy Office of Environmental Management (EM), Technology Innovation and Development is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of capabilities, which are organized into Platform and Integrated Tool-sets and a High-Performance Computing Multi-process Simulator. The Platform capabilities target a level of functionality to allow end-to-end model development, starting with definition of the conceptual model and management of data for model input. The High-Performance Computing capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The new capabilities are demonstrated through working groups, including one focused on the Hanford Site Deep Vadose Zone. The ASCEM program focused on planning during the first year and executing a prototype tool-set for an early demonstration of individual components. Subsequently, ASCEM has focused on developing and demonstrating an integrated set of capabilities, making progress toward a version of the capabilities that can be used to engage end users. Demonstration of capabilities continues to be implemented through working groups. Three different working groups, one focused on EM problems in the deep vadose zone, another investigating attenuation mechanisms for metals and radionuclides, and a third focusing on waste tank performance assessment, continue to make progress. The project

Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies

International Nuclear Information System (INIS)

Williams, J.A.; Wessels, B.W.; Wharam, M.D.; Order, S.E.; Wanek, P.M.; Poggenburg, J.K.; Klein, J.L.

1990-01-01

Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (microCi) of tumor activity per gram per 100 microCi injected activity compared to 4.5 microCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 microCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively

Exploding pusher targets for the SHIVA laser system

International Nuclear Information System (INIS)

Rosen, M.D.; Larsen, J.T.; Nuckolls, J.H.

1977-01-01

The first targets for the 20 TW SHIVA laser system were designed. They are simple glass micro-balloons, approximately 300 μm in diameter and 2 μm thick, filled with D-T gas. Using LASNEX, whose model physics was utilized successfully for ARGUS targets, we optimize for both gain and yield. The target behaves as an exploding pusher. Different simple analytic models for the physics of this mode are presented, and are tested by comparing their scaling predictions, at constant absorbed power, with those demonstrated by LASNEX. Emphasis is placed on successful prediction of the basic quantities of peak ion temperature and compression, rather than neutron yield or n tau

Thermal experiments in the ADS target model

International Nuclear Information System (INIS)

Efanov, A.D.; Orlov, Yu.I.; Sorokin, A.P.; Ivanov, E.F.; Bogoslovskaya, G.P.; Li, N.

2002-01-01

Experiments on the development of the target heat model project and method of investigation into heat exchange in target were conducted with the aim of analysis of thermomechanical and strength characteristics of device; experimental data on the temperature distribution in coolant and membrane were obtained. Obtained data demonstrate that the temperature heterogeneity of membrane and coolant are connected with the temperature distribution variability near the membrane. Peculiarities of the experiment are noted: maximal temperature of oscillations at high point of the membrane, and power bearing temperature oscillations in the range 0 - 1 Hz [ru

Electrostatic levitation and transport of laser fusion targets

International Nuclear Information System (INIS)

Johnson, W.L.; Hendricks, C.D.

1980-01-01

Several levitation concepts have been evaluated resulting in the electrostatic quadrupole being chosen as the most universal. A levitator has been constructed to handle laser fusion targets during and between the processing steps. The levitator is based on a quadrupole rail which is segmented to provide electrically controlled transport and confinement along the rail. This device has demonstrated transport both vertical and horizontal of targets with appropriate mass to size ratios and exhibits remarkably stable confinement at atmospheric pressure

Nanoparticle functionalization for brain targeting drug delivery and diagnostic

DEFF Research Database (Denmark)

Gomes, Maria João; Mendes, Bárbara; Martins, Susana

2016-01-01

carriers to cross the BBB and achieve brain, and their functionalization strategies are described; and finally the delivery of nanoparticles to the target moiety, as diagnostics or therapeutics. Therefore, this chapter is focused on how the nanoparticle surface may be functionalized for drug delivery......Nanobiotechnology has been demonstrated to be an efficient tool for targeted therapy as well as diagnosis, with particular emphasis on brain tumor and neurodegenerative diseases. On this regard, the aim of this chapter is focused on engineered nanoparticles targeted to the brain, so that they have...... and diagnostics. Furthermore, it is also mentioned that some BBB targets were already used as transport mediators to central nervous system by functionalization on nanoparticles. It summarizes the nanoparticles potential in therapeutics and molecular targeting to BBB, and also an approach of the nanoparticle...

Targeted assembly of short sequence reads.

Directory of Open Access Journals (Sweden)

René L Warren

Full Text Available As next-generation sequence (NGS production continues to increase, analysis is becoming a significant bottleneck. However, in situations where information is required only for specific sequence variants, it is not necessary to assemble or align whole genome data sets in their entirety. Rather, NGS data sets can be mined for the presence of sequence variants of interest by localized assembly, which is a faster, easier, and more accurate approach. We present TASR, a streamlined assembler that interrogates very large NGS data sets for the presence of specific variants by only considering reads within the sequence space of input target sequences provided by the user. The NGS data set is searched for reads with an exact match to all possible short words within the target sequence, and these reads are then assembled stringently to generate a consensus of the target and flanking sequence. Typically, variants of a particular locus are provided as different target sequences, and the presence of the variant in the data set being interrogated is revealed by a successful assembly outcome. However, TASR can also be used to find unknown sequences that flank a given target. We demonstrate that TASR has utility in finding or confirming genomic mutations, polymorphisms, fusions and integration events. Targeted assembly is a powerful method for interrogating large data sets for the presence of sequence variants of interest. TASR is a fast, flexible and easy to use tool for targeted assembly.

Targeted mutagenesis in sea urchin embryos using TALENs.

Science.gov (United States)

Hosoi, Sayaka; Sakuma, Tetsushi; Sakamoto, Naoaki; Yamamoto, Takashi

2014-01-01

Genome editing with engineered nucleases such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) has been reported in various animals. We previously described ZFN-mediated targeted mutagenesis and insertion of reporter genes in sea urchin embryos. In this study, we demonstrate that TALENs can induce mutagenesis at specific genomic loci of sea urchin embryos. Injection of TALEN mRNAs targeting the HpEts transcription factor into fertilized eggs resulted in the impairment of skeletogenesis. Sequence analyses of the mutations showed that deletions and/or insertions occurred at the HpEts target site in the TALEN mRNAs-injected embryos. The results suggest that targeted gene disruption using TALENs is feasible in sea urchin embryos. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Target Detection Based on EBPSK Satellite Passive Radar

Directory of Open Access Journals (Sweden)

Lu Zeyuan

2015-05-01

Full Text Available Passive radar is a topic anti stealth technology with simple structure, and low cost. Radiation source model, signal transmission model, and target detection are the key points of passive radar technology research. The paper analyzes the characteristics of EBPSK signal modulation and target detection method aspect of spaceborne radiant source. By comparison with other satellite navigation and positioning system, the characteristics of EBPSK satellite passive radar system are analyzed. It is proved that the maximum detection range of EBPSK satellite signal can satisfy the needs of the proposed model. In the passive radar model, sparse representation is used to achieve high resolution DOA detection. The comparison with the real target track by simulation demonstrates that effective detection of airborne target using EBPSK satellite passive radar system based on sparse representation is efficient.

Target scattering characteristics for OAM-based radar

Directory of Open Access Journals (Sweden)

Kang Liu

2018-02-01

Full Text Available The target scattering characteristics are crucial for radar systems. However, there is very little study conducted for the recently developed orbital angular momentum (OAM based radar system. To illustrate the role of OAM-based radar cross section (ORCS, conventional radar equation is modified by taking characteristics of the OAM waves into account. Subsequently, the ORCS is defined in analogy to classical radar cross section (RCS. The unique features of the incident OAM-carrying field are analyzed. The scattered field is derived, and the analytical expressions of ORCSs for metal plate and cylinder targets are obtained. Furthermore, the ORCS and RCS are compared to illustrate the influences of OAM mode number, target size and signal frequency on the ORCS. Analytical studies demonstrate that the mirror-reflection phenomenon disappears and peak values of ORCS are in the non-specular direction. Finally, the ORCS features are summarized to show its advantages in radar target detection. This work can provide theoretical guidance to the design of OAM-based radar as well as the target detection and identification applications.

Target scattering characteristics for OAM-based radar

Science.gov (United States)

Liu, Kang; Gao, Yue; Li, Xiang; Cheng, Yongqiang

2018-02-01

The target scattering characteristics are crucial for radar systems. However, there is very little study conducted for the recently developed orbital angular momentum (OAM) based radar system. To illustrate the role of OAM-based radar cross section (ORCS), conventional radar equation is modified by taking characteristics of the OAM waves into account. Subsequently, the ORCS is defined in analogy to classical radar cross section (RCS). The unique features of the incident OAM-carrying field are analyzed. The scattered field is derived, and the analytical expressions of ORCSs for metal plate and cylinder targets are obtained. Furthermore, the ORCS and RCS are compared to illustrate the influences of OAM mode number, target size and signal frequency on the ORCS. Analytical studies demonstrate that the mirror-reflection phenomenon disappears and peak values of ORCS are in the non-specular direction. Finally, the ORCS features are summarized to show its advantages in radar target detection. This work can provide theoretical guidance to the design of OAM-based radar as well as the target detection and identification applications.

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

Science.gov (United States)

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

2017-10-01

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

Shallow magma diversions during explosive diatreme-forming eruptions.

Science.gov (United States)

Le Corvec, Nicolas; Muirhead, James D; White, James D L

2018-04-13

The diversion of magma is an important mechanism that may lead to the relocation of a volcanic vent. Magma diversion is known to occur during explosive volcanic eruptions generating subterranean excavation and remobilization of country and volcanic rocks. However, feedbacks between explosive crater formation and intrusion processes have not been considered previously, despite their importance for understanding evolving hazards during volcanic eruptions. Here, we apply numerical modeling to test the impacts of excavation and subsequent infilling of diatreme structures on stress states and intrusion geometries during the formation of maar-diatreme complexes. Explosive excavation and infilling of diatremes affects local stress states which inhibits magma ascent and drives lateral diversion at various depths, which are expected to promote intra-diatreme explosions, host rock mixing, and vent migration. Our models demonstrate novel mechanisms explaining the generation of saucer-shaped sills, linked with magma diversion and enhanced intra-diatreme explosive fragmentation during maar-diatreme volcanism. Similar mechanisms will occur at other volcanic vents producing crater-forming eruptions.

Explicit demonstration of the convergence of the close-coupling method for a Coulomb three-body problem

International Nuclear Information System (INIS)

Bray, I.; Stelbovics, A.T.

1992-01-01

Convergence as a function of the number of states is studied and demonstrated for the Poet-Temkin model of electron-hydrogen scattering. In this Coulomb three-body problem only the l=0 partial waves are treated. By taking as many as thirty target states, obtained by diagonalizing the target Hamiltonian in a Laguerre basis, complete agreement with the smooth results of Poet is obtained at all energies. We show that the often-encountered pseudoresonance features in the cross sections are simply an indication of an inadequate target state representation

Estimating total evaporation at the field scale using the SEBS model ...

African Journals Online (AJOL)

Estimating total evaporation at the field scale using the SEBS model and data infilling ... of two infilling techniques to create a daily satellite-derived ET time series. ... and produced R2 and RMSE values of 0.33 and 2.19 mm∙d-1, respectively, ...

Is it wise to protect false targets?

International Nuclear Information System (INIS)

Levitin, Gregory; Hausken, Kjell

2011-01-01

The paper considers a system consisting of genuine elements and false targets that cannot be distinguished by the attacker's observation. The false targets can be destroyed with much less effort than the genuine elements. We show that even when an attacker cannot distinguish between the genuine elements and the false targets, in many cases it can enhance the attack efficiency using a double attack strategy in which it tries first to eliminate with minimal effort as many false targets as possible in the first attack and then distributes its entire remaining resource among all surviving targets in the second attack. The model for evaluating the system vulnerability in the double attack is suggested for a single genuine element, and multiple genuine elements configured in parallel or in series. This model assumes that in both attacks the attacking resource is distributed evenly among the attacked targets. The defender can optimize its limited resource distribution between deploying more false targets and protecting them better. The attacker can optimize its limited resource distribution between two attacks. The defense strategy is analyzed based on a two period minmax game. A numerical procedure is suggested that allows the defender to find the optimal resource distribution between deploying and protecting the false targets. The methodology of optimal attack and defense strategies analysis is demonstrated. It is shown that protecting the false targets may reduce the efficiency of the double attack strategy and make this strategy ineffective in situations with low contest intensity and few false targets. - Highlights: ► The efficiency of the double attack tactics against using false targets is analyzed. ► The role of the false target protection in system survivability enhancement is shown. ► The resource distribution between deploying more false targets and protecting them better is optimized. ► Both series and parallel systems are considered.

Buried Waste Integrated Demonstration lessons learned: 1993 technology demonstrations

International Nuclear Information System (INIS)

Kostelnik, K.M.; Owens, K.J.

1994-01-01

An integrated technology demonstration was conducted by the Buried Waste Integrated Demonstration (BWID) at the Idaho National Engineering Laboratory Cold Test Pit in the summer of 1993. This program and demonstration was sponsored by the US Department of Energy Office of Technology Development. The demonstration included six technologies representing a synergistic system for the characterization and retrieval of a buried hazardous waste site. The integrated technology demonstration proved very successful and a summary of the technical accomplishments is presented. Upon completion of the integrated technology demonstration, cognizant program personnel participated in a lessons learned exercise. This exercise was conducted at the Simplot Decision Support Center at Idaho State University and lessons learned activity captured additional information relative to the integration of technologies for demonstration purposes. This information will be used by BWID to enhance program planning and strengthen future technology demonstrations

Do overarching mitigation objectives dominate transport-specific targets in the EU?

OpenAIRE

GHERSI , Frédéric; Mcdonnell , Simon; Sassi , Olivier

2013-01-01

International audience; This research investigates if the stringent 2020 and 2050 overarching CO2 mitigation objectives set out by the European Union dominate its 2010 to 2020 targets specific to the transportation arena, specifically its biofuel penetration objectives and gram CO2 per kilometre emission caps. Using a dynamic recursive general equilibrium model, IMACLIM-R, we demonstrate that these overarching targets do not dominate the interim transportation targets when the carbon policy t...

Disturbance of semantic processing in temporal lobe epilepsy demonstrated with scalp ERPs.

Science.gov (United States)

Miyamoto, T; Katayama, J I; Kohsaka, M; Koyama, T

2000-12-01

We investigated event-related potentials (N400, LPC and CNV) elicited in temporal lobe epilepsy (TLE) patients and control subjects from scalp electrodes, using a word-pair category matching paradigm. Each prime consisted of a Japanese noun (constructed from 2-4 characters of the Hiragana) followed by a Chinese character (Kanji) as the target, the latter representing one of five semantic categories. There were two equally probable target conditions: match or mismatch. Each target was preceded by a prime, either belonging to, or not belonging to, the same semantic category. The subjects were required to respond with a specified button press to the given target, according to the condition. We found RTs to be longer under the mismatch condition in both subject groups. The N400 amplitude was reduced in TLE subjects under both conditions, although LPC and CNV amplitudes showed no significant differences. These results suggest that scalp N400 is capable of demonstrating disturbance of semantic processing in TLE non-invasively. Copyright 2000 BEA Trading Ltd.

Small target pre-detection with an attention mechanism

Science.gov (United States)

Wang, Yuehuan; Zhang, Tianxu; Wang, Guoyou

2002-04-01

We introduce the concept of predetection based on an attention mechanism to improve the efficiency of small-target detection by limiting the image region of detection. According to the characteristics of small-target detection, local contrast is taken as the only feature in predetection and a nonlinear sampling model is adopted to make the predetection adaptive to detect small targets with different area sizes. To simplify the predetection itself and decrease the false alarm probability, neighboring nodes in the sampling grid are used to generate a saliency map, and a short-term memory is adopted to accelerate the `pop-out' of targets. We discuss the fact that the proposed approach is simple enough in computational complexity. In addition, even in a cluttered background, attention can be led to targets in a satisfying few iterations, which ensures that the detection efficiency will not be decreased due to false alarms. Experimental results are presented to demonstrate the applicability of the approach.

A Mineralized Collagen-Polycaprolactone Composite Promotes Healing of a Porcine Mandibular Defect.

Science.gov (United States)

Weisgerber, Daniel W; Milner, Derek J; Lopez-Lake, Heather; Rubessa, Marcello; Lotti, Sammi; Polkoff, Kathryn; Hortensius, Rebecca A; Flanagan, Colleen L; Hollister, Scott J; Wheeler, Matthew B; Harley, Brendan A C

2018-02-01

A tissue engineering approach to address craniofacial defects requires a biomaterial that balances macro-scale mechanical stiffness and strength with the micron-scale features that promote cell expansion and tissue biosynthesis. Such criteria are often in opposition, leading to suboptimal mechanical competence or bioactivity. We report the use of a multiscale composite biomaterial that integrates a polycaprolactone (PCL) reinforcement structure with a mineralized collagen-glycosaminoglycan scaffold to circumvent conventional tradeoffs between mechanics and bioactivity. The composite promotes activation of the canonical bone morphogenetic protein 2 (BMP-2) pathway and subsequent mineralization of adipose-derived stem cells in the absence of supplemental BMP-2 or osteogenic media. We subsequently examined new bone infill in the acellular composite, scaffold alone, or PCL support in 10 mm dia. ramus mandibular defects in Yorkshire pigs. We report an analytical approach to quantify radial, angular, and depth bone infill from micro-computed tomography data. The collagen-PCL composite showed improved overall infill, and significantly increased radial and angular bone infill versus the PCL cage alone. Bone infill was further enhanced in the composite for defects that penetrated the medullary cavity, suggesting recruitment of marrow-derived cells. These results indicate a multiscale mineralized collagen-PCL composite offers strategic advantages for regenerative repair of craniofacial bone defects.

The specificity of targeted vaccines for APC surface molecules influences the immune response phenotype.

Directory of Open Access Journals (Sweden)

Gunnveig Grødeland

Full Text Available Different diseases require different immune responses for efficient protection. Thus, prophylactic vaccines should prime the immune system for the particular type of response needed for protection against a given infectious agent. We have here tested fusion DNA vaccines which encode proteins that bivalently target influenza hemagglutinins (HA to different surface molecules on antigen presenting cells (APC. We demonstrate that targeting to MHC class II molecules predominantly induced an antibody/Th2 response, whereas targeting to CCR1/3/5 predominantly induced a CD8(+/Th1 T cell response. With respect to antibodies, the polarizing effect was even more pronounced upon intramuscular (i.m delivery as compared to intradermal (i.d. vaccination. Despite these differences in induced immune responses, both vaccines protected against a viral challenge with influenza H1N1. Substitution of HA with ovalbumin (OVA demonstrated that polarization of immune responses, as a consequence of APC targeting specificity, could be extended to other antigens. Taken together, the results demonstrate that vaccination can be tailor-made to induce a particular phenotype of adaptive immune responses by specifically targeting different surface molecules on APCs.

Preliminary results on the cryogenic target for FIREX project

International Nuclear Information System (INIS)

Iwamoto, A.; Maekawa, R.; Mito, T.; Okamoto, M.; Motojima, O.; Nakai, M.; Norimatsu, T.; Nagai, K.

2006-01-01

Preliminary tests on the cryogenic target for the fast ignition realization experiment (FIREX) project has been conducted. A foam shell method is proposed to realize its target design. A foam target consists of three parts: a foam shell, a conical laser guide and a liquid or gas feeder made of glass. The shell is a hollow sphere (500 μm in diameter) with a uniform and thin foam layer (about 20 μm in thickness). Epoxy resin is utilized to assemble the parts into the target. Liquid fuel is fed into the shell by the feeder and is soaked up by the foam material through capillarity. The fuel is then solidified. Regarding target fabrication, one of the concerns is the influence on various thermal contractions from the different materials when it is cooled down to cryogenic environment. This paper describes the result on the validity check at cryogenic environment and the demonstration of H 2 liquefaction using a dummy target instead of the foam target. Judging from these results, the target assembled in the same process as the dummy target is sure to be practicable for the FIREX project. (authors)

Targeted Delivery of Protein Drugs by Nanocarriers

Directory of Open Access Journals (Sweden)

Antonella Battisti

2010-03-01

Full Text Available Recent advances in biotechnology demonstrate that peptides and proteins are the basis of a new generation of drugs. However, the transportation of protein drugs in the body is limited by their high molecular weight, which prevents the crossing of tissue barriers, and by their short lifetime due to immuno response and enzymatic degradation. Moreover, the ability to selectively deliver drugs to target organs, tissues or cells is a major challenge in the treatment of several human diseases, including cancer. Indeed, targeted delivery can be much more efficient than systemic application, while improving bioavailability and limiting undesirable side effects. This review describes how the use of targeted nanocarriers such as nanoparticles and liposomes can improve the pharmacokinetic properties of protein drugs, thus increasing their safety and maximizing the therapeutic effect.

Targeted Delivery of Immunomodulators to Lymph Nodes

Directory of Open Access Journals (Sweden)

Jamil Azzi

2016-05-01

Full Text Available Active-targeted delivery to lymph nodes represents a major advance toward more effective treatment of immune-mediated disease. The MECA79 antibody recognizes peripheral node addressin molecules expressed by high endothelial venules of lymph nodes. By mimicking lymphocyte trafficking to the lymph nodes, we have engineered MECA79-coated microparticles containing an immunosuppressive medication, tacrolimus. Following intravenous administration, MECA79-bearing particles showed marked accumulation in the draining lymph nodes of transplanted animals. Using an allograft heart transplant model, we show that targeted lymph node delivery of microparticles containing tacrolimus can prolong heart allograft survival with negligible changes in tacrolimus serum level. Using MECA79 conjugation, we have demonstrated targeted delivery of tacrolimus to the lymph nodes following systemic administration, with the capacity for immune modulation in vivo.

Targeted gene therapy and cell reprogramming in Fanconi anemia.

Science.gov (United States)

Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A

2014-06-01

Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Novel target configurations for selective ionization state studies in molybdenum

International Nuclear Information System (INIS)

Ilcisin, K.J.; Feldman, U.; Schwob, J.L.; Wouters, A.; Suckewer, S.; Princeton Univ., NJ

1990-03-01

Details of experiments aimed at achieving low ionization state selectivity in molybdenum are presented. Targets are excited with a 10 J CO 2 laser and the resultant VUV spectrum (300--700 Angstrom) has been studied. Combinations of focal spot size, target depth, and target geometries are compared. Simple attenuation of energy is shown not to vary ionization stage composition significantly. Experiments conducted with grazing incidence targets result only in a hot plasma. Modular targets with cooling cylinders of various radii demonstrated good selectivity of the ionization states, but with low absolute signals. Finally, results from combinations of focal spot adjustment and radiative cooling illustrate increased control over desired plasma temperature and density for spectroscopic studies of molybdenum. 7 refs., 14 figs

Bio-accessibility and Risk of Exposure to Metals and SVOCs in Artificial Turf Field Fill Materials and Fibers

Science.gov (United States)

Pavilonis, Brian T.; Weisel, Clifford P.; Buckley, Brian; Lioy, Paul J.

2014-01-01

To reduce maintenance costs, municipalities and schools are starting to replace natural grass fields with a new generation synthetic turf. Unlike Astro-Turf, which was first introduced in the 1960’s, synthetic field turf provides more cushioning to athletes. Part of this cushioning comes from materials like crumb rubber infill, which is manufactured from recycled tires and may contain a variety of chemicals. The goal of this study was to evaluate potential exposures from playing on artificial turf fields and associated risks to trace metals, semivolatile organic compounds (SVOCs), and polycyclic aromatic hydrocarbons (PAHs) by examining typical artificial turf fibers (n=8), different types of infill (n=8), and samples from actual fields (n=7). Three artificial biofluids were prepared which included: lung, sweat, and digestive fluids. Artificial biofluids were hypothesized to yield a more representative estimation of dose than the levels obtained from total extraction methods. PAHs were routinely below the limit of detection across all three biofluids precluding completion of a meaningful risk assessment. No SVOCs were identified at quantifiable levels in any extracts based on a match of their mass spectrum to compounds that are regulated in soil. The metals were measurable but at concentrations for which human health risk was estimated to be low. The study demonstrated that for the products and fields we tested, exposure to infill and artificial turf was generally considered de minimus, with the possible exception of lead for some fields and materials. PMID:23758133

Demonstration of a transient high gain nickel-like xenon ion x-ray laser

International Nuclear Information System (INIS)

Lu, Peixiang; Kawachi, Tetsuya; Kishimoto, Maki

2003-01-01

We demonstrate a high gain nickel-like xenon ion x-ray laser using a picosecond-laser-irradiated gas puff target. The elongated x-ray laser plasma column was produced by irradiating the gas puff target with line-focused double picosecond laser pulses with a total energy of 18 J in a travelling-wave excitation scheme. Strong lasing at 9.98 nm was observed, and a high gain coefficient of 17.4 cm -1 was measured on the transient collisionally excited 4d-4p, J=0-1 transition for nickel-like xenon ion with target lengths up to 0.45 cm. A weak nickel-like lasing line at a shorter wavelength of 9.64 nm was also observed with a gain coefficient of 5.9 cm -1 . (author)

Folate targeted polymeric 'green' nanotherapy for cancer

International Nuclear Information System (INIS)

Narayanan, Sreeja; Binulal, N S; Mony, Ullas; Manzoor, Koyakutty; Nair, Shantikumar; Menon, Deepthy

2010-01-01

The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)-'NanoGSE'-was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size ∼ 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC 50 values were lowered by a factor of ∼ 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.

Treat-to-target in systemic lupus erythematosus

DEFF Research Database (Denmark)

Mosca, Marta; Boumpas, Dimitrios T; Bruce, Ian N

2013-01-01

Multiple clinical trials performed over twenty years in the treatment of rheumatoid arthritis (RA) have clearly demonstrated that patients have better outcomes if their disease activity at each time-point for follow-up includes a pre-specified target. A European SLE expert panel met in Zurich...... on May 8, 2012 to discuss whether a treat-to-target approach could be applied in the treatment of systemic lupus erythematosus (SLE) (T2T/SLE), define a research agenda, and establish a plan for moving forward. In the present paper, observations raised at the meeting and literature data on potential...

Laser spectroscopy of collisionally prepared target species: atomic caesium

International Nuclear Information System (INIS)

Moreau, J.-P.; Tremblay, Julien; Knystautas, E.J.; Laperriere, S.C.; Larzilliere, Michel

1989-01-01

Fast ion beam bombardment was used to collisionally prepare a target gas in excited states, to which conventional laser spectroscopy was then applied. The versatility of this method is demonstrated with atomic targets of caesium, for a state of Cs + that is 16 eV above the ground state, as well as for a short-lived state (38 ns) of the neutral atom. The local temperature in the caesium oven is also obtained. (Author)

[Target volume margins for lung cancer: internal target volume/clinical target volume].

Science.gov (United States)

Jouin, A; Pourel, N

2013-10-01

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

Pancreatic cancer cell detection by targeted lipid microbubbles and multiphoton imaging

Science.gov (United States)

Cromey, Benjamin; McDaniel, Ashley; Matsunaga, Terry; Vagner, Josef; Kieu, Khanh Quoc; Banerjee, Bhaskar

2018-04-01

Surgical resection of pancreatic cancer represents the only chance of cure and long-term survival in this common disease. Unfortunately, determination of a cancer-free margin at surgery is based on one or two tiny frozen section biopsies, which is far from ideal. Not surprisingly, cancer is usually left behind and is responsible for metastatic disease. We demonstrate a method of receptor-targeted imaging using peptide ligands, lipid microbubbles, and multiphoton microscopy that could lead to a fast and accurate way of examining the entire cut surface during surgery. Using a plectin-targeted microbubble, we performed a blinded in-vitro study to demonstrate avid binding of targeted microbubbles to pancreatic cancer cells but not noncancerous cell lines. Further work should lead to a much-needed point-of-care diagnostic test for determining clean margins in oncologic surgery.

Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets.

Directory of Open Access Journals (Sweden)

Reini F Luco

2008-05-01

Full Text Available DNA binding transcriptional activators play a central role in gene-selective regulation. In part, this is mediated by targeting local covalent modifications of histone tails. Transcriptional regulation has also been associated with the positioning of genes within the nucleus. We have now examined the role of a transcriptional activator in regulating the positioning of target genes. This was carried out with primary beta-cells and hepatocytes freshly isolated from mice lacking Hnf1alpha, an activator encoded by the most frequently mutated gene in human monogenic diabetes (MODY3. We show that in Hnf1a-/- cells inactive endogenous Hnf1alpha-target genes exhibit increased trimethylated histone H3-Lys27 and reduced methylated H3-Lys4. Inactive Hnf1alpha-targets in Hnf1a-/- cells are also preferentially located in peripheral subnuclear domains enriched in trimethylated H3-Lys27, whereas active targets in wild-type cells are positioned in more central domains enriched in methylated H3-Lys4 and RNA polymerase II. We demonstrate that this differential positioning involves the decondensation of target chromatin, and show that it is spatially restricted rather than a reflection of non-specific changes in the nuclear organization of Hnf1a-deficient cells. This study, therefore, provides genetic evidence that a single transcriptional activator can influence the subnuclear location of its endogenous genomic targets in primary cells, and links activator-dependent changes in local chromatin structure to the spatial organization of the genome. We have also revealed a defect in subnuclear gene positioning in a model of a human transcription factor disease.

Etude du comportement sous charges laterales des ossatures de beton arme avec murs de remplissage de maconnerie, construites avant les annees 1960

Science.gov (United States)

Lefebvre, Karine

Reinforced concrete structures with unreinforced masonry infills (BMR) are considered vulnerable to earthquakes. Under seismic actions, infills could fail (causing injuries or death) and cause damages to columns. In Quebec and Canada, most of BMR structures have been constructed prior to the introduction of modern seismic design codes raising question on the contribution of the infill to the structure lateral resistance. The aim of this thesis is to improve modelling technique of BMR structures built in Quebec between 1915 and 1960. This type of structures is found in hospitals or schools buildings, which must comply with some post-earthquake functionality requirements. They could also be residential or office buildings. Actually, practicing engineers usually calculate seismic capacity of BMR structures without considering the infill's structural contribution to the lateral resistance. Yet, this contribution should not be omitted. The first part of the thesis investigates the construction techniques and material properties of the old BMR structures in the Province. The results are the material properties (concrete, reinforcing steel, brick, terra cotta tile, and mortar) and the characteristics of the assemblies (wall section, reinforcement details…). The second part of the thesis presents the results of series of parametric analyses to identify among modelling and geometric parameters, which ones are the most influent on the lateral load response (rigidity, fundamental period, normal modes). Linear and modal analyses were performed. The most influent parameters identified are: number of storeys, number of bays, bay's width, soft storey, openings, upper storeys modelized (instead of being replaced by punctual loads) and the modelization technique of infills panels (strut or shell). Nonlinear static analyses have been performed to identify the most influent parameters to be considered for evaluating the lateral resistance, the capacity (load / displacement) and the

Cathodic arc sputtering of functional titanium oxide thin films, demonstrating resistive switching

Energy Technology Data Exchange (ETDEWEB)

Shvets, Petr, E-mail: pshvets@innopark.kantiana.ru; Maksimova, Ksenia; Demin, Maxim; Dikaya, Olga; Goikhman, Alexander

2017-05-15

The formation of thin films of the different stable and metastable titanium oxide phases is demonstrated by cathode arc sputtering of a titanium target in an oxygen atmosphere. We also show that sputtering of titanium in vacuum yields the formation of titanium silicides on the silicon substrate. The crystal structure of the produced samples was investigated using Raman spectroscopy and X-ray diffraction. We conclude that cathode arc sputtering is a flexible method suitable for producing the functional films for electronic applications. The functionality is verified by the memory effect demonstration, based on the resistive switching in the titanium oxide thin film structure.

Breaking bad habits: Targeting MDSCs to alleviate immunosuppression in prostate cancer.

Science.gov (United States)

Pal, Sumanta K; Kortylewski, Marcin

2016-02-01

The myeloid-derived suppressor cells (MDSCs) contribute to tumor immune evasion and still remain an elusive therapeutic target. Our study identified granulocytic MDSCs accumulating in prostate cancer patients during disease progression. We demonstrate the feasibility of using STAT3siRNA-based strategy for targeting MDSCs to alleviate arginase-dependent suppression of T cell activity.

10 MMBt/Hr AFBC Commercial Demonstration Cedar Lane Farms

Energy Technology Data Exchange (ETDEWEB)

Harold M. Keener; Mary H. Wicks; Tom Machamer; Dave Hoecke; Don Bonk; Bob Brown

2005-10-31

The objective of this project was to demonstrate and promote the commercialization of coal-fired atmospheric fluidized bed combustion (AFBC) systems, with limestone addition for SO2 emissions control and a baghouse for particulate emissions control. This AFBC system was targeted for small scale industrial-commercial-institutional space and process heat applications in the 4-40 MMBtu/hr size range. A cost effective and environmentally acceptable AFBC technology in this size range could displace a considerable amount of heating gas and oil with coal, while resulting in significant total cost savings to the owner/operators.

Enabling Quantitative Optical Imaging for In-die-capable Critical Dimension Targets

Science.gov (United States)

Barnes, B.M.; Henn, M.-A.; Sohn, M. Y.; Zhou, H.; Silver, R. M.

2017-01-01

Dimensional scaling trends will eventually bring semiconductor critical dimensions (CDs) down to only a few atoms in width. New optical techniques are required to address the measurement and variability for these CDs using sufficiently small in-die metrology targets. Recently, Qin et al. [Light Sci Appl, 5, e16038 (2016)] demonstrated quantitative model-based measurements of finite sets of lines with features as small as 16 nm using 450 nm wavelength light. This paper uses simulation studies, augmented with experiments at 193 nm wavelength, to adapt and optimize the finite sets of features that work as in-die-capable metrology targets with minimal increases in parametric uncertainty. A finite element based solver for time-harmonic Maxwell's equations yields two- and three-dimensional simulations of the electromagnetic scattering for optimizing the design of such targets as functions of reduced line lengths, fewer number of lines, fewer focal positions, smaller critical dimensions, and shorter illumination wavelength. Metrology targets that exceeded performance requirements are as short as 3 μm for 193 nm light, feature as few as eight lines, and are extensible to sub-10 nm CDs. Target areas measured at 193 nm can be fifteen times smaller in area than current state-of-the-art scatterometry targets described in the literature. This new methodology is demonstrated to be a promising alternative for optical model-based in-die CD metrology. PMID:28757674

Southern Appalachian hillslope erosion rates measured by soil and detrital radiocarbon in hollows

Science.gov (United States)

T.C. Hales; K.M. Scharer; R.M. Wooten

2012-01-01

Understanding the dynamics of sediment generation and transport on hillslopes provides important constraints on the rate of sediment output from orogenic systems. Hillslope sediment fluxes are recorded by organic material found in the deposits infilling unchanneled convergent topographic features called hollows. This study describes the first hollow infilling rates...

Characterizing Tire Crumb Rubber for Exposure Assessment

Science.gov (United States)

Tire crumb rubber derived from recycled tires is widely used as infill material in synthetic turf fields in the United States. An estimated 95% of the over 12,000 installed fields in the U.S. use tire crumb rubber infill alone or mixed with sand or alternative materials. Concerns...

Identifying Drug-Target Interactions with Decision Templates.

Science.gov (United States)

Yan, Xiao-Ying; Zhang, Shao-Wu

2018-01-01

During the development process of new drugs, identification of the drug-target interactions wins primary concerns. However, the chemical or biological experiments bear the limitation in coverage as well as the huge cost of both time and money. Based on drug similarity and target similarity, chemogenomic methods can be able to predict potential drug-target interactions (DTIs) on a large scale and have no luxurious need about target structures or ligand entries. In order to reflect the cases that the drugs having variant structures interact with common targets and the targets having dissimilar sequences interact with same drugs. In addition, though several other similarity metrics have been developed to predict DTIs, the combination of multiple similarity metrics (especially heterogeneous similarities) is too naïve to sufficiently explore the multiple similarities. In this paper, based on Gene Ontology and pathway annotation, we introduce two novel target similarity metrics to address above issues. More importantly, we propose a more effective strategy via decision template to integrate multiple classifiers designed with multiple similarity metrics. In the scenarios that predict existing targets for new drugs and predict approved drugs for new protein targets, the results on the DTI benchmark datasets show that our target similarity metrics are able to enhance the predictive accuracies in two scenarios. And the elaborate fusion strategy of multiple classifiers has better predictive power than the naïve combination of multiple similarity metrics. Compared with other two state-of-the-art approaches on the four popular benchmark datasets of binary drug-target interactions, our method achieves the best results in terms of AUC and AUPR for predicting available targets for new drugs (S2), and predicting approved drugs for new protein targets (S3).These results demonstrate that our method can effectively predict the drug-target interactions. The software package can

Glypican-3 Targeting of Liver Cancer Cells Using Multifunctional Nanoparticles

Directory of Open Access Journals (Sweden)

James O. Park

2011-01-01

Full Text Available Imaging is essential in accurately detecting, staging, and treating primary liver cancer (hepatocellular carcinoma [HCC], one of the most prevalent and lethal malignancies. We developed a novel multifunctional nanoparticle (NP specifically targeting glypican-3 (GPC3, a proteoglycan implicated in promotion of cell growth that is overexpressed in most HCCs. Quantitative real-time polymerase chain reaction was performed to confirm the differential GPC3 expression in two human HCC cells, Hep G2 (high and HLF (negligible. These cells were treated with biotin-conjugated GPC3 monoclonal antibody (αGPC3 and subsequently targeted using superparamagnetic iron oxide NPs conjugated to streptavidin and Alexa Fluor 647. Flow cytometry demonstrated that only GPC3-expressing Hep G2 cells were specifically targeted using this αGPC3-NP conjugate (fourfold mean fluorescence over nontargeted NP, and magnetic resonance imaging (MRI experiments showed similar findings (threefold R2 relaxivity. Confocal fluorescence microscopy localized the αGPC3 NPs only to the cell surface of GPC3-expressing Hep G2 cells. Further characterization of this construct demonstrated a negatively charged, monodisperse, 50 nm NP, ideally suited for tumor targeting. This GPC3-specific NP system, with dual-modality imaging capability, may enhance pretreatment MRI, enable refined intraoperative HCC visualization by near-infrared fluorescence, and be potentially used as a carrier for delivery of tumor-targeted therapies, improving patient outcomes.

Direct target NOTES: prospective applications for next generation robotic platforms.

Science.gov (United States)

Atallah, S; Hodges, A; Larach, S W

2018-05-01

A new era in surgical robotics has centered on alternative access to anatomic targets and next generation designs include flexible, single-port systems which follow circuitous rather than straight pathways. Such systems maintain a small footprint and could be utilized for specialized operations based on direct organ target natural orifice transluminal endoscopic surgery (NOTES), of which transanal total mesorectal excision (taTME) is an important derivative. During two sessions, four direct target NOTES operations were conducted on a cadaveric model using a flexible robotic system to demonstrate proof-of-concept of the application of a next generation robotic system to specific types of NOTES operations, all of which required removal of a direct target organ through natural orifice access. These four operations were (a) robotic taTME, (b) robotic transvaginal hysterectomy in conjunction with (c) robotic transvaginal salpingo-oophorectomy, and in an ex vivo model, (d) trans-cecal appendectomy. Feasibility was demonstrated in all cases using the Flex ® Robotic System with Colorectal Drive. During taTME, the platform excursion was 17 cm along a non-linear path; operative time was 57 min for the transanal portion of the dissection. Robotic transvaginal hysterectomy was successfully completed in 78 min with transvaginal extraction of the uterus, although laparoscopic assistance was required. Robotic transvaginal unilateral salpingo-oophorectomy with transvaginal extraction of the ovary and fallopian tube was performed without laparoscopic assistance in 13.5 min. In an ex vivo model, a robotic trans-cecal appendectomy was also successfully performed for the purpose of demonstrating proof-of-concept only; this was completed in 24 min. A flexible robotic system has the potential to access anatomy along circuitous paths, making it a suitable platform for direct target NOTES. The conceptual operations posed could be considered suitable for next generation robotics once

PSMA-targeted bispecific Fab conjugates that engage T cells.

Science.gov (United States)

Patterson, James T; Isaacson, Jason; Kerwin, Lisa; Atassi, Ghazi; Duggal, Rohit; Bresson, Damien; Zhu, Tong; Zhou, Heyue; Fu, Yanwen; Kaufmann, Gunnar F

2017-12-15

Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity. Copyright © 2017. Published by Elsevier Ltd.

[Segment analysis of the target market of physiotherapeutic services].

Science.gov (United States)

Babaskin, D V

2010-01-01

The objective of the present study was to demonstrate the possibilities to analyse selected segments of the target market of physiotherapeutic services provided by medical and preventive-facilities of two major types. The main features of a target segment, such as provision of therapeutic massage, are illustrated in terms of two characteristics, namely attractiveness to the users and the ability of a given medical facility to satisfy their requirements. Based on the analysis of portfolio of the available target segments the most promising ones (winner segments) were selected for further marketing studies. This choice does not exclude the possibility of involvement of other segments of medical services in marketing activities.

Is it wise to leave some false targets unprotected?

International Nuclear Information System (INIS)

Levitin, Gregory; Hausken, Kjell

2013-01-01

The paper considers a system consisting of genuine elements and false targets that cannot be distinguished by the attacker's observation. The false targets can be destroyed with much less effort than the genuine elements. To enhance the attack efficiency the attacker uses a double attack strategy in which it tries first to eliminate with optimal effort as many false targets as possible in the first attack and then distributes its entire remaining resource among all surviving targets in the second attack. It is assumed that the defender can protect some of the false targets whereas the attacker attacks all targets it can observe. In both attacks the attacking resource is distributed evenly among the attacked targets. The model for evaluating the system vulnerability in the double attack is suggested for parallel and series systems. This model considers the cases of perfect and imperfect detection of the targets destroyed in the first attack. The defense strategy is analyzed based on a two period minmax game. The methodology of optimal attack and defense strategies analysis is demonstrated. In is shown that under certain conditions (high contest intensity, scarce defense resource, low FT cost, high probability of wrong identification of destroyed targets by the attacker) the defender benefits from protecting a subset of the false targets. An algorithm for determining the optimal number of false targets that should be protected is suggested

Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy

Science.gov (United States)

Joshi, Bishnu P.; Miller, Sharon J.; Lee, Cameron; Gustad, Adam; Seibel, Eric J.; Wang, Thomas D.

2012-02-01

We demonstrate a multi-spectral scanning fiber endoscope (SFE) that collects fluorescence images in vivo from three target peptides that bind specifically to murine colonic adenomas. This ultrathin endoscope was demonstrated in a genetically engineered mouse model of spontaneous colorectal adenomas based on somatic Apc (adenomatous polyposis coli) gene inactivation. The SFE delivers excitation at 440, 532, 635 nm with human patients by simultaneously visualizing multiple over expressed molecular targets unique to dysplasia.

Field Demonstration of the Ground to Space Laser Calibration: Illumination of NASA’s Earth Observing Sensors

Data.gov (United States)

National Aeronautics and Space Administration — We will capitalize on a NASA-NIST partnership to conduct a test illumination of an existing radiometric sensor on orbit. This preliminary demonstration would target...

Displaced/re-worked rhodolith deposits infilling parts of a complex Miocene multistorey submarine channel: A case history from the Sassari area (Sardinia, Italy)

Science.gov (United States)

Murru, Marco; Bassi, Davide; Simone, Lucia

2015-08-01

In the Sassari area (north-western Sardinia, Italy), the Miocene Porto Torres sub-basin sequences represent the complex multistorey mixed carbonate-siliciclastic submarine feature called the Sassari Channel. During the late Burdigalian-early Serravallian, repeated terrigenous supplies from uplifted Paleozoic crystalline substrata fed the Sassari Channel system by means of turbidity and locally hyper-concentrated turbidity flows. Shelfal areas were the source of terrigenous clasts, but open shelf rhodalgal/foramol carbonate areas were very productive and largely also contributed to the channel infilling. Re-worked sands and skeletal debris were discontinuously re-sedimented offshore as pure terrigenous, mixed and/or carbonate deposits. Major sediment supply was introduced between the latest Burdigalian and the start of the middle Langhian, during which a large amount of carbonate, mixed and siliciclastic sediments reached the Porto Torres Basin (Sassari Channel I). Contributions from shallow proximal source areas typify the lower intervals (Unit A) in marginal sectors of the channel. Upward, these evolve into autochthonous rhodolith deposits, winnowed by strong currents in relatively shallow well lit settings within a complex network of narrow tidally-controlled channels (Unit D) locally bearing coral assemblages. Conversely, re-sedimented rhodoliths from the Units B and C accumulated under conditions of higher turbidity. In deeper parts of the channel taxonomically diversified rhodoliths point to the mixing of re-deposited skeletal components from different relatively deep bathmetric settings. In the latest early Langhian, major re-sedimentation episodes, resulting in large prograding bodies (Unit D), triggered by repeated regression pulses in a frame of persistent still stand. During these episodes photophile assemblages dwelled in the elevated margin sectors of the channel. A significant latest early Langhian drop in relative sea-level resulted in impressive mass

Fluorescent imaging of cancerous tissues for targeted surgery

Science.gov (United States)

Bu, Lihong; Shen, Baozhong; Cheng, Zhen

2014-01-01

To maximize tumor excision and minimize collateral damage is the primary goal of cancer surgery. Emerging molecular imaging techniques have to “image-guided surgery” developing into “molecular imaging-guided surgery”, which is termed “targeted surgery” in this review. Consequently, the precision of surgery can be advanced from tissue-scale to molecule-scale, enabling “targeted surgery” to be a component of “targeted therapy”. Evidence from numerous experimental and clinical studies has demonstrated significant benefits of fluorescent imaging in targeted surgery with preoperative molecular diagnostic screening. Fluorescent imaging can help to improve intraoperative staging and enable more radical cytoreduction, detect obscure tumor lesions in special organs, highlight tumor margins, better map lymph node metastases, and identify important normal structures intraoperatively. Though limited tissue penetration of fluorescent imaging and tumor heterogeneity are two major hurdles for current targeted surgery, multimodality imaging and multiplex imaging may provide potential solutions to overcome these issues, respectively. Moreover, though many fluorescent imaging techniques and probes have been investigated, targeted surgery remains at a proof-of-principle stage. The impact of fluorescent imaging on cancer surgery will likely be realized through persistent interdisciplinary amalgamation of research in diverse fields. PMID:25064553

Robust Small Target Co-Detection from Airborne Infrared Image Sequences.

Science.gov (United States)

Gao, Jingli; Wen, Chenglin; Liu, Meiqin

2017-09-29

In this paper, a novel infrared target co-detection model combining the self-correlation features of backgrounds and the commonality features of targets in the spatio-temporal domain is proposed to detect small targets in a sequence of infrared images with complex backgrounds. Firstly, a dense target extraction model based on nonlinear weights is proposed, which can better suppress background of images and enhance small targets than weights of singular values. Secondly, a sparse target extraction model based on entry-wise weighted robust principal component analysis is proposed. The entry-wise weight adaptively incorporates structural prior in terms of local weighted entropy, thus, it can extract real targets accurately and suppress background clutters efficiently. Finally, the commonality of targets in the spatio-temporal domain are used to construct target refinement model for false alarms suppression and target confirmation. Since real targets could appear in both of the dense and sparse reconstruction maps of a single frame, and form trajectories after tracklet association of consecutive frames, the location correlation of the dense and sparse reconstruction maps for a single frame and tracklet association of the location correlation maps for successive frames have strong ability to discriminate between small targets and background clutters. Experimental results demonstrate that the proposed small target co-detection method can not only suppress background clutters effectively, but also detect targets accurately even if with target-like interference.

High-intensity, thin-target He-jet production source

International Nuclear Information System (INIS)

Bai, Y.; Vieira, D.J.; Wouters, J.M.; Butler, G.W.; Rosenauer, Dk; Loebner, K.E.G.; Lind, V.G.; Phillips, D.R.

1996-01-01

A thin-target He-jet system suited to the production and rapid transport of non-volatile radioactive species has been successfully operated with proton beam intensities of up to 700 μA. The system consists of a water-cooled, thin-target chamber, capillary gas transport system, moving tape/Ge detection system, and an aerosol generator/gas recirculator. The yields for a wide variety of uranium fission and deep spallation products have been measured and robust operation of the system demonstrated for several weeks. He-jet transport and collection efficiencies ranged between 15 and 25% with collection rates of 10 7 to 10 8 atoms/sec/isotope. The high-intensity, thin-target He-jet approach represents a robust production source for nonvolatile radioactive heavy ion beams

A polarized sup 3 He internal target for storage rings

CERN Document Server

Poolman, H R; Bulten, H J; Doets, M; Ent, R; Ferro-Luzzi, M; Geurts, D G; Harvey, M; Mul, F A

2000-01-01

A polarized sup 3 He internal target was employed at the internal target facility of the Amsterdam electron Pulse Stretcher and Storage ring (AmPS) at the Dutch National Institute for Nuclear and High-Energy Physics (NIKHEF). The unique features of internal targets such as chemical and isotopic purity, high and rapidly reversible polarization, and the ability to manipulate the target spin orientation were successfully demonstrated. A nuclear polarization of 0.50 (0.42) at a sup 3 He gas flow of 1.0 (2.0)x10 sup 1 sup 7 at s sup - sup 1 could be obtained. Operation at a nominal flow of 1x10 sup 1 sup 7 at s sup - sup 1 resulted in a target thickness of 0.7x10 sup 1 sup 5 at cm sup - sup 2 at a target temperature of 17 K.

Creation of targeted inversion mutations in plants using an RNA-guided endonuclease

Institute of Scientific and Technical Information of China (English)

Congsheng Zhang; Changlin Liu; Jianfeng Weng; Beijiu Cheng; Fang Liu; Xinhai Li; Chuanxiao Xie

2017-01-01

Inversions are DNA rearrangements that are essential for plant gene evolution and adaptation to environmental changes. We demonstrate the creation of targeted inversions and previously reported targeted deletion mutations via delivery of a pair of RNA-guided endonucleases (RGENs) of CRISPR/Cas9. The efficiencies of the targeted inversions were 2.6%and 2.2%in the Arabidopsis FLOWERING TIME (AtFT) and TERMINAL FLOWER 1 (AtTFL1) loci, respectively. Thus, we successfully established an approach that can potentially be used to introduce targeted DNA inversions of interest for functional studies and crop improvement.

Muon counting using silicon photomultipliers in the AMIGA detector of the Pierre Auger observatory

NARCIS (Netherlands)

Aab, A.; Abreu, P.; Aglietta, M.; Ahn, E. J.; Al Samarai, I.; Albuquerque, I. F. M.; Allekotte, I.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muniz, J.; Ambrosio, M.; Anastasi, G. A.; Anchordoqui, L.; Andrada, B.; Andringa, S.; Aramo, C.; Arqueros, F.; Arsene, N.; Asorey, H.; Assis, P.; Aublin, J.; Avila, G.; Badescu, A. M.; Balaceanu, A.; Baus, C.; Beatty, J. J.; Becker, K. H.; Bellido, J. A.; Berat, C.; Bertaina, M. E.; Bertou, X.; Biermann, P. L.; Billoir, P.; Biteau, J.; Blaess, S. G.; Blanco, A.; Blazek, J.; Bleve, C.; Bohacova, M.; Boncioli, D.; Bonifazi, C.; Borodai, N.; Botti, A. M.; Brack, J.; Brancus, I.; Bretz, T.; Bridgeman, A.; Briechle, F. L.; Buchholz, P.; Bueno, A.; Buitink, S.; Buscemi, M.; Caballero-Mora, K. S.; Caccianiga, B.; Caccianiga, L.; Cancio, A.; Canfora, F.; Caramete, L.; Caruso, R.; Castellina, A.; Cataldi, G.; Cazon, L.; Cester, R.; Chavez, A. G.; Chiavassa, A.; Chinellato, J. A.; Chudoba, J.; Clay, R. W.; Colalillo, R.; Coleman, A.; Collica, L.; Coluccia, M. R.; Conceicao, R.; Contreras, F.; Cooper, M. J.; Coutu, S.; Covault, C. E.; Cronin, J.; Dallier, R.; D'Amico, S.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; de Jong, S. J.; De Mauro, G.; de Mello Neto, J. R. T.; De Mitri, I.; de Oliveira, J.; de Souza, V.; Debatin, J.; del Peral, L.; Deligny, O.; Di Giulio, C.; Di Matteo, A.; Diaz Castro, M. L.; Diogo, F.; Dobrigkeit, C.; D'Olivo, J. C.; Dorofeev, A.; dos Anjos, R. C.; Dova, M. T.; Dundovic, A.; Ebr, J.; Engel, R.; Erdmann, M.; Erfani, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Falcke, H.; Fang, K.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Fick, B.; Figueira, J. M.; Filevich, A.; Filipcic, A.; Fratu, O.; Freire, M. M.; Fujii, T.; Fuster, A.; Garcia, B.; Garcia-Pinto, D.; Gate, F.; Gemmeke, H.; Gherghel-Lascu, A.; Ghia, P. L.; Giaccari, U.; Giammarchi, M.; Giller, M.; Glas, D.; Glaser, C.; Glass, H.; Golup, G.; Gomez Berisso, M.; Gomez Vitale, P. F.; Gonzalez, N.; Gookin, B.; Gordon, J.; Gorgi, A.; Gorham, P.; Gouffon, P.; Grillo, A. F.; Grubb, T. D.; Guarino, F.; Guedes, G. P.; Hampel, M. R.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Hasankiadeh, Q.; Haungs, A.; Hebbeker, T.; Heck, D.; Heimann, P.; Herve, A. E.; Hill, G. C.; Hojvat, C.; Holt, E.; Homola, P.; Horandel, J. R.; Horvath, P.; Hrabovsky, M.; Huege, T.; Hulsman, J.; Insolia, A.; Isar, P. G.; Jandt, I.; Jansen, S.; Johnsen, J. A.; Josebachuili, M.; Kaeaepae, A.; Kambeitz, O.; Kampert, K. H.; Kasper, P.; Katkov, I.; Keilhauer, B.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Krause, R.; Krohm, N.; Kuempel, D.; Mezek, G. Kukec; Kunka, N.; Awad, A. Kuotb; LaHurd, D.; Latronico, L.; Lauscher, M.; Lautridou, P.; Lebrun, P.; Legumina, R.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; Lopes, L.; Lopez, R.; Lopez Casado, A.; Luce, Q.; Lucero, A.; Malacari, M.; Mallamaci, M.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Maris, I. C.; Marsella, G.; Martello, D.; Martinez, H.; Martinez Bravo, O.; Masias Meza, J. J.; Mathes, H. J.; Mathys, S.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Mayotte, E.; Mazur, P. O.; Medina, C.; Medina-Tanco, G.; Melo, D.; Menshikov, A.; Messina, S.; Micheletti, M. I.; Middendorf, L.; Minaya, I. A.; Miramonti, L.; Mitrica, B.; Mockler, D.; Molina-Bueno, L.; Mollerach, S.; Montanet, F.; Morello, C.; Mostafa, M.; Mueller, G.; Muller, M. A.; Mueller, S.; Naranjo, I.; Navas, S.; Nellen, L.; Neuser, J.; Nguyenu, P. H.; Niculescu-Oglinzanu, M.; Niechciol, M.; Niemietz, L.; Niggemann, T.; Nitz, D.; Nosek, D.; Novotny, V.; Nozka, H.; Nunez, L. A.; Ochilo, L.; Oikonomou, F.; Olinto, A.; Selmi-Dei, D. Pakk; Palatka, M.; Pallotta, J.; Papenbreer, P.; Parente, G.; Parra, A.; Paul, T.; Pech, M.; Pedreira, F.; Pekala, J.; Pelayo, R.; Pena-Rodriguez, J.; Pereira, L. A. S.; Perrone, L.; Peters, C.; Petrera, S.; Phuntsok, J.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Porowski, C.; Prado, R. R.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Quinn, S.; Ramos-Pollant, R.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Reinert, D.; Revenue, B.; Ridky, J.; Risse, M.; Ristori, P.; Rizi, V.; Rodrigues de Carvalho, W.; Fernandez, G. Rodriguez; Rodriguez Rojo, J.; Rodriguez-Frias, M. D.; Rogozin, D.; Rosado, J.; Roth, M.; Roulet, E.; Rovero, A. C.; Saffi, S. J.; Saftoiu, A.; Salazar, H.; Saleh, A.; Greus, F. Salesa; Salina, G.; Sanabria Gomez, J. D.; Sanchez, F.; Sanchez-Lucas, P.; Santos, E. M.; Santos, E.; Sarazin, F.; Sarkar, B.; Sarmento, R.; Sarmiento-Cano, C.; Sato, R.; Scarso, C.; Schauer, M.; Scherini, V.; Schieler, H.; Schmidt, D.; Scholten, O.; Schovanek, P.; Schroeder, F. G.; Schulz, A.; Schulz, J.; Schumacher, J.; Sciutto, S. J.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sigl, G.; Silli, G.; Sima, O.; Smiaikowski, A.; Smida, R.; Snow, G. R.; Sommers, P.; Sonntag, S.; Sorokin, J.; Squartini, R.; Stanca, D.; Stanic, S.; Stasielak, J.; Strafella, F.; Suarez, F.; Suarez Duran, M.; Sudholz, T.; Suomijarvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Taborda, O. A.; Tapia, A.; Tepe, A.; Theodoro, V. M.; Timmermans, C.; Todero Peixoto, C. J.; Tomankova, L.; Tome, B.; Tonachini, A.; Torralba Elipe, G.; Torres Machado, D.; Torri, M.; Travnicek, P.; Trini, M.; Ulrich, R.; Unger, M.; Urban, M.; Valbuena-Delgado, A.; Valdes Galicia, J. F.; Valino, I.; Valore, L.; van Aar, G.; van Bodegom, P.; van den Berg, A. M.; van Vliet, A.; Varela, E.; Vargas Cardenas, B.; Varner, G.; Vazquez, J. R.; Vazquez, R. A.; Veberic, D.; Verzi, V.; Vicha, J.; Villasenor, L.; Vorobiov, S.; Wahlberg, H.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weindl, A.; Wiencke, L.; Wilczynski, H.; Winchen, T.; Wittkowski, D.; Wundheiler, B.; Wykes, S.; Yang, L.; Yelos, D.; Yushkov, A.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zepeda, A.; Zimmermann, B.; Ziolkowski, M.; Zong, Z.; Zuccarello, F.; collaboration, Pierre Auger

AMIGA (Auger Muons and Infill for the Ground Array) is an upgrade of the Pierre Auger Observatory designed to extend its energy range of detection and to directly measure the muon content of the cosmic ray primary particle showers. The array will be formed by an infill of surface water-Cherenkov

Polarimetric LIDAR with FRI sampling for target characterization

Science.gov (United States)

Wijerathna, Erandi; Creusere, Charles D.; Voelz, David; Castorena, Juan

2017-09-01

Polarimetric LIDAR is a significant tool for current remote sensing applications. In addition, measurement of the full waveform of the LIDAR echo provides improved ranging and target discrimination, although, data storage volume in this approach can be problematic. In the work presented here, we investigated the practical issues related to the implementation of a full waveform LIDAR system to identify polarization characteristics of multiple targets within the footprint of the illumination beam. This work was carried out on a laboratory LIDAR testbed that features a flexible arrangement of targets and the ability to change the target polarization characteristics. Targets with different retardance characteristics were illuminated with a linearly polarized laser beam and the return pulse intensities were analyzed by rotating a linear analyzer polarizer in front of a high-speed detector. Additionally, we explored the applicability and the limitations of applying a sparse sampling approach based on Finite Rate of Innovations (FRI) to compress and recover the characteristic parameters of the pulses reflected from the targets. The pulse parameter values extracted by the FRI analysis were accurate and we successfully distinguished the polarimetric characteristics and the range of multiple targets at different depths within the same beam footprint. We also demonstrated the recovery of an unknown target retardance value from the echoes by applying a Mueller matrix system model.

Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption.

Science.gov (United States)

Kadry, Hossam; Al-Hilal, Taslim A; Keshavarz, Ali; Alam, Farzana; Xu, Changxue; Joy, Abraham; Ahsan, Fakhrul

2018-04-20

Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loading, and instability. Here, we have sought to develop a filament using a single pharmaceutical polymer, with no additives, which can be multi-purposed and manipulated by computational design for the preparation of tablets with desired release and absorption patterns. As such, we have used hydroxypropyl-methylcellulose (HPMC) and diltiazem, a model drug, to prepare both drug-free and drug-impregnated filaments, and investigated their thermal and crystalline properties, studied the cytotoxicity of the filaments, designed and printed tablets with various infill densities and patterns. By alternating the drug-free and drug-impregnated filaments, we fabricated various types of tablets, studied the drug release profiles, and assessed oral absorption in rats. Both diltiazem and HPMC were stable at extrusion and printing temperatures, and the drug loading was 10% (w/w). The infill density, as well as infill patterns, influenced the drug release profile, and thus, when the infill density was increased to 100%, the percentage of drug released dramatically declined. Tablets with alternating drug-free and drug-loaded layers showed delayed and intermittent drug release, depending on when the drug-loaded layers encountered the dissolution media. Importantly, the oral absorption patterns accurately reproduced the drug release profiles and showed immediate, extended, delayed and episodic absorption of the drug from the rat gastrointestinal tract (GIT). Overall, we have demonstrated here that filaments for 3D printers can be prepared from a pharmaceutical polymer with no

WE-DE-BRA-08: A Linear Accelerator Target Allowing Rapid Switching Between Treatment and High-Contrast Imaging Modes

Energy Technology Data Exchange (ETDEWEB)

Yewondwossen, M; Robar, J; Parsons, D [Dalhousie University, Halifax, NS (Canada)

2016-06-15

Purpose: During radiotherapy treatment, lung tumors can display substantial respiratory motion. This motion usually necessitates enlarged treatment margins to provide full tumour coverage. Unfortunately, these margins limit the dose that can be prescribed for tumour control and cause complications to normal tissue. Options for real-time methods of direct detection of tumour position, and particularly those that obviate the need for inserted fiducial markers, are limited. We propose a method of tumor tracking without implanted fiducial markers using a novel fast switching-target that toggles between a FFF copper/tungsten therapy mode and a FFF low-Z target mode for imaging. In this work we demonstrate proof-of-concept of this new technology. Methods: The prototype includes two targets: i) a FFF copper/tungsten target equivalent to that in the Varian 2100 EX 6 MV, and ii) a low-Z (carbon) target with a thickness of 110% of continuous slowing down approximation range (CSDA) at 7 MeV. The two targets can be exchanged with a custom made linear slide and motor-driven actuator. The usefulness of the switching-target concept is demonstrated through experimental BEV Planar images acquired with continual treatment and imaging at a user-defined period. Results: The prototype switching-target demonstrates that two recent advances in linac technology (FFF target for therapy and low-Z target) can be combined with synergy. The switching-target approach offers the capacity for rapid switching between treatment and high-contrast imaging modes, allowing intrafractional tracking, as demonstrated in this work with dynamic breathing phantom. By using a single beam-line, the design is streamlined and may obviate the need for an auxiliary imaging system (e.g., kV OBI.) Conclusion: This switching-target approach is a feasible combination of two current advances in linac technology (FFF target for therapy and a FFF low-Z target) allowing new options in on-line IGRT.

Odour-baited targets to control New World screwworm: A preliminary field study in Mexico

International Nuclear Information System (INIS)

Torr, S.J.; Hall, M.J.R.

1992-01-01

Biconical, F3 and Wind Oriented (WOT) traps and black cloth targets, baited with swormlure-4, were assessed as catching and killing devices for the New World screwworm fly, Cochliomyia hominivorax, in Mexico. The WOT was significantly better than the other trap designs, with a mean catch 2.7 and 86.4 times better than those of the Biconical and F3, respectively. It was demonstrated that the release of swormlure-4 could be reduced from the standard 10 ml/day to 2 ml/day without a reduction in the numbers of screwworm caught in a WOT. Use of electric nets demonstrated that a visual target was not necessary for the precise location of a swormlure-4 source by screwworm. Target colour was important with respect to the landing response of screwworms on targets: in a two-choice situation, flies landed much more frequently on black than on blue or yellow, and more on these two colours than they did on white. Screwworm tend not to circle a target before landing on it: about 75% of the flies caught on a combination of electrified black target plus electric flanking net were caught on the target. 6 tabs

Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity.

Science.gov (United States)

Tacken, Paul J; Zeelenberg, Ingrid S; Cruz, Luis J; van Hout-Kuijer, Maaike A; van de Glind, Gerline; Fokkink, Remco G; Lambeck, Annechien J A; Figdor, Carl G

2011-12-22

Effective vaccines consist of 2 components: immunodominant antigens and effective adjuvants. Whereas it has been demonstrated that targeted delivery of antigens to dendritic cells (DCs) improves vaccine efficacy, we report here that co-targeting of TLR ligands (TLRLs) to DCs strongly enhances adjuvanticity and immunity. We encapsulated ligands for intracellular TLRs within biodegradable nanoparticles coated with Abs recognizing DC-specific receptors. Targeted delivery of TLRLs to human DCs enhanced the maturation and production of immune stimulatory cytokines and the Ag-specific activation of naive CD8(+) T cells. In vivo studies demonstrated that nanoparticles carrying Ag induced cytotoxic T-lymphocyte responses at 100-fold lower adjuvant dose when TLRLs were co-encapsulated instead of administered in soluble form. Moreover, the efficacy of these targeted TLRLs reduced the serum cytokine storm and related toxicity that is associated with administration of soluble TLRLs. We conclude that the targeted delivery of adjuvants may improve the efficacy and safety of DC-based vaccines.

Petawatt laser and target irradiation system at LLNL

International Nuclear Information System (INIS)

Pennington, D.M.; Perry, M.D.; Britten, J.A.; Brown, C.G.; Herman, S.; Homer, J.; Miller, J.L.; Stuart, B.C.; Tietbohl, G.; Van Lue, J.; Yanovsky, V.

1997-01-01

In May, 1996, we demonstrated the production over a petawatt of peak power in the Nova/Petawatt Laser Facility, generating 620 J in ∼ 430 fs. Results of the first focused irradiance tests, and recent deployment of a novel targeting system will be presented

Distributions of hit-numbers in single targets

Energy Technology Data Exchange (ETDEWEB)

Fowler, J F [Postgraduate Medical School, Hammersmith Hospital, London (United Kingdom)

1966-07-01

Very general models can be proposed for relating the surviving proportion of an irradiated population of cells or bacteria to the absorbed dose, but if the number of free parameters is large the model can never be tested experimentally (Zimmer; Zirkie; Tobias). A relatively simple model is therefore proposed here, based on the physical facts of energy deposition in small volumes which are currently under active investigation (Rossi), and on cell-survival experiments over a wide range of LET (e.g. Barendsen et al.; Barendsen). It is not suggested that the model is correct or final, but only that its shortcomings should be demonstrated by comparison with experimental results before more complicated models are worth pursuing. It is basically a multihit model applied first to a single target volume, but also applicable to the situation where only one out of many potential target volumes has to be inactivated to kill the organism. It can be extended to two or more target volumes if necessary. Emphasis is placed upon the amount of energy locally deposited in certain sensitive volumes called 'target volumes'.

Immunological targeting of cytomegalovirus for glioblastoma therapy

OpenAIRE

Nair, Smita K; Sampson, John H; Mitchell, Duane A

2014-01-01

Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are capable of recognizing and killing autologous GBM tumor cells. This data supports CMV antigen-directed immunotherapies against GBM.

Cancer gene therapy with targeted adenoviruses.

Science.gov (United States)

Bachtarzi, Houria; Stevenson, Mark; Fisher, Kerry

2008-11-01

Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. This manuscript aims to provide an overview of the techniques currently under development for improving adenovirus delivery to malignant cells in vivo. Primary research articles reporting improvements in adenoviral gene delivery are described. Strategies include genetic modification of viral coat proteins, non-genetic modifications including polymer encapsulation approaches and pharmacological interventions. Reprogramming adenovirus tropism in vitro has been convincingly demonstrated using a range of genetic and physical strategies. These studies have provided new insights into our understanding of virology and the field is progressing. However, there are still some limitations that need special consideration before adenovirus-targeted cancer gene therapy emerges as a routine treatment in the clinical setting.

Actinobacillus pleuropneumoniae osteomyelitis in pigs demonstrated by fluorescent in situ hybridization

DEFF Research Database (Denmark)

Jensen, Tim Kåre; Boye, Mette; Hagedorn-Olsen, T.

1999-01-01

Necrotizing osteomyelitis and fibrinopurulent arthritis with isolation of Actinobacillus pleuropneumoniae serotype 2 is reported in two pigs from a herd with lameness and mild coughing problems among 8 to 12-week-old pigs. Application of fluorescent in situ hybridization targeting 16S ribosomal R......, in joints with arthritis, and in bone necroses including lysis of growth plate and suppurative inflammation in the adjacent trabecular metaphysis, thus demonstrating that well-known infections manifest new, unusual lesions....

Long-Lived Folding Intermediates Predominate the Targeting-Competent Secretome

DEFF Research Database (Denmark)

Tsirigotaki, Alexandra; Chatzi, Katerina E; Koukaki, Marina

2018-01-01

is unknown, but is generally attributed to signal peptides and chaperones. We herein demonstrate that, during targeting, most mature domains maintain loosely packed folding intermediates. These largely soluble states are signal peptide independent and essential for translocase recognition...

Possible approaches to fast quality control of IFE targets

International Nuclear Information System (INIS)

Koresheva, E.R.; Nikitenko, A.I.; Aleksandrova, I.V.; Bazdenkov, S.V.; Belolipetskiy, A.A.; Chtcherbakov, V.I.; Osipov, I.E.

2006-01-01

In recent years, research into the development of reliable methods and techniques for characterization and quality control of ICF/IFE targets has been carried out very actively. This is motivated by the need to provide the means for precise and accurate knowledge of cryogenic target parameters. On the other hand, particular emphasis should be paid to the fact that fuelling of a commercial power plant requires ∼6 targets each second. This indicates that the development of fast quality control techniques is of critical importance as well. Therefore, in this report we discuss the issues underlying the construction of different algorithms for characterization and quality control of ICF/IFE targets. Among them are: (a) algorithm banks and their structure, (b) algorithm testing, (c) target reconstruction experiments. The algorithm bank incorporates the algorithms for two stages of target production: the stage of fuel layering technique development (motionless target) and the stage of cryogenic target delivery (injected target). In the first case an inverse algorithm for individual target characterization (3D target reconstruction) and two threshold algorithms for fast control of target quality are presented. They are based on tomographic information processing methods. Experimentally, tomographic data acquisition is carried out by a hundred projections microtomograph. The spatial resolution of the optical system of the microtomograph is 1 μm for 490 nm wavelength, the accuracy of target angular positioning is ±1.5-2.5 min. In the second case we describe the algorithm based on Fourier transform holography for ultra fast target characterization during its injection. The performed computer experiments have demonstrated much promise of this approach in the following directions: recognition of the target imperfections in both low- and high- harmonics; quality control of both a single target and a target batch; simultaneous control of both an injected target quality and

Target Localization with a Single Antenna via Directional Multipath Exploitation

Directory of Open Access Journals (Sweden)

Ali H. Muqaibel

2015-01-01

Full Text Available Target localization in urban sensing can benefit from angle dependency of the pulse shape at a radar receiver antenna. We propose a localization approach that utilizes the embedded directivity in ultra-wideband (UWB antennas to estimate target positions. A single radar unit sensing operation of indoor targets surrounded by interior walls is considered, where interior wall multipaths are exploited to provide target cross-range. This exploitation assumes resolvability of the multipath components, which is made possible by the virtue of using UWB radar signals. The proposed approach is most attractive when only few multipaths are detectable due to propagation obstructions or owing to low signal-to-noise ratios. Both simulated and experimental data are used to demonstrate the effectiveness of the proposed approach.

Characteristics of the volatile organic compounds -- Arid Integrated Demonstration Site

International Nuclear Information System (INIS)

Last, G.V.; Lenhard, R.J.; Bjornstad, B.N.; Evans, J.C.; Roberson, K.R.; Spane, F.A.; Amonette, J.E.; Rockhold, M.L.

1991-10-01

The Volatile Organic Compounds -- Arid Integrated Demonstration Program (VOC-Arid ID) is targeted at demonstration and testing of technologies for the evaluation and cleanup of volatile organic compounds and associated contaminants at arid DOE sites. The initial demonstration site is an area of carbon tetrachloride (CCl 4 ) contamination located near the center of the Hanford Site. The movement of CCl 4 and other volatile organic contaminants in the subsurface is very complex. The problem at the Hanford Site is further complicated by the concurrent discharge of other waste constituents including acids, lard oil, organic phosphates, and transuranic radionuclides. In addition, the subsurface environment is very complex, with large spatial variabilities in hydraulic properties. A thorough understanding of the problem is essential to the selection of appropriate containment, retrieval, and/or in situ remedial technologies. The effectiveness of remedial technologies depends on knowing where the contaminants are, how they are held up in a given physical and chemical subsurface environment; and knowing the physical, chemical, and microbiological changes that are induced by the various remedial technologies

Anticancer efficacy of the metabolic blocker 3-bromopyruvate: specific molecular targeting.

Science.gov (United States)

Ganapathy-Kanniappan, Shanmugasundaram; Kunjithapatham, Rani; Geschwind, Jean-Francois

2013-01-01

The anticancer efficacy of the pyruvate analog 3-bromopyruvate has been demonstrated in multiple tumor models. The chief principle underlying the antitumor effects of 3-bromopyruvate is its ability to effectively target the energy metabolism of cancer cells. Biochemically, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as the primary target of 3-bromopyruvate. Its inhibition results in the depletion of intracellular ATP, causing cell death. Several reports have also demonstrated that in addition to GAPDH inhibition, the induction of cellular stress also contributes to 3-bromopyruvate treatment-dependent apoptosis. Furthermore, recent evidence shows that 3-bromopyruvate is taken up selectively by tumor cells via the monocarboxylate transporters (MCTs) that are frequently overexpressed in cancer cells (for the export of lactate produced during aerobic glycolysis). The preferential uptake of 3-bromopyruvate via MCTs facilitates selective targeting of tumor cells while leaving healthy and non-malignant tissue untouched. Taken together, the specificity of molecular (GAPDH) targeting and selective uptake by tumor cells, underscore the potential of 3-bromopyruvate as a potent and promising anticancer agent. In this review, we highlight the mechanistic characteristics of 3-bromopyruvate and discuss its potential for translation into the clinic.

Learning through a portfolio of carbon capture and storage demonstration projects

Science.gov (United States)

Reiner, David M.

2016-01-01

Carbon dioxide capture and storage (CCS) technology is considered by many to be an essential route to meet climate mitigation targets in the power and industrial sectors. Deploying CCS technologies globally will first require a portfolio of large-scale demonstration projects. These first projects should assist learning by diversity, learning by replication, de-risking the technologies and developing viable business models. From 2005 to 2009, optimism about the pace of CCS rollout led to mutually independent efforts in the European Union, North America and Australia to assemble portfolios of projects. Since 2009, only a few of these many project proposals remain viable, but the initial rationales for demonstration have not been revisited in the face of changing circumstances. Here I argue that learning is now both more difficult and more important given the slow pace of deployment. Developing a more coordinated global portfolio will facilitate learning across projects and may determine whether CCS ever emerges from the demonstration phase.

A model expansion criterion for treating surface topography in ray path calculations using the eikonal equation

International Nuclear Information System (INIS)

Ma, Ting; Zhang, Zhongjie

2014-01-01

Irregular surface topography has revolutionized how seismic traveltime is calculated and the data are processed. There are two main schemes for dealing with an irregular surface in the seismic first-arrival traveltime calculation: (1) expanding the model and (2) flattening the surface irregularities. In the first scheme, a notional infill medium is added above the surface to expand the physical space into a regular space, as required by the eikonal equation solver. Here, we evaluate the chosen propagation velocity in the infill medium through ray path tracking with the eikonal equation-solved traveltime field, and observe that the ray paths will be physically unrealistic for some values of this propagation velocity. The choice of a suitable propagation velocity in the infill medium is crucial for seismic processing of irregular topography. Our model expansion criterion for dealing with surface topography in the calculation of traveltime and ray paths using the eikonal equation highlights the importance of both the propagation velocity of the infill physical medium and the topography gradient. (paper)

Determining the cortical target of transcranial magnetic stimulation.

Science.gov (United States)

Thielscher, A; Wichmann, F A

2009-10-01

Determining the cortical region that is effectively targeted by TMS to induce a reproducible behavioral effect is a non-trivial problem. In mapping experiments, a grid of coil positions is used to systematically assess the TMS effect on, e.g. muscle responses or error rates. The center-of-mass (CoM) of the response distribution is projected onto the cortex to determine the likely target site, implicitly assuming the existence of a single, contiguous target. The mapping results, however, often contain several local maxima. These could either stem from measurement noise, or hint towards a distributed target region. Critically, the calculation of a CoM, by design, treats multiple maxima as if they were noise. Here, a stringent hierarchical sigmoidal model fitting approach is developed that determines the cortical target(s) from TMS mapping based on electric field calculations. Monte-Carlo simulations are used to assess the significance and the goodness-of-fit of the sigmoidal fits, and to obtain confidence regions around the calculated targets. The approach was applied to mapping data on visual suppression (N=7). In all subjects, we reliably identified two or three neighboring targets commonly contributing to the suppression effect (average distance+/-SD: 7.7+/-2.3 mm). This demonstrates that (i) the assumption of a single CoM is not generally valid and (ii) the combination of TMS mapping with the fitting approach has a cortical resolution of TMS.

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

Science.gov (United States)

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

2017-09-26

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

Bacterial infection increases risk of carcinogenesis by targeting mitochondria

DEFF Research Database (Denmark)

Strickertsson, Jesper A.B.; Desler, Claus; Rasmussen, Lene Juel

2017-01-01

pathways, and compares the impact of the bacterial alteration of mitochondrial function to that of cancer. Bacterial virulence factors have been demonstrated to induce mutations of mitochondrial DNA (mtDNA) and to modulate DNA repair pathways of the mitochondria. Furthermore, virulence factors can induce...... or impair the intrinsic apoptotic pathway. The effect of bacterial targeting of mitochondria is analogous to behavior of mitochondria in a wide array of tumours, and this strongly suggests that mitochondrial targeting of bacteria is a risk factor for carcinogenesis....

Targeting the motor regulator Klar to lipid droplets

Directory of Open Access Journals (Sweden)

Einstein Jenifer

2011-02-01

Full Text Available Abstract Background In Drosophila, the transport regulator Klar displays tissue-specific localization: In photoreceptors, it is abundant on the nuclear envelope; in early embryos, it is absent from nuclei, but instead present on lipid droplets. Differential targeting of Klar appears to be due to isoform variation. Droplet targeting, in particular, has been suggested to occur via a variant C-terminal region, the LD domain. Although the LD domain is necessary and sufficient for droplet targeting in cultured cells, lack of specific reagents had made it previously impossible to analyze its role in vivo. Results Here we describe a new mutant allele of klar with a lesion specifically in the LD domain; this lesion abolishes both droplet localization of Klar and the ability of Klar to regulate droplet motion. It does not disrupt Klar's function for nuclear migration in photoreceptors. Using a GFP-LD fusion, we show that the LD domain is not only necessary but also sufficient for droplet targeting in vivo; it mediates droplet targeting in embryos, in ovaries, and in a number of somatic tissues. Conclusions Our analysis demonstrates that droplet targeting of Klar occurs via a cis-acting sequence and generates a new tool for monitoring lipid droplets in living tissues of Drosophila.

A programmable method for massively parallel targeted sequencing

Science.gov (United States)

Hopmans, Erik S.; Natsoulis, Georges; Bell, John M.; Grimes, Susan M.; Sieh, Weiva; Ji, Hanlee P.

2014-01-01

We have developed a targeted resequencing approach referred to as Oligonucleotide-Selective Sequencing. In this study, we report a series of significant improvements and novel applications of this method whereby the surface of a sequencing flow cell is modified in situ to capture specific genomic regions of interest from a sample and then sequenced. These improvements include a fully automated targeted sequencing platform through the use of a standard Illumina cBot fluidics station. Targeting optimization increased the yield of total on-target sequencing data 2-fold compared to the previous iteration, while simultaneously increasing the percentage of reads that could be mapped to the human genome. The described assays cover up to 1421 genes with a total coverage of 5.5 Megabases (Mb). We demonstrate a 10-fold abundance uniformity of greater than 90% in 1 log distance from the median and a targeting rate of up to 95%. We also sequenced continuous genomic loci up to 1.5 Mb while simultaneously genotyping SNPs and genes. Variants with low minor allele fraction were sensitively detected at levels of 5%. Finally, we determined the exact breakpoint sequence of cancer rearrangements. Overall, this approach has high performance for selective sequencing of genome targets, configuration flexibility and variant calling accuracy. PMID:24782526

ZnO film deposition by DC magnetron sputtering: Effect of target configuration on the film properties

Energy Technology Data Exchange (ETDEWEB)

Arakelova, E.; Khachatryan, A.; Kteyan, A.; Avjyan, K.; Grigoryan, S.

2016-08-01

Ballistic transport model for target-to-substrate atom transfer during magnetron sputter deposition was used to develop zinc target (cathode) configuration that enabled growth of uniform zinc oxide films on extensive surfaces and provided reproducibility of films characteristics irrespective of the cathode wear-out. The advantage of the developed target configuration for high-quality ZnO film deposition was observed in the sputtering pressure range of 5− 50 mTorr, and in the range of cathode-to-substrate distances 7–20 cm. Characteristics of the deposited films were demonstrated by using X-ray diffraction analysis, as well as optical and electrical measurements. - Highlights: • Change of target configuration for optimization of magnetron sputtering deposition is proposed. • Improvement of ZnO film properties due to use of this target is demonstrated. • This configuration provided reproducibility of the deposited films properties.

Fuels and targets for incineration and transmutation of actinides: the ITU programme

International Nuclear Information System (INIS)

Fernandez, A.; Glatz, J.P.; Haas, D.; Konings, R.J.M.; Somers, J.; Toscano, E.; Walker, C.T.; Wegen, D.

2000-01-01

The ITU programme for the development of fuels and targets for transmutation of actinides is presented. The fabrication of various types of oxide fuels/targets by dust-free processes is described. Selected results of post-irradiation examinations of irradiation experiments (SUPERFACT, TRABANT-1, EFTTRA-T4) are presented to demonstrate the irradiation behaviour of these fuels/targets. Finally, the future developments at ITU in this field are described, including the new shielded facility (the MA lab) for fabrication of minor actinide fuels. (authors)

Fuels and targets for incineration and transmutation of actinides: the ITU programme

Energy Technology Data Exchange (ETDEWEB)

Fernandez, A.; Glatz, J.P.; Haas, D.; Konings, R.J.M.; Somers, J.; Toscano, E.; Walker, C.T.; Wegen, D. [Eurpean Commission, Joint Research Centre, Institute for Transuranium Elements, Kurlsruhe (Germany)

2000-07-01

The ITU programme for the development of fuels and targets for transmutation of actinides is presented. The fabrication of various types of oxide fuels/targets by dust-free processes is described. Selected results of post-irradiation examinations of irradiation experiments (SUPERFACT, TRABANT-1, EFTTRA-T4) are presented to demonstrate the irradiation behaviour of these fuels/targets. Finally, the future developments at ITU in this field are described, including the new shielded facility (the MA lab) for fabrication of minor actinide fuels. (authors)

Immunocharacteristics of oestrogen and androgen target cells in the anterior pituitary gland of the chick as embryo demonstrated by a combined method of autoradiography and immunohistochemistry

International Nuclear Information System (INIS)

Gasc, J.-M.; Sar, M.; Stumpf, W.E.

1980-01-01

The distribution of oestrogen and androgen target cells in the anterior pituitary gland of the chick embryo on days 10, 12 and 15 of incubation was studied 1 h after the injection of tritium-labelled steroid hormone using the thaw-mount autoradiographic technique. Oestradiol target cells were localized in the caudal zone that corresponds to the so-called 'caudal lobe', while androgen target cells were found throughout the rostral and caudal lobes of the anterior gland. With a combined autoradiography and immunohistochemistry technique, most of the oestrogen target cells showed immunoreactivity to turkey LH antiserum but not to adrenocorticotrophin (1-24) and β-thyrotrophin antisera. In contrast, androgen target cells did not show positive immunoreactivity to the three antisera used. The results suggested a direct and early involvement of oestrogens but not of androgens in the feedback regulation of pituitary gonadotrophin secretion in the chick embryo. (U.K.)

Aptamers for Targeted Drug Delivery

Directory of Open Access Journals (Sweden)

Partha Ray

2010-05-01

Full Text Available Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX. SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

Evaluation of a dietary targets monitor.

Science.gov (United States)

Lean, M E J; Anderson, A S; Morrison, C; Currall, J

2003-05-01

To evaluate a two-page food frequency list for use as a Dietary Targets Monitor in large scale surveys to quantify consumptions of the key foods groups targeted in health promotion. Intakes of fruit and vegetables, starchy foods and fish estimated from a validated food frequency questionnaire (FFQ) were compared with a short food frequency list (the Dietary Targets Monitor) specifically designed to assess habitual frequency of consumption of foods in relation to dietary targets which form the basis of a National (Scottish) Food and Health Policy. A total of 1085 adults aged 25-64 y from the Glasgow MONICA Study. : The two questionnaires both collected data on frequencies of food consumption for fruit and vegetables, starchy foods and fish. Comparing the two questionnaires, there were consistent biases, best expressed as ratios (FFQ:Dietary Targets Monitor) between the methods for fruit and vegetables (1.33, 95% CI 1.29, 1.38) and 'starchy foods' (1.08, 95% CI 1.05, 1.12), the DTM showing systematic under-reporting by men. For fish consumption, there was essentially no bias between the methods (0.99, 95% CI 0.94, 1.03). Using calibration factors to adjust for biases, the Dietary Targets Monitor indicated that 16% of the subjects were achieving the Scottish Diet food target (400 g/day) for fruit and vegetable consumption. Nearly one-third (32%) of the subjects were eating the recommended intakes of fish (three portions per week). The Dietary Targets Monitor measure of starchy foods consumption was calibrated using FFQ data to be able to make quantitative estimates: 20% of subjects were eating six or more portions of starchy food daily. A similar estimation of total fat intake and saturated fat intake (g/day) allowed the categorization of subjects as low, moderate or high fat consumers, with broad agreement between the methods. The levels of agreement demonstrated by Bland-Altman analysis, were insufficient to permit use of the adjusted DTM to estimate quantitative

Targeting of deep-brain structures in nonhuman primates using MR and CT Images

Science.gov (United States)

Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Connolly, Brett; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

2015-03-01

In vivo gene delivery in central nervous systems of nonhuman primates (NHP) is an important approach for gene therapy and animal model development of human disease. To achieve a more accurate delivery of genetic probes, precise stereotactic targeting of brain structures is required. However, even with assistance from multi-modality 3D imaging techniques (e.g. MR and CT), the precision of targeting is often challenging due to difficulties in identification of deep brain structures, e.g. the striatum which consists of multiple substructures, and the nucleus basalis of meynert (NBM), which often lack clear boundaries to supporting anatomical landmarks. Here we demonstrate a 3D-image-based intracranial stereotactic approach applied toward reproducible intracranial targeting of bilateral NBM and striatum of rhesus. For the targeting we discuss the feasibility of an atlas-based automatic approach. Delineated originally on a high resolution 3D histology-MR atlas set, the NBM and the striatum could be located on the MR image of a rhesus subject through affine and nonrigid registrations. The atlas-based targeting of NBM was compared with the targeting conducted manually by an experienced neuroscientist. Based on the targeting, the trajectories and entry points for delivering the genetic probes to the targets could be established on the CT images of the subject after rigid registration. The accuracy of the targeting was assessed quantitatively by comparison between NBM locations obtained automatically and manually, and finally demonstrated qualitatively via post mortem analysis of slices that had been labelled via Evan Blue infusion and immunohistochemistry.

In vivo potency revisited - Keep the target in sight.

Science.gov (United States)

Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

2018-04-01

Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl (L) ), adding in parallel to the turnover (k syn , k deg ) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (k e(RL) ) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L 50 , is then derived. L 50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L 50 is then compared to the dissociation constant K d (target-ligand binding affinity), the conventional Black & Leff potency estimate EC 50

Bioaccessibility and Risk of Exposure to Metals and SVOCs in Artificial Turf Field Fill Materials and Fibers.

Science.gov (United States)

Pavilonis, Brian T; Weisel, Clifford P; Buckley, Brian; Lioy, Paul J

2014-01-01

To reduce maintenance costs, municipalities and schools are starting to replace natural grass fields with a new generation synthetic turf. Unlike Astro-Turf, which was first introduced in the 1960s, synthetic field turf provides more cushioning to athletes. Part of this cushioning comes from materials like crumb rubber infill, which is manufactured from recycled tires and may contain a variety of chemicals. The goal of this study was to evaluate potential exposures from playing on artificial turf fields and associated risks to trace metals, semi-volatile organic compounds (SVOCs), and polycyclic aromatic hydrocarbons (PAHs) by examining typical artificial turf fibers (n = 8), different types of infill (n = 8), and samples from actual fields (n = 7). Three artificial biofluids were prepared, which included: lung, sweat, and digestive fluids. Artificial biofluids were hypothesized to yield a more representative estimation of dose than the levels obtained from total extraction methods. PAHs were routinely below the limit of detection across all three biofluids, precluding completion of a meaningful risk assessment. No SVOCs were identified at quantifiable levels in any extracts based on a match of their mass spectrum to compounds that are regulated in soil. The metals were measurable but at concentrations for which human health risk was estimated to be low. The study demonstrated that for the products and fields we tested, exposure to infill and artificial turf was generally considered de minimus, with the possible exception of lead for some fields and materials. © 2013 Society for Risk Analysis.

Robust H∞ Control for Spacecraft Rendezvous with a Noncooperative Target

Directory of Open Access Journals (Sweden)

Shu-Nan Wu

2013-01-01

Full Text Available The robust H∞ control for spacecraft rendezvous with a noncooperative target is addressed in this paper. The relative motion of chaser and noncooperative target is firstly modeled as the uncertain system, which contains uncertain orbit parameter and mass. Then the H∞ performance and finite time performance are proposed, and a robust H∞ controller is developed to drive the chaser to rendezvous with the non-cooperative target in the presence of control input saturation, measurement error, and thrust error. The linear matrix inequality technology is used to derive the sufficient condition of the proposed controller. An illustrative example is finally provided to demonstrate the effectiveness of the controller.

Long-rod projectiles against oblique targets: analysis and design recommendations

International Nuclear Information System (INIS)

Norris, D.M.; McMaster, W.H.; Wilkins, M.L.

1976-01-01

Computer calculations provide an understanding of impact phenomena associated with long rod penetrators striking targets at oblique angles. The rod and target material behaviors are described by elastic-plastic work-hardening constitutive models. Ductile fracture is simulated by setting all tensile and shear stresses to zero when the calculated plastic deformation reaches a critical value. The important penetration material properties to defeat a given target are identified. There is no single material property of overriding importance; a combination of properties is required for an efficient penetrator. Experimental results are presented to demonstrate the effects of ductility and toughness on penetration performance. Recommendations for possible improvement are suggested

Post Inflation Targeting Monetary Policy: A Study of Britain, Japan and the United States

Directory of Open Access Journals (Sweden)

Mehdi Siamak MONADJEMI

2014-05-01

Full Text Available There is now considerable disquiet about the appropriate monetary strategy that central banks should follow in the aftermath of the global financial crisis. Several influential commentators have called for the abandonment of inflation targeting. Empirical research examining three major economies demonstrates that inflation targeting was effective prior to the crisis and a more flexible form of targeting may still be appropriate after the crisis.

How do how internal and external processes affect the behaviors of coupled marsh mudflat systems; infill, stabilize, retreat, or drown?

Science.gov (United States)

Carr, J. A.; Mariotti, G.; Wiberg, P.; Fagherazzi, S.; McGlathery, K.

2013-12-01

an eventual lateral equilibrium are possible only with large allochthonous sediment supply. Once marshes expanded, marsh retreat can be prevented by a sediment supply smaller than the one that filled the basin. At the GCE, the Altamaha River allows for enhanced allochthonous supply directly to the salt marsh platform, reducing the importance of waves on the tidal flat. As a result, infilling or retreat become the prevalent behaviors. For the VCR, the presence of seagrass decreases near bed shear stresses and sediment flux to the salt marsh platform, however, seagrass also reduces the wave energy acting on the boundary of the marsh reducing boundary erosion. Results indicate that the reduction in wave power allows for seagrass to provide a strong stabilizing affect on the coupled salt marsh tidal flat system, but as external sediment supply increases and light conditions decline the system reverts to that of a bare tidal flat. Across all systems and with current rates of sea level rise, retreat is a more likely marsh loss modality than drowning.

Adaptive Waveform Design for Cognitive Radar in Multiple Targets Situations

Directory of Open Access Journals (Sweden)

Xiaowen Zhang

2018-02-01

Full Text Available In this paper, the problem of cognitive radar (CR waveform optimization design for target detection and estimation in multiple extended targets situations is investigated. This problem is analyzed in signal-dependent interference, as well as additive channel noise for extended targets with unknown target impulse response (TIR. To address this problem, an improved algorithm is employed for target detection by maximizing the detection probability of the received echo on the promise of ensuring the TIR estimation precision. In this algorithm, an additional weight vector is introduced to achieve a trade-off among different targets. Both the estimate of TIR and transmit waveform can be updated at each step based on the previous step. Under the same constraint on waveform energy and bandwidth, the information theoretical approach is also considered. In addition, the relationship between the waveforms that are designed based on the two criteria is discussed. Unlike most existing works that only consider single target with temporally correlated characteristics, waveform design for multiple extended targets is considered in this method. Simulation results demonstrate that compared with linear frequency modulated (LFM signal, waveforms designed based on maximum detection probability and maximum mutual information (MI criteria can make radar echoes contain more multiple-target information and improve radar performance as a result.

Neighborhood Regularized Logistic Matrix Factorization for Drug-Target Interaction Prediction.

Science.gov (United States)

Liu, Yong; Wu, Min; Miao, Chunyan; Zhao, Peilin; Li, Xiao-Li

2016-02-01

In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF). Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs) than negative observations (i.e., the unknown pairs). Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches.

Purification-Free, Target-Selective Immobilization of a Protein from Cell Lysates.

Science.gov (United States)

Cha, Jaehyun; Kwon, Inchan

2018-02-27

Protein immobilization has been widely used for laboratory experiments and industrial processes. Preparation of a recombinant protein for immobilization usually requires laborious and expensive purification steps. Here, a novel purification-free, target-selective immobilization technique of a protein from cell lysates is reported. Purification steps are skipped by immobilizing a target protein containing a clickable non-natural amino acid (p-azidophenylalanine) in cell lysates onto alkyne-functionalized solid supports via bioorthogonal azide-alkyne cycloaddition. In order to achieve a target protein-selective immobilization, p-azidophenylalanine was introduced into an exogenous target protein, but not into endogenous non-target proteins using host cells with amber codon-free genomic DNAs. Immobilization of superfolder fluorescent protein (sfGFP) from cell lysates is as efficient as that of the purified sfGFP. Using two fluorescent proteins (sfGFP and mCherry), the authors also demonstrated that the target proteins are immobilized with a minimal immobilization of non-target proteins (target-selective immobilization). © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

VOC-Arid Integrated Demonstration guide to preparation of demonstration documents

International Nuclear Information System (INIS)

Jensen, E.J.; Brouns, T.M.; Koegler, K.J.; McCabe, G.H.; Morris, F.A.

1994-06-01

This guide has been prepared by Demonstration Operations of the Volatile Organic Compound-Arid Integrated Demonstration (VOC-Arid ID). Its purpose is to describe demonstration documents, designate responsibilities for these documents, and guide the Principal Investigator (PI) and others in their preparation. The main emphasis of this guide is to describe the documentation required of the PI. However, it does cover some of the responsibilities of other members of the VOC-Arid ID team. The VOC-Arid ID is one of several US Department of Energy (DOE) integrated demonstrations designed to support the demonstration of emerging environmental management and restoration technologies. The principal objective of the VOC-Arid ID is to identify, develop, and demonstrate new and innovative technologies for environmental restoration at arid or semiarid sites containing volatile organic compounds with or without associated contamination (e.g., radionuclides and metals)

Demonstrator of atmospheric reentry system with hyperbolic velocity—DASH

Science.gov (United States)

Morita, Yasuhiro; Kawaguchi, Jun'ichiro; Inatani, Yoshifumi; Abe, Takashi

2003-01-01

Among a wide variety of challenging projects planned for the coming decade is the MUSES-C mission designed by the ISAS of Japan. Despite huge amount of data collected by the previous interplanetary spacecraft and probes, the origin and evolution of the solar system still remains unveiled due to their limited information. Thus, our concern has been directed toward a sample return to carry sample from an asteroid back to the earth, which will contribute to better understanding of the system. One of the keys to success is considered the reentry technology with hyperbolic velocity, which has not been demonstrated yet. With this as background, the demonstrator of atmospheric reentry system with hyperbolic velocity, DASH, has been given a commitment to demonstrate the high-speed reentry technology, which will be launched in summer of next year by Japan's H-IIA rocket in a piggyback configuration. The spaceship, composed of a reentry capsule and its carrier, will be injected into a geostationary transfer orbit (GTO) and after several revolutions it will deorbit by burn of a solid propellant deorbit motor. The capsule, identical to that of the sample return mission, can experience the targeted level of thermal environment even from the GTO by tracing a specially designed reentry trajectory.

Inertial Confinement Fusion Target Component Fabrication and Technology Development report

International Nuclear Information System (INIS)

Steinman, D.

1994-03-01

On December 30, 1990, the US Department of Energy entered into a contract with General Atomics (GA) to be the Inertial Confinement Fusion Target Component Fabrication and Technology Development Support contractor. This report documents the technical activities which took place under this contract during the period of October 1, 1992 through September 30, 1993. During this period, GA was assigned 18 tasks in support of the Inertial Confinement Fusion program and its laboratories. These tasks included ''Capabilities Activation'' and ''Capabilities Demonstration'' to enable us to begin production of glass and composite polymer capsules. Capsule delivery tasks included ''Small Glass Shell Deliveries'' and ''Composite Polymer Capsules'' for Lawrence Livermore National Laboratory (LLNL) and Los Alamos National Laboratory (LANL). We also were asked to provide direct ''Onsite Support'' at LLNL and LANL. We continued planning for the transfer of ''Micromachining Equipment from Rocky Flats'' and established ''Target Component Micromachining and Electroplating Facilities'' at GA. We fabricated over 1100 films and filters of 11 types for Sandia National Laboratory and provided full-time onsite engineering support for target fabrication and characterization. We initiated development of methods to make targets for the Naval Research Laboratory. We investigated spherical interferometry, built an automated capsule sorter, and developed an apparatus for calorimetric measurement of fuel fill for LLNL. We assisted LANL in the ''Characterization of Opaque b-Layered Targets.'' We developed deuterated and UV-opaque polymers for use by the University of Rochester's Laboratory for Laser Energetics (UR/LLE) and devised a triple-orifice droplet generator to demonstrate the controlled-mass nature of the microencapsulation process

Improved laser-to-proton conversion efficiency in isolated reduced mass targets

Energy Technology Data Exchange (ETDEWEB)

Morace, A. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, 20133 Milano (Italy); Bellei, C.; Patel, P. K. [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550 (United States); Bartal, T.; Kim, J.; Beg, F. N. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); Willingale, L.; Maksimchuk, A.; Krushelnick, K. [University of Michigan, 2200 Bonisteel Blvd. Ann Arbor, Michigan 48109 (United States); Wei, M. S. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); General Atomics, 3550 General Atomics Court, San Diego, California 92121 (United States); Batani, D. [Univ. Bordeaux, CNRS, CEA, CELIA (Centre Lasers Intenses et Applications), UMR 5107, F-33405 Talence (France); Piovella, N. [Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, 20133 Milano (Italy); Stephens, R. B. [General Atomics, 3550 General Atomics Court, San Diego, California 92121 (United States)

2013-07-29

We present experimental results of laser-to-proton conversion efficiency as a function of lateral confinement of the refluxing electrons. Experiments were carried out using the T-Cubed laser at the Center for Ultrafast Optical Science, University of Michigan. We demonstrate that the laser-to-proton conversion efficiency increases by 50% with increased confinement of the target from surroundings with respect to a flat target of the same thickness. Three-dimensional hybrid particle-in-cell simulations using LSP code agree with the experimental data. The adopted target design is suitable for high repetition rate operation as well as for Inertial Confinement Fusion applications.

Inertial confinement fusion target insertion concepts for the National Ignition Facility

International Nuclear Information System (INIS)

Laughon, G.J.; Schultz, K.R.

1996-01-01

The National Ignition Facility (NIF) will be used to demonstrate fusion ignition in a laboratory environment in order to support development of inertial fusion as a potential fusion energy source for civilian use. However, target insertion must first be addressed before inertial fusion can become a practical energy source. Since target insertion systems currently utilized are not suitable for multiple shots in quick succession, insertion concepts involving free-falling and artificially accelerated targets are developed and evaluated against a set of predetermined guidelines. It is shown that a system involving a fast retraction positioner would be suitable. 5 refs., 4 figs

Low enrichment Mo-99 target development program at ANSTO

International Nuclear Information System (INIS)

Donlevy, Therese M.; Anderson, Peter J.; Beattie, David; Braddock, Ben; Fulton, Scott; Godfrey, Robert; Law, Russell; McNiven, Scott; Sirkka, Pertti; Storr, Greg; Wassink, David; Wong, Alan; Yeoh, Guan

2002-01-01

The Australian Nuclear Science and Technology Organisation (ANSTO, formerly AAEC) has been producing fission product Mo-99 in HIFAR, from the irradiation of Low Enrichment Uranium (LEU) UO 2 targets, for nearly thirty years. Over this period, the U-235 enrichment has been increased in stages, from natural to 1.8% to 2.2%. The decision to provide Australia with a replacement research reactor (RRR) for HIFAR has created an ideal opportunity to review and improve the current Mo-99 production process from target design through to chemical processing and waste management options. ANSTO has entered into a collaboration with Argonne National Laboratory (RERTR) to develop a target using uranium metal foil with U-235 enrichment of less than 20% The initial focus has been to demonstrate use of LEU foil targets in HIFAR, using existing irradiation methodology. The current effort focussed on designing a target assembly with optimised thermohydraulic characteristics to accommodate larger LEU foils to meet Mo-99 production needs. The ultimate goal is to produce an LEU target suitable for use in the Replacement Research Reactor when it is commissioned in 2005. This paper reports our activities on: - The regulatory approval processes required in order to undertake irradiation of this new target; -Supporting calculations (neutronics, computational fluid dynamics) for safety submission; - Design challenges and changes to prototype irradiation; - Trial irradiation of LEU foil target in HIFAR; - Future target and rig development program at ANSTO. (author)

Targeting Antibacterial Agents by Using Drug-Carrying Filamentous Bacteriophages

Science.gov (United States)

Yacoby, Iftach; Shamis, Marina; Bar, Hagit; Shabat, Doron; Benhar, Itai

2006-01-01

Bacteriophages have been used for more than a century for (unconventional) therapy of bacterial infections, for half a century as tools in genetic research, for 2 decades as tools for discovery of specific target-binding proteins, and for nearly a decade as tools for vaccination or as gene delivery vehicles. Here we present a novel application of filamentous bacteriophages (phages) as targeted drug carriers for the eradication of (pathogenic) bacteria. The phages are genetically modified to display a targeting moiety on their surface and are used to deliver a large payload of a cytotoxic drug to the target bacteria. The drug is linked to the phages by means of chemical conjugation through a labile linker subject to controlled release. In the conjugated state, the drug is in fact a prodrug devoid of cytotoxic activity and is activated following its dissociation from the phage at the target site in a temporally and spatially controlled manner. Our model target was Staphylococcus aureus, and the model drug was the antibiotic chloramphenicol. We demonstrated the potential of using filamentous phages as universal drug carriers for targetable cells involved in disease. Our approach replaces the selectivity of the drug itself with target selectivity borne by the targeting moiety, which may allow the reintroduction of nonspecific drugs that have thus far been excluded from antibacterial use (because of toxicity or low selectivity). Reintroduction of such drugs into the arsenal of useful tools may help to combat emerging bacterial antibiotic resistance. PMID:16723570

One gigasample per second transient recorder: a performance demonstration

International Nuclear Information System (INIS)

Linnenbrink, T.E.; Gradl, D.A.; Ritt, D.M.; DeWitte, G.J.; Hutton, J.D.

1982-01-01

The performance demonstrated by a one gigasample per second (1 Gs/s) transient recorder currently in advanced development portends an important new instrument for recording single transient data. A Charge-Coupled Device (CCD) is used to sample a continuous analog signal. Samples acquired at the full sampling rate (1 Gs/s) are temporarily stored in the CCD, then read out at a slow rate (e.g., 250 Ks/s) into a conventional analog-to-digital converter prior to storage in nonvolatile, digital memory. Enhanced circuitry and techniques developed over the past three years have yielded higher performance than originally anticipated. Accordingly, the target specification has been revised to reflect higher expectations

National Ignition Facility Target Chamber

International Nuclear Information System (INIS)

Wavrik, R W; Cox, J R; Fleming, P J

2000-01-01

On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at the precise center of the chamber. The laser beams will enter the chamber in two by two arrays to illuminate 10 millimeter long gold cylinders called hohlraums enclosing 2 millimeter capsule containing deuterium, tritium and isotopes of hydrogen. The two isotopes will fuse, thereby creating temperatures and pressures resembling those found only inside stars and in detonated nuclear weapons, but on a minute scale. The NIF Project will serve as an essential facility to insure safety and reliability of our nation's nuclear arsenal as well as demonstrating inertial fusion's contribution to creating electrical power. The paper will discuss the requirements that had to be addressed during the design, fabrication and testing of the target chamber. A team from Sandia National Laboratories (SNL) and LLNL with input from industry performed the configuration and basic design of the target chamber. The method of fabrication and construction of the aluminum target chamber was devised by Pitt-Des Moines, Inc. (PDM). PDM also participated in the design of the chamber in areas such as the Target Chamber Realignment and Adjustment System, which would allow realignment of the sphere laser beams in the event of earth settlement or movement from a seismic event. During the fabrication of the target chamber the sphericity tolerances had to be addressed for the individual plates. Procedures were developed for forming, edge preparation and welding of individual plates. Construction plans were developed to allow the field construction of the target chamber to occur parallel to other NIF construction activities. This was

Improved characterization of reservoir behavior by integration of reservoir performances data and rock type distributions

Energy Technology Data Exchange (ETDEWEB)

Davies, D.K.; Vessell, R.K. [David K. Davies & Associates, Kingwood, TX (United States); Doublet, L.E. [Texas A& M Univ., College Station, TX (United States)] [and others

1997-08-01

An integrated geological/petrophysical and reservoir engineering study was performed for a large, mature waterflood project (>250 wells, {approximately}80% water cut) at the North Robertson (Clear Fork) Unit, Gaines County, Texas. The primary goal of the study was to develop an integrated reservoir description for {open_quotes}targeted{close_quotes} (economic) 10-acre (4-hectare) infill drilling and future recovery operations in a low permeability, carbonate (dolomite) reservoir. Integration of the results from geological/petrophysical studies and reservoir performance analyses provide a rapid and effective method for developing a comprehensive reservoir description. This reservoir description can be used for reservoir flow simulation, performance prediction, infill targeting, waterflood management, and for optimizing well developments (patterns, completions, and stimulations). The following analyses were performed as part of this study: (1) Geological/petrophysical analyses: (core and well log data) - {open_quotes}Rock typing{close_quotes} based on qualitative and quantitative visualization of pore-scale features. Reservoir layering based on {open_quotes}rock typing {close_quotes} and hydraulic flow units. Development of a {open_quotes}core-log{close_quotes} model to estimate permeability using porosity and other properties derived from well logs. The core-log model is based on {open_quotes}rock types.{close_quotes} (2) Engineering analyses: (production and injection history, well tests) Material balance decline type curve analyses to estimate total reservoir volume, formation flow characteristics (flow capacity, skin factor, and fracture half-length), and indications of well/boundary interference. Estimated ultimate recovery analyses to yield movable oil (or injectable water) volumes, as well as indications of well and boundary interference.

APT target-blanket fabrication development

Energy Technology Data Exchange (ETDEWEB)

Fisher, D.L.

1997-06-13

Concepts for producing tritium in an accelerator were translated into hardware for engineering studies of tritium generation, heat transfer, and effects of proton-neutron flux on materials. Small-scale target- blanket assemblies were fabricated and material samples prepared for these performance tests. Blanket assemblies utilize composite aluminum-lead modules, the two primary materials of the blanket. Several approaches are being investigated to produce large-scale assemblies, developing fabrication and assembly methods for their commercial manufacture. Small-scale target-blanket assemblies, designed and fabricated at the Savannah River Site, were place in Los Alamos Neutron Science Center (LANSCE) for irradiation. They were subjected to neutron flux for nine months during 1996-97. Coincident with this test was the development of production methods for large- scale modules. Increasing module size presented challenges that required new methods to be developed for fabrication and assembly. After development, these methods were demonstrated by fabricating and assembling two production-scale modules.

Statistical Inference for Data Adaptive Target Parameters.

Science.gov (United States)

Hubbard, Alan E; Kherad-Pajouh, Sara; van der Laan, Mark J

2016-05-01

Consider one observes n i.i.d. copies of a random variable with a probability distribution that is known to be an element of a particular statistical model. In order to define our statistical target we partition the sample in V equal size sub-samples, and use this partitioning to define V splits in an estimation sample (one of the V subsamples) and corresponding complementary parameter-generating sample. For each of the V parameter-generating samples, we apply an algorithm that maps the sample to a statistical target parameter. We define our sample-split data adaptive statistical target parameter as the average of these V-sample specific target parameters. We present an estimator (and corresponding central limit theorem) of this type of data adaptive target parameter. This general methodology for generating data adaptive target parameters is demonstrated with a number of practical examples that highlight new opportunities for statistical learning from data. This new framework provides a rigorous statistical methodology for both exploratory and confirmatory analysis within the same data. Given that more research is becoming "data-driven", the theory developed within this paper provides a new impetus for a greater involvement of statistical inference into problems that are being increasingly addressed by clever, yet ad hoc pattern finding methods. To suggest such potential, and to verify the predictions of the theory, extensive simulation studies, along with a data analysis based on adaptively determined intervention rules are shown and give insight into how to structure such an approach. The results show that the data adaptive target parameter approach provides a general framework and resulting methodology for data-driven science.

Penalty dynamic programming algorithm for dim targets detection in sensor systems.

Science.gov (United States)

Huang, Dayu; Xue, Anke; Guo, Yunfei

2012-01-01

In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

Penalty Dynamic Programming Algorithm for Dim Targets Detection in Sensor Systems

Directory of Open Access Journals (Sweden)

Yunfei Guo

2012-04-01

Full Text Available In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD called penalty DP-TBD (PDP-TBD is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

Target recognition of ladar range images using even-order Zernike moments.

Science.gov (United States)

Liu, Zheng-Jun; Li, Qi; Xia, Zhi-Wei; Wang, Qi

2012-11-01

Ladar range images have attracted considerable attention in automatic target recognition fields. In this paper, Zernike moments (ZMs) are applied to classify the target of the range image from an arbitrary azimuth angle. However, ZMs suffer from high computational costs. To improve the performance of target recognition based on small samples, even-order ZMs with serial-parallel backpropagation neural networks (BPNNs) are applied to recognize the target of the range image. It is found that the rotation invariance and classified performance of the even-order ZMs are both better than for odd-order moments and for moments compressed by principal component analysis. The experimental results demonstrate that combining the even-order ZMs with serial-parallel BPNNs can significantly improve the recognition rate for small samples.

Development of 99Mo isotope production targets employing uranium metal foils

International Nuclear Information System (INIS)

Hofman, G.L.; Wiencek, T.C.; Wood, E.L.; Snelgrove, J.L.

1997-01-01

The Reduced Enrichment Research and Test Reactor Program has continued its effort in the past 3 yr to develop use of low-enriched uranium (LEU) to produce the fission product 99 Mo. This work comprises both target and chemical processing development and demonstration. Two major target systems are now being used to produce 99 Mo with highly enriched uranium-one employing research reactor fuel technology (either uranium-aluminum alloy or uranium aluminide-aluminum dispersion) and the other using a thin deposit of UO 2 on the inside of a stainless steel (SST) tube. This paper summarizes progress in irradiation testing of targets based on LEU uranium metal foils. Several targets of this type have been irradiated in the Indonesian RSG-GAS reactor operating at 22.5 MW

Actual Waste Demonstration of the Nitric-Glycolic Flowsheet for Sludge Batch 9 Qualification

Energy Technology Data Exchange (ETDEWEB)

Newell, J. D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Pareizs, J. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Martino, C. J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Reboul, S. H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Coleman, C. J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Edwards, T. B. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Johnson, F. C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2016-09-01

For each sludge batch that is processed in the Defense Waste Processing Facility (DWPF), the Savannah River National Laboratory (SRNL) performs qualification testing to demonstrate that the sludge batch is processable. Testing performed by the Savannah River National Laboratory has shown glycolic acid to be effective in replacing the function of formic acid in the DWPF chemical process. The nitric-glycolic flowsheet reduces mercury, significantly lowers the catalytic generation of hydrogen and ammonia which could allow purge reduction in the Sludge Receipt and Adjustment Tank (SRAT), stabilizes the pH and chemistry in the SRAT and the Slurry Mix Evaporator (SME), allows for effective rheology adjustment, and is favorable with respect to melter flammability. In order to implement the new flowsheet, SRAT and SME cycles, designated SC-18, were performed using a Sludge Batch (SB) 9 slurry blended from SB8 Tank 40H and Tank 51H samples. The SRAT cycle involved adding nitric and glycolic acids to the sludge, refluxing to steam strip mercury, and dewatering to a targeted solids concentration. Data collected during the SRAT cycle included offgas analyses, process temperatures, heat transfer, and pH measurements. The SME cycle demonstrated the addition of glass frit and the replication of six canister decontamination additions. The demonstration concluded with dewatering to a targeted solids concentration. Data collected during the SME cycle included offgas analyses, process temperatures, heat transfer, and pH measurements. Slurry and condensate samples were collected for subsequent analysis

Application of integrated reservoir management and reservoir characterization to optimize infill drilling, Class II

Energy Technology Data Exchange (ETDEWEB)

Bergeron, Jack; Blasingame, Tom; Doublet, Louis; Kelkar, Mohan; Freeman, George; Callard, Jeff; Moore, David; Davies, David; Vessell, Richard; Pregger, Brian; Dixon, Bill; Bezant, Bryce

2000-03-16

The major purpose of this project was to demonstrate the use of cost effective reservoir characterization and management tools that will be helpful to both independent and major operators for the optimal development of heterogeneous, low permeability carbonate reservoirs such as the North Robertson (Clearfork) Unit.

Post mitigation impact risk analysis for asteroid deflection demonstration missions

Science.gov (United States)

Eggl, Siegfried; Hestroffer, Daniel; Thuillot, William; Bancelin, David; Cano, Juan L.; Cichocki, Filippo

2015-08-01

Even though mankind believes to have the capabilities to avert potentially disastrous asteroid impacts, only the realization of mitigation demonstration missions can validate this claim. Such a deflection demonstration attempt has to be cost effective, easy to validate, and safe in the sense that harmless asteroids must not be turned into potentially hazardous objects. Uncertainties in an asteroid's orbital and physical parameters as well as those additionally introduced during a mitigation attempt necessitate an in depth analysis of deflection mission designs in order to dispel planetary safety concerns. We present a post mitigation impact risk analysis of a list of potential kinetic impactor based deflection demonstration missions proposed in the framework of the NEOShield project. Our results confirm that mitigation induced uncertainties have a significant influence on the deflection outcome. Those cannot be neglected in post deflection impact risk studies. We show, furthermore, that deflection missions have to be assessed on an individual basis in order to ensure that asteroids are not inadvertently transported closer to the Earth at a later date. Finally, we present viable targets and mission designs for a kinetic impactor test to be launched between the years 2025 and 2032.

Music-of-light stethoscope: a demonstration of the photoacoustic effect

Science.gov (United States)

Nikitichev, D. I.; Xia, W.; Hill, E.; Mosse, C. A.; Perkins, T.; Konyn, K.; Ourselin, S.; Desjardins, A. E.; Vercauteren, T.

2016-07-01

In this paper we present a system aimed at demonstrating the photoacoustic (PA) effect for educational purposes. PA imaging is a hybrid imaging modality that requires no contrast agent and has a great potential for spine and brain lesion characterisation, breast cancer and blood flow monitoring notably in the context of fetal surgery. It relies on combining light excitation with ultrasound reception. Our brief was to present and explain PA imaging in a public-friendly way suitable for a variety of ages and backgrounds. We developed a simple, accessible demonstration unit using readily available materials. We used a modulated light emitting diode (LED) torch and an electronic stethoscope. The output of a music player was used for light modulation and the chest piece of the stethoscope covered by a black tape was used as an absorbing target and an enclosed chamber. This demonstration unit was presented to the public at the Bloomsbury Festival On Light in October 2015. Our stall was visited by over 100 people of varying ages. Twenty families returned in-depth evaluation questionnaires, which show that our explanations of the photoacoustic effect were well understood. Their interest in biomedical engineering was increased.

Assessment of CASP7 structure predictions for template free targets.

Science.gov (United States)

Jauch, Ralf; Yeo, Hock Chuan; Kolatkar, Prasanna R; Clarke, Neil D

2007-01-01

In CASP7, protein structure prediction targets that lacked substantial similarity to a protein in the PDB at the time of assessment were considered to be free modeling targets (FM). We assessed predictions for 14 FM targets as well as four other targets that were deemed to be on the borderline between FM targets and template based modeling targets (TBM/FM). GDT_TS was used as one measure of model quality. Model quality was also assessed by visual inspection. Visual inspection was performed by three independent assessors who were blinded to GDT_TS scores and other quantitative measures of model quality. The best models by visual inspection tended to rank among the top few percent by GDT_TS, but were typically not the highest scoring models. Thus, visual inspection remains an essential component of assessment for FM targets. Overall, group TS020 (Baker) performed best, but success on individual targets was widely distributed among many groups. Among these other groups, TS024 and TS025 (Zhang and Zhang server) performed notably well without exceptionally large computing resources. This should be considered encouraging for future CASPs. There was a sense of progress in template FM relative to CASP6, but we were unable to demonstrate this progress objectively. (c) 2007 Wiley-Liss, Inc.

Nuclear EGFR as a molecular target in cancer

International Nuclear Information System (INIS)

Brand, Toni M.; Iida, Mari; Luthar, Neha; Starr, Megan M.; Huppert, Evan J.; Wheeler, Deric L.

2013-01-01

The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell’s nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future

A Simple Combinatorial Codon Mutagenesis Method for Targeted Protein Engineering.

Science.gov (United States)

Belsare, Ketaki D; Andorfer, Mary C; Cardenas, Frida S; Chael, Julia R; Park, Hyun June; Lewis, Jared C

2017-03-17

Directed evolution is a powerful tool for optimizing enzymes, and mutagenesis methods that improve enzyme library quality can significantly expedite the evolution process. Here, we report a simple method for targeted combinatorial codon mutagenesis (CCM). To demonstrate the utility of this method for protein engineering, CCM libraries were constructed for cytochrome P450 BM3 , pfu prolyl oligopeptidase, and the flavin-dependent halogenase RebH; 10-26 sites were targeted for codon mutagenesis in each of these enzymes, and libraries with a tunable average of 1-7 codon mutations per gene were generated. Each of these libraries provided improved enzymes for their respective transformations, which highlights the generality, simplicity, and tunability of CCM for targeted protein engineering.

Laser coupling to reduced-scale targets at Nif Early Light

Energy Technology Data Exchange (ETDEWEB)

Hinkel, D.E.; Schneider, M.B.; Young, B.K.; Holder, J.P.; Langdon, A.B.; Bonanno, G.; Bower, D.E.; Bruns, H.C.; Campbell, K.M.; Celeste, J.R.; Compton, S.; Costa, R.L.; Dewald, E.L.; Dixit, S.N.; Eckart, M.J.; Eder, D.C.; Edwards, M.J.; Ellis, A.D.; Emig, J.A.; Froula, D.H.; Glenzer, S.H.; Hargrove, D.; Haynam, C.A.; Heeter, R.F.; Henesian, M.A.; Holtmeier, G.; James, D.L.; Jancaitis, K.S.; Kalantar, K.H.; Kamperschroer, J.H.; Kauffman, R.L.; Kimbrough, J.; Kirkwood, R.K.; Koniges, A.E.; Landen, O.L.; Landon, M.; Lee, F.D.; MacGowan, B.J.; Mackinnon, A.J.; Manes, K.R.; Marshall, C.; May, M.J.; McDonald, J.W.; Menapace, J.; Moses, S.E.I.; Munro, D.H.; Murray, J.R.; Niemann, C.; Power, G.D.; Rekow, V.; Ruppe, J.A.; Schein, J.; Shepherd, R.; Singh, M.S.; Springer, P.T.; Still, C.H.; Suter, L.J.; Tietbohl, G.L.; Turner, R.E.; VanWonterghem, B.M.; Wallace, R.J.; Warrick, A.; Weber, F.; Wegner, P.J.; Williams, E.A.; Young, P.E. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Baldis, H.A. [California at Davis Univ., CA (United States); Pellinen, D.; Watts, P. [Bechtel Nevada Corporation, Livermore, CA (United States)

2006-06-15

Deposition of maximum laser energy into a small, high-Z enclosure in a short laser pulse creates a hot environment. Such targets were recently included in an experimental campaign using the first four of the 192 beams of the National Ignition Facility (NIF) under construction at the University of California Lawrence Livermore National Laboratory. These targets demonstrate good laser coupling, reaching a radiation temperature of 340 eV. In addition, the Raman backscatter spectrum contains features consistent with Brillouin backscatter of Raman forward scatter. Also, NIF Early Light diagnostics indicate that 20% of the direct backscatter from these reduced-scale targets is in the polarization orthogonal to that of the incident light. (authors)

Emerging molecular-targeted therapies—the challenging case of endometrial cancer

Directory of Open Access Journals (Sweden)

Ines Vasconcelos

2015-10-01

Full Text Available Endometrial cancer newly affects an estimated 54,870 women in the United States, being responsible for an estimated 10,170 deaths in 2015. It has demonstrated to harbor a complex carcinogenesis process, with limited treatment options for advanced or persistent disease. Identification and targeting of genetic alterations that lead to progressive disease and therapy resistance is not only challenging, but also often does not correlate with a clinical benefit. Targeted maintenance therapies in endometrial cancer have been largely disappointing. Nonetheless, targeted personalized treatment should be the main goal of treatment of advanced disease in the future. Due to the high variety of drugs being tested in early clinical trials, it is hard to keep pace with the latest developments and ongoing trials. This review aims to summarize the latest published and ongoing trials on targeted therapies in endometrial cancer.

System for measuring the proton polarization in a polarized target

International Nuclear Information System (INIS)

Karnaukhov, I.M.; Lukhanin, A.A.; Telegin, Yu.N.; Trotsenko, V.I.; Chechetenko, V.F.

1984-01-01

The system for measuring the proton polarization in a polarized target representing the high-sensitivity nuclear magnetic resonance (NMR) is described Q-meter with series connection and a circuit for measuring system resonance characteristic is used for NMR-absorption signal recording. Measuring coil is produced of a strip conductor in order to obtain uniform system sensitivity to polarization state in all target volume and improve signal-to-noise ratio. Polarization measuring system operates ion-line with the M-6000 computer. The total measuring error for the value of free proton polarization in target taking into account the error caused by local depolarization of working substance under irradiation by high-intense photon beam is <= 6%. Long-term application of the described system for measuring the proton polarization in the LUEh-20000 accelerator target used in the pion photoproduction experiments has demonstrated its high reliability

The National Long Term Care Demonstration: operational issues encountered in developing the research design.

Science.gov (United States)

Carcagno, G J; Kemper, P

1983-01-01

This paper describes the design of the National Long Term Care Demonstration and its evaluation and discusses a number of operational issues encountered in the design process: simultaneous design of research and operations, identification of the target population, randomization, collection of comparable data, development of an assessment instrument, potential changes in existing programs, and termination planning.

Collaborative In-Network Processing for Target Tracking

Directory of Open Access Journals (Sweden)

Juan Liu

2003-03-01

Full Text Available This paper presents a class of signal processing techniques for collaborative signal processing in ad hoc sensor networks, focusing on a vehicle tracking application. In particular, we study two types of commonly used sensors—acoustic-amplitude sensors for target distance estimation and direction-of-arrival sensors for bearing estimation—and investigate how networks of such sensors can collaborate to extract useful information with minimal resource usage. The information-driven sensor collaboration has several advantages: tracking is distributed, and the network is energy-efficient, activated only on a when-needed basis. We demonstrate the effectiveness of the approach to target tracking using both simulation and field data.

An efficient targeted drug delivery through apotransferrin loaded nanoparticles.

Directory of Open Access Journals (Sweden)

Athuluri Divakar Sai Krishna

Full Text Available BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano, and showed further increase in dimension (75-95 etam in conjugated nanoparticles (conj-nano. The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus (b pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in

Organelle targeting: third level of drug targeting

Directory of Open Access Journals (Sweden)

Sakhrani NM

2013-07-01

Full Text Available Niraj M Sakhrani, Harish PadhDepartment of Cell and Molecular Biology, BV Patel Pharmaceutical Education and Research Development (PERD Centre, Gujarat, IndiaAbstract: Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum.Keywords: intracellular drug delivery, cancer chemotherapy, therapeutic index, cell penetrating peptides

Losing memories during sleep after targeted memory reactivation.

Science.gov (United States)

Simon, Katharine C N S; Gómez, Rebecca L; Nadel, Lynn

2018-03-17

Targeting memories during sleep opens powerful and innovative ways to influence the mind. We used targeted memory reactivation (TMR), which to date has been shown to strengthen learned episodes, to instead induce forgetting (TMR-Forget). Participants were first trained to associate the act of forgetting with an auditory forget tone. In a second, separate, task they learned object-sound-location pairings. Shortly thereafter, some of the object sounds were played during slow wave sleep, paired with the forget tone to induce forgetting. One week later, participants demonstrated lower recall of reactivated versus non-reactivated objects and impaired recognition memory and lowered confidence for the spatial location of the reactivated objects they failed to spontaneously recall. The ability to target specific episodic memories for forgetting during sleep has implications for developing novel therapeutic techniques for psychological disorders such as PTSD and phobias. Copyright © 2018 Elsevier Inc. All rights reserved.

Growing Fixed With Age: Lay Theories of Malleability Are Target Age-Specific.

Science.gov (United States)

Neel, Rebecca; Lassetter, Bethany

2015-11-01

Beliefs about whether people can change ("lay theories" of malleability) are known to have wide-ranging effects on social motivation, cognition, and judgment. Yet rather than holding an overarching belief that people can or cannot change, perceivers may hold independent beliefs about whether different people are malleable-that is, lay theories may be target-specific. Seven studies demonstrate that lay theories are target-specific with respect to age: Perceivers hold distinct, uncorrelated lay theories of people at different ages, and younger targets are considered to be more malleable than older targets. Both forms of target-specificity are consequential, as target age-specific lay theories predict policy support for learning-based senior services and the rehabilitation of old and young drug users. The implications of target age-specific lay theories for a number of psychological processes, the social psychology of aging, and theoretical frameworks of malleability beliefs are discussed. © 2015 by the Society for Personality and Social Psychology, Inc.

New target for high-intensity laser-matter interaction: Gravitational flow of micrometer-sized powders

International Nuclear Information System (INIS)

Servol, M.; Quere, F.; Bougeard, M.; Monot, P.; Martin, Ph.; Faenov, A.Ya; Pikuz, T.A.; Audebert, P.; Francucci, M.; Petrocelli, G.

2005-01-01

The design of efficient targets for high-intensity laser-matter interaction is essential to fully exploit the advantages of laser-induced photons or particles sources. We present an advantageous kind of target, consisting in a free gravitational flow of micrometer-sized powder, and describe its main technical characteristics. We demonstrate a laser-induced keV x-ray source using this target, and show that the photon flux obtained for the Kα line of Si by irradiating different silica powders is comparable to the one obtained with a bulk silica target

Co-targeting the HER and IGF/insulin receptor axis in breast cancer, with triple targeting with endocrine therapy for hormone-sensitive disease.

Science.gov (United States)

Chakraborty, Ashok; Hatzis, Christos; DiGiovanna, Michael P

2017-05-01

Interactions between HER2, estrogen receptor (ER), and insulin-like growth factor I receptor (IGF1R) are implicated in resistance to monotherapies targeting these receptors. We have previously shown in pre-clinical studies synergistic anti-tumor effects for co-targeting each pairwise combination of HER2, IGF1R, and ER. Strikingly, synergy for HER2/IGF1R targeting occurred not only in a HER2+ model, but also in a HER2-normal model. The purpose of the current study was therefore to determine the generalizability of synergistic anti-tumor effects of co-targeting HER2/IGF1R, the anti-tumor activity of triple-targeting HER2/IGF1R/ER in hormone-dependent cell lines, and the effect of using the multi-targeting drugs neratinib (pan-HER) and BMS-754807 (dual IGF1R/insulin receptor). Proliferation and apoptosis assays were performed in a large panel of cell lines representing varying receptor expression levels. Mechanistic effects were studied using phospho-protein immunoblotting. Analyses of drug interaction effects were performed using linear mixed-effects regression models. Enhanced anti-proliferative effects of HER/IGF-insulin co-targeting were seen in most, though not all, cell lines, including HER2-normal lines. For ER+ lines, triple targeting with inclusion of anti-estrogen generally resulted in the greatest anti-tumor effects. Double or triple targeting generally resulted in marked increases in apoptosis in the sensitive lines. Mechanistic studies demonstrated that the synergy between drugs was correlated with maximal inhibition of Akt and ERK pathway signaling. Dual HER/IGF-insulin targeting, and triple targeting with inclusion of anti-estrogen drugs, shows striking anti-tumor activity across breast cancer types, and drugs with broader receptor specificity may be more effective than single receptor selective drugs, particularly for ER- cells.

Enhancing potency of siRNA targeting fusion genes by optimization outside of target sequence.

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Gavrilov, Kseniya; Seo, Young-Eun; Tietjen, Gregory T; Cui, Jiajia; Cheng, Christopher J; Saltzman, W Mark

2015-12-01

Canonical siRNA design algorithms have become remarkably effective at predicting favorable binding regions within a target mRNA, but in some cases (e.g., a fusion junction site) region choice is restricted. In these instances, alternative approaches are necessary to obtain a highly potent silencing molecule. Here we focus on strategies for rational optimization of two siRNAs that target the junction sites of fusion oncogenes BCR-ABL and TMPRSS2-ERG. We demonstrate that modifying the termini of these siRNAs with a terminal G-U wobble pair or a carefully selected pair of terminal asymmetry-enhancing mismatches can result in an increase in potency at low doses. Importantly, we observed that improvements in silencing at the mRNA level do not necessarily translate to reductions in protein level and/or cell death. Decline in protein level is also heavily influenced by targeted protein half-life, and delivery vehicle toxicity can confound measures of cell death due to silencing. Therefore, for BCR-ABL, which has a long protein half-life that is difficult to overcome using siRNA, we also developed a nontoxic transfection vector: poly(lactic-coglycolic acid) nanoparticles that release siRNA over many days. We show that this system can achieve effective killing of leukemic cells. These findings provide insights into the implications of siRNA sequence for potency and suggest strategies for the design of more effective therapeutic siRNA molecules. Furthermore, this work points to the importance of integrating studies of siRNA design and delivery, while heeding and addressing potential limitations such as restricted targetable mRNA regions, long protein half-lives, and nonspecific toxicities.

Targeting protein biotinylation enhances tuberculosis chemotherapy.

Science.gov (United States)

Tiwari, Divya; Park, Sae Woong; Essawy, Maram M; Dawadi, Surendra; Mason, Alan; Nandakumar, Madhumitha; Zimmerman, Matthew; Mina, Marizel; Ho, Hsin Pin; Engelhart, Curtis A; Ioerger, Thomas; Sacchettini, James C; Rhee, Kyu; Ehrt, Sabine; Aldrich, Courtney C; Dartois, Véronique; Schnappinger, Dirk

2018-04-25

Successful drug treatment for tuberculosis (TB) depends on the unique contributions of its component drugs. Drug resistance poses a threat to the efficacy of individual drugs and the regimens to which they contribute. Biologically and chemically validated targets capable of replacing individual components of current TB chemotherapy are a major unmet need in TB drug development. We demonstrate that chemical inhibition of the bacterial biotin protein ligase (BPL) with the inhibitor Bio-AMS (5'-[ N -(d-biotinoyl)sulfamoyl]amino-5'-deoxyadenosine) killed Mycobacterium tuberculosis ( Mtb ), the bacterial pathogen causing TB. We also show that genetic silencing of BPL eliminated the pathogen efficiently from mice during acute and chronic infection with Mtb Partial chemical inactivation of BPL increased the potency of two first-line drugs, rifampicin and ethambutol, and genetic interference with protein biotinylation accelerated clearance of Mtb from mouse lungs and spleens by rifampicin. These studies validate BPL as a potential drug target that could serve as an alternate frontline target in the development of new drugs against Mtb . Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Folate targeted polymeric 'green' nanotherapy for cancer

Energy Technology Data Exchange (ETDEWEB)

Narayanan, Sreeja; Binulal, N S; Mony, Ullas; Manzoor, Koyakutty; Nair, Shantikumar; Menon, Deepthy, E-mail: deepthymenon@aims.amrita.edu [Amrita Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi-682 041, Kerala (India)

2010-07-16

The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)-'NanoGSE'-was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size {approx} 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC{sub 50} values were lowered by a factor of {approx} 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.

A quick reality check for microRNA target prediction.

Science.gov (United States)

Kast, Juergen

2011-04-01

The regulation of protein abundance by microRNA (miRNA)-mediated repression of mRNA translation is a rapidly growing area of interest in biochemical research. In animal cells, the miRNA seed sequence does not perfectly match that of the mRNA it targets, resulting in a large number of possible miRNA targets and varied extents of repression. Several software tools are available for the prediction of miRNA targets, yet the overlap between them is limited. Jovanovic et al. have developed and applied a targeted, quantitative approach to validate predicted miRNA target proteins. Using a proteome database, they have set up and tested selected reaction monitoring assays for approximately 20% of more than 800 predicted let-7 targets, as well as control genes in Caenorhabditis elegans. Their results demonstrate that such assays can be developed quickly and with relative ease, and applied in a high-throughput setup to verify known and identify novel miRNA targets. They also show, however, that the choice of the biological system and material has a noticeable influence on the frequency, extent and direction of the observed changes. Nonetheless, selected reaction monitoring assays, such as those developed by Jovanovic et al., represent an attractive new tool in the study of miRNA function at the organism level.

Effect of Printing Parameters on Tensile, Dynamic Mechanical, and Thermoelectric Properties of FDM 3D Printed CABS/ZnO Composites

Directory of Open Access Journals (Sweden)

Yah Yun Aw

2018-03-01

Full Text Available Fused deposition modelling (FDM has been widely used in medical appliances, automobile, aircraft and aerospace, household appliances, toys, and many other fields. The ease of processing, low cost and high flexibility of FDM technique are strong advantages compared to other techniques for thermoelectric polymer composite fabrication. This research work focuses on the effect of two crucial printing parameters (infill density and printing pattern on the tensile, dynamic mechanical, and thermoelectric properties of conductive acrylonitrile butadiene styrene/zinc oxide (CABS/ZnO composites fabricated by FDM technique. Results revealed significant improvement in tensile strength and Young’s modulus, with a decrease in elongation at break with infill density. Improvement in dynamic storage modulus was observed when infill density changed from 50% to 100%. However, the loss modulus and damping factor reduced gradually. The increase of thermal conductivity was relatively smaller compared to the improvement of electrical conductivity and Seebeck coefficient, therefore, the calculated figure of merit (ZT value increased with infill density. Line pattern performed better than rectilinear, especially in tensile properties and electrical conductivity. From the results obtained, FDM-fabricated CABS/ZnO showed much potential as a promising candidate for thermoelectric application.

Effect of Printing Parameters on Tensile, Dynamic Mechanical, and Thermoelectric Properties of FDM 3D Printed CABS/ZnO Composites.

Science.gov (United States)

Aw, Yah Yun; Yeoh, Cheow Keat; Idris, Muhammad Asri; Teh, Pei Leng; Hamzah, Khairul Amali; Sazali, Shulizawati Aqzna

2018-03-22

Fused deposition modelling (FDM) has been widely used in medical appliances, automobile, aircraft and aerospace, household appliances, toys, and many other fields. The ease of processing, low cost and high flexibility of FDM technique are strong advantages compared to other techniques for thermoelectric polymer composite fabrication. This research work focuses on the effect of two crucial printing parameters (infill density and printing pattern) on the tensile, dynamic mechanical, and thermoelectric properties of conductive acrylonitrile butadiene styrene/zinc oxide (CABS/ZnO composites fabricated by FDM technique. Results revealed significant improvement in tensile strength and Young's modulus, with a decrease in elongation at break with infill density. Improvement in dynamic storage modulus was observed when infill density changed from 50% to 100%. However, the loss modulus and damping factor reduced gradually. The increase of thermal conductivity was relatively smaller compared to the improvement of electrical conductivity and Seebeck coefficient, therefore, the calculated figure of merit (ZT) value increased with infill density. Line pattern performed better than rectilinear, especially in tensile properties and electrical conductivity. From the results obtained, FDM-fabricated CABS/ZnO showed much potential as a promising candidate for thermoelectric application .

Robust H(∞) control for spacecraft rendezvous with a noncooperative target.

Science.gov (United States)

Wu, Shu-Nan; Zhou, Wen-Ya; Tan, Shu-Jun; Wu, Guo-Qiang

2013-01-01

The robust H(∞) control for spacecraft rendezvous with a noncooperative target is addressed in this paper. The relative motion of chaser and noncooperative target is firstly modeled as the uncertain system, which contains uncertain orbit parameter and mass. Then the H(∞) performance and finite time performance are proposed, and a robust H(∞) controller is developed to drive the chaser to rendezvous with the non-cooperative target in the presence of control input saturation, measurement error, and thrust error. The linear matrix inequality technology is used to derive the sufficient condition of the proposed controller. An illustrative example is finally provided to demonstrate the effectiveness of the controller.

Low-velocity ion stopping in a dense and low-temperature plasma target

Science.gov (United States)

Deutsch, Claude; Popoff, Romain

2007-07-01

We investigate the stopping specificities involved in the heating of thin foils irradiated by intense ion beams in the 0.3-3 MeV/amu energy range and in close vicinity of the Bragg peak. Considering a swiftly ionized target to eV temperatures before expansion while retaining solid-state density, a typical warm dense matter (WDM) situation thus arises. We stress low Vp stopping through ion diffusion in the given target plasma. This allows to include the case of a strongly magnetized target in a guiding center approximation. We also demonstrate that the ion projectile penetration depth in target is significantly affected by multiple scattering on target electrons. The given plasma target is taken weakly coupled with Maxwell electron either with no magnetic field ( B=0) or strongly magnetized ( B≠0). Dynamical coupling between ion projectiles energy losses and projectiles charge state will also be addressed.

Transorbital target localization in the porcine model

Science.gov (United States)

DeLisi, Michael P.; Mawn, Louise A.; Galloway, Robert L.

2013-03-01

Current pharmacological therapies for the treatment of chronic optic neuropathies such as glaucoma are often inadequate due to their inability to directly affect the optic nerve and prevent neuron death. While drugs that target the neurons have been developed, existing methods of administration are not capable of delivering an effective dose of medication along the entire length of the nerve. We have developed an image-guided system that utilizes a magnetically tracked flexible endoscope to navigate to the back of the eye and administer therapy directly to the optic nerve. We demonstrate the capabilities of this system with a series of targeted surgical interventions in the orbits of live pigs. Target objects consisted of NMR microspherical bulbs with a volume of 18 μL filled with either water or diluted gadolinium-based contrast, and prepared with either the presence or absence of a visible coloring agent. A total of 6 pigs were placed under general anesthesia and two microspheres of differing color and contrast content were blindly implanted in the fat tissue of each orbit. The pigs were scanned with T1-weighted MRI, image volumes were registered, and the microsphere containing gadolinium contrast was designated as the target. The surgeon was required to navigate the flexible endoscope to the target and identify it by color. For the last three pigs, a 2D/3D registration was performed such that the target's coordinates in the image volume was noted and its location on the video stream was displayed with a crosshair to aid in navigation. The surgeon was able to correctly identify the target by color, with an average intervention time of 20 minutes for the first three pigs and 3 minutes for the last three.

A new method of small target detection based on neural network

Science.gov (United States)

Hu, Jing; Hu, Yongli; Lu, Xinxin

2018-02-01

The detection and tracking of moving dim target in infrared image have been an research hotspot for many years. The target in each frame of images only occupies several pixels without any shape and structure information. Moreover, infrared small target is often submerged in complicated background with low signal-to-clutter ratio, making the detection very difficult. Different backgrounds exhibit different statistical properties, making it becomes extremely complex to detect the target. If the threshold segmentation is not reasonable, there may be more noise points in the final detection, which is unfavorable for the detection of the trajectory of the target. Single-frame target detection may not be able to obtain the desired target and cause high false alarm rate. We believe the combination of suspicious target detection spatially in each frame and temporal association for target tracking will increase reliability of tracking dim target. The detection of dim target is mainly divided into two parts, In the first part, we adopt bilateral filtering method in background suppression, after the threshold segmentation, the suspicious target in each frame are extracted, then we use LSTM(long short term memory) neural network to predict coordinates of target of the next frame. It is a brand-new method base on the movement characteristic of the target in sequence images which could respond to the changes in the relationship between past and future values of the values. Simulation results demonstrate proposed algorithm can effectively predict the trajectory of the moving small target and work efficiently and robustly with low false alarm.

Alternative splicing affects the targeting sequence of peroxisome proteins in Arabidopsis.

Science.gov (United States)

An, Chuanjing; Gao, Yuefang; Li, Jinyu; Liu, Xiaomin; Gao, Fuli; Gao, Hongbo

2017-07-01

A systematic analysis of the Arabidopsis genome in combination with localization experiments indicates that alternative splicing affects the peroxisomal targeting sequence of at least 71 genes in Arabidopsis. Peroxisomes are ubiquitous eukaryotic cellular organelles that play a key role in diverse metabolic functions. All peroxisome proteins are encoded by nuclear genes and target to peroxisomes mainly through two types of targeting signals: peroxisomal targeting signal type 1 (PTS1) and PTS2. Alternative splicing (AS) is a process occurring in all eukaryotes by which a single pre-mRNA can generate multiple mRNA variants, often encoding proteins with functional differences. However, the effects of AS on the PTS1 or PTS2 and the targeting of the protein were rarely studied, especially in plants. Here, we systematically analyzed the genome of Arabidopsis, and found that the C-terminal targeting sequence PTS1 of 66 genes and the N-terminal targeting sequence PTS2 of 5 genes are affected by AS. Experimental determination of the targeting of selected protein isoforms further demonstrated that AS at both the 5' and 3' region of a gene can affect the inclusion of PTS2 and PTS1, respectively. This work underscores the importance of AS on the global regulation of peroxisome protein targeting.

A modular platform for targeted RNAi therapeutics.

Science.gov (United States)

Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

2018-03-01

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs 1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting 4-8 , their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines▿

Science.gov (United States)

Yacoby, Iftach; Bar, Hagit; Benhar, Itai

2007-01-01

While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of ∼20,000 compared to the free drug. PMID:17404004

A modular platform for targeted RNAi therapeutics

Science.gov (United States)

Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

2018-01-01

Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting4-8, their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

Targeting Epigenetics to Prevent Obesity Promoted Cancers.

Science.gov (United States)

Berger, Nathan A; Scacheri, Peter C

2018-03-01

Epigenetic changes in DNA and associated chromatin proteins are increasingly being considered as important mediators of the linkage between obesity and cancer. Although multiple agents, targeted at epigenetic changes, are being tested for therapy of established cancers, this issue of Cancer Prevention Research carries two articles demonstrating that the bromodomain inhibitor I-BET-762 can attenuate adipose tissue-promoted cancers. Although I-BET-762 significantly delayed, rather than completely prevented, the onset of adiposity-promoted transformation and malignancy, these experiments provide important proof of principle for the strategies of targeting epigenetic changes to disrupt the obesity-cancer linkage. Because bromodomain proteins represent only one of multiple epigenetic mediators, it is probable that targeting other epigenetic processes, alone or in combination, may serve to even more effectively disrupt the obesity promotion of cancer. Given the magnitude of the current obesity pandemic and its impact on cancer, preventive measures to disrupt this linkage are critically important. Cancer Prev Res; 11(3); 125-8. ©2018 AACR See related article by Chakraborty et al., p. 129 . ©2018 American Association for Cancer Research.

Selective whole genome amplification for resequencing target microbial species from complex natural samples.

Science.gov (United States)

Leichty, Aaron R; Brisson, Dustin

2014-10-01

Population genomic analyses have demonstrated power to address major questions in evolutionary and molecular microbiology. Collecting populations of genomes is hindered in many microbial species by the absence of a cost effective and practical method to collect ample quantities of sufficiently pure genomic DNA for next-generation sequencing. Here we present a simple method to amplify genomes of a target microbial species present in a complex, natural sample. The selective whole genome amplification (SWGA) technique amplifies target genomes using nucleotide sequence motifs that are common in the target microbe genome, but rare in the background genomes, to prime the highly processive phi29 polymerase. SWGA thus selectively amplifies the target genome from samples in which it originally represented a minor fraction of the total DNA. The post-SWGA samples are enriched in target genomic DNA, which are ideal for population resequencing. We demonstrate the efficacy of SWGA using both laboratory-prepared mixtures of cultured microbes as well as a natural host-microbe association. Targeted amplification of Borrelia burgdorferi mixed with Escherichia coli at genome ratios of 1:2000 resulted in >10(5)-fold amplification of the target genomes with genomic extracts from Wolbachia pipientis-infected Drosophila melanogaster resulted in up to 70% of high-throughput resequencing reads mapping to the W. pipientis genome. By contrast, 2-9% of sequencing reads were derived from W. pipientis without prior amplification. The SWGA technique results in high sequencing coverage at a fraction of the sequencing effort, thus allowing population genomic studies at affordable costs. Copyright © 2014 by the Genetics Society of America.

Emotion causes targeted forgetting of established memories

Directory of Open Access Journals (Sweden)

Bryan A. Strange

2010-11-01

Full Text Available Reconsolidation postulates that reactivation of a memory trace renders it susceptible to disruption by treatments similar to those that impair initial memory consolidation. Despite evidence that implicit, or non-declarative, human memories can be disrupted at retrieval, a convincing demonstration of selective impairment in retrieval of target episodic memories following reactivation is lacking. In human subjects, we demonstrate that if reactivation of a verbal memory, through successful retrieval, is immediately followed by an emotionally aversive stimulus, a significant impairment is evident in its later recall. This effect is time-dependent and persists for at least six days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval.

Emotion causes targeted forgetting of established memories.

Science.gov (United States)

Strange, Bryan A; Kroes, Marijn C W; Fan, Judith E; Dolan, Raymond J

2010-01-01

Reconsolidation postulates that reactivation of a memory trace renders it susceptible to disruption by treatments similar to those that impair initial memory consolidation. Despite evidence that implicit, or non-declarative, human memories can be disrupted at retrieval, a convincing demonstration of selective impairment in retrieval of target episodic memories following reactivation is lacking. In human subjects, we demonstrate that if reactivation of a verbal memory, through successful retrieval, is immediately followed by an emotionally aversive stimulus, a significant impairment is evident in its later recall. This effect is time-dependent and persists for at least 6 days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval.

Demonstration of Efficient Core Heating of Magnetized Fast Ignition in FIREX project

Science.gov (United States)

Johzaki, Tomoyuki

2017-10-01

Extensive theoretical and experimental research in the FIREX ``I project over the past decade revealed that the large angular divergence of the laser generated electron beam is one of the most critical problems inhibiting efficient core heating in electron-driven fast ignition. To solve this problem, beam guiding using externally applied kilo-tesla class magnetic field was proposed, and its feasibility has recently been numerically demonstrated. In 2016, integrated experiments at ILE Osaka University demonstrated core heating efficiencies reaching > 5 % and heated core temperatures of 1.7 keV. In these experiments, a kilo-tesla class magnetic field was applied to a cone-attached Cu(II) oleate spherical solid target by using a laser-driven capacitor-coil. The target was then imploded by G-XII laser and heated by the PW-class LFEX laser. The heating efficiency was evaluated by measuring the number of Cu-K- α photons emitted. The heated core temperature was estimated by the X-ray intensity ratio of Cu Li-like and He-like emission lines. To understand the detailed dynamics of the core heating process, we carried out integrated simulations using the FI3 code system. Effects of magnetic fields on the implosion and electron beam transport, detailed core heating dynamics, and the resultant heating efficiency and core temperature will be presented. I will also discuss the prospect for an ignition-scale design of magnetized fast ignition using a solid ball target. This work is partially supported by JSPA KAKENHI Grant Number JP16H02245, JP26400532, JP15K21767, JP26400532, JP16K05638 and is performed with the support and the auspices of the NIFS Collaboration Research program (NIFS12KUGK057, NIFS15KUGK087).

Cell-specific targeting by heterobivalent ligands.

Science.gov (United States)

Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

2011-07-20

Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

Remote target removal for the Oak Ridge 86-inch Cyclotron

International Nuclear Information System (INIS)

Walls, A.A.

1982-01-01

A remotely operated target remover has been plaed in operation at the 86-Inch Cyclotron located in Oak Ridge. The system provides for the remote removal of a target from inside the cyclotron, loading it into a cask, and the removal of the cask from the 1.5 m (5-ft) shielding walls. The remote system consists of multiple electrical and pneumatically operated equipment which is designed for controlled step-by-step operation, operated with an electrical control panel, and monitored by a television system. The target remover has reduced the radiation exposures to operating personnel at the facility and has increased the effective operating time. The system is fast, requires a minimum of skill to operate, and has demonstrated both reliability and durability

Horizontal impact testing of quarter scale flasks using masonry targets

International Nuclear Information System (INIS)

Tufton, E.P.S.

1985-01-01

The programme leading up to the Train Crash Demonstration included investigation of flask impacts, in horizontal motion, against masonry targets representing abutment structures. An outline is given of a series of eight tests, of which five are described in detail. All the tests used quarter-scale flasks, and the design and construction of the appropriate brick and stone masonry targets is described. A summary of results is given in terms of damage to the model flask compared with the more severe damage seen in regulatory drop tests. (author)

FINDING SOLUTIONS AT THE WEST VALLEY DEMONSTRATION PROJECT

International Nuclear Information System (INIS)

Drake, John L.; Gramling, James M.; Houston, Helene M.

2003-01-01

The United States Department of Energy Office of Environmental Management (DOE-EM) faces a number of sizeable challenges as it begins to transform its mission from managing risk to reducing and eliminating risk throughout the DOE Complex. One of the greatest challenges being addressed by DOE-EM as this transformation takes place is accelerating the deactivation and decommissioning of thousands of facilities within the DOE Complex that were once used to support nuclear-related programs and projects. These facilities are now unused and aging. Finding solutions to complete the cleanup of these aging facilities more safely, efficiently, and effectively while reducing costs is critical to successfully meeting DOE-EM's cleanup challenge. The Large-Scale Demonstration and Deployment Project (LSDDP) of Hot Cells at the West Valley Demonstration Project (WVDP) is a near-term project funded through the DOE's National Energy Technology Laboratory (DOE-NETL) for the specific purpose of identifying, evaluating, demonstrating, and deploying commercially available technologies that are capable of streamlining the cleanup of hot cells in unused facilities while improving worker safety. Two DOE project sites are participating in this LSDDP: the WVDP site in West Valley, New York and the Hanford River Corridor Project (RCP) site in Richland, Washington. The WVDP site serves as the host site for the project. Technologies considered for demonstration and potential deployment at both LSDDP sites are targeted for application in hot cells that require the use of remote and semi-remote techniques to conduct various cleanup-related activities because of high radiation or high contamination levels. These hot cells, the type of cleanup activities being conducted, and technologies selected for demonstration are the main topics discussed in this paper. The range of cleanup-related activities addressed include in-situ characterization, size-reduction, contamination control, decontamination, in

High-power spallation target using a heavy liquid metal free surface flow

International Nuclear Information System (INIS)

Litfin, K.; Fetzer, J.R.; Batta, A.; Class, A.G.; Wetzel, Th.

2015-01-01

A prototype of a heavy liquid metal free surface target as proposed for the multi-purpose hybrid research reactor for high-tech applications in Mol, Belgium, has been set up and experimentally investigated at the Karlsruhe Liquid Metal Laboratory. A stable operation was demonstrated in a wide range of operating conditions and the surface shape was detected and compared with numerical pre-calculations employing Star-CD. Results show a very good agreement of experiment and numerical predictions which is an essential input for other windowless target designs like the META:LIC target for the European Spallation Source. (author)

LONG-TERM DEMONSTRATION OF SORBENT ENHANCEMENT ADDITIVE TECHNOLOGY FOR MERCURY CONTROL

Energy Technology Data Exchange (ETDEWEB)

Jason D. Laumb; Dennis L. Laudal; Grant E. Dunham; John P. Kay; Christopher L. Martin; Jeffrey S. Thompson; Nicholas B. Lentz; Alexander Azenkeng; Kevin C. Galbreath; Lucinda L. Hamre

2011-05-27

Long-term demonstration tests of advanced sorbent enhancement additive (SEA) technologies have been completed at five coal-fired power plants. The targeted removal rate was 90% from baseline conditions at all five stations. The plants included Hawthorn Unit 5, Mill Creek Unit 4, San Miguel Unit 1, Centralia Unit 2, and Hoot Lake Unit 2. The materials tested included powdered activated carbon, treated carbon, scrubber additives, and SEAs. In only one case (San Miguel) was >90% removal not attainable. The reemission of mercury from the scrubber at this facility prevented >90% capture.

Age-related changes in gait adaptability in response to unpredictable obstacles and stepping targets.

Science.gov (United States)

Caetano, Maria Joana D; Lord, Stephen R; Schoene, Daniel; Pelicioni, Paulo H S; Sturnieks, Daina L; Menant, Jasmine C

2016-05-01

A large proportion of falls in older people occur when walking. Limitations in gait adaptability might contribute to tripping; a frequently reported cause of falls in this group. To evaluate age-related changes in gait adaptability in response to obstacles or stepping targets presented at short notice, i.e.: approximately two steps ahead. Fifty older adults (aged 74±7 years; 34 females) and 21 young adults (aged 26±4 years; 12 females) completed 3 usual gait speed (baseline) trials. They then completed the following randomly presented gait adaptability trials: obstacle avoidance, short stepping target, long stepping target and no target/obstacle (3 trials of each). Compared with the young, the older adults slowed significantly in no target/obstacle trials compared with the baseline trials. They took more steps and spent more time in double support while approaching the obstacle and stepping targets, demonstrated poorer stepping accuracy and made more stepping errors (failed to hit the stepping targets/avoid the obstacle). The older adults also reduced velocity of the two preceding steps and shortened the previous step in the long stepping target condition and in the obstacle avoidance condition. Compared with their younger counterparts, the older adults exhibited a more conservative adaptation strategy characterised by slow, short and multiple steps with longer time in double support. Even so, they demonstrated poorer stepping accuracy and made more stepping errors. This reduced gait adaptability may place older adults at increased risk of falling when negotiating unexpected hazards. Copyright © 2016 Elsevier B.V. All rights reserved.

Target experimental area and systems of the Us national ignition facility

International Nuclear Information System (INIS)

Tobin, M.; Van Wonterghem, B.; MacGowan, B.J.; Hibbard, W.; Kalantar, D.; Lee, F.D.; Pittenger, L.; Wong, K.

2000-01-01

One of the major goals of the US National Ignition Facility is the demonstration of laser driven fusion ignition and burn of targets by inertial confinement and provide capability for a wide variety of high energy density physics experiments. The NIF target area houses the optical systems required to focus the 192 beamlets to a target precisely positioned at the center of the 10 meter diameter, 10-cm thick aluminum target chamber. The chamber serves as mounting surface for the 48 final optics assemblies, the target alignment and positioning equipment, and the target diagnostics. The internal surfaces of the chamber are protected by louvered steel beam dumps. The target area also provides the necessary shielding against target emission and environmental protection equipment. Despite its complexity, the design provides the flexibility to accommodate the needs of the various NIF user groups, such as direct and indirect drive irradiation geometries, modular final optics design, capability to handle cryogenic targets, and easily re-configurable diagnostic instruments. Efficient target area operations are ensured by using line-replaceable designs for systems requiring frequent inspection, maintenance and reconfiguration, such as the final optics, debris shields, phase plates and the diagnostic instruments. A precision diagnostic instrument manipulator (DIMS) allows fast removal and precise repositioning of diagnostic instruments. In addition we will describe several activities to enhance the target chamber availability, such as the target debris mitigation, the use of standard experimental configurations and the development of smart shot operations planning tools. (authors)

Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin.

Science.gov (United States)

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M; Das, Samir; Nag, Arundhati; Agnew, Heather D; Heath, James R

2015-06-08

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Matrine Is Identified as a Novel Macropinocytosis Inducer by a Network Target Approach

Directory of Open Access Journals (Sweden)

Bo Zhang

2018-01-01

Full Text Available Comprehensively understanding pharmacological functions of natural products is a key issue to be addressed for the discovery of new drugs. Unlike some single-target drugs, natural products always exert diverse therapeutic effects through acting on a “network” that consists of multiple targets, making it necessary to develop a systematic approach, e.g., network pharmacology, to reveal pharmacological functions of natural products and infer their mechanisms of action. In this work, to identify the “network target” of a natural product, we perform a functional analysis of matrine, a marketed drug in China extracted from a medical herb Ku-Shen (Radix Sophorae Flavescentis. Here, the network target of matrine was firstly predicted by drugCIPHER, a genome-wide target prediction method. Based on the network target of matrine, we performed a functional gene set enrichment analysis to computationally identify the potential pharmacological functions of matrine, most of which are supported by the literature evidence, including neurotoxicity and neuropharmacological activities of matrine. Furthermore, computational results demonstrated that matrine has the potential for the induction of macropinocytosis and the regulation of ATP metabolism. Our experimental data revealed that the large vesicles induced by matrine are consistent with the typical characteristics of macropinosome. Our verification results also suggested that matrine could decrease cellular ATP level. These findings demonstrated the availability and effectiveness of the network target strategy for identifying the comprehensive pharmacological functions of natural products.

Targeting Plasmodium PI(4)K to eliminate malaria

Science.gov (United States)

McNamara, Case W.; Lee, Marcus C. S.; Lim, Chek Shik; Lim, Siau Hoi; Roland, Jason; Nagle, Advait; Simon, Oliver; Yeung, Bryan K. S.; Chatterjee, Arnab K.; McCormack, Susan L.; Manary, Micah J.; Zeeman, Anne-Marie; Dechering, Koen J.; Kumar, T. R. Santha; Henrich, Philipp P.; Gagaring, Kerstin; Ibanez, Maureen; Kato, Nobutaka; Kuhen, Kelli L.; Fischli, Christoph; Rottmann, Matthias; Plouffe, David M.; Bursulaya, Badry; Meister, Stephan; Rameh, Lucia; Trappe, Joerg; Haasen, Dorothea; Timmerman, Martijn; Sauerwein, Robert W.; Suwanarusk, Rossarin; Russell, Bruce; Renia, Laurent; Nosten, Francois; Tully, David C.; Kocken, Clemens H. M.; Glynne, Richard J.; Bodenreider, Christophe; Fidock, David A.; Diagana, Thierry T.; Winzeler, Elizabeth A.

2013-12-01

Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.

Experimental results from a flowing-lithium target

International Nuclear Information System (INIS)

Annese, C.E.; Schwartz, K.E.

1982-01-01

Hydraulic stability of a free surface lithium jet was demonstrated at 260 0 C and from the middle-vacuum region of 0.01 Pa (10 - 4 Torr) up to 124 kPa (18 psia). The jet is formed by flowing lithium at rates to 0.04 m 3 /s (600 GPM) through a precisely defined nozzle which directs the flow along a curved wall where velocities of up to 17 m/s are attained. This nozzle and curved wall configuration form the basis of the Fusion Materials Irradiation Test (FMIT) Facility lithium target. A full-size experimental model of this target is presently under test with flowing lithium in the Experimental Lithium System (ELS). The FMIT is being developed for the Department of Energy by the Westinghouse Hanford Company at the Hanford Engineering Development Laboratory

PROSTVAC® targeted immunotherapy candidate for prostate cancer.

Science.gov (United States)

Shore, Neal D

2014-01-01

Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

Reliability demonstration test for load-sharing systems with exponential and Weibull components.

Directory of Open Access Journals (Sweden)

Jianyu Xu

Full Text Available Conducting a Reliability Demonstration Test (RDT is a crucial step in production. Products are tested under certain schemes to demonstrate whether their reliability indices reach pre-specified thresholds. Test schemes for RDT have been studied in different situations, e.g., lifetime testing, degradation testing and accelerated testing. Systems designed with several structures are also investigated in many RDT plans. Despite the availability of a range of test plans for different systems, RDT planning for load-sharing systems hasn't yet received the attention it deserves. In this paper, we propose a demonstration method for two specific types of load-sharing systems with components subject to two distributions: exponential and Weibull. Based on the assumptions and interpretations made in several previous works on such load-sharing systems, we set the mean time to failure (MTTF of the total system as the demonstration target. We represent the MTTF as a summation of mean time between successive component failures. Next, we introduce generalized test statistics for both the underlying distributions. Finally, RDT plans for the two types of systems are established on the basis of these test statistics.

Targeted Delivery of Hyaluronan-Immobilized Magnetic Ceramic Nanocrystals.

Science.gov (United States)

Wu, Hsi-Chin; Wang, Tzu-Wei; Hsieh, Shun-Yu; Sun, Jui-Sheng; Kang, Pei-Leun

2016-01-01

Effective cancer therapy relies on delivering the therapeutic agent precisely to the target site to improve the treatment outcome and to minimize side effects. Although surgery, chemotherapy, and radiotherapy are the standard methods commonly used in clinics, hyperthermia has been developed as a new and promising strategy for cancer therapy. In this study, magnetic bioceramic hydroxyapatite (mHAP) nanocrystals have been developed as heat mediator for intracellular hyperthermia. Hyaluronic acid (HA) modified mHAP nanocrystals are synthesized by a wet chemical precipitation process to achieve active targeting. The results demonstrate that the HA targeting moiety conjugated by a poly(ethylene glycol) (PEG) spacer arm is successfully immobilized on the surface of mHAP. The HA-modified mHAP possesses relatively good biocompatibility, an adequate biodegradation rate and superparamagnetic properties. The HA-modified mHAP could be localized and internalized into HA receptor-overexpressed malignant cells (e.g., MDA-MB-231 cell) and used as the heat generating agent for intracellular hyperthermia. The results from this study indicate that biocompatible HA-modified mHAP shows promise as a novel heat mediator and a specific targeting nanoagent for intracellular hyperthermia cancer therapy.

Novel target design for enhanced laser driven proton acceleration

Directory of Open Access Journals (Sweden)

Malay Dalui

2017-09-01

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

Activity of Nanobins Targeted to the Urokinase Plasminogen Activator System

Science.gov (United States)

Hankins, Patrick Leon

While innovations in nanotechnology have resulted in numerous medical advancements for the treatment of cancer, there remains an urgent unmet need for safe and efficient molecular platforms that facilitate the delivery of potent therapeutics to solid tumors. Nanoscale formulations help to overcome the poor bioavailability and systemic organ toxicity associated with many small molecule drugs. Of these nanoparticle drug delivery systems, the greatest clinical successes to date have employed simple nanoscale lipid bilayer assemblies which encase large payloads of chemotherapeutic. While the nanobin platform we have developed has seen initial success through the passive accumulation into tumors, actively targeting nanobins to tumor specific antigens has the potential to increase the therapeutic index of these nanoparticle drugs. We have identified the urokinase plasminogen activator (uPA) and its cell surface bound receptor (uPAR) as ideal targets for drug delivery due to their selective overexpression in metastatic cancers and their important role in tumor progression. From a panel of monoclonal antibodies targeted to uPA and uPAR, we have selected ATN291 and ATN658 as lead candidates for nanobin targeting based on their tumor cell binding and ability to be internalized by cells. A novel method of conjugating antibodies to liposomes was developed for our nanobin platform that preserves the high binding affinity and specificity of these antibodies. We evaluated these uPA- and uPAR-targeted nanobins in several xenograft tumor models and found that they were well-tolerated over a wide range of doses and demonstrated significantly increased antitumor efficacy over untargeted nanobins in multiple tumor types. Preliminary studies suggest that uPA-targeted nanobins are readily internalized by tumor cells, and we believe this is the mechanism for their increased antitumor effect. A method for radiolabeling nanobins with gallium-67 was developed, and preliminary SPECT

Exome sequencing generates high quality data in non-target regions

Directory of Open Access Journals (Sweden)

Guo Yan

2012-05-01

Full Text Available Abstract Background Exome sequencing using next-generation sequencing technologies is a cost efficient approach to selectively sequencing coding regions of human genome for detection of disease variants. A significant amount of DNA fragments from the capture process fall outside target regions, and sequence data for positions outside target regions have been mostly ignored after alignment. Result We performed whole exome sequencing on 22 subjects using Agilent SureSelect capture reagent and 6 subjects using Illumina TrueSeq capture reagent. We also downloaded sequencing data for 6 subjects from the 1000 Genomes Project Pilot 3 study. Using these data, we examined the quality of SNPs detected outside target regions by computing consistency rate with genotypes obtained from SNP chips or the Hapmap database, transition-transversion (Ti/Tv ratio, and percentage of SNPs inside dbSNP. For all three platforms, we obtained high-quality SNPs outside target regions, and some far from target regions. In our Agilent SureSelect data, we obtained 84,049 high-quality SNPs outside target regions compared to 65,231 SNPs inside target regions (a 129% increase. For our Illumina TrueSeq data, we obtained 222,171 high-quality SNPs outside target regions compared to 95,818 SNPs inside target regions (a 232% increase. For the data from the 1000 Genomes Project, we obtained 7,139 high-quality SNPs outside target regions compared to 1,548 SNPs inside target regions (a 461% increase. Conclusions These results demonstrate that a significant amount of high quality genotypes outside target regions can be obtained from exome sequencing data. These data should not be ignored in genetic epidemiology studies.

Targeted learning in data science causal inference for complex longitudinal studies

CERN Document Server

van der Laan, Mark J

2018-01-01

This textbook for graduate students in statistics, data science, and public health deals with the practical challenges that come with big, complex, and dynamic data. It presents a scientific roadmap to translate real-world data science applications into formal statistical estimation problems by using the general template of targeted maximum likelihood estimators. These targeted machine learning algorithms estimate quantities of interest while still providing valid inference. Targeted learning methods within data science area critical component for solving scientific problems in the modern age. The techniques can answer complex questions including optimal rules for assigning treatment based on longitudinal data with time-dependent confounding, as well as other estimands in dependent data structures, such as networks. Included in Targeted Learning in Data Science are demonstrations with soft ware packages and real data sets that present a case that targeted learning is crucial for the next generatio...

Confined zone dispersion flue gas desulfurization demonstration

Energy Technology Data Exchange (ETDEWEB)

1992-12-31

This is the fifth quarterly report for this project. This project is divided into three phases. Phase 1, which has been completed, involved design, engineering, and procurement for the CZD system, duct and facility modifications, and supporting equipment. Phase 2, also completed, included equipment acquisition and installation, facility construction, startup, and operator training for parametric testing. Phase 3 broadly covers testing, operation and disposition, but only a portion of Phase 3 was included in Budget Period 1. That portion was concerned with parametric testing of the CZD system to establish the optimum conditions for an extended, one-year, continuous demonstration. As of December 31, 1991, the following goals have been achieved. (1) Nozzle Selection - A modified Spraying Systems Company (SSC) atomizing nozzle has been selected for the one-year continuous CZD demonstration. (2) SO[sub 2] and NO[sub x] Reduction - Preliminary confirmation of 50% SO[sub 2] reduction has been achieved, but the NO[sub x] reduction target cannot be confirmed at this time. (3) Lime Selection - Testing indicated an injection rate of 40 to 50 gallons per minute with a lime slurry concentration of 8 to 10% to achieve 50% SO[sub 2] reduction. There has been no selection of the lime to be used in the one year demonstration. (4) ESP Optimization - Tests conducted to date have shown that lime injection has a very beneficial effect on ESP performance, and little adjustment may be necessary. (5) SO[sub 2] Removal Costs - Testing has not revealed any significant departure from the bases on which Bechtel's original cost estimates (capital and operating) were prepared. Therefore, SO[sub 2] removal costs are still expected to be in the range of $300/ton or less.

Some safety studies of the MEGAPIE spallation source target performed using computational fluid dynamics

International Nuclear Information System (INIS)

Smith, B.L.

2011-01-01

Such a target forms part of the evolutionary Accelerator-Driven System (ADS) concept in which neutrons are generated in an otherwise sub-critical core by spallation reactions resulting from bombardment by a proton beam. The international project MEGAPIE had the objective of demonstrating the feasibility of the spallation process for a particular target design under strict test conditions. The test was carried over a period of four months at the end of 2006 at the SINQ facility of the Paul Scherrer Institute in Switzerland. The design studies carried out for the MEGAPIE target prior to irradiation using Computational Fluid Dynamics (CFD) resulted in an optimum flow configuration being defined for the coolant circulation. Simultaneously, stresses in the structural components were examined using Finite Element Method (FEM) techniques. To this purpose, an interface program was written which enabled different specialist groups to carry out the thermal hydraulics and structural mechanics analyses within the project with fully consistent model data. Results for steady-state operation of the target show that the critical lower target components are adequately cooled, and that stresses and displacements are well within tolerances. Transient analyses were also performed to demonstrate the robustness of the design in the event of abnormal operation, including pump failure and burn-through of the target casing by the proton beam. In the latter case, the CFD analyses complemented and extended full-scale tests. (author)

Some safety studies of the MEGAPIE spallation source target performed using computational fluid dynamics

Energy Technology Data Exchange (ETDEWEB)

Smith, B.L., E-mail: brian.smith@psi.ch [Paul Scherrer Institute, OHSA/C08, 5232 Villigen PSI (Switzerland)

2011-07-01

Such a target forms part of the evolutionary Accelerator-Driven System (ADS) concept in which neutrons are generated in an otherwise sub-critical core by spallation reactions resulting from bombardment by a proton beam. The international project MEGAPIE had the objective of demonstrating the feasibility of the spallation process for a particular target design under strict test conditions. The test was carried over a period of four months at the end of 2006 at the SINQ facility of the Paul Scherrer Institute in Switzerland. The design studies carried out for the MEGAPIE target prior to irradiation using Computational Fluid Dynamics (CFD) resulted in an optimum flow configuration being defined for the coolant circulation. Simultaneously, stresses in the structural components were examined using Finite Element Method (FEM) techniques. To this purpose, an interface program was written which enabled different specialist groups to carry out the thermal hydraulics and structural mechanics analyses within the project with fully consistent model data. Results for steady-state operation of the target show that the critical lower target components are adequately cooled, and that stresses and displacements are well within tolerances. Transient analyses were also performed to demonstrate the robustness of the design in the event of abnormal operation, including pump failure and burn-through of the target casing by the proton beam. In the latter case, the CFD analyses complemented and extended full-scale tests. (author)

Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers.

Science.gov (United States)

Zhang, Fan; Nance, Elizabeth; Zhang, Zhi; Jasty, Venkatasai; Kambhampati, Siva P; Mishra, Manoj K; Burd, Irina; Romero, Roberto; Kannan, Sujatha; Kannan, Rangaramanujam M

2016-09-10

Cerebral Palsy (CP) is a chronic childhood disorder with limited therapeutic options. Maternal intrauterine inflammation/infection is a major risk factor in the pathogenesis of CP. In pre-clinical models, dendrimer-based therapies are viable in postnatal period, attenuating inflammation and improving motor function in vivo. However, treatment to the mother, in the prenatal period, may provide the possibility of preventing/resolving inflammation at early stages. Towards this goal, we used a maternal intrauterine inflammation-induced rabbit model of CP to study fetal-maternal transport and neuroinflammation targeting of intra-amniotically administrated dendrimers with neutral/anionic surface functionality. Our study suggested both hydroxyl-terminated 'neutral' (D-OH) and carboxyl-terminated 'anionic' (D-COOH) Polyamidoamine (PAMAM) dendrimers were absorbed by fetuses and demonstrated bi-directional transport between fetuses and mother. D-OH was more effective in crossing the fetal blood-brain barrier, and targeting activated microglia. The cell-specific targeting was associated with the extent of microglia activation. This study demonstrated intra-amniotically administered hydroxyl PAMAM dendrimers could be an effective drug delivery vehicle for targeting fetal inflammation and preventing subsequent neurologic injury associated with chorioamnionitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers☆

Science.gov (United States)

Zhang, Fan; Nance, Elizabeth; Zhang, Zhi; Jasty, Venkatasai; Kambhampati, Siva P.; Mishra, Manoj K.; Burd, Irina; Romero, Roberto; Kannan, Sujatha; Kannan, Rangaramanujam M.

2017-01-01

Cerebral Palsy (CP) is a chronic childhood disorder with limited therapeutic options. Maternal intrauterine inflammation/infection is a major risk factor in the pathogenesis of CP. In pre-clinical models, dendrimer-based therapies are viable in postnatal period, attenuating inflammation and improving motor function in vivo. However, treatment to the mother, in the prenatal period, may provide the possibility of preventing/resolving inflammation at early stages. Towards this goal, we used a maternal intrauterine inflammation-induced rabbit model of CP to study fetal-maternal transport and neuroinflammation targeting of intra-amniotically administrated dendrimers with neutral/anionic surface functionality. Our study suggested both hydroxyl-terminated ‘neutral’ (D-OH) and carboxyl-terminated ‘anionic’ (D-COOH) Polyamidoamine (PAMAM) dendrimers were absorbed by fetuses and demonstrated bi-directional transport between fetuses and mother. D-OH was more effective in crossing the fetal blood-brain barrier, and targeting activated microglia. The cell-specific targeting was associated with the extent of microglia activation. This study demonstrated intra-amniotically administered hydroxyl PAMAM dendrimers could be an effective drug delivery vehicle for targeting fetal inflammation and preventing subsequent neurologic injury associated with chorioamnionitis. PMID:27378700

CRISPR/Cas9-mediated target validation of the Splicing Inhibitor Pladienolide B

KAUST Repository

Aouida, Mustapha; Eid, Ayman; Mahfouz, Magdy M.

2016-01-01

CRISPR/Cas9 system confers molecular immunity in archeal and bacterial species against invading foreign nucleic acids. CRISPR/Cas9 system is used for genome engineering applications across diverse eukaryotic species. In this study, we demonstrate the utility of the CRISPR/Cas9 genome engineering system for drug target validation in human cells. Pladienolide B is a natural macrolide with antitumor activities mediated through the inhibition of pre-mRNA splicing. To validate the spliceosomal target of Pladienolide B, we employed the CRSIPR/Cas9 system to introduce targeted mutations in the subunits of the SF3B complex in the HEK293T cells. Our data reveal that targeted mutagenesis of the SF3b1 subunit exhibited higher levels of resistance to Pladienolide B. Therefore, our data validate the spliceosomal target of Pladienolide B and provide a proof of concept on using the CRISPR/Cas9 system for drug target identification and validation.

CRISPR/Cas9-mediated target validation of the Splicing Inhibitor Pladienolide B

KAUST Repository

Aouida, Mustapha

2016-02-24

CRISPR/Cas9 system confers molecular immunity in archeal and bacterial species against invading foreign nucleic acids. CRISPR/Cas9 system is used for genome engineering applications across diverse eukaryotic species. In this study, we demonstrate the utility of the CRISPR/Cas9 genome engineering system for drug target validation in human cells. Pladienolide B is a natural macrolide with antitumor activities mediated through the inhibition of pre-mRNA splicing. To validate the spliceosomal target of Pladienolide B, we employed the CRSIPR/Cas9 system to introduce targeted mutations in the subunits of the SF3B complex in the HEK293T cells. Our data reveal that targeted mutagenesis of the SF3b1 subunit exhibited higher levels of resistance to Pladienolide B. Therefore, our data validate the spliceosomal target of Pladienolide B and provide a proof of concept on using the CRISPR/Cas9 system for drug target identification and validation.

Covalent Targeting of Fibroblast Growth Factor Receptor Inhibits Metastatic Breast Cancer.

Science.gov (United States)

Brown, Wells S; Tan, Li; Smith, Andrew; Gray, Nathanael S; Wendt, Michael K

2016-09-01

Therapeutic targeting of late-stage breast cancer is limited by an inadequate understanding of how tumor cell signaling evolves during metastatic progression and by the currently available small molecule inhibitors capable of targeting these processes. Herein, we demonstrate that both β3 integrin and fibroblast growth factor receptor-1 (FGFR1) are part of an epithelial-mesenchymal transition (EMT) program that is required to facilitate metastatic outgrowth in response to fibroblast growth factor-2 (FGF2). Mechanistically, β3 integrin physically disrupts an interaction between FGFR1 and E-cadherin, leading to a dramatic redistribution of FGFR1 subcellular localization, enhanced FGF2 signaling and increased three-dimensional (3D) outgrowth of metastatic breast cancer cells. This ability of β3 integrin to drive FGFR signaling requires the enzymatic activity of focal adhesion kinase (FAK). Consistent with these mechanistic data, we demonstrate that FGFR, β3 integrin, and FAK constitute a molecular signature capable of predicting decreased survival of patients with the basal-like subtype of breast cancer. Importantly, covalent targeting of a conserved cysteine in the P-loop of FGFR1-4 with our newly developed small molecule, FIIN-4, more effectively blocks 3D metastatic outgrowth as compared with currently available FGFR inhibitors. In vivo application of FIIN-4 potently inhibited the growth of metastatic, patient-derived breast cancer xenografts and murine-derived metastases growing within the pulmonary microenvironment. Overall, the current studies demonstrate that FGFR1 works in concert with other EMT effector molecules to drive aberrant downstream signaling, and that these events can be effectively targeted using our novel therapeutics for the treatment of the most aggressive forms of breast cancer. Mol Cancer Ther; 15(9); 2096-106. ©2016 AACR. ©2016 American Association for Cancer Research.

ProtoDESI: First On-Sky Technology Demonstration for the Dark Energy Spectroscopic Instrument

Science.gov (United States)

Fagrelius, Parker; Abareshi, Behzad; Allen, Lori; Ballester, Otger; Baltay, Charles; Besuner, Robert; Buckley-Geer, Elizabeth; Butler, Karen; Cardiel, Laia; Dey, Arjun; Duan, Yutong; Elliott, Ann; Emmet, William; Gershkovich, Irena; Honscheid, Klaus; Illa, Jose M.; Jimenez, Jorge; Joyce, Richard; Karcher, Armin; Kent, Stephen; Lambert, Andrew; Lampton, Michael; Levi, Michael; Manser, Christopher; Marshall, Robert; Martini, Paul; Paat, Anthony; Probst, Ronald; Rabinowitz, David; Reil, Kevin; Robertson, Amy; Rockosi, Connie; Schlegel, David; Schubnell, Michael; Serrano, Santiago; Silber, Joseph; Soto, Christian; Sprayberry, David; Summers, David; Tarlé, Greg; Weaver, Benjamin A.

2018-02-01

The Dark Energy Spectroscopic Instrument (DESI) is under construction to measure the expansion history of the universe using the baryon acoustic oscillations technique. The spectra of 35 million galaxies and quasars over 14,000 square degrees will be measured during a 5-year survey. A new prime focus corrector for the Mayall telescope at Kitt Peak National Observatory will deliver light to 5,000 individually targeted fiber-fed robotic positioners. The fibers in turn feed ten broadband multi-object spectrographs. We describe the ProtoDESI experiment, that was installed and commissioned on the 4-m Mayall telescope from 2016 August 14 to September 30. ProtoDESI was an on-sky technology demonstration with the goal to reduce technical risks associated with aligning optical fibers with targets using robotic fiber positioners and maintaining the stability required to operate DESI. The ProtoDESI prime focus instrument, consisting of three fiber positioners, illuminated fiducials, and a guide camera, was installed behind the existing Mosaic corrector on the Mayall telescope. A fiber view camera was mounted in the Cassegrain cage of the telescope and provided feedback metrology for positioning the fibers. ProtoDESI also provided a platform for early integration of hardware with the DESI Instrument Control System that controls the subsystems, provides communication with the Telescope Control System, and collects instrument telemetry data. Lacking a spectrograph, ProtoDESI monitored the output of the fibers using a fiber photometry camera mounted on the prime focus instrument. ProtoDESI was successful in acquiring targets with the robotically positioned fibers and demonstrated that the DESI guiding requirements can be met.

A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia

Science.gov (United States)

Bray, Walter M.; White, Pamela M.; Ruybal, Jordan; Lokey, R. Scott; Debec, Alain; Sullivan, William

2012-01-01

Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular Wolbachia titer both in Drosophila melanogaster and Brugia malayi, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt Drosophila microtubule organization, suggesting that this compound reduces titer through direct targeting of Wolbachia. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces Wolbachia elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their Wolbachia endosymbionts. PMID:23028321

A Universal Method for Fishing Target Proteins from Mixtures of Biomolecules using Isothermal Titration Calorimetry

Energy Technology Data Exchange (ETDEWEB)

Zhou, X.; Sun, Q; Kini, R; Sivaraman, J

2008-01-01

The most challenging tasks in biology include the identification of (1) the orphan receptor for a ligand, (2) the ligand for an orphan receptor protein, and (3) the target protein(s) for a given drug or a lead compound that are critical for the pharmacological or side effects. At present, several approaches are available, including cell- or animal-based assays, affinity labeling, solid-phase binding assays, surface plasmon resonance, and nuclear magnetic resonance. Most of these techniques are not easy to apply when the target protein is unknown and the compound is not amenable to labeling, chemical modification, or immobilization. Here we demonstrate a new universal method for fishing orphan target proteins from a complex mixture of biomolecules using isothermal titration calorimetry (ITC) as a tracking tool. We took snake venom, a crude mixture of several hundred proteins/peptides, as a model to demonstrate our proposed ITC method in tracking the isolation and purification of two distinct target proteins, a major component and a minor component. Identities of fished out target proteins were confirmed by amino acid sequencing and inhibition assays. This method has the potential to make a significant advancement in the area of identifying orphan target proteins and inhibitor screening in drug discovery and characterization.

Gamma ray tracking with the AGATA demonstrator. A novel approach for in-beam spectroscopy

International Nuclear Information System (INIS)

Birkenbach, Benedikt

2014-01-01

The Advanced GAmma Tracking Array (AGATA) employs the novel method of γ-ray tracking (GRT), where all locations of energy depositions within the Ge crystal detector volume are used by computer algorithms to reconstruct the various simultaneous interactions of the measured radiation. The interaction positions are determined by Pulse Shape Analysis (PSA) algorithms that compare the measured and digitized signals with the information of a signal database comprising position dependent calculated sets of detector signals. The result of a detailed comparison between measured and calculated signals yields the position of each interaction point. The GRT algorithms rely on this precise position of the deposited energy as an input to reconstruct the initial γ-rays from the full sequence of the different interactions in the detector. Within this thesis a computer program library was developed, providing software routines to calculate the position dependent detector signals of the highly segmented HPGe detectors. The currently used signal databases of all AGATA detectors were generated by this software package and computer library. Part of the computing is based on individual detector properties which were deduced from detailed characterisation measurements. Details of the library, the used routines and the needed characteristics of the detector system are described, this includes a precise measurement of the crystal axis orientation of the AGATA HPGe crystals. The second part of this thesis is dealing with the analysis of one of the first in-beam experiments performed with the AGATA demonstrator setup at the LNL in Italy. The experiment aimed for a spectroscopic investigation of neutron rich actinides from Thorium to Plutonium produced after multi-nucleon transfer reactions. For this purpose a 136 Xe beam with an energy of 1 GeV bombarded onto a 238 U target. The fast beam like particles after the transfer reactions were identified by the magnetic spectrometer PRISMA. The �

Assessing cross-modal target transition effects with a visual-auditory oddball.

Science.gov (United States)

Kiat, John E

2018-04-30

Prior research has shown contextual manipulations involving temporal and sequence related factors significantly moderate attention-related responses, as indexed by the P3b event-related-potential, towards infrequent (i.e., deviant) target oddball stimuli. However, significantly less research has looked at the influence of cross-modal switching on P3b responding, with the impact of target-to-target cross-modal transitions being virtually unstudied. To address this gap, this study recorded high-density (256 electrodes) EEG data from twenty-five participants as they completed a cross-modal visual-auditory oddball task. This task was comprised of unimodal visual (70% Nontargets: 30% Deviant-targets) and auditory (70% Nontargets: 30% Deviant-targets) oddballs presented in fixed alternating order (i.e., visual-auditory-visual-auditory, etc.) with participants being tasked with detecting deviant-targets in both modalities. Differences in the P3b response towards deviant-targets as a function of preceding deviant-target's presentation modality was analyzed using temporal-spatial PCA decomposition. In line with predictions, the results indicate that the ERP response to auditory deviant-targets preceded by visual deviant-targets exhibits an elevated P3b, relative to the processing of auditory deviant-targets preceded by auditory deviant-targets. However, the processing of visual deviant-targets preceded by auditory deviant-targets exhibited a reduced P3b response, relative to the P3b response towards visual deviant-targets preceded by visual deviant-targets. These findings provide the first demonstration of temporally and perceptually decoupled target-to-target cross-modal transitions moderating P3b responses on the oddball paradigm, generally providing support for the context-updating interpretation of the P3b response. Copyright © 2017. Published by Elsevier B.V.

High-power liquid-lithium jet target for neutron production

Science.gov (United States)

Halfon, S.; Arenshtam, A.; Kijel, D.; Paul, M.; Berkovits, D.; Eliyahu, I.; Feinberg, G.; Friedman, M.; Hazenshprung, N.; Mardor, I.; Nagler, A.; Shimel, G.; Tessler, M.; Silverman, I.

2013-12-01

A compact liquid-lithium target (LiLiT) was built and tested with a high-power electron gun at the Soreq Nuclear Research Center. The lithium target, to be bombarded by the high-intensity proton beam of the Soreq Applied Research Accelerator Facility (SARAF), will constitute an intense source of neutrons produced by the 7Li(p,n)7Be reaction for nuclear astrophysics research and as a pilot setup for accelerator-based Boron Neutron Capture Therapy. The liquid-lithium jet target acts both as neutron-producing target and beam dump by removing the beam thermal power (>5 kW, >1 MW/cm3) with fast transport. The target was designed based on a thermal model, accompanied by a detailed calculation of the 7Li(p,n) neutron yield, energy distribution, and angular distribution. Liquid lithium is circulated through the target loop at ˜200 °C and generates a stable 1.5 mm-thick film flowing at a velocity up to 7 m/s onto a concave supporting wall. Electron beam irradiation demonstrated that the liquid-lithium target can dissipate electron power areal densities of >4 kW/cm2 and volume power density of ˜2 MW/cm3 at a lithium flow of ˜4 m/s while maintaining stable temperature and vacuum conditions. The LiLiT setup is presently in online commissioning stage for high-intensity proton beam irradiation (1.91-2.5 MeV, 1-2 mA) at SARAF.

Design of the MYRRHA Spallation Target Assembly

International Nuclear Information System (INIS)

Keijers, S.; Fernandez, R.; Stankovskiy, A.; Kennedy, G.; Van Tichelen, K.

2015-01-01

MYRRHA (Multi-purpose hybrid Research Reactor for High-tech Applications) is a multi-purpose research facility currently being developed at SCK.CEN. MYRRHA is based on the ADS (Accelerator Driven System) concept where a proton accelerator, a spallation target and a subcritical reactor are coupled. MYRRHA will demonstrate the ADS full concept by coupling these three components at a reasonable power level. As a flexible irradiation facility, the MYRRHA research reactor will be able to work in both critical and subcritical modes. In this way, MYRRHA will allow fuel developments for innovative reactor systems, material research for GEN IV and fusion reactors, and radioisotope production for medical and industrial applications. MYRRHA will be cooled by Lead Bismuth Eutectic (LBE) and will play an important role in the development of the Pb-alloys technology needed for the LFR (Lead Fast Reactor) GEN IV concept. This paper describes the evolution of the MYRRHA spallation target design. In the early phase of the MYRRHA project (XT-ADS), the target design was based on a dedicated spallation loop inside the primary reactor vessel. Within the core, the 3 central fuel assembly positions were occupied by the spallation target, which enabled a windowless design created by a free surface of LBE facing the proton beam. The windowless option was preferred because of high heat loads in combination with severe irradiation damage in the target region would result in unacceptably short lifetimes of a target window. The LBE in the loop served as spallation target and as target coolant, but was separated from the LBE cooling the reactor core. The loop was equipped with its own pump, heat exchanger and conditioning system. The change from cyclotron to linear accelerator allowed the increase in proton energy from 350 MeV to 600 MeV. This modification led to an important reduction of the specific heat load at the target level and an improvement of the neutronic performance. In addition to

Incorporating Financial Stability in Inflation Targeting Frameworks

OpenAIRE

Burcu Aydin; Engin Volkan

2011-01-01

The global financial crisis has exposed the limitations of a conventional inflation targeting (IT) framework in insulating an economy from shocks, and demonstrated that its rigid application may aggravate the effect of shocks on output and inflation. Accordingly, we investigate possible refinements to the IT framework by incorporating financial stability considerations. We propose a small open economy DSGE model, calibrated for Korea during the period of 2003 - 07, with real and financial fri...

Electron loss from heavy heliumlike projectiles in ultrarelativistic collisions with many-electron atomic targets

International Nuclear Information System (INIS)

Mueller, C.; Gruen, N.; Voitkiv, A.B.

2002-01-01

We study single- and double-electron loss from heavy heliumlike projectiles in ultrarelativistic collisions with neutral many-electron target atoms. The simultaneous interaction of the target with two projectile electrons is found to be the dominant process in the double-electron loss provided the atomic number of the projectile, Z p , that of the target, Z t , and the collision velocity, v, satisfy the condition Z p Z t /v>0.4. It is shown that for a wide range of projectile and target atomic numbers the asymptotic double-to-single loss ratio strongly depends on the target atomic number but is nearly independent of the nuclear charge of the projectile. It is also demonstrated that many-photon exchange between the target and each of the projectile electrons considerably influences the double loss in collisions with very heavy targets

Heavy-ion targets

International Nuclear Information System (INIS)

Adair, H.L.; Kobisk, E.H.

1985-01-01

This chapter examines the characteristics of targets required in heavy-ion accelerator physics experiments. The effects of target parameters on heavy-ion experimental results are reviewed. The target fabrication and characterization techniques used to minimize experimental problems during heavy-ion bombardment are described. Topics considered include target thickness and uniformity, target lifetime, target purity, substrate materials, Doppler shift effects, metal preparations, and target preparation methods

Robust H ∞ Control for Spacecraft Rendezvous with a Noncooperative Target

Science.gov (United States)

Wu, Shu-Nan; Zhou, Wen-Ya; Tan, Shu-Jun; Wu, Guo-Qiang

2013-01-01

The robust H ∞ control for spacecraft rendezvous with a noncooperative target is addressed in this paper. The relative motion of chaser and noncooperative target is firstly modeled as the uncertain system, which contains uncertain orbit parameter and mass. Then the H ∞ performance and finite time performance are proposed, and a robust H ∞ controller is developed to drive the chaser to rendezvous with the non-cooperative target in the presence of control input saturation, measurement error, and thrust error. The linear matrix inequality technology is used to derive the sufficient condition of the proposed controller. An illustrative example is finally provided to demonstrate the effectiveness of the controller. PMID:24027446

MPD model for radar echo signal of hypersonic targets

Directory of Open Access Journals (Sweden)

Xu Xuefei

2014-08-01

Full Text Available The stop-and-go (SAG model is typically used for echo signal received by the radar using linear frequency modulation pulse compression. In this study, the authors demonstrate that this model is not applicable to hypersonic targets. Instead of SAG model, they present a more realistic echo signal model (moving-in-pulse duration (MPD for hypersonic targets. Following that, they evaluate the performances of pulse compression under the SAG and MPD models by theoretical analysis and simulations. They found that the pulse compression gain has an increase of 3 dB by using the MPD model compared with the SAG model in typical cases.

Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis.

Science.gov (United States)

Pawlowski, Christa L; Li, Wei; Sun, Michael; Ravichandran, Kavya; Hickman, DaShawn; Kos, Clarissa; Kaur, Gurbani; Sen Gupta, Anirban

2017-06-01

Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger. Specifically, the PMINs can anchor onto thrombus via heteromultivalent ligand-mediated binding to active platelet integrin GPIIb-IIIa and P-selectin, and release the thrombolytic payload due to vesicle destabilization triggered by clot-relevant enzyme phospholipase-A 2 . Here we report on the evaluation of clot-targeting efficacy, lipase-triggered drug release and resultant thrombolytic capability of the PMINs in vitro, and subsequently demonstrate that intravenous delivery of thrombolytic-loaded PMINs can render targeted fibrinolysis without affecting systemic hemostasis, in vivo, in a carotid artery thrombosis model in mice. Our studies establish significant promise of the PMIN technology for safe and site-targeted nanomedicine therapies in the vascular compartment. Copyright © 2017. Published by Elsevier Ltd.

A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

Directory of Open Access Journals (Sweden)

Deng L

2012-09-01

Full Text Available Li Deng,1,# Xingfa Ke,4,# Zhiying He,3,# Daoqiu Yang,5 Hai Gong,6 Yingying Zhang,1 Xiaolong Jing,4 Jianzhong Yao,2 Jianming Chen11Department of Pharmaceutics, 2Department of Medicinal Chemistry, School of Pharmacy, 3Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China; 4Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People's Republic of China; 5Department of Dermatology, 107th Hospital of PLA, Yantai, People's Republic of China; 6Department of Radiation Oncology, General Hospital of Jinan Military Region, Jinan, People’s Republic of China#These authors contributed equally to this workAbstract: Pancreatic cancer is a highly lethal disease with a 5-year survival rate less than 5% due to the lack of an early diagnosis method and effective therapy. To provide a novel early diagnostic method and targeted therapy for pancreatic cancer, a multifunctional nanoimmunoliposome with high loading of ultrasmall superparamagnetic iron oxides (USPIOs and doxorubicin (DOX was prepared by transient binding and reverse-phase evaporation method, and was conjugated with anti-mesothelin monoclonal antibody by post-insertion method to target anti-mesothelin-overexpressed pancreatic cancer cells. The in vitro and in vivo properties of this anti-mesothelin antibody-conjugated PEGlyated liposomal DOX and USPIOs (M-PLDU; and PEGlyated nanoimmunoliposome without antibody conjugation [PLDU] were evaluated both in human pancreatic cancer cell line Panc-1 cell and in a pancreatic cancer xenograft animal model. Results showed that M-PLDUs were spherical and uniform with a diameter about ~180 nm, with a zeta potential of about −28~−30 mV, and had good efficacy encapsulating DOX and USPIOs. The in vitro study demonstrated that M-PLDUs possessed good magnetic resonance imaging (MRI capability with a transverse relaxivity (r2 of about 58.5 mM–1 • s–1. Confocal microscopy showed more

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation.

Science.gov (United States)

Dmochowski, Jacek P; Koessler, Laurent; Norcia, Anthony M; Bikson, Marom; Parra, Lucas C

2017-08-15

To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima.

Science.gov (United States)

Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Alexey V; Kutov, Danil C; Sobolev, Sergey I; Voevodin, Vladimir V; Sulimov, Vladimir B

2015-01-01

The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima

Directory of Open Access Journals (Sweden)

Igor V. Oferkin

2015-01-01

Full Text Available The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

Intra‐Target Microdosing – A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans

Science.gov (United States)

MacLeod, D; Lee, K; Santoro, A; DeMasi, DK; Hawk, T; Feinglos, M; Rowland, M; Noveck, RJ

2017-01-01

Abstract Intra‐Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first‐in‐human (FIH) testing of new molecular entities (NMEs). ITM combines intra‐target drug delivery and “microdosing,” the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic‐level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18F‐fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well‐tolerated. Results are consistent with ITM proof‐of‐concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach. PMID:28689370

Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

Science.gov (United States)

Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe

2014-02-12

Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international

Targeted Therapy for Biliary Tract Cancer

International Nuclear Information System (INIS)

Furuse, Junji; Okusaka, Takuji

2011-01-01

It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important

Forward Models for Following a Moving Target with the Puma 560 Robot Manipulator

Directory of Open Access Journals (Sweden)

Daniel Fernando Tello Gamarra

2015-12-01

Full Text Available This paper describes how a forward model could be applied in a manipulator robot to accomplish the task of following a moving target. The forward model has been implemented in the puma 560 robot manipulator in simulation after a babbling motor phase using ANFIS neural networks. The forward model delivers a rough estimation of the position in the operational space of a moving target. Using this information a Cartesian controller tracks the moving target. An implementation of the proposed architecture and the Piepmeir algorithm for the problem of following a moving target is also shown in the paper. The control architecture proposed in this paper was also tested with MLP and RBF neural networks. Results and simulations are shown to demonstrate the applicability of our proposed architecture for tracking a moving target.

Design of the deformable mirror demonstration CubeSat (DeMi)

Science.gov (United States)

Douglas, Ewan S.; Allan, Gregory; Barnes, Derek; Figura, Joseph S.; Haughwout, Christian A.; Gubner, Jennifer N.; Knoedler, Alex A.; LeClair, Sarah; Murphy, Thomas J.; Skouloudis, Nikolaos; Merck, John; Opperman, Roedolph A.; Cahoy, Kerri L.

2017-09-01

The Deformable Mirror Demonstration Mission (DeMi) was recently selected by DARPA to demonstrate in-space operation of a wavefront sensor and Microelectromechanical system (MEMS) deformable mirror (DM) payload on a 6U CubeSat. Space telescopes designed to make high-contrast observations using internal coronagraphs for direct characterization of exoplanets require the use of high-actuator density deformable mirrors. These DMs can correct image plane aberrations and speckles caused by imperfections, thermal distortions, and diffraction in the telescope and optics that would otherwise corrupt the wavefront and allow leaking starlight to contaminate coronagraphic images. DeMi is provide on-orbit demonstration and performance characterization of a MEMS deformable mirror and closed loop wavefront sensing. The DeMi payload has two operational modes, one mode that images an internal light source and another mode which uses an external aperture to images stars. Both the internal and external modes include image plane and pupil plane wavefront sensing. The objectives of the internal measurement of the 140-actuator MEMS DM actuator displacement are characterization of the mirror performance and demonstration of closed-loop correction of aberrations in the optical path. Using the external aperture to observe stars of magnitude 2 or brighter, assuming 3-axis stability with less than 0.1 degree of attitude knowledge and jitter below 10 arcsec RMSE, per observation, DeMi will also demonstrate closed loop wavefront control on an astrophysical target. We present an updated payload design, results from simulations and laboratory optical prototyping, as well as present our design for accommodating high-voltage multichannel drive electronics for the DM on a CubeSat.

A clip-based protocol for breast boost radiotherapy provides clear target visualisation and demonstrates significant volume reduction over time

Energy Technology Data Exchange (ETDEWEB)

Lewis, Lorraine [Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia); Cox, Jennifer [Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia); Faculty of Health Sciences, University of Sydney, Sydney, New South Wales (Australia); Morgia, Marita [Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia); Atyeo, John [Faculty of Health Sciences, University of Sydney, Sydney, New South Wales (Australia); Lamoury, Gillian [Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia)

2015-09-15

The clinical target volume (CTV) for early stage breast cancer is difficult to clearly identify on planning computed tomography (CT) scans. Surgical clips inserted around the tumour bed should help to identify the CTV, particularly if the seroma has been reabsorbed, and enable tracking of CTV changes over time. A surgical clip-based CTV delineation protocol was introduced. CTV visibility and its post-operative shrinkage pattern were assessed. The subjects were 27 early stage breast cancer patients receiving post-operative radiotherapy alone and 15 receiving post-operative chemotherapy followed by radiotherapy. The radiotherapy alone (RT/alone) group received a CT scan at median 25 days post-operatively (CT1rt) and another at 40 Gy, median 68 days (CT2rt). The chemotherapy/RT group (chemo/RT) received a CT scan at median 18 days post-operatively (CT1ch), a planning CT scan at median 126 days (CT2ch), and another at 40 Gy (CT3ch). There was no significant difference (P = 0.08) between the initial mean CTV for each cohort. The RT/alone cohort showed significant CTV volume reduction of 38.4% (P = 0.01) at 40 Gy. The Chemo/RT cohort had significantly reduced volumes between CT1ch: median 54 cm{sup 3} (4–118) and CT2ch: median 16 cm{sup 3}, (2–99), (P = 0.01), but no significant volume reduction thereafter. Surgical clips enable localisation of the post-surgical seroma for radiotherapy targeting. Most seroma shrinkage occurs early, enabling CT treatment planning to take place at 7 weeks, which is within the 9 weeks recommended to limit disease recurrence.

A clip-based protocol for breast boost radiotherapy provides clear target visualisation and demonstrates significant volume reduction over time

International Nuclear Information System (INIS)

Lewis, Lorraine; Cox, Jennifer; Morgia, Marita; Atyeo, John; Lamoury, Gillian

2015-01-01

The clinical target volume (CTV) for early stage breast cancer is difficult to clearly identify on planning computed tomography (CT) scans. Surgical clips inserted around the tumour bed should help to identify the CTV, particularly if the seroma has been reabsorbed, and enable tracking of CTV changes over time. A surgical clip-based CTV delineation protocol was introduced. CTV visibility and its post-operative shrinkage pattern were assessed. The subjects were 27 early stage breast cancer patients receiving post-operative radiotherapy alone and 15 receiving post-operative chemotherapy followed by radiotherapy. The radiotherapy alone (RT/alone) group received a CT scan at median 25 days post-operatively (CT1rt) and another at 40 Gy, median 68 days (CT2rt). The chemotherapy/RT group (chemo/RT) received a CT scan at median 18 days post-operatively (CT1ch), a planning CT scan at median 126 days (CT2ch), and another at 40 Gy (CT3ch). There was no significant difference (P = 0.08) between the initial mean CTV for each cohort. The RT/alone cohort showed significant CTV volume reduction of 38.4% (P = 0.01) at 40 Gy. The Chemo/RT cohort had significantly reduced volumes between CT1ch: median 54 cm 3 (4–118) and CT2ch: median 16 cm 3 , (2–99), (P = 0.01), but no significant volume reduction thereafter. Surgical clips enable localisation of the post-surgical seroma for radiotherapy targeting. Most seroma shrinkage occurs early, enabling CT treatment planning to take place at 7 weeks, which is within the 9 weeks recommended to limit disease recurrence

Target-mediated drug disposition model for drugs with two binding sites that bind to a target with one binding site.

Science.gov (United States)

Gibiansky, Leonid; Gibiansky, Ekaterina

2017-10-01

The paper extended the TMDD model to drugs with two identical binding sites (2-1 TMDD). The quasi-steady-state (2-1 QSS), quasi-equilibrium (2-1 QE), irreversible binding (2-1 IB), and Michaelis-Menten (2-1 MM) approximations of the model were derived. Using simulations, the 2-1 QSS approximation was compared with the full 2-1 TMDD model. As expected and similarly to the standard TMDD for monoclonal antibodies (mAb), 2-1 QSS predictions were nearly identical to 2-1 TMDD predictions, except for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. To illustrate properties of new equations and approximations, several variations of population PK data for mAbs with soluble (slow elimination of the complex) or membrane-bound (fast elimination of the complex) targets were simulated from a full 2-1 TMDD model and fitted to 2-1 TMDD models, to its approximations, and to the standard (1-1) QSS model. For a mAb with a soluble target, it was demonstrated that the 2-1 QSS model provided nearly identical description of the observed (simulated) free drug and total target concentrations, although there was some minor bias in predictions of unobserved free target concentrations. The standard QSS approximation also provided a good description of the observed data, but was not able to distinguish between free drug concentrations (with no target attached and both binding site free) and partially bound drug concentrations (with one of the binding sites occupied by the target). For a mAb with a membrane-bound target, the 2-1 MM approximation adequately described the data. The 2-1 QSS approximation converged 10 times faster than the full 2-1 TMDD, and its run time was comparable with the standard QSS model.

Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy.

Science.gov (United States)

Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Høgset, Anders; Selbo, Pål Kristian

2015-05-28